# Negative Results in Neonatal Trials: Clinical Lessons and Future Directions – A Narrative Review

**Authors:** Ashraf Gad, Ammar Yasser Nofal, Leena Khalid Al-Qassem, Loay Alkamel

PMC · DOI: 10.1159/000549325 · Biomedicine Hub · 2025-11-04

## TL;DR

This review highlights the importance of reporting negative results in neonatal clinical trials to improve evidence-based care and guide future research.

## Contribution

The paper emphasizes the value of negative trial outcomes in neonatology and calls for better reporting and interpretation.

## Key findings

- Negative trials help avoid unnecessary interventions and improve resource efficiency in neonatal care.
- Failure to report negative results contributes to publication bias and slows knowledge advancement.
- Properly interpreted negative outcomes guide future research and clinical practice in neonatology.

## Abstract

Clinical research involving neonates often presents unique ethical and practical challenges. These difficulties may lead to the early termination of clinical trials, particularly when negative or inconclusive results occur, contributing to publication bias. Failure to report such outcomes ultimately slows the advancement of knowledge and the development of evidence-based care in neonatology.

This review examines the significance of negative trial results in neonatal clinical research, with particular emphasis on interventional studies, and addresses their reliability, challenges in interpretation, and implications for clinical practice. Insights from selected negative neonatal trials were used to assess the impact of unfavorable outcomes on neonatal care. Non-interventional studies were excluded from this review to maintain a focus on controlled clinical trials.

Properly interpreted negative trials hold significant value in neonatal research. These studies help avoid unnecessary interventions, ensuring more efficient use of resources, and guide future research directions. Despite often being undervalued or overlooked, they remain fundamental to advancing evidence-based neonatal care. Enhanced reporting and interpretation of these findings could greatly benefit both clinical practice and research development in the neonatal population.

## Full-text entities

- **Genes:** PDLIM1 (PDZ and LIM domain 1) [NCBI Gene 9124] {aka CLIM1, CLP-36, CLP36, HEL-S-112, hCLIM1}, EPO (erythropoietin) [NCBI Gene 2056] {aka DBAL, ECYT5, EP, MVCD2}
- **Diseases:** cerebral palsy (MESH:D002547), fetal growth Restriction (MESH:D005317), MR (MESH:D008944), HIP (MESH:D007022), metabolic abnormalities (MESH:D008659), DCC (MESH:D013118), ROP (MESH:D012178), IVH (MESH:D000074042), BPD (MESH:D001997), UCM (MESH:C536938), EP (MESH:D047928), infection (MESH:D007239), PDA (MESH:D004374), brain injury (MESH:D001930), Encephalopathy (MESH:D001927), death (MESH:D003643), Hypothermia (MESH:D007035), neurodevelopmental impairment (MESH:D009422), pulmonary hypertension (MESH:D006976), sepsis (MESH:D018805), hyperbilirubinemia (MESH:D006932), HIE (MESH:D020925), NDI (MESH:D018500), NEC (MESH:D020345)
- **Chemicals:** choline (MESH:D002794), Hydrocortisone (MESH:D006854), oxygen (MESH:D010100), ibuprofen (MESH:D007052), Nitric Oxide (MESH:D009569), Vitamin A (MESH:D014801), dexamethasone (MESH:D003907), Indomethacin (MESH:D007213), N-acetylaspartate (MESH:C000179), Sildenafil (MESH:D000068677), EUNO (-), budesonide (MESH:D019819), morphine (MESH:D009020), uridine-5-monophosphate (MESH:D014542), dopamine (MESH:D004298), Docosahexaenoic acid (MESH:D004281), Steroids (MESH:D013256)
- **Species:** Lactobacillus (genus) [taxon 1578], Bifidobacterium animalis subsp. lactis (subspecies) [taxon 302911], Homo sapiens (human, species) [taxon 9606], Bifidobacterium longum subsp. infantis (subspecies) [taxon 1682], Streptococcus thermophilus (species) [taxon 1308], Bos taurus (bovine, species) [taxon 9913]

## Full text

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## References

85 references — full list in the complete paper: https://tomesphere.com/paper/PMC12788839/full.md

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Source: https://tomesphere.com/paper/PMC12788839