Ruth McCuaig, Fergus Gardiner, Thomas Cairns, Chris Arthur Retrospective cohort study into incidence and birth outcomes of Intrahepatic Obstetric Cholestasis of pregnancy at a tertiary teaching hospital Ruth McCuaig, Fergus Gardiner, Thomas Cairns, Chris Arthur

Background Intrahepatic cholestasis of pregnancy (ICP) increases pregnancy risk, and although uncommon the increased risk of stillbirth can cause maternal anxiety and depression. The incidence varies depending on population Stillbirth in ICP is likely due to acute anoxia Diagnostic criteria for and management of ICP are not well defined in Australia We aimed to determine the prevalence and pregnancy outcomes of ICP at The Canberra Hospital (TCH) ICP is characterised by pruritus in the absence of a skin rash as well as with abnormal LFTs, with neither an alternative cause and both resolving after delivery Classically itchy palms and soles Incidence from 0.7% up to 5% in selected populations English multiethnic population 0.7% Indian-Asian or Pakastani-Asian origin 1.2-1.5% Chilian 2.4% Araucanian-Indian 5% Given demise is not related to placental insufficiency Ultrasound and CTG are of little benefit but may help relieve maternal anxiety Limitations are concerning as ICP is associated with increased fetal risks including preterm birth, iatrogenic preterm birth and fetal death Furthermore the mental well being of the mother is associated with maternal morbidity relating to severe pruritis, sleep deprivation and stress and anxiety associated with linkages to preterm stillbirths in patients with ICP. RCOG guidelines state a discussion should take place with women regarding IOL from 37wks, with a stronger case in patients with severely deranged pathology (IE BA >40) We hypothesised that the prevalence of ICP would be low and ICO pregnancy outcomes would be statistically non-inferior to those without ICP

Methods – data collected during patient note audit Description Data collected Demographic information Age, ethnicity, BMI, family history, previous contraception, assisted conception, and previous pregnancy outcomes. Pathology result and ordering information LFT pathology, including Bilirubin, Aspartate aminotransferase, and Alanine aminotransferase. Bile acid pathology (µmol/1). Diagnosed pruritus Clinical itch with non-pregnancy causes excluded Direct mention of the following in the electronic note:   Obstetric cholestasis Intrahepatic cholestasis of pregnancy Liver disease of pregnancy Management and monitoring Medication use Pathology, CTG and ultrasound Pregnancy outcomes Gestational age of diagnosis, stillbirth, gestational age at delivery, birthweight, PPH, caesarean section rate, assisted delivery rate, IOL rate, NICU admission, follow-up Retrospective cohort study between 1st January 2014 to 31st December 2016 (36 months) Raw data gained through Birth Outcomes System, a record of all pregnancies at TCH and the medical records reviewed for all ICP pregnancies Exclusion criteria – women with pruritus but no elevation in serum bile acids or LFTs and/or pregnancies ending prior to 24 weeks gestation

Results – demographics comparing all pregnancies and ICP group Description Non-ICP (n=10364) ICP (n=66) P-value Maternal age 30 29.6 >0.05 Booking BMI >35 903 (8.7%) 8 (12.1%) Gestational age at delivery 39.3 37 <0.001 IOL 2841 (27.4%) 44 (66.7%) Mean birth weight 3.283 3.02 Caesarean section 2943 (28.4%) 25 (37.9%) Assisted – Forceps 707 (6.8%) 8.0 (12.2%) Assisted – Vacuum 711 (6.9%) 0 (0%) N/A Disbetes (GDM, T2DM, T1DM) 1760 (16.9%) 27 (40.9%) Admission to NICU (36.0-42.1) 365 (3.5%) 1 (1.5%) Stillbirths 121 (1.2%) Twin birth rate 252 (2.4%) 9 (13.6%) <0.01 There were 10364 births during the study period including 66 ICP pregnancies (0.64% incidence) The statistics The majority of women were Caucasian (68.2%) followed by sub-continental at 22.7% The primary clinical outcomes of ICP include a median gestational age at delivery of 37 compared to 39+3 weeks and despite an earlier gestational birth age and ;pwer birth weight there was no increase in NICU admission Perinatal mortality did not differ significantly

Results 99% of women presented with pruritic Management of ICP 100% pathology performed 87.9% had deranged LFTs 83.3% had elevated bile acids 35.7% induction booked at diagnosis 34.8% were monitored with CTG 63.6% were monitored with pathology 68.1% had an obstetric ultrasound 16.7% had a upper abdominal ultrasound and liver panel performed Treatment for ICP 65.2% ursodeoxyxholic acid prescribed 43.9% antihistamines 18.2% emolients The majority of patients had pruritis (99%), deranged LFTs (87.9%) and elevated bile acids (83.3%) It was also observed that the majority of patients were managed with ursodeoxycholic acid and symptoms treated with antihistamines and emolients

Conclusion ICP pregnancies had higher induction rates at earlier gestations This did not result in statistically significant lighter babies or more NICU admissions There was no difference in caesarean section rate, instrumental deliveries or stillbirths between ICP and all pregnancies The treatment methodology for ICP pregnancies results in similar outcomes to other pregnancies Larger multicentre observational studies are required to determine stillbirth rate and reduction with early IOL

References Kenyon AP, Tribe RM, Nelson-Piercy C, Girling JC, Williamson C, Seed PT, et al. Pruritus in pregnancy: a study of anatomical distribution and prevalence in relation to the development of obstetric cholestasis. Obstet Med. 2010;3(1):25–9. Abedin P, Weaver JB, Egginton E. Intrahepatic cholestasis of pregnancy: prevalence and ethnic distribution. Ethn Health. 1999;4(1-2):35-7. Reyes H, Gonzalez MC, Ribalta J, Alburto H, Matus C, Schramm G, et al. Prevalence of intrahepatic cholestasis of pregnancy in Chile. Ann Intern Med. 1978;88(4):487-93. Arthur C, Mahomed K. Intrahepatic cholestasis of pregnancy: diagnosis and management; a survey of Royal Australian and New Zealand College of Obstetrics and Gynaecology fellows. Aust N Z J Obstet Gynaecol. 2014;54(3):263-7. Royal College of Obstetricians and Gynaecologists. Obstetric Cholestasis. Green-top Guideline No432011. Fisk NM, Bye WB, Storey GN. Maternal features of obstetric cholestasis: 20 years experience at King George V Hospital. Aust N Z J Obstet Gynaecol. 1988;28(3):172-6. Bannister-Tyrrell M, Ford JB, Morris JM, Roberts CL. Intrahepatic cholestasis of pregnancy is not associated with stillbirth in an Australian maternity population. Eur J Obstet Gynecol Reprod Biol. 2014;176(1):204–5. Fisk NM, Storey GN. Fetal outcome in obstetric cholestasis. Br J Obstet Gynaecol. 1988;95(11):1137-43. Phillips C, Boyd M. Intrahepatic Cholestasis of Pregnancy. Nurs Womens Health. 2015;19(1):46-57. Roncaglia N, Arreghini A, Locatelli A, Bellini P, Andreotti C, Ghidini A. Obstetric cholestasis: outcome with active management. Eur J Obstet Gynecol Reprod Biol. 2002;100(2):167-70.