Intelligence and Neurodevelopmental Outcome After Prenatal Exposure to Labour Epidural Analgesia: a Sibling Matched Clinical Ambidirectional Cohort Study

NCT ID: NCT07014956

Last Updated: 2025-06-11

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Total Enrollment: 128 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2025-09-01
• Study Completion Date: 2028-09-01

Brief Summary

In Belgium, labour epidural analgesia (LEA) has been used for decades in the vast majority of vaginal deliveries (up to 83% of deliveries). Labour epidural analgesia is the most effective and safest way to allow pregnant women a nearly pain-free labour- and birth experience. Recent data showed that the use of LEA was associated with a reduced risk for severe maternal morbidity, neonatal resuscitation and with a reduced risk for low Apgar scores. However, prenatal exposure to labour epidural analgesia has been associated by several study groups with an increased risk for autism spectrum disorder (ASD) in the children, but these studies suffer from several important limitations which may have induced significant bias (e.g., not correcting for unmeasured confounders). Associations with other neurodevelopmental disorders (e.g., Attention Deficit Hyperactivity Disorder (ADHD), oppositional defiant disorder (ODD) and conduct disorder (CD)) and cognitive functioning have not been investigated yet. There is hence an urgent need for a study allowing definitive conclusions by overcoming the limitations of the previous studies. The investigators will perform the first sibling-matched clinical cohort study using a prospective investigator-assessment of multiple domains of cognitive functions. The investigators hypothesize that prenatal exposure to LEA will neither be associated with reduced intelligence nor with more neurodevelopmental disorders. Validating this hypothesis holds the potential to grant women the assurance to confidently receive the most efficacious method for labour analgesia, free from apprehension that it might have adverse implications for their children's neurodevelopment.

Detailed Description

Primary objective:

To compare the intelligence of children prenatally exposed to labour epidural analgesia with that of sibling matched unexposed children.

Secondary objective(s):

To compare parentally reported traits of ASD, ADHD, ODD and CD of children prenatally exposed to labour epidural analgesia with that of sibling matched unexposed children.

Endpoints:

• Primary endpoint: Wechsler full scale intelligence quotient
• Secondary endpoints: multiple indexes assessed by the Wechsler intelligence scale: verbal comprehension index, visual spatial index, working memory index, fluid reasoning index and processing speed index. Total scores and subscores of the parental questionnaires "social responsiveness scale" (SRS) and "vragenlijst voor gedragsproblemen bij kinderen 6-16" (VvGK6-16) are additional secondary endpoints.

Sample size:

At least 64 prenatally exposed children and 64 prenatally unexposed children

Summary of eligibility criteria:

Dutch speaking sibling pairs discordant for prenatal exposure to labour epidural analgesia will be included. Children born from 1st January 2014 until 1st November 2019 will be included. Children prenatally exposed to maternal surgery, foetal surgery/interventions, chemotherapy, radiotherapy, radiology and oncologic pathology will be excluded. Children with a diagnosis of severe disability of genetic origin (e.g., Fragil X, Down syndrome,…), history of head trauma, major congenital birth defects, children born at a gestational age < 37 weeks or > 42 weeks, or with a birth weight < 2.5 kg will be excluded. Children exposed to general anaesthesia after birth, twins/triplets/multiple births will be excluded. Elective and intrapartum caesarean sections will be excluded.

Maximum duration a research subject remains in the study:

Study will be conducted in 2024-2027. The end of the study for each individual participant is determined by the date at which the neuropsychological testing is planned. Neuropsychological testing usually takes no longer than 2 hours.

Conditions

Pregnancy; Epidural Analgesia, Obstetric

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: OTHER

Study Groups

Exposed

Children prenatally exposed to labour epidural analgesia

Labour epidural analgesia

Intervention Type: PROCEDURE

Prenatal exposure to labour epidural analgesia during delivery

Unexposed

Prenatally not exposed to labour epidural analgesia

No interventions assigned to this group

Interventions

Labour epidural analgesia

Prenatal exposure to labour epidural analgesia during delivery

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• Exposed children: Children prenatally exposed to labour epidural analgesia
• Unexposed children: Sibling of an exposed child, Prenatally not exposed to labour epidural analgesia
• Exposed & unexposed children: Children born from 1st January 2014 until 1st November 2019, Parental informed consent

Exclusion Criteria

• Children whose mothers underwent maternal surgery or foetal surgery/interventions during the same pregnancy.
• Children exposed to general anaesthesia after birth
• Children prenatally exposed to chemotherapy, radiotherapy, radiology, oncologic pathology
• Children born at a gestational age < 37 weeks or > 42 weeks, or with a birth weight < 2.5 kg
• Twins, triplets, multiple births
• No Dutch-speaking children
• Diagnosis of severe disability of genetic origin (e.g., Fragil X, Down syndrome,…), history of head trauma, major congenital birth defects
• Elective caesarean section and intrapartum caesarean section (the number of caesarean sections will be reported and compared between both groups)
• Foetus died before start of delivery

• Minimum Eligible Age: 6 Years
• Maximum Eligible Age: 16 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Universitaire Ziekenhuizen KU Leuven

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

University Hospitals Leuven

Leuven, , Belgium

Countries

Belgium

Central Contacts

Tom Bleeser, MD, PhD

Role: CONTACT

tom.bleeser@uzleuven.be

+3216344270

Facility Contacts

Tom Bleeser, MD, PhD

Role: primary

tom.bleeser@uzleuven.be

+3216344270

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

S69530

Identifier Type: -

Identifier Source: org_study_id