Objective Prenatal Maternal Stress Research Articles

Prenatal Maternal Stress and Pediatric Asthma Across Development: Adolescent Female-Specific Vulnerability.

Prenatal maternal stress (PNMS) is linked to physical sequelae in offspring, including childhood asthma. This study sought to examine the roles of objective and subjective PNMS in the development of asthma at offspring ages 5 and 15. The sample included 815 mother-child dyads from the Mater Misericordiae Mothers' Hospital-University of Queensland Study of Pregnancy. PNMS was measured via retrospective self-report during pregnancy and 3-5days after birth. Postnatal maternal stress was measured at offspring age 5. Objective PNMS was associated with elevated asthma risk at age 5 (OR 1.21, 95% CI 1.00, 1.45, p = 0.05), albeit not above concurrent postnatal stress. Sex moderated the association between PNMS and asthma at age 15, controlling for postnatal stress. Sex stratified analyses revealed a positive association between objective PNMS and age 15 asthma in females, but not males. Results provide evidence that PNMS may impact asthma outcomes in adolescence.

Larger Amygdala Volume Mediates the Association Between Prenatal Maternal Stress and Higher Levels of Externalizing Behaviors: Sex Specific Effects in Project Ice Storm.

Introduction: The amygdala is a brain structure involved in emotional regulation. Studies have shown that larger amygdala volumes are associated with behavioral disorders. Prenatal maternal depression is associated with structural changes in the amygdala, which in turn, is predictive of an increase in behavioral problems. Girls may be particularly vulnerable. However, it is not known whether disaster-related prenatal maternal stress (PNMS), or which aspect of the maternal stress experience (i.e., objective hardship, subjective distress, and cognitive appraisal), influences amygdala volumes. Nor is it known whether amygdala volumes mediate the effect of PNMS on behavioral problems in girls and boys.Aims: To assess whether aspects of PNMS are associated with amygdala volume, to determine whether timing of exposure moderates the effect, and to test whether amygdala volume mediates the association between PNMS and internalizing and externalizing problems in 11½ year old children exposed in utero, to varying levels of disaster-related PNMS.Methods: Bilateral amygdala volumes (AGV) and total brain volume (TBV) were acquired using magnetic resonance imaging, from 35 boys and 33 girls whose mothers were pregnant during the January 1998 Quebec Ice Storm. The mothers' disaster-related stress was assessed in June 1998. Child internalizing and externalizing problems were assessed at 11½ years using the Child Behavior Checklist (CBCL). Hierarchical regression analyses and mediation analyses were conducted on boys and girls separately, controlling for perinatal and postnatal factors.Results: In boys, subjective distress was associated with larger right AGV/TBV when mothers where exposed during late pregnancy, which in turn explained higher levels of externalizing behavior. However, when adjusting for postnatal factors, the effect was no longer significant. In girls, later gestational exposure to the ice storm was associated with larger AGV/TBV, but here, higher levels of objective PNMS were associated with more externalizing problems, which was, in part, mediated by larger AGV/TBV. No effects were detected on internalizing behaviors.Conclusion: These results suggest that the effects of PNMS on amygdala development and externalizing symptoms, as assessed in boys and girls in early adolescence, can be influenced by the timing of the stress in pregnancy, and the particular aspect of the mother's stress experience.

DNA methylation mediates the effect of exposure to prenatal maternal stress on cytokine production in children at age 13½ years: Project Ice Storm.

BackgroundPrenatal maternal stress (PNMS) is an important programming factor of postnatal immunity. We tested here the hypothesis that DNA methylation of genes in the NF-κB signaling pathway in T cells mediates the effect of objective PNMS on Th1 and Th2 cytokine production in blood from 13½ year olds who were exposed in utero to the 1998 Quebec ice storm.ResultsBootstrapping analyses were performed with 47 CpGs across a selection of 20 genes for Th1-type cytokines (IFN-γ and IL-2) and Th2-type cytokines (IL-4 and IL-13). Six CpGs in six different NF-κB signaling genes (PIK3CD, PIK3R2, NFKBIA, TRAF5, TNFRSF1B, and LTBR) remained as significant negative mediators of objective PNMS on IFN-γ secretion after correcting for multiple comparisons. However, no mediation effects on IL-2, IL-4 and IL-13 survived Bonferroni correction.ConclusionsThe present study provides preliminary evidence supporting the mediating role of DNA methylation in the association between objective aspects of PNMS and child immune states, favoring a Th2 shift.Electronic supplementary materialThe online version of this article (doi:10.1186/s13148-016-0219-0) contains supplementary material, which is available to authorized users.

DNA methylation mediates the impact of exposure to prenatal maternal stress on BMI and central adiposity in children at age 13½ years: Project Ice Storm

Prenatal maternal stress (PNMS) in animals and humans predicts obesity and metabolic dysfunction in the offspring. Epigenetic modification of gene function is considered one possible mechanism by which PNMS results in poor outcomes in offspring. Our goal was to determine the role of maternal objective exposure and subjective distress on child BMI and central adiposity at 13½ years of age, and to test the hypothesis that DNA methylation mediates the effect of PNMS on growth. Mothers were pregnant during the January 1998 Quebec ice storm. We assessed their objective exposure and subjective distress in June 1998. At age 13½ their children were weighed and measured (n = 66); a subsample provided blood samples for epigenetic studies (n = 31). Objective and subjective PNMS correlated with central adiposity (waist-to-height ratio); only objective PNMS predicted body mass index (BMI). Bootstrapping analyses showed that the methylation level of genes from established Type-1 and -2 diabetes mellitus pathways showed significant mediation of the effect of objective PNMS on both central adiposity and BMI. However, the negative mediating effects indicate that, although greater objective PNMS predicts greater BMI and adiposity, this effect is dampened by the effects of objective PNMS on DNA methylation, suggesting a protective role of the selected genes from Type-1 and -2 diabetes mellitus pathways. We provide data supporting that DNA methylation is a potential mechanism involved in the long-term adaptation and programming of the genome in response to early adverse environmental factors.

Pregnant women's cognitive appraisal of a natural disaster affects DNA methylation in their children 13 years later: Project Ice Storm.

Prenatal maternal stress (PNMS) can impact a variety of outcomes in the offspring throughout childhood and persisting into adulthood as shown in human and animal studies. Many of the effects of PNMS on offspring outcomes likely reflect the effects of epigenetic changes, such as DNA methylation, to the fetal genome. However, no animal or human research can determine the extent to which the effects of PNMS on DNA methylation in human offspring is the result of the objective severity of the stressor to the pregnant mother, or her negative appraisal of the stressor or her resulting degree of negative stress. We examined the genome-wide DNA methylation profile in T cells from 34 adolescents whose mothers had rated the 1998 Québec ice storm's consequences as positive or negative (that is, cognitive appraisal). The methylation levels of 2872 CGs differed significantly between adolescents in the positive and negative maternal cognitive appraisal groups. These CGs are affiliated with 1564 different genes and with 408 different biological pathways, which are prominently featured in immune function. Importantly, there was a significant overlap in the differentially methylated CGs or genes and biological pathways that are associated with cognitive appraisal and those associated with objective PNMS as we reported previously. Our study suggests that pregnant women's cognitive appraisals of an independent stressor may have widespread effects on DNA methylation across the entire genome of their unborn children, detectable during adolescence. Therefore, cognitive appraisals could be an important predictor variable to explore in PNMS research.

Prenatal maternal stress predicts autism traits in 6½ year-old children: Project Ice Storm

Research implicates prenatal maternal stress (PNMS) as a risk factor for neurodevelopmental disorders; however few studies report PNMS effects on autism risk in offspring. We examined, prospectively, the degree to which objective and subjective elements of PNMS explained variance in autism-like traits among offspring, and tested moderating effects of sex and PNMS timing in utero. Subjects were 89 (46F/43M) children who were in utero during the 1998 Quebec Ice Storm. Soon after the storm, mothers completed questionnaires on objective exposure and subjective distress, and completed the Autism Spectrum Screening Questionnaire (ASSQ) for their children at age 6½. ASSQ scores were higher among boys than girls. Greater objective and subjective PNMS predicted higher ASSQ independent of potential confounds. An objective-by-subjective interaction suggested that when subjective PNMS was high, objective PNMS had little effect; whereas when subjective PNMS was low, objective PNMS strongly affected ASSQ scores. A timing-by-objective stress interaction suggested objective stress significantly affected ASSQ in first-trimester exposed children, though less so with later exposure. The final regression explained 43% of variance in ASSQ scores; the main effect of sex and the sex-by-PNMS interactions were not significant. Findings may help elucidate neurodevelopmental origins of non-clinical autism-like traits from a dimensional perspective.

Prenatal exposure to a natural disaster increases risk for obesity in 5½-year-old children

An adverse environment in utero, including exposure to prenatal maternal stress (PNMS), can result in poor birth outcomes such as low birth weight, which increases risk of later cardiometabolic diseases such as hypertension and obesity. It is unclear to what extent PNMS influences obesity risk independent of its impact on birth characteristics, especially among humans. Our objective was to determine whether PNMS resulting from a natural disaster influenced risk of childhood obesity. Eight children with high objective PNMS exposure (14.5%) were obese compared to one child (1.8%) with low exposure (P = 0.02). Objective PNMS increased obesity risk (model 1, P = 0.02, odds ratio = 1.37) after controlling for other potential risk factors. Results suggest that PNMS might be an independent risk factor in the development of childhood obesity. Participants included 111 women who were pregnant during the January 1998 Québec Ice Storm or who conceived within the following 3 months and their children. We tested associations between objective and subjective PNMS from the storm and childhood obesity status at age 5½, controlling for children's birth characteristics and breastfeeding status; household socioeconomic status; maternal obstetric complications, life events and smoking during pregnancy, psychological functioning, and height (model 1, n = 111) or BMI (for a subset of 69 participants, model 2).

Disaster-related prenatal maternal stress influences birth outcomes: Project Ice Storm

BackgroundPrevious research suggests that prenatal maternal stress (PNMS) impacts birth outcomes, but many human studies cannot distinguish between the effects of different types of stressors or examine effects of exposure timing on outcomes. ObjectivesOur goal was to determine how timing and severity of exposure during pregnancy to objective and subjective stress due to a natural disaster influenced gestation length and fetal growth patterns. MethodsWe assessed objective and subjective PNMS levels among 172 women exposed to an ice storm during or shortly before pregnancy. We analyzed associations between PNMS levels and outcomes (gestation length, birth weight, birth length, head circumference, and growth ratios), controlling for other variables such as age, obstetric complications, socioeconomic status, and trait anxiety. ResultsGestation lengths and predicted birth weights were shorter among participants exposed to the ice storm during early to mid pregnancy, compared to 3rd trimester and pre-pregnancy exposure. Birth lengths were shorter in the sample compared to population references, and predicted values were shorter among participants with a “discrepancy” between their objective and subjective PNMS levels. High objective PNMS levels predicted smaller head circumferences in early pregnancy, but we also observed patterns in predicted values of head circumference to birth length ratios suggesting the sparing of brain development relative to birth length among boys in early pregnancy. These sparing effects decreased in later pregnancy. ConclusionsExposure to stressful events during pregnancy influences birth outcomes independently of other factors. Exposure timing, newborn sex, and the type of stressor influence the effects observed.

Functional Play at 2 Years of Age: Effects of Prenatal Maternal Stress.

Toddler toy play evolves in a predictable manner and provides a valid, nonverbal measure of cognitive function unbiased by social behaviors. Research on prenatal maternal stress (PNMS) indicates that exposure to stress in utero results in developmental deficits. We hypothesized that children exposed to high objective PNMS from a natural disaster early in pregnancy would exhibit higher rates of stereotypical play and lower rates of mature functional play than their low-stress counterparts would. We examined the functional play abilities of 52 2-year-olds exposed to low or high objective PNMS from a natural disaster within a nonstructured play session. Toddlers exposed to high objective PNMS, subjective PNMS, or both exhibited less functional and more stereotypical toy play, with less diversity, compared to toddlers exposed to low PNMS. PNMS appears to affect functional play development in toddlers negatively. These results replicate delays in language and intellectual functioning observed in these toddlers using the Bayley Scales.