Pregnancy Outcomes in Women with Autoimmune Hepatitis – a Nationwide Population-Based Cohort Study with Histopathology

Background: Autoimmune hepatitis (AIH) is a chronic inflammatory liver condition that predominantly affects women. However, pregnancy risks remain unclear in these women.    Methods: A nationwide population-based cohort study (ESPRESSO) in Sweden 1992-2016 including 309 singleton births in women with AIH and 1,532 matched births in women from the general population was performed. AIH was diagnosed as a combination of administrative coding from medical diagnosis of AIH and liver biopsy data from Sweden’s 28 pathology departments. Using conditional logistic regression, odds ratios (ORs) for adverse pregnancy outcomes were determined.  Findings: Among 306 live births to AIH women, 51 (16.7%) were preterm compared to 70 out of 1,524 (4.6%) reference births. This corresponded to an OR of 5.10 for preterm birth (95%CI=3.29-7.92), with similar odds seen when using sibling comparators. AIH women with and without cirrhosis had similar odds for preterm birth. The AIH association was particularly strong with medically indicated preterm birth (OR=13.01; 95%CI=5.50-30.79). In addition, AIH was associated with offspring low birth weight (OR=5.31; 95%CI=2.82-9.99) and low 5-min Apgar score (OR=3.46; 95%CI=1.14-10.49), but we found no association with congenital malformations (OR=1.14; 95%CI=0.68-1.91), small for gestational age (OR=1.04; 95%CI=0.38-2.85), stillbirth (OR=0.59; 95%CI=0.02-18.88), or neonatal death (OR=7.42; 95%CI=0.65-84.25). Maternal AIH was linked to an increased odds of cesarean section (OR=1.44; 5%CI=1.04-2.00) and preeclampsia (OR=3.65; 95%CI=2.01-6.64), but not to gestational diabetes.  Interpretation: Maternal AIH was associated with a 5-fold higher odds of preterm birth, and future studies are needed to elucidate mechanisms and identify interventions that can reduce this risk.  Funding: This project received funding through the Karolinska Institutet and Columbia University Irving Medical Center. Declaration of Interest: Jonas F Ludvigsson coordinates a study on behalf of the Swedish IBD quality register (SWIBREG). This study has received funding from Janssen corporation. Rajani Sharma is a speaker for Takeda on educational lectures, unrelated to this research. Hannes Hagstrom’s institution has received research funding from Intercept, Astra Zeneca and Gilead. Hannes Hagstrom has served as a scientific board advisor for BMS and Gilead. None of these are deemed relevant for the current study. Elizabeth C Verna is on the Gilead advisory board and receives Salix research support. Tracey G Simon reports grants to the institution from Amgen, and has previously served as a consultant to Aetion, for work unrelated to this manuscript. This study did not receive any support from these organizations and these organizations did not have a role in the design and conduct of the study. Authors not named here have disclosed no conflicts of interest. Ethical Approval: The ESPRESSO cohort was reviewed by the Stockholm Ethics Board (No. 2014/1287-31/4) approved on August 27, 2014.