Association between preconception paternal smoking and birth defects in offspring: evidence from the database of the National Free Preconception Health Examination Project in China

Abstract

Objective To clarify whether preconception paternal smoking has any adverse effects on the offspring. Design Prospective, population‐based study. Setting Preconception registry data from the National Free Preconception Health Examination Project. Population or sample Couples planning pregnancy, with complete information on preconception paternal smoking behaviour and pregnancy outcomes. Methods The effect of questionnaire‐based paternal smoking behaviour during preconception and pregnancy was assessed via logistic regression. Additionally, we performed a 1:1 case–control (birth defects versus normal pregnancy) analysis, matched for maternal province, folic acid supplementation and paternal alcohol consumption. Main outcome measures Risk of birth defects in offspring. Results In total, 566 439 couples with complete information on preconception paternal smoking behaviour and pregnancy outcomes were enrolled. The preconception paternal smoking rate was 28.7% (162 482) overall: 8.7% (49 303) stopped smoking, 13.3% (75 517) decreased their smoking, and 6.6% (37 662) continued smoking during early pregnancy. The risk of birth defects was higher in the continued‐smoking (P < .000, odds ratio [OR] 1.87, 95% CI 1.36–2.56) and decreased‐smoking groups (P = .007, OR 1.41, 95% CI 1.10–1.82). In the case–control analysis, infants whose fathers stopped (P = .003, OR 0.32, 95% CI 0.15–0.67) or decreased smoking (P = .000, OR 0.25, 95% CI 0.13–0.49) were at lower risk of congenital heart diseases, limb abnormalities, digestive tract anomalies and neural tube defects than those whose fathers continued smoking. Conclusion Preconception paternal smoking may be associated with congenital heart diseases, limb abnormalities and neural tube defects in the offspring. Changes in smoking behaviour may reduce this risk. Tweetable abstract This study suggests that preconception paternal smoking is associated with birth defects in offspring. Changes in smoking behaviour may reduce this risk.

Re: Association between preconception paternal smoking and birth defects in offspring: evidence from the database of the National Free Preconception Health Examination Project in China

“…We have read the commentary by Horne et al 1 and agree with the authors: placebocontrolled surgical trials for superficial peritoneal endometriosis (SPE) are needed. Such designs are the gold standard of testing treatment efficacy for chronic pain 2 and without placebo-control, it is ultimately unknown whether women with SPE are subjected to repeated surgeries that are not only unnecessary but also potentially harmful.…”

“…3 Further, placebo-controlled testing is required to ascertain that the therapeutic element or elements of surgery are responsible for the effect, particularly so when the effect is measured in patient-reported outcomes such as pain. 2,3 Second, while Horne et al 1 outline the problem of post-surgical pain in women with SPE, we believe more attention should be given to the women who develop neuropathic pain following surgery. Chronic post-surgical neuropathic pain (CPNP) is a serious complication that may amplify the patient's suffering, incur greater societal costs, and is difficult to treat.…”

“…First, when there is genuine doubt about the effect of a standard treatment (such as surgery for SPE, as described by Horne et al 1 ), placebo-controlled designs are needed to ascertain whether the treatment is effective. 2 For women with SPE, the placebo arm can be operationalised as a diagnostic laparoscopy without histology.…”

“…We would like to thank Wu and colleagues for their interesting comments. 1 The authors point out the key role of confounding factors such as paternal age for future interpretation when analysing the effect of paternal smoking on the risk of birth defects in offspring. 2 In their letter, they highlight the importance of paternal age in reproductive outcomes.…”

Evaluation of interactive effects between paternal alcohol consumption and paternal socioeconomic status and environmental exposures on congenital heart defects

“…However, the total response rate was over 70% and both the case and control groups had similar participation rates, which lessens this concern. To estimate potential selection bias, we compared paternal characteristics between controls and the general population in Guangdong province or China and found that most factors were comparable, especially paternal alcohol drinking rate (Wang et al, 2015), and paternal smoking rate (Zhou et al, 2020). To ensure complete ascertainment, we included all CHDs including live birth, fetal death, and still birth infants.…”