Fetal exposure to phthalates and bisphenols and fetal growth and adverse birth outcomes: an individual participant data meta-analysis.

Non-persistent endocrine disruptors, such as phthalates and bisphenols, are widely used in several consumer and diet products. Human exposure to these chemicals is ubiquitous and has been associated with several endocrine, metabolic and reproductive health outcomes. As is known from the developmental origins of health and disease hypothesis, fetal life is an important period for development and growth and exposure to phthalates or bisphenols during this vulnerable period might have life-long persisting health effects. Prenatal exposure to these chemicals might affect fetal growth and influence the risk of adverse birth outcomes, possibly through influences on placental development. In 1379 pregnant women within Generation R, we have previously shown that maternal phthalate urine concentrations during pregnancy are associated with lower fetal weight over pregnancy and that maternal urinary bisphenol S concentrations during pregnancy are associated with higher fetal weight and head circumference. In INMA, a positive association was found of maternal urinary mono-benzyl phthalate concentrations with femur length at 20-34 weeks of gestation and with birth weight among boys, while maternal urinary mono-n-butyl phthalate concentrations were associated with smaller head circumference at 12-20 weeks of gestation. However, most previous studies on these associations have small sample sizes and have shown inconsistent findings. To further elucidate the associations between maternal phthalate and bisphenol exposure during pregnancy and fetal growth and birth outcomes, it is important to increase the sample size and to assess these associations in multiple populations, while accounting for all relevant potential confounders.

The main objective is to assess the associations between maternal phthalates and bisphenols urine concentrations during pregnancy and fetal growth and adverse birth outcomes using an individual-participant data (IPD) meta-analysis approach.
• Main exposures are spot urine concentrations of phthalates and bisphenols (one, two or three time points during pregnancy)
• Main outcomes are ultrasound measures of fetal growth during second and third trimester, and the following birth outcomes: gestational-age and sex-adjusted birth weight, birth length, head circumference at birth, gestational age at birth, small size for gestational age (<10th percentile), large size for gestational age (>90th percentile) and preterm birth (<37 weeks))