Association of paternal smoking with the risk of neural tube defects in offspring: A systematic review and meta-analysis of observational studies.

PURPOSE: The present study aimed at providing some epidemiological evidences to assess the association of paternal smoking with the risk of neural tube defects (NTDs) and its specific subtypes in offspring, and explore the possible dose-response relationship between paternal smoking and risk of NTDs.

METHODS

English and Chinese databases were systematically searched from 1984 to May 2020. Either a fixed- or a random-effects model was used to calculate the overall combined risk estimates. We also examined the dose-response relationship between parental smoking and risk of NTDs in offspring. Subgroup analyses and sensitivity analyses were conducted to explore possible sources of heterogeneity.

RESULTS

A total of 10 case-control studies involving 2,593 cases of NTDs and 45,100 controls were included for analysis. Findings from our study showed that paternal smoking was significantly associated with risk of total NTDs (odds ratio [OR] = 1.68; 95% confidence interval (CI): 1.48-1.92) and two subtypes including anencephaly (OR = 1.41; 95% CI: 1.06-1.86) and encephaloceles (OR = 2.90; 95% CI: 1.00-8.41). Additionally, a linear dose-response relationship between paternal smoking and risk of NTDs was observed, which indicated that the risk of NTDs in offspring was significantly increased by 45% (OR = 1.45, 95% CI: 1.14-1.84) for each increment of half a pack of cigarettes per day. Sensitivity analyses yielded consistent results. No evidence of publication bias was found.

CONCLUSIONS

Paternal smoking is significantly associated with the risk of NTDs in offspring. Therefore, it should be recommended that fathers quit smoking before pregnancy to prevent NTDs in offspring.