Elevated Alanine Aminotransferase in Early Pregnancy and Subsequent Development of Gestational Diabetes and Preeclampsia

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is now considered as a hepatic manifestation of metabolic syndrome and elevated alanine aminotransferase (ALT) is commonly related to NAFLD in the absence of viral hepatitis or alcohol abuse. Previous studies have indicated that elevated ALT is associated with diabetes or metabolic syndrome in adults, but the clinical significance of ALT or NAFLD in pregnancy has not been well determined. The objective of this study was to determine the association between elevated ALT in early pregnancy and the development of gestational diabetes or preeclampsia in late pregnancy. METHODS: In this retrospective cohort study, pregnant women who met the following inclusion criteria were included: 1) singleton pregnancy; 2) ALT levels were measured in antenatal outpatient clinic at 4–20 weeks of gestation; 3) patients were screened for gestational diabetes and delivered in Cheil General Hospital and Women's Healthcare Center. Cases with viral hepatitis or other liver diseases were excluded. The early ALT levels were divided into two groups (normal ALT [≤ 95th percentile] and elevated ALT [> 95th percentile]), and the frequency of gestational diabetes and preeclampsia was compared between the two groups of cases. Gestational diabetes was screened and diagnosed by two-step procedure (50 g oral glucose challenge test and 75 g glucose challenge test with World Health Organization [WHO] criteria). RESULTS: A total of 2,322 women met the inclusion criteria. Cases with elevated early ALT levels (> 95th percentile) had a higher risk of subsequent gestational diabetes and preeclampsia (gestational diabetes by WHO criteria, 2.1% in normal ALT vs. 6.5% in elevated ALT, P < 0.01; preeclampsia, 1.0% in normal ALT vs. 4.1% in elevated ALT, P < 0.05). This relationship between elevated ALT and increased risk of gestational diabetes/preeclampsia remained significant after adjustment for maternal age and pre-pregnancy body mass index. CONCLUSION: Elevated unexplained ALT in early pregnancy is associated with the risk of subsequent development of gestational diabetes and preeclampsia in late pregnancy.