Quantification of selection bias in studies of risk factors for birth defects among live births

Details

• Alternative Title:
  Paediatr Perinat Epidemiol
• Personal Author:
  Heinke, Dominique ; Rich-Edwards, Janet W. ; Williams, Paige L. ; Hernandez-Diaz, Sonia ; Anderka, Marlene ; Fisher, Sarah C. ; Desrosiers, Tania A. ; Shaw, Gary M. ; Romitti, Paul A. ; Canfield, Mark ; Yazdy, Mahsa M.
• Description:
  Background
  
  Risk factors for birth defects are frequently investigated using data limited to liveborn infants. By conditioning on survival, results of such studies may be distorted by selection bias, also described as “live birth bias”. However, the implications of live birth bias on risk estimation remain poorly understood.
  
  Objectives
  
  We sought to quantify live birth bias and to investigate the conditions under which it arose.
  
  Methods
  
  We used data on 3,994 birth defects cases and 11,829 controls enrolled in the National Birth Defects Prevention Study to compare odds ratio (OR) estimates of the relationship between three established risk factors (antiepileptic drug use, smoking, and multifetal pregnancy) and four birth defects (anencephaly, spina bifida, omphalocele, and cleft palate) when restricted to live births as compared to among live births, stillbirths, and elective terminations. Exposures and birth defects represented varying strengths of association with live birth; all controls were liveborn. We performed a quantitative bias analysis to evaluate the sensitivity of our results to excluding terminated and stillborn controls.
  
  Results
  
  Cases ranged from 33% live born (anencephaly) to 99% (cleft palate). Smoking and multifetal pregnancy were associated with live birth among anencephaly (crude OR [cOR] 0.61 and cOR 3.15, respectively) and omphalocele cases (cOR 2.22 and cOR 5.22, respectively). For analyses of the association between exposures and birth defects, restricting to live births produced negligible differences in estimates except for anencephaly and multifetal pregnancy, which was two-fold higher among live births (adjusted OR [aOR] 4.93) as among all pregnancy outcomes (aOR 2.44). Within tested scenarios, bias analyses suggested that results were not sensitive to the restriction to liveborn controls.
  
  Conclusions
  
  Selection bias was generally limited except for high mortality defects in the context of exposures strongly associated with livebirth. Findings indicate that substantial live birth bias is unlikely to affect studies of risk factors for most birth defects.
  
  
• Subjects:
  Article Birth Defects Live Birth Live Birth Bias Selection Bias Stillbirth Termination Of Pregnancy
• Source:
  Paediatr Perinat Epidemiol. 34(6):655-664
• Pubmed ID:
  32249969
• Pubmed Central ID:
  PMC7541428
• Document Type:
  Journal Article
• Funding:
  P30 ES010126/ES/NIEHS NIH HHSUnited States/ ; U01 DD000491/DD/NCBDD CDC HHSUnited States/ ; U01 DD001224/DD/NCBDD CDC HHSUnited States/ ; T32HD060454/HD/NICHD NIH HHSUnited States/ ; U01 DD001227/DD/NCBDD CDC HHSUnited States/ ; U01 DD000493/DD/NCBDD CDC HHSUnited States/ ; T03MC07648/HRSA/HRSA HHSUnited States/ ; EP-D-18-001/EPA/EPAUnited States/ ; T32 HD060454/HD/NICHD NIH HHSUnited States/ ; U01DD001037/DD/NCBDD CDC HHSUnited States/ ; U01 DD001226/DD/NCBDD CDC HHSUnited States/ ; U01 DD001223/DD/NCBDD CDC HHSUnited States/ ; U01DD000493/DD/NCBDD CDC HHSUnited States/ ; 5U01DD000491/DD/NCBDD CDC HHSUnited States/ ; CDP 13-003/HX/HSRD VAUnited States/ ; U01DD001037/ACL/ACL HHSUnited States/ ; U01 DD001035/DD/NCBDD CDC HHSUnited States/
• Volume:
  34
• Issue:
  6
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:26a7382f4e38a2c8fe7d7c86678c5ace1aa7c82668072ff589c0a99676c79768
• Download URL:
  https://stacks.cdc.gov/view/cdc/95042/cdc_95042_DS1.pdf
• File Type:
  [PDF - 774.99 KB ]