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Therapeutic hypothermia in mild neonatal encephalopathy: a national survey of practice in the UK
  1. Vânia Oliveira1,
  2. Dev Prya Singhvi1,
  3. Paolo Montaldo1,
  4. Peter J Lally1,
  5. Josephine Mendoza1,
  6. Swati Manerkar2,
  7. Seetha Shankaran3,
  8. Sudhin Thayyil1
  1. 1 Centre for Perinatal Neuroscience, Department of Paediatrics, Imperial College London, London, London, UK
  2. 2 Neonatal Unit, Lokmanya Tilak Municipal General Hospital, Mumbai, Maharashtra, India
  3. 3 Department of Neonatal-Perinatal Medicine, Wayne State University, Detroit, Michigan, USA
  1. Correspondence to Vânia Oliveira, Centre for Perinatal Neuroscience, Imperial College London, London W12 0HS, UK; v.oliveira{at}imperial.ac.uk

Abstract

Although major cooling trials (and subsequent guidelines) excluded babies with mild encephalopathy, anecdotal evidence suggests that cooling is often offered to these infants. We report a national survey on current cooling practices for babies with mild encephalopathy in the UK. From 74 neonatal units contacted, 68 were cooling centres. We received 54 responses (79%) and included 48 (five excluded due to incomplete data and one found later not to offer cooling). Of these, 36 centres (75%) offered cooling to infants with mild encephalopathy. Although most of the participating units reported targeting 33–34°C core temperature, seven (19%) considered initiating cooling beyond 6 hours of age and 13 (36%) discontinued cooling prior to 72 hours. Babies were ventilated for cooling in two (6%) units and 13 (36%) sedated all cooled babies. Enteral feeding was withheld in 15 (42%) units and reduced below 25% of requirements in eight (22%) units. MRI and neurodevelopmental outcome evaluation were offered to all cooled babies in 29 (80%) and 27 (75%) units, respectively. Further research is necessary to ensure optimal neuroprotection in mild encephalopathy.

  • neonatal encephalopathy
  • therapeutic hypothermia
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What is already known on this topic?

Although therapeutic hypothermia improves neurodevelopmental outcomes after moderate or severe neonatal encephalopathy, the risk–benefit of cooling therapy in mild encephalopathy is unknown.

What this study adds?

Most cooling centres in the UK offer therapeutic hypothermia to babies with mild neonatal encephalopathy and variations from established cooling protocols are common.

Background

Although National Institute of Clinical Excellence recommends cooling treatment only for term infants who suffer moderate or severe neonatal encephalopathy (NE),1 anecdotal evidence suggests that cooling therapy is increasingly offered to babies with mild NE.2 Here, we report a national survey of cooling practices for babies with mild NE in the UK.

Methodology

We designed an electronic survey on Qualtrics (Qualtrics LLC, Provo, Utah, USA) including both multiple choice and free text questions. We contacted all cooling centres in the UK included in the National Perinatal Epidemiology Unit database and obtained the contact details of the clinical leads, if the centre was still offering cooling therapy. The survey was then distributed to the clinical leads by email. Responses were screened for duplications and data completeness assessed before analysis, using Microsoft Excel.

Results

Of the 74 centres contacted, 68 offered cooling treatment. We received 54 responses (79% response rate). Neonatal consultants (clinical lead or neurology lead) completed all surveys, except in two cases—one senior clinical fellow and one neonatal clinical manager. We excluded five responses due to incomplete data and one was found later not to offer cooling. A total of 48 centres were included in the analysis. All centres reported using a servo-controlled device for whole body cooling (eg, Tecotherm, CritiCool, Blanketrol) and none used selective head cooling or manual cooling methods.

Overall, 36 (75%) of the centres included in the analysis, currently offered cooling to babies with mild NE and 12 (25%) did not (figure 1). Within the 36 units which cool babies with mild encephalopathy, decision to cool was based on neurological examination and abnormal aEEG in 26 (72%) units or neurological examination alone (despite normal aEEG) in seven (19%) units. Other cooling criteria were reported in three units including ‘continuing cooling started at other centre despite mild encephalopathy (one centre); ‘combination of encephalopathy grading and blood gas results (one centre) and ‘clinical judgement (one centre). The reasons justifying the unit’s decision to offer cooling or not to babies with mild NE are described in table 1. Interestingly, approximately half of the units which offer cooling justified this by the high risk of neurological problems and approximately half of the units which do not offer cooling justified this by the low risk of neurological problems.

Figure 1
Figure 1

Study flow diagram. NE, neonatal encephalopathy; NPEU, National Perinatal Epidemiology Unit.

Table 1

Reasons for offering cooling therapy or not for babies with mild neonatal encephalopathy (NE)

The majority (25 (69%)) of units who offer cooling to babies with mild NE targeted the same core temperature as used for babies with moderate/severe NE (33°C–34°C), whereas 10 (28%) units used 33.5°C–34.5°C and one (3%) reported using 33.5°C–34°C as a target range. Rewarming mode and rate were also similar with only one (3%) unit using passive rewarming and all the other units using active rewarming at no more than 0.5°C per hour.

The extension of the time window for initiation of cooling beyond 6 hours from birth (7 (19%)) and early cessation of cooling treatment (13 (36%)) were also reported. Babies with mild NE were not routinely ventilated for cooling (only two units (6%) ventilated all cooled babies) but were often sedated for cooling (13 (36%) sedated all cooled babies and 20 (56%) sedated cooled babies sometimes). Treatment duration, sedative choice and enteral feeding practices are described in table 2. Most of the respondents offered MRI scans and neurodevelopmental follow-up to babies with mild NE only if they were cooled.

Table 2

Clinical management practices of cooling in babies with mild NE

Discussion

Despite a lack of evidence to support this practice, most tertiary centres in the UK now offer cooling therapy to babies with mild NE. Although the cooling protocol in mild NE was similar to that of infants with moderate or severe NE in terms of the target core temperature, there were a number of key differences.

First, cooling therapy in babies with moderate and severe encephalopathy is supported by convincing clinical evidence from seven randomised controlled trials. Only one of these trials included babies with mild NE and it is unclear if cooling therapy is beneficial for these babies.3 It is also worrying that cooling in the absence of NE can increase apoptosis in preclinical models.4Second, one-third of the cooling centres, discontinued cooling therapy prior to 72 hours, if there was a rapid clinical improvement. Shorter duration of cooling therapy is associated with suboptimal neuroprotection in preclinical models.5 Furthermore, brain injury and adverse neurodevelopmental outcomes may occur in babies with mild neonatal encephalopathy, after premature cessation of cooling therapy.6

A significant amount of variance in practice was also reported in relation to enteral feeds and, in reality, this may not be restricted to babies with mild NE. In the NICHD cooling trials, enteral feeds during cooling were withheld due to the presence of an oesophageal probe, and it is likely that most clinicians would be cautious with enteral feeds in encephalopathic babies with evidence gut hypoperfusion. Nonetheless, babies with mild NE may not have such gut hypoperfusion and sucking and rooting may normalise soon after birth. These babies might even be able to breastfeed within a couple of days after birth, which makes the restriction of enteral feeds more questionable.

One of the most challenging aspects of cooling in mild NE is to accurately identify these babies within 6 hours of birth. Some babies might have had a relatively normal neurological examination soon after birth, only to deteriorate in the subsequent hours or have a seizure after 6 hours of age. Thus, an accurate clinical staging of NE can only be based retrospectively on the evolution of clinical signs during the first few days after birth. The landmark encephalopathy outcome studies defined mild NE based on the worst Sarnat assessment during the entire hospital stay,7 and not within 6 hours of birth as is now done in clinical practice, for the purpose of therapeutic decision-making. In addition, neurological examination may be often performed by trainees with little experience in neurological exam, and structured neurological examinations are rarely undertaken outside the context of clinical trials.

Controversy exists about the contribution of aEEG abnormalities in clinical decision-making for neuroprotective therapies and effective bedside tools are lacking to support early decisions. Thus, it is not surprising that many clinicians faced with these challenges opt to err on the side of caution and offer cooling to all babies with mild NE and discontinue cooling if the baby improves subsequently. Nevertheless, without adequate evaluation about the safety and efficacy or such practices, potential risk–benefit ratios cannot be assessed.

Additionally, adverse outcome was originally defined as the presence of significant handicap measured by (a) cerebral palsy, (b) visual impairment or focal blindness, (c) cognitive delay (Stanley Binet more than 3SD below the mean), (d) severe convulsive disorders and (e) neurosensory hearing loss >70 dB. As a consequence of this high-severity threshold, all babies with severe NE then had adverse outcome and none of the babies with mild NE had adverse outcome.7 This highlights the need of further evaluating other long-term outcomes and needs of babies with mild NE, particularly in cognitive and behavioural domains, which only become apparent during later childhood.

In summary, our survey suggests a wide spread therapeutic drift of cooling therapy for babies with mild NE in the UK. Until more evidence from clinical trials is available, clinicians should carefully discuss the risk–benefit of cooling therapy with parents before offering this to babies with mild NE and adhere to established cooling protocols.

Acknowledgments

We would like to thank all the clinical leads who gave their time to complete the survey and participated in this study. This research was funded by the National Institute for Health Research (NIHR) Biomedical Research Centre based at Imperial College Healthcare NHS Trust and Imperial College London. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health.

References

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Footnotes

  • Contributors VO and DPS conducted the survey, analysed the data and wrote the first draft of the manuscript. PM, PJL, JM, SM and SS assisted in the interpretation of the data and preparation of the manuscript. ST conceived the idea, supervised the project, interpreted the data and prepared the manuscript.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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