Heterogeneity of spina bifida

Splitting birth defects into dysmorphologically homogeneous groups might improve the ability to detect a genetic risk factor or teratogenic exposure. With regard to spina bifida, recent studies suggest that etiologic heterogeneity exists within the group of spina bifida, although exogenous risk factors have been sparsely evaluated for subgroups. In the present study, 210 spina bifida patients were classified into relatively homogeneous groups, based on retrospective information on appearance and functional aspects of the lesion abstracted from medical records of the patients. We compared high with low spina bifida, and open with closed spina bifida, and investigated whether risk factors for spina bifida such as maternal age, antiepileptic drug use, parental occupation, and genetic factors were specifically associated with these homogeneous subclasses. For these comparisons, a referent group of 671 children was used. Although classifying spina bifida into homogeneous subclasses presented some difficulties and numbers were small, this study provides some evidence for different risk profiles for subclasses of spina bifida. The sex ratio, the proportion of miscarriages of siblings, and maternal age did not differ among the different subclasses of spina bifida. However, children with a positive family history of neural tube defects (NTDs) had a higher risk of high spina bifida [odds ratio (OR) = 6.3, 95% confidence interval (CI): 1.7-19.2] than of low spina bifida (OR = 2.1, 95% CI: 1.0-4.2). Siblings with NTDs were more common in cases with high spina bifida and cases with open spina bifida. A strongly increased risk of high spina bifida was found for male welders (OR = 12.1, 95% CI: 1.5-64.2), whereas the risk of low spina bifida was much lower (OR = 1.6, 95% CI: 0.2-7.9). For mothers with agricultural occupations, a strongly increased risk was observed for open spina bifida (OR = 14.3, 95% CI: 2.9-77.7), whereas none of 107 cases with closed spina bifida had a mother with an occupation in agriculture. Due to small numbers, the results must be interpreted with caution.