Alan R. Horn

Should Neonates Sleep Alone

BACKGROUND Maternal-neonate separation (MNS) in mammals is a model for studying the effects of stress on the development and function of physiological systems. In contrast, for humans, MNS is a Western norm and standard medical practice. However, the physiological impact of this is unknown. The physiological stress-response is orchestrated by the autonomic nervous system and heart rate variability (HRV) is a means of quantifying autonomic nervous system activity. Heart rate variability is influenced by level of arousal, which can be accurately quantified during sleep. Sleep is also essential for optimal early brain development. METHODS To investigate the impact of MNS in humans, we measured HRV in 16 2-day-old full-term neonates sleeping in skin-to-skin contact with their mothers and sleeping alone, for 1 hour in each place, before discharge from hospital. Infant behavior was observed continuously and manually recorded according to a validated scale. Cardiac interbeat intervals and continuous electrocardiogram were recorded using two independent devices. Heart rate variability (taken only from sleep states to control for level of arousal) was analyzed in the frequency domain using a wavelet method. RESULTS Results show a 176% increase in autonomic activity and an 86% decrease in quiet sleep duration during MNS compared with skin-to-skin contact. CONCLUSIONS Maternal-neonate separation is associated with a dramatic increase in HRV power, possibly indicative of central anxious autonomic arousal. Maternal-neonate separation also had a profoundly negative impact on quiet sleep duration. Maternal separation may be a stressor the human neonate is not well-evolved to cope with and may not be benign.

Induced Hypothermia for Infants With Hypoxic- Ischemic Encephalopathy Using a Servo-Controlled Fan: An Exploratory Pilot Study

OBJECTIVE. Several trials suggest that hypothermia is beneficial in selected infants with hypoxic-ischemic encephalopathy. However, the cooling methods used required repeated interventions and were either expensive or reported significant temperature variation. The objective of this pilot study was to describe the use, efficacy, and physiologic impact of an inexpensive servo-controlled cooling fan blowing room-temperature air. PATIENTS AND METHODS. A servo-controlled fan was manufactured and used to cool 10 infants with hypoxic-ischemic encephalopathy to a rectal temperature of 33°C to 34°C. The infants were sedated with phenobarbital, but clonidine was administered to some infants if shivering or discomfort occurred. A servo-controlled radiant warmer was used simultaneously with the fan to prevent overcooling. The settings used on the fan and radiant warmer differed slightly between some infants as the technique evolved. RESULTS. A rectal temperature of 34°C was achieved in a median time of 58 minutes. Overcooling did not occur, and the mean temperature during cooling was 33.6°C ± 0.2°C. Inspired oxygen requirements increased in 6 infants, and 5 infants required inotropic support during cooling, but this was progressively reduced after 1 to 2 days. Dehydration did not occur. Five infants shivered when faster fan speeds were used, but 4 of the 5 infants had hypomagnesemia. Shivering was controlled with clonidine in 4 infants, but 1 infant required morphine. CONCLUSIONS. Servo-controlled fan cooling with room-temperature air, combined with servo-controlled radiant warming, was an effective, simple, and safe method of inducing and maintaining rectal temperatures of 33°C to 34°C in sedated infants with hypoxic-ischemic encephalopathy. After induction of hypothermia, a low fan speed facilitated accurate temperature control, and warmer-controlled rewarming at 0.2°C increments every 30 minutes resulted in more appropriate rewarming than when 0.5°C increments every hour were used.

Selective cerebral hypothermia for post-hypoxic neuroprotection in neonates using a solid ice cap

OBJECTIVE The main objective of this study was to study the safety and efficacy of a simple, cost-effective method of selective head cooling with mild systemic hypothermia in newborn infants with hypoxic ischaemic encephalopathy. DESIGN Ethical approval was obtained for a randomized controlled study in which 20 asphyxiated neonates with clinical signs of hypoxic ischaemic encephalopathy would be randomised into cooled and non-cooled groups. However, after cooling the first 4 babies, it was clear that repeated revisions to the cooling technique had to be made which was inappropriate in the context of a randomised controlled trial. The study was therefore stopped and the data for the 4 cooled infants are presented here in the form of a technical report. Hypothermia was achieved by applying an insulated ice cap to the heads of the infants and replacing it at 2-3-hourly intervals, aiming to achieve a target rectal temperature of 35-35.5 degrees C and a target scalp temperature of 10-28 degrees C. SETTING This study was carried out between July 2000 and September 2001 in the neonatal units of Groote Schuur Hospital and Mowbray Maternity Hospital, Cape Town. SUBJECTS Term infants with signs of encephalopathy were recruited within the first 8 hours of life if they had required resuscitation at birth and had significant acidosis within the first hour of life. RESULTS Target rectal temperature was achieved in all infants, but large variations in incubator and scalp temperatures occurred in 3 of the 4 infants. Reducing the target core temperature in a stepwise manner did not prevent excessive temperature variation and resulted in a longer time to reach target temperature. There was least variation in scalp temperature when the ice pack was covered in two layers of mutton cloth before application, but the resulting scalp temperatures were above the target temperature. The maximum scalp temperature variation was reduced from 22 degrees C to 12 degrees C using this method. Nasopharyngeal temperatures varied excessively within less than a minute, suggesting that air cooling via mouth breathing was occurring. The surface site that correlated best with deep rectal temperature was the back, with the infant supine. During cooling, the respiratory rate and heart rate dropped while the mean arterial blood pressure was elevated. There were no irreversible adverse events due to cooling, but infants did become agitated and exhibited shivering which required sedation and analgesia. CONCLUSIONS Nasopharyngeal temperature monitoring was not reliable as an acute clinical indicator of brain temperature in these spontaneously breathing infants, and the back temperature in supine infants correlated better with deep rectal temperature than did exposed skin temperature. This method of cooling achieved systemic cooling but there were large variations in regional temperatures in 3 of the 4 infants. The variations in temperature were probably due to the excessive cooling effect of the ice cap, coupled with the use of external heating to maintain systemic temperature at 35-35.5 degrees C. Variation in temperature was reduced when additional insulation was provided. However, the additional insulation resulted in the loss of the selective cerebral cooling effect. This cooling technique was therefore not an appropriate method of selective head cooling, but did successfully induce systemic hypothermia. This method of insulating an ice cap could therefore be used to induce whole-body cooling but the use of lower core temperatures of 33-34 degrees C is recommended as this will probably result in fewer regional temperature fluctuations. Ideally a more uniform method of cooling should be used.

Early clinical signs in neonates with hypoxic ischemic encephalopathy predict an abnormal amplitude-integrated electroencephalogram at age 6 hours

BackgroundAn early clinical score predicting an abnormal amplitude-integrated electroencephalogram (aEEG) or moderate-severe hypoxic ischemic encephalopathy (HIE) may allow rapid triage of infants for therapeutic hypothermia. We aimed to determine if early clinical examination could predict either an abnormal aEEG at age 6 hours or moderate-severe HIE presenting within 72 hours of birth.MethodsSixty infants ≥ 36 weeks gestational age were prospectively enrolled following suspected intrapartum hypoxia and signs of encephalopathy. Infants who were moribund, had congenital conditions that could contribute to the encephalopathy or had severe cardio-respiratory instability were excluded. Predictive values of the Thompson HIE score, modified Sarnat encephalopathy grade (MSEG) and specific individual signs at age 3–5 hours were calculated.ResultsAll of the 60 infants recruited had at least one abnormal primitive reflex. Visible seizures and hypotonia at 3–5 hours were strongly associated with an abnormal 6-hour aEEG (specificity 88% and 92%, respectively), but both had a low sensitivity (47% and 33%, respectively). Overall, 52% of the infants without hypotonia at 3–5 hours had an abnormal 6-hour aEEG. Twelve of the 29 infants (41%) without decreased level of consciousness at 3–5 hours had an abnormal 6-hour aEEG (sensitivity 67%; specificity 71%). A Thompson score ≥ 7 and moderate-severe MSEG at 3–5 hours, both predicted an abnormal 6-hour aEEG (sensitivity 100 vs. 97% and specificity 67 vs. 71% respectively). Both assessments predicted moderate-severe encephalopathy within 72 hours after birth (sensitivity 90%, vs. 88%, specificity 92% vs. 100%). The 6-hour aEEG predicted moderate-severe encephalopathy within 72 hours (sensitivity 75%, specificity 100%) but with lower sensitivity (p = 0.0156) than the Thompson score (sensitivity 90%, specificity 92%). However, all infants with a normal 3- and 6-hour aEEG with moderate-severe encephalopathy within 72 hours who were not cooled had a normal 24-hour aEEG.ConclusionsThe encephalopathy assessment described by the Thompson score at age 3–5 hours is a sensitive predictor of either an abnormal 6-hour aEEG or moderate-severe encephalopathy presenting within 72 hours after birth. An early Thompson score may be useful to assist with triage and selection of infants for therapeutic hypothermia.

Defining hypoxic ischemic encephalopathy in newborn infants: benchmarking in a South African population.

Abstract Objectives: There are few population-based studies of hypoxic ischemic encephalopathy (HIE) in sub-Saharan Africa, and the published criteria that are used to define and grade HIE are too variable for meaningful comparisons between studies and populations. Our objectives were (1) to investigate how the incidence of HIE in our region varies with different criteria for intrapartum hypoxia and (2) to determine how encephalopathy severity varies with different grading systems. Method: We reviewed the records of infants with a diagnosis of HIE born between September 2008 and March 2009 in public facilities in the Southern Cape Peninsula, South Africa. The incidence of HIE was calculated according to four definitions of intrapartum hypoxia and graded according to three methods. Results: Depending on which defining criteria were applied, the incidence of HIE varied from 2.3 to 4.3 per 1000 live births, of mild HIE ranged from 0.4 to 1.3 per 1000 live births, and of moderate-severe HIE ranged from 1.5 to 3.7 per 1000 live births. Ninety-seven of the 110 (88%) infants reviewed had at least one intrapartum-related abnormality. Only 62 (56%) infants had a blood gas performed in the first hour of life. Conclusion: The incidence and grade of HIE can vary more than 2-fold in the same population, depending on which defining criteria are used. Consensus definitions are needed for benchmarking.

Nevirapine Concentrations in Preterm and Low Birth Weight HIV-Exposed Infants: Implications for Dosing Recommendations

World Health Organisation guidelines recommend nevirapine 2 mg/kg/d for HIV-exposed infants <2 kg, but 4–6 mg/kg/d for infants >2 kg. In 116 low birth weight infants, nevirapine 2 mg/kg/d until 14 days, and 4 mg/kg/d thereafter, was safe (1 mild possibly related rash) and achieved target plasma concentrations. Concentrations decreased with treatment duration. Routine dose increase at 14 days should be considered.

Therapeutic hypothermia for hypoxic ischaemic encephalopathy using low-technology methods: a systematic review and meta-analysis

A systematic review and meta‐analysis were performed to determine the effect of therapeutic hypothermia using low‐technology methods, in settings with facilities for intensive care, in term or near‐term infants with hypoxic‐ischaemic encephalopathy on mortality, neurological morbidity at discharge and neurological morbidity at 6–24 months.

Early clinical predictors of a severely abnormal amplitude-integrated electroencephalogram at 48 hours in cooled neonates

There is a need to identify infants with hypoxic ischaemic encephalopathy who have a poor outcome despite therapeutic hypothermia. A severely abnormal amplitude‐integrated electroencephalogram at 48 h predicts death or disability. Our aim was to determine whether clinical assessment at age 3–5 h predicts a severely abnormal amplitude‐integrated electroencephalogram at 48 h or death in cooled infants.

Therapeutic hypothermia and hypoxic ischemic encephalopathy: opinion and practice of pediatricians in South Africa

Abstract Background: Recent newborn resuscitation guidelines recommend therapeutic hypothermia (TH) as a treatment to reduce long-term neurological deficit in hypoxic ischemic encephalopathy (HIE) survivors. In South Africa, varied resource constraints may present difficulties in the implementation of TH. Objective: To determine the opinions and practice of South African pediatricians, regarding TH and the management of HIE. Methods: We invited 288 South African pediatricians and neonatologists to participate in a web-based survey by e-mail. Practitioners were identified using the Medpages™ database. Results: Responses were received from 37.8% of the e-mails. Seventy-six percent of respondents stated that hypothermia was either effective or very effective while 4% stated TH was ineffective in the management of HIE. Only 42% of respondents offered TH and a further 9% transferred patients to other units for cooling. Twenty-four percent had not implemented TH nor planned to introduce it into practice in the near future. Ninety-eight percent of respondents stated TH should be the standard of care in tertiary neonatal units. Conclusion: Most pediatricians in South Africa who responded to the survey stated that TH is effective to reduce the neurological deficit in HIE, however, less than half offered it as a treatment.

Growth Velocity of Extremely Low Birth Weight Preterms at a Tertiary Neonatal Unit in South Africa

INTRODUCTION There is wide variation in the feeding practices of extreme low birth weight (ELBW) preterms often guided by tradition and resources. The feeding regimen at Groote Schuur Hospital (GSH) nursery, a tertiary neonatal unit, follows a restricted use of parenteral nutrition and concentrates on early introduction of breast milk. There is a need to determine whether this approach achieves acceptable growth velocity. OBJECTIVES This study aims to describe the growth velocity of ELBW babies at GSH. DESIGN This was a retrospective cohort study. METHODOLOGY Infant hospital records of all ELBW babies born at GSH from 1 March to 31 August 2010 were accessed from a previously collected database and relevant data extracted. Growth data were collected from birth to 8 weeks postnatal age or discharge, whichever came first. RESULTS Ninety-one ELBW babies were born during the study period. Forty were excluded from the study. Thirty died before discharge, and 10 were excluded for other reasons. The mean (SD) gestation of the cohort was 28.5 (1.6) weeks, and the median (range) birth weight was 875 (640-995) g. The overall mean (SD) growth velocity was 14 (2.9) g/kg/day. There was no statistically significant association between the growth velocity and the type of feed given, days to establishing full enteral feeds, time to regaining birth weight, HIV exposure status, intra-uterine growth restriction or exposure to antenatal steroids. CONCLUSION In our cohort of ELBW infants, growth velocity was within the range currently deemed acceptable by international consensus.