Reproductive Medicine Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
The Key Laboratory for Reproductive Medicine of Guangdong Province, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China.
Front Endocrinol (Lausanne). 2024 Jun 28;15:1327849. doi: 10.3389/fendo.2024.1327849. eCollection 2024.
Previous observational studies have shown that polycystic ovary syndrome (PCOS) was associated with adverse pregnancy and perinatal outcomes. However, it remains controversial whether PCOS is an essential risk factor for these adverse pregnancy and perinatal outcomes. We aimed to use instrumental variables in a two-sample Mendelian randomization (MR) study to determine causality between PCOS and adverse pregnancy and perinatal outcomes.
Summary statistics were extracted from a recent genome-wide association study (GWAS) meta-analysis conducted in PCOS, which included 10,074 cases and 103,164 controls of European ancestry. Data on Adverse pregnancy and perinatal outcomes were summarized from the FinnGen database of European ancestry, which included more than 180,000 samples. The inverse variance weighted (IVW) method of MR was applied for the main outcome. To assess heterogeneity and pleiotropy, we conducted sensitivity analyses, including leave-one-out analysis, weighted median, MR-PRESSO (Mendelian Randomization Pleiotropy RESidual Sum and Outlier), and MR-Egger regression.
Two-sample MR analysis with the IVW method suggested that PCOS exerted causal effects on the risk of hypertensive disorders of pregnancy [odds ratio (OR) 1.170, 95% confidence interval (CI) 1.051-1.302, p = 0.004], in particular gestational hypertension (OR 1.083, 95% CI 1.007-1.164, p = 0.031), but not other pregnancy and perinatal diseases (all > 0.05). Sensitivity analyses demonstrated pleiotropy only in pre-eclampsia or eclampsia ( = 0.0004), but not in other pregnancy and perinatal diseases (all > 0.05). The results remained consistent after excluding two outliers (all > 0.05).
We confirmed a causal relationship between PCOS and hypertensive disorders of pregnancy, in particular gestational hypertension, but no association with any other adverse pregnancy or perinatal outcome. Therefore, we suggest that women with PCOS who are pregnant should have their blood pressure closely monitored.
先前的观察性研究表明多囊卵巢综合征（PCOS）与不良妊娠和围产结局相关。然而，PCOS 是否是这些不良妊娠和围产结局的基本危险因素仍存在争议。我们旨在使用两样本孟德尔随机化（MR）研究中的工具变量来确定 PCOS 与不良妊娠和围产结局之间的因果关系。
从最近的一项多囊卵巢综合征全基因组关联研究（GWAS）荟萃分析中提取汇总统计数据，该研究包括 10074 例病例和 103164 例欧洲血统对照。欧洲血统的 FinnGen 数据库中汇总了不良妊娠和围产结局的数据，该数据库包含超过 180000 个样本。主要结局采用逆方差加权（IVW）方法进行 MR。为评估异质性和多效性，我们进行了敏感性分析，包括单样本剔除分析、加权中位数、MR-PRESSO（孟德尔随机化多效性残余和异常值）和 MR-Egger 回归。
采用 IVW 方法的两样本 MR 分析表明，PCOS 对妊娠高血压疾病的风险具有因果作用[比值比（OR）1.170，95%置信区间（CI）1.051-1.302，p=0.004]，特别是妊娠期高血压（OR 1.083，95%CI 1.007-1.164，p=0.031），但与其他妊娠和围产疾病无关（均>0.05）。敏感性分析表明，仅在子痫前期或子痫中存在多效性（=0.0004），而在其他妊娠和围产疾病中则没有（均>0.05）。排除两个异常值后，结果仍然一致（均>0.05）。
我们证实了 PCOS 与妊娠高血压疾病之间存在因果关系，特别是妊娠期高血压，但与其他任何不良妊娠或围产结局均无关。因此，我们建议患有 PCOS 的孕妇应密切监测血压。
