Nonalcoholic fatty liver disease is a risk factor for large-for-gestational-age birthweight

Abstract

Objective 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. Method 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 >90 th percentile for gestational age. Results 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. Conclusion 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.

Maternal lipid levels in pregnant women without complications in developing risk of large for gestational age newborns: a meta-analysis

“…There were 12 prospective cohort studies that reported a total of 17,731 cases, 4,430 of which included LGA newborns. Maternal lipid profiles were measured in the first trimester in four articles 3,9,14,15 ; in the second trimester Fasting TC, TG, HDL-C, LDL-C Table 3. Mean values of lipid profiles during pregnancy in women with LGA newborns and controls.…”

“…Most of the studies 4,6,7,15 used the INTERGROWTH-21st definition of >90th percentile for LGA newborns. Some studies in China 3,19 used a referred percentile standard based on a Chinese population, and some 14,16,18 used their country's definition of LGA. A detailed list of the implemented eligibility criteria for each study is shown in Table 2, and the mean values of the determined biochemical lipids are presented in Table 3.…”

“…There were 11 studies that assessed TG levels during pregnancy; 4,761 case subjects and 14,174 control subjects were included. Maternal serum TG levels were found to be significantly associated with LGA foetuses in the first trimester, according to three of the included studies 3,14,15 . One study reported that maternal serum TG levels in the second trimester were significantly related with the risk for LGA newborns before and after data adjustment 9 .…”

“…Data on 2,225 patients and 13,218 controls from nine studies 3,6,9,[14][15][16][17]19,20 were included to evaluate the relationship between TC and LGA newborns. In contrast to all the studies that reported an insignificant association between TC levels and…”

“…The analysis of HDL-C and risk for LGA newborns included 1,881 patients and 8,603 controls from seven studies 3,6,14,16,17,19,20 . HDL-C levels were reported to be significantly associated with the risk for LGA and SGA foetuses in the third trimester of pregnancy 16,20 .…”