Independent and Combined Effects of Prenatal Alcohol Exposure and Prenatal Stress on Fetal HPA Axis Development.

Prenatal alcohol exposure (PAE) and prenatal stress (PS) are highly prevalent conditions known to affect fetal programming of the hypothalamic-pituitary-adrenal (HPA) axis. The objectives of this study were to assess the effect of light PAE, PS, and PAE-PS interaction on fetal HPA axis activity assessed via placental and umbilical cord blood biomarkers. Participants of the ENRICH-2 cohort were recruited during the second trimester and classified into the PAE and unexposed control groups. PS was assessed by the Perceived Stress Scale. Placental tissue was collected promptly after delivery; gene and protein analysis for 11ß-HSD1, 11ß-HSD2, and pCRH were conducted by qPCR and ELISA, respectively. Umbilical cord blood was analyzed for cortisone and cortisol. Pearson correlation and multivariable linear regression examined the association of PAE and PS with HPA axis biomarkers. Mean alcohol consumption in the PAE group was ~2 drinks/week. Higher PS was observed in the PAE group (p < 0.01). In multivariable modeling, PS was associated with pCRH gene expression (ß = 0.006, p < 0.01), while PAE was associated with 11ß-HSD2 protein expression (ß = 0.56, p < 0.01). A significant alcohol-by-stress interaction was observed with respect to 11ß-HSD2 protein expression (p < 0.01). Results indicate that PAE and PS may independently and in combination affect fetal programming of the HPA axis.

Dose-response effect of prenatal alcohol exposure on perinatal outcomes.

BACKGROUND: A better understanding of the effects of lower levels of prenatal alcohol exposure (PAE), as a common exposure, is needed. The goal of this study was to examine the effects of mild-moderate PAE and episodic binge drinking on perinatal outcomes. METHODS: The data were obtained from three prospective cohorts with a combined sample of 281 participants: 125 with PAE and 156 without PAE. Alcohol-related measures included the Alcohol Use Disorders Identification Test, timeline follow-back questionnaires (covering the periconceptional period, mid-gestation, and late gestation), and biomarkers. Absolute alcohol per day (AAD) and per drinking day (AADD), number of binge episodes, and maximum number of drinks in a 24-h period were estimated. Perinatal outcomes included gestational age and anthropometric measures. Data were analyzed using correlation and multivariable regression analysis. RESULTS: Among women with PAE, average alcohol consumption across the periconceptional period and pregnancy was 0.37 oz ± 0.74 AA/day (~5 drinks/week). After adjusting for tobacco co-exposure and sociodemographic characteristics, significant associations between all alcohol measures and gestational age at delivery were observed, including cumulative measures of AAD (ß = -0.58; 95% CI: -0.98; -0.17) and AADD (ß = -0.58; 95% CI: -0.90; -0.26) during pregnancy and the periconceptional period. A significant association between the maximum number of drinks in a 24-h period and birth length percentile (ß = -0.70; 95% CI: -1.36; -0.04) was observed in the final model. PAE was associated with lower birth weight percentile in univariate analyses only. CONCLUSIONS: Results of this study demonstrate a negative association between mild-moderate PAE and episodic binge drinking with gestational age at delivery and birth length percentile after controlling for other factors. Robust negative effects of PAE, including in the periconceptional period before pregnancy recognition, on duration of gestation highlight the need for primary prevention efforts aimed at PAE in persons of reproductive age.