Metabolic Syndrome features and risk of neural tube defects

Joel G Ray,Philip R Wyatt,Miles D Thompson,Sandra A Farrell,Pui-Yuen Wong,David Ec Cole,Anne M Summers,Chris Meier,Marian J Vermeulen

doi:10.1186/1471-2393-7-21

Abstract

BackgroundMaternal obesity and pre-pregnancy diabetes mellitus, features of the metabolic syndrome (MetSyn), are individual risk factors for neural tube defects (NTD). Whether they, in combination with additional features of MetSyn, alter this risk is not known. We evaluated the risk of NTD in association with maternal features of the MetSyn.MethodsWe used a population-based case-control study design in the province of Ontario, Canada. Cases and controls were derived from women who underwent antenatal maternal screening (MSS) at 15 to 20 weeks' gestation. There were 89 maternal cases with, and 434 controls without, an NTD-affected singleton pregnancy. Maternal features of MetSyn were defined by the presence of pre-pregnancy diabetes mellitus, body weight ≥ 90th centile among controls, non-white ethnicity and/or serum highly sensitive C-reactive protein (hsCRP) ≥ 75th centile of controls. Since hsCRP naturally increases in pregnancy, analyses were performed with, and without, the inclusion of hsCRP in the model.ResultsMean hsCRP concentrations were exceptionally high among study cases and controls (6.1 and 6.4 mg/L, respectively). When hsCRP was excluded from the model, the adjusted odds ratios for NTD were 1.9 (95% confidence interval 1.1–3.4) in the presence 1 feature of MetSyn, and 6.1 (1.1–32.9) in the presence of 2 or more features. When hsCRP was included, the respective risk estimates were attenuated to 1.6 (0.88–2.8) and 3.1 (1.2–8.3).ConclusionWe found about 2-fold and 6-fold higher risk for NTD in the presence 1, and 2 or more features, of the metabolic syndrome, respectively. It is not clear whether this risk is altered by the presence of a high serum hsCRP concentration.

Highlights

Maternal obesity and pre-pregnancy diabetes mellitus, features of the metabolic syndrome (MetSyn), are individual risk factors for neural tube defects (NTD)
When highly sensitive serum C-reactive protein (hsCRP) was excluded from the model, the crude odds ratios (OR) for NTD were 1.9 (1.2–3.1) and 6.1 (1.2–30.9) in the presence 1 and 2 or more features of MetSyn, respectively, relative to none (Table 2)
It was not known how many cases or controls were taking folic acid tablet supplements periconceptionally, a major determinant of NTD risk [1], we did adjust for serum folate status at the time of screening, as well as socioeconomic status, which itself is a predictor of periconceptional folic acid supplement use [20]

Summary

Introduction

Maternal obesity and pre-pregnancy diabetes mellitus, features of the metabolic syndrome (MetSyn), are individual risk factors for neural tube defects (NTD). The metabolic syndrome (MetSyn) is characterized by a cluster of metabolic risk factors including abdominal obesity, DM or insulin resistance, non-white ethnicity [4], dyslipidemia, chronic hypertension and elevated inflammatory highly sensitive serum C-reactive protein (hsCRP) [5]. If obesity and pre-pregnancy DM are each independent risk factors for NTD, it is valuable to know how they interact together, and with other features of MetSyn, namely, non-white ethnicity and elevated serum hsCRP.

Methods

Results

Discussion

Conclusion