Impact of Intrahepatic Cholestasis of Pregnancy on Neonatal Respiratory Outcomes (CHOLE-RESP)

Intrahepatic Cholestasis of Pregnancy and the Respiratory Challenges of Bile Acids Pneumonia in Neonates (The CHOLE-RESP Trial)

Intrahepatic cholestasis of pregnancy is a liver condition in late pregnancy, causing itching and high bile acid levels that return to normal after birth. Babies born to mothers with this condition may have a higher risk of breathing issues. Researchers suspect bile acids might lead to a specific type of lung problem in newborns, but more studies are needed to confirm this.

Study Overview

• Status: Enrolling by invitation
• Conditions: Respiratory Distress Syndrome, Newborn; Intrahepatic Cholestasis of Pregnancy

Detailed Description

Intrahepatic cholestasis of pregnancy is a hepatic complication that predominantly arises during the second or third trimester. It is characterized by serum bile acid levels above 10 micromol/L and persistent pruritus, which resolves after delivery. To date, it has been observed that respiratory distress syndrome occurs more frequently in neonates born to mothers with cholestasis of pregnancy, and a potential new entity, 'acute bile acid-induced pneumonia,' has been proposed, though statistical confirmation is lacking. Therefore, the investigators deem it imperative to conduct a study in the neonatal population to establish a definitive conclusion regarding neonatal pulmonary impairment secondary to maternal bile acid accumulation.

• Study Type: Observational
• Enrollment (Estimated): 120

Contacts and Locations

Study Locations

• Romania
  • Bucharest
    • Bucharest, Bucharest, Romania, 060251
      • Clinical Hospital of Obstetrics and Gynecology "Prof. Dr. Panait Sârbu"

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

The study will include selected neonates born at term or preterm age, in a third degree neonatal unit in Bucharest, Romania (Clinical Hospital of Obstetrics and Gynecology "Prof.Dr. Panait Sirbu"). For the ICP-exposed group, the study population is represented by neonates born to mothers with intrahepatic cholestasis diagnosed during pregnancy. The unexposed group will include neonates of similar gestational age/weight/sex at birth born to mothers with no hepatic diseases.

Description

ICP-EXPOSED GROUP

Inclusion Criteria:

• mother with recent diagnosis of intrahepatic cholestasis of pregnancy (serum bile acids over 10 micromol/l in the last 7 days before birth), with informed consent given a few hours before giving birth
• ursodeoxycholic acid, independent of dosage or initiation of treatment
• neonates born in Clinical Hospital of Obstetrics and Gynecology "Prof.Dr. Panait Sirbu" or transferred to our unit in the first 24 hours of life

Exclusion Criteria:

• no informed consent
• serum bile acids under 10 micromol/l in the last 7 days before birth
• newborns transferred from other neonatal units after 24 hours of life

UNEXPOSED GROUP

Inclusion Criteria:

• mother with no history of hepatic disease during or before the current pregnancy, with informed consent given a few hours before giving birth
• neonates born in Clinical Hospital of Obstetrics and Gynecology "Prof.Dr. Panait Sirbu", of similar gestational age/weight/sex at birth to corresponding neonates in the ICP-exposed group

Exclusion Criteria:

- ursodeoxycholic acid, independent of dosage or initiation of treatment (suspected hepatic disease/elevated transaminases)

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
ICP-Exposed Group; This group will include all neonates born to mothers with intrahepatic cholestasis of pregnancy.
Unexposed Group; This group will include neonates born to mothers without a known history of hepatic disease prior to or during the index pregnancy. Controls will be matched according to gestational age at birth, birthweight and sex.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of respiratory distress syndrome	RDS is defined as a clinical diagnosis made within the first 72 hours of life, based on signs of respiratory compromise (tachypnea, grunting, nasal flaring, chest retractions), supportive radiographic findings and a need for supplemental oxygen or respiratory support.	First 72 hours of life
The need for exogenous surfactant administration	Surfactant administration refers to any administration of exogenous surfactant therapy within the first 72 hours of life, regardless of dosing or mode of delivery.	First 72 hours of life
Biomarkers related to pulmonary injury and surfactant deficiency	This trial seeks to determine whether neonates exposed to intrahepatic cholestasis of pregnancy exhibit distinct serum biomarker profiles consistent with lung injury and surfactant impairment, compared to those of similar gestational age/birthweight/sex born to mothers with no liver disease.	In the first 24 hours, at 48-72 hours and at 7 days of life

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Respiratory morbidity	This includes the need for mechanical ventilation and non-invasive respiratory support, as well as the occurrence of serious respiratory complications including pneumothorax, pulmonary hemorrhage and persistent pulmonary hypertension.	First 7 days of life
NICU admission		First 48-72 hours of life
Length of hospitalization		From day 1 of life until discharge
Neonatal mortality		From day 1 of life until 28 days of life

Collaborators and Investigators

• Sponsor: Carol Davila University of Medicine and Pharmacy

Publications and helpful links

General Publications

• Niculae LE, Niculae AS, Tocariu R, Petca A. Impact of intrahepatic cholestasis of pregnancy on neonatal respiratory outcomes (CHOLE-RESP): protocol for a prospective cohort study. Front Pediatr. 2026 Feb 2;14:1640579. doi: 10.3389/fped.2026.1640579. eCollection 2026.

Study record dates

Study Major Dates

• Study Start (Actual): October 28, 2024
• Primary Completion (Estimated): December 10, 2027
• Study Completion (Estimated): March 1, 2028

Study Registration Dates

• First Submitted: November 6, 2024
• First Submitted That Met QC Criteria: November 7, 2024
• First Posted (Actual): November 8, 2024

Study Record Updates

• Last Update Posted (Actual): February 18, 2026
• Last Update Submitted That Met QC Criteria: February 14, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: RDS; respiratory distress syndrome; intrahepatic cholestasis; bile-acid pneumonia; cholestasis of pregnancy
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Digestive System Diseases; Lung Diseases; Respiration Disorders; Infant, Premature, Diseases; Infant, Newborn, Diseases; Biliary Tract Diseases; Liver Diseases; Bile Duct Diseases; Cholestasis; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Cholestasis, Intrahepatic; Intrahepatic Cholestasis of Pregnancy
• Other Study ID Numbers: 34/15.10.2024

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No