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Compromised Cerebral Oxygenation May Explain Worse Neurodevelopmental Outcome Seen In Infants With Necrotising Enterocolitis

Claire Howarth1,2; Joan Morris3; Jayanta Banerjee4,5; Terence Leung6; Simon Eaton7; Narendra Aladangady1,2

Institution(s)

1 = Homerton University Hospital NHS Foundation Trust, London, England; 2 = Queen Mary University of London, England; 3 = St George’s, University of London, London, England; 4 = Imperial College Healthcare NHS Trust, London, England; 5 = Imperial College London, UK; 6 = University College London, England; 7 = University College London Great Ormond Street Institute of Child Health, England

Introduction (include hypothesis)

Necrotising Enterocolitis (NEC) is a recognised independent risk factor of worse neurodevelopmental outcomes in premature infants1,2. Although the pathogenesis of this is likely multifactorial there is no substantial evidence to support a pathogenic mechanism. We aimed to establish whether cerebral oxygenation differed in those infants who develop NEC compared with those who do not.

Methods (include source of funding and ethical approval if required)

We recruited 48 infants <30w gestation admitted to our tertiary level NICU (after ethical approval and informed consent) from Oct 2016 to May 2018. Exclusion criteria: birthweight ≤2nd centile, abnormal antenatal dopplers, major congenital anomalies or Twin to Twin Transfusion Syndrome. Each recruit was monitored from birth to 36w post conceptional age or discharge from the neonatal unit (whichever was sooner). NIRS (NIRO-300, Hamamatsu KK, Japan) probes were placed on the abdomen and forehead weekly for 60 minutes allowing simultaneous measurement of gut (sTOI) and cerebral (cTOI) Tissue Oxygenation Index. Subsequently Fractional Tissue Oxygen Extraction (FTOE) and Splanchnic Cerebral Oxygenation Ratio (SCOR) were calculated. Weekly clinical status was also recorded, and NEC was defined as ≥ Bells stage 2.

Results

Median birthweight 884g (460-1600), median gestational age 26+3 weeks (23+0-29+6) and 52% female. 271 NIRS measurements were completed. NIRS measurements from 5 infants who developed Haemorrhagic Parenchymal Infarcts (HPI) were excluded from analysis in order to examine the relationship between cerebral NIRS and NEC. The mean cerebral oxygenation in infants with NEC (n = 7) was 56.9% and in infants without NEC (n = 34) was 63.9% over the first 7 weeks of life. Infants with NEC had significantly lower cerebral oxygenation levels than those that did not develop NEC, even when adjusted for confounders such as gestational age, birthweight, gender, PDA, enteral feeds, and Haemoglobin levels (table 1).

Table 1: Cerebral NIRS measurements in those infants with NEC compared to infants without NEC

Compromised Cerebral Oxygenation May Explain Worse Neurodevelopmental Outcome Seen In Infants With Necrotising Enterocolitis

Conclusions

Preterm infants with NEC have significantly lower cerebral tissue oxygenation in comparison to those who did not develop NEC, even when adjusted for confounders such as gestational age, birthweight, gender, PDA, enteral feeds and haemoglobin levels (table 1). This is a novel finding which could explain worse neurodevelopmental outcome in infants with NEC. Furthermore, continuous cerebral NIRS monitoring has the potential to alert clinicians to cerebral hypoxia allowing timely intervention and could also identify a subset of infants with NEC with a particularly low cTOI who could then be targeted for specific neurodevelopmental interventions.

References

1) Salhab, W.A., et al., Necrotizing enterocolitis and neurodevelopmental outcome in extremely low birth weight infants < 1000 g,. Journal of Perinatology, 2004. 24(9): p. 534-540. 2) Sonntag, J., et al., Growth and neurodevelopmental outcome of very low birthweight infants with necrotizing enterocolitis. Acta Paediatrica, 2000. 89(5): p. 528-532.

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