The Risk of Hypertensive Disorders of Pregnancy Is Not Increased Among Individuals with Non-Alcoholic Fatty Liver Disease

Introduction: The prevalence of non-alcoholic fatty liver disease (NAFLD) continues to rise among pregnant individuals. While NAFLD has a strong link to hypertension outside of pregnancy, data on the risk of hypertensive disorders of pregnancy (HDP) in NAFLD are limited. Among pregnant individuals with overweight or obese body mass index (BMI), we aimed to compare the risk of HDP in those with and without NAFLD. Methods: We performed a retrospective cohort study of pregnancies cared for at a US academic center from 1998 to 2016. Singleton pregnancies were included if BMI was ≥25 kg/m2 at 12 weeks’ gestation and at least 2 ALT prior to pregnancy or at less than 20 weeks’ gestation were available. After excluding individuals with alternative causes of liver disease (alcohol, viral, genetic, autoimmune), hepatotoxic medications, or AST/ALT >500 U/L, we defined NAFLD as 2 ALT >40 U/L at least 6 months apart prior to 20 weeks’ gestation in the index pregnancy. This NAFLD definition was validated with blinded chart review in 100 patients (88% sensitivity, 88% specificity). The primary outcome was HDP (defined using outpatient blood pressures and labor and delivery records). Generalized linear mixed models examined the association between NAFLD and HDP, adjusting for age, race/ethnicity, BMI, diastolic BP, marital and insurance status, neonatal sex, and parity. Models were fit with/without adjustment for gestational diabetes mellitus (GDM) status. Results: Of the 2,745 pregnancies (2,288 individuals) included, 146 (5.3%) met criteria for NAFLD. Those with NAFLD had higher BMI at 12 weeks’ gestation (mean of 31.3 kg/m2 vs 30.0 in non-NAFLD, P=0.005), were more likely to be Hispanic/Latina (32.4% vs 17.3%, P< 0.001), and were more likely to have public health insurance (48.1% vs 39.8%, P=0.001). Age and diastolic BP were similar between both groups. Comparing NAFLD with non-NAFLD pregnancies, the rate of HDP was 11.1% vs 11.6% (P=0.876). NAFLD was not associated with increased odds of HDP in adjusted models (adjusted odds ratio [aOR]= 0.70, 95% CI [0.34, 1.47], P=0.35). Adjusting for GDM status did not change the results (aOR=0.65, 95% CI [0.29, 1.46], P=0.30). Conclusion: Among pregnant individuals with overweight and obese BMI, NAFLD was not associated with an increased risk of HDP. Rates of NAFLD may be underestimated using our strict laboratory-based definition. Further studies are needed to delineate specific risks in pregnant individuals with NAFLD.