Obstetrics

Investigators from the Stanford Hospital and Clinics in California found that while absolute risk is low, women who have received an infertility diagnosis or who have received fertility treatment are at higher risk of several markers of severe maternal morbidity than women who never received an infertility diagnosis or fertility treatment.¹ The study results were presented at the American Society for Reproductive Medicine (ASRM) 2018 annual meeting (October 6 to 10, Denver, Colorado).

Gaya Murugappan, MD, lead investigator on the study, explained in an interview with OBG Management, “We know that in the last decade or so the rate of maternal morbidity has been rising gradually in the US, and we know that the utilization of fertility technology and the incidence of infertility are also rising.” The retrospective analysis set out to determine if a connection exists.

Methods. The investigators used a large insurance claims database to look at data from 2003 to 2016. They identified a group of infertile women who later conceived without fertility treatment (n=1822 deliveries) and a group of women who received fertility treatment (n=782 deliveries) and compared them with a control group of women who never received an infertility diagnosis or fertility treatment (n=37,944 deliveries). Women who currently or previously had cancer were excluded from the study.

The primary outcome was the number of indicators of severe maternal morbidity that occurred during the 6 months prior to or following delivery.

Findings. Compared with the control group, the women diagnosed with infertility were almost 4 times as likely to experience severe anesthesia complications (0.38% vs 0.11%; odds ratio [OR], 3.83; 95% confidence interval [CI], 1.69–8.70), about twice as likely to experience intraoperative heart failure (0.71% vs 0.31%; OR, 1.88; 95% CI, 1.05–3.34), and more than 3 times as likely to receive a hysterectomy (1.04% vs 0.28%; OR, 3.30; 95% CI, 2.02–5.40).

Similarly, compared with controls, women who had received fertility treatment had an OR of 2.66 for disseminated intravascular coagulation (2.81% vs 0.91%; 95% CI, 1.66–4.24), an OR of 5.17 for shock (0.90% vs 0.15%; 95% CI, 2.21–12.06), an OR of 1.61 for blood transfusions (3.71% vs 1.64%; 95% CI, 1.07–2.42), and an OR of 1.43 for cardiac monitoring (13.17% vs 8.14%; 95% CI, 1.14–1.79).

More research is needed. Dr. Murugappan noted, “I hope that these data help us identify high-risk populations of women so that we can minimize the occurrence of these potentially devastating health outcomes. Women need to be telling their ObGyns that they have a history of infertility and/or fertility treatment. Some women may not want to say that they conceived with donor egg, for example, but that could be a critical element of a patient’s history that an ObGyn should be aware of.”

More study is necessary, she added. For instance, “a study in the future looking at risk of maternal morbidity in patients who are infertile but then who go on to conceive spontaneously. Then we can tease out what is the effect of infertility versus the effect of fertility treatment.”

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Investigators from the Stanford Hospital and Clinics in California found that while absolute risk is low, women who have received an infertility diagnosis or who have received fertility treatment are at higher risk of several markers of severe maternal morbidity than women who never received an infertility diagnosis or fertility treatment.¹ The study results were presented at the American Society for Reproductive Medicine (ASRM) 2018 annual meeting (October 6 to 10, Denver, Colorado).

Gaya Murugappan, MD, lead investigator on the study, explained in an interview with OBG Management, “We know that in the last decade or so the rate of maternal morbidity has been rising gradually in the US, and we know that the utilization of fertility technology and the incidence of infertility are also rising.” The retrospective analysis set out to determine if a connection exists.

Methods. The investigators used a large insurance claims database to look at data from 2003 to 2016. They identified a group of infertile women who later conceived without fertility treatment (n=1822 deliveries) and a group of women who received fertility treatment (n=782 deliveries) and compared them with a control group of women who never received an infertility diagnosis or fertility treatment (n=37,944 deliveries). Women who currently or previously had cancer were excluded from the study.

The primary outcome was the number of indicators of severe maternal morbidity that occurred during the 6 months prior to or following delivery.

Findings. Compared with the control group, the women diagnosed with infertility were almost 4 times as likely to experience severe anesthesia complications (0.38% vs 0.11%; odds ratio [OR], 3.83; 95% confidence interval [CI], 1.69–8.70), about twice as likely to experience intraoperative heart failure (0.71% vs 0.31%; OR, 1.88; 95% CI, 1.05–3.34), and more than 3 times as likely to receive a hysterectomy (1.04% vs 0.28%; OR, 3.30; 95% CI, 2.02–5.40).

Similarly, compared with controls, women who had received fertility treatment had an OR of 2.66 for disseminated intravascular coagulation (2.81% vs 0.91%; 95% CI, 1.66–4.24), an OR of 5.17 for shock (0.90% vs 0.15%; 95% CI, 2.21–12.06), an OR of 1.61 for blood transfusions (3.71% vs 1.64%; 95% CI, 1.07–2.42), and an OR of 1.43 for cardiac monitoring (13.17% vs 8.14%; 95% CI, 1.14–1.79).

More research is needed. Dr. Murugappan noted, “I hope that these data help us identify high-risk populations of women so that we can minimize the occurrence of these potentially devastating health outcomes. Women need to be telling their ObGyns that they have a history of infertility and/or fertility treatment. Some women may not want to say that they conceived with donor egg, for example, but that could be a critical element of a patient’s history that an ObGyn should be aware of.”

More study is necessary, she added. For instance, “a study in the future looking at risk of maternal morbidity in patients who are infertile but then who go on to conceive spontaneously. Then we can tease out what is the effect of infertility versus the effect of fertility treatment.”

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Investigators from the Stanford Hospital and Clinics in California found that while absolute risk is low, women who have received an infertility diagnosis or who have received fertility treatment are at higher risk of several markers of severe maternal morbidity than women who never received an infertility diagnosis or fertility treatment.¹ The study results were presented at the American Society for Reproductive Medicine (ASRM) 2018 annual meeting (October 6 to 10, Denver, Colorado).

Gaya Murugappan, MD, lead investigator on the study, explained in an interview with OBG Management, “We know that in the last decade or so the rate of maternal morbidity has been rising gradually in the US, and we know that the utilization of fertility technology and the incidence of infertility are also rising.” The retrospective analysis set out to determine if a connection exists.

Methods. The investigators used a large insurance claims database to look at data from 2003 to 2016. They identified a group of infertile women who later conceived without fertility treatment (n=1822 deliveries) and a group of women who received fertility treatment (n=782 deliveries) and compared them with a control group of women who never received an infertility diagnosis or fertility treatment (n=37,944 deliveries). Women who currently or previously had cancer were excluded from the study.

The primary outcome was the number of indicators of severe maternal morbidity that occurred during the 6 months prior to or following delivery.

Findings. Compared with the control group, the women diagnosed with infertility were almost 4 times as likely to experience severe anesthesia complications (0.38% vs 0.11%; odds ratio [OR], 3.83; 95% confidence interval [CI], 1.69–8.70), about twice as likely to experience intraoperative heart failure (0.71% vs 0.31%; OR, 1.88; 95% CI, 1.05–3.34), and more than 3 times as likely to receive a hysterectomy (1.04% vs 0.28%; OR, 3.30; 95% CI, 2.02–5.40).

Similarly, compared with controls, women who had received fertility treatment had an OR of 2.66 for disseminated intravascular coagulation (2.81% vs 0.91%; 95% CI, 1.66–4.24), an OR of 5.17 for shock (0.90% vs 0.15%; 95% CI, 2.21–12.06), an OR of 1.61 for blood transfusions (3.71% vs 1.64%; 95% CI, 1.07–2.42), and an OR of 1.43 for cardiac monitoring (13.17% vs 8.14%; 95% CI, 1.14–1.79).

More research is needed. Dr. Murugappan noted, “I hope that these data help us identify high-risk populations of women so that we can minimize the occurrence of these potentially devastating health outcomes. Women need to be telling their ObGyns that they have a history of infertility and/or fertility treatment. Some women may not want to say that they conceived with donor egg, for example, but that could be a critical element of a patient’s history that an ObGyn should be aware of.”

More study is necessary, she added. For instance, “a study in the future looking at risk of maternal morbidity in patients who are infertile but then who go on to conceive spontaneously. Then we can tease out what is the effect of infertility versus the effect of fertility treatment.”

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Unplanned pregnancy among women with epilepsy was associated with twice the risk of spontaneous fetal loss when compared against women with epilepsy who planned their pregnancy, according to recent results from a retrospective study published in JAMA Neurology.

“This analysis adds the finding that unplanned pregnancy may increase the risk of [spontaneous fetal loss] in women with epilepsy and identifies pregnancy planning, maternal age, and interpregnancy interval as significant modifiable variables,” Andrew G. Herzog, MD, of the Harvard Neuroendocrine Unit at Beth Israel Deaconess Medical Center in Wellesley, Mass., and colleagues wrote in their study.

The researchers examined results from a web-based survey completed by 1,144 women in the Epilepsy Birth Control Registry (EBCR) between 2010 and 2014 with data on contraception use, pregnancy history, and antiepileptic drug (AED) treatment. Patients were aged 18-47 years (mean 28.5 years) with 8.7% of the cohort consisting of minority women and 39.8% having household incomes of $25,000 or less.

Pregnancy history data included number of pregnancies, number of planned or unplanned pregnancies, AED type used during pregnancies, pregnancy outcomes such as live birth, induced abortion, and spontaneous fetal loss (SFL), while AED data included categorizing patients into no therapy, monotherapy, and polytherapy groups. AED use was further subdivided into no AED, enzyme-inducing AED, non–enzyme-inducing AED, enzyme-inhibiting AED, glucuronidated AED, and mixed category groups.

Of 794 pregnancies, 530 pregnancies (66.8%) were unplanned and 264 (33.2%) were planned, with 473 live births (59.6%), 141 induced abortions (17.8%), and 180 SFL (22.7%). Among patients who did not have an induced abortion, SFL risk was higher if the pregnancy was unplanned (137 patients, 35.0%), compared with those who planned (43 patients, 16.4%) their pregnancy (risk ratio = 2.14; 95% confidence interval, 1.59-2.90; P less than .001). According to a regression analysis, SFL risk was higher for patients where “planning was entered alone” in unplanned pregnancies (odds ratio = 2.75; 95% CI, 1.87-4.05; P less than .001) as well as when adjusted for AED category, maternal age, and interpregnancy interval (OR = 3.57; 95% CI, 1.54-8.78; P = .003).

There was an association between maternal age (OR = 0.957; 95% CI, 0.928-0.986; P = .02) and risk of SFL, with lower risk seen in the 18- to 27-year-old group (118 patients, 29.5%; RR = 0.57; 95% CI, 0.39-0.84; P less than .004) and 28- to 37-year-old group (44 patients, 20.8%; RR = 0.40; 95% CI, 0.26-0.62; P less than .001), compared with the under-18 group (15 patients, 51.7%). There was also a higher risk of SFL with regard to interpregnancy interval (OR = 2.878; 95% CI, 1.8094-4.5801; P = .008), with a greater risk seen if the interpregnancy interval was under 1 year (56 patients, 45.9%), compared with 1 year (56 patients, 22.8%) or higher (RR = 2.02; 95% CI, 1.49-2.72; P less than .001).

“In view of the finding of increased risk for SFL in unplanned pregnancies in women with epilepsy, and because a history of SFL in women with epilepsy may increase the risk that subsequent live-born offspring will develop epilepsy, the finding warrants prospective investigation with medical record verification of pregnancy outcomes,” Dr. Herzog and his colleagues wrote.

The Epilepsy Foundation and Lundbeck funded the study. Dr. Herzog reports support by grants, and two coauthors received salary support from grants, from the two organizations.

SOURCE: Herzog AG et al. JAMA Neurol. 2018 Oct 15. doi: 10.1001/jamaneurol.2018.3089.

Unplanned pregnancy among women with epilepsy was associated with twice the risk of spontaneous fetal loss when compared against women with epilepsy who planned their pregnancy, according to recent results from a retrospective study published in JAMA Neurology.

“This analysis adds the finding that unplanned pregnancy may increase the risk of [spontaneous fetal loss] in women with epilepsy and identifies pregnancy planning, maternal age, and interpregnancy interval as significant modifiable variables,” Andrew G. Herzog, MD, of the Harvard Neuroendocrine Unit at Beth Israel Deaconess Medical Center in Wellesley, Mass., and colleagues wrote in their study.

The researchers examined results from a web-based survey completed by 1,144 women in the Epilepsy Birth Control Registry (EBCR) between 2010 and 2014 with data on contraception use, pregnancy history, and antiepileptic drug (AED) treatment. Patients were aged 18-47 years (mean 28.5 years) with 8.7% of the cohort consisting of minority women and 39.8% having household incomes of $25,000 or less.

Pregnancy history data included number of pregnancies, number of planned or unplanned pregnancies, AED type used during pregnancies, pregnancy outcomes such as live birth, induced abortion, and spontaneous fetal loss (SFL), while AED data included categorizing patients into no therapy, monotherapy, and polytherapy groups. AED use was further subdivided into no AED, enzyme-inducing AED, non–enzyme-inducing AED, enzyme-inhibiting AED, glucuronidated AED, and mixed category groups.

Of 794 pregnancies, 530 pregnancies (66.8%) were unplanned and 264 (33.2%) were planned, with 473 live births (59.6%), 141 induced abortions (17.8%), and 180 SFL (22.7%). Among patients who did not have an induced abortion, SFL risk was higher if the pregnancy was unplanned (137 patients, 35.0%), compared with those who planned (43 patients, 16.4%) their pregnancy (risk ratio = 2.14; 95% confidence interval, 1.59-2.90; P less than .001). According to a regression analysis, SFL risk was higher for patients where “planning was entered alone” in unplanned pregnancies (odds ratio = 2.75; 95% CI, 1.87-4.05; P less than .001) as well as when adjusted for AED category, maternal age, and interpregnancy interval (OR = 3.57; 95% CI, 1.54-8.78; P = .003).

There was an association between maternal age (OR = 0.957; 95% CI, 0.928-0.986; P = .02) and risk of SFL, with lower risk seen in the 18- to 27-year-old group (118 patients, 29.5%; RR = 0.57; 95% CI, 0.39-0.84; P less than .004) and 28- to 37-year-old group (44 patients, 20.8%; RR = 0.40; 95% CI, 0.26-0.62; P less than .001), compared with the under-18 group (15 patients, 51.7%). There was also a higher risk of SFL with regard to interpregnancy interval (OR = 2.878; 95% CI, 1.8094-4.5801; P = .008), with a greater risk seen if the interpregnancy interval was under 1 year (56 patients, 45.9%), compared with 1 year (56 patients, 22.8%) or higher (RR = 2.02; 95% CI, 1.49-2.72; P less than .001).

“In view of the finding of increased risk for SFL in unplanned pregnancies in women with epilepsy, and because a history of SFL in women with epilepsy may increase the risk that subsequent live-born offspring will develop epilepsy, the finding warrants prospective investigation with medical record verification of pregnancy outcomes,” Dr. Herzog and his colleagues wrote.

The Epilepsy Foundation and Lundbeck funded the study. Dr. Herzog reports support by grants, and two coauthors received salary support from grants, from the two organizations.

SOURCE: Herzog AG et al. JAMA Neurol. 2018 Oct 15. doi: 10.1001/jamaneurol.2018.3089.

Unplanned pregnancy among women with epilepsy was associated with twice the risk of spontaneous fetal loss when compared against women with epilepsy who planned their pregnancy, according to recent results from a retrospective study published in JAMA Neurology.

“This analysis adds the finding that unplanned pregnancy may increase the risk of [spontaneous fetal loss] in women with epilepsy and identifies pregnancy planning, maternal age, and interpregnancy interval as significant modifiable variables,” Andrew G. Herzog, MD, of the Harvard Neuroendocrine Unit at Beth Israel Deaconess Medical Center in Wellesley, Mass., and colleagues wrote in their study.

The researchers examined results from a web-based survey completed by 1,144 women in the Epilepsy Birth Control Registry (EBCR) between 2010 and 2014 with data on contraception use, pregnancy history, and antiepileptic drug (AED) treatment. Patients were aged 18-47 years (mean 28.5 years) with 8.7% of the cohort consisting of minority women and 39.8% having household incomes of $25,000 or less.

Pregnancy history data included number of pregnancies, number of planned or unplanned pregnancies, AED type used during pregnancies, pregnancy outcomes such as live birth, induced abortion, and spontaneous fetal loss (SFL), while AED data included categorizing patients into no therapy, monotherapy, and polytherapy groups. AED use was further subdivided into no AED, enzyme-inducing AED, non–enzyme-inducing AED, enzyme-inhibiting AED, glucuronidated AED, and mixed category groups.

Of 794 pregnancies, 530 pregnancies (66.8%) were unplanned and 264 (33.2%) were planned, with 473 live births (59.6%), 141 induced abortions (17.8%), and 180 SFL (22.7%). Among patients who did not have an induced abortion, SFL risk was higher if the pregnancy was unplanned (137 patients, 35.0%), compared with those who planned (43 patients, 16.4%) their pregnancy (risk ratio = 2.14; 95% confidence interval, 1.59-2.90; P less than .001). According to a regression analysis, SFL risk was higher for patients where “planning was entered alone” in unplanned pregnancies (odds ratio = 2.75; 95% CI, 1.87-4.05; P less than .001) as well as when adjusted for AED category, maternal age, and interpregnancy interval (OR = 3.57; 95% CI, 1.54-8.78; P = .003).

There was an association between maternal age (OR = 0.957; 95% CI, 0.928-0.986; P = .02) and risk of SFL, with lower risk seen in the 18- to 27-year-old group (118 patients, 29.5%; RR = 0.57; 95% CI, 0.39-0.84; P less than .004) and 28- to 37-year-old group (44 patients, 20.8%; RR = 0.40; 95% CI, 0.26-0.62; P less than .001), compared with the under-18 group (15 patients, 51.7%). There was also a higher risk of SFL with regard to interpregnancy interval (OR = 2.878; 95% CI, 1.8094-4.5801; P = .008), with a greater risk seen if the interpregnancy interval was under 1 year (56 patients, 45.9%), compared with 1 year (56 patients, 22.8%) or higher (RR = 2.02; 95% CI, 1.49-2.72; P less than .001).

“In view of the finding of increased risk for SFL in unplanned pregnancies in women with epilepsy, and because a history of SFL in women with epilepsy may increase the risk that subsequent live-born offspring will develop epilepsy, the finding warrants prospective investigation with medical record verification of pregnancy outcomes,” Dr. Herzog and his colleagues wrote.

The Epilepsy Foundation and Lundbeck funded the study. Dr. Herzog reports support by grants, and two coauthors received salary support from grants, from the two organizations.

SOURCE: Herzog AG et al. JAMA Neurol. 2018 Oct 15. doi: 10.1001/jamaneurol.2018.3089.

BARCELONA – Brexanolone injection provided rapid and durable improvement in postpartum depression in an integrated analysis of three pivotal randomized trials collectively known as the Hummingbird trials, Christine Clemson, PhD, reported at the annual congress of the European College of Neuropsychopharmacology.

Bruce Jancin/MDedge News

This was accomplished with a favorable safety experience. The most common treatment-emergent adverse events – dizziness and sleepiness – were roughly twice as common as with placebo in the 247-patient Hummingbird safety analysis.

Because of the urgent unmet need for an effective therapy for postpartum depression (PPD) and early promising clinical trial results, brexanolone was developed under a Breakthrough Therapy designation by the Food and Drug Administration. On Dec. 19, 2018, the agency is expected to respond to SAGE Therapeutics’s application for marketing approval of intravenous brexanolone given as a continuous 60-hour infusion at 90 mcg/kg per hour, according to Dr. Clemson, senior medical director at Cambridge, Mass.–based SAGE Therapeutics, which is developing the therapy.

Brexanolone is a proprietary IV formulation of allopregnanolone, a metabolite of progesterone. The drug’s mechanism of action involves modulation of the neurotransmitter gamma-aminobutyric acid (GABA). The drug binds to both synaptic and extra-synaptic GABA A receptors, thereby increasing receptor functionality.

The decision to target GABA as a novel therapeutic strategy in PPD was based upon translational studies demonstrating that GABA is the chief neuroinhibitory mechanism in the brain, and its actions are mediated mainly by GABA A receptors. Brexanolone’s efficacy is consistent with a theory that the pathogenesis of PPD involves triggers such as inflammation, hormonal fluctuations, or chronic stress, which in some women cause GABA hypofunction, both at the receptors and in terms of tissue GABA levels. This, in turn, leads to an overactive HPA axis and dysregulated neural networks, with resultant PPD, Dr. Clemson explained.

The three Hummingbird clinical trials were double blind, randomized, and placebo controlled. Two were restricted to women with severe PPD. The third and largest focused on moderately affected patients as defined by a baseline Hamilton Depression Scale for Depression (HAM-D) score of 20-25.

The efficacy analysis included 207 patients who received brexanolone at 90 mcg/kg per hour or placebo for 60 hours in an inpatient setting and were followed for 30 days. The primary endpoint was the change in HAM-D total score from baseline to 60 hours. The mean 17-point reduction in the active treatment arm was significantly better than the 12.8-point decrease with placebo. The between-group difference was significant within the first 24 hours and remained so at all time points out to the study’s end at day 30. There was no individual item on the HAM-D in which the drug performed worse than placebo, and there were many in which brexanolone performed significantly better, including depressed mood, anxiety, insomnia, and feelings of guilt.

In terms of the rigorous secondary endpoint of HAM-D remission as defined by a total score of 7 or less, the brexanolone injection significantly outperformed placebo at every time point except for day 30.

There was a 2% rate of serious adverse events in both study arms. These included suicidal ideation, an intentional overdose attempt post discharge, altered state of consciousness, and syncope.

A vastly more convenient once-daily oral formulation of brexanolone is now in phase 3 clinical trials for PPD and major depressive disorder, and in phase 2 for insomnia and bipolar depression.

Elsewhere at the ECNP congress, other investigators from Sage Therapeutics presented for the first time the outcomes of an 89-patient, randomized, double-blind, multicenter, placebo-controlled, phase 2 clinical trial of SAGE-217 for treatment of major depressive disorder.

Participants received a nightly 30-mg dose of the drug or placebo for 2 weeks, with a primary study endpoint being the change in HAM-D total score from baseline to day 15. Patients on the oral GABA A receptor positive modulator averaged a 17.4-point improvement, significantly better than the 10.3-point spread in placebo-treated controls. A statistically significant between-group difference was noted on days 2 through 28. HAM-D remission at day 15 was documented in 64% of the oral brexanolone group, compared with 26% of controls.

Those improvements in depression were accompanied by significant gains in numerous domains of health-related quality of life as assessed via the 36-Item Short Form Health Survey. Indeed, day 15 health-related quality of life scores in the oral brexanolone group approached normative values for the general population.

The studies were funded by SAGE Therapeutics.

[email protected]

BARCELONA – Brexanolone injection provided rapid and durable improvement in postpartum depression in an integrated analysis of three pivotal randomized trials collectively known as the Hummingbird trials, Christine Clemson, PhD, reported at the annual congress of the European College of Neuropsychopharmacology.

Bruce Jancin/MDedge News

This was accomplished with a favorable safety experience. The most common treatment-emergent adverse events – dizziness and sleepiness – were roughly twice as common as with placebo in the 247-patient Hummingbird safety analysis.

Because of the urgent unmet need for an effective therapy for postpartum depression (PPD) and early promising clinical trial results, brexanolone was developed under a Breakthrough Therapy designation by the Food and Drug Administration. On Dec. 19, 2018, the agency is expected to respond to SAGE Therapeutics’s application for marketing approval of intravenous brexanolone given as a continuous 60-hour infusion at 90 mcg/kg per hour, according to Dr. Clemson, senior medical director at Cambridge, Mass.–based SAGE Therapeutics, which is developing the therapy.

Brexanolone is a proprietary IV formulation of allopregnanolone, a metabolite of progesterone. The drug’s mechanism of action involves modulation of the neurotransmitter gamma-aminobutyric acid (GABA). The drug binds to both synaptic and extra-synaptic GABA A receptors, thereby increasing receptor functionality.

The decision to target GABA as a novel therapeutic strategy in PPD was based upon translational studies demonstrating that GABA is the chief neuroinhibitory mechanism in the brain, and its actions are mediated mainly by GABA A receptors. Brexanolone’s efficacy is consistent with a theory that the pathogenesis of PPD involves triggers such as inflammation, hormonal fluctuations, or chronic stress, which in some women cause GABA hypofunction, both at the receptors and in terms of tissue GABA levels. This, in turn, leads to an overactive HPA axis and dysregulated neural networks, with resultant PPD, Dr. Clemson explained.

The three Hummingbird clinical trials were double blind, randomized, and placebo controlled. Two were restricted to women with severe PPD. The third and largest focused on moderately affected patients as defined by a baseline Hamilton Depression Scale for Depression (HAM-D) score of 20-25.

The efficacy analysis included 207 patients who received brexanolone at 90 mcg/kg per hour or placebo for 60 hours in an inpatient setting and were followed for 30 days. The primary endpoint was the change in HAM-D total score from baseline to 60 hours. The mean 17-point reduction in the active treatment arm was significantly better than the 12.8-point decrease with placebo. The between-group difference was significant within the first 24 hours and remained so at all time points out to the study’s end at day 30. There was no individual item on the HAM-D in which the drug performed worse than placebo, and there were many in which brexanolone performed significantly better, including depressed mood, anxiety, insomnia, and feelings of guilt.

In terms of the rigorous secondary endpoint of HAM-D remission as defined by a total score of 7 or less, the brexanolone injection significantly outperformed placebo at every time point except for day 30.

There was a 2% rate of serious adverse events in both study arms. These included suicidal ideation, an intentional overdose attempt post discharge, altered state of consciousness, and syncope.

A vastly more convenient once-daily oral formulation of brexanolone is now in phase 3 clinical trials for PPD and major depressive disorder, and in phase 2 for insomnia and bipolar depression.

Elsewhere at the ECNP congress, other investigators from Sage Therapeutics presented for the first time the outcomes of an 89-patient, randomized, double-blind, multicenter, placebo-controlled, phase 2 clinical trial of SAGE-217 for treatment of major depressive disorder.

Participants received a nightly 30-mg dose of the drug or placebo for 2 weeks, with a primary study endpoint being the change in HAM-D total score from baseline to day 15. Patients on the oral GABA A receptor positive modulator averaged a 17.4-point improvement, significantly better than the 10.3-point spread in placebo-treated controls. A statistically significant between-group difference was noted on days 2 through 28. HAM-D remission at day 15 was documented in 64% of the oral brexanolone group, compared with 26% of controls.

Those improvements in depression were accompanied by significant gains in numerous domains of health-related quality of life as assessed via the 36-Item Short Form Health Survey. Indeed, day 15 health-related quality of life scores in the oral brexanolone group approached normative values for the general population.

The studies were funded by SAGE Therapeutics.

[email protected]

BARCELONA – Brexanolone injection provided rapid and durable improvement in postpartum depression in an integrated analysis of three pivotal randomized trials collectively known as the Hummingbird trials, Christine Clemson, PhD, reported at the annual congress of the European College of Neuropsychopharmacology.

Bruce Jancin/MDedge News

This was accomplished with a favorable safety experience. The most common treatment-emergent adverse events – dizziness and sleepiness – were roughly twice as common as with placebo in the 247-patient Hummingbird safety analysis.

Because of the urgent unmet need for an effective therapy for postpartum depression (PPD) and early promising clinical trial results, brexanolone was developed under a Breakthrough Therapy designation by the Food and Drug Administration. On Dec. 19, 2018, the agency is expected to respond to SAGE Therapeutics’s application for marketing approval of intravenous brexanolone given as a continuous 60-hour infusion at 90 mcg/kg per hour, according to Dr. Clemson, senior medical director at Cambridge, Mass.–based SAGE Therapeutics, which is developing the therapy.

Brexanolone is a proprietary IV formulation of allopregnanolone, a metabolite of progesterone. The drug’s mechanism of action involves modulation of the neurotransmitter gamma-aminobutyric acid (GABA). The drug binds to both synaptic and extra-synaptic GABA A receptors, thereby increasing receptor functionality.

The decision to target GABA as a novel therapeutic strategy in PPD was based upon translational studies demonstrating that GABA is the chief neuroinhibitory mechanism in the brain, and its actions are mediated mainly by GABA A receptors. Brexanolone’s efficacy is consistent with a theory that the pathogenesis of PPD involves triggers such as inflammation, hormonal fluctuations, or chronic stress, which in some women cause GABA hypofunction, both at the receptors and in terms of tissue GABA levels. This, in turn, leads to an overactive HPA axis and dysregulated neural networks, with resultant PPD, Dr. Clemson explained.

The three Hummingbird clinical trials were double blind, randomized, and placebo controlled. Two were restricted to women with severe PPD. The third and largest focused on moderately affected patients as defined by a baseline Hamilton Depression Scale for Depression (HAM-D) score of 20-25.

The efficacy analysis included 207 patients who received brexanolone at 90 mcg/kg per hour or placebo for 60 hours in an inpatient setting and were followed for 30 days. The primary endpoint was the change in HAM-D total score from baseline to 60 hours. The mean 17-point reduction in the active treatment arm was significantly better than the 12.8-point decrease with placebo. The between-group difference was significant within the first 24 hours and remained so at all time points out to the study’s end at day 30. There was no individual item on the HAM-D in which the drug performed worse than placebo, and there were many in which brexanolone performed significantly better, including depressed mood, anxiety, insomnia, and feelings of guilt.

In terms of the rigorous secondary endpoint of HAM-D remission as defined by a total score of 7 or less, the brexanolone injection significantly outperformed placebo at every time point except for day 30.

There was a 2% rate of serious adverse events in both study arms. These included suicidal ideation, an intentional overdose attempt post discharge, altered state of consciousness, and syncope.

A vastly more convenient once-daily oral formulation of brexanolone is now in phase 3 clinical trials for PPD and major depressive disorder, and in phase 2 for insomnia and bipolar depression.

Elsewhere at the ECNP congress, other investigators from Sage Therapeutics presented for the first time the outcomes of an 89-patient, randomized, double-blind, multicenter, placebo-controlled, phase 2 clinical trial of SAGE-217 for treatment of major depressive disorder.

Participants received a nightly 30-mg dose of the drug or placebo for 2 weeks, with a primary study endpoint being the change in HAM-D total score from baseline to day 15. Patients on the oral GABA A receptor positive modulator averaged a 17.4-point improvement, significantly better than the 10.3-point spread in placebo-treated controls. A statistically significant between-group difference was noted on days 2 through 28. HAM-D remission at day 15 was documented in 64% of the oral brexanolone group, compared with 26% of controls.

Those improvements in depression were accompanied by significant gains in numerous domains of health-related quality of life as assessed via the 36-Item Short Form Health Survey. Indeed, day 15 health-related quality of life scores in the oral brexanolone group approached normative values for the general population.

The studies were funded by SAGE Therapeutics.

[email protected]

Citation: Raffaelli B, Neeb L, Israel-Willner, et al. Brain imaging in pregnant women with acute headache. J Neurol. 2018;265(8):1836–1843.

Citation: Raffaelli B, Neeb L, Israel-Willner, et al. Brain imaging in pregnant women with acute headache. J Neurol. 2018;265(8):1836–1843.

Citation: Raffaelli B, Neeb L, Israel-Willner, et al. Brain imaging in pregnant women with acute headache. J Neurol. 2018;265(8):1836–1843.

Delayed pushing during the second stage of labor does not reduce the risk of cesarean delivery and increases the duration of labor without evidence of benefit to mother or baby, according to the results of a randomized trial.

Photodisc/Thinkstock

“The optimal technique for managing maternal pushing during the second stage of labor is unknown,” wrote Alison G. Cahill, MD, of Washington University, St. Louis, and her coauthors, who published their study in JAMA on Oct. 9. “The two most common approaches to the second stage of labor management are to either initiate pushing with uterine contractions once complete cervical dilation occurs (immediate pushing) or to allow for spontaneous descent (delayed pushing),” they noted. “Both approaches are commonly used, and neither is considered the gold standard.”

They addressed this question in the multicenter trial of nulliparous women (mean age, 26.5 years) who, during May 2014 to December 2017, were at or past 37 weeks’ gestation and had received neuraxial analgesia. The primary outcome was the rate of spontaneous vaginal delivery; secondary outcomes included maternal and neonatal morbidity outcomes. When they reached complete cervical dilation, women were randomized to immediate pushing or delayed pushing, in which they were instructed to wait 60 minutes.

The study was terminated after the data and safety monitoring board conducted a planned interim analysis; the analysis found futility in the delayed pushing group and raised concerns about increased morbidity in that group.

Among the 1,031 women in the immediate pushing group, the rate of spontaneous vaginal delivery was 85.9%; the rate was 86.5% among the 1,041 women in the delayed pushing group (P = .67).

The mean duration of the second stage of labor was significantly shorter in the immediate pushing group (102.4 minutes), compared with that seen in the delayed pushing group (134.2 minutes; P less than .001). The mean duration of active pushing was significantly longer in the immediate pushing group (83.7 minutes), compared with that seen in the delayed pushing group (74.5 minutes; P less than .001).

In terms of secondary outcomes, rates of postpartum hemorrhage were lower in the immediate pushing group (2.3%), compared with the rate among those in the delayed pushing group (4%; P = .03). During the second stage of labor, chorioamnionitis was significantly more common among women in the delayed pushing group (9.1%), compared with rate among women in the immediate pushing group (6.7%; P = .005). There was no significant difference between the two groups in the rates of a composite neonatal morbidity outcome (which included birth injury, respiratory distress, and neonatal acidemia), which was 7.3% in the immediate pushing group and 9.9% in the delayed pushing group. There were no neonatal deaths.

Among prespecified exploratory outcomes, the rates of neonatal acidemia and suspected neonatal sepsis were significantly higher in the delayed pushing group, whereas the rate of third-degree perineal lacerations was significantly higher in the immediate pushing group.

“The finding of no effect on spontaneous vaginal delivery for pushing timing during the second stage of labor and the evidence suggesting increased maternal and neonatal complications in the delayed pushing group support the view that women immediately pushing after complete cervical dilation may be preferred because women without neuraxial analgesia reflexively push immediately,” the authors pointed out. Their results, they concluded, “may help inform decisions about the preferred timing of second stage pushing efforts when considered with other maternal and neonatal outcomes.”

They noted that the trial had several limitations, including the unblinded design, which raised the possibility of bias that may have influenced the management of patients or diagnoses.

The authors had no disclosures. The study was supported by a grant from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and by funding from the department of obstetrics and gynecology at Washington University, St. Louis.

SOURCE: Cahill AG et al. JAMA. 2018;320(14):1444-54.

Delayed pushing during the second stage of labor does not reduce the risk of cesarean delivery and increases the duration of labor without evidence of benefit to mother or baby, according to the results of a randomized trial.

Photodisc/Thinkstock

“The optimal technique for managing maternal pushing during the second stage of labor is unknown,” wrote Alison G. Cahill, MD, of Washington University, St. Louis, and her coauthors, who published their study in JAMA on Oct. 9. “The two most common approaches to the second stage of labor management are to either initiate pushing with uterine contractions once complete cervical dilation occurs (immediate pushing) or to allow for spontaneous descent (delayed pushing),” they noted. “Both approaches are commonly used, and neither is considered the gold standard.”

They addressed this question in the multicenter trial of nulliparous women (mean age, 26.5 years) who, during May 2014 to December 2017, were at or past 37 weeks’ gestation and had received neuraxial analgesia. The primary outcome was the rate of spontaneous vaginal delivery; secondary outcomes included maternal and neonatal morbidity outcomes. When they reached complete cervical dilation, women were randomized to immediate pushing or delayed pushing, in which they were instructed to wait 60 minutes.

The study was terminated after the data and safety monitoring board conducted a planned interim analysis; the analysis found futility in the delayed pushing group and raised concerns about increased morbidity in that group.

Among the 1,031 women in the immediate pushing group, the rate of spontaneous vaginal delivery was 85.9%; the rate was 86.5% among the 1,041 women in the delayed pushing group (P = .67).

The mean duration of the second stage of labor was significantly shorter in the immediate pushing group (102.4 minutes), compared with that seen in the delayed pushing group (134.2 minutes; P less than .001). The mean duration of active pushing was significantly longer in the immediate pushing group (83.7 minutes), compared with that seen in the delayed pushing group (74.5 minutes; P less than .001).

In terms of secondary outcomes, rates of postpartum hemorrhage were lower in the immediate pushing group (2.3%), compared with the rate among those in the delayed pushing group (4%; P = .03). During the second stage of labor, chorioamnionitis was significantly more common among women in the delayed pushing group (9.1%), compared with rate among women in the immediate pushing group (6.7%; P = .005). There was no significant difference between the two groups in the rates of a composite neonatal morbidity outcome (which included birth injury, respiratory distress, and neonatal acidemia), which was 7.3% in the immediate pushing group and 9.9% in the delayed pushing group. There were no neonatal deaths.

Among prespecified exploratory outcomes, the rates of neonatal acidemia and suspected neonatal sepsis were significantly higher in the delayed pushing group, whereas the rate of third-degree perineal lacerations was significantly higher in the immediate pushing group.

“The finding of no effect on spontaneous vaginal delivery for pushing timing during the second stage of labor and the evidence suggesting increased maternal and neonatal complications in the delayed pushing group support the view that women immediately pushing after complete cervical dilation may be preferred because women without neuraxial analgesia reflexively push immediately,” the authors pointed out. Their results, they concluded, “may help inform decisions about the preferred timing of second stage pushing efforts when considered with other maternal and neonatal outcomes.”

They noted that the trial had several limitations, including the unblinded design, which raised the possibility of bias that may have influenced the management of patients or diagnoses.

The authors had no disclosures. The study was supported by a grant from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and by funding from the department of obstetrics and gynecology at Washington University, St. Louis.

SOURCE: Cahill AG et al. JAMA. 2018;320(14):1444-54.

Delayed pushing during the second stage of labor does not reduce the risk of cesarean delivery and increases the duration of labor without evidence of benefit to mother or baby, according to the results of a randomized trial.

Photodisc/Thinkstock

“The optimal technique for managing maternal pushing during the second stage of labor is unknown,” wrote Alison G. Cahill, MD, of Washington University, St. Louis, and her coauthors, who published their study in JAMA on Oct. 9. “The two most common approaches to the second stage of labor management are to either initiate pushing with uterine contractions once complete cervical dilation occurs (immediate pushing) or to allow for spontaneous descent (delayed pushing),” they noted. “Both approaches are commonly used, and neither is considered the gold standard.”

They addressed this question in the multicenter trial of nulliparous women (mean age, 26.5 years) who, during May 2014 to December 2017, were at or past 37 weeks’ gestation and had received neuraxial analgesia. The primary outcome was the rate of spontaneous vaginal delivery; secondary outcomes included maternal and neonatal morbidity outcomes. When they reached complete cervical dilation, women were randomized to immediate pushing or delayed pushing, in which they were instructed to wait 60 minutes.

The study was terminated after the data and safety monitoring board conducted a planned interim analysis; the analysis found futility in the delayed pushing group and raised concerns about increased morbidity in that group.

Among the 1,031 women in the immediate pushing group, the rate of spontaneous vaginal delivery was 85.9%; the rate was 86.5% among the 1,041 women in the delayed pushing group (P = .67).

The mean duration of the second stage of labor was significantly shorter in the immediate pushing group (102.4 minutes), compared with that seen in the delayed pushing group (134.2 minutes; P less than .001). The mean duration of active pushing was significantly longer in the immediate pushing group (83.7 minutes), compared with that seen in the delayed pushing group (74.5 minutes; P less than .001).

In terms of secondary outcomes, rates of postpartum hemorrhage were lower in the immediate pushing group (2.3%), compared with the rate among those in the delayed pushing group (4%; P = .03). During the second stage of labor, chorioamnionitis was significantly more common among women in the delayed pushing group (9.1%), compared with rate among women in the immediate pushing group (6.7%; P = .005). There was no significant difference between the two groups in the rates of a composite neonatal morbidity outcome (which included birth injury, respiratory distress, and neonatal acidemia), which was 7.3% in the immediate pushing group and 9.9% in the delayed pushing group. There were no neonatal deaths.

Among prespecified exploratory outcomes, the rates of neonatal acidemia and suspected neonatal sepsis were significantly higher in the delayed pushing group, whereas the rate of third-degree perineal lacerations was significantly higher in the immediate pushing group.

“The finding of no effect on spontaneous vaginal delivery for pushing timing during the second stage of labor and the evidence suggesting increased maternal and neonatal complications in the delayed pushing group support the view that women immediately pushing after complete cervical dilation may be preferred because women without neuraxial analgesia reflexively push immediately,” the authors pointed out. Their results, they concluded, “may help inform decisions about the preferred timing of second stage pushing efforts when considered with other maternal and neonatal outcomes.”

They noted that the trial had several limitations, including the unblinded design, which raised the possibility of bias that may have influenced the management of patients or diagnoses.

The authors had no disclosures. The study was supported by a grant from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and by funding from the department of obstetrics and gynecology at Washington University, St. Louis.

SOURCE: Cahill AG et al. JAMA. 2018;320(14):1444-54.

New data on neonatal screening, protocols for adults and pregnant women, and approaches to genital reconstruction surgery are key elements of the guidelines on the congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency recently updated by the Endocrine Society.

The guidelines are an update to the 2010 Endocrine Society Clinical Practice Guideline on congenital adrenal hyperplasia (CAH) due to steroid 21-hydroxylase deficiency. They were published in The Journal of Clinical Endocrinology and Metabolism.

Richard J. Auchus, MD, PhD, of the University of Michigan, Ann Arbor, and coauthor of the 2018 guidelines, said many of the guidelines remain the same, such as use of neonatal screening. However, neonatal diagnosis methods should use gestational age and birth weight or liquid chromatography–tandem mass spectrometry for secondary screening. The authors also noted that the addition of commercially available serum 21-deoxycortisol measurements, while untested, could potentially help identify CAH carriers.

Changes in genital reconstructive surgery were also addressed in the new guidelines, and a recent systematic review and meta-analysis found a “favorable benefit to risk ratio” for both early and late genital reconstructive surgery. Dr. Auchus said the timing of the surgery remains controversial and that there were “downsides of both approaches.”

“I wish there was a straightforward and perfect solution, but I don’t think there is,” he said in an interview.

Dexamethasone for the prenatal treatment of CAH, and prenatal therapy in general is still regarded as experimental and is not recommended, Dr. Auchus said. The authors encouraged pregnant women who are considering prenatal treatment of CAH to go through Institutional Review Board–approved centers that can obtain outcomes. Pregnant women should not receive a glucocorticoid that traverses the placenta, such as dexamethasone.

Classical CAH should be treated with hydrocortisone maintenance therapy, while nonclassic CAH patients should receive glucocorticoid treatment, such as in cases of early onset and rapid progression of pubarche or bone age in children and overt virilization in adolescents.

Dr. Auchus said the new guidelines have been reorganized so information is easier to find, with recommendations beginning at birth before transitioning into recommendations for childhood and adulthood.

“I think the pediatric endocrinologists are familiar with the management of this disease, but I think a lot of the internal medicine endocrinologists don’t get much training in fellowships, and I think it will be easy for them now to find the information,” Dr. Auchus said. “[I]n the previous set of guidelines, it would’ve been difficult for them to find the information that’s scattered throughout.”

However, Dr. Auchus noted, the guidelines were careful to avoid recommendations of specific levels for analyzing biomarkers for monitoring treatment and specific doses. “[W]e gave some general ideas about ranges: that they should be low, they should be normal, they should be not very high, but it’s okay if it’s a little bit high,” he added.

Also, the evidence for the recommendations is limited to best practice guidelines because of a lack of randomized controlled trials, he noted.

“We certainly do need additional long-term data on these patients,” Dr. Auchus said. “[I]t’s our hope that with some of the networks that have been developed for studying adrenal diseases that we can collect that information in a minimally intrusive way for the benefit of all the current and future patients.”

The guidelines were funded by the Intramural Research Program of the National Institutes of Health. The authors report various personal and organizational financial interests in the form of paid consultancies, researcher support positions, advisory board memberships and investigator roles. See the full study for a complete list of disclosures.

SOURCE: Speiser PW et al. J Clin Endocrinol Metab. 2018 Sep 27. doi: 10.1210/jc.2018-01865.

New data on neonatal screening, protocols for adults and pregnant women, and approaches to genital reconstruction surgery are key elements of the guidelines on the congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency recently updated by the Endocrine Society.

The guidelines are an update to the 2010 Endocrine Society Clinical Practice Guideline on congenital adrenal hyperplasia (CAH) due to steroid 21-hydroxylase deficiency. They were published in The Journal of Clinical Endocrinology and Metabolism.

Richard J. Auchus, MD, PhD, of the University of Michigan, Ann Arbor, and coauthor of the 2018 guidelines, said many of the guidelines remain the same, such as use of neonatal screening. However, neonatal diagnosis methods should use gestational age and birth weight or liquid chromatography–tandem mass spectrometry for secondary screening. The authors also noted that the addition of commercially available serum 21-deoxycortisol measurements, while untested, could potentially help identify CAH carriers.

Changes in genital reconstructive surgery were also addressed in the new guidelines, and a recent systematic review and meta-analysis found a “favorable benefit to risk ratio” for both early and late genital reconstructive surgery. Dr. Auchus said the timing of the surgery remains controversial and that there were “downsides of both approaches.”

“I wish there was a straightforward and perfect solution, but I don’t think there is,” he said in an interview.

Dexamethasone for the prenatal treatment of CAH, and prenatal therapy in general is still regarded as experimental and is not recommended, Dr. Auchus said. The authors encouraged pregnant women who are considering prenatal treatment of CAH to go through Institutional Review Board–approved centers that can obtain outcomes. Pregnant women should not receive a glucocorticoid that traverses the placenta, such as dexamethasone.

Classical CAH should be treated with hydrocortisone maintenance therapy, while nonclassic CAH patients should receive glucocorticoid treatment, such as in cases of early onset and rapid progression of pubarche or bone age in children and overt virilization in adolescents.

Dr. Auchus said the new guidelines have been reorganized so information is easier to find, with recommendations beginning at birth before transitioning into recommendations for childhood and adulthood.

“I think the pediatric endocrinologists are familiar with the management of this disease, but I think a lot of the internal medicine endocrinologists don’t get much training in fellowships, and I think it will be easy for them now to find the information,” Dr. Auchus said. “[I]n the previous set of guidelines, it would’ve been difficult for them to find the information that’s scattered throughout.”

However, Dr. Auchus noted, the guidelines were careful to avoid recommendations of specific levels for analyzing biomarkers for monitoring treatment and specific doses. “[W]e gave some general ideas about ranges: that they should be low, they should be normal, they should be not very high, but it’s okay if it’s a little bit high,” he added.

Also, the evidence for the recommendations is limited to best practice guidelines because of a lack of randomized controlled trials, he noted.

“We certainly do need additional long-term data on these patients,” Dr. Auchus said. “[I]t’s our hope that with some of the networks that have been developed for studying adrenal diseases that we can collect that information in a minimally intrusive way for the benefit of all the current and future patients.”

The guidelines were funded by the Intramural Research Program of the National Institutes of Health. The authors report various personal and organizational financial interests in the form of paid consultancies, researcher support positions, advisory board memberships and investigator roles. See the full study for a complete list of disclosures.

SOURCE: Speiser PW et al. J Clin Endocrinol Metab. 2018 Sep 27. doi: 10.1210/jc.2018-01865.

New data on neonatal screening, protocols for adults and pregnant women, and approaches to genital reconstruction surgery are key elements of the guidelines on the congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency recently updated by the Endocrine Society.

The guidelines are an update to the 2010 Endocrine Society Clinical Practice Guideline on congenital adrenal hyperplasia (CAH) due to steroid 21-hydroxylase deficiency. They were published in The Journal of Clinical Endocrinology and Metabolism.

Richard J. Auchus, MD, PhD, of the University of Michigan, Ann Arbor, and coauthor of the 2018 guidelines, said many of the guidelines remain the same, such as use of neonatal screening. However, neonatal diagnosis methods should use gestational age and birth weight or liquid chromatography–tandem mass spectrometry for secondary screening. The authors also noted that the addition of commercially available serum 21-deoxycortisol measurements, while untested, could potentially help identify CAH carriers.

Changes in genital reconstructive surgery were also addressed in the new guidelines, and a recent systematic review and meta-analysis found a “favorable benefit to risk ratio” for both early and late genital reconstructive surgery. Dr. Auchus said the timing of the surgery remains controversial and that there were “downsides of both approaches.”

“I wish there was a straightforward and perfect solution, but I don’t think there is,” he said in an interview.

Dexamethasone for the prenatal treatment of CAH, and prenatal therapy in general is still regarded as experimental and is not recommended, Dr. Auchus said. The authors encouraged pregnant women who are considering prenatal treatment of CAH to go through Institutional Review Board–approved centers that can obtain outcomes. Pregnant women should not receive a glucocorticoid that traverses the placenta, such as dexamethasone.

Classical CAH should be treated with hydrocortisone maintenance therapy, while nonclassic CAH patients should receive glucocorticoid treatment, such as in cases of early onset and rapid progression of pubarche or bone age in children and overt virilization in adolescents.

Dr. Auchus said the new guidelines have been reorganized so information is easier to find, with recommendations beginning at birth before transitioning into recommendations for childhood and adulthood.

“I think the pediatric endocrinologists are familiar with the management of this disease, but I think a lot of the internal medicine endocrinologists don’t get much training in fellowships, and I think it will be easy for them now to find the information,” Dr. Auchus said. “[I]n the previous set of guidelines, it would’ve been difficult for them to find the information that’s scattered throughout.”

However, Dr. Auchus noted, the guidelines were careful to avoid recommendations of specific levels for analyzing biomarkers for monitoring treatment and specific doses. “[W]e gave some general ideas about ranges: that they should be low, they should be normal, they should be not very high, but it’s okay if it’s a little bit high,” he added.

Also, the evidence for the recommendations is limited to best practice guidelines because of a lack of randomized controlled trials, he noted.

“We certainly do need additional long-term data on these patients,” Dr. Auchus said. “[I]t’s our hope that with some of the networks that have been developed for studying adrenal diseases that we can collect that information in a minimally intrusive way for the benefit of all the current and future patients.”

The guidelines were funded by the Intramural Research Program of the National Institutes of Health. The authors report various personal and organizational financial interests in the form of paid consultancies, researcher support positions, advisory board memberships and investigator roles. See the full study for a complete list of disclosures.

SOURCE: Speiser PW et al. J Clin Endocrinol Metab. 2018 Sep 27. doi: 10.1210/jc.2018-01865.

CHICAGO – A common reason why a women stops breastfeeding is the use of medication her doctor has claimed is unsafe during lactation. But most drugs have little or no effect on an infant’s well-being or milk supply, explained Jenny Eileen Murase, MD, of Palo Alto (Calif.) Foundation Medical Group.

“The bottom line I want you to take away from this [session] is that the vast majority of the medicines you are prescribing as a dermatologist are safe during lactation,” Dr. Murase told attendees at the American Academy of Dermatology summer meeting. “I really want everyone in this room to understand that most of the time, you should not be recommending that a woman is pumping and dumping her milk or stopping breastfeeding because she’s on an agent.”

Dr. Murase, also affiliated with the University of California, San Francisco, provided an overview of drug safety during lactation for major categories of medications that dermatologists prescribe. She recommended that physicians get a copy of Medications and Mother’s Milk by Thomas Hale, PhD, which she considers the best reference for looking up specific drugs. It categorizes drugs as L1 (safest) to L5 (contraindicated), and L2 as “safer,” L3 as “moderately safe,” and L4 as “possibly hazardous.”

Steroids

Contrary to what many believe, prednisone is not contraindicated in breastfeeding, Dr. Murase said. Instead of advising patients to “pump and dump their milk,” she said, “the only recommendation you need to make is that they wait 4 hours after taking the medicine to breastfeed.” For example, a mother can take prednisone before bed and then wake 4 hours later to nurse. Higher doses, such as more than 40 mg daily over long periods, may have the potential to affect growth and development, but more typical doses don’t pose the same risk.

Topical steroids (except for those that are class 1) also are safe to apply directly to the nipple in breastfeeding women, she noted.

Biologics and immunosuppressants

One of the few medications that are contraindicated are topical pimecrolimus and tacrolimus if applied directly to the nipple, since “oral consumption in the infant could be significant,” Dr. Murase said.

Biologics, on the other hand, are not a concern during lactation. “They have low oral bioavailability because of their large molecular size,” and are broken down in the stomach “in a proteolytic environment,” Dr. Murase explained. The CRADLE study, for example, examined the concentration of certolizumab (Cimzia) in mothers’ mature breast milk and found the highest concentration to be just 0.077 mcg/mL, resulting in an average daily infant dose of less than 0.01 mg/kg per day.

Antihistamines and cosmetic topicals

The major antihistamines – brompheniramine, chlorpheniramine, diphenhydramine, hydroxyzine, cetirizine, fexofenadine and loratadine – are likewise safe as L1-L3 drugs. It is preferable to prescribe nonsedating antihistamines, opting for loratadine as the first-line choice. But dermatologists should be reassured that no data support concerns about milk supply reduction from antihistamines, Dr. Murase said.

It’s best to avoid cosmetic topical products, but hydroquinone (L3), topical minoxidil (L2), and botulinum toxin A (L3) do not pose significant risk to the infant. Neither do the anesthetics lidocaine (L2) and epinephrine (L1) for breastfeeding women who need surgery.

Antibiotics

The vast majority of antibiotics are safe for women to use while breastfeeding, but a few notable exceptions exist, including erythromycin.

“People associate erythromycin as safe in lactation because it’s safe in pregnancy, but that’s not the case,” Dr. Murase pointed out. Erythromycin has been linked to pyloric stenosis in newborns and therefore should be avoided in the early months of breastfeeding. In older infants, however, erythromycin becomes an L1 medication.”

Tetracyclines fall into a borderline category. “Tetracyclines would be fine for a complicated infection,” but should not be used for more than 3 weeks, at which point they are regarded as L4, Dr. Murase said. “So long-term use of the tetracyclines should be avoided.”

Aside from these, topical antibiotics are considered safe. Women taking other oral antibiotics should be monitored for gastrointestinal symptoms or allergic responses.

Antifungals

As for antifungals, topicals are safe, and nystatin and clotrimazole are the best first-line options (both L1). Oral antifungals are similarly fine, with griseofulvin, fluconazole, ketoconazole, itraconazole, and terbinafine all classified as L2 and amphotericin B as L3.

If antifungals or antibiotics are being prescribed for a breast fungal infection or for mastitis, Dr. Murase underscored the importance of not stopping breastfeeding.

“The most important thing is that they continue to actually breastfeed on the affected breast that has the staph infection,” she said. She then reiterated that physicians should “reassure new mothers that the majority of oral and topical medications are safe.”

Dr. Murase disclosed serving on the advisory boards of Dermira, UCB, and Genzyme/Sanofi, and she has consulted for Ferndale and UpToDate.

CHICAGO – A common reason why a women stops breastfeeding is the use of medication her doctor has claimed is unsafe during lactation. But most drugs have little or no effect on an infant’s well-being or milk supply, explained Jenny Eileen Murase, MD, of Palo Alto (Calif.) Foundation Medical Group.

“The bottom line I want you to take away from this [session] is that the vast majority of the medicines you are prescribing as a dermatologist are safe during lactation,” Dr. Murase told attendees at the American Academy of Dermatology summer meeting. “I really want everyone in this room to understand that most of the time, you should not be recommending that a woman is pumping and dumping her milk or stopping breastfeeding because she’s on an agent.”

Dr. Murase, also affiliated with the University of California, San Francisco, provided an overview of drug safety during lactation for major categories of medications that dermatologists prescribe. She recommended that physicians get a copy of Medications and Mother’s Milk by Thomas Hale, PhD, which she considers the best reference for looking up specific drugs. It categorizes drugs as L1 (safest) to L5 (contraindicated), and L2 as “safer,” L3 as “moderately safe,” and L4 as “possibly hazardous.”

Steroids

Contrary to what many believe, prednisone is not contraindicated in breastfeeding, Dr. Murase said. Instead of advising patients to “pump and dump their milk,” she said, “the only recommendation you need to make is that they wait 4 hours after taking the medicine to breastfeed.” For example, a mother can take prednisone before bed and then wake 4 hours later to nurse. Higher doses, such as more than 40 mg daily over long periods, may have the potential to affect growth and development, but more typical doses don’t pose the same risk.

Topical steroids (except for those that are class 1) also are safe to apply directly to the nipple in breastfeeding women, she noted.

Biologics and immunosuppressants

One of the few medications that are contraindicated are topical pimecrolimus and tacrolimus if applied directly to the nipple, since “oral consumption in the infant could be significant,” Dr. Murase said.

Biologics, on the other hand, are not a concern during lactation. “They have low oral bioavailability because of their large molecular size,” and are broken down in the stomach “in a proteolytic environment,” Dr. Murase explained. The CRADLE study, for example, examined the concentration of certolizumab (Cimzia) in mothers’ mature breast milk and found the highest concentration to be just 0.077 mcg/mL, resulting in an average daily infant dose of less than 0.01 mg/kg per day.

Antihistamines and cosmetic topicals

The major antihistamines – brompheniramine, chlorpheniramine, diphenhydramine, hydroxyzine, cetirizine, fexofenadine and loratadine – are likewise safe as L1-L3 drugs. It is preferable to prescribe nonsedating antihistamines, opting for loratadine as the first-line choice. But dermatologists should be reassured that no data support concerns about milk supply reduction from antihistamines, Dr. Murase said.

It’s best to avoid cosmetic topical products, but hydroquinone (L3), topical minoxidil (L2), and botulinum toxin A (L3) do not pose significant risk to the infant. Neither do the anesthetics lidocaine (L2) and epinephrine (L1) for breastfeeding women who need surgery.

Antibiotics

The vast majority of antibiotics are safe for women to use while breastfeeding, but a few notable exceptions exist, including erythromycin.

“People associate erythromycin as safe in lactation because it’s safe in pregnancy, but that’s not the case,” Dr. Murase pointed out. Erythromycin has been linked to pyloric stenosis in newborns and therefore should be avoided in the early months of breastfeeding. In older infants, however, erythromycin becomes an L1 medication.”

Tetracyclines fall into a borderline category. “Tetracyclines would be fine for a complicated infection,” but should not be used for more than 3 weeks, at which point they are regarded as L4, Dr. Murase said. “So long-term use of the tetracyclines should be avoided.”

Aside from these, topical antibiotics are considered safe. Women taking other oral antibiotics should be monitored for gastrointestinal symptoms or allergic responses.

Antifungals

As for antifungals, topicals are safe, and nystatin and clotrimazole are the best first-line options (both L1). Oral antifungals are similarly fine, with griseofulvin, fluconazole, ketoconazole, itraconazole, and terbinafine all classified as L2 and amphotericin B as L3.

If antifungals or antibiotics are being prescribed for a breast fungal infection or for mastitis, Dr. Murase underscored the importance of not stopping breastfeeding.

“The most important thing is that they continue to actually breastfeed on the affected breast that has the staph infection,” she said. She then reiterated that physicians should “reassure new mothers that the majority of oral and topical medications are safe.”

Dr. Murase disclosed serving on the advisory boards of Dermira, UCB, and Genzyme/Sanofi, and she has consulted for Ferndale and UpToDate.

CHICAGO – A common reason why a women stops breastfeeding is the use of medication her doctor has claimed is unsafe during lactation. But most drugs have little or no effect on an infant’s well-being or milk supply, explained Jenny Eileen Murase, MD, of Palo Alto (Calif.) Foundation Medical Group.

“The bottom line I want you to take away from this [session] is that the vast majority of the medicines you are prescribing as a dermatologist are safe during lactation,” Dr. Murase told attendees at the American Academy of Dermatology summer meeting. “I really want everyone in this room to understand that most of the time, you should not be recommending that a woman is pumping and dumping her milk or stopping breastfeeding because she’s on an agent.”

Dr. Murase, also affiliated with the University of California, San Francisco, provided an overview of drug safety during lactation for major categories of medications that dermatologists prescribe. She recommended that physicians get a copy of Medications and Mother’s Milk by Thomas Hale, PhD, which she considers the best reference for looking up specific drugs. It categorizes drugs as L1 (safest) to L5 (contraindicated), and L2 as “safer,” L3 as “moderately safe,” and L4 as “possibly hazardous.”

Steroids

Contrary to what many believe, prednisone is not contraindicated in breastfeeding, Dr. Murase said. Instead of advising patients to “pump and dump their milk,” she said, “the only recommendation you need to make is that they wait 4 hours after taking the medicine to breastfeed.” For example, a mother can take prednisone before bed and then wake 4 hours later to nurse. Higher doses, such as more than 40 mg daily over long periods, may have the potential to affect growth and development, but more typical doses don’t pose the same risk.

Topical steroids (except for those that are class 1) also are safe to apply directly to the nipple in breastfeeding women, she noted.

Biologics and immunosuppressants

One of the few medications that are contraindicated are topical pimecrolimus and tacrolimus if applied directly to the nipple, since “oral consumption in the infant could be significant,” Dr. Murase said.

Biologics, on the other hand, are not a concern during lactation. “They have low oral bioavailability because of their large molecular size,” and are broken down in the stomach “in a proteolytic environment,” Dr. Murase explained. The CRADLE study, for example, examined the concentration of certolizumab (Cimzia) in mothers’ mature breast milk and found the highest concentration to be just 0.077 mcg/mL, resulting in an average daily infant dose of less than 0.01 mg/kg per day.

Antihistamines and cosmetic topicals

The major antihistamines – brompheniramine, chlorpheniramine, diphenhydramine, hydroxyzine, cetirizine, fexofenadine and loratadine – are likewise safe as L1-L3 drugs. It is preferable to prescribe nonsedating antihistamines, opting for loratadine as the first-line choice. But dermatologists should be reassured that no data support concerns about milk supply reduction from antihistamines, Dr. Murase said.

It’s best to avoid cosmetic topical products, but hydroquinone (L3), topical minoxidil (L2), and botulinum toxin A (L3) do not pose significant risk to the infant. Neither do the anesthetics lidocaine (L2) and epinephrine (L1) for breastfeeding women who need surgery.

Antibiotics

The vast majority of antibiotics are safe for women to use while breastfeeding, but a few notable exceptions exist, including erythromycin.

“People associate erythromycin as safe in lactation because it’s safe in pregnancy, but that’s not the case,” Dr. Murase pointed out. Erythromycin has been linked to pyloric stenosis in newborns and therefore should be avoided in the early months of breastfeeding. In older infants, however, erythromycin becomes an L1 medication.”

Tetracyclines fall into a borderline category. “Tetracyclines would be fine for a complicated infection,” but should not be used for more than 3 weeks, at which point they are regarded as L4, Dr. Murase said. “So long-term use of the tetracyclines should be avoided.”

Aside from these, topical antibiotics are considered safe. Women taking other oral antibiotics should be monitored for gastrointestinal symptoms or allergic responses.

Antifungals

As for antifungals, topicals are safe, and nystatin and clotrimazole are the best first-line options (both L1). Oral antifungals are similarly fine, with griseofulvin, fluconazole, ketoconazole, itraconazole, and terbinafine all classified as L2 and amphotericin B as L3.

If antifungals or antibiotics are being prescribed for a breast fungal infection or for mastitis, Dr. Murase underscored the importance of not stopping breastfeeding.

“The most important thing is that they continue to actually breastfeed on the affected breast that has the staph infection,” she said. She then reiterated that physicians should “reassure new mothers that the majority of oral and topical medications are safe.”

Dr. Murase disclosed serving on the advisory boards of Dermira, UCB, and Genzyme/Sanofi, and she has consulted for Ferndale and UpToDate.

SAN FRANCISCO – Children exposed to efavirenz in utero were 60% more likely than were those exposed to other antiretrovirals to later develop seizures, eye problems, and other neurologic abnormalities, according to a review of 3,747 children in the Surveillance Monitoring for ART Toxicities (SMARTT) study, an ongoing effort to monitor children exposed to antiretrovirals in the womb.

Overall, 237 children developed a neurologic complication at a mean age of 2; 16 of them were exposed to efavirenz. The study team estimated that 9.6% of children exposed to efavirenz had a neurological complication, versus 6.2% born to women on ART regimens without efavirenz. There was also a nonsignificant trend toward dolutegravir exposure and later neurological abnormalities, which occurred in four of 94 children exposed to the drug. Results were adjusted for maternal smoking and other risk factors.

No other safety signals were detected with the 19 other antiretrovirals analyzed in the study, lead investigator Claudia S. Crowell, MD, assistant professor of pediatrics at the University of Washington, Seattle, said at the annual scientific meeting on infectious diseases.

Efavirenz isn’t used much in the United States because there are more effective options with fewer side effects, but current guidelines recommend that women who are doing well on the drug stay on it while pregnant. Meanwhile, dolutegravir exposure at the time of conception was recently linked to an increased risk of neural tube defects in infants. The drug is commonly used in the United States, and guidelines have been strengthened to highlight the need for contraception use by women taking dolutegravir.

Dr. Crowell said she was surprised by her study’s findings, in part because efavirenz is not a teratogen. The work highlights how important it is to look beyond birth defects and follow children exposed to antiretrovirals for later problems. “We still haven’t determined what the safest regimen is for use in pregnancy,” she said.

Dr. Crowell explained the problem, and what her work means for practice in an interview at the meeting.

[email protected]

SOURCE: Crowell C et al. ID Week 2018 abstract LB5.

SAN FRANCISCO – Children exposed to efavirenz in utero were 60% more likely than were those exposed to other antiretrovirals to later develop seizures, eye problems, and other neurologic abnormalities, according to a review of 3,747 children in the Surveillance Monitoring for ART Toxicities (SMARTT) study, an ongoing effort to monitor children exposed to antiretrovirals in the womb.

Overall, 237 children developed a neurologic complication at a mean age of 2; 16 of them were exposed to efavirenz. The study team estimated that 9.6% of children exposed to efavirenz had a neurological complication, versus 6.2% born to women on ART regimens without efavirenz. There was also a nonsignificant trend toward dolutegravir exposure and later neurological abnormalities, which occurred in four of 94 children exposed to the drug. Results were adjusted for maternal smoking and other risk factors.

No other safety signals were detected with the 19 other antiretrovirals analyzed in the study, lead investigator Claudia S. Crowell, MD, assistant professor of pediatrics at the University of Washington, Seattle, said at the annual scientific meeting on infectious diseases.

Efavirenz isn’t used much in the United States because there are more effective options with fewer side effects, but current guidelines recommend that women who are doing well on the drug stay on it while pregnant. Meanwhile, dolutegravir exposure at the time of conception was recently linked to an increased risk of neural tube defects in infants. The drug is commonly used in the United States, and guidelines have been strengthened to highlight the need for contraception use by women taking dolutegravir.

Dr. Crowell said she was surprised by her study’s findings, in part because efavirenz is not a teratogen. The work highlights how important it is to look beyond birth defects and follow children exposed to antiretrovirals for later problems. “We still haven’t determined what the safest regimen is for use in pregnancy,” she said.

Dr. Crowell explained the problem, and what her work means for practice in an interview at the meeting.

[email protected]

SOURCE: Crowell C et al. ID Week 2018 abstract LB5.

SAN FRANCISCO – Children exposed to efavirenz in utero were 60% more likely than were those exposed to other antiretrovirals to later develop seizures, eye problems, and other neurologic abnormalities, according to a review of 3,747 children in the Surveillance Monitoring for ART Toxicities (SMARTT) study, an ongoing effort to monitor children exposed to antiretrovirals in the womb.

Overall, 237 children developed a neurologic complication at a mean age of 2; 16 of them were exposed to efavirenz. The study team estimated that 9.6% of children exposed to efavirenz had a neurological complication, versus 6.2% born to women on ART regimens without efavirenz. There was also a nonsignificant trend toward dolutegravir exposure and later neurological abnormalities, which occurred in four of 94 children exposed to the drug. Results were adjusted for maternal smoking and other risk factors.

No other safety signals were detected with the 19 other antiretrovirals analyzed in the study, lead investigator Claudia S. Crowell, MD, assistant professor of pediatrics at the University of Washington, Seattle, said at the annual scientific meeting on infectious diseases.

Efavirenz isn’t used much in the United States because there are more effective options with fewer side effects, but current guidelines recommend that women who are doing well on the drug stay on it while pregnant. Meanwhile, dolutegravir exposure at the time of conception was recently linked to an increased risk of neural tube defects in infants. The drug is commonly used in the United States, and guidelines have been strengthened to highlight the need for contraception use by women taking dolutegravir.

Dr. Crowell said she was surprised by her study’s findings, in part because efavirenz is not a teratogen. The work highlights how important it is to look beyond birth defects and follow children exposed to antiretrovirals for later problems. “We still haven’t determined what the safest regimen is for use in pregnancy,” she said.

Dr. Crowell explained the problem, and what her work means for practice in an interview at the meeting.

[email protected]

SOURCE: Crowell C et al. ID Week 2018 abstract LB5.

New evidence provides estimates of the pregnancy rates for American women with multiple sclerosis (MS), their complication rates, and the rates of relapse and disease-modifying drug treatment during different phases before and after pregnancy.

The two new studies, conducted by Maria K. Houtchens, MD, of Brigham and Women’s Hospital and Harvard Medical School, Boston, and her colleagues involved retrospective mining of U.S. commercial health plan data in the IQVIA Real-World Data Adjudicated Claims–U.S. database between Jan. 1, 2006, and June 30, 2015.

The mean age of pregnant women in the nine annual cohorts during that period was just over 32 years for those with MS and just over 29 years for those without. The percentage of women without MS who had a pregnancy-related claim in the database declined from 8.83% in 2006 to 7.75% in 2014 after adjusting for age, region, payer, and Charlson Comorbidity Index score, whereas the percentage increased in women with MS during the same period, from 7.91% to 9.47%. The investigators matched 2,115 women with MS and 2,115 without MS who had live births for a variety of variables and found that women with MS had higher rates of premature labor (31.4% vs. 27.4%; P = .005), infection in pregnancy (13.3% vs. 10.9%; P = .016), maternal cardiovascular disease (3.0% vs. 1.9%; P = .028), anemia or acquired coagulation disorder (2.5% vs. 1.3%; P = .007), neurologic complications in pregnancy (1.6% vs. 0.6%; P = .005), and sexually transmitted diseases in pregnancy (0.4% vs. 0%; P = .045). During labor and delivery, women with MS who had a live birth more often had a claim for acquired damage to the fetus (27.8% vs. 23.5%; P = .002) and congenital fetal malformations (13.2% vs. 10.3%; P = .004) than did women without MS.

In the second study, Dr. Houtchens and two coauthors from the first study of the database reported on a set of 2,158 women who had a live birth during the study period and had 1 year of continuous insurance eligibility before and after pregnancy. The odds for having an MS relapse declined during pregnancy (odds ratio, 0.623; 95% confidence interval, 0.521-0.744), rose during the 6-week postpartum puerperium (OR, 1.710; 95% CI, 1.358-2.152), and leveled off during the last three postpartum quarters to remain at a higher level than before pregnancy (OR, 1.216; 95% CI, 1.052-1.406). Disease-modifying drug treatment followed the same pattern with 20% using it before pregnancy, dropping to about 2% in the second trimester, and peaking in about a quarter of all patients 9-12 months post partum.

[email protected]

SOURCES: Houtchens MK et al. Neurology. 2018 Sep 28. doi: 10.1212/WNL.0000000000006382; Houtchens MK et al. Neurology. 2018 Sep 28. doi: 10.1212/WNL.0000000000006384.

New evidence provides estimates of the pregnancy rates for American women with multiple sclerosis (MS), their complication rates, and the rates of relapse and disease-modifying drug treatment during different phases before and after pregnancy.

The two new studies, conducted by Maria K. Houtchens, MD, of Brigham and Women’s Hospital and Harvard Medical School, Boston, and her colleagues involved retrospective mining of U.S. commercial health plan data in the IQVIA Real-World Data Adjudicated Claims–U.S. database between Jan. 1, 2006, and June 30, 2015.

The mean age of pregnant women in the nine annual cohorts during that period was just over 32 years for those with MS and just over 29 years for those without. The percentage of women without MS who had a pregnancy-related claim in the database declined from 8.83% in 2006 to 7.75% in 2014 after adjusting for age, region, payer, and Charlson Comorbidity Index score, whereas the percentage increased in women with MS during the same period, from 7.91% to 9.47%. The investigators matched 2,115 women with MS and 2,115 without MS who had live births for a variety of variables and found that women with MS had higher rates of premature labor (31.4% vs. 27.4%; P = .005), infection in pregnancy (13.3% vs. 10.9%; P = .016), maternal cardiovascular disease (3.0% vs. 1.9%; P = .028), anemia or acquired coagulation disorder (2.5% vs. 1.3%; P = .007), neurologic complications in pregnancy (1.6% vs. 0.6%; P = .005), and sexually transmitted diseases in pregnancy (0.4% vs. 0%; P = .045). During labor and delivery, women with MS who had a live birth more often had a claim for acquired damage to the fetus (27.8% vs. 23.5%; P = .002) and congenital fetal malformations (13.2% vs. 10.3%; P = .004) than did women without MS.

In the second study, Dr. Houtchens and two coauthors from the first study of the database reported on a set of 2,158 women who had a live birth during the study period and had 1 year of continuous insurance eligibility before and after pregnancy. The odds for having an MS relapse declined during pregnancy (odds ratio, 0.623; 95% confidence interval, 0.521-0.744), rose during the 6-week postpartum puerperium (OR, 1.710; 95% CI, 1.358-2.152), and leveled off during the last three postpartum quarters to remain at a higher level than before pregnancy (OR, 1.216; 95% CI, 1.052-1.406). Disease-modifying drug treatment followed the same pattern with 20% using it before pregnancy, dropping to about 2% in the second trimester, and peaking in about a quarter of all patients 9-12 months post partum.

[email protected]

SOURCES: Houtchens MK et al. Neurology. 2018 Sep 28. doi: 10.1212/WNL.0000000000006382; Houtchens MK et al. Neurology. 2018 Sep 28. doi: 10.1212/WNL.0000000000006384.

New evidence provides estimates of the pregnancy rates for American women with multiple sclerosis (MS), their complication rates, and the rates of relapse and disease-modifying drug treatment during different phases before and after pregnancy.

The two new studies, conducted by Maria K. Houtchens, MD, of Brigham and Women’s Hospital and Harvard Medical School, Boston, and her colleagues involved retrospective mining of U.S. commercial health plan data in the IQVIA Real-World Data Adjudicated Claims–U.S. database between Jan. 1, 2006, and June 30, 2015.

The mean age of pregnant women in the nine annual cohorts during that period was just over 32 years for those with MS and just over 29 years for those without. The percentage of women without MS who had a pregnancy-related claim in the database declined from 8.83% in 2006 to 7.75% in 2014 after adjusting for age, region, payer, and Charlson Comorbidity Index score, whereas the percentage increased in women with MS during the same period, from 7.91% to 9.47%. The investigators matched 2,115 women with MS and 2,115 without MS who had live births for a variety of variables and found that women with MS had higher rates of premature labor (31.4% vs. 27.4%; P = .005), infection in pregnancy (13.3% vs. 10.9%; P = .016), maternal cardiovascular disease (3.0% vs. 1.9%; P = .028), anemia or acquired coagulation disorder (2.5% vs. 1.3%; P = .007), neurologic complications in pregnancy (1.6% vs. 0.6%; P = .005), and sexually transmitted diseases in pregnancy (0.4% vs. 0%; P = .045). During labor and delivery, women with MS who had a live birth more often had a claim for acquired damage to the fetus (27.8% vs. 23.5%; P = .002) and congenital fetal malformations (13.2% vs. 10.3%; P = .004) than did women without MS.

In the second study, Dr. Houtchens and two coauthors from the first study of the database reported on a set of 2,158 women who had a live birth during the study period and had 1 year of continuous insurance eligibility before and after pregnancy. The odds for having an MS relapse declined during pregnancy (odds ratio, 0.623; 95% confidence interval, 0.521-0.744), rose during the 6-week postpartum puerperium (OR, 1.710; 95% CI, 1.358-2.152), and leveled off during the last three postpartum quarters to remain at a higher level than before pregnancy (OR, 1.216; 95% CI, 1.052-1.406). Disease-modifying drug treatment followed the same pattern with 20% using it before pregnancy, dropping to about 2% in the second trimester, and peaking in about a quarter of all patients 9-12 months post partum.

[email protected]

SOURCES: Houtchens MK et al. Neurology. 2018 Sep 28. doi: 10.1212/WNL.0000000000006382; Houtchens MK et al. Neurology. 2018 Sep 28. doi: 10.1212/WNL.0000000000006384.

SAN FRANCISCO – Influenza season is upon us, and Helen Chu, MD, MPH, is here at ID Week 2018 to talk vaccines, especially for pregnant women.

They are at greater risk for more severe illness, and influenza can lead to adverse outcomes in infants. The good news is that recent studies have shown that flu vaccines are safe and effective in pregnant women.

The bad news is that many women are hesitant to be vaccinated out of concerns over safety, in a trend that reflects broader societal worries over vaccination, said Dr. Chu, of the University of Washington, Seattle. In a video interview at an annual scientific meeting on infectious diseases, Dr. Chu advised steps to ensure that pregnant women are aware of the safety and efficacy of flu vaccines, and the benefits to the infant who acquires immunity through the mother. It’s also a good idea to have vaccine on hand to be able to offer it immediately during an office visit.

SAN FRANCISCO – Influenza season is upon us, and Helen Chu, MD, MPH, is here at ID Week 2018 to talk vaccines, especially for pregnant women.

They are at greater risk for more severe illness, and influenza can lead to adverse outcomes in infants. The good news is that recent studies have shown that flu vaccines are safe and effective in pregnant women.

The bad news is that many women are hesitant to be vaccinated out of concerns over safety, in a trend that reflects broader societal worries over vaccination, said Dr. Chu, of the University of Washington, Seattle. In a video interview at an annual scientific meeting on infectious diseases, Dr. Chu advised steps to ensure that pregnant women are aware of the safety and efficacy of flu vaccines, and the benefits to the infant who acquires immunity through the mother. It’s also a good idea to have vaccine on hand to be able to offer it immediately during an office visit.

SAN FRANCISCO – Influenza season is upon us, and Helen Chu, MD, MPH, is here at ID Week 2018 to talk vaccines, especially for pregnant women.

They are at greater risk for more severe illness, and influenza can lead to adverse outcomes in infants. The good news is that recent studies have shown that flu vaccines are safe and effective in pregnant women.

The bad news is that many women are hesitant to be vaccinated out of concerns over safety, in a trend that reflects broader societal worries over vaccination, said Dr. Chu, of the University of Washington, Seattle. In a video interview at an annual scientific meeting on infectious diseases, Dr. Chu advised steps to ensure that pregnant women are aware of the safety and efficacy of flu vaccines, and the benefits to the infant who acquires immunity through the mother. It’s also a good idea to have vaccine on hand to be able to offer it immediately during an office visit.