Dear editor,

This further study of selected infants from the ALSPAC cohort (1) gives welcome evidence that although babies who are asymptomatic for encephalopathy following resuscitation at birth may have reduced intelligence quotient (IQ) scores in childhood (2), they have normal neuropsychological functioning and educational attainment at school.(1) This still leaves a significant number of babies who develop encephalopathy following successful resuscitation and do not recover so well. It might be expected that the degree of the hypoxic insult would inflict an equivalent degree of brain injury. This does not appear to be the case and there appears to be threshold above which full or almost full brain recovery can occur. Odd et al showed that resuscitation was strongly associated with an increased risk of a low IQ score and they suggested that this result was a biologically plausible outcome from physiological compromise at birth--eg, only a subgroup of infants who had experienced sufficient compromise to damage the relevant brain regions and impair cognitive performance. There is thus an urgent need to identify why some babies develop encephalopathy after resuscitation while others do not and are able to make a complete or almost complete recovery. While efforts to reduce the risk of hypoxia in labour must continue other possibilities need to be explored.

Weindling, discussing HIE, (3) asked us to consider why delayed cord clamping has not been generally adopted as an option despite evidence of benefit from randomised controlled trials. There are several theoretical reasons why asphyxiated babies may benefit from a physiological transition. (8) Firstly the risk of hypovolaemia is largely avoided, secondly the babies benefit from a continued supply of oxygenated blood for at least 90 seconds (6) and thirdly the increased supply of umbilical cord stem cells may help the immediate repair of damaged cerebral or cardiac tissue.

The recent ILCOR recommendation (4) is that umbilical cord clamping should be delayed for at least one minute in uncompromised babies. They go on to explain that "As yet there is insufficient evidence to recommend an appropriate time for clamping the cord in babies who are severely compromised at birth." And indeed we are not aware of any randomised controlled trails comparing outcomes of resuscitation at birth with differing cord clamping timing. However neither are we aware of any randomised controlled trials comparing standard resuscitation interventions with no intervention at all. (Note that cord clamping before natural closure of the circulation is an intervention.) This is highly relevant because it is common for the paediatrician to be presented with a neonate for resuscitation after the obstetrician has already intervened. It is often forgotten that prematurely clamping off the umbilical circulation is an intervention which has a significant effect on physiological transition at birth. Recent studies by Farrar et al (5) showed that the mean placental transfusion is about 80mls but 8% of babies will lose over 160mls when the cord is clamped immediately after birth. Even in a 4.5kg baby, 160 mls represents over 30% of the circulating blood volume. If a baby is already hypoxic, is it possible that the additional hypovolaemia is sufficient to interfere with the cerebral circulation and provide the critical injury response of encephopathy? Wiberg et al (6) reported three cases to show that even when there is significant intrapartum hypoxia and acidaemia the neonate can transistion successfully without any assistance, provided the placental circulation is left intact. They showed high levels of oxygenated blood returning in the umbilical vein from the placenta for up to 90 seconds after birth. One of these three babies (case 14) had an Apgar score of 4 at one minute while the other two had Apgars of 8. However it should be pointed out that in normal clinical practice even one minute Apgar scores are usually taken well after the placental circulation has already been interrupted by cord clamping.

The hypothesis that hypovolaemia and increased hypoxia resulting from premature cord clamping is significant in the development of encephalopathy is not particularly difficult to test. Ideally equipment which allows all the facilities of the current resuscitaire to be available to the paediatrician but close enough to the mother to allow the cord to remain intact needs to be available. However even simple extension tubing from the resuscitaire together with a suitable flat surface close to the mother on which to initiate resuscitation is another possible approach. Evidence could become available very quickly by simply following the new ILCOR recommendations.(4) They call for accurately assessing the condition of the newborn to determine whether or not resuscitation is necessary and thus determining whether or not it is appropriate to delay clamping the cord for at least one minute.

At present, especially when delivery has been expedited for fetal distress, a baby who is pale and does not immediately cry at birth is considered to need resuscitation, and will be handed over to the paediatrician with the cord clamped within seconds of birth. Proper assessment of the condition of the baby is only undertaken by the paediatrician on the resuscitaire. The one minute Apgar is usually measured after some resuscitation has already been initiated.

ILCOR consider the heart rate to be the most important parameter and this can only be assessed accurately by auscultation of the neonatal chest or by oximetry. Further, determining a heart rate accurately requires a moderate interval over which to count. During these 20 to 30 seconds it may become clear that the condition of the baby is improving. We wonder how Wiberg et al dealt with case 14 with a one minute Apgar of 4. Was pulse oximetry already in place and the improving heart rate sufficient to continue with monitoring?

It is clearly important that during the assessment of the baby, it is kept at or slightly below the level of the placenta and that hypothermia is prevented. These criteria should not be difficult to meet for at least one minute. For babies who have no detectable heart activity, cord milking should be considered before clamping the cord, ideally with as much cord length on the baby as is possible to allow further milking once the baby is on the resuscitaire. (7)

References

1. Odd DE, Whitelaw A, Gunnell D, et al. The association between birth condition and neuropsychological functioning and educational attainment at school age: a cohort study. Arch Dis Child 2011;96:30-37.

2. Odd DE, Lewis G, Whitelaw A, et al. Resuscitation at birth and cognition at 8 years of age: a cohort study. Lancet 2009;373:7.

3. Weindling A M. How has research in the last 5 years changed my clinical practice? Arch Dis Child Fetal Neonatal Ed 2010;95:F59-F63.

4. Perlman JM, Wyllie J, Kattwinkel J, et al. Part 11: Neonatal Resuscitation 2010 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations.Circulation 2010;122;S516-S538.

5. Farrar D, Airey R, Tuffnell D, et al. Measuring Placental Transfusion For Term Births:Weighing Babies At Birth With Cord Intact. Poster Presentation at BMFMS Liverpool 2009. Arch Dis Child Fetal Neonatal Ed 2009;94: Fa4-Fa10.

6. Wiberg N, Kallen K, Olofsson P. Delayed umbilical cord clamping at birth has effects on arterial and venous blood gases and lactate concentrations. BJOG 2008;115:697-703.

7. Hosono S. Umbilical cord milking reduces the need for red cell transfusions and improves neonatal adaptation in infants born at less than 29 weeks' gestation: a randomised controlled trial. Arch Dis Child Fetal Neonatal Ed 93:F14-9.

8. Mercer J, Bewley S. Could early cord clamping harm neonatal stabilisation? Lancet 2009;374:378.