Evidence map›Paper›PMID 41670746›Full record

Observational studyEuropean journal of pediatrics2026

Stress exposure, stress responses, and short-term outcomes in very preterm neonates: a national cohort study.

Judith A Ten Barge, Naomi J Meesters, Manon Benders, Anton H van Kaam, Bertrand D van Zelst, Henriette van Zanten, Christ-Jan van Ganzewinkel, Maria Luisa Tataranno, Frank A B A Schuerman, Chris H P van den Akker and 8 more

Abstract readMulticenter StudyObservational Study
In one paragraph

Observational study in European journal of pediatrics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
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

18 authors.

Judith A Ten BargeDepartment of Neonatal and Pediatric Intensive Care, Division of Neonatology, Erasmus MC - Sophia Children's Hospital, Rotterdam, The Netherlands. j.tenbarge@erasmusmc.nl.
Naomi J MeestersDepartment of Neonatal and Pediatric Intensive Care, Division of Neonatology, Erasmus MC - Sophia Children's Hospital, Rotterdam, The Netherlands.
Manon BendersDepartment of Neonatology, University Medical Center Utrecht, Wilhelmina Children's Hospital, Utrecht, The Netherlands.
Anton H van KaamDepartment of Neonatology, Emma Children's Hospital, Amsterdam UMC, Amsterdam Reproduction and Development Research Institute, University of Amsterdam, Amsterdam, The Netherlands.
Bertrand D van ZelstDepartment of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands.
Henriette van ZantenDepartment of Neonatology, Leiden University Medical Center, Leiden, The Netherlands.
Christ-Jan van GanzewinkelDepartment of Neonatology, Máxima Medical Centre, Veldhoven, The Netherlands.
Maria Luisa TatarannoDepartment of Neonatology, University Medical Center Utrecht, Wilhelmina Children's Hospital, Utrecht, The Netherlands.
Frank A B A SchuermanDepartment of Neonatology, Isala Clinics, Zwolle, The Netherlands.
Chris H P van den AkkerDepartment of Neonatology, Emma Children's Hospital, Amsterdam UMC, Amsterdam Reproduction and Development Research Institute, University of Amsterdam, Amsterdam, The Netherlands.
Marlou M A RaetsDepartment of Neonatology, Maastricht University Medical Center, MosaKids Children's Hospital, Maastricht, The Netherlands.
Willem P de BoodeDepartment of Neonatology, RadboudUMC Amalia Children's Hospital, Nijmegen, The Netherlands.
Peter H DijkDepartment of Neonatology, Beatrix Children's Hospital, University Medical Center Groningen, Groningen, The Netherlands.
Kirsten S MullerDepartment of Neonatal and Pediatric Intensive Care, Division of Neonatology, Erasmus MC - Sophia Children's Hospital, Rotterdam, The Netherlands.
Irwin K M ReissDepartment of Neonatal and Pediatric Intensive Care, Division of Neonatology, Erasmus MC - Sophia Children's Hospital, Rotterdam, The Netherlands.
Sjoerd A A van den BergDepartment of Clinical Chemistry, Erasmus MC, Rotterdam, The Netherlands.
Sinno H P SimonsDepartment of Neonatal and Pediatric Intensive Care, Division of Neonatology, Erasmus MC - Sophia Children's Hospital, Rotterdam, The Netherlands.
Gerbrich E van den BoschDepartment of Neonatal and Pediatric Intensive Care, Division of Neonatology, Erasmus MC - Sophia Children's Hospital, Rotterdam, The Netherlands.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Very preterm neonates admitted to the neonatal intensive care unit (NICU) face daily stressors that activate their hypothalamic-pituitary-adrenal (HPA) axis, triggering cortisol release and potentially affecting their outcomes. We examined the relationship between NICU stressors, urinary cortisol levels, and short-term outcomes in very preterm neonates. This study was part of a multicenter cohort study (HIPPO) including 446 neonates (gestational age < 29 weeks) across all Dutch NICUs. Data on daily stress exposure for the first 28 days and outcomes were prospectively collected, along with urine samples on postnatal days 8 (T1) and 28 (T2) to determine cortisol levels as markers of the stress response. Urinary samples were available for 391 (88%) neonates. In general, the most preterm born neonates had the highest cortisol levels, though highly variable with similar stress exposure. At T1, cortisol levels rose with increasing stress exposure in neonates born after gestational ages ≥ 27 weeks but decreased in the most preterm. At T2, cortisol levels tended to rise with stress exposure across all gestational ages. Though cortisol levels were higher in neonates that died or developed intraventricular hemorrhage, bronchopulmonary dysplasia or retinopathy of prematurity, cortisol was not independently associated with any of these outcomes.

conclusionHigh cortisol levels are linked to neonatal morbidity and mortality, but not independently, since urinary cortisol levels are moderated by gestational age. To protect preterm infants' future, it is key to understand their responses to stress in order to develop and evaluate stress protection strategies. WHAT IS KNOWN: • Very preterm neonates in the neonatal intensive care unit (NICU) are exposed to high levels of stress on a daily basis. • Stress exposure and altered cortisol responses in very preterm neonates have both been linked to adverse outcomes. WHAT IS NEW: • This study reveals gestational age-dependent effects of stress exposure on very preterm neonates' cortisol levels. • In general, high cortisol was associated with morbidity and mortality. • This study provides insight in hypothalamic-pituitary-adrenal axis development and highlights the importance of reducing stress.

Indexed as

HydrocortisoneInfant, Extremely PrematureInfant, Premature, DiseasesStress, PhysiologicalStress, PsychologicalBiomarkersCohort StudiesFemaleGestational AgeHumansHypothalamo-Hypophyseal SystemInfant, NewbornInfant, PrematureIntensive Care Units, NeonatalMaleNetherlandsBiomarkersHydrocortisoneCortisolNeonatal Intensive CarePremature infantStress

Identifiers

PMID41670746
PMCPMC12894146

What OpenQuestion holds

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Registered trials

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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.