Bias from Conditioning on Live Birth in Pregnancy Cohorts: An Illustration Based on Neurodevelopment in Children after Prenatal Exposure to Organic Pollutants

摘要

Only 60-70% of fertilized eggs may result in a live birth and very early fetal loss mainly goes unnoticed. Outcomes that can only be ascertained in live born children will be missing for those who do not survive till birth. We illustrated a common bias structure (leading to 'live-birth bias') that arises from studying the effects of prenatal exposure to environmental factors on long-term health outcomes among live births only in pregnancy cohorts. We used prenatal exposure to perfluoroalkyl substances (PFAS) and the risk of attention-deficit/hyperactivity disorder (ADHD) in school-aged children as an example. PFAS are persistent organic pollutants that may impact human fecundity and be toxic for neurodevelopment. We simulated several scenarios based on characteristics from the Danish National Birth Cohort (DNBC), and we found that a weak inverse-association may appear even if PFAS do not cause ADHD but have a considerable effect on fetal survival. Our example highlights the need for knowing the determinants of pregnancy loss and the importance of quantifying bias arising from conditioning on live birth in observational studies.