Therapeutic Hypothermia For Neonatal Encephalopathy Research Articles

Therapeutic hypothermia for neonatal encephalopathy in developing countries: Current evidence

Problem consideredBirth asphyxia and resultant brain injury are an important cause of neonatal mortality and morbidity in resource-limited countries. Prevention of birth asphyxia needs effective coverage of evidence-based interventions during antenatal care, childbirth, and high-risk pregnancies, close intrapartum monitoring, access to emergency obstetric care, and neonatal resuscitation. Therapeutic hypothermia is the only specific therapy proven to reduce the incidence of death and disability in neonates with hypoxic-ischemic encephalopathy (HIE). While therapeutic hypothermia is the standard of care in high-income contours, its benefit in low- and middle-income countries remains unproven. MethodsThis article analyzes the evidence from randomized controlled trials conducted in different settings. As systematic reviews of these trials have shown significant statistical heterogeneity in the efficacy of therapeutic hypothermia, this article examines the reasons behind heterogeneity in the outcome of death before discharge from the hospital. ResultsThe following factors were found to be associated with the loss of efficacy of therapeutic hypothermia – the absence of objective evidence of acute birth asphyxia, suboptimal care during transport of extramural neonates, uncontrolled hypothermia before admission to a neonatal unit, and the severity of HIE. ConclusionA sufficiently powered randomized controlled trial that takes into account these effect modifiers needs to be conducted in rescue-limited settings.

Abstract 11798: Comparison of Echocardiographic Measurements and Cardiac Biomarkers Between Neonates With Neonatal Encephalopathy Who Developed Brain Injury or Not During Therapeutic Hypothermia

Background: Despite therapeutic hypothermia (TH), many newborns with neonatal encephalopathy (NE) develop brain injury (BI). We hypothesis that newborns with NE have with brain injury have different echocardiographic (ECHO) parameters to those with no brain injury. Aims: To compare the ECHO parameters on day of life (DOL) 2 between neonates with NE undergoing TH developing or not brain injury. Methods: Prospective cohort study in a single tertiary unit enrolling neonate (born ≥36weeks and ≥1800 grams) undergoing TH for NE, between 2016 and 2020. All neonates presented on admission with moderate to severe NE by amplitude-integrated electroencephalogram (aEEG) profile and underwent a brain magnetic resonance (MRI) on DOL 2. ECHO was performed on the MRI day and data were extracted offline. Multiple logistic regression analyses were constructed to determine which parameters best predicted brain injury or not. Results: A total of 34 neonates were recruited, of which 19 (56%) had brain injury. Those with BI had a higher gestational age (GA) at birth (39.6±1.6 vs 38.2±1.5, p=0.01) and more severe pattern on aEEG (p=0.007) (Table 1). Mortality was also more frequent. Left and right ventricular performance were similar between groups by standard ECHO measures, strain and tissue Doppler imaging (Table 2). Although TAPSE was increased in those with brain injury (p=0.04), the Z-Score accounting for GA was similar. Initial aEEG pattern was the best predictor of brain injury, when accounting for GA and ECHO parameters/biomarkers. Conclusion: Initial aEEG pattern and not hemodynamic profile was most predictive of brain injury on MRI.

Differences between early and late MRI in infants with neonatal encephalopathy following therapeutic hypothermia.

MRI is the gold standard test to define brain injury in infants with neonatal encephalopathy(NE). As imaging findings evolve considerably over the first week, early imaging may not fully reflect the final nature of the injury. This study aimed to compare day 4 versus second week MRI in infants with NE. Retrospective cohort study including infants who received therapeutic hypothermia(TH) for NE and had two MRIs: early (≤7days) and late (>7days). MRIs were clinically reported and also reviewed by study investigators. 94infants with NE were included (40mild,49moderate,5severe). Twenty-four infants(26%) had a normal early scan of which 3/24(13%) had injury noted on repeat MRI. Seventy infants(74%) had abnormal findings noted on early MRI, of which 4/70(6%) had further evolution of injury while 11/70(16%) had complete resolution of findings. Applying a grading system resulted in a change of grade in 7 infants. In infants who received TH for NE, 19% had changes noted between their early and late MRIs. While the impact on predicting neurodevelopmental outcome was not studied, relying solely on early MRI may overestimate injury in a proportion of infants and miss injury in others. Combining early and late MRI allows for better characterization of injury. MRI is the gold standard tool to define brain injury in infants with NE, however, imaging findings evolve considerably over the first week of life. Most centers perform a single MRI on day 4 after rewarming. In our cohort, 19% of infants had a notable change in their MRI findings between early (within the first week) and late (beyond the first week) scans. Relying solely on early MRI may overestimate injury in a proportion of infants and miss injury in others. Combining early and late MRI following hypothermia allows for better characterization of brain injury.

Variations in care of neonates during therapeutic hypothermia: call for care practice bundle implementation.

Therapeutic hypothermia (TH) is the gold-standard treatment for moderate and severe neonatal encephalopathy (NE). Care during TH has implications for long-term outcomes. Outcome variability exists among neonatal intensive care units (NICUs) in Canada, but care variations are not understood well. This study examines variations in care practices for neonates with NE treated with TH in NICUs across Canada. A non-anonymous, web-based questionnaire was emailed to tertiary NICUs in Canada providing TH for NE to assess care practices during the first days of life and neurodevelopmental follow-up. Ninety-two percent (24/26) responded. Centres followed national guidelines regarding the use of the modified Sarnat score to assess the initial severity of NE, the need to initiate TH within the first 6 h of birth, and the importance of follow-up. However, other practices varied, including ventilation mode, definition/treatment of hypotension, routine echocardiography, use of sedation, use of electroencephalogram (EEG), MRI timing, placental analysis, and follow-up duration. NICUs across Canada follow available national guidelines, but variations exist in practices for managing NE during TH. Development and implementation of a consensus-based care bundle for neonates during TH may reduce practice variability and improve outcomes. This survey describes the current HIE care practices and variation among tertiary centres in Canada. Variations exist in the care of neonates with NE treated with TH in NICUs across Canada. This paper Identifies areas of variation that are not discussed in detail in the national guidelines and will help to set up quality improvement initiatives. Elucidating the variation in care practices calls for the creation and implementation of a national, consensus-based care bundle, with the objective to improve the outcomes of these critically ill neonates.

Factors associated with MRI success in children cooled for neonatal encephalopathy and controls

ObjectiveTo investigate if an association exists between motion artefacts on brain MRI and comprehension, co-ordination, or hyperactivity scores in children aged 6–8 years, cooled for neonatal encephalopathy (cases) and controls.MethodsCase children (n = 50) without cerebral palsy were matched with 43 controls for age, sex, and socioeconomic status. Children underwent T1-weighted (T1w), diffusion-weighted image (DWI) brain MRI and cognitive, behavioural, and motor skills assessment. Stepwise multivariable logistic regression assessed associations between unsuccessful MRI and comprehension (including Weschler Intelligence Scale for Children (WISC-IV) verbal comprehension, working memory, processing speed and full-scale IQ), co-ordination (including Movement Assessment Battery for Children (MABC-2) balance, manual dexterity, aiming and catching, and total scores) and hyperactivity (including Strengths and Difficulties Questionnaire (SDQ) hyperactivity and total difficulties scores).ResultsCases had lower odds of completing both T1w and DWIs (OR: 0.31, 95% CI 0.11–0.89). After adjusting for case-status and sex, lower MABC-2 balance score predicted unsuccessful T1w MRI (OR: 0.81, 95% CI 0.67–0.97, p = 0.022). Processing speed was negatively correlated with relative motion on DWI (r = −0.25, p = 0.026) and SDQ total difficulties score was lower for children with successful MRIs (p = 0.049).ConclusionsMotion artefacts on brain MRI in early school-age children are related to the developmental profile.ImpactChildren who had moderate/severe neonatal encephalopathy are less likely to have successful MRI scans than matched controls.Motion artefact on MRI is associated with lower MABC-2 balance scores in both children who received therapeutic hypothermia for neonatal encephalopathy and matched controls, after controlling for case-status and sex.Exclusion of children with motion artefacts on brain MRI can introduce sampling bias, which impacts the utility of neuroimaging to understand the brain–behaviour relationship in children with functional impairments.

Comparative evaluation of approach to cardiovascular care in neonatal encephalopathy undergoing therapeutic hypothermia.

To analyze the association between cardiovascular care and adverse outcome in infants undergoing therapeutic hypothermia for neonatal encephalopathy (NE). This was a retrospective cohort study of 176 infants with NE and hypotension, admitted to the SickKids Hospital (Center A, n = 86) or Semmelweis University (Center B, n = 90). The lowest systolic/diastolic blood pressures were comparable amongst centers; however, proportion of cardiovascular support was lower in Center A (51% vs 97% in Center B). Overall rate of death or abnormal MRI (adverse outcome) were comparable between centers, although pattern differed with more basal ganglia injury in Center B. A 24-hour longer duration of cardiovascular support increased the odds for adverse outcome by 14%. We demonstrated that management of hemodynamic instability in infants with NE was markedly different in two high-volume NICUs and showed that longer duration of cardiovascular medication is an independent risk factor for adverse outcome.

Magnetic resonance venography to evaluate cerebral sinovenous thrombosis in infants receiving therapeutic hypothermia.

The incidence of cerebral sinovenous thrombosis (CSVT) in infants receiving therapeutic hypothermia for neonatal encephalopathy remains controversial. The aim of this study was to identify if the routine use of magnetic resonance venography (MRV) in term-born infants receiving hypothermia is associated with diagnostic identification of CSVT. We performed a retrospective review of 291 infants who received therapeutic hypothermia from January 2014 to March 2020. Demographic and clinical data, as well as the incidence of CSVT, were compared between infants born before and after adding routine MRV to post-rewarming magnetic resonance imaging (MRI). Before routine inclusion of MRV, 209 babies were cooled, and 25 (12%) underwent MRV. Only one baby (0.5%) was diagnosed with CSVT in that period, and it was detected by structural MRI, then confirmed with MRV. After the inclusion of routine MRV, 82 infants were cooled. Of these, 74 (90%) had MRV and none were diagnosed with CSVT. CSVT is uncommon in our cohort of infants receiving therapeutic hypothermia for neonatal encephalopathy. Inclusion of routine MRV in the post-rewarming imaging protocol was not associated with increased detection of CSVT in this population. Cerebral sinovenous thrombosis (CSVT) in infants with NE receiving TH may not be as common as previously indicated. The addition of MRV to routine post-rewarming imaging protocol did not lead to increased detection of CSVT in infants with NE. Asymmetry on MRV of the transverse sinus is a common anatomic variant. MRI alone may be sufficient in indicating the presence of CSVT.

Serum Creatinine Patterns in Neonates Treated with Therapeutic Hypothermia for Neonatal Encephalopathy

Introduction: There is large variability in kidney function and injury in neonates with neonatal encephalopathy (NE) treated with therapeutic hypothermia (TH). Acute kidney injury (AKI) definitions that apply categorical approaches may lose valuable information about kidney function in individual patients. Centile serum creatinine (SCr) over postnatal age (PNA) may provide more valuable information in TH neonates. Methods: Data from seven TH neonates and one non-TH-treated, non-NE control cohorts were pooled in a retrospective study. SCr centiles over PNA, and AKI incidence (definition: SCr ↑≥0.3 mg/dL within 48 h, or ↑ ≥1.5 fold vs. the lowest prior SCr within 7 days) and mortality were calculated. Repeated measurement linear models were applied to SCr trends, modeling SCr on PNA, birth weight or gestational age (GA), using heterogeneous autoregressive residual covariance structure and maximum likelihood methods. Findings were compared to patterns in the control cohort. Results: Among 1,136 TH neonates, representing 4,724 SCr observations, SCr (10th–25th–50th–75th–90th–95th) PNA centiles (day 1–10) were generated. In TH neonates, the AKI incidence was 132/1,136 (11.6%), mortality 193/1,136 (17%). AKI neonates had a higher mortality (37.2–14.3%, p < 0.001). Median SCr patterns over PNA were significantly higher in nonsurvivors (p < 0.01) or AKI neonates (p < 0.001). In TH-treated neonates, PNA and GA or birth weight explained SCr variability. Patterns over PNA were significantly higher in TH neonates to controls (801 neonates, 2,779 SCr). Conclusions: SCr patterns in TH-treated NE neonates are specific. Knowing PNA-related patterns enable clinicians to better assess kidney function and tailor pharmacotherapy, fluids, or kidney supportive therapies.

Transcutaneous carbon dioxide monitoring during therapeutic hypothermia for neonatal encephalopathy.

In neonates with post-asphyxial neonatal encephalopathy, further neuronal damage is prevented with therapeutic hypothermia (TH). In addition, fluctuations in carbon dioxide levels have been associated with poor neurodevelopmental outcome, demanding close monitoring. This study investigated the accuracy and clinical value of transcutaneous carbon dioxide (tcPCO2) monitoring during TH. In this retrospective cohort study in neonates, agreement between arterial carbon dioxide (PaCO2) values and tcPCO2 measurements during TH was determined. TcPCO2 levels during the first 24 h of hypothermia were tested for an association with ischemic brain injury on magnetic resonance imaging (MRI). Thirty-four neonates were included. Agreement (bias (95% limits of agreement)) between tcPCO2 and PaCO2 levels was 3.9 (-12.4-20.2) mm Hg. No relation was found between the body temperature and tcPCO2 levels. TcPCO2 levels differed significantly between patients with considerable and minimal damage on MRI; after 6 h (P = 0.02) and 9 h (P = 0.04). Although tcPCO2 provided a limited estimation of PaCO2, it can be used for trend monitoring during TH. TcPCO2 levels after birth could provide an early indicator of ischemic brain injury. This relation should be investigated in large prospective studies, in which adjustments for confounders can be made. Transcutaneous carbon dioxide measurements during therapeutic hypothermia in neonates show limited accuracy similar to measurements reported in normothermic neonates and can be used for trend monitoring. Low transcutaneous carbon dioxide levels during the first 24 h were associated with considerable ischemic brain injury on MRI. The value of transcutaneous carbon dioxide measurements during the first 24 h as an indicator of considerable ischemic brain injury on MRI should be investigated in future studies, adjusting for confounders. Transcutaneous oxygen measurements during therapeutic hypothermia showed an inaccuracy that could not be related to a low body temperature.

Therapeutic Hypothermia for Neonatal Encephalopathy in Low- and Middle-Income Countries: A Meta-Analysis

Background: Perinatal asphyxia and hypoxic-ischemic encephalopathy (HIE) represent substantial sources of neonatal morbidity and mortality in low- and middle-income countries (LMICs), leading to high rates of adverse long-term neurological outcomes. Methods: A systematic review with meta-analysis of randomized controlled trials in LMICs was conducted. PubMed, Scopus, Web of Science, CENTRAL, ClinicalTrials.gov, and Google Scholar were searched from inception to August 20, 2021. The population of the study consisted of neonates with gestational age ≥34 weeks and HIE. The main endpoints were overall mortality and the composite outcome of death or severe disability. The certainty of evidence was evaluated with the GRADE approach. Results: Ten studies were included comprising 1,293 neonates. Some concerns of bias were raised due to the nonblinded nature of the intervention. The risk of death was similar between the two groups (risk ratio [RR]: 0.78, 95% confidence interval [CI]: 0.52–1.18). No significant differences were observed in the composite outcome of death or severe disability between the two groups (RR: 0.78, 95% CI: 0.56–1.10, very low quality of evidence). Furthermore, no significant differences were observed in the endpoints of sepsis, shock, acute kidney injury, major arrhythmia, and length of hospital stay. Therapeutic hypothermia was associated with significantly higher risk of thrombocytopenia (RR: 2.13, 95% CI: 1.34–3.38) and clinically significant hemorrhage (RR: 1.57, 95% CI: 1.25–1.97). Conclusion: Therapeutic hypothermia probably results in little to no difference in clinical outcomes among neonates with HIE in LMICs. Further large-scale research targeting proper patient selection is needed to elucidate the utility of therapeutic hypothermia in resource-limited settings. Protocol Registration: The protocol of the study has been prospectively registered by Prospero, CRD42021272284.

Therapeutic Hypothermia for Neonatal Encephalopathy in Low- and Middle-Income Countries: A Literature Review.

This structured review aimed to discuss the existing literature on therapeutic hypothermia for moderate to severe neonatal encephalopathy exclusively in low- and middle-income countries (LMICs). Medline, Embase, CINHAL and Cochrane Registry were searched for original papers with therapeutic hypothermia (TH) for treating neonatal encephalopathy in LMIC with no language restrictions. The search identified 1413 papers from 1990 to 31 August 2021. Twenty-one original papers were included after duplicates removal and full-text screening in the final review. Fourteen randomized control studies and seven non-randomized studies were discussed with various modes of cooling (servo-controlled, phase changing material, traditional methods), complications during cooling, mortality and long-term neurodevelopmental assessment. Although there is sufficient evidence in LMIC favouring cooling for the reduction in mortality and improving the neurodevelopmental outcomes, nonetheless these studies were widely heterogeneous in terms of method of cooling, tools for assessing developmental outcomes, age at assessment and variations in neuroimaging tools and reporting. Therapeutic hypothermia is beneficial in LMICs with low certainty of evidence in reducing mortality and improving neurodevelopmental outcomes.

EBNEO commentary: Should we abandon therapeutic hypothermia for neonatal encephalopathy in low- and middle-income countries?

Therapeutic hypothermia (TH) is the standard of care in neonates with moderate and severe hypoxic ischemic encephalopathy (HIE) as it lowers the rates of mortality, cerebral palsy, hearing and visual impairment, and neurodevelopmental delay1, 2 . The majority of evidence towards the effectiveness and safety of TH has been pooled out from data of well-designed randomized controlled trials which were conducted in high-income countries3-7 .

Therapeutic hypothermia for neonatal encephalopathy: importance of early management

It is now over 25 years since publication of the first experimental study demonstrating that mild hypothermia after transient hypoxia-ischaemia ameliorates delayed energy failure in a newborn piglet model.1 Since...

Value of cranial ultrasound at initiation of therapeutic hypothermia for neonatal encephalopathy.

There is variation in the clinical practice for the use of cranial ultrasound (cUS) at the time of initiation of therapeutic hypothermia (TH) for neonatal encephalopathy. The role of cUS in selecting patients who may benefit from TH or excluding those where TH may impose risk is unknown. A retrospective study was conducted on infants who received TH at a single tertiary center. Findings from cUS at initiation of TH were compared to findings from MRI following the completion of TH. One hundred and eight infants were studied. Of the 55 with abnormalities on early cUS, 50 did not have corresponding MRI abnormalities. In contrast, 16 infants had some degree of intracranial hemorrhage detected on their MRI that was not noted on earlier cUS. This study challenges whether cUS is an essential universal screening tool prior to the commencement of TH.

Early Magnetic Resonance Imaging Predicts 30-Month Outcomes after Therapeutic Hypothermia for Neonatal Encephalopathy

To evaluate the association of therapeutic hypothermia with magnetic resonance imaging (MRI) findings and 30-month neurodevelopment in term neonatal encephalopathy. Cross-sectional analysis of 30-month neurodevelopment (IQR 19.0-31.4) in a prospective cohort of mild-to-severe neonatal encephalopathy imaged on day 4 (1993-2017 with institutional implementation of therapeutic hypothermia in 2007). MRI injury was classified as normal, watershed, or basal ganglia/thalamus. Abnormal motor outcome was defined as Bayley-II psychomotor developmental index <70, Bayley-III motor score <85 or functional motor deficit. Abnormal cognitive outcome was defined as Bayley-II mental developmental index <70 or Bayley-III cognitive score <85. Abnormal composite outcome was defined as abnormal motor and/or cognitive outcome, or death. The association of therapeutic hypothermia with MRI and outcomes was evaluated with multivariable logistic regression adjusted for propensity to receive therapeutic hypothermia. Follow-up was available in 317 (78%) surviving children, of whom 155 (49%) received therapeutic hypothermia. Adjusting for propensity, therapeutic hypothermia was independently associated with decreased odds of abnormal motor (OR 0.15, 95% CI 0.06-0.40, P<.001) and cognitive (OR 0.11, 95% CI 0.04-0.33, P<.001) outcomes. This association remained statistically significant after adjustment for injury pattern. The predictive accuracy of MRI pattern for abnormal composite outcome was unchanged between therapeutic hypothermia-treated (area under the receiver operating curve 0.76; 95% CI 0.61-0.91) and untreated (area under the receiver operating curve 0.74; 95% CI 0.67-0.81) infants. The negative predictive value of normal MRI was high in therapeutic hypothermia-treated and untreated infants (motor 96% vs 90%; cognitive 99% vs 95%). Therapeutic hypothermia is associated with lower rates of brain injury and adverse 30-month outcomes after neonatal encephalopathy. The predictive accuracy of MRI in the first week of life is unchanged by therapeutic hypothermia. Normal MRI remains reassuring for normal 30-month outcome after therapeutic hypothermia.

Association between cerebral oxygen saturation and brain injury in neonates receiving therapeutic hypothermia for neonatal encephalopathy.

To assess the association of cerebral oxygen saturation (CrSO2) collected by near infrared spectroscopy (NIRS) during therapeutic hypothermia (TH) and rewarming with evidence of brain injury on post-rewarming MRI. This retrospective cohort study included 49 infants, who received TH for mild to severe neonatal encephalopathy. Of those, 26 presented with brain injury assessed by a novel MRI grading system, whereas 23 had normal MRI scans. CrSO2 increased significantly from the first to the second day of TH in infants with brain injury, whereas it remained stable in patients with normal MRI.Increasing mean CrSO2 values during rewarming was associated with brain injury (aOR 1.14; 95% CI 1.00-1.28), specifically with gray matter (GM) injury (aOR 1.23; 95% CI 1.02-1.49). The area under the ROC curve showed an excellent discrimination for GM involvement. Clinically applied NIRS during TH and rewarming can assist in identifying the risk for brain injury.

Disrupted brain connectivity in children treated with therapeutic hypothermia for neonatal encephalopathy

Therapeutic hypothermia following neonatal encephalopathy due to birth asphyxia reduces death and cerebral palsy. However, school-age children without cerebral palsy treated with therapeutic hypothermia for neonatal encephalopathy still have reduced performance on cognitive and motor tests, attention difficulties, slower reaction times and reduced visuo-spatial processing abilities compared to typically developing controls. We acquired diffusion-weighted imaging data from school-age children without cerebral palsy treated with therapeutic hypothermia for neonatal encephalopathy at birth, and a matched control group. Voxelwise analysis (33 cases, 36 controls) confirmed reduced fractional anisotropy in widespread areas of white matter in cases, particularly in the fornix, corpus callosum, anterior and posterior limbs of the internal capsule bilaterally and cingulum bilaterally. In structural brain networks constructed using probabilistic tractography (22 cases, 32 controls), graph-theoretic measures of strength, local and global efficiency, clustering coefficient and characteristic path length were found to correlate with IQ in cases but not controls. Network-based statistic analysis implicated brain regions involved in visuo-spatial processing and attention, aligning with previous behavioural findings. These included the precuneus, thalamus, left superior parietal gyrus and left inferior temporal gyrus. Our findings demonstrate that, despite the manifest successes of therapeutic hypothermia, brain development is impaired in these children.

High-Dose Melatonin and Ethanol Excipient Combined with Therapeutic Hypothermia in a Newborn Piglet Asphyxia Model

With the current practice of therapeutic hypothermia for neonatal encephalopathy, disability rates and the severity spectrum of cerebral palsy are reduced. Nevertheless, safe and effective adjunct therapies are needed to optimize outcomes. This study’s objective was to assess if 18 mg/kg melatonin given rapidly over 2 h at 1 h after hypoxia-ischemia with cooling from 1–13 h was safe, achieved therapeutic levels within 3 h and augmented hypothermic neuroprotection. Following hypoxia-ischemia, 20 newborn piglets were randomized to: (i) Cooling 1–13 h (HT; n = 6); (ii) HT+ 2.5% ethanol vehicle (HT+V; n = 7); (iii) HT + Melatonin (HT+M; n = 7). Intensive care was maintained for 48 h; aEEG was acquired throughout, brain MRS acquired at 24 and 48 h and cell death (TUNEL) evaluated at 48 h. There were no differences for insult severity. Core temperature was higher in HT group for first hour after HI. Comparing HT+M to HT, aEEG scores recovered more quickly by 19 h (p < 0.05); comparing HT+V to HT, aEEG recovered from 31 h (p < 0.05). Brain phosphocreatine/inorganic phosphate and NTP/exchangeable phosphate were higher at 48 h in HT+M versus HT (p = 0.036, p = 0.049 respectively). Including both 24 h and 48 h measurements, the rise in Lactate/N-acetyl aspartate was reduced in white (p = 0.030) and grey matter (p = 0.038) after HI. Reduced overall TUNEL positive cells were observed in HT+M (47.1 cells/mm2) compared to HT (123.8 cells/mm2) (p = 0.0003) and HT+V (97.5 cells/mm2) compared to HT (p = 0.012). Localized protection was seen in white matter for HT+M versus HT (p = 0.036) and internal capsule for HT+M compared to HT (p = 0.001) and HT+V versus HT (p = 0.006). Therapeutic melatonin levels (15–30mg/l) were achieved at 2 h and were neuroprotective following HI, but ethanol vehicle was partially protective.

Attention and visuo-spatial function in children without cerebral palsy who were cooled for neonatal encephalopathy: a case-control study

ABSTRACTObjectives: Dorsal-stream functions are vulnerable to early brain injury associated with neonatal encephalopathy (NE) following perinatal asphyxia, even in children not developing cerebral palsy (CP). Since therapeutic hypothermia (TH) became the standard treatment for NE, the incidence of CP is reduced but the impact on dorsal-stream functions is unknown. We aimed to compare dorsal-stream functions in TH-treated survivors of NE, without CP, with those of matched controls.Methods: We administered tests of dorsal-stream function to 29 case children aged 6-to-8 years treated with TH for NE and without CP, and 20 age, sex and social class matched controls. We used the Conner’s Continuous Performance Test (CPT) 2nd Edition to assess attentiveness, based upon Hit Reaction Time (HRT) percentile score and HRT standard error percentile, the CPT HRT block change measure to assess sustained attention and the NEPSY-II block construction and arrows tests to assess visuo-spatial performance and mental rotation.Results: Case children performed significantly worse than controls on measures of attention and visuo-spatial function.Conclusions: Children given TH treatment for NE can have subtle attention difficulties with slower reaction times and reduced visuo-spatial processing. These findings illustrate the continued vulnerability of dorsal-stream functions following NE despite the use of TH.

Maternal holding during therapeutic hypothermia for infants with neonatal encephalopathy is feasible.

Concerns for infant destabilisation often prohibit parental holding of infants during therapeutic hypothermia (TH). We assessed the feasibility of maternal holding during TH, as the inability to hold can impede bonding. Vital signs were assessed in stable infants before, at two-minute intervals during and 30minutes after a single 30-minute holding session. The infant remained on the blanket throughout holding, and both infant and blanket were placed into the mother's arms on top of a thin foam insulating barrier. Mothers and nurses were surveyed about their experience. Ten infants undergoing TH for neonatal encephalopathy had no equipment malfunctions or dislodgement. The mean temperature was 33.4°C prior to and 33.5°C (p=0.18) after holding. There was no significant bradycardia (heart rate <80 beats per minute), hypotension (mean arterial pressure <40mm Hg) or oxygen desaturation (<93%). Nurses either strongly agreed (75%) or agreed (25%) with the statement 'After assisting with the holding protocol, I feel that holding during cooling is safe'. Mothers (100%) strongly agreed that other parents would benefit from holding. In a small sample of ten stable infants treated with TH for neonatal encephalopathy, holding resulted in no adverse events and positive feedback from mothers and nurses.