Maternal Lifetime Stress and Prenatal Psychological Functioning and Decreased Placental Mitochondrial DNA Copy Number in the PRISM Study.

Psychosocial stress contributes to placental oxidative stress. Mitochondria are vulnerable to oxidative stress, which can lead to changes in mitochondrial DNA copy number (mtDNAcn). We examined associations of maternal lifetime stress, current negative life events, and depressive and posttraumatic-stress-disorder symptom scores with placental mtDNAcn in a racially/ethnically diverse sample (n = 147) from the Programming of Intergenerational Stress Mechanisms (PRISM) study (Massachusetts, March 2011 to August 2012). In linear regression analyses adjusted for maternal age, race/ethnicity, education, prenatal fine particulate matter exposure, prenatal smoking exposure, and the sex of the child, all measures of stress were associated with decreased placental mtDNAcn (all P values < 0.05). Weighted-quantile-sum (WQS) regression showed that higher lifetime stress and depressive symptoms accounted for most of the effect on mtDNAcn (WQS weights: 0.25 and 0.39, respectively). However, among white individuals, increased lifetime stress and posttraumatic stress disorder symptoms explained the majority of the effect (WQS weights: 0.20 and 0.62, respectively) while among nonwhite individuals, lifetime stress and depressive symptoms accounted for most of the effect (WQS weights: 0.27 and 0.55, respectively). These analyses are first to link increased maternal psychosocial stress with reduced placental mtDNAcn and add to literature documenting racial/ethnic differences in the psychological sequelae of chronic stress that may contribute to maternal-fetal health.

Impact of Maternal Lifetime Interpersonal Trauma on Children's Asthma: Mediation Through Maternal Active Asthma During Pregnancy.

OBJECTIVE: Traumatic stressors, including child abuse and/or interpersonal violence over a woman's lifecourse, can affect the health of her children. This study examines the associations between maternal lifetime interpersonal trauma (IPT) and children's asthma by age 6 years (n = 857). METHODS: Pregnant women completed the Revised Conflict Tactics Scale; IPT exposure was categorized as unexposed (55%), early (childhood and/or teen years only, 25%), late (adulthood and/or index pregnancy, 7%), and chronic (early and late, 13%). Clinician-diagnosed asthma in children was reported by mothers at each follow-up visit until the child reached age 6 years. We examined the effects of maternal IPT categories and child's asthma using logistic regression. Using structural equation models, we also examined indirect relationships between maternal chronic IPT and child asthma operating through active asthma in pregnancy, prepregnancy BMI, prenatal smoking, and/or increased exposure to other adverse life events or environmental toxins prenatally. Effect modification by the child's sex was examined. RESULTS: Mothers were primarily Hispanic (55%) or black (30%) with less than high school education (62%). In logistic regression models, chronic maternal IPT (compared with unexposed) was associated with asthma in boys (odds ratio = 2.87, 95% confidence interval = 1.48-5.57) but not girls (odds ratio = 0.69, 95% confidence interval = 0.23-2.12; pinteraction = .042). In structural equation models, chronic IPT was associated with maternal active asthma in pregnancy (ß = 0.59, p < .001), maternal active asthma was associated with children's asthma (ß = 0.20, p = .009), and the total indirect effect for this path was significant (ß = 0.12, p = .031). Associations were most evident among boys. CONCLUSIONS: Mothers' history of chronic IPT was associated with asthma in boys. This association was mediated through active maternal asthma in pregnancy.

Prenatal and postnatal stress and asthma in children: Temporal- and sex-specific associations.

BACKGROUND: Temporal- and sex-specific effects of perinatal stress have not been examined for childhood asthma. OBJECTIVES: We examined associations between prenatal and/or postnatal stress and children's asthma (n = 765) and effect modification by sex in a prospective cohort study. METHODS: Maternal negative life events were ascertained prenatally and postpartum. Negative life event scores were categorized as 0, 1 to 2, 3 to 4, or 5 or greater to assess exposure-response relationships. We examined effects of prenatal and postnatal stress on children's asthma by age 6 years, modeling each as independent predictors, mutually adjusting for prenatal and postnatal stress, and finally considering interactions between prenatal and postnatal stress. Effect modification by sex was examined in stratified analyses and by fitting interaction terms. RESULTS: When considering stress in each period independently, among boys, a dose-response relationship was evident for each level increase on the ordinal scale prenatally (odds ratio [OR], 1.38; 95% CI, 1.06-1.79; P value for trend = .03) and postnatally (OR, 1.53; 95% CI, 1.16-2.01; P value for trend = .001); among girls, only the postnatal trend was significant (OR, 1.60; 95% CI, 1.14-2.22; P value for trend = .005). Higher stress in both the prenatal and postnatal periods was associated with increased odds of receiving a diagnosis of asthma in girls (OR, 1.37; 95% CI, 0.98-1.91; Pinteraction = .07) but not boys (OR, 1.08; 95% CI, 0.82-1.42; Pinteraction = .61). CONCLUSIONS: Although boys were more vulnerable to stress during the prenatal period, girls were more affected by postnatal stress and cumulative stress across both periods in relation to asthma. Understanding sex and temporal differences in response to early-life stress might provide unique insight into the cause and natural history of asthma.

Detection of long non-coding RNAs in human breastmilk extracellular vesicles: Implications for early child development.

Breastmilk has many documented beneficial effects on the developing human infant, but the components of breastmilk that influence these developmental pathways have not been fully elucidated. Increasing evidence suggests that non-coding RNAs encapsulated in extracellular vesicles (EVs) represent an important mechanism of communication between the mother and child. Long non-coding RNAs (lncRNAs) are of particular interest given their key role in gene expression and development. However, it is not known whether breastmilk EVs contain lncRNAs. We used qRT-PCR to determine whether EVs isolated from human breastmilk contain lncRNAs previously reported to be important for developmental processes. We detected 55 of the 87 screened lncRNAs in EVs from the 30 analyzed breastmilk samples, and CRNDE, DANCR, GAS5, SRA1 and ZFAS1 were detected in >90% of the samples. GAS5, SNHG8 and ZFAS1 levels were highly correlated (Spearman's rho > 0.9; P < 0.0001), which may indicate that the loading of these lncRNAs into breastmilk EVs is regulated by the same pathways. The detected lncRNAs are important epigenetic regulators involved in processes such as immune cell regulation and metabolism. They may target a repertoire of recipient cells in offspring and could be essential for child development and health. Further experimental and epidemiological studies are warranted to determine the impact of breastmilk EV-encapsulated lnRNAs in mother to child signaling.