Caffeine treatment for stimulation of spontaneous breathing in preterm infants at birth

Although ample research has improved our respiratory and hemodynamic care for
very preterm infants during the neonatal period, our care at birth has been a
neglected area until recent years. For successful transition to life after
birth some major respiratory and hemodynamic physiological changes have to
occur. The transition is often hampered in very preterm infants because of the
immature respiratory system. Consequently, preterm infants often need
respiratory support immediately after birth.

In the recent years it has become evident that positive pressure ventilation
can adversely affect the cardio-respiratory system and cerebral perfusion
during this vulnerable period. Ventilation at birth can cause lung injury,
initiating pulmonary inflammatory responses, resulting in systemic involvement.
Furthermore, the inflammatory cascade and cerebral flow instability at birth
can be a direct source for brain injury. This makes the degree of brain injury
dependent upon the nature of the initial ventilation strategy employed.

There is now a progressive shift in the management of these infants towards
avoiding intubation and mechanical ventilation by the use of non-invasive
continuous positive airway pressure (CPAP) in babies capable of breathing
spontaneously. However, most very preterm infants breathe at birth, but
respiratory effort is weak and still a large proportion of these infants fail
CPAP and need to be intubated and ventilated. Thus, to reduce the injury at
birth, ventilation should be avoided if possible.

As standard of care, all preterm infants receive caffeine to stimulate their
breathing and is the primary treatment for prematurity related apnoea*s. A
large RCT has shown that caffeine is safe to use in preterm infants, reduces
the incidence of bronchopulmonary dysplasia and improves long term outcome.

Caffeine is standard treatment in infants born <30 weeks of gestation, with the
first dose administered either in the delivery room or in the NICU. Some NICU
centres recommend to start caffeine right after birth as, it is possible that
there is a direct effect and stimulate breathing at birth. In this way the
stimulated breathing effort has the potential to increase the chance for a
smoother transition at birth.

When caffeine has a direct effect at birth and improves respiratory effort,
then this treatment could have the potential to decrease the chance that
preterm infants show respiratory failure during transition. The benefit of this
is that ventilation during the most vulnerable period, directly after birth,
could then be avoided and less lung injury would occur.

Although there are a few studies reporting the effect of caffeine on
respiratory effort, so far no data has been published reporting the direct
effect and also there are no studies describing the effect on respiratory
effort at birth. We wish to perform a pilot study to investigate the effect of
caffeine on the respiratory effort of preterm infants at birth. The results of
this study will be used for generating hypothesis/rationale for a larger
randomized study with a primary clinical outcome.

To investigate the direct effect of caffeine on the respiratory effort of the
preterm infant at birth.

Randomized study

All measurements are observational and will not influence the treatment of the
neoanate. Giving Caffeïne directly after birth or on the unit is according to
protocol. Only the timing of administering Caffeïne will be randomized.
Therefore the burden and risks are mnimal.