CALIFORNIA trial

Rationale: Necrotizing enterocolitis (NEC) is the most frequent, often life threatening, gastrointestinal disease in neonates. Mortality can reach 40%, and both short and long term morbidity are significant. Its cause is yet unknown. The risk of developing NEC is inversely related to gestational age and birth weight. Other risk factors for NEC are cardiovascular disorders associated with decreased intestinal circulation and maternal tocolysis with NSAIDs. However, it is not possible yet to identify neonates who will ultimately develop NEC. Identification of these patients is the key in both prevention and early treatment of NEC.



Objective: To identify non-invasive markers for NEC in neonates at risk to develop this disease.



Study design: prospective cohort study



Study population: 100 consecutive neonates considered to have risk factors for NEC, i.e. gestational age ¡Ü 30 weeks, birth weight ¡Ü 1000 gram, gestational age ¡Ü 32 weeks and birth weight ¡Ü 1200 gram, antenatal exposure to NSAIDs, cardiovascular disorders associated with decreased intestinal circulation.



Intervention (if applicable): There are no interventions



Main study parameters/endpoints:
Study parameters: urinary Intestinal Fatty Acid Binding Protein (I-FABP) to Creatinine ratio, urinary 8-hydroxy-2¡¯-deoxyguanosine (8-OHdG) to creatinine ratio, urinary F2-isoprostanes (F2-IsoPs) to creatinine ratio, faecal Calprotectin, faecal bile acids, faecal microbial analysis, genexpression (e.g. TLR-4 on shedded enterocytes in the faeces), plasma levels of Glucagon Like Peptide-1,2 and bile acids, Near Infrared Spectroscopy (NIRS) of abdomen and cerebrum.
Endpoint: the development of NEC as demonstrated radiologically (defined as the presence of pneumatosis intestinalis on an abdominal X-ray, diagnosed by an independent paediatric radiologist) or diagnosed during surgery.

We hypothesize that before clinical manifestation of NEC, urine I-FABP, serum GLP1/2, faecal Calprotectin, faecal TLR4 (on shedded enterocytes) and faecal bile acids can be used as predictive markers for NEC.
We also hypothesize that Near Infrared Spectroscopy is able to identify neonates at high risk for NEC by early identification of decreased bowel oxygenation.
Finally we hypothesize that the faecal microbiota is different in high risk neonates who develop NEC versus those who do not.

Collection/measurement Day
(until development of abdominal emergency
or
until NICU discharge
(with a maximum of 5 weeks))



Urine collection Day 1 postnatal afterwards three times a week

Faeces collection Day 1 postnatal afterwards two times a week

Blood collection - within first 7days post-natal

- Cerebral and abdominal NIRS measurement Day 1 up to and including day 5 postnatal, day 8 + weekly

none