Background Infants who have an Apgar score of zero at 10 min of age are known to have poor long-term prognosis. Expert committee guidelines suggest that it is reasonable to cease resuscitation efforts if the asphyxiated infant does not demonstrate a heart beat by 10 min of life. These guidelines are based on data from the era when therapeutic hypothermia was not the standard of care for hypoxic ischaemic encephalopathy (HIE). Hence, we aimed to review our unit data from the era of therapeutic hypothermia to evaluate the outcomes of infants who had an Apgar score of zero at 10 min and had survived to reach the neonatal intensive care unit.
Methods Retrospective chart review. Study period: 2007–2013.
Results 13 infants (gestational age ≥35 weeks) with Apgar scores of zero at 10 min were admitted to the neonatal intensive care unit. All were born outside the tertiary perinatal centre. Of them, eight died before discharge. The type and duration of follow-up varied. Of the five survivors, three had normal cognitive scores (100, 100 and 110) on Bayley III assessment at 2 years of age and one had normal Griffiths score (general quotient (GQ) 103) at 1 year. Only one infant developed severe spastic quadriplegia.
Conclusions 4 out of 13 (30.7%) infants with 10 min Apgar scores of zero who survived to reach the neonatal intensive care unit had normal scores on formal developmental assessments. Information from large databases (preferably population based) is necessary to review recommendations regarding stopping delivery room resuscitation in term infants.
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What is already known on this topic
Guidelines state that delivery room resuscitation may be discontinued if a heart beat does not appear by 10 min in spite of adequate resuscitative efforts.
The recommendations are based on data when therapeutic hypothermia was not the standard of care for hypoxic ischaemic encephalopathy (HIE), when outcomes for such infants were uniformly poor.
What this study adds
Long-term outcome of term and near-term infants with Apgar score of zero at 10 min may not be uniformly poor.
Large database studies (preferably population based) are needed to review recommendation regarding stopping delivery room resuscitation in term infants.
The decision to continue delivery room resuscitation beyond 10 min in a newborn with no heart rate is a dilemma for clinicians. The International Liaison Committee on Resuscitation (ILCOR),1 Australian Resuscitation Council (ARC)2 and the American Academy of Pediatrics3 guidelines suggest that it may be justifiable to stop resuscitation if there are no signs of life after 10 min of continuous and adequate resuscitation. Such a recommendation is based on observational data4–6 that had shown universally poor outcomes for infants with Apgar scores of zero at 10 min. However, those studies were done during an era when therapeutic hypothermia was not the standard of care for hypoxic ischaemic encephalopathy (HIE).
Therapeutic hypothermia has improved the outcomes of HIE. The Cochrane review7 found that therapeutic hypothermia resulted in significant reduction in the combined outcome of mortality or major neurodevelopmental disability at 18 months of age (relative risk (RR) 0.75; 95% confidence interval (CI) 0.68 to 0.83). In addition, improvements in neonatal intensive care, such as avoidance of hypocarbia and hypoglycaemia, use of inhaled nitric oxide for persistent pulmonary hypertension of the neonate (PPHN), room air resuscitation in delivery suite and many other advances, have improved the outcomes of infants in recent years.
Recently, few studies have explored the issue of long-term outcomes of infants with Apgar scores of zero at 10 min. Sarkar et al8 reported uniformly poor outcomes for infants with Apgar scores of zero at 10 min. In their cohort of 12 infants who were asystolic at and beyond 10 min of life, nine died from HIE, two had spastic quadriparesis and global delay at 18–24 months and one had extensive encephalomalacia on brain MRI during follow-up. However, Natarajan et al9 reported that, of the 24 children who had an Apgar score of zero at 10 min, there were 11 survivors of whom five (20.8%) survived without moderate-to-severe disability at 6–7 years of age. Their median IQ was 90 (range 77–99). Similar encouraging findings were observed by Kasdorf et al10 who reviewed data from four hypothermia randomised controlled trials (RCTs) and an observational study. Hence, Natarajan et al9 and Kasdorf et al10 expressed caution about discontinuation of delivery room resuscitation efforts where no heart beat is present by 10 min of age.
Hence, we conducted this study to evaluate the outcomes of our cohort of infants with Apgar scores of zero at 10 min of age.
Aim: To determine the outcomes of term and near-term infants with Apgar score of zero at 10 min of age and survived to reach neonatal intensive care unit (NICU).
Design: Retrospective observational study.
Duration: 2007–2013 (era of routine therapeutic hypothermia for HIE).
Ethics approval: The study was approved by our hospital's Quality Improvement Committee as having met the ‘Australian National Health and Medical Research Council requirements for quality assurance and audit projects’.11 Parental consent was deemed not necessary considering the retrospective chart review nature of the study.
Participants: All infants (≥35 weeks’ gestation) admitted to the NICU with Apgar scores of zero at 10 min.
Cases were identified by interrogating Neonatal Databases at the King Edward Memorial Hospital (KEMH) for Women and Princess Margaret Hospital (PMH) for Children, Perth, Western Australia. Clinical details of all neonates admitted to the NICUs of these two hospitals are entered into these databases by trained, dedicated staff members. The information from these databases is provided annually to the Australia and New Zealand Neonatal Network (ANZNN), which in turn publishes annual reports (https://npesu.unsw.edu.au/surveillance/report-australian-and-new-zealand-neonatal-network). Regular audits are conducted by the ANZNN to ensure accuracy of the data in our databases.
There are approximately 35 000 births annually in the state of Western Australia. KEMH is the sole tertiary perinatal centre for this state with approximately 7000 high-risk deliveries and 2200 neonatal admissions annually. PMH is the sole tertiary children's hospital in Western Australia and approximately 700 neonates are admitted annually to its NICU.
Clinical characteristics, including resuscitation details and Apgar scores as well as 2-year developmental outcomes, were collected from the medical records by two authors (PS and AA).
Since 2007, infants (≥35 weeks) with moderate-to-severe HIE are offered whole body hypothermia (temp: 33.0°C–34.0°C) in our unit. Unlike majority of the hypothermia RCTs, which had enrolled infants ≥36 weeks, the Australian Infant Cooling Evaluation (ICE) trial12 had enrolled infants ≥35 weeks gestation. Hence, our unit's policy is to offer hypothermia for infants ≥35 weeks with HIE. This policy is similar to the ones used all over Australia. All infants who receive therapeutic hypothermia are enrolled into a follow-up programme and are seen by a neonatologist at 4 and 8 months of age. They are assessed by a developmental paediatrician (JM) at 12 months of age using the Griffiths Mental Development Scales.13 The infants are also assessed by a developmental psychologist using the Bayley Scales of Infant and Toddler Development (BSID-III) at 24 months.14
On Griffiths Mental Development Scales, a combined general quotient (GQ) of 100.2 (SD 12.8) is considered normal. A GQ of <75 is >2 SD below the mean and hence denotes significant disability.13 On the BSID-III assessment, the composite scores for the cognitive, language, motor and social/emotional subtests are calculated; the scales are age-standardised. A score of 100 (SD 15) is considered normal.14
Thirteen infants (gestational age ≥35 weeks) with Apgar scores of zero at 10 min and admitted to the NICU were identified. Their clinical details are given in table 1. The mean (SD) gestational age and birth weight were 38.4 (2.1) weeks and 3237 (446.6) g respectively. All were out-born. All except two (serial no. 1 and 7 in table 1) received therapeutic hypothermia. Eight out of 13 (61.5%) infants died before discharge. The mean age at appearance of first heart beat was 22.3 min (SD 6.5) in those who died and 16.6 min (SD 2.4) in those who survived. The mean time for heart rate to reach >100/min from birth was 26.9 min (SD 7.9) among those who died and 18 min (SD 2.1) in those who survived. All eight deaths were because of withdrawal of life support in view of severe encephalopathy on clinical examination, electrocortical inactivity on electroencephalogram (EEG) and extensive damage to the brain on MRI. All deceased infants had Sarnat stage III HIE. Two out of the five survivors had stage II HIE.
Of the five survivors, one had normal Griffiths score of 103 at 1 year of age, one had normal Bayley cognitive composite score of 110 at 2 years of age, but needed hearing aids and two had normal Bayley cognitive composite scores of 100 at 2 years. Only one had severe spastic quadriplegia. In effect, four out of 13 (30.7%) infants with Apgar scores of zero at 10 min had normal scores on formal developmental assessments. There were no deaths after initial discharge.
Our results add to the growing body of evidence that the long-term outcomes of infants with Apgar score of zero at 10 min may not be uniformly poor.9 ,10 In a recently published study by Kasdorf et al10 that included data from four hypothermia RCTs and an observational study, 90 infants with Apgar scores of zero at 10 min were identified; 56 had been treated with hypothermia and 34 with normothermia. A total of 15/56 (27%) in the hypothermia group and 7/34 (21%) in the normothermia group were found to be developmentally normal at 18–24 months of age. Overall mortality was 45/90 (50%).
In both studies,9 ,10 improved outcomes were seen not only in the hypothermia group, but also in normothermic infants. The overall advances in neonatal intensive care management that have occurred over the recent years might have contributed to the improved outcomes even in the normothermic group. Similar data from the remaining hypothermia RCTs might throw more light on whether the improved outcomes are significantly greater in the hypothermia group compared to normothermia, even though such a meta-analysis would not have adequate power to answer the question definitively.
The limitations of our study were the small sample size and the fact that the tools used for developmental assessment were heterogeneous. In addition, the cohort of infants was highly selective because even though they had Apgar scores of zero at 10 min, they managed to survive and reach the NICU. Hence, our results might have been spuriously optimistic. Another limitation was the fact that it was difficult to objectively assess the adequacy of the delivery room resuscitation because the competency of the attending clinicians varied from centre to centre, especially considering the fact that the state of Western Australia was vast.
The main strength of our study is the fact that all infants with HIE undergoing therapeutic hypothermia has received uniformly standardised care.
In summary, the long-term outcomes of infants with Apgar scores of zero at 10 min may not be uniformly poor. Information from large databases (preferably population based) is needed to review recommendations regarding continuation of resuscitation for infants with no heart beat at 10 min of age.
Contributors PS collected the data, performed data analysis, drafted the initial manuscript and approved the final manuscript as submitted. AA assisted in data collection and analysis, and approved the final manuscript as submitted. JM provided developmental outcome data, and reviewed and approved the final manuscript as submitted. SR conceptualised and designed the study, revised the manuscript and approved the final manuscript as submitted.
Competing interests None.
Ethics approval QI Neonatal Clinical Care Unit WNHS.
Provenance and peer review Not commissioned; externally peer reviewed.
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