懷孕期間angiopoietin-like protein 4與葡萄糖和脂質代謝、胎盤功能及胎兒生長的關聯

Abstract

背景：異常的胎兒生長，包括胎兒過大(large for gestational age)和胎兒過小(small for gestational age)，會增加周產期併發症的風險。然而，目前對於異常胎兒生長的致病機轉並不是完全了解，也沒有好用並且準確的預測模型。Angiopoietin-like protein 4 (ANGPTL4)是一種會被分泌至血漿中的蛋白質，已知會影響脂質和葡萄糖代謝，同時可能影響胎盤發育。在本研究中，我們將探討血漿中ANGPTL4在懷孕期間與胎兒生長是否有關，並探索其與葡萄糖代謝、脂質代謝和胎盤功能之間的關係。 方法：我們在國立臺灣大學醫院進行了一項前瞻性研究，收錄時間從2013年11月到2018年4月。我們在懷孕的第一和第二孕期紀錄了母親的臨床特徵和收集血液樣本，並在生產後測量胎兒出生體重和收集臍帶血樣本。以上資料被用來分析母親血漿中ANGPTL4濃度與SGA、LGA、葡萄糖代謝、脂質代謝和胎盤功能之間的關係。 結果：本研究共招募了852名懷孕婦女。與正常胎兒大小組別相比，LGA組和SGA組的母親血漿ANGPTL4濃度均較高。出生體重與懷孕第一孕期血漿ANGPTL4濃度呈曲線關係。在調整了其他相關因子後，母親血漿ANGPTL4與LGA和SGA均呈顯著相關。相較於其他傳統風險因子，母親血漿ANGPTL4可額外增加對LGA和SGA的預測力。此外，血漿ANGPTL4濃度與母親血中growth hormone variant、糖化血色素、三酸甘油脂與游離脂肪酸濃度呈正相關，但與臍帶血內的各種生長相關因子無關連。 結論：母親血漿中ANGPTL4濃度與葡萄糖和脂質代謝、以及胎兒生長有關。懷孕早期母親的血漿ANGPTL4可以作為早期指標，用於預測LGA和SGA的風險。

Introduction: Abnormal fetal growth, including large-for-gestational-age (LGA) and small-for-gestational-age (SGA), is associated with adverse pregnancy outcomes. However, the underlying mechanisms and accurate predictive models for abnormal fetal growth remain limited. Angiopoietin-like protein 4 (ANGPTL4) is a secreted protein known to affect lipid and glucose metabolism and may have a role in placental development. In this study, we aimed to investigate the relationship between plasma ANGPTL4, glucose metabolism, lipid metabolism, placental function, and fetal growth during pregnancy. Method: A prospective cohort study was conducted at National Taiwan University Hospital between November 2013 and April 2018. Clinical features and blood samples were collected during the first and second trimesters, while birth weight measurements and cord blood samples were obtained at delivery. We utilized the data to analyze the relationship between maternal plasma ANGPTL4 levels and SGA, LGA, glucose metabolism, lipid metabolism, and placental function. Result: In this study, a total of 852 pregnant women were enrolled. Both the LGA and SGA groups had higher plasma ANGPTL4 concentrations compared to the appropriate-for-gestational-age group. A quadratic relationship was observed between birthweight and first trimester plasma ANGPTL4 concentration. Maternal plasma ANGPTL4 showed significant associations with LGA and SGA after adjusting for potential confounders. The predictive ability of maternal plasma ANGPTL4, measured by the area under the ROC curve, was superior to traditional risk factors in identifying LGA and SGA cases. Besides, plasma ANGPTL4 levels were positively correlated with plasma growth hormone variant, hemoglobin A1c, triglyceride, and free fatty acid levels but were not associated with cord blood growth factors. Conclusion: Plasma ANGPTL4 is associated with glucose metabolism, lipid metabolism, and fetal growth during pregnancy. Plasma ANGPTL4 during the first trimester is an early biomarker to predict the risk of delivering LGA and SGA newborns.