A significant proportion of term and preterm infants develop neonatal jaundice. Jaundice in an otherwise healthy term infant is the most common reason for readmission to hospital. Jaundice is caused by an increase in serum bilirubin levels, largely as a result of breakdown of red blood cells. Bilirubin is conveyed in the blood as ‘unconjugated’ bilirubin, largely bound to albumin. The liver converts bilirubin into a conjugated form which is excreted in the bile. Very high levels of unconjugated bilirubin are neurotoxic. Phototherapy is a simple and effective way to reduce the bilirubin level. Most term babies have ‘physiological’ jaundice which responds to a short period of phototherapy, and requires no other treatment. A few babies have rapidly rising bilirubin levels which place them at risk of kernicterus. Current management of jaundice in the UK is guided by the NICE guideline. Any infant with high serum bilirubin or a rapidly rising bilirubin level needs to be treated urgently to avoid neurotoxicity. High levels of conjugated bilirubin in a term baby can indicate biliary atresia, and babies with persisting jaundice must have their level of conjugated bilirubin measured. Preterm infants on long-term parenteral nutrition may develop conjugated jaundice which generally improves with the introduction of enteral feed and weaning of intravenous nutrition.

This review discusses an approach to determining the cause of neonatal encephalopathy, as well as current evidence on resuscitation and subsequent management of hypoxic-ischaemic encephalopathy (HIE). Encephalopathy in neonates can be due to varied aetiologies in addition to hypoxic-ischaemia. A combination of careful history, examination and the judicious use of investigations can help determine the cause. Over the last 7 years, infants with moderate to severe HIE have benefited from the introduction of routine therapeutic hypothermia; the number needed to treat for an additional beneficial outcome is 7 (95% CI 5 to 10). More recent research has focused on optimal resuscitation practices for babies with cardiorespiratory depression, such as delayed cord clamping after establishment of ventilation and resuscitation in air. Around a quarter of infants with asystole at 10 min after birth who are subsequently cooled have normal outcomes, suggesting that individualised decision making on stopping resuscitation is needed, based on access to intensive treatment unit and early cooling. The full benefit of cooling appears to have been exploited in our current treatment protocols of 72 hours at 33.5°C; deeper and longer cooling showed adverse outcome. The challenge over the next 5–10 years will be to assess which adjunct therapies are safe and optimise hypothermic brain protection in phase I and phase II trials. Optimal care may require tailoring treatments according to gender, genetic risk, injury severity and inflammatory status.

Despite the availability of continuous conventional electroencephalography (cEEG), accurate diagnosis of neonatal seizures is challenging in clinical practice. Algorithms for decision support in the recognition of neonatal seizures could improve detection. We aimed to assess the diagnostic accuracy of an automated seizure detection algorithm called Algorithm for Neonatal Seizure Recognition (ANSeR). This multicentre, randomised, two-arm, parallel, controlled trial was done in eight neonatal centres across Ireland, the Netherlands, Sweden, and the UK. Neonates with a corrected gestational age between 36 and 44 weeks with, or at significant risk of, seizures requiring EEG monitoring, received cEEG plus ANSeR linked to the EEG monitor displaying a seizure probability trend in real time (algorithm group) or cEEG monitoring alone (non-algorithm group). The primary outcome was diagnostic accuracy (sensitivity, specificity, and false detection rate) of health-care professionals to identify neonates with electrographic seizures and seizure hours with and without the support of the ANSeR algorithm. Neonates with data on the outcome of interest were included in the analysis. This study is registered with ClinicalTrials.gov, NCT02431780. Between Feb 13, 2015, and Feb 7, 2017, 132 neonates were randomly assigned to the algorithm group and 132 to the non-algorithm group. Six neonates were excluded (four from the algorithm group and two from the non-algorithm group). Electrographic seizures were present in 32 (25·0%) of 128 neonates in the algorithm group and 38 (29·2%) of 130 neonates in the non-algorithm group. For recognition of neonates with electrographic seizures, sensitivity was 81·3% (95% CI 66·7-93·3) in the algorithm group and 89·5% (78·4-97·5) in the non-algorithm group; specificity was 84·4% (95% CI 76·9-91·0) in the algorithm group and 89·1% (82·5-94·7) in the non-algorithm group; and the false detection rate was 36·6% (95% CI 22·7-52·1) in the algorithm group and 22·7% (11·6-35·9) in the non-algorithm group. We identified 659 h in which seizures occurred (seizure hours): 268 h in the algorithm versus 391 h in the non-algorithm group. The percentage of seizure hours correctly identified was higher in the algorithm group than in the non-algorithm group (177 [66·0%; 95% CI 53·8-77·3] of 268 h vs 177 [45·3%; 34·5-58·3] of 391 h; difference 20·8% [3·6-37·1]). No significant differences were seen in the percentage of neonates with seizures given at least one inappropriate antiseizure medication (37·5% [95% CI 25·0 to 56·3] vs 31·6% [21·1 to 47·4]; difference 5·9% [-14·0 to 26·3]). ANSeR, a machine-learning algorithm, is safe and able to accurately detect neonatal seizures. Although the algorithm did not enhance identification of individual neonates with seizures beyond conventional EEG, recognition of seizure hours was improved with use of ANSeR. The benefit might be greater in less experienced centres, but further study is required. Wellcome Trust, Science Foundation Ireland, and Nihon Kohden.

We present a novel lens-based broadband near-infrared spectroscopy system to simultaneously measure cerebral changes in tissue oxygenation and haemodynamics via estimation of the changes in haemoglobin concentration; in addition to oxygen utilization via the measurement of the oxidation state of cytochrome-c-oxidase (CCO). We demonstrate the use of the system in a cohort of 6 newborn infants with neonatal encephalopathy in the Neonatal Intensive Care Unit for continuous measurement periods of up to 5 days. NIRS data was collected from above the frontal lobe on the left and right hemispheres simultaneously with systemic data to allow multimodal data analysis. This allowed us to study the NIRS variables in response to global pathophysiological events and we focused our analysis to spontaneous oxygen desaturations. We identified changes from the NIRS variables during 236 oxygen desaturations from over 212 hours of data with a change from the baseline to nadir of −12 ± 3%. There was a consistent negative change in the Δ[HbD] (= oxygenated – deoxygenated haemoglobin) and Δ[oxCCO] measurements, mean decreases were 3.0 ± 1.7μM and 0.22 ± 0.11μM, and a positive change in the Δ[HbT] (= oxygenated + deoxygenated haemoglobin) measurements across all subjects, mean increase was 0.85 ± 0.58μM. We have shown with a feasibility study that the relationship between haemoglobin oxygenation changes and CCO oxidation changes during these desaturation events was significantly associated with a magnetic resonance spectroscopy (MRS)-measured biomarker of injury severity (r = 0.91, p<0.01).

Objective: Brain proton (¹H) magnetic resonance spectroscopy (MRS) lactate/N-acetylaspartate (Lac/NAA) peak area ratio is used for prognostication in neonatal encephalopathy (NE). At 3 Tesla in NE babies, the objectives were to assess: (1) sensitivity and specificity of basal ganglia and thalamus (BGT) ¹H MRS Lac/NAA for the prediction of Bayley III outcomes at 2 years using optimised metabolite fitting (Tarquin) with threonine and total NAA; (2) prediction of motor outcome with diffusion-weighted MRI; (3) BGT Lac/NAA correlation with the National Institute of Child Health and Human Development (NICHD) MRI score. Subjects and methods: 55 (16 inborn, 39 outborn) infants at 39w+5 d (35w+5d–42w+0d) with NE admitted between February 2012 and August 2014 to University College London Hospitals for therapeutic hypothermia underwent MRI and ¹H MRS at 3T on day 2–14 (median day 5). MRIs were scored. Bayley III was assessed at 24 (22–26) months. Results: 16 babies died (1 inborn, 15 outborn); 20, 19 and 21 babies had poor motor, cognitive and language outcomes. Using a threshold of 0.39, sensitivity and specificity of BGT Lac/NAA for 2-year motor outcome was 100% and 97%, cognition 90% and 97% and language 81% and 97%, respectively. Sensitivity and specificity for motor outcome of mean diffusivity (threshold 0.001 mm²/s) up to day 9 was 72% and 100% and fractional anisotropy (threshold 0.198) was 39% and 94%, respectively. Lac/NAA correlated with BGT injury on NICHD scores (2A, 2B, 3). Conclusion: BGT Lac/NAA on ¹H MRS at 3T within 14 days accurately predicts 2-year motor, cognitive and language outcome and may be a marker directing decisions for therapies after cooling.