Characteristics of pulmonary hypertension in preterm neonates

Persistent pulmonary hypertension (PHT) of the newborn is a severe and potentially fatal cardio-respiratory complication of the transition to extrauterine life. This condition occurs mainly in term infants but raised pulmonary arterial pressures have been demonstrated in preterm infants with hyaline membrane disease. PHT in preterm infants may derive from hypoxic respiratory failure secondary to lung pathology, from pulmonary hypoplasia secondary to maternal factors such as preterm premature rupture of membranes (PPROM) and oligohydramnios or, later, from bronchopulmonary dysplasia (BPD).
Inhaled nitric oxide (iNO) has been approved for the management of PHT in newborns. However, its role in the management of hypoxic respiratory failure in preterm infants is still not clear. In fact, although effects of iNO on gas exchange, pulmonary vascular disease and inflammation have led to its use in the prevention of BPD, evidence from some clinical trials published does not support the use of iNO to decrease death or BPD in preterm infants. However, preliminary data from more recent large randomized trials may support a role for iNO in the prevention of BPD in established lung injury and in reducing neurological injury. It is important to notice that these trials were not conducted in patients with documented PHT. Therefore, the study of factors predisposing to PHT and their response to iNO may help in the management of PHT in preterm infants.
On these basis, a paediatric group in Buffalo University conducted a retrospective chart review to study prenatal and postnatal characteristics of preterm infants with documented PHT in the first 4 weeks of life and their response to iNO.
This analysis was conducted in infants <37 weeks gestational age (GA), with diagnosis of PHT in the first 4 weeks of life. Data on prenatal and postnatal characteristics, response to iNO and mortality were collected Results were compared with a non-PHT group.
Results show that low Apgar scores, PPROM, oligohydramnios, pulmonary hypoplasia and sepsis were independently predictive of PHT. It was also observed that mortality was significantly higher in the PHT group if compared to controls (26.2% versus 4.1%; p<0.0001). Low birth weight, severe intraventricular hemorrhage and male sex were significantly associated with death in infants with PHT. Thirty-seven percent (23/61) of infants with PHT were treated with inhaled NO. In this group, 65% (15/23) of preterm infants responded to iNO. Statistical analysis disclosed that infants <29-week GA had poor response to iNO and the response to iNO significantly increased with GA (P<0.02).
Taken together, the results of this study suggest that low Apgar score at 5 min, PPROM, oligohydramnios, pulmonary hypoplasia and sepsis may be associated with PHT in preterm infants. PHT was shown to be an independent predictor of mortality in preterm infants. Preterm infants (<29 weeks GA) are generally refractory to iNO, whereas infants >29 weeks seem to respond better to iNO. This information may be useful in the understanding and management of documented PHT in preterm infants.

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