1. Cardiometabolic health in offspring of women with PCOS compared to healthy controls: a systematic review and individual participant data meta-analysis.
- Author
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Gunning, Marlise N, Petermann, Teresa Sir, Crisosto, Nicolas, Rijn, Bas B van, Wilde, Marlieke A de, Christ, Jacob P, Uiterwaal, C S P M, Jager, Wilco de, Eijkemans, Marinus J C, Kunselman, Allen R, Legro, Richard S, Fauser, Bart C J M, Sir Petermann, Teresa, van Rijn, Bas B, de Wilde, Marlieke A, and de Jager, Wilco
- Subjects
META-analysis ,WOMEN'S health ,MATERNAL age ,POLYCYSTIC ovary syndrome ,HIGH density lipoproteins - Abstract
Background: Women diagnosed with polycystic ovary syndrome (PCOS) suffer from an unfavorable cardiometabolic risk profile, which is already established by child-bearing age.Objective and Rationale: The aim of this systematic review along with an individual participant data meta-analysis is to evaluate whether cardiometabolic features in the offspring (females and males aged 1-18 years) of women with PCOS (OPCOS) are less favorable compared to the offspring of healthy controls.Search Methods: PubMed, Embase and gray literature databases were searched by three authors independently (M.N.G., M.A.W and J.C.) (last updated on 1 February 2018). Relevant key terms such as 'offspring' and 'PCOS' were combined. Outcomes were age-specific standardized scores of various cardiometabolic parameters: BMI, blood pressure, glucose, insulin, lipid profile and the sum scores of various cardiometabolic features (metabolic sum score). Linear mixed models were used for analyses with standardized beta (β) as outcome.Outcomes: Nine relevant observational studies could be identified, which jointly included 1367 children: OPCOS and controls, originating from the Netherlands, Chile and the USA. After excluding neonates, duplicate records and follow-up screenings, a total of 885 subjects remained. In adjusted analyses, we observed that OPCOS (n = 298) exhibited increased plasma levels of fasting insulin (β = 0.21(95%CI: 0.01-0.41), P = 0.05), insulin-resistance (β = 0.21(95%CI: 0.01-0.42), P = 0.04), triglycerides (β = 0.19(95%CI: 0.02-0.36), P = 0.03) and high-density lipoprotein (HDL)-cholesterol concentrations (β = 0.31(95%CI: 0.08-0.54), P < 0.01), but a reduced birthweight (β = -116(95%CI: -195 to 38), P < 0.01) compared to controls (n = 587). After correction for multiple testing, however, differences in insulin and triglycerides lost their statistical significance. Interaction tests for sex revealed differences between males and females when comparing OPCOS versus controls. A higher 2-hour fasting insulin was observed among female OPCOS versus female controls (estimated difference for females (βf) = 0.45(95%CI: 0.07 to 0.83)) compared to the estimated difference between males ((βm) = -0.20(95%CI: -0.58 to 0.19)), with interaction-test: P = 0.03. Low-density lipoprotein-cholesterol differences in OPCOS versus controls were lower among females (βf = -0.39(95%CI: -0.62 to 0.16)), but comparable between male OPCOS and male controls (βm = 0.27(95%CI: -0.03 to 0.57)), with interaction-test: P < 0.01. Total cholesterol differences in OPCOS versus controls were also lower in females compared to the difference in male OPCOS and male controls (βf = -0.31(95%CI: -0.57 to 0.06), βm = 0.28(95%CI: -0.01 to 0.56), interaction-test: P = 0.01). The difference in HDL-cholesterol among female OPCOS versus controls (βf = 0.53(95%CI: 0.18-0.88)) was larger compared to the estimated mean difference among OPCOS males and the male controls (βm = 0.13(95%CI: -0.05-0.31), interaction-test: P < 0.01). Interaction test in metabolic sum score revealed a significant difference between females (OPCOS versus controls) and males (OPCOS versus controls); however, sub analyses performed in both sexes separately did not reveal a difference among females (OPCOS versus controls: βf = -0.14(95%CI: -1.05 to 0.77)) or males (OPCOS versus controls: βm = 0.85(95%CI: -0.10 to 1.79)), with P-value < 0.01.Wider Implications: We observed subtle signs of altered cardiometabolic health in OPCOS. Therefore, the unfavorable cardiovascular profile of women with PCOS at childbearing age may-next to a genetic predisposition-influence the health of their offspring. Sensitivity analyses revealed that these differences were predominantly observed among female offspring aged between 1 and 18 years. Moreover, studies with minimal risk of bias should elucidate the influence of a PCOS diagnosis in mothers on both sexes during fetal development and subsequently during childhood. [ABSTRACT FROM AUTHOR]- Published
- 2020
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