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A major problem in the care of preterm infants is instability of blood pressure; high and low blood pressure occurs frequently and is associated with cranial haemorrhages and periventricular leucomalacia, while the preterm brain is still immaturely developed and vulnerable.Hypertension can be induced by activities such as crying, body movement, feeding, and therapeutic interventions, including endotracheal intubation or suctioning. 23 Hypotension is often seen during severe infection or sepsis. 24,25 Fluctuations in systemic blood pressure during mechanical ventilation have been associated with the occurrence of IVH and PVL. 25,26 Neonatal morbidity, as a result of pulmonary immaturity, intracranial events and infections in the preterm infant consequently affects morbidity later on in live.Almost 10% of all very preterm infants are diagnosed with severe handicaps before the age of five. 27 This percentage remains unchanged since 1960-1970.Around 50% of all preterm infants develop disabilities or impairments, measured at school age. [1][2][3][][5][6][7][8][9][10][11][12][13][28][29][30][31][32] Comparison with healthy term peers results in a six times higher chance on impairments. 33 Initially it was thought that these infants would overcome their developmental problems when aging.However this appeared not to be the case.These infants demonstrate difficulties with attention, behaviour, visual-motor integration, language performance and/or academic skills. 5,[30][31][32]34][35][36][37][38][39][40] Overall optimal development and performance is seen in 31% of children born in 1983 of <32 weeks gestational age and in 41% of children born in 1993. 5,30,31 Neonatal intensive care Neonatal intensive care treatment and the environment of the neonatal unit have a major impact on the infants and hence their development.Intensive care treatment and caregiving activities cause a lot of pain and (di)stress apart from environmental disturbances like noise and light.This results in periods without rest and undisturbed sleep for preterm infants.Handling a preterm infant for more than 200 times per 24 hours is not uncommon. 41Three out of four hypoxemic episodes are associated with caregiving itself. [42][3][44][45][46] Mechanical ventilation, a common treatment in the majority of these infants, is accompanied by a lot of potential stressful interventions like (re)intubation, endotra cheal suctioning, punctures, skin lesions, and the use of adhesive materials.A-synchronized spontaneous breathing known as "fighting the ventilator" is a known phenomenon, therefore, the mechanical ventilation period can be described as a very stressful and uncomforta b le period. [47][48]][49][50] Excessive handling is also a factor that encroaches upon the vulnerability of the brain.PVL and IVH are the result of impaired cerebral vascular auto regulation, which is needed to maintain adequate cerebral blood pressure when systemic blood pressure varies. 25 The number of invasive procedures infants undergo while in the NICU is staggering.A case described an infant born at 23 weeks gestation underwent 488 painful procedures during the NICU stay. 51Other reports on invasive procedures mention between two and 15 Chapter 1