Feto-Maternal outcomes in Intrahepatic Cholestasis in Pregnancy in a Tertiary Care Centre in Eastern Nepal

Background Intrahepatic cholestasis of pregnancy has poor feto-maternal outcomes. To date there has been sparse publications regarding impact of intrahepatic cholestasis in feto-maternal outcomes in our setting. Therefore, we aimed to study the feto-maternal outcome in patients with intrahepatic cholestasis of pregnancy. Material and Methods A hospital based prospective cross-sectional study carried out in department of Obstetrics and Gynecology of Nobel Medical College, Biratnagar, Nepal from 1 January 2014 to 30 December 2015 in women who presented with pruritus in third trimester of pregnancy and having deranged liver function tests. All the cases were followed from admission to discharge. Socio-demographic, clinico-laboratory profile and feto-maternal outcomes were recorded in a preformed structured proforma. Descriptive statistics was used to present the data. Results Among 6,780 women admitted for delivery, 80 had cholestasis of pregnancy with incidence of 1.15%. 83% were of 18-35 years and 65% were primigravida. Most distressing symptom was generalized pruritus (75.0 %). The cesarean delivery rate was 46.25% and labor induction rate was (47.5%). Fetal complications were seen in majority of cases that included meconium aspiration syndrome 26 (32.5%), intrapartum fetal distress 21 (26.25%) and requirement of: intensive care 38 (48.75%). There were 7 perinatal and 3 neonatal deaths. Conclusion Intrahepatic cholestasis of pregnancy seems fairly common among pregnant women. It may be responsible for a large number of perinatal and neonatal deaths especially after 36 weeks of gestation. A large prospective study is needed to address the problems in time.


Introduction
Intrahepatic Cholestasis in pregnancy (ICP) is defined as pruritus with onset in pregnancy which is associated with abnormal liver function test in the absence of other diseases which resolves following delivery.It typically occurs during third trimester of pregnancy and seldom occurs before 25 weeks period of gestation [1].Its incidence varies in different countries and is very low in Europe (0.1 to 1.5%) whereas in Chile it is very high (14%) [2].
It is 1.2-1.5% in India and Pakistan [3].Maternal consequences in ICP occurs due to increase in plasma protein concentration leading to alteration in carbohydrate metabolism and renal and intestinal function [4].Steatorrhoea leading to deficiency in vitamin K dependent clotting factors and subsequent Post partum haemorrhage (PPH) has been reported [5].In women of ICP, there is chance of 1.5 fold increase in cesarean delivery and 8 fold increase in duration of hospital stay for more than 10 days, 3 fold increase in induction of labor [6].Adverse perinatal outcome is a major concern in intrahepatic cholestasis in pregnancy(ICP).The potential risks are fetal distress, intrauterine fetal death (IUFD), iatrogenic preterm delivery, meconium stained liquor, low birth weight and still birth [7 ,8].Most distressing pruritus leads to sleep deprivation in pregnant women [9].To the best of my knowledge, till this date,there are hardly any studies regarding this obstetric problem in our country.When data are extrapolated from different south Asian studies to our country, it is high likely that, ICP is common in our setting with poor fetomaternal outcomes.With this hypothesis, we aimed to study the fetomaternal outcomes in ICP in our setting.

Material and Methods
It was a Cross-sectional study design carried out in department of Obstetrics and Gynecology of Nobel Medical College, Biratnagar, Nepal from 1 st January 2014 to 30 th December 2015.Ethical clearance from institutional ethical review board (IERB) was obtained before conducting the study.Informed verbal and written consent was taken from the women before enrollment in the study.Any women with pruritus in 3 rd trimester pregnancy underwent liver function test.Patients with history of itching and deranged liver function tests for which there was no explanation other than pregnancy were included in our study.Every case was evaluated in detail, demographic, clinical and laboratory parameters were recorded in well-structured proforma.Cases were followed from admission to discharge.All the maternal and fetal outcomes were noted.Information

Results
During the one-year period, 6,780 women came for delivery and 87 had pruritus in third trimester.Liver Function test were abnormal in nearly 98% of the cases.Among them seven women were lost to follow up.The incidence of ICP was found to be 1.15%   Nepal.During the study period, there were 6,908 women admitted for deliveries.The incidence of obstetric cholestasis was 1.15% which is comparable to the previous study done by Sultana and her colleagues [3].In our study 38(47.5%) of women were induced which is almost similar to study done by Turunen et al [6].Eight (10%) women were induced at 34-36 weeks period of gestation for increasing level of liver enzymes despite medical treatment with ursodeoxycholic acid.However, 17(21.25%)women were induced at 37-38 weeks period of gestation for persistent pruritus though liver parameters were improving.Six women (7.5%) went induction postdated as they were lost in follow up and were admitted after crossing 40 weeks period of gestation only and rest 7(8.75%) women were induced at 38-40 weeks period of gestation.Out of 25 cases (31.25%) of early induction i.e. before 37 weeks,11 women (13.75%) underwent cesarean delivery for failed induction.In our study, out of 80 women, 46.25% underwent cesarean section, out of which 10% were elective cesarean section and 36.25%emergency cesarean section.It is comparatively higher than previous study [6] (14.8%), the reason maybe we had gone for early induction in 31.25%,so increased rate of cesarean for failed induction 11(44%).In our study 11.25% women had postpartum hemorrhage whereas Wang et al (2010) found it to be 1.4% [10].The reason for high incidence of PPH in our study is attributed to high incidence of anemia in our area, poor antenatal visits and low socioeconomic status and only 72% of women had injecton vitamin k before delivery.While analyzing Neonatal outcomes the incidence of low APGAR score <7 in 5 minutes was in 13.75% which is almost similar to previous study done by Alokananda et al in 2005 (18.5%) [2].However, it is very high (4.4%) when compared with next study done in India [11].The reason maybe we have 87% unbooked obstetric cholestasis cases and their higher rate of cesarean section (93.3%).The disease has been related to a high incidence of perinatal complications leading to 45 % meconium stained liquor, 44% preterm delivery and higher incidence of fetal distress (upto22%) [12,13].It is suggested that both intrapartum fetal distress and increase incidence of meconium stained liquor is due to the stimulation of colonic motility by bile acids on Obstetric Cholestasis [13].Like other study [14] (33.3%) we have also observed higher incidence of meconium stained liquor in 32.5%.But Padmaja M et al had not shown significant incidence of meconium stained liquor,which is attributed to proper antenatal visit leading to on time intervention of Obstetric Cholestasis [11].In our study we observed that 15(18.75%)were preterm (iatrogenic 7 and spontaneous 8) which is almost similar to study done by Roncaglia N et al showing incidence of 19.5% [15].Our study had similar finding 6.25% to previous study by Sultana et al 6.67% in relation to intra uterine fetal death [3].But it is high when compared to study done by Aloknanda [2] where incidence of IUFD was found to be only 3.1% which is attributed to our poor number of booked cases and all 5 cases had intrauterine fetal death before being admitted in hospital.We found only two (2.5%)case of fresh stillbirth like in study done by Turunen et al [6] (1.2%) where as another study done in India [11] had shown very low i.e only 0.02% which is attributed to booking status, good antepartum care and higher incidence of cesarean section.In a study conducted by Zecca E and colleagues, IUFD was found to be in 6% patients which is similar to our study (6.25%) [16] .We had 38(47.55%)NICU admissions which are comparatively higher then study done by Deveer et al where the incidence was only 27% [17] which is due to higher number of intrapartum fetal distress and higher percentage of meconium stained liquor (32.5%) in our study.Another study by Sebiha et al had also found almost similar to our finding where incidence of meconium stained liquor to be 25-45%, pretem labor 44% and IUFD upto 5% [18].Obstetric cholestasis is associated with premature delivery both spontaneous and iatrogenic and increase incidence of IUFD and the perinatal mortality from Obstetric Cholestasis is 10.6\1000 live birth [19].Intrauterine fetal death is usually sudden and seems to be due to Acute anoxia [20].

Conclusion
Intrahepatic cholestasis of pregnancy seems fairly common among pregnant women in our setting.It was found to be responsible for a large number of perinatal and neonatal deaths especially after 36 weeks of gestation.A large prospective study is needed to find the clinicepidemiological pattern of this obstetric problem.In the mean time, it is important to realise that by increasing awareness among the health personnel caring for the pregnant women that pruritus of pregnancy is a high risk condition and close fetal monitoring and timely intervention will decrease perinatal mortality significantly.