Maternal hyperthermia and the risk for neural tube defects in offspring: systematic review and meta-analysis.
BACKGROUND
In animals, excessive core body temperatures have been documented to cause malformations; neural tube defects (NTDs) are among the most frequently reported. In humans, data are inconclusive and often conflicting. The objective of our report is to determine the risk for neural tube defects associated with maternal hyperthermia in early pregnancy.


METHODS
We conducted a systematic review and meta-analysis to evaluate available evidence on this topic in humans. MEDLINE, EMBASE, references from published reports, and biologic abstracts from meetings were searched for relevant studies. Reviewers evaluated all the retrieved articles and extracted the relevant data. Individual and summary odds ratios and relative risks were calculated using the Mantel-Haenszel method.


RESULTS
Fifteen studies, reporting on 1,719 cases and 37,898 noncases, were included in the meta-analysis. The overall odds ratio for neural tube defects associated with maternal hyperthermia was 1.92 (95% confidence interval = 1.61-2.29). When analyzed separately, the 9 case-control studies had an odds ratio of 1.93 (1.53-2.42). The summary relative risk for the 6 cohort studies was 1.95 (1.30-2.92).


CONCLUSIONS
Maternal hyperthermia in early pregnancy is associated with increased risk for neural tube defects and may be a human teratogen.
Moretti
Myla E
ME
The Motherisk Program, The Hospital for Sick Children, Toronto, Canada. momrisk@sickkids.ca
Bar-Oz
Benjamin
B
Fried
Shawn
S
Koren
Gideon
G
D000328:Adult; D016022:Case-Control Studies; D005260:Female; D005334:Fever / Q000150:complications*; D006801:Humans; D009436:Neural Tube Defects / Q000453:epidemiology* / Q000209:etiology*; D016017:Odds Ratio; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D012307:Risk Factors