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Effect of abnormal liver function test on maternal and perinatal outcome in pregnancy: observational study

Liver disease is a rare complication of pregnancy affecting approximately 3% to 5% of all pregnancies. Liver involvement in pregnancy can be of 3 types i.e. liver disease as a consequence to pregnancy, liver disease coincidental to pregnancy and pregnancy in patients with pre-existing liver disease. Liver diseases which can be due to pregnancy as a consequence of changes in pregnancy include intrahepatic cholestasis of pregnancy (ICP), acute fatty liver of pregnancy (AFLP) and, hemolysis, elevated liver enzymes and low platelets count (HELLP) syndrome. Apart from these, liver abnormalities are often encountered in patients with pre-eclampsia (PE) and hyperemesis gravidarum (HG). Coincidental or preexisting liver disease include acute and chronic viral hepatitis, cirrhosis of liver, vascular alterations such as Budd–Chiari syndrome (BCS), drug induced hepatotoxicity, autoimmune liver diseases, and metabolic disorders. These liver disorders in pregnancy may adversely affect maternal and fetal outcome.

the level of antithrombin III and protein S, serum albumin and total proteins are observed, however, level of liver transaminase, serum bilirubin level and prothombin time remain unchanged. 4 Thus elevations in aminotransferases or gamma-glutamyl transpeptidase (GGTP) signify pathology, and should prompt a search for disease diagnosis of liver disease during pregnancy.
There is insufficient information about the frequency, etiological profile, outcome, and management guidelines for pregnancy-related liver disease in India. Therefore the present study was conducted with the objective to assess the spectrum of liver disease in pregnancy, and its course and effect on maternal and fetal outcomes.

METHODS
The present study was conducted as a prospective follow up study in the Department of Obstetrics and Gynecology, Laxmi Narayan Medical College and associated J. K. Hospital, Bhopal for the period of 1 year i.e. from 01 January 2019 to 30 December 2019. All pregnant women attending the outdoor department or admitted between the age group of 18-35 years were screened over the study period. Inclusion criteria was pregnant females between 18-35 years presenting with pruritis, abdominal pain, jaundice, fever, pedal edema, raised blood pressure, bleeding disorder, hepatosplenomegaly, known case of portal hypertension, hepatitis, cirrhosis alcoholism and gall stone disease, history of cholestasis, pre-eclampsia and eclampsia in previous pregnancy; or any liver disease under current treatment ,normal asymptomatic patients were excluded from the study.
All patients included were then subjected to liver function tests after obtaining informed consent. The protocol was approved by the ethics research committee of the institute. Apart from LFT, viral markers hepatitis B surface antigen (HBsAg), hepatitis A virus (HAV), hepatitis E virus (HEV), hepatitis C virus (HCV) and other viral marker, ultrasonography (USG) of hepatobiliary system were also done if indicated. Patients with abnormal LFT reports were observed for complications, and patients managed accordingly by standard management protocols.
Fetomaternal outcomes was noted and patients were prospectively followed up till two weeks post-partum. A total of 8091 females attended outpatient department (OPD) and inpatient department (IPD) during the study period, out of them, 180 females fulfilling inclusion criteria were screened and liver function tests were conducted among them. Screening was done, 136 females were observed to have abnormal liver function; of them, 16 patient lost to follow-up, hence excluded from study (4 of hyper emesis, 2 of jaundice and 10 of pregnancy induced hypertension-PIH) in statistical data analysis. Maternal deaths were noted in 2 cases to severe PIH with disseminated intravascular coagulation (DIC) and other with multiorgan failure in post-partum period. Thus the present study was conducted on a total of 120 patients.

Statistical analysis
Data was compiled using Microsoft Excel and analyzed using IBM Statistical Package for the Social Sciences (SPSS) version 20 software.

RESULTS
The incidence of liver disease during pregnancy in present study was 1.68%. The study was conducted on 120 pregnant females between 18 to 35 years with mean age of 25.3±4.8 years.
Majority of patients in present study belonged to 25 to 29 years of age (49.17%) followed by 47 (39.17%) cases belonging to 20-24 years of age. About 65% females were nulliparous whereas 19.2% were parity 1. Most common presenting complaints was oedema observed in 22 (18.33%) cases followed by itching all over body noted in 19 (15.8%) cases. Vomiting was presenting complaints in 10 (8.3%) cases with hyperemesis gravidarum presenting in first trimester of pregnancy. About 4 patients (3.3%) presented with convulsions, blurring of vision and altered sensorium. Only 1 (0.8%) female presented with acute abdominal pain. (Table 1).  (Figure 1).

Figure 1: Distribution of pregnant females according to cause of abnormal liver function test.
History of liver disease in previous pregnancy was observed 18 cases, of them, 6 patients (5%) gave history of high blood pressure, 4 patients (3.33%) gave history of jaundice in previous pregnancy, history of itching was present in 4 (3.33%) patients, 3 patients (2.50%) gave history of gall stones and 1 patient (0.83%) had history of eclampsia during previous pregnancy.
About 76 (63.3%) patients had normal vaginal deliveries, of them, 63 patients had spontaneous vaginal delivery whereas induction was require in 13 cases. Caesarean section was done in 36.7% cases ( Table 2). Most of the patients with abnormal liver function test delivered at term whereas preterm delivered were observed in 18 (15%) patients which were mostly due to severe PIH. Maternal complications were observed in 10.82% of all cases. Most common complication was abruption placentae (4.16%) followed by PPH and sepsis observed in 3.33% and 1.7% respectively. DIC was observed in only 1 (0.83%) patient only. Cholecystectomy was done in one case of cholestasis and maternal deaths were noted in 2 cases which were attributed to severe PIH associated with DIC and multi-organ failure respectively (Table 3).
Fetal outcome in majority of cases was alive and healthy at term (57.5%) whereas 18 (15%) cases had preterm live births. Intrauterine growth restriction was observed among 27 (22.5%) cases and intrauterine death was seen among 6 (5.0%) cases (Table 4).  In present study, about 31.6% cases were low birth weight (<2.5 kg) which was due to IUGR or preterm delivery and Apgar score at 5 min was <4 in 7.9% cases i.e. mostly among neonates born to mothers with pregnancy induced hypertension (Table 5).

DISCUSSION
Liver diseases in pregnancy is associated with various complications among both mother and fetus. The present study documented incidence of liver disease in 1.68% in pregnancy. However Rathi et al in their study reported much lower prevalence (0.9%) of liver disease in pregnancy. 2 Mishra et al also documented 0.9% incidence of liver disease. 5 The observed discrepancy in incidence rate of liver disease between present study and reference study could be due to difference in inclusion criteria. The present study had certain limitations. Mother and neonates were followed up only till 2 weeks, thus late complications associated with liver disease could not be studies.

CONCLUSION
Our study shows that though liver disease is uncommon in Indian pregnant women, it is associated with high maternal and perinatal morbidity. PIH-associated liver dysfunction, AFLP and viral hepatitis are serious conditions. A high index of suspicion of liver disease, early diagnosis, prompt referral to a higher centre when required, appropriate supportive management, and a proactive policy of early delivery when indicated may improve the maternal and fetal outcomes in pregnant women with liver disease. Thus LFT should be conducted as a routine investigation in all pregnant females during first and second trimester.