TY - JOUR
T1 - Ursodeoxycholic acid in intrahepatic cholestasis of pregnancy: an individual participant data meta-analysis
AU - Ovadia, Caroline
AU - Sajous, Jenna
AU - Seed, Paul Townsend
AU - Patel, Kajol
AU - Williamson, Nicholas J
AU - Attilakos, George
AU - Azzaroli, Francesco
AU - Bacq, Yannick
AU - Batsry, Linoy
AU - Broom, Kelsey
AU - Brun-Furrer, Romana
AU - Bull, Laura
AU - Chambers, Jenny
AU - Cui, Yue
AU - Ding, Min
AU - Dixon, Peter
AU - Estiu, Maria
AU - Gardiner, Fergus
AU - Geenes, Victoria
AU - Grymowicz, Monika
AU - Gunaydin, Berrin
AU - Hague, William
AU - Haslinger, Christian
AU - Hu, Yayi
AU - Indraccolo, Ugo
AU - Juusela, Alexander
AU - Kane, Stefan
AU - Kebapcilar, Ayse
AU - Kebapcilar, Levent
AU - Kohari, Katherine
AU - Kondrackiene, Jurate
AU - Koster, Maria
AU - Lee, Richard
AU - Liu, Xiaohua
AU - Locatelli, Anna
AU - Macias, Rocio
AU - Madazli, Riza
AU - Majewska, Agata
AU - Maksym, Kasia
AU - Marathe, Jessica
AU - Morton, Adam
AU - Oudijk, Martijn
AU - Oztekin, Deniz
AU - Peek, Michael
AU - Shennan, Andrew
AU - Tribe, Rachel
AU - Tripodi, Valeria
AU - Turk Ozterlemez, Naciye
AU - Vasavan, Tharni
AU - Wong, L.F. Audris
AU - Yinon, Yoav
AU - Zhang, Qianweng
AU - Zloto, Keren
AU - Marschall, Hanns-Ulrich
AU - Thornton, Jim
AU - Chappell, Lucy
AU - Williamson, Catherine
PY - 2021/2/22
Y1 - 2021/2/22
N2 - BackgroundUrsodeoxycholic acid (UDCA) is commonly used to treat intrahepatic cholestasis of pregnancy (ICP), yet its largest trial detected minimal benefit for a composite outcome (stillbirth, preterm birth, and neonatal unit admission). We aimed to determine whether UDCA affects specific adverse perinatal outcomes.MethodsFollowing systematic review of the literature, authors of selected studies were invited to submit individual participant data for meta-analysis. Studies of all design without evidence of selection bias were eligible for inclusion, reported by January 2020. The primary outcome was stillbirth, although we anticipated insufficient data to achieve statistical power, and included a composite of stillbirth and preterm birth as a main secondary outcome. A mixed-effects meta-analysis was performed using multilevel modelling, adjusting for bile acid concentration, parity, and multifetal pregnancy. Analyses were performed in Stata version 16·0; the study was registered in PROSPERO: CRD42019131495. FindingsEighty-five studies were selected, from which data were provided for 6974 women from 34 studies, of whom 4726 (67·8%) took UDCA. With adjustment for confounders, the results including observational studies were similar to those of randomised controlled trials (RCT). In RCTs, UDCA treatment had no statistically significant effect on stillbirth (adjusted odds ratio (aOR) 0·29, 0·04 to 2·42, p=0·25), but was associated with a reduced composite outcome (aOR 0·60, 0·39 to 0·91, p=0·016), largely due to reduced total preterm birth (aOR 0·61, 0·40 to 0·92, p=0·019). This was likely due to reduced spontaneous preterm birth, which was reduced when comparing participants of all studies (aOR 0·55, 0·35 to 0·88, p=0·012). InterpretationIPD revealed no significant effect of UDCA on stillbirth, likely limited by the low overall event rate. However, rates in combination with preterm birth were reduced, providing evidence for the clinical benefit of antenatal UDCA treatment. FundingTommy’s, Wellcome Trust, ICP Support, and the National Institute for Health Research.
AB - BackgroundUrsodeoxycholic acid (UDCA) is commonly used to treat intrahepatic cholestasis of pregnancy (ICP), yet its largest trial detected minimal benefit for a composite outcome (stillbirth, preterm birth, and neonatal unit admission). We aimed to determine whether UDCA affects specific adverse perinatal outcomes.MethodsFollowing systematic review of the literature, authors of selected studies were invited to submit individual participant data for meta-analysis. Studies of all design without evidence of selection bias were eligible for inclusion, reported by January 2020. The primary outcome was stillbirth, although we anticipated insufficient data to achieve statistical power, and included a composite of stillbirth and preterm birth as a main secondary outcome. A mixed-effects meta-analysis was performed using multilevel modelling, adjusting for bile acid concentration, parity, and multifetal pregnancy. Analyses were performed in Stata version 16·0; the study was registered in PROSPERO: CRD42019131495. FindingsEighty-five studies were selected, from which data were provided for 6974 women from 34 studies, of whom 4726 (67·8%) took UDCA. With adjustment for confounders, the results including observational studies were similar to those of randomised controlled trials (RCT). In RCTs, UDCA treatment had no statistically significant effect on stillbirth (adjusted odds ratio (aOR) 0·29, 0·04 to 2·42, p=0·25), but was associated with a reduced composite outcome (aOR 0·60, 0·39 to 0·91, p=0·016), largely due to reduced total preterm birth (aOR 0·61, 0·40 to 0·92, p=0·019). This was likely due to reduced spontaneous preterm birth, which was reduced when comparing participants of all studies (aOR 0·55, 0·35 to 0·88, p=0·012). InterpretationIPD revealed no significant effect of UDCA on stillbirth, likely limited by the low overall event rate. However, rates in combination with preterm birth were reduced, providing evidence for the clinical benefit of antenatal UDCA treatment. FundingTommy’s, Wellcome Trust, ICP Support, and the National Institute for Health Research.
M3 - Article
SN - 2468-1253
SP - 1
EP - 25
JO - The Lancet Gastroenterology & Hepatology
JF - The Lancet Gastroenterology & Hepatology
ER -