Page 150 - Physiological based CPAP for preterm infants at birth Tessa Martherus

General discussion
provided insight in how the PB-CPAP approach can be improved when studied in future studies.
Future perspectives
This thesis provided the scientific rationale to base the CPAP strategy following the physiological changes at birth. We also provided the first steps in clinical use but more studies are needed before PB-CPAP can be recommended for standard care during resuscitation at birth.
Preclinical studies may further expose the underlying mechanisms and indicate if more changes are needed to improve PB-CPAP. These studies may explore the effect of CPAP levels on laryngeal function, how this changes throughout the transition and which reflexes can be triggered during PB-CPAP.
Future studies could also focus on an optimal approach to decrease CPAP levels during PB-CPAP. In this thesis we found that decreasing CPAP too soon increases the FiO2 requirement (Chapter 4) but decreasing CPAP levels too late may increase the risk of adverse events (Chapter 1, 2). In our clinical trial (Chapter 5), the PB-CPAP approach involved many predefined evaluations and changes in CPAP levels that were needed to ensure the optimal trajectory for CPAP decrease. As caregivers indicated that the approach was too difficult to execute (when combined with standard delivery room care), we learned that PB-CPAP should also consider feasibility. Future studies may find the optimal PB-CPAP approach and decrease in CPAP levels that considers both effectiveness and feasibility.
Automatization of respiratory support would be a good alternative instead of simplifying the PB-CPAP approach. Algorithms could be developed and based on parameters 1) iPPV would be applied instead of CPAP, automatically decreasing the CPAP/PEEP level and 2) CPAP would be decreased after lung aeration.
Clinical trials may meanwhile investigate our proposed simplified PB-CPAP approach. Larger trials could further explore the potential benefits and allow us to make appropriate conclusions on the potential adverse events. In these future trials, we should reconsider measuring heart rate using pulse oximetry. This measuring technique is only accurate if sufficient cardiac output is established to facilitate adequate peripheral tissue perfusion. As the increase in cardiac output at birth is dependent on the establishment of aeration (43) and PB-CPAP improve aeration and subsequent cardiac output, groups may have an unbalanced timeframe wherein heart rate is underestimated. Therefore, we should consider devices that monitor heart rate more accurately.
In recent years, small clinical trials have studied interventions that stimulate and support spontaneous breathing e.g. repetitive tactile stimulation (8), caffeine (9), FiO2 levels (10) and now PB-CPAP (Chapter 5). While these studies demonstrated potential benefits, all interventions require further evaluation in a larger trial. Because of the low incidence of
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