Neonatal Hyperthermia Research Articles

Increased thrombospondin-1 levels contribute to epileptic susceptibility in neonatal hyperthermia without seizures via altered synaptogenesis

Childhood febrile seizures (FS) represent one of the most common types of seizures and may lead to severe neurological damage and an increased risk of epilepsy. However, most children with fevers do not show clinical manifestations of convulsions, and the consequences of hyperthermia without seizures remain elusive. This study focused on hyperthermia not reaching the individual’s seizure threshold (sub-FS stimulus). Changes in thrombospondin-1 (TSP-1) levels, synapses, seizure susceptibility, and seizure severity in subsequent FS were investigated in rats exposed to sub-FS stimuli. Pharmacological and genetic interventions were used to explore the role of TSP-1 in sub-FS-induced effects. We found that after sub-FS stimuli, the levels of TSP-1 and synapses, especially excitatory synapses, were concomitantly increased, with increased epilepsy and FS susceptibility. Moreover, more severe neuronal damage was found in subsequent FS. These changes were temperature dependent. Reducing TSP-1 levels by genetic intervention or inhibiting the activation of transforming growth factor-β1 (TGF-β1) by Leu-Ser-Lys-Leu (LSKL) led to lower synapse/excitatory synapse levels, decreased epileptic susceptibility, and attenuated neuronal injury after FS stimuli. Our study confirmed that even without seizures, hyperthermia may promote synaptogenesis, increase epileptic and FS susceptibility, and lead to more severe neuronal damage by subsequent FS. Inhibition of the TSP-1/TGF-β1 pathway may be a new therapeutic target to prevent detrimental sub-FS sequelae.

Identifying additional risk factors for early asymptomatic neonatal hypoglycemia in term and late preterm babies.

Neonatal hypoglycemia is a common metabolic disorder in newborns, which may present with non-specific symptoms or even be asymptomatic. Current guidelines recommend screening for hypoglycemia in at-risk babies (late preterm, small for gestational age, large for gestational age, and infants of diabetic mothers). Past studies have suggested other potential risk factors, such as maternal obesity, gestational hypertension, cesarean section, etc. In this study, we aim to identify additional prenatal and perinatal maternal/fetal characteristics associated with early asymptomatic hypoglycemia in term and late preterm babies. We performed a retrospective review on medical charts of all newborns, born between January, 2017 and December, 2020, in the well-baby newborn nursery of a tertiary medical center. We identified newborns who had received blood glucose concentration monitor after birth. Detailed prenatal and perinatal maternal/newborn information were collected for analysis. In the study period, 841 newborns had received blood glucose screening after birth. After matching by sex and indication for postnatal blood glucose screen (SGA, LGA, and GDM), 148 newborns were included in the "hypoglycemia group" and 296 newborns were included in the "euglycemia group". In the univariate analysis, parity, insulin treatment for gestational diabetes mellitus (GDM), and cesarean section were associated with an increased risk for neonatal hypoglycemia. Factors associated with decreased risk included higher gestational age, longer duration of skin-to-skin contact, neonatal hyperthermia, higher maternal labor pain score, and epidural anesthesia administration. By multivariable analysis, insulin treatment for GDM was identified as an independent factor associated with increased risk for neonatal hypoglycemia. Our study showed insulin treatment for GDM to be independently associated with neonatal hypoglycemia. Other risk factors noted in the univariate analysis, such as decreased skin-to-skin contact duration, hypothermia, Cesarean section, and preterm delivery, would require further investigation to confirm the findings.

Updated management protocols of common situations in neonatal intensive care units

Objective To review the updated management protocols of common situations in the neonatal intensive care unit (NICU). Data sources A systematic search of MEDLINE (PubMed, Medscape, ScienceDirect, EMF-Portal) and Internet was conducted on all articles published from 2000 to 2018. Study selection English-language reports of the updated management protocols of common situations in the NICU. The initial search presented 160 articles where 23 had inclusion criteria. Data extraction Articles not reporting on updated management protocols of common situations in the NICU in the title or abstract were not included. Fifteen independent investigators extracted data on the methods. Data synthesis Comparisons were made by a structured review with the results tabulated. Seven authors emphasized on the new approaches for managing neonatal hypoglycemia, 16 about the management of neonatal hyperthermia, seizures, and transport. Findings Dextrose gel is safe and has the potential to decrease health-care costs and other risks related to the treatment of hypoglycemia. Antiepileptic drugs are then administered according to clinical preference, independent of the seizure cause. It should only be initiated once seizure activity is confirmed, due to a lack of evidence for any positive outcomes if they are administered in the absence of seizures. As a mobile ICU, transport vehicles, equipment, and supplies must reflect the needs of the patient population. Conclusion Further phrasing of guidelines to cover all aspects of neonatal care in the NICU, following the application of the set protocols in the practical field. Detecting improvement or deterioration of the outcome after applying these protocols to have an 'evidence-based' judgment over these selected guidelines.

Predictive power of a single body temperature at different cutoff values for neonates in the nursery transferring to special care nursery.

The aim of this study was to identify the clinical parameters indicative of serious etiology of neonatal hyperthermia and to determine the appropriate cutoff value of body temperature (BT) for predicting the need to transfer the newborn to the special care (SC) nursery.The nursery records of newborns diagnosed with hyperthermia between 2007 and 2013 were retrospectively reviewed. The clinical characteristics of newborns with hyperthermia remained in the nursery were compared with those transferred to the SC nursery. In addition, the receiver operating characteristic analysis was used to determine the appropriate cutoff BT for predicting further septic workup in the SC nursery.Among the 92 newborns with hyperthermia evaluated, 30 (32.6%) were transferred to the SC nursery and 62 (67.4%) remained in the nursery. Clinical characteristics associated with transfer to the SC nursery included the highest BT, BT at first measurement during hyperthermia, frequency of hyperthermia, duration of hyperthermia, irritable crying, decreased appetite, poor activity, vomiting with abdominal distension, tachypnea, and tachycardia (all P < .05). BT for predicting the need for transferring newborns with hyperthermia to the SC nursery had an area under the curve of 0.976 (P < .001). A BT of 38 °C was determined as the optimal cutoff value for predicting the need to monitoring for suspicious clinical symptoms (sensitivity (Sn), 93%; specificity (Sp), 87%). Furthermore, BT≥38.2 °C (Sn, 70%; Sp 100%) and BT≤37.8 °C (Sn, 100%; Sp, 61%) respectively were determined as the cutoff values for transferring newborns to the SC nursery or allowing them to remain in the regular nursery.Our results suggest a BT of 38 °C represents the optimal cutoff indicating newborns for close monitoring for suspicious clinical presentations including irritable crying, decreased appetite, poor activity, vomiting with abdominal distension, tachypnea, and tachycardia. Newborns with BT < 37.8 °C may remain in the nursery but should be transferred to the SC nursery for septic workup and empiric antibiotics if the BT is above 38.2 °C.

The impact of a quality improvement effort in reducing admission hypothermia in preterm infants following delivery.

Purpose Hypothermia at admission is associated with increased mortality and morbidity in preterm infants. We performed a quality improvement (QI) effort to determine the impact of a decrease in admission hypothermia in preterm infants.Methods The study enrolled very low birth weight (VLBW) infants born at Gangnam Severance Hospital between January 2013 and December 2016. This multidisciplinary QI effort included the use of occlusive wraps, warm blankets, and caps; the delivery room temperature was maintained above 23.0˚C, and a check-list was used for feedback.Results Among 259 preterm infants, the incidence of hypothermia (defined as body temperature <36.0˚C) decreased significantly from 68% to 41%, and the mean body temperature on neonatal intensive care unit admission increased significantly from 35.5˚C to 36.0˚C. In subgroup analysis of VLBW infants, admission hypothermia and neonatal outcomes were compared between the pre-QI (n=55) and post-QI groups (n=75). Body temperature on admission increased significantly from 35.4˚C to 35.9˚C and the number of infants with hypothermia decreased significantly from 71% to 45%. There were no cases of neonatal hyperthermia. The incidence of pulmonary hemorrhage was significantly decreased (P=0.017). Interaction analysis showed that birth weight and gestational age were not correlated with hypothermia following implementation of the protocol.Conclusion Our study demonstrated a significant reduction in admission hypothermia following the introduction of a standardized protocol in our QI effort. This resulted in an effective reduction in the incidence of massive pulmonary hemorrhage.

Remote effects of short-term neonatal hyperthermia in Krushinsky-Molodkina rats prone to audiogenic seizures strain.

Using the audiogenic seizure prone Krushinsky-Molodkina rat strain, it was demonstrated that short-term (5 min) exposure of 14-day-old pups to an elevated temperature (42°C) resulted in a significant decrease in audiogenic seizure severity at the age of 1 month. Presumably, this effect is determined by the activation of the heat-shock protein system (stress proteins).

Neonatal hyperthermia and thermal stress in low- and middle-income countries: a hidden cause of death in extremely low-birthweight neonates

Background:Over 70% of neonatal deaths in Nigeria occur within the first 7 days of life and, despite the millennium development goals, there has been no significant reduction of this figure.Objective:To investigate how rapid changes of temperature outside the physiologically allowable range in extremely low-birthweight infants are associated with increased mortality.Methods:Ninety-eight neonatal cases in three Nigerian tertiary-care hospitals were retrospectively recruited; on the basis of birthweight < 1500 g, this number was reduced to 41 for a two-stage analysis. In the first stage, 34 cases recruited over 24 months were analysed. In the second stage, seven cases recruited over 6 months were analysed; these were neonates managed with a new temperature control technique (the ‘handy approach’) to enable comparison of outcomes. The mean (SD) birthweight of the infants analysed was 991 g (251), and 28 of them were of extremely low-birthweight (ELBW) [mean (SD) 846 g (128)]. A lifetime temperature plot with a clearly visible reference zone was developed, from which all thermal stresses and their duration associated with mortality were identified and defined on the basis of their characteristics. Methods of quantifying the magnitude and duration of these thermal stresses were devised to enable definition of critical values. This was then applied to calculate a measure of the various thermal stresses which may have contributed to neonatal death.Results:Hypothermic events were very common in all the infants in the study period, but were not significantly associated with mortality. However, hyperthermic events occurred in 35% of the infants and were more likely to be associated with mortality. Most neonates with prolonged hypothermia culminating in rapid hyperthermia survived. However, all ELBW neonates who experienced prolonged hyperthermia culminating in rapid hypothermia died within 8 hours of the event. There was greater ELBW survival (6/6) in the second stage using the ‘handy approach’ than in the first stage (2/22).Conclusion:Hyperthermia is a high-risk event in ELBW infants and methods of cooling a high and prolonged temperature must be reviewed.

Fetal and neonatal hyperthermia

Abstract This article explores the concerns related to adverse neurological outcomes associated with fetal and neonatal hyperthermia. Maternal temperature is the most important determinant of fetal temperature; here we draw attention to the changing epidemiology of intrapartum maternal pyrexia and consequent fetal hyperthermia, particularly its association with labour epidural analgesia. The implications of potential adverse neonatal outcomes demand a greater understanding of the pathophysiology of intrapartum maternal fever and exploration of monitoring, preventative and therapeutic options encompassing the modern obstetric, anaesthetic and neonatal practice.

Neonatal asphyxia and hyperthermia and cognitive deficits in adult rats: Role of iron

We compared effects of a critical neonatal anoxia, applied in Wistar rats at body temperatures of 33, 37 and 39 °C, on memory performance in adulthood. Because hyperthermic–anoxic neonates suffer from hyperferremia an additional group of rats, exposed to anoxia at 39 °C, was injected with deferoxamine, a chelator of iron. At the age of 4 and 12 months all rats were examined in hole board, typical maze and Morris maze. The memory was disturbed by neonatal anoxia at 39 °C. The disturbances were prevented by both the naturally reduced body temperature and by deferoxamine. In conclusion, neonatal hyperthermia induces iron-mediated, extremely delayed postanoxic cognitive disturbances in adulthood.

Hyperthermia From Malfunctioning Radiant Heaters

The use of infant radiant warmers poses a hazard of neonatal hyperthermia. Serious overheating can result from mechanical failure of the controls, from dislodgment of the sensor probe, or from manual operation without careful monitoring. Deaths have been associated with hyperthermia induced by radiant warmers (reports will be published). Therefore, when a warmer is purchased, adequacy of the safety mechanisms to prevent overheating should be given prime consideration. Radiant warmers should be used with caution and awareness of this lethal potential.