9 October 2011

Dear Editor,

Therapeutic hypothermia after perinatal asphyxia in term neonates is associated with improvement in long-term outcome.

In 2005, Salhab and Perlman published a study looking at preterm neonates 31–36 weeks of gestation with severe fetal acidemia and encephalopathy – postulating that these neonates would be potential candidates for neuro-protective strategies.1

We wished to assess how many of the approximately 550 infants born at >29+6–<36 weeks in our unit/year would be eligible for treatment with therapeutic hypothermia after perinatal asphyxia.

We searched our database for the period 01/01/2003 to 01/11/2008 for inborn infants with gestational age >29+6–<36 weeks, without congenital malformations, presenting at birth with either severe acidosis (pH ≤ 7.0; Base deficit (BD) ≥16) with Apgar score ≤5 at 5 min or prolonged resuscitation, or moderate acidosis (pH 7.01–7.15; BD 10–15.9) with Apgar score ≤5 at 5 min and prolonged resuscitation. Infants with hypoxic ischemic encephalopathy (HIE) grade 2 or 3 combined with either of the above were also included.

Fifteen infants between 30 and 36 weeks met the criteria for therapeutic hypothermia. Eight of the neonates had HIE grade 2 or 3. Six of the neonates underwent prolonged resuscitation.

According to our findings, approximately two to three cases per year in our unit (approximately 4–6 per 1000 late preterm neonates) would fit the criteria for therapeutic cooling for perinatal asphyxia.

Gunn and Bennett2 recently published a paper on brain cooling in the preterm neonate, looking at the evidence from animal studies in the preterm fetus on hypoxic-ischemic brain injury and therapeutic hypothermia. They concluded that the larger premature neonates (31–36 weeks of gestation), being less at risk for intraventricular haemorrhage, infections and respiratory distress than the younger preterm neonates, would most likely benefit from therapeutic hypothermia.

There is paucity of evidence on neuro-protective strategies for this group, but a recent study looking at hypothermia (48 h) in preterm neonates with advanced necrotising enterocolitis (NEC) found it to be a safe intervention. This was, however, a pilot study without follow-up data, and unfortunately too small to fully assess the safety. A larger, randomised trial is planned.3

The findings on hypothermia in preterm neonates with NEC3 combined with the evidence from animal research2 support the conclusion that larger preterm neonate should be considered for neuro-protective strategies.1 However, therapeutic hypothermia in preterm neonates can not be recommended at present due to the paucity of evidence on safety.

Several units are already using therapeutic hypothermia in neonates >35 weeks of gestation, and there are data from the larger trials on therapeutic hypothermia in this group. The numbers are however small, and more research is needed on these neonates as well. There is clearly a need for further safety studies before planning randomised controlled trials in the mentioned patient group.

Our findings indicate that approximately 4–6 per 1000 late preterm neonates per year could potentially benefit from therapeutic hypothermia. There is a need for both further safety studies and subsequently randomised controlled trials looking at this interventional strategy in the late preterm neonate, with emphasis on safety, adverse effects and long-term outcome.