Birth outcomes in mothers with hypertensive disorders and polycystic ovary syndrome: a population-based cohort study

Abstract

Is PCOS associated with higher risks of extreme birth size and/or preterm birth in mothers with different hypertension types? PCOS was associated with additional risks of preterm birth in mothers with chronic hypertension and in singleton pregnancies of mothers with pre-eclampsia, and with increased risks of offspring being large for gestational age (LGA) in mothers with gestational hypertension. Women with PCOS are more likely to develop gestational hypertension, preeclampsia, and chronic hypertension. Although adverse birth outcomes have been frequently reported in mothers with PCOS, such associations in the setting of a hypertensive disorder remain unknown. This is a population-based cohort study including all live births 2004-2014 in Finland (n = 652 732), excluding mothers with diagnoses that could cause signs and symptoms like PCOS to ensure diagnosis specificity. Maternal diagnoses of PCOS, gestational hypertension, chronic hypertension, and pre-eclampsia were identified from the Finnish national registries. Generalized estimating equation and multivariable logistic regression were used to assess the adjusted odds ratio (aOR) and 95% CIs of preterm birth, very preterm birth and offspring being small (SGA) or large (LGA) for gestational age in hypertensive mothers with or without PCOS, using normotensive mothers without PCOS as reference. Of 43 902 (6.7%) mothers with hypertensive disorders, 1709 (3.9%) had PCOS. Significant interactions were detected for PCOS with hypertension on preterm birth, very preterm birth, offspring being SGA and LGA (F = 504.1, pinteraction <0.001; F = 124.2, pinteraction <0.001; F = 99.5, pinteraction <0.001; F = 2.7, pinteraction =0.012, respectively). Using mothers with no hypertensive disorder and no PCOS as reference, the risks of preterm and very preterm birth were overrepresented in mothers with chronic hypertension and pre-eclampsia without PCOS. PCOS was associated with higher risks of preterm birth (aOR PCOS 4.02, 3.14–5.15 vs. aOR non-PCOS 2.51, 2.32–2.71) in mothers with chronic hypertension, with significant interaction between the exposures (F = 32.7, pinteraction <0.001). Comorbid PCOS was also associated with a higher risk of preterm birth in singleton pregnancies of mothers with pre-eclampsia (aOR PCOS 7.33, 5.92–9.06 vs. aOR non-PCOS 5.72, 5.43–6.03; F = 50.0, pinteraction<0.001). Furthermore, the combined associations of PCOS with chronic hypertension or pre-eclampsia persisted for spontaneous births. Moreover, the risk of offspring LGA was increased in mothers with PCOS and gestational hypertension although decreased in those with gestational hypertension alone (aOR PCOS 2.04, 1.48–2.80 vs. aOR non-PCOS 0.80, 0.72–0.89; F = 9.7, pinteraction=0.002), whereas for offspring SGA the risks were comparable between hypertensive mothers with and those without PCOS. Information on medication treatment, gestational weeks of onset for pre-eclampsia and gestational hypertension, weight gain during pregnancy, and PCOS phenotypes were not available. All diagnoses were retrieved from registries, representing only those seeking medical care for their symptoms. The ICD-9 codes used to identify PCOS before year 1996 are known to underestimate the prevalence of PCOS, while the inclusion of anovulatory infertility as PCOS might introduce an overrepresentation bias, although PCOS constitutes 80% of anovulatory infertility. The risk of very preterm birth in relation to maternal PCOS and hypertensive disorders should be interpreted with caution owing to limited sample sizes. Multifetal pregnancies among maternal PCOS were too few for a subgroup analysis. Moreover, ART included IVF/ICSI only. Potential effects of other treatments, such as ovulation induction, were not examined. PCOS was associated with additional risks of preterm birth or offspring being LGA in hypertensive mothers, which varied between hypertension types. The exacerbated risks highlight consideration of PCOS in pregnancy counseling and management for women with hypertensive disorders. This study was supported by Shandong Provincial Natural Science Foundation, China [ZR2020MH064 to X.C], the joint research funding of Shandong University and Karolinska Institute [SDU-KI-2019-08 to X.C and C.L.], the Finnish Institute for Health and Welfare: Drug and pregnancy project [M.G.], the Swedish Research Council [2022-01188 to C.L.], the regional agreement on medical training and clinical research (ALF) between Stockholm County Council and Karolinska Institute Stockholm County Council [SLL20190589 to C.L.], the Swedish Brain Foundation [FO2021-0412 to C.L.]. The funders had no role in study design, data collection, analysis, and interpretation, writing of the report or decision to submit for publication. The authors report no conflicts of interest. Not applicable.