Ovadia, C.Seed, P.T.Sklavounos, A.Geenes, V.Di Illio, C.Chambers, J.Kohari, K.Bacq, Y.Bozkurt, N.Brun-Furrer, R.Bull, L.Estiú, M.C.Grymowicz, M.Gunaydin, B.Hague, W.M.Haslinger, C.Hu, Y.Kawakita, T.Kebapcilar, A.G.Kebapcilar, L.et al.2025-07-292025-07-292019Obstetrical and Gynecological Survey, 2019; 74(7):388-3900029-78281533-9866https://hdl.handle.net/2440/146382Editorial Comment for Lancet 2019; 393(10174): 899-909 article.Intrahepatic cholestasis of pregnancy (ICP) affects less than 0.1% to 0.2% of pregnant women. It is diagnosed in women with gestational pruritus and increased serum bile acids and can be complicated by preterm labor, fetal asphyxia, meconium-stained amniotic fluid, and stillbirth. Some studies have found that pregnancies in which the maternal serum bile acid concentration was 40 μmol/L or more particularly led to birth complications, including spontaneous preterm labor, meconium-stained amniotic fluid, fetal asphyxia, intrauterine fetal death, and ICP. However, no studies have been adequately powered enough to determine whether fetal death associated with ICP occurs above a specific bile acid threshold. The researchers performed a systematic review and meta-analysis, using data published from published studies reporting outcomes for women with ICP and control pregnancies. They also used individual patient data (IPD) to determine the relationships between biochemical markers and adverse perinatal outcomes. Assessing 109 full-text articles, the researchers found 23 studies were eligible for the aggregate data meta-analysis (5557 ICP cases and 165,136 controls), and 27 provided IPD (5269 ICP cases). Stillbirth occurred in 45 (0.83%) of 4936 ICP cases and 519 (0.32%) of 163,947 control pregnancies (odds ratio [OR], 1.46; 95%confidence interval [CI], 0.73–2.89; I2 = 59.8%). In singleton pregnancies, stillbirth was associated with maximum total bile acid concentration (area under the receiver operating characteristic curve, 0.83; 95% CI, 0.74–0.92), but not alanine aminotransferase (area under the receiver operating characteristic curve, 0.46 [0.35–0.57). For singleton pregnancies, the incidence of stillbirth was 3 (0.13%; 95% CI, 0.02–0.38) of 2310 ICP cases in women with serum total bile acids of less than 40 μmol/L versus 4 (0.28%; 95% CI, 0.08–0.72) of 1412 cases with total bile acids of 40 to 99 μmol/L (hazard ratio, 2.35; 95% CI, 0.52–10.50; P = 0.26) and versus 18 (3.44%; 95% CI, 2.05–5.37) of 524 cases for bile acids of 100 μmol/L or more (hazard ratio, 30.50; 95% CI, 8.83–105.30; P < 0.0001). The systematic review found no increased stillbirth risk for women with singleton ICP who were included in the IPD analysis with total bile acids of less than 40 μmol/L or 40 to 99 μmol/L when compared with the pooled national prevalence of stillbirth from 2000 (0.42%) or 2015 (0.33%). The meta-analysis showed that women with ICP had higher ORs of preterm birth (OR, 3.54; 95% CI, 2.72–4.62). The prevalence of iatrogenic preterm birth was high for all categories of bile acid concentration (<40 μmol/L, 16.5% [95% CI, 15.1–18.0]; 40–99 μmol/L, 19.1% [17.1–21.1]; and ≥100 μmol/L, 30.5% [26.8–34.6]). The researchers concluded that the risk of stillbirth is increased in women with ICP and singleton pregnancies when serum bile acids concentrations are of 100 μmol/L or more. Because most women with ICP have bile acids below this concentration, they found that most women can be reassured that the risk of stillbirth is similar to that of pregnant women in the general population, provided that repeat bile acid testing is done until delivery. The researchers recommend that future research target mechanistic explanations for the increased risk of stillbirth in ICP and the potential of specific treatments to prevent fetal deathen© 2019 Wolters Kluwer Health, Inc. All rights reserved.Editorial Comment; Pregnancy; ICP; Intrahepatic Cholestasis of Pregnancy; Women; Women's healthJournal article10.1097/01.ogx.0000569528.40287.d0492465Hague, W.M. [0000-0002-5355-2955]