*2.3.1 Patent ductus arteriosus*

Up to 80% of ELBW infants have a clinically significant patent ductus arteriosus (PDA). As a consequence of the left-to-right systemic to pulmonary shunting various symptoms may appear, most notably, systolic murmur, hypotension, bounding pulses, decreased urine output, pulmonary hyperemia and edema, as well as and reduced mesenteric and cerebral perfusion [29]. Contrary to term newborn who exhibit spontaneous ductus closure in 90% at 48 hours, it occurs in only 30 to 35% of infants with BW < 1000 grams during the neonatal period [29].

The diagnosis is set by echocardiography, also Doppler ultrasound of the cerebral blood vessels in search for signs of diminished perfusion. Ideal management of the PDA in premature infants is still a topic of debate, despite more than three decades of active study [29, 30]. Indomethacin was the conventional drug of choice for ductus closure, but concerns regarding its negative effects on cerebral, renal and gastrointestinal perfusion have led to investigation of other agents such as ibuprofen [30]. A 2020 Cochrane review concluded equal effectiveness of ibuprofen and indomethacin in closing a PDA. However, in the light more favorable safety profile, ibuprofen was highlighted the drug of choice with an equal effectiveness of orogastric and intravenous administration [31]. Oral paracetamol was also supported by clinical studies as equally potent drug for ductus closure [32]. Surgical ligation should only be considered in the light of failed medicaments' treatment [17].

#### *2.3.2 Variable hemodynamics*

Blood pressure (BP) of preterm newborns is marked with wide range of observed values for every GA. It is generally accepted that lower BP values are seen with decreasing gestational age and birth weight. Usually, mean arterial blood pressure corresponds to the gestational age, but this relationship is less clear for the extremely premature infants [33]. The variations in BP are related to dynamic changes in physiology during neonatal transition and various disease processes in this group of patients. It has not been proven that institution of any kind of anti-hypotensive therapy, fluid bolus or dopamine could significantly influence the rise of BP 4–24 hours after birth. Therefore, it has been suggested not to rely on a single numerical BP cutoff value for predicting infants that could benefit from anti-hypotensive treatments [33].

Recent randomized controlled trial could not show differences in hemodynamic parameters, amplitude integrated EEG variables, clinical complications or brain ultrasound findings between groups of active, moderate or permissive BP treatment of patients ≤29 GW [34]. The last composite guideline for management of neonatal respiratory distress syndrome recommends treatment of hypotension when evidenced by signs of poor tissue perfusion such as oliguria or poor capillary return, rather than treating sole numerical values [17]. Dopamine has been found more efficient than dobutamine for treatment of systemic hypotension in preterm infants, while dobutamine and epinephrine could be opted for treatment of reduced ventricular function [35]. Hydrocortisone is an alternative medicament for treatment of hypotension in extremely preterm infants [36].

Hypovolemic shock should be managed by giving non-cross-matched O-Rhesus-negative blood or alternatively by administering an isotonic crystalloid solution; the proposed dose is 10–20 mL/kg [37]. Delayed cord clamping apart from expanding blood volume, was proven in clinical studies to yield multiple potential benefits for preterm infants such as improved neurodevelopmental outcomes, reduced blood transfusions, possible autologous transfusion of stem cells, and reduced incidence of intraventricular hemorrhage [38]. However, in infants who need immediate resuscitative measures, it is recommended that placental transfusion should be discontinued [37].

#### **2.4 Central nervous system problems**

Intraventricular hemorrhage (IVH) is an extravasation of blood in the brain that originates from the subependymal germinal matrix and advances into the ventricular system, most frequently occurring in the first 3 days of life [39]. The classical grading system of the extent of cerebral bleeding includes 4 grades of hemorrhages: grade I - confined to the germinal matrix, grade II – progression to the lateral ventricle without ventricle dilatation, grade III – blood in the ventricle results in ventricular dilatation, grade IV – periventricular hemorrhagic infarction. Our study group reported an incidence of IVH in almost a third of the ELBW cohort [12]. An inverse relationship exists between the incidence and severity of IVH and gestational age; the lowermost gestations and weights are most heavily affected.

IVH has been recognized as one of the crucial morbidities in ELBW infants, with serious potential short-term sequelae in survivors such as hemorrhagic periventricular infarction, post-hemorrhagic hydrocephalus or seizures, and in the long term, developmental delay, cerebral palsy, deafness, and blindness. [40]. A shift to milder forms of neurosensory impairment has been noted reflecting better practices in perinatal care [41]. Generally, a straightforward correlation exists between the IVH grade and its prognosis. However, close neurodevelopmental follow-up is also

#### *The Extremely Low Birth Weight Infant DOI: http://dx.doi.org/10.5772/intechopen.96921*

required for infants assigned to grades I and II IVH. Associations have been found between low-grade hemorrhages and reduced cortical volume at near term age [42]. Likewise, adverse neurodevelopmental outcomes for grades I and II IVH have been observed in follow up studies [41]. Forty four percent of ELBW children with grades III and IV intracranial hemorrhage present with disabling cerebral palsy (CP), and 45–85% of children with grade IV intracranial hemorrhage have mental retardation and CP at school age [43].

Periventricular leukomalacia (PVL) is damage to the periventricular white matter developed as a result of perinatal adverse insults such as hypoxia, hypo or hyper-perfusion, hypocarbia and chorioamnionitis combined with the defective cerebral vascular autoregulation in preterm infants. The estimated incidence of PVL is 4–15% in ELBW babies. We demonstrated an incidence of 19% in our ELBW cohort [44]. While strong correlation has been observed between diffuse cystic PVL and cerebral palsy, the clinical correlates of diffuse white mater injuries and localized cysts are not so clear-cut and might be related to a spectrum of behavioral/cognitive deficits [43].
