Risk of Autism after Prenatal Topiramate, Valproate, or Lamotrigine Exposure.

BACKGROUND: Maternal use of valproate during pregnancy has been associated with an increased risk of neurodevelopmental disorders in children. Although most studies of other antiseizure medications have not shown increased risks of these disorders, there are limited and conflicting data regarding the risk of autism spectrum disorder associated with maternal topiramate use. METHODS: We identified a population-based cohort of pregnant women and their children within two health care utilization databases in the United States, with data from 2000 through 2020. Exposure to specific antiseizure medications was defined on the basis of prescription fills from gestational week 19 until delivery. Children who had been exposed to topiramate during the second half of pregnancy were compared with those unexposed to any antiseizure medication during pregnancy with respect to the risk of autism spectrum disorder. Valproate was used as a positive control, and lamotrigine was used as a negative control. RESULTS: The estimated cumulative incidence of autism spectrum disorder at 8 years of age was 1.9% for the full population of children who had not been exposed to antiseizure medication (4,199,796 children). With restriction to children born to mothers with epilepsy, the incidence was 4.2% with no exposure to antiseizure medication (8815 children), 6.2% with exposure to topiramate (1030 children), 10.5% with exposure to valproate (800 children), and 4.1% with exposure to lamotrigine (4205 children). Propensity score-adjusted hazard ratios in a comparison with no exposure to antiseizure medication were 0.96 (95% confidence interval [CI], 0.56 to 1.65) for exposure to topiramate, 2.67 (95% CI, 1.69 to 4.20) for exposure to valproate, and 1.00 (95% CI, 0.69 to 1.46) for exposure to lamotrigine. CONCLUSIONS: The incidence of autism spectrum disorder was higher among children prenatally exposed to the studied antiseizure medications than in the general population. However, after adjustment for indication and other confounders, the association was substantially attenuated for topiramate and lamotrigine, whereas an increased risk remained for valproate. (Funded by the National Institute of Mental Health.).

Depression in Persons With Epilepsy: Lessons From Case Review.

BACKGROUND: Major depressive disorder is highly prevalent among persons with epilepsy (PWEs). Between 30% and 50% of PWEs suffer from depression. Many factors contribute to this prevalence, including the psychosocial impact of the diagnosis, restrictions on driving and certain types of work, and adverse effects associated with antiseizure medications. Without proper treatment, depressed PWEs have increased risks for suicide, strained relationships, lowered seizure control, and impairment in functioning. Our objective was to use the existing literature and insights from our experience in treating depression and anxiety in PWEs within an academic mood disorders center. We aimed to provide practical guidance for health care professionals who treat depression in this population. METHODS: Persons with epilepsy and depression were identified by their treating psychiatrists. Their electronic health records were reviewed and compiled for this report, with a total of 12 included in this review. Records were reviewed regarding antiseizure medications, psychotropic medications, light therapy, psychotherapy, other interventions, and treatment response. RESULTS: Based on our review of literature, as well as review of cases of individuals with epilepsy and comorbid psychiatric conditions, we recommend a step-wise evidence-based approach of optimizing psychiatric medication doses, augmenting with additional medication and/or implementing nonpharmacological interventions such as light therapy and psychotherapy. CONCLUSIONS: In PWEs, improvement in depression, other psychiatric symptoms, and function are the goals of drug and nondrug interventions. Depression care has the potential to significantly improve the quality of life of PWEs and reduce both morbidity and mortality.

Concentrations of Fluoxetine Enantiomers Decline During Pregnancy and Increase After Birth.

RATIONALE: Few studies of the effect of the dynamic physiologic changes during pregnancy on plasma concentrations of fluoxetine (FLX) have been published. OBJECTIVES: We determined the change in concentration to dose (C/D) ratios of R- and S-FLX and R- and S-norfluoxetine monthly during pregnancy and postpartum, assessed their relationships to cytochrome P450 (CYP) 2D6 and CYP2C9 metabolizer phenotypes, and evaluated the course of their depressive and anxiety symptoms. METHODS: In this observational study, 10 FLX-treated pregnant individuals provided blood samples at steady state every 4 weeks during pregnancy and once postpartum for measurement of plasma FLX and norfluoxetine enantiomer concentrations. Participants were genotyped for variants in CYP2C9 and CYP2D6 using commercial assays with Taqman probes. At each assessment, depressive and anxiety symptoms were quantified. RESULTS: The C/D ratios of all FLX and norfluoxetine enantiomers, and the active moiety, decreased steadily through pregnancy and rose after birth. In the final trimester, the mean C/D ratio of the active moiety was 24.9% lower compared with the mean nonpregnant, 12-week postpartum C/D ratio. One individual with CYP2D6 ultrarapid metabolizer status was prescribed the highest FLX dose among participants. In these treated individuals, the mean depressive and anxiety symptoms remained in the mild range across the perinatal period. CONCLUSIONS: These data do not support a recommendation for routine plasma concentration monitoring or CYP2D6 pharmacogenetic testing for pregnant people treated with FLX; however, monitoring for symptom relapse is recommended because of declining plasma drug concentrations.

The pathophysiology of estrogen in perinatal depression: conceptual update.

PURPOSE: Estrogen levels fall sharply after parturition and have long been considered an etiologic contributor to postpartum depression (PPD); however, no differences have been reported in plasma hormone concentrations in people who develop PPD. We examine the question: What is the current view of estrogen and the neurophysiologic processes it impacts in the development and treatment of PPD? METHODS: A literature review of the role of estrogen on candidate hormonal and epigenetic systems in the peripartum period was performed, including landmark historical studies and recent publications on estrogen-related research. The authors reviewed these papers and participated in reaching consensus on a conceptual framework of estrogen activity within the complexity of pregnancy physiology to examine its potential role for driving novel interventions. RESULTS: Estrogen fluctuations must be conceptualized in the context of multiple dramatic and interacting changes inherent in pregnancy and after birth, including progesterone, corticosteroids, inflammation, circadian biology and psychosocial challenges. Individuals who develop PPD have increased sensitivity to epigenetic alteration at estrogen-responsive genes, and these changes are highly predictive of PPD. An effective estrogen-based treatment for PPD has yet to be found, but interventions focused on associated inflammation and circadian rhythms are promising. CONCLUSIONS: Our understanding of the biological basis of PPD, one of the most common morbidities of the perinatal period, is expanding beyond changes in gynecologic hormone concentrations to include their impact on other systems. This growing understanding of the many processes influencing PPD will allow for the development of novel prevention and treatment strategies.

Long-term neurodevelopmental follow-up of children exposed to pravastatin in utero.

BACKGROUND: Preeclampsia, especially before term, increases the risk of child neurodevelopmental adverse outcomes. Biological plausibility, preclinical studies, and pilot clinical trials conducted by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the Obstetric-Fetal Pharmacology Research Centers Network support the safety and use of pravastatin to prevent preeclampsia. OBJECTIVE: This study aimed to determine the effect of antenatal pravastatin treatment in high-risk pregnant individuals on their child's health, growth, and neurodevelopment. STUDY DESIGN: This was an ancillary follow-up cohort study of children born to mothers who participated in the Obstetric-Fetal Pharmacology Research Centers Network pilot trials of pravastatin vs placebo in individuals at high risk of preeclampsia (ClinicalTrials.gov; identifier NCT01717586). After obtaining written informed consent (and assent as appropriate), the parent was instructed to complete the Child Behavior Checklist. To assess the child's motor, cognitive, and developmental outcomes, a certified and blinded study psychologist completed child motor, cognitive, emotional, and behavioral assessments using validated tools. Given the small number of individuals in the studies, the 10- and 20-mg pravastatin groups were combined into 1 group, and the results of the pravastatin group were compared with that of the placebo group. RESULTS: Of 40 children born to mothers in the original trial, 30 (15 exposed in utero to pravastatin and 15 to placebo) were enrolled in this follow-up study. The time of follow-up, which was 4.7 years (interquartile range, 2.5-6.9), was not different between children in the pravastatin group and children in the placebo group. There was no difference in the child's body mass index percentiles per sex and corrected age, the rates of extremes of body mass index percentiles, or the report of any other medical or developmental complications between the 2 groups. No child born in the pravastatin group had any limitation in motor assessment compared with 2 children (13.3%) who walked with difficulty and 4 children (26.7%) who had reduced manual abilities in the placebo group. Moreover, children born to mothers who received pravastatin had a higher general mean conceptual ability score (98.2±16.7 vs 89.7±11.0; P=.13) and a lower frequency (15.4% vs 35.7%; P=.38) of having a score of <85 (ie, 1 standard deviation lower than the mean) compared with those in the placebo group. Finally, there was no difference in the parents' report on the Child Behavior Checklist between the 2 groups. CONCLUSION: This study reported on the long-term neuromotor, cognitive, and behavioral outcomes among children exposed to pravastatin in utero during the second and third trimesters of pregnancy. Although the data were limited by the original trial's sample size, no identifiable long-term neurodevelopmental safety signal was evident with the use of pravastatin during pregnancy. This favorable neonatal risk-benefit analysis justifies continued research using pravastatin in clinical trials.

The Association between Immediate Postpartum Depot Medroxyprogesterone Acetate Use and Postpartum Depressive Symptoms.

OBJECTIVE: While postpartum depot medroxyprogesterone acetate (DMPA) is a highly effective form of contraception, some data suggest an association with depressive symptoms. Our objective was to evaluate the relationship between receipt of DMPA in the immediate postpartum period and postpartum depressive symptoms. STUDY DESIGN: This retrospective cohort study included all women who received prenatal and postpartum care at academic obstetric clinics affiliated with a tertiary care institution between January 1, 2008 and December 31, 2014. All women were counseled on contraception prior to hospital discharge. DMPA was available in the hospital pharmacy, and its utilization was documented in the electronic health record. The Patient Health Questionnaire 9 (PHQ-9) was used to screen for postpartum depression for all women at all postpartum visits. A score of 10 or greater was categorized as positive. Bivariable and multivariable analyses were used to identify the association between immediate postpartum DMPA use and a positive postpartum depression screen. RESULTS: Of the 5,073 women who met inclusion criteria, 410 (8.1%) received DMPA prior to hospital discharge. Compared with women who did not receive DMPA, women who received DMPA prior to hospital discharge were younger, more likely to identify as Black race or Latinx ethnicity, and more likely to be publicly insured. Clinical characteristics also differed. Women who received DMPA were more likely to be obese and to have experienced prenatal depressive symptoms, been diagnosed with a hypertensive disorder of pregnancy, delivered preterm, and delivered vaginally. Receipt of immediate postpartum DMPA was not associated with having a positive screen for postpartum depression in bivariable (5.4 vs. 6.0%, p = 0.29) or multivariable (adjusted odds ratio 0.94, confidence interval 0.53-1.68) analyses. CONCLUSION: Receipt of postpartum DMPA is not associated with a positive postpartum PHQ-9 screen. Concerns about precipitating postpartum depression should not preclude the utilization of DMPA as a contraceptive agent. KEY POINTS: · Contraception is an important issue for obstetricians to address with postpartum patients.. · Concerns have been raised over the relationship between DMPA and depression.. · Our study shows that DMPA is not associated with a positive postpartum depression screen..

C-Reactive protein concentrations in reproductive-aged women with major mood disorders.

To examine associations between high sensitivity C-reactive protein (CRP) concentrations and depressive symptoms in reproductive-aged women with mood disorders. Women (N = 86) with major depressive or bipolar disorder in a specialized mood disorders program provided plasma samples which were analyzed for CRP concentrations and categorized by tertiles (T1, low; T2, middle; T3 high). Depressive symptoms were assessed with the Inventory of Depressive Symptoms. We hypothesized that CRP concentrations would be significantly associated with the following: (1) depressive symptoms; (2) pregnancy, (3) body mass index, and (4) counts of white blood cells and absolute neutrophils and percentage of segmented neutrophils. The distribution of CRP concentrations was highly skewed with a median of 2.45 mg/L and an interquartile range 0.90 - 8.17 mg/L. Elevated plasma levels of CRP were not associated with depressive symptoms, which did not differ by tertile group either before or after adjusting for BMI, pregnancy status, and their interactions. Women in T3 had 5 times greater odds of pregnancy compared to women in T1 (p = .021). However, women in T2 had 11% greater BMI on average (p = 0.023), and women in T3 had 47% greater BMI compared to those in T1 (p < 0.001). Women in T3 had higher mean white blood cell counts than those in T1 and T2, the percentage of neutrophils was higher in T2 and T3 compared to T1, and women in T3 had higher absolute neutrophil counts compared to T1. CRP concentrations varied widely and were significantly elevated in reproductive-aged women with high BMI and current pregnancy, but not with depressive symptoms in this sample of depressed women.

Acute Delivery Room Resuscitation of Neonates Exposed to Selective Serotonin Reuptake Inhibitors.

OBJECTIVE: To determine whether full-term neonates with in utero exposure to selective serotonin reuptake inhibitors (SSRI) require respiratory support in the delivery room, as indicated by the standardized Neonatal Resuscitation Program algorithm, significantly more often than nonexposed neonates. STUDY DESIGN: In this retrospective cohort study, we extracted data from medical records of full-term neonates with and without in utero SSRI exposure, defined as documentation of third trimester maternal SSRI treatment. A hospital-based sample was identified at Northwestern Medical Hospital in Chicago, Illinois. Full-term singleton newborns identified in a 6-month period (n = 4933) were selected for study. Neonates with a major congenital anomaly were excluded. The primary outcome was initiation of respiratory support in the delivery room, as indicated by the Neonatal Resuscitation Program algorithm. RESULTS: Of the 4933 full-term singleton neonates, 3.3% were exposed to SSRI in utero. Respiratory support was initiated significantly more often in SSRI exposed (12.9%) than unexposed (4.2%) neonates (covariate-adjusted OR, 4.04; 95% CI, 2.40-6.49). In utero SSRI exposure also was associated with a higher rate of neonatal intensive care unit admission (covariate-adjusted OR, 2.19; 95% CI, 1.30-3.50) and 1-minute Apgar score of ≤5 (covariate-adjusted OR, 3.51; 95% CI, 2.07-5.67). CONCLUSIONS: In this cohort, in utero SSRI exposure was associated with a significantly greater odds of resuscitation in the delivery room as well as neonatal intensive care unit admission. Although the mechanism underlying these associations have not been determined and causality cannot be assumed, these findings support a recommendation that third trimester SSRI exposure be considered a risk factor for needing resuscitation.

A randomized pilot clinical trial of pravastatin versus placebo in pregnant patients at high risk of preeclampsia.

BACKGROUND: Preeclampsia remains a major cause of maternal and neonatal morbidity and mortality. Biologic plausibility, compelling preliminary data, and a pilot clinical trial support the safety and utility of pravastatin for the prevention of preeclampsia. OBJECTIVE: We previously reported the results of a phase I clinical trial using a low dose (10 mg) of pravastatin in high-risk pregnant women. Here, we report a follow-up, randomized trial of 20 mg pravastatin versus placebo among pregnant women with previous preeclampsia who required delivery before 34+6 weeks' gestation with the objective of evaluating the safety and pharmacokinetic parameters of pravastatin. STUDY DESIGN: This was a pilot, multicenter, blinded, placebo-controlled, randomized trial of women with singleton, nonanomalous pregnancies at high risk for preeclampsia. Women between 12+0 and 16+6 weeks of gestation were assigned to receive a daily pravastatin dose of 20 mg or placebo orally until delivery. In addition, steady-state pravastatin pharmacokinetic studies were conducted in the second and third trimesters of pregnancy and at 4 to 6 months postpartum. Primary outcomes included maternal-fetal safety and pharmacokinetic parameters of pravastatin during pregnancy. Secondary outcomes included maternal and umbilical cord blood chemistries and maternal and neonatal outcomes, including rates of preeclampsia and preterm delivery, gestational age at delivery, and birthweight. RESULTS: Of note, 10 women assigned to receive pravastatin and 10 assigned to receive the placebo completed the trial. No significant differences were observed between the 2 groups in the rates of adverse or serious adverse events, congenital anomalies, or maternal and umbilical cord blood chemistries. Headache followed by heartburn and musculoskeletal pain were the most common side effects. We report the pravastatin pharmacokinetic parameters including pravastatin area under the curve (total drug exposure over a dosing interval), apparent oral clearance, half-life, and others during pregnancy and compare it with those values measured during the postpartum period. In the majority of the umbilical cord and maternal samples at the time of delivery, pravastatin concentrations were below the limit of quantification of the assay. The pregnancy and neonatal outcomes were more favorable in the pravastatin group. All newborns passed their brainstem auditory evoked response potential or similar hearing screening tests. The average maximum concentration and area under the curve values were more than 2-fold higher following a daily 20 mg dose compared with a 10 mg daily pravastatin dose, but the apparent oral clearance, half-life, and time to reach maximum concentration were similar, which is consistent with the previously reported linear, dose-independent pharmacokinetics of pravastatin in nonpregnant subjects. CONCLUSION: This study confirmed the overall safety and favorable pregnancy outcomes for pravastatin in women at high risk for preeclampsia. This favorable risk-benefit analysis justifies a larger clinical trial to evaluate the efficacy of pravastatin for the prevention of preeclampsia. Until then, pravastatin use during pregnancy remains investigational.

Impact of the peripartum period on the longitudinal course of obsessive-compulsive disorder.

Some women are vulnerable to developing new onset obsessive-compulsive disorder (OCD) or having an exacerbation of pre-existing OCD during reproductive cycle events. Reports on the impact of the peripartum period on pre-existing OCD are inconsistent, with both worsening and improving symptom severity described. Studies have primarily been retrospective or have collected few data points, which limits the investigators' ability to capture the range of OCD symptoms during this time period, systematically and prospectively. The objective of this investigation was to add to the existing literature on the impact of the peripartum period on the course of pre-existing OCD. We conducted a secondary analysis of a subset data from the Brown Longitudinal Obsessive Compulsive Study, a prospective, observational study of OCD course. Nineteen women who experienced a pregnancy during the course of the study (9.5% of overall sample of women) were followed on average for 486 ± 133 weeks. Weekly psychiatric status ratings (PSRs) of OCD severity were compared between peripartum and non-peripartum periods. We found that the peripartum period did not significantly impact the course of OCD severity in the majority of women (N = 13, 69%). Of the minority of women with measurable variability in OCD symptoms, no statistically significant difference in PSR scores was observed between peripartum and non-peripartum periods. In this novel yet small dataset, the severity of OCD does not appear to worsen for most women during the peripartum period.

A prospective pilot study to assess the impact of the etonogestrel implant on postpartum depression.

OBJECTIVES: To assess the feasibility of comparing the rates of positive depression screens at 6 weeks and 3 months postpartum in women using immediate postpartum etonogestrel implant (ENG-implant) and women using non-hormonal contraception or sterilisation. METHODS: This was a pilot prospective cohort study performed to test the design adequacy of comparing the rates of positive postpartum PHQ-9 screens (≥10) in women using immediate postpartum ENG-implant and women using non-hormonal contraception or sterilisation. Participants were recruited during the third trimester of pregnancy or during delivery hospitalisation. They self-allocated to one of the two comparison groups. PHQ-9 surveys were administered during the third trimester of pregnancy, immediately postpartum, and at 6 weeks and 3 months postpartum. RESULTS: Between June 2017 and March 2018, 91 patients were recruited. Of these patients, 11 were excluded and the remaining 80 were split evenly into each cohort. The women in the ENG-implant group were younger, less educated, and more often publicly insured. The percentage of participants with positive PHQ-9 screens were: 3% during the postpartum hospitalisation, 6.2% at 6 weeks postpartum, and 10.2% at 3 months postpartum. PHQ-9 scores were similar between groups at both postpartum time points. CONCLUSION: The rates of positive PHQ-9 screens at 6 weeks postpartum were similar between groups. These preliminary data suggest that immediate postpartum placement of the ENG-implant does not negatively impact the risk for a positive depression screen. Larger-scale, adequately powered studies are warranted to further investigate this finding.

Plasma and cerebrospinal fluid inflammatory cytokines in perinatal depression.

BACKGROUND: While perinatal depression is one of the most common complications of pregnancy, there is an insufficient understanding of the mechanistic underpinnings of disease. While an association between peripheral inflammatory cytokines and major depressive disorder has been demonstrated, cytokines cannot freely cross the blood-brain barrier, and thus, they give little insight into alternations in brain function. Because the brain is in direct communication with the cerebrospinal fluid, assessment of inflammation in the cerebrospinal fluid may be more directly related to the biologic markers of affective change. OBJECTIVE: Our objectives were to examine the association between perinatal depression and inflammatory cytokines in plasma, the association between perinatal depression and inflammatory cytokines in cerebrospinal fluid, and the correlations between plasma and cerebrospinal fluid inflammatory cytokines. STUDY DESIGN: This was a prospective, observational study of women with a singleton gestation at term undergoing a scheduled cesarean delivery. Women were screened for depression and those with depressive symptomatology preferentially enrolled. The Mini-International Neuropsychiatric Interview was administered to confirm the clinical diagnosis of depression. Maternal plasma and cerebrospinal fluid were collected preoperatively and cytokines measured via flow cytometry. Bivariable and multivariable analyses were used to determine the association between each cytokine and perinatal depression. Correlations were measured between the cytokines in plasma and cerebrospinal fluid. RESULTS: Of the 117 women who met inclusion criteria, 76 (65%) screened positive for depression, 15 (20%) of whom met the clinical diagnostic criteria for depression. There were no significant associations between any of the plasma cytokines and perinatal depression in our sample. Conversely, in multivariable analyses, higher cerebrospinal fluid interleukin-1ß (adjusted odds ratio, 232.7, 95% confidence interval, 5.9-9148.5), interleukin-23 (adjusted odds ratio, 22.1, 95% confidence interval, 1.7-294.5), and interleukin-33 (adjusted odds ratio, 1.7, 95% confidence interval, 1.1-2.6) concentrations were significantly associated with increased odds of perinatal depression. The plasma and cerebrospinal fluid cytokine concentrations were not strongly correlated. CONCLUSION: Higher concentrations of cerebrospinal fluid cytokines were associated with perinatal depression. These cerebrospinal fluid cytokines were not strongly correlated with plasma cytokines, and accordingly, plasma cytokines were not significantly associated with perinatal depression. Central neuroinflammation, as opposed to peripheral inflammation, may represent a mechanistic pathway that contributes to perinatal depression.

Four maternal characteristics determine the 12-month course of chronic severe postpartum depressive symptoms.

BACKGROUND: Postpartum depression is a heterogeneous disorder in phenotype and etiology. Characterizing the longitudinal course of depressive symptoms over the first year after birth and identifying variables that predict distinct symptom trajectories will expedite efficient mental health treatment planning. The purpose was to determine 12-month trajectories of postpartum depressive symptoms, identify characteristics that predict the trajectories, and provide a computational algorithm that predicts trajectory membership. METHODS: A prospective cohort of women delivering at an academic medical center (2006-2011) was recruited from an urban women's hospital in Pittsburgh, PA. Women with a postpartum depressive disorder (n = 507) participated and completed symptom severity assessments at 4-8 weeks (intake), 3 months, 6 months, and 12 months. Women were predominantly Caucasian (71.8%), married (53.3%), and college educated (38.7%). Clinician interviews of depressive symptom severity, medical and psychiatric history, assessment of function, obstetric experience, and infant status were conducted. RESULTS: Analyses resulted in identification of three distinct trajectories of depressive symptoms: (1) gradual remission (50.4%), (2) partial improvement (41.8%), and (3) chronic severe (7.8%). Key predictive characteristics of the chronic severe versus gradual remission and partial improvement trajectories included parity, education, and baseline global functioning and depression severity. We were able to predict trajectory membership with 72.8% accuracy from these characteristics. CONCLUSIONS: Four maternal characteristics predicted membership in the chronic severe versus gradual remission and partial improvement trajectories with 72.8% accuracy. The trajectory groups comprise clinically relevant subgroups with the potential for tailored treatments to reduce the disease burden of postpartum depression.

The association of serum C-reactive protein with the occurrence and course of postpartum depression.

CRP has been positively correlated with depressive symptomatology but this has received less study in postpartum depression (PPD). In this secondary analysis of a trial of PPD treatment, depressive symptoms (Structured Interview Guide for the Hamilton Depression Rating Scale-Atypical Depression Symptoms (SIGH-ADS29)) and serum CRP levels were assessed and associations between CRP and SIGH-ADS29 scores evaluated. The associations between baseline log CRP and depression response and remission were also assessed. Of the 35 women included, neither baseline log CRP nor exit log CRP was significantly associated with SIGH-ADS29 score. Baseline CRP was not associated with response or remission. In this sample of women with PPD, CRP was not associated with depressive symptoms nor response to treatment.

Obstetric patients' perspectives on functional magnetic neuroimaging research in pregnant women.

Magnetic resonance neuroimaging (MRI) studies of healthy pregnant women could identify key mechanisms of spontaneous health behavior changes observed in expectant mothers as novel intervention targets, but are currently unprecedented. As balancing potential benefits of research with unknown risks, including participant perceptions of risk, is foundational to ethical conduct, we surveyed a convenience obstetric sample to understand pregnant women's perspectives on this issue. Respondents were 76 pregnant women (modal age of 30-39 years; 64% multiparous) presenting for obstetric care from April to June 2016 at privately and publicly funded clinics at an urban academic medical center in the Midwestern USA. Following a written description about functional magnetic resonance neuroimaging (fMRI) and its known and unknown risks, women were queried on their willingness to participate in a hypothetical study involving fMRI during pregnancy, and specific concerns about doing so, if hesitant or unwilling. Willingness to participate was "yes" (28.4%, n = 21), "maybe" (28.4%, n = 21), and "no" (43.2%, n = 32). Among those responding "maybe" or "no" (n = 53, 73.6%), 11 women (20.7%) articulated concern about the fetus. Other concerns expressed were time commitment (n = 11, 20.7%) and discomfort being in an MRI machine (n = 4; 7.5%). Pregnant women may be open to participating in research involving MRI provided concerns about fetal health, time, and personal comfort are addressed.

Risk-Benefit assessment of infant exposure to lithium through breast milk: a systematic review of the literature.

The continuation of lithium while breastfeeding is a controversial topic, and clinical recommendations vary. A systematic review was completed of available data on lithium and breastfeeding to determine the degree of lithium exposure through breast milk and assess the potential risk to the infant. Databases, including PubMed MEDLINE, Embase, PsycINFO, Web of Science, Scopus, and Cochrane CENTRAL Register of Controlled Trials databases, were searched for articles on lithium and breastfeeding from the start dates of the databases through December 2018. Articles were included if the report included at least one maternal serum/plasma and/or breast milk lithium concentration and one infant serum/plasma lithium concentration. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. Twelve articles, all case reports, were selected for inclusion out of 441 articles that were found and 230 that were reviewed from the search. Data are limited on the safety of lithium continuation while breastfeeding. Among the adverse effects reported, it is difficult to differentiate poor outcomes from factors affecting infant health, concomitant medications, and gestational lithium exposure. Recommendations on whether to continue lithium while breastfeeding must be personalized to the individual woman and her infant.

Mood symptoms in pregnant and postpartum women with bipolar disorder: a naturalistic study.

OBJECTIVE: We conducted a prospective naturalistic study of pregnant women with bipolar disorder (BD) to evaluate symptoms of BD across childbearing and assess whether pharmacotherapy reduced their severity. METHODS: Assessments were scheduled at 20, 30, and 36 weeks' gestation and 2, 12, 26, and 52 weeks postpartum. Symptoms were assessed using the Structured Interview Guide for the Hamilton Depression Rating Scale-Atypical Depression Supplement (SIGH-ADS) and Mania Rating Scale (MRS). RESULTS: Pregnant women (N=152) with BD were evaluated; 88 women (58%) were treated and 64 untreated (42%) with psychotropic drugs during pregnancy. Among the 88 women treated, 23 (26%) discontinued their medication in the first trimester and the remaining 65 (74%) were exposed throughout pregnancy or in the second and third trimesters. More than two-thirds (73%) of the women who remained in the study took psychotropic agents postpartum. The mean scores on the SIGH-ADS were in the mild range of depressive symptoms in both the psychotropic-treated and untreated groups in both pregnancy and postpartum. The majority of women had no or few symptoms of mania. Of the pregnant women treated with psychotropic agents, 66% received a guideline-concordant drug, and 34% received either antidepressant monotherapy (for BD I) or mono- or polypharmacy with a variety of other agents. CONCLUSIONS: This sample of perinatal women with BD was characterized by mild residual symptoms of depression independent of pharmacotherapy, which poses a risk for recurrence and impaired parenting. The treatment of childbearing women with BD deserves urgent clinical and research attention to improve psychiatric outcomes.

Treatment options for hyperemesis gravidarum.

Hyperemesis gravidarum (HG) is a severe and prolonged form of nausea and/or vomiting during pregnancy. HG affects 0.3-2% of pregnancies and is defined by dehydration, ketonuria, and more than 5% body weight loss. Initial pharmacologic treatment for HG includes a combination of doxylamine and pyridoxine. Additional interventions include ondansetron or dopamine antagonists such as metoclopramide or promethazine. The options are limited for women who are not adequately treated with these medications. We suggest that mirtazapine is a useful drug in this context and its efficacy has been described in case studies. Mirtazapine acts on noradrenergic, serotonergic, histaminergic, and muscarinic receptors to produce antidepressant, anxiolytic, antiemetic, sedative, and appetite-stimulating effects. Mirtazapine is not associated with an independent increased risk of birth defects. Further investigation of mirtazapine as a treatment for HG holds promise to expand treatment options for women suffering from HG.

Is maternal disclosure of HIV serostatus associated with a reduced risk of postpartum depression?

BACKGROUND: Patients with chronic diseases that include HIV infection are at increased risk of experiencing postpartum depression. In addition, social isolation has been associated with depression among women with HIV. Yet, it is unclear whether disclosure of HIV serostatus before the birth is associated with the risk of postpartum depression. OBJECTIVE: The purpose of this study was to determine whether maternal disclosure of her positive HIV serostatus before the delivery is associated with the risk of early postpartum depression. STUDY DESIGN: In this retrospective cohort study, women who received obstetric care in a specialty perinatal HIV clinic (2007-2014) were stratified by whether, before the delivery, they had disclosed their HIV serostatus to (1) their sexual partner(s) or (2) at least 1 family member aside from sexual partner(s). Postpartum depression was identified initially by a positive result on a validated depression screening tool (Patient Health Questionnaire-9 or Edinburgh Postnatal Depression Scale) at the 6-week postpartum visit and then confirmed by evaluation with a mental health professional. Postpartum depression rates were compared by disclosure status. Multivariable logistic regression was performed to identify whether disclosure to either sexual partner(s) or family members remained associated independently with postpartum depression after we controlled for potential confounders that included antenatal mental health disorders. RESULTS: Of the 215 women who received perinatal HIV care in this center and who had a documented disclosure status, 149 women (71.3%) had disclosed to their sexual partner(s), and 78 women (42.9%) had disclosed to at least 1 family member who was not a sexual partner. Although disclosure to sexual partner(s) was associated with a reduction in the proportion of women with postpartum depression (15.6% vs 25.5%), this difference did not reach statistical significance (P = .126) and remained statistically insignificant after we controlled for potential confounders (adjusted odds ratio, 0.47; 95% confidence interval, 0.15-1.41). In contrast, disclosure to family member(s) was associated with a decreased prevalence of postpartum depression (11.4% vs 24.7%; P = .03), and this difference persisted in multivariable regression (adjusted odds ratio, 0.35; 95% confidence interval, 0.13-0.95). CONCLUSION: In this cohort, maternal disclosure of HIV serostatus to family members (other than sexual partner[s]) was associated independently with a reduction in postpartum depression by more than one-half. Disclosure of HIV serostatus to a family member may be a marker for psychosocial well-being and enhanced support that affords protection against postpartum depression.

Recollections on the early days of the Marcé Society for Perinatal Mental Health from Professor John Cox.

Dr. Katherine Wisner interviewed Dr. John Cox, a founding member of the Marcé Society. Dr. Cox discussed the beginnings of the Marcé Society, his views about the current Society, and his vision for the future.