Maternal Oxidative Stress Biomarkers in Pregnancy and Child Growth from Birth to Age 6

Abstract

Background Maternal oxidative stress in pregnancy can arise through a multitude of sources and may have lifelong consequences for the child. Animal studies suggest that prenatal oxidative stress may contribute to metabolic dysfunction and excessive weight gain in the offspring. However, this relationship has been studied minimally in humans. Methods Within The Infant Development and the Environment Study (TIDES) prospective pregnancy cohort, we calculated age- and sex-specific Z-scores for child weight and body mass index (BMI), measured between birth and age 6 (N=736). Three oxidative stress biomarkers were quantified in third trimester urine, including 8-iso-prostaglandin F2α (8-iso-PGF2α), its primary metabolite, and prostaglandin F2α (PGF2α). We examined associations between each biomarker and Z-scores using linear regression as well as group-based trajectory modeling. Results Prenatal 8-iso-PGF2α and its metabolite were associated with lower birth weight and higher weight at age 4. For example, an ln-unit increase 8-iso-PGF2α was associated with 0.17 SD higher weight at age 4 (95% confidence interval [CI]: 0.01, 0.33). These biomarkers were also associated with higher BMI at age 4. Finally, within four unique weight trajectories (low, normal, high, and low-high), children of mothers with higher 8-iso-PGF2α were 2.56 times more likely (95% CI: 1.22, 5.41) to be in the low-high trajectory compared to children in the normal group. Conclusions We observed associations between third trimester oxidative stress and lower birth weight as well as higher early childhood weight and BMI. These findings have important implications for understanding the developmental origins of childhood weight gain and metabolic disease.

Environmental Nanoparticles Reach Human Fetal Brains

“…The vulnerability of the brain is key, essentially because there is no question that a number of chemicals, and certainly NPs, can interfere with the highly precise neurodevelopmental processes taking place in intrauterine life [ 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 24 , 25 , 26 , 27 , 45 , 46 , 47 , 48 , 91 , 96 ]. Of critical importance is the relationship between intrauterine toxic exposures and risk for major neurological, psychiatric, and cardiovascular diseases, a subject discussed for a number of years since the pioneering work of Barker [ 19 ] and 21 century researchers discussing fetal and perinatal programming and neuropsychiatric, metabolic, and cardiovascular diseases [ 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 ].…”

“…NP (used here interchangeably with UFPM) size, shape, charge, surface composition, coating with biocompatible molecules, corona formation, and, certainly, stage of embryonic/fetus/placental maturation are key factors impacting free radical oxidative stress, inflammation, restricted placental growth, and the activation of placental toll-like receptors (TLRs), to name a few [ 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 ]. There is a deep concern regarding uterine environmental exposures, the developmental origins of disease, and the fetal programming model predicting lifelong consequences from early intrauterine and/or postnatal exposures to insults significant in length, cumulative doses, and properties favoring specific cell damage [ 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 ]. Experimentally, NPs cause fetal developmental toxicity, and the early stages of brain organogenesis are highly vulnerable to reactive oxygen species (ROS); ultrastructural alterations in mitochondria, endoplasmic reticulum (ER), and Golgi complexes; downregulation of neuronal glutamate transporters; and, ultimately, the impairment of cognition and alterations in animal behavior [ 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 ].…”

“…There is a deep concern regarding uterine environmental exposures, the developmental origins of disease, and the fetal programming model predicting lifelong consequences from early intrauterine and/or postnatal exposures to insults significant in length, cumulative doses, and properties favoring specific cell damage [ 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 ]. Experimentally, NPs cause fetal developmental toxicity, and the early stages of brain organogenesis are highly vulnerable to reactive oxygen species (ROS); ultrastructural alterations in mitochondria, endoplasmic reticulum (ER), and Golgi complexes; downregulation of neuronal glutamate transporters; and, ultimately, the impairment of cognition and alterations in animal behavior [ 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 ]. The early development of the radial microvasculature in the telencephalon cortical plate (CP) and the correct micro vessel formation are the basis for the later perivascular glia coverage formation and endothelial barrier maturation critical for setting up the brain–blood barrier (BBB) [ 31 , 32 , 33 , 34 ].…”

Umbilical Cord Blood Metal Mixtures and Birth Size in Bangladeshi Children

“…Another animal study found that fetal weight, crown-rump length, and placental growth (weight and diameter) were decreased in Cd-treated mice (Wang et al 2016). In humans, maternal oxidative stress during pregnancy has been associated with lower birth weight (Arogbokun et al 2021). During pregnancy, Cd accumulates in the placenta which may impair placental function to transfer oxygen, nutrients, and waste (Esteban-Vasallo et al 2012;Geng and Wang 2019).…”

“…2016 ). In humans, maternal oxidative stress during pregnancy has been associated with lower birth weight ( Arogbokun et al. 2021 ).…”