Periconceptional maternal fever, folic acid intake, and the risk for neural tube defects

Abstract

Purpose: Previous studies have shown an association between maternal fever in early pregnancy and neural tube defects (NTDs) such as spina bifida. Periconceptional folic acid intake has been shown to reduce the risk of these outcomes.

Methods: Using data from the Slone Epidemiology Center Birth Defects Study (1998-2015), we examined the impact of folic acid on the relationship between maternal fever in the periconceptional period (28 days before and after the last menstrual period) and NTDs. Logistic regression models were used to calculate adjusted odds ratios (ORs) and 95% confidence intervals (CIs).

Results: Mothers of 375 cases and 8247 nonmalformed controls were included. We observed an elevated risk for NTDs for fever in the periconceptional period (OR: 2.4; 95% CI: 1.5-4.0). This association was weaker for mothers who reported consuming the recommended amount of folic acid (≥400 μg per day; OR: 1.8; 95% CI: 0.8-4.0) than mothers with low folic acid intake (<400 μg per day; OR: 4.2; 95% CI: 2.2-8.2).

Conclusions: Our data support an association between maternal periconceptional fever and an increased risk for NTDs and also provide evidence that this association was attenuated for mothers who reported consuming folic acid at recommended levels in the periconceptional period.

Keywords: Fever; Folic acid; Neural tube defects; Spina bifida.