Background: Several studies have investigated the possible association between prenatal exposure to perfluoroalkyl substances (PFASs) and birth anthropometry. However, none has assessed fetal size longitudinally. We studied the possible association between PFASs and fetal biometry. Methods: In 1230 mother-child pairs of three cohorts from the Spanish INMA-Project, we analyzed perfluorohexanesulfonic acid (PFHxS), perfluorooctanesulfonic acid (PFOS), perfluorooctanoic acid (PFOA), and perfluorononanoic acid (PFNA) in first-trimester maternal plasma (collection: 2003-2008). We measured abdominal circumference (AC), femur length (FL), biparietal diameter (BPD), and estimated fetal weight (EFW) by ultrasounds at 12, 20, and 34 gestational weeks. We conducted multivariable linear regression analyses between log2-transformed (PFASs) and SD-scores of fetal parameters in each cohort and subsequent meta-analysis. We also assessed effect modification by sex and maternal smoking. Results: PFHxS, PFOA, PFOS, and PFNA medians were: 0.58, 2.35, 6.05, and 0.65 ng/mL, respectively. There were no associations for the whole population in any trimester of pregnancy. However, we found an indication that maternal smoking modified the effect in different directions depending on the PFAS. Among smokers (31%), we found negative associations between both PFOA and PFNA and FL or EFW at week 20 (% change ranging between -6.8% and -5.7% per twofold PFAS increase) and positive associations between PFHxS or PFOS and BPD at week 34 (6.8% and 6.3%, respectively). Conclusions: Results did not suggest an overall association between prenatal PFASs and fetal growth. The results among smokers should be taken with caution and further studies are warranted to elucidate the possible role of smoking in this association.

This work was supported by grants from the European Union [FP7-ENV-2011 cod 282957 and HEALTH.2010.2.4.5-1] and from Spain: Instituto de Salud Carlos III [Red INMA G03/176, CB06/02/0041, FIS-FEDER: PI03/1615, PI041436, PI04/1509, PI04/1112, PI04/1931, PI05/1079, PI05/1052, PI06/0867, PI06/1213, PI07/0314, PI081151, PI09/02647, PI09/00090, PI11/01007, PI11/02591, PI11/02038, PI12/01890, PI13/1944, PI13/2032, PI14/00891, PI14/01687, PI16/1288, and PI17/00663; Miguel Servet-FEDER CP11/0178, Miguel Servet-FSE: MS16/00128, and MSII16/00051; and PFIS-FI14/00099]; Alicia Koplowitz Foundation 2017; Generalitat Valenciana [FISABIO-UGP 15-230, 15-244, and 15-249]; Department of Health of the Basque Government [2005111093 and 2009111069]; the Provincial Government of Gipuzkoa [DFG06/004 and DFG08/001]; and the Generalitat de Catalunya-CIRIT [1999SGR 00241].