Latent Class Analysis of Prenatal Substance Exposure and Child Behavioral Outcomes.

OBJECTIVES: To predict behavioral disruptions in middle childhood, we identified latent classes of prenatal substance use. STUDY DESIGN: As part of the Environmental influences on Child Health Outcomes Program, we harmonized prenatal substance use data and child behavior outcomes from 2195 women and their 6- to 11-year-old children across 10 cohorts in the US and used latent class-adjusted regression models to predict parent-rated child behavior. RESULTS: Three latent classes fit the data: low use (90.5%; n = 1986), primarily using no substances; licit use (6.6%; n = 145), mainly using nicotine with a moderate likelihood of using alcohol and marijuana; and illicit use (2.9%; n = 64), predominantly using illicit substances along with a moderate likelihood of using licit substances. Children exposed to primarily licit substances in utero had greater levels of externalizing behavior than children exposed to low or no substances (P = .001, d = .64). Children exposed to illicit substances in utero showed small but significant elevations in internalizing behavior than children exposed to low or no substances (P < .001, d = .16). CONCLUSIONS: The differences in prenatal polysubstance use may increase risk for specific childhood problem behaviors; however, child outcomes appeared comparably adverse for both licit and illicit polysubstance exposure. We highlight the need for similar multicohort, large-scale studies to examine childhood outcomes based on prenatal substance use profiles.

Challenges and opportunities faced by nurse scientists in integrating data and technology in research to promote health equity.

Advances in technologies including omics, apps, imaging, sensors, and big data are increasingly being integrated into research by nurse scientists, but the impact on improving health equity is still unclear. In this article, nursing research faculty from one institution discuss challenges and opportunities experienced when integrating various technologies into their research aimed at promoting health equity. Using exemplars from faculty experiences, a three-pronged approach to keeping patients and communities and the goal of health equity central in research while incorporating advancing technologies is described. This approach includes establishing long-term engagement with populations underrepresented in research, adopting strategies to increase diversity in study participant recruitment, and training and collaboration among a diverse workforce of educators, clinicians, and researchers. Training nurse scientists in integrating data and technology for advancing the science on health equity will shift the culture of how we understand, collaborate, and grow with the communities in which we train and practice as nurse scientists.

Severity of neonatal opioid withdrawal syndrome with prenatal exposure to serotonin reuptake inhibitors.

OBJECTIVE: To evaluate the severity of neonatal opioid withdrawal syndrome (NOWS) in infants prenatally exposed to medications for opioid use disorder (MOUD) and serotonin reuptake inhibitors (SRI). METHODS: A prospective cohort included 148 maternal-infant pairs categorized into MOUD (n = 127) and MOUD + SRI (n = 27) groups. NOWS severity was operationalized as the infant's need for pharmacologic treatment with opioids, duration of hospitalization, and duration of treatment. The association between prenatal SRI exposure and the need for pharmacologic treatment (logistic regression), time-to-discharge, and time-to-treatment discontinuation (Cox proportional hazards modeling) was examined after adjusting for the type of maternal MOUD, use of hydroxyzine, other opioids, benzodiazepines/sedatives, alcohol, tobacco, marijuana, gestational age, and breastfeeding. RESULTS: Infants in the MOUD + SRI group were more likely to receive pharmacologic treatment for NOWS (OR = 3.58; 95% CI: 1.31; 9.76) and had a longer hospitalization (median: 11 vs. 6 days; HR = 0.54; 95% CI: 0.33; 0.89) compared to the MOUD group. With respect to time-to-treatment discontinuation, no association was observed in infants who received treatment (HR = 0.59; 95% CI: 0.26, 1.32); however, significant differences were observed in the entire sample (HR = 0.55; 95% CI: 0.34, 0.89). CONCLUSIONS: Use of SRIs among pregnant women on MOUD might be associated with more severe NOWS. IMPACT: A potential drug-drug interaction between maternal SRIs and opioid medications that inhibit the reuptake of serotonin has been hypothesized but not carefully evaluated in clinical studies. Results of this prospective cohort indicate that the use of SRIs among pregnant women on MOUD is associated with more severe neonatal opioid withdrawal syndrome. This is the first prospective study which carefully examined effect modification between the type of maternal MOUD and SRI use on neonatal outcomes. This report lays the foundation for treatment optimization in pregnant women with co-occurring mental health and substance use disorders.

Geotemporal analysis of perinatal care changes and maternal mental health: an example from the COVID-19 pandemic.

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.

Happiness in Pregnant African American Women: What Are the Biobehavioral Correlates?

The detrimental effects of prenatal stress on maternal-infant well-being have been well established and highlight increased concern for pregnant African American women. Research supports the notion that positive emotions may have a beneficial impact on the stress process and outcomes. However, the data have been largely restricted to non-African American pregnant women. This study's purpose was to examine potential relationships of both positive (happiness) and negative (stress, anxiety, and depressive symptoms) emotions and pro-inflammatory cytokines (interleukins-1ß, -6, -8, -12, -17, tumor necrosis factor, and interferon-γ) in 72 pregnant African American women for a more complete picture of the stress process in this at-risk population. Results of this exploratory secondary data analysis show strong positive correlations between negative emotions and strong negative correlations between happiness and negative emotions. Interleukin-8 was positively correlated with negative emotions and negatively correlated with happiness. Results show mean ratings of negative emotions were higher than previously reported with more heterogeneous samples, while happiness ratings were in the moderate range. Findings suggest that pregnant African American women may experience higher stress and depressive symptoms than women in more heterogeneous samples. However, moderate levels of happiness might contribute to buffering the stress response.

Prenatal antidepressant exposures and gastrointestinal complaints in childhood: A gut-brain axis connection?

Selective serotonin/norepinephrine reuptake inhibitors (collectively, SRIs) are the most commonly prescribed antidepressant agents for the treatment of depression in pregnancy. SRIs affect maternal and placental serotonin signaling, which might impact fetal brain development. Alterations in serotonin signaling might also impact the developing gut-brain axis (GBA) via alterations in the fetal enteric nervous system (ENS). Emerging evidence suggests that gestational SRI exposure may be associated with offspring gastrointestinal problems. However, prospective human studies of the effects of fetal SRI exposure on the ENS and function are absent in the literature. In this paper we present data demonstrating significant associations between prenatal SRI exposure and children's gastrointestinal (GI) problems in two well-characterized, prospective cohorts of preschool and later childhood individuals. The results support the hypothesis that prenatal SRI exposure can increase the risk for childhood GI difficulties. Further research is warranted on the potential SRI-induced changes to the child gut including the role of the microbiome and the GBA in the development of GI problems.

Impact of maternal prenatal smoking on fetal to infant neurobehavioral development.

Despite recent emphasis on the profound importance of the fetal environment in "programming" postnatal development, measurement of offspring development typically begins after birth. Using a novel coding strategy combining direct fetal observation via ultrasound and actocardiography, we investigated the impact of maternal smoking during pregnancy (MSDP) on fetal neurobehavior; we also investigated links between fetal and infant neurobehavior. Participants were 90 pregnant mothers and their infants (52 MSDP-exposed; 51% minorities; ages 18-40). Fetal neurobehavior at baseline and in response to vibro-acoustic stimulus was assessed via ultrasound and actocardiography at M = 35 weeks gestation and coded via the Fetal Neurobehavioral Assessment System (FENS). After delivery, the NICU Network Neurobehavioral Scale was administered up to seven times over the first postnatal month. MSDP was associated with increased fetal activity and fetal limb movements. Fetal activity, complex body movements, and cardiac-somatic coupling were associated with infants' ability to attend to stimuli and to self-regulate over the first postnatal month. Furthermore, differential associations emerged by MSDP group between fetal activity, complex body movements, quality of movement, and coupling, and infant attention and self-regulation. The present study adds to a growing literature establishing the validity of fetal neurobehavioral measures in elucidating fetal programming pathways.

Pregnancy and postpartum antidepressant use moderates the effects of sleep on depression.

This study examined the course of antidepressant use, sleep quality, and depression severity from pregnancy through 6-month postpartum in women with and without a depressive disorder during pregnancy. Women (N = 215) were interviewed during pregnancy, 1- and 6-month postpartum. Mixed linear models were used to examine the longitudinal course and inter-relationships for the time-varying variables of antidepressant use, subjective sleep quality, and depression severity. Pregnant women with a depressive disorder who did not use antidepressants had more variable depression severity over time with improvements in depression severity by 6-month postpartum. In contrast, the depression severity of their medicated counterparts remained stable and high throughout. Pregnant women without a depressive disorder had worse sleep quality when using antidepressants compared with when they were not. Antidepressant use significantly strengthened the magnitude of the effect of sleep quality on depression severity in women with a depressive disorder during pregnancy. When prenatally depressed women use antidepressants, their sleep disturbance is more highly linked to depression severity than when they do not. Furthermore, antidepressants are not adequately treating the sleep disturbance of these women or their remitted counterparts, leaving both groups vulnerable to significant negative mental and physical health outcomes.

Maternal pre-pregnancy obesity and gestational weight gain influence neonatal neurobehaviour.

Maternal weight before and during pregnancy is associated with offspring neurobehaviour in childhood. We investigated maternal weight prior to and during pregnancy in relation to neonatal neurobehaviour. We hypothesized that maternal obesity and excessive gestational weight gain would be associated with poor neonatal attention and affective functioning. Participants (n = 261) were recruited, weighed and interviewed during their third trimester of pregnancy. Pre-pregnancy weight was self-reported and validated for 210 participants, with robust agreement with medical chart review (r = 0.99). Neurobehaviour was measured with the NICU Network Neurobehavioural Scale (NNNS) administered on Days 2 and 32 postpartum. Maternal exclusion criteria included severe or persistent physical or mental health conditions (e.g. chronic disease or diagnoses of Bipolar Disorder or Psychotic Spectrum Disorders), excessive substance use, and social service/foster care involvement or difficulty understanding English. Infants were from singleton, full-term (37-42 weeks gestation) births with no major medical concerns. Outcome variables were summary scores on the NNNS (n = 75-86). For women obese prior to pregnancy, those gaining in excess of Institute of Medicine guidelines had infants with poorer regulation, lower arousal and higher lethargy. There were no main effects of maternal pre-pregnancy body mass index on neurobehaviour. Women gaining above Institute of Medicine recommendations had neonates with better quality of movement. Additional studies to replicate and extend results past the neonatal period are needed. Results could support underlying mechanisms explaining associations between maternal perinatal weight and offspring outcomes. These mechanisms may inform future prevention/intervention strategies. © 2016 Blackwell Publishing Ltd.

Fine Motor Differences and Prenatal Serotonin Reuptake Inhibitors Exposure.

OBJECTIVE: To examine fine motor differences between preschoolers with prenatal exposure to serotonin reuptake inhibitor (SRI) and children of mothers with major depressive disorder. STUDY DESIGN: A subset of children (N = 40) from a larger study on the effects of prenatal SRI and untreated major depressive disorder participated in a kinematic task of visual motor and fine motor functions at ages 4-5 years: exposure to SRI (n = 15), untreated major depressive disorder exposure (n = 10), and the control group (n = 15). The task was to reach and secure a peg, then drop it in a small hole near the start position in the light condition with full visibility or in the glow condition in which a phosphorescent peg glows in the dark. Movement-tracking software measured the positioning of the moving hand and fingers. RESULTS: In the glow condition, the group exposed to SRIs had a greater proportion of maximum aperture than the group with major depressive disorder, and the group exposed to SRIs was slower than the group with major depressive disorder to drop the peg into the hole. In the glow condition, the trajectory of the group exposed to SRI was less straight than the group with major depressive disorder, and the group with major depressive disorder had a straighter trajectory than the control group. CONCLUSION: This study provides evidence that preschool aged children with prenatal SRI exposure have poorer fine motor and visual-motor control compared with those with prenatal untreated major depressive disorder.

18-Month Follow-Up of Infants Cared for in a Single-Family Room Neonatal Intensive Care Unit.

OBJECTIVES: To determine whether the single-family room (SFR)-neonatal intensive care unit (NICU) is associated with improved 18-month neurodevelopmental outcome, especially in infants of mothers with high maternal involvement. STUDY DESIGN: An 18-month follow-up was undertaken that compared infants born <30 weeks gestational age; 123 from a SFR-NICU vs 93 from an open-bay NICU. Infants were divided into high vs low maternal involvement based on days/week of kangaroo care, breast/bottle feeding, and maternal care. Infants with high vs low maternal involvement in the SFR and open-bay NICUs were compared on the Bayley Cognitive, Language, and Motor scores and Pervasive Developmental Disorders autism screen. RESULTS: There were more mothers in the high maternal involvement SFR than in the high maternal involvement open-bay group (P = .002). Infants with high maternal involvement in both NICUs had greater Cognitive (P = .029) and Language (P < .000) scores than infants with low maternal involvement. Effect sizes within NICU were moderate to large in the SFR-NICU for Language scores and moderate for the Language composite in the open-bay NICU. The number of days of maternal involvement was greater in the SFR than open-bay NICU (P < .000), and length of stay was shorter in the high maternal involvement SFR than high maternal involvement open-bay NICU (P = .024). Kangaroo and maternal care predicted Cognitive (kangaroo, P = .003) and Language scores (P = .015, P = .032, respectively). Infants with ≥1 symptom of autism were more likely to be in the open-bay low maternal involvement group vs the SFR high maternal involvement group (OR = 4.91, 95% CI = 2.2-11.1). CONCLUSIONS: High maternal involvement is associated with improved 18-month neurodevelopmental outcome, especially in infants cared for in a SFR-NICU.

Prenatal Major Depressive Disorder, Placenta Glucocorticoid and Serotonergic Signaling, and Infant Cortisol Response.

OBJECTIVES: Extending prior studies of prenatal adversity and depressive symptoms, we tested associations between maternal prenatal major depressive disorder (MDD) and infant cortisol regulation. Based on prior findings by our group, we also tested placenta glucocorticoid (HSD11B2 methylation) and serotonin (SLC6A4 gene expression) signaling as moderators of links between prenatal MDD and infant cortisol. METHODS: Participants were 153 mother-infant pairs from a low-income, diverse sample (M [SD] age = 26 [6] years). Repeated structured diagnostic interviews were used to identify mothers with (a) prenatal MDD, (b) preconception-only MDD, and (c) controls. Placenta samples were assayed for HSD11B2 methylation and SLC6A4 gene expression. Infant salivary cortisol response to a neurobehavioral examination was assessed at 1 month. RESULTS: Daughters of prenatal MDD mothers had 51% higher baseline (ratio = 1.51; 95% confidence interval [CI] = 1.01-2.27; p = .045) and 64% higher stress responsive cortisol (ratio = 1.64; 95% CI = 1.05-2.56; p = .03) than daughters of controls and 75% higher stress-responsive cortisol (ratio = 1.75; 95% CI = 1.04-2.94; p = .04) than daughters of preconception-only MDD mothers. HSD11B2 methylation moderated links between prenatal MDD and baseline cortisol (p = .02), with 1% methylation decreases associated with 9% increased baseline cortisol in infants of prenatal MDD mothers (ratio = 1.09; 95% CI = 1.01-1.16). SLC6A4 expression moderated links between prenatal MDD and cortisol response among boys alone (p = .007), with 10-fold increases in expression associated with threefold increases in stress-responsive cortisol (ratio = 2.87; 95% CI = 1.39-5.93) in sons of control mothers. CONCLUSIONS: Results highlight specificity of associations between prenatal versus preconception MDD and cortisol regulation and the importance and complexity of placenta glucocorticoid and serotonergic pathways underlying the intergenerational transmission of risk from maternal adversity.

Epigenetic Regulation of Placental NR3C1: Mechanism Underlying Prenatal Programming of Infant Neurobehavior by Maternal Smoking?

Epigenetic regulation of the placental glucocorticoid receptor gene (NR3C1) was investigated as a mechanism underlying links between maternal smoking during pregnancy (MSDP) and infant neurobehavior in 45 mother-infant pairs (49% MSDP-exposed; 52% minorities; ages 18-35). The Neonatal Intensive Care Unit (NICU) Network Neurobehavioral Scale was administered 7 times over the 1st postnatal month; methylation of placental NR3C1 was assessed via bisulfite pyrosequencing. Increased placental NR3C1 methylation was associated with increased infant attention and self-regulation, and decreased lethargy and need for examiner soothing over the 1st postnatal month. A causal steps approach revealed that NR3C1 methylation and MSDP were independently associated with lethargic behavior. Although preliminary, results highlight the importance of epigenetic mechanisms in elucidating pathways to neurobehavioral alterations from MSDP.

The relationship between maternal-fetal attachment and cigarette smoking over pregnancy.

Cigarette smoking during pregnancy is one of the most preventable causes of infant morbidity and mortality, yet 80 % of women who smoked prior to pregnancy continue to smoke during pregnancy. Past studies have found that lower maternal-fetal attachment predicts smoking status in pregnancy, yet past research has not examined whether maternal-fetal attachment predicts patterns or quantity of smoking among pregnant smokers. The aim of this study was to examine the relationship between maternal-fetal attachment and patterns of maternal smoking among pregnant smokers. We used self-reported and biochemical markers of cigarette smoking in order to better understand how maternal-fetal attachment relates to the degree of fetal exposure to nicotine. Fifty-eight pregnant smokers participated in the current study. Women completed the Maternal-Fetal Attachment Scale, reported weekly smoking behaviors throughout pregnancy using the Timeline Follow Back interview, and provided a saliva sample at 30 and 35 weeks gestation and 1 day postpartum to measure salivary cotinine concentrations. Lower maternal-fetal attachment scores were associated with higher salivary cotinine at 30 weeks gestation and 1 day postpartum. As well, women who reported lower fetal attachment reported smoking a greater maximum number of cigarettes per day, on average, over pregnancy. Lower maternal-fetal attachment is associated with greater smoking in pregnancy. Future research might explore whether successful smoking cessation programs improve maternal assessments of attachment to their infants.

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

IMPORTANCE: The prevalence, pathophysiology, and long-term outcomes of COVID-19 (post-acute sequelae of SARS-CoV-2 [PASC] or "Long COVID") in children and young adults remain unknown. Studies must address the urgent need to define PASC, its mechanisms, and potential treatment targets in children and young adults. OBSERVATIONS: We describe the protocol for the Pediatric Observational Cohort Study of the NIH's REsearching COVID to Enhance Recovery (RECOVER) Initiative. RECOVER-Pediatrics is an observational meta-cohort study of caregiver-child pairs (birth through 17 years) and young adults (18 through 25 years), recruited from more than 100 sites across the US. This report focuses on two of four cohorts that comprise RECOVER-Pediatrics: 1) a de novo RECOVER prospective cohort of children and young adults with and without previous or current infection; and 2) an extant cohort derived from the Adolescent Brain Cognitive Development (ABCD) study (n = 10,000). The de novo cohort incorporates three tiers of data collection: 1) remote baseline assessments (Tier 1, n = 6000); 2) longitudinal follow-up for up to 4 years (Tier 2, n = 6000); and 3) a subset of participants, primarily the most severely affected by PASC, who will undergo deep phenotyping to explore PASC pathophysiology (Tier 3, n = 600). Youth enrolled in the ABCD study participate in Tier 1. The pediatric protocol was developed as a collaborative partnership of investigators, patients, researchers, clinicians, community partners, and federal partners, intentionally promoting inclusivity and diversity. The protocol is adaptive to facilitate responses to emerging science. CONCLUSIONS AND RELEVANCE: RECOVER-Pediatrics seeks to characterize the clinical course, underlying mechanisms, and long-term effects of PASC from birth through 25 years old. RECOVER-Pediatrics is designed to elucidate the epidemiology, four-year clinical course, and sociodemographic correlates of pediatric PASC. The data and biosamples will allow examination of mechanistic hypotheses and biomarkers, thus providing insights into potential therapeutic interventions. CLINICAL TRIALS.GOV IDENTIFIER: Clinical Trial Registration: http://www.clinicaltrials.gov. Unique identifier: NCT05172011.

Development of the Edinburgh Postnatal Depression Scale-United States: An Updated Perinatal Mental Health Screening Tool Using a Respectful Care and Trauma-Informed Approach.

Purpose: To present the development protocol of the Edinburgh Postnatal Depression Scale-United States (EPDS-US), an adapted version of the EPDS, that is inclusive and easy to understand for U.S. populations and incorporates a trauma-informed approach to perinatal mental health (PMH). Methods: Our team adapted the wording of the original EPDS to be more linguistically appropriate for current use with U.S. populations by incorporating principles from Trauma-Informed Care and the Cycle to Respectful Care. Results: Through small but impactful linguistic updates, the EPDS-US offers inclusive person-first language and eliminates confusing phrases or wording that may be perceived as judgmental. The goal of the adapted EPDS-US is to foster symptom disclosure in an environment of safety and trust. The EPDS-US removes preidentified barriers patients experience related to PMH screenings. Conclusions: The EPDS-US, a trauma-informed and respectful care screening tool, may lead to earlier recognition of symptoms, may allow for more person-focused treatment plans, and may serve as a platform for a culture change in addressing PMH, particularly when the screening tool is accompanied by open conversation, education, and resources. Validation studies are required at this time and this team welcomes direct communication with research and clinical sites interested in doing so.

A Systematic Review of Studies Examining Associations between Sleep Characteristics with Dietary Intake and Eating Behaviors during Pregnancy.

Little is known about the association between sleep and diet in pregnancy, despite both behaviors impacting maternal and fetal health. We aimed to perform a systematic review of the available literature on associations between sleep characteristics and dietary intake and eating behaviors during pregnancy, reporting on both maternal and fetal outcomes. We followed the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and conducted our search on 27 May 2021 in the PubMed, EMBASE, and CINAHL databases. The search yielded 6785 unique articles, of which 25 met our eligibility criteria. The studies, mostly observational, published 1993-2021, include data from 168,665 participants. Studies included examinations of associations between various maternal sleep measures with a diverse set of diet-related measures, including energy or nutrient intake (N = 12), dietary patterns (N = 9), and eating behaviors (N = 11). Associations of maternal exposures with fetal/infant outcomes were also examined (N = 5). We observed considerable heterogeneity across studies precluding our ability to perform a meta-analysis or form strong conclusions; however, several studies did report significant findings. Results from this systematic review demonstrate the need for consistency in methods across studies to better understand relationships between diet and sleep characteristics during pregnancy.

Prenatal Antidepressant Exposures and Autism Spectrum Disorder or Traits: A Retrospective, Multi-Cohort Study.

Prenatal antidepressant exposure has been associated with increased risk for neurodevelopmental disorders in childhood, including autism spectrum disorder (ASD). The current study utilized multi-cohort data from the Environmental influences on Child Health Outcomes (ECHO) program (N = 3129) to test for this association, and determine whether the association remained after adjusting for maternal prenatal depression and other potential confounders. Antidepressants and a subset of selective serotonin reuptake inhibitors (SSRIs) were examined in relation to binary (e.g., diagnostic) and continuous measures of ASD and ASD related traits (e.g., social difficulties, behavior problems) in children 1.5 to 12 years of age. Child sex was tested as an effect modifier. While prenatal antidepressant exposure was associated with ASD related traits in univariate analyses, these associations were statistically non-significant in models that adjusted for prenatal maternal depression and other maternal and child characteristics. Sex assigned at birth was not an effect modifier for the prenatal antidepressant and child ASD relationship. Overall, we found no association between prenatal antidepressant exposures and ASD diagnoses or traits. Discontinuation of antidepressants in pregnancy does not appear to be warranted on the basis of increased risk for offspring ASD.

Assessment of Psychosocial and Neonatal Risk Factors for Trajectories of Behavioral Dysregulation Among Young Children From 18 to 72 Months of Age.

Importance: Emotional and behavioral dysregulation during early childhood are associated with severe psychiatric, behavioral, and cognitive disorders through adulthood. Identifying the earliest antecedents of persisting emotional and behavioral dysregulation can inform risk detection practices and targeted interventions to promote adaptive developmental trajectories among at-risk children. Objective: To characterize children's emotional and behavioral regulation trajectories and examine risk factors associated with persisting dysregulation across early childhood. Design, Setting, and Participants: This cohort study examined data from 20 United States cohorts participating in Environmental influences on Child Health Outcomes, which included 3934 mother-child pairs (singleton births) from 1990 to 2019. Statistical analysis was performed from January to August 2022. Exposures: Standardized self-reports and medical data ascertained maternal, child, and environmental characteristics, including prenatal substance exposures, preterm birth, and multiple psychosocial adversities. Main Outcomes and Measures: Child Behavior Checklist caregiver reports at 18 to 72 months of age, with Dysregulation Profile (CBCL-DP = sum of anxiety/depression, attention, and aggression). Results: The sample included 3934 mother-child pairs studied at 18 to 72 months. Among the mothers, 718 (18.7%) were Hispanic, 275 (7.2%) were non-Hispanic Asian, 1220 (31.8%) were non-Hispanic Black, 1412 (36.9%) were non-Hispanic White; 3501 (89.7%) were at least 21 years of age at delivery. Among the children, 2093 (53.2%) were male, 1178 of 2143 with Psychosocial Adversity Index [PAI] data (55.0%) experienced multiple psychosocial adversities, 1148 (29.2%) were exposed prenatally to at least 1 psychoactive substance, and 3066 (80.2%) were term-born (≥37 weeks' gestation). Growth mixture modeling characterized a 3-class CBCL-DP trajectory model: high and increasing (2.3% [n = 89]), borderline and stable (12.3% [n = 479]), and low and decreasing (85.6% [n = 3366]). Children in high and borderline dysregulation trajectories had more prevalent maternal psychological challenges (29.4%-50.0%). Multinomial logistic regression analyses indicated that children born preterm were more likely to be in the high dysregulation trajectory (adjusted odds ratio [aOR], 2.76; 95% CI, 2.08-3.65; P < .001) or borderline dysregulation trajectory (aOR, 1.36; 95% CI, 1.06-1.76; P = .02) vs low dysregulation trajectory. High vs low dysregulation trajectories were less prevalent for girls compared with boys (aOR, 0.60; 95% CI, 0.36-1.01; P = .05) and children with lower PAI (aOR, 1.94; 95% CI, 1.51-2.49; P < .001). Combined increases in PAI and prenatal substance exposures were associated with increased odds of high vs borderline dysregulation (aOR, 1.28; 95% CI, 1.08-1.53; P = .006) and decreased odds of low vs high dysregulation (aOR, 0.77; 95% CI, 0.64-0.92; P = .005). Conclusions and Relevance: In this cohort study of behavioral dysregulation trajectories, associations were found with early risk factors. These findings may inform screening and diagnostic practices for addressing observed precursors of persisting dysregulation as they emerge among at-risk children.

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

Importance: The prevalence, pathophysiology, and long-term outcomes of COVID-19 (post-acute sequelae of SARS-CoV-2 [PASC] or "Long COVID") in children and young adults remain unknown. Studies must address the urgent need to define PASC, its mechanisms, and potential treatment targets in children and young adults. Observations: We describe the protocol for the Pediatric Observational Cohort Study of the NIH's RE searching COV ID to E nhance R ecovery (RECOVER) Initiative. RECOVER-Pediatrics is an observational meta-cohort study of caregiver-child pairs (birth through 17 years) and young adults (18 through 25 years), recruited from more than 100 sites across the US. This report focuses on two of five cohorts that comprise RECOVER-Pediatrics: 1) a de novo RECOVER prospective cohort of children and young adults with and without previous or current infection; and 2) an extant cohort derived from the Adolescent Brain Cognitive Development (ABCD) study ( n =10,000). The de novo cohort incorporates three tiers of data collection: 1) remote baseline assessments (Tier 1, n=6000); 2) longitudinal follow-up for up to 4 years (Tier 2, n=6000); and 3) a subset of participants, primarily the most severely affected by PASC, who will undergo deep phenotyping to explore PASC pathophysiology (Tier 3, n=600). Youth enrolled in the ABCD study participate in Tier 1. The pediatric protocol was developed as a collaborative partnership of investigators, patients, researchers, clinicians, community partners, and federal partners, intentionally promoting inclusivity and diversity. The protocol is adaptive to facilitate responses to emerging science. Conclusions and Relevance: RECOVER-Pediatrics seeks to characterize the clinical course, underlying mechanisms, and long-term effects of PASC from birth through 25 years old. RECOVER-Pediatrics is designed to elucidate the epidemiology, four-year clinical course, and sociodemographic correlates of pediatric PASC. The data and biosamples will allow examination of mechanistic hypotheses and biomarkers, thus providing insights into potential therapeutic interventions. Clinical Trialsgov Identifier: Clinical Trial Registration: http://www.clinicaltrials.gov . Unique identifier: NCT05172011.