Association of maternal risk factors with the recent rise of neural tube defects in Canada

Abstract

BACKGROUND We sought to assess the recent trend in NTD prevalence at birth in the post-folic acid food fortification era and to identify the maternal risk factors associated with that trend. METHODS We carried out a population-based study of all livebirths and stillbirths (including late pregnancy terminations) delivered in hospitals in Canada (excluding Quebec) from 2004 to 2015 (n = 3 439 330). We examined NTD birth prevalence by year, multiple pregnancy, maternal age, parity, pregestational diabetes, chronic illness, and problematic substance use. Poisson regression was used to quantify the association between spina bifida and cranial defects and maternal characteristics and other risk factors. RESULTS We identified 1517 non-chromosomal NTDs, yielding a birth prevalence of 4.4 per 10 000 total births. NTD prevalence rose from 3.6 in 2004 to 4.6 per 10 000 in 2015 (Ptrend = 0.03). Among NTD subtypes, only spina bifida showed a temporal increase (Ptrend = 0.03). Birth prevalence of spina bifida was higher among younger mothers, those with type 2 diabetes (rate ratio (RR) 3.74, 95% confidence interval (CI) 2.21, 6.35), chronic illness (RR 3.16, 95% CI 1.97, 5.07), and problematic substance use (RR 1.88, 95% CI 1.31, 2.71). Adjusting for risk factors attenuated the significant temporal trend in spina bifida (unadjusted average annual prevalence ratio (aAAPR) 1.016, 95% CI 1.001, 1.032; adjusted AAPR 1.014, 95% CI 0.998, 1.029). CONCLUSIONS Increases in the frequency of maternal risk factors such as pregestational diabetes mellitus, substance use, and chronic illness may be partly responsible for the recent rise in NTDs, particularly spina bifida.