Prevalence of elevated alanine aminotransferase (ALT) in pregnancy: A cross-sectional labor and delivery-based assessment

Abstract

Since liver tests are not routinely checked in pregnancy, the prevalence of abnormal liver tests and liver-related abnormalities in pregnancy in a US-based population is not known. We sought to determine the prevalence of abnormal alanine aminotransferase (ALT) among pregnant Individuals who present to labor and delivery for evaluation and to evaluate prevalence of underlying diagnosed liver conditions. Prospective study evaluating liver tests in consecutive samples obtained on the labor and delivery unit. Patient characteristics were compared between those with and without abnormal ALT and those with and without abnormal ALT without a liver-related diagnosis made in clinical practice, using t tests for continuous measures and χ2 or Fisher's exact tests as appropriate for categorical measures. Logistic regression was utilized to identify factors associated with abnormal ALT in this subcohort to determine predictors of abnormal ALT in those without a known liver-related diagnosis. We collected 1024 laboratory specimens from 996 patients. Of these patients, 131 of 996 (13.2%) had elevated ALT ≥25 IU/L; 20 (2%) had ALT ≥50, 6 (0.6%) had ALT ≥125 and 3 (0.3%) had ALT ≥250. 61/131 (46.6%) of patients with ALT ≥25 IU/L had not had LTs checked during routine pregnancy care. 20 (15%) of individuals with abnormal LT had preeclampsia; 5 (4%) had cholestasis of pregnancy; 1 (0.8%) had hepatitis C; there were no other chronic liver diseases diagnosed. There were no significant demographic or clinical differences between those with and without ALT ≥25, whether liver disease diagnosis was made or not. We identified an over 10% prevalence of abnormal LTs in consecutive pregnant individuals who presented to L&D, most of whom did not have a liver-related condition diagnosed in clinical practice. Among those with liver-related diagnoses, PE and ICP were the most common among individuals with ALT≥25 IU/mL, with chronic liver disease rarely diagnosed. Further evaluation of the role of ALT testing as part of routine prenatal care is needed, particularly in establishing a baseline prevalence of liver test abnormalities in pregnancy and independent association with pregnancy outcomes.

Diagnostic Approach to Elevated Liver Function Tests during Pregnancy: A Pragmatic Narrative Review

“…The true incidence of elevated LFTs during pregnancy is very difficult to establish because these tests are not routinely performed in all pregnant women and there is substantial heterogeneity among laboratories and centers regarding the definition of “normal” values of liver enzymes. However, some studies have shown that the prevalence of elevated LFTs is up to 5–13% [ 5 , 77 , 79 , 85 ], which is much higher than the canonic 3% prevalence of pregnancy-related liver disease [ 86 ], suggesting that there may be more to it than what was previously thought. Most studies have evaluated LFTs during the first trimester [ 77 , 85 , 87 , 88 ], showing that higher ALT levels are associated with an increased risk of future gestational diabetes [ 77 , 87 , 88 ], large-for-gestational-age babies [ 85 , 89 , 90 ], and pre-eclampsia [ 77 , 78 , 79 ].…”

“…Most studies have evaluated LFTs during the first trimester [ 77 , 85 , 87 , 88 ], showing that higher ALT levels are associated with an increased risk of future gestational diabetes [ 77 , 87 , 88 ], large-for-gestational-age babies [ 85 , 89 , 90 ], and pre-eclampsia [ 77 , 78 , 79 ]. In other studies, altered LFTs were investigated in the third trimester (or at delivery), with a reported prevalence of 11–13% [ 5 ]. Elevated LFTs were not always explained with pre-existing or pregnancy-related liver disease (30–50%) [ 5 , 91 ], and more importantly, could be associated with a higher risk of complications [ 5 ].…”

“…In other studies, altered LFTs were investigated in the third trimester (or at delivery), with a reported prevalence of 11–13% [ 5 ]. Elevated LFTs were not always explained with pre-existing or pregnancy-related liver disease (30–50%) [ 5 , 91 ], and more importantly, could be associated with a higher risk of complications [ 5 ]. Finally, the incidence of NAFLD among pregnant women is rapidly increasing and is associated with an elevated risk of maternal complications and pre-term birth [ 92 , 93 ].…”

“…Moreover, LFTs are not routinely recommended during pregnancy or prenatal testing, so the true prevalence of elevated LFTs or whether the pregnancy-specific upper limit of normal (ULN) values should be used is currently unknown. Indeed, a recent study found that up to 12% of pregnant women without known liver disease had ALT ≥ 25 IU/L at labor, and almost half of the patients with elevated LFTs did not have a clinical diagnosis of liver disease or have liver tests ever checked as part of routine pregnancy care [ 5 ]. So, the true burden of liver dysfunction and its prognostic impact on pregnancy outcomes remain largely unknown.…”

Evaluation of alanine aminotransferase/aspartate aminotransferase ratio and high-density lipoprotein for predicting neonatal adverse outcomes associated with intrahepatic cholestasis of pregnancy

“…The treatment for ICP patients and fetuses is limited to symptomatic support and close monitoring. In addition, although ALT and AST, which are commonly used indicators to reflect the degree of liver damage, have also received widespread attention, some studies have found that serum ALT and AST are also significantly elevated in pregnant women with ICP, just as liver function impairment occurs in normal population, suggesting that serum ALT and AST can be used as indicators to evaluate ICP-related adverse pregnancy outcomes ( Juusela et al, 2020 ; Ekiz et al, 2016 ; Kushner et al, 2022 ). However, there are few reports on whether the ratio of serum ALT/AST in ICP pregnant women is also higher than that in normal pregnant women and whether it is associated with ICP-related adverse maternal and neonatal outcomes.…”