Frequent bile acid level checks urged to predict stillbirth in severe ICP
Risk increased by 28% for each added week into pregnancy peak levels reached
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Women who develop severe intrahepatic cholestasis of pregnancy (ICP) at a later time in pregnancy have a higher risk of stillbirth, a study shows.
ICP is reflected by very high blood levels of bile acids, the main component of the digestive fluid bile.
The risk of stillbirth increased by 28% for each additional week into the pregnancy the woman reached the highest bile acid levels, or peak levels, with levels higher than 100 micromole per liter (mcmol/L) being the threshold after which the risk no longer increases. In most stillbirths, there was a sudden increase in blood bile acid levels in the five days preceding it.
“This sudden increase in bile acid concentration often preceding stillbirth, and findings that babies with later peak bile acid concentrations are at higher risk, suggest the benefit of continued … bile acid surveillance at less than five-day intervals,” the study’s researchers wrote. The study, “Stillbirth in intrahepatic cholestasis of pregnancy and timing of severely elevated bile acid concentrations: an observational cohort study,” was published in the European Journal of Obstetrics & Gynecology and Reproductive Biology.
ICP develops during pregnancy when bile doesn’t flow properly within the liver, where it’s produced. As a result, bile acids build up in the liver, affecting its function, and leak into the bloodstream, causing symptoms such as jaundice, which is a yellowing of the skin and the whites of the eyes, itching, and fatigue.
The condition typically appears during late pregnancy, when hormone levels are at their highest, and is associated with an increased risk of preterm birth (before 37 weeks of gestation), neonatal unit admission, and stillbirth.
“The risk of complications increases with higher peak [blood] bile acid concentrations,” the researchers wrote, noting that blood bile acids of at least 100 mcmol/L are linked to a 3.44% stillbirth rate — “approximately 10 times the background population rate.” The risk of stillbirth “increases markedly from 35 to 36 gestational weeks,” but “no monitoring strategies [are] able to delineate which of these babies are at higher risk,” they wrote.
Stillbirths and blood bile acid levels
A team of researchers in the U.K. retrospectively analyzed data from 198 pregnant women with severe ICP, reflected by blood bile acid levels of 100 mcmol/L or higher, who were selected from two studies at 15 hospitals in U.K., Argentina, Australia, and Sweden.
Overall, 183 women had live births, while 15 (7.6%) had a stillbirth, which occurred most often between 34 and 36 gestational weeks. Most births occurred preterm (67.7%), usually between weeks 34 and 36. More than half of the preterm births were medically induced by clinicians.
This sudden increase in bile acid concentration often preceding stillbirth, and findings that babies with later peak bile acid concentrations are at higher risk, suggest the benefit of continued … bile acid surveillance at less than five-day intervals
It’s recommended that women with severe ICP be offered birth between 35 and 36 weeks of pregnancy. Of the 180 women whose bile acids were above 100 mcmol/L before 36 weeks, 79 (44%) gave birth after the recommended pregnancy time, two being stillbirths.
Statistical analyses indicated that women experiencing a stillbirth first reached blood bile acid levels of 100 umol/L or higher significantly later than those with a live birth (33 vs. 30 weeks), and that their peak bile acid concentration also occurred significantly later (34 vs. 31 weeks).
Risk increases
The strongest association occurred between the week of peak bile acid concentration and stillbirth, with the risk of stillbirth increasing by 28% per additional week of gestation.
Also, the proportion of stillbirths was about three times higher among women reaching bile acid levels of 100 mcmol/L or higher after 28 weeks relative to those achieving those levels before 28 weeks (9.8% vs. 3.1%).
Nearly 40% of the women with live births whose first and peak bile acid levels of at least 100 mcmol/L occurred before 28 weeks had early preterm births before 34 weeks, “which could have resulted in the pregnancy not reaching the gestational age at which stillbirth risk increases (typically from 35 weeks),” the researchers wrote. “This study reveals that the gestational ages at which [blood] bile acid concentrations increase [to 100 mcmol/L or higher], and peak, are additional factors that may affect the risk of stillbirth in severe ICP, with those at a later gestational age of severe ICP onset or peak at higher risk of stillbirth.”
Also, while bile acid levels “varied markedly over time for ICP patients experiencing either a live birth or stillbirth,” most of the women with stillbirth (73.3%) recorded their highest blood bile acid levels in the five days before giving birth.
“Whilst the extent of peak [blood] bile acid elevation was not associated with stillbirth once above 100 [mcmol/L], the observation of a rise in bile acid concentration in the five days preceding stillbirth could influence decisions regarding the appropriate gestational age for expedited birth,” the researchers wrote.
