Sally L Jary

Time Is Brain: Starting Therapeutic Hypothermia within Three Hours after Birth Improves Motor Outcome in Asphyxiated Newborns

Objective: Therapeutic hypothermia (HT) is the standard treatment for newborns after perinatal asphyxia. Preclinical studies report that HT is more effective when started early. Methods: Eighty cooled newborns were analyzed and grouped according to when cooling was started after birth: early (≤180 min) or late (>181 min). For survivors we analyzed whether starting cooling early was associated with a better psychomotor or mental developmental index (PDI or MDI, Bayley Scales of Infant Development II) than late cooling. Results: Forty-three newborns started cooling early and 37 started late. There was no significant difference in the severity markers of perinatal asphyxia between the groups; however, nonsurvivors (n = 15) suffered more severe asphyxia and had significantly lower centiles for weight (BWC; p = 0.009). Of the 65 infants that survived, 35 were cooled early and 30 were cooled late. There was no difference in time to start cooling between those who survived and those who did not. For survivors, median PDI (IQR) was significantly higher when cooled early [90 (77-99)] compared to being cooled later [78 (70-90); p = 0.033]. There was no increase in cardiovascular adverse effects in those cooled early. There was no significant difference in MDI between early and late cooling [93 (77-103) vs. 89 (76-106), p = 0.594]. Conclusion: Starting cooling before 3 h of age in surviving asphyxiated newborns is safe and significantly improves motor outcome. Cooling should be initiated as soon as possible after birth in eligible infants.

Comparison of Bayley-2 and Bayley-3 scores at 18 months in term infants following neonatal encephalopathy and therapeutic hypothermia

Neuroprotection trials for neonatal encephalopathy use moderate or severe disability as an outcome, with the Bayley Scales of Infant Development, Second Edition (Bayley‐2) Index scores of <70 as part of the criteria. The Bayley Scales of Infant and Toddler, 3rd Development, Third Edition (Bayley‐3) have superseded Bayley‐2 and yield higher than expected scores in typically developing and high‐risk infants. The aim of this study, therefore, was to compare Bayley‐2 scores and Bayley‐3 scores in term‐born infants surviving neonatal encephalopathy treated with hypothermia.

Impaired brain growth and neurodevelopment in preterm infants with posthaemorrhagic ventricular dilatation.

Aim:  To correlate volumetric magnetic resonance imaging at term with neurodevelopmental outcome at 2 years in infants with posthaemorrhagic ventricular dilatation. Preterm infants with posthaemorrhagic ventricular dilatation have high risk of disabilities, but the range is wide and predicting severity of motor and mental disability is difficult.

Cooling neonates who do not fulfil the standard cooling criteria – short‐ and long‐term outcomes

Therapeutic hypothermia is effective and without serious adverse effects in term infants with hypoxic–ischaemic encephalopathy. It is unknown whether other neonatal patient groups could benefit from therapeutic hypothermia. Since 2006, our centre has offered cooling to infants fulfilling the standard cooling criteria, but also to those who did not.

Lactate dehydrogenase in hypothermia-treated newborn infants with hypoxic-ischaemic encephalopathy

Aims:  We investigated whether plasma lactate dehydrogenase (LDH) predicts outcome in hypothermia (HT)‐treated term infants with moderate/severe hypoxic‐ischaemic encephalopathy (HIE) and additionally whether LDH differs between infants with evidence for acute and nonacute perinatal insults and postnatal collapse (PNC).

Factors Associated with Permanent Hearing Impairment in Infants Treated with Therapeutic Hypothermia

OBJECTIVE To define the incidence of hearing impairment, document plasma gentamicin concentrations, and identify factors associated with permanent hearing impairment in infants subjected to therapeutic hypothermia for moderate or severe neonatal encephalopathy. STUDY DESIGN Data were collected prospectively in a regional center providing therapeutic hypothermia. Cooled infants at ≥ 36 weeks gestation with moderate or severe neonatal encephalopathy were analyzed if a full dataset was available (n = 108), including clinical variables and gentamicin trough levels. Infants with hearing impairment were identified, and survivors were followed up with neurodevelopmental evaluation at age 18 months. Stepwise logistic regression identified factors associated with hearing impairment. RESULTS Nine infants died, and among the survivors, 10.1% developed a permanent hearing impairment. The trough gentamicin level was above the recommended cutoff of 2 mg/L in 37% of the infants in the entire cohort and in 90% of the infants with hearing impairment. Logistic regression analysis identified high trough gentamicin level, low cord pH, and hypoglycemia (<46.8 mg/dL) in the first postnatal hour as significantly associated with hearing impairment. The need for inotropic support was close to significant (P = .055). CONCLUSION Hearing impairment was a common finding among cooled infants. Plasma gentamicin levels were commonly >2 mg/L. Based on these findings, we propose changes in gentamicin dosing interval and trough level monitoring to minimize the risk of potentially toxic levels in cooled newborns.

Quantitative cranial ultrasound prediction of severity of disability in premature infants with post-haemorrhagic ventricular dilatation

Background Infants with post-haemorrhagic ventricular dilatation (PHVD) have a high risk of severe disability and parenchymal infarction increases this risk. Existing cranial ultrasound (CUS) markers of neurodevelopmental outcome are based on categorical features. Objective To investigate to what extent quantitative CUS measurements correlated with severity of developmental outcome and the need for ventriculoperitoneal (VP) shunt at 2 years of age. Design 69 premature infants with PHVD had lateral ventricle area, intraventricular echodensity and parenchymal lesion dimensions measured at the start of treatment for PHVD. Outcome measures were the Bayley Scales of Infant Development-II and functional ability at 2 years of age. Bayley developmental quotients (DQ) were used in preference to index scores to enable inclusion of severely disabled children. Results Quantitative CUS measurements of parenchymal lesion area correlated significantly with later mental and motor DQ. Intraventricular echodensity area correlated with motor DQ in infants with grade 4 intraventricular haemorrhage (IVH). Neither ventricular area nor ventricular width correlated with DQ in grade 3 IVH. Infants who ultimately required a VP shunt had a significantly larger intraventricular echodensity area. Conclusions CUS measurement of parenchymal lesions in infants with PHVD can increase the precision of predicting severe mental and motor disability, but ventricular size at the start of treatment is not predictive of outcome in infants with PHVD following grade 3 IVH.

Differentiating developmental outcome between infants with severe disability in research studies- the role of Bayley Developmental Quotients

OBJECTIVES To investigate whether infants with a score <50 on the Bayley Scales of Infant Development, Second Edition (BSID-II) demonstrated differences in functional ability, and to assess whether the Bayley Developmental Quotients (DQs) indicated such differences. STUDY DESIGN Preterm infants (n = 67; 47 boys) with posthemorrhagic ventricular dilatation were evaluated at 25 months past term age using the BSID-II and grading of functional ability. Mental and Motor Bayley DQs were derived and compared with functional ability. RESULTS Among the 34 subjects (51%) with a BSID-II score <50, there were clinically significant differences in the ability to walk, sit, eat, speak, and see. In all subjects, there were significant differences in Mental and Motor Bayley DQs based on grade of disability in each domain except hearing. CONCLUSIONS Bayley DQ quantified the spread of functional ability in all children, provided a continuous parameter to compare ability in severely delayed children, and should be considered in future therapeutic trials of infants with brain injury.

The impact of a sepsis quality improvement project on neurodisability rates in very low birthweight infants

Objective Very low birthweight (VLBW; <1500 g) infants with late-onset sepsis (LOS) have an increased risk of neurodisability. Care bundles to reduce bloodstream infections in neonatal intensive care unit (NICU) are effective in reducing LOS. Our aim was to determine if a sepsis reduction bundle introduced through a quality improvement project would impact neurodevelopmental outcomes in VLBW infants. Design Cohort study. Setting Level 3 regional NICU in the South West of England. Patients VLBW infants born between 2002 and 2011. Interventions A sepsis reduction care bundle implemented between July 2006 and December 2007. Main outcome measures The primary outcome was risk of coagulase-negative Staphylococcus (CONS) infection diagnosed >3 days of age. Secondary outcomes were death and moderate cognitive impairment. A logistic regression model was derived using the birth era as the independent variable with adjustment for typical confounders. Results In total, 379 infants were born in the preintervention cohort and 378 in the postintervention cohort. The CONS infection rate was reduced after the intervention (26.7% vs 14.1% p<0.001). Death prior to discharge reduced without reaching statistical significance (14.1% vs10.9%, p=0.195). The rate of cognitive disability reduced in the postintervention cohort (18.8% vs 6.1%, p=0.042). The adjusted ORs (95% CI) for CONS infection, death and cognitive impairment were 0.46 (0.29 to 0.72), 0.73 (0.43 to 1.24) and 0.3 (0.07 to 1.33), respectively. Conclusions There appears to be an association between reduced cognitive disability and the implementation of a sepsis reduction bundle. Further study in larger series is required to confirm these findings.

Reduced infancy and childhood epilepsy following hypothermia-treated neonatal encephalopathy

To investigate what proportion of a regional cohort of cooled infants with neonatal encephalopathy develop epilepsy (determined by the International League Against Epilepsy [ILAE] definition and the number of antiepileptic drugs [AEDs]) up to 8 years of age.