Associations of maternal bisphenol urine concentrations during pregnancy with neonatal metabolomic profiles

Sophia M Blaauwendraad,Leonardo Trasande,Romy Gaillard,Chalana M Sol,Susana Santos,Engy Shokry,Ellis Voerman,Vincent W V Jaddoe,Berthold Koletzko,Linda Marchioro,George J G Ruijter,Kurunthachalam Kannan

doi:10.1007/s11306-021-01836-w

Sophia M Blaauwendraad, Leonardo Trasande + Show 10 more

Open Access

https://doi.org/10.1007/s11306-021-01836-w

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Abstract

BackgroundFetal 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.MethodsIn 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.ResultsNo 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.DiscussionHigher 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.

Highlights

The plastic monomers and plasticizers bisphenol A (BPA), bisphenol F (BPF) and bisphenol S (BPS) are among the most produced chemical compounds worldwide and are widely used in the production of common consumer goods such as plastic bottles, food can coatings and thermal paper products (Hormann et al, 2014; Liao & Kannan, 2014; Liao et al, 2012; Vandenberg et al, 2010)
Children without cord blood sampling for metabolomics showed no important differences compared to children with cord blood sampling for metabolomics (Supplementary Table S8)
The strongest associations were present for maternal third trimester bisphenol F and S exposure with phosphatidylcholine, sphingomyelins and acyl-carnitines

Summary

Introduction

The plastic monomers and plasticizers bisphenol A (BPA), bisphenol F (BPF) and bisphenol S (BPS) are among the most produced chemical compounds worldwide and are widely used in the production of common consumer goods such as plastic bottles, food can coatings and thermal paper products (Hormann et al, 2014; Liao & Kannan, 2014; Liao et al, 2012; Vandenberg et al, 2010). Higher maternal exposure to BPA and to a lesser extent BPF and BPS may be associated with a higher childhood body mass index (BMI), waist circumference, blood pressure, and risk of overweight, findings across studies are inconsistent (Harley et al, 2013; Lee et al, 2008, 2014; Philippat et al, 2014; Sol et al, 2020; Valvi et al, 2013) The mechanisms underlying these associations of bisphenol exposure with adverse birth outcomes and adverse cardio-metabolic profiles in later life are not well-known but may involve alterations in metabolism. 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

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