We have expressed descriptive data as absolute frequencies and percentages. To make comparisons, we used the chi square test and Fisher exact test for qualitative variables, and the Mann–Whitney U test and the Kruskal–Wallis test for quantitative variables. We defined statistical significance as a p-value of less than 0.05.

In Spain, all neonatal units in tertiary care hospitals have specific protocols for the resuscitation and stabilisation in the delivery room of NBs that exhibit signs of perinatal asphyxia. In adherence with current recommendations, these hospitals have staff specifically trained on neonatal resuscitation and avoid the administration of calcium and sodium bicarbonate.15,16 They also report turning off the radiant heat of the incubator once the NB has stabilised after resuscitation. While current guidelines call for preventing hyperthermia and initiating TH in NBs with moderate to severe HIE, they do not specify the measures that should be initiated during resuscitation.16,17 In any case, given the usual decline in body temperature in NBs with asphyxia, monitoring the core temperature is a must in the delivery room, especially if external heat sources are withdrawn.18,19

After the initial stabilisation, monitoring of various physiological parameters, including heart rate, blood pressure, respiratory function and body temperature, is standard practice in the management of these patients. A point that remains controversial is whether NBs that recover quickly in the delivery room should be allowed to stay with their mothers to promote skin-to-skin contact and initiation of breastfeeding or, on the contrary, should be transferred to the neonatal unit for a period of monitoring, and enteral feeding delayed due to the potential risk of intestinal hypoperfusion. In our study, most hospitals reported admitting NBs with asphyxia to the neonatal unit, although 25% contemplated the possibility of having the NB remain with the mother if they recovered quickly and well.

A key aspect in the care of NBs with perinatal asphyxia is the control of body temperature from minutes after birth until the decision is made whether to use TH or not. For each 1°C increase in body temperature, there is an up to 4-fold increase in the odds ratio for death or moderate-to-severe neurologic impairment.20 Consistently with this knowledge, 98% of hospitals reported transferring the NB to the neonatal unit with the heat of the transport incubator off and monitoring the rectal temperature in the first hours of life to avoid excessive cooling and, more importantly, hyperthermia.21 In addition, most hospitals reported that they generally maintained body temperature below 36°C. At present, there is no evidence on the benefits or risks of lowering the body temperature below the normal range or even to the range of TH (33–34°C) in NBs with perinatal asphyxia before establishing the presence of moderate-to-severe HIE.

Following a hypoxic-ischaemic insult, the brain is particularly vulnerable to comorbid factors with the potential to damage the CNS, shorten the therapeutic window and increase the severity of the injury. These factors include hypoglycaemia, hypocarbia and hyperoxia or hypoxia.

Perinatal asphyxia is an important cause of hypoglycaemia due to the anaerobic metabolism of glucose. Furthermore, the concomitant presence of hypoxaemia and ischaemia may increase the vulnerability of the neonatal brain to hypoglycaemia. A blood glucose level of less than 40–46.8mg/dL in the early hours of life increases the risk of developing moderate-to-severe HIE22–25 and of subsequent death or neurologic impairment.24,25 All hospitals reported measuring blood glucose levels at least once and initiated fluid therapy at admission. There is no scientific evidence supporting the routine initiation of an intravenous dextrose infusion16 as opposed to monitoring blood glucose levels and initiating enteral feeding. In this regard, it is important to assess for the presence of acidosis or hyperlactatemia, which could be signs of poor intestinal perfusion.

Another universal practice across hospitals was measurement of blood gases in the first 6h of life with the purpose of detecting abnormalities such as severe hypocarbia (pCO2<20mmHg) or sustained moderate hypocarbia (pCO2, 20–25mmHg), which appear to carry an increased risk of death or moderate-to-severe neurologic impairment in NBs with HIE.26–28

Besides monitoring vital signs and potential comorbid factors through laboratory tests, the most important task in the management of NBs with perinatal asphyxia is to determine whether the patient does or not have acute encephalopathy. Since this is a dynamic condition that may change with time and its diagnosis and severity are established based on clinical manifestations, it is recommended that several neurologic assessments be performed in the first 6h of life.2,3,7,13 Consistent with this, 90% of the hospitals reported that they usually performed 2 or more assessments. As an orientation for practice, 3h post birth could be a good time to determine the need for active hypothermia in a NB with perinatal asphyxia that exhibits moderate-to-severe HIE at this time point.5 If the decision were made to prescribe TH immediately after birth to pursue the maximum possible benefits, numerous NBs that would have recovered with a good outcome without treatment would be subjected to the latter. On the other hand, if initiation of TH were delayed past 6h post birth, the optimal benefit of treatment would not be achieved, as treatment is more effective the sooner it starts after the hypoxic-ischaemic insult.29,30

All hospitals reported using scales to assess the severity of encephalopathy, most frequently the scale proposed by García-Alix,10 followed by the scale proposed by Sarnat.11 These scales offer a standardised, systematic and organised approach to the assessment of severity, allowing homogeneous assessment by professionals with varying degrees of training in neurology as well as the comparison of patients classified into homogeneous groups. It would be beneficial for every hospital to become confident and experienced in the use of the same scale. While awaiting data from clinical trials in NBs with mild HIE, we ought to remember that at present TH is only indicated for treatment of NBs with moderate-to-severe HIE, although there are studies in the literature that have reported including 15–30% of NBs with mild HIE in the group treated with hypothermia.31–33

Abnormalities in electrocortical activity detected by aEEG have been used to determine the indication of TH in NBs with perinatal asphyxia34,35 and, more commonly, to monitor brain function during the acute phase of encephalopathy36 and detect silent seizures. Furthermore, the simplicity of its interpretation combined with its high predictive value makes aEEG extremely valuable in NBs with neurologic involvement, and particularly in NBs with HIE.35,36 We ought to highlight that 35% of the neonatal units reported not having access to aEEG, even though all of were Level III units and some were in hospitals that offered TH. This finding suggests an opportunity for improvement, as it does not seem possible to offer optimal care with TH to NBs without the information that can be obtained through aEEG monitoring.

While the data from the survey demonstrate an adequate quality of care, with similar scores in hospitals that offer TH versus those that do not, there is room for improvement, as only 50% of the 89 tertiary care hospitals delivered “optimal care.” We also found differences based on the level of care of the neonatal units and on whether they did or did not offer TH, with the quality of care in the delivery room and the 6h of life being higher in level IIIC and IIIB units that offered TH compared to level IIIA units, and the availability of experienced professionals being greater in level IIIC units compared to all others.

One key element in the improvement of the response within this narrow time frame is adequate training of paediatricians that manage deliveries such that they would be able to quickly identify newborns eligible for TH and activate the “hypothermia code” very early on.37 In Spain, the incidence of perinatal asphyxia is of approximately 7 cases per 1000 births,7 and while most newborns will not require transport, the activation of this code and the implementation of a sequence of actions that we call “brain neuroprotection chain” serve to put the transport team and referral hospital on alert, closely monitor the neurologic condition of the NB, control potential comorbid factors and identify the presence of HIE, all within the 6-hour “golden window” (Fig. 4). Our study has identified areas for improvement, such as technological resources and staff training; at minimum, all hospitals that offer TH should have aEEG equipment and neonatologists trained in the use of the various tools employed for neurologic assessment and with experience in the management of the complications associated with HIE.12,38

Figure 4.

Protocol for care in the first 6h of life and the “brain neuroprotection chain.” aEEG, amplitude-integrated electroencephalogram; BD, base deficit; BP, arterial blood pressure; BS, burst suppression pattern; LV, low voltage pattern; FiO2, fraction of inspired oxygen; FT, flat trace; GA, gestational age; HIE, hypoxic-ischaemic encephalopathy; HR, heart rate; hypoCa++, hypocalcaemia; hypoMg++, hypomagnesemia; RS, resuscitation; NB, newborn; RR, respiratory rate; PaO2, partial pressure of oxygen in arterial blood; PaCO2, partial pressure of carbon dioxide in arterial blood; rScO2: regional cerebral oxygen saturation; SatO2: arterial oxygen saturation; T, body temperature.

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The main strength of this study is that practically every tertiary care hospital provided information, thanks to which we have unique data previously unknown that provide a global perspective of the management in Spain of NBs with perinatal asphyxia eligible for TH in the first hours of life. On the other hand, there are also limitations. The survey methodology carries risks of bias, as the dataset may have incomplete or inaccurate information. Since there are no validated criteria for the assessment of health care quality in the first 6h of life in the context of perinatal asphyxia, we rated clinical practices by comparing them to the recommendations of current clinical practice guidelines.2,3,12–14 Furthermore, we excluded the items that are most controversial from the rating, and chose to apply an asymmetrical rating scale to emphasise the value of acting in adherence to recommended standards in contrast to “rarely or never” doing so. Last of all, we ought to note that our survey assessed the general protocols established in each hospital, and thus could not provide information on the quality of the actual care delivered to patients.

The information contributed by our study is particularly relevant to shape care practices in Spain during the golden window in NBs with asphyxia at risk of HIE and has identified potential areas for improvement so that efforts can be targeted to deliver adequate care in this time frame.