Association of Preconception Paternal Alcohol Consumption With Increased Fetal Birth Defect Risk
Summary
Introduction
Maternal alcohol consumption is closely associated with alcohol-related birth defects and neurodevelopment, and therefore, it is widely recommended for women to quit consuming alcohol before and during pregnancy. Paternal alcohol exposure biologically increases the risk of genetic and epigenetic sperm abnormalities. The epidemiological association is less evident and likely interfered with by maternal confounders, such as a maternal alcohol consumption rate as high as 30% in Western countries. A previous preconception care project showed that among Chinese married couples, who were a unique study population, nearly one-third of fathers and only 3% of mothers consumed alcohol before pregnancy, suggesting minor effects of maternal alcohol consumption on offspring, and the Chinese population is a good model to analyze the association of preconception paternal alcohol use and birth defect. Thus, this study aimed to investigate the association between paternal alcohol use before pregnancy and birth defects to provide supportive evidence for paternal alcohol cessation in preconception health care.
Methods
This prospective, population-based study used data from the National Free Preconception Health Examination Project in all 31 provinces of mainland China from April 2010 to December 2012. This project was approved by the Chinese Association of Maternal and Child Health Studies. Written informed consent was obtained from each participant. This study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline.
Couples planning a pregnancy within 6 months were included, and those with incomplete information regarding paternal alcohol consumption or pregnancy outcomes were excluded. Paternal alcohol consumption before conception was defined as at least 1 time using alcohol per week. Birth defects were reported by parents in the follow-up at 42 days after delivery. Logistic regression analysis and case-control analysis were conducted to minimize bias. Matching was based on maternal province of origin, folic acid supplementation, alcohol consumption, and paternal smoking behavior. Significance was set at a P value less than .05, and all P values were 2-tailed. The study used R version 4.0.2 (The R Foundation) in the analyses. Analyses began September 2020.
Results
Complete data of 529,090 couples with pregnancy outcomes and alcohol consumption behaviors were extracted for final analysis, and data were missing for 43,899 couples (8.3%). In total, 165,151 couples (31.2%) were classified has having paternal alcohol consumption and 17,491 couples (3.3%) as having maternal consumption. A total of 609 birth defects were reported. The paternal alcohol consumption rate was 40.4% (95% CI, 36.5-44.3) for couples with fetuses with birth defects and was 31.5% (95% CI, 27.8-35.2) for couples with fetuses without birth defects (difference, 8.9 percentage points; 95% CI, 6.6-11.2; P = .002). To minimize bias, this study adjusted for confounders, including maternal age, medical history, folic acid timing, exposure to harmful substances, maternal alcohol consumption, and paternal smoking. In the multiple logistic regression analyses, the risk of birth defects was higher among couples with paternal alcohol consumption (odds ratio [OR], 1.35; 95% CI, 1.14-1.59; P < .001), especially the risk of clefts (OR, 1.55; 95% CI, 1.04-2.30; P = .03). This association was confirmed by case-control analysis (OR, 1.38; 95% CI, 1.08-1.77; P = .01). Additionally, specific birth defects were of no significance considering the limited number of cases.
Discussion
This study first provided epidemiological evidence that preconception paternal alcohol consumption may increase the risks of birth defects in offspring by affecting sperm cells. The finding suggests that future fathers should be encouraged to modify their alcohol intake before conceiving to reduce fetal risk, considering a paternal alcohol use rate of 31.2% substantially elevated the risk of birth defects. Strengths of this study include the use of data from the Chinese National Free Preconception Health Examination Project, a 3.3% maternal alcohol consumption rate, adjusted potential baseline and clinical parameters, and matched known possible interfering factors, especially exact matching of maternal province of origin. A well-designed randomized clinical study of the effect of preconception paternal alcohol consumption on birth defects is difficult and seems impossible in the near future due to ethical considerations. This study was limited by lacking the exact amount of alcohol consumed, potential factors, proportion of missing data, and underestimated birth defects; nevertheless, the database used in the present study is still ideal for analyzing the association of paternal alcohol consumption with birth defects. Given the priority of preconception care, this study provides evidence for clinical recommendation and public health strategy making to improve offspring life quality.
Research in context
As Healthline reports, evidence suggests paternal alcohol use can cause birth defects by changing the shape, size, and motility of sperm which could alter the DNA that’s passed down to children.
This study found that birth defects were more common in babies whose fathers consumed alcohol before pregnancy compared to babies whose fathers did not. Overall, 609 total birth defects were reported, including congenital heart disease, limb anomalies, clefts, digestive tract anomalies, gastroschisis, and neural tube defects. Among the fathers who consumed alcohol, there were 363 birth defects. Among the fathers who did not consume alcohol, there were 246 birth defects.
There was a 35% greater chance of having a birth defect and a 55% chance of developing a cleft if the father regularly had alcohol once a week or more in the 6 months leading up to conception.
This study raises questions that maybe both partners should be equally responsible in terms of when they are planning to create the new life,” said Dr. Lubna Pal, a Yale Medicine reproductive endocrinologist and professor of obstetrics, gynecology, and reproductive services at Yale School of Medicine, as per, Healthline.
Dr. Lubna Pal, reproductive endocrinologist, Yale Medicine and professor of obstetrics, gynecology, and reproductive services, Yale School of Medicine
The study is important as historically expecting mothers are advised to refrain from alcohol use to reduce harm to the unborn child, but the same advise is not given to expecting fathers. This study shows that it is important for both expecting parents to be alcohol-free prior to conception to reduce risk to their unborn child.
