Pregnancy-related hemodynamic biomarkers in relation to trimester-specific maternal per - and polyfluoroalkyl substances exposures and adverse birth outcomes

Abstract

The fate of environmental chemicals in maternal and fetal tissues might be affected by pregnancy-related hemodynamic changes that occur across gestation. Specifically, hemodilution and renal function are hypothesized to confound associations between per- and polyfluoroalkyl substances (PFAS) exposure measures in late pregnancy with gestational length and fetal growth. We sought to analyze two pregnancy-related hemodynamic biomarkers, creatinine and estimated glomerular filtration rate (eGFR), as confounders of the trimester-specific relationships between maternal serum PFAS concentrations and adverse birth outcomes. Participants were enrolled in the Atlanta African American Maternal-Child Cohort between 2014 and 2020. Biospecimens were collected at up to two timepoints, which were categorized into the 1st trimester (N = 278; 11 mean weeks gestation), 2nd trimester (N = 162; 24 mean weeks gestation), and 3rd trimester (N = 110; 29 mean weeks gestation). We quantified six PFAS in serum, creatinine in serum and urine, and eGFR using the Cockroft-Gault equation. Multivariable regression models estimated the associations between single PFAS and their sum with gestational age at delivery (weeks), preterm birth (PTB, <37 gestational weeks), birthweight z-scores, and small for gestational age (SGA). Primary models were adjusted for sociodemographics. We additionally adjusted for serum creatinine, urinary creatinine, or eGFR in the confounding assessments. An interquartile range increase in perfluorooctanoic acid (PFOA) produced a non-significant reduction in birthweight z-score during the 1st and 2nd trimesters (β = -0.01 g [95% CI = -0.14, 0.12] and β = -0.07 g [95% CI = -0.19, 0.06], respectively) whereas the relationship was significant and positive during the 3rd trimester (β = 0.15 g; 95% CI = 0.01, 0.29). Trimester-specific effects were similar for the other PFAS and adverse birth outcomes, which persisted after adjusting for creatinine or eGFR. The relationships between prenatal PFAS exposure and adverse birth outcomes were not strongly confounded by renal function or hemodilution. However, 3rd trimester samples consistently exhibited different effects than those collected during the 1st and 2nd trimesters.

Keywords: Adverse birth outcomes; Confounding; Hemodynamics; Maternal and child health; PFAS; Pregnancy.