Association Between Methemoglobin Levels and Necrotizing Enterocolitis in Preterm Infants: A Retrospective Cohort Study
In brief
Higher methemoglobin levels were linked to NEC, but poorly identified cases
In a single-center study of 291 preterm infants, each doubling of methemoglobin was associated with higher odds of necrotizing enterocolitis after adjustment for sex and gestational age. But the test distinguished infants with and without NEC poorly, did not separate disease stages, and was not significantly linked to death after adjustment; it is not ready for diagnosis or prediction.
- Journal
- Children (Basel, Switzerland) (Q2)
- Published
- 30 September 2026
- Study design
- Prospective / inception cohort
- Evidence level
- Level 2, Moderate (CEBM 2b)
- Authors
- Muhammet Asena, Duygu Tuncel, Leyla Şero, Nilüfer Okur
- PMID
- 42940645
- DOI
- 10.3390/children13101326
Why clinicians should know about it
- Picked for Pediatric Surgery (top studies of the week, 1 November 2026): NEC biomarker study relevant to neonatal surgical disease
Abstract
Background: Necrotizing enterocolitis (NEC) is a leading cause of morbidity and mortality in preterm infants, and there remains a need for simple, easily measured parameters reflecting its prevalence and severity. This study tested the hypothesis that methemoglobin (MetHb), a molecule implicated in nitric oxide metabolism, is associated with the presence and severity of NEC, as well as with its complications. Methods: We performed a single-center, retrospective cohort study on 291 premature infants (<32 weeks' gestational age). A total of 217 had no NEC and 74 had Bell stages II-III NEC. MetHb expressed as a percent of the total hemoglobin (% MetHb) was studied for its relationship with NEC and outcomes. Logistic regression and receiver operating characteristic analysis were performed. Results: % MetHb was higher among neonates who developed NEC compared to controls [2.55% (1.70-4.95) vs. 2.20% (1.70-2.80); p = 0.040]. For every twofold increase in % MetHb, there was an association with the development of NEC after adjustment for sex and gestational age (aOR: 1.74; 95% CI: 1.24-2.45; p = 0.001). Discrimination of NEC was poor, with an area under the curve of 0.580 (95% CI: 0.493-0.667); at a cutoff of ≥4.6% (exploration purposes), the test had a sensitivity of 28.4% and a specificity of 94.5%. The test failed to differentiate stage II from stage III NEC, and its association with all-cause death and death with an NEC association, after adjustment, failed to reach significance. Conclusions: Elevated MetHb levels were independently associated with NEC, although they lacked adequate standalone predictive and discriminatory ability; these data do not support current utilization for prediction or diagnosis, and further prospective study with standardized sampling, external validation, and a multimarker approach is needed.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.