Analysis of Preconception Paternal Smoking and Neonatal Outcomes

This cohort study evaluates the associations of preconception paternal smoking with neonatal outcomes.


Introduction
There is growing emphasis on optimizing maternal health before conception to improve offspring outcomes, as per the Developmental Origins of Health and Disease paradigm. 1However, there has been little analogous consideration of paternal health at conception, despite growing evidence linking paternal exposures to offspring health. 2 Indeed, the emerging Paternal Origins of Health and Disease (POHaD) paradigm posits that factors, such as paternal age and weight, can modify the sperm epigenome, yielding epigenetic changes that are maintained in the offspring, in whom they may affect gene regulation and physiology. 2 In this context, smoking is an exposure of interest because maternal smoking in pregnancy is associated with placental DNA methylation and adverse neonatal outcomes, such as low birth weight and preterm birth. 3Moreover, tobacco smoke may affect the sperm genome and epigenome. 4However, little is known about the potential impact of preconception paternal smoking.Thus, we sought to prospectively evaluate the associations of preconception paternal smoking with neonatal outcomes.

Methods
This cohort study was approved by the research ethics boards of Central South University in Changsha, China, Ottawa Hospital Research Institute in Ottawa, Canada, and Mount Sinai Hospital in Toronto, Canada.All participants provided written informed consent.This study has been reported in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline.
In this prospective preconception observational cohort study, we recruited newly married couples in Liuyang, China, that intended to conceive within 6 months.The protocol has been described in detail. 5,6Between February 1, 2009, and November 4, 2015, both partners underwent baseline (pregravid) assessment and were monitored throughout pregnancy.Associations of paternal smoking with birth weight and categorical neonatal outcomes were assessed by multiple linear regression and logistic regression analyses, respectively, with P < .05considered significant.
We used t tests to evaluate the P values for the multiple linear regression analyses and χ 2 tests to calculate P values for multiple logistic regression analyses.All tests were 2-sided, and all analyses were performed using the Statistical Analysis System version 9.4 (SAS Institute).Statistical analyses were done between January 2021 and August 2021.

Results
The study population consisted of 1174 couples who underwent baseline assessment at median of 23.3 (IQR, 5.6-65.6)weeks before a singleton pregnancy.The mean (SD) age of the sample was 24 (3.0) years for women and 26 (3.5) years for men.At preconception assessment, 538 male partners (45.8%) reported currently smoking, in contrast to only 5 women (0.4%) doing so.The Table shows pregravid characteristics and delivery outcomes of the couples, stratified into 3 groups based on the degree of paternal smoking before conception: none (636 [54.2%]); 1 to 10 cigarettes per day  inclusive (343 [29.2%]); and more than 10 cigarettes per day (195 [16.6%]).Birth weight and length of gestation did not differ between the groups.
In the multiple linear regression analysis, positive independent factors associated with birth weight were maternal pregravid body mass index (BMI), calculated as weight in kilograms divided by height in meters squared, (regression coefficient, 39.

Discussion
Previous studies have focused on paternal smoking during pregnancy as an indicator of passive maternal exposure rather than prior to conception as per the POHaD paradigm.In contrast, we have prospectively evaluated paternal smoking before conception in a population showing marked disparity in smoking rates between women and men, which enables isolated evaluation of paternal smoking.This study was limited because maternal passive smoke exposure was not assessed; however, our prospective evaluation of paternal smoking before conception does not reveal associations with birth weight or adverse neonatal outcomes at delivery.These findings cannot rule out the possibility that POHaD programming effects of preconception paternal smoking may yet emerge later in life.

Figure .
Figure.Adjusted Odds Ratios for Association of Pregravid Paternal Smoking of 1 to 10 Cigarettes Per Day and More Than 10 Cigarettes Per Day With Adverse Delivery Outcomes Favors decreased risk Favors increased risk

Table .
Characteristics of Study Population Before Pregnancy and at Delivery, Stratified Into 3 Strata of Paternal Smoking Prior to Conception