title: Bias from conditioning on live birth in pregnancy cohorts: an illustration based on neurodevelopment in children after prenatal exposure to organic pollutants.
abstract: 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. In this article, we illustrate 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. To illustrate this we used prenatal exposure to perfluoroalkyl substances (PFAS) and 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 hypothetical scenarios based on characteristics from the Danish National Birth Cohort and found that a weak inverse association may appear even if PFAS do not cause ADHD but have a considerable effect on fetal survival. The magnitude of the negative bias was generally small, and adjusting for common causes of the outcome and fetal loss can reduce the bias. Our example highlights the need to identify the determinants of pregnancy loss and the importance of quantifying bias arising from conditioning on live birth in observational studies.
authors.affiliation: Department of Epidemiology, Fielding School of Public Health, University of California Los Angeles (UCLA), Los Angeles, CA, USA, Department of Public Health, Section for Epidemiology, University of Aarhus, Aarhus, Denmark, Department of Neurology, Geffen School of Medicine, UCLA, Los Angeles, CA, USA, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands and UCLA Center for Health Policy Research, Los Angeles, CA, USA zeyanliew@ucla.edu.
authors.forename: Zeyan
authors.initials: Z
authors.lastname: Liew
authors.affiliation: Department of Epidemiology, Fielding School of Public Health, University of California Los Angeles (UCLA), Los Angeles, CA, USA, Department of Public Health, Section for Epidemiology, University of Aarhus, Aarhus, Denmark, Department of Neurology, Geffen School of Medicine, UCLA, Los Angeles, CA, USA, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands and UCLA Center for Health Policy Research, Los Angeles, CA, USA Department of Epidemiology, Fielding School of Public Health, University of California Los Angeles (UCLA), Los Angeles, CA, USA, Department of Public Health, Section for Epidemiology, University of Aarhus, Aarhus, Denmark, Department of Neurology, Geffen School of Medicine, UCLA, Los Angeles, CA, USA, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands and UCLA Center for Health Policy Research, Los Angeles, CA, USA.
authors.forename: Jørn
authors.initials: J
authors.lastname: Olsen
authors.affiliation: Department of Epidemiology, Fielding School of Public Health, University of California Los Angeles (UCLA), Los Angeles, CA, USA, Department of Public Health, Section for Epidemiology, University of Aarhus, Aarhus, Denmark, Department of Neurology, Geffen School of Medicine, UCLA, Los Angeles, CA, USA, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands and UCLA Center for Health Policy Research, Los Angeles, CA, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Cui
authors.affiliation: Department of Epidemiology, Fielding School of Public Health, University of California Los Angeles (UCLA), Los Angeles, CA, USA, Department of Public Health, Section for Epidemiology, University of Aarhus, Aarhus, Denmark, Department of Neurology, Geffen School of Medicine, UCLA, Los Angeles, CA, USA, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands and UCLA Center for Health Policy Research, Los Angeles, CA, USA Department of Epidemiology, Fielding School of Public Health, University of California Los Angeles (UCLA), Los Angeles, CA, USA, Department of Public Health, Section for Epidemiology, University of Aarhus, Aarhus, Denmark, Department of Neurology, Geffen School of Medicine, UCLA, Los Angeles, CA, USA, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands and UCLA Center for Health Policy Research, Los Angeles, CA, USA.
authors.forename: Beate
authors.initials: B
authors.lastname: Ritz
authors.affiliation: Department of Epidemiology, Fielding School of Public Health, University of California Los Angeles (UCLA), Los Angeles, CA, USA, Department of Public Health, Section for Epidemiology, University of Aarhus, Aarhus, Denmark, Department of Neurology, Geffen School of Medicine, UCLA, Los Angeles, CA, USA, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands and UCLA Center for Health Policy Research, Los Angeles, CA, USA Department of Epidemiology, Fielding School of Public Health, University of California Los Angeles (UCLA), Los Angeles, CA, USA, Department of Public Health, Section for Epidemiology, University of Aarhus, Aarhus, Denmark, Department of Neurology, Geffen School of Medicine, UCLA, Los Angeles, CA, USA, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands and UCLA Center for Health Policy Research, Los Angeles, CA, USA Department of Epidemiology, Fielding School of Public Health, University of California Los Angeles (UCLA), Los Angeles, CA, USA, Department of Public Health, Section for Epidemiology, University of Aarhus, Aarhus, Denmark, Department of Neurology, Geffen School of Medicine, UCLA, Los Angeles, CA, USA, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands and UCLA Center for Health Policy Research, Los Angeles, CA, USA.
authors.forename: Onyebuchi A
authors.initials: OA
authors.lastname: Arah
mesh_terms: D001289:Attention Deficit Disorder with Hyperactivity / Q000453:epidemiology*; D015982:Bias; D003718:Denmark; D004785:Environmental Pollutants / Q000633:toxicity*; D005260:Female; D005313:Fetal Death; D005466:Fluorocarbons / Q000633:toxicity*; D006801:Humans; D050498:Live Birth; D009010:Monte Carlo Method; D011247:Pregnancy; D011256:Pregnancy Outcome / Q000453:epidemiology*; D011297:Prenatal Exposure Delayed Effects / Q000453:epidemiology*
chemical_list: D004785:Environmental Pollutants; D005466:Fluorocarbons
keywords: Bias analysis; attention-deficit/hyperactivity disorder; birth cohort; live-birth bias; perfluoroalkyl substances; prenatal exposure; reproductive epidemiology