Association of Preconception Paternal Alcohol Consumption With Increased Fetal Birth Defect Risk | Congenital Defects | JAMA Pediatrics | JAMA Network
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Figure.  Enrollment of the Participating Couples
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
Risk of Birth Defects Associated With Paternal Alcohol Consumption Before Conception
1.
Lees  B, Mewton  L, Jacobus  J,  et al.  Association of prenatal alcohol exposure with psychological, behavioral, and neurodevelopmental outcomes in children from the Adolescent Brain Cognitive Development study.   Am J Psychiatry. 2020;177(11):1060-1072. doi:10.1176/appi.ajp.2020.20010086PubMedGoogle ScholarCrossref
2.
Denny  CH, Acero  CS, Naimi  TS, Kim  SY.  Consumption of alcohol beverages and binge drinking among pregnant women aged 18-44 years—United States, 2015-2017.   MMWR Morb Mortal Wkly Rep. 2019;68(16):365-368. doi:10.15585/mmwr.mm6816a1PubMedGoogle ScholarCrossref
3.
Salas-Huetos  A, Bulló  M, Salas-Salvadó  J.  Dietary patterns, foods and nutrients in male fertility parameters and fecundability: a systematic review of observational studies.   Hum Reprod Update. 2017;23(4):371-389. doi:10.1093/humupd/dmx006PubMedGoogle ScholarCrossref
4.
Ethen  MK, Ramadhani  TA, Scheuerle  AE,  et al; National Birth Defects Prevention Study.  Alcohol consumption by women before and during pregnancy.   Matern Child Health J. 2009;13(2):274-285. doi:10.1007/s10995-008-0328-2PubMedGoogle ScholarCrossref
5.
D’Angelo  D, Williams  L, Morrow  B,  et al; Centers for Disease Control and Prevention (CDC).  Preconception and interconception health status of women who recently gave birth to a live-born infant—Pregnancy Risk Assessment Monitoring System (PRAMS), United States, 26 reporting areas, 2004.   MMWR Surveill Summ. 2007;56(10):1-35.PubMedGoogle Scholar
6.
Zhou  Q, Acharya  G, Zhang  S, Wang  Q, Shen  H, Li  X.  A new perspective on universal preconception care in China.   Acta Obstet Gynecol Scand. 2016;95(4):377-381. doi:10.1111/aogs.12865PubMedGoogle ScholarCrossref
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    Research Letter
    April 19, 2021

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

    Author Affiliations
    • 1Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China
    • 2Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai, China
    • 3Department of Maternal and Child Health, National Health and Family Planning Commission of the People´s Republic of China, Beijing, China
    JAMA Pediatr. 2021;175(7):742-743. doi:10.1001/jamapediatrics.2021.0291

    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.

    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.

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    Article Information

    Accepted for Publication: February 9, 2021.

    Published Online: April 19, 2021. doi:10.1001/jamapediatrics.2021.0291

    Correction: This article was corrected on May 28, 2021, to fix the number of couples classified as having paternal alcohol consumption.

    Corresponding Author: Xiaotian Li, MD, PhD, Obstetrics and Gynecology Hospital of Fudan University, No. 419 Fangxie Rd, Shanghai 200011, China (xiaotianli555@163.com).

    Author Contributions: Dr Zhou and Li had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

    Study concept and design: Zhou, Li.

    Acquisition, analysis, or interpretation of data: All authors.

    Drafting of the manuscript: Zhou, Song, Li.

    Critical revision of the manuscript for important intellectual content: Zhou, Chen, Wang, Shen, Zhang, Li.

    Statistical analysis: Zhou, Song, Chen, Li.

    Obtained funding: Zhang.

    Administrative, technical, or material support: Wang, Shen, Zhang.

    Study supervision: Zhou, Chen, Li.

    Conflict of Interest Disclosures: None reported.

    Funding/Support: This study was funded by Chinese Association of Maternal and Child Health Studies grant AMCHS-2014-4 for the design and conduct of the study.

    Role of the Funder/Sponsor: The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

    Additional Contributions: We thank Jian-Zhong Sheng, PhD (Department of Pathology and Pathophysiology, School of Medicine, Zhejiang University, Hangzhou, China), for editing assistance. We thank the health workers in the 220 counties of the 31 provinces for their strong collaboration and great efforts made as part of the National Free Preconception Health Examination Project. Dr Sheng was not compensated for his work.

    References
    1.
    Lees  B, Mewton  L, Jacobus  J,  et al.  Association of prenatal alcohol exposure with psychological, behavioral, and neurodevelopmental outcomes in children from the Adolescent Brain Cognitive Development study.   Am J Psychiatry. 2020;177(11):1060-1072. doi:10.1176/appi.ajp.2020.20010086PubMedGoogle ScholarCrossref
    2.
    Denny  CH, Acero  CS, Naimi  TS, Kim  SY.  Consumption of alcohol beverages and binge drinking among pregnant women aged 18-44 years—United States, 2015-2017.   MMWR Morb Mortal Wkly Rep. 2019;68(16):365-368. doi:10.15585/mmwr.mm6816a1PubMedGoogle ScholarCrossref
    3.
    Salas-Huetos  A, Bulló  M, Salas-Salvadó  J.  Dietary patterns, foods and nutrients in male fertility parameters and fecundability: a systematic review of observational studies.   Hum Reprod Update. 2017;23(4):371-389. doi:10.1093/humupd/dmx006PubMedGoogle ScholarCrossref
    4.
    Ethen  MK, Ramadhani  TA, Scheuerle  AE,  et al; National Birth Defects Prevention Study.  Alcohol consumption by women before and during pregnancy.   Matern Child Health J. 2009;13(2):274-285. doi:10.1007/s10995-008-0328-2PubMedGoogle ScholarCrossref
    5.
    D’Angelo  D, Williams  L, Morrow  B,  et al; Centers for Disease Control and Prevention (CDC).  Preconception and interconception health status of women who recently gave birth to a live-born infant—Pregnancy Risk Assessment Monitoring System (PRAMS), United States, 26 reporting areas, 2004.   MMWR Surveill Summ. 2007;56(10):1-35.PubMedGoogle Scholar
    6.
    Zhou  Q, Acharya  G, Zhang  S, Wang  Q, Shen  H, Li  X.  A new perspective on universal preconception care in China.   Acta Obstet Gynecol Scand. 2016;95(4):377-381. doi:10.1111/aogs.12865PubMedGoogle ScholarCrossref
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