Worse outcomes risk rises with liver ailment ICP, gestational diabetes

Having both conditions linked with preterm labor, polyhydramnios

Steve Bryson, PhD avatar

by Steve Bryson, PhD |

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A drawing shows a pregnant woman cradling her belly with one hand and holding a teddy bear with the other.

Having gestational diabetes increases the risk of adverse outcomes in pregnancy for women with intrahepatic cholestasis of pregnancy (ICP), the most common pregnancy-related liver complication, a study suggests.

Outcomes associated with both conditions included preterm labor, that is, before 37 weeks of gestation, and polyhydramnios, an excess amount of amniotic fluid surrounding the fetus. The study, “Gestational diabetes mellitus aggravates adverse perinatal outcomes in women with intrahepatic cholestasis of pregnancy,” was published in Diabetology & Metabolic Syndrome.

ICP is a specific form of cholestasis that typically occurs during the third trimester of pregnancy. A feature of cholestasis is stalled flow of bile, a digestive fluid, which builds up in the liver, impeding its function and causing symptoms such as elevated bile acids in the bloodstream and severe itchiness. The disease is associated with an increased risk of adverse fetal outcomes, including preterm birth, amniotic fluid abnormalities, and stillbirth.

Studies have suggested that pregnant women with ICP are more likely to have gestational diabetes mellitus (GDM), a common pregnancy complication marked by intolerance to blood sugar, or glucose, due to low levels of insulin.

Here, researchers in China identified 2,178 pregnant women with ICP from two large maternity hospitals from January 2018 to December 2021 to see if GMD with ICP leads to more serious adverse pregnancy outcomes than ICP alone. In the study, 390 women also had GMD, 1,788 did not.

“Considering the potential relationship between ICP and GDM, it is important to understand the differences in perinatal outcomes between those with ICP and GDM and those with ICP alone,” the researchers wrote.

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Increased risk with ICP, GMD

Those with both ICP and GMD were significantly older, had higher prepregnancy weight and body mass index (BMI), and used assisted reproductive technology more often than those without GMD.

The ICP with GDM group also had higher total bile acid levels in the blood than the ICP group and were more likely to be treated with ursodeoxycholic acid (UDCA) after a diagnosis. UDCA is a nontoxic bile acid that helps bile flow through the liver.

There were no significant group differences regarding predelivery weight, pregnancy BMI, history of ICP, smoking, drinking, or of adverse pregnancy.

When analyses were adjusted for potentially influencing factors, including age, weight, bile acid levels, and UDCA use, the researchers found that women with both ICP and GMD were twice as likely to have polyhydramnios (4.6% vs. 2%) and 67% more likely to have preterm labor (24.6% vs. 13.9%) than those with ICP alone.

In the ICP with GMD group, whether a woman was treated with UDCA or not didn’t appear to affect the risk of adverse outcomes.

Further analyses found that in women with ICP, every doubling of blood bile acid levels increased the risk of GMD by 8.1%, preterm labor by 16.7%, meconium-stained amniotic fluid by 14.2%, and low birth weight by 21.9%. Meconium-stained amniotic fluid is an abnormality where the fetus’ meconium stool passes to the amniotic fluid.

When researchers divided patients into ICP severity groups based on bile acid blood levels, the significantly elevated risk of preterm labor linked to GMD occurred only in those with mild ICP. Preterm labor, meconium-stained amniotic fluid, and low birth weight were up to three times more likely to occur with both severe ICP and GMD than in those with severe ICP alone, but the differences failed to reach statistical significance.

Adjusted analyses also showed the strongest independent risk factors for preterm labor among women with ICP were the use of assisted reproductive technology, which increased the risk by five times, and GMD, which increased the risk by 65%.

These findings show that “when ICP was with GDM, adverse pregnancy outcomes were further exacerbated,” wrote the researchers, who said “intervention measures beyond ursodeoxycholic acid should be considered for pregnant women with ICP and GDM.”