PregnancyNCT07014956
Intelligence and Neurodevelopmental Outcome After Prenatal Exposure to Labour Epidural Analgesia: a Sibling Matched Clinical Ambidirectional Cohort Study
An observational study of Pregnancy and Epidural Analgesia, Obstetric, run by Universitaire Ziekenhuizen KU Leuven at 1 site in Belgium.
Trial 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. Read more about this study
- Who is it for?
- Ages 6 to 16 yearsHealthy volunteers can take part
- Conditions the study is for
- Pregnancy, Epidural Analgesia, Obstetric
- What is being tested?
- Labour epidural analgesia
- Type of treatment
- Surgery or procedure
- How many people
- 128 participants
- Where
- 1 siteBelgium
- Study dates
- 1 Sep 2025to 1 Sep 2028
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 to 16 years
- All sexes
- Healthy volunteers accepted
- Child
Study population: Sibling pairs discordant for prenatal exposure to labour epidural analgesia will be included
Who may be able to join
- 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
Who cannot join
- 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
Show all 9Show fewer
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Belgium1 site
University Hospitals Leuven
Leuven, 3000
Tom Bleeser, MD, PhD, +3216344270, tom.bleeser@uzleuven.be
About this study
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.
Read the 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
- Being tested
- Labour epidural analgesia
- Keywords
- Labour epidural analgesia, Neurodevelopmental outcome, Intelligence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Labour epidural analgesiaProcedure or surgery
Prenatal exposure to labour epidural analgesia during delivery
| Study group | Role | What they receive |
|---|---|---|
| Exposed | Children prenatally exposed to labour epidural analgesia Receives: Procedure: Labour epidural analgesia | |
| Unexposed | Prenatally not exposed to labour epidural analgesia |
What is being measured
The primary outcome is the main question the study is designed to answer.
Wechsler full-scale intelligence quotient
Will be assessed using the Wechsler Intelligence Scale for Children (WISC). Minimum value: 40, maximum value: 160. Higher scores mean a better outcome.
Measured: At te moment of neuropsychological testing
Secondary outcomes (4)
Indices of the Wechsler intelligence scale
Verbal comprehension, working memory, visual spatial, fluid reasoning, processing speed. Minimum value: 40, maximum value: 160. Higher scores mean a better outcome.
Measured: At te moment of neuropsychological testing
Clinically relevantly decreased intelligence quotient
The absolute risk reduction for a clinically relevantly decreased intelligence quotient, defined as an IQ<85, will be calculated.
Measured: At te moment of neuropsychological testing
Social responsiveness scale (SRS)
Parental reported social deficits in the autism spectrum. Minimum value: 0, maximum value: 195. Higher scores represent a worse outcome.
Measured: At te moment of neuropsychological testing
Disruptive Behavior Disorders Rating Scale (DBDRS)
Parental reported traits of inattention, hyperactivity and impulsivity (ADHD), oppositional defiant disorder (ODD) and conduct disorder (CD). Minimum value: 0, maximum value: 135. Higher scores mean a worse outcome.
Measured: At te moment of neuropsychological testing
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jun 2025
- Study start1 Sep 2025 (estimated)
- Primary completion1 Sep 2028 (estimated)
- Study completion1 Sep 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for PregnancyStudies of the same condition, open and under way.
- More trials run by Universitaire Ziekenhuizen KU LeuvenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Other
- Enrolment
- 128 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Universitaire Ziekenhuizen KU Leuven
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07014956
- Sponsor's protocol ID
- S69530
- Status last verified
- May 2025
- First submitted
- 19 May 2025
- Last updated
- 11 Jun 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Can be requested from authors.
Study at a glance
From the registry record, last updated by the sponsor on 11 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Intelligence and Neurodevelopmental Outcome After Prenatal Exposure to Labour Epidural Analgesia: a Sibling Matched Clinical Ambidirectional Cohort Study
- ClinicalTrials.gov ID
- NCT07014956
- Acronym / sponsor ID
- S69530
- Conditions
- Pregnancy, Epidural Analgesia, Obstetric
- Keywords
- Labour epidural analgesia, Neurodevelopmental outcome, Intelligence
- Study type
- Observational
- Recruitment status
- Not yet recruiting
- Enrolment
- 128 participants (estimated)
- Lead sponsor
- Universitaire Ziekenhuizen KU LeuvenUniversity, hospital or other
- Study start
- 1 Sep 2025 (estimated)
- Primary completion
- 1 Sep 2028 (estimated)
- Study completion
- 1 Sep 2028 (estimated)
- First posted
- 11 Jun 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Other
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Exposed | – | Procedure: Labour epidural analgesiaChildren prenatally exposed to labour epidural analgesia |
| Unexposed | – | –Prenatally not exposed to labour epidural analgesia |
Who may qualify
- Ages
- 6 to 16 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
- Study population
- Sibling pairs discordant for prenatal exposure to labour epidural analgesia will be included
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Labour epidural analgesiaPrenatal exposure to labour epidural analgesia during delivery | Procedure or surgery | Exposed |
Primary outcome
Wechsler full-scale intelligence quotient
Time frame: At te moment of neuropsychological testing
Will be assessed using the Wechsler Intelligence Scale for Children (WISC). Minimum value: 40, maximum value: 160. Higher scores mean a better outcome.
4 secondary outcomes
Indices of the Wechsler intelligence scale
Time frame: At te moment of neuropsychological testing
Clinically relevantly decreased intelligence quotient
Time frame: At te moment of neuropsychological testing
Social responsiveness scale (SRS)
Time frame: At te moment of neuropsychological testing
Disruptive Behavior Disorders Rating Scale (DBDRS)
Time frame: At te moment of neuropsychological testing
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jun 2025.
- Individual participant dataSharing planned: Yes. Can be requested from authors.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Pregnancy and Epidural Analgesia, Obstetric, run by Universitaire Ziekenhuizen KU Leuven at 1 site in Belgium.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 11 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Tom Bleeser, MD, PhD (+3216344270, tom.bleeser@uzleuven.be), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Wechsler full-scale intelligence quotient (time frame: At te moment of neuropsychological testing). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jun 2025.