J Korean Med Sci.  2023 Apr;38(14):e111. 10.3346/jkms.2023.38.e111.

Maternal Polycystic Ovary Syndrome and the Risk of Early Childhood Obesity in Female Offspring: A Nationwide Population-Based Study

• Ryu KJ
• Wi WY
• Nam S
• Jeong HG
• Cho GJ
• Park H
• Kim T

• KMID: 2541551
• DOI: http://doi.org/10.3346/jkms.2023.38.e111

Abstract

Background
To investigate the relationship between polycystic ovary syndrome (PCOS) in Korean women and childhood growth and obesity of their offspring.
Methods
This longitudinal case-control study using the Korean National Health Insurance claims database and the National Health Screening Program for Infants and Children database included women who delivered singletons between January 2007 and December 2008. Offspring’s body mass index (BMI) measurements taken between 42 and 80 months of age were compared according to a maternal history of PCOS.
Results
Among a total of 131,805 participants, 1,213 women had a history of PCOS and 130,592 women did not. Female offspring aged 66–80 months born to women with PCOS had significantly higher BMI than those born to women without PCOS; there was no significant difference in that of male offspring regardless of maternal PCOS. In the generalized estimating equation and multivariable logistic regression analyses, the female offspring born to women with PCOS had a significantly higher risk of obesity during the age of 42–54 and 66–80 months (odds ratio [OR], 1.6; 95% confidence interval [CI], 1.09–2.21 and OR, 1.5; 95% CI, 1.05–2.15, respectively), than those born to women without PCOS, after adjusting for several confounding factors.
Conclusion
Maternal PCOS is independently associated with an increased incidence of childhood obesity in female offspring among Korean women. Women with PCOS should consider the risk of early childhood obesity in their daughters, even if they maintain a healthy weight themselves.

Keyword

Polycystic Ovary Syndrome; Offspring; Daughter; Obesity; Childhood

Figure

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  Fig. 1 A flowchart of the study.NHSP-IC = National Health Screening Program for Infants and Children, NHSE = National Health Screening Examination.

Reference

1. Ehrmann DA. Polycystic ovary syndrome. N Engl J Med. 2005; 352(12):1223–1236. PMID: 15788499.

2. Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil Steril. 2004; 81(1):19–25.

3. Teede HJ, Misso ML, Costello MF, Dokras A, Laven J, Moran L, et al. Recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome. Fertil Steril. 2018; 110(3):364–379. PMID: 30033227.

4. Ryu KJ, Kim MS, Kim HK, Kim YJ, Yi KW, Shin JH, et al. Risk of type 2 diabetes is increased in nonobese women with polycystic ovary syndrome: the National Health Insurance Service-National Sample Cohort Study. Fertil Steril. 2021; 115(6):1569–1575. PMID: 33509630.

5. Osibogun O, Ogunmoroti O, Michos ED. Polycystic ovary syndrome and cardiometabolic risk: Opportunities for cardiovascular disease prevention. Trends Cardiovasc Med. 2020; 30(7):399–404. PMID: 31519403.

6. Puttabyatappa M, Cardoso RC, Padmanabhan V. Effect of maternal PCOS and PCOS-like phenotype on the offspring’s health. Mol Cell Endocrinol. 2016; 435:29–39. PMID: 26639019.

7. Boomsma CM, Eijkemans MJ, Hughes EG, Visser GH, Fauser BC, Macklon NS. A meta-analysis of pregnancy outcomes in women with polycystic ovary syndrome. Hum Reprod Update. 2006; 12(6):673–683. PMID: 16891296.

8. Goodarzi MO, Dumesic DA, Chazenbalk G, Azziz R. Polycystic ovary syndrome: etiology, pathogenesis and diagnosis. Nat Rev Endocrinol. 2011; 7(4):219–231. PMID: 21263450.

9. Risal S, Pei Y, Lu H, Manti M, Fornes R, Pui HP, et al. Prenatal androgen exposure and transgenerational susceptibility to polycystic ovary syndrome. Nat Med. 2019; 25(12):1894–1904. PMID: 31792459.

10. Doherty DA, Newnham JP, Bower C, Hart R. Implications of polycystic ovary syndrome for pregnancy and for the health of offspring. Obstet Gynecol. 2015; 125(6):1397–1406. PMID: 26000511.

11. Wilde MA, Eising JB, Gunning MN, Koster MPH, Evelein AMV, Dalmeijer GW, et al. Cardiovascular and metabolic health of 74 children from women previously diagnosed with polycystic ovary syndrome in comparison with a population-based reference cohort. Reprod Sci. 2018; 25(10):1492–1500. PMID: 29320957.

12. Gunning MN, Sir Petermann T, Crisosto N, van Rijn BB, de Wilde MA, Christ JP, et al. Cardiometabolic health in offspring of women with PCOS compared to healthy controls: a systematic review and individual participant data meta-analysis. Hum Reprod Update. 2020; 26(1):103–117. PMID: 31867675.

13. Palomba S, de Wilde MA, Falbo A, Koster MP, La Sala GB, Fauser BC. Pregnancy complications in women with polycystic ovary syndrome. Hum Reprod Update. 2015; 21(5):575–592. PMID: 26117684.

14. Littlejohn EE, Weiss RE, Deplewski D, Edidin DV, Rosenfield R. Intractable early childhood obesity as the initial sign of insulin resistant hyperinsulinism and precursor of polycystic ovary syndrome. J Pediatr Endocrinol Metab. 2007; 20(1):41–51. PMID: 17315528.

15. He Y, Tian J, Blizzard L, Oddy WH, Dwyer T, Bazzano LA, et al. Associations of childhood adiposity with menstrual irregularity and polycystic ovary syndrome in adulthood: the Childhood Determinants of Adult Health Study and the Bogalusa Heart Study. Hum Reprod. 2020; 35(5):1185–1198. PMID: 32344436.

16. Finnbogadóttir SK, Glintborg D, Jensen TK, Kyhl HB, Nohr EA, Andersen M. Insulin resistance in pregnant women with and without polycystic ovary syndrome, and measures of body composition in offspring at birth and three years of age. Acta Obstet Gynecol Scand. 2017; 96(11):1307–1314. PMID: 28804876.

17. Bell GA, Sundaram R, Mumford SL, Park H, Broadney M, Mills JL, et al. Maternal polycystic ovarian syndrome and offspring growth: the upstate KIDS study. J Epidemiol Community Health. 2018; 72(9):852–855. PMID: 29789346.

18. Hanem LGE, Stridsklev S, Júlíusson PB, Salvesen Ø, Roelants M, Carlsen SM, et al. Metformin use in PCOS pregnancies increases the risk of offspring overweight at 4 years of age: follow-up of two RCTs. J Clin Endocrinol Metab. 2018; 103(4):1612–1621. PMID: 29490031.

19. Cho GJ, Kim HY, Park JH, Ahn KH, Hong SC, Oh MJ, et al. Prepregnancy liver enzyme levels and risk of preeclampsia in a subsequent pregnancy: a population-based cohort study. Liver Int. 2018; 38(5):949–954. PMID: 29094446.

20. Ravn P, Haugen AG, Glintborg D. Overweight in polycystic ovary syndrome. An update on evidence based advice on diet, exercise and metformin use for weight loss. Minerva Endocrinol. 2013; 38(1):59–76. PMID: 23435443.

21. Bell GA, Sundaram R, Mumford SL, Park H, Mills J, Bell EM, et al. Maternal polycystic ovarian syndrome and early offspring development. Hum Reprod. 2018; 33(7):1307–1315. PMID: 29668891.

22. Chen X, Koivuaho E, Piltonen TT, Gissler M, Lavebratt C. Association of maternal polycystic ovary syndrome or anovulatory infertility with obesity and diabetes in offspring: a population-based cohort study. Hum Reprod. 2021; 36(8):2345–2357. PMID: 34046665.

23. Xita N, Tsatsoulis A. Review: fetal programming of polycystic ovary syndrome by androgen excess: evidence from experimental, clinical, and genetic association studies. J Clin Endocrinol Metab. 2006; 91(5):1660–1666. PMID: 16522691.

24. Sir-Petermann T, Maliqueo M, Codner E, Echiburú B, Crisosto N, Pérez V, et al. Early metabolic derangements in daughters of women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2007; 92(12):4637–4642. PMID: 17848407.

25. Xu N, Chua AK, Jiang H, Liu NA, Goodarzi MO. Early embryonic androgen exposure induces transgenerational epigenetic and metabolic changes. Mol Endocrinol. 2014; 28(8):1329–1336. PMID: 24992182.

26. Barrett ES, Hoeger KM, Sathyanarayana S, Abbott DH, Redmon JB, Nguyen RHN, et al. Anogenital distance in newborn daughters of women with polycystic ovary syndrome indicates fetal testosterone exposure. J Dev Orig Health Dis. 2018; 9(3):307–314. PMID: 29310733.

27. Carlsen SM, Vanky E. Metformin influence on hormone levels at birth, in PCOS mothers and their newborns. Hum Reprod. 2010; 25(3):786–790. PMID: 20023292.

28. Abbott DH, Kraynak M, Dumesic DA, Levine JE. In utero androgen excess: a developmental commonality preceding polycystic ovary syndrome? Front Horm Res. 2019; 53:1–17. PMID: 31499494.

29. Noroozzadeh M, Rahmati M, Behboudi-Gandevani S, Ramezani Tehrani F. Maternal hyperandrogenism is associated with a higher risk of type 2 diabetes mellitus and overweight in adolescent and adult female offspring: a long-term population-based follow-up study. J Endocrinol Invest. 2022; 45(5):963–972. PMID: 35043365.

30. Vanky E, Engen Hanem LG, Abbott DH. Children born to women with polycystic ovary syndrome-short- and long-term impacts on health and development. Fertil Steril. 2019; 111(6):1065–1075. PMID: 31056313.

31. Qi X, Yun C, Sun L, Xia J, Wu Q, Wang Y, et al. Gut microbiota-bile acid-interleukin-22 axis orchestrates polycystic ovary syndrome. Nat Med. 2019; 25(8):1225–1233. PMID: 31332392.

32. Dumesic DA, Goodarzi MO, Chazenbalk GD, Abbott DH. Intrauterine environment and polycystic ovary syndrome. Semin Reprod Med. 2014; 32(3):159–165. PMID: 24715510.