Skip to main content
Top
Published in: BMC Medicine 1/2022

Open Access 01-12-2022 | Polycystic Ovary Syndrome | Research article

Polycystic ovary syndrome and risk of adverse obstetric outcomes: a retrospective population-based matched cohort study in England

Authors: Anuradhaa Subramanian, Siang Ing Lee, Katherine Phillips, Konstantinos A. Toulis, Punith Kempegowda, Michael W. O’Reilly, Nicola J. Adderley, Shakila Thangaratinam, Wiebke Arlt, Krishnarajah Nirantharakumar

Published in: BMC Medicine | Issue 1/2022

Login to get access

Abstract

Background

Polycystic ovary syndrome (PCOS) affects up to one in five women of childbearing age. Observational studies assessing the association between maternal PCOS and adverse obstetric outcomes have reported varying results, depending on patient population, diagnostic criteria for PCOS and covariates accounted for in their analyses. We aimed to assess the risk of obstetric outcomes among a population-based representative cohort of women with PCOS compared to an age-matched cohort of women without PCOS.

Methods

A retrospective cohort study was conducted of pregnancies of women in England aged 15–49 years identified from the Clinical Practice Research Datalink (CPRD) GOLD pregnancy register and linked Hospital Episodes Statistic (HES) data between March 1997 and March 2020. Pregnancies from the register that had a linked HES delivery record were included. Linked CPRD primary care data was used to ascertain maternal PCOS exposure prior to pregnancy. To improve detection of PCOS, in addition to PCOS diagnostic codes, codes for (1) polycystic ovaries or (2) hyperandrogenism and anovulation together were also considered. Sensitivity analysis was limited to only pregnant women with a diagnostic code for PCOS.
Primary outcomes ascertained from linked HES data were (1) preterm delivery (gestation < 37 weeks), (2) mode of delivery, (3) high (> 4000 g) or low birthweight (< 2500 g) and (4) stillbirth. Secondary outcomes were (1) very preterm delivery (< 32 weeks), (2) extremely preterm delivery (< 28 weeks), (3) small and (4) large for gestational age.
Conditional logistic regression models were performed adjusting for age, ethnicity, deprivation, dysglycaemia, hypertension, thyroid disorders, number of babies born at index pregnancy, and pre-gravid BMI. Multiple imputation was performed for missing outcome data.

Results

27,586 deliveries with maternal PCOS were matched for age (± 1 year) to 110,344 deliveries without PCOS. In the fully adjusted models, maternal PCOS was associated with an increased risk of (1) preterm birth [aOR: 1.11 (95% CI 1.06–1.17)], and (2) emergency caesarean, elective caesarean and instrumental vaginal compared to spontaneous delivery [aOR: 1.10 (1.05–1.15), 1.07 (1.03–1.12) and 1.04 (1.00–1.09), respectively]. There was absence of association with low birthweight, high birthweight and stillbirth. In the sensitivity analysis, the association with preterm birth [aOR: 1.31 (95% CI 1.13–1.52)], emergency caesarean [aOR: 1.15 (95% CI 1.02–1.30)], and elective caesarean [aOR: 1.03 (95% CI 1.02–1.03)] remained.
While there was no significant association with any of the secondary outcomes in the primary analysis, in the sensitivity analysis maternal PCOS was associated with increased risk of extremely preterm delivery [aOR: 1.86 (95% CI 1.31–2.65)], and lower risk of small for gestational age babies [aOR: 0.74 (95% CI 0.59–0.94)].

Conclusions

Maternal PCOS was associated with increased risk of preterm and caesarean delivery. Association with low birthweight may be largely mediated by lower gestational age at birth.
Appendix
Available only for authorised users
Literature
2.
go back to reference Ding T, Baio G, Hardiman PJ, Petersen I, Sammon C. Diagnosis and management of polycystic ovary syndrome in the UK (2004–2014): a retrospective cohort study. BMJ Open. 2016;6: e012461.PubMedPubMedCentralCrossRef Ding T, Baio G, Hardiman PJ, Petersen I, Sammon C. Diagnosis and management of polycystic ovary syndrome in the UK (2004–2014): a retrospective cohort study. BMJ Open. 2016;6: e012461.PubMedPubMedCentralCrossRef
3.
go back to reference Bozdag G, Mumusoglu S, Zengin D, Karabulut E, Yildiz BO. The prevalence and phenotypic features of polycystic ovary syndrome: A systematic review and meta-Analysis. Hum Reprod. 2016;31:2841–55.PubMedCrossRef Bozdag G, Mumusoglu S, Zengin D, Karabulut E, Yildiz BO. The prevalence and phenotypic features of polycystic ovary syndrome: A systematic review and meta-Analysis. Hum Reprod. 2016;31:2841–55.PubMedCrossRef
4.
go back to reference Fernandez RC, et al. Diagnosis delayed: health profile differences between women with undiagnosed polycystic ovary syndrome and those with a clinical diagnosis by age 35 years. Hum Reprod. 2021;36:2275–84.PubMedPubMedCentralCrossRef Fernandez RC, et al. Diagnosis delayed: health profile differences between women with undiagnosed polycystic ovary syndrome and those with a clinical diagnosis by age 35 years. Hum Reprod. 2021;36:2275–84.PubMedPubMedCentralCrossRef
5.
go back to reference Teede HJ, et al. Recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome. Hum Reprod. 2018;33:1602–18.PubMedPubMedCentralCrossRef Teede HJ, et al. Recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome. Hum Reprod. 2018;33:1602–18.PubMedPubMedCentralCrossRef
6.
go back to reference Zeng X, Xie Jie Y, Ting Liu Y, Lian Long S, Cheng Mo Z. Polycystic ovarian syndrome: Correlation between hyperandrogenism, insulin resistance and obesity. Clin Chim Acta. 2020;502:214–21.PubMedCrossRef Zeng X, Xie Jie Y, Ting Liu Y, Lian Long S, Cheng Mo Z. Polycystic ovarian syndrome: Correlation between hyperandrogenism, insulin resistance and obesity. Clin Chim Acta. 2020;502:214–21.PubMedCrossRef
7.
go back to reference Glintborg D, Andersen M. MANAGEMENT OF ENDOCRINE DISEASE: Morbidity in polycystic ovary syndrome. Eur J Endocrinol. 2017;176:R53–65.PubMedCrossRef Glintborg D, Andersen M. MANAGEMENT OF ENDOCRINE DISEASE: Morbidity in polycystic ovary syndrome. Eur J Endocrinol. 2017;176:R53–65.PubMedCrossRef
8.
go back to reference Yu HF, Chen HS, Rao DP, Gong J. Association between polycystic ovary syndrome and the risk of pregnancy complications A PRISMA-compliant systematic review and meta-analysis. Med. (United States). 2016;95:e4863. Yu HF, Chen HS, Rao DP, Gong J. Association between polycystic ovary syndrome and the risk of pregnancy complications A PRISMA-compliant systematic review and meta-analysis. Med.  (United States). 2016;95:e4863.
9.
go back to reference Morris A. Transgenerational effects of polycystic ovary syndrome identified. Nat Rev Endocrinol. 2019;16(2):67.CrossRef Morris A. Transgenerational effects of polycystic ovary syndrome identified. Nat Rev Endocrinol. 2019;16(2):67.CrossRef
10.
go back to reference Palomba S, Santagni S, Falbo A, La Sala GB. Complications and challenges associated with polycystic ovary syndrome: current perspectives. Int J Womens Health. 2015;7:745.PubMedPubMedCentralCrossRef Palomba S, Santagni S, Falbo A, La Sala GB. Complications and challenges associated with polycystic ovary syndrome: current perspectives. Int J Womens Health. 2015;7:745.PubMedPubMedCentralCrossRef
11.
go back to reference Kjerulff LE, Sanchez-Ramos L, Duffy D. Pregnancy outcomes in women with polycystic ovary syndrome: a metaanalysis. Am J Obstet Gynecol. 2011;204(558):e1-558.e6. Kjerulff LE, Sanchez-Ramos L, Duffy D. Pregnancy outcomes in women with polycystic ovary syndrome: a metaanalysis. Am J Obstet Gynecol. 2011;204(558):e1-558.e6.
12.
go back to reference Qin JZ, et al. Obstetric complications in women with polycystic ovary syndrome: A systematic review and meta-analysis. Reprod Biol Endocrinol. 2013;11:1–14.CrossRef Qin JZ, et al. Obstetric complications in women with polycystic ovary syndrome: A systematic review and meta-analysis. Reprod Biol Endocrinol. 2013;11:1–14.CrossRef
13.
go back to reference Boomsma CM, et al. A meta-analysis of pregnancy outcomes in women with polycystic ovary syndrome. Hum Reprod Update. 2006;12:673–83.PubMedCrossRef Boomsma CM, et al. A meta-analysis of pregnancy outcomes in women with polycystic ovary syndrome. Hum Reprod Update. 2006;12:673–83.PubMedCrossRef
14.
go back to reference Hu S, Leonard A, Seifalian A, Hardiman P. Vascular dysfunction during pregnancy in women with polycystic ovary syndrome. Hum Reprod. 2007;22:1532–9.PubMedCrossRef Hu S, Leonard A, Seifalian A, Hardiman P. Vascular dysfunction during pregnancy in women with polycystic ovary syndrome. Hum Reprod. 2007;22:1532–9.PubMedCrossRef
15.
go back to reference Maliqueo M, et al. Metabolic parameters in cord blood of newborns of women with polycystic ovary syndrome. Fertil Steril. 2009;92:277–82.PubMedCrossRef Maliqueo M, et al. Metabolic parameters in cord blood of newborns of women with polycystic ovary syndrome. Fertil Steril. 2009;92:277–82.PubMedCrossRef
16.
17.
go back to reference Han AR, et al. Adverse pregnancy outcomes with assisted reproductive technology in non-obese women with polycystic ovary syndrome: a case-control study. Clin Exp Reprod Med. 2011;38:103–8.PubMedPubMedCentralCrossRef Han AR, et al. Adverse pregnancy outcomes with assisted reproductive technology in non-obese women with polycystic ovary syndrome: a case-control study. Clin Exp Reprod Med. 2011;38:103–8.PubMedPubMedCentralCrossRef
18.
go back to reference Barber TM, Hanson P, Weickert MO, Franks S. Obesity and Polycystic Ovary Syndrome: Implications for Pathogenesis and Novel Management Strategies. Clin Med Insights Reprod Heal. 2019;13:117955811987404.CrossRef Barber TM, Hanson P, Weickert MO, Franks S. Obesity and Polycystic Ovary Syndrome: Implications for Pathogenesis and Novel Management Strategies. Clin Med Insights Reprod Heal. 2019;13:117955811987404.CrossRef
19.
go back to reference Chan JL, et al. Racial and ethnic differences in the prevalence of metabolic syndrome and its components of metabolic syndrome in women with polycystic ovary syndrome: a regional cross-sectional study. Am J Obstet Gynecol. 2017;217(189):e1-189.e8. Chan JL, et al. Racial and ethnic differences in the prevalence of metabolic syndrome and its components of metabolic syndrome in women with polycystic ovary syndrome: a regional cross-sectional study. Am J Obstet Gynecol. 2017;217(189):e1-189.e8.
20.
go back to reference Kumarendran B, et al. Polycystic Ovary Syndrome, Combined Oral Contraceptives, and the Risk of Dysglycemia: A Population-Based Cohort Study With a Nested Pharmacoepidemiological Case-Control Study. Diabetes Care. 2021;44:2758–66.PubMedPubMedCentralCrossRef Kumarendran B, et al. Polycystic Ovary Syndrome, Combined Oral Contraceptives, and the Risk of Dysglycemia: A Population-Based Cohort Study With a Nested Pharmacoepidemiological Case-Control Study. Diabetes Care. 2021;44:2758–66.PubMedPubMedCentralCrossRef
21.
go back to reference Wu CH, et al. Hypertension Risk in Young Women With Polycystic Ovary Syndrome: A Nationwide Population-Based Cohort Study. Front Med. 2020;7:585.CrossRef Wu CH, et al. Hypertension Risk in Young Women With Polycystic Ovary Syndrome: A Nationwide Population-Based Cohort Study. Front Med. 2020;7:585.CrossRef
22.
go back to reference Gaberšček S, et al. MECHANISMS IN ENDOCRINOLOGY: Thyroid and polycystic ovary syndrome. Eur J Endocrinol. 2015;172:R9–21.PubMedCrossRef Gaberšček S, et al. MECHANISMS IN ENDOCRINOLOGY: Thyroid and polycystic ovary syndrome. Eur J Endocrinol. 2015;172:R9–21.PubMedCrossRef
24.
go back to reference Minassian C, et al. Methods to generate and validate a Pregnancy Register in the UK Clinical Practice Research Datalink primary care database. Pharmacoepidemiol Drug Saf. 2019;28:923–33.PubMedPubMedCentralCrossRef Minassian C, et al. Methods to generate and validate a Pregnancy Register in the UK Clinical Practice Research Datalink primary care database. Pharmacoepidemiol Drug Saf. 2019;28:923–33.PubMedPubMedCentralCrossRef
25.
go back to reference Kumarendran B, et al. Polycystic ovary syndrome, androgen excess, and the risk of nonalcoholic fatty liver disease in women: A longitudinal study based on a United Kingdom primary care database. PLoS Med. 2018;15(3):e1002542.PubMedPubMedCentralCrossRef Kumarendran B, et al. Polycystic ovary syndrome, androgen excess, and the risk of nonalcoholic fatty liver disease in women: A longitudinal study based on a United Kingdom primary care database. PLoS Med. 2018;15(3):e1002542.PubMedPubMedCentralCrossRef
26.
go back to reference Villar J, et al. International standards for newborn weight, length, and head circumference by gestational age and sex: the Newborn Cross-Sectional Study of the INTERGROWTH-21st Project. Lancet. 2014;384:857–68.PubMedCrossRef Villar J, et al. International standards for newborn weight, length, and head circumference by gestational age and sex: the Newborn Cross-Sectional Study of the INTERGROWTH-21st Project. Lancet. 2014;384:857–68.PubMedCrossRef
28.
go back to reference Sullivan TR, Lee KJ, Ryan P, Salter AB. Multiple imputation for handling missing outcome data when estimating the relative risk. BMC Med Res Methodol. 2017;17:1–10.CrossRef Sullivan TR, Lee KJ, Ryan P, Salter AB. Multiple imputation for handling missing outcome data when estimating the relative risk. BMC Med Res Methodol. 2017;17:1–10.CrossRef
29.
go back to reference Jakobsen JC, Gluud C, Wetterslev J, Winkel P. When and how should multiple imputation be used for handling missing data in randomised clinical trials - A practical guide with flowcharts. BMC Med Res Methodol. 2017;17:1–10.CrossRef Jakobsen JC, Gluud C, Wetterslev J, Winkel P. When and how should multiple imputation be used for handling missing data in randomised clinical trials - A practical guide with flowcharts. BMC Med Res Methodol. 2017;17:1–10.CrossRef
30.
go back to reference Kontopantelis E, White IR, Sperrin M, Buchan I. Outcome-sensitive multiple imputation: A simulation study. BMC Med Res Methodol. 2017;17:1–13.CrossRef Kontopantelis E, White IR, Sperrin M, Buchan I. Outcome-sensitive multiple imputation: A simulation study. BMC Med Res Methodol. 2017;17:1–13.CrossRef
33.
go back to reference Mills G, Badeghiesh A, Suarthana E, Baghlaf H, Dahan MH. Polycystic ovary syndrome as an independent risk factor for gestational diabetes and hypertensive disorders of pregnancy: a population-based study on 9.1 million pregnancies. Hum Reprod. 2020;35:1666–74.PubMedCrossRef Mills G, Badeghiesh A, Suarthana E, Baghlaf H, Dahan MH. Polycystic ovary syndrome as an independent risk factor for gestational diabetes and hypertensive disorders of pregnancy: a population-based study on 9.1 million pregnancies. Hum Reprod. 2020;35:1666–74.PubMedCrossRef
34.
go back to reference Mulualem G, Wondim A, Woretaw A. The effect of pregnancy induced hypertension and multiple pregnancies on preterm birth in Ethiopia: A systematic review and meta-analysis. BMC Res Notes. 2019;12:1–7.CrossRef Mulualem G, Wondim A, Woretaw A. The effect of pregnancy induced hypertension and multiple pregnancies on preterm birth in Ethiopia: A systematic review and meta-analysis. BMC Res Notes. 2019;12:1–7.CrossRef
35.
go back to reference Hedderson MM, Ferrara A, Sacks DA. Gestational diabetes mellitus and lesser degrees of pregnancy hyperglycemia: association with increased risk of spontaneous preterm birth. Obstet Gynecol. 2003;102:850–6.PubMed Hedderson MM, Ferrara A, Sacks DA. Gestational diabetes mellitus and lesser degrees of pregnancy hyperglycemia: association with increased risk of spontaneous preterm birth. Obstet Gynecol. 2003;102:850–6.PubMed
37.
go back to reference Yu HF, Chen HS, Rao DP, Gong J. Association between polycystic ovary syndrome and the risk of pregnancy complications: A PRISMA-compliant systematic review and meta-analysis. Medicine (Baltimore). 2016;95:e4863.PubMedPubMedCentralCrossRef Yu HF, Chen HS, Rao DP, Gong J. Association between polycystic ovary syndrome and the risk of pregnancy complications: A PRISMA-compliant systematic review and meta-analysis. Medicine (Baltimore). 2016;95:e4863.PubMedPubMedCentralCrossRef
38.
go back to reference Palomba S, et al. Pregnancy complications in women with polycystic ovary syndrome. Hum Reprod Update. 2015;21:575–92.PubMedCrossRef Palomba S, et al. Pregnancy complications in women with polycystic ovary syndrome. Hum Reprod Update. 2015;21:575–92.PubMedCrossRef
39.
go back to reference d’Alterio MN, et al. Pregnancy outcomes in women with polycystic ovarian syndrome. Minerva Obstet Gynecol. 2022;74:45–59.PubMedCrossRef d’Alterio MN, et al. Pregnancy outcomes in women with polycystic ovarian syndrome. Minerva Obstet Gynecol. 2022;74:45–59.PubMedCrossRef
40.
42.
go back to reference Devarbhavi P, et al. Identification of key pathways and genes in polycystic ovary syndrome via integrated bioinformatics analysis and prediction of small therapeutic molecules. Reprod Biol Endocrinol. 2021;19:31.PubMedPubMedCentralCrossRef Devarbhavi P, et al. Identification of key pathways and genes in polycystic ovary syndrome via integrated bioinformatics analysis and prediction of small therapeutic molecules. Reprod Biol Endocrinol. 2021;19:31.PubMedPubMedCentralCrossRef
43.
go back to reference Kempegowda P, Melson E, Manolopoulos KN, Arlt W, O’Reilly MW. Implicating androgen excess in propagating metabolic disease in polycystic ovary syndrome. Ther Adv Endocrinol Metab. 2020;11:204201882093431.CrossRef Kempegowda P, Melson E, Manolopoulos KN, Arlt W, O’Reilly MW. Implicating androgen excess in propagating metabolic disease in polycystic ovary syndrome. Ther Adv Endocrinol Metab. 2020;11:204201882093431.CrossRef
45.
go back to reference Valgeirsdottir H, et al. Polycystic ovary syndrome and risk of stillbirth: a nationwide register-based study. BJOG An Int J Obstet Gynaecol. 2021;128:2073–82.CrossRef Valgeirsdottir H, et al. Polycystic ovary syndrome and risk of stillbirth: a nationwide register-based study. BJOG An Int J Obstet Gynaecol. 2021;128:2073–82.CrossRef
46.
go back to reference Holton S, Hammarberg K, Johnson L. Fertility concerns and related information needs and preferences of women with PCOS. Hum Reprod Open. 2018;2018:1–7.CrossRef Holton S, Hammarberg K, Johnson L. Fertility concerns and related information needs and preferences of women with PCOS. Hum Reprod Open. 2018;2018:1–7.CrossRef
Metadata
Title
Polycystic ovary syndrome and risk of adverse obstetric outcomes: a retrospective population-based matched cohort study in England
Authors
Anuradhaa Subramanian
Siang Ing Lee
Katherine Phillips
Konstantinos A. Toulis
Punith Kempegowda
Michael W. O’Reilly
Nicola J. Adderley
Shakila Thangaratinam
Wiebke Arlt
Krishnarajah Nirantharakumar
Publication date
01-12-2022
Publisher
BioMed Central
Published in
BMC Medicine / Issue 1/2022
Electronic ISSN: 1741-7015
DOI
https://doi.org/10.1186/s12916-022-02473-3

Other articles of this Issue 1/2022

BMC Medicine 1/2022 Go to the issue