The transition to extra‐uterine life by extremely preterm infants – handle with care

Abstract

Advances in the immediate postnatal management of premature infants have been very successful in improving mortality and morbidity among extremely low gestational age newborns (ELGAN) during the last few decades. Resuscitation protocols, such as the guidelines by the International Liaison Committee on Resuscitation (ILCOR) 1, have contributed to improving and standardising management. A number of advancements have made it possible to resuscitate premature infants born at progressively earlier gestational ages. These include providing a temperature secure environment, administering surfactant, supporting breathing using continuous positive airway pressure (CPAP) and positive pressure ventilation (PPV) with positive end expiratory pressure (PEEP) and securing skin humidity and temperature by wrapping the baby in a polyethylene bag. In addition, routines outside the resuscitation room have also helped to improve survival, for example antenatal corticosteroids and centralisation of care, when possible, due to maternal factors. Continuous training has also helped to drive improvements, including simulated training. There are still gaps in the evidence and knowledge regarding the neonatal resuscitation of preterm and term infants 2. The ILCOR group outlined the most pressing gaps in 2012 and, for preterm infants, these included uncertainty about optimal saturation targets, the use of prolonged inspiratory time (sustained inflation), the optimal devices and techniques to deliver PPV, PEEP and CPAP, room temperature, the use of polyethylene wrap or bags with, or without, an exothermic mattress to maintain body temperature and delayed cord clamping during resuscitation 2. As levels of mortality and morbidity have decreased, neonatal teams have gradually started to resuscitate babies at lower gestational ages, in many cases down to 22–23 weeks of gestation. The difficulties that are experienced increase almost exponentially at these ages, as the immature lung provides hard challenges, with a small area of respiratory epithelia and gas exchange surface, little if any surfactant production and underdeveloped concomitant blood vessels with a longer distance between the alveolar sacks and capillaries 3. The immediate post-natal management of preterm infants in, or in the close vicinity of, the delivery room is very successful today, as shown by the EPICure 2 and Extremely Preterm Infants in Sweden Study (EXPRESS) cohorts 4, 5. However, the odds for survival at 22–24 weeks are much less in favour of the baby and the neonatal care team than at later gestational ages. Patterns of major neonatal morbidities, and the proportion of survivors who were affected, were unchanged in the EPICure cohorts from 1995 and 2006, despite an overall increase in survival 4. In this issue of Acta Paediatrica, Lamberska et al. 6 present a prospective observational study to evaluate their resuscitation protocol for ELGANs, by analysing video recordings taken simultaneously of the resuscitation interventions and the monitors. They divided the 73 preterm infants into three age groups, 22–24, 25–26 and 27–28 weeks, and chose the percentage of bradycardic infants at each minute of life and the times to reach defined targets of oxygen as primary outcomes, with bradycardic defined as a heart rate of less than 100 beats per minute. The reference curves on heart rate and oxygen saturation published by Dawson et al. were used for comparison. Compared to other reports, the ELGANs in this study showed excellent results in the two older groups, while, as expected, the infants born at <25 weeks responded poorly and took longer time to reach the oxygen saturation targets. The authors concluded that the current recommendations may fail to achieve timely lung aeration in this gestational age group. In addition, the need for endotracheal intubation was significantly larger among the 22–24 week group, due to their slower response to resuscitations efforts, and the rates of death and intraventricular haemorrhage (IVH) were higher. In a post hoc analysis, the authors found an association between the occurrence of IVH and lower values of heart rate and oxygen saturation. Of course, this association cannot prove any causality, but it makes the authors ask the relevant question, which is whether we should act differently when taking care of ELGANs on the verge of viability? In their conclusion, Lamberska et al. suggested that sustained inflation and delayed cord clamping may be effective alternatives when it comes to reducing the high mortality and morbidity among preterm infants born at early gestational ages 6. The term ‘resuscitation’ has been questioned when it comes to the management of the preterm transition and adaption to extra-uterine life 7, 8. In 2005, Jobe argued that few infants needed resuscitation and the majority only need a bit of assistance, like drying and stimulation to allow transition. He also stated, in a perhaps provocative tone, that ‘there is perhaps nothing more dangerous for the preterm lung than an anxious physician with an endo-tracheal tube and a bag’ 7. In 2008, O'Donnell called for another term than resuscitation to be used, suggesting that approaches such as delayed cord clamping, sustained inflation and early surfactant were areas where more research was needed 8. Pursuing the aim that ELGANs should be cared for in a more gentle way, Kribs et al. have published several reports of observational studies and randomised trials from Germany on their less invasive surfactant application protocol (LISA) 3. The LISA protocol also included delayed umbilical cord clamping, which is associated with a more gentle transition to extra-uterine life and stabilises cardio-vascular adaption. Delayed cord clamping also seems safe in early gestational ages and has been associated with less IVH and a lower risk of necrotising enterocolitis 9, 10. One can conclude that, as neonatology advances, we must continuously question our management. In the same way that a moderately preterm infant needs a different care approach after delivery than a term infant, an extremely low gestational age infant may also benefit from a different approach than more mature infants. The revised 2015 guidelines from ILCOR only contained a small number of minor changes 1, and this is necessary and desirable when existing protocols have reached the maturity where only smaller modifications to optimise management are needed. General international recommendations may impede the development of newer, more effective approaches in more unexplored areas, where the care of infants born before 25 weeks of gestational age clearly belongs. While large multicentre trials and registry reports help us to map our knowledge in greater detail and ensure that changes are warranted, it is important that pioneers question the prevailing paradigms, whether it is what levels of oxygen to deliver, when to clamp the umbilical cord, how to expand immature lungs or how to administer surfactant in a less invasive way. Animal experiments can lead the way to ensure safety, but it is important to continue to design appropriate dimensioned trials to expand our knowledge and perhaps also increase the pace of implementing new advances. Just as societies and technologies around us change more and more rapidly, we also have to contemplate ways to speed up the application of new routines in the management of preterm and term infants while still maintaining safety measures. Should international recommendations such as the ILCOR guidelines limit themselves to well explored gestational ages? Should we allow for smaller renowned groups to issue knowledge documents annually or at least every 2 years? The continuous re-evaluation of practice is always warranted, and, after a long history of successful invasive interventions, it may be time to embrace the thought that the most fragile infants do not need an even more invasive approach, but to be handled with the upmost delicacy.