Prenatal bisphenol A exposure is associated with language development but not with ADHD-related behavior in toddlers from the Odense Child Cohort
Introduction
Bisphenol A (BPA) is a non-persistent chemical produced in very large quantities worldwide to make polycarbonate plastics and epoxy resins. It is widely used in a variety of consumer products including some food and beverage storage plastic containers, food can linings, thermal paper receipts, medical equipment, dental sealants, and children's toys, clothes among other applications (Vandenberg et al., 2007, Xue et al., 2017). The primary source of exposure to BPA is through the diet and BPA has been detected in urine samples of 95% of the general population in the US and Europe (LaKind and Naiman, 2015, Vandenberg et al., 2007). BPA has weak estrogenic properties and has been recently recognized as a suspected agent causing developmental neurotoxicity (Grandjean and Landrigan, 2014).
The fetal brain may be particularly sensitive to endocrine disrupting effects of BPA due to its rapid growth and complexity, and exposure occurring during this vulnerable time window can have a lifelong health impact (Schug et al., 2011, Schug et al., 2015). A number of epidemiologic studies have reported associations between maternal urinary BPA concentrations at different time points during gestation and child behavior, including more symptoms of hyperactivity, aggression and anxiety, especially in boys (Braun et al., 2009, Braun et al., 2011, Casas et al., 2015, Evans et al., 2014, Harley et al., 2013, Hong et al., 2013, Maserejian, 2014, Perera et al., 2016, Perez-Lobato et al., 2016, Philippat et al., 2017, Roen et al., 2015). Only one study did not find association in boys but found increased externalizing behavior in girls (Braun et al., 2011). Few studies have assessed neuropsychological outcomes and most have reported no associations (Braun et al., 2017b, Casas et al., 2015, Nakiwala et al., 2018, Stacy et al., 2017). However, these studies are characterized by differences in the exposure assessment (urine or dental composite), the time window of exposure (pre- or postnatal), the sex-specific directions of the associations, the specific behavioral domain tested and/or the sociodemographic characteristics of the populations (Mustieles et al., 2015). Importantly, the relationship between BPA exposure and language development as an independent outcome and not a part of IQ assessment has not been previously addressed. In a previous study among 518 mother-child pairs from the Odense Child Cohort, we found associations between higher maternal phthalate exposure and poorer language development in 20–36 months old boys, whereas no association was found in girls (Olesen et al., 2018). We therefore wanted to explore if this association was also found for prenatal BPA exposure.
Given the importance of language development for the prediction of future educational success and neuropsychological health (Bleses et al., 2016, Elbro et al., 2011), and that the relationship between BPA exposure and children’s neurobehavior is in the spotlight (Mustieles et al., 2018), we aimed to assess whether maternal urinary BPA concentration during pregnancy was associated with language development and attention-deficit and hyperactivity disorder (ADHD) symptoms in toddlers aged 18–36 months among mother-child pairs from the Odense Child Cohort.
Section snippets
Study population
All pregnant women living in the Municipality of Odense from 2010 to 2012 were invited to participate in the prospective Odense Child Cohort (OCC) at a voluntary information meeting introducing the ultrasound examinations at Odense University Hospital or at their first antenatal visit at gestational week 8–16 (Kyhl et al., 2015). A total of 2874 pregnant women were recruited and 2490 families are still participating in 2018. The non-participants were on average younger, more often smokers and
Characteristics of the study population
A total of 2217 singletons of Caucasian origin are still enrolled in the cohort. Of these, 796 had BPA measured in maternal urine, 1360 responded to the MB-CDI subscales and 1707 responded to the CBCL-ADHD subscale (Fig. 1). The women with and without BPA measurements did not differ according to age, parity or gestational age at birth. However, the women with BPA measurements had higher BMI and less often smoked (data not shown). Responders of the MB-CDI did not differ from non-responders
Discussion
In the present study of mother-child pairs from the Odense Child Cohort, higher prenatal exposure to BPA was significantly associated with a higher risk of a language development score below the 15th percentile for vocabulary (number of words or lexicon) and complexity (morphosyntax) among toddler boys, but not among girls, as measured by the two corresponding subscales in the Danish MB-CDI parent report. Since we previously found associations between certain phthalate metabolites and language
Conclusions
In this study of 535 mother-child pairs from the Odense Child Cohort, higher prenatal BPA concentrations were significantly and positively associated with a higher risk of poorer language skills among toddler boys, but not girls, suggesting a possible sex-specific effect of BPA on early language development. No evidence of a deleterious effect of prenatal BPA exposure on the risk of ADHD symptoms was observed. To the best of our knowledge, this is the first study that has addressed the
Acknowledgments
The families in OCC are acknowledged for their participation and commitment to the study. The technicians at Hans Christian Andersen's Children's Hospital and at the Department Growth and Reproduction are acknowledged for their careful examination of the children and analysis of bisphenol A.
Funding sources
This work was supported by the Danish Center for Hormone Disrupting Chemicals, the Danish Council for Independent Research, medical sciences (4004-00352B_FSS and), Odense University Hospital and Region of Southern Denmark, Municipality of Odense, the Mental Health Service of the Region of Southern Denmark, Odense University Hospital Research Foundation and Odense Patient data Explorative Network (OPEN), the Novo Nordisk Foundation (Grant no. NNF15OC00017734 and NNF17OC0029404), Helsefonden and
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