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.

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.

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.

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.

Using machine learning to understand age and gender classification based on infant temperament.

Age and gender differences are prominent in the temperament literature, with the former particularly salient in infancy and the latter noted as early as the first year of life. This study represents a meta-analysis utilizing Infant Behavior Questionnaire-Revised (IBQ-R) data collected across multiple laboratories (N = 4438) to overcome limitations of smaller samples in elucidating links among temperament, age, and gender in early childhood. Algorithmic modeling techniques were leveraged to discern the extent to which the 14 IBQ-R subscale scores accurately classified participating children as boys (n = 2,298) and girls (n = 2,093), and into three age groups: youngest (< 24 weeks; n = 1,102), mid-range (24 to 48 weeks; n = 2,557), and oldest (> 48 weeks; n = 779). Additionally, simultaneous classification into age and gender categories was performed, providing an opportunity to consider the extent to which gender differences in temperament are informed by infant age. Results indicated that overall age group classification was more accurate than child gender models, suggesting that age-related changes are more salient than gender differences in early childhood with respect to temperament attributes. However, gender-based classification was superior in the oldest age group, suggesting temperament differences between boys and girls are accentuated with development. Fear emerged as the subscale contributing to accurate classifications most notably overall. This study leads infancy research and meta-analytic investigations more broadly in a new direction as a methodological demonstration, and also provides most optimal comparative data for the IBQ-R based on the largest and most representative dataset to date.

Neonatal opioid withdrawal syndrome: a review of the science and a look toward the use of buprenorphine for affected infants.

Neonates born to mothers taking opioids during pregnancy are at risk for neonatal opioid withdrawal syndrome (NOWS), for which there is no recognized standard approach to care. Nonpharmacologic treatment is typically used as a first-line approach for management, and pharmacologic treatment is added when clinical signs are not responding to nonpharmacologic measures alone. Although morphine and methadone are the most commonly used pharmacotherapies for NOWS, buprenorphine has emerged as a treatment option based on its pharmacologic profile and results from initial single site clinical trials. The objective of this report is to provide an overview of NOWS including a summary of ongoing work in the field and to review the state of the science, knowledge gaps, and practical considerations specific to the use of buprenorphine for the treatment of NOWS as discussed by a panel of experts during a virtual workshop hosted by the National Institutes of Health.

An E-Textile Respiration Sensing System for NICU Monitoring: Design and Validation.

The world is witnessing a rising number of preterm infants who are at significant risk of medical conditions. These infants require continuous care in Neonatal Intensive Care Units (NICU). Medical parameters are continuously monitored in premature infants in the NICU using a set of wired, sticky electrodes attached to the body. Medical adhesives used on the electrodes can be harmful to the baby, causing skin injuries, discomfort, and irritation. In addition, respiration rate (RR) monitoring in the NICU faces challenges of accuracy and clinical quality because RR is extracted from electrocardiogram (ECG). This research paper presents a design and validation of a smart textile pressure sensor system that addresses the existing challenges of medical monitoring in NICU. We designed two e-textile, piezoresistive pressure sensors made of Velostat for noninvasive RR monitoring; one was hand-stitched on a mattress topper material, and the other was embroidered on a denim fabric using an industrial embroidery machine. We developed a data acquisition system for validation experiments conducted on a high-fidelity, programmable NICU baby mannequin. We designed a signal processing pipeline to convert raw time-series signals into parameters including RR, rise and fall time, and comparison metrics. The results of the experiments showed that the relative accuracies of hand-stitched sensors were 98.68 (top sensor) and 98.07 (bottom sensor), while the accuracies of embroidered sensors were 99.37 (left sensor) and 99.39 (right sensor) for the 60 BrPM test case. The presented prototype system shows promising results and demands more research on textile design, human factors, and human experimentation.

Stress, coping and silver linings: How depressed perinatal women experienced the COVID-19 pandemic.

BACKGROUND: Research on perinatal mental health during the COVID-19 pandemic has largely focused on data from community samples. This study sought to understand the experiences of pregnant and postpartum women with histories of clinically elevated symptoms of depression. METHODS: Participants included 60 perinatal women who participated in wellness intervention trials for women with antenatal depression. We used a mixed methods approach, assessing depression, anxiety, stressors and coping behaviors, along with narrative responses to questions regarding COVID-specific effects on mental health. RESULTS: Over three-fourths of the sample indicated a worsening of mental health during the pandemic, with 31.7% of women endorsing clinically elevated depression symptoms and 36.7% screening positive for anxiety. Women reported negative impacts on their emotional wellbeing, especially a resurgence of mental health symptoms. Participants also articulated positive experiences during the pandemic, including an appreciation for increased time with family, especially infants. Women detailed numerous, mostly adaptive, coping strategies they had used to mitigate stress; self-isolation and spending time outdoors were associated with having depression above or below the clinical cut off, respectively. LIMITATIONS: The study had a small sample, and the generalizability of findings may be limited, given that participants were clinical trial completers. CONCLUSIONS: Although the pandemic upended many aspects of life for perinatal women and raised mental health concerns, many also reported adaptive means of coping and positive experiences or 'silver linings' related to pandemic restrictions. Some coping strategies that were utilized, including wellness-based behaviors, may have helped to mitigate the impact of COVID-19 related stress.

Depression, Anxiety, Resilience, and Coping: The Experience of Pregnant and New Mothers During the First Few Months of the COVID-19 Pandemic.

Background: It is well-documented that the mental health of pregnant and postpartum women is essential for maternal, child, and family well-being. Of major public health concern is the perinatal mental health impacts that may occur during the ongoing coronavirus disease 2019 (COVID-19) pandemic. It is essential to explore the symptom experience and predictors of mental health status, including the relationship between media use and mental health. Materials and Methods: The purpose of this study is to evaluate the experiences of pregnant and postpartum women (n = 524) in the United States in the early phase of the COVID-19 pandemic. This cross-sectional online observational study collected psychosocial quantitative and qualitative survey data in adult pregnant and postpartum (up to 6 months postdelivery) women in April-June 2020. Results: Multivariable linear regression models were used to evaluate predictors of depressive symptoms, anxiety, and post-traumatic stress disorder. The most common predictors were job insecurity, family concerns, eating comfort foods, resilience/adaptability score, sleep, and use of social and news media. Qualitative themes centered on pervasive uncertainty and anxiety; grief about losses; gratitude for shifting priorities; and use of self-care methods including changing media use. Conclusions: This study provides information to identify risk for anxiety, depression, and PTSD symptoms in perinatal women during acute public health situations. Women with family and job concerns and low resilience/adaptability scores seem to be at high risk of psychological sequelae. Although use of social media is thought to improve social connectedness, our results indicate that increased media consumption is related to increased anxiety symptoms.

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.

Maternal smoking in pregnancy, fetal activity & newborn behavioral state: An observational ultrasound study.

Maternal smoking during pregnancy (MSDP) remains one of the most common prenatal drug exposures in the US and worldwide. MSDP is associated with medical risk for the fetus and altered behavioral development in infants; however, fewer studies have examined the impact of MSDP on fetal behavior or newborn behavioral state. We investigated associations between MSDP and (a) fetal motor activity and (b) newborn behavioral state following handling. Participants were 79 healthy mother-fetus/newborn pairs (57% MSDP-exposed). MSDP was measured by maternal interview and verified by saliva biomarkers. Mothers completed an observational fetal ultrasound assessment between 24 and 37 weeks gestation (M = 28 weeks), including baseline, vibro-acoustic stimulus and recovery periods. Total fetal motor activity and complex body movements were coded from ultrasound videos. Following delivery, newborn post-handling behavioral state was assessed by direct observational coding. MSDP exposure was associated with higher baseline fetal motor activity, particularly at younger gestational ages. Further, motor reactivity to stimulation emerged at later gestational ages in MSDP-exposed fetuses, while motor reactivity was consistent across gestational ages in unexposed fetuses. Finally, heavy MSDP exposure was associated with more arousal following handling and greater need for soothing interventions in the newborn period. Monitoring of fetal behavior via ultrasound may offer a unique opportunity to identify at-risk infants and provides data for stronger public health messaging regarding risks of MSDP. Associations between MSDP and increased newborn fussiness highlight opportunities for education and anticipatory guidance in the postpartum period.

Prenatal tobacco and marijuana co-use: Sex-specific influences on infant cortisol stress response.

Although tobacco (TOB) and marijuana (MJ) are often co-used in pregnancy, little is known regarding the joint impact of MJ + TOB on offspring development, including the developing neuroendocrine stress system. Further, despite evidence for sex-specific impacts of prenatal exposures in preclinical models, the sex-specific impact of prenatal MJ + TOB exposure on offspring neuroendocrine regulation in humans is also unknown. In the current study, overall and sex-specific influences of MJ + TOB co-use on offspring cortisol regulation were investigated over the first postnatal month. 111 mother-infant pairs from a low-income, racially and ethnically diverse sample participated. Based on Timeline Followback data with biochemical verification, three groups were identified: (1) prenatal MJ + TOB, (2) TOB only, and (3) controls. Baseline cortisol and cortisol stress response were assessed at seven points over the first postnatal month using a handling paradigm in which saliva cortisol was assessed before, during, and following a standard neurobehavioral assessment (NICU Network Neurobehavioral Scale). A significant exposure group by offspring sex interaction emerged for baseline cortisol over the first postnatal month (p = .043); MJ + TOB-exposed males showed 35-36% attenuation of baseline cortisol levels vs. unexposed and TOB-exposed males (ps ≤ .003), while no effects of exposure emerged for females. Both MJ + TOB and TOB-exposed infants showed a 22% attenuation of cortisol stress response over the first postnatal month vs. unexposed infants (ps < .03), with evidence for sex-specific effects in exploratory analyses. Although results are preliminary, this is the first human study to investigate the impact of prenatal MJ exposure on infant cortisol and the first to reveal a sex-specific impact of prenatal MJ + TOB on cortisol regulation in humans. Future, larger-scale studies are needed to elucidate mechanisms and consequences of sex-specific effects of MJ and MJ + TOB on the developing neuroendocrine stress system.

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.

Prenatal tobacco and marijuana co-use: Impact on newborn neurobehavior.

Tobacco and marijuana are some of the most common prenatal substance exposures worldwide. The social acceptability and political landscape of marijuana and its potency have changed dramatically in the last two decades leading to increased use by pregnant women. Despite evidence for increasing marijuana use and high rates of co-use of tobacco (TOB) and marijuana (MJ) during pregnancy, the impact of prenatal exposure to each substance is typically studied in isolation. We investigated the influence of co-exposure to TOB and MJ on infant neurobehavioral development over the first postnatal month. Participants were 111 mother-infant pairs from a low-income, diverse sample (Mean age = 25 ±â€¯5; 54% minorities). TOB and MJ use were assessed by Timeline Followback interview with biochemical confirmation. Three groups were identified: (a) prenatal MJ + TOB, (b) prenatal TOB only, (c) controls. Newborn neurobehavior was assessed at seven time points over the first postnatal month using the NICU Network Neurobehavioral Scale. MJ + TOB-exposed infants showed decreased ability to self-soothe (Self-regulation) and attend to stimuli (Attention), and increased need for examiner soothing (Handling) and low motor activity (Lethargy) versus unexposed infants. Despite low levels of MJ use in MJ + TOB co-users, co-exposure was associated with nearly double the impact on infant self-soothing and need for examiner soothing versus TOB-exposure alone. Effects of MJ + TOB co-exposure appeared more pronounced for daughters than for sons. Although results are preliminary, they highlight additional risk from dual exposure to MJ + TOB vs. TOB exposure alone, particularly for daughters. Results also highlight the critical importance of investigating prenatal exposures in concert and the need for intervention efforts to address MJ co-use in pregnant TOB users.

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.

Prenatal exposure to methadone or buprenorphine: Early childhood developmental outcomes.

BACKGROUND: Methadone and buprenorphine are recommended to treat opioid use disorders during pregnancy. However, the literature on the relationship between longer-term effects of prenatal exposure to these medications and childhood development is both spare and inconsistent. METHODS: Participants were 96 children and their mothers who participated in MOTHER, a randomized controlled trial of opioid-agonist pharmacotherapy during pregnancy. The present study examined child growth parameters, cognition, language abilities, sensory processing, and temperament from 0 to 36 months of the child's life. Maternal perceptions of parenting stress, home environment, and addiction severity were also examined. RESULTS: Tests of mean differences between children prenatally exposed to methadone vs. buprenorphine over the three-year period yielded 2/37 significant findings for children. Similarly, tests of mean differences between children treated for NAS relative to those not treated for NAS yielded 1/37 significant finding. Changes over time occurred for 27/37 child outcomes including expected child increases in weight, head and height, and overall gains in cognitive development, language abilities, sensory processing, and temperament. For mothers, significant changes over time in parenting stress (9/17 scales) suggested increasing difficulties with their children, notably seen in increasing parenting stress, but also an increasingly enriched home environment (4/7 scales) CONCLUSIONS: Findings strongly suggest no deleterious effects of buprenorphine relative to methadone or of treatment for NAS severity relative to not-treated for NAS on growth, cognitive development, language abilities, sensory processing, and temperament. Moreover, findings suggest that prenatal opioid agonist exposure is not deleterious to normal physical and mental development.

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.

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.