A Multicentre Prospective Study on Magnetic Resonance Biomarkers in Neonatal Encephalopathy

2. 1 PRIMARY OBJECTIVE To examine the accuracy of 1H MRS thalamic [NAA] for predicting adverse neurodevelopment in infants with NE undergoing therapeutic hypothermia

2.2 SECONDARY OBJECTIVE 2.2.1 To examine inter and intra-center variability of thalamic [NAA] levels in healthy adult volunteers 2.2.2 To further develop normative ranges for 1H MRS thalamic [NAA] and other quantitative measures of potential utility in healthy term newborn infants 2.2.3 To compare the prognostic accuracy of 1H MRS thalamic [NAA] and other MRS quantities with that of the Lactate/NAA peak-area ratio acquired early (aged ≤ 4 days) and with that acquired late (aged 5 to 14 days) 2.2.4 To examine parental attitudes towards MR use in decisions about withdrawal of life support and counselling about long term outcomes

3. METHODS Prospective observational study; the index test (1H MRS) and gold-standard test (neurological outcome at 18 months) will be performed independently and blinded to each other.

3.3 Recruitment Control infants will be recruited from the postnatal wards at the participating hospitals. The MR scans will be performed before the infant is first discharged from hospital as far as possible (for example following a Caesarean delivery) i.e. within the first week of life. A lead research midwife will be identified in each of the participating hospitals who will approach the parents for recruitment and informed consent.

NE infants will be recruited from neonatal intensive care units. MR scans will be performed twice after informed parental consent. The first scan at less than 4 days of age (if clinically feasible) and the second scan between 5 to 14 days of age. The first scan will be performed while the infant is still in the intensive care unit at the participating centre. At the time of the second MR scan, it is likely most babies would be off the ventilator. Sedation would be used if required in these babies.