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

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.

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

“…Major risk factors for preterm birth have long been elucidated [ 8 , 9 ], such as prior preterm birth, early rupture of membranes, or co-existing medical conditions such as polycystic ovary syndrome (PCOS), as reported by others in this special collection [ 12 ]. Rocha and colleagues address an interesting question: for those in their second pregnancy and birth preterm, do risk factors associated with their preterm birth differ depending on whether or not their first infant was born preterm?…”

“…In another contribution to this collection, Subramanian and colleagues [ 12 ] present data indicating a convincing link between preterm birth and PCOS, a condition affecting 10% of women. While defined by a varied constellation of signs and symptoms—cysts on the ovary, biochemical or clinical evidence of androgen excess, oligo/anovulation [ 14 ]—PCOS is, at its heart, a metabolic disorder [ 15 ].…”

Polycystic Ovarian Syndrome (PCOS): Does the Challenge End at Conception?

“…A recent population-based study conducted in the UK [ 26 ] also found that maternal PCOS was associated with an increased risk of preterm and caesarean delivery. The authors were, however, unable to evaluate any effect modification attributable to in vitro fertilization when assessing the association between PCOS and the risk of obstetric outcomes or adjusting for pregnancy-induced complications or gestational weight gain.…”

Higher free testosterone in the third trimester was associated with lower abdominal circumference at birth in boys: Odense child cohort

“…Hyperandrogenism is present in ~70% women with polycystic ovary syndrome (PCOS), 14,15 and pregnant women with PCOS have higher FT and TT levels during the third trimester compared with controls 10 . PCOS in pregnancy was reported to be associated with higher risk of pregnancy‐induced hypertension, pre‐eclampsia and preterm birth (gestational week <37), 16–18 and lower BW was observed in offspring of women with PCOS compared with controls in two register‐based retrospective studies 16,18 . However, the associations became insignificant after adjusting for gestational age 16,18 .…”

“…PCOS in pregnancy was reported to be associated with higher risk of pregnancy‐induced hypertension, pre‐eclampsia and preterm birth (gestational week <37), 16–18 and lower BW was observed in offspring of women with PCOS compared with controls in two register‐based retrospective studies 16,18 . However, the associations became insignificant after adjusting for gestational age 16,18 . Data from the Odense Child Cohort (OCC) showed an increased risk of preterm birth, but no increased risk of pregnancy‐induced hypertension and/or pre‐eclampsia in women with PCOS compared with controls 19 .…”