Necrotising enterocolitis is a serious gastrointestinal disease seen principally in neonatal intensive care units. The reported mortality in established cases is between 20% and 40%.
No single aetiological factor seems to explain neonatal necrotising enterocolitis; its mucosal lesion can be provoked in several ways. It is important therefore to determine whether risk factors exist which can be avoided readily in clinical practice. Feeding policy is one such amenable factor. A recent prospective study carried out in five centres suggested that breast milk protects babies born prematurely from necrotising enterocolitis(1). In babies fed exclusively with formula milk the incidence of confirmed disease was six to ten times greater than those fed breast milk alone, and three times greater than in those who received formula plus breast milk. Pasteurised breast milk seemed to be as protective as raw breast milk. From this data and crude estimates of the proportion of premature babies who receive no breast milk in neonatal care, it has been estimated that 500 cases of necrotising enterocolitis in Britain each year could be attributed to exclusive formula feeding. These cases would account for at least 100 deaths and 150 laparotomies.
This study was introduced to establish the incidence of necrotising enterocolitis and to determine whether early diet can influence its onset and severity.
Grade 1 Cases have at least two of the following features: pneumatosis intestinalis seen on abdominal radiograph; abdominal distension, or an abdominal radiograph that shows gaseous distension or frothy appearance of bowel lumen (or both); blood in the stool; lethargy, hypotonia, or apnoeic episodes, or a combination of all three.
Grade 2 Cases have, as well as features of Grade 1, one or more of: abdominal bleeding in response to trauma; tenderness or rigidity; mucosal tissue in the stool; abnormal bleeding in response to trauma, or spontaneous bleeding; peripheral white blood cell count below 6 x 109/l at the time of illness; peripheral platelet count below 100 x 109/l at the time of illness; or an abdominal radiograph that shows gas in the portal vein or free air in the abdomen.
This study began in October 1993 and ended in October 1994.
Four hundred and twenty nine cases were reported during the twelve months of the study. Fifty two of the cases were duplicate reportings, 28 were reported outside the twelve months in question, 21 were reconsidered not to be true cases of NEC, 28 cases were `lost cases' - where identification details of the case had not been retained.
Therefore out of the 429 reported, 300 actual cases remain that fulfilled criteria for Grade I or II disease. Cases were confirmed if one of the following criteria was met: gas in the bowel wall or portal tract, diagnosis confirmed at surgery, diagnosis confirmed at autopsy. 185 out of the 300 were thus confirmed as cases by this more stringent criterion and 115 were suspected.
A retrospective survey was also undertaken being sent to 262 NICU's and SCBU’s, 109 replied reporting 197 cases of NEC. The second survey helped with validate the total number of case reported (see discussion).
Confirmed cases of NEC had a much higher proportion of grade 2 disease than suspected cases: 78% (145/185) versus 37% (42/115); (p<0.001).
The range of birthweight for all cases was 460-4870g, with 65% of all cases under 1500g.
NEC was found to be most severe in those infants with the lowest birthweight and lower gestation. Fifty-four percent of all cases were less than 30 weeks gestation and 12% were 37 weeks or older (i.e. term). There was a significant negative correlation with gestational age and day of onset of NEC (R=0.47, P<0.001), whether the disease was confirmed or not
Overall 52% of reported cases were male and 48% female..
The most common presenting clinical features for confirmed cases were abdominal distension (77% - 86% in suspected cases), lethargy, hypotonia, or apnoea (64% - 71% in suspected cases), abdominal tenderness (58%), pneumatosis intestinalis (57% - 5% in suspected cases), and blood in stool (39%).
Ninety-one cases representing 30% of all NEC cases (n=300) and 49% of confirmed cases (n=185) received surgical management. Surgical intervention for full term infants was under half that in preterm infants.
Overall mortality rate was 22% (65/300). Mortality rates for confirmed cases were significantly higher than that for suspected cases. It was also found that as birthweight or gestation increased, mortality was reduced whether NEC was confirmed or not.
Feeding practices differed between gestational groups. Those under 30 weeks gestation received at least some human milk compared to infants who were 30 weeks gestation or over. Those fed predominately on human milk were significantly less likely to develop confirmed disease, than those predominately on formulae milk.
Mortality rates between those fed predominately on human milk versus predominately formula did not differ. Though those above 30 weeks had a significant lower mortality if fed predominately human-milk fed.
This is only the second study in the United Kingdom with over 100 cases of NEC, and has permitted a detailed description of the clinical epidemiology of the disease. The study provides further support for the protective role of breast milk in the development of NEC, with reduced disease severity in the human milk-fed group.
The estimated incidence of confirmed NEC was 0.23 per 1000 live births, increasing to 2.1 per 1000 neonatal unit admissions. These figures are probably an underestimate since probably not every case of NEC was reported. This was confirmed through the retrospective survey of NICU’s and SCBU’s. It is estimated that about 58 additional cases should have been reported along with the estimate that 90% of the 28 cases reported but where no clinical data was available were NEC - bringing the total to 384, a 28% increase. Taking this figure, and assuming the same proportion of confirmed cases, the estimated incidence of confirmed NEC would rise to 0.30 per 1000 live births and 2.7 NICU admissions.
Mortality rates for all reported NEC was 22%, increasing to 28% for cases of confirmed disease. Age of onset was significantly correlated with gestation, demonstrating that the late onset of NEC was more common in the infants with low gestation and vice versa. Perhaps this could relate to the earlier use of enteral feeds at higher gestation. As expected, mortality was higher in infants with very low birthweight and with more severe disease; in babies under 750g with grade 2 disease, mortality was 50%.
Human milk intake was associated with reduced severity of disease. Amongst all infants who had evidence of NEC, irrespective of gestation, those fed predominately on human milk were significantly less likely to have confirmed disease than those fed predominately formula. Since infants with confirmed disease were more likely to require major surgery or die than those with suspected disease, the lower risk of confirmed disease in the human milk fed group is of potential clinical importance.
This study also supported the hypothesis that the possible benefits of human milk were greater in babies over 30 weeks gestation. Thus above 30 weeks gestation infants feed exclusively on human milk had less than half the rate of confirmed disease than those who were not exclusively human milk-fed (29% v 62% with confirmed disease respectively
Mortality was also significantly lower in predominantly human milk-fed infants than those fed predominantly formula in the subgroup 30 weeks gestation or above (5% -v- 26%, p=0.05).).
In summary the survey provides further evidence in support of a protective role of breast milk against necrotising enterocolitis. Disease severity was reduced in those fed predominately or exclusively on ‘man milk; and we found evidence in support of the hypothesis that human feeding is associated with the most marked benefits at 30 weeks gestation or above, in whom mortality from NEC was substantially reduced in predominately human milk-fed infants. These data add weight to the view, based now on several lines of evidence, that the inclusion of human milk in the diets of preterm infants may be clinically beneficial.
Further data and information will be included in the paper currently be prepared for publication. Additional references are available from the researcher.
1 Lucas, A, Cole TJ. Breast milk and neonatal necrotising enterocolitis. Lancet 1990; 336: 1519-23
Professor A Lucas, Ms R Abbott. MRC Childhood Nutrition Research Centre, Institute of Child Health, 30 Gulford Street, London WC1N 1EH.