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

Shiliang Liu; Jane Evans; Amanda J MacFarlane; Cande V Ananth; Julian Little; Michael S Kramer; K S Joseph

doi:10.1111/ppe.12543

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

Paediatr Perinat Epidemiol. 2019 Mar;33(2):145-153. doi: 10.1111/ppe.12543.

Authors

Shiliang Liu^{1

2}, Jane Evans³, Amanda J MacFarlane⁴, Cande V Ananth⁵, Julian Little², Michael S Kramer^{6

7}, K S Joseph⁸

Affiliations

¹ Maternal, Child and Youth Health Division, Centre for Surveillance and Applied Research, Public Health Agency of Canada, Ottawa, Ontario, Canada.
² School of Epidemiology and Public Health, University of Ottawa, Ottawa, Ontario, Canada.
³ Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, Manitoba, Canada.
⁴ Nutrition Research Division, Bureau of Nutritional Sciences, Food Directorate, Health Products and Food Branch, Health Canada, Ottawa, Ontario, Canada.
⁵ Division of Epidemiology and Biostatistics, Department of Obstetrics, Gynecology, and Reproductive Sciences, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey.
⁶ Department of Pediatrics, McGill University, Montreal, Quebec, Canada.
⁷ Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Quebec, Canada.
⁸ Department of Obstetrics and Gynaecology and the School of Population and Public Health, University of British Columbia and the Children's and Women's Hospital of British Columbia, Vancouver, British Columbia, Canada.

PMID: 30920008
DOI: 10.1111/ppe.12543

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 (P_trend = 0.03). Among NTD subtypes, only spina bifida showed a temporal increase (P_trend = 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.

Keywords: neural tube defects; risk factor; substance use; temporal trend.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Canada / epidemiology
Diabetes Mellitus, Type 2 / complications*
Diabetes Mellitus, Type 2 / physiopathology
Female
Folic Acid / therapeutic use*
Humans
Infant, Newborn
Maternal Age
Mothers*
Neural Tube Defects / epidemiology*
Neural Tube Defects / etiology
Population Surveillance
Pregnancy
Pregnancy in Diabetics / epidemiology*
Pregnancy in Diabetics / physiopathology
Prevalence
Risk Factors
Substance-Related Disorders / complications*
Substance-Related Disorders / epidemiology
Young Adult

Substances

Folic Acid