title: Bias Against the Null Hypothesis in Retrospective Registries of Gestational Drug Exposure.
abstract: The findings in retrospective pregnancy registries related to prenatal drug exposure (collected after pregnancy outcome is known) are commonly reported in regulatory documents and in the medical literature. However, there is little information about the accuracy of the estimates of risk from such registries. We therefore sought to compare the rates of major congenital malformations reported in retrospective and prospective registries for the same drug to quantify the potential bias of retrospective reports.
  
  
  
  We searched for all fetal safety reports related to medications for which information from both prospective and retrospective registries was available. These were published either in the peer-reviewed literature or as pharmaceutical company documents between 1984 and 2011.
  
  
  
  For all drugs registries studied, estimates of major congenital malformations from retrospective registries tended to be higher than the rates in prospective registries; median estimates of risk were higher by a factor of 4.18 ± 1.23 (range 2.13-5.97).
  
  
  
  The present study confirms a major and consistent bias against the null hypothesis in studies of teratogenic risk using retrospective registries, and this must be considered when interpreting such data. Spontaneous reporting of outcomes after exposure to a drug is highly selective towards adverse events, which families with normal pregnancy outcomes are less likely to report.
authors.affiliation: Department of Physiology/Pharmacology, Western University, London ON; The Motherisk Program, Department of Pediatrics, The Hospital for Sick Children, Toronto ON.
authors.forename: Fatma
authors.initials: F
authors.lastname: Etwel
authors.affiliation: Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, Western University, London ON.
authors.forename: Gideon
authors.initials: G
authors.lastname: Koren
mesh_terms: D000014:Abnormalities, Drug-Induced / Q000453:epidemiology*; D005260:Female; D006801:Humans; D018811:Maternal Exposure / Q000706:statistics & numerical data*; D011247:Pregnancy; D055553:Prescription Drugs / Q000009:adverse effects* / Q000627:therapeutic use; D012042:Registries; D012189:Retrospective Studies
chemical_list: D055553:Prescription Drugs
keywords: Retrospective registries; drug safety; malformation; pregnancy