Maternal alcoholic consumption during pregnancy and the risk of childhood cancer in offspring: a systematic review and meta-analysis_Chinese Journal of Evidence-Based Medicine

Authors：

HUANG Danqi ¹ , LIU Jingyi ¹ , XIONG Wei ² , WANG Huilin ¹ , YANG Min ³ , WANG Quan ⁴ , ZHENG Bobo ⁵ , TIAN Jinhui ^6,7 ,  YUAN Jinqiu ⁸ ,  LI Jiang ¹ ,  ZHAI Jingbo ⁹

1. Office for Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, P. R. China;
2. Department of Gynecology Endocrine&Reproductive Center, National Clinical Research Center for Obstetric&Gynecologic Diseases Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Peking Union Medical College/Chinese Academy of Medical Sciences, Beijing 100730, P. R. China;
3. Comprehensive Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital. Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, P. R. China;
4. Ambulatory Surgery Center of Xijing Hospital, Fourth Military Medical University, Xi’an 710068, P. R. China;
5. Department of General Surgery, Shaanxi Provincial People’ s Hospital, Xi'an 710068, P. R. China;
6. Evidence-Based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, P. R. China;
7. Key Laboratory of Evidence-Based Medicine and Knowledge Translation of Gansu Province, Lanzhou University, Lanzhou 730000, P. R. China;
8. Clinical Research Center, the Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen 518107, P. R. China;
9. School of Public Health, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, P. R. China;

Corresponding author：

YUAN Jinqiu, Email: yuanjq5@mail.sysu.edu.cn; LI Jiang, Email: lij@cicams.ac.cn; ZHAI Jingbo, Email: zhaijingbo@foxmail.com

Keywords：

Pregnancy; Alcohol drinking; Childhood tumors; Meta-analysis

DOI：

10.7507/1672-2531.202412165

Video：

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Objective To systematically review the relationship between maternal alcoholic consumption during pregnancy and the occurrence of childhood cancer in offspring. Methods PubMed, Embase, Web of Science, Cochrane library, CNKI, WanFang, VIP, and CBM databases were electronically searched to obtain related case-control and cohort studies from inception to December 2024. Two reviewers independently screened articles, extracted data and assessed the risk of bias of the included articles. Meta-analysis was performed by using the RevMan 5.4 software. Results A total of 18 articles involving 9 childhood tumors' outcome were included. The results of meta-analysis showed that compared with women who never drink alcohol during pregnancy, alcoholic consumption during pregnancy increased the incidence risk of childhood cancer by 13% (OR=1.13, 95%CI 1.01 to 1.26, P=0.040). Subgroup analysis showed that alcoholic consumption during pregnancy significantly increased the incidence risk of acute leukemia (OR=1.17, 95%CI 1.06 to 1.30, P=0.002) and acute lymphocytic leukemia (OR=1.23, 95%CI 1.02 to 1.48, P=0.030). We conducted further meta-analysis involving articles with better control of confounding factors, and found that alcoholic consumption during pregnancy increased the risk of childhood acute myeloid leukaemia (OR=1.38, 95%CI 1.00 to 1.90, P=0.050). Conclusion The current evidence suggests that alcoholic consumption during pregnancy significantly increases the incidence risk of childhood cancer in offspring, particularly acute leukemia and acute lymphocytic leukemia. As for childhood cancer prevention, it is of great practical significance to formulate and implement the publicity and education program for pregnant women to abstain from alcohol. Due to the limited quantity and quality of the included articles, more high-quality birth cohort studies are needed to verify the above conclusion.

1.	Jin Y, Lyu Q. Basic research in childhood cancer: progress and future directions in China. Cancer Lett, 2020, 495: 156-164.
2.	GBD 2017 Childhood Cancer Collaborators. The global burden of childhood and adolescent cancer in 2017: an analysis of the global burden of disease study 2017. Lancet Oncol, 2019, 20(9): 1211-1225.
3.	Zhu B, Wu X, An W, et al. The systematic analysis and 10-year prediction on disease burden of childhood cancer in China. Front Public Health, 2022, 10: 908955.
4.	Ni X, Li Z, Li X, et al. Socioeconomic inequalities in cancer incidence and access to health services among children and adolescents in China: a cross-sectional study. Lancet, 2022, 400(10357): 1020-1032.
5.	Kattner P, Strobel H, Khoshnevis N, et al. Compare and contrast: pediatric cancer versus adult malignancies. Cancer Metastasis Rev, 2019, 38(4): 673-682.
6.	Hoang TT, Scheurer ME, Lupo PJ. Overview of the etiology of childhood cancer and future directions. Curr Opin Pediatr, 2025, 37(1): 59-66.
7.	Siegel DA, King JB, Lupo PJ, et al. Counts, incidence rates, and trends of pediatric cancer in the United States, 2003-2019. J Natl Cancer Inst, 2023, 115(11): 1337-1354.
8.	Navarrete-Meneses MDP, Salas-Labadía C, Gómez-Chávez F, et al. Environmental pollution and risk of childhood cancer: a scoping review of evidence from the last decade. Int J Mol Sci, 2024, 25(6): 3284.
9.	Lange S, Probst C, Rehm J, et al. Prevalence of binge drinking during pregnancy by country and World Health Organization region: systematic review and meta-analysis. Reprod Toxicol, 2017, 73: 214-221.
10.	Bestry M, Larcombe AN, Kresoje N, et al. Early moderate prenatal alcohol exposure and maternal diet impact offspring DNA methylation across species. Elife, 2024, 12: RP92135.
11.	Gutherz OR, Deyssenroth M, Li Q, et al. Potential roles of imprinted genes in the teratogenic effects of alcohol on the placenta, somatic growth, and the developing brain. Exp Neurol, 2022, 347: 113919.
12.	Orsi L, Rudant J, Ajrouche R, et al. Parental smoking, maternal alcohol, coffee and tea consumption during pregnancy, and childhood acute leukemia: the ESTELLE study. Cancer Causes Control, 2015, 26(7): 1003-1017.
13.	Bailey HD, Lacour B, Guerrini-Rousseau L, et al. Parental smoking, maternal alcohol, coffee and tea consumption and the risk of childhood brain tumours: the ESTELLE and ESCALE studies (SFCE, France). Cancer Causes Control, 2017, 28(7): 719-732.
14.	Karalexi MA, Katsimpris A, Panagopoulou P, et al. Maternal lifestyle factors and risk of neuroblastoma in the offspring: a meta-analysis including Greek NARECHEM-ST primary data. Cancer Epidemiol, 2022, 77: 102055.
15.	Karalexi MA, Dessypris N, Clavel J, et al. Coffee and tea consumption during pregnancy and risk of childhood acute myeloid leukemia: a Childhood Leukemia International Consortium (CLIC) study. Cancer Epidemiol, 2019, 62: 101581.
16.	Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol, 2010, 25(9): 603-605.
17.	Menegaux F, Ripert M, Hémon D, et al. Maternal alcohol and coffee drinking, parental smoking and childhood leukaemia: a French population-based case-control study. Paediatr Perinat Epidemiol, 2007, 21(4): 293-299.
18.	Shu XO, Ross JA, Pendergrass TW, et al. Parental alcohol consumption, cigarette smoking, and risk of infant leukemia: a Childrens Cancer Group study. J Natl Cancer Inst, 1996, 88(1): 24-31.
19.	MacArthur AC, McBride ML, Spinelli JJ, et al. Risk of childhood leukemia associated with parental smoking and alcohol consumption prior to conception and during pregnancy: the cross-Canada childhood leukemia study. Cancer Causes Control, 2008, 19(3): 283-295.
20.	Bonaventure A, Rudant J, Goujon-Bellec S, et al. Childhood acute leukemia, maternal beverage intake during pregnancy, and metabolic polymorphisms. Cancer Causes Control, 2013, 24(4): 783-793.
21.	Clavel J, Bellec S, Rebouissou S, et al. Childhood leukaemia, polymorphisms of metabolism enzyme genes, and interactions with maternal tobacco, coffee and alcohol consumption during pregnancy. Eur J Cancer Prev, 2005, 14(6): 531-540.
22.	van Steensel-Moll HA, Valkenburg HA, Vandenbroucke JP, et al. Are maternal fertility problems related to childhood leukaemia. Int J Epidemiol, 1985, 14(4): 555-559.
23.	Infante-Rivard C, Krajinovic M, Labuda D, et al. Childhood acute lymphoblastic leukemia associated with parental alcohol consumption and polymorphisms of carcinogen-metabolizing genes. Epidemiology, 2002, 13(3): 277-281.
24.	Rudant J, Menegaux F, Leverger G, et al. Childhood hematopoietic malignancies and parental use of tobacco and alcohol: the ESCALE study (SFCE). Cancer Causes Control, 2008, 19(10): 1277-1290.
25.	Ferreira JD, Couto AC, Emerenciano M, et al. Maternal alcohol consumption during pregnancy and early age leukemia risk in Brazil. Biomed Res Int, 2015, 2015: 732495.
26.	Shu XO, Linet MS, Steinbuch M, et al. Breast-feeding and risk of childhood acute leukemia. J Natl Cancer Inst, 1999, 91(20): 1765-1772.
27.	Menegaux F, Steffen C, Bellec S, et al. Maternal coffee and alcohol consumption during pregnancy, parental smoking and risk of childhood acute leukaemia. Cancer Detect Prev, 2005, 29(6): 487-493.
28.	Plichart M, Menegaux F, Lacour B, et al. Parental smoking, maternal alcohol, coffee and tea consumption during pregnancy and childhood malignant central nervous system tumours: the ESCALE study (SFCE). Eur J Cancer Prev, 2008, 17(4): 376-383.
29.	Rios P, Bailey HD, Poulalhon C, et al. Parental smoking, maternal alcohol consumption during pregnancy and the risk of neuroblastoma in children. A pooled analysis of the ESCALE and ESTELLE French studies. Int J Cancer, 2019, 145(11): 2907-2916.
30.	Rios P, Bauer H, Schleiermacher G, et al. Environmental exposures related to parental habits in the perinatal period and the risk of Wilms' tumor in children. Cancer Epidemiol, 2020, 66: 101706.
31.	Johnson KJ, Williams KS, Ross JA, et al. Parental tobacco and alcohol use and risk of hepatoblastoma in offspring: a report from the children's oncology group. Cancer Epidemiol Biomarkers Prev, 2013, 22(10): 1837-1843.
32.	刘艳雪, 薛伟, 孙俊威. 儿童急性淋巴细胞白血病与危险环境暴露因素的相关性研究. 医学临床研究, 2024, 41(7): 1072-1074.
33.	Krewski D, Rice JM, Bird M, et al. Concordance between sites of tumor development in humans and in experimental animals for 111 agents that are carcinogenic to humans. J Toxicol Environ Health B Crit Rev, 2019, 22(7-8): 203-236.
34.	Zeng X, Cai Y, Wu M, et al. An overview of current advances in perinatal alcohol exposure and pathogenesis of fetal alcohol spectrum disorders. J Neurodev Disord, 2024, 16(1): 20.
35.	Infante-Rivard C, El-Zein M. Parental alcohol consumption and childhood cancers: a review. J Toxicol Environ Health B Crit Rev, 2007, 10(1-2): 101-129.
36.	Karalexi MA, Dessypris N, Thomopoulos TP, et al. Parental alcohol consumption and risk of leukemia in the offspring: a systematic review and meta-analysis. Eur J Cancer Prev, 2017, 26(5): 433-441.
37.	Hu Z, Ye J, Shi S, et al. Maternal smoking, consumption of alcohol, and caffeinated beverages during pregnancy and the risk of childhood brain tumors: a meta-analysis of observational studies. BMC Public Health, 2024, 24(1): 1238.
38.	Glynn LM, Liu SR, Lucas CT, et al. Leveraging the science of early life predictability to inform policies promoting child health. Dev Cogn Neurosci, 2024, 69: 101437.

1. Jin Y, Lyu Q. Basic research in childhood cancer: progress and future directions in China. Cancer Lett, 2020, 495: 156-164.
2. GBD 2017 Childhood Cancer Collaborators. The global burden of childhood and adolescent cancer in 2017: an analysis of the global burden of disease study 2017. Lancet Oncol, 2019, 20(9): 1211-1225.
3. Zhu B, Wu X, An W, et al. The systematic analysis and 10-year prediction on disease burden of childhood cancer in China. Front Public Health, 2022, 10: 908955.
4. Ni X, Li Z, Li X, et al. Socioeconomic inequalities in cancer incidence and access to health services among children and adolescents in China: a cross-sectional study. Lancet, 2022, 400(10357): 1020-1032.
5. Kattner P, Strobel H, Khoshnevis N, et al. Compare and contrast: pediatric cancer versus adult malignancies. Cancer Metastasis Rev, 2019, 38(4): 673-682.
6. Hoang TT, Scheurer ME, Lupo PJ. Overview of the etiology of childhood cancer and future directions. Curr Opin Pediatr, 2025, 37(1): 59-66.
7. Siegel DA, King JB, Lupo PJ, et al. Counts, incidence rates, and trends of pediatric cancer in the United States, 2003-2019. J Natl Cancer Inst, 2023, 115(11): 1337-1354.
8. Navarrete-Meneses MDP, Salas-Labadía C, Gómez-Chávez F, et al. Environmental pollution and risk of childhood cancer: a scoping review of evidence from the last decade. Int J Mol Sci, 2024, 25(6): 3284.
9. Lange S, Probst C, Rehm J, et al. Prevalence of binge drinking during pregnancy by country and World Health Organization region: systematic review and meta-analysis. Reprod Toxicol, 2017, 73: 214-221.
10. Bestry M, Larcombe AN, Kresoje N, et al. Early moderate prenatal alcohol exposure and maternal diet impact offspring DNA methylation across species. Elife, 2024, 12: RP92135.
11. Gutherz OR, Deyssenroth M, Li Q, et al. Potential roles of imprinted genes in the teratogenic effects of alcohol on the placenta, somatic growth, and the developing brain. Exp Neurol, 2022, 347: 113919.
12. Orsi L, Rudant J, Ajrouche R, et al. Parental smoking, maternal alcohol, coffee and tea consumption during pregnancy, and childhood acute leukemia: the ESTELLE study. Cancer Causes Control, 2015, 26(7): 1003-1017.
13. Bailey HD, Lacour B, Guerrini-Rousseau L, et al. Parental smoking, maternal alcohol, coffee and tea consumption and the risk of childhood brain tumours: the ESTELLE and ESCALE studies (SFCE, France). Cancer Causes Control, 2017, 28(7): 719-732.
14. Karalexi MA, Katsimpris A, Panagopoulou P, et al. Maternal lifestyle factors and risk of neuroblastoma in the offspring: a meta-analysis including Greek NARECHEM-ST primary data. Cancer Epidemiol, 2022, 77: 102055.
15. Karalexi MA, Dessypris N, Clavel J, et al. Coffee and tea consumption during pregnancy and risk of childhood acute myeloid leukemia: a Childhood Leukemia International Consortium (CLIC) study. Cancer Epidemiol, 2019, 62: 101581.
16. Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol, 2010, 25(9): 603-605.
17. Menegaux F, Ripert M, Hémon D, et al. Maternal alcohol and coffee drinking, parental smoking and childhood leukaemia: a French population-based case-control study. Paediatr Perinat Epidemiol, 2007, 21(4): 293-299.
18. Shu XO, Ross JA, Pendergrass TW, et al. Parental alcohol consumption, cigarette smoking, and risk of infant leukemia: a Childrens Cancer Group study. J Natl Cancer Inst, 1996, 88(1): 24-31.
19. MacArthur AC, McBride ML, Spinelli JJ, et al. Risk of childhood leukemia associated with parental smoking and alcohol consumption prior to conception and during pregnancy: the cross-Canada childhood leukemia study. Cancer Causes Control, 2008, 19(3): 283-295.
20. Bonaventure A, Rudant J, Goujon-Bellec S, et al. Childhood acute leukemia, maternal beverage intake during pregnancy, and metabolic polymorphisms. Cancer Causes Control, 2013, 24(4): 783-793.
21. Clavel J, Bellec S, Rebouissou S, et al. Childhood leukaemia, polymorphisms of metabolism enzyme genes, and interactions with maternal tobacco, coffee and alcohol consumption during pregnancy. Eur J Cancer Prev, 2005, 14(6): 531-540.
22. van Steensel-Moll HA, Valkenburg HA, Vandenbroucke JP, et al. Are maternal fertility problems related to childhood leukaemia. Int J Epidemiol, 1985, 14(4): 555-559.
23. Infante-Rivard C, Krajinovic M, Labuda D, et al. Childhood acute lymphoblastic leukemia associated with parental alcohol consumption and polymorphisms of carcinogen-metabolizing genes. Epidemiology, 2002, 13(3): 277-281.
24. Rudant J, Menegaux F, Leverger G, et al. Childhood hematopoietic malignancies and parental use of tobacco and alcohol: the ESCALE study (SFCE). Cancer Causes Control, 2008, 19(10): 1277-1290.
25. Ferreira JD, Couto AC, Emerenciano M, et al. Maternal alcohol consumption during pregnancy and early age leukemia risk in Brazil. Biomed Res Int, 2015, 2015: 732495.
26. Shu XO, Linet MS, Steinbuch M, et al. Breast-feeding and risk of childhood acute leukemia. J Natl Cancer Inst, 1999, 91(20): 1765-1772.
27. Menegaux F, Steffen C, Bellec S, et al. Maternal coffee and alcohol consumption during pregnancy, parental smoking and risk of childhood acute leukaemia. Cancer Detect Prev, 2005, 29(6): 487-493.
28. Plichart M, Menegaux F, Lacour B, et al. Parental smoking, maternal alcohol, coffee and tea consumption during pregnancy and childhood malignant central nervous system tumours: the ESCALE study (SFCE). Eur J Cancer Prev, 2008, 17(4): 376-383.
29. Rios P, Bailey HD, Poulalhon C, et al. Parental smoking, maternal alcohol consumption during pregnancy and the risk of neuroblastoma in children. A pooled analysis of the ESCALE and ESTELLE French studies. Int J Cancer, 2019, 145(11): 2907-2916.
30. Rios P, Bauer H, Schleiermacher G, et al. Environmental exposures related to parental habits in the perinatal period and the risk of Wilms' tumor in children. Cancer Epidemiol, 2020, 66: 101706.
31. Johnson KJ, Williams KS, Ross JA, et al. Parental tobacco and alcohol use and risk of hepatoblastoma in offspring: a report from the children's oncology group. Cancer Epidemiol Biomarkers Prev, 2013, 22(10): 1837-1843.
32. 刘艳雪, 薛伟, 孙俊威. 儿童急性淋巴细胞白血病与危险环境暴露因素的相关性研究. 医学临床研究, 2024, 41(7): 1072-1074.
33. Krewski D, Rice JM, Bird M, et al. Concordance between sites of tumor development in humans and in experimental animals for 111 agents that are carcinogenic to humans. J Toxicol Environ Health B Crit Rev, 2019, 22(7-8): 203-236.
34. Zeng X, Cai Y, Wu M, et al. An overview of current advances in perinatal alcohol exposure and pathogenesis of fetal alcohol spectrum disorders. J Neurodev Disord, 2024, 16(1): 20.
35. Infante-Rivard C, El-Zein M. Parental alcohol consumption and childhood cancers: a review. J Toxicol Environ Health B Crit Rev, 2007, 10(1-2): 101-129.
36. Karalexi MA, Dessypris N, Thomopoulos TP, et al. Parental alcohol consumption and risk of leukemia in the offspring: a systematic review and meta-analysis. Eur J Cancer Prev, 2017, 26(5): 433-441.
37. Hu Z, Ye J, Shi S, et al. Maternal smoking, consumption of alcohol, and caffeinated beverages during pregnancy and the risk of childhood brain tumors: a meta-analysis of observational studies. BMC Public Health, 2024, 24(1): 1238.
38. Glynn LM, Liu SR, Lucas CT, et al. Leveraging the science of early life predictability to inform policies promoting child health. Dev Cogn Neurosci, 2024, 69: 101437.

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Latest ArticlesMaternal alcoholic consumption during pregnancy and the risk of childhood cancer in offspring: a systematic review and meta-analysis

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