Sharon Worcester

MIAMI BEACH – Worry less about reactions, and more about counseling patients on what to expect following actinic keratosis treatments, according to Dr. Neal Bhatia.

“I just want to take everyone’s finger off the panic button when it comes to managing reactions of actinic keratoses,” he said at the South Beach Symposium.

© Dr-Strangelove / ThinkStockPhotos.com

It’s easy to get hung up on side effects and redness, as well as other issues related to treatment, said Dr. Bhatia of Therapeutics Dermatology in San Diego.

“Let’s not forget we’re treating something that could cause skin cancer if left alone,” he added.

AKs are “no longer a Medicare disease,” he said, explaining that AKs are increasingly common in 30- and 40-year-old patients, and the focus of their care should be on outcomes, not reactions.

“The reactions, more often than not, are anticipated,” Dr. Bhatia said.

Patients should be counseled in advance about possible side effects from AK treatments, as well as about anticipated responses, and they should be advised about how to modify symptoms, he said.

“More importantly, we want to give them something that’s going to keep them adherent to the program … we tell them ‘these are things that are going to happen. Be prepared. If you have a problem, you can call the office,’ ” he said.

A patient who doesn’t know what to expect will run to a primary care doctor and post negative reviews on every rating site out there, he cautioned, but that can be prevented by counseling in advance and by choosing the correct therapy with a duration that is a good fit for the patient. He noted that clinicians who suspect a patient won’t be compliant should choose a 2-day treatment, and if they think the patient can handle it – choose a 90-day treatment.

There are numerous treatment choices that will have some benefit for the right patient, Dr. Bhatia added.

When it comes to managing an aggressive treatment response, consider the mechanism of the response. Antibiotics can be used to reduce inflammation without changing the immune process, while steroids can undo the immune response that some therapies are trying to recruit.

“We can emphasize keeping the lesion calmed down while reducing symptoms that are going to be dose limiting,” he said.

Dr. Bhatia advised prescribing medications to be filled only on Monday-Thursday to avoid substitutions being given on Friday-Sunday when “we can’t defend them.” He recommends that patients start treatment on Sunday, so any reactions occur mid-week and can be addressed by the office.

To further reduce the chance of reactions, be sure to avoid office procedures in the 4-7 days before or after AK treatment. Also, when starting any AK drugs, advise the patient to use as many adjunctive therapies as possible, including topical anesthetics, moisturizers, sunblock – “anything to reduce the potential for going overboard,” he said.

Dr Bhatia has been a consultant, researcher, and/or speaker for companies including Allergan, Aqua Pharmaceuticals, Bayer Healthcare Pharmaceuticals, DUSA Pharmaceuticals, Exeltis, Ferndale Pharma, Galderma Laboratories, Genentech, LEO Pharmaceuticals, Nerium Novartis, Promius Pharma, Sandoz, Novartis, and Valeant.

MIAMI BEACH – Worry less about reactions, and more about counseling patients on what to expect following actinic keratosis treatments, according to Dr. Neal Bhatia.

“I just want to take everyone’s finger off the panic button when it comes to managing reactions of actinic keratoses,” he said at the South Beach Symposium.

© Dr-Strangelove / ThinkStockPhotos.com

It’s easy to get hung up on side effects and redness, as well as other issues related to treatment, said Dr. Bhatia of Therapeutics Dermatology in San Diego.

“Let’s not forget we’re treating something that could cause skin cancer if left alone,” he added.

AKs are “no longer a Medicare disease,” he said, explaining that AKs are increasingly common in 30- and 40-year-old patients, and the focus of their care should be on outcomes, not reactions.

“The reactions, more often than not, are anticipated,” Dr. Bhatia said.

Patients should be counseled in advance about possible side effects from AK treatments, as well as about anticipated responses, and they should be advised about how to modify symptoms, he said.

“More importantly, we want to give them something that’s going to keep them adherent to the program … we tell them ‘these are things that are going to happen. Be prepared. If you have a problem, you can call the office,’ ” he said.

A patient who doesn’t know what to expect will run to a primary care doctor and post negative reviews on every rating site out there, he cautioned, but that can be prevented by counseling in advance and by choosing the correct therapy with a duration that is a good fit for the patient. He noted that clinicians who suspect a patient won’t be compliant should choose a 2-day treatment, and if they think the patient can handle it – choose a 90-day treatment.

There are numerous treatment choices that will have some benefit for the right patient, Dr. Bhatia added.

When it comes to managing an aggressive treatment response, consider the mechanism of the response. Antibiotics can be used to reduce inflammation without changing the immune process, while steroids can undo the immune response that some therapies are trying to recruit.

“We can emphasize keeping the lesion calmed down while reducing symptoms that are going to be dose limiting,” he said.

Dr. Bhatia advised prescribing medications to be filled only on Monday-Thursday to avoid substitutions being given on Friday-Sunday when “we can’t defend them.” He recommends that patients start treatment on Sunday, so any reactions occur mid-week and can be addressed by the office.

To further reduce the chance of reactions, be sure to avoid office procedures in the 4-7 days before or after AK treatment. Also, when starting any AK drugs, advise the patient to use as many adjunctive therapies as possible, including topical anesthetics, moisturizers, sunblock – “anything to reduce the potential for going overboard,” he said.

Dr Bhatia has been a consultant, researcher, and/or speaker for companies including Allergan, Aqua Pharmaceuticals, Bayer Healthcare Pharmaceuticals, DUSA Pharmaceuticals, Exeltis, Ferndale Pharma, Galderma Laboratories, Genentech, LEO Pharmaceuticals, Nerium Novartis, Promius Pharma, Sandoz, Novartis, and Valeant.

MIAMI BEACH – Worry less about reactions, and more about counseling patients on what to expect following actinic keratosis treatments, according to Dr. Neal Bhatia.

“I just want to take everyone’s finger off the panic button when it comes to managing reactions of actinic keratoses,” he said at the South Beach Symposium.

© Dr-Strangelove / ThinkStockPhotos.com

It’s easy to get hung up on side effects and redness, as well as other issues related to treatment, said Dr. Bhatia of Therapeutics Dermatology in San Diego.

“Let’s not forget we’re treating something that could cause skin cancer if left alone,” he added.

AKs are “no longer a Medicare disease,” he said, explaining that AKs are increasingly common in 30- and 40-year-old patients, and the focus of their care should be on outcomes, not reactions.

“The reactions, more often than not, are anticipated,” Dr. Bhatia said.

Patients should be counseled in advance about possible side effects from AK treatments, as well as about anticipated responses, and they should be advised about how to modify symptoms, he said.

“More importantly, we want to give them something that’s going to keep them adherent to the program … we tell them ‘these are things that are going to happen. Be prepared. If you have a problem, you can call the office,’ ” he said.

A patient who doesn’t know what to expect will run to a primary care doctor and post negative reviews on every rating site out there, he cautioned, but that can be prevented by counseling in advance and by choosing the correct therapy with a duration that is a good fit for the patient. He noted that clinicians who suspect a patient won’t be compliant should choose a 2-day treatment, and if they think the patient can handle it – choose a 90-day treatment.

There are numerous treatment choices that will have some benefit for the right patient, Dr. Bhatia added.

When it comes to managing an aggressive treatment response, consider the mechanism of the response. Antibiotics can be used to reduce inflammation without changing the immune process, while steroids can undo the immune response that some therapies are trying to recruit.

“We can emphasize keeping the lesion calmed down while reducing symptoms that are going to be dose limiting,” he said.

Dr. Bhatia advised prescribing medications to be filled only on Monday-Thursday to avoid substitutions being given on Friday-Sunday when “we can’t defend them.” He recommends that patients start treatment on Sunday, so any reactions occur mid-week and can be addressed by the office.

To further reduce the chance of reactions, be sure to avoid office procedures in the 4-7 days before or after AK treatment. Also, when starting any AK drugs, advise the patient to use as many adjunctive therapies as possible, including topical anesthetics, moisturizers, sunblock – “anything to reduce the potential for going overboard,” he said.

Dr Bhatia has been a consultant, researcher, and/or speaker for companies including Allergan, Aqua Pharmaceuticals, Bayer Healthcare Pharmaceuticals, DUSA Pharmaceuticals, Exeltis, Ferndale Pharma, Galderma Laboratories, Genentech, LEO Pharmaceuticals, Nerium Novartis, Promius Pharma, Sandoz, Novartis, and Valeant.

SAN DIEGO – Maternal glycemia was associated with anthropometric measures of obesity in offspring during childhood, but not with childhood body mass index, fasting glucose, or insulin resistance in a secondary analysis of a long-term follow-up study of women with mild gestational diabetes mellitus.

Baseline maternal body mass index (BMI), maternal weight gain, and Hispanic ethnicity, however, were consistently related to childhood BMI (P < .01) in the study of 236 children born to women who had untreated mild gestational diabetes mellitus (GDM) and 480 children whose mothers had a normal oral glucose tolerance test during pregnancy.

Courtesy Ohio State University

The findings underscore the importance of reducing obesity prior to pregnancy, and suggest that obesity reduction efforts should be emphasized in clinical practice, Dr. Mark B. Landon said at the annual Pregnancy Meeting sponsored by the Society for Maternal-Fetal Medicine.

“The obesity epidemic certainly has not spared the pediatric population,” said Dr. Landon, chair of obstetrics and gynecology at the Ohio State University in Columbus.

And a serious concern is that overweight and obesity are associated with a downstream risk of both metabolic and cardiovascular abnormalities into adulthood, he added.

Hispanic ethnicity and maternal BMI were also associated with childhood homeostatic model assessment-insulin resistance (HOMA-IR), and Hispanic ethnicity was associated with fasting glucose, Dr. Landon reported on behalf of the National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network.

There was a significant correlation between fasting, 1-hour, 2-hour, and 3-hour maternal glucose and subscapular/triceps skin fold ratio (Spearman correlation coefficients, 0.10, 0.08, 0.11, and 0.12, respectively). Similar correlations were seen between maternal glucose and HOMA-IR, and maternal glucose and sum of skin folds.

Fasting maternal glucose and fasting child glucose were also significantly correlated (Spearman correlation coefficients, 0.09).

On multivariable regression analysis – after controlling for maternal and neonatal factors – the only significant correlations between maternal glycemia and childhood outcomes were for 1-hour, 2-hour, and 3-hour maternal glucose measures, sum of skin folds, and subscapular/triceps skin fold ratio, he said.

Study subjects were the offspring of women who underwent a 3-hour oral glucose tolerance test between 27 and 31 weeks’ gestation, and childhood outcomes were assessed between the ages of 5 and 10 years.

Prior to the widespread recognition of the concept of fetal programming over 3 decades ago, Dr. Norbert Freinkel proposed that mild forms of diabetes, such as GDM, might exaggerate the normal dependency of the fetus on maternal fuels and that the concept of teratogenesis should be expanded to include alterations which could have long-range effects on behavioral, anthropometric, and metabolic functions, Dr. Landon said.

Multiple subsequent studies have demonstrated a link between in utero exposure to maternal hyperglycemia and the development of obesity in childhood – findings that are independent of both birth weight and maternal obesity.

©moodboard/ thinkstockphotos.com

A 2013 study showed that GDM was associated with both overweight status in childhood and childhood obesity (Diabet. Med. 2013;30:1449-56). Also, the landmark Hyperglycemia and Adverse Pregnancy Outcomes study showed that with increasing maternal glucose levels lower than the threshold for GDM diagnosis, the frequency of large-for-gestational-age infants increased proportionately – and this risk also remained after adjustment for maternal BMI and other confounders (N. Engl. J. Med. 2008;358:1991-2002).

“We have similarly reported a monotonic relationship between maternal glucose levels and the frequency of large-for-gestational-age infants in a secondary analysis from the Mild GDM Network randomized controlled trial. Recognizing that maternal glycemia clearly contributes to fetal growth, we sought to determine in this analysis whether the degree of maternal glucose tolerance during pregnancy affects the risk of childhood obesity and metabolic dysfunction,” Dr. Landon said.

Although the findings do not address the potential long-term effects of more significant hyperglycemia during pregnancy, they do confirm that maternal obesity has a greater impact on childhood obesity risk than exposure to mild hyperglycemia during pregnancy, he said in an interview.

Dr. Landon reported having no financial disclosures.

SAN DIEGO – Maternal glycemia was associated with anthropometric measures of obesity in offspring during childhood, but not with childhood body mass index, fasting glucose, or insulin resistance in a secondary analysis of a long-term follow-up study of women with mild gestational diabetes mellitus.

Baseline maternal body mass index (BMI), maternal weight gain, and Hispanic ethnicity, however, were consistently related to childhood BMI (P < .01) in the study of 236 children born to women who had untreated mild gestational diabetes mellitus (GDM) and 480 children whose mothers had a normal oral glucose tolerance test during pregnancy.

Courtesy Ohio State University

The findings underscore the importance of reducing obesity prior to pregnancy, and suggest that obesity reduction efforts should be emphasized in clinical practice, Dr. Mark B. Landon said at the annual Pregnancy Meeting sponsored by the Society for Maternal-Fetal Medicine.

“The obesity epidemic certainly has not spared the pediatric population,” said Dr. Landon, chair of obstetrics and gynecology at the Ohio State University in Columbus.

And a serious concern is that overweight and obesity are associated with a downstream risk of both metabolic and cardiovascular abnormalities into adulthood, he added.

Hispanic ethnicity and maternal BMI were also associated with childhood homeostatic model assessment-insulin resistance (HOMA-IR), and Hispanic ethnicity was associated with fasting glucose, Dr. Landon reported on behalf of the National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network.

There was a significant correlation between fasting, 1-hour, 2-hour, and 3-hour maternal glucose and subscapular/triceps skin fold ratio (Spearman correlation coefficients, 0.10, 0.08, 0.11, and 0.12, respectively). Similar correlations were seen between maternal glucose and HOMA-IR, and maternal glucose and sum of skin folds.

Fasting maternal glucose and fasting child glucose were also significantly correlated (Spearman correlation coefficients, 0.09).

On multivariable regression analysis – after controlling for maternal and neonatal factors – the only significant correlations between maternal glycemia and childhood outcomes were for 1-hour, 2-hour, and 3-hour maternal glucose measures, sum of skin folds, and subscapular/triceps skin fold ratio, he said.

Study subjects were the offspring of women who underwent a 3-hour oral glucose tolerance test between 27 and 31 weeks’ gestation, and childhood outcomes were assessed between the ages of 5 and 10 years.

Prior to the widespread recognition of the concept of fetal programming over 3 decades ago, Dr. Norbert Freinkel proposed that mild forms of diabetes, such as GDM, might exaggerate the normal dependency of the fetus on maternal fuels and that the concept of teratogenesis should be expanded to include alterations which could have long-range effects on behavioral, anthropometric, and metabolic functions, Dr. Landon said.

Multiple subsequent studies have demonstrated a link between in utero exposure to maternal hyperglycemia and the development of obesity in childhood – findings that are independent of both birth weight and maternal obesity.

©moodboard/ thinkstockphotos.com

A 2013 study showed that GDM was associated with both overweight status in childhood and childhood obesity (Diabet. Med. 2013;30:1449-56). Also, the landmark Hyperglycemia and Adverse Pregnancy Outcomes study showed that with increasing maternal glucose levels lower than the threshold for GDM diagnosis, the frequency of large-for-gestational-age infants increased proportionately – and this risk also remained after adjustment for maternal BMI and other confounders (N. Engl. J. Med. 2008;358:1991-2002).

“We have similarly reported a monotonic relationship between maternal glucose levels and the frequency of large-for-gestational-age infants in a secondary analysis from the Mild GDM Network randomized controlled trial. Recognizing that maternal glycemia clearly contributes to fetal growth, we sought to determine in this analysis whether the degree of maternal glucose tolerance during pregnancy affects the risk of childhood obesity and metabolic dysfunction,” Dr. Landon said.

Although the findings do not address the potential long-term effects of more significant hyperglycemia during pregnancy, they do confirm that maternal obesity has a greater impact on childhood obesity risk than exposure to mild hyperglycemia during pregnancy, he said in an interview.

Dr. Landon reported having no financial disclosures.

SAN DIEGO – Maternal glycemia was associated with anthropometric measures of obesity in offspring during childhood, but not with childhood body mass index, fasting glucose, or insulin resistance in a secondary analysis of a long-term follow-up study of women with mild gestational diabetes mellitus.

Baseline maternal body mass index (BMI), maternal weight gain, and Hispanic ethnicity, however, were consistently related to childhood BMI (P < .01) in the study of 236 children born to women who had untreated mild gestational diabetes mellitus (GDM) and 480 children whose mothers had a normal oral glucose tolerance test during pregnancy.

Courtesy Ohio State University

The findings underscore the importance of reducing obesity prior to pregnancy, and suggest that obesity reduction efforts should be emphasized in clinical practice, Dr. Mark B. Landon said at the annual Pregnancy Meeting sponsored by the Society for Maternal-Fetal Medicine.

“The obesity epidemic certainly has not spared the pediatric population,” said Dr. Landon, chair of obstetrics and gynecology at the Ohio State University in Columbus.

And a serious concern is that overweight and obesity are associated with a downstream risk of both metabolic and cardiovascular abnormalities into adulthood, he added.

Hispanic ethnicity and maternal BMI were also associated with childhood homeostatic model assessment-insulin resistance (HOMA-IR), and Hispanic ethnicity was associated with fasting glucose, Dr. Landon reported on behalf of the National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network.

There was a significant correlation between fasting, 1-hour, 2-hour, and 3-hour maternal glucose and subscapular/triceps skin fold ratio (Spearman correlation coefficients, 0.10, 0.08, 0.11, and 0.12, respectively). Similar correlations were seen between maternal glucose and HOMA-IR, and maternal glucose and sum of skin folds.

Fasting maternal glucose and fasting child glucose were also significantly correlated (Spearman correlation coefficients, 0.09).

On multivariable regression analysis – after controlling for maternal and neonatal factors – the only significant correlations between maternal glycemia and childhood outcomes were for 1-hour, 2-hour, and 3-hour maternal glucose measures, sum of skin folds, and subscapular/triceps skin fold ratio, he said.

Study subjects were the offspring of women who underwent a 3-hour oral glucose tolerance test between 27 and 31 weeks’ gestation, and childhood outcomes were assessed between the ages of 5 and 10 years.

Prior to the widespread recognition of the concept of fetal programming over 3 decades ago, Dr. Norbert Freinkel proposed that mild forms of diabetes, such as GDM, might exaggerate the normal dependency of the fetus on maternal fuels and that the concept of teratogenesis should be expanded to include alterations which could have long-range effects on behavioral, anthropometric, and metabolic functions, Dr. Landon said.

Multiple subsequent studies have demonstrated a link between in utero exposure to maternal hyperglycemia and the development of obesity in childhood – findings that are independent of both birth weight and maternal obesity.

©moodboard/ thinkstockphotos.com

A 2013 study showed that GDM was associated with both overweight status in childhood and childhood obesity (Diabet. Med. 2013;30:1449-56). Also, the landmark Hyperglycemia and Adverse Pregnancy Outcomes study showed that with increasing maternal glucose levels lower than the threshold for GDM diagnosis, the frequency of large-for-gestational-age infants increased proportionately – and this risk also remained after adjustment for maternal BMI and other confounders (N. Engl. J. Med. 2008;358:1991-2002).

“We have similarly reported a monotonic relationship between maternal glucose levels and the frequency of large-for-gestational-age infants in a secondary analysis from the Mild GDM Network randomized controlled trial. Recognizing that maternal glycemia clearly contributes to fetal growth, we sought to determine in this analysis whether the degree of maternal glucose tolerance during pregnancy affects the risk of childhood obesity and metabolic dysfunction,” Dr. Landon said.

Although the findings do not address the potential long-term effects of more significant hyperglycemia during pregnancy, they do confirm that maternal obesity has a greater impact on childhood obesity risk than exposure to mild hyperglycemia during pregnancy, he said in an interview.

Dr. Landon reported having no financial disclosures.

MIAMI BEACH – Acne flares on the chin can usually be managed in women with oral contraceptive therapy and spironolactone, according to Dr. Diane Berson.

These acne breakouts may be just a few pimples and are often related to the menstrual cycle, Dr. Berson of Cornell University and New York Presbyterian Hospital, both in New York, said at the South Beach Symposium.

“We know that women do develop premenstrual acne,” she said, citing a 2014 survey in which 65% of 105 respondents reported worsening of acne with their menstrual cycles, and 56% of those women reported acne in the week preceding menses (J. Clin. Aesthet. Dermatol. 2014;7:30-4).

Stress also seems to play a role, with another recent study showing that various stress factors including noise, socioeconomic pressures, light stimuli, and sleep deprivation also contribute to acne breakouts – again, often on the chin, she noted.

Oral contraceptives decrease testosterone, thereby reducing sebum production and, hopefully, acne breakouts, she said. With the traditional 21-day active/7-day inactive oral contraceptives, women tend to have acne flares during the 7-day inactive part of the treatment cycle, so increasing the active treatment cycle to 24 days of active therapy and 4 days of “blanks” can limit premenstrual syndrome and acne breakouts.

Contraceptive patches and rings provide a more continuous release of estrogen, so these products may also be helpful for women with hormonally induced acne, she added.

“Spironolactone is a great adjunct,” she said, noting that “it is inexpensive, really has minimal side effects, and women notice they get fewer hormonal breakouts when they are on it.”

A dose of 25-50 mg of spironolactone is usually sufficient, she said. “I have gone up to 100 mg, but my average patient is on 50 mg.” Patients also taking a drospirenone-containing oral contraceptive such as Yaz or Yasmin, get 25 mg of spironolactone, because they are already getting the equivalent of 25 mg in the oral contraceptive.

In another study, adding spironolactone to topical retinoid treatment led to a superior response to retinoids alone in the treatment of female adult cyclical acne (J. Drugs Dermatol. 2014;13:126-9), she noted.

“For our women patients with acne, a big part of our management is maintenance therapy,” she concluded. With hormonal flares, “I find that the best maintenance is a topical retinoid paired with either an oral contraceptive pill or spironolactone. That way you are giving them a topical comedolytic to decrease their clogging, and the hormonal treatment to decrease their hormonally induced flares.”

Dr. Berson is a consultant for Allergan, Galderma, Kythera Biopharmaceuticals, La Roche-Posay, Procter & Gamble, and Valeant Pharmaceuticals International.

MIAMI BEACH – Acne flares on the chin can usually be managed in women with oral contraceptive therapy and spironolactone, according to Dr. Diane Berson.

These acne breakouts may be just a few pimples and are often related to the menstrual cycle, Dr. Berson of Cornell University and New York Presbyterian Hospital, both in New York, said at the South Beach Symposium.

“We know that women do develop premenstrual acne,” she said, citing a 2014 survey in which 65% of 105 respondents reported worsening of acne with their menstrual cycles, and 56% of those women reported acne in the week preceding menses (J. Clin. Aesthet. Dermatol. 2014;7:30-4).

Stress also seems to play a role, with another recent study showing that various stress factors including noise, socioeconomic pressures, light stimuli, and sleep deprivation also contribute to acne breakouts – again, often on the chin, she noted.

Oral contraceptives decrease testosterone, thereby reducing sebum production and, hopefully, acne breakouts, she said. With the traditional 21-day active/7-day inactive oral contraceptives, women tend to have acne flares during the 7-day inactive part of the treatment cycle, so increasing the active treatment cycle to 24 days of active therapy and 4 days of “blanks” can limit premenstrual syndrome and acne breakouts.

Contraceptive patches and rings provide a more continuous release of estrogen, so these products may also be helpful for women with hormonally induced acne, she added.

“Spironolactone is a great adjunct,” she said, noting that “it is inexpensive, really has minimal side effects, and women notice they get fewer hormonal breakouts when they are on it.”

A dose of 25-50 mg of spironolactone is usually sufficient, she said. “I have gone up to 100 mg, but my average patient is on 50 mg.” Patients also taking a drospirenone-containing oral contraceptive such as Yaz or Yasmin, get 25 mg of spironolactone, because they are already getting the equivalent of 25 mg in the oral contraceptive.

In another study, adding spironolactone to topical retinoid treatment led to a superior response to retinoids alone in the treatment of female adult cyclical acne (J. Drugs Dermatol. 2014;13:126-9), she noted.

“For our women patients with acne, a big part of our management is maintenance therapy,” she concluded. With hormonal flares, “I find that the best maintenance is a topical retinoid paired with either an oral contraceptive pill or spironolactone. That way you are giving them a topical comedolytic to decrease their clogging, and the hormonal treatment to decrease their hormonally induced flares.”

Dr. Berson is a consultant for Allergan, Galderma, Kythera Biopharmaceuticals, La Roche-Posay, Procter & Gamble, and Valeant Pharmaceuticals International.

MIAMI BEACH – Acne flares on the chin can usually be managed in women with oral contraceptive therapy and spironolactone, according to Dr. Diane Berson.

These acne breakouts may be just a few pimples and are often related to the menstrual cycle, Dr. Berson of Cornell University and New York Presbyterian Hospital, both in New York, said at the South Beach Symposium.

“We know that women do develop premenstrual acne,” she said, citing a 2014 survey in which 65% of 105 respondents reported worsening of acne with their menstrual cycles, and 56% of those women reported acne in the week preceding menses (J. Clin. Aesthet. Dermatol. 2014;7:30-4).

Stress also seems to play a role, with another recent study showing that various stress factors including noise, socioeconomic pressures, light stimuli, and sleep deprivation also contribute to acne breakouts – again, often on the chin, she noted.

Oral contraceptives decrease testosterone, thereby reducing sebum production and, hopefully, acne breakouts, she said. With the traditional 21-day active/7-day inactive oral contraceptives, women tend to have acne flares during the 7-day inactive part of the treatment cycle, so increasing the active treatment cycle to 24 days of active therapy and 4 days of “blanks” can limit premenstrual syndrome and acne breakouts.

Contraceptive patches and rings provide a more continuous release of estrogen, so these products may also be helpful for women with hormonally induced acne, she added.

“Spironolactone is a great adjunct,” she said, noting that “it is inexpensive, really has minimal side effects, and women notice they get fewer hormonal breakouts when they are on it.”

A dose of 25-50 mg of spironolactone is usually sufficient, she said. “I have gone up to 100 mg, but my average patient is on 50 mg.” Patients also taking a drospirenone-containing oral contraceptive such as Yaz or Yasmin, get 25 mg of spironolactone, because they are already getting the equivalent of 25 mg in the oral contraceptive.

In another study, adding spironolactone to topical retinoid treatment led to a superior response to retinoids alone in the treatment of female adult cyclical acne (J. Drugs Dermatol. 2014;13:126-9), she noted.

“For our women patients with acne, a big part of our management is maintenance therapy,” she concluded. With hormonal flares, “I find that the best maintenance is a topical retinoid paired with either an oral contraceptive pill or spironolactone. That way you are giving them a topical comedolytic to decrease their clogging, and the hormonal treatment to decrease their hormonally induced flares.”

Dr. Berson is a consultant for Allergan, Galderma, Kythera Biopharmaceuticals, La Roche-Posay, Procter & Gamble, and Valeant Pharmaceuticals International.

SAN DIEGO – A shift from a conventional private practice model to a 24-hour obstetrician and midwifery model was associated with a dramatic decrease in the nulliparous term single vertex cesarean delivery rate, and an increase in the vaginal birth after cesarean delivery rate among privately insured women who were delivered at a community hospital in California.

But in a larger cross-sectional population-based study involving multiple community hospitals, no difference was seen in the primary cesarean rate, the successful vaginal birth after cesarean (VBAC) rate, or maternal morbidity for laboring women who gave birth in hospitals with an obstetrician available around the clock versus hospitals not using a laborist model.

Researchers who worked on the two studies said the differences might be explained by multiple factors, including the midwifery component in the single-center study, and a lack of information about exactly how laborists functioned at the various centers included in the larger, multicenter study.

In the single-center prospective cohort study, conducted at Marin General Hospital in Greenbrae, Calif., the nulliparous term single vertex cesarean delivery (NTSV CD) rate among privately insured women fell from 32.2% prior to the model change, to 25% after the switch. There was an immediate 5% decrease, followed by a nearly 2% decrease each year thereafter.

Prior to the switch to a laborist model, the NTSV CD rate had been increasing by 0.6% annually, similar to national trends, Dr. Melissa Rosenstein of the University of California, San Francisco, reported at the annual Pregnancy Meeting sponsored by the Society for Maternal-Fetal Medicine.

Further, the VBAC rate, which had been decreasing slightly each year before the change, increased from 13% to 22% after the change, and increased by about 8% per year thereafter, she said.

Previously, privately insured women were managed by their individual obstetricians; only publicly insured women utilized the laborist model at the hospital.

The rates of NTSV CD and VBAC among publicly insured women did not change significantly during the study period – the NTSV CD rates were 15.7% and 15.8% before and after the change, and VBAC rates were 33.9% and 27.9% before and after the change, she said.

The study included all singleton term deliveries at the community hospital between January 2005 and April 2014. The model shift occurred in April 2011. Overall, 3,684 NTSV deliveries and 1,375 deliveries in women with a prior cesarean delivery were included in the analysis.

“The changes were seen to a statistically significant degree only in the group of women exposed to the practice change, suggesting causation rather than secular trends for other hospitalwide interventions,” Dr. Rosenstein said.

But a larger, multicenter study found no difference between 43 hospitals with laborists and 139 without laborists on a range of outcomes, including the primary cesarean delivery rate (13.9% vs. 14.1%), the rate of maternal composite morbidity (10.3% vs. 10.8%), the rate of severe maternal complications (1.25% vs. 1.07%), and the successful VBAC rate (55.8% vs. 59.8%).

The researchers relied on structured 1-hour interviews conducted with labor and delivery nurse managers from 182 community hospitals with 221,247 deliveries in California between November 2012 and January 2014. They also considered discharge data and information regarding hospital policies and practices.

So why were the findings so different? Dr. Rosenstein, who worked on the single-center study, stressed the importance of the midwives in the laborist model used at Marin General Hospital.

“The other study didn’t include the midwifery component, which I think is a very important part of the Marin General Hospital experience,” Dr. Rosenstein said. “Not only does our hospital have midwives, but they work closely and collaboratively with physicians and participate in twice-daily rounds to discuss patient management.”

The principal investigator in the multicenter study, Dr. Kimberly Gregory, director of the division of maternal-fetal medicine at Cedars-Sinai Medical Center in Los Angeles, agreed, noting that midwifery is already known to make a difference.

“What we don’t know is what model of laborists, if any, makes a difference,” she said.

Other models that employ both midwives and dedicated obstetricians in labor and delivery, while having separate physicians for gynecologic and emergency care, are showing promise, Dr. Gregory said.

Another major difference between the two studies was the lack of categorization of hospitals by “how laborists actually functioned on the unit” in her study, Dr. Gregory said.

Since the multicenter study didn’t look at the specific roles of laborists on the hospital unit, it’s unclear whether they took care of just a few patients, or whether they managed all of the obstetrics patients, Dr. Rosenstein said.

Additionally, the multicenter study defined a laborist hospital as one where there was an obstetrician present 24/7. By that definition, the Marin General Hospital, where the single-center study was conducted, would have been considered a laborist hospital both before and after the intervention, she said.

Dr. Gregory also pointed out that all of the patients in the single-hospital study were exposed to the same “culture,” whereas patients in the multicenter study were subject to varying approaches and cultures.

The findings of both studies are of value for identifying the best approach to improving outcomes, Dr. Rosenstein said.

“Studies at the hospital level and at the population level are both important to determine the most optimal labor and delivery staffing pattern,” she said.

The single-center study was funded by the National Institutes of Health and the Prima Medical Foundation. The multicenter study was funded by the Agency for Healthcare Research and Quality, the American College of Obstetricians and Gynecologists, and the March of Dimes. The researchers reported having no relevant financial disclosures.

SAN DIEGO – A shift from a conventional private practice model to a 24-hour obstetrician and midwifery model was associated with a dramatic decrease in the nulliparous term single vertex cesarean delivery rate, and an increase in the vaginal birth after cesarean delivery rate among privately insured women who were delivered at a community hospital in California.

But in a larger cross-sectional population-based study involving multiple community hospitals, no difference was seen in the primary cesarean rate, the successful vaginal birth after cesarean (VBAC) rate, or maternal morbidity for laboring women who gave birth in hospitals with an obstetrician available around the clock versus hospitals not using a laborist model.

Researchers who worked on the two studies said the differences might be explained by multiple factors, including the midwifery component in the single-center study, and a lack of information about exactly how laborists functioned at the various centers included in the larger, multicenter study.

In the single-center prospective cohort study, conducted at Marin General Hospital in Greenbrae, Calif., the nulliparous term single vertex cesarean delivery (NTSV CD) rate among privately insured women fell from 32.2% prior to the model change, to 25% after the switch. There was an immediate 5% decrease, followed by a nearly 2% decrease each year thereafter.

Prior to the switch to a laborist model, the NTSV CD rate had been increasing by 0.6% annually, similar to national trends, Dr. Melissa Rosenstein of the University of California, San Francisco, reported at the annual Pregnancy Meeting sponsored by the Society for Maternal-Fetal Medicine.

Further, the VBAC rate, which had been decreasing slightly each year before the change, increased from 13% to 22% after the change, and increased by about 8% per year thereafter, she said.

Previously, privately insured women were managed by their individual obstetricians; only publicly insured women utilized the laborist model at the hospital.

The rates of NTSV CD and VBAC among publicly insured women did not change significantly during the study period – the NTSV CD rates were 15.7% and 15.8% before and after the change, and VBAC rates were 33.9% and 27.9% before and after the change, she said.

The study included all singleton term deliveries at the community hospital between January 2005 and April 2014. The model shift occurred in April 2011. Overall, 3,684 NTSV deliveries and 1,375 deliveries in women with a prior cesarean delivery were included in the analysis.

“The changes were seen to a statistically significant degree only in the group of women exposed to the practice change, suggesting causation rather than secular trends for other hospitalwide interventions,” Dr. Rosenstein said.

But a larger, multicenter study found no difference between 43 hospitals with laborists and 139 without laborists on a range of outcomes, including the primary cesarean delivery rate (13.9% vs. 14.1%), the rate of maternal composite morbidity (10.3% vs. 10.8%), the rate of severe maternal complications (1.25% vs. 1.07%), and the successful VBAC rate (55.8% vs. 59.8%).

The researchers relied on structured 1-hour interviews conducted with labor and delivery nurse managers from 182 community hospitals with 221,247 deliveries in California between November 2012 and January 2014. They also considered discharge data and information regarding hospital policies and practices.

So why were the findings so different? Dr. Rosenstein, who worked on the single-center study, stressed the importance of the midwives in the laborist model used at Marin General Hospital.

“The other study didn’t include the midwifery component, which I think is a very important part of the Marin General Hospital experience,” Dr. Rosenstein said. “Not only does our hospital have midwives, but they work closely and collaboratively with physicians and participate in twice-daily rounds to discuss patient management.”

The principal investigator in the multicenter study, Dr. Kimberly Gregory, director of the division of maternal-fetal medicine at Cedars-Sinai Medical Center in Los Angeles, agreed, noting that midwifery is already known to make a difference.

“What we don’t know is what model of laborists, if any, makes a difference,” she said.

Other models that employ both midwives and dedicated obstetricians in labor and delivery, while having separate physicians for gynecologic and emergency care, are showing promise, Dr. Gregory said.

Another major difference between the two studies was the lack of categorization of hospitals by “how laborists actually functioned on the unit” in her study, Dr. Gregory said.

Since the multicenter study didn’t look at the specific roles of laborists on the hospital unit, it’s unclear whether they took care of just a few patients, or whether they managed all of the obstetrics patients, Dr. Rosenstein said.

Additionally, the multicenter study defined a laborist hospital as one where there was an obstetrician present 24/7. By that definition, the Marin General Hospital, where the single-center study was conducted, would have been considered a laborist hospital both before and after the intervention, she said.

Dr. Gregory also pointed out that all of the patients in the single-hospital study were exposed to the same “culture,” whereas patients in the multicenter study were subject to varying approaches and cultures.

The findings of both studies are of value for identifying the best approach to improving outcomes, Dr. Rosenstein said.

“Studies at the hospital level and at the population level are both important to determine the most optimal labor and delivery staffing pattern,” she said.

The single-center study was funded by the National Institutes of Health and the Prima Medical Foundation. The multicenter study was funded by the Agency for Healthcare Research and Quality, the American College of Obstetricians and Gynecologists, and the March of Dimes. The researchers reported having no relevant financial disclosures.

SAN DIEGO – A shift from a conventional private practice model to a 24-hour obstetrician and midwifery model was associated with a dramatic decrease in the nulliparous term single vertex cesarean delivery rate, and an increase in the vaginal birth after cesarean delivery rate among privately insured women who were delivered at a community hospital in California.

But in a larger cross-sectional population-based study involving multiple community hospitals, no difference was seen in the primary cesarean rate, the successful vaginal birth after cesarean (VBAC) rate, or maternal morbidity for laboring women who gave birth in hospitals with an obstetrician available around the clock versus hospitals not using a laborist model.

Researchers who worked on the two studies said the differences might be explained by multiple factors, including the midwifery component in the single-center study, and a lack of information about exactly how laborists functioned at the various centers included in the larger, multicenter study.

In the single-center prospective cohort study, conducted at Marin General Hospital in Greenbrae, Calif., the nulliparous term single vertex cesarean delivery (NTSV CD) rate among privately insured women fell from 32.2% prior to the model change, to 25% after the switch. There was an immediate 5% decrease, followed by a nearly 2% decrease each year thereafter.

Prior to the switch to a laborist model, the NTSV CD rate had been increasing by 0.6% annually, similar to national trends, Dr. Melissa Rosenstein of the University of California, San Francisco, reported at the annual Pregnancy Meeting sponsored by the Society for Maternal-Fetal Medicine.

Further, the VBAC rate, which had been decreasing slightly each year before the change, increased from 13% to 22% after the change, and increased by about 8% per year thereafter, she said.

Previously, privately insured women were managed by their individual obstetricians; only publicly insured women utilized the laborist model at the hospital.

The rates of NTSV CD and VBAC among publicly insured women did not change significantly during the study period – the NTSV CD rates were 15.7% and 15.8% before and after the change, and VBAC rates were 33.9% and 27.9% before and after the change, she said.

The study included all singleton term deliveries at the community hospital between January 2005 and April 2014. The model shift occurred in April 2011. Overall, 3,684 NTSV deliveries and 1,375 deliveries in women with a prior cesarean delivery were included in the analysis.

“The changes were seen to a statistically significant degree only in the group of women exposed to the practice change, suggesting causation rather than secular trends for other hospitalwide interventions,” Dr. Rosenstein said.

But a larger, multicenter study found no difference between 43 hospitals with laborists and 139 without laborists on a range of outcomes, including the primary cesarean delivery rate (13.9% vs. 14.1%), the rate of maternal composite morbidity (10.3% vs. 10.8%), the rate of severe maternal complications (1.25% vs. 1.07%), and the successful VBAC rate (55.8% vs. 59.8%).

The researchers relied on structured 1-hour interviews conducted with labor and delivery nurse managers from 182 community hospitals with 221,247 deliveries in California between November 2012 and January 2014. They also considered discharge data and information regarding hospital policies and practices.

So why were the findings so different? Dr. Rosenstein, who worked on the single-center study, stressed the importance of the midwives in the laborist model used at Marin General Hospital.

“The other study didn’t include the midwifery component, which I think is a very important part of the Marin General Hospital experience,” Dr. Rosenstein said. “Not only does our hospital have midwives, but they work closely and collaboratively with physicians and participate in twice-daily rounds to discuss patient management.”

The principal investigator in the multicenter study, Dr. Kimberly Gregory, director of the division of maternal-fetal medicine at Cedars-Sinai Medical Center in Los Angeles, agreed, noting that midwifery is already known to make a difference.

“What we don’t know is what model of laborists, if any, makes a difference,” she said.

Other models that employ both midwives and dedicated obstetricians in labor and delivery, while having separate physicians for gynecologic and emergency care, are showing promise, Dr. Gregory said.

Another major difference between the two studies was the lack of categorization of hospitals by “how laborists actually functioned on the unit” in her study, Dr. Gregory said.

Since the multicenter study didn’t look at the specific roles of laborists on the hospital unit, it’s unclear whether they took care of just a few patients, or whether they managed all of the obstetrics patients, Dr. Rosenstein said.

Additionally, the multicenter study defined a laborist hospital as one where there was an obstetrician present 24/7. By that definition, the Marin General Hospital, where the single-center study was conducted, would have been considered a laborist hospital both before and after the intervention, she said.

Dr. Gregory also pointed out that all of the patients in the single-hospital study were exposed to the same “culture,” whereas patients in the multicenter study were subject to varying approaches and cultures.

The findings of both studies are of value for identifying the best approach to improving outcomes, Dr. Rosenstein said.

“Studies at the hospital level and at the population level are both important to determine the most optimal labor and delivery staffing pattern,” she said.

The single-center study was funded by the National Institutes of Health and the Prima Medical Foundation. The multicenter study was funded by the Agency for Healthcare Research and Quality, the American College of Obstetricians and Gynecologists, and the March of Dimes. The researchers reported having no relevant financial disclosures.

SAN DIEGO – The use of electronic fetal monitoring is ubiquitous in the United States, but a case-control study shows that monitoring patterns do not differ between term infants with evidence of brain injury on magnetic resonance imaging and those without injury.

Of 220 apparently normal term infants who underwent MRI, 25 had injury identified by the MRI, including 23 with mild injury, 1 with moderate injury, and 1 with severe injury. None of several electronic fetal monitoring characteristics – including moderate, minimal, marked, or absent variability, or late, prolonged, or variable repetitive decelerations – predicted injury, Dr. Alison Cahill reported at the annual Pregnancy Meeting sponsored by the Society for Maternal-Fetal Medicine.

The researchers also did not find a significant association between the injuries and several clinical factors known to increase the odds of injury, such as cesarean delivery (odds ratio, 1.8), nulliparity (OR, 1.0), acidemia (OR, 2.8), and labor induction (OR, 0.7).

The study results are based on findings at both 30 and 60 minutes prior to delivery.

Although white race and a complete absence of moderate variability on EFM in the 1-2 hours prior to birth were more common in those with injury, the predictive value of these factors alone was poor, said Dr. Cahill of Washington University, St. Louis.

The patients included in this study were from a prospective cohort of 8,340 women with vertex anatomically normal singleton pregnancies, who were in labor after at least 37 weeks’ gestation.

Case infants had an arterial cord gas pH less than 7.10, and control infants were temporally-, age-, and sex-matched infants with a normal arterial cord gas pH of 7.20 or greater. All infants underwent nonsedated MRI between 24 and 72 hours after birth.

The MRI findings were independently interpreted by a pediatric neuroradiologist and intensivist, who were blinded to clinical data and patient outcomes, and EFM patterns were interpreted by obstetric research nurses who were blinded to clinical outcomes, Dr. Cahill said.

Cerebral MRI has become the clinical imaging modality of choice for preterm infants and those with hypoxic-ischemic encephalopathy (HIE), because MRI findings in these populations have been correlated with neonatal outcomes, and enable increased surveillance and early intervention, she said.

However, more than three-quarters of neurologic disability occurs among infants born after 36 weeks without HIE, she said.

The aim of the current study was to characterize neurologic injury in neonates and term infants without HIE, and to identify intrapartum EFM patterns and peripartum risk factors for injury. But no such risk factors emerged, she said.

Though limited by the inherent subjectivity in EFM and MRI interpretation, the study involves the largest cohort to date in which the ability of clinical and EFM characteristics to predict brain injury is examined, Dr. Cahill said.

“We believe it is important to acknowledge the limitations of our clinical ability to use EFM based on our current knowledge and the manner in which we use it at the bedside,” she said. “Clinicians cannot predict brain injury in apparently normal term infants with EFM patterns preceding birth.”

The study was supported by a grant from the National Institute of Child Health and Human Development. Dr. Cahill reported having no relevant financial disclosures.

SAN DIEGO – The use of electronic fetal monitoring is ubiquitous in the United States, but a case-control study shows that monitoring patterns do not differ between term infants with evidence of brain injury on magnetic resonance imaging and those without injury.

Of 220 apparently normal term infants who underwent MRI, 25 had injury identified by the MRI, including 23 with mild injury, 1 with moderate injury, and 1 with severe injury. None of several electronic fetal monitoring characteristics – including moderate, minimal, marked, or absent variability, or late, prolonged, or variable repetitive decelerations – predicted injury, Dr. Alison Cahill reported at the annual Pregnancy Meeting sponsored by the Society for Maternal-Fetal Medicine.

The researchers also did not find a significant association between the injuries and several clinical factors known to increase the odds of injury, such as cesarean delivery (odds ratio, 1.8), nulliparity (OR, 1.0), acidemia (OR, 2.8), and labor induction (OR, 0.7).

The study results are based on findings at both 30 and 60 minutes prior to delivery.

Although white race and a complete absence of moderate variability on EFM in the 1-2 hours prior to birth were more common in those with injury, the predictive value of these factors alone was poor, said Dr. Cahill of Washington University, St. Louis.

The patients included in this study were from a prospective cohort of 8,340 women with vertex anatomically normal singleton pregnancies, who were in labor after at least 37 weeks’ gestation.

Case infants had an arterial cord gas pH less than 7.10, and control infants were temporally-, age-, and sex-matched infants with a normal arterial cord gas pH of 7.20 or greater. All infants underwent nonsedated MRI between 24 and 72 hours after birth.

The MRI findings were independently interpreted by a pediatric neuroradiologist and intensivist, who were blinded to clinical data and patient outcomes, and EFM patterns were interpreted by obstetric research nurses who were blinded to clinical outcomes, Dr. Cahill said.

Cerebral MRI has become the clinical imaging modality of choice for preterm infants and those with hypoxic-ischemic encephalopathy (HIE), because MRI findings in these populations have been correlated with neonatal outcomes, and enable increased surveillance and early intervention, she said.

However, more than three-quarters of neurologic disability occurs among infants born after 36 weeks without HIE, she said.

The aim of the current study was to characterize neurologic injury in neonates and term infants without HIE, and to identify intrapartum EFM patterns and peripartum risk factors for injury. But no such risk factors emerged, she said.

Though limited by the inherent subjectivity in EFM and MRI interpretation, the study involves the largest cohort to date in which the ability of clinical and EFM characteristics to predict brain injury is examined, Dr. Cahill said.

“We believe it is important to acknowledge the limitations of our clinical ability to use EFM based on our current knowledge and the manner in which we use it at the bedside,” she said. “Clinicians cannot predict brain injury in apparently normal term infants with EFM patterns preceding birth.”

The study was supported by a grant from the National Institute of Child Health and Human Development. Dr. Cahill reported having no relevant financial disclosures.

SAN DIEGO – The use of electronic fetal monitoring is ubiquitous in the United States, but a case-control study shows that monitoring patterns do not differ between term infants with evidence of brain injury on magnetic resonance imaging and those without injury.

Of 220 apparently normal term infants who underwent MRI, 25 had injury identified by the MRI, including 23 with mild injury, 1 with moderate injury, and 1 with severe injury. None of several electronic fetal monitoring characteristics – including moderate, minimal, marked, or absent variability, or late, prolonged, or variable repetitive decelerations – predicted injury, Dr. Alison Cahill reported at the annual Pregnancy Meeting sponsored by the Society for Maternal-Fetal Medicine.

The researchers also did not find a significant association between the injuries and several clinical factors known to increase the odds of injury, such as cesarean delivery (odds ratio, 1.8), nulliparity (OR, 1.0), acidemia (OR, 2.8), and labor induction (OR, 0.7).

The study results are based on findings at both 30 and 60 minutes prior to delivery.

Although white race and a complete absence of moderate variability on EFM in the 1-2 hours prior to birth were more common in those with injury, the predictive value of these factors alone was poor, said Dr. Cahill of Washington University, St. Louis.

The patients included in this study were from a prospective cohort of 8,340 women with vertex anatomically normal singleton pregnancies, who were in labor after at least 37 weeks’ gestation.

Case infants had an arterial cord gas pH less than 7.10, and control infants were temporally-, age-, and sex-matched infants with a normal arterial cord gas pH of 7.20 or greater. All infants underwent nonsedated MRI between 24 and 72 hours after birth.

The MRI findings were independently interpreted by a pediatric neuroradiologist and intensivist, who were blinded to clinical data and patient outcomes, and EFM patterns were interpreted by obstetric research nurses who were blinded to clinical outcomes, Dr. Cahill said.

Cerebral MRI has become the clinical imaging modality of choice for preterm infants and those with hypoxic-ischemic encephalopathy (HIE), because MRI findings in these populations have been correlated with neonatal outcomes, and enable increased surveillance and early intervention, she said.

However, more than three-quarters of neurologic disability occurs among infants born after 36 weeks without HIE, she said.

The aim of the current study was to characterize neurologic injury in neonates and term infants without HIE, and to identify intrapartum EFM patterns and peripartum risk factors for injury. But no such risk factors emerged, she said.

Though limited by the inherent subjectivity in EFM and MRI interpretation, the study involves the largest cohort to date in which the ability of clinical and EFM characteristics to predict brain injury is examined, Dr. Cahill said.

“We believe it is important to acknowledge the limitations of our clinical ability to use EFM based on our current knowledge and the manner in which we use it at the bedside,” she said. “Clinicians cannot predict brain injury in apparently normal term infants with EFM patterns preceding birth.”

The study was supported by a grant from the National Institute of Child Health and Human Development. Dr. Cahill reported having no relevant financial disclosures.

SAN DIEGO – Labor induction and augmentation were not associated with an increased likelihood of autism spectrum disorder during childhood in a large cohort study.

While the findings conflict with those of a recently published, large epidemiologic study, they fit with the preponderance of evidence, which refutes an association between labor induction and/or augmentation and autism spectrum disorder (ASD), Dr. Erin Clark reported at the annual Pregnancy Meeting sponsored by the Society for Maternal-Fetal Medicine.

© MattZ90/Thinkstockphotos.com

Of the more than 166,000 children in the current cohort, 2,547 (or about 1 in 65) had a diagnosis of ASD. After adjusting for numerous potential confounders related to socioeconomic status, maternal health, pregnancy-related events and conditions, and birth cohort, there were no significant differences found between those with and without ASD with respect to exposure to labor induction and/or augmentation, said Dr. Clark of the University of Utah, Salt Lake City.

The odds ratios compared with no exposure to induction or augmentation were 0.897 for induction with augmentation, 0.959 for induction only, and 0.978 for augmentation only.

The findings were similar among boys and girls with ASD, although about 1 in 45 boys in the cohort and 1 in 130 girls had ASD, figures which are consistent with the known case prevalence for boys versus girls, she said.

“This work supports current recommendations from [the Society for Maternal-Fetal Medicine] and [the American College of Obstetricians and Gynecologists] that recommend against a change in current guidance regarding counseling and indications for, and methods of labor induction and augmentation,” she said.

Dr. Clark and her colleagues performed the epidemiologic analysis using data from the Utah Registry of Autism and Developmental Disabilities (URADD) for the 1998, 2000, 2002, 2004, and 2006 birth cohorts from a four-county surveillance area, and from the Utah Department of Health Vital Records and Statistics.

The registry data represent about 70% of the state’s population, and the vital records and statistics data include information about exposure to induction and/or augmentation and known ASD risk factors.

ASD increased in prevalence by 120% between 2002 and 2010, and the reasons for this are multifactorial. The increase is at least partially due to changes in case ascertainment, but the extent to which legitimate changes in case prevalence have contributed to the increase is unclear and concerning, Dr. Clark said.

“So the hunt for risk factors is on as we seek etiologic clues and possible prevention and treatment strategies,” she said.

When it comes to perinatal risk factors, the data have been conflicting, but because alterations in oxytocin and oxytocin signaling have been linked to autism, labor induction and augmentation are potential risk factors “of great interest and controversy,” Dr. Clark said.

Of nine studies published before 2012 that evaluated the association between induction/augmentation and ASD, one found an association that persisted after controlling for confounders, but a subsequent meta-analysis was negative (Br. J. Psychiatry 2009;195:7-14).

In 2013, a large epidemiologic study showed an association, particularly in boys (JAMA Pediatr. 2013;167:959-66).

The current study was undertaken with these previous studies in mind, Dr. Clark said, noting that the differences in outcomes might be due to differences in population characteristics or methodologic approach, including management of confounding variables.

In response to an audience member who asked if the researchers had controlled for vaccination status, Dr. Clark said vaccination information was not available, but that it likely would not have been included in the analysis regardless as “that association has been completely debunked.”

Dr. Clark reported having no financial disclosures.

SAN DIEGO – Labor induction and augmentation were not associated with an increased likelihood of autism spectrum disorder during childhood in a large cohort study.

While the findings conflict with those of a recently published, large epidemiologic study, they fit with the preponderance of evidence, which refutes an association between labor induction and/or augmentation and autism spectrum disorder (ASD), Dr. Erin Clark reported at the annual Pregnancy Meeting sponsored by the Society for Maternal-Fetal Medicine.

© MattZ90/Thinkstockphotos.com

Of the more than 166,000 children in the current cohort, 2,547 (or about 1 in 65) had a diagnosis of ASD. After adjusting for numerous potential confounders related to socioeconomic status, maternal health, pregnancy-related events and conditions, and birth cohort, there were no significant differences found between those with and without ASD with respect to exposure to labor induction and/or augmentation, said Dr. Clark of the University of Utah, Salt Lake City.

The odds ratios compared with no exposure to induction or augmentation were 0.897 for induction with augmentation, 0.959 for induction only, and 0.978 for augmentation only.

The findings were similar among boys and girls with ASD, although about 1 in 45 boys in the cohort and 1 in 130 girls had ASD, figures which are consistent with the known case prevalence for boys versus girls, she said.

“This work supports current recommendations from [the Society for Maternal-Fetal Medicine] and [the American College of Obstetricians and Gynecologists] that recommend against a change in current guidance regarding counseling and indications for, and methods of labor induction and augmentation,” she said.

Dr. Clark and her colleagues performed the epidemiologic analysis using data from the Utah Registry of Autism and Developmental Disabilities (URADD) for the 1998, 2000, 2002, 2004, and 2006 birth cohorts from a four-county surveillance area, and from the Utah Department of Health Vital Records and Statistics.

The registry data represent about 70% of the state’s population, and the vital records and statistics data include information about exposure to induction and/or augmentation and known ASD risk factors.

ASD increased in prevalence by 120% between 2002 and 2010, and the reasons for this are multifactorial. The increase is at least partially due to changes in case ascertainment, but the extent to which legitimate changes in case prevalence have contributed to the increase is unclear and concerning, Dr. Clark said.

“So the hunt for risk factors is on as we seek etiologic clues and possible prevention and treatment strategies,” she said.

When it comes to perinatal risk factors, the data have been conflicting, but because alterations in oxytocin and oxytocin signaling have been linked to autism, labor induction and augmentation are potential risk factors “of great interest and controversy,” Dr. Clark said.

Of nine studies published before 2012 that evaluated the association between induction/augmentation and ASD, one found an association that persisted after controlling for confounders, but a subsequent meta-analysis was negative (Br. J. Psychiatry 2009;195:7-14).

In 2013, a large epidemiologic study showed an association, particularly in boys (JAMA Pediatr. 2013;167:959-66).

The current study was undertaken with these previous studies in mind, Dr. Clark said, noting that the differences in outcomes might be due to differences in population characteristics or methodologic approach, including management of confounding variables.

In response to an audience member who asked if the researchers had controlled for vaccination status, Dr. Clark said vaccination information was not available, but that it likely would not have been included in the analysis regardless as “that association has been completely debunked.”

Dr. Clark reported having no financial disclosures.

SAN DIEGO – Labor induction and augmentation were not associated with an increased likelihood of autism spectrum disorder during childhood in a large cohort study.

While the findings conflict with those of a recently published, large epidemiologic study, they fit with the preponderance of evidence, which refutes an association between labor induction and/or augmentation and autism spectrum disorder (ASD), Dr. Erin Clark reported at the annual Pregnancy Meeting sponsored by the Society for Maternal-Fetal Medicine.

© MattZ90/Thinkstockphotos.com

Of the more than 166,000 children in the current cohort, 2,547 (or about 1 in 65) had a diagnosis of ASD. After adjusting for numerous potential confounders related to socioeconomic status, maternal health, pregnancy-related events and conditions, and birth cohort, there were no significant differences found between those with and without ASD with respect to exposure to labor induction and/or augmentation, said Dr. Clark of the University of Utah, Salt Lake City.

The odds ratios compared with no exposure to induction or augmentation were 0.897 for induction with augmentation, 0.959 for induction only, and 0.978 for augmentation only.

The findings were similar among boys and girls with ASD, although about 1 in 45 boys in the cohort and 1 in 130 girls had ASD, figures which are consistent with the known case prevalence for boys versus girls, she said.

“This work supports current recommendations from [the Society for Maternal-Fetal Medicine] and [the American College of Obstetricians and Gynecologists] that recommend against a change in current guidance regarding counseling and indications for, and methods of labor induction and augmentation,” she said.

Dr. Clark and her colleagues performed the epidemiologic analysis using data from the Utah Registry of Autism and Developmental Disabilities (URADD) for the 1998, 2000, 2002, 2004, and 2006 birth cohorts from a four-county surveillance area, and from the Utah Department of Health Vital Records and Statistics.

The registry data represent about 70% of the state’s population, and the vital records and statistics data include information about exposure to induction and/or augmentation and known ASD risk factors.

ASD increased in prevalence by 120% between 2002 and 2010, and the reasons for this are multifactorial. The increase is at least partially due to changes in case ascertainment, but the extent to which legitimate changes in case prevalence have contributed to the increase is unclear and concerning, Dr. Clark said.

“So the hunt for risk factors is on as we seek etiologic clues and possible prevention and treatment strategies,” she said.

When it comes to perinatal risk factors, the data have been conflicting, but because alterations in oxytocin and oxytocin signaling have been linked to autism, labor induction and augmentation are potential risk factors “of great interest and controversy,” Dr. Clark said.

Of nine studies published before 2012 that evaluated the association between induction/augmentation and ASD, one found an association that persisted after controlling for confounders, but a subsequent meta-analysis was negative (Br. J. Psychiatry 2009;195:7-14).

In 2013, a large epidemiologic study showed an association, particularly in boys (JAMA Pediatr. 2013;167:959-66).

The current study was undertaken with these previous studies in mind, Dr. Clark said, noting that the differences in outcomes might be due to differences in population characteristics or methodologic approach, including management of confounding variables.

In response to an audience member who asked if the researchers had controlled for vaccination status, Dr. Clark said vaccination information was not available, but that it likely would not have been included in the analysis regardless as “that association has been completely debunked.”

Dr. Clark reported having no financial disclosures.

SAN DIEGO – Nifedipine and atosiban for tocolysis in women with threatened preterm delivery had similar rates of adverse perinatal outcomes in a randomized clinical trial, but an increase in perinatal mortality in those treated with nifedipine is raising concerns about its safety.

The rate of the composite primary outcome of perinatal death, bronchopulmonary dysplasia, culture-proven sepsis, intraventricular hemorrhage worse than stage II, periventricular leukomalacia worse than stage I, and necrotizing enterocolitis worse than stage I was 14.2% among the 248 women randomized to receive nifedipine. Similarly, it was 15.1% in the 254 women randomized to receive atosiban in the multicenter Assessment of Perinatal Outcome After Specific Tocolysis in Early Labor (APOSTEL III trial), Dr. Elvira Vliet reported at the annual Pregnancy Meeting sponsored by the Society for Maternal-Fetal Medicine.

There also was no difference between the nifedipine and atosiban groups on a number of secondary outcomes, including prolongation of pregnancy (6 days and 4 days, respectively) and the percentage of patients undelivered at 48 hours after randomization (66% and 69%, respectively). No cases of maternal mortality occurred.

But the rate of perinatal mortality was 5.4% in the nifedipine group vs. 2.1% in the atosiban group for a relative risk of 2.567, said Dr. Vliet of University Medical Center Utrecht, the Netherlands. Two of the perinatal deaths in the nifedipine group and one in the atosiban group were associated with congenital abnormalities, she noted.

Study participants were women with either a singleton or twin pregnancy between the 25th and 34th week of gestation who presented to one of 19 perinatal or large teaching hospitals with symptoms of threatened preterm delivery. Treatment with nifedipine or atosiban was given for 48 hours.

The groups did not differ with respect to baseline characteristics such as maternal age, body mass index, previous preterm birth, and gestational age.

The current findings suggest that most perinatal outcomes are similar in patients treated with either nifedipine or atosiban, but the higher perinatal death rate in the nifedipine group requires further in-depth analysis, Dr. Vliet said.

Dr. Vliet reported having no financial disclosures.

SAN DIEGO – Nifedipine and atosiban for tocolysis in women with threatened preterm delivery had similar rates of adverse perinatal outcomes in a randomized clinical trial, but an increase in perinatal mortality in those treated with nifedipine is raising concerns about its safety.

The rate of the composite primary outcome of perinatal death, bronchopulmonary dysplasia, culture-proven sepsis, intraventricular hemorrhage worse than stage II, periventricular leukomalacia worse than stage I, and necrotizing enterocolitis worse than stage I was 14.2% among the 248 women randomized to receive nifedipine. Similarly, it was 15.1% in the 254 women randomized to receive atosiban in the multicenter Assessment of Perinatal Outcome After Specific Tocolysis in Early Labor (APOSTEL III trial), Dr. Elvira Vliet reported at the annual Pregnancy Meeting sponsored by the Society for Maternal-Fetal Medicine.

There also was no difference between the nifedipine and atosiban groups on a number of secondary outcomes, including prolongation of pregnancy (6 days and 4 days, respectively) and the percentage of patients undelivered at 48 hours after randomization (66% and 69%, respectively). No cases of maternal mortality occurred.

But the rate of perinatal mortality was 5.4% in the nifedipine group vs. 2.1% in the atosiban group for a relative risk of 2.567, said Dr. Vliet of University Medical Center Utrecht, the Netherlands. Two of the perinatal deaths in the nifedipine group and one in the atosiban group were associated with congenital abnormalities, she noted.

Study participants were women with either a singleton or twin pregnancy between the 25th and 34th week of gestation who presented to one of 19 perinatal or large teaching hospitals with symptoms of threatened preterm delivery. Treatment with nifedipine or atosiban was given for 48 hours.

The groups did not differ with respect to baseline characteristics such as maternal age, body mass index, previous preterm birth, and gestational age.

The current findings suggest that most perinatal outcomes are similar in patients treated with either nifedipine or atosiban, but the higher perinatal death rate in the nifedipine group requires further in-depth analysis, Dr. Vliet said.

Dr. Vliet reported having no financial disclosures.

SAN DIEGO – Nifedipine and atosiban for tocolysis in women with threatened preterm delivery had similar rates of adverse perinatal outcomes in a randomized clinical trial, but an increase in perinatal mortality in those treated with nifedipine is raising concerns about its safety.

The rate of the composite primary outcome of perinatal death, bronchopulmonary dysplasia, culture-proven sepsis, intraventricular hemorrhage worse than stage II, periventricular leukomalacia worse than stage I, and necrotizing enterocolitis worse than stage I was 14.2% among the 248 women randomized to receive nifedipine. Similarly, it was 15.1% in the 254 women randomized to receive atosiban in the multicenter Assessment of Perinatal Outcome After Specific Tocolysis in Early Labor (APOSTEL III trial), Dr. Elvira Vliet reported at the annual Pregnancy Meeting sponsored by the Society for Maternal-Fetal Medicine.

There also was no difference between the nifedipine and atosiban groups on a number of secondary outcomes, including prolongation of pregnancy (6 days and 4 days, respectively) and the percentage of patients undelivered at 48 hours after randomization (66% and 69%, respectively). No cases of maternal mortality occurred.

But the rate of perinatal mortality was 5.4% in the nifedipine group vs. 2.1% in the atosiban group for a relative risk of 2.567, said Dr. Vliet of University Medical Center Utrecht, the Netherlands. Two of the perinatal deaths in the nifedipine group and one in the atosiban group were associated with congenital abnormalities, she noted.

Study participants were women with either a singleton or twin pregnancy between the 25th and 34th week of gestation who presented to one of 19 perinatal or large teaching hospitals with symptoms of threatened preterm delivery. Treatment with nifedipine or atosiban was given for 48 hours.

The groups did not differ with respect to baseline characteristics such as maternal age, body mass index, previous preterm birth, and gestational age.

The current findings suggest that most perinatal outcomes are similar in patients treated with either nifedipine or atosiban, but the higher perinatal death rate in the nifedipine group requires further in-depth analysis, Dr. Vliet said.

Dr. Vliet reported having no financial disclosures.

Oseltamivir treatment in adults with influenza shortens the time to clinical symptom alleviation by about 1 day and substantially reduces the risk of lower respiratory tract complications and hospitalization, according to findings from a meta-analysis of nine randomized, controlled trials involving 4,328 adult patients.

The findings of the study, which is the first to use individual patient data to evaluate the neuraminidase inhibitor, should put to rest persistent doubts its efficacy and safety, according to Dr. Arnold S. Monto of the University of Michigan School of Public Health, Ann Arbor, who was lead investigator, and his colleagues.

The intention-to-treat population of 1,591 patients with confirmed influenza had a significant 21% shorter time to clinical symptom alleviation, compared with the intention-to-treat infected population of 1,302 patients who received placebo (97.5 hours vs. 122.7 hours, difference of 25.2 hours; time ratio, 0.79), the investigators reported online Jan. 30 in the Lancet.

The effects were somewhat attenuated in the 2,402 treated patients in the overall intention-to-treat population – with a 15% reduction in time to symptom alleviation – compared with the 1,926 placebo patients in that population. But the difference remained significant (median of 17.8 hours; time ratio, 0.85), the investigators said (Lancet 2015 Jan. 30 [doi:10.106/S0140-6736(14)62449-1]).

“In the intention-to-treat noninfected population, the estimated time ratio was close to unity (time ratio, 0.99), so only participants identified as influenza infected benefited from oseltamivir,” the study authors wrote. That suggests efficacy is “confined to the antiviral activity of the drug.”

In addition, treatment significantly reduced the risk of lower respiratory tract complications occurring more than 48 hours after randomization by 44% in the intention-to-treat infected population. Only 4.2% of oseltamivir-treated patients requiring such treatment, compared with 8.7% of those who received placebo (risk ratio, 0.56). The risk of hospitalization for any cause was significantly reduced by 63% (0.6% vs. 1.7% in the groups, respectively; RR, 0.37).

The risk ratios for lower respiratory tract complications and hospitalization were 0.62 and 0.61, respectively, in the overall intention-to-treat population, but the difference in hospitalization between the groups was no longer statistically significant.

The benefits of treatment came at the cost of increased risk of nausea and vomiting (RR, 1.60 and 2.43, respectively), but no effect was seen with respect to neurologic or psychiatric disorders or serious adverse events in either of the groups.

To overcome previous concerns regarding potential publication bias, the investigators included all published and unpublished Roche-sponsored randomized, placebo-controlled, double-blind trials of the standard prescribed oseltamivir dose of 75 mg twice daily in adults, as well other applicable trials of the Roche drug for the treatment of naturally occurring influenzalike illness. The trials were conducted between 1997 and 2001, and included patients who were within 36 hours of feeling unwell, and who had a fever and at least one respiratory symptom and one additional constitutional symptom.

Treatment was administered at 12-hour intervals for 5 days, and patients were followed for 21 days, during which time virus cultures were performed in most cases.

“The safety and effectiveness of oseltamivir has been hotly debated, with some researchers claiming there is little evidence that oseltamivir works,” Dr. Monto said in a press statement. “Our meta-analysis provides compelling evidence that oseltamivir therapy reduces by 1 day the typical length of illness in adults infected with influenza and also prevents complications and reduces the number of people needing hospital treatment. Whether the magnitude of these benefits outweighs the harms of nausea and vomiting needs careful consideration.”

The Multiparty Group for Advice on Science funded the study and assembled a multidisciplinary team to examine available data. The group obtained an unrestricted grant from Roche to cover the costs.

Dr. Monto reported receiving fees from BioCryst and Roche outside of the submitted work. His coauthor, Dr. Richard J. Whitely, reported receiving fees as a board member of Gilead Sciences and travel funding from Roche. The remaining authors reported having no disclosures.

Oseltamivir treatment in adults with influenza shortens the time to clinical symptom alleviation by about 1 day and substantially reduces the risk of lower respiratory tract complications and hospitalization, according to findings from a meta-analysis of nine randomized, controlled trials involving 4,328 adult patients.

The findings of the study, which is the first to use individual patient data to evaluate the neuraminidase inhibitor, should put to rest persistent doubts its efficacy and safety, according to Dr. Arnold S. Monto of the University of Michigan School of Public Health, Ann Arbor, who was lead investigator, and his colleagues.

The intention-to-treat population of 1,591 patients with confirmed influenza had a significant 21% shorter time to clinical symptom alleviation, compared with the intention-to-treat infected population of 1,302 patients who received placebo (97.5 hours vs. 122.7 hours, difference of 25.2 hours; time ratio, 0.79), the investigators reported online Jan. 30 in the Lancet.

The effects were somewhat attenuated in the 2,402 treated patients in the overall intention-to-treat population – with a 15% reduction in time to symptom alleviation – compared with the 1,926 placebo patients in that population. But the difference remained significant (median of 17.8 hours; time ratio, 0.85), the investigators said (Lancet 2015 Jan. 30 [doi:10.106/S0140-6736(14)62449-1]).

“In the intention-to-treat noninfected population, the estimated time ratio was close to unity (time ratio, 0.99), so only participants identified as influenza infected benefited from oseltamivir,” the study authors wrote. That suggests efficacy is “confined to the antiviral activity of the drug.”

In addition, treatment significantly reduced the risk of lower respiratory tract complications occurring more than 48 hours after randomization by 44% in the intention-to-treat infected population. Only 4.2% of oseltamivir-treated patients requiring such treatment, compared with 8.7% of those who received placebo (risk ratio, 0.56). The risk of hospitalization for any cause was significantly reduced by 63% (0.6% vs. 1.7% in the groups, respectively; RR, 0.37).

The risk ratios for lower respiratory tract complications and hospitalization were 0.62 and 0.61, respectively, in the overall intention-to-treat population, but the difference in hospitalization between the groups was no longer statistically significant.

The benefits of treatment came at the cost of increased risk of nausea and vomiting (RR, 1.60 and 2.43, respectively), but no effect was seen with respect to neurologic or psychiatric disorders or serious adverse events in either of the groups.

To overcome previous concerns regarding potential publication bias, the investigators included all published and unpublished Roche-sponsored randomized, placebo-controlled, double-blind trials of the standard prescribed oseltamivir dose of 75 mg twice daily in adults, as well other applicable trials of the Roche drug for the treatment of naturally occurring influenzalike illness. The trials were conducted between 1997 and 2001, and included patients who were within 36 hours of feeling unwell, and who had a fever and at least one respiratory symptom and one additional constitutional symptom.

Treatment was administered at 12-hour intervals for 5 days, and patients were followed for 21 days, during which time virus cultures were performed in most cases.

“The safety and effectiveness of oseltamivir has been hotly debated, with some researchers claiming there is little evidence that oseltamivir works,” Dr. Monto said in a press statement. “Our meta-analysis provides compelling evidence that oseltamivir therapy reduces by 1 day the typical length of illness in adults infected with influenza and also prevents complications and reduces the number of people needing hospital treatment. Whether the magnitude of these benefits outweighs the harms of nausea and vomiting needs careful consideration.”

The Multiparty Group for Advice on Science funded the study and assembled a multidisciplinary team to examine available data. The group obtained an unrestricted grant from Roche to cover the costs.

Dr. Monto reported receiving fees from BioCryst and Roche outside of the submitted work. His coauthor, Dr. Richard J. Whitely, reported receiving fees as a board member of Gilead Sciences and travel funding from Roche. The remaining authors reported having no disclosures.

Oseltamivir treatment in adults with influenza shortens the time to clinical symptom alleviation by about 1 day and substantially reduces the risk of lower respiratory tract complications and hospitalization, according to findings from a meta-analysis of nine randomized, controlled trials involving 4,328 adult patients.

The findings of the study, which is the first to use individual patient data to evaluate the neuraminidase inhibitor, should put to rest persistent doubts its efficacy and safety, according to Dr. Arnold S. Monto of the University of Michigan School of Public Health, Ann Arbor, who was lead investigator, and his colleagues.

The intention-to-treat population of 1,591 patients with confirmed influenza had a significant 21% shorter time to clinical symptom alleviation, compared with the intention-to-treat infected population of 1,302 patients who received placebo (97.5 hours vs. 122.7 hours, difference of 25.2 hours; time ratio, 0.79), the investigators reported online Jan. 30 in the Lancet.

The effects were somewhat attenuated in the 2,402 treated patients in the overall intention-to-treat population – with a 15% reduction in time to symptom alleviation – compared with the 1,926 placebo patients in that population. But the difference remained significant (median of 17.8 hours; time ratio, 0.85), the investigators said (Lancet 2015 Jan. 30 [doi:10.106/S0140-6736(14)62449-1]).

“In the intention-to-treat noninfected population, the estimated time ratio was close to unity (time ratio, 0.99), so only participants identified as influenza infected benefited from oseltamivir,” the study authors wrote. That suggests efficacy is “confined to the antiviral activity of the drug.”

In addition, treatment significantly reduced the risk of lower respiratory tract complications occurring more than 48 hours after randomization by 44% in the intention-to-treat infected population. Only 4.2% of oseltamivir-treated patients requiring such treatment, compared with 8.7% of those who received placebo (risk ratio, 0.56). The risk of hospitalization for any cause was significantly reduced by 63% (0.6% vs. 1.7% in the groups, respectively; RR, 0.37).

The risk ratios for lower respiratory tract complications and hospitalization were 0.62 and 0.61, respectively, in the overall intention-to-treat population, but the difference in hospitalization between the groups was no longer statistically significant.

The benefits of treatment came at the cost of increased risk of nausea and vomiting (RR, 1.60 and 2.43, respectively), but no effect was seen with respect to neurologic or psychiatric disorders or serious adverse events in either of the groups.

To overcome previous concerns regarding potential publication bias, the investigators included all published and unpublished Roche-sponsored randomized, placebo-controlled, double-blind trials of the standard prescribed oseltamivir dose of 75 mg twice daily in adults, as well other applicable trials of the Roche drug for the treatment of naturally occurring influenzalike illness. The trials were conducted between 1997 and 2001, and included patients who were within 36 hours of feeling unwell, and who had a fever and at least one respiratory symptom and one additional constitutional symptom.

Treatment was administered at 12-hour intervals for 5 days, and patients were followed for 21 days, during which time virus cultures were performed in most cases.

“The safety and effectiveness of oseltamivir has been hotly debated, with some researchers claiming there is little evidence that oseltamivir works,” Dr. Monto said in a press statement. “Our meta-analysis provides compelling evidence that oseltamivir therapy reduces by 1 day the typical length of illness in adults infected with influenza and also prevents complications and reduces the number of people needing hospital treatment. Whether the magnitude of these benefits outweighs the harms of nausea and vomiting needs careful consideration.”

The Multiparty Group for Advice on Science funded the study and assembled a multidisciplinary team to examine available data. The group obtained an unrestricted grant from Roche to cover the costs.

Dr. Monto reported receiving fees from BioCryst and Roche outside of the submitted work. His coauthor, Dr. Richard J. Whitely, reported receiving fees as a board member of Gilead Sciences and travel funding from Roche. The remaining authors reported having no disclosures.

A validated genomic classifier score based on 22 prespecified biomarkers is prognostic for the development of clinical metastasis after radical prostatectomy, and could help inform decision making about the timing of subsequent radiotherapy, according to a review of 188 patients who were treated with post–radical prostatectomy radiotherapy.

The findings suggest that patients with a low genomic classifier (GC) score are best treated with salvage radiotherapy (SRT), and those with a high score are best treated with adjuvant radiotherapy (ART), reported Dr. Robert B. Den of Thomas Jefferson University, Philadelphia, and his colleagues. The study was published online Feb. 9 in the Journal of Clinical Oncology.

The 5-year cumulative incidence of metastasis in the study subjects, who were identified from the GenomeDx prostate cancer genomic database, was 0%, 9%, and 29% in those with low (less than 0.4), average (0.4-0.6), and high (greater than 0.6) GC scores, respectively. On multivariable analysis, pre–radical prostatectomy prostate-specific antigen levels and GC were independent predictors of metastasis (hazard ratio, 2.12; hazard ratio, 1.90 for every 10% increase in GC score, respectively). No differences were seen in the cumulative incidence of metastasis when patients with GC scores less than 0.4 were compared based on whether they received ART or SRT, but among those with GC scores of 0.4 or higher, the cumulative incidence of metastasis at 5 years was 6% in those who received ART, and 23% in those who received SRT (J. Clin. Oncol. 2015 Feb. 9 [doi:10.1200/JCO.2014.59.0026]).

Use of the GC scoring model either alone or in combination with the Cancer of the Prostate Risk Assessment Postsurgical (CAPRA-S) scoring model was superior to other clinicopathological models for predicting metastasis, and had “a higher net benefit than clinical models across a wide range of decision threshold probabilities,” they noted.

The patients were men with pT3 or margin-positive prostate cancer who received radiotherapy after radical prostatectomy (post-RP RT) at either Thomas Jefferson University, Philadelphia, or the Mayo Clinic, Rochester, Minn., between 1990 and 2009. They were treated at a median dose of 66.6 Gy with conventional fractionation by either three-dimensional conformal RT or by intensity-modulated RT techniques, and followed for a median of 10 years after radical prostatectomy and 8 years after radiotherapy.

The findings have important implications for the treatment of contemporary prostate cancer patients who harbor adverse pathologic characteristics at the time of radical prostatectomy; these patients are often treated with postoperative radiotherapy alone or with hormonal therapy, but the optimal timing of post-RP RT has been unclear, the investigators explained.

“Advocates for adjuvant RT argue that this treatment modality might maximize cancer control outcomes. However, salvage RT can minimize overtreatment while offering acceptable oncologic outcomes,” they wrote, adding that trials comparing the two are underway, but because of the rarity of data in the field and the unresolved controversy about the best approach to treatment, they “sought to integrate a novel biomarker test to improve clinical decision making regarding post-RP RT.

“We demonstrate that the GC is highly prognostic in the setting of postprostatectomy RT and that the GC may be a predictive marker that can help determine which patient will benefit from ART as opposed to SRT. This supports the importance of local therapy in the setting of presumed occult metastatic disease,” they said, noting that the findings are “particularly intriguing and provide a unique, more individualized approach in the management of postprostatectomy patients with adverse pathologic findings.”

While a biomarker shouldn’t replace shared patient-physician decision making, the use of the GC could provide insight into the aggressiveness of disease and aid in decision making regarding postprostatectomy therapy, they said.

Intensification of therapy in men with a high GC score who are receiving salvage radiotherapy is currently being examined in the Radiation Therapy Oncology Group 9601 randomized, phase III trial comparing SRT with SRT plus high-dose bicalutamide, the noted.

“Given that this cohort consists of high-risk patients by clinicopathologic nomograms and the utilization of a GC allowed for significant downstaging, this study has major ramifications in terms of both potential for overtreatment and substantial cost savings to the U.S. health care system. Thus, the GC is a valuable tool to aid in management of men with prostate cancer undergoing prostatectomy,” they concluded.

Dr. Den and several coauthors disclosed ties with GenomeDx Biosciences, Janssen, Medivation, CE Outcomes, Photocure, Dendreon, Astellas, Celgene, Varian, Merck KGaA, Vertex, Glenview Consulting, Bayer, NRG Oncology, and Myriad Genetics.

A validated genomic classifier score based on 22 prespecified biomarkers is prognostic for the development of clinical metastasis after radical prostatectomy, and could help inform decision making about the timing of subsequent radiotherapy, according to a review of 188 patients who were treated with post–radical prostatectomy radiotherapy.

The findings suggest that patients with a low genomic classifier (GC) score are best treated with salvage radiotherapy (SRT), and those with a high score are best treated with adjuvant radiotherapy (ART), reported Dr. Robert B. Den of Thomas Jefferson University, Philadelphia, and his colleagues. The study was published online Feb. 9 in the Journal of Clinical Oncology.

The 5-year cumulative incidence of metastasis in the study subjects, who were identified from the GenomeDx prostate cancer genomic database, was 0%, 9%, and 29% in those with low (less than 0.4), average (0.4-0.6), and high (greater than 0.6) GC scores, respectively. On multivariable analysis, pre–radical prostatectomy prostate-specific antigen levels and GC were independent predictors of metastasis (hazard ratio, 2.12; hazard ratio, 1.90 for every 10% increase in GC score, respectively). No differences were seen in the cumulative incidence of metastasis when patients with GC scores less than 0.4 were compared based on whether they received ART or SRT, but among those with GC scores of 0.4 or higher, the cumulative incidence of metastasis at 5 years was 6% in those who received ART, and 23% in those who received SRT (J. Clin. Oncol. 2015 Feb. 9 [doi:10.1200/JCO.2014.59.0026]).

Use of the GC scoring model either alone or in combination with the Cancer of the Prostate Risk Assessment Postsurgical (CAPRA-S) scoring model was superior to other clinicopathological models for predicting metastasis, and had “a higher net benefit than clinical models across a wide range of decision threshold probabilities,” they noted.

The patients were men with pT3 or margin-positive prostate cancer who received radiotherapy after radical prostatectomy (post-RP RT) at either Thomas Jefferson University, Philadelphia, or the Mayo Clinic, Rochester, Minn., between 1990 and 2009. They were treated at a median dose of 66.6 Gy with conventional fractionation by either three-dimensional conformal RT or by intensity-modulated RT techniques, and followed for a median of 10 years after radical prostatectomy and 8 years after radiotherapy.

The findings have important implications for the treatment of contemporary prostate cancer patients who harbor adverse pathologic characteristics at the time of radical prostatectomy; these patients are often treated with postoperative radiotherapy alone or with hormonal therapy, but the optimal timing of post-RP RT has been unclear, the investigators explained.

“Advocates for adjuvant RT argue that this treatment modality might maximize cancer control outcomes. However, salvage RT can minimize overtreatment while offering acceptable oncologic outcomes,” they wrote, adding that trials comparing the two are underway, but because of the rarity of data in the field and the unresolved controversy about the best approach to treatment, they “sought to integrate a novel biomarker test to improve clinical decision making regarding post-RP RT.

“We demonstrate that the GC is highly prognostic in the setting of postprostatectomy RT and that the GC may be a predictive marker that can help determine which patient will benefit from ART as opposed to SRT. This supports the importance of local therapy in the setting of presumed occult metastatic disease,” they said, noting that the findings are “particularly intriguing and provide a unique, more individualized approach in the management of postprostatectomy patients with adverse pathologic findings.”

While a biomarker shouldn’t replace shared patient-physician decision making, the use of the GC could provide insight into the aggressiveness of disease and aid in decision making regarding postprostatectomy therapy, they said.

Intensification of therapy in men with a high GC score who are receiving salvage radiotherapy is currently being examined in the Radiation Therapy Oncology Group 9601 randomized, phase III trial comparing SRT with SRT plus high-dose bicalutamide, the noted.

“Given that this cohort consists of high-risk patients by clinicopathologic nomograms and the utilization of a GC allowed for significant downstaging, this study has major ramifications in terms of both potential for overtreatment and substantial cost savings to the U.S. health care system. Thus, the GC is a valuable tool to aid in management of men with prostate cancer undergoing prostatectomy,” they concluded.

Dr. Den and several coauthors disclosed ties with GenomeDx Biosciences, Janssen, Medivation, CE Outcomes, Photocure, Dendreon, Astellas, Celgene, Varian, Merck KGaA, Vertex, Glenview Consulting, Bayer, NRG Oncology, and Myriad Genetics.

A validated genomic classifier score based on 22 prespecified biomarkers is prognostic for the development of clinical metastasis after radical prostatectomy, and could help inform decision making about the timing of subsequent radiotherapy, according to a review of 188 patients who were treated with post–radical prostatectomy radiotherapy.

The findings suggest that patients with a low genomic classifier (GC) score are best treated with salvage radiotherapy (SRT), and those with a high score are best treated with adjuvant radiotherapy (ART), reported Dr. Robert B. Den of Thomas Jefferson University, Philadelphia, and his colleagues. The study was published online Feb. 9 in the Journal of Clinical Oncology.

The 5-year cumulative incidence of metastasis in the study subjects, who were identified from the GenomeDx prostate cancer genomic database, was 0%, 9%, and 29% in those with low (less than 0.4), average (0.4-0.6), and high (greater than 0.6) GC scores, respectively. On multivariable analysis, pre–radical prostatectomy prostate-specific antigen levels and GC were independent predictors of metastasis (hazard ratio, 2.12; hazard ratio, 1.90 for every 10% increase in GC score, respectively). No differences were seen in the cumulative incidence of metastasis when patients with GC scores less than 0.4 were compared based on whether they received ART or SRT, but among those with GC scores of 0.4 or higher, the cumulative incidence of metastasis at 5 years was 6% in those who received ART, and 23% in those who received SRT (J. Clin. Oncol. 2015 Feb. 9 [doi:10.1200/JCO.2014.59.0026]).

Use of the GC scoring model either alone or in combination with the Cancer of the Prostate Risk Assessment Postsurgical (CAPRA-S) scoring model was superior to other clinicopathological models for predicting metastasis, and had “a higher net benefit than clinical models across a wide range of decision threshold probabilities,” they noted.

The patients were men with pT3 or margin-positive prostate cancer who received radiotherapy after radical prostatectomy (post-RP RT) at either Thomas Jefferson University, Philadelphia, or the Mayo Clinic, Rochester, Minn., between 1990 and 2009. They were treated at a median dose of 66.6 Gy with conventional fractionation by either three-dimensional conformal RT or by intensity-modulated RT techniques, and followed for a median of 10 years after radical prostatectomy and 8 years after radiotherapy.

The findings have important implications for the treatment of contemporary prostate cancer patients who harbor adverse pathologic characteristics at the time of radical prostatectomy; these patients are often treated with postoperative radiotherapy alone or with hormonal therapy, but the optimal timing of post-RP RT has been unclear, the investigators explained.

“Advocates for adjuvant RT argue that this treatment modality might maximize cancer control outcomes. However, salvage RT can minimize overtreatment while offering acceptable oncologic outcomes,” they wrote, adding that trials comparing the two are underway, but because of the rarity of data in the field and the unresolved controversy about the best approach to treatment, they “sought to integrate a novel biomarker test to improve clinical decision making regarding post-RP RT.

“We demonstrate that the GC is highly prognostic in the setting of postprostatectomy RT and that the GC may be a predictive marker that can help determine which patient will benefit from ART as opposed to SRT. This supports the importance of local therapy in the setting of presumed occult metastatic disease,” they said, noting that the findings are “particularly intriguing and provide a unique, more individualized approach in the management of postprostatectomy patients with adverse pathologic findings.”

While a biomarker shouldn’t replace shared patient-physician decision making, the use of the GC could provide insight into the aggressiveness of disease and aid in decision making regarding postprostatectomy therapy, they said.

Intensification of therapy in men with a high GC score who are receiving salvage radiotherapy is currently being examined in the Radiation Therapy Oncology Group 9601 randomized, phase III trial comparing SRT with SRT plus high-dose bicalutamide, the noted.

“Given that this cohort consists of high-risk patients by clinicopathologic nomograms and the utilization of a GC allowed for significant downstaging, this study has major ramifications in terms of both potential for overtreatment and substantial cost savings to the U.S. health care system. Thus, the GC is a valuable tool to aid in management of men with prostate cancer undergoing prostatectomy,” they concluded.

Dr. Den and several coauthors disclosed ties with GenomeDx Biosciences, Janssen, Medivation, CE Outcomes, Photocure, Dendreon, Astellas, Celgene, Varian, Merck KGaA, Vertex, Glenview Consulting, Bayer, NRG Oncology, and Myriad Genetics.

SAN DIEGO– Early treatment of pregnant women with prediabetes led to lower hemoglobin A_1C (HbA_1C) levels during the second trimester and at delivery in a randomized, controlled trial.

Study subjects were 83 women with a first trimester HbA_1C of 5.7%-6.4% (median of 5.8%) indicative of prediabetes. HbA_1C levels during the second trimester were 5.2% and 5.3% in the 42 women who were randomized to receive early treatment and in the 41 who received routine care, respectively, and the levels at delivery were 5.5% and 5.8%, respectively, Dr. Sarah Osmundson reported at the annual Pregnancy Meeting sponsored by the Society for Maternal-Fetal Medicine.

The overall rate of positive glucose tolerance tests (GTT) or insulin use prior to the GTT – the primary study outcome – did not differ significantly between the groups but did trend toward lower in the early treatment group (45.2% vs. 55%; relative risk, 0.82), said Dr. Osmundson of Stanford (Calif.) University.

Further, although no difference was seen in the rate of gestational diabetes mellitus (GDM) among women with prepregnancy obesity in the early treatment and routine care groups, early treatment was associated with a 50% lower rate of GDM in nonobese women (29.6% vs. 59.1%, relative risk, 0.50), she said.

The participants had a singleton pregnancy, no chronic steroid use, and no preexisting diabetes. They were enrolled between May 2012 and June 2014, and all met with a certified diabetes educator at study entry to discuss healthy weight gain strategies in pregnancy and to set personalized weight gain goals.

Those in the early treatment group also were counseled to keep a diary to track food intake, were advised to monitor portion size, and limit carbohydrate intake to no more than 45% of total diet, and were seen by a dietitian or obstetrician every 2 weeks. They self-monitored blood glucose levels four times daily, and insulin was initiated if more than 20% of values were elevated.

The routine care group received usual prenatal care, including a visit with a provider every 4 weeks.

Patients in both groups underwent an oral GTT between 26 and 28 weeks of gestation.

Continue for more on the early treatment group >>

Patients in the early treatment group with a positive GTT continued treatment, and those with a negative GTT continued treatment, but reduced monitoring to twice daily – returning to four times daily testing if levels increased. Those in the routine care group initiated treatment if the GTT was positive, and continued usual care if it was negative.

The groups gained a similar amount of weight during the study and did not differ in terms of insulin use, but the early treatment group started insulin at an earlier gestational age, and nonsignificant trends were seen toward a decrease in the primary outcome and toward lower GTT values in that group. The early treatment group patients also had a lower cesarean delivery rate (29.4% vs. 47,2%; RR, 0.63), but the difference did not reach statistical significance, Dr. Osmundson said.

Similarly, nonsignificant trends were seen toward lower infant birth weight, less macrosomia, and lower umbilical cord C-peptide levels in the early treatment group.

Glycosylated HbA_1C is widely used for monitoring glycemic control, but was only recently adopted as an additional method of screening for diabetes. The measure has several advantages over the oral GTT, as it can be performed in a nonfasting state, requires only one blood draw, and provides information about average glucose exposure over time, she said.

The American Diabetes Association accepted HbA_1C as an additional method for diagnosing type 2 diabetes in 2009, and classified those with levels between 5.7% and 6.4% as having prediabetes. That same year, an International Association of Diabetes in Pregnancy study group recommended that HbA_1C of 6.5% or greater in pregnancy be considered overt diabetes, but made no recommendations regarding the management of those with prediabetic HbA_1C, Dr. Osmundson said.

Next page: Prediabetes in pregnant women >>

Prediabetes predicts a 50% cumulative incidence of type 2 diabetes within 5 years in nonpregnant patients, but much less is known about the condition in pregnant women, she added, noting that recent studies suggest a threefold increased risk for gestational diabetes in the second trimester – and perhaps even greater risk in obese women – among those with prediabetes.

The addition of HbA_1C to the prenatal panel in California, along with a recommendation that those with prediabetes be diagnosed with and treated for gestational diabetes, provided the opportunity to evaluate whether such treatment affected the incidence of gestational diabetes as compared with usual care, she noted.

“We hypothesized that treatment would lower the risk of GDM, especially among obese women,” she said.

Though limited by the sample size and the fact that providers were not blinded to patients’ treatment group, the randomized, controlled study design is a strength, and the findings add to the limited data on HbA_1C in pregnancy and the management of prediabetes in pregnant patients, she said.

The study was underpowered to determine whether early treatment reduces the risk of GDM in women with prediabetes, but the findings suggest that such treatment may reduce the risk among nonobese women.

“While this finding is unexpected, we think the findings are consistent with literature suggesting that women with prepregnancy obesity remain at higher risk of adverse perinatal outcomes even in absence of GDM or excessive weight gain. We hypothesize that any small effect may be attenuated by the morbidity associated with prepregnancy adiposity. Larger studies powered to examine the primary outcomes and perinatal outcomes are required,” she concluded.

This study was funded by the American College of Obstetricians and Gynecologists Abbott Nutrition Research Fellowship, the Stanford Child Health Institute, and the Valley Foundation for the California Institute of Medical Research. Dr. Osmundson reported having no disclosures.

SAN DIEGO– Early treatment of pregnant women with prediabetes led to lower hemoglobin A_1C (HbA_1C) levels during the second trimester and at delivery in a randomized, controlled trial.

Study subjects were 83 women with a first trimester HbA_1C of 5.7%-6.4% (median of 5.8%) indicative of prediabetes. HbA_1C levels during the second trimester were 5.2% and 5.3% in the 42 women who were randomized to receive early treatment and in the 41 who received routine care, respectively, and the levels at delivery were 5.5% and 5.8%, respectively, Dr. Sarah Osmundson reported at the annual Pregnancy Meeting sponsored by the Society for Maternal-Fetal Medicine.

The overall rate of positive glucose tolerance tests (GTT) or insulin use prior to the GTT – the primary study outcome – did not differ significantly between the groups but did trend toward lower in the early treatment group (45.2% vs. 55%; relative risk, 0.82), said Dr. Osmundson of Stanford (Calif.) University.

Further, although no difference was seen in the rate of gestational diabetes mellitus (GDM) among women with prepregnancy obesity in the early treatment and routine care groups, early treatment was associated with a 50% lower rate of GDM in nonobese women (29.6% vs. 59.1%, relative risk, 0.50), she said.

The participants had a singleton pregnancy, no chronic steroid use, and no preexisting diabetes. They were enrolled between May 2012 and June 2014, and all met with a certified diabetes educator at study entry to discuss healthy weight gain strategies in pregnancy and to set personalized weight gain goals.

Those in the early treatment group also were counseled to keep a diary to track food intake, were advised to monitor portion size, and limit carbohydrate intake to no more than 45% of total diet, and were seen by a dietitian or obstetrician every 2 weeks. They self-monitored blood glucose levels four times daily, and insulin was initiated if more than 20% of values were elevated.

The routine care group received usual prenatal care, including a visit with a provider every 4 weeks.

Patients in both groups underwent an oral GTT between 26 and 28 weeks of gestation.

Continue for more on the early treatment group >>

Patients in the early treatment group with a positive GTT continued treatment, and those with a negative GTT continued treatment, but reduced monitoring to twice daily – returning to four times daily testing if levels increased. Those in the routine care group initiated treatment if the GTT was positive, and continued usual care if it was negative.

The groups gained a similar amount of weight during the study and did not differ in terms of insulin use, but the early treatment group started insulin at an earlier gestational age, and nonsignificant trends were seen toward a decrease in the primary outcome and toward lower GTT values in that group. The early treatment group patients also had a lower cesarean delivery rate (29.4% vs. 47,2%; RR, 0.63), but the difference did not reach statistical significance, Dr. Osmundson said.

Similarly, nonsignificant trends were seen toward lower infant birth weight, less macrosomia, and lower umbilical cord C-peptide levels in the early treatment group.

Glycosylated HbA_1C is widely used for monitoring glycemic control, but was only recently adopted as an additional method of screening for diabetes. The measure has several advantages over the oral GTT, as it can be performed in a nonfasting state, requires only one blood draw, and provides information about average glucose exposure over time, she said.

The American Diabetes Association accepted HbA_1C as an additional method for diagnosing type 2 diabetes in 2009, and classified those with levels between 5.7% and 6.4% as having prediabetes. That same year, an International Association of Diabetes in Pregnancy study group recommended that HbA_1C of 6.5% or greater in pregnancy be considered overt diabetes, but made no recommendations regarding the management of those with prediabetic HbA_1C, Dr. Osmundson said.

Next page: Prediabetes in pregnant women >>

Prediabetes predicts a 50% cumulative incidence of type 2 diabetes within 5 years in nonpregnant patients, but much less is known about the condition in pregnant women, she added, noting that recent studies suggest a threefold increased risk for gestational diabetes in the second trimester – and perhaps even greater risk in obese women – among those with prediabetes.

The addition of HbA_1C to the prenatal panel in California, along with a recommendation that those with prediabetes be diagnosed with and treated for gestational diabetes, provided the opportunity to evaluate whether such treatment affected the incidence of gestational diabetes as compared with usual care, she noted.

“We hypothesized that treatment would lower the risk of GDM, especially among obese women,” she said.

Though limited by the sample size and the fact that providers were not blinded to patients’ treatment group, the randomized, controlled study design is a strength, and the findings add to the limited data on HbA_1C in pregnancy and the management of prediabetes in pregnant patients, she said.

The study was underpowered to determine whether early treatment reduces the risk of GDM in women with prediabetes, but the findings suggest that such treatment may reduce the risk among nonobese women.

“While this finding is unexpected, we think the findings are consistent with literature suggesting that women with prepregnancy obesity remain at higher risk of adverse perinatal outcomes even in absence of GDM or excessive weight gain. We hypothesize that any small effect may be attenuated by the morbidity associated with prepregnancy adiposity. Larger studies powered to examine the primary outcomes and perinatal outcomes are required,” she concluded.

This study was funded by the American College of Obstetricians and Gynecologists Abbott Nutrition Research Fellowship, the Stanford Child Health Institute, and the Valley Foundation for the California Institute of Medical Research. Dr. Osmundson reported having no disclosures.

SAN DIEGO– Early treatment of pregnant women with prediabetes led to lower hemoglobin A_1C (HbA_1C) levels during the second trimester and at delivery in a randomized, controlled trial.

Study subjects were 83 women with a first trimester HbA_1C of 5.7%-6.4% (median of 5.8%) indicative of prediabetes. HbA_1C levels during the second trimester were 5.2% and 5.3% in the 42 women who were randomized to receive early treatment and in the 41 who received routine care, respectively, and the levels at delivery were 5.5% and 5.8%, respectively, Dr. Sarah Osmundson reported at the annual Pregnancy Meeting sponsored by the Society for Maternal-Fetal Medicine.

The overall rate of positive glucose tolerance tests (GTT) or insulin use prior to the GTT – the primary study outcome – did not differ significantly between the groups but did trend toward lower in the early treatment group (45.2% vs. 55%; relative risk, 0.82), said Dr. Osmundson of Stanford (Calif.) University.

Further, although no difference was seen in the rate of gestational diabetes mellitus (GDM) among women with prepregnancy obesity in the early treatment and routine care groups, early treatment was associated with a 50% lower rate of GDM in nonobese women (29.6% vs. 59.1%, relative risk, 0.50), she said.

The participants had a singleton pregnancy, no chronic steroid use, and no preexisting diabetes. They were enrolled between May 2012 and June 2014, and all met with a certified diabetes educator at study entry to discuss healthy weight gain strategies in pregnancy and to set personalized weight gain goals.

Those in the early treatment group also were counseled to keep a diary to track food intake, were advised to monitor portion size, and limit carbohydrate intake to no more than 45% of total diet, and were seen by a dietitian or obstetrician every 2 weeks. They self-monitored blood glucose levels four times daily, and insulin was initiated if more than 20% of values were elevated.

The routine care group received usual prenatal care, including a visit with a provider every 4 weeks.

Patients in both groups underwent an oral GTT between 26 and 28 weeks of gestation.

Continue for more on the early treatment group >>

Patients in the early treatment group with a positive GTT continued treatment, and those with a negative GTT continued treatment, but reduced monitoring to twice daily – returning to four times daily testing if levels increased. Those in the routine care group initiated treatment if the GTT was positive, and continued usual care if it was negative.

The groups gained a similar amount of weight during the study and did not differ in terms of insulin use, but the early treatment group started insulin at an earlier gestational age, and nonsignificant trends were seen toward a decrease in the primary outcome and toward lower GTT values in that group. The early treatment group patients also had a lower cesarean delivery rate (29.4% vs. 47,2%; RR, 0.63), but the difference did not reach statistical significance, Dr. Osmundson said.

Similarly, nonsignificant trends were seen toward lower infant birth weight, less macrosomia, and lower umbilical cord C-peptide levels in the early treatment group.

Glycosylated HbA_1C is widely used for monitoring glycemic control, but was only recently adopted as an additional method of screening for diabetes. The measure has several advantages over the oral GTT, as it can be performed in a nonfasting state, requires only one blood draw, and provides information about average glucose exposure over time, she said.

The American Diabetes Association accepted HbA_1C as an additional method for diagnosing type 2 diabetes in 2009, and classified those with levels between 5.7% and 6.4% as having prediabetes. That same year, an International Association of Diabetes in Pregnancy study group recommended that HbA_1C of 6.5% or greater in pregnancy be considered overt diabetes, but made no recommendations regarding the management of those with prediabetic HbA_1C, Dr. Osmundson said.

Next page: Prediabetes in pregnant women >>

Prediabetes predicts a 50% cumulative incidence of type 2 diabetes within 5 years in nonpregnant patients, but much less is known about the condition in pregnant women, she added, noting that recent studies suggest a threefold increased risk for gestational diabetes in the second trimester – and perhaps even greater risk in obese women – among those with prediabetes.

The addition of HbA_1C to the prenatal panel in California, along with a recommendation that those with prediabetes be diagnosed with and treated for gestational diabetes, provided the opportunity to evaluate whether such treatment affected the incidence of gestational diabetes as compared with usual care, she noted.

“We hypothesized that treatment would lower the risk of GDM, especially among obese women,” she said.

Though limited by the sample size and the fact that providers were not blinded to patients’ treatment group, the randomized, controlled study design is a strength, and the findings add to the limited data on HbA_1C in pregnancy and the management of prediabetes in pregnant patients, she said.

The study was underpowered to determine whether early treatment reduces the risk of GDM in women with prediabetes, but the findings suggest that such treatment may reduce the risk among nonobese women.

“While this finding is unexpected, we think the findings are consistent with literature suggesting that women with prepregnancy obesity remain at higher risk of adverse perinatal outcomes even in absence of GDM or excessive weight gain. We hypothesize that any small effect may be attenuated by the morbidity associated with prepregnancy adiposity. Larger studies powered to examine the primary outcomes and perinatal outcomes are required,” she concluded.

This study was funded by the American College of Obstetricians and Gynecologists Abbott Nutrition Research Fellowship, the Stanford Child Health Institute, and the Valley Foundation for the California Institute of Medical Research. Dr. Osmundson reported having no disclosures.