Study design: A retrospective medical record review of cases with congenital vertebral malformations (CVMs) and controls with normal spine morphology.
Objective: To determine the relative contribution of maternal environmental factors (MEFs) during pregnancy to CVM development.
Summary of background data: CVMs represent defects in formation and segmentation of somites occurring with an estimated incidence of between 0.13 and 0.50 per 1000 live births. CVMs may be associated with various phenotypes and represent significant morbidity due to pain and cosmetic disfigurement.
Methods: A multicenter retrospective medical record review of 229 cases with CVM and 267 controls with normal spine morphology between the ages of 1 and 50 years was performed to obtain the odds ratio (OR) of MEF related to CVM among cases versus controls. An imputation-based analysis was performed in which subjects with no documentation of MEF history were treated as "no maternal exposure." Univariate and multivariate analyses were conducted to calculate the OR.
Results: Of the 229 total cases, 104 cases had single or multiple CVMs without additional congenital malformations (group 1) and 125 cases had single or multiple CVMs and additional congenital malformations (group 2). Nineteen percent of total cases had an identified MEF. The OR for MEF history for group 1 was 6.0 (95% confidence interval, 2.4-15.1; P < 0.001) in the univariate analysis. The OR for MEF history in group 2 was 9.1 (95% confidence interval, 3.8-21.6, P < 0.001) in the univariate analysis. The results were confirmed in the multivariate analysis after adjusting for age, sex, and institution.
Conclusions: These results support a hypothesis for an association between these MEFs during pregnancy and CVM and have implications for development of prevention strategies. Further prospective studies are needed to quantify association between CVMs and specific MEF.
Level of evidence: 4.