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.

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).

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.

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.

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.

Researching COVID to enhance recovery (RECOVER) pregnancy study: Rationale, objectives and design.

IMPORTANCE: Pregnancy induces unique physiologic changes to the immune response and hormonal changes leading to plausible differences in the risk of developing post-acute sequelae of SARS-CoV-2 (PASC), or Long COVID. Exposure to SARS-CoV-2 during pregnancy may also have long-term ramifications for exposed offspring, and it is critical to evaluate the health outcomes of exposed children. The National Institutes of Health (NIH) Researching COVID to Enhance Recovery (RECOVER) Multi-site Observational Study of PASC aims to evaluate the long-term sequelae of SARS-CoV-2 infection in various populations. RECOVER-Pregnancy was designed specifically to address long-term outcomes in maternal-child dyads. METHODS: RECOVER-Pregnancy cohort is a combined prospective and retrospective cohort that proposes to enroll 2,300 individuals with a pregnancy during the COVID-19 pandemic and their offspring exposed and unexposed in utero, including single and multiple gestations. Enrollment will occur both in person at 27 sites through the Eunice Kennedy Shriver National Institutes of Health Maternal-Fetal Medicine Units Network and remotely through national recruitment by the study team at the University of California San Francisco (UCSF). Adults with and without SARS-CoV-2 infection during pregnancy are eligible for enrollment in the pregnancy cohort and will follow the protocol for RECOVER-Adult including validated screening tools, laboratory analyses and symptom questionnaires followed by more in-depth phenotyping of PASC on a subset of the overall cohort. Offspring exposed and unexposed in utero to SARS-CoV-2 maternal infection will undergo screening tests for neurodevelopment and other health outcomes at 12, 18, 24, 36 and 48 months of age. Blood specimens will be collected at 24 months of age for SARS-CoV-2 antibody testing, storage and anticipated later analyses proposed by RECOVER and other investigators. DISCUSSION: RECOVER-Pregnancy will address whether having SARS-CoV-2 during pregnancy modifies the risk factors, prevalence, and phenotype of PASC. The pregnancy cohort will also establish whether there are increased risks of adverse long-term outcomes among children exposed in utero. CLINICAL TRIALS.GOV IDENTIFIER: Clinical Trial Registration: http://www.clinicaltrials.gov. Unique identifier: NCT05172011.

Researching COVID to enhance recovery (RECOVER) pregnancy study: Rationale, objectives and design.

Importance: Pregnancy induces unique physiologic changes to the immune response and hormonal changes leading to plausible differences in the risk of developing post-acute sequelae of SARS-CoV-2 (PASC), or Long COVID. Exposure to SARS-CoV-2 during pregnancy may also have long-term ramifications for exposed offspring, and it is critical to evaluate the health outcomes of exposed children. The National Institutes of Health (NIH) Researching COVID to Enhance Recovery (RECOVER) Multi-site Observational Study of PASC aims to evaluate the long-term sequelae of SARS-CoV-2 infection in various populations. RECOVER- Pregnancy was designed specifically to address long-term outcomes in maternal-child dyads. Methods: RECOVER-Pregnancy cohort is a combined prospective and retrospective cohort that proposes to enroll 2,300 individuals with a pregnancy during the COVID-19 pandemic and their offspring exposed and unexposed in utero, including single and multiple gestations. Enrollment will occur both in person at 27 sites through the Eunice Kennedy Shriver National Institutes of Health Maternal-Fetal Medicine Units Network and remotely through national recruitment by the study team at the University of California San Francisco (UCSF). Adults with and without SARS-CoV-2 infection during pregnancy are eligible for enrollment in the pregnancy cohort and will follow the protocol for RECOVER-Adult including validated screening tools, laboratory analyses and symptom questionnaires followed by more in-depth phenotyping of PASC on a subset of the overall cohort. Offspring exposed and unexposed in utero to SARS-CoV-2 maternal infection will undergo screening tests for neurodevelopment and other health outcomes at 12, 18, 24, 36 and 48 months of age. Blood specimens will be collected at 24 months of age for SARS-CoV-2 antibody testing, storage and anticipated later analyses proposed by RECOVER and other investigators. Discussion: RECOVER-Pregnancy will address whether having SARS-CoV-2 during pregnancy modifies the risk factors, prevalence, and phenotype of PASC. The pregnancy cohort will also establish whether there are increased risks of adverse long-term outcomes among children exposed in utero. Registration: 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.

Maternal adverse childhood experiences and infant subcortical brain volume.

Background: A large body of research supports the deleterious effects of adverse childhood experiences (ACEs) on disease susceptibility and health for both the exposed individual and the next generation. It is likely that there is an intergenerational transmission of risk from mother to child; however, the mechanisms through which such risk is conferred remain unknown. The current study evaluated the association between maternal ACEs, neonatal brain development of the amygdala and hippocampus, and later infant negative emotionality at six months of age. Methods: The sample included 85 mother-infant dyads (44 female infants) from a longitudinal study. Maternal ACEs were assessed with the Adverse Childhood Experiences Questionnaire (ACE-Q) and neonatal hippocampal and amygdala volume was assessed using structural magnetic resonance imaging (MRI). Infant negative emotionality was assessed at 6 months using the Infant Behavior Questionnaire (IBQ). Results: Multivariate analyses demonstrated that maternal ACEs were associated with bilateral amygdala volume (F(2,78) = 3.697,p = .029). Specifically, higher maternal ACEs were associated with smaller left (ß = -0.220, t(79) = -2.661, p = .009, R2 = 0.494, and right (ß = -0.167, t(79) = -2.043, p = .044, R2 = 0.501) amygdala volume. No significant association between maternal ACEs and bilateral hippocampal volume (F(2,78) = 0.215,p = .0807) was found. Follow-up regression analyses demonstrated that both high maternal ACEs and smaller left amygdala volume were associated with higher infant negative emotionality at six months of age (ß = .232, p = .040, R2 = 0.094, and ß = -0.337, p = .022, R2 = 0.16, respectively) although statistically significant mediation of this effect was not observed (Indirect effect = 0.0187, 95% CI [-0.0016-0.0557]). Conclusions: Maternal ACEs are associated with both newborn amygdala volume and subsequent infant negative emotionality. These findings linking maternal adverse childhood experiences and infant brain development and temperament provide evidence to support the intergenerational transmission of adversity from mother to child.

Longitudinal and prospective assessment of prenatal maternal sleep quality and associations with newborn hippocampal and amygdala volume.

BACKGROUND: The rapid maturation of the fetal brain renders the fetus susceptible to prenatal environmental signals. Prenatal maternal sleep quality is known to have important health implications for newborns including risk for preterm birth, however, the effect on the fetal brain is poorly understood. METHOD: Participants included 94 pregnant participants and their newborns (53% female). Pregnant participants (Mage = 30; SDage= 5.29) reported on sleep quality three times throughout pregnancy. Newborn hippocampal and amygdala volumes were assessed using structural magnetic resonance imaging. Multilevel modeling was used to test the associations between trajectories of prenatal maternal sleep quality and newborn hippocampal and amygdala volume. RESULTS: The overall trajectory of prenatal maternal sleep quality was associated with hippocampal volume (left: b = 0.00003, p = 0.013; right: b = 0.00003, p = .008). Follow up analyses assessing timing of exposure indicate that poor sleep quality early in pregnancy was associated with larger hippocampal volume bilaterally (e.g., late gestation left: b = 0.002, p = 0.24; right: b = 0.004, p = .11). Prenatal sleep quality was not associated with amygdala volume. CONCLUSION: These findings highlight the implications of poor prenatal maternal sleep quality and its role in contributing to newborn hippocampal development.

The transition to parenthood in obstetrics: enhancing prenatal care for 2-generation impact.

Obstetrics, the specialty overseeing infant and parent health before birth, could be expanded to address the interrelated areas of parents' prenatal impact on children's brain development and their own psychosocial needs during a time of immense change and neuroplasticity. Obstetrics is primed for the shift that is happening in pediatrics, which is moving from its traditional focus on physical health to a coordinated, whole-child, 2- or multigeneration approach. Pediatric care now includes developmental screening, parenting education, parent coaching, access to developmental specialists, brain-building caregiving skills, linkages to community resources, and tiered interventions with psychologists. Drawing on decades of developmental origins of health and disease research highlighting the prenatal beginnings of future health and new studies on the transition to parenthood describing adult development from pregnancy to early postpartum, we have proposed that, similar to pediatrics, the integration of education and intervention strategies into the prenatal care ecosystem should be tested for its potential to improve child cognitive and social-emotional development and parental mental health. Pediatric care programs can serve as models of change for the systematic development, testing and, incorporation of new content into prenatal care as universal, first-tier treatment and evidenced-based, triaged interventions according to the level of need. To promote optimal beginnings for the whole family, we have proposed an augmented prenatal care ecosystem that aligns with, and could build on, current major efforts to enhance perinatal care individualization through consideration of medical, social, and structural determinants of health.

A Mindfulness Application for Reducing Prenatal Stress.

INTRODUCTION: Up to 40% of patients report depression or anxiety symptoms in pregnancy; feelings of increased stress are nearly universal. Antepartum stress is linked to adverse outcomes including preterm birth, low birthweight, postpartum depression, and maternal self harm. Unfortunately, limited treatment options exist, and patients are often hesitant to initiate medications prenatally. Thus, the development of efficacious nonpharmacologic interventions is crucial. This pilot study investigated the feasibility and impact of an application (app)-based mindfulness practice, begun in the first trimester, on maternal stress and pregnancy outcomes. METHODS: The study enrolled patients prior to 15 weeks' gestation and followed them prospectively through birth. Patients were provided with a free subscription to Expectful, a commercially available prenatal mindfulness app, and asked to complete daily meditations. Patients completed the Perceived Stress Scale (PSS) self-assessment at 15 weeks and 28 weeks. PSS scores and pregnancy outcomes were compared with a historical control group of pregnant people who did not use the app. RESULTS: Of 68 patients approached, 59 consented to enrollment. Of these, 21 used the app, with an average use of 170 minutes (range, 1.3-1315 min). The average PSS score was significantly lower in the app group at 28 weeks. Additionally, the change in PSS score for app users was greater compared with that of the historical control between enrollment and 28 weeks (-6.3 vs -0.95, P = .0008). Pregnancy outcomes were similar for app users and the historical control. DISCUSSION: Our recruitment rate suggests pregnant patients are eager for a nonmedication intervention to decrease stress. However, adherence after enrollment was limited. For a subset of motivated patients, an app-based mindfulness practice significantly reduced perceived stress between the second and third trimesters compared with non-app users. Prenatal mindfulness apps represent an important low-intervention, low-cost, highly accessible tool for managing perinatal mood and stress.

Pharmacologic Treatment for Perinatal Mental Health Disorders.

SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42019124057.

Choline, folic acid, Vitamin D, and fetal brain development in the psychosis spectrum.

Choline, folic acid, and Vitamin D are essential for fetal brain development that may be the first steps in the pathogenesis of the psychotic spectrum. Micronutrient deficiencies have been associated with changes in fetal brain development, manifest as early problems in childhood behavior, and cognition, and later as increased incidence of psychotic and autism spectrum disorders. Micronutrient supplements may not only prevent deficiency, but they may also positively affect brain development in the context of other maternal risk factors, including maternal infection, stress, inflammation, and substance abuse. Many genes associated with later psychotic illness are highly expressed in the fetal brain, where they are responsible for various neurodevelopmental mechanisms. Interaction of micronutrient vitamins with these genetically programmed mechanisms to prevent pathological brain development associated with later psychosis is under active investigation. In addition to their effects on brain development, micronutrient vitamins have effects on other aspects of gestation and fetal development, including the prevention of premature delivery and other developmental abnormalities. Supplemental micronutrient vitamins should be part of good prenatal care, as has already happened for folic acid and Vitamin D and is now advocated by the American Medical Association for choline. The benefits of these micronutrient supplements include protection of brain development and the possibility of decreased risk for future psychotic disorders in those children who are either genetically or environmentally vulnerable. The purpose of this review is to present the current evidence supporting the safety and effectiveness of micronutrients in gestation and to suggest areas for future research.

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.

Maternal corticosteroids and depression during gestation and decreased fetal heart rate variability.

OBJECTIVE: Maternal depression during gestation is an adverse factor in fetal brain development that manifests in later childhood behavioral problems. Fetal heart rate variability (FHRV) mediated by parasympathetic input is a marker of gestational nervous system development. Biological mediators of adverse effects of maternal depression may involve the mother's corticosteroids; however, links between depression, corticosteroids, and early nervous system development remain inconclusive. METHODS: Heart rate was recorded in 23 fetuses by transabdominal Doppler at 28-33 weeks gestation. The SD of interbeat intervals over 20 min assessed FHRV. Maternal depression ratings and hair concentrations of cortisol and cortisone were assayed. An auditory sensory gating paradigm assessed newborn development of cerebral inhibition. Parents rated their infant's temperament characteristics on the Infant Behavior Questionnaire-Revised Short Form (IBQ-R). RESULTS: Maternal depression was associated with lower FHRV, especially for male fetuses, ß = -0.633, P = 0.045. Maternal depression was associated with lower cortisol to total corticosteroids ratios, ß = -0.519, P = 0.033. Lower cortisol ratios were associated with decreased FHRV, ß = 0.485, P = 0.019. Decreased FHRV was associated with increased newborn sensory gating deficits, ß = -0.992, P = 0.035, indicating poorer development of cerebral inhibition. Higher FHRV was related to increased infant IBQ-R self-regulatory behaviors, r = 0.454, P = 0.029. CONCLUSION: Maternal depression is associated via corticosteroids with decreased development of nervous system control of fetal heart rate. Decreased FHRV indicates developmental alterations in gestation that correlate with altered brain function and subsequent regulatory challenges in early infancy.

Maternal prenatal choline and inflammation effects on 4-year-olds' performance on the Wechsler Preschool and Primary Scale of Intelligence-IV.

Maternal gestational inflammation from infection, obesity, depression, and adverse childhood experiences negatively affects offspring cognitive development. Choline is a key nutrient in fetal brain development. We investigated whether higher maternal plasma choline concentrations have a positive association with offspring cognition, specifically processing speed, in the presence of inflammation. Forty-eight children were evaluated at 4 years of age. Processing Speed Composite Score on the Wechsler Preschool & Primary Scales of Intelligence was the principal outcome. Maternal C-reactive protein (CRP), a marker of inflammation, and choline plasma concentration had been measured at 16 weeks' gestation. Choline concentrations >7.07µM were compared to lower levels. Mothers with lower choline levels reported more depression and stress. Head circumference was larger for neonates of mothers with higher choline levels. In analyses with maternal CRP, higher maternal choline was associated with higher offspring Processing Speed Composite Scores for both sexes. For males, higher maternal choline competed with the negative association of maternal CRP on Processing Speed. Higher Processing Speed was related to the child's behavioral ratings, with fewer Withdrawn Problems on the Child Behavior Checklist 1 ½-5 years at 4 years and higher Infant Behavior Questionnaire Orienting/Regulation at 3 months of age, consistent with persistent developmental effects. Higher processing speed and decreased problems in social withdrawal are positively associated with prenatal maternal choline. Both lower processing speed and social withdrawal problems are precursors to later mental difficulties. Choline supplementation in pregnancy may mitigate effects of maternal inflammation that contribute to problems in offspring's' cognition and behavior.

Maternal nutrients and effects of gestational COVID-19 infection on fetal brain development.

BACKGROUND & AIMS: Maternal gestational infection is a well-characterized risk factor for offsprings' development of mental disorders including schizophrenia, autism, and attention deficit disorder. The inflammatory response elicited by the infection is partly directed against the placenta and fetus and is the putative pathogenic mechanism for fetal brain developmental abnormalities. Fetal brain abnormalities are generally irreversible after birth and increase risk for later mental disorders. Maternal immune activation in animals models this pathophysiology. SARS-CoV-2 produces maternal inflammatory responses during pregnancy similar to previously studied common respiratory viruses. METHOD: Choline, folic acid, Vitamin D, and n-3 polyunsaturated fatty acids are among the nutrients that have been studied as possible mitigating factors for effects of maternal infection and inflammation on fetal development. Clinical and animal studies relevant to their use in pregnant women who have been infected are reviewed. RESULTS: Higher maternal choline levels have positive effects on the development of brain function for infants of mothers who experienced viral infections in early pregnancy. No other nutrient has been studied in the context of viral inflammation. Vitamin D reduces pro-inflammatory cytokines in some, but not all, studies. Active folic acid metabolites decrease anti-inflammatory cytokines. N-3 polyunsaturated fatty acids have no effect. CONCLUSIONS: Vitamin D and folic acid are already supplemented in food additives and in prenatal vitamins. Despite recommendations by several public health agencies and medical societies, choline intake is often inadequate in early gestation when the brain is forming. A public health initiative for choline supplements during the pandemic could be helpful for women planning or already pregnant who also become exposed or infected with SARS-CoV-2.

Targeting Treatments to Health Disparities.

These initial data suggest that with prenatal vitamins and choline supplements, we might decrease one risk factor associated with poorer health outcomes disproportionally affecting Black families, ie, preterm birth. Dissemination of this research fulfills the principle of Justice in the Belmont Report, to ensure that participants from different racial, ethnic and socioeconomic groups receive benefits from research directed to their specific problems.