Effects of prenatal oxidative stress levels on fetal programming: Results from the NELA birth cohort

Introduction The Developmental Origins of Health and Diseases (DOHaD) hypothesis states that both the pre- and postnatal environments shape health and disease later in life. Prenatal oxidative stress can have long term health consequences in the offspring through developmental programming, including an increased risk of adiposity; however studies in humans are limited. We aim to investigate the effects of prenatal oxidative stress levels on birth size measures used as proxies of fetal adiposity development. Methods Data come from the Nutrition and Early Life Asthma (NELA) study, a population-based birth cohort set up in 2015 in Spain. Maternal fasting blood samples were drawn at 24 weeks of gestation and newborn cord blood samples were collected at birth to analyze for oxidative stress markers, including protein carbonyl (protein oxidation), hydroperoxides (lipid oxidation), and 8-hydroxy-2’ -deoxyguanosine (DNA oxidation). Maternal and newborn antioxidant status was assessed by glutathione peroxidase, catalase, the trolox equivalent antioxidant capacity (TEAC), and the ferric reducing ability of plasma (FRAP). In addition, vitamin A and E levels were assessed as a measured of exogenous antioxidant markers. In multivariable regression models we assessed the association between maternal and newborn biomarkers with birth size measures including weight and length-derived anthropometric indicators: weight-for-age z score, weight-for-length z score, and BMI-for age z score as proxies of body composition; skinfold thickness as a proxy for subcutaneous adiposity; and length z score, which is considered as a proxy for lean mass. Results Maternal and newborn FRAP, TEAC and protein carbonyl levels were positively correlated (correlation coefficients range 0.45–0.63, P -values  P -value  P -value = 0.053), weight-for-age z-score (coefficient = 0.493, P -value = 0.059), and BMI-for-age z-score (coefficient = 0.625, P -value = 0.045). In addition, higher levels of newborn vitamin A were positively associated with birth weight (coefficient = 0.014, P P -value  P -value  P -value = 0.005). Conclusions Fetal antioxidant capacity and exogenous antioxidant levels (i.e. vitamin A) may influence body composition at birth. These results could help to unravel the link between prenatal oxidative stress with fetal programming and long term health consequences for the offspring. In addition, the results will shed new light on prenatal factors that may perturb maternal and fetal oxidative stress status providing new insights of the biological pathways central to fetal programming.