Prenatal Phthalate Exposure and Child Weight and Adiposity from in Utero to 6 Years of Age.

BACKGROUND: Prenatal phthalate exposure has been associated with lower birth weight but also higher weight in childhood. Few studies have examined weight or adiposity from birth to childhood and thus cannot assess growth trajectories associated with exposure. OBJECTIVE: We assessed associations between maternal phthalate exposures in pregnancy and child weight and adiposity measured prenatally through childhood (3-6 years of age). METHODS: Within The Infant Development and the Environment Study (TIDES), a prospective pregnancy cohort, we analyzed a panel of phthalate metabolites in urine collected at two visits from early and late gestation (N=780). We estimated average phthalate metabolite associations with child weight z-scores from ∼20wk gestation (estimated by ultrasound), birth, and 1, 3, 4, and 6 years of age using linear mixed-effects (LME) models. We also modeled associations with adiposity z-scores from birth (weight for length) and 1, 3, 4, and 6 years of age [body mass index (BMI)] using LME models. RESULTS: For weight, we observed inverse associations between several phthalate metabolites and birth weight z-scores, but no associations were observed with postnatal weight z-scores in LME models. Regarding adiposity, we observed inverse associations between phthalate metabolites and weight-for-length z-scores at birth, but positive associations were observed with BMI z-scores at 3-4 years of age in LME models. For example, mono-ethyl phthalate was associated with a 0.17-unit decrease in birth weight-for-length z-score [95% confidence interval (CI): -0.29, -0.05] and a 0.18-unit increase in 4-years-of-age BMI z-score (95% CI: 0.04, 0.32). DISCUSSION: We observed associations between prenatal exposure to phthalates and lower weight at birth but not at childhood follow-up visits. However, for adiposity, we observed an interesting pattern of association with low adiposity at delivery as well as high adiposity at 3-4 years of age. Although it is not clear from our results whether these associations occur within the same children, such a pattern of adiposity in early life has been linked to cardiometabolic disease in adulthood and deserves special attention as an outcome in the study of prenatal exposures in the developmental origins of health and disease. https://doi.org/10.1289/EHP10077.

Distinguishing gene flow between malaria parasite populations.

Measuring gene flow between malaria parasite populations in different geographic locations can provide strategic information for malaria control interventions. Multiple important questions pertaining to the design of such studies remain unanswered, limiting efforts to operationalize genomic surveillance tools for routine public health use. This report examines the use of population-level summaries of genetic divergence (FST) and relatedness (identity-by-descent) to distinguish levels of gene flow between malaria populations, focused on field-relevant questions about data size, sampling, and interpretability of observations from genomic surveillance studies. To do this, we use P. falciparum whole genome sequence data and simulated sequence data approximating malaria populations evolving under different current and historical epidemiological conditions. We employ mobile-phone associated mobility data to estimate parasite migration rates over different spatial scales and use this to inform our analysis. This analysis underscores the complementary nature of divergence- and relatedness-based metrics for distinguishing gene flow over different temporal and spatial scales and characterizes the data requirements for using these metrics in different contexts. Our results have implications for the design and implementation of malaria genomic surveillance studies.

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

CONTEXT: 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. OBJECTIVE: Determine the association between prenatal oxidative stress biomarkers and child weight and body mass index (BMI) z-scores from birth to age 6. 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 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 in 8-iso-PGF2α was associated with 0.17 SD higher weight at age 4 (95% CI 0.01, 0.33). These biomarkers were also associated with higher BMI at age 4. Finally, within 4 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 than children in the normal group. CONCLUSION: 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.

Traditional African remedies induce hemolysis in a glucose-6-phopshate dehydrogenase deficient zebrafish model.

Traditional remedies are widely used throughout Africa in routine care for infants. However, such remedies could have detrimental effects. Acute bilirubin encephalopathy (ABE) and kernicterus spectrum disorder (KSD) are common newborn health conditions in the developing world, contributing to substantial neonatal mortality and morbidity. They frequently occur in children with glucose-6-phopshate dehydrogenase (G6PD) deficiency. Using our established zebrafish model of G6PD deficiency, we tested the effects of three traditional compounds used in the care of the newborn umbilical cord: eucalyptus oil, methylated spirits, and Yoruba herbal tea. We found that eucalyptus oil induced a 13.4% increase in a hemolytic phenotype versus control, while methylated spirits showed a 39.7% increase in affected phenotype. Yoruba herbal tea exposure showed no effect. While methylated spirits are already a known pro-oxidant, these data indicate that eucalyptus oil may also be a hemolytic trigger in those with G6PD deficiency. Discovering which agents may contribute to the pathophysiology of G6PD deficiency is critical to eliminate ABE and KSD, especially in countries with a high prevalence of G6PD deficiency. The next step in elucidating the role of these agents is to determine the clinical correlation between the use of these agents and ABE/KSD.