Early-onset pregnancy cholestasis increases risk of diabetes: Study

Having both conditions raises preterm birth, C-section risk

Andrea Lobo, PhD avatar

by Andrea Lobo, PhD |

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Women diagnosed with intrahepatic cholestasis of pregnancy (ICP) before 24 weeks of gestation, or about six months, are significantly more likely to develop gestational diabetes, a study shows. ICP.

And having both ICP, the most common pregnancy-related liver complication, and gestational diabetes increased the risk for preterm birth, that is, before 37 weeks of gestation, cesarean section, and having smaller and lighter newborns for their gestational age relative to having gestational diabetes alone. The finding adds to previous studies that show having both conditions increases the risk of worse outcomes.

“Further research is warranted to explore the mechanisms behind this association and to develop strategies for early identification and intervention to mitigate [gestational diabetes] risk,” the researchers wrote.

The study, “Early-onset intrahepatic cholestasis of pregnancy increased the incidence of gestational diabetes mellitus: a retrospective cohort study,” was published in Frontiers in Medicine.

ICP is a type of cholestasis wherein the flow of the digestive fluid bile from the liver to the intestines is slowed or stalled, typically during the third trimester of pregnancy. This results in bile acids accumulating in the liver, disrupting its function. The acids also may leak into the bloodstream, which poses serious health risks for mother and fetus, including preterm birth and respiratory difficulties for the newborn. Gestational diabetes mellitus (GDM), a common pregnancy complication marked by intolerance to blood sugar, or glucose, due to low insulin levels, can also increase the risk of worse maternal and fetal outcomes.

Some studies have reported an increased risk of GDM in women with ICP, while others found no association, leading researchers in China to retrospectively analyze data from pregnancies that reached at least 28 weeks (about seven months) and that were delivered at the Shangai Public Health Clinical Center between January 2015 and December 2023.

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The connection between ICP, GDM examined

A total of 742 pregnant women (mean age, 29.8) were included in the study, 427 of whom had ICP (57.5%). Along with exploring a potential link between ICP and GDM, the researchers evaluated whether the timing of the onset of ICP, liver dysfunction, and total bile acid levels in the blood influenced the risk of GDM.

Most women with ICP were diagnosed after 28 weeks of pregnancy (52.2%), while 28.6% were diagnosed before 24 weeks and 19.2% between 24 and 28 weeks.

“In light of the diagnosis of gestational diabetes occurring after the 24th week of pregnancy, for this study, we have defined patients diagnosed with ICP prior to 24 weeks as early-onset ICP,” the researchers wrote.

Compared with pregnant women without ICP, those with early-onset ICP had a significantly higher body mass index, which is a ratio of height and weight, before pregnancy, and more frequently had a history of abortion. They also had significantly higher blood levels of liver enzymes, indicating more liver damage, and of the fatty molecule cholesterol.

Similar results were seen for women in the other ICP onset groups, except regarding abortion history. Particularly, those with ICP onset between 24 and 28 weeks of pregnancy were significantly more likely to have a family history of diabetes.

Compared with the non-ICP group, women with early-onset ICP had a significantly higher rate of GDM (26.2% vs. 15.6%), but no significant difference was found for those with late-onset ICP, that is, after 28 weeks of gestation.

Further analysis that accounted for several factors showed early-onset ICP was an independent risk factor of GDM, increasing the risk by two times. Other strong risk factors included a history of abortion and family history of diabetes, each linked to about an eight times higher risk of GDM. Data from women not diagnosed with ICP before 24 weeks, but diagnosed with GDM between 24 and 28 weeks, showed no evidence that having gestational diabetes was significantly associated with a higher risk of subsequent late-onset ICP, however.

Early delivery, higher rates of preterm birth

Also, women with both GDM and ICP delivered their babies significantly earlier — about 8.5 versus 9 months of gestation — and had a significantly higher rate of preterm birth (45.1% vs. 7.5%) than those with GDM alone.

The GMD with ICP group was also significantly more likely to have babies born with lower weight (2.9 vs. 3.3 kg, or about 6.4 vs. 7.3 pounds) and who were small for their gestational age (18.6% vs. 2.5%). Rates of cesarean section were also significantly higher (51% vs. 20%), except for those with late-onset ICP.

Finally, higher blood levels of total bile acids at early-onset ICP diagnosis were significantly associated with a higher risk of subsequently developing GDM. A level of 27.75 micromoles per liter was identified as the cutoff value.

“The strong connection … between early-onset ICP and GDM revealed by our study has important implications for clinical practice,” wrote the researchers, who noted the need to detect and monitor liver function early in pregnant women, especially those with risk factors, and more frequent glucose level monitoring. “Future studies should focus on the underlying mechanisms of ICP’s impact on gestational metabolism and explore how early diagnosis and intervention can reduce the incidence of GDM.”