Early Amplitude-integrated Electroencephalogram Predicts Long-term Outcomes In Term And Near-term Newborns With Severe Hyperbilirubinemia

Research backgroundNeonatal jaundice continues to be a major cause of neonatal mortality as well as hospitalization,about 18%(or 24 million)of the 134 million liveborn babies in 2010 developed clinically significant jaundice and 481000 late-preterm and term neonates developed extreme hyperbilirubinaemia(TSB >25 mg/dL),with 114 000 deaths and more than 63000 survivors who had moderate or severe long-term neurological impairments.Data from the Global Burden of Disease study in 2016 showed that neonatal jaundice accounted for 1309.3 deaths per 100 000 livebirths and ranked seventh globally among all causes of neonatal deaths in the early-neonatal period(0–6 days).In the late-neonatal period(7–27 days)jaundice accounted for 187.1 deaths per 100000 and ranked ninth globally.It was the 16 th globally leading cause of mortality in children younger than 5 years.Bilirubin encephalopathy is the serious complication of neonatal hyperbilirubinaemia.In the early stage,it was characterized by persistent mild to moderate hypotonia and poor suck.In the medium term,it was characterized by lethargy,irritable,Shrill,Mild to moderate hypertonia alternating with hypotonia,beginning arching of neck and trunk on stimulation.While in the advanced stage,it was characterized persistent retrocollis and opisthotonos,inconsolable crying or cry weak or absent,semi-coma,apnea,unable to feed,seizures,coma,even death.When described in terms of the chronic phase,manifested as long-term neurodevelopmental impairments,including cerebral palsy(CP),auditory disorders,dental enamel dysplasia,paralysis of upward gaze and/or general developmental delays.However,prompt and effective monitoring and interventions might reverse bilirubin neurotoxicity during the early phases of ABE,Thus,successful early detection and treatment procedures is particularly important.Amplitude-integrated electroencephalogram(aEEG),characterized by simple operation and analysis,image intuition,and sustainable bedside dynamic monitoring,is a neonatal cerebral function monitoring technology developed in the 1970 s,and widely used in infants with hypoxic-ischemic encephalopathy,for monitoring seizures and for indicating the level of neurological maturation in preterm infants.However,whether aEEG also predicts ABE and its neurological outcome remains unclear.Previous research using conventional EEG has identified diverse abnormal courses of EEG patterns under varying degrees of hyperbilirubinemia in full-term neonates.Video EEG in newborns with jaundice clearly predicts the onset of seizures in the temporal and occipital lobes of newborns.However,knowledge of aEEG in relation to icteric infants remains controversial and mostly concentrated on one single parameter of the aEEG.In the present work we have incorporated three individual component variables of aEEG,including amplitude,SWC,and electrographic seizures,to discuss the predictive and prognostic value of severely abnormal aEEG for severe neonatal hyperbilirubinemia.Objective:To determine the predictive neurological prognostic value of early continuous amplitude-integrated electroencephalogram(aEEG)in term and near-term neonates with severe hyperbilirubinemia compared to cranial MRI and auditory brainstem response(ABR).Methods:Term and near-term infants of ≥ 35 weeks of gestation with severe hyperbilirubinemia(TSB levels ≥ 340 μmol/L)or with hyperbilirubinemia(TSB levels ≥ 257 μmol/L)in association with the presence of bilirubin-induced neurological dysfunction were recruited.All the subjects had an aEEG after being admitted to the NICU,while cranial MRI and ABR were performed when the total serum bilirubin level had come down to normal range.All the infants were followed up to 12 months,Bayley Scales of Infant Development was used to evaluate mental or psychological development.Adverse outcome was defined as death due to ABE,or survival with one or more of CP,hypophrenia,audio-visual disorders,dental enamel dysplasia.To assess the predictive value of aEEG contributing to adverse neurological outcome of severe hyperbilirubinemia.Results:During the study period,77 out of 83 infants were eligible,of which 71 had severe hyperbilirubinemia and 6 had hyperbilirubinemia in association with the presence of bilirubin-induced neurological dysfunction.Thirty-three were diagnosed with acute bilirubin encephalopathy(ABE),and 2 died of ABE,and 62 completed the follow-up,of which 12 infants had adverse outcomes.Sixty-four infants underwent aEEG,40 infants had cranial MRI,and 39 infants had ABR evaluations.Logistic regression and the receiver-operator characteristic curve analysis showed that the ability of severely abnormal aEEG could predicted adverse neurological outcome with its sensitivity of only 35.7%,specificity of 92.0%,positive predictive value of 55.6%,and negative predictive value of 83.6%,but was not so good as ABR abnormality with its sensitivity of 83.3 %,specificity of 74.1%,positive predictive value of 58.8%,and negative predictive value of 90.9%.Conclusion:Early aEEG could predict adverse neurodevelopmental outcomes in neonates with severe hyperbilirubinemia,although the sensitivity was lower than ABR.