Preconception Paternal Smoking As a Risk Factor of Birth Defects in Offspring: Evidence from the Database of National Free Preconception Health Examination Project in China

Abstract

Background: The association between paternal smoking and birth defects in offspring was indicated. However, there lacks prospective evidence to recommend father smoking quit before pregnancy for eliminating birth defects risk in his offspring. This study aimed to investigate the effect of preconception paternal smoking on birth defects in offspring in a prospective population based study. Methods: We carried out a prospective, population-based study utilizing preconception registry data from National Free Preconception Health Examination Project during 2010-12, and a matched case control study (1:1) with birth defects and normal pregnancy by maternal province, supplement of folic acid matched, and paternal alcohol consumption as well. Findings: A total of 566439 couples with complete preconception father smoking behavior were enrolled. Total paternal smoking rate before conception was 28.7% (162482), among whom 8.7% (49303) stopped smoking, 13.3% (75517) decreased and 6.6% (37662) continued in early pregnancy. Logistic regression models were used to examine the association between birth defects and smoking behavior. Paternal continued smoking group (P=0.000, OR=1.868, 95% CI: 1.361-2.564) and pre-conception paternal decreased smoking group in early pregnancy (P=0.007, OR=1.414, 95% CI: 1.100-1.816) were at higher risk of birth defects, while there was no difference with those father quitting smoking compared to paternal never smoking group (P=0.407). In addition, preconception paternal smoking behavior change was associated with birth defects in offspring in matched case control analysis, compared to those fetus whose father continued smoked, the fetus whose father quitted (P=0.003, OR=0.316, 95% CI: 0.149-0.669) or decreased smoking (P=0.000, OR=0.250, 95% CI: 0.129-0.485) were at lower risk of birth defects, especially for congenital heart diseases, limb abnormalities, digestive tract anomalies and neural tube defects. Interpretation: Preconception paternal smoking demonstrated to be associated with birth defects including congenital heart diseases, limb abnormalities and neural tube defects. Preconception paternal smoking cessation should be strengthened for eliminating related birth defects as part of pregnancy education program before pregnancy. Funding Statement: Database reported in this publication was supported by Chinese government, a national nonprofit project which benefits rural reproductive aged population. This study was supported by Chinese association of maternal and child health studies. Declaration of Interests: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Zhang SK reports National Free Preconception Health Examination Project (NFPHEP) supported by Chinese government, a national nonprofit project which benefits rural reproductive aged population. No other disclosures were reported. Ethics Approval Statement: The Institutional Review Board of Chinese Association of Maternal and Child Health Studies approved the project, and written informed consent was obtained from the participants (IRB201001).