Bile acids in a multicenter, population-based case-control study of stillbirth

Abstract

OBJECTIVE We sought to compare bile acids in women with and without stillbirth in a population-based study. STUDY DESIGN The Stillbirth Collaborative Research Network conducted a multisite, population-based case-control study of stillbirth (fetal deaths ≥20 weeks). Maternal sera were obtained at the time of enrollment and frozen at −80° until assay for bile acids. RESULTS Assays were performed in 581 women with stillbirth and 1546 women with live births. Bile acid levels were slightly higher in women with stillbirth (geometric mean [95% confidence interval {CI}] = 3.2 [3.0–3.5]) compared to live births (2.9 [2.7–3.1], P = .0327). However, the difference was not significant after adjustment for baseline risk factors for stillbirth. The proportion of women with elevated levels (≥10 or ≥40 μmol/L) was similar in stillbirths and live births. Results were similar when the analysis was limited to subsets of stillbirths and live births. In women with stillbirths not associated with fetal anomalies or obstetric complications bile acid levels were higher than in women with term live births (geometric mean [95% CI] = 3.4 [3.0–3.8] vs 2.9 [2.7–3.0], P = .0152, unadjusted; P = .06, adjusted). However, a similar proportion of women in both groups had levels ≥10 mmol/L (10.7 vs 7.2%; odds ratio [OR], 1.54; 95% CI, 0.97–2.44; adjusted OR, 1.29; 95% CI, 0.78–2.15) and ≥40 μmol/L (1.7 vs 0.7%; OR, 2.58; 95% CI, 0.85–7.84; adjusted OR, 2.28; 95% CI, 0.79–6.56). CONCLUSION Our data do not support testing for bile acids in cases of stillbirth in the absence of clinical evidence of intrahepatic cholestasis of pregnancy.

Perinatal death investigations: What is current practice?

“…Several pregnancy complications are associated with an increased risk for SB (Box 1). For example, untreated intrahepatic cholestasis of pregnancy (ICP) has an estimated SB risk of between 2% and 11% [10]. However, a study of 581 women with SB compared to 1546 women with live births reported that routine screening for bile acids is not of value if there are no clinical features to suggest ICP [10].…”

DLK1: A Novel Biomarker of Placental Insufficiency in Stillbirth and Live Birth

“…However, other proteins have been stable after storage at -80 o C from the same sample set. [16][17][18] Additionally, prior work has been successful in assessing DLK1 levels in stored maternal plasma. 11 Another explanation for low DLK1 levels may be that we included both preterm and term deliveries.…”

Intrahepatic Cholestasis of Pregnancy

“…It was also concluded that induction of birth at the 37-gestational week in patients with severe bile acid levels above 40 μmol / L reduces the risk of intrauterine fetal death and neonatal asphyxia but increase the need for cesarean delivery and neonatal intensive care unit (33,34). In another recent study, it was emphasized that there was no difference in the risk of stillbirth between patients with mild or severe ICP, and there was no specific gestational week criterion for birth planning (35). In the compilation of Henderson et al's studies of between 1968 and 2012, it had been emphasized that stillbirths over 37 weeks are exaggerated in studies, that these studies are finalized without highly variable analyzes, that deficiency may lead to misconceptions, that there is no single correct timing in terms of the week of birth and that each patient should be evaluated individually (36).…”