Maternal risk factors for congenital vertebral formation and mixed defects: A population-based case–control study

The etiology and risk factors of congenital vertebral anomalies are mainly unclear in isolated cases. Also, there are no reports on the risk factors for different subgroups of vertebral anomalies. Therefore, we assessed and identified potential maternal risk factors for these anomalies and hypothesized that diabetes, other chronic diseases, smoking, obesity, and medication in early pregnancy would increase the risk of congenital vertebral anomalies. All cases with congenital vertebral anomalies were identified in the Finnish Register of Congenital Malformations from 1997 to 2016 for this nationwide register-based case–control study. Five matched controls without vertebral malformations were randomly selected. Analyzed maternal risk factors included maternal age, body mass index, parity, smoking, history of miscarriages, chronic diseases, and prescription drug purchases in early pregnancy. The register search identified 256 cases with congenital vertebral malformations. After excluding 66 syndromic cases, 190 non-syndromic malformations (74 formation defects, 4 segmentation defects, and 112 mixed anomalies) were included in the study. Maternal smoking was a significant risk factor for formation defects (adjusted odds ratio 2.33, 95% confidence interval 1.21–4.47). Also, pregestational diabetes (adjusted odds ratio 8.53, 95% confidence interval 2.33–31.20) and rheumatoid arthritis (adjusted odds ratio 13.19, 95% confidence interval 1.31–132.95) were associated with mixed vertebral anomalies. Maternal pregestational diabetes and rheumatoid arthritis were associated with an increased risk of mixed vertebral anomalies. Maternal smoking increases the risk of formation defects and represents an avoidable risk factor for congenital scoliosis. III