Evidence map›Paper›PMID 40060937›Full record

ArticleThe Lancet regional health. Europe2025

Neurodevelopmental outcomes at five years in children born very preterm (24-31 weeks) exposed to opioids with or without midazolam: results from the French nationwide EPIPAGE-2 cohort study.

Elizabeth Walter-Nicolet, Laetitia Marchand-Martin, Andrei S Morgan, Monique Kaminski, Valérie Benhammou, Pierre-Yves Ancel, Pierre Tourneux, Véronique Pierrat, Xavier Durrmeyer

Registry-linked trialAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Lancet regional health. Europe, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03078439 (Epidemiologic Study on Small-for-gestational-age Children), which is not on this map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT03078439 completednot on this map

Epidemiologic Study on Small-for-gestational-age Children (EPIPAGE2 Cohort Study) - Follow up at Five and a Half Years

Typeobservational_patient_registrySponsorInstitut National de la Santé Et de la Recherche Médicale, FranceRan2016 to 2018Enrolled3,404ConditionsVery Preterm BirthArmsMedical and neuropsychological assessments
3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

  1. Cumulative exposure to opioids and benzodiazepines in extremely preterm neonates.Journal of perinatology : official journal of the California Perinatal Association · 2026
    Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Elizabeth Walter-NicoletUniversity Paris-Cité, CRESS, Obstétrical Perinatal and Pediatric Epidemiology Research Team, EPOPé, INSERM, INRAE, Paris, France.
Laetitia Marchand-MartinUniversity Paris-Cité, CRESS, Obstétrical Perinatal and Pediatric Epidemiology Research Team, EPOPé, INSERM, INRAE, Paris, France.
Andrei S MorganUniversity Paris-Cité, CRESS, Obstétrical Perinatal and Pediatric Epidemiology Research Team, EPOPé, INSERM, INRAE, Paris, France.
Monique KaminskiUniversity Paris-Cité, CRESS, Obstétrical Perinatal and Pediatric Epidemiology Research Team, EPOPé, INSERM, INRAE, Paris, France.
Valérie BenhammouUniversity Paris-Cité, CRESS, Obstétrical Perinatal and Pediatric Epidemiology Research Team, EPOPé, INSERM, INRAE, Paris, France.
Pierre-Yves AncelUniversity Paris-Cité, CRESS, Obstétrical Perinatal and Pediatric Epidemiology Research Team, EPOPé, INSERM, INRAE, Paris, France.
Pierre TourneuxNeonatal and Paediatric Intensive Care Unit, University Hospital, Amiens, France.
Véronique PierratUniversity Paris-Cité, CRESS, Obstétrical Perinatal and Pediatric Epidemiology Research Team, EPOPé, INSERM, INRAE, Paris, France.
Xavier DurrmeyerUniversity Paris-Cité, CRESS, Obstétrical Perinatal and Pediatric Epidemiology Research Team, EPOPé, INSERM, INRAE, Paris, France.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: Data on preschool neurodevelopment of preterm infants according to the duration of their neonatal exposure to opioids with/without midazolam is limited. We aimed to assess neurodevelopment outcome in children aged five years, born very preterm (24-31 weeks), according to exposure to these drugs. Methods: Secondary analysis from the French prospective cohort study EPIPAGE-2 (Etude Epidémiologique sur les Petits Ages Gestationnels, 2011). Exposure to opioids with/without midazolam was classified as none, ≤7 or >7 days. Percentages were weighted to account for the study design. The primary outcome was moderate/severe neurodevelopmental disabilities (NDD). Analyses were conducted using logistic regression and adjusted for perinatal confounders. Findings: Among 3117 survivors, 1165 (35.9%) were exposed (762/1165 (68.0%) ≤7 days, 403/1165 (32.0%) >7 days). Of these 49.5% received opioids only, 41.4% opioids and midazolam, and 9.1% midazolam only. Moderate/severe NDD occurred in 17.8%, 18.9%, and 31.7% in the unexposed, exposed ≤7 days, and exposed >7 days groups, respectively. After adjustment for baseline confounders, only exposure >7 days was associated with increased rates of moderate/severe NDD (adjusted odds ratio 2.07; 95% CI 1.32-3.26). After additional adjustment for severe neonatal morbidities no significant association was found between any duration of exposure and NDD. Interpretation: Exposure to opioids with/without midazolam >7 days might be associated with a higher prevalence of moderate/severe NDD at five years in very preterm born children but severe neonatal morbidities are a major modulator of this association. Funding: French Institute of Public Health Research, National Institute of Health and Medical Research, National Institute of Cancer, National Solidarity Fund for Autonomy, PremUp, APICIL Foundations.

Indexed as

Cumulative exposureFive years neurodevelopmentMidazolamNationwide cohort studyOpioidsVery preterm neonates

Identifiers

PMID40060937
PMCPMC11883393

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.