A definition of the beginning of human life
The concept that the breakthrough between foetus and new-born is determined by the occurrence of a first respiratory action affects different medical fields, such as paediatrics, obstetrics and neonatology. While brain inactivity is widely accepted and acknowledged as the operative condition to decide life-end, definition of the initial extreme of human life still relies on the common, popular idea that life begins with ‘first breath’, despite the fact that several different events have been shown to take place beforehand. The mechanisms that are at the basis of the beginning of human life are expected to be multifactorial and still not well-characterized. As a consequence, the regions/structures of the brain that are needed for regular brain functioning at birth have still not been clearly or definitively identified.
WHO Guidelines consider that, rather than immediately at birth, first breath can physiologically occur up to 60 s after birth. This delay varies inter-individually, averaging to about 20 s and has been well-documented by several reports [5, 6].
This observation entails two different alternatives: either the newborn is not actually ‘alive’ in the first few seconds of extrauterine existence or human life begins with something else, an unidentified quid, a trigger that is responsible for the initial stimulation of the complex cascade that precedes and leads to first breath.
A recent paper by André and co-workers  addresses the newborn’s subjective perception of a totally new environment at birth, which is defined as the UmweltFootnote 2 by carefully and accurately identifying changes in the external surrounding. André and co-workers also highlight the existence of a significant discontinuity between the intrauterine and post-natal sensorial activities, which strongly suggests that the Central Nervous System (CNS) plays a pivotal role in the passage from one condition to the other, generating specific physiological responses that characterize human birth and ‘the beginning of human life’. Starting from what has been observed , we suggest that this quid is at the basis of an extremely rapid activation of the CNS following sensorial stimulation by the new environment. This activation of the CNS, in turn, triggers the neuro-muscular activity that is needed for first breath.
Physiological events that lead to first breath: the primacy of the Central Nervous System at birth
First respiratory action must necessarily be preceded by the clearance of the fluid from the lungs. The adrenaline-mediated activation of sodium channels on the apical pulmonary surface stops the secretion of the fluid and initiates its reabsorption . Clearance process happens simultaneously with labour, with uterine contractions that causes foetal chest wall to change, thereby driving the fluid outside the lungs. Approaching term, the release of pulmonary surfactant by alveolar cells lowers air-to-liquid interfacial tension, thereby facilitating the expansion of the lungs. All these steps start before first respiratory action and make it possible. Also, in order to take place, first breath needs active contraction of the diaphragm, which causes an expansion of thoracic cage, a dilation of intra-thoracic trachea and the movement of air into the lungs. Contraction is controlled by multiple factors and stimuli, all originating in diverse areas of the CNS, and involves many afferent and efferent neural arcs, including volitional, sensory, and biochemical inputs as well as motor outputs to respiratory muscles, facial structures, and airway effectors. All these signals are integrated, modulated and transmitted to effector organs by the brain . This explains why brain death is associated with the abrogation of autonomous breathing function. Recent clinical studies have shown that, at birth, abrupt activation of the Kölliker-Fuse pontine nucleus takes place and initiates the first inspiratory action . This happens via direct stimulation of the facial/parafacial complex that, in turn, activates the pre-Bötzinger nucleus, which is the actual activator of the diaphragm. At birth, motoneurons allow for the generation of more substantial movements of the thoracic cage that can thus be expanded to meet new breathing requirements ex utero .
Upstream of the above-mentioned well-known physiological events, the very first trigger of the activation of the brain has still not been identified nor characterized. Capability to react to sensory stimuli is key to viability of both pre-term and term newborns, as also measured by the Apgar score [12, 13]. Only when neural connections between sense organs and the cortex have been established, which corresponds with the formation of thalamo-cortical connections (23–24th GW) , does the foetus become potentially able to react to sensory stimuli and therefore viable. Moreover, based on Virginia Apgar’s method, the presence of heart rate at birth is considered as a sign of life and demands manoeuvres for resuscitation. However, after resuscitation, the presence of the capability to react to stimuli, with higher Apgar scores, establishes that the infant is improving and is likely to survive.
Significant discontinuity between the intrauterine and postnatal environment and complete novelty of the latter  suggests how the CNS, which is sensitive to the external stimulation, plays a pivotal role in the passage from one stage to the other, characterising human birth and ‘the beginning of human life’. This rapid transition opens the way to the possibility that actual trigger for fully-developed brain activation may be immediate stimuli from the Umwelt.
Evidence of a number of neurological events occurring before first breath opens the way to the primacy of the CNS at birth, due to an ‘extrauterine’ activation induced by a necessary but still undefined specific quid in the environment. This activation is expected to set the basis for the occurrence of all those specific physiological conditions that lead to events determining the influx of air in the lungs, first breath and continuous and successful extra-uterine breathing. We strongly believe that knowledge about the physiological events that occur at birth, once they have been acknowledged by the scientific community and accepted by society, would help both physicians and parents to decide whether and when to resuscitate extremely preterm infants .