Background: Fetal exposure to bisphenols is associated with altered fetal growth, adverse birth outcomes and childhood cardio-metabolic risk factors. Metabolomics may serve as a tool to identify the mechanisms underlying these associations. We examined the associations of maternal bisphenol urinary concentrations in pregnancy with neonatal metabolite profiles from cord blood. Methods: In a population-based prospective cohort study among 225 mother–child pairs, maternal urinary bisphenol A, S and F concentrations in first, second and third trimester were measured. LC–MS/MS was used to determine neonatal concentrations of amino acids, non-esterified fatty acids (NEFA), phospholipids (PL), and carnitines in cord blood. Results: No associations of maternal total bisphenol concentrations with neonatal metabolite profiles were present. Higher maternal average BPA concentrations were associated with higher neonatal mono-unsaturated alkyl-lysophosphatidylcholine concentrations, whereas higher maternal average BPS was associated with lower neonatal overall and saturated alkyl-lysophosphatidylcholine (p-values < 0.05).Trimester-specific analyses showed that higher maternal BPA, BPS and BPF were associated with alterations in neonatal NEFA, diacyl-phosphatidylcholines, acyl-alkyl-phosphatidylcholines, alkyl-lysophosphatidylcholine, sphingomyelines and acyl-carnitines, with the strongest effects for third trimester maternal bisphenol and neonatal diacyl-phosphatidylcholine, sphingomyeline and acyl-carnitine metabolites (p-values < 0.05). Associations were not explained by maternal socio-demographic and lifestyle characteristics or birth characteristics. Discussion: Higher maternal bisphenol A, F and S concentrations in pregnancy are associated with alterations in neonatal metabolite profile, mainly in NEFA, PL and carnitines concentrations. These findings provide novel insight into potential mechanisms underlying associations of maternal bisphenol exposure during pregnancy with adverse offspring outcomes but need to be replicated among larger, diverse populations.
Bibliographical noteFunding Information:
The Generation R Study is financially supported by the Erasmus Medical Center, Rotterdam, the Erasmus University Rotterdam and the Netherlands Organization for Health Research and Development. VWVJ received a grant from the Netherlands Organization for Health Research and Development (NWO, ZonMw-VIDI 016.136.361) and a European Research Council Consolidator Grant (ERC-2014-CoG-648916). RG received funding from the Dutch Heart Foundation (Grant No. 2017T013), the Dutch Diabetes Foundation (Grant No. 2017.81.002) and the Netherlands Organization for Health Research and Development (ZonMW, Grant No. 543003109). Also, this project has received funding from the European Union’s Horizon 2020 research and innovation program under the ERA-NET Cofund action (No. 727565), European Joint Programming Initiative “A Healthy Diet for a Healthy Life” (JPI HDHL), EndObesity, ZonMW the Netherlands (No. 529051026), and from the European Union’s Horizon 2020 research and innovation program under grant agreement 874583 (ATHLETE project). The metabolomic analyses were financially supported in part by the European Research Council Advanced Grant META-GROWTH ERC-2012-AdG–no.322605, the European Joint Programming Initiative Project NutriPROGRAM, the German Ministry of Education and Research, Berlin (Grant No. 01 GI 0825), and the German Research Council (INST 409/224-1 FUGG). The bisphenol analyses were financially supported by the National Institutes of Health, USA (Grant Nos. R01ES022972 and R01ES029779). The content is solely the responsibility of the authors and does not represent the official views of the National Institutes of Health.
© 2021, The Author(s).