Elevations in maternal total bile acid concentrations are associated with low birth weight and risk for intrauterine growth restrictions, especially in pregnancies with hypertensive disorders, according to study findings published in JAMA Network Open.

The association between elevated serum total bile acid (sTBA) concentrations alone or with other gestational complications with fetal weight is still not well understood. In addition, epidemiological evidence to determine the link between sTBA levels and intrauterine growth restrictions in human pregnancies has not yet been found.

To address these knowledge gaps, a team of investigators conducted a retrospective cohort study to determine the association between maternal gestational sTBA concentration and the risk for intrauterine growth restrictions. The main outcomes of the study were fetal birth weight and the probability of low birth weight, as well as intrauterine growth restrictions.

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A total of 68,245 singleton pregnancies with live births in Shanghai, China were included in the study. The mean age of pregnant patients was 30.5 years, 98.4% were Han, and 73.5% were nulliparous.

Findings from nonlinear regression models suggested that there was a correlation between maternal sTBA levels during pregnancy and fetal birth weight. The inverse relation showed a stark decrease in birth weight with high sTBA levels and greater birth weights with lower concentrations of sTBA.

Compared with individuals who did not have hypercholanemia, the incidence of low birth weight (P =.005) and intrauterine growth restriction (P <.001) was more common among patients with hypercholanemia (sTBA ≥4.08 μg/mL). The risk for low birth weight and intrauterine growth restriction was much greater among patients with hypercholanemia vs those with sTBA levels less than 4.08 μg/mL (adjusted odds ratios [aORs], 1.29 and 2.18, respectively).

The risks for low birth weight and intrauterine growth restriction were highest among patients with hypertensive disorders in pregnancy in addition to hypercholanemia, compared with patients who had normotensive pregnancies and sTBA levels below 4.08 μg/mL (low birth weight aOR, 9.15; intrauterine growth restriction aOR, 19.14).

A limitation of note was that the study applied a retrospective, hospital-based cohort design in Shanghai with a population that was at relatively low-risk for intrauterine growth restrictions. Another limitation was the lack of clarity on how generalized the findings could be to other populations, as the majority of persons in the analysis were ethnically homogenous Chinese and predominantly of Han race. 

“[I]t is suggested that more attention should be paid to the recognition and management of gestational hypercholanemia, especially in pregnant individuals with [hypertensive disorders in pregnancy],” the authors wrote. “Additional studies, including prospective cohort studies and randomized clinical trials, are needed to confirm the current findings and potential benefits of lowering sTBA concentrations using drugs (such as ursodesoxycholic acid) in these patients,” the researchers concluded.


Song F, Chen Y, Chen L, Li H, Cheng X, Wu W. Association of elevated maternal serum total bile acids with low birth weight and intrauterine fetal growth restriction. JAMA Netw Open. 2021;4(7):e2117409. doi:10.1001/jamanetworkopen.2021.17409