Intrahepatic cholestasis of pregnancy (ICP) is thought to have a hormonal cause and is therefore more likely to occur in a twin pregnancy due to increased levels of hormones.
Rates of ICP in twin pregnancies are between 20-25%.1,2 In contrast, ICP only occurs about 0.3-0.5% of singleton pregnancies.3 Twin pregnancies conceived by In vitro fertilization (IVF) also have an increased risk of ICP compared to spontaneous twin pregnancies.4 The ICP is often more severe and diagnosed earlier in IVF pregnancies.5 This could be due to the use of hormonal medications in IVF pregnancies.
In twin pregnancies, ICP is often diagnosed earlier (average 33 weeks) and has been shown to be more severe with higher bile acids.1
There are only a few studies that look at the risks of ICP specifically in a twin pregnancy. One study by Xu et al showed that the risks of cesarean section, preterm delivery, fetal distress and need for admission to the NICU were increased in twin pregnancies.6 As in singleton pregnancies, the bile acid levels have been shown to affect these rates with higher bile acids having increased risks.7 One study also showed that if ALT (one of the liver function tests), indirect bilirubin or albumin is severely elevated, there may be more risks.8
Other studies have also shown an increased risk of stillbirth in twin pregnancies with ICP and also stillbirth that occurs earlier in twin ICP pregnancies.9 Even without ICP, twin pregnancies are at a 2 times increased risk of stillbirth over a singleton pregnancy. ICP seems to increase this risk of stillbirth further.
From a chart review of twin ICP pregnancies vs single ICP pregnancies, the stillbirth rate is increased even at lower levels of bile acids.9 For singleton pregnancies, the risk of stillbirth is not increased significantly until bile acids are over 100 µmol/L.10 Unfortunately for twin pregnancies, there is a significantly increased risk of stillbirth even with low bile acid levels. Therefore, following bile acid levels may not be as sensitive at predicting stillbirth as in a singleton pregnancy.
| Bile Acid Level | Stillbirth Risk for Singleton (1 baby) Pregnancy | Stillbirth Risk for Twin Pregnancy |
|---|---|---|
| 10-39 µmol/L | 0.13% | 3.3% |
| Greater than 40 µmol/L | 0.28-3.44%* | 5.1% |
*3.44% was only for singleton pregnancies with bile acids measured at over 100 µmol/L
Stillbirths were also shown to occur at earlier points in the twin pregnancies. In a singleton pregnancy, most stillbirths occur later in the pregnancy after 36 weeks of gestation. The stillbirths in the twin pregnancies occurred earlier between 33-35 weeks of gestation. 9,10
Unfortunately there are no clear recommendations for when twin pregnancies should be delivered. While the research is pointing to increased risks of stillbirth at earlier weeks of pregnancy in twins, no consensus from the OB/Gyn governing boards has been specified for twins. With the research out there, one could consider twins to be a higher risk group of ICP and consider aggressive management.
Increasing bile acid levels or elevated liver function tests (ALT, AST or bilirubin) seem to confer more risk in twins and these levels could be used to inform delivery guidelines.2 However, some twin pregnancies still are complicated by stillbirth at lower levels.
More research is needed to further clarify the true risks of ICP in twin pregnancies. Until then, it is recommended that each twin pregnancy be treated with shared decision making between physician and patient.3
Patient Information Article: Twin Pregnancies and ICP: What Expecting Parents Need to Know
References
2 Mei Y, Gao L, Lin Y, Luo D, Zhou X, He L. Predictors of adverse perinatal outcomes in intrahepatic cholestasis of pregnancy with dichorionic diamniotic twin pregnancies. J Matern Fetal Neonatal Med. 2019 Feb;32(3):472-476. doi: 10.1080/14767058.2017.1384461. Epub 2017 Oct 11. PMID: 29020816.
3 Society for Maternal-Fetal Medicine (SMFM). Electronic address: pubs@smfm.org; Lee RH, Mara Greenberg, Metz TD, Pettker CM. Society for Maternal-Fetal Medicine Consult Series #53: Intrahepatic cholestasis of pregnancy: Replaces Consult #13, April 2011. Am J Obstet Gynecol. 2021 Feb;224(2):B2-B9. doi: 10.1016/j.ajog.2020.11.002. Epub 2020 Nov 13. PMID: 33197417.
4 Çelik S, Çalışkan C. The Impact of Assisted Reproductive Technology in Twin Pregnancies Complicated by Intrahepatic Cholestasis of Pregnancy: a Retrospective Cohort Study. Z Geburtshilfe Neonatol. 2021 Feb;225(1):34-38. doi: 10.1055/a-1129-7358. Epub 2020 Mar 20. PMID: 32198731.
5 Feng C, Li WJ, He RH, Sun XW, Wang G, Wang LQ. Impacts of different methods of conception on the perinatal outcome of intrahepatic cholestasis of pregnancy in twin pregnancies. Sci Rep. 2018 Mar 5;8(1):3985. doi: 10.1038/s41598-018-22387-6. PMID: 29507303; PMCID: PMC5838236.
6 Xu T, Deng C, Zhan Y, Hu Q, Huang G, Wang X, Guo B, Yu H, Wang X. Perinatal outcomes associated with ICP in twin pregnancies were worse than singletons: an almost 5-year retrospective cohort study. BMC Pregnancy Childbirth. 2022 Nov 5;22(1):820. doi: 10.1186/s12884-022-05160-6. PMID: 36335293; PMCID: PMC9636774.
7 Zhao Y, Zhang Q, Sheng Y, Zhang M, He G, Liu X. Preterm birth and stillbirth: total bile acid levels in intrahepatic cholestasis of pregnancy and outcomes of twin pregnancies: a retrospective cohort study from 2014 to 2022. BMC Pregnancy Childbirth. 2025 May 19;25(1):588. doi: 10.1186/s12884-025-07644-7. PMID: 40389846; PMCID: PMC12087052.
8 Luo S, Mao J, Wen L, Chen Y, Li J, You W, Yang Y. A retrospective cohort study on perinatal outcomes of monochorionic and dichorionic twin pregnancies complicated by intrahepatic cholestasis of pregnancy. Sci Rep. 2025 Jul 17;15(1):25984. doi: 10.1038/s41598-025-09792-4. PMID: 40676023; PMCID: PMC12271304.
9 Liu X, Landon MB, Chen Y, Cheng W. Perinatal outcomes with intrahepatic cholestasis of pregnancy in twin pregnancies. J Matern Fetal Neonatal Med. 2016;29(13):2176-81. doi: 10.3109/14767058.2015.1079612. Epub 2015 Sep 12. PMID: 26364658.
10 Ovadia C, Seed PT, Sklavounos A, Geenes V, Di Ilio C, Chambers J, Kohari K, Bacq Y, Bozkurt N, Brun-Furrer R, Bull L, Estiú MC, Grymowicz M, Gunaydin B, Hague WM, Haslinger C, Hu Y, Kawakita T, Kebapcilar AG, Kebapcilar L, Kondrackienė J, Koster MPH, Kowalska-Kańka A, Kupčinskas L, Lee RH, Locatelli A, Macias RIR, Marschall HU, Oudijk MA, Raz Y, Rimon E, Shan D, Shao Y, Tribe R, Tripodi V, Yayla Abide C, Yenidede I, Thornton JG, Chappell LC, Williamson C. Association of adverse perinatal outcomes of intrahepatic cholestasis of pregnancy with biochemical markers: results of aggregate and individual patient data meta-analyses. Lancet. 2019 Mar 2;393(10174):899-909. doi: 10.1016/S0140-6736(18)31877-4. Epub 2019 Feb 14. Erratum in: Lancet. 2019 Mar 16;393(10176):1100. doi: 10.1016/S0140-6736(19)30504-5. PMID: 30773280; PMCID: PMC6396441.
1. Batsry L, Zloto K, Kalter A, Baum M, Mazaki-Tovi S, Yinon Y. Perinatal outcomes of intrahepatic cholestasis of pregnancy in twin versus singleton pregnancies: is plurality associated with adverse outcomes? Arch Gynecol Obstet. 2019 Oct;300(4):881-887. doi: 10.1007/s00404-019-05247-0. Epub 2019 Jul 25. PMID: 31346701
2. Mei Y, Gao L, Lin Y, Luo D, Zhou X, He L. Predictors of adverse perinatal outcomes in intrahepatic cholestasis of pregnancy with dichorionic diamniotic twin pregnancies. J Matern Fetal Neonatal Med. 2019 Feb;32(3):472-476. doi: 10.1080/14767058.2017.1384461. Epub 2017 Oct 11. PMID: 29020816.
3.Society for Maternal-Fetal Medicine (SMFM). Electronic address: pubs@smfm.org; Lee RH, Mara Greenberg, Metz TD, Pettker CM. Society for Maternal-Fetal Medicine Consult Series #53: Intrahepatic cholestasis of pregnancy: Replaces Consult #13, April 2011. Am J Obstet Gynecol. 2021 Feb;224(2):B2-B9. doi: 10.1016/j.ajog.2020.11.002. Epub 2020 Nov 13. PMID: 33197417.
4. Çelik S, Çalışkan C. The Impact of Assisted Reproductive Technology in Twin Pregnancies Complicated by Intrahepatic Cholestasis of Pregnancy: a Retrospective Cohort Study. Z Geburtshilfe Neonatol. 2021 Feb;225(1):34-38. doi: 10.1055/a-1129-7358. Epub 2020 Mar 20. PMID: 32198731.https://doi.org/10.1016/j.jhep.2020.11.038
5. Feng C, Li WJ, He RH, Sun XW, Wang G, Wang LQ. Impacts of different methods of conception on the perinatal outcome of intrahepatic cholestasis of pregnancy in twin pregnancies. Sci Rep. 2018 Mar 5;8(1):3985. doi: 10.1038/s41598-018-22387-6. PMID: 29507303; PMCID: PMC5838236.
6. Xu T, Deng C, Zhan Y, Hu Q, Huang G, Wang X, Guo B, Yu H, Wang X. Perinatal outcomes associated with ICP in twin pregnancies were worse than singletons: an almost 5-year retrospective cohort study. BMC Pregnancy Childbirth. 2022 Nov 5;22(1):820. doi: 10.1186/s12884-022-05160-6. PMID: 36335293; PMCID: PMC9636774.
7. Zhao Y, Zhang Q, Sheng Y, Zhang M, He G, Liu X. Preterm birth and stillbirth: total bile acid levels in intrahepatic cholestasis of pregnancy and outcomes of twin pregnancies: a retrospective cohort study from 2014 to 2022. BMC Pregnancy Childbirth. 2025 May 19;25(1):588. doi: 10.1186/s12884-025-07644-7. PMID: 40389846; PMCID: PMC12087052.
8. Luo S, Mao J, Wen L, Chen Y, Li J, You W, Yang Y. A retrospective cohort study on perinatal outcomes of monochorionic and dichorionic twin pregnancies complicated by intrahepatic cholestasis of pregnancy. Sci Rep. 2025 Jul 17;15(1):25984. doi: 10.1038/s41598-025-09792-4. PMID: 40676023; PMCID: PMC12271304.
9. Liu X, Landon MB, Chen Y, Cheng W. Perinatal outcomes with intrahepatic cholestasis of pregnancy in twin pregnancies. J Matern Fetal Neonatal Med. 2016;29(13):2176-81. doi: 10.3109/14767058.2015.1079612. Epub 2015 Sep 12. PMID: 26364658.
10. Ovadia C, Seed PT, Sklavounos A, Geenes V, Di Ilio C, Chambers J, Kohari K, Bacq Y, Bozkurt N, Brun-Furrer R, Bull L, Estiú MC, Grymowicz M, Gunaydin B, Hague WM, Haslinger C, Hu Y, Kawakita T, Kebapcilar AG, Kebapcilar L, Kondrackienė J, Koster MPH, Kowalska-Kańka A, Kupčinskas L, Lee RH, Locatelli A, Macias RIR, Marschall HU, Oudijk MA, Raz Y, Rimon E, Shan D, Shao Y, Tribe R, Tripodi V, Yayla Abide C, Yenidede I, Thornton JG, Chappell LC, Williamson C. Association of adverse perinatal outcomes of intrahepatic cholestasis of pregnancy with biochemical markers: results of aggregate and individual patient data meta-analyses. Lancet. 2019 Mar 2;393(10174):899-909. doi: 10.1016/S0140-6736(18)31877-4. Epub 2019 Feb 14. Erratum in: Lancet. 2019 Mar 16;393(10176):1100. doi: 10.1016/S0140-6736(19)30504-5. PMID: 30773280; PMCID: PMC6396441.