The role of maternal obesity in infant outcomes in polycystic ovary syndrome—A systematic review, meta‐analysis, and meta‐regression

Khomami, Mahnaz Bahri; Joham, Anju E.; Boyle, Jacqueline; Piltonen, Terhi; Arora, Chavy; Silagy, Michael; Misso, Marie; Teede, Helena; Moran, Lisa J.

doi:10.1111/obr.12832

Cited by 49 publications

(50 citation statements)

References 73 publications

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“…Taken together, our findings suggest that PCOS status alone is a risk factor for offspring neurodevelopment, with more detrimental influences if joint with obesity. Given that mothers with PCOS are often obese before pregnancy and are likely to gain excess weight during gestation ( Bahri Khomami et al , 2019 ), health professionals should be aware of their offspring as targets for mental health care.…”

Section: Discussionmentioning

confidence: 99%

Association of polycystic ovary syndrome or anovulatory infertility with offspring psychiatric and mild neurodevelopmental disorders: a Finnish population-based cohort study

et al. 2020

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STUDY QUESTION Is maternal polycystic ovary syndrome (PCOS) associated with increased risks for a broad spectrum of psychiatric and mild neurodevelopmental disorders in offspring? SUMMARY ANSWER Maternal PCOS and/or anovulatory infertility is independently, and jointly with maternal obesity, perinatal problems, cesarean delivery and gestational diabetes, associated with increased risks in offspring for almost all groups of psychiatric and mild neurodevelopmental disorders with onset in childhood or adolescence. WHAT IS KNOWN ALREADY Maternal PCOS was previously associated with autism spectrum disorder, attention-deficit/hyperactivity disorders and possibly developmental delay in offspring. Few studies have investigated the association between maternal PCOS and other psychiatric and neurodevelopmental disorders in offspring. STUDY DESIGN, SIZE, DURATION This was a population-based cohort study in Finland including all live births between 1996 and 2014 (n = 1 105 997). After excluding births to mothers with symptoms similar to PCOS, a total of 1 097 753 births by 590 939 mothers remained. Children were followed up until 31 December 2018, i.e. up to the age of 22 years. PARTICIPANTS/MATERIALS, SETTING, METHODS National registries were used to link data of the included births and their mothers. Data from 24 682 (2.2%) children born to mothers with PCOS were compared with 1 073 071 (97.8%) children born to mothers without PCOS. Cox proportional hazards modeling was used to evaluate the hazard ratio (HR) and 95% CI for the risk of neuropsychiatric disorders in relation to maternal PCOS. Stratified analyses were performed to test the independent role of PCOS and the joint effects of PCOS with maternal obesity, perinatal problems, cesarean delivery, gestational diabetes and use of fertility treatment. The analysis was adjusted for maternal age, country of birth, marriage status at birth, smoking, parity, psychiatric disorders, prescription of psychotropic N05/N06 during pregnancy and systemic inflammatory diseases when applicable. MAIN RESULTS AND THE ROLE OF CHANCE A total of 105 409 (9.8%) children were diagnosed with a neurodevelopmental or psychiatric disorder. Firstly, maternal PCOS was associated with any psychiatric diagnosis (HR 1.32; 95% CI 1.27–1.38) in offspring. Particularly, the risk was increased for sleeping disorders (HR 1.46; 95% CI 1.27–1.67), attention-deficit/hyperactivity disorders and conduct disorders (HR 1.42; 95% CI 1.33–1.52), tic disorders (HR 1.42; 95% CI 1.21–1.68), intellectual disabilities (HR 1.41; 95% CI 1.24–1.60), autism spectrum disorder (HR 1.40; 95% CI 1.26–1.57), specific developmental disorders (HR 1.37; 95% CI 1.30–1.43), eating disorders (HR 1.36; 95% CI 1.15–1.61), anxiety disorders (HR 1.33; 95% CI 1.26–1.41), mood disorders (HR 1.27; 95% CI 1.18–1.35) and other behavioral and emotional disorders (ICD-10 F98, HR 1.49; 95% CI 1.39–1.59). In short, there was no significant difference between sexes. The results were robust when restricting the analyses to the first-born children or births to mothers without psychiatric diagnosis or purchase of psychotropic medication. Secondly, stratified analysis according to maternal BMI showed that the risk of any neuropsychiatric disorder was increased in offspring to normal-weight mothers with PCOS (HR 1.20; 95% CI 1.09–1.32), and markedly higher in those to severely obese mothers with PCOS (HR 2.11; 95% CI 1.76–2.53) compared to offspring to normal-weight mothers without PCOS. When excluding perinatal problems, mothers with PCOS were still associated with increased risks of any neuropsychiatric disorders in offspring (HR 1.28; 95% CI 1.22–1.34) compared to mothers without PCOS. However, an additional increase was observed for PCOS in combination with perinatal problems (HR 1.99; 95% CI 1.84–2.16). Likewise, excluding cases with maternal gestational diabetes (HR 1.30; 95% CI 1.25–1.36), cesarean delivery (HR 1.29; 95% CI 1.23–1.35) or fertility treatment (HR 1.31; 95% CI 1.25–1.36) did not eliminate the associations. LIMITATIONS, REASONS FOR CAUTION The register-based prevalence of PCOS was lower than previously reported, suggesting that this study may capture the most severe cases. To combine anovulatory infertility with PCOS diagnosis as PCOS exposure might introduce diagnostic bias. It was not feasible to distinguish between subtypes of PCOS. Furthermore, familial factors might confound the association between maternal PCOS and neuropsychiatric disorders in offspring. Maternal BMI was available for birth cohort 2004–2014 only and there was no information on gestational weight gain. WIDER IMPLICATIONS OF THE FINDINGS This study provides further evidence that maternal PCOS and/or anovulatory infertility, independently and jointly with maternal obesity, perinatal problems, gestational diabetes and cesarean delivery, implies a broad range of adverse effects on offspring neurodevelopment. These findings may potentially help in counseling and managing pregnancies. STUDY FUNDING/COMPETING INTEREST(S) This study was supported by the joint research funding of Shandong University and Karolinska Institute (SDU-KI-2019-08 to X.C and C.L.), THL Finnish Institute for Health and Welfare: Drug and pregnancy project [M.G.], the Swedish Research Council [2014-10171 to C.L.], the regional agreement on medical training and clinical research (ALF) between Stockholm County Council and Karolinska Institute Stockholm County Council [SLL20170292 to C.L.], the Swedish Brain Foundation [FO2018-0141 and FO2019-0201 to C.L.]. X.C. was supported by the China Scholarship Council during her training in Karolinska Institute. L.K. was supported by the China Scholarship Council for his PhD study in Karolinska Institute. The authors have no competing interests to disclose. TRIAL REGISTRATION NUMBER N/A.

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Section: Discussionmentioning

confidence: 99%

Association of polycystic ovary syndrome or anovulatory infertility with offspring psychiatric and mild neurodevelopmental disorders: a Finnish population-based cohort study

et al. 2020

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“…High‐risk status was based on a pregestational diagnosis of PCOS, obesity, or insulin resistance. PCOS was included as a high‐risk feature because gestational weight gain is higher in women with PCOS and increases their risk for GDM just as in prepregnancy obesity …”

Section: Methodsmentioning

confidence: 99%

Metformin in pregnancy to avert gestational diabetes in women at high risk: Meta‐analysis of randomized controlled trials

et al. 2019

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Previous randomized and observational studies on the efficacy of metformin in pregnancy to reduce incident gestational diabetes mellitus (GDM) in women at high risk (obesity, polycystic ovary syndrome [PCOS], or pregestational insulin resistance) have been conflicting and several groups are planning further randomized controlled trials (RCTs) to answer this question conclusively. This work assesses the efficacy of metformin in pregnancy to avert one outcome-incident GDM in women at high risk.We included RCTs comparing metformin with usual care or placebo controls in terms of incident GDM and recruiting women at high risk during early pregnancy. Eleven eligible trials enrolled 2370 adult women whose intervention arm consisted of metformin started at conception or before 20 weeks of gestation. Risk of GDM was similar in intervention compared with controls (risk ratio [RR] 1.03; 95% confidence interval [CI], 0.85-1.24). The data were of sufficient quality meeting the criteria for consistency and directness. We conclude that metformin does not contribute to averting the GDM outcome in women at high risk when initiated in pregnancy. The evidence provided by this synthesis affirms that further broad clinical trials investigating this question are no longer needed.

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“…However, this condition has increased the risk of complications during pregnancy or delivery, such as prevalence of gestational diabetes mellitus (GDM), preeclampsia, and premature delivery (3). For example, women with PCOS are more prone to be overweight/obese and to experience higher GWG, than their normal counterparts (4,5). GWG in women is crucial to optimize maternal, fetal, and neonatal health, with previous studies associating inappropriate pre-pregnancy BMI and GWG were at higher risks of adverse neonatal and maternal outcomes in general pregnant women (6)(7)(8)(9)(10)(11).…”

Section: Introductionmentioning

confidence: 99%

Associations between pre-pregnancy body mass index and gestational weight gain with pregnancy outcomes in women with polycystic ovary syndrome

Zhang

Zheng

Liu

et al. 2020

Preprint

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BackgroundPolycystic ovary syndrome (PCOS), a reproductive endocrine disorder affecting females of childbearing age, is associated with poor pregnancy outcomes. Both inappropriate pre-pregnancy body mass index (BMI) and gestational weight gain (GWG) could affect the perinatal outcomes in general pregnant women, which raises the question whether various BMI or GWG has impact on pregnancy outcomes in PCOS women. Therefore, we conducted a retrospective study in 722 PCOS women to explore the associations between pre-pregnancy BMI and GWG with pregnancy outcomes among PCOS women with the view of generating vital information that can guide weight management in this group of individuals.MethodsA retrospective study was conducted targeting baseline characteristics, laboratory data and pregnancy outcomes in 722 singleton pregnant women. We performed multivariable logistic regression analysis to investigate the relationship between BMI and GWG with perinatal outcomes after controlling for appropriate confounding factors.ResultsOur results showed that being underweight were increased the risk of small for gestational age (SGA), but reduced the risk of large for gestational age (LGA). In addition, we found overweight but not obesity individuals were more susceptible to develop preeclampsia compared those with normal weights. For PCOS women with BMI＜25 kg/m2 before pregnancy, inadequate GWG was a protective factor for gestational hypertension and postpartum hemorrhage(PPH). However, excessive GWG increased the possibility of LGA birth in individuals with BMI＜25 kg/m2 . Excessive GWG also increased the chances of undergoing a cesarean section in individuals with BMI ≥ 25 kg/m2. Inadequate GWG didn’t reduce the risk of LGA for women with BMI ≥ 25 kg/m2, similarly, excessive GWG didn’t decrease the chance of delivering SGA infant for women with BMI＜25 kg/m2.ConclusionThe impacts of pre-pregnancy BMI, GWG on maternal and infant outcomes among PCOS women are similar to what has been reported in general pregnant women. However, some unique trends exist in PCOS women. Overall, these findings indicate that women with PCOS need to begin weight management before pregnancy.

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The role of maternal obesity in infant outcomes in polycystic ovary syndrome—A systematic review, meta‐analysis, and meta‐regression

Cited by 49 publications

References 73 publications

Association of polycystic ovary syndrome or anovulatory infertility with offspring psychiatric and mild neurodevelopmental disorders: a Finnish population-based cohort study

Association of polycystic ovary syndrome or anovulatory infertility with offspring psychiatric and mild neurodevelopmental disorders: a Finnish population-based cohort study

Metformin in pregnancy to avert gestational diabetes in women at high risk: Meta‐analysis of randomized controlled trials

Associations between pre-pregnancy body mass index and gestational weight gain with pregnancy outcomes in women with polycystic ovary syndrome

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