Candice Y Johnson1,2, Margaret A Honein2, Sonja A Rasmussen3, Penelope P Howards1, Matthew J Strickland4, W Dana Flanders1. 1. Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia, USA. 2. National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, Georgia, USA. 3. Department of Pediatrics and Epidemiology, University of Florida College of Medicine and College of Public Health and Health Professions, Gainesville, Florida, USA. 4. School of Community Health Sciences, University of Nevada Reno, Reno, Nevada, USA.
Abstract
BACKGROUND: Epidemiologists have consistently observed associations between prepregnancy obesity and spina bifida in offspring. Most studies, however, used self-reported body mass index (potential for exposure misclassification) and incompletely ascertained cases of spina bifida among terminations of pregnancy (potential for selection bias). We conducted a quantitative bias analysis to explore the potential effects of these biases on study results. METHODS: We included 808 mothers of fetuses or infants with spina bifida (case mothers) and 7,685 mothers of infants without birth defects (control mothers) from a population-based case-control study, the National Birth Defects Prevention Study (1997-2011). First, we performed a conventional epidemiologic analysis, adjusting for potential confounders using logistic regression. Then, we used 5,000 iterations of probabilistic bias analysis to adjust for the combination of confounding, exposure misclassification, and selection bias. RESULTS: In the conventional confounding-adjusted analysis, prepregnancy obesity was associated with spina bifida (odds ratio 1.4, 95% confidence interval: 1.2, 1.7). In the probabilistic bias analysis, we tested nine different models for the combined effects of confounding, exposure misclassification, and selection bias. Results were consistent with a weak to moderate association between prepregnancy obesity and spina bifida, with the median odds ratios across the nine models ranging from 1.1 to 1.4. CONCLUSIONS: Given our assumptions about the occurrence of bias in the study, our results suggest that exposure misclassification, selection bias, and confounding do not completely explain the association between prepregnancy obesity and spina bifida.
BACKGROUND: Epidemiologists have consistently observed associations between prepregnancy obesity and spina bifida in offspring. Most studies, however, used self-reported body mass index (potential for exposure misclassification) and incompletely ascertained cases of spina bifida among terminations of pregnancy (potential for selection bias). We conducted a quantitative bias analysis to explore the potential effects of these biases on study results. METHODS: We included 808 mothers of fetuses or infants with spina bifida (case mothers) and 7,685 mothers of infants without birth defects (control mothers) from a population-based case-control study, the National Birth Defects Prevention Study (1997-2011). First, we performed a conventional epidemiologic analysis, adjusting for potential confounders using logistic regression. Then, we used 5,000 iterations of probabilistic bias analysis to adjust for the combination of confounding, exposure misclassification, and selection bias. RESULTS: In the conventional confounding-adjusted analysis, prepregnancy obesity was associated with spina bifida (odds ratio 1.4, 95% confidence interval: 1.2, 1.7). In the probabilistic bias analysis, we tested nine different models for the combined effects of confounding, exposure misclassification, and selection bias. Results were consistent with a weak to moderate association between prepregnancy obesity and spina bifida, with the median odds ratios across the nine models ranging from 1.1 to 1.4. CONCLUSIONS: Given our assumptions about the occurrence of bias in the study, our results suggest that exposure misclassification, selection bias, and confounding do not completely explain the association between prepregnancy obesity and spina bifida.
Authors: Sonja A Rasmussen; Richard S Olney; Lewis B Holmes; Angela E Lin; Kim M Keppler-Noreuil; Cynthia A Moore Journal: Birth Defects Res A Clin Mol Teratol Date: 2003-03
Authors: Hilda Razzaghi; Sarah C Tinker; Amy H Herring; Penelope P Howards; D Kim Waller; Candice Y Johnson Journal: Matern Child Health J Date: 2016-07
Authors: Candice Y Johnson; Penelope P Howards; Matthew J Strickland; D Kim Waller; W Dana Flanders Journal: Ann Epidemiol Date: 2018-06-02 Impact factor: 3.797