Screening, Assessment, and Treatment of Perinatal Mental Health in Obstetrical Settings.

Perinatal mood and anxiety disorders (PMADs) are common, yet obstetricians receive little training prior to independent practice on screening, assessing, diagnosing, and treating patients with depression and anxiety. Untreated PMADs lead to adverse pregnancy and fetal outcomes. Obstetricians are in a unique position to address PMADs. The following serves as a resource for addressing PMADs in obstetric practice.

Developmental Windows for Effects of Choline and Folate on Excitatory and Inhibitory Neurotransmission During Human Gestation.

Choline and folate are critical nutrients for fetal brain development, but the timing of their influence during gestation has not been previously characterized. At different periods during gestation, choline stimulation of α7-nicotinic receptors facilitates conversion of γ-aminobutyric acid (GABA) receptors from excitatory to inhibitory and recruitment of GluR1-R2 receptors for faster excitatory responses to glutamate. The outcome of the fetal development of inhibition and excitation was assessed in 159 newborns by P50 cerebral auditory-evoked responses. Paired stimuli, S1, S2, were presented 500 msec apart. Higher P50 amplitude in response to S1 (P50S1microV) assesses excitation, and lower P50S2microV assesses inhibition in this paired-stimulus paradigm. Development of inhibition was related solely to maternal choline plasma concentration and folate supplementation at 16 weeks' gestation. Development of excitation was related only to maternal choline at 28 weeks. Higher maternal choline concentrations later in gestation did not compensate for earlier lower concentrations. At 4 years of age, increased behavior problems on the Child Behavior Checklist 1½-5yrs were related to both newborn inhibition and excitation. Incomplete development of inhibition and excitation associated with lower choline and folate during relatively brief periods of gestation thus has enduring effects on child development.

Intrinsic Infant Hippocampal Function Supports Inhibitory Processing.

Impaired cerebral inhibition is commonly observed in neurodevelopmental disorders and may represent a vulnerability factor for their development. The hippocampus plays a key role in inhibition among adults and undergoes significant and rapid changes during early brain development. Therefore, the structure represents an important candidate region for early identification of pathology that is relevant to inhibitory dysfunction. To determine whether hippocampal function corresponds to inhibition in the early postnatal period, the present study evaluated relationships between hippocampal activity and sensory gating in infants 4-20 weeks of age (N = 18). Resting-state functional magnetic resonance imaging was used to measure hippocampal activity, including the amplitude of low-frequency fluctuations (ALFFs) and fractional ALFF. Electroencephalography during a paired-stimulus paradigm was used to measure sensory gating (P50). Higher activity of the right hippocampus was associated with better sensory gating (P50 ratio), driven by a reduction in response to the second stimulus. These findings suggest that meaningful effects of hippocampal function can be detected early in infancy. Specifically, higher intrinsic hippocampal activity in the early postnatal period may support effective inhibitory processing. Future work will benefit from longitudinal analysis to clarify the trajectory of hippocampal function, alterations of which may contribute to the risk of neurodevelopmental disorders and represent an intervention target.

Prenatal choline, cannabis, and infection, and their association with offspring development of attention and social problems through 4 years of age.

BACKGROUND: Prenatal choline is a key nutrient, like folic acid and vitamin D, for fetal brain development and subsequent mental function. We sought to determine whether effects of higher maternal plasma choline concentrations on childhood attention and social problems, found in an initial clinical trial of choline supplementation, are observed in a second cohort. METHODS: Of 183 mothers enrolled from an urban safety net hospital clinic, 162 complied with gestational assessments and brought their newborns for study at 1 month of age; 83 continued assessments through 4 years of age. Effects of maternal 16 weeks of gestation plasma choline concentrations ⩾7.07 µM, 1 s.d. below the mean level obtained with supplementation in the previous trial, were compared to lower levels. The Attention Problems and Withdrawn Syndrome scales on Child Behavior Checklist 1½-5 were the principal outcomes. RESULTS: Higher maternal plasma choline was associated with lower mean Attention Problems percentiles in children, and for male children, with lower Withdrawn percentiles. Higher plasma choline concentrations also reduced Attention Problems percentiles for children of mothers who used cannabis during gestation as well as children of mothers who had gestational infection. CONCLUSIONS: Prenatal choline's positive associations with early childhood behaviors are found in a second, more diverse cohort. Increases in attention problems and social withdrawal in early childhood are associated with later mental illnesses including attention deficit disorder and schizophrenia. Choline concentrations in the pregnant women in this study replicate other research findings suggesting that most pregnant women do not have adequate choline in their diets.

Male fetus susceptibility to maternal inflammation: C-reactive protein and brain development.

BACKGROUND: Maternal inflammation in early pregnancy has been identified epidemiologically as a prenatal pathogenic factor for the offspring's later mental illness. Early newborn manifestations of the effects of maternal inflammation on human fetal brain development are largely unknown. METHODS: Maternal infection, depression, obesity, and other factors associated with inflammation were assessed at 16 weeks gestation, along with maternal C-reactive protein (CRP), cytokines, and serum choline. Cerebral inhibition was assessed by inhibitory P50 sensory gating at 1 month of age, and infant behavior was assessed by maternal ratings at 3 months of age. RESULTS: Maternal CRP diminished the development of cerebral inhibition in newborn males but paradoxically increased inhibition in females. Similar sex-dependent effects were seen in mothers' assessment of their infant's self-regulatory behaviors at 3 months of age. Higher maternal choline levels partly mitigated the effect of CRP in male offspring. CONCLUSIONS: The male fetal-placental unit appears to be more sensitive to maternal inflammation than females. Effects are particularly marked on cerebral inhibition. Deficits in cerebral inhibition 1 month after birth, similar to those observed in several mental illnesses, including schizophrenia, indicate fetal developmental pathways that may lead to later mental illness. Deficits in early infant behavior follow. Early intervention before birth, including prenatal vitamins, folate, and choline supplements, may help prevent fetal development of pathophysiological deficits that can have life-long consequences for mental health.

Exposure to prenatal maternal distress and infant white matter neurodevelopment.

The prenatal period represents a critical time for brain growth and development. These rapid neurological advances render the fetus susceptible to various influences with life-long implications for mental health. Maternal distress signals are a dominant early life influence, contributing to birth outcomes and risk for offspring psychopathology. This prospective longitudinal study evaluated the association between prenatal maternal distress and infant white matter microstructure. Participants included a racially and socioeconomically diverse sample of 85 mother-infant dyads. Prenatal distress was assessed at 17 and 29 weeks' gestational age (GA). Infant structural data were collected via diffusion tensor imaging at 42-45 weeks' postconceptional age. Findings demonstrated that higher prenatal maternal distress at 29 weeks' GA was associated with increased fractional anisotropy (b = .283, t(64) = 2.319, p = .024) and with increased axial diffusivity (b = .254, t(64) = 2.067, p = .043) within the right anterior cingulate white matter tract. No other significant associations were found with prenatal distress exposure and tract fractional anisotropy or axial diffusivity at 29 weeks' GA, nor earlier in gestation.

Interaction of maternal choline levels and prenatal Marijuana's effects on the offspring.

BACKGROUND: This study investigated whether higher maternal choline levels mitigate effects of marijuana on fetal brain development. Choline transported into the amniotic fluid from the mother activates α7-nicotinic acetylcholine receptors on fetal cerebro-cortical inhibitory neurons, whose development is impeded by cannabis blockade of their cannabinoid-1(CB1) receptors. METHODS: Marijuana use was assessed during pregnancy from women who later brought their newborns for study. Mothers were informed about choline and other nutrients, but not specifically for marijuana use. Maternal serum choline was measured at 16 weeks gestation. RESULTS: Marijuana use for the first 10 weeks gestation or more by 15% of mothers decreased newborns' inhibition of evoked potentials to repeated sounds (d' = 0.55, p < 0.05). This effect was ameliorated if women had higher gestational choline (rs = -0.50, p = 0.011). At 3 months of age, children whose mothers continued marijuana use through their 10th gestational week or more had poorer self-regulation (d' = -0.79, p < 0.05). This effect was also ameliorated if mothers had higher gestational choline (rs = 0.54, p = 0.013). Maternal choline levels correlated with the children's improved duration of attention, cuddliness, and bonding with parents. CONCLUSIONS: Prenatal marijuana use adversely affects fetal brain development and subsequent behavioral self-regulation, a precursor to later, more serious problems in childhood. Stopping marijuana use before 10 weeks gestational age prevented these effects. Many mothers refuse to cease use because of familiarity with marijuana and belief in its safety. Higher maternal choline mitigates some of marijuana's adverse effects on the fetus.

Maternal and child delivery charges, postpartum charges, and utilization of care among women with bipolar disorder: a cohort study.

Bipolar disorder (BD) during pregnancy is known to be a morbid condition associated with poor outcomes for both the mother and her infant. We aimed to determine if women with BD and their children have higher charges and health service utilization than mother-infant dyads with and without other mental health (MH) diagnoses. The International Classification of Diseases, Ninth Revision (ICD9) codes were used to identify mutually exclusive groups of women who gave birth between January 1, 2011, and December 31, 2012, coding first for BD, then diagnoses that comprised an "other MH diagnoses group" that included post-traumatic stress disorder, anxiety, and depression. Health service utilization and related charges were obtained for the dyad for delivery and for 2 years post-delivery at a single tertiary care center. Analyses included 4440 dyads. A BD diagnosis occurred in 1.8% of medical record codes, other MH diagnoses in 10%, and no known MH diagnosis in 88%. Compared with women with both other MH and no known MH diagnoses, women with BD had higher delivery charges (p < 0.001), higher cumulative charges in the 2 years postpartum (p < 0.001), higher preterm birth and low birthweight rates (15.5% v. 6.9% and 20.8% v. 6.4%, p < 0.001, BD v. no known MH, respectively), and greater utilization of inpatient and emergency psychiatric care services (p < 0.001). Compared with women with and without other mental health diagnoses, women with BD have the highest care utilization and charges. They also have higher preterm birth and low birthweight infant rates, two clinically relevant predictors of long-term health for the child. Given the low prevalence of BD and severity of the disease versus the magnitude of systems costs, women with BD, and their children, deserve the heightened attention afforded to other high-risk perinatal conditions.

Self-Reported Alcohol, Tobacco, and Marijuana Use in Pregnant Women with Depressive Symptomatology.

OBJECTIVE: Substance use disorders often coexist with depression. The objective of this study was to establish whether pregnant women who report depressive symptomatology were more likely to report use of alcohol, tobacco, and marijuana during pregnancy. STUDY DESIGN: This was a secondary analysis of prospectively collected data from the Maternal-Fetal Medicine Units Network Preterm Prediction Study. Self-reported history of alcohol, tobacco, and marijuana use was compared between pregnant women with and without depressive symptomatology with adjustment for demographic factors. RESULTS: After adjustment for demographic factors, women with depressive symptomatology were more likely to report: any alcohol use (odds ratio [OR]: 1.4, 95% confidence interval [CI]: 1.1-1.8), >1 drink per week (OR: 1.3, 95% CI: 1.0-1.8), and >1 drink per day (OR: 2.2, 95% CI: 1.5-3.4). Women with depressive symptomatology were also more likely to report use of marijuana (OR: 1.8, 95% CI: 1.2-2.6) and cigarettes (OR: 1.4, 95% CI: 1.1-1.7). CONCLUSION: Depressive symptomatology was associated with an increase in self-reported the use of alcohol, tobacco, and marijuana during pregnancy. These data reveal the importance of targeted screening of pregnant women with depressive symptomatology for substance use.

Higher Gestational Choline Levels in Maternal Infection Are Protective for Infant Brain Development.

OBJECTIVE: To assess whether maternal choline decreases effects of mothers' infections on fetal brain circuit development and on expression of infant behavior at 1 year of age. STUDY DESIGN: A cross-sectional study was conducted in a public hospital obstetrics and midwifery service, with prenatal assessments of maternal infection, C-reactive protein, and choline level and postnatal assessments of cerebral neuronal inhibition in 162 newborns. At 1 year, 136 parents completed reports of their child's behavior. RESULTS: Maternal infection at 16 weeks of gestation, experienced by 41% of mothers, raised mean maternal C-reactive protein (d' = 0.47, P = .002) and decreased the development of cerebral inhibition of auditory response at 1 month of age (d' = 0.39, P < .001). Decreased newborn cerebral inhibition manifested as decreased behavioral self-regulation at 1 year. Greater choline levels in mothers with infections were associated with improved newborn inhibition of auditory cerebral response, mitigating the effect of infection (ß = -0.34 [95% CI, -5.35 to -0.14], P = .002). At 1 year of age, children of mothers with infection and greater gestational choline levels had improved development of self-regulation, approaching the level of children of mothers without infection (ß = 0.29 [95% CI 0.05-0.54], P = .03). CONCLUSIONS: Greater maternal choline, recommended by the American Medical Association as a prenatal supplement, is associated with greater self-regulation among infants who experienced common maternal infections during gestation. Behavioral problems with diminished self-regulation often lead to referrals to pediatricians and might lead to later mental illness.

Maternal self-harm deaths: an unrecognized and preventable outcome.

Maternal mortality continues to be a public health priority in national and international communities. Maternal death rates secondary to medical illnesses such as cardiovascular disease, preeclampsia, and postpartum hemorrhage are well documented. The rates of maternal death secondary to self-harm, including suicide and overdose, have been omitted from published rates of maternal mortality, despite growing attention to the prevalence of perinatal mood disorders, estimated at up to 15% of pregnant and postpartum women in the United States. Underlying psychiatric disorder, including depression, is consistently identified as a risk factor in substance abuse and suicide. The rate of opioid-associated morbidity and mortality has recently been deemed a national crisis. Pregnancy does not protect against these risks, and the postpartum period has been identified as a particularly vulnerable time. The lack of consistent and inclusive data on self-harm deaths in the pregnancy-postpartum period is alarming. This review will identify barriers to reporting and ascertainment of maternal suicide and overdose deaths, summarize geographic-specific data available, address potential social and psychological biases that have led to neglect of the topic of maternal self-harm deaths, and suggest recommendations that incorporate the whole woman in prenatal care and thus prevention of this devastating outcome.

An experimental test of the fetal programming hypothesis: Can we reduce child ontogenetic vulnerability to psychopathology by decreasing maternal depression?

Maternal depression is one of the most common prenatal complications, and prenatal maternal depression predicts many child psychopathologies. Here, we apply the fetal programming hypothesis as an organizational framework to address the possibility that fetal exposure to maternal depressive symptoms during pregnancy affects fetal development of vulnerabilities and risk mechanisms, which enhance risk for subsequent psychopathology. We consider four candidate pathways through which maternal prenatal depression may affect the propensity of offspring to develop later psychopathology across the life span: brain development, physiological stress regulation (hypothalamic-pituitary-adrenocortical axis), negative emotionality, and cognitive (effortful) control. The majority of past research has been correlational, so potential causal conclusions have been limited. We describe an ongoing experimental test of the fetal programming influence of prenatal maternal depressive symptoms using a randomized controlled trial design. In this randomized controlled trial, interpersonal psychotherapy is compared to enhanced usual care among distressed pregnant women to evaluate whether reducing prenatal maternal depressive symptoms has a salutary impact on child ontogenetic vulnerabilities and thereby reduces offspring's risk for emergence of later psychopathology.

Cortisol during human fetal life: Characterization of a method for processing small quantities of newborn hair from 26 to 42 weeks gestation.

OBJECTIVE: Fetal cortisol may be reflected in hair collected shortly after birth. The objective of this study was to determine the range of human fetal hair cortisol concentrations (HCC) in live-born neonates using an approach for processing small quantities of hair. MATERIALS AND METHODS: Hair was cut on the day of birth from neonates and their mothers, born between 26 and 42 weeks gestational age (GA). HCC was determined by enzyme immunoassay. Maternal sociodemographics and birth data were collected. T-tests, ANOVA, Pearson correlation, and Wilcoxon Signed Rank test were used as appropriate. RESULTS: Ninety maternal and neonatal hair samples were cut from 79 term (T) and 11 preterm (PT) delivered pregnancies. All samples weighed ≥2.5 mg. Fetal HCC correlated with GA (r = .25, p = .02) and birth weight (r = .25, p = .03) and was lower in PT (4.3 ± .3 LN pg/mg) than T (5.3 ± .1, LN pg/mg, p < .001) neonates. No significant relationships were seen between fetal HCC and maternal characteristics or maternal HCC. Fetal HCC was significantly higher than maternal HCC. CONCLUSION: Fetal cortisol exposure was determined using this approach for processing small amounts of hair. Preterm neonates have significantly lower HCC than term neonates and fetal HCC is associated with GA at delivery and birth weight. Fetal HCC is significantly higher than maternal HCC cut on the same day. These data provide novel information on the intrauterine fetal cortisol environment.

Chemical processing and shampooing impact cortisol measured in human hair.

PURPOSE: The assessment of cortisol in hair has gained popularity as a means to measure retrospective hypothalamic-pituitary-adrenal activity in a number of species; however, cortisol levels from human hair subjected to typical chemicals for cosmetic or hygienic purposes may be altered by the chemicals used. The purposed of this study was to determine if exposure of hair to chemical processing or shampooing impacts cortisol values. METHODS: Human hair not exposed to prior chemical processing was cut from the posterior vertex region of the head of 106 human subjects as close to the scalp as possible. The hair sample was divided into 4-6 full-length clusters depending on quantity of hair available. Each hair sample was processed for baseline (native) cortisol and remaining clusters were exposed to five standard chemical hair treatments (Experiment 1) or were shampooed 15 or 30 times (Experiment 2). Hair was ground and cortisol levels were determined by enzyme immunoassay (EIA). Comparisons were made between native hair and processed hair using paired t-tests and Pearson correlation. RESULTS: Hair cortisol as assessed by EIA was significantly altered by chemical processing but in somewhat different ways. Exposure to bleach (harshest exposure), demi-perm (least exposure) or 15-30 shampoos resulted in a significant decrease in cortisol level while exposure to varying percentages of peroxides increased cortisol measured. There were no differences in cortisol levels associated with sex, age or tobacco use in the native hair for this particular group. CONCLUSION: Chemical processing and frequent shampooing affect cortisol levels measured in hair. Chemically processed or excessively shampooed hair should be avoided when recruiting subjects for hair cortisol studies.

Impact of prenatal maternal depression on gestational length: post hoc analysis of a randomized clinical trial.

Background: Shortened gestation is a leading cause of childhood morbidity and mortality with lifelong consequences for health. There is a need for public health initiatives on increasing gestational age at birth. Prenatal maternal depression is a pervasive health problem robustly linked via correlational and epidemiological studies to shortened gestational length. This proof-of-concept study tests the impact of reducing prenatal maternal depression on gestational length with analysis of a randomized clinical trial (RCT). Methods: Participants included 226 pregnant individuals enrolled into an RCT and assigned to receive either interpersonal psychotherapy (IPT) or enhanced usual care (EUC). Recruitment began in July 2017 and participants were enrolled August 10, 2017 to September, 8 2021. Depression diagnosis (Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition; DSM 5) and symptoms (Edinburgh Postnatal Depression Scale and Symptom Checklist) were evaluated at baseline and longitudinally throughout gestation to characterize depression trajectories. Gestational dating was collected based on current guidelines via medical records. The primary outcome was gestational age at birth measured dichotomously (≥39 gestational weeks) and the secondary outcome was gestational age at birth measured continuously. Posthoc analyses were performed to test the effect of reducing prenatal maternal depression on gestational length. This trial is registered with ClinicalTrials.gov (NCT03011801). Findings: Steeper decreases in depression trajectories across gestation predicted later gestational age at birth, specifically an increase in the number of full-term babies born ≥39 gestational weeks (EPDS linear slopes: OR = 1.54, 95% CI 1.10-2.16; and SCL-20 linear slopes: OR = 1.67, 95% CI 1.16-2.42). Causal mediation analyses supported the hypothesis that participants assigned to IPT experienced greater reductions in depression symptom trajectories, which in turn, contributed to longer gestation. Supporting mediation, the natural indirect effect (NIE) showed that reduced depression trajectories resulting from intervention were associated with birth ≥39 gestational weeks (EPDS, OR = 1.65, 95% CI 1.02-2.66; SCL-20, OR = 1.85, 95% CI 1.16-2.97). Interpretation: We used a RCT design and found that reducing maternal depression across pregnancy was associated with lengthened gestation. Funding: This research was supported by the NIH (R01 HL155744, R01 MH109662, R21 MH124026, P50 MH096889).

Higher prenatal anxiety predicts lower neonatal hair cortisol.

BACKGROUND: Prenatal glucocorticoids are one of the most widely proposed prenatal programming mechanisms, yet few studies exist that measure fetal cortisol via neonatal hair. Neonatal hair provides a window into the fetal experience and represents cortisol accumulation in the third trimester of pregnancy. In the current study, we test the links between two types of anxiety over the course of gestation (pregnancy-related anxiety and general anxiety) with neonatal hair cortisol. METHOD: Pregnant individuals (N = 107) and their neonates (59.8% female) participated in the current study. Prenatal pregnancy-related anxiety and general anxiety were measured using the Pregnancy Related Anxiety Scale (PRAS) and the State-Trait Anxiety Inventory (STAI), in each trimester of pregnancy. Hierarchical linear modeling was used to model the intercept and slope of each type of anxiety over gestation. Neonatal hair samples were collected shortly after birth (Median days = 1.17, IQR = 0.75-2.00). RESULTS: Both higher pregnancy-related anxiety and general anxiety at the beginning of pregnancy and a flatter decline of pregnancy-related anxiety over gestation were associated with lower neonatal hair cortisol. After inclusion of gestational age at birth and parity as covariates, pregnancy-related anxiety (intercept: ß = -0.614, p =.012; slope: ß = -0.681, p =.006), but not general anxiety (intercept: ß = -0.389, p =.114; slope: ß = -0.302, p =.217) remained a significant predictor. Further, when both general and pregnancy-related anxiety were entered into the same model, only pregnancy-related anxiety (intercept and slope) were significant predictors of neonatal hair cortisol, indicating an association with pregnancy-related anxiety above and beyond general anxiety. CONCLUSION: Cortisol plays a central role in maturation of fetal organ systems, and at the end of gestation, higher cortisol has beneficial effects such as promoting fetal lung maturation. Further, lower maternal cortisol is linked to less optimal cognitive development and altered brain development. As maternal higher anxiety in early pregnancy and a flatter decrease over time are both associated with lower neonatal hair cortisol, maternal pregnancy-related anxiety could be a target of future intervention efforts.

Maternal anxiety during pregnancy predicts infant attention to affective faces.

BACKGROUND: Prenatal maternal anxiety is a known influence on offspring development. General anxiety and pregnancy-related anxiety (a distinct type of anxiety encompassing fears associated with pregnancy) are associated with offspring socioemotional development, with potential consequences for later emotional and behavioral problems. This study examines whether maternal pregnancy-related and general anxiety relate to infant attention to affective faces, a process which plays an integral role in early socioemotional development. METHODS: Participants included 86 mothers and their 6-month-old infants (56.3 % female). Mothers completed measures of pregnancy-related and general anxiety three times through gestation. Infants' attention to affective faces was assessed with an eye-tracking task during which a series of face pairs were presented (happy, angry, or sad face paired with a neutral face). Overall attention measures included attention-holding (total looking time) and attention-orienting (latency to faces); affect-biased attention measures included proportion of total looking time to emotional faces and latency difference score. RESULTS: Higher maternal pregnancy-related anxiety across gestation predicted decreased infant attention-holding to affective faces [F(1,80) = 7.232, p = .009, partial η2 = 0.083]. No differences were found in infant attention-orienting or affect-biased attention. LIMITATIONS: Reliance on a correlational study design precludes the ability to make causal inferences. CONCLUSIONS: Maternal pregnancy-related anxiety is an important predictor of child outcomes. We provide novel evidence that pregnancy-related anxiety predicts infant attention to emotional faces, behaviors which have important implications for socioemotional development. Providers may consider pregnancy-related anxiety as a target for screening and treatment that may benefit both pregnant individual and offspring.

Post-Acute Sequelae of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) After Infection During Pregnancy.

OBJECTIVE: To estimate the prevalence of post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (PASC) after infection with SARS-CoV-2 during pregnancy and to characterize associated risk factors. METHODS: In a multicenter cohort study (NIH RECOVER [Researching COVID to Enhance Recovery]-Pregnancy Cohort), individuals who were pregnant during their first SARS-CoV-2 infection were enrolled across the United States from December 2021 to September 2023, either within 30 days of their infection or at differential time points thereafter. The primary outcome was PASC, defined as score of 12 or higher based on symptoms and severity as previously published by the NIH RECOVER-Adult Cohort, at the first study visit at least 6 months after the participant's first SARS-CoV-2 infection. Risk factors for PASC were evaluated, including sociodemographic characteristics, clinical characteristics before SARS-CoV-2 infection (baseline comorbidities, trimester of infection, vaccination status), and acute infection severity (classified by need for oxygen therapy). Multivariable logistic regression models were fitted to estimate associations between these characteristics and presence of PASC. RESULTS: Of the 1,502 participants, 61.1% had their first SARS-CoV-2 infection on or after December 1, 2021 (ie, during Omicron variant dominance); 51.4% were fully vaccinated before infection; and 182 (12.1%) were enrolled within 30 days of their acute infection. The prevalence of PASC was 9.3% (95% CI, 7.9-10.9%) measured at a median of 10.3 months (interquartile range 6.1-21.5) after first infection. The most common symptoms among individuals with PASC were postexertional malaise (77.7%), fatigue (76.3%), and gastrointestinal symptoms (61.2%). In a multivariable model, the proportion PASC positive with vs without history of obesity (14.9% vs 7.5%, adjusted odds ratio [aOR] 1.65, 95% CI, 1.12-2.43), depression or anxiety disorder (14.4% vs 6.1%, aOR 2.64, 95% CI, 1.79-3.88) before first infection, economic hardship (self-reported difficulty covering expenses) (12.5% vs 6.9%, aOR 1.57, 95% CI, 1.05-2.34), and treatment with oxygen during acute SARS-CoV-2 infection (18.1% vs 8.7%, aOR 1.86, 95% CI, 1.00-3.44) were associated with increased prevalence of PASC. CONCLUSION: The prevalence of PASC at a median time of 10.3 months after SARS-CoV-2 infection during pregnancy was 9.3% in the NIH RECOVER-Pregnancy Cohort. The predominant symptoms were postexertional malaise, fatigue, and gastrointestinal symptoms. Several socioeconomic and clinical characteristics were associated with PASC after infection during pregnancy. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT05172024.

Effect of Brief Interpersonal Therapy on Depression During Pregnancy: A Randomized Clinical Trial.

Importance: Prenatal depression is prevalent with negative consequences for both the mother and developing fetus. Brief, effective, and safe interventions to reduce depression during pregnancy are needed. Objective: To evaluate depression improvement (symptoms and diagnosis) among pregnant individuals from diverse backgrounds randomized to brief interpersonal psychotherapy (IPT) vs enhanced usual care (EUC). Design, Setting, and Participants: A prospective, evaluator-blinded, randomized clinical trial, the Care Project, was conducted among adult pregnant individuals who reported elevated symptoms during routine obstetric care depression screening in general practice in obstetrics and gynecology (OB/GYN) clinics. Participants were recruited between July 2017 and August 2021. Repeated measures follow-up occurred across pregnancy from baseline (mean [SD], 16.7 [4.2] gestational weeks) through term. Pregnant participants were randomized to IPT or EUC and included in intent-to-treat analyses. Interventions: Treatment comprised an engagement session and 8 active sessions of brief IPT (MOMCare) during pregnancy. EUC included engagement and maternity support services. Main Outcomes and Measures: Two depression symptom scales, the 20-item Symptom Checklist and the Edinburgh Postnatal Depression Scale, were assessed at baseline and repeatedly across pregnancy. Structured Clinical Interview for DSM-5 ascertained major depressive disorder (MDD) at baseline and the end of gestation. Results: Of 234 participants, 115 were allocated to IPT (mean [SD] age, 29.7 [5.9] years; 57 [49.6%] enrolled in Medicaid; 42 [36.5%] had current MDD; 106 [92.2%] received intervention) and 119 to EUC (mean [SD] age, 30.1 [5.9] years; 62 [52.1%] enrolled in Medicaid; 44 [37%] had MDD). The 20-item Symptom Checklist scores improved from baseline over gestation for IPT but not EUC (d = 0.57; 95% CI, 0.22-0.91; mean [SD] change for IPT vs EUC: 26.7 [1.14] to 13.6 [1.40] vs 27.1 [1.12] to 23.5 [1.34]). IPT participants more rapidly improved on Edinburgh Postnatal Depression Scale compared with EUC (d = 0.40; 95% CI, 0.06-0.74; mean [SD] change for IPT vs EUC: 11.4 [0.38] to 5.4 [0.57] vs 11.5 [0.37] to 7.6 [0.55]). MDD rate by end of gestation had decreased significantly for IPT participants (7 [6.1%]) vs EUC (31 [26.1%]) (odds ratio, 4.99; 95% CI, 2.08-11.97). Conclusions and Relevance: In this study, brief IPT significantly reduced prenatal depression symptoms and MDD compared with EUC among pregnant individuals from diverse racial, ethnic, and socioeconomic backgrounds recruited from primary OB/GYN clinics. As a safe, effective intervention to relieve depression during pregnancy, brief IPT may positively affect mothers' mental health and the developing fetus. Trial Registration: ClinicalTrials.gov Identifier: NCT03011801.