Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Korea.
Department of Obstetrics and Gynecology, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Korea.
PLoS One. 2019 Aug 26;14(8):e0221400. doi: 10.1371/journal.pone.0221400. eCollection 2019.
Nonalcoholic fatty liver disease (NAFLD) is a well-recognized hepatic manifestation of metabolic disease in adults and has been associated with the development of gestational diabetes (GDM). Hepatic insulin resistance can result in increased release of glucose (from gluconeogenesis) and free fatty acids (due to enhanced lipolysis), which can lead in turn to fetal overgrowth. However, the relationship between maternal metabolic factors (such as circulating levels of triglycerides, free fatty acids [FFA], or adipokines) and excessive fetal birthweight in NAFLD has not been carefully examined. In this study, we evaluated the relationship between NAFLD and the subsequent risk of large-for-gestational-age (LGA) birthweight.
Singleton nondiabetic pregnant women were evaluated for the presence of fatty liver at 10-14 weeks of gestation by abdominal ultrasound. The degree of fatty liver was classified as Grade 0-3 steatosis. At the time of liver ultrasound, maternal blood was taken after fasting and measured for adiponectin and FFA. LGA was defined as birthweight >90th percentile for gestational age.
A total of 623 women were included in the analysis. The frequency of LGA was 10.9% (68/623), and the frequency of NAFLD was 18.9%. The risk of LGA increased significantly in patients with Grade 2-3 steatosis in the first trimester. The relationship between Grade 2-3 steatosis and LGA remained significant after adjustment for maternal age, pre-pregnancy BMI, GDM, and maternal serum triglyceride levels. The concentration of maternal blood adiponectin at 10-14 weeks was significantly lower in cases with LGA than non-LGA, but the maternal blood FFA concentrations were not different between the groups.
The presence of Grade 2-3 steatosis on ultrasound in early pregnancy was associated with the increased risk of delivering an LGA infant, even after adjustment for multiple confounding factors including GDM. Adiponectin may be the linking biomarker between NAFLD and LGA.
非酒精性脂肪性肝病（NAFLD）是成人代谢性疾病的一种公认的肝脏表现，并且与妊娠糖尿病（GDM）的发生有关。肝胰岛素抵抗可导致葡萄糖（来自糖异生）和游离脂肪酸（由于脂肪分解增强）的释放增加，这反过来又可导致胎儿过度生长。然而，尚未仔细检查母体代谢因素（如循环中的甘油三酯，游离脂肪酸[FFA]或脂肪因子的水平）与 NAFLD 中胎儿过大出生体重之间的关系。在这项研究中，我们评估了 NAFLD 与巨大儿（LGA）出生体重的随后风险之间的关系。
在 10-14 周的妊娠时通过腹部超声评估了非糖尿病孕妇的脂肪肝的存在。脂肪肝的程度分为 0-3 级脂肪变性。在进行肝脏超声检查时，空腹采集母亲的血液并测量脂联素和 FFA。LGA 的定义为出生体重>胎龄的第 90 百分位数。
共有 623 名妇女被纳入分析。LGA 的发生率为 10.9％（68/623），NAFLD 的发生率为 18.9％。在孕早期患有 2-3 级脂肪变性的患者中，LGA 的风险显着增加。在调整了母亲的年龄，孕前 BMI，GDM 和母亲的血清甘油三酯水平后，2-3 级脂肪变性与 LGA 之间的关系仍然具有统计学意义。与非 LGA 相比，LGA 病例中母亲血液脂联素的浓度在孕 10-14 周时明显降低，但两组之间的母亲血液 FFA 浓度没有差异。
即使在调整了包括 GDM 在内的多种混杂因素后，孕早期超声检查存在 2-3 级脂肪变性与发生 LGA 婴儿的风险增加相关。脂联素可能是 NAFLD 和 LGA 之间的关联生物标志物。
