Faculty Bibliography

IMPORTANCE/UNASSIGNED:Prenatal alcohol exposure (PAE) and prenatal tobacco exposure (PTE) are risk factors associated with adverse neurobehavioral and cognitive outcomes. OBJECTIVE/UNASSIGNED:To quantify long-term associations of PAE and PTE with brain activity in early and middle childhood via electroencephalography (EEG). DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This cohort study included participants enrolled in the Safe Passage Study (August 2007 to January 2015), from which a subset of 649 participants were followed up in the Environmental Influences on Child Health Outcomes Program. From September 2018 through November 2022, EEG recordings were obtained at ages 4, 5, 7, 9, or 11 years. Data were analyzed from November 2022 to November 2023. EXPOSURES/UNASSIGNED:Maternal self-reported consumptions of alcohol and tobacco during pregnancy were captured at the recruitment interview and at up to 3 visits during pregnancy (20-24, 28-32, and ≥34 weeks' gestation). Classifications of PAE (continuous drinking, quit-early drinking, and nondrinking) and PTE (continuous smoking, quit-early smoking, and nonsmoking) were previously obtained. MAIN OUTCOMES AND MEASURES/UNASSIGNED:EEG band powers (theta, alpha, beta, gamma) were extracted from the EEG recordings. Linear regression models were used to estimate the associations of PAE and PTE with EEG estimates. RESULTS/UNASSIGNED:The final sample included 649 participants (333 [51.3%] female) aged 4, 5, 7, 9, or 11 years. Children whose mothers were in the quit-early drinking cluster had increased alpha power (0.116 [95% CI, 0.023 to 0.209] μV2; P = .02) compared with individuals without PAE. The magnitude of this increase was approximately double for children exposed to continuous drinking (0.211 [95% CI, 0.005 to 0.417] μV2; P = .04). Children whose mothers were in the continuous smoking cluster had decreased beta power (-0.031 [95% CI, -0.059 to -0.003] μV2; P = .03) and gamma power (-0.020 [95% CI, -0.039 to -0.000] μV2; P = .04) compared with the nonsmoking cluster. In exploratory sex-stratified models, male participants in the quit-early PAE cluster had greater EEG power in the alpha band (0.159 [95% CI, 0.003 to 0.315] μV2; P = .04) compared with those with no PAE, and the difference was approximately double for male participants with continuous PAE (0.354 [95% CI, 0.041 to 0.667] μV2; P = .03). Male participants in the continuous PTE cluster had decreased beta (-0.048 [95% CI, -0.090 to - 0.007] μV2; P = .02) and gamma (-0.032 [95% CI, -0.061 - 0.002] μV2; P = .04) power compared with those with no PTE. CONCLUSIONS AND RELEVANCE/UNASSIGNED:These findings suggest that even low levels of PAE and PTE were associated with long-term alterations of brain activity.

BACKGROUND:Prenatal smoking and drinking are associated with sudden infant death syndrome and neurodevelopmental disorders. Infants with these outcomes also have altered autonomic nervous system (ANS) regulation. We examined the effects of prenatal smoking and drinking on newborn ANS function. METHODS:Pregnant women were enrolled in Northern Plains, USA (NP) and Cape Town (CT), South Africa. Daily drinking and weekly smoking data were collected prenatally. Physiological measures were obtained during sleep 12-96 h post-delivery. RESULTS:In all, 2913 infants from NP and 4072 from CT were included. In active sleep, newborns of mothers who smoked throughout pregnancy, compared to non-smokers, had higher breathing rates (2.2 breaths/min; 95% CI: 0.95, 3.49). Quit-early smoking was associated with reductions in beat-to-beat heart rate variability (HRV) in active (-0.08 s) and quiet sleep (-0.11 s) in CT. In girls, moderate-high continuous smoking was associated with increased systolic (3.0 mmHg, CI: 0.70, 5.24) and diastolic blood pressure (2.9 mmHg, CI: 0.72, 5.02). In quiet sleep, low-continuous drinking was associated with slower heart rate (-4.5 beat/min). In boys, low-continuous drinking was associated with a reduced ratio of low-to-high frequency HRV (-0.11, CI: -0.21, -0.02). CONCLUSIONS:These findings highlight potential ANS pathways through which prenatal drinking and smoking may contribute to neurodevelopment outcomes. IMPACT/CONCLUSIONS:In this prospective cohort study of 6985 mother-infant dyads prenatal drinking and smoking were associated with multiple ANS parameters. Smoking was associated with increased neonatal breathing rates among all infants, and heart rate variability (HRV) and blood pressure (BP) among girls. Drinking was associated with reductions in HR and BP among all newborns, and reductions in the ratio of low to-high frequency HRV among boys. These findings suggest that prenatal smoking and drinking alter newborn ANS which may presage future neurodevelopmental disorders.

This study examined the association of gestational diabetes mellitus (GDM), prenatal, and postnatal maternal depressive symptoms with externalizing, internalizing, and autism spectrum problems on the Preschool Child Behavior Checklist in 2379 children aged 4.12 ± 0.60 (48% female; 47% White, 32% Black, 15% Mixed Race, 4% Asian, <2% American Indian/Alaskan Native, <2% Native Hawaiian; 23% Hispanic). Data were collected from the NIH Environmental influences on Child Health Outcomes (ECHO) Program from 2009-2021. GDM, prenatal, and postnatal maternal depressive symptoms were each associated with increased child externalizing and internalizing problems. GDM was associated with increased autism behaviors only among children exposed to perinatal maternal depressive symptoms above the median level. Stratified analyses revealed a relation between GDM and child outcomes in males only.

BACKGROUND:Immune dysregulation has been linked to both psychiatric illness and pregnancy morbidity, including perinatal depression, but little is known about the immune phenotype of perinatal anxiety. Here, we sought to identify the unique immune profile of antenatal anxiety. MATERIALS AND METHODS/METHODS:Pregnant women (n = 107) were followed prospectively at 2nd and 3rd trimesters (T2, T3) and 6 weeks postpartum (PP6). Each visit included a blood draw and psychological evaluation, with clinical anxiety assessed using the Spielberg State-Trait Anxiety Scale. We enrolled both healthy controls and participants with anxiety alone; those with comorbid depression were excluded. Multiplex cytokine assays and flow cytometry were used to examine the association of anxiety symptoms with secreted immune markers and PBMC-derived immune cells. RESULTS:cells in the postpartum as compared with Non-Anxiety women. CONCLUSION/CONCLUSIONS:These data suggest that the immune response throughout the antenatal period differs for women with anxiety symptoms compared to those without, suggestive of a unique immune phenotype of perinatal anxiety.

BACKGROUND:Prior research has demonstrated bidirectional associations between gestational diabetes mellitus (GDM) and perinatal maternal depression. However, the association between GDM, prenatal depression, and postpartum depression (PPD) has not been examined in a prospective cohort longitudinally. METHODS:Participants in the current analysis included 5,822 women from the National Institutes of Health's Environmental influences on Child Health Outcomes (ECHO) Research Program: N = 4,606 with Neither GDM nor Prenatal Maternal Depression (Reference Category); N = 416 with GDM only; N = 689 with Prenatal Maternal Depression only; and N = 111 with Comorbid GDM and Prenatal Maternal Depression. The PROMIS-D scale was used to measure prenatal and postnatal maternal depressive symptoms. Primary analyses consisted of linear regression models to estimate the independent and joint effects of GDM and prenatal maternal depression on maternal postpartum depressive symptoms. RESULTS:A higher proportion of women with GDM were classified as having prenatal depression (N = 111; 21%) compared to the proportion of women without GDM who were classified as having prenatal depression (N = 689; 13%), however this finding was not significant after adjustment for covariates. Women with Comorbid GDM and Prenatal Maternal Depression had significantly increased postpartum depressive symptoms measured by PROMIS-D T-scores compared to women with Neither GDM nor Prenatal Maternal Depression (mean difference 7.02, 95% CI 5.00, 9.05). Comorbid GDM and Prenatal Maternal Depression was associated with an increased likelihood of PPD (OR 7.38, 95% CI 4.05, 12.94). However, women with GDM only did not have increased postpartum PROMIS-D T-scores or increased rates of PPD. CONCLUSIONS:Our findings underscore the importance of universal depression screening during pregnancy and in the first postpartum year. Due to the joint association of GDM and prenatal maternal depression on risk of PPD, future studies should examine potential mechanisms underlying this relation.

Our primary objective was to document COVID-19 induced changes to perinatal care across the USA and examine the implication of these changes for maternal mental health. We performed an observational cross-sectional study with convenience sampling using direct patient reports from 1918 postpartum and 3868 pregnant individuals collected between April 2020 and December 2020 from 10 states across the USA. We leverage a subgroup of these participants who gave birth prior to March 2020 to estimate the pre-pandemic prevalence of specific birthing practices as a comparison. Our primary analyses describe the prevalence and timing of perinatal care changes, compare perinatal care changes depending on when and where individuals gave birth, and assess the linkage between perinatal care alterations and maternal anxiety and depressive symptoms. Seventy-eight percent of pregnant participants and 63% of postpartum participants reported at least one change to their perinatal care between March and August 2020. However, the prevalence and nature of specific perinatal care changes occurred unevenly over time and across geographic locations. The separation of infants and mothers immediately after birth and the cancelation of prenatal visits were associated with worsened depression and anxiety symptoms in mothers after controlling for sociodemographic factors, mental health history, number of pregnancy complications, and general stress about the COVID-19 pandemic. Our analyses reveal widespread changes to perinatal care across the US that fluctuated depending on where and when individuals gave birth. Disruptions to perinatal care may also exacerbate mental health concerns, so focused treatments that can mitigate the negative psychiatric sequelae of interrupted care are warranted.

OBJECTIVE:Investigate racial and ethnic differences in infant sleep and examine associations with insurance status and parent-infant bedtime behavioral factors (PIBBF). METHODS:Participants are part of the COVID-19 Mother Baby Outcomes (COMBO) Initiative, Columbia University. Data on infant sleep (night, day and overall sleep duration, night awakenings, latency, infant's sleep as a problem) were collected at 4 months postpartum. Regressions estimated associations between race/ethnicity, insurance status, PIBBF and infants' sleep. RESULTS:A total of 296 infants were eligible (34.4% non-Hispanic White [NHW], 10.1% Black/African American [B/AA], 55.4% Hispanic). B/AA and Hispanic mothers were more likely to have Medicaid, bed/room-share, and report later infant bedtime compared to NHW mothers. Infants of B/AA mothers had longer sleep latency compared to NHW. Infants of Hispanic mothers slept less at night (∼70 ± 12 minutes) and more during the day (∼41 ± 12 minutes) and Hispanic mothers were less likely to consider infants' sleep as a problem compared to NHW (odds ratio 0.4; 95% confidence interval: 0.2-0.7). After adjustment for insurance status and PIBBF, differences by race/ethnicity for night and day sleep duration and perception of infant's sleep as a problem persisted (∼32 ± 14 minutes, 35 ± 15 minutes, and odds ratio 0.4; 95% confidence interval: 0.2-0.8 respectively). Later bedtime was associated with less sleep at night (∼21 ± 4 minutes) and overall (∼17 ± 5 minutes), and longer latency. Infants who did not fall asleep independently had longer sleep latency, and co-sleeping infants had more night awakenings. CONCLUSIONS:Results show racial/ethnic differences in sleep in 4-month-old infants across sleep domains. The findings of our study suggest that PIBBF have an essential role in healthy infant sleep, but they may not be equitably experienced across racial/ethnic groups.

In the United States, racial/ethnic minoritized groups experience worse sleep than non-Hispanic Whites (nHW), but less is known about pregnant people. This is a key consideration since poor sleep during pregnancy is common and associated with increased risk of adverse perinatal outcomes. This study reports the prevalence of subjective sleep measures in a multi-racial/ethnic pregnant population from the Environmental influences on Child Health Outcomes (ECHO) program. Participants' self-reported race and ethnicity were grouped into: nHW, non-Hispanic Black/African American (nHB/AA), Hispanic, non-Hispanic Asian (nHA). Analyses examined trimester-specific (first (T1), second (T2), third (T3)) nocturnal sleep duration, quality, and disturbances (Pittsburgh Sleep Quality Index and ECHO maternal sleep health questionnaire). Linear or multinomial regressions estimated the associations between race/ethnicity and each sleep domain by trimester, controlling for body mass index and age, with nHW as reference group. We repeated analyses within maternal education strata. nHB/AA participants reported shorter sleep duration (T2: β = -0.55 [-0.80,-0.31]; T3: β = -0.65 [-0.99,-0.31]) and more sleep disturbances (T2: β = 1.92 [1.09,2.75]; T3: β = 1.41 [0.09,2.74]). Hispanic participants reported longer sleep duration (T1: β = 0.22 [0.00004,0.44]; T2: β = 0.61 [0.47,0.76]; T3: β = 0.46 [0.22,0.70]), better sleep quality (Reference group: Very good. Fairly good T1: OR = 0.48 [0.32,0.73], T2: OR = 0.36 [0.26,0.48], T3: OR = 0.31 [0.18,0.52]. Fairly bad T1: OR = 0.27 [0.16,0.44], T2: OR = 0.46 [0.31, 0.67], T3: OR = 0.31 [0.17,0.55]), and fewer sleep disturbances (T2: β = -0.5 [-1.0,-0.12]; T3: β = -1.21 [-2.07,-0.35]). Differences persisted within the high-SES subsample. Given the stark racial/ethnic disparities in perinatal outcomes and their associations with sleep health, further research is warranted to investigate the determinants of these disparities.

Hyperserotonemia, or elevated levels of whole blood serotonin (WB5-HT), was the first biomarker linked to autism spectrum disorder (ASD). Despite numerous studies investigating the etiology of hyperserotonemia, results have been inconsistent. Recent findings suggest a relationship between the immune system and hyperserotonemia. The current study investigated whether intestinal 5-HT levels, 5-HT gene expression, or intestinal cell types predict WB5-HT. Participants included thirty-one males aged 3-18 who were classified into one of three groups: ASD and functional GI issues, typically developing with GI issues, and typically developing without GI issues. Samples from a lower endoscopy were analyzed to examine the pathways in predicting WB-5HT. Results demonstrated an association between T-Lymphocytes and WB5-HT.