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.

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.

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.

Prevalence and Perceptions of Electronic Cigarette Use during Pregnancy.

Objectives The current study is the first to assess pregnant women's perceptions of e-cigarettes and the prevalence of e-cigarette use during pregnancy, using a national sample of pregnant women (N = 445) recruited online. Methods An online survey was used to assess the prevalence and perceptions of e-cigarette use among pregnant women, including perceptions of e-cigarette safety. Results In our sample, 5.62% (n = 25) of women solely used tobacco cigarettes, 6.52% (n = 29) solely used e-cigarettes, 8.54% (n = 38) used both tobacco cigarettes and e-cigarettes, and 79.33% (n = 353) used neither tobacco cigarettes nor e-cigarettes during their current pregnancy. Overall, 64.27% (n = 286) of participants viewed e-cigarettes as being safer than tobacco cigarettes. Having seen advertisements for e-cigarettes increased likelihood of viewing them as safer than tobacco cigarettes (OR [Odds Ratio] = 2.5, p < .01). Conclusions for Practice Taken together, findings from this study suggest that at least as many women use e-cigarettes during pregnancy as tobacco cigarettes, that pregnant women view e-cigarettes as being safer than tobacco cigarettes, and that these views may be influenced by exposure to e-cigarette advertisements.

Birth Weight, Birth Length, and Gestational Age as Indicators of Favorable Fetal Growth Conditions in a US Sample.

The "fetal origins" hypothesis suggests that fetal conditions not only affect birth characteristics such as birth weight and gestational age, but also have lifelong health implications. Despite widespread interest in this hypothesis, few methodological advances have been proposed to improve the measurement and modeling of fetal conditions. A Statistics in Medicine paper by Bollen, Noble, and Adair examined favorable fetal growth conditions (FFGC) as a latent variable. Their study of Filipino children from Cebu provided evidence consistent with treating FFGC as a latent variable that largely mediates the effects of mother's characteristics on birth weight, birth length, and gestational age. This innovative method may have widespread utility, but only if the model applies equally well across diverse settings. Our study assesses whether the FFGC model of Cebu replicates and generalizes to a very different population of children from North Carolina (N=705) and Pennsylvania (N=494). Using a series of structural equation models, we find that key features of the Cebu analysis replicate and generalize while we also highlight differences between these studies. Our results support treating fetal conditions as a latent variable when researchers test the fetal origins hypothesis. In addition to contributing to the substantive literature on measuring fetal conditions, we also discuss the meaning and challenges involved in replicating prior research.