Necrotizing enterocolitis as a prognostic factor for the neurodevelopmental outcome of preterm infants - match control study after 2  years

Allendorf, Antje; Dewitz, R; Weber, J.; Bakthiar, Shahrzad; Schloesser, Rolf; Rolle, Udo

doi:10.1016/j.jpedsurg.2018.01.006

Cited by 28 publications

(28 citation statements)

References 20 publications

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“…The overall incidence of NDI in NEC infants was 40% (IQR 28%–64%), as calculated from 31 studies (n=952/2403 infants with NEC; table 2). 11 12 19–28 30 31 33 36 38–52 When we analysed the 17 comparative studies,11 12 21–23 25–27 31 33 39–41 45 47 50 51 we found that the risk of NDI was significantly higher in NEC infants (40%, 751/1876 patients) versus premature age-matched controls without NEC (29%, 7955/27 287 patients; p<0.00001; RR 1.59, 95% CI 1.42 to 1.79; figure 2A).…”

Section: Resultsmentioning

confidence: 99%

“…Of 10 674 abstracts screened, 203 full-text articles were thoroughly examined, and 53 studies were included in the final analysis (figure 1). Of the latter, 21 were designed to address neurodevelopmental outcome and/or neuroimaging abnormalities in NEC survivors,11 12 19–37 and 11 of these were prospective studies 11 20 22 23 26–29 32 35 37…”

Section: Resultsmentioning

confidence: 99%

“…In the 10 studies that compared surgical versus medical NEC, we detected a higher incidence of NDI in infants with surgical NEC (43%) than in those with medical NEC (27%; p<0.00001; RR 1.60, 95% CI 1.34 to 1.90; figure 3). 11 19 21 22 25 28 31 36 40 41 Furthermore, compared with those with medical NEC or without NEC, infants with surgical NEC were more likely to have cerebral palsy (surgical NEC: 24% vs medical/no NEC: 15%) 25. Infants who underwent surgery for NEC were reported to have a delay in verbal skills and non-verbal performance compared with aged-matched control infants without NEC 26 36.…”

Section: Resultsmentioning

confidence: 99%

“…11 19 21 22 25 28 31 36 40 41 Furthermore, compared with those with medical NEC or without NEC, infants with surgical NEC were more likely to have cerebral palsy (surgical NEC: 24% vs medical/no NEC: 15%) 25. Infants who underwent surgery for NEC were reported to have a delay in verbal skills and non-verbal performance compared with aged-matched control infants without NEC 26 36. Moreover, infants with surgical NEC had a higher risk of developing head growth failure and microcephaly compared with those with medical NEC 28 61.…”

Section: Resultsmentioning

confidence: 99%

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Neurodevelopmental impairment in necrotising enterocolitis survivors: systematic review and meta-analysis

Matei

Montalva

Goodbaum

et al. 2019

Arch Dis Child Fetal Neonatal Ed

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AimTo determine (1) the incidence of neurodevelopmental impairment (NDI) in necrotising enterocolitis (NEC), (2) the impact of NEC severity on NDI in these babies and (3) the cerebral lesions found in babies with NEC.MethodsSystematic review: three independent investigators searched for studies reporting infants with NDI and a history of NEC (PubMed, Medline, Cochrane Collaboration, Scopus). Meta-analysis: using RevMan V.5.3, we compared NDI incidence and type of cerebral lesions between NEC infants versus preterm infants and infants with medical vs surgical NEC.ResultsOf 10 674 abstracts screened, 203 full-text articles were examined. In 31 studies (n=2403 infants with NEC), NDI incidence was 40% (IQR 28%–64%) and was higher in infants with surgically treated NEC (43%) compared with medically managed NEC (27%, p<0.00001). The most common NDI in NEC was cerebral palsy (18%). Cerebral lesions: intraventricular haemorrhage (IVH) was more common in NEC babies (26%) compared with preterm infants (18%; p<0.0001). There was no difference in IVH incidence between infants with surgical NEC (25%) and those treated medically (20%; p=0.4). The incidence of periventricular leukomalacia (PVL) was significantly increased in infants with NEC (11%) compared with preterm infants (5%; p<0.00001).ConclusionsThis study shows that a large proportion of NEC survivors has NDI. NEC babies are at higher risk of developing IVH and/or PVL than babies with prematurity alone. The degree of NDI seems to correlate to the severity of gut damage, with a worse status in infants with surgical NEC compared with those with medical NEC.Trial registration numberCRD42019120522.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

See 2 more Smart Citations

Neurodevelopmental impairment in necrotising enterocolitis survivors: systematic review and meta-analysis

Matei

Montalva

Goodbaum

et al. 2019

Arch Dis Child Fetal Neonatal Ed

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“…Mortality rates range from 20-40 percent 2,4-6 and survivors encounter hospital stays on average of 11 days longer than infants born at similar estimated gestational age that did not develop NEC 7 . Disease-associate costs of surgical NEC can extend beyond initial diagnosis, including development of short bowel syndrome and increased risk of neurodevelopmental morbidity 8,9 . While prematurity 10,11 , enteral feeding 12 and intestinal bacterial colonization 13,14 are recognized as major risk factors, definitive mechanisms of NEC pathophysiology have yet to be established and treatments remain primarily supportive.…”

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confidence: 99%

Elevated Coefficient of Variation in Total Fecal Bile Acids Precedes Diagnosis of Necrotizing Enterocolitis

Knapp

Kehring

Stepp

et al. 2020

Sci Rep

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Accumulation of bile acids (BAs) may mediate development of necrotizing enterocolitis (NEC). Serial fecal samples were collected from premature infants with birth weight (BW) ≤ 1800 g, estimated gestational age (EGA) ≤ 32 weeks, and <30 days old prior to initiation of enteral feeding. Nine infants that developed Bell's Stage ≥ II NEC were matched with control infants based on BW, EGA, day of life (DOL) enteral feeding was initiated and DOL of the first sample. From each subject, five samples matched by DOL collected were analyzed for BA levels and composition. Fifteen individual BA species were measured via LC-MS/MS and total BA levels were measured using the Diazyme Total Bile Acid Assay kit. No statistically significant differences in composition were observed between control and NEC at the level of individual species (p = 0.1133) or grouped BAs (p = 0.0742). However, there was a statistically significant difference (p = 0.000012) in the mean coefficient of variation (CV) between the two groups with infants developing NEC having more than four-fold higher mean CV than controls. Importantly, these variations occurred prior to NEC diagnosis. These data suggest fluctuations in total fecal BA levels could provide the basis for the first predictive clinical test for NEC.protective responses 20 , and the concomitant dysregulation of hepatic BA transporters 21 during development of NEC. This novel paradigm encompasses major disease-associated findings and risk factors: 1) the more premature an infant, the more likely they will develop NEC 10,11 . Many of the key processes of BA homeostasis are not fully developed in neonates, but reach maturity at weaning [22][23][24][25][26][27] . 2) Formula-fed preemies are 6-10 times more likely to develop NEC 12 and have higher fecal BA levels than breast-fed preemies 28 . Further, formula feeding is required to develop experimental NEC 29,30 . 3) The majority of BA reclamation occurs in the ileum and colon, the primary sites of NEC injury 31 , and ileal BA levels increase 24-hours before inflammation or histological damage in experimental NEC 32 . 4) Bacterial colonization is required for both development of NEC and formation of secondary BAs. While no specific pathogen has been conclusively associated with NEC 33-43 , disease cannot be developed in germ free conditions 13,14 and pneumatosis intestinalis, the most pathognomonic radiological finding of NEC, is thought to be caused by bacterial overgrowth 44 . Bacteria are also required for formation of more toxic, hydrophobic BAs 45-47 , which are higher in both experimental 18 and human NEC 48 .To further characterize how BAs are dysregulated in human NEC, we prospectively collected fecal samples from premature infants and determined BA levels and composition from matched-pairs diagnosed with NEC versus those without NEC. Contrary to a previous study 48 , we found no statistically significant differences in BA composition between control and NEC. However, there was a statistically significant difference (p = 0.000012) in the mean...

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Modified NEOMOD score as a neonatal mortality prediction tool in a medium‐income country: A validation diagnostic test study

Torres‐Canchala

Molina

Barco

et al. 2023

Health Science Reports

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Background and Aims: Multiple organ dysfunction (MOD) is a potentially reversible physiological disorder that involves two or more systems. Modified NEOMOD (Neonatal Multiple Organ Dysfunction score) scale could be a useful instrument to measure MOD and predict mortality. Our aim was to validate modified NEOMOD in patients from a neonatal intensive care unit (NICU) of a middle-income country.Methods: Diagnostic test study. Preterm newborns admitted NICU were included.Daily values were collected from birthday to Day 14. MOD was defined as at least one point in two or more systems. The lowest score is 0 and the maximum is 16. The outcome variable was mortality. Secondary outcomes were bronchopulmonary dysplasia, retinopathy of prematurity (ROP), late-onset neonatal sepsis (LONS), intraventricular hemorrhage (IVH) and length of hospital stay. Area under the curve (AUC) and Hosmer-Lemeshow test were calculated to evaluate scale discrimination and calibration. Logistic regression was used to estimate the association between daily modified NEOMOD score and death.Results: We included 273 patients who met the inclusion criteria. MOD incidence was 74.4%. The median gestational age in patients with MOD was 30 (interquartile range [IQR]: 27-33) and in patients without MOD it was 32 (IQR: 31-33) (p < 0.001).There were 40 deaths (14.6%), 38 (18.7%) from the MOD group and 2 (2.9%) from non-MOD group. On accumulated Day 7, AUC was 0.89 (95% confidence interval [CI]: 0.83-0.95). Modified NEOMOD had good calibration (X 2 = 2.94, p = 0.982). DBP (12.8% vs. 2.9%, p = 0.001), ROP (3.9% vs. 0%, p = 0.090), IVH (33% vs. 12.9%, p < 0.001), and LONS (36.5% vs. 8.6%, p < 0.001) frequency was higher in the MOD group than non-MOD group. Length of hospital stay also was higher in MOD group (median 21 days [IQR 7-44] vs. median 5 days [IQR 4-9], p = 0.004). Conclusion:Modified NEOMOD scale presents good discrimination and calibration for death in preterm children. This scale could help in clinical decision-making in real-time.

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Necrotizing enterocolitis as a prognostic factor for the neurodevelopmental outcome of preterm infants - match control study after 2 years

Cited by 28 publications

References 20 publications

Neurodevelopmental impairment in necrotising enterocolitis survivors: systematic review and meta-analysis

Neurodevelopmental impairment in necrotising enterocolitis survivors: systematic review and meta-analysis

Elevated Coefficient of Variation in Total Fecal Bile Acids Precedes Diagnosis of Necrotizing Enterocolitis

Modified NEOMOD score as a neonatal mortality prediction tool in a medium‐income country: A validation diagnostic test study

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