Therapeutic Hypothermia In Infants Research Articles

Racial and Ethnic Inequities in Therapeutic Hypothermia and Neonatal Hypoxic–Ischemic Encephalopathy: A Retrospective Cohort Study

ObjectiveTo investigate racial inequities in the use of therapeutic hypothermia (TH) and outcomes in infants with hypoxic ischemic encephalopathy (HIE). Study designWe queried an administrative birth cohort of mother-baby pairs in California from 2010 through 2019 using ICD codes to evaluate the association between race and ethnicity and the application of TH in infants with HIE. We identified 4,779 infants with HIE. Log-linear regression was used to calculate risk ratios (RR) for TH, adjusting for hospital transfer, rural location, gestational age between 35 and 37 weeks, and HIE severity. Risk of adverse infant outcome was calculated by race and ethnicity and stratified by TH. ResultsFrom our identified cohort, 1338 (28.0%) neonates underwent TH. White infants were used as the reference sample and 410 (28.4%) received TH. Black infants were significantly less likely to receive TH with 74 (20.0%) with an adjusted risk ratio (aRR) of 0.7 (95% confidence interval 0.5 to 0.9). Black infants with any HIE who did not receive TH were more likely to have a hospital readmission (aRR 1.36, 95% CI 1.10 to 1.68) and a tracheostomy (aRR 3.07, 95% CI 1.19 to 7.97). Black infants with moderate/severe HIE who did not receive TH were more likely to have cerebral palsy (aRR 2.72, 95% CI 1.07 to 6.91). ConclusionsIn this study cohort, Black infants with HIE were significantly less likely to receive TH. Black infants also had significantly increased risk of some adverse outcomes of HIE. Possible reasons for this inequity include systemic barriers to care and systemic bias.

Clinical and Neuroimaging Profile of Neonates With Moderate-to-Severe Encephalopathy Treated With Therapeutic Hypothermia

Objective: To demonstrate the clinical and neuroimaging profile of infants with moderate-to-severe encephalopathy after therapeutic hypothermia (TH) in the Indian setting. The secondary objective was to determine the logistics involved in performing neuroimaging in these infants. Design and Setting: A retrospective descriptive study in 2 tertiary centers. Methods: All infants who underwent cooling in both centers from January 2019 to December 2019 were included. Demographic data, details of cooling, clinical and neuroimaging profile (magnetic resonance imaging [MRI] and magnetic resonance spectroscopy [MRS]), and details of the logistics involved in performing the imaging (sedation, neonatal transport, personnel, distance traveled, and time taken) were collected and analyzed. Results: A total of 44 infants were enrolled of which 37 (84.0%) underwent both TH and neuroimaging (MRI and MRS). A total of 33 (75.0%) of infants were outborn, 20 (45.5%) of them had sentinel events before delivery and 17 (38.6%) were intubated at birth. Apgar score <5 min was seen in 8 (18.2%) and seizures in 23 (52.3%) of infants. A total of 37 (84.1%) survived until discharge and underwent neuroimaging. Neuroimaging was performed between 5 and 14 days after birth. The most common abnormal finding on MRI brain was the signal changes in watershed areas of brain 8 (18.2%) and on MRS was low N-acetyl aspartate and high lactate 13 (29.5%). Midazolam (68.2%) and Triclofos (15.2%) were the sedatives used during neuroimaging these infants. Conclusion: TH for infants with neonatal encephalopathy resulted in excellent survival outcomes in tertiary private sector hospitals.

A Case of an Infant with Hydrops Fetalis and Hypoxic–Ischemic Encephalopathy Treated with Therapeutic Hypothermia

Hydrops fetalis (HF) is a serious fetal condition. Infants born with HF are often critically unwell, requiring resuscitation and prolonged intensive care admission. Despite medical advances, morbidity and mortality remain high. Therapeutic hypothermia is the standard of care for term and late preterm infants with moderate-to-severe hypoxic-ischemic encephalopathy (HIE), as it improves neurodevelopmental outcomes in surviving infants. To our knowledge, the use of therapeutic hypothermia has not previously been reported in infants with HF. We report the case of a term infant with undiagnosed HF, who required resuscitation and received 72 hours of therapeutic hypothermia for moderate HIE. We describe the cardiovascular instability encountered during therapeutic hypothermia and how it was successfully managed. She responded well to treatment and was discharged home bottle-feeding, with normal neurology and a normal brain magnetic resonance imaging scan. From this case, therapeutic hypothermia in infants with HF and HIE is feasible and can be beneficial in carefully selected HF infants meeting cooling criteria.

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.

Increased Use of Therapeutic Hypothermia in Infants with Milder Neonatal Encephalopathy due to Presumed Perinatal Asphyxia

Introduction: Adverse outcomes have been reported in infants with mild neonatal encephalopathy (NE). Increasing clinical experience with the application of therapeutic hypothermia (TH) may have resulted in the treatment of newborns with milder NE during recent years. Objective: To determine whether infants treated with TH in the initial years following implementation had a higher degree of NE than infants treated during subsequent years. Methods: Infants with NE treated with TH from February 2008 until July 2017 were included. Thompson and Sarnat scores, amplitude-integrated electroencephalography (aEEG) background patterns before the start of TH, and neurodevelopmental outcome at 2 years were compared between infants treated from February 2008 until October 2012 (period 1) and infants treated from November 2012 until July 2017 (period 2). Results: 211 newborns with NE were treated with TH (period 1: n = 109, period 2: n = 102). Sarnat scores in period 1 and 2 were mild in 7.3 vs. 28.4%, moderate in 66.1 vs. 44.1%, and severe in 26.6 vs. 22.5%, respectively (p = 0.008). Thompson scores were lower in period 2 (median = 9, IQR 7–12) than in period 1 (median = 10, IQR 8.5–13.5, p = 0.018). The aEEGs and neurodevelopmental outcomes were comparable between the periods. Conclusions: Based on Thompson and Sarnat scores, but not aEEG background patterns, infants treated during the second period had milder NE than infants treated during the first years following implementation of TH. There was no difference in 2 years neurodevelopmental outcome. Further research is necessary to evaluate the value of TH for infants with clinically mild NE.

Selective head cooling and acute kidney injury in neonates with hypoxic ischemic encephalopathy.

The reno-protective effect of therapeutic hypothermia in infants with hypoxic ischemic encephalopathy (HIE) is still debatable. We aimed to study the effect of therapeutic hypothermia on the development and progress of acute kidney injury (AKI) in neonates with HIE. Thirty full term infants with HIE were equally distributed between cooling group (selective head cooling) or non-cooling group (late presentation after 6 hours of birth). Serum creatinine, urine output (UOP), serum neutrophil gelatinase-associated lipocalin (NGAL), and serum cystatin C were measured at baseline, day 4 and day 10 of life. The incidence of AKI as per Acute Kidney Injury Network (AKIN) criteria was comparable in cooling and non-cooling groups (40% versus 53%, respectively). Serum creatinine and UOP were significantly improved on day-4 and day-10 samples compared to base-line samples in both groups regardless of cooling. Therapeutic hypothermia was associated with a significant reduction in serum NGAL, but not cystatin C, level in day-4 and day-10 samples compared to the non-cooling group. Serum NGAL and cystatin C did not show a significant decline in day-4 and day-10 samples compared to baseline samples in both the cooled and non-cooled groups indicating an ongoing AKI. Therapeutic hypothermia was associated with less renal impairment when compared to infants with HIE who were not cooled. Continuing kidney injury may persist in asphyxiated newborns despite improvement in serum creatinine and UOP. NCT02683915.

Impact of therapeutic hypothermia on infantile spasms: an observational cohort study.

AimTo establish the incidence of infantile spasms in children in the southern region of the Republic of Ireland and to compare the incidence of infantile spasms before and after the introduction of therapeutic hypothermia in infants with hypoxic‐ischemic encephalopathy (HIE).MethodChildren born between 2003 and 2015 and diagnosed with infantile spasms (epileptic spasms with or without hypsarrhythmia) in the first 2 years of life were identified through audits of electroencephalography reports and paediatric neurology patient lists. Data on live births were obtained from the regional hospital statistics databases. Medical charts of infantile spasm cases were reviewed for demographic information, diagnostic workup results, treatment response, disease course, and developmental outcome.ResultsForty‐two infants with infantile spasms were identified. The cumulative incidence of infantile spasms up to the age of 2 years was 4.01 per 10 000 live births. Difference due to sex was minimal (22 males, 20 females) and most infants were delivered at or near term with gestational ages ranging between 30.0 and 41.8 weeks (median [interquartile range] 39.6wks [38.1–40.0wks]). The aetiology for infantile spasms was identified in almost two‐thirds of cases, with HIE being the single most common cause (n=7). Other causes included chromosomal and monogenetic abnormalities (n=8). Infantile spasms occurred in moderate and severe grades of HIE, with a significantly higher incidence in those with severe HIE (p=0.029). Infants with severe HIE who did not receive therapeutic hypothermia were six times more likely to develop infantile spasms compared to those who did, but the difference was not statistically significant (4 out of 16 vs 1 out of 24, p=0.138).InterpretationThis study provides detailed information about infantile spasms before and after the introduction of therapeutic hypothermia. HIE severity is a risk factor for the development of infantile spasms. The introduction of therapeutic hypothermia may have had an impact, but the effect was hard to ascertain in this cohort due to the small number of infants.What this paper adds The incidence of infantile spasms and patient characteristics in the southern region of the Republic of Ireland is similar to internationally published data.None of the infants with a history of mild hypoxic‐ischemic encephalopathy (HIE) developed infantile spasms.The risk of infantile spasms was higher in infants with severe HIE.Infantile spasms were more frequent in infants with severe HIE not treated with therapeutic hypothermia.

Current Practice of Therapeutic Hypothermia for Mild Hypoxic Ischemic Encephalopathy.

Therapeutic hypothermia is the recommended treatment for neonates with moderate or severe hypoxic ischemic encephalopathy (HIE). There is an increasing trend to use therapeutic hypothermia even in infants with mild hypoxic ischemic encephalopathy, even though there is little evidence to support/refute this. To estimate the incidences of mild hypoxic ischemic encephalopathy among infants who received therapeutic hypothermia, and its short- and long-term outcomes. PubMed, Embase, CINAHL, and Cochrane library were searched to identify observational studies reporting on therapeutic hypothermia in term and near-term infants with mild hypoxic ischemic encephalopathy. The JBI (Joanna Briggs Institute) tools were used to assess the risk of bias in the included studies. Random effects meta-analysis was conducted to find out the percentage of cooled infants who had only mild hypoxic ischemic encephalopathy. A total of 3590 citations were screened, of which 13 were included. Of the 2783 infants who received therapeutic hypothermia, 573 had mild hypoxic ischemic encephalopathy. Meta-analysis found that 22% of the infants who underwent therapeutic hypothermia had only mild hypoxic ischemic encephalopathy (95% confidence interval: 16%-27%; I2 statistic = 90.5%). Five studies provided information on adverse effects of therapeutic hypothermia in mild hypoxic ischemic encephalopathy. The reported adverse effects were extreme hypothermia, bradycardia, hypoglycemia, sepsis, skin necrosis, pulmonary hypertension, and systemic hypotension. Limitation: The limitations included relatively small sample size and the lack of data for short- and long-term neurodevelopmental outcome. A significant proportion of infants who received therapeutic hypothermia had mild hypoxic ischemic encephalopathy. Randomized trials are urgently needed to evaluate the efficacy and safety of therapeutic hypothermia in infants with mild hypoxic ischemic encephalopathy.

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.

Can we further optimize therapeutic hypothermia for hypoxic-ischemic encephalopathy?

Perinatal hypoxic-ischemic encephalopathy is a leading cause of neonatal death and disability. Therapeutic hypothermia significantly reduces death and major disability associated with hypoxic-ischemic encephalopathy; however, many infants still experience lifelong disabilities to movement, sensation and cognition. Clinical guidelines, based on strong clinical and preclinical evidence, recommend therapeutic hypothermia should be started within 6 hours of birth and continued for a period of 72 hours, with a target brain temperature of 33.5 ± 0.5°C for infants with moderate to severe hypoxic-ischemic encephalopathy. The clinical guidelines also recommend that infants be rewarmed at a rate of 0.5°C per hour, but this is not based on strong evidence. There are no randomized controlled trials investigating the optimal rate of rewarming after therapeutic hypothermia for infants with hypoxic-ischemic encephalopathy. Preclinical studies of rewarming are conflicting and results were confounded by treatment with sub-optimal durations of hypothermia. In this review, we evaluate the evidence for the optimal start time, duration and depth of hypothermia, and whether the rate of rewarming after treatment affects brain injury and neurological outcomes.

2186 Feasibility of maternal holding during therapeutic hypothermia for infants with encephalopathy

OBJECTIVES/SPECIFIC AIMS: Therapeutic hypothermia (TH) is a neuroprotective therapy regularly used in newborn infants following traumatic births. The infant’s temperature is maintained at 33.5°C for 72 hours by a cooling blanket upon which the infant is placed. Parents are not permitted to hold their infant while TH is ongoing due to concerns for unintentional rewarming or accidental dislodging of catheters or other monitoring equipment. Our prior qualitative research with nurse and parent interviews described the inability to hold an infant during TH as a significant source of stress. We assessed the feasibility of a 30-minute period of maternal holding for infants being actively treated with TH and assessed both the maternal experience of holding and the nurse experience of supporting holding. METHODS/STUDY POPULATION: This was a feasibility study employing a mixed-methods approach. Inclusion criteria were gestational age at birth of 35 weeks or greater, absence of clinical or electrographic seizures during the first 24 hours of TH, and designation as “clinically stable” by the attending neonatologist with the infant on room air, nasal cannula, or continuous positive airway pressure. Quantitative data were obtained from vital sign monitoring every 2 minutes before, during and after holding and from maternal and nurse research surveys. Qualitative data were obtained from nurse surveys. Infant rewarming was prevented through use of a thin foam insulating barrier placed between mother and infant during holding. Adverse events were defined as a change in infant temperature greater than 0.5°C above or below 33.5°C, accidental dislodging of central lines/disruption of EEG leads or early termination of holding due vital sign instability present for greater than 2 recorded measurements including infant bradycardia defined as heart rate less than 80 beats per minute, hypotension defined as mean arterial pressure less than 40 mmHg or oxygen saturation of less than 93%. RESULTS/ANTICIPATED RESULTS: There were 10 newborn infants undergoing TH for neonatal encephalopathy (median gestational age 39.4 weeks) and their mothers (median age=31 years) were recruited. Infants remained on the hypothermia blanket during holding and were transferred safely to their mother’s arms without medical equipment malfunction/dislodgement. Holding occurred at a median of 47 hours of life. The mean temperature prior to holding was 33.4°C and at completion of holding the mean temperature was 33.5°C (p=0.18). There were no significant bradycardia, hypotension or oxygen desaturation events. In total, 80% of mothers reported difficulty bonding with their baby prior to holding and 90% reported a high level of stress before holding. After holding, all mothers felt their bond was “stronger” or “much stronger” and all felt “less stressed” or “much less stressed.” After holding, 75% of nurses reported that they felt a more positive emotional response to the infant. One nurse stated, “being a part of this emotional experience made me feel closer and more connected to this family and gave me a different perspective on just what they had been dealing with and feeling since giving birth to their child.” In free text responses, on 5 separate occasions, nurses commented on the relaxed, calmed or less irritable appearance of the infant while being held during TH. DISCUSSION/SIGNIFICANCE OF IMPACT: In this sample of term infants treated with TH, a 30-minute period of maternal holding was not associated with increased temperature or other adverse events. Holding during TH was associated with extremely positive feedback from mothers and nurses. Future larger studies could consider assessing the impact of holding on endocrinological markers of stress and bonding, on infant glycemic control, on breastfeeding success rates, and the impact of earlier and improved bonding on the developmental outcomes of children held during their treatment with TH. Increasing the duration of holding and allowing both parents to hold on more than one occasion during the 72 hours of TH may increase the proposed benefits of this intervention.

Population-Based Study of the National Implementation of Therapeutic Hypothermia in Infants with Hypoxic-Ischemic Encephalopathy.

Data on the incidence of hypoxic-ischemic encephalopathy (HIE) in the first 6 hours of life together with the implementation of therapeutic hypothermia (TH) are relevant to delineate actions to achieve the lowest rates of neonatal mortality, morbidity, and long-term impact on health associated with HIE. This is population-based national survey study, including newborns ≥35 weeks of gestation with moderate-to-severe HIE from all level III neonatal care units, to provide the incidence of HIE for the period 2012-2013, and the implementation of TH up to June 2015 in Spain. Incidence rate was 0.77 per 1000 live births (95% confidence interval 0.72-0.83). By June 2015, 63% (57/90) of the units had implemented TH; 95% of them performed servo-controlled whole-body TH. For the 2-year period, 86% of the newborns diagnosed with moderate-to-severe HIE received TH. Active TH increased in use from 78% in 2012 to 85% in 2013 (p = 0.01). The main reasons for not cooling were a delay in the diagnosis (31/682) and the fact that the treatment was not offered (20/682). Interhospital patient transfer was performed using passive hypothermia, by appropriately trained personnel in 61% of centers. Eighteen percent of newborns with moderate or severe HIE died, without significant differences between the 2 years. Up-to-date knowledge of the national coverage of neonatal care of infants with HIE in developed countries is a prerequisite to reducing the load of HIE in this area and to facilitating coordinated, eliminate investigation.

Safety and Short-Term Outcomes of Therapeutic Hypothermia in Preterm Neonates 34-35 Weeks Gestational Age with Hypoxic-Ischemic Encephalopathy

To evaluate the safety and short-term outcomes of preterm neonates born at 34-35 weeks gestation with hypoxic-ischemic encephalopathy (HIE) treated with therapeutic hypothermia. Medical records of preterm neonates born at 34-35 weeks gestational age with HIE treated with therapeutic hypothermia were retrospectively reviewed. Short-term safety outcomes and the presence, severity (mild, moderate, severe), and patterns of brain injury on magnetic resonance imaging were reviewed using a standard scoring system, and compared with a cohort of term neonates with HIE treated with therapeutic hypothermia. Thirty-one preterm and 32 term neonates were identified. Therapeutic hypothermia-associated complications were seen in 90% of preterm infants and 81.3% of term infants (P = .30). In the preterm infants, hyperglycemia (58.1% vs31.3%, P = .03) and rewarming before completion of therapeutic hypothermia (19.4% vs 0.0%, P = .009) were more likely compared with term infants. All deaths occurred in the preterm group (12.9% vs 0%, P = .04). Neuroimaging showed the presence of injury in 80.6% of preterm infants and 59.4% of term infants (P = .07), with no differences in injury severity. Injury to the white matter was more prevalent in preterm infants compared with term infants (66.7% vs 25.0%, P = .001). Therapeutic hypothermia in infants born at 34-35 weeks gestational age appears feasible. Risks of mortality and side effects warrant caution with use of therapeutic hypothermia in preterm infants.

MRI and spectroscopy in (near) term neonates with perinatal asphyxia and therapeutic hypothermia

BackgroundPrevious studies have demonstrated the association of abnormalities on diffusion-weighted MRI (DW-MRI) and proton magnetic resonance spectroscopy (1H-MRS) in infants with perinatal asphyxia. The use of therapeutic hypothermia might change...

Heart rate response to therapeutic hypothermia in infants with hypoxic–ischaemic encephalopathy

Aim of the studyNeonatal encephalopathy (NE) of hypoxic–ischaemic origin may cause death or life-long disability which is reduced by therapeutic hypothermia (TH). Our objective was to assess HR response in infants undergoing TH after perinatal asphyxia. MethodsWe performed a retrospective case series, from a single-centre tertiary care NICU. We included ninety-two infants with NE of likely hypoxic–ischaemic origin, moderate or severe, treated with TH (n=60) or normothermia (n=32) who had 18 month outcome data and at least 12 HR recordings the first 24h after birth (1998–2010) Bristol, UK. Poor outcome was defined as death or severe disability. Data are reported as medians and 95% confidence intervals (CI). ResultsTH to 33.5°C decreased HR by 30bpm to 92bpm (95% CI: 88, 96) 12h after birth in infants with NE and good outcome as compared to infants treated at normothermia 118bpm (95% CI: 110, 130). Despite constant low rectal temperature, HR increased gradually during cooling from 36 to 72h to 97bpm (89, 106) approaching the normothermia group, 117bpm (96, 133). During TH, infants with poor outcome had higher HR at 12h after birth (112bpm, 95% CI: 92, 115) as compared to infants with good outcome (p=0.004). Inotropic support increased HR by 17bpm in infants with good outcome and by 22bpm in infants with poor outcome. ConclusionsIn NE, TH decreases HR the first day of life. HR remained lower during TH, but increased during the last day of TH. Infants with poor outcome have higher HR.

Earlier Initiation of Therapeutic Hypothermia by Non-Tertiary Neonatal Units in Victoria, Australia

Background: Therapeutic hypothermia is an effective treatment for moderate or severe hypoxic-ischaemic encephalopathy (HIE), with maximal neuroprotective benefit when initiated soon after birth. Early initiation of therapeutic hypothermia in infants with HIE born in geographically distant settings is challenging. Objective: To audit temperature control in infants with HIE treated with hypothermia during neonatal transport in Victoria, Australia. Methods: A retrospective database review from September 1, 2008 to August 31, 2012 compared temperatures of transported outborn infants with HIE treated with hypothermia initiated by the referring non-tertiary neonatal unit, with hypothermia initiated by the transport team. Results: 123 infants received therapeutic hypothermia during the study period. Hypothermia treatment commenced significantly earlier [median (interquartile range [IQR]) 1.1 h (0.6-1.7) vs. 3.3 h (2.1-4.5); p < 0.01] with the target temperature (33-34°C) achieved sooner [median (IQR) 3.4 h (2.4-4.6) vs. 4.5 h (3.6-5.5)] when initiated by the referring hospital (n = 71) than by the transport team (n = 52). There was no statistically significant difference in achieving the target temperature before admission to the tertiary neonatal intensive care unit when hypothermia was initiated by the referring unit, compared with by the transport team [51/71 (71.8%) vs. 28/52 (53.9%), odds ratio (95% CI) 2.19 (0.96, 4.96)]. Infants in whom hypothermia was initiated by the referring hospital were more likely to have a recorded temperature below 33°C [22/71 (31.0%) vs. 4/52 (7.7%), odds ratio (95% CI) 5.39 (1.64, 22.83)]. Conclusions: The target temperature is achieved sooner in infants with moderate or severe HIE when therapeutic hypothermia is initiated by referring non-tertiary neonatal units under guidance from the regional transport service. This practice may enhance neuroprotection for infants with HIE born in non-tertiary units, particularly in remote locations.

Therapeutic Hypothermia in Perinatal Asphyxia

Therapeutic hypothermia for infants with perinatal asphyxia has been studied in several randomised controlled trials. There is convincing evidence that moderate therapeutic hypothermia (33-34°C for 72 h), when initiated within 6 h after birth among term & near-term infants (≥35 weeks) with moderate to severe HIE reduces the risk of death or major disability & increases the rate of disability-free survival at 6-7 years of age.

Hypoxic-Ischemic Encephalopathy and Serum Magnesium Monitoring and Maintenance.

Magnesium plays important roles in many physiologic functions including protein synthesis, bone development, and cell membrane function. There is some evidence to suggest a role for magnesium sulfate as a therapeutic neuroprotective agent along with therapeutic hypothermia in infants with hypoxic-ischemic encephalopathy, but studies are inconclusive. Ischemic insult and hypothermia may both play a role in altered magnesium levels in this population.

Allopurinol for preventing mortality and morbidity in newborn infants with hypoxic-ischaemic encephalopathy

Delayed neuronal death following a perinatal hypoxic insult is due partly to xanthine oxidase-mediated production of cytotoxic free radicals. Evidence exists that allopurinol, a xanthine-oxidase inhibitor, reduces delayed cell death in experimental models of perinatal asphyxia and in people with organ reperfusion injury. To determine the effect of allopurinol on mortality and morbidity in newborn infants with hypoxic-ischaemic encephalopathy. We used the standard search strategy of the Cochrane Neonatal Group. We searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, 2012, Issue 1), MEDLINE (1966 to March 2012), EMBASE (1980 to March 2012), CINAHL (1982 to March 2012), conference proceedings, and previous reviews. Randomised or quasi-randomised controlled trials that compared allopurinol administration versus placebo or no drug in newborn infants with hypoxic-ischaemic encephalopathy. We extracted data using the standard methods of the Cochrane Neonatal Review Group with separate evaluation of trial quality and data extraction by two review authors. We included three trials in which a total of 114 infants participated. In one trial, participants were exclusively infants with severe encephalopathy. The other trials also included infants with mild and moderately severe encephalopathy. These studies were generally of good methodological quality, but were too small to exclude clinically important effects of allopurinol on mortality and morbidity. Meta-analysis did not reveal a statistically significant difference in the risk of death (typical risk ratio 0.88; 95% confidence interval (95% CI) 0.56 to 1.38; risk difference -0.04; 95% CI -0.18 to 0.10) or a composite of death or severe neurodevelopmental disability (typical risk ratio 0.78; 95% CI 0.56 to 1.08; risk difference -0.14; 95% CI -0.31 to 0.04). The available data are not sufficient to determine whether allopurinol has clinically important benefits for newborn infants with hypoxic-ischaemic encephalopathy. Much larger trials are needed. Such trials could assess allopurinol as an adjunct to therapeutic hypothermia in infants with moderate and severe encephalopathy and should be designed to exclude important effects on mortality and adverse long-term neurodevelopmental outcomes.

Impact of Clinically Identifiable Intrapartum Sentinel Events on Short Term Outcome After Therapeutic Hypothermia in Infants with Hypoxic-Ischemic Encephalopathy

Objective: To determine the impact of intrapartum sentinel events on short term outcome following therapeutic hypothermia. Methods: Medical records of 77 infants ≥ 36 weeks' gestation, who received hypothermia were reviewed. Some of these infants were delivered after a clinically identifiable intrapartum sentinel event (IISE). All surviving infants had brain MRI at 7 to 10 days of life. The primary outcome of neonatal death related to hypoxic-ischemic encephalopathy (HIE) with worsening multiorgan dysfunction despite maximal treatment was compared between infants born after an IISE (n= 39) and infants who did not (non-IISE, n= 38). The pattern of MRI abnormalities consistent with hypoxic-ischemic brain injury was also compared. Logistic regression analysis was used to determine which of the variables predicts the primary outcome. Results: The two groups had similar Apgar scores, initial blood pH, and early neurologic examination. Base deficit was more severe in the IISE group. Neonatal death and global injury on brain MRI with basal nuclei, cortical, and subcortical white matter lesions extending beyond the watershed areas in infants surviving beyond the neonatal period were also more frequent in infants from this group (IISE 23% versus non-IISE 2.6%, p=0.014, OR 11.1, 95% CI 1.3-92.6 and IISE 33% versus non-IISE 11%, p=0.034, OR 4.1, 95% CI 1.1-14.9 respectively). Multivariate analysis identified IISE (p=0.023, OR 12.2, 95% CI 1.4-105.8) to be independently associated with neonatal death. Conclusions: An IISE is associated with an increase in neonatal death and more severe injury on brain MRI, even after hypothermia.