Periconceptional Folic Acid Supplementation and Infant Risk of Congenital Heart Defects inNorway 1999–2009

Elisabeth Leirgul,Nina Øyen,Henrik Holmstrøm,Kristoffer Brodwall,Tatiana Fomina,Stein Emil Vollset,Grethe S Tell,Trude Gildestad,Roy Miodini Nilsen,Gottfried Greve

doi:10.1111/ppe.12212

Abstract

The birth prevalence of congenital heart defects (CHDs) has decreased in Canada and Europe. Recommended intake of folic acid in pregnancy is a suggestive risk-reducing factor for CHDs. We investigated the association between periconceptional intake of folic acid supplements and infant risk of CHDs. Information on maternal intake of folic acid supplements before and during pregnancy in the Medical Birth Registry of Norway 1999-2009 was updated with information on CHD diagnoses from national health registers and the Cardiovascular Diseases in Norway Project. The association between folic acid intake and infant risk of CHD was estimated as relative risk (RR) with binomial log linear regression. Among 517 784 non-chromosomal singleton births, 6200 children were identified with CHD and 1153 with severe CHD. For all births, 18.4% of the mothers initiated folic acid supplements before pregnancy and 31.6% during pregnancy. The adjusted RR for severe CHD was 0.99 [95% confidence interval [CI] 0.86, 1.13] comparing periconceptional intake of folic acid with no intake. Specifically, RR for conotruncal defects was 0.99 [95% CI 0.80, 1.22], atrioventricular septal defects 1.19 [95% CI 0.78, 1.81], left ventricular outflow tract obstructions 1.02 [95% CI 0.78, 1.32], and right ventricular outflow tract obstructions 0.97 [95% CI 0.72, 1.29]. Birth prevalence of septal defects was higher in the group exposed to folic acid supplements with RR 1.19 [95% CI 1.10, 1.30]. Periconceptional folic acid supplement use showed no association with severe CHDs in the newborn. An unexpected association with an increased risk of septal defects warrants further investigation.

Highlights

In the Medical Birth Registry of Norway, information on the use of folic acid and multivitamin supplements has been recorded for all women giving birth since 1999.17 We have taken advantage of Norway’s national health registries and the Cardiovascular Disease in Norway project (CVDNOR) to investigate infant risk of specific types of congenital heart defects (CHDs) among mothers using folic acid supplements in the periconceptional period
Among 517 784 individuals, 6200 children had any type of CHD and 1153 had a severe CHD; the birth prevalence was 119.7 per 10 000 births and 22.3 per 10 000 births, respectively
The birth prevalence increased for total CHD until 2004, and decreased thereafter (Figure 1)

Summary

Introduction

In the Medical Birth Registry of Norway, information on the use of folic acid and multivitamin supplements has been recorded for all women giving birth since 1999.17 We have taken advantage of Norway’s national health registries and the Cardiovascular Disease in Norway project (CVDNOR) to investigate infant risk of specific types of CHDs among mothers using folic acid supplements in the periconceptional period. Maternal periconceptional use of folic acid was not associated with infant risk of severe CHD; the aRR was 0.99 [95% CI 0.86, 1.13] comparing pregnancies exposed to folic acid with non-exposed pregnancies (Table 3).

Results

Conclusion