Search

Background: Maternal functional status is important to capture in the 12 months after childbirth, as this period marks a critical window for both mother and child. In most cases, mothers are the primary caregivers and are, therefore, responsible for the majority of the work related to infant care tasks, such as feeding, diaper changes, and doctor's appointments. Additionally, the quality of mother-child interaction in the year after childbirth affects child development. To date, postpartum functioning has exacted scarce coverage, with only one instrument claiming to measure the concept explicitly. This necessitated the development of the Barkin Index of Maternal Functioning (BIMF), which was designed to measure functioning in the year after childbirth. Methods: Three focus groups comprised of 31 new mothers were held to elicit women's concept of functioning in the first postpartum year. Women were asked to discuss the responsibilities associated with new motherhood as well as the circumstances surrounding high and low functioning periods. Results: The qualitative data produced by the focus groups were coded by emotive tone and content and translated into item construction for the BIMF, a 20-item self-report measure of functioning intended for use in the year after childbirth. Before implementation into the screening study, the BIMF was critiqued by a panel of experts and cross-checked with the literature to ensure that no major contextual domains were absent. Psychometric testing revealed adequate internal reliability and construct validity, and the BIMF has been implemented successfully in clinical settings. Conclusions: The high level of patient engagement and psychometric properties associated with the BIMF are indicative of its potential to become a valuable tool for assessing maternal wellness. [ABSTRACT FROM AUTHOR]

Bipolar disorder is a chronic condition characterized by periods of mania, depression, or mixed states (co-occurring mania and depression). The postpartum period is associated with a high risk for symptom relapse or intensification, which can be reduced with the use of medications. Abrupt discontinuation of these medications increases the probability of relapse, which is associated with high-risk behaviors, significant family dysfunction, and suicide. Drugs used to treat patients with bipolar disorder vary in teratogenic potential. Although first trimester lithium use is associated with Ebstein's anomaly, the risk was overestimated in the past. Valproate and its derivatives and carbamazepine are human teratogens. Lamotrigine does not negatively impact major reproductive outcomes, but the data are limited. Typical antipsychotic medications are relatively well studied and the data do not identify major morphologic teratogenicity. There are fewer studies of newer atypical antipsychotic medications, and registries have been developed to collect prospective data. Clinical management of bipolar disorder during pregnancy, postpartum, and lactation requires a careful balancing of maternal and fetal risks and benefits. Communication and careful comanagement between the obstetric and psychiatric team is essential when treating women with bipolar disorder during the reproductive years. [ABSTRACT FROM AUTHOR]

Objective: Valproate is associated with polycystic ovary syndrome as well as congenital malformations and developmental delays of infants who were prenatally exposed. The frequency of valproate use for mental health conditions among women of childbearing age was determined.Methods: Using New York State Medicaid claims for persons with psychiatric disorders, 40,526 individuals with active prescriptions for mood stabilizers (non-antipsychotic) on May 1, 2009, were identified. Chi square tests were used to compare valproate use among women of childbearing age with similarly aged men and older women.Results: Valproate was the most commonly prescribed agent for young women (23.4%). Men were more likely than women, and older women more likely than younger women, to take valproate.Conclusions: Over 20% of childbearing-aged women receiving mood stabilizers were treated with valproate, although increasing data on the reproductive toxicity of this agent compel consideration of other non-antipsychotic mood stabilizers as first-line choices. [ABSTRACT FROM AUTHOR]

Perinatal depression is a significant health problem, especially among inner-city women. The authors explored the feasibility of an innovative model that integrated depression screening and treatment within an agency for maternal-child health. The team conducted depression screening with the Edinburgh Postnatal Depression Scale; they confirmed the primary diagnosis with the PRIME-MD instrument for 29 women with positive screens. Most participants had moderate or severe major depressive disorder. Women contended with multiple treatment barriers. Colocated depression care was highly acceptable and enabled evidence-based care delivery for at-risk mothers. [ABSTRACT FROM AUTHOR]

Background: Mental health conditions and epilepsy frequently coexist and have independently been associated with severe maternal morbidity (SMM). Since little is known about the risks of these conditions when they occur together in pregnancy, we evaluated the associations of mental health conditions, epilepsy, and SMM. Methods: We conducted a population-based study of births in California between 2007 and 2018. Antenatal epilepsy and mental health conditions (defined as depression, anxiety, posttraumatic stress disorder, and other) were identified using billing codes. We categorized individuals into the following mutually exclusive exposure groups: no epilepsy or mental health conditions (referent), mental health conditions alone, epilepsy alone, or both epilepsy and mental health conditions. Our primary outcome was SMM, defined by the 20-indicator Centers for Disease Control and Prevention Index. We conducted multivariable logistic regression models adjusted for sociodemographic and clinical confounding factors. Results: In a cohort of 5,275,994 births, SMM occurred more frequently in individuals with mental health conditions alone, epilepsy alone, and both mental health conditions and epilepsy (1.8%, 3.0%, 4.2%, respectively) compared with the referent group (0.8%). The odds of SMM were significantly increased for each exposure group: adjusted odds ratio (aOR) 2.13, 95% confidence interval (CI) 2.05-2.22 for mental health conditions; aOR 3.79, 95% CI 3.45-4.18 for epilepsy; and aOR 4.91, 95% CI 4.01-6.00 for both. Conclusion: Epilepsy and mental health conditions were independently associated with SMM, and individuals carrying both diagnoses had the highest odds of SMM. Our results highlight the need for awareness of SMM risks in this population.

Determination of the relationships between drug dosage, maternal and infant (cord blood) plasma drug concentrations, and serotonin reuptake inhibitor (SRI) bioeffect on offspring neurobehavior is crucial to assessing the effects of gestational SRI exposure. Measurement of maternal and cord blood platelet serotonin (5-HT) provides an index of inhibitory bioeffect at the 5-HT transporter and complements other measures of drug exposure. Three groups of mother-infant pairs were evaluated: (1) mothers with depression untreated with SRIs (DEP, n = 17), (2) mothers treated for depression with SRIs (DEP + SRI, n = 17), and (3) mothers who were not depressed and untreated (ND, n = 29). Fetal movement was assessed using a standardized ultrasound imaging and rating protocol. Maternal and cord blood platelet 5-HT levels were obtained from all participants. For the SRI + DEP group, maternal and infant plasma drug concentrations and an estimate of third-trimester maternal SRI drug exposure were obtained. As expected, substantially lower median platelet 5-HT levels were observed in the DEP + SRI group than in the non-exposed, combined ND and DEP groups. In non-exposed mothers and infants, platelet 5-HT levels were not affected by the presence of maternal depression. Lower maternal and infant platelet 5-HT levels were associated with more immature fetal movement quality. Although these data are limited by small sample size, the bioeffect index of in vivo platelet 5-HT transporter inhibition appears to provide a valuable approach for elucidating and possibly predicting the effects of gestational SRI exposure on fetal and perinatal neurobehavior., (© 2024. The Author(s).)

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., Competing Interests: Declarations. The authors have no acknowledgements or disclosures, (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Purpose: Somatic symptoms are commonly seen in major depressive disorder (MDD) with postpartum onset and can be similar to side effects of antidepressant medications. The aim of this study is to determine whether the decline in depressive symptoms measured by the Structured Interview Guide for the Hamilton Depression Rating Scale with Atypical Depression Supplement (SIGH-ADS) is significantly associated with the decrease in somatic symptoms identified by the Asberg scale., Methods: A secondary analysis of data from a randomized controlled trial was conducted. The original 8-week trial included 62 participants and assessed the efficacy of sertraline versus estradiol transdermal patches and their respective placebos for MDD with postpartum onset. The SIGH-ADS scale was used to assess depression severity and the Asberg scale was used to evaluate treatment emergent side effects, defined as an increase of ≥2 from baseline measures. Correlation analyses were performed between total scale scores. The scales were compared to establish symptoms, which overlapped across scales versus symptoms, which were unique to each scale., Results: Positive correlations were observed between the SIGH-ADS and Asberg scales and across the 8-week trial in all 3 treatment groups (correlation coefficient range 0.468-0.712). Headache was the most frequent treatment emergent side effect (10 occurrences). Fourteen symptoms were found to overlap between the 2 scales., Conclusions: These findings underscore the importance of reviewing somatic symptoms before administering medication to discern true treatment emergent side effects, especially in populations recovering from labor and delivery. Somatic symptoms decline in parallel with depressive symptom scores during treatment, suggesting they are indicative of underlying illness rather than side effects., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Importance: Little is known about differences between Black and White women with respect to the prevalence of postpartum mood disorders or symptom presentations., Objective: To determine the prevalence and characteristics of postpartum major mood disorders in Black and White women at 4-6 weeks after birth., Methods: This is a secondary analysis of a large-scale study designed to screen women for postpartum depression with the Edinburgh Postnatal Depression Scale (EPDS) and collect symptom data. Data were collected at an urban maternity hospital in an academic setting in Pittsburgh, Pennsylvania. Of the 2,019 women who screened positive and accepted a psychiatric diagnostic interview, 163 and 85 Black women had major depressive and bipolar disorders, respectively, and 508 and 177 White women had major depressive and bipolar disorders, respectively. Those with an EPDS score greater than or equal to 10 were offered a psychiatric assessment (in-person at home or by telephone) with the Structured Clinical Interview for DSM IV using the Structured Interview Guide for the Hamilton Rating Scale for Depression, Atypical Depression Version symptom inventory, a questionnaire related to childhood and adulthood physical and sexual abuse, and the Short Form Survey 12. Participants who self-identified as Black or White were included in this analysis., Results: Among screen-positive participants, no significant difference in the rate of major depressive disorder (40% Black and 35% White) was observed. However, bipolar disorder significantly differed between Black (19.2%) and White (11.5%) women. Additionally, symptom profiles differed between Black and White participants with major depressive disorder, and a high rate of traumatic experiences was reported by participants with major depression and bipolar disorder in both racial groups., Conclusion: An understanding of the different presentations of postpartum mood disorders between Black and White women, as well as trauma-informed care, can optimize postpartum health care through supporting advocacy efforts for resource allocation and health care delivery., Trial Registration: Dataset from study at ClinicalTrials.gov identifier: NCT00282776., (© Copyright 2024 Physicians Postgraduate Press, Inc.)

Objective: The effectiveness of antidepressant treatment for mood disorders is often limited by either a poor response or the emergence of adverse effects. These complications often necessitate multiple drug trials. This clinical challenge intensifies during pregnancy, when medications must be selected to improve the likelihood of response and optimize reproductive outcomes. We determined the distribution of common pharmacogenetic variants, metabolizer phenotypes, past medication responses, and side effects in childbearing-aged individuals seeking treatment in a tertiary care perinatal mental health clinic., Methods: Sixty treatment-seeking women (based on sex at birth) with DSM-5- defined bipolar disorder (n = 28) or major depressive disorder (n = 32) provided DNA samples and completed psychiatric diagnostic and severity assessments between April 2014 and December 2017. Samples were genotyped for single-nucleotide variants in drug metabolizing enzyme genes of commonly prescribed antidepressants (cytochrome P450 [CYP] 1A2, 2B6, 2C9, 2C19, 2D6, 3A4, and 3A5), and the frequency of normative metabolizer status was compared to reference populations data from Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines. The Antidepressant Treatment History Form was used to record historic medication trials and side effects., Results: A significantly greater proportion of extensive metabolizers for CYP2B6 was observed in the study population when compared to CPIC population frequency databases in Caucasians (0.64 vs 0.43 [95% CI: 0.49-0.76]; P value = .006) and African Americans (0.71 vs 0.33 [95% CI: 0.29-0.96]; P value = .045). No significant association was found between metabolizer phenotype and the likelihood of a medication side effect., Conclusion: Pharmacogenomic testing may have value for personalized prescribing in individuals capable of or considering pregnancy., (© Copyright 2024 Physicians Postgraduate Press, Inc.)

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., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Importance: Use of medications for attention-deficit/hyperactivity disorder (ADHD) during pregnancy is increasing in the US. Whether exposure to these medications in utero impacts the risk of neurodevelopmental disorders in children is uncertain., Objective: To evaluate the association of childhood neurodevelopmental disorders with in utero exposure to stimulant medications for ADHD., Design, Setting, and Participants: This cohort study included health care utilization data from publicly insured (Medicaid data from 2000 to 2018) and commercially insured (MarketScan Commercial Claims Database data from 2003 to 2020) pregnant individuals aged 12 to 55 years in the US with enrollment from 3 months prior to pregnancy through 1 month after delivery, linked to children. Children were monitored from birth until outcome diagnosis, disenrollment, death, or end of the study (December 2018 for Medicaid and December 2020 for MarketScan)., Exposures: Dispensing of amphetamine/dextroamphetamine or methylphenidate in the second half of pregnancy., Main Outcomes and Measures: Autism spectrum disorder, ADHD, and a composite of any neurodevelopmental disorder were defined using validated algorithms. Hazard ratios were estimated comparing amphetamine/dextroamphetamine and methylphenidate to no exposure., Results: The publicly insured cohort included 2 496 771 stimulant-unexposed, 4693 amphetamine/dextroamphetamine-exposed, and 786 methylphenidate-exposed pregnancies with a mean (SD) age of 25.2 (6.0) years. The commercially insured cohort included 1 773 501 stimulant-unexposed, 2372 amphetamine/dextroamphetamine-exposed, and 337 methylphenidate-exposed pregnancies with a mean (SD) age of 31.6 (4.6) years. In unadjusted analyses, amphetamine/dextroamphetamine and methylphenidate exposure were associated with a 2- to 3-fold increased risk of the neurodevelopmental outcomes considered. After adjustment for measured confounders, amphetamine/dextroamphetamine exposure was not associated with any outcome (autism spectrum disorder: hazard ratio [HR], 0.80; 95% CI, 0.56-1.14]; ADHD: HR, 1.07; 95% CI, 0.89-1.28; any neurodevelopmental disorder: HR, 0.91; 95% CI, 0.81-1.28). Methylphenidate exposure was associated with an increased risk of ADHD (HR, 1.43; 95% CI, 1.12-1.82]) but not other outcomes after adjustment (autism spectrum disorder: HR, 1.06; 95% CI, 0.62-1.81; any neurodevelopmental disorder: HR, 1.15; 95% CI, 0.97-1.36). The association between methylphenidate and ADHD did not persist in sensitivity analyses with stricter control for confounding by maternal ADHD., Conclusions and Relevance: The findings in this study suggest that amphetamine/dextroamphetamine and methylphenidate exposure in utero are not likely to meaningfully increase the risk of childhood neurodevelopmental disorders.

Importance: The rate of maternal mortality in the United States is 2-fold to 3-fold greater than that in other high-income countries. While many national initiatives have been developed to combat maternal mortality, these efforts often fail to include mental illness., Objective: To highlight the underrecognized contribution of mental illness to maternal mortality, which is nearly double that of postpartum hemorrhage., Evidence Review: A topic outline was developed to include challenges in measuring perinatal mental conditions and mortality rates; contributions of social determinants of health to mental conditions and mortality; perinatal psychiatric disorder characterization; mechanisms by which maternal mental illness increases mortality, specifically, suicide and addictive disorders; access limitations and care "deserts"; prenatal stress and its impact on reproductive outcomes; increasing clinician expertise through cross-disciplinary education; intervention sites and models; and asserting that mental health is fundamental to maternal health. Publications in the last 3 years were prioritized, particularly those relating to policy. References were selected through consensus. Sources were PubMed, Ovid, direct data published on government websites, and health policy sources such as the Policy Center for Maternal Mental Health., Findings: Priority was given to recent sources. Citations from 2022-2023 numbered 26; within the last 5 years, 14; and historical references, 15. Recommendations to address each topic area serve as concluding statements for each section. To mitigate the contributions of mental illness to the maternal mortality risk, a coordinated effort is required across professional and governmental organizations., Conclusions and Relevance: Concrete programmatic and policy changes are needed to reduce perinatal stress and address trauma, standardize the collection of social determinant of health data among perinatal patients, increase access to reproductive psychiatry curricula among prescribers, reduce perinatal mental health and obstetrical deserts, institute paid parental leave, and support seamless integration of perinatal and behavioral health care. Moreover, instead of focusing on a relatively minor portion of the contributors to health that current medical practice targets, fortifying the social foundation strengthens the prospects for the health of families for our current and future generations.

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.)., (Copyright © 2024 Massachusetts Medical Society.)

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., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

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.., Competing Interests: None declared., (Thieme. All rights reserved.)

Importance: A substantial number of births in the US are to sexual minority women (17% based on a nationally representative survey), yet there is little research on perinatal depression screening rates or symptom endorsement among sexual minority women (including women who identify as lesbian, bisexual, queer, pansexual, asexual, demisexual, and kinky as well as other-identified women who have sex with women). High rates of risk factors for perinatal depression (eg, intimate partner violence and history of mental illness) among sexual minority individuals magnify this gap in the literature., Objective: To describe the prevalence of female-identified sexual minority people giving birth in an academic medical center and compare perinatal depression screening rates and scores among sexual minority women and heterosexual cisgender women., Design, Setting, and Participants: This retrospective cohort study used deidentified medical record review of 18 243 female-identified individuals who gave birth at an academic medical center in Chicago, Illinois, between January 1 and December 31, 2019. Data were analyzed from April 5, 2021, to August 1, 2022., Main Outcomes and Measures: Proportion of women identified as having sexual minority status in the medical record, rates of standard care administration of the 9-item Patient Health Questionnaire between sexual minority women and heterosexual women, and depression screening scores and rates of positive depression screening results for sexual minority and heterosexual women., Results: Among 18 243 women (mean [SD] age, 33.8 [5.1] years; 10 453 [57.3%] of non-Hispanic White race and ethnicity), only 280 (1.5%; 95% CI, 1.3%-1.7%) were identified as having sexual minority status in the medical record. Significantly more sexual minority women vs heterosexual women attended at least 1 prenatal care visit (56 [20.0%] vs 2459 [13.7%]; P = .002) and at least 1 postpartum care visit (52 [18.6%] vs 2304 [12.8%]; P = .004). Sexual minority women were more likely to be screened for depression during postpartum care (odds ratio, 1.77; 95% CI, 1.22-2.52; P = .002) and more likely to screen positive for depression during the postpartum period (odds ratio, 2.38; 95% CI, 0.99-5.02; P = .03) than heterosexual women., Conclusions and Relevance: In this cohort study, sexual minority women identified in the medical record were highly engaged in obstetric care yet at high risk of postpartum depression. In addition, their sexual orientation was largely undocumented in medical records. These results highlight the need for investigations that include strategies for measuring sexual orientation because medical record review is unlikely to reliably capture these sexual identities during the perinatal period.

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., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: The primary purpose of this article is to identify factors that are associated with worsening mood and anxiety trajectories across the perinatal period among pregnant individuals receiving treatment with a selective-serotonin reupdate inhibitor., Methods: This secondary analysis of primary data from the original article, Trajectories of Depressive and Anxiety Symptoms Across Pregnancy and Postpartum in Selective Serotonin Reuptake Inhibitor-Treated Women, explores if number of lifetime episodes of depression as characterized in the Mini-International Neuropsychiatric Interview, elevated maternal adverse childhood experiences (ACE) score, or specific obstetric or neonatal factors from the Peripartum Events Scale (PES) were associated with membership in trajectory groups with the highest symptom burden., Results: No difference in ACE scores or obstetric or neonatal factors were associated with membership in the trajectory groups using Wilcoxon rank sum tests and bi-variable logistic regression. The trajectory group with the highest anxiety symptom burden experienced more lifetime episodes of depression compared to other groups (odds ratio = 1.17, 95% confidence intervals, 1.02-1.34, p  = 0.03)., Conclusions: Congruent with other studies, we found a high prevalence of co-occurring mood and anxiety symptoms and that past episodes of depression remain an important historical risk factor for perinatal symptom burden. This reinforces that past experiences of depression increase not only the risk of future symptoms but also higher symptom burden during antidepressant treatment., (© 2023 The Authors. Psychiatric Research and Clinical Practice published by Wiley Periodicals LLC on behalf of American Psychiatric Association.)

Background: Mindfulness-based interventions have been shown to improve psychological outcomes including stress, anxiety, and depression in general population studies. However, effectiveness has not been sufficiently examined in racially and ethnically diverse community-based settings. We will evaluate the effectiveness and implementation of a mindfulness-based intervention on depressive symptoms among predominantly Black women at a Federally Qualified Health Center in a metropolitan city., Methods: In this 2-armed, stratified, individually randomized group-treated controlled trial, 274 English-speaking participants with depressive symptoms ages 18-65 years old will be randomly assigned to (1) eight weekly, 90-min group sessions of a mindfulness-based intervention (M-Body), or (2) enhanced usual care. Exclusion criteria include suicidal ideation in 30 days prior to enrollment and regular (>4x/week) meditation practice. Study metrics will be assessed at baseline and 2, 4, and 6 months after baseline, through clinical interviews, self-report surveys, and stress biomarker data including blood pressure, heart rate, and stress related biomarkers. The primary study outcome is depressive symptom score after 6 months., Discussion: If M-Body is found to be an effective intervention for adults with depressive symptoms, this accessible, scalable treatment will widely increase access to mental health treatment in underserved, racial/ethnic minority communities., Trial Registration: ClinicalTrials.gov NCT03620721. Registered on 8 August 2018., (© 2023. The Author(s).)

Retinoids and vitamin A are essential for multiple biological functions, including vision and immune responses, as well as the development of an embryo during pregnancy. Despite its importance, alterations in retinoid homeostasis during normal human pregnancy are incompletely understood. We aimed to characterize the temporal changes in the systemic retinoid concentrations across pregnancy and postpartum period. Monthly blood samples were collected from twenty healthy pregnant women, and plasma concentrations of retinol, all-trans-retinoic acid (atRA), 13-cis-retinoic acid (13cisRA), and 4-oxo-retinoic acids were measured using liquid chromatography-tandem mass spectrometry. Significant decreases in 13cisRA concentrations over the pregnancy were observed, with rebound increases in retinol and 13cisRA levels after delivery. Of note, atRA concentrations exhibited a unique temporal pattern with levels peaking at mid-pregnancy. While the 4-oxo-atRA concentration was below the limit of quantification, 4-oxo-13cisRA was readily detectable, and its temporal change mimicked that of 13cisRA. The time profiles of atRA and 13cisRA remained similar after correction by albumin levels for plasma volume expansion adjustment. Together, the comprehensive profiling of systemic retinoid concentrations over the course of pregnancy provides insights into pregnancy-mediated changes in retinoid disposition to maintain its homeostasis., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Jeong et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Severe nausea and vomiting of pregnancy is too common and devastating to be trivialized any longer. Authors of recent studies observed that children exposed in utero to severe nausea and vomiting of pregnancy had an increased risk for autism spectrum disorder, a decreased brain cortical volume, and developmental deficits. Research on severe nausea and vomiting of pregnancy and hyperemesis gravidarum has been disturbingly slow. It was not until 2021 that an international consensus definition was published. Hyperemesis gravidarum starts before 16 weeks' gestation, is characterized by severe nausea with or without vomiting and an inability to eat and drink normally, and greatly limits daily activities. Maternal misery is caused by unrelenting nausea, intractable retching or vomiting, ptyalism, dehydration, reflux, malnutrition, and social isolation. Hyperemesis gravidarum is the second most common reason for hospitalization in pregnancy. Symptoms can persist until delivery in one-third of individuals who experience extreme weight loss. Significant associations have been identified between hyperemesis gravidarum and multiple adverse outcomes. Maternal deaths owing to hyperemesis gravidarum continue to be reported, and hyperemesis gravidarum is associated with high fetal loss and termination rates. These grim findings highlight the critical public health importance of treating severe nausea and vomiting of pregnancy early to mitigate serious complications that compromise maternal and offspring health during pregnancy and beyond. Despite suffering extreme debility, individuals with hyperemesis gravidarum report feeling that their experiences were dismissed by healthcare professionals, contributing to therapeutic termination, suicidal ideation, perinatal depression, and posttraumatic stress disorder. Hyperemesis gravidarum must be recognized early and treated aggressively with frequent monitoring. Although medications can be effective in reducing symptoms, many patients do not gain adequate relief, and new treatments are needed. A promising new avenue for treatment comes from genetic discoveries. The gene, growth differentiation factor-15, which codes for a nausea and vomiting hormone produced by the placenta, is the greatest genetic risk factor for hyperemesis gravidarum, and therapies are currently in clinical trials in cancer. However, until treatment is universally effective, abortion access must be available for refractory hyperemesis gravidarum. Herein, we emphasize data published since the most recent American College of Obstetrics and Gynecology report (2018), such as long-term neuropsychiatric consequences in offspring exposed to hyperemesis gravidarum and suggest interventions anticipated to prevent progression of early symptoms to hyperemesis gravidarum., (© 2022 The Authors.)

Major depressive disorder (MDD) is a common disorder in pregnancy. Although sertraline is the most frequently prescribed antidepressant for pregnant people in the United States, limited information about its pharmacokinetics in pregnancy is available. Our objectives were to characterize plasma sertraline concentration to dose (C/D) ratios across pregnancy and postpartum and investigate the effect of pharmacogenetic variability on sertraline elimination. We performed a prospective observational cohort study in people with a singleton pregnancy ≤ 18 weeks gestation and a lifetime diagnosis of MDD at the 3 Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)-funded Obstetrical-Fetal Pharmacology Research Center sites. Subjects (N = 47) were receiving maintenance sertraline therapy and chose to continue it during pregnancy. Blood samples were obtained 24-hours postdose every 4 weeks across pregnancy and twice postpartum for measurement of plasma concentrations of sertraline and desmethylsertraline. Overall mean sertraline C/D ratios were decreased at study onset and remained consistently low until after delivery. During the last 4 weeks of pregnancy the mean sertraline C/D ratio (95% confidence interval (CI)), 0.25 (95% CI, 0.19, 0.3) ng/mL/dose (mg/day), was smaller than the mean ratio at ≥ 8 weeks after delivery, 0.32 (95% CI, 0.27, 0.37) ng/mL/dose (mg/day), a 22% difference. Mean sertraline/desmethylsertraline ratios were highest after birth, which confirmed increased sertraline elimination during pregnancy. Sertraline C/D ratios in participants with functional CYP2C19 activity did not change significantly during pregnancy, whereas ratios in participants with poor or intermediate CYP2C19 activity decreased by 51%. Exploratory pharmacogenomic analysis indicated that pregnant people with poor or intermediate CYP2C19 activity are at risk for subtherapeutic sertraline concentrations during pregnancy., (© 2022 The Authors. Clinical Pharmacology & Therapeutics © 2022 American Society for Clinical Pharmacology and Therapeutics.)

The pharmacokinetics of lithium, the gold standard for the treatment of bipolar disorder, are well described in nonpregnant patients. Because lithium is commonly prescribed to women of childbearing age, more data are essential to characterize lithium pharmacokinetics during the perinatal period. Lithium is primarily eliminated by the kidney. As a result, shifts in lithium elimination clearance parallel pregnancy-related changes in glomerular filtration rate. Lithium's narrow therapeutic window increases the risk for therapeutic failure and toxicity when lithium elimination clearance is altered. To characterize the pharmacokinetics of lithium in pregnancy and postpartum, 3 women treated with lithium for bipolar disorder completed serial blood sampling protocols during each trimester of pregnancy and at least once postpartum. The trajectory of lithium elimination clearance, creatinine clearance, and serum lithium concentrations were determined. Manic, depressive, and anxiety symptoms were also assessed at each study visit. Compared to the nonpregnant state, lithium elimination clearance increased an average of 63.5% by the third trimester. Lithium elimination clearance was inversely related to changes in serum lithium concentration. Mood symptoms worsened with declines in serum lithium concentration. Lithium elimination clearance returned to baseline at 4 to 9 weeks postpartum. To maintain lithium effectiveness during pregnancy and prevent toxicity postpartum, lithium therapeutic drug monitoring and dose adjustments are warranted., (© 2022 The Authors. The Journal of Clinical Pharmacology published by Wiley Periodicals LLC on behalf of American College of Clinical Pharmacology.)

Importance: Antidepressant use during pregnancy has been associated with neurodevelopmental disorders in children in some studies. However, results may be explained by uncontrolled confounding by parental mental health status, genetics, and environmental factors., Objective: To evaluate the association between antidepressant use in pregnancy and neurodevelopmental outcomes in children., Design, Setting, and Participants: This cohort study of health care utilization data was separated into cohorts of publicly and privately insured pregnant individuals and their children nested in the Medicaid Analytic eXtract (MAX; 2000-2014) and the IBM MarketScan Research Database (MarketScan; 2003-2015). A total of 1.93 million pregnancies in MAX and 1.25 million pregnancies in MarketScan were recorded. Children were followed from birth until outcome diagnosis, disenrollment, death, or end of study (maximum 14 years). Analyses were conducted between August 2020 and July 2021., Exposures: Dispensing of antidepressant medication from gestational week 19 until delivery, the period of synaptogenesis., Main Outcomes and Measures: Neurodevelopmental disorders in children defined using validated algorithms. Early pregnancy exposure was considered in sensitivity analyses, and approaches to confounding adjustment included propensity score fine stratification, discontinuers comparison, and sibling analyses., Results: Among the individuals included in the analysis, there were 145 702 antidepressant-exposed and 3 032 745 unexposed pregnancies; the mean (SD) age among the antidepressant exposed and unexposed was 26.2 (5.7) and 24.3 (5.8) years in MAX and 32.7 (4.6) and 31.9 (4.6) years in MarketScan, respectively; and in MAX, which collected information on race and ethnicity, 72.4% of the antidepressant-exposed and 37.1% of the unexposed individuals were White. Crude results suggested up to a doubling in risk of neurodevelopmental outcomes associated with antidepressant exposure; however, no association was observed in the most fully adjusted analyses. When comparing antidepressant-exposed and unexposed siblings, hazard ratios were 0.97 (95% CI, 0.88-1.06) for any neurodevelopmental disorder, 0.86 (95% CI, 0.60-1.23) for autism spectrum disorder, 0.94 (95% CI, 0.81-1.08) for attention-deficit/hyperactivity disorder, 0.77 (95% CI, 0.42-1.39) for specific learning disorders, 1.01 (95% CI, 0.88-1.16) for developmental speech/language disorder, 0.79 (95% CI, 0.54-1.17) for developmental coordination disorder, 1.00 (95% CI, 0.45-2.22) for intellectual disability, and 0.95 (95% CI, 0.80-1.12) for behavioral disorders. Results were generally consistent for antidepressant classes and drugs and across exposure windows., Conclusions and Relevance: The results of this cohort study suggest that antidepressant use in pregnancy itself does not increase the risk of neurodevelopmental disorders in children. However, given strong crude associations, antidepressant exposure in pregnancy may be an important marker for the need of early screening and intervention.

Background: Spontaneous cessation and reduction in smoking by pregnant women suggest that concern about others, or empathy, could be a malleable target for intervention. We examined various empathy-related processes in relations to reported and biochemically assessed smoking during pregnancy., Methods: Participants were 154 pregnant women (M = 12.4 weeks gestation, SD = 4.6) who were smoking cigarettes immediately prior to pregnancy recognition (85 had quit and 69 were still smoking at enrollment). Empathy-related processes were measured with performance-based paradigms (affect sharing, empathic concern, and theory of mind) and a speech sample (expressed emotion). Smoking was assessed with timeline follow back interviews and urine cotinine assays. Using zero-inflated Poisson regression models, we tested direct and interactive effects of empathy-related processes with respect to biologically verified smoking cessation (zero portion); and mean cigarettes/day smoked after pregnancy recognition among persistent smokers (count portion)., Results: Affect sharing was inversely related to post-recognition cigarettes/day (B(SE) = -0.17(0.07), 95%C.I. -0.30,-0.04, p = .011) and moderated the relationship between pre-recognition smoking and post-recognition smoking consistent with a buffering effect (B(SE) = -.17(0.05); 95%C.I. - 0.28,-0.06; p = .002). Other empathy related processes showed neither direct nor interactive effects on smoking outcomes., Conclusions: Further research is recommended to clarify the role of empathy in pregnancy smoking., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

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., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Importance: Although antipsychotic drugs cross the placenta and animal data suggest potential neurotoxic effects, information regarding human neurodevelopmental teratogenicity is limited., Objective: To evaluate whether children prenatally exposed to antipsychotic medication are at an increased risk of neurodevelopmental disorders (NDD)., Design, Settings, and Participants: This birth cohort study used data from the Medicaid Analytic eXtract (MAX, 2000-2014) and the IBM Health MarketScan Research Database (MarketScan, 2003-2015) for a nationwide sample of publicly (MAX) and privately (MarketScan) insured mother-child dyads with up to 14 years of follow-up. The MAX cohort consisted of 2 034 883 children who were not prenatally exposed and 9551 who were prenatally exposed to antipsychotic medications; the MarketScan consisted of 1 306 408 and 1221 children, respectively. Hazard ratios were estimated through Cox proportional hazards regression, using propensity score overlap weights for confounding control. Estimates from both cohorts were combined through meta-analysis., Exposures: At least 1 dispensing of a medication during the second half of pregnancy (period of synaptogenesis), assessed for any antipsychotic drug, at the class level (atypical and typical), and for the most commonly used drugs (aripiprazole, olanzapine, quetiapine, risperidone, and haloperidol)., Main Outcomes and Measures: Autism spectrum disorder, attention-deficit/hyperactivity disorder, learning disability, speech or language disorder, developmental coordination disorder, intellectual disability, and behavioral disorder, identified using validated algorithms, and the composite outcome of any NDD. Data were analyzed from April 2020 to January 2022., Results: The MAX cohort consisted of 2 034 883 unexposed pregnancies and 9551 pregnancies with 1 or more antipsychotic drug dispensings among women with a mean (SD) age of 26.8 (6.1) years, 204 (2.1%) of whom identified as Asian/Pacific Islander, 2720 (28.5%) as Black, 500 (5.2%) as Hispanic/Latino, and 5356 (56.1%) as White. The MarketScan cohort consisted of 1 306 408 unexposed and 1221 exposed pregnancies among women with a mean (SD) age of 33.1 (5.0) years; race and ethnicity data were not available. Although the unadjusted results were consistent with an approximate 2-fold increased risk for most exposure-outcome contrasts, risks were no longer meaningfully increased after adjustment (eg, pooled unadjusted vs adjusted hazard ratios [95% CI] for any NDD after any antipsychotic exposure: 1.91 [1.79-2.03] vs 1.08 [1.01-1.17]), with the possible exception of aripiprazole (1.36 [1.14-1.63]). Results were consistent across sensitivity analyses., Conclusions and Relevance: The findings of this birth cohort study suggest that the increased risk of NDD seen in children born to women who took antipsychotic drugs late in pregnancy seems to be explained by maternal characteristics and is not causally related with prenatal antipsychotic exposure. This finding highlights the importance of closely monitoring the neurodevelopment of the offspring of women with mental illness to ensure early intervention and support. The potential signal for aripiprazole requires replication in other data before causality can be assumed.

Background: Distinguishing postpartum women with bipolar from unipolar depression remains challenging, particularly in obstetrical and primary care settings. The post-birth period carries the highest lifetime risk for the onset or recurrence of Bipolar Disorder (BD). Characterization of differences between unipolar and bipolar depression symptom presentation and severity is critical to differentiate the two disorders., Methods: We performed a secondary analysis of a study of 10,000 women screened by phone with the Edinburgh Postnatal Depression Scale at 4-6 weeks post-birth. Screen-positive mothers completed the Structured Clinical Interview for DSM-4 and those diagnosed with BD and unipolar Major Depressive Disorder (UD) were included. Depressive symptoms were assessed with the 29-item Structured Interview Guide for the Hamilton Rating Scale for Depression (SIGH-ADS)., Results: The sample consisted of 728 women with UD and 272 women with BD. Women with BD had significantly elevated levels of depression severity due to the higher scores on 8 of the 29 SIGH-ADS symptoms. Compared to UD, women with BD had significantly higher rates of comorbid anxiety disorders and were twice as likely to report sexual and/or physical abuse., Limitations: Only women who screened positive for depression were included in this analysis. Postpartum women with unstable living situations, who were hospitalized or did not respond to contact attempts did not contribute data., Conclusions: Severity of specific symptom constellations may be a useful guide for interviewing postpartum depressed women along with the presence of anxiety disorder comorbidity and physical and/or sexual abuse., (Copyright © 2022. Published by Elsevier B.V.)

Objective: Tracking perinatal mood and anxiety disorders is championed by the American Psychiatric Association and the International Marcé Society for Perinatal Mental Health. We conducted this study to examine trajectories of monthly depressive and anxiety symptoms through pregnancy and postpartum., Methods: This is a prospective longitudinal observational cohort study of pregnant women interviewed at baseline (≤18th gestational week), every four weeks through delivery and at 6 and 14 weeks postpartum at three urban academic medical centers ( N  = 85) and a single rural health center ( N  = 3) from 2016 to 2020. Pregnant women had at least one prior episode of major depressive disorder, were not in a current episode, and were treated with sertraline, fluoxetine, citalopram, or escitalopram. Of 192 women screened, 88 (46%) women enrolled, and 77 (88%) women completed the postpartum follow-up. Symptom trajectories were generated with scores from the Edinburgh Postnatal Depression Scale, the Quick Inventory of Depressive Symptoms, the Generalized Anxiety Disorder Scale, 7-item, and the Patient-Reported Outcomes Measurement Information System Global Health measure. A semi-parametric, group-based mixture model (trajectory analysis) was applied., Results: Three relatively stable depression trajectories emerged, described as Minimal, Mild, and Subthreshold, in each group across pregnancy. Two of the four anxiety trajectories were stable, including Asymptomatic and Minimal, while the third, termed Breakthrough, was ascending with increasing symptoms and the fourth trajectory, described as Mild, had descending symptoms., Conclusions: Screening for anxiety with depression for pregnant women will yield a comprehensive view of psychiatric symptoms and treatment targets in perinatal women., (© 2022 The Authors. Psychiatric Research and Clinical Practice published by Wiley Periodicals LLC on behalf of American Psychiatric Association.)

Importance: Neurodevelopmental disorders are associated with poor health and social outcomes. Population-based data on incidence, age at diagnosis, and demographic variations are essential to identify modifiable risk factors and inform the planning of services and interventions., Objectives: To assess the incidence and timing of diagnosis of neurodevelopmental disorders during childhood in the US and to evaluate differences by population characteristics., Design, Setting, and Participants: This population-based cohort study used nationwide data on birth cohorts nested in the 2000-2014 Medicaid Analytic eXtract and the 2003-2015 IBM MarketScan Research Database on 2 070 541 publicly and 1 309 900 privately insured children enrolled at birth. Data were analyzed between May 1, 2020, and June 30, 2021., Main Outcomes and Measures: Neurodevelopmental disorders, autism spectrum disorders, attention-deficit/hyperactivity disorder, learning disabilities, speech or language disorders, developmental coordination disorders, intellectual disabilities, and behavioral disorders were identified based on validated algorithms. Kaplan-Meier analyses were used to estimate the incidence and timing of diagnosis, stratified by child's sex, birth year, maternal age at delivery, and race and ethnicity., Results: The cohorts comprised 2 070 541 publicly insured children (1 045 426 boys [50.5%]) and 1 309 900 privately insured children (667 607 boys [51.0%]) enrolled at birth. By 8 years of age, 23.9% of publicly insured children and 11.0% of privately insured children received a diagnosis of 1 or more neurodevelopmental disorders (autism spectrum disorder, 1.6% and 1.3%; attention-deficit/hyperactivity disorder, 14.5% and 5.8%; learning disability, 1.2% and 0.6%; speech or language disorder, 8.4% and 4.5%; developmental coordination disorder, 0.9% and 0.7%; intellectual disability, 0.7% and 0.1%; and behavioral disorder, 8.4% and 1.5%). Risks were substantially higher among boys (incidence of ≥1 neurodevelopmental disorder by age 8 years for boys vs girls: 30.7% vs 16.7% among publicly insured children and 15.0% vs 6.7% among privately insured children) and White children (30.2% vs 9.1% among Asian children, 23.0% among Black children, 15.4% among Hispanic children, and 22.7% among children of unknown race or ethnicity; information on race and ethnicity was available only for publicly insured children). The association of maternal age and birth year with incidence of neurodevelopmental disorders varied by outcome. Except for attention-deficit/hyperactivity disorder, the diagnosis tended to be established somewhat earlier for privately insured children. The association of race and ethnicity with age at diagnosis varied by outcome. Co-occurring neurodevelopmental disorders were common, especially among children with autism spectrum disorder and intellectual disability (>70% had ≥1 other disorder)., Conclusions and Relevance: In this population-based cohort study, a relatively high incidence of and co-occurrence of neurodevelopmental disorders as well as the disparity in incidence and timing of diagnosis by insurance type and race and ethnicity were found. These findings represent important public health concerns and underscore the need for timely and accessible developmental assessments and educational services to help reduce the burden of these disorders.

The objective of this study was to identify differences in the longitudinal course anhedonia symptoms during postpartum in women diagnosed with unipolar or bipolar disorder. Female participants diagnosed with either bipolar (n = 104) or unipolar (n = 136) depression at week 20 during pregnancy were evaluated prospectively at weeks 2, 12, 26, and 52 postpartum using clinical interviews. A semi-parametric, group-based mixture model was applied to separate distinct longitudinal patterns of symptoms of anhedonia. Across time, among those who reported anhedonia, twice as many women had the diagnoses of bipolar depression relative to unipolar depression (65.03% versus 39.47%, respectively). Moreover, the rate and stability of anhedonia was higher in women with bipolar relative to unipolar depression. Across groups, anhedonia was associated with significantly higher depressive symptom severity. Anhedonia is a more stable and frequent symptom in women with postpartum bipolar relative to unipolar depressive disorder., (Copyright © 2021. Published by Elsevier B.V.)

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., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

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., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: The study evaluated whether implementation of perinatal collaborative care is associated with improvements in screening and treatment recommendations for perinatal depression by obstetric clinicians., Methods: This cohort study, conducted from January 2015 to January 2019, included all women who received prenatal care in five obstetric clinics and delivered at a single quaternary care hospital in Chicago. In January 2017, a perinatal collaborative care program (COMPASS) was implemented. Completion of depression screening and recommendations for treatment following a positive depression screen were compared before and after COMPASS implementation. Adjusted analyses included inverse probability weighting by using propensity scores to impose control over imbalance between exposure groups with respect to prespecified covariates., Results: A total of 7,028 women were included in these analyses: 3,227 (46%) before and 3,801 (54%) after COMPASS implementation. Women who received obstetric care after implementation were significantly more likely than those who received care before implementation to receive antenatal screening for depression (81% versus 33%; adjusted odds ratio [aOR]=8.5, 95% confidence interval [CI]=7.6-9.5). After implementation, women with a positive antenatal screen for depression were more likely to receive a treatment recommendation (61% versus 44%; aOR=2.1, 95% CI=1.2-3.7). After implementation of perinatal collaborative care, combined psychotherapy and pharmacotherapy were more frequently recommended, compared with before implementation., Conclusions: Implementation of a perinatal collaborative care program was associated with improvements in perinatal depression screening and recommendations for treatment by obstetric clinicians.

Background: The prevention of postpartum depression is an important area of investigation given its association with major maternal and neonatal sequelae, yet few evidence-based treatments to reduce the frequency of postpartum depression are used. Recent data suggest that N-methyl-D-aspartate receptor antagonists may lead to rapid improvement of depressive symptoms lasting up to 2 weeks. We hypothesized that the N-methyl-D-aspartate receptor antagonist magnesium sulfate would elicit antidepressant effects subsequent to its receipt by women receiving peripartum seizure prophylaxis for a hypertensive disorder of pregnancy., Objective: This study aimed to compare the frequency of depressive symptoms at 2 weeks and 6 weeks after delivery between women who did and did not receive peripartum magnesium sulfate for a hypertensive disorder of pregnancy., Study Design: This prospective cohort study included women with a hypertensive disorder of pregnancy at ≥34 weeks' gestation with singleton gestations. Magnesium sulfate for seizure prophylaxis was administered at the obstetrician's discretion. The Quick Inventory of Depressive Symptomatology survey was administered before hospital discharge and again at 2 weeks and 6 weeks after delivery to assess for postpartum depressive symptoms. The primary outcome for this study was the change in Quick Inventory of Depressive Symptomatology score from baseline to 2 weeks after delivery, which was analyzed both continuously and categorically (any symptom worsening vs stability or improvement). Secondary outcomes included the change in Quick Inventory of Depressive Symptomatology score from baseline to 6 weeks after delivery and the proportion of women who experienced an increase in Quick Inventory of Depressive Symptomatology score at 6 weeks after delivery., Results: Of the 342 women enrolled, 39% (n=134) received magnesium sulfate. Compared with women who did not receive magnesium, women who received magnesium had a significantly smaller change in their mean Quick Inventory of Depressive Symptomatology score (0.6±3.4 vs 1.6±3.0; P=.015) and also were less likely to have an increase in Quick Inventory of Depressive Symptomatology score at 2 weeks after delivery (52% vs 67%; P=.022). These differences were not present at 6 weeks after delivery. After controlling for potential confounders, women who received magnesium continued to have a lower odds of having an increased Quick Inventory of Depressive Symptomatology score from baseline at 2 weeks after delivery than women who did not receive magnesium (adjusted odds ratio, 0.88; 95% confidence interval, 0.78-0.98)., Conclusion: Peripartum magnesium was associated with less of an exacerbation in depressive symptoms in the immediate postpartum period. Given the implications of postpartum depression on maternal and child health and the lack of existing prophylaxis, randomized trials should examine this novel potential prophylactic therapy., (Copyright © 2021 Elsevier Inc. All rights reserved.)

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., (Copyright © 2021 Elsevier Inc. All rights reserved.)