Is It Necessary to Perform the Pharmacological Interventions for Intrahepatic Cholestasis of Pregnancy? A Bayesian Network Meta-Analysis

Shen, Yi; Zhou, Jie; Zhang, Sheng; Wang, Xulin; Jia, Yulong; He, Sang; Wang, Yuan‐Yuan; Li, Wenchao; Shao, Jianghua; Zhuang, Xun; Liu, Yuanlin; Qin, Gang

doi:10.1007/s40261-018-0717-2

Cited by 20 publications

(19 citation statements)

References 53 publications

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“…Ursodeoxycholic acid has been prescribed to women with ICP to decrease symptoms of itching and improve liver function test values with the hope that this improvement would result in better perinatal outcomes. However, a recent network meta‐analysis of 13 randomized trials with over 600 women showed that ursodeoxycholic acid neither improved itching nor improved perinatal outcomes . Confirming the association with stillbirth and having greater clarity about which women are at risk for stillbirth would be an important step in targeting intensive surveillance among those women at greatest risk.…”

Section: Meta‐analytic Results Helping To Clarify Intrahepatic Cholesmentioning

confidence: 99%

Current Resources for Evidence‐Based Practice, July/August 2019

Barger

2019

J Midwife Womens Health

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Intrahepatic cholestasis of pregnancy (ICP) can be a puzzling diagnosis and at times a management dilemma. ICP is a multifactorial disorder whose risk factors are a combination of genetics, hormonal exposure to estrogen and progesterone, and environmental factors, such as seasonal variation (incidence highest in winter), geography, and dietary deficiencies (selenium and vitamin D). 1 There is a wide variation in the reported incidence, ranging from 0.3% in Sweden and Connecticut 2 to 5.6% in a Latina population in Los Angeles 3 and 16% in Aracanos Indians in Chile. 4 Adverse perinatal outcomes associated with ICP include preterm birth, meconium amniotic fluid, neonatal respiratory complications requiring neonatal intensive care treatment, and stillbirth. 5-7 Unfortunately, antenatal fetal testing with ICP, unlike with pregnancies unaffected by ICP, is not reliable in preventing stillbirth. 8 Therefore, many guidelines for managing women with ICP call for early labor induction prior to term. 9 Ursodeoxycholic acid has been prescribed to women with ICP to decrease symptoms of itching and improve liver function test values with the hope that this improvement would result in better perinatal outcomes. However, a recent network meta-analysis of 13 randomized trials with over 600 women showed that ursodeoxycholic acid neither improved itching nor improved perinatal outcomes. 10 Confirming the association with stillbirth and having greater clarity about which women are at risk for stillbirth would be an important step in targeting intensive surveillance among those women at greatest risk.The meta-analysis by Ovadia and colleagues from The Lancet may be the evidence needed for revising clinical guidelines related to women with ICP. 11 A key strength of this study was its specific definition for ICP, which included serum bile acid as one of the diagnostic criteria. This meta-analysis used 2 approaches to examining the data. The researchers performed an aggregate study meta-analysis from 23 studies with over 5500 women with ICP and over 165,000 women without ICP. More importantly, this is the first study to conduct an individual patient meta-analysis collecting individual-level data, which included serum bile acid and liver function values. The researchers were able to obtain this patient-level data for 5269 women with ICP from 14 countries.

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Section: Meta‐analytic Results Helping To Clarify Intrahepatic Cholesmentioning

confidence: 99%

Current Resources for Evidence‐Based Practice, July/August 2019

Barger

2019

J Midwife Womens Health

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“…Ursodeoksikolikasit olumlu maternal-fetal etkisi ile perinatal morbiditeyi azaltarak erken doğum riskini azaltığı düşünülse de bu konuda net bir kanıt yoktur (21,22). Başka türlü açıklanamayan prurit ve serum safra asidi konsantrasyonları 10-14 μmol/L veya daha fazla olan kadınlarda ursodeoksikolik asidin çok merkezli, randomize, plasebo ile kontrollü bir çalışması olan PITCHES çalışmasında 20. gebelik haftasından sonra 605 kadına günde 1000 mg ursodeoksikolik asit (n=305) veya plasebo (n=300) rastgele verilmiş ve perinatal (intrauterin veya neonatal) ölüm, erken doğum (<37 gebelik haftası) veya yenidoğan yoğun bakımda yatış gerekliliği açısından gruplar arasında istatistiksel olarak anlamlı bir fark bulunmadığı belirtilmiştir (23).…”

Section: Gereç Ve Yöntemunclassified

Gebeliğe Bağlı İntrahepatik Kolestaz: 48 Vakanın Fetal ve Maternal Sonuçlarının Değerlendirilmesi Due to Pregnancy İntrahepatic Cholestasis: Evaluation of Fetal & Maternal Outcomes of 48 Pregnancies

Öçal¹,

Fındık²,

İçen³

2018

TFK

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“… 16 Whether ursodeoxycholic acid improves perinatal outcomes is unclear; contradictory findings, which were dependent on the method of comparison, have been reported from previous meta-analyses of aggregate data of trials of its use. 15 , 17 , 18 , 19 However, these meta-analyses were limited by study sizes, including 600–700 women from all contributing studies. A randomised controlled trial (RCT) of ursodeoxycholic acid in 605 women with intrahepatic cholestasis of pregnancy showed no improvement in the primary outcome (a composite of perinatal death, preterm birth, and neonatal unit admission) with ursodeoxycholic acid; the incidence of meconium-stained amniotic fluid was the only secondary perinatal outcome to improve (ie, decrease) with ursodeoxycholic acid.…”

Section: Introductionmentioning

confidence: 99%

Ursodeoxycholic acid in intrahepatic cholestasis of pregnancy: a systematic review and individual participant data meta-analysis

Ovadia

Sajous

Seed

et al. 2021

The Lancet Gastroenterology & Hepatology

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Summary Background Ursodeoxycholic acid is commonly used to treat intrahepatic cholestasis of pregnancy, yet its largest trial detected minimal benefit for a composite outcome (stillbirth, preterm birth, and neonatal unit admission). We aimed to examine whether ursodeoxycholic acid affects specific adverse perinatal outcomes. Methods In this systematic review and individual participant data meta-analysis, we searched PubMed, Web of Science, Embase, MEDLINE, CINAHL, Global Health, MIDIRS, and Cochrane without language restrictions for relevant articles published between database inception, and Jan 1, 2020, using search terms referencing intrahepatic cholestasis of pregnancy, ursodeoxycholic acid, and perinatal outcomes. Eligible studies had 30 or more study participants and reported on at least one individual with intrahepatic cholestasis of pregnancy and bile acid concentrations of 40 μmol/L or more. We also included two unpublished cohort studies. Individual participant data were collected from the authors of selected studies. The primary outcome was the prevalence of stillbirth, for which we anticipated there would be insufficient data to achieve statistical power. Therefore, we included a composite of stillbirth and preterm birth as a main secondary outcome. A mixed-effects meta-analysis was done using multi-level modelling and adjusting for bile acid concentration, parity, and multifetal pregnancy. Individual participant data analyses were done for all studies and in different subgroups, which were produced by limiting analyses to randomised controlled trials only, singleton pregnancies only, or two-arm studies only. This study is registered with PROSPERO, CRD42019131495. Findings The authors of the 85 studies fulfilling our inclusion criteria were contacted. Individual participant data from 6974 women in 34 studies were included in the meta-analysis, of whom 4726 (67·8%) took ursodeoxycholic acid. Stillbirth occurred in 35 (0·7%) of 5097 fetuses among women with intrahepatic cholestasis of pregnancy treated with ursodeoxycholic acid and in 12 (0·6%) of 2038 fetuses among women with intrahepatic cholestasis of pregnancy not treated with ursodeoxycholic acid (adjusted odds ratio [aOR] 1·04, 95% CI 0·35–3·07; p=0·95). Ursodeoxycholic acid treatment also had no effect on the prevalence of stillbirth when considering only randomised controlled trials (aOR 0·29, 95% CI 0·04–2·42; p=0·25). Ursodeoxycholic acid treatment had no effect on the prevalence of the composite outcome in all studies (aOR 1·28, 95% CI 0·86–1·91; p=0·22), but was associated with a reduced composite outcome when considering only randomised controlled trials (0·60, 0·39–0·91; p=0·016). Interpretation Ursodeoxycholic acid treatment had no significant effect on the prevalence of stillbirth in women with intrahepatic cholestasis of pregnancy, but our analysis was probably limited by the low overall event rate. However, when consideri...

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Is It Necessary to Perform the Pharmacological Interventions for Intrahepatic Cholestasis of Pregnancy? A Bayesian Network Meta-Analysis

Cited by 20 publications

References 53 publications

Current Resources for Evidence‐Based Practice, July/August 2019

Current Resources for Evidence‐Based Practice, July/August 2019

Gebeliğe Bağlı İntrahepatik Kolestaz: 48 Vakanın Fetal ve Maternal Sonuçlarının Değerlendirilmesi Due to Pregnancy İntrahepatic Cholestasis: Evaluation of Fetal & Maternal Outcomes of 48 Pregnancies

Ursodeoxycholic acid in intrahepatic cholestasis of pregnancy: a systematic review and individual participant data meta-analysis

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