Association of Preconception Paternal Alcohol Consumption With Increased Fetal Birth Defect Risk

Abstract

This cohort study investigates the association of paternal drinking before pregnancy with risk of fetal birth defect.

Maternal alcohol consumption is closely associated with alcohol-related birth defects and neurodevelopment,¹ and therefore, it is widely recommended for women to quit consuming alcohol before and during pregnancy.² Paternal alcohol exposure biologically increases the risk of genetic and epigenetic sperm abnormalities.³ 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.^4,5 Our 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,^4,5 suggesting minor effects of maternal alcohol consumption on offspring, and the Chinese population is a good model to analyze the association of preconception paternal drinking and birth defect. Thus, this study aimed to investigate the association between paternal drinking 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 2012.⁶ 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 drinking 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. We used R version 4.0.2 (The R Foundation) in our 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, 164 151 couples (31.0%) were classified as having paternal alcohol consumption and 17 491 couples (3.3%) as having maternal consumption. A total of 609 birth defects were reported (Figure). 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, we 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) (Table). Additionally, specific birth defects were of no significance considering the limited number of cases.

Figure. Enrollment of the Participating Couples.

NFPHEP indicates National Free Preconception Health Examination Project.

Table. Risk of Birth Defects Associated With Paternal Alcohol Consumption Before Conception.

Outcome	Fetal defect, No.	Total participants (N = 529 090)			Case-matched participants (n = 1218)
		OR (95% CI)a		P value	OR (95% CI)a		P value
		Crude	Adjustedb		Crude	Adjustedb
Total birth defects	609	1.51 (1.28-1.77)	1.35 (1.14-1.59)	<.001	1.47 (1.16-1.86)	1.38 (1.08-1.77)	.01
Congenital heart disease	148	1.47 (1.06-2.05)	1.29 (0.92-1.81)	.14	1.21 (0.85-1.72)	1.13 (0.78-1.62)	.53
Limb anomalies	54	1.02 (0.58-1.81)	0.91 (0.5-1.63)	.74	0.81 (0.45-1.46)	0.77 (0.41-1.41)	.39
Clefts	105	1.8 (1.23-2.65)	1.55 (1.04-2.3)	.03	1.50 (1-20.240)	1.50 (0.98-2.28)	.06
Digestive tract anomalies	42	1.67 (0.90-3.07)	1.38 (0.73-2.58)	.32	1.35 (0.72-2.52)	1.27 (0.66-2.45)	.48
Gastroschisis	82	1.09 (0.69-1.73)	1.01 (0.63-1.62)	.97	0.87 (0.54-1.39)	0.89 (0.54-1.45)	.63
Neural tube defects	125	1.21 (0.84-1.74)	1.16 (0.8-1.69)	.44	0.96 (0.65-1.42)	0.96 (0.64-1.44)	.86

Abbreviation: OR, odd ratio.

^aThe reference population was couples with no alcohol consumption before conception.

^bAdjusted for maternal age, maternal anemia, maternal adverse pregnancy, maternal birth defects, folic acid timing, maternal exposure to harmful substances, and paternal smoking after conception.

Discussion

We first provided epidemiological evidence that preconception paternal alcohol consumption may increase the risks of birth defects in offspring by affecting sperm cells. Our finding suggests that future fathers should be encouraged to modify their alcohol intake before conceiving to reduce fetal risk, considering a paternal drinking rate of 31.0% 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, our study provides evidence for clinical recommendation and public health strategy making to improve offspring life quality.