Preterm Infant Transport Stress (PremiTranS) Study - A Feasibility Study of the Impact of Inter-hospital Transport on the Preterm Infant

Neonatal intensive care has advanced significantly in recent years resulting in a marked decrease in mortality, especially in the extremely low birth weight (ELBW) infants (<1000g). However, we have not observed a parallel improvement in long term outcomes such as neurological disability as observed with the EPICure and EPICure 2 data.

There is a need to explore new avenues in neonatal care that can reduce the long term neurodevelopment complications of extremely preterm birth. One area that has received little attention is that of inter-hospital transfer of these preterm babies. In the UK, like other countries such as USA and Australia, the centralisation of neonatal intensive care in large tertiary units (NICU's) has resulted in reduced mortality but not significant morbidity. Data from Australia suggests there is 4-fold increase in death for those ELBW infants transferred between tertiary neonatal units within the same city (Melbourne). Furthermore, data from the USA, where 69,000 neonatal transports occur each year, have demonstrated a significant increase in severe intraventricular haemorrhages (IVH) in transported infants. Severe IVH is associated with a poor neurological outcome including cerebral palsy. Many of the ELBW infants are transferred within a few hours of life in order to receive specialist care and services. However, it is the first few days of life that represent the greatest risk of developing an IVH with up to 50% developing IVH before 3 days and if severe 75% could go on to develop cerebral palsy.

No causation has been identified for the associated significant increase in risk of IVH and it is likely to be multifactorial. Such factors could include resuscitation at birth and early care on the NICU. However, in developed countries some of these factors are likely to be less important with the establishment of neonatal networks (sharing common practice and guidelines) and international and national guidelines/training programmes for newborn resuscitation. This raises the actual transfer of the preterm infant which could represent a significant stress to the infant. Inter-hospital transfer, usually many miles away from the birth hospital, is at a time during early life when transition from fetus to newborn is still occurring and there is often cardiorespiratory instability. The combination of these factors can increase the risk of neurological injury to the immature developing brain, especially during the period of greatest risk of IVH. Although IVH is easy to identify and define as a risk to the long term neurodevelopment of the baby there is also the possibility that more subtle neurological injury can occur. Such injury may not be detectable from ultrasound imaging alone but may require novel biochemical markers that can be detected in the bodily fluids (blood, urine) or by more detailed imaging techniques (magnetic resonance imaging - MRI). A recent study has highlighted this with early markers of stress correlating with poor neurological predictors, such as regional alterations in brain volume (on MRI) and functional motor deficits, in ex-preterm infants at term corrected gestation.

As more ELBW infants are reaching school age, there are growing concerns surrounding the increased in incidence of neurodevelopmental problems in these children. Many predict that such problems may stem from early life exposure to environmental stressors which could potentially have adverse effects on the infant's physiological and neurological stability. The presence of these stressors is very much evident during inter-hospital transportation and on neonatal units where preterm infants are exposed to noise and mechanical vibration.

On all neonatal units, the characteristic loud noises contributed by alarms, ventilators, phones and even conversations often exceed the recommended hourly level of 45 decibels on an A-weighted scale. Excessive noise levels have been shown to increase heart rate in both preterm and term infants. A maturing biphasic pattern with initial cardiac acceleration and rebound deceleration has been observed in higher birth weight infants, this which was absent or milder in ELBW infants. Noise has also been shown to increase blood pressure, increase respiratory rates, and affect sleep cycles. Decreased autonomic and self-regulatory abilities make these ELBW infants vulnerable to high noise levels due to their inability to filter and process noxious stimuli. This could potentially hinder neurodevelopment during such a critical time.