Prenatal Exposure to PFAS and Neuropsychological Development throughout the First 6 Years of Life: The INMA Study, Spain

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Background/Aim: Animal studies indicate that perfluoroalkyl substances (PFAS), including perfluorohexanesulfonic acid (PFHxS), perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), and perfluorononanoic acid (PFNA), may be neurotoxicants. Few birth cohorts have studied possible PFAS effects in child brain development longitudinally. We investigated the association between plasma PFAS concentrations at gestational week 12 and neuropsychological development throughout the first 6 years of life. Methods: The study population was 1,239 mother-child pairs from the Gipuzkoa, Sabadell, and Valencia INMA-cohorts, Spain (recruitment period: 2003-2008). Brain development was assessed using two Bayley scales at age 11-18 months (Cognitive and Motor Scales) and three McCarthy scales at age 4-6.5 years (General Cognitive Index, which is a combination of verbal, perceptual-performance, and quantitative domains, and Gross and Fine Motor Scales). Raw scores were standardized to a mean (SD) of 100(15) for child's age in days at evaluation and the psychologist who administered the test. Multivariate regression analyses between log2-transformed (PFAS) and neuropsychological scores were conducted in each sub-cohort and estimates were then pooled by meta-analysis to account for possible heterogeneity. Linearity was accepted after using generalized additive models. Results: Median concentrations of PFHxS, PFOA, PFOS, and PFNA were: 0.58, 2.36, 6.06, and 0.66 ng/mL, respectively. Inverse significant associations (p≤0.05) were found between PFAS and the Bayley Motor Scale with betas ranging between -1.45 (PFNA) and -1.87 (PFOS) per doubling of PFAS concentrations. Negative associations were also found with the Gross Motor McCarthy Scale, but statistical significance was only reached for PFOA (Beta [95%CI]: -1.22[-2.43, 0.00]). No association was found between PFAS and the Bayley or the McCarthy Cognitive scales. Conclusions: Results suggest a possible effect of prenatal PFAS exposure on psychomotor but not cognitive development during childhood, this being clearer during the 1st-2nd years of life. Funding: ISCIII (FIS-FEDER: PI12/01890, PI13/1944, PI14/00891; PFIS-FI14/00099; Miguel Servet-FEDER: CP11/0178, CPII16/00051); FISABIO (UGP-15-230, UGP-15-249, and UGP-15-244).