Low vitamin D in early pregnancy tied to ICP risk, if fetus is a girl
Study in China covered almost 95,000 women
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Low vitamin D levels in the first trimester of pregnancy are significantly associated with an increased risk of developing intrahepatic cholestasis of pregnancy (ICP), a form of cholestasis that develops during pregnancy, if the unborn baby is a girl.
That’s according to an analysis of nearly 95,000 pregnancies, which did not find a significant association for women carrying male fetuses.
“Further research should clarify sex-specific mechanisms and evaluate whether vitamin D supplementation … can prevent ICP,” researchers wrote.
The study, “Early Pregnancy Vitamin D Deficiency and the Risk of Intrahepatic Cholestasis of Pregnancy,” was published in the American Journal of Obstetrics and Gynecology.
Cholestasis is a liver disease in which the normal flow of bile, a digestive fluid, from the liver to the intestines is reduced or blocked. This leads to the leakage of bile acids, the main component of bile, into the bloodstream, most commonly causing intense itching.
ICP can pose risks to developing fetus
ICP is a type of cholestasis that typically develops in the second or third trimester and resolves after delivery. Although symptoms for the mother are often manageable, elevated bile acids in the bloodstream can increase risks to the developing fetus, including preterm birth, fetal distress, and stillbirth.
Previous studies have reported that women with ICP have lower levels of 25-hydroxyvitamin D, the primary circulating form of vitamin D. However, most of these studies were limited due to small sample sizes, and evidence from larger populations remains scarce.
A team in China conducted a large-scale retrospective study to examine whether low vitamin D levels in pregnant women at weeks 9-13 of gestation were associated with an elevated risk of ICP.
“To our knowledge, this is the first large cohort study to investigate the association between vitamin D status in early pregnancy and ICP risk,” the team wrote.
Of the nearly 95,000 pregnant women included in the analyses, 35% had sufficient vitamin D levels, defined as levels higher than 50 nanomol/L. The remainder either had insufficient levels (47.3%), defined as levels between 25.1 and 50.0 nanomol/L, or were deemed vitamin D deficient (17.7%), with levels below 25.0 nanomol/L.
Overall, fewer than one in 100 (0.85%) developed ICP. But results showed that women with vitamin D deficiency had a 36% higher risk of ICP compared with those with sufficient levels. Lower vitamin D levels were also associated with higher blood total bile acid levels.
The results remained the same when taking into account factors such as maternal age, obesity status, ethnicity, education level, insurance type, number of pregnancies, fetal sex, and smoking and drinking status. A sensitivity analysis that factored in multiple pregnancies or a history of hepatitis (inflammation of the liver) yielded similar results.
However, the association between low vitamin D levels and ICP was strongest among women carrying female fetuses. These women had a 74% higher risk of ICP if their vitamin D levels were deficient relative to those with sufficient levels.
There was a trend toward a higher risk of ICP also in women with deficient vitamin D levels carrying male fetuses, but the results did not reach statistical significance.
The researchers proposed that vitamin D may influence bile acid synthesis and transport, as well as immune pathways. As a result, vitamin D deficiency may trigger ICP through mechanisms such as impaired bile acid transporters, altered liver enzyme activity, or modulation of inflammation.
On the other hand, fetal sex may induce changes in maternal estrogen, which can potentially lead to cholestasis, the team suggested.
“Early-pregnancy vitamin D deficiency significantly increased ICP risk,” the researchers concluded. “The association was observed only in pregnancies with female fetuses.”
