BACKGROUND AND PURPOSE:

• Increased serum total bile acid (sTBA) levels during pregnancy are associated with adverse perinatal outcomes
  • Connection between sTBA concentration, intrahepatic cholestasis of pregnancy (ICP) and intrauterine growth restriction (IUGR) remains unclear
• Song et al. (JAMA Network Open, 2021) examined the association between maternal sTBA concentration during pregnancy and risk for IUGR

METHODS:

• Retrospective cohort study
• Participants
  • Live singleton neonates
  • Antenatal examination records available
• Exposures
  • Maternal sTBA concentration during pregnancy
• Study design
  • Regression modeling used to determine relationship between maternal sTBA and fetal birth weight
  • Adjustments for counfounders: Gestational age | Maternal age | Prepregnancy BMI | Race | Parity | Education level | Fetal sex
  • Gestational hypercholanemia definition: sTBA ≥4.08 μg/mL
• Primary outcomes
  • Fetal birth weight
    • Macrosomia: Fetal birth weight ≥4000 g
    • LBW: Fetal birth weight <2500 g
  • IUGR: Ultrasound estimation based on EFW or AC <10% of birth population (adjusted for fetal sex, gestational age, potential causative pathologic conditions)

RESULTS:

• 68,245 singleton pregnancies
  • Mean (SD) age: 30.5 (3.8) years
  • 98.4% were Han Chinese
  • 73.5% were nulliparous
• There was an inverted J-shaped association between maternal sTBA level during pregnancy and fetal birth weight
  • Steep decrease in birth weight at high sTBA levels
    • Estimated mean birth weight for sTBA of 40.8 ug/mL: 2879 g
  • Greater birth weights at lower sTBA levels
    • Estimated mean birth weight for sTBA 0.4 μg/mL: 3290 g
    • Estimated mean birth weight for sTBA 4.1 μg/mL: 3334 g
• Gestational hypercholanemia was associated with lower birth weight and higher incidence of IUGR
  • Birth weight (P=0.005)
    • With gestational hypercholanemia: Estimated adjusted mean birth weight 3309 g
    • Without: 3338 g
  • Incidence of IUGR (P<0.001)
    • With gestational hypercholanemia: 1.4%
    • Without: 0.5%
• Gestational hypercholanemia was associated with an increased risk for
  • LBW: Adjusted odds ratio (aOR) 1.29 (95% CI, 1.09 to 1.53)
  • IUGR: aOR 2.18 (95% CI, 1.62 to 2.91)
• The highest risk for LBW and IUGR occurred among pregnant individuals with both hypertensive disorders of pregnancy and hypercholanemia
  • LBW: aOR 9.13 (95% CI, 6.88 to 12.12)
  • IUGR: aOR 19.14 (95% CI, 12.09 to 30.28)

CONCLUSION:

• Gestational hypercholanemia (sTBA ≥4.08 μg/mL) was associated with an increased risk for LBW and IUGR
• Of note, hypertensive disorders of pregnancy and hypercholanemia resulted in highest (additive) risks for LBW and IUGR
• The authors state

…it is suggested that more attention should be paid to the recognition and management of gestational hypercholanemia, especially in pregnant individuals with HDP

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

Learn More – Primary Sources:

Association of Elevated Maternal Serum Total Bile Acids With Low Birth Weight and Intrauterine Fetal Growth Restriction

Related ObG Topics:

Risk of Stillbirth with Intrahepatic Cholestasis of Pregnancy: What do Bile Acid Concentrations Tell Us?

More from the PITCHES Trial: Subgroup Analysis of Participants with Intrahepatic Cholestasis of Pregnancy and UDCA Treatment