Polycystic ovary syndrome and extremely preterm birth: A nationwide register-based study

Valgeirsdottir, Heiddis; Poromaa, Inger Sundström; Kallak, Theodora Kunovac; Akhter, Tansim; Roos, Nathalie; Stephansson, Olof; Wikström, Anna‐Karin

doi:10.1371/journal.pone.0246743

Cited by 15 publications

(12 citation statements)

References 35 publications

(51 reference statements)

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“…Our study is in agreement with existing reviews [ 37 – 39 ] and a recent Swedish nationwide cohort study [ 40 ] and confirms the association between maternal PCOS and preterm birth of varying degrees. However, the adjusted odds ratios observed in our study for preterm birth are modest compared to the odds ratios reported in the literature.…”

Section: Discussionsupporting

confidence: 93%

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

Subramanian

Lee

Phillips

et al. 2022

BMC Med

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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.

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Section: Discussionsupporting

confidence: 93%

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

Subramanian

Lee

Phillips

et al. 2022

BMC Med

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“…While the lift in preterm birth risk in women affected by PCOS was modest (an 11% relative rise on the adjusted odds ratio), it could be substantiated by further sub-analyses. These findings concur with a recent study in a Swedish population, indicating an apparent doubling in the risk of extreme preterm birth < 28 weeks gestation in women suffering from PCOS and, thus, an even larger effect size [ 16 ].…”

Section: Towards Better Health Of Mother and Child—novel Insights And...supporting

confidence: 92%

Maternal factors during pregnancy influencing maternal, fetal, and childhood outcomes

Muglia

Benhalima

Tong

et al. 2022

BMC Med

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Enhancing pregnancy health is known to improve the mother’s and offspring’s life-long well-being. The maternal environment, encompassing genetic factors, impacts of social determinants, the nutritional/metabolic milieu, and infections and inflammation, have immediate consequences for the in utero development of the fetus and long-term programming into childhood and adulthood. Moreover, adverse pregnancy outcomes such as preterm birth or preeclampsia, often attributed to the maternal environmental factors listed above, have been associated with poor maternal cardiometabolic health after pregnancy. In this BMC Medicine article collection, we explore a broad spectrum of maternal characteristics across pregnancy and postnatal phenotypes, anticipating substantial cross-fertilization of new understanding and shared mechanisms around diverse outcomes. Advances in the ability to leverage ‘omics across different platforms (genome, transcriptome, proteome, metabolome, microbiome, lipidome), large high-dimensional population databases, and unique cohorts are generating exciting new insights: The first articles in this collection highlight the role of placental biomarkers of preterm birth, metabolic influences on fetal and childhood growth, and the impact of common pre-existing maternal disorders, obesity and smoking on pregnancy outcomes, and the child’s health. As the collection grows, we look forward to seeing the connections emerge across maternal, fetal, and childhood outcomes that will foster new insights and preventative strategies for women.

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“…In non‐pregnancy, women with hyperandrogenic PCOS have a greater risk of insulin resistance and cardiovascular disease than women with normo‐androgenic PCOS 4 . Women with PCOS have increased risk of pregnancy complications such as preterm birth, 5,6 gestational diabetes, pregnancy‐induced hypertension and pre‐eclampsia 7 . Hyperandrogenism may further increase the risk of PCOS‐related pregnancy complications 8 …”

Section: Introductionmentioning

confidence: 99%

Polycystic ovary syndrome and risk of stillbirth: a nationwide register‐based study

Valgeirsdottir

Kallak

Poromaa

et al. 2021

BJOG

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Objective To investigate whether polycystic ovary syndrome (PCOS) is associated with increased risk of stillbirth and whether any such association is linked to PCOS with a severe hyperandrogenic profile. Design Nationwide register‐based cohort study. Setting Sweden. Population The cohort consisted of women giving birth to singleton infants in 1997–2015. All women with a diagnosis of PCOS in the period 1997–2017 and a randomly selected reference group of women without PCOS diagnosis were included. PCOS with a severe hyperandrogenic profile was defined as a PCOS diagnosis with at least two dispensations of prescribed anti‐androgens during 2005–2017. Methods The risk of stillbirth in women with PCOS was estimated through multiple logistic regression, using women without PCOS as a reference. Risks were expressed as adjusted odds ratios (aORs) with 95% confidence intervals (95% CIs), adjusted for maternal age, parity, body mass index, type‐1 diabetes, educational level and country of birth. Main outcome measures Stillbirth, at ≥22 weeks of gestation in 2008–2015 and at ≥28 weeks of gestation in 1997–2007. Results Compared with women without PCOS (n = 241 750), women with PCOS (n = 41 851) had a 50% increased risk of stillbirth (aOR 1.50, 95% CI 1.28–1.77). The incidence of stillbirth in women with PCOS was particularly increased at term. Women with PCOS and a severe hyperandrogenic profile (n = 13 713) did not have a stronger association with stillbirth than women with PCOS who did not have such a profile. Conclusions PCOS is associated with stillbirth and should be considered as a possible risk factor in antenatal care. Further research is warranted to investigate possible causal mechanisms. Tweetable abstract Women with PCOS have increased risk of stillbirth, and the incidence is particularly increased at term.

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Polycystic ovary syndrome and extremely preterm birth: A nationwide register-based study

Cited by 15 publications

References 35 publications

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

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

Maternal factors during pregnancy influencing maternal, fetal, and childhood outcomes

Polycystic ovary syndrome and risk of stillbirth: a nationwide register‐based study

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