Preeclampsia, Fetal Growth Restriction, and 24-Month Neurodevelopment in Very Preterm Infants.

Importance: Preeclampsia has direct influences on a developing fetus and may impact postnatal health, and fetal growth restriction (FGR) is often seen co-occurring with preeclampsia. The development of children born very preterm after preeclampsia diagnosis with and without FGR is not well characterized. Objective: To examine the associations of preeclampsia and FGR with developmental and/or behavioral outcomes in a cohort of very preterm infants. Design, Setting, and Participants: In this cohort study, infants in the prospective Neonatal Neurobehavior and Outcomes in Very Preterm Infants study were enrolled between April 2014 and June 2016 from 9 US university-affiliated neonatal intensive care units (NICUs). Eligible infants were born before 30 weeks' gestation. Infants were excluded for any major congenital anomalies and for maternal age younger than 18 years or cognitive impairment impacting the ability to provide informed consent. Data analysis was performed from November 2023 to January 2024. Exposure: Maternal preeclampsia and FGR in very preterm infants. Main Outcomes and Measures: The Bayley-III cognition, motor, and language scores less than 85 (-1 SD) indicated developmental delay. Child Behavior Checklist/Preschool 1.5-5 T-scores greater than or equal to 64 for internalizing, externalizing, or total problems indicated clinical importance. Results: Of 704 infants enrolled, 529 (mean [SD] gestational age, 27.0 [1.9] weeks; 287 male [54.3%]) were studied at 24-month follow-up. A total of 94 infants' mothers had preeclampsia (23.2%), and 46 infants (8.7%) had FGR. In adjusted models, preeclampsia was not associated with Bayley-III (cognitive, B = 3.43 [95% CI, -0.19 to 6.66]; language, B = 3.92 [95% CI, 0.44 to 7.39]; motor, B = 1.86 [95% CI, -1.74 to 5.47]) or Child Behavior Checklist/Preschool 1.5-5 (internalizing, B = -0.08 [95% CI, -2.58 to 2.73]; externalizing, B = 0.69 [95% CI, -1.76 to 3.15]; total, B = 0.21 [95% CI, -2.48 to 2.91]) outcomes. FGR was associated with significantly lower Bayley-III scores (cognitive, B = -8.61 [95% CI, -13.33 to -3.89]; language, B = -8.29 [95% CI, -12.95 to -3.63]; motor, B = -7.60 [95% CI, -12.40 to -2.66]), regardless of preeclampsia status. Conclusions and Relevance: In this cohort study of preterm infants, preeclampsia was not associated with developmental and/or behavioral outcomes, but infants with FGR may be prone to developmental delays. These findings suggest future areas of research for understanding the roles of preeclampsia and FGR separately and together in early child development for preterm infants.

Neonatal neurobehavior associated with developmental changes from age 2 to 3 in very preterm infants.

OBJECTIVE: Understand how high-risk infants' development changes over time. Examine whether NICU Network Neurobehavioral Scale (NNNS) profiles are associated with decrements in developmental outcomes between ages 2 and 3 years in infants born very preterm. STUDY DESIGN: The Neonatal Outcomes for Very preterm Infants (NOVI) cohort is a multisite prospective study of 704 preterm infants born <30 weeks' gestation across nine university and VON affiliated NICUs. Data included infant neurobehavior measured by NNNS profiles at NICU discharge and the Bayley Scales of Infant and Toddler Development (BSID-III) at ages 2 and 3 years. Generalized estimating equations tested associations between NNNS profiles and BSID-III composite score changes between ages 2 and 3 years. RESULTS: The final study sample included 433 infants with mean gestational age of 27 weeks at birth. Infants with dysregulated NNNS profiles were more likely to have decreases in BSID-III Cognitive (OR = 2.66) and Language scores (OR = 2.53) from age 2 to 3 years compared to infants with more well-regulated neurobehavioral NNNS profiles. Further, infants with more well-regulated NNNS profiles were more likely to have increases in BSID-III Cognitive scores (OR = 2.03), rather than no change, compared to infants with dysregulated NNNS profiles. CONCLUSIONS AND RELEVANCE: Prior to NICU discharge, NNNS neurobehavioral profiles identified infants at increased risk for developing later language and cognitive challenges. Findings suggests that neonatal neurobehavior provides a unique, clinically significant contribution to the evaluation of very preterm infants to inform treatment planning for the most vulnerable.

Toward a more holistic approach to the study of exposures and child outcomes.

Aim: The current work was designed to demonstrate the application of the exposome framework in examining associations between exposures and children's long-term neurodevelopmental and behavioral outcomes. Methods: Longitudinal data were collected from birth through age 6 from 402 preterm infants. Three statistical methods were utilized to demonstrate the exposome framework: exposome-wide association study, cumulative exposure and machine learning models, with and without epigenetic data. Results: Each statistical approach answered a distinct research question regarding the impact of exposures on longitudinal child outcomes. Findings highlight associations between exposures, epigenetics and executive function. Conclusion: Findings demonstrate how an exposome-based approach can be utilized to understand relationships between internal (e.g., DNA methylation) and external (e.g., prenatal risk) exposures and long-term developmental outcomes in preterm children.

Contributions of prenatal risk factors and neonatal epigenetics to cognitive outcome in children born very preterm.

Children born less than 30 weeks gestational age (GA) are at high risk for neurodevelopmental delay compared to term peers. Prenatal risk factors and neonatal epigenetics could help identify preterm children at highest risk for poor cognitive outcomes. We aimed to understand the associations among cumulative prenatal risk, neonatal DNA methylation, and child cognitive ability at age 3 years, including whether DNA methylation mediates the association between prenatal risk and cognitive ability. We studied 379 neonates (54% male) born less than 30 weeks GA who had DNA methylation measured at neonatal intensive care unit discharge along with 3-year follow-up data. Cumulative prenatal risk was calculated from 24 risk factors obtained from maternal report and medical record and epigenome-wide neonatal DNA methylation was assayed from buccal swabs. At 3-year follow-up, child cognitive ability was assessed using the Bayley Scales of Infant and Toddler Development (third edition). Cumulative prenatal risk and DNA methylation at two cytosine-phosphate-guanines (CpGs) were uniquely associated with child cognitive ability. Using high-dimensional mediation analysis, we also identified differential methylation of 309 CpGs that mediated the association between cumulative prenatal risk and child cognitive ability. Many of the associated CpGs were located in genes (TNS3, TRAPPC4, MAD1L1, APBB2, DIP2C, TRAPPC9, DRD2) that have previously been associated with prenatal exposures and/or neurodevelopmental phenotypes. Our findings suggest a role for both prenatal risk factors and DNA methylation in explaining outcomes for children born preterm and suggest we should further study DNA methylation as a potential mechanism underlying the association between prenatal risk and child neurodevelopment. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Epigenome-wide association study identifies neonatal DNA methylation associated with two-year attention problems in children born very preterm.

Prior research has identified epigenetic predictors of attention problems in school-aged children but has not yet investigated these in young children, or children at elevated risk of attention problems due to preterm birth. The current study evaluated epigenome-wide associations between neonatal DNA methylation and attention problems at age 2 years in children born very preterm. Participants included 441 children from the Neonatal Neurobehavior and Outcomes in Very Preterm Infants (NOVI) Study, a multi-site study of infants born < 30 weeks gestational age. DNA methylation was measured from buccal swabs collected at NICU discharge using the Illumina MethylationEPIC Bead Array. Attention problems were assessed at 2 years of adjusted age using the attention problems subscale of the Child Behavior Checklist (CBCL). After adjustment for multiple testing, DNA methylation at 33 CpG sites was associated with child attention problems. Differentially methylated CpG sites were located in genes previously linked to physical and mental health, including several genes associated with ADHD in prior epigenome-wide and genome-wide association studies. Several CpG sites were located in genes previously linked to exposure to prenatal risk factors in the NOVI sample. Neonatal epigenetics measured at NICU discharge could be useful in identifying preterm children at risk for long-term attention problems and related psychiatric disorders, who could benefit from early prevention and intervention efforts.

Neurodevelopmental and behavioral outcomes of very preterm infants: latent profile analysis in the Environmental influences on Child Health Outcomes (ECHO) Program.

BACKGROUND: Very preterm infants are at high risk for neurodevelopmental impairments. We used a child-centered approach (latent profile analysis [LPA]) to describe 2-year neurobehavioral profiles for very preterm infants based on cognitive, motor, and behavioral outcomes. We hypothesized that distinct outcome profiles would differ in the severity and co-occurrence of neurodevelopmental and behavioral impairment. METHODS: We studied children born <33 weeks' gestation from the Environmental influences on Child Health Outcomes Program with at least one neurobehavioral assessment at age 2 (Bayley Scales of Infant and Toddler Development, Child Behavior Checklist, Modified Checklist for Autism in Toddlers, cerebral palsy diagnosis). We applied LPA to identify subgroups of children with different patterns of outcomes. RESULTS: In 2036 children (52% male; 48% female), we found four distinct neurobehavioral profiles. Most children (~85%) were categorized into one of two profiles characterized by no/mild neurodevelopmental delay and a low prevalence of behavioral problems. Fewer children (~15%) fell into one of two profiles characterized by severe neurodevelopmental impairments. One profile consisted of children (5%) with co-occurring neurodevelopmental impairment and behavioral problems. CONCLUSION: Child-centered approaches provide a comprehensive, parsimonious description of neurodevelopment following preterm birth and can be useful for clinical and research purposes. IMPACT: Most research on outcomes for children born very preterm have reported rates of impairment in single domains. Child-centered approaches describe profiles of children with unique combinations of cognitive, motor, and behavioral strengths and weaknesses. We capitalized on data from the nationwide Environmental influences on Child Health Outcomes Program to examine these profiles in a large sample of children born <33 weeks gestational age. We found four distinct neurobehavioral profiles consisting of different combinations of cognitive, motor, and behavioral characteristics. This information could aid in the development of clinical interventions that target different profiles of children with unique developmental needs.

Agreement Between Two Behavioral Rating Scales in Preschoolers Born Very Preterm.

OBJECTIVE: Broadband parent rating scales are commonly used to assess behavioral problems in children. Multiple rating scales are available, yet agreement between them is not well-understood. The objective of this study was to evaluate agreement between the Behavior Assessment System for Children, Third Edition (BASC-3), and Child Behavior Checklist 1.5 to 5 years (CBCL) in a sample of children born very preterm. METHOD: We assessed 73 children born < 30 weeks' gestational age whose caregivers completed the BASC-3 and CBCL at age 4. We examined correlations, within-person differences, and agreement in clinical categorization for all corresponding subscales and composites. RESULTS: Comparable subscales on the BASC-3 and CBCL were significantly correlated, albeit to differing magnitudes. Subscales indexing hyperactivity and attention problems were the most comparable across the 2 measures, evidenced by strong correlations and few to no differences in mean T-scores. Composite scores indexing internalizing, externalizing, and total problems were also strongly correlated, and there were no differences in the mean T-scores for externalizing or total problems across measures. Agreement in clinical classifications were weak to moderate, though again, the highest agreement was found for hyperactivity, attention, externalizing, and total problems. CONCLUSION: Agreement between BASC-3 and CBCL subscales was weak to moderate, with the exception of subscales related to attention and hyperactivity, as well as composite scores indicating overall behavior problems. Researchers and clinicians should consider these discrepancies when interpreting the results of behavior rating scales with preschool children because conclusions could differ based on the assessment that is used.

Epigenetic age acceleration, neonatal morbidities, and neurobehavioral profiles in infants born very preterm.

Epigenetic age acceleration is a risk factor for chronic diseases of ageing and may reflect aspects of biological ageing. However, few studies have examined epigenetic ageing during the early neonatal period in preterm infants, who are at heightened risk of developmental problems. We examined relationships between neonatal age acceleration, neonatal morbidities, and neurobehavioral domains among very preterm (<30 weeks gestation) infants to characterize whether infants with early morbidities or different neurobehavioral characteristics had accelerated or decelerated epigenetic ageing. This study uses data from the Neonatal Neurobehavior and Outcomes in Very Preterm Infants (NOVI) study, restricted to infants with data on variables assessed (n = 519). We used generalized estimating equations to test for differences in age acceleration associated with severe neonatal medical morbidities and neurobehavioral characteristics. We found that infants with neonatal morbidities, in particular, bronchopulmonary dysplasia (BPD), had accelerated epigenetic age - and some evidence that infants with hypertonicity and asymmetric reflexes had increased and decreased age acceleration, respectively. Adjustment for gestational age attenuated some associations, suggesting that the relationships observed may be driven by the duration of gestation. Our most robust finding shows that very preterm infants with neonatal morbidities (BPD in particular) exhibit age acceleration, but most neonatal neurobehavioral characteristics and morbidities are not associated with early life age acceleration. Lower gestational age at birth may be an upstream factor driving these associations.

Maternal Prenatal Risk Phenotypes and Neurobehavioral Outcomes among Infants Born Very Preterm.

OBJECTIVE: To assess whether prenatal risk phenotypes are associated with neurobehavioral impairment for children born <30 weeks of gestation at discharge from the neonatal intensive care unit (NICU) and at 24-month follow-up. STUDY DESIGN: We studied infants from the Neonatal Neurobehavior and Outcomes in Very Preterm Infants (NOVI) study, a multisite investigation of infants born <30 weeks of gestation. There were 704 newborns enrolled in the NOVI study; of these, 679 (96%) had neonatal neurobehavioral data and 556 (79%) had 24-month follow-up data. Maternal prenatal phenotypes (physical and psychological risk groups) were characterized from 24 physical and psychological health risk factors. Neurobehavior was assessed at NICU discharge using the NICU Network Neurobehavioral Scales and at 2-year follow-up using the Bayley Scales of Infant and Toddler Development and the Child Behavior Checklist. RESULTS: Children born to mothers in the psychological risk group were at increased risk for dysregulated neonatal neurobehavior (OR, 2.04; 95% CI, 1.08-3.87) at NICU discharge, and for severe motor delay (OR, 3.80; 95% CI, 1.48-9.75), and clinically significant externalizing problems (OR, 2.54; 95% CI, 1.15-5.56) at age 24 months, compared with children born to mothers in the low-risk group. Children born to mothers in the physical risk group were more likely to have severe motor delay (OR, 2.70; 95% CI, 1.07-6.85) compared with the low-risk group. CONCLUSIONS: High-risk maternal prenatal phenotypes were associated with neurobehavioral impairment for children born very preterm. This information could identify newborns at risk for adverse neurodevelopmental outcomes.

Annual Research Review: Prenatal opioid exposure - a two-generation approach to conceptualizing neurodevelopmental outcomes.

Opioid use during pregnancy impacts the health and well-being of two generations: the pregnant person and the child. The factors that increase risk for opioid use in the adult, as well as those that perpetuate risk for the caregiver and child, oftentimes replicate across generations and may be more likely to affect child neurodevelopment than the opioid exposure itself. In this article, we review the prenatal opioid exposure literature with the perspective that this is not a singular event but an intergenerational cascade of events. We highlight several mechanisms of transmission across generations: biological factors, including genetics and epigenetics and the gut-brain axis; parent-child mechanisms, such as prepregnancy experience of child maltreatment, quality of parenting, infant behaviors, neonatal opioid withdrawal diagnosis, and broader environmental contributors including poverty, violence exposure, stigma, and Child Protective Services involvement. We conclude by describing ways in which intergenerational transmission can be disrupted by early intervention.

Prenatal and perinatal factors associated with neonatal neurobehavioral profiles in the ECHO Program.

BACKGROUND: Single-cohort studies have identified distinct neurobehavioral profiles that are associated with prenatal and neonatal factors based on the NICU Network Neurobehavioral Scale (NNNS). We examined socioeconomic, medical, and substance use variables as predictors of NNNS profiles in a multi-cohort study of preterm and term-born infants with different perinatal exposures. METHODS: We studied 1112 infants with a neonatal NNNS exam from the Environmental influences on Child Health Outcomes (ECHO) consortium. We used latent profile analysis to characterize infant neurobehavioral profiles and generalized estimating equations to determine predictors of NNNS profiles. RESULTS: Six distinct neonatal neurobehavioral profiles were identified, including two dysregulated profiles: a hypo-aroused profile (16%) characterized by lethargy, hypotonicity, and nonoptimal reflexes; and a hyper-aroused profile (6%) characterized by high arousal, excitability, and stress, with low regulation and poor movement quality. Infants in the hypo-aroused profile were more likely to be male, have younger mothers, and have mothers who were depressed prenatally. Infants in the hyper-aroused profile were more likely to be Hispanic/Latino and have mothers who were depressed or used tobacco prenatally. CONCLUSIONS: We identified two dysregulated neurobehavioral profiles with distinct perinatal antecedents. Further understanding of their etiology could inform targeted interventions to promote positive developmental outcomes. IMPACT: Prior research on predictors of neonatal neurobehavior have included single-cohort studies, which limits generalizability of findings. In a multi-cohort study of preterm and term-born infants, we found six distinct neonatal neurobehavioral profiles, with two profiles being identified as dysregulated. Hypo- and hyper-aroused neurobehavioral profiles had distinct perinatal antecedents. Understanding perinatal factors associated with dysregulated neurobehavior could help promote positive developmental outcomes.

Leveraging item-level accuracy and reaction time to address ceiling effects in the measurement of inhibitory control in preschool-aged children.

Preschool-aged children's performance on inhibitory control tasks is typically represented by the overall accuracy of their item responses (e.g., mean proportion correct). However, in settings where children vary widely in age or ability level, inhibitory control tasks are susceptible to ceiling effects, which undermine measurement precision. We have previously demonstrated a general approach for scoring inhibitory control tasks that combines item-level accuracy and reaction-time information to minimize ceiling effects. Here, we extend that approach by incorporating additional item-level reaction time data from an adjunct (simple reaction time) task. We contrast three approaches for scoring inhibitory control tasks, two of which rely exclusively on item accuracy information and a third which also considers item reaction time information. We demonstrate the impacts of these different approaches to scoring with two inhibitory control tasks that were included in a recent evaluation of the Red Light, Purple Light intervention in preprimary classrooms in Nairobi County, Kenya. We limited our study to children who met inclusion criteria at pre-test (N = 418; 51% male; mean age = 4.8 years) or post-test (N = 386; 51% male; mean age = 4.8 years). Children's performance on individual inhibitory control tasks was strongly correlated regardless of the scoring approach (rs = 0.73-0.97 across two tasks). However, the combined accuracy and reaction time scores eliminated ceiling effects that were common when only accuracy information was used. The combined accuracy and reaction time models also distinguished item-level RT into inhibitory control and processing speed components, which are distinct constructs. Results are discussed with respect to the challenges and nuances of the estimation and interpretation of inhibitory control task scores with children of varied ages and ability levels.

CpG methylation patterns in placenta and neonatal blood are differentially associated with neonatal inflammation.

BACKGROUND: Infants born extremely premature are at increased risk for health complications later in life for which neonatal inflammation may be a contributing biological driver. Placental CpG methylation provides mechanistic information regarding the relationship between prenatal epigenetic programming, prematurity, neonatal inflammation, and later-in-life health. METHODS: We contrasted CpG methylation in the placenta and neonatal blood spots in relation to neonatal inflammation in the Extremely Low Gestational Age Newborn (ELGAN) cohort. Neonatal inflammation status was based on the expression of six inflammation-related proteins, assessed as (1) day-one inflammation (DOI) or (2) intermittent or sustained systemic inflammation (ISSI, inflammation on ≥2 days in the first 2 postnatal weeks). Epigenome-wide CpG methylation was assessed in 354 placental samples and 318 neonatal blood samples. RESULTS: Placental CpG methylation displayed the strongest association with ISSI (48 CpG sites) but was not associated with DOI. This was in contrast to CpG methylation in blood spots, which was associated with DOI (111 CpG sites) and not with ISSI (one CpG site). CONCLUSIONS: Placental CpG methylation was strongly associated with ISSI, a measure of inflammation previously linked to later-in-life cognitive impairment, while day-one neonatal blood methylation was associated with DOI. IMPACT: Neonatal inflammation increases the risk of adverse later-life outcomes, especially in infants born extremely preterm. CpG methylation in the placenta and neonatal blood spots were evaluated in relation to neonatal inflammation assessed via circulating proteins as either (i) day-one inflammation (DOI) or (ii) intermittent or sustained systemic inflammation (ISSI, inflammation on ≥2 days in the first 2 weeks). Tissue specificity was observed in epigenetic-inflammatory relationships: placental CpG methylation was associated with ISSI, neonatal blood CpG methylation was associated with DOI. Supporting the placental origins of disease framework, placental epigenetic patterns are associated with a propensity for ISSI in neonates.

Analysis of Neonatal Neurobehavior and Developmental Outcomes Among Preterm Infants.

Importance: The ability to identify poor outcomes and treatable risk factors among very preterm infants remains challenging; improving early risk detection and intervention targets to potentially address developmental and behavioral delays is needed. Objective: To determine associations between neonatal neurobehavior using the Neonatal Intensive Care Unit (NICU) Network Neurobehavioral Scale (NNNS), neonatal medical risk, and 2-year outcomes. Design, Setting, and Participants: This multicenter cohort enrolled infants born at less than 30 weeks' gestation at 9 US university-affiliated NICUs. Enrollment was conducted from April 2014 to June 2016 with 2-year adjusted age follow-up assessment. Data were analyzed from December 2019 to January 2022. Exposures: Adverse medical and psychosocial conditions; neurobehavior. Main Outcomes and Measures: Bayley Scales of Infant and Toddler Development, third edition (Bayley-III), cognitive, language, and motor scores of less than 85 and Child Behavior Checklist (CBCL) T scores greater than 63. NNNS examinations were completed the week of NICU discharge, and 6 profiles of neurobehavior were identified by latent profile analysis. Generalized estimating equations tested associations among NNNS profiles, neonatal medical risk, and 2-year outcomes while adjusting for site, maternal socioeconomic and demographic factors, maternal psychopathology, and infant sex. Results: A total of 679 enrolled infants had medical and NNNS data; 2-year follow-up data were available for 479 mothers and 556 infants (mean [SD] postmenstrual age at birth, 27.0 [1.9] weeks; 255 [45.9%] female). Overall, 268 mothers (55.9%) were of minority race and ethnicity, and 127 (26.6%) lived in single-parent households. The most common neonatal medical morbidity was BPD (287 [51.7%]). Two NNNS behavior profiles, including 157 infants, were considered high behavioral risk. Infants with at least 2 medical morbidities (n = 123) were considered high medical risk. Infants with high behavioral and high medical risk were 4 times more likely to have Bayley-III motor scores less than 85 compared with those with low behavioral and low medical risk (adjusted relative risk [aRR], 4.1; 95% CI, 2.9-5.1). Infants with high behavioral and high medical risk also had increased risk for cognitive scores less than 85 (aRR, 2.7; 95% CI, 1.8-3.4). Only infants with high behavioral and low medical risk were in the clinical range for CBCL internalizing and total problem scores (internalizing: aRR, 2.3; 95% CI, 1.1-4.5; total: aRR, 2.5; 95% CI, 1.2-4.4). Conclusions and Relevance: In this study, high-risk neonatal neurobehavioral patterns at NICU discharge were associated with adverse cognitive, motor, and behavioral outcomes at 2 years. Used in conjunction with medical risk, neonatal neurobehavioral assessments could enhance identification of infants at highest risk for delay and offer opportunities to provide early, targeted therapies.

Testing a cascade model linking prenatal inflammation to child executive function.

Inflammation during pregnancy is beginning to be understood as a risk factor predicting poor infant health and neurodevelopmental outcomes. The long-term sequelae associated with exposure to prenatal inflammation are less well established. The current study examined associations between maternal inflammation during pregnancy, markers of infant neurodevelopment (general cognitive ability, negative affect, and sleep quality), and preschool executive function (EF) in a longitudinal sample of 40 African American mother-infant dyads. Mothers completed a blood draw in the third trimester of pregnancy to measure plasma levels of C-reactive protein (CRP) and pro-inflammatory cytokines (e.g., interleukin 6 [IL-6], tumor necrosis factor-alpha [TNF-α]). When infants were 6 months of age, we assessed general cognitive ability via the Bayley-III, negative affect via the Still-Face Paradigm, and sleep quality via actigraphy monitoring. When children were 4 years of age, we assessed their EF ability using four tasks from the EF Touch battery. Elevated levels of maternal CRP, IL-6, and TNF-α were associated with poorer infant general cognitive ability. Although there were no direct effects of prenatal inflammation on preschool EF, we observed an indirect relationship between IL-6 and preschool EF ability via infant general cognitive ability. Our findings suggest that prenatal inflammation may have long-lasting, cascading implications for child neurodevelopment. Implications of these findings for health disparities in women and children of color are discussed.

Relations between infant sleep quality, physiological reactivity, and emotional reactivity to stress at 3 and 6 months.

The study examines the association between infant sleep, physiological, and emotional reactivity at 3 and 6 months of age in 89 African American infants and their caregivers. Infant sleep was objectively measured at 3 and 6months using actigraphy for 7 days and nights. At 6 months of age, dyads participated in the Still-Face Paradigm (SFP) (Tronick et al., 1978) to assess infants' physiological reactivity (via respiratory sinus arrhythmia (RSA)) and emotional reactivity. Findings revealed that infant night wakings at 3 months was positively correlated with baseline RSA at 6 months (ß = .35, p < .001). Night wakings at 3 months marginally predicted negative affect during the recovery episode of SFP (ß = -.26, p = .057). Further, night wakings at 6-months-old predicted more positive affect during the recovery episode of SFP (ß = .34, p = .007). We discuss potential explanations for these findings such as an exuberant temperament style, parenting behavior, and lack of sleep consolidation at this early age to be the focus of future studies in this area. The current study adds to the limited research examining the relationship between sleep and reactivity in the earliest months of development. Findings reveal that it is critical to take developmental timing into account as all results were unexpected in relation to the childhood literature. Moreover, this is the first study of its kind to focus on an African American sample.

Parenting and maternal reported child sleep problems in infancy predict school-age aggression and inattention.

OBJECTIVE: To examine caregiving predictors of maternal reported sleep problems and child behavioral and cognitive outcomes in early childhood. DESIGN: A prospective longitudinal study from 6 to 84 months of age. SETTING: Lab visits, assessments, and questionnaires conducted with a community-based sample. PARTICIPANTS: One hundred sixty-four African American and White children, their mothers, and teachers. MEASUREMENT: Parenting behavior was measured during a free-play task at 6 months of age, maternal-report of child sleep problems was completed at 6 timepoints, and teacher report of child aggression and attention was collected in kindergarten and second grade. RESULTS: Latent growth curve modeling revealed that maternal reported sleep problems decreased in children from 18 to 84 months and harsh-intrusive parenting at 6 months predicted sleep problems at 18 months. Maternal reported sleep problems at 18 months predicted aggressive behaviors in kindergarten and second grade. CONCLUSION: Parenting at 6 months of age exerts an influence on sleep quality at 18 months which is associated with aggressive behavior in early childhood.

Effects of Pharmacologic Treatment for Neonatal Abstinence Syndrome on DNA Methylation and Neurobehavior: A Prospective Cohort Study.

OBJECTIVE: To determine whether pharmacologic treatment for neonatal abstinence syndrome (NAS) is associated with changes in DNA methylation (DNAm) of the mu-opioid receptor gene (OPRM1) and improvements in neonatal neurobehavior. STUDY DESIGN: Buccal swabs were collected from 37 neonates before and after morphine treatment for NAS. Genomic DNA was extracted, and DNAm was examined at 4 cytosine-phosphate-guanine (CpG) sites within the OPRM1 gene. Assessment with the NICU Network Neurobehavioral Scales (NNNS) was also performed before and after NAS treatment. Changes in DNAm (DNAmpost-tx - DNAmpre-tx) and NNNS summary scores (NNNSpost-tx - NNNSpre-tx) were then calculated. Path analysis was used to examine associations among pharmacologic treatment (length of treatment [LOT] and total dose of morphine), changes in DNAm, and changes in NNNS summary scores. RESULTS: DNAm was significantly decreased from pretreatment to post-treatment at 1 of 4 CpG sites within the OPRM1 gene. Neonates also demonstrated decreased excitability, hypertonia, lethargy, signs of stress and abstinence, and increased quality of movement and regulation from pretreatment to post-treatment. Longer LOT and higher morphine dose were associated with greater decreases in DNAm; greater decreases in DNAm were associated with greater decreases in excitability and hypertonia on the NNNS. CONCLUSIONS: Pharmacologic treatment of NAS is associated with decreased DNAm of the OPRM1 gene and improved neonatal neurobehavior. Epigenetic changes may play a role in these changes in neonatal neurobehavior.