Expert Commentary

Stadnytskyi and colleagues explored the size of droplets created by speech using a highly sensitive laser system. They reported in PNAS that speaking resulted in the generation of a high number of medium-sized droplets (10- to 100-µm in diameter). Under the conditions of their experiment (27% humidity and 23° C) they reported that speech probably generates droplets that originate at a size of 12 to 21 µm in diameter and quickly dehydrate to an estimated diameter of 4 µm. The 4 µm-sized particles had a falling rate of only 0.06 cm·s⁻¹ and remained airborne for 8 to 14 minutes.¹

As reported by Hamner and colleagues, on March 10, 2020, 61 persons attended a 2.5-hour choir practice. One choir member had symptoms of an upper respiratory infection that began on March 7. Eventually that choir member tested positive for SARS-CoV-2. Of the 60 remaining persons, 52 (86.7%) eventually developed an upper respiratory illness. In total, 33 cases of SARS-CoV-2 were confirmed by nucleic acid testing and 20 probable cases were diagnosed (these individuals declined testing). The  choir attendees developed symptoms at a median of 3 days following the practice, with a range of 1 to 12 days. Three of the 53 ill people were hospitalized, and two died.²

The Stadnytskyi study suggests that speech generates large respiratory droplets that dehydrate into very small droplets that may remain in the air for an extended period of time. If the SARS-CoV-2 virus were in the original large droplet, the rapid dehydration of the droplet would result in prolonged airborne presence of the virus and enhance its infectivity.

The Hamner study highlights the importance of vocalization and respiratory particles in transmitting the SARS-CoV-2 virus. For clinicians and patients, both studies support many recommendations to reduce viral transmission, including:

• all clinicians and patients need to wear face masks
• all clinicians and patients should avoid face-to-face contact if alternative approaches to communication are possible
• all clinicians and patients should avoid gathering in large groups or crowded public spaces and need to maintain physical distancing.

The COVID pandemic has dramatically changed how we practice medicine and socialize.

Stadnytskyi and colleagues explored the size of droplets created by speech using a highly sensitive laser system. They reported in PNAS that speaking resulted in the generation of a high number of medium-sized droplets (10- to 100-µm in diameter). Under the conditions of their experiment (27% humidity and 23° C) they reported that speech probably generates droplets that originate at a size of 12 to 21 µm in diameter and quickly dehydrate to an estimated diameter of 4 µm. The 4 µm-sized particles had a falling rate of only 0.06 cm·s⁻¹ and remained airborne for 8 to 14 minutes.¹

As reported by Hamner and colleagues, on March 10, 2020, 61 persons attended a 2.5-hour choir practice. One choir member had symptoms of an upper respiratory infection that began on March 7. Eventually that choir member tested positive for SARS-CoV-2. Of the 60 remaining persons, 52 (86.7%) eventually developed an upper respiratory illness. In total, 33 cases of SARS-CoV-2 were confirmed by nucleic acid testing and 20 probable cases were diagnosed (these individuals declined testing). The  choir attendees developed symptoms at a median of 3 days following the practice, with a range of 1 to 12 days. Three of the 53 ill people were hospitalized, and two died.²

The Stadnytskyi study suggests that speech generates large respiratory droplets that dehydrate into very small droplets that may remain in the air for an extended period of time. If the SARS-CoV-2 virus were in the original large droplet, the rapid dehydration of the droplet would result in prolonged airborne presence of the virus and enhance its infectivity.

The Hamner study highlights the importance of vocalization and respiratory particles in transmitting the SARS-CoV-2 virus. For clinicians and patients, both studies support many recommendations to reduce viral transmission, including:

• all clinicians and patients need to wear face masks
• all clinicians and patients should avoid face-to-face contact if alternative approaches to communication are possible
• all clinicians and patients should avoid gathering in large groups or crowded public spaces and need to maintain physical distancing.

The COVID pandemic has dramatically changed how we practice medicine and socialize.

Stadnytskyi and colleagues explored the size of droplets created by speech using a highly sensitive laser system. They reported in PNAS that speaking resulted in the generation of a high number of medium-sized droplets (10- to 100-µm in diameter). Under the conditions of their experiment (27% humidity and 23° C) they reported that speech probably generates droplets that originate at a size of 12 to 21 µm in diameter and quickly dehydrate to an estimated diameter of 4 µm. The 4 µm-sized particles had a falling rate of only 0.06 cm·s⁻¹ and remained airborne for 8 to 14 minutes.¹

As reported by Hamner and colleagues, on March 10, 2020, 61 persons attended a 2.5-hour choir practice. One choir member had symptoms of an upper respiratory infection that began on March 7. Eventually that choir member tested positive for SARS-CoV-2. Of the 60 remaining persons, 52 (86.7%) eventually developed an upper respiratory illness. In total, 33 cases of SARS-CoV-2 were confirmed by nucleic acid testing and 20 probable cases were diagnosed (these individuals declined testing). The  choir attendees developed symptoms at a median of 3 days following the practice, with a range of 1 to 12 days. Three of the 53 ill people were hospitalized, and two died.²

The Stadnytskyi study suggests that speech generates large respiratory droplets that dehydrate into very small droplets that may remain in the air for an extended period of time. If the SARS-CoV-2 virus were in the original large droplet, the rapid dehydration of the droplet would result in prolonged airborne presence of the virus and enhance its infectivity.

The Hamner study highlights the importance of vocalization and respiratory particles in transmitting the SARS-CoV-2 virus. For clinicians and patients, both studies support many recommendations to reduce viral transmission, including:

• all clinicians and patients need to wear face masks
• all clinicians and patients should avoid face-to-face contact if alternative approaches to communication are possible
• all clinicians and patients should avoid gathering in large groups or crowded public spaces and need to maintain physical distancing.

The COVID pandemic has dramatically changed how we practice medicine and socialize.

Since the 1950s, when Shirodkar (1955) and McDonald (1957) published their seminal works detailing a transvaginal method to suture a “weak” cervix, clinicians and researchers have debated the indications for and utility of cerclage for preventing pregnancy loss and preterm birth.^1,2

Originally based on a history of recurrent mid-trimester loss (that is, a clinical diagnosis of cervical insufficiency), cerclage has been expanded to capture both ultrasonography and physical-exam indications. While cerclage has proven useful in select patient populations, an infrequent but vexing problem is what to do when a woman has experienced 1 or more (transvaginal) cerclage “failures.”

With a dearth of well-controlled, randomized data to support the use of cerclage for either history- or physical-exam indications, it is not surprising that we still debate whether the Shirodkar method is superior to the McDonald technique as well as how to best manage a patient when either or both methods previously resulted in an unsatisfactory outcome.

First randomized study to directly compare cerclage techniques

Fortunately, Shennan and colleagues in the United Kingdom have greatly enlarged our knowledge in this area by performing the first well-powered, 3-arm, randomized trial of transabdominal cerclage (TAC) compared with both high and low vaginal cerclage (HVC, LVC).³ They analyzed data for 111 women who were randomly assigned to TAC
(n = 39), HVC (n = 39), or LVC (n = 33).

Interestingly, the investigators chose to not attach conventional eponymous labels to their transvaginal methods, and they do not even provide a reference or detailed description of the surgical methods, telling us instead that, “Techniques used were left to the local clinician’s discretion.” Writing also that HVC cases, like the transabdominal surgeries, were carried out in specialty centers, they implied that additional training was required for the HVC. I inferred that indeed they actually were performing the McDonald and Shirodkar transvaginal methods and with possible by-physician, local modifications.

I am certain that the authors’ results did not surprise proponents of transabdominal cerclage for transvaginal cerclage failures, defined in this trial as prior birth from 14 to 28 weeks’ gestation. Since some clinicians use a more generous definition of cerclage failure (such as birth at less than 34 weeks), this study population was clearly at high risk for poor outcomes; in fact, more than 90% of each group had experienced at least 2 prior mid-trimester losses. As anticipated with randomization, other characteristics were well distributed across the 3 groups.

Continue to: Transabdominal cerclage significantly reduced preterm birth rates...

Transabdominal cerclage significantly reduced preterm birth rates

Using a primary outcome of preterm birth less than 32 weeks, which concentrates neonatal morbidities, the investigators observed an overall 4.5-fold higher rate of preterm birth in the transvaginal cohorts compared with the transabdominal patients (33% and 38% versus 8%, respectively). Comparing the TAC group individually with both LVC and HVC groups, the relative risk of preterm birth was 0.20 compared with the HVC group and 0.23 compared with the LVC group, reflecting an approximate 80% reduction.

Not surprising to me, the investigators observed nearly identical outcomes between the HVC and LVC cohorts, substantiating my bias that the 2 transvaginal methods are similarly effective. Opponents will quickly remind me that the study was not well-powered to detect a clinically significant difference between these 2 groups; touché!

Risks of TAC. We all know that, despite its now-proven benefits, the transabdominal approach is associated with a risk of special complications, including the surgical risks of placement (and removal) of the cerclage, the management of fetal death beyond approximately 14 weeks, and the absolute requisite for hysterotomy/cesarean birth. While serious complications are rare, in the trial by Shennan and colleagues none were recorded in the 39 TAC cases. Nevertheless, for women with no children or only prior early births, the risks seem to be justified; the number needed to treat was less than 4 to prevent 1 birth at less than 32 weeks and was 5.3 to prevent a fetal loss.

TAC is an option for select patients

Given that TAC now can be successfully placed using minimally invasive surgery, either prior to or following conception, this study provides unique level I evidence that should not be discounted and should further be considered in the context of confirming prior cohort studies that suggested a significant benefit. Although specialized training is required and the procedure may involve travel to a specialty center, the weight of clinical data clearly supports the use of TAC.

In summary, based largely on the trial by Shennan and colleagues, women with prior failed vaginal cerclage can and should be counseled regarding the availability of TAC and given the opportunity to weigh the reported risks and benefits. ●

Since the 1950s, when Shirodkar (1955) and McDonald (1957) published their seminal works detailing a transvaginal method to suture a “weak” cervix, clinicians and researchers have debated the indications for and utility of cerclage for preventing pregnancy loss and preterm birth.^1,2

Originally based on a history of recurrent mid-trimester loss (that is, a clinical diagnosis of cervical insufficiency), cerclage has been expanded to capture both ultrasonography and physical-exam indications. While cerclage has proven useful in select patient populations, an infrequent but vexing problem is what to do when a woman has experienced 1 or more (transvaginal) cerclage “failures.”

With a dearth of well-controlled, randomized data to support the use of cerclage for either history- or physical-exam indications, it is not surprising that we still debate whether the Shirodkar method is superior to the McDonald technique as well as how to best manage a patient when either or both methods previously resulted in an unsatisfactory outcome.

First randomized study to directly compare cerclage techniques

Fortunately, Shennan and colleagues in the United Kingdom have greatly enlarged our knowledge in this area by performing the first well-powered, 3-arm, randomized trial of transabdominal cerclage (TAC) compared with both high and low vaginal cerclage (HVC, LVC).³ They analyzed data for 111 women who were randomly assigned to TAC
(n = 39), HVC (n = 39), or LVC (n = 33).

Interestingly, the investigators chose to not attach conventional eponymous labels to their transvaginal methods, and they do not even provide a reference or detailed description of the surgical methods, telling us instead that, “Techniques used were left to the local clinician’s discretion.” Writing also that HVC cases, like the transabdominal surgeries, were carried out in specialty centers, they implied that additional training was required for the HVC. I inferred that indeed they actually were performing the McDonald and Shirodkar transvaginal methods and with possible by-physician, local modifications.

I am certain that the authors’ results did not surprise proponents of transabdominal cerclage for transvaginal cerclage failures, defined in this trial as prior birth from 14 to 28 weeks’ gestation. Since some clinicians use a more generous definition of cerclage failure (such as birth at less than 34 weeks), this study population was clearly at high risk for poor outcomes; in fact, more than 90% of each group had experienced at least 2 prior mid-trimester losses. As anticipated with randomization, other characteristics were well distributed across the 3 groups.

Continue to: Transabdominal cerclage significantly reduced preterm birth rates...

Transabdominal cerclage significantly reduced preterm birth rates

Using a primary outcome of preterm birth less than 32 weeks, which concentrates neonatal morbidities, the investigators observed an overall 4.5-fold higher rate of preterm birth in the transvaginal cohorts compared with the transabdominal patients (33% and 38% versus 8%, respectively). Comparing the TAC group individually with both LVC and HVC groups, the relative risk of preterm birth was 0.20 compared with the HVC group and 0.23 compared with the LVC group, reflecting an approximate 80% reduction.

Not surprising to me, the investigators observed nearly identical outcomes between the HVC and LVC cohorts, substantiating my bias that the 2 transvaginal methods are similarly effective. Opponents will quickly remind me that the study was not well-powered to detect a clinically significant difference between these 2 groups; touché!

Risks of TAC. We all know that, despite its now-proven benefits, the transabdominal approach is associated with a risk of special complications, including the surgical risks of placement (and removal) of the cerclage, the management of fetal death beyond approximately 14 weeks, and the absolute requisite for hysterotomy/cesarean birth. While serious complications are rare, in the trial by Shennan and colleagues none were recorded in the 39 TAC cases. Nevertheless, for women with no children or only prior early births, the risks seem to be justified; the number needed to treat was less than 4 to prevent 1 birth at less than 32 weeks and was 5.3 to prevent a fetal loss.

TAC is an option for select patients

Given that TAC now can be successfully placed using minimally invasive surgery, either prior to or following conception, this study provides unique level I evidence that should not be discounted and should further be considered in the context of confirming prior cohort studies that suggested a significant benefit. Although specialized training is required and the procedure may involve travel to a specialty center, the weight of clinical data clearly supports the use of TAC.

In summary, based largely on the trial by Shennan and colleagues, women with prior failed vaginal cerclage can and should be counseled regarding the availability of TAC and given the opportunity to weigh the reported risks and benefits. ●

Since the 1950s, when Shirodkar (1955) and McDonald (1957) published their seminal works detailing a transvaginal method to suture a “weak” cervix, clinicians and researchers have debated the indications for and utility of cerclage for preventing pregnancy loss and preterm birth.^1,2

Originally based on a history of recurrent mid-trimester loss (that is, a clinical diagnosis of cervical insufficiency), cerclage has been expanded to capture both ultrasonography and physical-exam indications. While cerclage has proven useful in select patient populations, an infrequent but vexing problem is what to do when a woman has experienced 1 or more (transvaginal) cerclage “failures.”

With a dearth of well-controlled, randomized data to support the use of cerclage for either history- or physical-exam indications, it is not surprising that we still debate whether the Shirodkar method is superior to the McDonald technique as well as how to best manage a patient when either or both methods previously resulted in an unsatisfactory outcome.

First randomized study to directly compare cerclage techniques

Fortunately, Shennan and colleagues in the United Kingdom have greatly enlarged our knowledge in this area by performing the first well-powered, 3-arm, randomized trial of transabdominal cerclage (TAC) compared with both high and low vaginal cerclage (HVC, LVC).³ They analyzed data for 111 women who were randomly assigned to TAC
(n = 39), HVC (n = 39), or LVC (n = 33).

Interestingly, the investigators chose to not attach conventional eponymous labels to their transvaginal methods, and they do not even provide a reference or detailed description of the surgical methods, telling us instead that, “Techniques used were left to the local clinician’s discretion.” Writing also that HVC cases, like the transabdominal surgeries, were carried out in specialty centers, they implied that additional training was required for the HVC. I inferred that indeed they actually were performing the McDonald and Shirodkar transvaginal methods and with possible by-physician, local modifications.

I am certain that the authors’ results did not surprise proponents of transabdominal cerclage for transvaginal cerclage failures, defined in this trial as prior birth from 14 to 28 weeks’ gestation. Since some clinicians use a more generous definition of cerclage failure (such as birth at less than 34 weeks), this study population was clearly at high risk for poor outcomes; in fact, more than 90% of each group had experienced at least 2 prior mid-trimester losses. As anticipated with randomization, other characteristics were well distributed across the 3 groups.

Continue to: Transabdominal cerclage significantly reduced preterm birth rates...

Transabdominal cerclage significantly reduced preterm birth rates

Using a primary outcome of preterm birth less than 32 weeks, which concentrates neonatal morbidities, the investigators observed an overall 4.5-fold higher rate of preterm birth in the transvaginal cohorts compared with the transabdominal patients (33% and 38% versus 8%, respectively). Comparing the TAC group individually with both LVC and HVC groups, the relative risk of preterm birth was 0.20 compared with the HVC group and 0.23 compared with the LVC group, reflecting an approximate 80% reduction.

Not surprising to me, the investigators observed nearly identical outcomes between the HVC and LVC cohorts, substantiating my bias that the 2 transvaginal methods are similarly effective. Opponents will quickly remind me that the study was not well-powered to detect a clinically significant difference between these 2 groups; touché!

Risks of TAC. We all know that, despite its now-proven benefits, the transabdominal approach is associated with a risk of special complications, including the surgical risks of placement (and removal) of the cerclage, the management of fetal death beyond approximately 14 weeks, and the absolute requisite for hysterotomy/cesarean birth. While serious complications are rare, in the trial by Shennan and colleagues none were recorded in the 39 TAC cases. Nevertheless, for women with no children or only prior early births, the risks seem to be justified; the number needed to treat was less than 4 to prevent 1 birth at less than 32 weeks and was 5.3 to prevent a fetal loss.

TAC is an option for select patients

Given that TAC now can be successfully placed using minimally invasive surgery, either prior to or following conception, this study provides unique level I evidence that should not be discounted and should further be considered in the context of confirming prior cohort studies that suggested a significant benefit. Although specialized training is required and the procedure may involve travel to a specialty center, the weight of clinical data clearly supports the use of TAC.

In summary, based largely on the trial by Shennan and colleagues, women with prior failed vaginal cerclage can and should be counseled regarding the availability of TAC and given the opportunity to weigh the reported risks and benefits. ●

Wiesenfeld HC, Meyn LA, Darville T, et al. A randomized controlled trial of ceftriaxone and doxycycline, with or without metronidazole, for the treatment of acute pelvic inflammatory disease. Clin Infect Dis. February 13, 2020. doi:10.1093/cid/ciaa101.

EXPERT COMMENTARY

Pelvic inflammatory disease remains prevalent among young women and is commonly diagnosed in emergency departments and sexually transmitted disease (STD) clinics. This tubal infection is associated with significant reproductive sequelae, including tubal factor infertility, ectopic pregnancy, and chronic pelvic pain. In addition, these women remain at risk for recurrent PID.

Bacterial vaginosis is present in more than half of women with PID. Not surprisingly, anaerobic microorganisms are more commonly isolated from the upper genital tract of patients with acute PID than either Neisseria gonorrhoeae or Chlamydia trachomatis, yet recommended antimicrobial regimens do not necessarily include antibiotics with an excellent antianaerobic spectrum.

Details of the study

In a randomized, double-blind, placebo-controlled trial, Wiesenfeld and colleagues enrolled women from hospital emergency departments or an STD clinic with symptoms of lower abdominal or pelvic pain associated with pelvic organ tenderness. The 233 study participants were randomly assigned to 2 treatment arms: ceftriaxone, doxycycline, and placebo (n = 117) or ceftriaxone, doxycycline, and metronidazole (n = 116).

Findings. Women treated with metronidazole were less likely to have pelvic organ tenderness a month after enrollment compared with the placebo group (9% vs 20%, respectively). Although the clinical cure rates at 30 days were statistically similar in both arms of the study, those receiving metronidazole had a 97% clinical cure rate while those not treated with metronidazole had a 90% clinical cure rate
(P = .38).

Moreover, the concurrent disorders of bacterial vaginosis and trichomonas vaginitis were more effectively treated in the metronidazole group, and fewer women had positive follow-up endometrial cultures for anaerobic bacteria compared with the placebo group (8% vs 21%, respectively).

The anticipated gastrointestinal adverse effects of a combination doxycycline-and-metronidazole regimen was a significant concern; however, combination therapy was no more likely to cause gastrointestinal adverse effects than doxycycline alone.

Continue to: Study strengths and limitations...

Study strengths and limitations

This well-designed randomized, double-blinded clinical trial was performed by clinical investigators experienced in the clinical diagnosis of PID. The demography of the population and their history of C trachomatis, N gonorrhoeae, plus the concurrent diagnosis of bacterial vaginosis make the diagnosis believable and real world, and these factors contribute to the generalizability of the study results.

However, PID is an imprecise clinical diagnosis (specificity averages 65%) when held to the gold standard of diagnostic laparoscopy to confirm the presence of acute salpingitis. Given the reticence of investigators and clinicians to embark on such an invasive procedure to confirm this diagnosis, endometrial biopsy showing evidence of histologic acute endometritis has been offered as an alternative gold standard. Confirmation of acute endometritis in the trial participants would have enhanced the validity of this study.

This study challenges a long held, but never proven, belief that the combination of doxycycline and metronidazole would be poorly tolerated as a combination antimicrobial regimen. It also further solidifies the role of anaerobic bacteria as major players in the microbial etiology of acute PID. In addition, it appears that treating bacterial vaginosis concurrently may lessen the likelihood of endometrial recolonization with anaerobic bacteria. ●

Wiesenfeld HC, Meyn LA, Darville T, et al. A randomized controlled trial of ceftriaxone and doxycycline, with or without metronidazole, for the treatment of acute pelvic inflammatory disease. Clin Infect Dis. February 13, 2020. doi:10.1093/cid/ciaa101.

EXPERT COMMENTARY

Pelvic inflammatory disease remains prevalent among young women and is commonly diagnosed in emergency departments and sexually transmitted disease (STD) clinics. This tubal infection is associated with significant reproductive sequelae, including tubal factor infertility, ectopic pregnancy, and chronic pelvic pain. In addition, these women remain at risk for recurrent PID.

Bacterial vaginosis is present in more than half of women with PID. Not surprisingly, anaerobic microorganisms are more commonly isolated from the upper genital tract of patients with acute PID than either Neisseria gonorrhoeae or Chlamydia trachomatis, yet recommended antimicrobial regimens do not necessarily include antibiotics with an excellent antianaerobic spectrum.

Details of the study

In a randomized, double-blind, placebo-controlled trial, Wiesenfeld and colleagues enrolled women from hospital emergency departments or an STD clinic with symptoms of lower abdominal or pelvic pain associated with pelvic organ tenderness. The 233 study participants were randomly assigned to 2 treatment arms: ceftriaxone, doxycycline, and placebo (n = 117) or ceftriaxone, doxycycline, and metronidazole (n = 116).

Findings. Women treated with metronidazole were less likely to have pelvic organ tenderness a month after enrollment compared with the placebo group (9% vs 20%, respectively). Although the clinical cure rates at 30 days were statistically similar in both arms of the study, those receiving metronidazole had a 97% clinical cure rate while those not treated with metronidazole had a 90% clinical cure rate
(P = .38).

Moreover, the concurrent disorders of bacterial vaginosis and trichomonas vaginitis were more effectively treated in the metronidazole group, and fewer women had positive follow-up endometrial cultures for anaerobic bacteria compared with the placebo group (8% vs 21%, respectively).

The anticipated gastrointestinal adverse effects of a combination doxycycline-and-metronidazole regimen was a significant concern; however, combination therapy was no more likely to cause gastrointestinal adverse effects than doxycycline alone.

Continue to: Study strengths and limitations...

Study strengths and limitations

This well-designed randomized, double-blinded clinical trial was performed by clinical investigators experienced in the clinical diagnosis of PID. The demography of the population and their history of C trachomatis, N gonorrhoeae, plus the concurrent diagnosis of bacterial vaginosis make the diagnosis believable and real world, and these factors contribute to the generalizability of the study results.

However, PID is an imprecise clinical diagnosis (specificity averages 65%) when held to the gold standard of diagnostic laparoscopy to confirm the presence of acute salpingitis. Given the reticence of investigators and clinicians to embark on such an invasive procedure to confirm this diagnosis, endometrial biopsy showing evidence of histologic acute endometritis has been offered as an alternative gold standard. Confirmation of acute endometritis in the trial participants would have enhanced the validity of this study.

This study challenges a long held, but never proven, belief that the combination of doxycycline and metronidazole would be poorly tolerated as a combination antimicrobial regimen. It also further solidifies the role of anaerobic bacteria as major players in the microbial etiology of acute PID. In addition, it appears that treating bacterial vaginosis concurrently may lessen the likelihood of endometrial recolonization with anaerobic bacteria. ●

Wiesenfeld HC, Meyn LA, Darville T, et al. A randomized controlled trial of ceftriaxone and doxycycline, with or without metronidazole, for the treatment of acute pelvic inflammatory disease. Clin Infect Dis. February 13, 2020. doi:10.1093/cid/ciaa101.

EXPERT COMMENTARY

Pelvic inflammatory disease remains prevalent among young women and is commonly diagnosed in emergency departments and sexually transmitted disease (STD) clinics. This tubal infection is associated with significant reproductive sequelae, including tubal factor infertility, ectopic pregnancy, and chronic pelvic pain. In addition, these women remain at risk for recurrent PID.

Bacterial vaginosis is present in more than half of women with PID. Not surprisingly, anaerobic microorganisms are more commonly isolated from the upper genital tract of patients with acute PID than either Neisseria gonorrhoeae or Chlamydia trachomatis, yet recommended antimicrobial regimens do not necessarily include antibiotics with an excellent antianaerobic spectrum.

Details of the study

In a randomized, double-blind, placebo-controlled trial, Wiesenfeld and colleagues enrolled women from hospital emergency departments or an STD clinic with symptoms of lower abdominal or pelvic pain associated with pelvic organ tenderness. The 233 study participants were randomly assigned to 2 treatment arms: ceftriaxone, doxycycline, and placebo (n = 117) or ceftriaxone, doxycycline, and metronidazole (n = 116).

Findings. Women treated with metronidazole were less likely to have pelvic organ tenderness a month after enrollment compared with the placebo group (9% vs 20%, respectively). Although the clinical cure rates at 30 days were statistically similar in both arms of the study, those receiving metronidazole had a 97% clinical cure rate while those not treated with metronidazole had a 90% clinical cure rate
(P = .38).

Moreover, the concurrent disorders of bacterial vaginosis and trichomonas vaginitis were more effectively treated in the metronidazole group, and fewer women had positive follow-up endometrial cultures for anaerobic bacteria compared with the placebo group (8% vs 21%, respectively).

The anticipated gastrointestinal adverse effects of a combination doxycycline-and-metronidazole regimen was a significant concern; however, combination therapy was no more likely to cause gastrointestinal adverse effects than doxycycline alone.

Continue to: Study strengths and limitations...

Study strengths and limitations

This well-designed randomized, double-blinded clinical trial was performed by clinical investigators experienced in the clinical diagnosis of PID. The demography of the population and their history of C trachomatis, N gonorrhoeae, plus the concurrent diagnosis of bacterial vaginosis make the diagnosis believable and real world, and these factors contribute to the generalizability of the study results.

However, PID is an imprecise clinical diagnosis (specificity averages 65%) when held to the gold standard of diagnostic laparoscopy to confirm the presence of acute salpingitis. Given the reticence of investigators and clinicians to embark on such an invasive procedure to confirm this diagnosis, endometrial biopsy showing evidence of histologic acute endometritis has been offered as an alternative gold standard. Confirmation of acute endometritis in the trial participants would have enhanced the validity of this study.

This study challenges a long held, but never proven, belief that the combination of doxycycline and metronidazole would be poorly tolerated as a combination antimicrobial regimen. It also further solidifies the role of anaerobic bacteria as major players in the microbial etiology of acute PID. In addition, it appears that treating bacterial vaginosis concurrently may lessen the likelihood of endometrial recolonization with anaerobic bacteria. ●

While often compared with the Spanish influenza contagion of 1918, the current COVID-19 pandemic is arguably unprecedented in scale and scope, global reach, and the rate at which it has spread across the world.
 

Unprecedented times

The United States now has the greatest burden of COVID-19 disease worldwide.¹ Although Boston has thus far been spared the full force of the disease’s impact, it is likely only a matter of time before it reaches here. To prepare for the imminent surge, we at Tufts Medical Center defined 4 short-term strategic imperatives to help guide our COVID-19 preparedness. Having a single unified strategy across our organization has helped to maintain focus and consistency in the messaging amidst all of the uncertainty. Our focus areas are outlined below.
 

1 Flatten the curve

This term refers to the use of “social distancing” and community isolation measures to keep the number of disease cases at a manageable level. COVID-19 is spread almost exclusively through contact with contaminated respiratory droplets. While several categories of risk have been described, the US Centers for Disease Control and Prevention (CDC) defines disease “exposure” as face-to-face contact within 6 feet of an infected individual for more than 15 minutes without wearing a mask.² Intervening at all 3 of these touchpoints effectively reduces transmission. Interventions include limiting in-person meetings, increasing the space between individuals (both providers and patients), and routinely using personal protective equipment (PPE).

Another effective strategy is to divide frontline providers into smaller units or teams to limit cross-contamination: the inpatient team versus the outpatient team, the day team versus the night team, the “on” team versus the “off” team. If the infection lays one team low, other providers can step in until they recover and return to work.

Visitor policies should be developed and strictly implemented. Many institutions do allow one support person in labor and delivery (L&D) regardless of the patient’s COVID-19 status, although that person should not be symptomatic or COVID-19 positive. Whether to test all patients and support persons for COVID-19 on arrival at L&D remains controversial.³ At a minimum, these individuals should be screened for symptoms. Although it was a major focus of initial preventative efforts, taking a travel and exposure history is no longer informative as the virus is now endemic and community spread is common.

Initial preventative efforts focused also on high-risk patients, but routine use of PPE for all encounters clearly is more effective because of the high rate of asymptomatic shedding. The virus can survive suspended in the air for up to 2 hours following an aerosol-generating procedure (AGP) and on surfaces for several hours or even days. Practices such as regular handwashing, cleaning of exposed work surfaces, and avoiding face touching should by now be part of our everyday routine.

Institutions throughout the United States have established inpatient COVID-19 units—so-called “dirty” units—with mixed success. As the pandemic spreads and the number of patients with asymptomatic shedding increases, it is harder to determine who is and who is not infected. Cross-contamination has rendered this approach largely ineffective. Whether this will change with the introduction of rapid point-of-care testing remains to be seen.

Continue to: 2 Preserve PPE...

2 Preserve PPE

PPE use is effective in reducing transmission. This includes tier 1 PPE with or without enhanced droplet precaution (surgical mask, eye protection, gloves, yellow gown) and tier 2 PPE (tier 1 plus N95 respirators or powered air-purifying respirators [PAPR]). Given the acute PPE shortage in many parts of the country, appropriate use of PPE is critical to maintain an adequate supply. For example, tier 2 PPE is required only in the setting of an AGP. This includes intubation and, in our determination, the second stage of labor for COVID-19–positive patients and patients under investigation (PUIs); we do not employ tier 2 PPE for all patients in the second stage of labor, although some hospitals endorse this practice.

Creative solutions to the impending PPE shortage abound, such as the use of 3D printers to make face shields and novel techniques to sterilize and reuse N95 respirators.

3 Create capacity

In the absence of effective treatment for COVID-19 and with a vaccine still many months away, supportive care is critical. The pulmonary sequelae with cytokine storm and acute hypoxemia can come on quickly, require urgent mechanical ventilatory support, and take several weeks to resolve.

Our ability to create inpatient capacity to accommodate ill patients, monitor them closely, and intubate early will likely be the most critical driver of the case fatality rate. This requires deferring outpatient visits (or doing them via telemedicine), expanding intensive care unit capabilities (especially ventilator beds), and canceling elective surgeries. What constitutes “elective surgery” is not always clear. Our institution, for example, regards abortion services as essential and not elective, but this is not the case throughout the United States.

Creating capacity also refers to staffing. Where necessary, providers should be retrained and redeployed. This may require emergency credentialing of providers in areas outside their usual clinical practice and permission may be needed from the Accreditation Council for Graduate Medical Education to engage trainees outside their usual duty hours.
 

4 Support and protect your workforce

Everyone is anxious, and people convey their anxiety in different ways. I have found it helpful to acknowledge those feelings and provide a forum for staff to express and share their anxieties. That said, hospitals are not a democracy. While staff members should be encouraged to ask questions and voice their opinions, everyone is expected to follow protocol regarding patient care.

Celebrating small successes and finding creative ways to alleviate the stress and inject humor can help. Most institutions are using electronic conferencing platforms (such as Zoom or Microsoft Teams) to stay in touch and to continue education initiatives through interactive didactic sessions, grand rounds, morbidity and mortality conferences, and e-journal clubs. These are also a great platform for social events, such as w(h)ine and book clubs and virtual karaoke.

Since many ObGyn providers are women, the closure of day-care centers and schools is particularly challenging. Share best practices among your staff on how to address this problem, such as alternating on-call shifts or matching providers needing day care with ‘furloughed’ college students who are looking to keep busy and make a little money.

Continue to: Avoid overcommunicating...

Avoid overcommunicating

Clear, concise, and timely communication is key. This can be challenging given the rapidly evolving science of COVID-19 and the daily barrage of information from both reliable and unreliable sources. Setting up regular online meetings with your faculty 2 or 3 times per week can keep people informed, promote engagement, and boost morale.

If an urgent e-mail announcement is needed, keep the message focused. Highlight only updated information and changes to existing policies and guidelines. And consider adding a brief anecdote to illustrate the staff’s creativity and resilience: a “best catch” story, for example, or a staff member who started a “commit to sit” program (spending time in the room with patients who want company but are not able to have their family in attendance).
 

Look to the future

COVID-19 will pass. Herd immunity will inevitably develop. The question is how quickly and at what cost. Children delivered today are being born into a society already profoundly altered by COVID-19. Some have started to call them Generation C.

Exactly what life will look like at the back end of this pandemic depends on how effectively we leverage this crisis. There are numerous opportunities to change the way we think about health care and educate the next generation of providers. These include increasing the use of telehealth and remote education, redesigning our traditional prenatal care paradigms, and reinforcing the importance of preventive medicine. This is an opportunity to put the “health” back into “health care.”

Look after yourself

Amid all the chaos and uncertainty, do not forget to take care of yourself and your family. Be calm, be kind, and be flexible. Stay safe.

While often compared with the Spanish influenza contagion of 1918, the current COVID-19 pandemic is arguably unprecedented in scale and scope, global reach, and the rate at which it has spread across the world.
 

Unprecedented times

The United States now has the greatest burden of COVID-19 disease worldwide.¹ Although Boston has thus far been spared the full force of the disease’s impact, it is likely only a matter of time before it reaches here. To prepare for the imminent surge, we at Tufts Medical Center defined 4 short-term strategic imperatives to help guide our COVID-19 preparedness. Having a single unified strategy across our organization has helped to maintain focus and consistency in the messaging amidst all of the uncertainty. Our focus areas are outlined below.
 

1 Flatten the curve

This term refers to the use of “social distancing” and community isolation measures to keep the number of disease cases at a manageable level. COVID-19 is spread almost exclusively through contact with contaminated respiratory droplets. While several categories of risk have been described, the US Centers for Disease Control and Prevention (CDC) defines disease “exposure” as face-to-face contact within 6 feet of an infected individual for more than 15 minutes without wearing a mask.² Intervening at all 3 of these touchpoints effectively reduces transmission. Interventions include limiting in-person meetings, increasing the space between individuals (both providers and patients), and routinely using personal protective equipment (PPE).

Another effective strategy is to divide frontline providers into smaller units or teams to limit cross-contamination: the inpatient team versus the outpatient team, the day team versus the night team, the “on” team versus the “off” team. If the infection lays one team low, other providers can step in until they recover and return to work.

Visitor policies should be developed and strictly implemented. Many institutions do allow one support person in labor and delivery (L&D) regardless of the patient’s COVID-19 status, although that person should not be symptomatic or COVID-19 positive. Whether to test all patients and support persons for COVID-19 on arrival at L&D remains controversial.³ At a minimum, these individuals should be screened for symptoms. Although it was a major focus of initial preventative efforts, taking a travel and exposure history is no longer informative as the virus is now endemic and community spread is common.

Initial preventative efforts focused also on high-risk patients, but routine use of PPE for all encounters clearly is more effective because of the high rate of asymptomatic shedding. The virus can survive suspended in the air for up to 2 hours following an aerosol-generating procedure (AGP) and on surfaces for several hours or even days. Practices such as regular handwashing, cleaning of exposed work surfaces, and avoiding face touching should by now be part of our everyday routine.

Institutions throughout the United States have established inpatient COVID-19 units—so-called “dirty” units—with mixed success. As the pandemic spreads and the number of patients with asymptomatic shedding increases, it is harder to determine who is and who is not infected. Cross-contamination has rendered this approach largely ineffective. Whether this will change with the introduction of rapid point-of-care testing remains to be seen.

Continue to: 2 Preserve PPE...

2 Preserve PPE

PPE use is effective in reducing transmission. This includes tier 1 PPE with or without enhanced droplet precaution (surgical mask, eye protection, gloves, yellow gown) and tier 2 PPE (tier 1 plus N95 respirators or powered air-purifying respirators [PAPR]). Given the acute PPE shortage in many parts of the country, appropriate use of PPE is critical to maintain an adequate supply. For example, tier 2 PPE is required only in the setting of an AGP. This includes intubation and, in our determination, the second stage of labor for COVID-19–positive patients and patients under investigation (PUIs); we do not employ tier 2 PPE for all patients in the second stage of labor, although some hospitals endorse this practice.

Creative solutions to the impending PPE shortage abound, such as the use of 3D printers to make face shields and novel techniques to sterilize and reuse N95 respirators.

3 Create capacity

In the absence of effective treatment for COVID-19 and with a vaccine still many months away, supportive care is critical. The pulmonary sequelae with cytokine storm and acute hypoxemia can come on quickly, require urgent mechanical ventilatory support, and take several weeks to resolve.

Our ability to create inpatient capacity to accommodate ill patients, monitor them closely, and intubate early will likely be the most critical driver of the case fatality rate. This requires deferring outpatient visits (or doing them via telemedicine), expanding intensive care unit capabilities (especially ventilator beds), and canceling elective surgeries. What constitutes “elective surgery” is not always clear. Our institution, for example, regards abortion services as essential and not elective, but this is not the case throughout the United States.

Creating capacity also refers to staffing. Where necessary, providers should be retrained and redeployed. This may require emergency credentialing of providers in areas outside their usual clinical practice and permission may be needed from the Accreditation Council for Graduate Medical Education to engage trainees outside their usual duty hours.
 

4 Support and protect your workforce

Everyone is anxious, and people convey their anxiety in different ways. I have found it helpful to acknowledge those feelings and provide a forum for staff to express and share their anxieties. That said, hospitals are not a democracy. While staff members should be encouraged to ask questions and voice their opinions, everyone is expected to follow protocol regarding patient care.

Celebrating small successes and finding creative ways to alleviate the stress and inject humor can help. Most institutions are using electronic conferencing platforms (such as Zoom or Microsoft Teams) to stay in touch and to continue education initiatives through interactive didactic sessions, grand rounds, morbidity and mortality conferences, and e-journal clubs. These are also a great platform for social events, such as w(h)ine and book clubs and virtual karaoke.

Since many ObGyn providers are women, the closure of day-care centers and schools is particularly challenging. Share best practices among your staff on how to address this problem, such as alternating on-call shifts or matching providers needing day care with ‘furloughed’ college students who are looking to keep busy and make a little money.

Continue to: Avoid overcommunicating...

Avoid overcommunicating

Clear, concise, and timely communication is key. This can be challenging given the rapidly evolving science of COVID-19 and the daily barrage of information from both reliable and unreliable sources. Setting up regular online meetings with your faculty 2 or 3 times per week can keep people informed, promote engagement, and boost morale.

If an urgent e-mail announcement is needed, keep the message focused. Highlight only updated information and changes to existing policies and guidelines. And consider adding a brief anecdote to illustrate the staff’s creativity and resilience: a “best catch” story, for example, or a staff member who started a “commit to sit” program (spending time in the room with patients who want company but are not able to have their family in attendance).
 

Look to the future

COVID-19 will pass. Herd immunity will inevitably develop. The question is how quickly and at what cost. Children delivered today are being born into a society already profoundly altered by COVID-19. Some have started to call them Generation C.

Exactly what life will look like at the back end of this pandemic depends on how effectively we leverage this crisis. There are numerous opportunities to change the way we think about health care and educate the next generation of providers. These include increasing the use of telehealth and remote education, redesigning our traditional prenatal care paradigms, and reinforcing the importance of preventive medicine. This is an opportunity to put the “health” back into “health care.”

Look after yourself

Amid all the chaos and uncertainty, do not forget to take care of yourself and your family. Be calm, be kind, and be flexible. Stay safe.

While often compared with the Spanish influenza contagion of 1918, the current COVID-19 pandemic is arguably unprecedented in scale and scope, global reach, and the rate at which it has spread across the world.
 

Unprecedented times

The United States now has the greatest burden of COVID-19 disease worldwide.¹ Although Boston has thus far been spared the full force of the disease’s impact, it is likely only a matter of time before it reaches here. To prepare for the imminent surge, we at Tufts Medical Center defined 4 short-term strategic imperatives to help guide our COVID-19 preparedness. Having a single unified strategy across our organization has helped to maintain focus and consistency in the messaging amidst all of the uncertainty. Our focus areas are outlined below.
 

1 Flatten the curve

This term refers to the use of “social distancing” and community isolation measures to keep the number of disease cases at a manageable level. COVID-19 is spread almost exclusively through contact with contaminated respiratory droplets. While several categories of risk have been described, the US Centers for Disease Control and Prevention (CDC) defines disease “exposure” as face-to-face contact within 6 feet of an infected individual for more than 15 minutes without wearing a mask.² Intervening at all 3 of these touchpoints effectively reduces transmission. Interventions include limiting in-person meetings, increasing the space between individuals (both providers and patients), and routinely using personal protective equipment (PPE).

Another effective strategy is to divide frontline providers into smaller units or teams to limit cross-contamination: the inpatient team versus the outpatient team, the day team versus the night team, the “on” team versus the “off” team. If the infection lays one team low, other providers can step in until they recover and return to work.

Visitor policies should be developed and strictly implemented. Many institutions do allow one support person in labor and delivery (L&D) regardless of the patient’s COVID-19 status, although that person should not be symptomatic or COVID-19 positive. Whether to test all patients and support persons for COVID-19 on arrival at L&D remains controversial.³ At a minimum, these individuals should be screened for symptoms. Although it was a major focus of initial preventative efforts, taking a travel and exposure history is no longer informative as the virus is now endemic and community spread is common.

Initial preventative efforts focused also on high-risk patients, but routine use of PPE for all encounters clearly is more effective because of the high rate of asymptomatic shedding. The virus can survive suspended in the air for up to 2 hours following an aerosol-generating procedure (AGP) and on surfaces for several hours or even days. Practices such as regular handwashing, cleaning of exposed work surfaces, and avoiding face touching should by now be part of our everyday routine.

Institutions throughout the United States have established inpatient COVID-19 units—so-called “dirty” units—with mixed success. As the pandemic spreads and the number of patients with asymptomatic shedding increases, it is harder to determine who is and who is not infected. Cross-contamination has rendered this approach largely ineffective. Whether this will change with the introduction of rapid point-of-care testing remains to be seen.

Continue to: 2 Preserve PPE...

2 Preserve PPE

PPE use is effective in reducing transmission. This includes tier 1 PPE with or without enhanced droplet precaution (surgical mask, eye protection, gloves, yellow gown) and tier 2 PPE (tier 1 plus N95 respirators or powered air-purifying respirators [PAPR]). Given the acute PPE shortage in many parts of the country, appropriate use of PPE is critical to maintain an adequate supply. For example, tier 2 PPE is required only in the setting of an AGP. This includes intubation and, in our determination, the second stage of labor for COVID-19–positive patients and patients under investigation (PUIs); we do not employ tier 2 PPE for all patients in the second stage of labor, although some hospitals endorse this practice.

Creative solutions to the impending PPE shortage abound, such as the use of 3D printers to make face shields and novel techniques to sterilize and reuse N95 respirators.

3 Create capacity

In the absence of effective treatment for COVID-19 and with a vaccine still many months away, supportive care is critical. The pulmonary sequelae with cytokine storm and acute hypoxemia can come on quickly, require urgent mechanical ventilatory support, and take several weeks to resolve.

Our ability to create inpatient capacity to accommodate ill patients, monitor them closely, and intubate early will likely be the most critical driver of the case fatality rate. This requires deferring outpatient visits (or doing them via telemedicine), expanding intensive care unit capabilities (especially ventilator beds), and canceling elective surgeries. What constitutes “elective surgery” is not always clear. Our institution, for example, regards abortion services as essential and not elective, but this is not the case throughout the United States.

Creating capacity also refers to staffing. Where necessary, providers should be retrained and redeployed. This may require emergency credentialing of providers in areas outside their usual clinical practice and permission may be needed from the Accreditation Council for Graduate Medical Education to engage trainees outside their usual duty hours.
 

4 Support and protect your workforce

Everyone is anxious, and people convey their anxiety in different ways. I have found it helpful to acknowledge those feelings and provide a forum for staff to express and share their anxieties. That said, hospitals are not a democracy. While staff members should be encouraged to ask questions and voice their opinions, everyone is expected to follow protocol regarding patient care.

Celebrating small successes and finding creative ways to alleviate the stress and inject humor can help. Most institutions are using electronic conferencing platforms (such as Zoom or Microsoft Teams) to stay in touch and to continue education initiatives through interactive didactic sessions, grand rounds, morbidity and mortality conferences, and e-journal clubs. These are also a great platform for social events, such as w(h)ine and book clubs and virtual karaoke.

Since many ObGyn providers are women, the closure of day-care centers and schools is particularly challenging. Share best practices among your staff on how to address this problem, such as alternating on-call shifts or matching providers needing day care with ‘furloughed’ college students who are looking to keep busy and make a little money.

Continue to: Avoid overcommunicating...

Avoid overcommunicating

Clear, concise, and timely communication is key. This can be challenging given the rapidly evolving science of COVID-19 and the daily barrage of information from both reliable and unreliable sources. Setting up regular online meetings with your faculty 2 or 3 times per week can keep people informed, promote engagement, and boost morale.

If an urgent e-mail announcement is needed, keep the message focused. Highlight only updated information and changes to existing policies and guidelines. And consider adding a brief anecdote to illustrate the staff’s creativity and resilience: a “best catch” story, for example, or a staff member who started a “commit to sit” program (spending time in the room with patients who want company but are not able to have their family in attendance).
 

Look to the future

COVID-19 will pass. Herd immunity will inevitably develop. The question is how quickly and at what cost. Children delivered today are being born into a society already profoundly altered by COVID-19. Some have started to call them Generation C.

Exactly what life will look like at the back end of this pandemic depends on how effectively we leverage this crisis. There are numerous opportunities to change the way we think about health care and educate the next generation of providers. These include increasing the use of telehealth and remote education, redesigning our traditional prenatal care paradigms, and reinforcing the importance of preventive medicine. This is an opportunity to put the “health” back into “health care.”

Look after yourself

Amid all the chaos and uncertainty, do not forget to take care of yourself and your family. Be calm, be kind, and be flexible. Stay safe.

Schlaff WD, Ackerman RT, Al-Hendy A, et al. Elagolix for heavy menstrual bleeding in women with uterine fibroids. N Engl J Med. 2020;382:328-340.

Expert Commentary

Any women’s health care provider is extremely aware of how common uterine fibroids (leiomyomas) are in reproductive-aged women. Bleeding associated with such fibroids is a common source of medical morbidity and reduced quality of life for many patients. The mainstay treatment approach for such patients has been surgical, which over time has become minimally invasive. Finding a nonsurgical treatment for patients with fibroid-associated HMB is of huge importance. The recent failure of the selective progesterone receptor modulator ulipristal acetate to be approved by the US Food and Drug Administration (FDA) was a significant setback to finding an excellent option for medical management. A gonadotropin-releasing hormone (GnRH) antagonist like elagolix could become an incredibly important “arrow in the quiver” of women’s health clinicians.

Details about elagolix

As mentioned, elagolix was FDA approved in 2-dose regimens for the treatment of dysmenorrhea, nonmenstrual pelvic pain, and dyspareunia associated with endometriosis. One would expect that such a GnRH antagonist would reduce or eliminate HMB in patients with fibroids, although formal study had never been undertaken. Previous studies of elagolix had shown the most common adverse reaction to be vasomotor symptoms—hot flashes and night sweats. In addition, the drug shows a dose-dependent decrease in bone mineral density (BMD), although its effect on long-term bone health and future fracture risk is unknown.¹

Study specifics. The current study by Schlaff and colleagues was performed including 3 arms: a placebo arm, an elagolix 300 mg twice daily arm, and a third arm that received elagolix 300 mg twice daily and hormonal “add-back” therapy in the form of estradiol 1 mg and norethindrone acetate 0.5 mg daily. The authors actually report on two phase 3 six-month trials that were identical, double-blind, and randomized in nature. Both trials involved approximately 400 women. About 70% of the study participants overall were black, and the average age was approximately 42 years (range, 18 to 51). At baseline, BMD scores were mostly in the normal range. HMB for inclusion was defined as a volume of more than 80 mL per month.

The primary end point was menstrual blood loss volume less than 80 mL in the final month and at least a 50% reduction in menstrual blood loss from baseline to the final month. In the placebo group, only 9% and 10%, respectively, met these criteria.

Continue to: Results...

Results. In the first study group, 84% of those receiving elagolix alone achieved the primary end point, while the group that received elagolix plus add-back therapy had 69% success.

In the second study, both the elagolix group and the add-back group showed that 77% of patients met the primary end point criteria.

The incidences of hot flashes in the elagolix-alone groups were 64% and 43%, respectively, while with add-back therapy, they were 20% in both trials. In the placebo groups, 9% and 4% of participants reported hot flashes. At 6 months, the elagolix-only groups in both trials lost more BMD than the placebo groups, while BMD loss in both add-back groups was not statistically significant from the placebo groups.

Study strengths

Schlaff and colleagues conducted a very well-designed study. The two phase 3 clinical trials in preparation for drug approval were thorough and well reported. The authors are to be commended for including nearly 70% black women as study participants, since this is a racial group known to be affected by HMB resulting from fibroids.

Another strength was the addition of add-back therapy to the doses of elagolix. Concerns about bone loss from a health perspective and vasomotor symptoms from a quality-of-life perspective are not insignificant with elagolix-alone treatment, and proof that add-back therapy significantly diminishes or attenuates the efficacy of this entity is extremely important.

Schlaff WD, Ackerman RT, Al-Hendy A, et al. Elagolix for heavy menstrual bleeding in women with uterine fibroids. N Engl J Med. 2020;382:328-340.

Expert Commentary

Any women’s health care provider is extremely aware of how common uterine fibroids (leiomyomas) are in reproductive-aged women. Bleeding associated with such fibroids is a common source of medical morbidity and reduced quality of life for many patients. The mainstay treatment approach for such patients has been surgical, which over time has become minimally invasive. Finding a nonsurgical treatment for patients with fibroid-associated HMB is of huge importance. The recent failure of the selective progesterone receptor modulator ulipristal acetate to be approved by the US Food and Drug Administration (FDA) was a significant setback to finding an excellent option for medical management. A gonadotropin-releasing hormone (GnRH) antagonist like elagolix could become an incredibly important “arrow in the quiver” of women’s health clinicians.

Details about elagolix

As mentioned, elagolix was FDA approved in 2-dose regimens for the treatment of dysmenorrhea, nonmenstrual pelvic pain, and dyspareunia associated with endometriosis. One would expect that such a GnRH antagonist would reduce or eliminate HMB in patients with fibroids, although formal study had never been undertaken. Previous studies of elagolix had shown the most common adverse reaction to be vasomotor symptoms—hot flashes and night sweats. In addition, the drug shows a dose-dependent decrease in bone mineral density (BMD), although its effect on long-term bone health and future fracture risk is unknown.¹

Study specifics. The current study by Schlaff and colleagues was performed including 3 arms: a placebo arm, an elagolix 300 mg twice daily arm, and a third arm that received elagolix 300 mg twice daily and hormonal “add-back” therapy in the form of estradiol 1 mg and norethindrone acetate 0.5 mg daily. The authors actually report on two phase 3 six-month trials that were identical, double-blind, and randomized in nature. Both trials involved approximately 400 women. About 70% of the study participants overall were black, and the average age was approximately 42 years (range, 18 to 51). At baseline, BMD scores were mostly in the normal range. HMB for inclusion was defined as a volume of more than 80 mL per month.

The primary end point was menstrual blood loss volume less than 80 mL in the final month and at least a 50% reduction in menstrual blood loss from baseline to the final month. In the placebo group, only 9% and 10%, respectively, met these criteria.

Continue to: Results...

Results. In the first study group, 84% of those receiving elagolix alone achieved the primary end point, while the group that received elagolix plus add-back therapy had 69% success.

In the second study, both the elagolix group and the add-back group showed that 77% of patients met the primary end point criteria.

The incidences of hot flashes in the elagolix-alone groups were 64% and 43%, respectively, while with add-back therapy, they were 20% in both trials. In the placebo groups, 9% and 4% of participants reported hot flashes. At 6 months, the elagolix-only groups in both trials lost more BMD than the placebo groups, while BMD loss in both add-back groups was not statistically significant from the placebo groups.

Study strengths

Schlaff and colleagues conducted a very well-designed study. The two phase 3 clinical trials in preparation for drug approval were thorough and well reported. The authors are to be commended for including nearly 70% black women as study participants, since this is a racial group known to be affected by HMB resulting from fibroids.

Another strength was the addition of add-back therapy to the doses of elagolix. Concerns about bone loss from a health perspective and vasomotor symptoms from a quality-of-life perspective are not insignificant with elagolix-alone treatment, and proof that add-back therapy significantly diminishes or attenuates the efficacy of this entity is extremely important.

Schlaff WD, Ackerman RT, Al-Hendy A, et al. Elagolix for heavy menstrual bleeding in women with uterine fibroids. N Engl J Med. 2020;382:328-340.

Expert Commentary

Any women’s health care provider is extremely aware of how common uterine fibroids (leiomyomas) are in reproductive-aged women. Bleeding associated with such fibroids is a common source of medical morbidity and reduced quality of life for many patients. The mainstay treatment approach for such patients has been surgical, which over time has become minimally invasive. Finding a nonsurgical treatment for patients with fibroid-associated HMB is of huge importance. The recent failure of the selective progesterone receptor modulator ulipristal acetate to be approved by the US Food and Drug Administration (FDA) was a significant setback to finding an excellent option for medical management. A gonadotropin-releasing hormone (GnRH) antagonist like elagolix could become an incredibly important “arrow in the quiver” of women’s health clinicians.

Details about elagolix

As mentioned, elagolix was FDA approved in 2-dose regimens for the treatment of dysmenorrhea, nonmenstrual pelvic pain, and dyspareunia associated with endometriosis. One would expect that such a GnRH antagonist would reduce or eliminate HMB in patients with fibroids, although formal study had never been undertaken. Previous studies of elagolix had shown the most common adverse reaction to be vasomotor symptoms—hot flashes and night sweats. In addition, the drug shows a dose-dependent decrease in bone mineral density (BMD), although its effect on long-term bone health and future fracture risk is unknown.¹

Study specifics. The current study by Schlaff and colleagues was performed including 3 arms: a placebo arm, an elagolix 300 mg twice daily arm, and a third arm that received elagolix 300 mg twice daily and hormonal “add-back” therapy in the form of estradiol 1 mg and norethindrone acetate 0.5 mg daily. The authors actually report on two phase 3 six-month trials that were identical, double-blind, and randomized in nature. Both trials involved approximately 400 women. About 70% of the study participants overall were black, and the average age was approximately 42 years (range, 18 to 51). At baseline, BMD scores were mostly in the normal range. HMB for inclusion was defined as a volume of more than 80 mL per month.

The primary end point was menstrual blood loss volume less than 80 mL in the final month and at least a 50% reduction in menstrual blood loss from baseline to the final month. In the placebo group, only 9% and 10%, respectively, met these criteria.

Continue to: Results...

Results. In the first study group, 84% of those receiving elagolix alone achieved the primary end point, while the group that received elagolix plus add-back therapy had 69% success.

In the second study, both the elagolix group and the add-back group showed that 77% of patients met the primary end point criteria.

The incidences of hot flashes in the elagolix-alone groups were 64% and 43%, respectively, while with add-back therapy, they were 20% in both trials. In the placebo groups, 9% and 4% of participants reported hot flashes. At 6 months, the elagolix-only groups in both trials lost more BMD than the placebo groups, while BMD loss in both add-back groups was not statistically significant from the placebo groups.

Study strengths

Schlaff and colleagues conducted a very well-designed study. The two phase 3 clinical trials in preparation for drug approval were thorough and well reported. The authors are to be commended for including nearly 70% black women as study participants, since this is a racial group known to be affected by HMB resulting from fibroids.

Another strength was the addition of add-back therapy to the doses of elagolix. Concerns about bone loss from a health perspective and vasomotor symptoms from a quality-of-life perspective are not insignificant with elagolix-alone treatment, and proof that add-back therapy significantly diminishes or attenuates the efficacy of this entity is extremely important.

He Y, Zhong J, Zhou W, et al. Four surgical strategies for the treatment of cesarean scar defect: a systematic review and network meta-analysis. J Minim Invasive Gynecol. 2020;27:593-602.

EXPERT COMMENTARY

With the increase in cesarean deliveries performed over the decades, the sequelae of the surgery are now arising. Cesarean scar defects (CSDs) are a complication seen when the endometrium and muscular layers from a prior uterine scar are damaged. This damage in the uterine scar can lead to abnormal uterine bleeding and the implantation of an ectopic pregnancy, which can be life-threatening. Ultrasonography can be used to diagnose this defect, which can appear as a hypoechoic space filled with postmenstrual blood, representing a myometrial tear at the wound site.¹ There are several risk factors for CSD, including multiple cesarean deliveries, cesarean delivery during advanced stages of labor, and uterine incisions near the cervix. Elevated body mass index as well as gestational diabetes also have been found to be associated with inadequate healing of the prior cesarean incision.² Studies have shown that both single- and double-layer closure of the hysterotomy during a cesarean delivery have similar incidences of CSDs.^3,4 There are multiple ways to correct a CSD; however, there is no gold standard that has been identified in the literature.

Details about the study

The study by He and colleagues is a meta-analysis aimed at comparing the treatment of CSDs via laparoscopy, hysteroscopy, combined hysteroscopy and laparoscopy, and vaginal repair. The primary outcome measures were reduction in abnormal uterine bleeding and scar defect depth. A total of 10 studies (n = 858) were reviewed: 4 randomized controlled trials (RCTs) and 6 observational studies. The studies analyzed varied in terms of which techniques were compared.

Patients who underwent uterine scar resection by combined laparoscopy and hysteroscopy had a shorter duration of abnormal uterine bleeding when compared with hysteroscopy alone (standardized mean difference [SMD] = 1.36; 95% confidence interval [CI], 0.37−2.36; P = .007) and vaginal repair (SMD = 1.58; 95% CI, 0.97−2.19; P<.0001). Combined laparoscopic and hysteroscopic technique also was found to reduce the diverticulum depth more than in vaginal repair (SMD = 1.57; 95% CI, 0.54−2.61; P = .003).

Continue to: Study strengths and weaknesses...

Study strengths and weaknesses

This is the first meta-analysis to compare the different surgical techniques to correct a CSD. The authors were able to compare many of the characteristics regarding the routes of repair, including hysteroscopy, laparoscopy, and vaginal. The authors were able to analyze the combined laparoscopic and hysteroscopic approach, which facilitates evaluation of the location and satisfaction of defect repair during the procedure.

Some weaknesses of this study include the limited amount of RCTs available for review. All studies were also from China, where the rate of CSDs is higher. Therefore, the results may not be generalizable to all populations. Given that the included studies were done at different sites, it is difficult to determine surgical expertise and surgical technique. Additionally, the studies analyzed varied by which techniques were compared; therefore, indirect analyses were conducted to compare certain techniques. There was limited follow-up for these patients (anywhere from 3 to 6 months), so long-term data and future pregnancy data are needed to determine the efficacy of these procedures.

He Y, Zhong J, Zhou W, et al. Four surgical strategies for the treatment of cesarean scar defect: a systematic review and network meta-analysis. J Minim Invasive Gynecol. 2020;27:593-602.

EXPERT COMMENTARY

With the increase in cesarean deliveries performed over the decades, the sequelae of the surgery are now arising. Cesarean scar defects (CSDs) are a complication seen when the endometrium and muscular layers from a prior uterine scar are damaged. This damage in the uterine scar can lead to abnormal uterine bleeding and the implantation of an ectopic pregnancy, which can be life-threatening. Ultrasonography can be used to diagnose this defect, which can appear as a hypoechoic space filled with postmenstrual blood, representing a myometrial tear at the wound site.¹ There are several risk factors for CSD, including multiple cesarean deliveries, cesarean delivery during advanced stages of labor, and uterine incisions near the cervix. Elevated body mass index as well as gestational diabetes also have been found to be associated with inadequate healing of the prior cesarean incision.² Studies have shown that both single- and double-layer closure of the hysterotomy during a cesarean delivery have similar incidences of CSDs.^3,4 There are multiple ways to correct a CSD; however, there is no gold standard that has been identified in the literature.

Details about the study

The study by He and colleagues is a meta-analysis aimed at comparing the treatment of CSDs via laparoscopy, hysteroscopy, combined hysteroscopy and laparoscopy, and vaginal repair. The primary outcome measures were reduction in abnormal uterine bleeding and scar defect depth. A total of 10 studies (n = 858) were reviewed: 4 randomized controlled trials (RCTs) and 6 observational studies. The studies analyzed varied in terms of which techniques were compared.

Patients who underwent uterine scar resection by combined laparoscopy and hysteroscopy had a shorter duration of abnormal uterine bleeding when compared with hysteroscopy alone (standardized mean difference [SMD] = 1.36; 95% confidence interval [CI], 0.37−2.36; P = .007) and vaginal repair (SMD = 1.58; 95% CI, 0.97−2.19; P<.0001). Combined laparoscopic and hysteroscopic technique also was found to reduce the diverticulum depth more than in vaginal repair (SMD = 1.57; 95% CI, 0.54−2.61; P = .003).

Continue to: Study strengths and weaknesses...

Study strengths and weaknesses

This is the first meta-analysis to compare the different surgical techniques to correct a CSD. The authors were able to compare many of the characteristics regarding the routes of repair, including hysteroscopy, laparoscopy, and vaginal. The authors were able to analyze the combined laparoscopic and hysteroscopic approach, which facilitates evaluation of the location and satisfaction of defect repair during the procedure.

Some weaknesses of this study include the limited amount of RCTs available for review. All studies were also from China, where the rate of CSDs is higher. Therefore, the results may not be generalizable to all populations. Given that the included studies were done at different sites, it is difficult to determine surgical expertise and surgical technique. Additionally, the studies analyzed varied by which techniques were compared; therefore, indirect analyses were conducted to compare certain techniques. There was limited follow-up for these patients (anywhere from 3 to 6 months), so long-term data and future pregnancy data are needed to determine the efficacy of these procedures.

He Y, Zhong J, Zhou W, et al. Four surgical strategies for the treatment of cesarean scar defect: a systematic review and network meta-analysis. J Minim Invasive Gynecol. 2020;27:593-602.

EXPERT COMMENTARY

With the increase in cesarean deliveries performed over the decades, the sequelae of the surgery are now arising. Cesarean scar defects (CSDs) are a complication seen when the endometrium and muscular layers from a prior uterine scar are damaged. This damage in the uterine scar can lead to abnormal uterine bleeding and the implantation of an ectopic pregnancy, which can be life-threatening. Ultrasonography can be used to diagnose this defect, which can appear as a hypoechoic space filled with postmenstrual blood, representing a myometrial tear at the wound site.¹ There are several risk factors for CSD, including multiple cesarean deliveries, cesarean delivery during advanced stages of labor, and uterine incisions near the cervix. Elevated body mass index as well as gestational diabetes also have been found to be associated with inadequate healing of the prior cesarean incision.² Studies have shown that both single- and double-layer closure of the hysterotomy during a cesarean delivery have similar incidences of CSDs.^3,4 There are multiple ways to correct a CSD; however, there is no gold standard that has been identified in the literature.

Details about the study

The study by He and colleagues is a meta-analysis aimed at comparing the treatment of CSDs via laparoscopy, hysteroscopy, combined hysteroscopy and laparoscopy, and vaginal repair. The primary outcome measures were reduction in abnormal uterine bleeding and scar defect depth. A total of 10 studies (n = 858) were reviewed: 4 randomized controlled trials (RCTs) and 6 observational studies. The studies analyzed varied in terms of which techniques were compared.

Patients who underwent uterine scar resection by combined laparoscopy and hysteroscopy had a shorter duration of abnormal uterine bleeding when compared with hysteroscopy alone (standardized mean difference [SMD] = 1.36; 95% confidence interval [CI], 0.37−2.36; P = .007) and vaginal repair (SMD = 1.58; 95% CI, 0.97−2.19; P<.0001). Combined laparoscopic and hysteroscopic technique also was found to reduce the diverticulum depth more than in vaginal repair (SMD = 1.57; 95% CI, 0.54−2.61; P = .003).

Continue to: Study strengths and weaknesses...

Study strengths and weaknesses

This is the first meta-analysis to compare the different surgical techniques to correct a CSD. The authors were able to compare many of the characteristics regarding the routes of repair, including hysteroscopy, laparoscopy, and vaginal. The authors were able to analyze the combined laparoscopic and hysteroscopic approach, which facilitates evaluation of the location and satisfaction of defect repair during the procedure.

Some weaknesses of this study include the limited amount of RCTs available for review. All studies were also from China, where the rate of CSDs is higher. Therefore, the results may not be generalizable to all populations. Given that the included studies were done at different sites, it is difficult to determine surgical expertise and surgical technique. Additionally, the studies analyzed varied by which techniques were compared; therefore, indirect analyses were conducted to compare certain techniques. There was limited follow-up for these patients (anywhere from 3 to 6 months), so long-term data and future pregnancy data are needed to determine the efficacy of these procedures.

Most J, St Amant M, Hsia DS, et al. Evidence-based recommendations for energy intake in pregnant women with obesity. J Clin Invest. 2019;129:4682-4690.

EXPERT COMMENTARY

In 2009, the Institute of Medicine, now known as the National Academy of Medicine, updated its gestational weight gain guideline. This guideline’s major difference, compared with the 1990 guideline, is a specific weight gain range for women with obesity: 5 to 9 kg, or 11 to 20 lb.¹ This weight gain range was chosen in part because it allows for a minimum weight gain that supports the growth and development of tissues (fetus, placenta, breast, uterus) and fluids (blood volume, intracellular and extracellular fluid), also known as the “fat-free” mass.

Many studies have since shown not only associations between lower-than-guideline-recommended weight gain and improved pregnancy outcomes (for example, reductions in preeclampsia and cesarean deliveries), but also increases in low birth weight for infants of women with obesity.^2,3 Although the weight gain guideline differs based on a woman’s prepregnancy body mass index, the energy requirements, or how many additional calories a woman should consume daily, are the same for all, regardless of weight prior to pregnancy: an increase by 340 to 452 kcal/day in the second and third trimesters.¹

Recently, Most and colleagues challenged this recommendation for energy requirements with results from their prospective observational study of 54 women with obesity during pregnancy.⁴ They aimed to evaluate energy intake with the energy intake-balance method (doubly labeled water and whole-room indirect calorimetry and body composition) according to tests done at 13 to 16 weeks’ gestation and 35 to 37 weeks’ gestation and according to the current National Academy of Medicine gestational weight gain guideline (inadequate, recommended, or excessive weight gain groups).⁴

Details of the study

Women who participated in this study were recruited from the Pennington Biomedical Research Center in Louisiana and were mostly multiparas (57%); about half had a college degree or higher (52%) and 41% were African American. The investigators found that gestational weight gain in their participants was similar to that found in other large epidemiologic studies in that 67% of women had excessive gestational weight gain.⁵

Findings. For women who gained the recommended amount of weight (n = 8), mean (SD) daily energy intake was 2,698 (99) kcal/day and energy expenditure was 2,824 (105) kcal/day. Therefore, to meet the recommended amount of weight gain, these women had a negative energy balance (-125 [52] kcal/day). Women with inadequate weight gain
(n = 10) also had a negative energy balance (-262 [32] kcal/day), but the difference was not significantly different compared with that in the recommended gestational weight gain group (P = .08). By contrast, women with excessive gestational weight gain (n = 36) had a mean (SD) positive energy balance of 186 (29) kcal/day.

Fat-free mass and fat mass weight gains. The body weight gains of the fat-free and fat mass compartments also were compared with linear mixed effect models among the 3 weight gain groups. There were no differences in the amount of fat-free mass gained among the 3 weight gain groups (P>.05), but women with excessive gestational weight gain had significantly higher increases in fat mass compared with the other 2 weight gain groups (P<.001).

Pregnancy outcomes. Although there were no differences in cesarean deliveries or birth weight among the 3 weight gain groups, the study was not powered to detect these differences.

Continue to: Study strengths and limitations...

Study strengths and limitations

It is important to note that this study by Most and colleagues was not a health behavior intervention for gestational weight gain. Women who participated in the study did not receive specific directions or advice on diet or physical activity. Furthermore, the study used the current gestational weight gain guideline as a reference to determine energy intake. As such, findings from this study alone cannot be used to adapt the current gestational weight gain guideline for women with obesity.

The study methods were rigorous in terms of the energy intake measurements, but a larger and more diverse sample size is needed to confirm the study findings.

Most J, St Amant M, Hsia DS, et al. Evidence-based recommendations for energy intake in pregnant women with obesity. J Clin Invest. 2019;129:4682-4690.

EXPERT COMMENTARY

In 2009, the Institute of Medicine, now known as the National Academy of Medicine, updated its gestational weight gain guideline. This guideline’s major difference, compared with the 1990 guideline, is a specific weight gain range for women with obesity: 5 to 9 kg, or 11 to 20 lb.¹ This weight gain range was chosen in part because it allows for a minimum weight gain that supports the growth and development of tissues (fetus, placenta, breast, uterus) and fluids (blood volume, intracellular and extracellular fluid), also known as the “fat-free” mass.

Many studies have since shown not only associations between lower-than-guideline-recommended weight gain and improved pregnancy outcomes (for example, reductions in preeclampsia and cesarean deliveries), but also increases in low birth weight for infants of women with obesity.^2,3 Although the weight gain guideline differs based on a woman’s prepregnancy body mass index, the energy requirements, or how many additional calories a woman should consume daily, are the same for all, regardless of weight prior to pregnancy: an increase by 340 to 452 kcal/day in the second and third trimesters.¹

Recently, Most and colleagues challenged this recommendation for energy requirements with results from their prospective observational study of 54 women with obesity during pregnancy.⁴ They aimed to evaluate energy intake with the energy intake-balance method (doubly labeled water and whole-room indirect calorimetry and body composition) according to tests done at 13 to 16 weeks’ gestation and 35 to 37 weeks’ gestation and according to the current National Academy of Medicine gestational weight gain guideline (inadequate, recommended, or excessive weight gain groups).⁴

Details of the study

Women who participated in this study were recruited from the Pennington Biomedical Research Center in Louisiana and were mostly multiparas (57%); about half had a college degree or higher (52%) and 41% were African American. The investigators found that gestational weight gain in their participants was similar to that found in other large epidemiologic studies in that 67% of women had excessive gestational weight gain.⁵

Findings. For women who gained the recommended amount of weight (n = 8), mean (SD) daily energy intake was 2,698 (99) kcal/day and energy expenditure was 2,824 (105) kcal/day. Therefore, to meet the recommended amount of weight gain, these women had a negative energy balance (-125 [52] kcal/day). Women with inadequate weight gain
(n = 10) also had a negative energy balance (-262 [32] kcal/day), but the difference was not significantly different compared with that in the recommended gestational weight gain group (P = .08). By contrast, women with excessive gestational weight gain (n = 36) had a mean (SD) positive energy balance of 186 (29) kcal/day.

Fat-free mass and fat mass weight gains. The body weight gains of the fat-free and fat mass compartments also were compared with linear mixed effect models among the 3 weight gain groups. There were no differences in the amount of fat-free mass gained among the 3 weight gain groups (P>.05), but women with excessive gestational weight gain had significantly higher increases in fat mass compared with the other 2 weight gain groups (P<.001).

Pregnancy outcomes. Although there were no differences in cesarean deliveries or birth weight among the 3 weight gain groups, the study was not powered to detect these differences.

Continue to: Study strengths and limitations...

Study strengths and limitations

It is important to note that this study by Most and colleagues was not a health behavior intervention for gestational weight gain. Women who participated in the study did not receive specific directions or advice on diet or physical activity. Furthermore, the study used the current gestational weight gain guideline as a reference to determine energy intake. As such, findings from this study alone cannot be used to adapt the current gestational weight gain guideline for women with obesity.

The study methods were rigorous in terms of the energy intake measurements, but a larger and more diverse sample size is needed to confirm the study findings.

Most J, St Amant M, Hsia DS, et al. Evidence-based recommendations for energy intake in pregnant women with obesity. J Clin Invest. 2019;129:4682-4690.

EXPERT COMMENTARY

In 2009, the Institute of Medicine, now known as the National Academy of Medicine, updated its gestational weight gain guideline. This guideline’s major difference, compared with the 1990 guideline, is a specific weight gain range for women with obesity: 5 to 9 kg, or 11 to 20 lb.¹ This weight gain range was chosen in part because it allows for a minimum weight gain that supports the growth and development of tissues (fetus, placenta, breast, uterus) and fluids (blood volume, intracellular and extracellular fluid), also known as the “fat-free” mass.

Many studies have since shown not only associations between lower-than-guideline-recommended weight gain and improved pregnancy outcomes (for example, reductions in preeclampsia and cesarean deliveries), but also increases in low birth weight for infants of women with obesity.^2,3 Although the weight gain guideline differs based on a woman’s prepregnancy body mass index, the energy requirements, or how many additional calories a woman should consume daily, are the same for all, regardless of weight prior to pregnancy: an increase by 340 to 452 kcal/day in the second and third trimesters.¹

Recently, Most and colleagues challenged this recommendation for energy requirements with results from their prospective observational study of 54 women with obesity during pregnancy.⁴ They aimed to evaluate energy intake with the energy intake-balance method (doubly labeled water and whole-room indirect calorimetry and body composition) according to tests done at 13 to 16 weeks’ gestation and 35 to 37 weeks’ gestation and according to the current National Academy of Medicine gestational weight gain guideline (inadequate, recommended, or excessive weight gain groups).⁴

Details of the study

Women who participated in this study were recruited from the Pennington Biomedical Research Center in Louisiana and were mostly multiparas (57%); about half had a college degree or higher (52%) and 41% were African American. The investigators found that gestational weight gain in their participants was similar to that found in other large epidemiologic studies in that 67% of women had excessive gestational weight gain.⁵

Findings. For women who gained the recommended amount of weight (n = 8), mean (SD) daily energy intake was 2,698 (99) kcal/day and energy expenditure was 2,824 (105) kcal/day. Therefore, to meet the recommended amount of weight gain, these women had a negative energy balance (-125 [52] kcal/day). Women with inadequate weight gain
(n = 10) also had a negative energy balance (-262 [32] kcal/day), but the difference was not significantly different compared with that in the recommended gestational weight gain group (P = .08). By contrast, women with excessive gestational weight gain (n = 36) had a mean (SD) positive energy balance of 186 (29) kcal/day.

Fat-free mass and fat mass weight gains. The body weight gains of the fat-free and fat mass compartments also were compared with linear mixed effect models among the 3 weight gain groups. There were no differences in the amount of fat-free mass gained among the 3 weight gain groups (P>.05), but women with excessive gestational weight gain had significantly higher increases in fat mass compared with the other 2 weight gain groups (P<.001).

Pregnancy outcomes. Although there were no differences in cesarean deliveries or birth weight among the 3 weight gain groups, the study was not powered to detect these differences.

Continue to: Study strengths and limitations...

Study strengths and limitations

It is important to note that this study by Most and colleagues was not a health behavior intervention for gestational weight gain. Women who participated in the study did not receive specific directions or advice on diet or physical activity. Furthermore, the study used the current gestational weight gain guideline as a reference to determine energy intake. As such, findings from this study alone cannot be used to adapt the current gestational weight gain guideline for women with obesity.

The study methods were rigorous in terms of the energy intake measurements, but a larger and more diverse sample size is needed to confirm the study findings.