Associations between urinary biomarkers of oxidative stress in the third trimester of pregnancy and behavioral outcomes in the offspring at 4 years of age

Abstract

Background/Aim: Prenatal oxidative stress has been linked to adverse pregnancy outcomes, including intrauterine growth restriction and preterm birth. However, little is known about neurodevelopmental outcomes following intrauterine oxidative stress exposure. We examined the association of prenatal oxidative stress with behavioral problems and social impairment in children at 4 years of age.Methods: Urinary concentrations of 8-iso-prostaglandin F2α (8-iso-PGF2α), its primary metabolite 2,3-dinor-5,6-dihydro-15-F2T-isoprostane, and prostaglandin F2α (PGF2α) were measured in the third trimester in 512 pregnant women from The Infant Development and Environment Study (TIDES), a multi-center pregnancy cohort study. Behavioral problems and social impairment in the child were assessed using parent-rated Behavioral Symptoms Index (BSI) scores on the Behavior Assessment System for Children (BASC), and total Social Responsiveness Scale (SRS) scores, respectively. For the analysis, we used linear models, stratified by maternal education level, and adjusted for urinary-specific gravity, gestational age at urine collection, BMI, race, and maternal age.Results: Mean BSI and total SRS t-scores were 53.17 (SD=12.85) and 51.7 (SD=8.39), respectively, in less educated mothers (≤high school, n=60), and 48.47 (SD=7.91) and 44.17 (SD=6.24), respectively, in more educated mothers (>high school, n=452). Among less educated mothers, none of the oxidative stress biomarkers were related to BSI or total SRS scores. Among more educated mothers, 8-iso-PGF2α was positively related to BSI (ß=0.03; 95% CI=0.01-0.06) and total SRS (ß=0.02; 95% CI=0.002-0.04) scores. Moreover, 2,3-dinor-5,6-dihydro-15-F2T-isoprostane showed a significant association with higher total SRS scores (ß=0.03, 95% CI=0.001-0.06), while PGF2α showed a significant positive association with BSI scores (ß=0.03; 95% CI=0.01-0.05).Conclusions: In TIDES, associations between biomarkers of oxidative stress and behavioral outcomes were modified by maternal education. In more educated mothers increased levels of oxidative stress during the third trimester of pregnancy were associated with increased behavioral problems and social impairment in the child at 4 years of age.