Page 16 - Physiological based CPAP for preterm infants at birth Tessa Martherus

General introduction
Introduction
Although most infants are born after 37 completed weeks of gestation, 10.6% of all liveborn infants are born preterm (1). Preterm birth can be categorised, based on gestational age, into late preterm (32-37 weeks gestation), very preterm (28-32 weeks gestation) and extremely preterm (<28 weeks gestation) (2). As the mortality, morbidity and required medical assistance are all inversely related to the duration of pregnancy, infants who are born extremely preterm are affected the most and require intensive care for a long period (1, 3, 4). These extremely preterm infants are most vulnerable immediately after birth when they exchange the intrauterine environment for an air-filled environment and undergo a major transition from the fetal to newborn state. Most preterm infants require respiratory support instantly after birth, and in recent years, the respiratory support strategies provided during the neonatal transition have undergone major changes (5). To further improve these support strategies, we need to consider the underlying physiological changes that characterise the respiratory transition at birth.
The respiratory transition at birth
During pregnancy, the fetal lung is a liquid filled organ. The fetal lung produces liquid that accumulates within the airway during fetal life. The larynx is predominantly closed and liquid only leaves the lung via the trachea during brief moments of fetal breathing movements. The accumulation of liquid creates a pressure gradient between the airways and the environment, which maintains the lungs in a distended state that is crucial for lung growth and development. Indeed, the volume of liquid retained in the future airways is greater than the volume of air in an aerated lung after birth. Blood flow in the pulmonary vessels (PBF) is low as the vessels are vasoconstricted and pulmonary vascular resistance (PVR) is considerably higher than systemic vascular resistance. As the placenta functions as a low resistance pathway, a substantial part of cardiac output flows through the placenta which provides gas exchange during the pregnancy and provides a considerable part of the venous return to the heart (6-10). After birth, the placenta will be separated from the fetal circulation and the liquid-filled in utero environment will be replaced by a gaseous ex utero environment. For an infant to survive, gas exchange needs to shift from the placenta to the lungs and the airways need to be cleared of liquid to allow the entry of air and the onset of pulmonary gas exchange. Also, PVR needs to decrease and PBF needs to increase considerably, to facilitate gas exchange. This increase in PBF is also important for further cardiovascular changes that are required when transitioning from a fetus to newborn infant.
The first steps of lung liquid clearance can commence when labour starts. During the stress of active labour, the release of adrenaline and vasopressin can increase, which stimulates sodium uptake across the airway epithelium, thereby reversing the osmotic gradient and promoting liquid absorption into lung interstitial tissue (11-13). The uterine contractions during active labour can also increase transpulmonary pressure causing liquid to leave the
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