Gestational PFAS exposure and newborn size: The modifying effect of cord blood fatty acids

Abstract

Per- and polyfluoroalkyl substances (PFASs) can disrupt lipid metabolism, and changes in cord blood fatty acid composition have been observed in small newborns. Emerging evidence suggests that exposure to PFASs during pregnancy is linked to decreased newborn size, although the evidence is not consistent. The modifying effect of fatty acids on the associations of gestational PFAS exposure with newborn size is still unknown. Here we show that the nutritional status of the fetus, as indicated by the level of fatty acids in the cord blood, mitigates the adverse effects of gestational PFAS exposure on the size of the newborn. Our study confirms the adverse developmental effects of PFASs and identifies emerging short-chain PFASs as the primary drivers of reduced newborn size, despite their lower exposure burden compared to legacy PFASs. Additionally, we find the protective role of cord blood fatty acids, suggesting potential strategies for mitigating the detrimental effects of emerging environmental exposures on human health. Our findings provide new evidence of the potential toxicity of emerging PFASs and call for further toxicity evaluations of these pollutants for regulatory purposes. Future studies should consider the complex interaction between exposure and nutrition within the human body, particularly during the first thousand days of life, to promote lifelong health.

Keywords: Fatty acid status; Fetal nutrition; Gestational exposure; Newborn size; Per- and polyfluoroalkyl substance.

Graphical abstract

Fig. 1

Associations between individual PFAS exposure and newborn size parameters, including weight z-score, length z-score, and weight-for-length-ratio z-score, as determined by linear regression (left) and restricted cubic spline regression (right). Results were adjusted for maternal age, birthweight category (<2500 g; ≥2500, <4000 g; ≥4000 g), maternal pre-pregnancy body mass index, gestational weight gain, sex of newborn, and gestational age at birth. Red text highlight refers to statistically significant associations identified. Please refer to Table S3 (Supplementary Materials) in the supplementary material for detailed information regarding estimates, 95% CI and P-values for both linear and non-linear associations.

Fig. 2

Mixture effect of PFASs with a detection frequency of greater than 60% (n = 16) on the newborn size parameters, including weight z-score, length z-score, and weight-for-length-ratio z-score, as determined by quantile-based computation model. Results were adjusted for maternal age, birthweight category (<2500 g; ≥2500, <4000 g; ≥4000 g), maternal pre-pregnancy body mass index, gestational weight gain, sex of newborn, and gestational age at birth. The asterisk (∗) indicates that the mixed effect of PFAS on newborn size parameters is statistically significant (P < 0.05).

Fig. 3

Mixture effect of PFASs with a detection frequency of greater than 60% (n = 16) on cord blood fatty acids, as determined by quantile-based g-computation model. Results were adjusted for maternal age, birthweight category (<2500 g; ≥2500, <4000 g; ≥4000 g), maternal pre-pregnancy body mass index, gestational weight gain, sex of newborn, and gestational age at birth. The circle size represents the absolute value of β, the color represents the significance level, and the negative weight carried by individual PFASs is shown in the stack plot.

Fig. 4

Associations between individual PFAS exposures and newborn size parameters (weight z-score, length z-score, and weight-for-length-ratio z-score) moderated by cord blood fatty acids, determined by generalized linear regression or restrict cubic spline regression for linear (top half) and non-linear (bottom half) associations, respectively. All models were adjusted for maternal age, birthweight category (<2500 g; ≥2500, <4000 g; ≥4000 g), maternal pre-pregnancy body mass index, gestational weight gain, sex of newborn, and gestational age at birth.