Does mild intrahepatic cholestasis of pregnancy require an aggressive management? Evidence from a prospective observational study focused on adverse perinatal outcomes and pathological placental findings

Abstract

Objective

To ascertain the most effective approach in pregnancies complicated by mild intrahepatic cholestasis of pregnancy (mICP) by evaluating rates of adverse perinatal outcomes (APOs) and pathological placental findings.

Methods

A total of 89 pregnancies complicated by mICP (defined as total serum bile acids (TSBAs) levels <40 µmol/L) were included. One-drug (ursodeoxycholic acid [UDCA]) (n = 49, 55.1%) and combined (UDCA plus S-adenosyl methionine (SAMe)) (n = 40, 44.9%) therapies were compared.

Results

No differences were found in demographic, obstetric, and placental characteristics. In UDCA plus SAMe group, premature delivery was a common clinical decision (14.3 versus 25%, p-value = .201), with increased rates of instrumental vaginal delivery (VD; 28.6 versus 40%, p-value = .522), but similar cesarean section (CS) rates (26.5 versus 25%, p-value = .498). Mean placental weight was comparable (UDCA, mean 595.7 g, SD 213.1 g versus UDCA plus SAMe, mean 586.4 g, SD 102.9 g, p-value = .875). A total of 110 lesions were identified, 64 in 25 placentas of patients assigned to the UDCA and 46 in 15 placentas of patients managed by UDCA plus SAMe. Placental findings attributable to maternal malperfusion were found in 41/25 and 32/15 cases treated by UCDA and UDCA plus SAMe (165 versus 213%, p-value = .774), pathological fetal vascular supply in 17/25 and 8/15 placentas (68 versus 53%, p-value = .777), and inflammatory lesions in 6/25 and 6/15 cases (24 versus 40%, p-value = .757).

Conclusions

Pregnancies complicated by mICP and managed by UDCA alone present similar APO rates and placental histopathology if compared with those treated by UDCA plus SAMe, failing to recognize advantages in the combined therapy. Further prospective studies and data sharing from ongoing RTCs could drive changes in therapeutic plan.

Keywords:

• Intrahepatic cholestasis
• perinatal outcomes
• placenta
• therapy
• women-centered care

Author contributions

Each author listed on the manuscript saw and approved the submission of this version of the manuscript and took full responsibility for the manuscript. There is not anyone else who fulfills the criteria that have been excluded as an author. Stefania Triunfo gave substantial contributions to the conception and design of the work. She was responsible for the analysis of data and their interpretation. She wrote the first draft of the work and approved the final revised version. Marta Tomaselli, Maria Immacolata Ferraro, Elisabetta Latartara, and Giulia Maria Sassara were responsible for the acquisition of data. Cinzia Carrozza collaborated with their interpretation, and she contributed to writing the first draft of the work and approved the final revised version. All revisited the work critically and approved the final revised version. All authors agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Acknowledgments

We acknowledge Dr. Vincenzo Arena for the placental examinations in the context of his clinical activity at the Area of Pathology, Fondazione Policlinico Universitario “A Gemelli” IRCCS, Rome, Italy.

Disclosure statement

No potential conflict of interest was reported by the authors.

Data availability

Additional data are available upon justified request.