Women's Health

Women with type 2 diabetes who take metformin during pregnancy to control their blood glucose levels experience a range of benefits, including reduced weight gain, reduced insulin doses, and fewer large-for-gestational-age babies, suggest the results of a randomized controlled trial.

However, the drug was associated with an increased risk of small-for-gestational-age babies, which poses the question as to risk versus benefit of metformin on the health of offspring.

“Better understanding of the short- and long-term implications of these effects on infants will be important to properly advise patients with type 2 diabetes contemplating use of metformin during pregnancy,” said lead author Denice S. Feig, MD, Mount Sinai Hospital, Toronto.

The research was presented at the Diabetes UK Professional Conference: Online Series on Nov. 17 and recently published in The Lancet Diabetes & Endocrinology.

Summing up, Dr. Feig said that, on balance, she would be inclined to give metformin to most pregnant women with type 2 diabetes, perhaps with the exception of those who may have risk factors for small-for-gestational-age babies; for example, women who’ve had intrauterine growth restriction, who are smokers, and have significant renal disease, or have a lower body mass index.
 

Increased prevalence of type 2 diabetes in pregnancy

Dr. Feig said that across the developed world there have been huge increases in the prevalence of type 2 diabetes in pregnancy in recent years.

Insulin is the standard treatment for the management of type 2 diabetes in pregnancy, but these women have marked insulin resistance that worsens in pregnancy, which means their insulin requirements increase, leading to weight gain, painful injections, high cost, and noncompliance.

So despite treatment with insulin, these women continue to face increased rates of adverse maternal and fetal outcomes.

And although metformin is increasingly being used in women with type 2 diabetes during pregnancy, there is a scarcity of data on the benefits and harms of metformin use on pregnancy outcomes in these women.

The MiTy trial was therefore undertaken to determine whether metformin could improve outcomes.

The team recruited 502 women from 29 sites in Canada and Australia who had type 2 diabetes prior to pregnancy or were diagnosed during pregnancy, before 20 weeks’ gestation. The women were randomized to metformin 1 g twice daily or placebo, in addition to their usual insulin regimen, at between 6 and 28 weeks’ gestation.

Type 2 diabetes was diagnosed prior to pregnancy in 83% of women in the metformin group and in 90% of those assigned to placebo. The mean hemoglobin A1c level at randomization was 47 mmol/mol (6.5%) in both groups.

The average maternal age at baseline was approximately 35 years and mean gestational age at randomization was 16 weeks. Mean prepregnancy BMI was approximately 34 kg/m².

Of note, only 30% were of European ethnicity.
 

Less weight gain, lower A1c, less insulin needed with metformin

Dr. Feig reported that there was no significant difference between the treatment groups in terms of the proportion of women with the composite primary outcome of pregnancy loss, preterm birth, birth injury, respiratory distress, neonatal hypoglycemia, or admission to neonatal intensive care lasting more than 24 hours (P = 0.86).

However, women in the metformin group had significantly less overall weight gain during pregnancy than did those in the placebo group, at –1.8 kg (P < .0001).

They also had a significantly lower last A1c level in pregnancy, at 41 mmol/mol (5.9%) versus 43.2 mmol/mol (6.1%) in those given placebo (P = .015), and required fewer insulin doses, at 1.1 versus 1.5 units/kg/day (P < .0001), which translated to a reduction of almost 44 units/day.

Women given metformin were also less likely to require Cesarean section delivery, at 53.4% versus 62.7% in the placebo group (P = .03), although there was no difference between groups in terms of gestational hypertension or preeclampsia.

The most common adverse events were gastrointestinal complications, which occurred in 27.3% of women in the metformin group and 22.3% of those given placebo.

There were no significant differences between the metformin and placebo groups in rates of pregnancy loss (P = .81), preterm birth (P = .16), birth injury (P = .37), respiratory distress (P = .49), and congenital anomalies (P = .16).
 

Average birth weight lower with metformin

However, Dr. Feig showed that the average birth weight was lower for offspring of women given metformin than those assigned to placebo, at 3.2 kg (7.05 lb) versus 3.4 kg (7.4 lb) (P = .002).

Women given metformin were also less likely to have a baby with a birth weight of 4 kg (8.8 lb) or more, at 12.1% versus 19.2%, or a relative risk of 0.65 (P = .046), and a baby that was extremely large for gestational age, at 8.6% versus 14.8%, or a relative risk of 0.58 (P = .046).

But of concern, metformin was associated with an increased risk of small-for-gestational-age babies, at 12.9% versus 6.6% with placebo, or a relative risk of 1.96 (P = .03).

Dr. Feig suggested that this may be due to a direct effect of metformin “because as we know metformin inhibits the mTOR pathway,” which is a “primary nutrient sensor in the placenta” and could “attenuate nutrient flux and fetal growth.”

She said it is not clear whether the small-for-gestational-age babies were “healthy or unhealthy.”

To investigate further, the team has launched the MiTy Kids study, which will follow the offspring in the MiTy trial to determine whether metformin during pregnancy is associated with a reduction in adiposity and improvement in insulin resistance in the babies at 2 years of age.
 

Who should be given metformin?

During the discussion, Helen R. Murphy, MD, PhD, Norwich Medical School, University of East Anglia, England, asked whether Dr. Feig would recommend continuing metformin in pregnancy if it was started preconception for fertility issues rather than diabetes.

She replied: “If they don’t have diabetes and it’s simply for PCOS [polycystic ovary syndrome], then I have either stopped it as soon as they got pregnant or sometimes continued it through the first trimester, and then stopped.

“If the person has diabetes, however, I think given this work, for most people I would continue it,” she said.

The study was funded by the Canadian Institutes of Health Research, Lunenfeld-Tanenbaum Research Institute, and the University of Toronto. The authors have reported no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

Women with type 2 diabetes who take metformin during pregnancy to control their blood glucose levels experience a range of benefits, including reduced weight gain, reduced insulin doses, and fewer large-for-gestational-age babies, suggest the results of a randomized controlled trial.

However, the drug was associated with an increased risk of small-for-gestational-age babies, which poses the question as to risk versus benefit of metformin on the health of offspring.

“Better understanding of the short- and long-term implications of these effects on infants will be important to properly advise patients with type 2 diabetes contemplating use of metformin during pregnancy,” said lead author Denice S. Feig, MD, Mount Sinai Hospital, Toronto.

The research was presented at the Diabetes UK Professional Conference: Online Series on Nov. 17 and recently published in The Lancet Diabetes & Endocrinology.

Summing up, Dr. Feig said that, on balance, she would be inclined to give metformin to most pregnant women with type 2 diabetes, perhaps with the exception of those who may have risk factors for small-for-gestational-age babies; for example, women who’ve had intrauterine growth restriction, who are smokers, and have significant renal disease, or have a lower body mass index.
 

Increased prevalence of type 2 diabetes in pregnancy

Dr. Feig said that across the developed world there have been huge increases in the prevalence of type 2 diabetes in pregnancy in recent years.

Insulin is the standard treatment for the management of type 2 diabetes in pregnancy, but these women have marked insulin resistance that worsens in pregnancy, which means their insulin requirements increase, leading to weight gain, painful injections, high cost, and noncompliance.

So despite treatment with insulin, these women continue to face increased rates of adverse maternal and fetal outcomes.

And although metformin is increasingly being used in women with type 2 diabetes during pregnancy, there is a scarcity of data on the benefits and harms of metformin use on pregnancy outcomes in these women.

The MiTy trial was therefore undertaken to determine whether metformin could improve outcomes.

The team recruited 502 women from 29 sites in Canada and Australia who had type 2 diabetes prior to pregnancy or were diagnosed during pregnancy, before 20 weeks’ gestation. The women were randomized to metformin 1 g twice daily or placebo, in addition to their usual insulin regimen, at between 6 and 28 weeks’ gestation.

Type 2 diabetes was diagnosed prior to pregnancy in 83% of women in the metformin group and in 90% of those assigned to placebo. The mean hemoglobin A1c level at randomization was 47 mmol/mol (6.5%) in both groups.

The average maternal age at baseline was approximately 35 years and mean gestational age at randomization was 16 weeks. Mean prepregnancy BMI was approximately 34 kg/m².

Of note, only 30% were of European ethnicity.
 

Less weight gain, lower A1c, less insulin needed with metformin

Dr. Feig reported that there was no significant difference between the treatment groups in terms of the proportion of women with the composite primary outcome of pregnancy loss, preterm birth, birth injury, respiratory distress, neonatal hypoglycemia, or admission to neonatal intensive care lasting more than 24 hours (P = 0.86).

However, women in the metformin group had significantly less overall weight gain during pregnancy than did those in the placebo group, at –1.8 kg (P < .0001).

They also had a significantly lower last A1c level in pregnancy, at 41 mmol/mol (5.9%) versus 43.2 mmol/mol (6.1%) in those given placebo (P = .015), and required fewer insulin doses, at 1.1 versus 1.5 units/kg/day (P < .0001), which translated to a reduction of almost 44 units/day.

Women given metformin were also less likely to require Cesarean section delivery, at 53.4% versus 62.7% in the placebo group (P = .03), although there was no difference between groups in terms of gestational hypertension or preeclampsia.

The most common adverse events were gastrointestinal complications, which occurred in 27.3% of women in the metformin group and 22.3% of those given placebo.

There were no significant differences between the metformin and placebo groups in rates of pregnancy loss (P = .81), preterm birth (P = .16), birth injury (P = .37), respiratory distress (P = .49), and congenital anomalies (P = .16).
 

Average birth weight lower with metformin

However, Dr. Feig showed that the average birth weight was lower for offspring of women given metformin than those assigned to placebo, at 3.2 kg (7.05 lb) versus 3.4 kg (7.4 lb) (P = .002).

Women given metformin were also less likely to have a baby with a birth weight of 4 kg (8.8 lb) or more, at 12.1% versus 19.2%, or a relative risk of 0.65 (P = .046), and a baby that was extremely large for gestational age, at 8.6% versus 14.8%, or a relative risk of 0.58 (P = .046).

But of concern, metformin was associated with an increased risk of small-for-gestational-age babies, at 12.9% versus 6.6% with placebo, or a relative risk of 1.96 (P = .03).

Dr. Feig suggested that this may be due to a direct effect of metformin “because as we know metformin inhibits the mTOR pathway,” which is a “primary nutrient sensor in the placenta” and could “attenuate nutrient flux and fetal growth.”

She said it is not clear whether the small-for-gestational-age babies were “healthy or unhealthy.”

To investigate further, the team has launched the MiTy Kids study, which will follow the offspring in the MiTy trial to determine whether metformin during pregnancy is associated with a reduction in adiposity and improvement in insulin resistance in the babies at 2 years of age.
 

Who should be given metformin?

During the discussion, Helen R. Murphy, MD, PhD, Norwich Medical School, University of East Anglia, England, asked whether Dr. Feig would recommend continuing metformin in pregnancy if it was started preconception for fertility issues rather than diabetes.

She replied: “If they don’t have diabetes and it’s simply for PCOS [polycystic ovary syndrome], then I have either stopped it as soon as they got pregnant or sometimes continued it through the first trimester, and then stopped.

“If the person has diabetes, however, I think given this work, for most people I would continue it,” she said.

The study was funded by the Canadian Institutes of Health Research, Lunenfeld-Tanenbaum Research Institute, and the University of Toronto. The authors have reported no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

Women with type 2 diabetes who take metformin during pregnancy to control their blood glucose levels experience a range of benefits, including reduced weight gain, reduced insulin doses, and fewer large-for-gestational-age babies, suggest the results of a randomized controlled trial.

However, the drug was associated with an increased risk of small-for-gestational-age babies, which poses the question as to risk versus benefit of metformin on the health of offspring.

“Better understanding of the short- and long-term implications of these effects on infants will be important to properly advise patients with type 2 diabetes contemplating use of metformin during pregnancy,” said lead author Denice S. Feig, MD, Mount Sinai Hospital, Toronto.

The research was presented at the Diabetes UK Professional Conference: Online Series on Nov. 17 and recently published in The Lancet Diabetes & Endocrinology.

Summing up, Dr. Feig said that, on balance, she would be inclined to give metformin to most pregnant women with type 2 diabetes, perhaps with the exception of those who may have risk factors for small-for-gestational-age babies; for example, women who’ve had intrauterine growth restriction, who are smokers, and have significant renal disease, or have a lower body mass index.
 

Increased prevalence of type 2 diabetes in pregnancy

Dr. Feig said that across the developed world there have been huge increases in the prevalence of type 2 diabetes in pregnancy in recent years.

Insulin is the standard treatment for the management of type 2 diabetes in pregnancy, but these women have marked insulin resistance that worsens in pregnancy, which means their insulin requirements increase, leading to weight gain, painful injections, high cost, and noncompliance.

So despite treatment with insulin, these women continue to face increased rates of adverse maternal and fetal outcomes.

And although metformin is increasingly being used in women with type 2 diabetes during pregnancy, there is a scarcity of data on the benefits and harms of metformin use on pregnancy outcomes in these women.

The MiTy trial was therefore undertaken to determine whether metformin could improve outcomes.

The team recruited 502 women from 29 sites in Canada and Australia who had type 2 diabetes prior to pregnancy or were diagnosed during pregnancy, before 20 weeks’ gestation. The women were randomized to metformin 1 g twice daily or placebo, in addition to their usual insulin regimen, at between 6 and 28 weeks’ gestation.

Type 2 diabetes was diagnosed prior to pregnancy in 83% of women in the metformin group and in 90% of those assigned to placebo. The mean hemoglobin A1c level at randomization was 47 mmol/mol (6.5%) in both groups.

The average maternal age at baseline was approximately 35 years and mean gestational age at randomization was 16 weeks. Mean prepregnancy BMI was approximately 34 kg/m².

Of note, only 30% were of European ethnicity.
 

Less weight gain, lower A1c, less insulin needed with metformin

Dr. Feig reported that there was no significant difference between the treatment groups in terms of the proportion of women with the composite primary outcome of pregnancy loss, preterm birth, birth injury, respiratory distress, neonatal hypoglycemia, or admission to neonatal intensive care lasting more than 24 hours (P = 0.86).

However, women in the metformin group had significantly less overall weight gain during pregnancy than did those in the placebo group, at –1.8 kg (P < .0001).

They also had a significantly lower last A1c level in pregnancy, at 41 mmol/mol (5.9%) versus 43.2 mmol/mol (6.1%) in those given placebo (P = .015), and required fewer insulin doses, at 1.1 versus 1.5 units/kg/day (P < .0001), which translated to a reduction of almost 44 units/day.

Women given metformin were also less likely to require Cesarean section delivery, at 53.4% versus 62.7% in the placebo group (P = .03), although there was no difference between groups in terms of gestational hypertension or preeclampsia.

The most common adverse events were gastrointestinal complications, which occurred in 27.3% of women in the metformin group and 22.3% of those given placebo.

There were no significant differences between the metformin and placebo groups in rates of pregnancy loss (P = .81), preterm birth (P = .16), birth injury (P = .37), respiratory distress (P = .49), and congenital anomalies (P = .16).
 

Average birth weight lower with metformin

However, Dr. Feig showed that the average birth weight was lower for offspring of women given metformin than those assigned to placebo, at 3.2 kg (7.05 lb) versus 3.4 kg (7.4 lb) (P = .002).

Women given metformin were also less likely to have a baby with a birth weight of 4 kg (8.8 lb) or more, at 12.1% versus 19.2%, or a relative risk of 0.65 (P = .046), and a baby that was extremely large for gestational age, at 8.6% versus 14.8%, or a relative risk of 0.58 (P = .046).

But of concern, metformin was associated with an increased risk of small-for-gestational-age babies, at 12.9% versus 6.6% with placebo, or a relative risk of 1.96 (P = .03).

Dr. Feig suggested that this may be due to a direct effect of metformin “because as we know metformin inhibits the mTOR pathway,” which is a “primary nutrient sensor in the placenta” and could “attenuate nutrient flux and fetal growth.”

She said it is not clear whether the small-for-gestational-age babies were “healthy or unhealthy.”

To investigate further, the team has launched the MiTy Kids study, which will follow the offspring in the MiTy trial to determine whether metformin during pregnancy is associated with a reduction in adiposity and improvement in insulin resistance in the babies at 2 years of age.
 

Who should be given metformin?

During the discussion, Helen R. Murphy, MD, PhD, Norwich Medical School, University of East Anglia, England, asked whether Dr. Feig would recommend continuing metformin in pregnancy if it was started preconception for fertility issues rather than diabetes.

She replied: “If they don’t have diabetes and it’s simply for PCOS [polycystic ovary syndrome], then I have either stopped it as soon as they got pregnant or sometimes continued it through the first trimester, and then stopped.

“If the person has diabetes, however, I think given this work, for most people I would continue it,” she said.

The study was funded by the Canadian Institutes of Health Research, Lunenfeld-Tanenbaum Research Institute, and the University of Toronto. The authors have reported no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

Patients with a primary humoral immunodeficiency (PID) are 91% more likely to have a psychiatric disorder and 84% more likely to exhibit suicidal behavior, compared against those without the condition, new research shows.

Results showed that this association, which was stronger in women, could not be fully explained by comorbid autoimmune diseases or by familial confounding.

These findings have important clinical implications, study investigator Josef Isung, MD, PhD, Centre for Psychiatry Research, Karolinska Institute, Stockholm, Sweden, told Medscape Medical News.

Clinicians managing patients with PID “should be aware of this increased association with psychiatric disorders and perhaps screen for them,” said Isung.

The study was published in the November issue of JAMA Psychiatry.
 

Registry study

Mounting evidence suggests immune disruption plays a role in psychiatric disorders through a range of mechanisms, including altered neurodevelopment. However, little is known about the neuropsychiatric consequences resulting from the underproduction of homeostatic antibodies.

PIDs involve a deficiency in antibody production, mainly affecting immunoglobulin, “or the humoral aspect of the immune system,” said Isung. They’re associated with an increased risk for recurrent infections and of developing autoimmune diseases.

The immunodeficiency can be severe, even life threatening, but can also be relatively mild. One of the less severe PID types is selective IgA deficiency, which is linked to increased infections within the mucosa-associated lymphoid tissue (MALT), an important immune barrier.

Experts have long suspected that infections within the MALT are associated with certain forms of psychopathology in children, particularly obsessive-compulsive disorder and chronic tic disorders.

While patients with this selective IgA subtype may be at some increased risk for infection and autoimmune disease, their overall health otherwise is good, said Isung.

The prevalence of PIDs ranges from about 1:250 to 1:20,000, depending on the type of humoral immunodeficiency, although most would fall into the relatively rare category, he added.

Using several linked national Swedish registries, researchers identified individuals with any PID diagnosis affecting immunoglobulin levels, their full siblings, and those with a lifetime diagnosis of selective IgA deficiency. In addition, they collected data on autoimmune diseases.

The study outcome was a lifetime record of a psychiatric disorder, a suicide attempt, or death by suicide.
 

Strong link to autism

Researchers identified 8378 patients (59% women) with PID affecting immunoglobulin levels (median age at first diagnosis, 47.8 years). They compared this group with almost 14.3 million subjects without PID.

In those with PID, 27.6% had an autoimmune disease vs 6.8% of those without PID, a statistically significant difference (P < .001).

About 20.5% of those with PID and 10.7% of unexposed subjects had at least one diagnosis of a psychiatric disorder.

In a model adjusted for year of birth, sex, and history of autoimmune disease, subjects with PID had a 91% higher likelihood of any psychiatric disorder (adjusted odds ratio [AOR] 1.91; 95% CI, 1.81 - 2.01; P < .001) vs their counterparts without PID.

The AORs for individual psychiatric disorders ranged from 1.34 (95% CI, 1.17 - 1.54; P < .001) for schizophrenia and other psychotic disorders to 2.99 (95% CI, 2.42 - 3.70; P < .001) for autism spectrum disorders (ASDs)

It’s unclear why the association with PID was strongest for autism, “but being a neurodevelopmental disorder, maybe autism is logically more associated with this type of disruption,” said Isung.

Research suggests that immunologic disruption may play a role in ASD, either through altered maternal immune function in utero or through immune disruption after birth, the researchers note.

Compared to those without PID, individuals with it had a significantly increased likelihood of any suicidal behavior (AOR, 1.84; 95% CI, 1.66 - 2.04, P < .001) as well as individual outcomes of death by suicide and suicide attempts.

The association with psychiatric disorders and suicidal behavior was markedly stronger for exposure to both PID and autoimmune disease than for exposure to either of these alone, which suggest an additive effect for these immune-related conditions.
 

Sex differences

“It was unclear to us why women seemed particularly vulnerable,” said Isung. He noted that PIDs are generally about as common in women as in men, but women tend to have higher rates of psychiatric disorders.

The analysis of the sibling cohort also revealed an elevated risk for psychiatric disorders, including ASD and suicidal behavior, but to a lesser degree.

“From this we could infer that at least part of the associations would be genetic, but part would be related to the disruption in itself,” said Isung.

An analysis examining selective IgA subtype also revealed a link with psychiatric disorders and suicidal behavior, suggesting this link is not exclusive to severe PID cases.

“Our conclusion here was that it seems like PID itself, or the immune disruption in itself, could explain the association rather than the burden of illness,” said Isung.

However, he acknowledged that the long-term stress and mental health fallout of having a chronic illness like PID may also explain some of the increased risk for psychiatric disorders.

This study, he said, provides more evidence that immune disruptions affect neurodevelopment and the brain. However, he added, the underlying mechanism still isn’t fully understood.

The results highlight the need to raise awareness of the association between immunodeficiency and mental illness, including suicidality among clinicians, patients, and advocates.

These findings may also have implications in patients with other immune deficiencies, said Isung, noting, “it would be interesting to further explore associations with other immunocompromised populations.”
 

No surprises

Commenting on the findings for Medscape Medical News, Igor Galynker, MD, professor of psychiatry at Icahn School of Medicine at Mount Sinai, New York City, said the study was “very well-done” and used “reliable and well-controlled” databases.

However, he added, the results “are neither particularly dramatic nor conclusive” as it makes sense that medical illnesses like PID would “increase risk of psychopathology,” said Galynker.

PID patients are much more likely to have contact with clinicians and to receive a psychiatric diagnosis, he said.

“People with a chronic illness are more stressed and generally have high incidences of depression, anxiety, and suicidal behavior. In addition to that, they may be more likely to be diagnosed with those conditions because they see a clinician more frequently.”

However, that reasoning doesn’t apply to autism, which manifests in early childhood and so is unlikely to be the result of stress, said Galynker, which is why he believes the finding that ASD is the psychiatric outcome most strongly associated with PID is “the most convincing.”

Galynker wasn’t surprised that the association between PID and psychiatric illnesses, and suicidal behaviors, was stronger among women.

“Women attempt suicide four times more often than men to begin with, so you would expect this to be more pronounced” in those with PID.

The study was supported by grants from the Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institute; Stockholm Care Services; the Soderstrom Konig Foundation; and the Fredrik & Ingrid Thurings Foundation. Isung and Galynker have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Patients with a primary humoral immunodeficiency (PID) are 91% more likely to have a psychiatric disorder and 84% more likely to exhibit suicidal behavior, compared against those without the condition, new research shows.

Results showed that this association, which was stronger in women, could not be fully explained by comorbid autoimmune diseases or by familial confounding.

These findings have important clinical implications, study investigator Josef Isung, MD, PhD, Centre for Psychiatry Research, Karolinska Institute, Stockholm, Sweden, told Medscape Medical News.

Clinicians managing patients with PID “should be aware of this increased association with psychiatric disorders and perhaps screen for them,” said Isung.

The study was published in the November issue of JAMA Psychiatry.
 

Registry study

Mounting evidence suggests immune disruption plays a role in psychiatric disorders through a range of mechanisms, including altered neurodevelopment. However, little is known about the neuropsychiatric consequences resulting from the underproduction of homeostatic antibodies.

PIDs involve a deficiency in antibody production, mainly affecting immunoglobulin, “or the humoral aspect of the immune system,” said Isung. They’re associated with an increased risk for recurrent infections and of developing autoimmune diseases.

The immunodeficiency can be severe, even life threatening, but can also be relatively mild. One of the less severe PID types is selective IgA deficiency, which is linked to increased infections within the mucosa-associated lymphoid tissue (MALT), an important immune barrier.

Experts have long suspected that infections within the MALT are associated with certain forms of psychopathology in children, particularly obsessive-compulsive disorder and chronic tic disorders.

While patients with this selective IgA subtype may be at some increased risk for infection and autoimmune disease, their overall health otherwise is good, said Isung.

The prevalence of PIDs ranges from about 1:250 to 1:20,000, depending on the type of humoral immunodeficiency, although most would fall into the relatively rare category, he added.

Using several linked national Swedish registries, researchers identified individuals with any PID diagnosis affecting immunoglobulin levels, their full siblings, and those with a lifetime diagnosis of selective IgA deficiency. In addition, they collected data on autoimmune diseases.

The study outcome was a lifetime record of a psychiatric disorder, a suicide attempt, or death by suicide.
 

Strong link to autism

Researchers identified 8378 patients (59% women) with PID affecting immunoglobulin levels (median age at first diagnosis, 47.8 years). They compared this group with almost 14.3 million subjects without PID.

In those with PID, 27.6% had an autoimmune disease vs 6.8% of those without PID, a statistically significant difference (P < .001).

About 20.5% of those with PID and 10.7% of unexposed subjects had at least one diagnosis of a psychiatric disorder.

In a model adjusted for year of birth, sex, and history of autoimmune disease, subjects with PID had a 91% higher likelihood of any psychiatric disorder (adjusted odds ratio [AOR] 1.91; 95% CI, 1.81 - 2.01; P < .001) vs their counterparts without PID.

The AORs for individual psychiatric disorders ranged from 1.34 (95% CI, 1.17 - 1.54; P < .001) for schizophrenia and other psychotic disorders to 2.99 (95% CI, 2.42 - 3.70; P < .001) for autism spectrum disorders (ASDs)

It’s unclear why the association with PID was strongest for autism, “but being a neurodevelopmental disorder, maybe autism is logically more associated with this type of disruption,” said Isung.

Research suggests that immunologic disruption may play a role in ASD, either through altered maternal immune function in utero or through immune disruption after birth, the researchers note.

Compared to those without PID, individuals with it had a significantly increased likelihood of any suicidal behavior (AOR, 1.84; 95% CI, 1.66 - 2.04, P < .001) as well as individual outcomes of death by suicide and suicide attempts.

The association with psychiatric disorders and suicidal behavior was markedly stronger for exposure to both PID and autoimmune disease than for exposure to either of these alone, which suggest an additive effect for these immune-related conditions.
 

Sex differences

“It was unclear to us why women seemed particularly vulnerable,” said Isung. He noted that PIDs are generally about as common in women as in men, but women tend to have higher rates of psychiatric disorders.

The analysis of the sibling cohort also revealed an elevated risk for psychiatric disorders, including ASD and suicidal behavior, but to a lesser degree.

“From this we could infer that at least part of the associations would be genetic, but part would be related to the disruption in itself,” said Isung.

An analysis examining selective IgA subtype also revealed a link with psychiatric disorders and suicidal behavior, suggesting this link is not exclusive to severe PID cases.

“Our conclusion here was that it seems like PID itself, or the immune disruption in itself, could explain the association rather than the burden of illness,” said Isung.

However, he acknowledged that the long-term stress and mental health fallout of having a chronic illness like PID may also explain some of the increased risk for psychiatric disorders.

This study, he said, provides more evidence that immune disruptions affect neurodevelopment and the brain. However, he added, the underlying mechanism still isn’t fully understood.

The results highlight the need to raise awareness of the association between immunodeficiency and mental illness, including suicidality among clinicians, patients, and advocates.

These findings may also have implications in patients with other immune deficiencies, said Isung, noting, “it would be interesting to further explore associations with other immunocompromised populations.”
 

No surprises

Commenting on the findings for Medscape Medical News, Igor Galynker, MD, professor of psychiatry at Icahn School of Medicine at Mount Sinai, New York City, said the study was “very well-done” and used “reliable and well-controlled” databases.

However, he added, the results “are neither particularly dramatic nor conclusive” as it makes sense that medical illnesses like PID would “increase risk of psychopathology,” said Galynker.

PID patients are much more likely to have contact with clinicians and to receive a psychiatric diagnosis, he said.

“People with a chronic illness are more stressed and generally have high incidences of depression, anxiety, and suicidal behavior. In addition to that, they may be more likely to be diagnosed with those conditions because they see a clinician more frequently.”

However, that reasoning doesn’t apply to autism, which manifests in early childhood and so is unlikely to be the result of stress, said Galynker, which is why he believes the finding that ASD is the psychiatric outcome most strongly associated with PID is “the most convincing.”

Galynker wasn’t surprised that the association between PID and psychiatric illnesses, and suicidal behaviors, was stronger among women.

“Women attempt suicide four times more often than men to begin with, so you would expect this to be more pronounced” in those with PID.

The study was supported by grants from the Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institute; Stockholm Care Services; the Soderstrom Konig Foundation; and the Fredrik & Ingrid Thurings Foundation. Isung and Galynker have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Patients with a primary humoral immunodeficiency (PID) are 91% more likely to have a psychiatric disorder and 84% more likely to exhibit suicidal behavior, compared against those without the condition, new research shows.

Results showed that this association, which was stronger in women, could not be fully explained by comorbid autoimmune diseases or by familial confounding.

These findings have important clinical implications, study investigator Josef Isung, MD, PhD, Centre for Psychiatry Research, Karolinska Institute, Stockholm, Sweden, told Medscape Medical News.

Clinicians managing patients with PID “should be aware of this increased association with psychiatric disorders and perhaps screen for them,” said Isung.

The study was published in the November issue of JAMA Psychiatry.
 

Registry study

Mounting evidence suggests immune disruption plays a role in psychiatric disorders through a range of mechanisms, including altered neurodevelopment. However, little is known about the neuropsychiatric consequences resulting from the underproduction of homeostatic antibodies.

PIDs involve a deficiency in antibody production, mainly affecting immunoglobulin, “or the humoral aspect of the immune system,” said Isung. They’re associated with an increased risk for recurrent infections and of developing autoimmune diseases.

The immunodeficiency can be severe, even life threatening, but can also be relatively mild. One of the less severe PID types is selective IgA deficiency, which is linked to increased infections within the mucosa-associated lymphoid tissue (MALT), an important immune barrier.

Experts have long suspected that infections within the MALT are associated with certain forms of psychopathology in children, particularly obsessive-compulsive disorder and chronic tic disorders.

While patients with this selective IgA subtype may be at some increased risk for infection and autoimmune disease, their overall health otherwise is good, said Isung.

The prevalence of PIDs ranges from about 1:250 to 1:20,000, depending on the type of humoral immunodeficiency, although most would fall into the relatively rare category, he added.

Using several linked national Swedish registries, researchers identified individuals with any PID diagnosis affecting immunoglobulin levels, their full siblings, and those with a lifetime diagnosis of selective IgA deficiency. In addition, they collected data on autoimmune diseases.

The study outcome was a lifetime record of a psychiatric disorder, a suicide attempt, or death by suicide.
 

Strong link to autism

Researchers identified 8378 patients (59% women) with PID affecting immunoglobulin levels (median age at first diagnosis, 47.8 years). They compared this group with almost 14.3 million subjects without PID.

In those with PID, 27.6% had an autoimmune disease vs 6.8% of those without PID, a statistically significant difference (P < .001).

About 20.5% of those with PID and 10.7% of unexposed subjects had at least one diagnosis of a psychiatric disorder.

In a model adjusted for year of birth, sex, and history of autoimmune disease, subjects with PID had a 91% higher likelihood of any psychiatric disorder (adjusted odds ratio [AOR] 1.91; 95% CI, 1.81 - 2.01; P < .001) vs their counterparts without PID.

The AORs for individual psychiatric disorders ranged from 1.34 (95% CI, 1.17 - 1.54; P < .001) for schizophrenia and other psychotic disorders to 2.99 (95% CI, 2.42 - 3.70; P < .001) for autism spectrum disorders (ASDs)

It’s unclear why the association with PID was strongest for autism, “but being a neurodevelopmental disorder, maybe autism is logically more associated with this type of disruption,” said Isung.

Research suggests that immunologic disruption may play a role in ASD, either through altered maternal immune function in utero or through immune disruption after birth, the researchers note.

Compared to those without PID, individuals with it had a significantly increased likelihood of any suicidal behavior (AOR, 1.84; 95% CI, 1.66 - 2.04, P < .001) as well as individual outcomes of death by suicide and suicide attempts.

The association with psychiatric disorders and suicidal behavior was markedly stronger for exposure to both PID and autoimmune disease than for exposure to either of these alone, which suggest an additive effect for these immune-related conditions.
 

Sex differences

“It was unclear to us why women seemed particularly vulnerable,” said Isung. He noted that PIDs are generally about as common in women as in men, but women tend to have higher rates of psychiatric disorders.

The analysis of the sibling cohort also revealed an elevated risk for psychiatric disorders, including ASD and suicidal behavior, but to a lesser degree.

“From this we could infer that at least part of the associations would be genetic, but part would be related to the disruption in itself,” said Isung.

An analysis examining selective IgA subtype also revealed a link with psychiatric disorders and suicidal behavior, suggesting this link is not exclusive to severe PID cases.

“Our conclusion here was that it seems like PID itself, or the immune disruption in itself, could explain the association rather than the burden of illness,” said Isung.

However, he acknowledged that the long-term stress and mental health fallout of having a chronic illness like PID may also explain some of the increased risk for psychiatric disorders.

This study, he said, provides more evidence that immune disruptions affect neurodevelopment and the brain. However, he added, the underlying mechanism still isn’t fully understood.

The results highlight the need to raise awareness of the association between immunodeficiency and mental illness, including suicidality among clinicians, patients, and advocates.

These findings may also have implications in patients with other immune deficiencies, said Isung, noting, “it would be interesting to further explore associations with other immunocompromised populations.”
 

No surprises

Commenting on the findings for Medscape Medical News, Igor Galynker, MD, professor of psychiatry at Icahn School of Medicine at Mount Sinai, New York City, said the study was “very well-done” and used “reliable and well-controlled” databases.

However, he added, the results “are neither particularly dramatic nor conclusive” as it makes sense that medical illnesses like PID would “increase risk of psychopathology,” said Galynker.

PID patients are much more likely to have contact with clinicians and to receive a psychiatric diagnosis, he said.

“People with a chronic illness are more stressed and generally have high incidences of depression, anxiety, and suicidal behavior. In addition to that, they may be more likely to be diagnosed with those conditions because they see a clinician more frequently.”

However, that reasoning doesn’t apply to autism, which manifests in early childhood and so is unlikely to be the result of stress, said Galynker, which is why he believes the finding that ASD is the psychiatric outcome most strongly associated with PID is “the most convincing.”

Galynker wasn’t surprised that the association between PID and psychiatric illnesses, and suicidal behaviors, was stronger among women.

“Women attempt suicide four times more often than men to begin with, so you would expect this to be more pronounced” in those with PID.

The study was supported by grants from the Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institute; Stockholm Care Services; the Soderstrom Konig Foundation; and the Fredrik & Ingrid Thurings Foundation. Isung and Galynker have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

The more time older women spent sitting or lying down, the more likely their risk of hospitalization for heart failure, based on data from more than 80,000 postmenopausal women.

Cecilie_Arcurs/E+

The 2018 Physical Activity Guidelines show evidence of the impact of physical activity on reducing heart failure risk, but the association between activity, sedentary behavior (SB) and heart failure (HF) in older women in particular has not been well studied, wrote Michael J. LaMonte, PhD, MPH, of the State University of New York at Buffalo, and colleagues in a study published in Circulation: Heart Failure. “Given the high prevalence of prolonged sedentary time among U.S. adults aged 65 and older, among whom HF burden is substantial, understanding the role SB has in HF development is relevant to future HF prevention strategies,” the researchers wrote.

The researchers identified 80,982 women aged 50-79 years who were enrolled in the Women’s Health Initiative Observational Study, had no known HF, and could walk at least one block unassisted. The average follow-up period was 9 years, and a total of 1,402 women were hospitalized for heart failure during the period of time they were observed.

The time spent sedentary (combined sitting or lying down) was divided into tertiles of 6.5 hours or less, 6.6-9.5 hours, and more than 9.5 hours. Time spent sitting was divided into tertiles of 4.5 hours or less; 4.6-8.5 hours; and more than 8.5 hours.
 

Heart failure risk goes up with more down time

After controlling for multiple variables including age, race, education, income, smoking status alcohol use, menopausal hormone therapy, and hysterectomy status, the researchers found that patients in the second tertile for sedentary behavior had a significantly increased heart failure risk than patients in the first tertile for sedentary behavior. This risk was even greater for patients falling in the third tertile for sedentary behavior. Odds ratios were 1.00 (referent), 1.15, and 1.42 for the lowest to highest tertiles for total sedentary behavior, respectively, and 1.00 (referent), 1.14, and 1.54 for sitting (P < .001 for both total sedentary behavior and sitting only).

The trends remained significant after controlling for comorbidities including MI and coronary revascularization, and the associations were similar among categories of women with additional HF risk factors, including body mass index, diabetes, hypertension, and coronary heart disease.

Notably, the association between hours spent sitting or lying down and HF risk persisted even in women who met recommended activity levels, the researchers wrote.

The study findings were limited by the use of self-reports and by the inability to evaluate SB patterns or SB and HF subtypes, the researchers noted. However, the results were strengthened by the large sample size, use of time-varying SB exposure, and extensive controlling, and the data support the risk of increased SB on adverse cardiovascular outcomes.

“Results of this study underscore the need for effective strategies to reduce daily SB time, in addition to increasing recreational physical activity, as part of population efforts for HF prevention,” they concluded.

Clinicians know the value of a physically active lifestyle for heart health, said lead author Dr. LaMonte in a statement accompanying the study’s release. “However, our study clearly shows that we also need to increase efforts to reduce daily sedentary time and encourage adults to frequently interrupt their sedentary time. This does not necessarily require an extended bout of physical activity; it might simply be standing up for 5 minutes or standing and moving one’s feet in place.

“We do not have sufficient evidence on the best approach to recommend for interrupting sedentary time. However, accumulating data suggest that habitual activities such as steps taken during household and other activities of daily living are an important aspect of cardiovascular disease prevention and healthy aging,” Dr. LaMonte added.
 

Promote more movement and less sitting

“This is the first study to assess sedentary time and the risk for incident heart failure hospitalization in postmenopausal women,” said Robert H. Hopkins Jr., MD, of the University of Arkansas for Medical Sciences, Little Rock, in an interview.

“Heart failure is the cause of approximately 35% of cardiovascular mortalities in women, and sedentary behaviors are common in older adults,” he noted.

Kashif J. Piracha, MD, of Houston Methodist Willowbrook Hospital, agreed that there is a lack of existing data looking at the relationship between sedentary behavior and the risk of the development of heart failure in postmenopausal women. In an interview, he cited this as a reason “it was important to conduct this study.”

Dr. Hopkins added that he was not surprised by the study results “There are a number of studies which have demonstrated reduction in risk for heart failure in men and in combined populations of men and women with increased physical activity.” There are fewer data (but similar outcomes) in studies of men with increased levels of sedentary behaviors, he said.

“This study adds one more reason that other clinicians in primary care and me need to encourage our older patients to get up and move,” said Dr. Hopkins, who also serves on the editorial advisory board of Internal Medicine News. “Many of us have focused our efforts in the past on achieving exercise goals and this study provides a foundation for a recommendation that ‘it is not just about exercise;’ we need to also encourage our patients to minimize their time in sedentary pursuits in addition to exercise if we are to optimize their health into older age.”

Dr. Hopkins noted that the large size of the study was a strength, but the observational design and use of patient surveys were limitations.

“We need further studies to better tease out whether there are risk differences in different sedentary behavior patterns, whether this applies across heart failure with reduced ejection fraction versus heart failure with preserved ejection fraction, and whether there are additional ways we can mitigate these risks as our society ages,” he said.
 

Findings differ from California Men’s Health Study’s

“The results corroborate the fact that there is less risk of heart failure in physically active patients,” Dr. Piracha noted.

The message for clinicians is to encourage postmenopausal female patients to engage in physical activity as much as possible, said Dr. Piracha. “Also, it appears that in this population, even with good physical activity, prolonged sedentary behavior of more than 8.5 hours a day was still associated with a higher risk of incident HF hospitalization. Therefore, a case can be made to focus on carrying out physical activity with an intensity that can be sustained for longer, rather than shorter periods of time.”

Notably, the finding of increased HF hospitalization in women who reported high amounts of physical activity but were still sedentary for more than 8.5 hours a day “is contrary to what was seen in the California Men’s Health Study.” In that study, “men with high physical activity levels who also had prolonged sitting time did not have increased risk of HF hospitalization,” Dr. Piracha noted. “Further research is needed to elucidate what hormonal or other factors contribute to this difference.”

The new study was supported by the National Heart, Lung, and Blood Institute. The researchers had no financial conflicts to disclose. Dr. Hopkins and Dr. Piracha had no financial conflicts to disclose.

SOURCE: LaMonte MJ et al. Circ Heart Fail. 2020 Nov 24. doi: 10.1161/CIRCHEARTFAILURE.120.007508.

The more time older women spent sitting or lying down, the more likely their risk of hospitalization for heart failure, based on data from more than 80,000 postmenopausal women.

Cecilie_Arcurs/E+

The 2018 Physical Activity Guidelines show evidence of the impact of physical activity on reducing heart failure risk, but the association between activity, sedentary behavior (SB) and heart failure (HF) in older women in particular has not been well studied, wrote Michael J. LaMonte, PhD, MPH, of the State University of New York at Buffalo, and colleagues in a study published in Circulation: Heart Failure. “Given the high prevalence of prolonged sedentary time among U.S. adults aged 65 and older, among whom HF burden is substantial, understanding the role SB has in HF development is relevant to future HF prevention strategies,” the researchers wrote.

The researchers identified 80,982 women aged 50-79 years who were enrolled in the Women’s Health Initiative Observational Study, had no known HF, and could walk at least one block unassisted. The average follow-up period was 9 years, and a total of 1,402 women were hospitalized for heart failure during the period of time they were observed.

The time spent sedentary (combined sitting or lying down) was divided into tertiles of 6.5 hours or less, 6.6-9.5 hours, and more than 9.5 hours. Time spent sitting was divided into tertiles of 4.5 hours or less; 4.6-8.5 hours; and more than 8.5 hours.
 

Heart failure risk goes up with more down time

After controlling for multiple variables including age, race, education, income, smoking status alcohol use, menopausal hormone therapy, and hysterectomy status, the researchers found that patients in the second tertile for sedentary behavior had a significantly increased heart failure risk than patients in the first tertile for sedentary behavior. This risk was even greater for patients falling in the third tertile for sedentary behavior. Odds ratios were 1.00 (referent), 1.15, and 1.42 for the lowest to highest tertiles for total sedentary behavior, respectively, and 1.00 (referent), 1.14, and 1.54 for sitting (P < .001 for both total sedentary behavior and sitting only).

The trends remained significant after controlling for comorbidities including MI and coronary revascularization, and the associations were similar among categories of women with additional HF risk factors, including body mass index, diabetes, hypertension, and coronary heart disease.

Notably, the association between hours spent sitting or lying down and HF risk persisted even in women who met recommended activity levels, the researchers wrote.

The study findings were limited by the use of self-reports and by the inability to evaluate SB patterns or SB and HF subtypes, the researchers noted. However, the results were strengthened by the large sample size, use of time-varying SB exposure, and extensive controlling, and the data support the risk of increased SB on adverse cardiovascular outcomes.

“Results of this study underscore the need for effective strategies to reduce daily SB time, in addition to increasing recreational physical activity, as part of population efforts for HF prevention,” they concluded.

Clinicians know the value of a physically active lifestyle for heart health, said lead author Dr. LaMonte in a statement accompanying the study’s release. “However, our study clearly shows that we also need to increase efforts to reduce daily sedentary time and encourage adults to frequently interrupt their sedentary time. This does not necessarily require an extended bout of physical activity; it might simply be standing up for 5 minutes or standing and moving one’s feet in place.

“We do not have sufficient evidence on the best approach to recommend for interrupting sedentary time. However, accumulating data suggest that habitual activities such as steps taken during household and other activities of daily living are an important aspect of cardiovascular disease prevention and healthy aging,” Dr. LaMonte added.
 

Promote more movement and less sitting

“This is the first study to assess sedentary time and the risk for incident heart failure hospitalization in postmenopausal women,” said Robert H. Hopkins Jr., MD, of the University of Arkansas for Medical Sciences, Little Rock, in an interview.

“Heart failure is the cause of approximately 35% of cardiovascular mortalities in women, and sedentary behaviors are common in older adults,” he noted.

Kashif J. Piracha, MD, of Houston Methodist Willowbrook Hospital, agreed that there is a lack of existing data looking at the relationship between sedentary behavior and the risk of the development of heart failure in postmenopausal women. In an interview, he cited this as a reason “it was important to conduct this study.”

Dr. Hopkins added that he was not surprised by the study results “There are a number of studies which have demonstrated reduction in risk for heart failure in men and in combined populations of men and women with increased physical activity.” There are fewer data (but similar outcomes) in studies of men with increased levels of sedentary behaviors, he said.

“This study adds one more reason that other clinicians in primary care and me need to encourage our older patients to get up and move,” said Dr. Hopkins, who also serves on the editorial advisory board of Internal Medicine News. “Many of us have focused our efforts in the past on achieving exercise goals and this study provides a foundation for a recommendation that ‘it is not just about exercise;’ we need to also encourage our patients to minimize their time in sedentary pursuits in addition to exercise if we are to optimize their health into older age.”

Dr. Hopkins noted that the large size of the study was a strength, but the observational design and use of patient surveys were limitations.

“We need further studies to better tease out whether there are risk differences in different sedentary behavior patterns, whether this applies across heart failure with reduced ejection fraction versus heart failure with preserved ejection fraction, and whether there are additional ways we can mitigate these risks as our society ages,” he said.
 

Findings differ from California Men’s Health Study’s

“The results corroborate the fact that there is less risk of heart failure in physically active patients,” Dr. Piracha noted.

The message for clinicians is to encourage postmenopausal female patients to engage in physical activity as much as possible, said Dr. Piracha. “Also, it appears that in this population, even with good physical activity, prolonged sedentary behavior of more than 8.5 hours a day was still associated with a higher risk of incident HF hospitalization. Therefore, a case can be made to focus on carrying out physical activity with an intensity that can be sustained for longer, rather than shorter periods of time.”

Notably, the finding of increased HF hospitalization in women who reported high amounts of physical activity but were still sedentary for more than 8.5 hours a day “is contrary to what was seen in the California Men’s Health Study.” In that study, “men with high physical activity levels who also had prolonged sitting time did not have increased risk of HF hospitalization,” Dr. Piracha noted. “Further research is needed to elucidate what hormonal or other factors contribute to this difference.”

The new study was supported by the National Heart, Lung, and Blood Institute. The researchers had no financial conflicts to disclose. Dr. Hopkins and Dr. Piracha had no financial conflicts to disclose.

SOURCE: LaMonte MJ et al. Circ Heart Fail. 2020 Nov 24. doi: 10.1161/CIRCHEARTFAILURE.120.007508.

The more time older women spent sitting or lying down, the more likely their risk of hospitalization for heart failure, based on data from more than 80,000 postmenopausal women.

Cecilie_Arcurs/E+

The 2018 Physical Activity Guidelines show evidence of the impact of physical activity on reducing heart failure risk, but the association between activity, sedentary behavior (SB) and heart failure (HF) in older women in particular has not been well studied, wrote Michael J. LaMonte, PhD, MPH, of the State University of New York at Buffalo, and colleagues in a study published in Circulation: Heart Failure. “Given the high prevalence of prolonged sedentary time among U.S. adults aged 65 and older, among whom HF burden is substantial, understanding the role SB has in HF development is relevant to future HF prevention strategies,” the researchers wrote.

The researchers identified 80,982 women aged 50-79 years who were enrolled in the Women’s Health Initiative Observational Study, had no known HF, and could walk at least one block unassisted. The average follow-up period was 9 years, and a total of 1,402 women were hospitalized for heart failure during the period of time they were observed.

The time spent sedentary (combined sitting or lying down) was divided into tertiles of 6.5 hours or less, 6.6-9.5 hours, and more than 9.5 hours. Time spent sitting was divided into tertiles of 4.5 hours or less; 4.6-8.5 hours; and more than 8.5 hours.
 

Heart failure risk goes up with more down time

After controlling for multiple variables including age, race, education, income, smoking status alcohol use, menopausal hormone therapy, and hysterectomy status, the researchers found that patients in the second tertile for sedentary behavior had a significantly increased heart failure risk than patients in the first tertile for sedentary behavior. This risk was even greater for patients falling in the third tertile for sedentary behavior. Odds ratios were 1.00 (referent), 1.15, and 1.42 for the lowest to highest tertiles for total sedentary behavior, respectively, and 1.00 (referent), 1.14, and 1.54 for sitting (P < .001 for both total sedentary behavior and sitting only).

The trends remained significant after controlling for comorbidities including MI and coronary revascularization, and the associations were similar among categories of women with additional HF risk factors, including body mass index, diabetes, hypertension, and coronary heart disease.

Notably, the association between hours spent sitting or lying down and HF risk persisted even in women who met recommended activity levels, the researchers wrote.

The study findings were limited by the use of self-reports and by the inability to evaluate SB patterns or SB and HF subtypes, the researchers noted. However, the results were strengthened by the large sample size, use of time-varying SB exposure, and extensive controlling, and the data support the risk of increased SB on adverse cardiovascular outcomes.

“Results of this study underscore the need for effective strategies to reduce daily SB time, in addition to increasing recreational physical activity, as part of population efforts for HF prevention,” they concluded.

Clinicians know the value of a physically active lifestyle for heart health, said lead author Dr. LaMonte in a statement accompanying the study’s release. “However, our study clearly shows that we also need to increase efforts to reduce daily sedentary time and encourage adults to frequently interrupt their sedentary time. This does not necessarily require an extended bout of physical activity; it might simply be standing up for 5 minutes or standing and moving one’s feet in place.

“We do not have sufficient evidence on the best approach to recommend for interrupting sedentary time. However, accumulating data suggest that habitual activities such as steps taken during household and other activities of daily living are an important aspect of cardiovascular disease prevention and healthy aging,” Dr. LaMonte added.
 

Promote more movement and less sitting

“This is the first study to assess sedentary time and the risk for incident heart failure hospitalization in postmenopausal women,” said Robert H. Hopkins Jr., MD, of the University of Arkansas for Medical Sciences, Little Rock, in an interview.

“Heart failure is the cause of approximately 35% of cardiovascular mortalities in women, and sedentary behaviors are common in older adults,” he noted.

Kashif J. Piracha, MD, of Houston Methodist Willowbrook Hospital, agreed that there is a lack of existing data looking at the relationship between sedentary behavior and the risk of the development of heart failure in postmenopausal women. In an interview, he cited this as a reason “it was important to conduct this study.”

Dr. Hopkins added that he was not surprised by the study results “There are a number of studies which have demonstrated reduction in risk for heart failure in men and in combined populations of men and women with increased physical activity.” There are fewer data (but similar outcomes) in studies of men with increased levels of sedentary behaviors, he said.

“This study adds one more reason that other clinicians in primary care and me need to encourage our older patients to get up and move,” said Dr. Hopkins, who also serves on the editorial advisory board of Internal Medicine News. “Many of us have focused our efforts in the past on achieving exercise goals and this study provides a foundation for a recommendation that ‘it is not just about exercise;’ we need to also encourage our patients to minimize their time in sedentary pursuits in addition to exercise if we are to optimize their health into older age.”

Dr. Hopkins noted that the large size of the study was a strength, but the observational design and use of patient surveys were limitations.

“We need further studies to better tease out whether there are risk differences in different sedentary behavior patterns, whether this applies across heart failure with reduced ejection fraction versus heart failure with preserved ejection fraction, and whether there are additional ways we can mitigate these risks as our society ages,” he said.
 

Findings differ from California Men’s Health Study’s

“The results corroborate the fact that there is less risk of heart failure in physically active patients,” Dr. Piracha noted.

The message for clinicians is to encourage postmenopausal female patients to engage in physical activity as much as possible, said Dr. Piracha. “Also, it appears that in this population, even with good physical activity, prolonged sedentary behavior of more than 8.5 hours a day was still associated with a higher risk of incident HF hospitalization. Therefore, a case can be made to focus on carrying out physical activity with an intensity that can be sustained for longer, rather than shorter periods of time.”

Notably, the finding of increased HF hospitalization in women who reported high amounts of physical activity but were still sedentary for more than 8.5 hours a day “is contrary to what was seen in the California Men’s Health Study.” In that study, “men with high physical activity levels who also had prolonged sitting time did not have increased risk of HF hospitalization,” Dr. Piracha noted. “Further research is needed to elucidate what hormonal or other factors contribute to this difference.”

The new study was supported by the National Heart, Lung, and Blood Institute. The researchers had no financial conflicts to disclose. Dr. Hopkins and Dr. Piracha had no financial conflicts to disclose.

SOURCE: LaMonte MJ et al. Circ Heart Fail. 2020 Nov 24. doi: 10.1161/CIRCHEARTFAILURE.120.007508.

Oral agents are taking on an ever-greater role in the management of gynecologic cancers. However, women being treated for these cancers have less than ideal adherence to such medications, a new study has found – with just over half reporting taking them exactly as prescribed.

Ingram Publishing/Thinkstock

The findings reported in Obstetrics & Gynecology are consistent with reports from other populations taking oral anticancer agents, in which adherence is generally lower than with intravenous therapies.

For their research, Catherine Watson, MD, and colleagues at Duke University, Durham, N.C., recruited 100 women at their institution taking a variety of oral anticancer agents for uterine or ovarian cancer for 30 days or more (median time, 6 months). The women answered a questionnaire that measured adherence as well as health literacy, quality of life, and distress. The researchers also collected information on the subjects’ race, age, insurance type, medication burden, and medication costs.

Fourteen of the women in the study additionally underwent qualitative interviews about their experiences with oral anticancer drugs. The researchers also queried physicians and nurse practitioners about their thoughts on adherence.

Dr. Watson and colleagues reported that 54% of women self-reported perfect adherence to their medication in the previous week, while 21% had missed or skipped one dose, and 25% reported skipping or missing more than one dose.

The researchers saw no significant differences between the adherent and nonadherent groups corresponding with race, age, or other demographic or clinical characteristics, but they noted that their study was not powered to detect such associations. The small sample size and self-reported data were among this study’s limitations, Dr. Watson and colleagues acknowledged.

Interviews with patients revealed some surprising reasons for the less-than-optimal adherence, with 43% of women reporting feeling anxiety about the burden of administering medication at home. While patients acknowledged the convenience of oral regimens, some also expressed a wish for more physician contact and support. Some women who were nonadherent said they perceived the efficacy of oral agents to be less than intravenous therapies.

Physicians and nurse practitioners interviewed by the researchers “tended to assume that their patients were adherent to oral anticancer therapy because of the therapy’s importance, and many did not routinely ask their patients about adherence,” Dr. Watson and colleagues wrote.

Emma Rossi, MD, a gynecologic oncologist at the University of North Carolina at Chapel Hill, commented in an interview that the study highlighted “the importance of not generalizing our perception of patients. As providers we have to spend the time asking patients where they’re at and how they’re thinking about taking an oral medication, with special attention to their fears, their expectations, and their concerns. We should be touching base with them not just before starting drugs, but during the course of treatment.”

Dr. Rossi stressed that compliance in real-life settings is likely to be different from that seen in clinical trials of oral anticancer drugs. “It’s important to recognize that real-world efficacy of treatments may be different from trial efficacy. We see these differences a lot in medicine where studies show a large magnitude of effect that doesn’t play out in real life practice – because of factors like this.”

Some 57% of the women in the study were taking their medications as maintenance, while the rest were taking the medications as active treatment. This too might have an effect on adherence, she said, with the active-treatment group potentially more motivated to maintain perfect adherence.

“You see in the interviews that doctors assume patients would be compliant because of the seriousness of the disease,” Dr. Rossi said. “But some patients said they perceived oral drugs as less strong or effective. If a patient is cancer free on a scan and doesn’t have measurable disease, prescribing an oral medication may be sending the subliminal message that it’s not as important.”

Physicians “may need to take the extra steps to individualize our counseling of patients – especially with therapies that they’re responsible for administering,” Dr. Rossi continued. “As this study shows, every patient sees treatment through her own individual lens. We really need to meet them where they’re at to make them comfortable with their treatment and optimize compliance.”

Dr. Watson and colleagues’ study was supported by their institution. One coauthor reported financial ties with drug manufacturers in the form of grant and clinical trial support and honoraria. Another coauthor is the member of various boards and steering committees, which are uncompensated. Dr. Rossi reported no financial conflicts of interest.

SOURCE: Watson C et al. Obstet Gynecol. 2020. doi: 10.1097/AOG.0000000000004170.

Oral agents are taking on an ever-greater role in the management of gynecologic cancers. However, women being treated for these cancers have less than ideal adherence to such medications, a new study has found – with just over half reporting taking them exactly as prescribed.

Ingram Publishing/Thinkstock

The findings reported in Obstetrics & Gynecology are consistent with reports from other populations taking oral anticancer agents, in which adherence is generally lower than with intravenous therapies.

For their research, Catherine Watson, MD, and colleagues at Duke University, Durham, N.C., recruited 100 women at their institution taking a variety of oral anticancer agents for uterine or ovarian cancer for 30 days or more (median time, 6 months). The women answered a questionnaire that measured adherence as well as health literacy, quality of life, and distress. The researchers also collected information on the subjects’ race, age, insurance type, medication burden, and medication costs.

Fourteen of the women in the study additionally underwent qualitative interviews about their experiences with oral anticancer drugs. The researchers also queried physicians and nurse practitioners about their thoughts on adherence.

Dr. Watson and colleagues reported that 54% of women self-reported perfect adherence to their medication in the previous week, while 21% had missed or skipped one dose, and 25% reported skipping or missing more than one dose.

The researchers saw no significant differences between the adherent and nonadherent groups corresponding with race, age, or other demographic or clinical characteristics, but they noted that their study was not powered to detect such associations. The small sample size and self-reported data were among this study’s limitations, Dr. Watson and colleagues acknowledged.

Interviews with patients revealed some surprising reasons for the less-than-optimal adherence, with 43% of women reporting feeling anxiety about the burden of administering medication at home. While patients acknowledged the convenience of oral regimens, some also expressed a wish for more physician contact and support. Some women who were nonadherent said they perceived the efficacy of oral agents to be less than intravenous therapies.

Physicians and nurse practitioners interviewed by the researchers “tended to assume that their patients were adherent to oral anticancer therapy because of the therapy’s importance, and many did not routinely ask their patients about adherence,” Dr. Watson and colleagues wrote.

Emma Rossi, MD, a gynecologic oncologist at the University of North Carolina at Chapel Hill, commented in an interview that the study highlighted “the importance of not generalizing our perception of patients. As providers we have to spend the time asking patients where they’re at and how they’re thinking about taking an oral medication, with special attention to their fears, their expectations, and their concerns. We should be touching base with them not just before starting drugs, but during the course of treatment.”

Dr. Rossi stressed that compliance in real-life settings is likely to be different from that seen in clinical trials of oral anticancer drugs. “It’s important to recognize that real-world efficacy of treatments may be different from trial efficacy. We see these differences a lot in medicine where studies show a large magnitude of effect that doesn’t play out in real life practice – because of factors like this.”

Some 57% of the women in the study were taking their medications as maintenance, while the rest were taking the medications as active treatment. This too might have an effect on adherence, she said, with the active-treatment group potentially more motivated to maintain perfect adherence.

“You see in the interviews that doctors assume patients would be compliant because of the seriousness of the disease,” Dr. Rossi said. “But some patients said they perceived oral drugs as less strong or effective. If a patient is cancer free on a scan and doesn’t have measurable disease, prescribing an oral medication may be sending the subliminal message that it’s not as important.”

Physicians “may need to take the extra steps to individualize our counseling of patients – especially with therapies that they’re responsible for administering,” Dr. Rossi continued. “As this study shows, every patient sees treatment through her own individual lens. We really need to meet them where they’re at to make them comfortable with their treatment and optimize compliance.”

Dr. Watson and colleagues’ study was supported by their institution. One coauthor reported financial ties with drug manufacturers in the form of grant and clinical trial support and honoraria. Another coauthor is the member of various boards and steering committees, which are uncompensated. Dr. Rossi reported no financial conflicts of interest.

SOURCE: Watson C et al. Obstet Gynecol. 2020. doi: 10.1097/AOG.0000000000004170.

Oral agents are taking on an ever-greater role in the management of gynecologic cancers. However, women being treated for these cancers have less than ideal adherence to such medications, a new study has found – with just over half reporting taking them exactly as prescribed.

Ingram Publishing/Thinkstock

The findings reported in Obstetrics & Gynecology are consistent with reports from other populations taking oral anticancer agents, in which adherence is generally lower than with intravenous therapies.

For their research, Catherine Watson, MD, and colleagues at Duke University, Durham, N.C., recruited 100 women at their institution taking a variety of oral anticancer agents for uterine or ovarian cancer for 30 days or more (median time, 6 months). The women answered a questionnaire that measured adherence as well as health literacy, quality of life, and distress. The researchers also collected information on the subjects’ race, age, insurance type, medication burden, and medication costs.

Fourteen of the women in the study additionally underwent qualitative interviews about their experiences with oral anticancer drugs. The researchers also queried physicians and nurse practitioners about their thoughts on adherence.

Dr. Watson and colleagues reported that 54% of women self-reported perfect adherence to their medication in the previous week, while 21% had missed or skipped one dose, and 25% reported skipping or missing more than one dose.

The researchers saw no significant differences between the adherent and nonadherent groups corresponding with race, age, or other demographic or clinical characteristics, but they noted that their study was not powered to detect such associations. The small sample size and self-reported data were among this study’s limitations, Dr. Watson and colleagues acknowledged.

Interviews with patients revealed some surprising reasons for the less-than-optimal adherence, with 43% of women reporting feeling anxiety about the burden of administering medication at home. While patients acknowledged the convenience of oral regimens, some also expressed a wish for more physician contact and support. Some women who were nonadherent said they perceived the efficacy of oral agents to be less than intravenous therapies.

Physicians and nurse practitioners interviewed by the researchers “tended to assume that their patients were adherent to oral anticancer therapy because of the therapy’s importance, and many did not routinely ask their patients about adherence,” Dr. Watson and colleagues wrote.

Emma Rossi, MD, a gynecologic oncologist at the University of North Carolina at Chapel Hill, commented in an interview that the study highlighted “the importance of not generalizing our perception of patients. As providers we have to spend the time asking patients where they’re at and how they’re thinking about taking an oral medication, with special attention to their fears, their expectations, and their concerns. We should be touching base with them not just before starting drugs, but during the course of treatment.”

Dr. Rossi stressed that compliance in real-life settings is likely to be different from that seen in clinical trials of oral anticancer drugs. “It’s important to recognize that real-world efficacy of treatments may be different from trial efficacy. We see these differences a lot in medicine where studies show a large magnitude of effect that doesn’t play out in real life practice – because of factors like this.”

Some 57% of the women in the study were taking their medications as maintenance, while the rest were taking the medications as active treatment. This too might have an effect on adherence, she said, with the active-treatment group potentially more motivated to maintain perfect adherence.

“You see in the interviews that doctors assume patients would be compliant because of the seriousness of the disease,” Dr. Rossi said. “But some patients said they perceived oral drugs as less strong or effective. If a patient is cancer free on a scan and doesn’t have measurable disease, prescribing an oral medication may be sending the subliminal message that it’s not as important.”

Physicians “may need to take the extra steps to individualize our counseling of patients – especially with therapies that they’re responsible for administering,” Dr. Rossi continued. “As this study shows, every patient sees treatment through her own individual lens. We really need to meet them where they’re at to make them comfortable with their treatment and optimize compliance.”

Dr. Watson and colleagues’ study was supported by their institution. One coauthor reported financial ties with drug manufacturers in the form of grant and clinical trial support and honoraria. Another coauthor is the member of various boards and steering committees, which are uncompensated. Dr. Rossi reported no financial conflicts of interest.

SOURCE: Watson C et al. Obstet Gynecol. 2020. doi: 10.1097/AOG.0000000000004170.

Among patients with polycystic ovary syndrome (PCOS), those with obstructive sleep apnea (OSA) are more likely to have moderate to severe depression or anxiety, a study suggests.

This finding could have implications for screening and treatment, Diana Xiaojie Zhou, MD, said at the American Society for Reproductive Medicine’s 2020 annual meeting, held virtually this year.

“Routine OSA screening in women with PCOS should be considered in the setting of existing depression and anxiety,” said Dr. Zhou, a reproductive endocrinology and infertility fellow at the University of California, San Francisco. “Referral for OSA diagnosis and treatment in those who screen positive may have added psychological benefits in this population, as has been seen in the general population.”

Patients with PCOS experience a range of comorbidities, including higher rates of psychological disorders and OSA, she said.

OSA has been associated with depression and anxiety in the general population, and research indicates that treatment, such as with continuous positive airway pressure (CPAP), may have psychological benefits, such as reduced depression symptoms.

PCOS guidelines recommend screening for OSA to identify and alleviate symptoms such as fatigue that may to contribute to mood disorders. “However, there is a lack of studies assessing the relationship between OSA and depression and anxiety specifically in women with PCOS,” Dr. Zhou said.
 

A cross-sectional study

To evaluate whether OSA is associated with depression and anxiety in women with PCOS, Dr. Zhou and colleagues conducted a cross-sectional study of all women seen at a multidisciplinary PCOS clinic at university between June 2017 and June 2020.

Participants had a diagnosis of PCOS clinically confirmed by the Rotterdam criteria. Researchers determined OSA risk using the Berlin questionnaire, which is divided into three domains. A positive score in two or more domains indicates a high risk of OSA.

The investigators used the Patient Health Questionnaire-9 (PHQ-9) to assess depression symptoms, and they used the Generalized Anxiety Disorder-7 (GAD-7) to assess anxiety symptoms.

Researchers used two-sided t-test, chi-square test, and Fisher’s exact test to evaluate for differences in patient characteristics. They performed multivariate logistic regression analyses to determine the odds of moderate to severe symptoms of depression (that is, a PHQ-9 score of 10 or greater) and anxiety (a GAD-7 score of 10 or greater) among patients with a high risk of OSA, compared with patients with a low risk of OSA. They adjusted for age, body mass index, free testosterone level, and insulin resistance using the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR).

The researchers examined data from 201 patients: 125 with a low risk of OSA and 76 with a high risk of OSA. The average age of the patients was 28 years.

On average, patients in the high-risk OSA group had a greater body mass index (37.9 vs. 26.5), a higher level of free testosterone (6.5 ng/dL vs. 4.5 ng/dL), and a higher HOMA-IR score (7 vs. 3.1), relative to those with a low risk of OSA. In addition, a greater percentage of patients with a high risk of OSA experienced oligomenorrhea (84.9% vs. 70.5%).

The average PHQ-9 score was significantly higher in the high-risk OSA group (12 vs. 8.3), as was the average GAD-7 score (8.9 vs. 6.1).

In univariate analyses, having a high risk of OSA increased the likelihood of moderate or severe depression or anxiety approximately threefold.

In multivariate analyses, a high risk of OSA remained significantly associated with moderate or severe depression or anxiety, with an odds ratio of about 2.5. “Of note, BMI was a statistically significant predictor in the univariate analyses, but not so in the multivariate analyses,” Dr. Zhou said.

Although the investigators assessed OSA, depression, and anxiety using validated questionnaires, a study with clinically confirmed diagnoses of those conditions would strengthen these findings, she said.
 

Various possible links

Investigators have proposed various links between PCOS, OSA, and depression and anxiety, Dr. Zhou noted. Features of PCOS such as insulin resistance, obesity, and hyperandrogenemia increase the risk of OSA. “The sleep loss and fragmentation and hypoxia that define OSA then serve to increase sympathetic tone and oxidative stress, which then potentially can lead to an increase in depression and anxiety,” Dr. Zhou said.

The results suggests that treating OSA “may have added psychological benefits for women with PCOS and highlights the broad health implications of this condition,” Marla Lujan, PhD, chair of the ASRM’s androgen excess special interest group, said in a society news release.

“The cause of PCOS is still not well understood, but we do know that 1 in 10 women in their childbearing years suffer from PCOS,” said Dr. Lujan, of Cornell University, Ithaca, N.Y. “In addition to infertility, PCOS is also associated with type 2 diabetes and cardiovascular complications such as hypertension and abnormal blood lipids.”

In a discussion following Dr. Zhou’s presentation, Alice D. Domar, PhD, said the study was eye opening.

Dr. Domar, director of integrative care at Boston IVF and associate professor of obstetrics, gynecology, and reproductive biology at Harvard Medical School, Boston, said that she does not typically discuss sleep apnea with patients. “For those of us who routinely work with PCOS patients, we are always looking for more information.”

Although PCOS guidelines mention screening for OSA, Dr. Zhou expects that few generalists who see PCOS patients or even subspecialists actually do.

Nevertheless, the potential for intervention is fascinating, she said. And if treating OSA also reduced a patient’s need for psychiatric medications, there could be added benefit in PCOS due to the metabolic side effects that accompany some of the drugs.

Dr. Zhou and Dr. Lujan had no relevant disclosures. Dr. Domar is a co-owner of FertiCalm, FertiStrong, and Aliz Health Apps, and a speaker for Ferring, EMD Serono, Merck, and Abbott.

jremaly@mdedge.com

SOURCE: Zhou DX et al. ASRM 2020. Abstract O-146.

Among patients with polycystic ovary syndrome (PCOS), those with obstructive sleep apnea (OSA) are more likely to have moderate to severe depression or anxiety, a study suggests.

This finding could have implications for screening and treatment, Diana Xiaojie Zhou, MD, said at the American Society for Reproductive Medicine’s 2020 annual meeting, held virtually this year.

“Routine OSA screening in women with PCOS should be considered in the setting of existing depression and anxiety,” said Dr. Zhou, a reproductive endocrinology and infertility fellow at the University of California, San Francisco. “Referral for OSA diagnosis and treatment in those who screen positive may have added psychological benefits in this population, as has been seen in the general population.”

Patients with PCOS experience a range of comorbidities, including higher rates of psychological disorders and OSA, she said.

OSA has been associated with depression and anxiety in the general population, and research indicates that treatment, such as with continuous positive airway pressure (CPAP), may have psychological benefits, such as reduced depression symptoms.

PCOS guidelines recommend screening for OSA to identify and alleviate symptoms such as fatigue that may to contribute to mood disorders. “However, there is a lack of studies assessing the relationship between OSA and depression and anxiety specifically in women with PCOS,” Dr. Zhou said.
 

A cross-sectional study

To evaluate whether OSA is associated with depression and anxiety in women with PCOS, Dr. Zhou and colleagues conducted a cross-sectional study of all women seen at a multidisciplinary PCOS clinic at university between June 2017 and June 2020.

Participants had a diagnosis of PCOS clinically confirmed by the Rotterdam criteria. Researchers determined OSA risk using the Berlin questionnaire, which is divided into three domains. A positive score in two or more domains indicates a high risk of OSA.

The investigators used the Patient Health Questionnaire-9 (PHQ-9) to assess depression symptoms, and they used the Generalized Anxiety Disorder-7 (GAD-7) to assess anxiety symptoms.

Researchers used two-sided t-test, chi-square test, and Fisher’s exact test to evaluate for differences in patient characteristics. They performed multivariate logistic regression analyses to determine the odds of moderate to severe symptoms of depression (that is, a PHQ-9 score of 10 or greater) and anxiety (a GAD-7 score of 10 or greater) among patients with a high risk of OSA, compared with patients with a low risk of OSA. They adjusted for age, body mass index, free testosterone level, and insulin resistance using the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR).

The researchers examined data from 201 patients: 125 with a low risk of OSA and 76 with a high risk of OSA. The average age of the patients was 28 years.

On average, patients in the high-risk OSA group had a greater body mass index (37.9 vs. 26.5), a higher level of free testosterone (6.5 ng/dL vs. 4.5 ng/dL), and a higher HOMA-IR score (7 vs. 3.1), relative to those with a low risk of OSA. In addition, a greater percentage of patients with a high risk of OSA experienced oligomenorrhea (84.9% vs. 70.5%).

The average PHQ-9 score was significantly higher in the high-risk OSA group (12 vs. 8.3), as was the average GAD-7 score (8.9 vs. 6.1).

In univariate analyses, having a high risk of OSA increased the likelihood of moderate or severe depression or anxiety approximately threefold.

In multivariate analyses, a high risk of OSA remained significantly associated with moderate or severe depression or anxiety, with an odds ratio of about 2.5. “Of note, BMI was a statistically significant predictor in the univariate analyses, but not so in the multivariate analyses,” Dr. Zhou said.

Although the investigators assessed OSA, depression, and anxiety using validated questionnaires, a study with clinically confirmed diagnoses of those conditions would strengthen these findings, she said.
 

Various possible links

Investigators have proposed various links between PCOS, OSA, and depression and anxiety, Dr. Zhou noted. Features of PCOS such as insulin resistance, obesity, and hyperandrogenemia increase the risk of OSA. “The sleep loss and fragmentation and hypoxia that define OSA then serve to increase sympathetic tone and oxidative stress, which then potentially can lead to an increase in depression and anxiety,” Dr. Zhou said.

The results suggests that treating OSA “may have added psychological benefits for women with PCOS and highlights the broad health implications of this condition,” Marla Lujan, PhD, chair of the ASRM’s androgen excess special interest group, said in a society news release.

“The cause of PCOS is still not well understood, but we do know that 1 in 10 women in their childbearing years suffer from PCOS,” said Dr. Lujan, of Cornell University, Ithaca, N.Y. “In addition to infertility, PCOS is also associated with type 2 diabetes and cardiovascular complications such as hypertension and abnormal blood lipids.”

In a discussion following Dr. Zhou’s presentation, Alice D. Domar, PhD, said the study was eye opening.

Dr. Domar, director of integrative care at Boston IVF and associate professor of obstetrics, gynecology, and reproductive biology at Harvard Medical School, Boston, said that she does not typically discuss sleep apnea with patients. “For those of us who routinely work with PCOS patients, we are always looking for more information.”

Although PCOS guidelines mention screening for OSA, Dr. Zhou expects that few generalists who see PCOS patients or even subspecialists actually do.

Nevertheless, the potential for intervention is fascinating, she said. And if treating OSA also reduced a patient’s need for psychiatric medications, there could be added benefit in PCOS due to the metabolic side effects that accompany some of the drugs.

Dr. Zhou and Dr. Lujan had no relevant disclosures. Dr. Domar is a co-owner of FertiCalm, FertiStrong, and Aliz Health Apps, and a speaker for Ferring, EMD Serono, Merck, and Abbott.

jremaly@mdedge.com

SOURCE: Zhou DX et al. ASRM 2020. Abstract O-146.

Among patients with polycystic ovary syndrome (PCOS), those with obstructive sleep apnea (OSA) are more likely to have moderate to severe depression or anxiety, a study suggests.

This finding could have implications for screening and treatment, Diana Xiaojie Zhou, MD, said at the American Society for Reproductive Medicine’s 2020 annual meeting, held virtually this year.

“Routine OSA screening in women with PCOS should be considered in the setting of existing depression and anxiety,” said Dr. Zhou, a reproductive endocrinology and infertility fellow at the University of California, San Francisco. “Referral for OSA diagnosis and treatment in those who screen positive may have added psychological benefits in this population, as has been seen in the general population.”

Patients with PCOS experience a range of comorbidities, including higher rates of psychological disorders and OSA, she said.

OSA has been associated with depression and anxiety in the general population, and research indicates that treatment, such as with continuous positive airway pressure (CPAP), may have psychological benefits, such as reduced depression symptoms.

PCOS guidelines recommend screening for OSA to identify and alleviate symptoms such as fatigue that may to contribute to mood disorders. “However, there is a lack of studies assessing the relationship between OSA and depression and anxiety specifically in women with PCOS,” Dr. Zhou said.
 

A cross-sectional study

To evaluate whether OSA is associated with depression and anxiety in women with PCOS, Dr. Zhou and colleagues conducted a cross-sectional study of all women seen at a multidisciplinary PCOS clinic at university between June 2017 and June 2020.

Participants had a diagnosis of PCOS clinically confirmed by the Rotterdam criteria. Researchers determined OSA risk using the Berlin questionnaire, which is divided into three domains. A positive score in two or more domains indicates a high risk of OSA.

The investigators used the Patient Health Questionnaire-9 (PHQ-9) to assess depression symptoms, and they used the Generalized Anxiety Disorder-7 (GAD-7) to assess anxiety symptoms.

Researchers used two-sided t-test, chi-square test, and Fisher’s exact test to evaluate for differences in patient characteristics. They performed multivariate logistic regression analyses to determine the odds of moderate to severe symptoms of depression (that is, a PHQ-9 score of 10 or greater) and anxiety (a GAD-7 score of 10 or greater) among patients with a high risk of OSA, compared with patients with a low risk of OSA. They adjusted for age, body mass index, free testosterone level, and insulin resistance using the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR).

The researchers examined data from 201 patients: 125 with a low risk of OSA and 76 with a high risk of OSA. The average age of the patients was 28 years.

On average, patients in the high-risk OSA group had a greater body mass index (37.9 vs. 26.5), a higher level of free testosterone (6.5 ng/dL vs. 4.5 ng/dL), and a higher HOMA-IR score (7 vs. 3.1), relative to those with a low risk of OSA. In addition, a greater percentage of patients with a high risk of OSA experienced oligomenorrhea (84.9% vs. 70.5%).

The average PHQ-9 score was significantly higher in the high-risk OSA group (12 vs. 8.3), as was the average GAD-7 score (8.9 vs. 6.1).

In univariate analyses, having a high risk of OSA increased the likelihood of moderate or severe depression or anxiety approximately threefold.

In multivariate analyses, a high risk of OSA remained significantly associated with moderate or severe depression or anxiety, with an odds ratio of about 2.5. “Of note, BMI was a statistically significant predictor in the univariate analyses, but not so in the multivariate analyses,” Dr. Zhou said.

Although the investigators assessed OSA, depression, and anxiety using validated questionnaires, a study with clinically confirmed diagnoses of those conditions would strengthen these findings, she said.
 

Various possible links

Investigators have proposed various links between PCOS, OSA, and depression and anxiety, Dr. Zhou noted. Features of PCOS such as insulin resistance, obesity, and hyperandrogenemia increase the risk of OSA. “The sleep loss and fragmentation and hypoxia that define OSA then serve to increase sympathetic tone and oxidative stress, which then potentially can lead to an increase in depression and anxiety,” Dr. Zhou said.

The results suggests that treating OSA “may have added psychological benefits for women with PCOS and highlights the broad health implications of this condition,” Marla Lujan, PhD, chair of the ASRM’s androgen excess special interest group, said in a society news release.

“The cause of PCOS is still not well understood, but we do know that 1 in 10 women in their childbearing years suffer from PCOS,” said Dr. Lujan, of Cornell University, Ithaca, N.Y. “In addition to infertility, PCOS is also associated with type 2 diabetes and cardiovascular complications such as hypertension and abnormal blood lipids.”

In a discussion following Dr. Zhou’s presentation, Alice D. Domar, PhD, said the study was eye opening.

Dr. Domar, director of integrative care at Boston IVF and associate professor of obstetrics, gynecology, and reproductive biology at Harvard Medical School, Boston, said that she does not typically discuss sleep apnea with patients. “For those of us who routinely work with PCOS patients, we are always looking for more information.”

Although PCOS guidelines mention screening for OSA, Dr. Zhou expects that few generalists who see PCOS patients or even subspecialists actually do.

Nevertheless, the potential for intervention is fascinating, she said. And if treating OSA also reduced a patient’s need for psychiatric medications, there could be added benefit in PCOS due to the metabolic side effects that accompany some of the drugs.

Dr. Zhou and Dr. Lujan had no relevant disclosures. Dr. Domar is a co-owner of FertiCalm, FertiStrong, and Aliz Health Apps, and a speaker for Ferring, EMD Serono, Merck, and Abbott.

jremaly@mdedge.com

SOURCE: Zhou DX et al. ASRM 2020. Abstract O-146.

More than 60% of patients at a center for reproductive medicine in Utah who had fertility treatments canceled because of the COVID-19 pandemic opted to resume treatment once the suspension was lifted about 7 weeks later.

At another fertility center in New York, a survey found that 96% of respondents who had a cycle canceled because of the pandemic found it upsetting, and 22% found it extremely upsetting, with extremely upsetting defined as equivalent to the loss of a child.

The indefinite time frame for resuming treatment when the New York survey was conducted may have been a major source of distress for patients, one of the researchers said at the American Society for Reproductive Medicine’s 2020 annual meeting, held virtually this year.

“They don’t know when they might have that chance again,” said Jenna M. Turocy, MD, of Columbia University Fertility Center, New York.

COVID-19 guidelines published by ASRM on March 17 recommended the suspension of new treatment cycles, including ovulation induction, intrauterine inseminations, and in vitro fertilization (IVF).

An ASRM COVID-19 task force has since supported “the measured resumption of fertility care following the easing of restrictions,” said Paul C. Lin, MD, president of the Society for Assisted Reproductive Technology and a member of the task force.

“Over the past several months, significant knowledge has been gained regarding the COVID-19 virus and its impact on patients and the medical system,” he said in a news release about the two studies that assessed the pandemic’s effects.

Certain precautions remain. “It has become clear that we will need to be practicing COVID-19 protocols at least until an effective and safe vaccine or broadly effective treatment becomes widely available,” Dr. Lin said.
 

Desire to proceed during a pandemic

The Utah Center for Reproductive Medicine on March 15 suspended new IVF cycles and frozen embryo transfers. The center continued to offer IVF cycles for oncofertility patients on an urgent basis.

In early May, patients whose cycles had been suspended had the option to receive treatment.

“Upon reopening, every patient received standardized counseling from their primary IVF physician,” Lauren Verrilli, MD, a reproductive endocrinology and infertility fellow at the University of Utah, Salt Lake City, said at the virtual meeting.

Doctors explained that much remained unknown about COVID-19 in pregnancy, and that it was unclear whether the clinic would need to shut down again. In addition, patients had to undergo COVID-19 testing.

To identify factors associated with proceeding with treatment after the suspension, the researchers compared patients who resumed treatment with patients who did not.

Their analysis included 278 patients who had planned an IVF cycle or frozen embryo transfer (FET) prior to the shutdown. The researchers examined factors such as age, parity, anti-Müllerian hormone, antral follicle count, history of prior IVF cycles or FET, number of frozen blastocysts, gamete source, and use of a gestational carrier.

In all, 62% of patients opted to receive treatment once restrictions were lifted, including 69 of the 133 (52%) patients with planned fresh cycles and 104 of the 145 (72%) patients with planned FET cycles.

Among those with planned fresh cycles, those who opted to resume treatment tended to be older than those who did not resume treatment, with a median age of 37 years versus 35 years, but the difference was not statistically significant.

Among patients with planned FET cycles, those who did not resume treatment were more likely to have a gestational carrier, compared with those who resumed treatment (7% vs. 1%). In some cases, gestational carriers lived in another state and the pandemic complicated travel arrangements, which contributed to delays, Dr. Verrilli said.

The analysis did not include information about income or socioeconomic status, which may play a role in patients’ decisions, Dr. Verrilli said.
 

Emotional impact of indefinite delay

Fertility treatment is often time sensitive, particularly for patients with advanced reproductive age or diminished ovarian reserve, and indefinite postponement of fertility treatment potentially could lead some patients to lose the ability to conceive with their own gametes, Dr. Turocy said.

In early April, Dr. Turocy and colleagues surveyed patients at their academic fertility center in New York City to assess patients’ reactions to the ASRM recommendations. They decided to conduct the study after they realized that treatment cancellations were having a significant emotional effect.

Investigators emailed an 18-item survey to more than 3,000 patients.

In all, 518 patients completed the survey, a response rate of 17%. Patients had an average age of 37 years (range, 23-52 years), and 92% were female. About 24% had children, and 66% had received at least one fertility treatment.

Half had a cycle canceled because of the COVID-19 pandemic, including timed intercourse cycles (5%), intrauterine insemination cycles (23%), IVF cycles with a planned fresh embryo transfer (10%), IVF with all frozen embryos (27%), egg freeze cycles (3%), and FET cycles (30%).

In response to survey questions about whether they agreed with ASRM recommendations, “the reactions were mixed,” Dr. Turocy said.

About 36% of patients agreed all fertility cycles should be canceled, 22% were unsure, and 43% disagreed with the recommendation. Patients who had a cycle canceled were slightly more likely to agree with the cancellations (40% agreed) than those who did not have a cycle canceled (30% agreed), Dr. Turocy said.

Most respondents would have preferred an option to start a treatment cycle in consultation with their doctor. Half “would have chosen to start a new cycle during the height of the pandemic in New York City,” Dr. Turocy said.

Patient opinions may vary by region and depend on the severity of COVID-19 outbreaks there, and they also might change over time, Dr. Turocy suggested. In addition, the opinions and characteristics of patients who responded to the anonymous survey may differ from those of patients who did not respond.

Dr. Verrilli, Dr. Turocy, and Dr. Lin had no relevant financial disclosures.

jremaly@mdedge.com

More than 60% of patients at a center for reproductive medicine in Utah who had fertility treatments canceled because of the COVID-19 pandemic opted to resume treatment once the suspension was lifted about 7 weeks later.

At another fertility center in New York, a survey found that 96% of respondents who had a cycle canceled because of the pandemic found it upsetting, and 22% found it extremely upsetting, with extremely upsetting defined as equivalent to the loss of a child.

The indefinite time frame for resuming treatment when the New York survey was conducted may have been a major source of distress for patients, one of the researchers said at the American Society for Reproductive Medicine’s 2020 annual meeting, held virtually this year.

“They don’t know when they might have that chance again,” said Jenna M. Turocy, MD, of Columbia University Fertility Center, New York.

COVID-19 guidelines published by ASRM on March 17 recommended the suspension of new treatment cycles, including ovulation induction, intrauterine inseminations, and in vitro fertilization (IVF).

An ASRM COVID-19 task force has since supported “the measured resumption of fertility care following the easing of restrictions,” said Paul C. Lin, MD, president of the Society for Assisted Reproductive Technology and a member of the task force.

“Over the past several months, significant knowledge has been gained regarding the COVID-19 virus and its impact on patients and the medical system,” he said in a news release about the two studies that assessed the pandemic’s effects.

Certain precautions remain. “It has become clear that we will need to be practicing COVID-19 protocols at least until an effective and safe vaccine or broadly effective treatment becomes widely available,” Dr. Lin said.
 

Desire to proceed during a pandemic

The Utah Center for Reproductive Medicine on March 15 suspended new IVF cycles and frozen embryo transfers. The center continued to offer IVF cycles for oncofertility patients on an urgent basis.

In early May, patients whose cycles had been suspended had the option to receive treatment.

“Upon reopening, every patient received standardized counseling from their primary IVF physician,” Lauren Verrilli, MD, a reproductive endocrinology and infertility fellow at the University of Utah, Salt Lake City, said at the virtual meeting.

Doctors explained that much remained unknown about COVID-19 in pregnancy, and that it was unclear whether the clinic would need to shut down again. In addition, patients had to undergo COVID-19 testing.

To identify factors associated with proceeding with treatment after the suspension, the researchers compared patients who resumed treatment with patients who did not.

Their analysis included 278 patients who had planned an IVF cycle or frozen embryo transfer (FET) prior to the shutdown. The researchers examined factors such as age, parity, anti-Müllerian hormone, antral follicle count, history of prior IVF cycles or FET, number of frozen blastocysts, gamete source, and use of a gestational carrier.

In all, 62% of patients opted to receive treatment once restrictions were lifted, including 69 of the 133 (52%) patients with planned fresh cycles and 104 of the 145 (72%) patients with planned FET cycles.

Among those with planned fresh cycles, those who opted to resume treatment tended to be older than those who did not resume treatment, with a median age of 37 years versus 35 years, but the difference was not statistically significant.

Among patients with planned FET cycles, those who did not resume treatment were more likely to have a gestational carrier, compared with those who resumed treatment (7% vs. 1%). In some cases, gestational carriers lived in another state and the pandemic complicated travel arrangements, which contributed to delays, Dr. Verrilli said.

The analysis did not include information about income or socioeconomic status, which may play a role in patients’ decisions, Dr. Verrilli said.
 

Emotional impact of indefinite delay

Fertility treatment is often time sensitive, particularly for patients with advanced reproductive age or diminished ovarian reserve, and indefinite postponement of fertility treatment potentially could lead some patients to lose the ability to conceive with their own gametes, Dr. Turocy said.

In early April, Dr. Turocy and colleagues surveyed patients at their academic fertility center in New York City to assess patients’ reactions to the ASRM recommendations. They decided to conduct the study after they realized that treatment cancellations were having a significant emotional effect.

Investigators emailed an 18-item survey to more than 3,000 patients.

In all, 518 patients completed the survey, a response rate of 17%. Patients had an average age of 37 years (range, 23-52 years), and 92% were female. About 24% had children, and 66% had received at least one fertility treatment.

Half had a cycle canceled because of the COVID-19 pandemic, including timed intercourse cycles (5%), intrauterine insemination cycles (23%), IVF cycles with a planned fresh embryo transfer (10%), IVF with all frozen embryos (27%), egg freeze cycles (3%), and FET cycles (30%).

In response to survey questions about whether they agreed with ASRM recommendations, “the reactions were mixed,” Dr. Turocy said.

About 36% of patients agreed all fertility cycles should be canceled, 22% were unsure, and 43% disagreed with the recommendation. Patients who had a cycle canceled were slightly more likely to agree with the cancellations (40% agreed) than those who did not have a cycle canceled (30% agreed), Dr. Turocy said.

Most respondents would have preferred an option to start a treatment cycle in consultation with their doctor. Half “would have chosen to start a new cycle during the height of the pandemic in New York City,” Dr. Turocy said.

Patient opinions may vary by region and depend on the severity of COVID-19 outbreaks there, and they also might change over time, Dr. Turocy suggested. In addition, the opinions and characteristics of patients who responded to the anonymous survey may differ from those of patients who did not respond.

Dr. Verrilli, Dr. Turocy, and Dr. Lin had no relevant financial disclosures.

jremaly@mdedge.com

More than 60% of patients at a center for reproductive medicine in Utah who had fertility treatments canceled because of the COVID-19 pandemic opted to resume treatment once the suspension was lifted about 7 weeks later.

At another fertility center in New York, a survey found that 96% of respondents who had a cycle canceled because of the pandemic found it upsetting, and 22% found it extremely upsetting, with extremely upsetting defined as equivalent to the loss of a child.

The indefinite time frame for resuming treatment when the New York survey was conducted may have been a major source of distress for patients, one of the researchers said at the American Society for Reproductive Medicine’s 2020 annual meeting, held virtually this year.

“They don’t know when they might have that chance again,” said Jenna M. Turocy, MD, of Columbia University Fertility Center, New York.

COVID-19 guidelines published by ASRM on March 17 recommended the suspension of new treatment cycles, including ovulation induction, intrauterine inseminations, and in vitro fertilization (IVF).

An ASRM COVID-19 task force has since supported “the measured resumption of fertility care following the easing of restrictions,” said Paul C. Lin, MD, president of the Society for Assisted Reproductive Technology and a member of the task force.

“Over the past several months, significant knowledge has been gained regarding the COVID-19 virus and its impact on patients and the medical system,” he said in a news release about the two studies that assessed the pandemic’s effects.

Certain precautions remain. “It has become clear that we will need to be practicing COVID-19 protocols at least until an effective and safe vaccine or broadly effective treatment becomes widely available,” Dr. Lin said.
 

Desire to proceed during a pandemic

The Utah Center for Reproductive Medicine on March 15 suspended new IVF cycles and frozen embryo transfers. The center continued to offer IVF cycles for oncofertility patients on an urgent basis.

In early May, patients whose cycles had been suspended had the option to receive treatment.

“Upon reopening, every patient received standardized counseling from their primary IVF physician,” Lauren Verrilli, MD, a reproductive endocrinology and infertility fellow at the University of Utah, Salt Lake City, said at the virtual meeting.

Doctors explained that much remained unknown about COVID-19 in pregnancy, and that it was unclear whether the clinic would need to shut down again. In addition, patients had to undergo COVID-19 testing.

To identify factors associated with proceeding with treatment after the suspension, the researchers compared patients who resumed treatment with patients who did not.

Their analysis included 278 patients who had planned an IVF cycle or frozen embryo transfer (FET) prior to the shutdown. The researchers examined factors such as age, parity, anti-Müllerian hormone, antral follicle count, history of prior IVF cycles or FET, number of frozen blastocysts, gamete source, and use of a gestational carrier.

In all, 62% of patients opted to receive treatment once restrictions were lifted, including 69 of the 133 (52%) patients with planned fresh cycles and 104 of the 145 (72%) patients with planned FET cycles.

Among those with planned fresh cycles, those who opted to resume treatment tended to be older than those who did not resume treatment, with a median age of 37 years versus 35 years, but the difference was not statistically significant.

Among patients with planned FET cycles, those who did not resume treatment were more likely to have a gestational carrier, compared with those who resumed treatment (7% vs. 1%). In some cases, gestational carriers lived in another state and the pandemic complicated travel arrangements, which contributed to delays, Dr. Verrilli said.

The analysis did not include information about income or socioeconomic status, which may play a role in patients’ decisions, Dr. Verrilli said.
 

Emotional impact of indefinite delay

Fertility treatment is often time sensitive, particularly for patients with advanced reproductive age or diminished ovarian reserve, and indefinite postponement of fertility treatment potentially could lead some patients to lose the ability to conceive with their own gametes, Dr. Turocy said.

In early April, Dr. Turocy and colleagues surveyed patients at their academic fertility center in New York City to assess patients’ reactions to the ASRM recommendations. They decided to conduct the study after they realized that treatment cancellations were having a significant emotional effect.

Investigators emailed an 18-item survey to more than 3,000 patients.

In all, 518 patients completed the survey, a response rate of 17%. Patients had an average age of 37 years (range, 23-52 years), and 92% were female. About 24% had children, and 66% had received at least one fertility treatment.

Half had a cycle canceled because of the COVID-19 pandemic, including timed intercourse cycles (5%), intrauterine insemination cycles (23%), IVF cycles with a planned fresh embryo transfer (10%), IVF with all frozen embryos (27%), egg freeze cycles (3%), and FET cycles (30%).

In response to survey questions about whether they agreed with ASRM recommendations, “the reactions were mixed,” Dr. Turocy said.

About 36% of patients agreed all fertility cycles should be canceled, 22% were unsure, and 43% disagreed with the recommendation. Patients who had a cycle canceled were slightly more likely to agree with the cancellations (40% agreed) than those who did not have a cycle canceled (30% agreed), Dr. Turocy said.

Most respondents would have preferred an option to start a treatment cycle in consultation with their doctor. Half “would have chosen to start a new cycle during the height of the pandemic in New York City,” Dr. Turocy said.

Patient opinions may vary by region and depend on the severity of COVID-19 outbreaks there, and they also might change over time, Dr. Turocy suggested. In addition, the opinions and characteristics of patients who responded to the anonymous survey may differ from those of patients who did not respond.

Dr. Verrilli, Dr. Turocy, and Dr. Lin had no relevant financial disclosures.

jremaly@mdedge.com

Having a low threshold to biopsy atypical pigmented lesions on the vulva may identify melanoma early, according to a lecture at virtual conference on diseases of the vulva and vagina, hosted by the International Society for the Study of Vulvovaginal Disease.

Pigmented brown or black vulvar lesions occur in approximately 10% of women, and they may be normal and benign.

“Often we will see a pigmented lesion on the vulva and think that there is nothing to worry about,” said Melissa Mauskar, MD.

Lesions could be angiokeratomas, petechiae, purpura, melanosis, and nevi, for example. Seborrheic keratoses can mimic melanoma. “If it looks odd, don’t be afraid to biopsy it,” said Dr. Mauskar, assistant professor of dermatology and obstetrics and gynecology at the University of Texas Southwestern Medical Center in Dallas.

Characteristics of melanoma, covered by the mnemonic ABCDE, include asymmetry, borders that are irregular, coloring that is uneven, diameter greater than 7 mm, and evolution over time.

When biopsying a lesion because of concerns about melanoma, the goal is to remove the whole lesion at once, Dr. Mauskar said.

In a recent U.S. population-based study of more than 1,800 patients with malignant melanoma of the vulva or vagina (including 1,400 patients with vulvar melanoma and 463 patients with vaginal melanoma), median disease-specific survival was 99 months for vulvar melanoma and 19 months for vaginal melanoma.

Patients with vaginal melanoma were more likely than patients with vulvar melanoma to have nodular lesions. The American Joint Committee on Cancer staging system predicts vulvar melanoma outcomes, the researchers found. In addition, lymph node status and mitotic rate were important predictors of survival.

A wide local excision is the mainstay of therapy for melanoma. Other therapeutic advances are “changing the survival curves for these patients, especially when we can find things early,” Dr. Mauskar said.

Photographing lesions can help doctors monitor them over time, she added.

It is important for dermatologists to include the vulva in skin exams and for gynecologists to have a low threshold to biopsy atypical pigmented lesions, Dr. Mauskar said. “Having a very low threshold for biopsy ... will increase our chances of finding these lesions when they are more at the superficial spreading phase as opposed to the nodular phase,” she said.

Capturing the depth of a tumor within the confines of a biopsy may help accurately stage malignant melanoma, Jason Reutter, MD, a pathologist in Hickory, N.C., said in a separate presentation. He suggested trying to get around the lesion with a punch biopsy if possible. A shave biopsy may be advantageous for larger macular lesions. To diagnose one melanoma, doctors may have to biopsy many lesions, Dr. Reutter noted.

At one institution, the number of skin biopsies needed to diagnose skin cancer ranged from 2.82 to 6.55, depending on the type of clinician, according to a recent study. The number of biopsies needed to detect one melanoma was greater – between 14 and 54 – depending on type of clinician.

For larger lesions, scouting biopsies of different areas may be the best approach, Dr. Reutter said.

Dr. Mauskar and Dr. Reutter had no relevant financial conflicts of interest.
 

jremaly@mdedge.com

Having a low threshold to biopsy atypical pigmented lesions on the vulva may identify melanoma early, according to a lecture at virtual conference on diseases of the vulva and vagina, hosted by the International Society for the Study of Vulvovaginal Disease.

Pigmented brown or black vulvar lesions occur in approximately 10% of women, and they may be normal and benign.

“Often we will see a pigmented lesion on the vulva and think that there is nothing to worry about,” said Melissa Mauskar, MD.

Lesions could be angiokeratomas, petechiae, purpura, melanosis, and nevi, for example. Seborrheic keratoses can mimic melanoma. “If it looks odd, don’t be afraid to biopsy it,” said Dr. Mauskar, assistant professor of dermatology and obstetrics and gynecology at the University of Texas Southwestern Medical Center in Dallas.

Characteristics of melanoma, covered by the mnemonic ABCDE, include asymmetry, borders that are irregular, coloring that is uneven, diameter greater than 7 mm, and evolution over time.

When biopsying a lesion because of concerns about melanoma, the goal is to remove the whole lesion at once, Dr. Mauskar said.

In a recent U.S. population-based study of more than 1,800 patients with malignant melanoma of the vulva or vagina (including 1,400 patients with vulvar melanoma and 463 patients with vaginal melanoma), median disease-specific survival was 99 months for vulvar melanoma and 19 months for vaginal melanoma.

Patients with vaginal melanoma were more likely than patients with vulvar melanoma to have nodular lesions. The American Joint Committee on Cancer staging system predicts vulvar melanoma outcomes, the researchers found. In addition, lymph node status and mitotic rate were important predictors of survival.

A wide local excision is the mainstay of therapy for melanoma. Other therapeutic advances are “changing the survival curves for these patients, especially when we can find things early,” Dr. Mauskar said.

Photographing lesions can help doctors monitor them over time, she added.

It is important for dermatologists to include the vulva in skin exams and for gynecologists to have a low threshold to biopsy atypical pigmented lesions, Dr. Mauskar said. “Having a very low threshold for biopsy ... will increase our chances of finding these lesions when they are more at the superficial spreading phase as opposed to the nodular phase,” she said.

Capturing the depth of a tumor within the confines of a biopsy may help accurately stage malignant melanoma, Jason Reutter, MD, a pathologist in Hickory, N.C., said in a separate presentation. He suggested trying to get around the lesion with a punch biopsy if possible. A shave biopsy may be advantageous for larger macular lesions. To diagnose one melanoma, doctors may have to biopsy many lesions, Dr. Reutter noted.

At one institution, the number of skin biopsies needed to diagnose skin cancer ranged from 2.82 to 6.55, depending on the type of clinician, according to a recent study. The number of biopsies needed to detect one melanoma was greater – between 14 and 54 – depending on type of clinician.

For larger lesions, scouting biopsies of different areas may be the best approach, Dr. Reutter said.

Dr. Mauskar and Dr. Reutter had no relevant financial conflicts of interest.
 

jremaly@mdedge.com

Having a low threshold to biopsy atypical pigmented lesions on the vulva may identify melanoma early, according to a lecture at virtual conference on diseases of the vulva and vagina, hosted by the International Society for the Study of Vulvovaginal Disease.

Pigmented brown or black vulvar lesions occur in approximately 10% of women, and they may be normal and benign.

“Often we will see a pigmented lesion on the vulva and think that there is nothing to worry about,” said Melissa Mauskar, MD.

Lesions could be angiokeratomas, petechiae, purpura, melanosis, and nevi, for example. Seborrheic keratoses can mimic melanoma. “If it looks odd, don’t be afraid to biopsy it,” said Dr. Mauskar, assistant professor of dermatology and obstetrics and gynecology at the University of Texas Southwestern Medical Center in Dallas.

Characteristics of melanoma, covered by the mnemonic ABCDE, include asymmetry, borders that are irregular, coloring that is uneven, diameter greater than 7 mm, and evolution over time.

When biopsying a lesion because of concerns about melanoma, the goal is to remove the whole lesion at once, Dr. Mauskar said.

In a recent U.S. population-based study of more than 1,800 patients with malignant melanoma of the vulva or vagina (including 1,400 patients with vulvar melanoma and 463 patients with vaginal melanoma), median disease-specific survival was 99 months for vulvar melanoma and 19 months for vaginal melanoma.

Patients with vaginal melanoma were more likely than patients with vulvar melanoma to have nodular lesions. The American Joint Committee on Cancer staging system predicts vulvar melanoma outcomes, the researchers found. In addition, lymph node status and mitotic rate were important predictors of survival.

A wide local excision is the mainstay of therapy for melanoma. Other therapeutic advances are “changing the survival curves for these patients, especially when we can find things early,” Dr. Mauskar said.

Photographing lesions can help doctors monitor them over time, she added.

It is important for dermatologists to include the vulva in skin exams and for gynecologists to have a low threshold to biopsy atypical pigmented lesions, Dr. Mauskar said. “Having a very low threshold for biopsy ... will increase our chances of finding these lesions when they are more at the superficial spreading phase as opposed to the nodular phase,” she said.

Capturing the depth of a tumor within the confines of a biopsy may help accurately stage malignant melanoma, Jason Reutter, MD, a pathologist in Hickory, N.C., said in a separate presentation. He suggested trying to get around the lesion with a punch biopsy if possible. A shave biopsy may be advantageous for larger macular lesions. To diagnose one melanoma, doctors may have to biopsy many lesions, Dr. Reutter noted.

At one institution, the number of skin biopsies needed to diagnose skin cancer ranged from 2.82 to 6.55, depending on the type of clinician, according to a recent study. The number of biopsies needed to detect one melanoma was greater – between 14 and 54 – depending on type of clinician.

For larger lesions, scouting biopsies of different areas may be the best approach, Dr. Reutter said.

Dr. Mauskar and Dr. Reutter had no relevant financial conflicts of interest.
 

jremaly@mdedge.com

Seeing patients with vulvar problems via telemedicine can lead to efficient and successful care, but there are challenges and limitations with this approach, doctors are finding.

Image quality is one key factor that determines whether a clinician can assess and manage a condition remotely, said Aruna Venkatesan, MD, chief of dermatology and director of the genital dermatology clinic at Santa Clara Valley Medical Center in San Jose, Calif. Other issues may be especially relevant to televulvology, including privacy concerns.

“Who is helping with the positioning? Who is the photographer? Is the patient comfortable with having photos taken of this part of their body and submitted, even if they know it is submitted securely? Because they might not be,” Dr. Venkatesan said in a lecture at a virtual conference on diseases of the vulva and vagina, hosted by the International Society for the Study of Vulvovaginal Disease.

When quality photographs from referring providers are available, Dr. Venkatesan has conducted virtual new consultations. “But sometimes I will do a virtual telemedicine visit as the first visit and then figure out, okay, this isn’t really sufficient. I need to see them in person.”

Melissa Mauskar, MD, assistant professor of dermatology and obstetrics and gynecology at the University of Texas Southwestern Medical Center, Dallas, described a case early on during the COVID-19 pandemic that illustrates a limitation of virtual visits.

A patient sent in a photograph that appeared to show lichen sclerosus. “There looked like some classic lichen sclerosus changes,” Dr. Mauskar said during a discussion at the meeting. “But she was having a lot of pain, and after a week, her pain still was not better.”

Dr. Mauskar brought the patient into the office and ultimately diagnosed a squamous cell carcinoma. “What I thought was a normal erosion was actually an ulcerated plaque,” she said.

Like Dr. Venkatesan, Dr. Mauskar has found that image quality can be uneven. Photographs may be out of focus. Video visits have been a mixed bag. Some are successful. Other times, Dr. Mauskar has to tell the patient she needs to see her in the office.

Certain clinical scenarios require a vaginal exam, Dr. Venkatesan noted. Although some type of assessment may be possible if a patient is with a primary care provider during the telemedicine visit, the examination may not be equivalent. Doctors also should anticipate where a patient might go to have a biopsy if one is necessary.

Another telemedicine caveat pertains to patient counseling. When using store-and-forward telemedicine systems, advising patients in a written report can be challenging. “Is there an easy way ... to counsel patients how to apply their topical medications?” Dr. Venkatesan said.
 

Excellent care is possible

Vulvology is a small part of Dr. Venkatesan’s general dermatology practice, which has used telemedicine extensively since the pandemic.

In recent years, Dr. Venkatesan’s clinic began encouraging providers in their health system to submit photographs with referrals. “That has really paid off now because we have been able to help provide a lot of excellent quality care for patients without them having to come in,” she said. “We may be able to say: ‘These are excellent photos. We know what this patient has. We can manage it. They don’t need to come see us in person.’ ” That could be the case for certain types of acne, eczema, and psoriasis.

In other cases, they may be able to provide initial advice remotely but still want to see the patient. For a patient with severe acne, “I may be able to tell the referring doctor: ‘Please start the patient on these three medicines. It will take 2 months for those medicines to start working and then we will plan to have an in-person dermatology visit.’ ” In this case, telemedicine essentially replaces one in-person visit.

If photographs are poor, the differential diagnosis is broad, a procedure is required, the doctor needs to touch the lesion, or more involved history taking or counseling are required, the patient may need to go into the office.

Beyond its public health advantages during a pandemic, telemedicine can improve access for patients who live far away, lack transportation, or are unable to take time off from work. It also can decrease patient wait times. “Once we started doing some telemedicine work … we went from having a 5-month wait time for patients to see us in person to a 72-hour wait time for providing some care for patients if they had good photos as part of their referral,” Dr. Venkatesan said.

Telemedicine has been used in inpatient and outpatient dermatology settings. Primary care providers who consult with dermatologists using a store-and-forward telemedicine system may improve their dermatology knowledge and feel more confident in their ability to diagnose and manage dermatologic conditions, research indicates.

In obstetrics and gynecology, telemedicine may play a role in preconception, contraception, and medical abortion care, prenatal visits, well-woman exams, mental health, and pre- and postoperative counseling, a recent review suggests.
 

Image quality is key

“Quality of the image is so critical for being able to provide good care, especially in such a visual exam field as dermatology,” Dr. Venkatesan said.

To that end, doctors have offered recommendations on how to photograph skin conditions. A guide shared by the mobile telehealth system company ClickMedix suggests focusing on the area of importance, capturing the extent of involvement, and including involved and uninvolved areas.

Good lighting and checking the image resolution can help, Dr. Venkatesan offered. Nevertheless, patients may have difficulty photographing themselves. If a patient is with their primary care doctor, “we are much more likely to be able to get good quality photos,” she said.

Dr. Venkatesan is a paid consultant for DirectDerm, a store-and-forward teledermatology company. Dr. Mauskar had no relevant disclosures.

jremaly@mdedge.com

Seeing patients with vulvar problems via telemedicine can lead to efficient and successful care, but there are challenges and limitations with this approach, doctors are finding.

Image quality is one key factor that determines whether a clinician can assess and manage a condition remotely, said Aruna Venkatesan, MD, chief of dermatology and director of the genital dermatology clinic at Santa Clara Valley Medical Center in San Jose, Calif. Other issues may be especially relevant to televulvology, including privacy concerns.

“Who is helping with the positioning? Who is the photographer? Is the patient comfortable with having photos taken of this part of their body and submitted, even if they know it is submitted securely? Because they might not be,” Dr. Venkatesan said in a lecture at a virtual conference on diseases of the vulva and vagina, hosted by the International Society for the Study of Vulvovaginal Disease.

When quality photographs from referring providers are available, Dr. Venkatesan has conducted virtual new consultations. “But sometimes I will do a virtual telemedicine visit as the first visit and then figure out, okay, this isn’t really sufficient. I need to see them in person.”

Melissa Mauskar, MD, assistant professor of dermatology and obstetrics and gynecology at the University of Texas Southwestern Medical Center, Dallas, described a case early on during the COVID-19 pandemic that illustrates a limitation of virtual visits.

A patient sent in a photograph that appeared to show lichen sclerosus. “There looked like some classic lichen sclerosus changes,” Dr. Mauskar said during a discussion at the meeting. “But she was having a lot of pain, and after a week, her pain still was not better.”

Dr. Mauskar brought the patient into the office and ultimately diagnosed a squamous cell carcinoma. “What I thought was a normal erosion was actually an ulcerated plaque,” she said.

Like Dr. Venkatesan, Dr. Mauskar has found that image quality can be uneven. Photographs may be out of focus. Video visits have been a mixed bag. Some are successful. Other times, Dr. Mauskar has to tell the patient she needs to see her in the office.

Certain clinical scenarios require a vaginal exam, Dr. Venkatesan noted. Although some type of assessment may be possible if a patient is with a primary care provider during the telemedicine visit, the examination may not be equivalent. Doctors also should anticipate where a patient might go to have a biopsy if one is necessary.

Another telemedicine caveat pertains to patient counseling. When using store-and-forward telemedicine systems, advising patients in a written report can be challenging. “Is there an easy way ... to counsel patients how to apply their topical medications?” Dr. Venkatesan said.
 

Excellent care is possible

Vulvology is a small part of Dr. Venkatesan’s general dermatology practice, which has used telemedicine extensively since the pandemic.

In recent years, Dr. Venkatesan’s clinic began encouraging providers in their health system to submit photographs with referrals. “That has really paid off now because we have been able to help provide a lot of excellent quality care for patients without them having to come in,” she said. “We may be able to say: ‘These are excellent photos. We know what this patient has. We can manage it. They don’t need to come see us in person.’ ” That could be the case for certain types of acne, eczema, and psoriasis.

In other cases, they may be able to provide initial advice remotely but still want to see the patient. For a patient with severe acne, “I may be able to tell the referring doctor: ‘Please start the patient on these three medicines. It will take 2 months for those medicines to start working and then we will plan to have an in-person dermatology visit.’ ” In this case, telemedicine essentially replaces one in-person visit.

If photographs are poor, the differential diagnosis is broad, a procedure is required, the doctor needs to touch the lesion, or more involved history taking or counseling are required, the patient may need to go into the office.

Beyond its public health advantages during a pandemic, telemedicine can improve access for patients who live far away, lack transportation, or are unable to take time off from work. It also can decrease patient wait times. “Once we started doing some telemedicine work … we went from having a 5-month wait time for patients to see us in person to a 72-hour wait time for providing some care for patients if they had good photos as part of their referral,” Dr. Venkatesan said.

Telemedicine has been used in inpatient and outpatient dermatology settings. Primary care providers who consult with dermatologists using a store-and-forward telemedicine system may improve their dermatology knowledge and feel more confident in their ability to diagnose and manage dermatologic conditions, research indicates.

In obstetrics and gynecology, telemedicine may play a role in preconception, contraception, and medical abortion care, prenatal visits, well-woman exams, mental health, and pre- and postoperative counseling, a recent review suggests.
 

Image quality is key

“Quality of the image is so critical for being able to provide good care, especially in such a visual exam field as dermatology,” Dr. Venkatesan said.

To that end, doctors have offered recommendations on how to photograph skin conditions. A guide shared by the mobile telehealth system company ClickMedix suggests focusing on the area of importance, capturing the extent of involvement, and including involved and uninvolved areas.

Good lighting and checking the image resolution can help, Dr. Venkatesan offered. Nevertheless, patients may have difficulty photographing themselves. If a patient is with their primary care doctor, “we are much more likely to be able to get good quality photos,” she said.

Dr. Venkatesan is a paid consultant for DirectDerm, a store-and-forward teledermatology company. Dr. Mauskar had no relevant disclosures.

jremaly@mdedge.com

Seeing patients with vulvar problems via telemedicine can lead to efficient and successful care, but there are challenges and limitations with this approach, doctors are finding.

Image quality is one key factor that determines whether a clinician can assess and manage a condition remotely, said Aruna Venkatesan, MD, chief of dermatology and director of the genital dermatology clinic at Santa Clara Valley Medical Center in San Jose, Calif. Other issues may be especially relevant to televulvology, including privacy concerns.

“Who is helping with the positioning? Who is the photographer? Is the patient comfortable with having photos taken of this part of their body and submitted, even if they know it is submitted securely? Because they might not be,” Dr. Venkatesan said in a lecture at a virtual conference on diseases of the vulva and vagina, hosted by the International Society for the Study of Vulvovaginal Disease.

When quality photographs from referring providers are available, Dr. Venkatesan has conducted virtual new consultations. “But sometimes I will do a virtual telemedicine visit as the first visit and then figure out, okay, this isn’t really sufficient. I need to see them in person.”

Melissa Mauskar, MD, assistant professor of dermatology and obstetrics and gynecology at the University of Texas Southwestern Medical Center, Dallas, described a case early on during the COVID-19 pandemic that illustrates a limitation of virtual visits.

A patient sent in a photograph that appeared to show lichen sclerosus. “There looked like some classic lichen sclerosus changes,” Dr. Mauskar said during a discussion at the meeting. “But she was having a lot of pain, and after a week, her pain still was not better.”

Dr. Mauskar brought the patient into the office and ultimately diagnosed a squamous cell carcinoma. “What I thought was a normal erosion was actually an ulcerated plaque,” she said.

Like Dr. Venkatesan, Dr. Mauskar has found that image quality can be uneven. Photographs may be out of focus. Video visits have been a mixed bag. Some are successful. Other times, Dr. Mauskar has to tell the patient she needs to see her in the office.

Certain clinical scenarios require a vaginal exam, Dr. Venkatesan noted. Although some type of assessment may be possible if a patient is with a primary care provider during the telemedicine visit, the examination may not be equivalent. Doctors also should anticipate where a patient might go to have a biopsy if one is necessary.

Another telemedicine caveat pertains to patient counseling. When using store-and-forward telemedicine systems, advising patients in a written report can be challenging. “Is there an easy way ... to counsel patients how to apply their topical medications?” Dr. Venkatesan said.
 

Excellent care is possible

Vulvology is a small part of Dr. Venkatesan’s general dermatology practice, which has used telemedicine extensively since the pandemic.

In recent years, Dr. Venkatesan’s clinic began encouraging providers in their health system to submit photographs with referrals. “That has really paid off now because we have been able to help provide a lot of excellent quality care for patients without them having to come in,” she said. “We may be able to say: ‘These are excellent photos. We know what this patient has. We can manage it. They don’t need to come see us in person.’ ” That could be the case for certain types of acne, eczema, and psoriasis.

In other cases, they may be able to provide initial advice remotely but still want to see the patient. For a patient with severe acne, “I may be able to tell the referring doctor: ‘Please start the patient on these three medicines. It will take 2 months for those medicines to start working and then we will plan to have an in-person dermatology visit.’ ” In this case, telemedicine essentially replaces one in-person visit.

If photographs are poor, the differential diagnosis is broad, a procedure is required, the doctor needs to touch the lesion, or more involved history taking or counseling are required, the patient may need to go into the office.

Beyond its public health advantages during a pandemic, telemedicine can improve access for patients who live far away, lack transportation, or are unable to take time off from work. It also can decrease patient wait times. “Once we started doing some telemedicine work … we went from having a 5-month wait time for patients to see us in person to a 72-hour wait time for providing some care for patients if they had good photos as part of their referral,” Dr. Venkatesan said.

Telemedicine has been used in inpatient and outpatient dermatology settings. Primary care providers who consult with dermatologists using a store-and-forward telemedicine system may improve their dermatology knowledge and feel more confident in their ability to diagnose and manage dermatologic conditions, research indicates.

In obstetrics and gynecology, telemedicine may play a role in preconception, contraception, and medical abortion care, prenatal visits, well-woman exams, mental health, and pre- and postoperative counseling, a recent review suggests.
 

Image quality is key

“Quality of the image is so critical for being able to provide good care, especially in such a visual exam field as dermatology,” Dr. Venkatesan said.

To that end, doctors have offered recommendations on how to photograph skin conditions. A guide shared by the mobile telehealth system company ClickMedix suggests focusing on the area of importance, capturing the extent of involvement, and including involved and uninvolved areas.

Good lighting and checking the image resolution can help, Dr. Venkatesan offered. Nevertheless, patients may have difficulty photographing themselves. If a patient is with their primary care doctor, “we are much more likely to be able to get good quality photos,” she said.

Dr. Venkatesan is a paid consultant for DirectDerm, a store-and-forward teledermatology company. Dr. Mauskar had no relevant disclosures.

jremaly@mdedge.com

The U.S. Department of Agriculture and the Department of Health & Human Services aim to release new dietary guidelines by the end of 2020. For the first time, the guidelines are mandated to include dietary recommendations from birth to 24 months and for women who are pregnant or lactating.

Bonnie Becker/MDedge News

An advisory committee submitted to the agencies a scientific report that examines relationships between diet and health at various life stages. Four chapters focus on dietary considerations for infants and toddlers, and two chapters focus on diet during pregnancy and lactation.

The report may inform the development of the new guidelines. The advisory committee’s recommendations include introducing infants to foods that are rich in zinc and iron at about age 6 months and having women who are lactating eat sources of omega-3 and omega-6 fatty acids, such as fish, to improve the fatty acid status of infants.

Ahead of the release of the 2020-2025 Dietary Guidelines for Americans, Joan Younger Meek, MD, discussed parts of the scientific report at the annual meeting of the American Academy of Pediatrics, held virtually this year.

While the 2015-2020 guidelines use ChooseMyPlate to help people implement the recommendations, it is not known how the new guidelines will be presented to the public, she said. “Many of you will remember the pyramids earlier and different food groups before that.”
 

Promote healthy dietary patterns

The advisory committee’s report notes that diet in the first years of life contributes to long-term health and shapes taste preferences, said Dr. Meek, professor of clinical sciences at Florida State University, Orlando. Human milk or infant formula are primary sources of nutrition until approximately 6 months, when families may introduce complementary foods and beverages. Between 6 months and 24 months, children transition to the typical family diet.

Dr. Meek highlighted some of the advisory committee’s findings and recommendations.

• Infants who are ever breastfed have a reduced risk of overweight or obesity, type 1 diabetes, and asthma. Likewise, longer duration of breastfeeding is associated with lower risk of type 1 diabetes and asthma, and exclusive breastfeeding is associated with lower risk of type 1 diabetes.
• Complementary foods and beverages should not be introduced before age 4 months. Limited evidence indicates that their introduction before 4 months may be associated with increased odds of overweight or obesity. Introducing complementary foods or beverages at 4 or 5 months, compared with 6 months, is not associated with long-term advantages or disadvantages.
• Introducing peanut and egg after age 4 months may reduce the risk of food allergies.
• From age 12 months to 24 months, children should consume a variety of nutrient-rich protein sources from animals – including meat, poultry, seafood, eggs, and dairy – plus nuts, seeds, fruits, vegetables, and grains.
• The report prioritizes oils over solid fats, and whole grains over refined grains. It also discourages added sugars, particularly from sugar-sweetened beverages. Other sources of added sugars include sweets, baked goods, and sweetened dairy products.

The report acknowledges that dietary guidelines should accommodate cultural preferences and cost considerations.
 

Recommendations during pregnancy

Healthy dietary patterns before or during pregnancy may modestly reduce the odds of gestational diabetes, hypertensive disorders of pregnancy, and preterm birth, according to the report.

The report recommends that during pregnancy women consume 8-12 ounces per week of seafood with high levels of omega-3 fatty acids and low levels of methylmercury, consistent with existing recommendations.

Egg and milk consumption during pregnancy does not influence the risk of food allergy, asthma, or atopic disease in the child, according to the report.

The advisory committee recommended universal folic acid supplementation during pregnancy.
 

Addressing a gap

The Agricultural Act of 2014 required that infants and toddlers and women who are pregnant or lactating be included in the 2020-2025 guidelines. Covering these populations in the scientific report was a substantial undertaking, said Kathryn Dewey, PhD, of the Institute for Global Nutrition at the University of California, Davis. Dr. Dewey chaired the subcommittee on birth to 24 months for the 2020 Dietary Guidelines Advisory Committee.

“Given that this age group had not been covered before, we could not rely on previous dietary guidelines’ reports,” Dr. Dewey said in an interview.

Outlining food patterns for infants and toddlers proved challenging. The committee explored models that considered various scenarios including children who consumed human milk, children who consumed formula, and those with vegetarian diets. Future research should clarify dietary reference intakes for these age groups, Dr. Dewey said.

Dr. Dewey sees the committee’s report on dietary guidance for birth to 24 months as a starting point and not necessarily an exhaustive look at the subject.

For one, the committee focused more on what to feed infants and toddlers rather than on how to feed them. Information about how to feed children is considered more in depth in a 2020 report from the National Academies of Sciences, Engineering, and Medicine. That report summarizes existing guidance from various organizations on feeding infants and children from birth to 24 months. Dr. Dewey chaired the committee that created the National Academies report.

Sharing the new USDA and HHS guidelines after they are released could be the next important step. “The public does not necessarily know about the guidelines or they do not necessarily seek them out unless there is a very well-constructed strategy for dissemination and implementation,” Dr. Dewey said.

To that end, health care providers can play a role, Dr. Meek said. “Be aware of changes in guidance, adopt those new recommendations, and then advocate those with our patients as well as with the public at large.”

Dr. Meek and Dr. Dewey had no relevant financial disclosures.

jremaly@mdedge.com

The U.S. Department of Agriculture and the Department of Health & Human Services aim to release new dietary guidelines by the end of 2020. For the first time, the guidelines are mandated to include dietary recommendations from birth to 24 months and for women who are pregnant or lactating.

Bonnie Becker/MDedge News

An advisory committee submitted to the agencies a scientific report that examines relationships between diet and health at various life stages. Four chapters focus on dietary considerations for infants and toddlers, and two chapters focus on diet during pregnancy and lactation.

The report may inform the development of the new guidelines. The advisory committee’s recommendations include introducing infants to foods that are rich in zinc and iron at about age 6 months and having women who are lactating eat sources of omega-3 and omega-6 fatty acids, such as fish, to improve the fatty acid status of infants.

Ahead of the release of the 2020-2025 Dietary Guidelines for Americans, Joan Younger Meek, MD, discussed parts of the scientific report at the annual meeting of the American Academy of Pediatrics, held virtually this year.

While the 2015-2020 guidelines use ChooseMyPlate to help people implement the recommendations, it is not known how the new guidelines will be presented to the public, she said. “Many of you will remember the pyramids earlier and different food groups before that.”
 

Promote healthy dietary patterns

The advisory committee’s report notes that diet in the first years of life contributes to long-term health and shapes taste preferences, said Dr. Meek, professor of clinical sciences at Florida State University, Orlando. Human milk or infant formula are primary sources of nutrition until approximately 6 months, when families may introduce complementary foods and beverages. Between 6 months and 24 months, children transition to the typical family diet.

Dr. Meek highlighted some of the advisory committee’s findings and recommendations.

• Infants who are ever breastfed have a reduced risk of overweight or obesity, type 1 diabetes, and asthma. Likewise, longer duration of breastfeeding is associated with lower risk of type 1 diabetes and asthma, and exclusive breastfeeding is associated with lower risk of type 1 diabetes.
• Complementary foods and beverages should not be introduced before age 4 months. Limited evidence indicates that their introduction before 4 months may be associated with increased odds of overweight or obesity. Introducing complementary foods or beverages at 4 or 5 months, compared with 6 months, is not associated with long-term advantages or disadvantages.
• Introducing peanut and egg after age 4 months may reduce the risk of food allergies.
• From age 12 months to 24 months, children should consume a variety of nutrient-rich protein sources from animals – including meat, poultry, seafood, eggs, and dairy – plus nuts, seeds, fruits, vegetables, and grains.
• The report prioritizes oils over solid fats, and whole grains over refined grains. It also discourages added sugars, particularly from sugar-sweetened beverages. Other sources of added sugars include sweets, baked goods, and sweetened dairy products.

The report acknowledges that dietary guidelines should accommodate cultural preferences and cost considerations.
 

Recommendations during pregnancy

Healthy dietary patterns before or during pregnancy may modestly reduce the odds of gestational diabetes, hypertensive disorders of pregnancy, and preterm birth, according to the report.

The report recommends that during pregnancy women consume 8-12 ounces per week of seafood with high levels of omega-3 fatty acids and low levels of methylmercury, consistent with existing recommendations.

Egg and milk consumption during pregnancy does not influence the risk of food allergy, asthma, or atopic disease in the child, according to the report.

The advisory committee recommended universal folic acid supplementation during pregnancy.
 

Addressing a gap

The Agricultural Act of 2014 required that infants and toddlers and women who are pregnant or lactating be included in the 2020-2025 guidelines. Covering these populations in the scientific report was a substantial undertaking, said Kathryn Dewey, PhD, of the Institute for Global Nutrition at the University of California, Davis. Dr. Dewey chaired the subcommittee on birth to 24 months for the 2020 Dietary Guidelines Advisory Committee.

“Given that this age group had not been covered before, we could not rely on previous dietary guidelines’ reports,” Dr. Dewey said in an interview.

Outlining food patterns for infants and toddlers proved challenging. The committee explored models that considered various scenarios including children who consumed human milk, children who consumed formula, and those with vegetarian diets. Future research should clarify dietary reference intakes for these age groups, Dr. Dewey said.

Dr. Dewey sees the committee’s report on dietary guidance for birth to 24 months as a starting point and not necessarily an exhaustive look at the subject.

For one, the committee focused more on what to feed infants and toddlers rather than on how to feed them. Information about how to feed children is considered more in depth in a 2020 report from the National Academies of Sciences, Engineering, and Medicine. That report summarizes existing guidance from various organizations on feeding infants and children from birth to 24 months. Dr. Dewey chaired the committee that created the National Academies report.

Sharing the new USDA and HHS guidelines after they are released could be the next important step. “The public does not necessarily know about the guidelines or they do not necessarily seek them out unless there is a very well-constructed strategy for dissemination and implementation,” Dr. Dewey said.

To that end, health care providers can play a role, Dr. Meek said. “Be aware of changes in guidance, adopt those new recommendations, and then advocate those with our patients as well as with the public at large.”

Dr. Meek and Dr. Dewey had no relevant financial disclosures.

jremaly@mdedge.com

The U.S. Department of Agriculture and the Department of Health & Human Services aim to release new dietary guidelines by the end of 2020. For the first time, the guidelines are mandated to include dietary recommendations from birth to 24 months and for women who are pregnant or lactating.

Bonnie Becker/MDedge News

An advisory committee submitted to the agencies a scientific report that examines relationships between diet and health at various life stages. Four chapters focus on dietary considerations for infants and toddlers, and two chapters focus on diet during pregnancy and lactation.

The report may inform the development of the new guidelines. The advisory committee’s recommendations include introducing infants to foods that are rich in zinc and iron at about age 6 months and having women who are lactating eat sources of omega-3 and omega-6 fatty acids, such as fish, to improve the fatty acid status of infants.

Ahead of the release of the 2020-2025 Dietary Guidelines for Americans, Joan Younger Meek, MD, discussed parts of the scientific report at the annual meeting of the American Academy of Pediatrics, held virtually this year.

While the 2015-2020 guidelines use ChooseMyPlate to help people implement the recommendations, it is not known how the new guidelines will be presented to the public, she said. “Many of you will remember the pyramids earlier and different food groups before that.”
 

Promote healthy dietary patterns

The advisory committee’s report notes that diet in the first years of life contributes to long-term health and shapes taste preferences, said Dr. Meek, professor of clinical sciences at Florida State University, Orlando. Human milk or infant formula are primary sources of nutrition until approximately 6 months, when families may introduce complementary foods and beverages. Between 6 months and 24 months, children transition to the typical family diet.

Dr. Meek highlighted some of the advisory committee’s findings and recommendations.

• Infants who are ever breastfed have a reduced risk of overweight or obesity, type 1 diabetes, and asthma. Likewise, longer duration of breastfeeding is associated with lower risk of type 1 diabetes and asthma, and exclusive breastfeeding is associated with lower risk of type 1 diabetes.
• Complementary foods and beverages should not be introduced before age 4 months. Limited evidence indicates that their introduction before 4 months may be associated with increased odds of overweight or obesity. Introducing complementary foods or beverages at 4 or 5 months, compared with 6 months, is not associated with long-term advantages or disadvantages.
• Introducing peanut and egg after age 4 months may reduce the risk of food allergies.
• From age 12 months to 24 months, children should consume a variety of nutrient-rich protein sources from animals – including meat, poultry, seafood, eggs, and dairy – plus nuts, seeds, fruits, vegetables, and grains.
• The report prioritizes oils over solid fats, and whole grains over refined grains. It also discourages added sugars, particularly from sugar-sweetened beverages. Other sources of added sugars include sweets, baked goods, and sweetened dairy products.

The report acknowledges that dietary guidelines should accommodate cultural preferences and cost considerations.
 

Recommendations during pregnancy

Healthy dietary patterns before or during pregnancy may modestly reduce the odds of gestational diabetes, hypertensive disorders of pregnancy, and preterm birth, according to the report.

The report recommends that during pregnancy women consume 8-12 ounces per week of seafood with high levels of omega-3 fatty acids and low levels of methylmercury, consistent with existing recommendations.

Egg and milk consumption during pregnancy does not influence the risk of food allergy, asthma, or atopic disease in the child, according to the report.

The advisory committee recommended universal folic acid supplementation during pregnancy.
 

Addressing a gap

The Agricultural Act of 2014 required that infants and toddlers and women who are pregnant or lactating be included in the 2020-2025 guidelines. Covering these populations in the scientific report was a substantial undertaking, said Kathryn Dewey, PhD, of the Institute for Global Nutrition at the University of California, Davis. Dr. Dewey chaired the subcommittee on birth to 24 months for the 2020 Dietary Guidelines Advisory Committee.

“Given that this age group had not been covered before, we could not rely on previous dietary guidelines’ reports,” Dr. Dewey said in an interview.

Outlining food patterns for infants and toddlers proved challenging. The committee explored models that considered various scenarios including children who consumed human milk, children who consumed formula, and those with vegetarian diets. Future research should clarify dietary reference intakes for these age groups, Dr. Dewey said.

Dr. Dewey sees the committee’s report on dietary guidance for birth to 24 months as a starting point and not necessarily an exhaustive look at the subject.

For one, the committee focused more on what to feed infants and toddlers rather than on how to feed them. Information about how to feed children is considered more in depth in a 2020 report from the National Academies of Sciences, Engineering, and Medicine. That report summarizes existing guidance from various organizations on feeding infants and children from birth to 24 months. Dr. Dewey chaired the committee that created the National Academies report.

Sharing the new USDA and HHS guidelines after they are released could be the next important step. “The public does not necessarily know about the guidelines or they do not necessarily seek them out unless there is a very well-constructed strategy for dissemination and implementation,” Dr. Dewey said.

To that end, health care providers can play a role, Dr. Meek said. “Be aware of changes in guidance, adopt those new recommendations, and then advocate those with our patients as well as with the public at large.”

Dr. Meek and Dr. Dewey had no relevant financial disclosures.

jremaly@mdedge.com

Women who used injectable contraceptives had the longest delay in return to normal fertility after discontinuing use, according to a new prospective cohort study.

Women who used hormonal intrauterine devices, copper intrauterine devices, and implants had the shortest delays, based on the same research project, which involved analyzing data from approximately 18,000 women in North America and Denmark.

“Most research on the use of contraceptives and fertility has focused on the effect of oral contraceptives on fecundability,” and data on the association between fertility and other contraceptive methods are limited, wrote Jennifer J. Yland, MS, of Boston University School of Public Health and colleagues.

“Given the increasing popularity of long acting reversible contraceptive methods and other alternatives to oral contraceptives, more research into their short- and long-term effects on fertility is needed,” the researchers noted.

In the study, which was published in the BMJ, the researchers reviewed data from a total of 17,954 women from three cohort studies of individuals planning pregnancies between 2007 and 2019. Participants reported their contraceptive use and typical menstrual cycle at baseline, then responded to questionnaires every 2 months for up to a year or until pregnancy.

On average, users of injectable contraceptives had the longest delay in return of normal fertility (five to eight menstrual cycles), compared with four cycles for patch contraceptives, three cycles for oral and ring contraceptives, and two cycles for hormonal and copper intrauterine devices and implants.

A total of 10,729 pregnancies were reported within 66,759 menstrual cycles; approximately 77% of the women conceived within 12 months, and 56% conceived within 6 months.

Oral contraceptives were the most common method of contraception (38%), followed by barrier methods (31%), natural methods (15%), and long-acting reversible contraceptives (13%). Intrauterine devices were the most frequently used of long-acting reversible contraceptives (8% hormonal, 4% copper).

The time until fertility returned after discontinuing contraceptives was not associated with duration of contraceptive use.

The study findings were limited by several factors including the potential misclassification of menstrual cycles and the use of self-reports for the time of contraceptive discontinuation, especially for users of injectable contraceptives, the researchers noted.

However, the results were strengthened by the large study size and show “little or no lasting effect” of long-term use of any of the reported contraceptive methods on fertility, the researchers noted. “Understanding the comparative effects of different contraceptives on fecundity is essential for family planning, counseling for contraception, and management of infertility,” they said.
 

Comparison of contraceptives can inform counseling

The study is important because the use of long-acting reversible contraceptive (LARC) methods (IUDs, implants, patches, and injectable contraceptives) has become increasingly common worldwide, corresponding author Jennifer J. Yland, MS, said in an interview. “Many women are concerned about the potential effects of contraception on future fertility. However, previous research on this topic has focused mostly on oral contraceptives,” she said.

Ms. Yland said that the findings on oral and injectable contraceptives were consistent with previous publications. However, “we were surprised to find that women who had recently used the hormonal IUD had a shorter time to pregnancy, compared with women who used barrier methods,” she said.

The take-home message for clinicians is that delays in the return to normal fertility were temporary for all hormonal contraceptive methods, Ms. Yland emphasized. “However, delays in the return of fertility after discontinuing certain hormonal methods, such as injectables, were considerably longer than that shown for oral contraceptives. These findings should be taken into account when women are considering contraceptive choice in the context of family planning and infertility management,” she noted.

“Future research should evaluate the potential associations between recent use of hormonal contraceptives and perinatal outcomes,” she added.
 

Managing expectations helps patients plan

“The question of return to fertility is one that many patients who use contraception have unless they have completed their child bearing,” said Sarah W. Prager, MD, of the University of Washington, Seattle, in an interview. “For patients who want to plan a pregnancy, knowing what to expect in terms of return to fertility is important so they can make sure they are in the space and place they want to be with their health, life, job, and partner,” she said.

Dr. Prager said she was not surprised by the study findings because they agree with previously published data. “Overall, except for the injection, people using any form of contraception are back to their baseline fertility within a few months,” she noted. “It also makes perfect sense for return to fertility to be longer with the injection, as it is designed to prevent pregnancy for 16 weeks after the injection is given. Unlike all the other methods, it cannot be removed from the body once given,” she said.

“Clinicians should continue to advise patients that their return to baseline fertility is relatively rapid with any contraception other than the Depo-Provera injection,” said Dr. Prager. “There are no data to support a benefit in switching from an IUD or implant to a combination hormonal method (pills, patch, ring) before starting to try to conceive,” she said.

“This study tries to account for differences in baseline fertility for people using the different methods, but since the choice of method was not randomized, there could still be baseline differences that were not measured or accounted for,” Dr. Prager noted. “A randomized study would certainly eliminate some of these biases; however, I don’t think the differences found in this study are so profound as to require such study,” she said. “Generally speaking, almost 80% of people using any form of contraception were able to conceive within 1 year of trying, which has been the stated fertility data for decades,” she said.

The study was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health. Lead author Ms. Yland had no financial conflicts to disclose. Dr. Prager had no financial conflicts to disclose.

SOURCE: Yland JJ et al. BMJ. 2020 Nov 12. doi: 10.1136/bmj.m3966.

Women who used injectable contraceptives had the longest delay in return to normal fertility after discontinuing use, according to a new prospective cohort study.

Women who used hormonal intrauterine devices, copper intrauterine devices, and implants had the shortest delays, based on the same research project, which involved analyzing data from approximately 18,000 women in North America and Denmark.

“Most research on the use of contraceptives and fertility has focused on the effect of oral contraceptives on fecundability,” and data on the association between fertility and other contraceptive methods are limited, wrote Jennifer J. Yland, MS, of Boston University School of Public Health and colleagues.

“Given the increasing popularity of long acting reversible contraceptive methods and other alternatives to oral contraceptives, more research into their short- and long-term effects on fertility is needed,” the researchers noted.

In the study, which was published in the BMJ, the researchers reviewed data from a total of 17,954 women from three cohort studies of individuals planning pregnancies between 2007 and 2019. Participants reported their contraceptive use and typical menstrual cycle at baseline, then responded to questionnaires every 2 months for up to a year or until pregnancy.

On average, users of injectable contraceptives had the longest delay in return of normal fertility (five to eight menstrual cycles), compared with four cycles for patch contraceptives, three cycles for oral and ring contraceptives, and two cycles for hormonal and copper intrauterine devices and implants.

A total of 10,729 pregnancies were reported within 66,759 menstrual cycles; approximately 77% of the women conceived within 12 months, and 56% conceived within 6 months.

Oral contraceptives were the most common method of contraception (38%), followed by barrier methods (31%), natural methods (15%), and long-acting reversible contraceptives (13%). Intrauterine devices were the most frequently used of long-acting reversible contraceptives (8% hormonal, 4% copper).

The time until fertility returned after discontinuing contraceptives was not associated with duration of contraceptive use.

The study findings were limited by several factors including the potential misclassification of menstrual cycles and the use of self-reports for the time of contraceptive discontinuation, especially for users of injectable contraceptives, the researchers noted.

However, the results were strengthened by the large study size and show “little or no lasting effect” of long-term use of any of the reported contraceptive methods on fertility, the researchers noted. “Understanding the comparative effects of different contraceptives on fecundity is essential for family planning, counseling for contraception, and management of infertility,” they said.
 

Comparison of contraceptives can inform counseling

The study is important because the use of long-acting reversible contraceptive (LARC) methods (IUDs, implants, patches, and injectable contraceptives) has become increasingly common worldwide, corresponding author Jennifer J. Yland, MS, said in an interview. “Many women are concerned about the potential effects of contraception on future fertility. However, previous research on this topic has focused mostly on oral contraceptives,” she said.

Ms. Yland said that the findings on oral and injectable contraceptives were consistent with previous publications. However, “we were surprised to find that women who had recently used the hormonal IUD had a shorter time to pregnancy, compared with women who used barrier methods,” she said.

The take-home message for clinicians is that delays in the return to normal fertility were temporary for all hormonal contraceptive methods, Ms. Yland emphasized. “However, delays in the return of fertility after discontinuing certain hormonal methods, such as injectables, were considerably longer than that shown for oral contraceptives. These findings should be taken into account when women are considering contraceptive choice in the context of family planning and infertility management,” she noted.

“Future research should evaluate the potential associations between recent use of hormonal contraceptives and perinatal outcomes,” she added.
 

Managing expectations helps patients plan

“The question of return to fertility is one that many patients who use contraception have unless they have completed their child bearing,” said Sarah W. Prager, MD, of the University of Washington, Seattle, in an interview. “For patients who want to plan a pregnancy, knowing what to expect in terms of return to fertility is important so they can make sure they are in the space and place they want to be with their health, life, job, and partner,” she said.

Dr. Prager said she was not surprised by the study findings because they agree with previously published data. “Overall, except for the injection, people using any form of contraception are back to their baseline fertility within a few months,” she noted. “It also makes perfect sense for return to fertility to be longer with the injection, as it is designed to prevent pregnancy for 16 weeks after the injection is given. Unlike all the other methods, it cannot be removed from the body once given,” she said.

“Clinicians should continue to advise patients that their return to baseline fertility is relatively rapid with any contraception other than the Depo-Provera injection,” said Dr. Prager. “There are no data to support a benefit in switching from an IUD or implant to a combination hormonal method (pills, patch, ring) before starting to try to conceive,” she said.

“This study tries to account for differences in baseline fertility for people using the different methods, but since the choice of method was not randomized, there could still be baseline differences that were not measured or accounted for,” Dr. Prager noted. “A randomized study would certainly eliminate some of these biases; however, I don’t think the differences found in this study are so profound as to require such study,” she said. “Generally speaking, almost 80% of people using any form of contraception were able to conceive within 1 year of trying, which has been the stated fertility data for decades,” she said.

The study was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health. Lead author Ms. Yland had no financial conflicts to disclose. Dr. Prager had no financial conflicts to disclose.

SOURCE: Yland JJ et al. BMJ. 2020 Nov 12. doi: 10.1136/bmj.m3966.

Women who used injectable contraceptives had the longest delay in return to normal fertility after discontinuing use, according to a new prospective cohort study.

Women who used hormonal intrauterine devices, copper intrauterine devices, and implants had the shortest delays, based on the same research project, which involved analyzing data from approximately 18,000 women in North America and Denmark.

“Most research on the use of contraceptives and fertility has focused on the effect of oral contraceptives on fecundability,” and data on the association between fertility and other contraceptive methods are limited, wrote Jennifer J. Yland, MS, of Boston University School of Public Health and colleagues.

“Given the increasing popularity of long acting reversible contraceptive methods and other alternatives to oral contraceptives, more research into their short- and long-term effects on fertility is needed,” the researchers noted.

In the study, which was published in the BMJ, the researchers reviewed data from a total of 17,954 women from three cohort studies of individuals planning pregnancies between 2007 and 2019. Participants reported their contraceptive use and typical menstrual cycle at baseline, then responded to questionnaires every 2 months for up to a year or until pregnancy.

On average, users of injectable contraceptives had the longest delay in return of normal fertility (five to eight menstrual cycles), compared with four cycles for patch contraceptives, three cycles for oral and ring contraceptives, and two cycles for hormonal and copper intrauterine devices and implants.

A total of 10,729 pregnancies were reported within 66,759 menstrual cycles; approximately 77% of the women conceived within 12 months, and 56% conceived within 6 months.

Oral contraceptives were the most common method of contraception (38%), followed by barrier methods (31%), natural methods (15%), and long-acting reversible contraceptives (13%). Intrauterine devices were the most frequently used of long-acting reversible contraceptives (8% hormonal, 4% copper).

The time until fertility returned after discontinuing contraceptives was not associated with duration of contraceptive use.

The study findings were limited by several factors including the potential misclassification of menstrual cycles and the use of self-reports for the time of contraceptive discontinuation, especially for users of injectable contraceptives, the researchers noted.

However, the results were strengthened by the large study size and show “little or no lasting effect” of long-term use of any of the reported contraceptive methods on fertility, the researchers noted. “Understanding the comparative effects of different contraceptives on fecundity is essential for family planning, counseling for contraception, and management of infertility,” they said.
 

Comparison of contraceptives can inform counseling

The study is important because the use of long-acting reversible contraceptive (LARC) methods (IUDs, implants, patches, and injectable contraceptives) has become increasingly common worldwide, corresponding author Jennifer J. Yland, MS, said in an interview. “Many women are concerned about the potential effects of contraception on future fertility. However, previous research on this topic has focused mostly on oral contraceptives,” she said.

Ms. Yland said that the findings on oral and injectable contraceptives were consistent with previous publications. However, “we were surprised to find that women who had recently used the hormonal IUD had a shorter time to pregnancy, compared with women who used barrier methods,” she said.

The take-home message for clinicians is that delays in the return to normal fertility were temporary for all hormonal contraceptive methods, Ms. Yland emphasized. “However, delays in the return of fertility after discontinuing certain hormonal methods, such as injectables, were considerably longer than that shown for oral contraceptives. These findings should be taken into account when women are considering contraceptive choice in the context of family planning and infertility management,” she noted.

“Future research should evaluate the potential associations between recent use of hormonal contraceptives and perinatal outcomes,” she added.
 

Managing expectations helps patients plan

“The question of return to fertility is one that many patients who use contraception have unless they have completed their child bearing,” said Sarah W. Prager, MD, of the University of Washington, Seattle, in an interview. “For patients who want to plan a pregnancy, knowing what to expect in terms of return to fertility is important so they can make sure they are in the space and place they want to be with their health, life, job, and partner,” she said.

Dr. Prager said she was not surprised by the study findings because they agree with previously published data. “Overall, except for the injection, people using any form of contraception are back to their baseline fertility within a few months,” she noted. “It also makes perfect sense for return to fertility to be longer with the injection, as it is designed to prevent pregnancy for 16 weeks after the injection is given. Unlike all the other methods, it cannot be removed from the body once given,” she said.

“Clinicians should continue to advise patients that their return to baseline fertility is relatively rapid with any contraception other than the Depo-Provera injection,” said Dr. Prager. “There are no data to support a benefit in switching from an IUD or implant to a combination hormonal method (pills, patch, ring) before starting to try to conceive,” she said.

“This study tries to account for differences in baseline fertility for people using the different methods, but since the choice of method was not randomized, there could still be baseline differences that were not measured or accounted for,” Dr. Prager noted. “A randomized study would certainly eliminate some of these biases; however, I don’t think the differences found in this study are so profound as to require such study,” she said. “Generally speaking, almost 80% of people using any form of contraception were able to conceive within 1 year of trying, which has been the stated fertility data for decades,” she said.

The study was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health. Lead author Ms. Yland had no financial conflicts to disclose. Dr. Prager had no financial conflicts to disclose.

SOURCE: Yland JJ et al. BMJ. 2020 Nov 12. doi: 10.1136/bmj.m3966.