Pulmonary Hypertension Associated with Hypoxic-Ischemic Encephalopathy-Antecedent Characteristics and Comorbidities

Abstract

Objective: To determine the characteristics of term infants with persistent pulmonary hypertension of the newborn (PPHN) associated with moderate or severe hypoxic ischemic encephalopathy (HIE).

Methods: We compared infants with and without PPHN enrolled in 2 randomized trials of therapeutic hypothermia: the induced hypothermia trial of cooling to 33.5°C for 72 hours vs normothermia, and the "usual-care" arm (33.5°C for 72 hours) of the optimizing cooling trial.

Results: Among 303 infants with HIE from these 2 studies, 67 (22%) had PPHN and 236 (78%) did not. We compared infants with PPHN with those without PPHN. The proportion of patients treated with therapeutic hypothermia was similar in PPHN and no-PPHN groups (66% vs 65%). Medication use during resuscitation (58% vs 44%), acidosis after birth (pH: 7.0 ± 0.2 vs 7.1 ± 0.2), severe HIE (43% vs 28%), meconium aspiration syndrome (39% vs 7%), pulmonary hemorrhage (12% vs 3%), culture-positive sepsis (12% vs 3%), systemic hypotension (65% vs 28%), inhaled nitric oxide therapy (64% vs 3%), and extracorporeal membrane oxygenation (12% vs 0%) were more common in the PPHN group. Length of stay (26 ± 21 vs 16 ± 14 days) and mortality (27% vs 16%) were higher in the PPHN group.

Conclusions: PPHN is common among infants with moderate/severe HIE and is associated with severe encephalopathy, lung disease, sepsis, systemic hypotension, and increased mortality. The prevalence of PPHN was not different between those infants receiving therapeutic hypothermia at 33.5°C in these 2 trials (44/197 = 22%) compared with infants receiving normothermia in the induced hypothermia trial (23/106 = 22%).

Keywords: acidosis; asphyxia; cooling; hypoxia.

Figure 1

Flow chart depicting the source of subjects and classification based the presence of persistent pulmonary hypertension of the newborn (PPHN - clinical and echocardiographic) and severity of hypoxic-ischemic encephalopathy (HIE). *one patient in the no-PPHN group did not have the severity of HIE documented and is missing from the reminder of the flow-chart.

Figure 2. (online only). Oxygenation at baseline and during 72h of intervention: PPHN (closed blue circles) vs. no-PPHN (open red squares)

Changes in F_IO₂, and arterial PO₂, at baseline and during 72 hours of intervention (based on randomization to normothermia or hypothermia) in 67 infants with PPHN (black circles) and 236 infants without PPHN (open squares). * p < 0.05 compared with no-PPHN group. Data are shown as mean ± standard deviation.

Figure 3. (online only). Acid-base balance at birth, during the postnatal period prior to intervention and during 72h of intervention

Changes in pH and PCO₂ on cord gas, first postnatal gas, baseline and during 72 hours of intervention (based on randomization to normothermia or hypothermia) in 67 infants with PPHN (blue closed circles) and 236 infants without PPHN (open red squares). * p < 0.05 compared with no-PPHN group. Data are shown as mean ± standard deviation. PCO₂ levels were not reported/collected on cord gases.