Mother-infant interaction sets the behavioral foundation and trajectory for infant social/cognitive development. Parental social behaviors are especially vulnerable to endocrine-disrupting chemicals because these behaviors are shaped by hormonal priming and by the organization of the social/parental brain. It is known that in utero bisphenol A (BPA) exposure disturbs neurobehavioral development in animals and in humans. The pathways linking in utero BPA exposure to neurobehavioral development likely involve direct effects in utero, and indirect effects via disruption of postnatal mother-infant interactions. To date, little human study has linked prenatal BPA exposure to altered mother-infant interaction or examined the consequence of this effect on neurobehavioral development. Most of the human literature identifies effects of BPA in older children. In rodent and primate models, prenatal exposure to BPA disrupts maternal care and offspring social behavior via epigenetic changes. In humans, these indirect effects on mother-infant interaction and the associated epigenetic mechanisms have not been examined. We thus risk underestimating the full impact of BPA exposure, and we currently do not know the pathways through which BPA may disrupt development. Although BPA has been removed from many consumer products, it has been replaced by structural analogs, bisphenol-s (BPS) and bisphenol-f (BPF), which may have similar detrimental effects. This study aims to translate findings from animal models to ask whether increased prenatal BPA, BPS, BPF (BP) exposure in humans predicts less optimal maternal care/mother-infant interaction and infant/toddler development. Moreover we ask whether this exposure is associated with corresponding epigenetic changes in mother and infant in genes previously shown to be impacted by prenatal BPA exposure in rodents: estrogen receptor alpha (ESR1: implicated in maternal behavior) and brain-derived neurotrophic factor (BDNF; implicated in infant neural plasticity and cognition). In our translational approach, we recruit women during pregnancy, assess prenatal BP exposure using multiple urine samples collected during the 3rd trimester of pregnancy. We assess mother-infant interaction with measures of moment-by-moment reciprocal influences between mother and infant, providing a more nuanced measure of the effects of BP in humans, and we assess infant/toddler social and cognitive development at 12 and 24 months. In serially collected buccal swabs, we assess DNA methylation of ESR1 in the mother and infant and of BDNF in the infant to understand how early life BP exposure alters these pathways. Understanding the effects of BP on maternal care and mother-infant interaction is essential to revealing the pathways through which BP acts to disrupt neurodevelopment. This R01 addresses a critical gap in our understanding of how prenatal endocrine-disrupting chemicals alter mother-infant interaction, infant/toddler development, and associated epigenetic processes, with implications for strategies to prevent and mitigate the impact of BP on neurodevelopment.
Mother-infant interaction, and social and cognitive development across the first two years of life, have a lifelong impact. Prenatal exposure to bisphenol compounds alters these endpoints in animal models, but human studies have not evaluated the impact of exposure on maternal-infant interaction, which may explain why the extant literature examining effects on social and cognitive endpoints have been equivocal. This study will evaluate this important endpoint in the context of bisphenol-induced neurotoxicity and can inform public health policy.