Premature ChildbirthBETANINONCT04021485
BETAmethasone Dose Reduction: Non-Inferiority on the Neurocognitive Outcomes of Children Born Before 32 Weeks of Gestation
A study testing neurodevelopmental assessment in people with Premature Childbirth, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
Maternal antenatal corticosteroid therapy is the last major advance in the antenatal management of fetuses to prevent neonatal complications associated with prematurity. Long-term neurological outcomes in infants exposed to antenatal steroids have been assessed in few cohorts and suggest that this therapy is able to… Read more about this study
- Who is it for?
- Ages 5 to 6 years
- Conditions the study is for
- Premature Childbirth
- What is being tested?
- neurodevelopmental assessment
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 386 participants
- Where
- 1 siteFrance
- Study dates
- 23 Mar 2022to 9 Sep 2025
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 5 to 6 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Singleton child born from mother enrolled in the BETADOSE trial,
- Gestational age at birth less than 32 weeks of gestation,
- Age ≥ 5 years and < 6 years, alive and not lost of follow up
- Informed consent of the holder (s) of the exercise of parental authority
- Affiliation to a social security scheme.
Who cannot join
- Major malformations and chromosomal aberrations evidenced after birth,
- Parents' refuse to participate.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 5-year Follow-up of the BETADOSE Trial: Non-inferiority of a 50% Dose Reduction of Antenatal Betamethasone Therapy on the Neurodevelopment of Children Born Before 32 Weeks of Gestation.
Maternal antenatal corticosteroid therapy is the last major advance in the antenatal management of fetuses to prevent neonatal complications associated with prematurity. Long-term neurological outcomes in infants exposed to antenatal steroids have been assessed in few cohorts and suggest that this therapy is able to prevent some neurodevelopmental impairments including cerebral palsy. While >85% of neonates born very preterm in Europe have been exposed to antenatal betamethasone, Cochrane collaborative networks stated that trials of dosages comparing different regimens of commonly used corticosteroids are most urgently needed to avoid useless fetal exposure to excessive dosage of corticosteroids.
- Because a half dosage was associated with maximal benefits on lung function in ewes, a randomized controlled trial (BETADOSE, NCT02897076) has been conducted to demonstrate that a 50% reduced betamethasone dose regimen is not inferior to a full dose to prevent respiratory distress syndrome in preterm neonates. BETADOSE trial demonstrated that half dose did not show noninferiority to full antenatal betamethasone dose regimen to prevent severe RDS in preterm neonates while other prematurity-associated complications, including those usually prevented by ACS, did not differ between the two groups.
- Results of the 5-year BETANINO follow-up study of the BETADOSE neonates are needed before deciding whether reducing ACS dose is possible The main hypothesis of BETANINO is that half dose regimen of betamethasone is not inferior to full dose regimen of betamethasone to prevent neurodevelopmental impairments in these high-risk children born very preterm at 5 years of age.
Read the detailed description
Maternal antenatal corticosteroids (ACS) therapy is considered to be the last major advance in the antenatal management of fetuses at risk of preterm birth. It was adopted worldwide to prevent neonatal death and neonatal complications following preterm birth, including respiratory distress syndrome, necrotizing enterocolitis and severe intraventricular hemorrhage. While short-term benefits of ACS were extensively investigated, long-term neurological outcomes in infants exposed antenatally to betamethasone have been assessed in few cohorts only. A recent report from the Cochrane collaborative network suggest that ACS is able to prevent some neurodevelopmental impairments associated with preterm delivery and related to postnatal adverse events .
As of today, in Europe and France, more than 85% of neonates born very preterm have been exposed to antenatal corticosteroids, mostly betamethasone for a total dose of 24 mg. Cochrane collaborative networks stated that trials of dosages comparing different regimens of commonly used corticosteroids are most urgently needed. Because a half dosage was associated with maximal benefits on lung function in ewes, a randomized controlled trial (BETADOSE, NCT02897076) is currently conducted to demonstrate that a 50% reduced betamethasone dose regimen is not inferior to a full dose regimen to prevent respiratory distress syndrome in neonates. Whatever the results of this ongoing clinical trial, follow-up of infants born from enrolled women is mandatory both to confirm the non-inferiority of the dose reduction on neurocognition and to assess the long-term effect of dose reduction on survival, on complex aspects of cognition, on behavioral aspects and on others neurodevelopmental impairments. Indeed, changes in clinical practices following BETADOSE trials will be depending on both short- and long-term outcomes. If non inferiority is demonstrated, dramatic changes will occur in the clinical use of antenatal betamethasone in women at risk of preterm birth in France and worldwide. If non inferiority is rejected, the neurocognitive follow-up of enrolled patients will be also of interest to (i) assess the long-term impact of the early consequences associated with betamethasone dose reduction and (ii) to find out domains of neurocognitive development sensitive to ACS exposure.
BETANINO study aims at assessing the impact of a 50% dose reduction on neurocognition at 5 years of age in infants born from mothers enrolled in the BETADOSE trial before 32 weeks of gestation, children that are at highest risk of neurocognitive impairments during childhood.
The main hypothesis of this cohort study following a randomized clinical trial is that half dose betamethasone (12 mg) is not inferior to full dose betamethasone (24 mg) to prevent neurodevelopmental impairment in children born very preterm.
- Conditions
- Premature Childbirth
- Being tested
- neurodevelopmental assessment
- Medical subject headings
- Premature Birth
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
neurodevelopmental assessmentOther
As part of the usual follow-up of premature children, a follow-up consultation is planned around the age of 5 years. During this visit, a neurodevelopmental assessment will be carried out for the Betanino study. The duration of this evaluation is evaluated around 3h in total.
Interventions will include:
- Standardized neurological exam
- Morphometric measurements including height, weight, head circumference
- Blood pressure measurement
- Multiple aspects of cognition using ancillary indexes of WPPSI-IV subtests, NEPSY-II subtests,
- Social Relativeness, using Social Relativeness Scale parental questionnaire,
- Parental stress using PSI questionnaire
| Study group | Role | What they receive |
|---|---|---|
| neurodevelopmental assessment | Other | As part of the usual follow-up of premature children, a follow-up consultation is planned around the age of 5 years. During this visit, a neurodevelopmental assessment will be carried out for the Betanino study. The duration of this evaluation is evaluated around 3h in total.
Interventions will include:
* Standardized neurological exam
* Morphometric measurements including height, weight, head circumference
* Blood pressure measurement
* Multiple aspects of cognition using ancillary indexes of WPPSI-IV subtests, NEPSY-II subtests,
* Social Relativeness, using Social Relativeness Scale parental questionnaire,
* Parental stress using PSI questionnaire Receives: Other: neurodevelopmental assessment |
What is being measured
The primary outcome is the main question the study is designed to answer.
neurocognitive development
Cognition will be assessed by certified neuropsychologists at 5 years of age using full scale IQ generated by Wechsler Preschool and Primary Scale of Intelligence (WPPSI-IV) test.
Measured: 5 years
Secondary outcomes (6)
5-year survival without moderate-to-severe impairment
Measured: 5 years
neurocognitive development
Measured by WPPSI-IV subtests
Measured: 5 years
Parental stress
Using Social Relativeness Scale
Measured: 5 years
Parental stress
Parental stress using PSI questionnaire All assessments will be based on internationally recognized tests that have been validated for infants at 3 years of age and conducted by certified neuropsychologists.
Measured: 5 years
cerebral palsy
cerebral palsy using the GMFCS notation system,
Measured: 5 years
neurocognitive development
Measured by NEPSY subtests
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jul 2019
- Study start23 Mar 2022
- Primary completion9 Sep 2025
- Study completion9 Sep 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Premature ChildbirthStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 386 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Biran Valerie, PHD, Principal investigator, APHPBaud Olivier, PHD, Study chair, Hôpitaux Universitaires de Genève - Inserm U1141 Hôpital Robert DebréSchmitz Thomas, PHD, Study chair, APHP
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04021485
- Sponsor's protocol ID
- K170920J
- Acronym
- BETANINO
- Status last verified
- Sep 2026
- First submitted
- 8 Jul 2019
- Last updated
- 8 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 5-year Follow-up of the BETADOSE Trial: Non-inferiority of a 50% Dose Reduction of Antenatal Betamethasone Therapy on the Neurodevelopment of Children Born Before 32 Weeks of Gestation.
- ClinicalTrials.gov ID
- NCT04021485
- Acronym / sponsor ID
- BETANINO / K170920J
- Conditions
- Premature Childbirth
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 386 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- 23 Mar 2022 (actual)
- Primary completion
- 9 Sep 2025 (actual)
- Study completion
- 9 Sep 2025 (actual)
- First posted
- 16 Jul 2019 (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.
Maternal antenatal corticosteroid therapy is the last major advance in the antenatal management of fetuses to prevent neonatal complications associated with prematurity. Long-term neurological outcomes in infants exposed to antenatal steroids have been assessed in few cohorts and suggest that this therapy is able to prevent some neurodevelopmental impairments including cerebral palsy. While >85% of neonates born very preterm in Europe have been exposed to antenatal betamethasone, Cochrane collaborative networks stated that trials of dosages comparing different regimens of commonly used corticosteroids are most urgently needed to avoid useless fetal exposure to excessive dosage of corticosteroids.
- Because a half dosage was associated with maximal benefits on lung function in ewes, a randomized controlled trial (BETADOSE, NCT02897076) has been conducted to demonstrate that a 50% reduced betamethasone dose regimen is not inferior to a full dose to prevent respiratory distress syndrome in preterm neonates. BETADOSE trial demonstrated that half dose did not show noninferiority to full antenatal betamethasone dose regimen to prevent severe RDS in preterm neonates while other prematurity-associated complications, including those usually prevented by ACS, did not differ between the two groups.
- Results of the 5-year BETANINO follow-up study of the BETADOSE neonates are needed before deciding whether reducing ACS dose is possible The main hypothesis of BETANINO is that half dose regimen of betamethasone is not inferior to full dose regimen of betamethasone to prevent neurodevelopmental impairments in these high-risk children born very preterm at 5 years of age.
Detailed description
Maternal antenatal corticosteroids (ACS) therapy is considered to be the last major advance in the antenatal management of fetuses at risk of preterm birth. It was adopted worldwide to prevent neonatal death and neonatal complications following preterm birth, including respiratory distress syndrome, necrotizing enterocolitis and severe intraventricular hemorrhage. While short-term benefits of ACS were extensively investigated, long-term neurological outcomes in infants exposed antenatally to betamethasone have been assessed in few cohorts only. A recent report from the Cochrane collaborative network suggest that ACS is able to prevent some neurodevelopmental impairments associated with preterm delivery and related to postnatal adverse events .
As of today, in Europe and France, more than 85% of neonates born very preterm have been exposed to antenatal corticosteroids, mostly betamethasone for a total dose of 24 mg. Cochrane collaborative networks stated that trials of dosages comparing different regimens of commonly used corticosteroids are most urgently needed. Because a half dosage was associated with maximal benefits on lung function in ewes, a randomized controlled trial (BETADOSE, NCT02897076) is currently conducted to demonstrate that a 50% reduced betamethasone dose regimen is not inferior to a full dose regimen to prevent respiratory distress syndrome in neonates. Whatever the results of this ongoing clinical trial, follow-up of infants born from enrolled women is mandatory both to confirm the non-inferiority of the dose reduction on neurocognition and to assess the long-term effect of dose reduction on survival, on complex aspects of cognition, on behavioral aspects and on others neurodevelopmental impairments. Indeed, changes in clinical practices following BETADOSE trials will be depending on both short- and long-term outcomes. If non inferiority is demonstrated, dramatic changes will occur in the clinical use of antenatal betamethasone in women at risk of preterm birth in France and worldwide. If non inferiority is rejected, the neurocognitive follow-up of enrolled patients will be also of interest to (i) assess the long-term impact of the early consequences associated with betamethasone dose reduction and (ii) to find out domains of neurocognitive development sensitive to ACS exposure.
BETANINO study aims at assessing the impact of a 50% dose reduction on neurocognition at 5 years of age in infants born from mothers enrolled in the BETADOSE trial before 32 weeks of gestation, children that are at highest risk of neurocognitive impairments during childhood.
The main hypothesis of this cohort study following a randomized clinical trial is that half dose betamethasone (12 mg) is not inferior to full dose betamethasone (24 mg) to prevent neurodevelopmental impairment in children born very preterm.
Study design
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| neurodevelopmental assessment | Other | Other: neurodevelopmental assessmentAs part of the usual follow-up of premature children, a follow-up consultation is planned around the age of 5 years. During this visit, a neurodevelopmental assessment will be carried out for the Betanino study. The duration of this evaluation is evaluated around 3h in total. Interventions will include: * Standardized neurological exam * Morphometric measurements including height, weight, head circumference * Blood pressure measurement * Multiple aspects of cognition using ancillary indexes of WPPSI-IV subtests, NEPSY-II subtests, * Social Relativeness, using Social Relativeness Scale parental questionnaire, * Parental stress using PSI questionnaire |
Who may qualify
- Ages
- 5 to 6 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (5 listed)
- Singleton child born from mother enrolled in the BETADOSE trial,
- Gestational age at birth less than 32 weeks of gestation,
- Age ≥ 5 years and < 6 years, alive and not lost of follow up
- Informed consent of the holder (s) of the exercise of parental authority
- Affiliation to a social security scheme.
Key exclusion criteria (2 listed)
- Major malformations and chromosomal aberrations evidenced after birth,
- Parents' refuse to participate.
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 |
|---|---|---|
| neurodevelopmental assessmentAs part of the usual follow-up of premature children, a follow-up consultation is planned around the age of 5 years. During this visit, a neurodevelopmental assessment will be carried out for the Betanino study. The duration of this evaluation is evaluated around 3h in total. Interventions will include: * Standardized neurological exam * Morphometric measurements including height, weight, head circumference * Blood pressure measurement * Multiple aspects of cognition using ancillary indexes of WPPSI-IV subtests, NEPSY-II subtests, * Social Relativeness, using Social Relativeness Scale parental questionnaire, * Parental stress using PSI questionnaire | Other | neurodevelopmental assessment |
Primary outcome
neurocognitive development
Time frame: 5 years
Cognition will be assessed by certified neuropsychologists at 5 years of age using full scale IQ generated by Wechsler Preschool and Primary Scale of Intelligence (WPPSI-IV) test.
6 secondary outcomes
5-year survival without moderate-to-severe impairment
Time frame: 5 years
neurocognitive development
Time frame: 5 years
Parental stress
Time frame: 5 years
Parental stress
Time frame: 5 years
cerebral palsy
Time frame: 5 years
neurocognitive development
Time frame: 5 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Sep 2026.
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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. This study is not recruiting at the moment.
Biran Valerie, PHD principal investigator
APHP
Baud Olivier, PHD study chair
Hôpitaux Universitaires de Genève - Inserm U1141 Hôpital Robert Debré
Schmitz Thomas, PHD study chair
APHP
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing neurodevelopmental assessment in people with Premature Childbirth, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
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 5 inclusion and 2 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: finished, as of the sponsor's last update on 8 Sep 2026. 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 France. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
neurocognitive development (time frame: 5 years). 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 8 Sep 2026.