ABCA3 deficiency presenting as persistent pulmonary hypertension of the newborn.

A newborn with persistent pulmonary hypertension (PH) unresponsive to conventional therapies was found to be homozygous for a mutation in the gene encoding adenosine triphosphate binding cassette protein, member A3 (ABCA3). Most causes of PH respond to lung recruitment, inhaled nitric oxide, and hemodynamic support. When PH is prolonged and does not respond to standard therapies, genetic causes of surfactant abnormalities should be considered in the differential diagnosis.

Echocardiographic outcome of infants treated as newborns with inhaled nitric oxide for severe hypoxemic respiratory failure.

OBJECTIVE: To determine the cardiovascular outcome of a group of term newborns treated with inhaled nitric oxide (iNO) for severe hypoxemic respiratory failure with associated persistent pulmonary hypertension. STUDY DESIGN: We performed echocardiographic evaluations in 40 survivors treated for severe neonatal hypoxemic respiratory failure. Each of the 40 had at least 2 follow-up echocardiograms at 3 or 6 and 24 months. These studies were compared with echocardiograms done in infants in a normal, age-matched control group. RESULTS: Three of 31 infants met echocardiographic criteria for pulmonary hypertension at the 3-month examination. Two of the 3 had associated structural heart disease (1 with an atrial septal defect and 1 with a ventricular septal defect). At 24 months only 1 patient had pulmonary hypertension. This infant had an atrial septal defect that was surgically closed shortly after the 24-month echocardiogram because of the pulmonary hypertension. Group comparisons of 3- and 24-month echocardiographic variables showed no differences between the study and control groups. In the 31 infants in whom serial studies were completed, expected age-related changes were demonstrated between the 3- and 24-month examinations. CONCLUSIONS: The incidence of residual pulmonary hypertension in infants treated as newborns for severe hypoxemic respiratory failure is low. The group at highest risk is those with structural heart disease.

Inhaled nitric oxide in term infants with hypoxemic respiratory failure.

OBJECTIVE: To determine whether inhaled nitric oxide (NO) administered during conventional mechanical ventilation could produce improvements in oxygenation and reduce the incidence of meeting extracorporeal membrane oxygenation (ECMO) criteria in infants with hypoxemia. DESIGN: Prospective, randomized, controlled trial. Enrolled infants were assigned to conventional treatment with or without adjunctive inhaled NO. Control infants meeting failure criteria (partial pressure of arterial oxygen (PaO2)<80 mm Hg (10.7 kPa)) were allowed to cross over. Caregivers were not masked to group assignment. SETTING: Neonatal intensive care units at the University of Alabama Hospital and the Children's Hospital of Alabama, October 1993 to May 1994. PATIENTS: Newborn infants, both term and near-term, with PaO2 less than 100 mm Hg (13.3 kPa) who were receiving mechanical ventilation with 100% oxygen. Exclusion criteria included major congenital anomalies, diaphragmatic hernia, profound asphyxia, and significant bleeding. INTERVENTIONS: Inhaled NO was initiated in the NO group at a dose of 20 to 40 ppm and advanced stepwise to 80 ppm if PaO2 remained less than 100 mm Hg (13.3 kPa). OUTCOME MEASURES: Primary outcome variables were treatment failure and meeting of ECMO criteria before crossover. Improvement in oxygenation and ultimate use of ECMO or high-frequency oscillatory ventilation were secondary outcome variables. RESULTS: Seventeen neonates with hypoxemia were enrolled; 16 had echocardiographic evidence of pulmonary hypertension, and eight had extrapulmonary shunting. At 1 hour of treatment, two infants in the NO group responded with increases in PaO2 of more than 100 mm Hg (13.3 kPa); after crossover, two had increases in PaO2 of more than 10 mm Hg (1.3 kPa) and one control infant had an increase in PaO2 of more than 10 mm Hg (1.3 kPa). All control infants met failure criteria and crossed over to receive NO; two had increases in PaO2 of more than 10 mm Hg (1.3 kPa) with NO treatment. Despite initial responses, all subjects in both groups eventually met failure criteria. There were no differences between groups in primary outcome variables. CONCLUSIONS: Although inhaled NO produced a transient improvement in oxygenation in some infants, it did not reduce the incidence of meeting ECMO criteria in this population.

Early changes in the neonatal circulatory transition.

To define the course of neonatal circulatory transition and to identify clinically relevant echocardiographic measurements in the diagnosis of persistent pulmonary hypertension, we prospectively studied 32 healthy term infants from 30 minutes to 24 hours after birth with color and quantitative Doppler echocardiography on the first day of life, and compared them with 33 term infants supported by mechanical ventilation for respiratory failure. Color Doppler imaging included measurements of cardiac output, left pulmonary artery flow, aortopulmonary pressure difference, ductal flow, left-to-right color-flow jet area of the ductus arteriosus, and ductal flow characteristics. In healthy infants the majority of measurable changes in cardiopulmonary hemodynamics had occurred by 8 hours after birth, although some degree of right-to-left ductal shunting was found up to 12 hours after birth. In the infants with respiratory failure, ductal flow and maximum aortopulmonary pressure difference measurements at 8, 12, and 24 hours showed a significant delay in ductal closure and a high incidence of persistent pulmonary hypertension, which correlated well with the severity of their respiratory failure. Factors such as aortopulmonary pressure difference, prolonged right-to-left shunting with decreased left pulmonary artery flow, and failure to develop a left-to-right ductal color-flow jet were found to be practical markers for assessing the course of neonatal circulatory transition in sick term infants.

Clinical responses to prolonged treatment of persistent pulmonary hypertension of the newborn with low doses of inhaled nitric oxide.

We studied the efficacy of low-dose nitric oxide inhalation in nine consecutive patients with severe persistent pulmonary hypertension of the newborn (PPHN) who were candidates for extracorporeal membrane oxygenation (ECMO). All patients had marked hypoxemia despite aggressive ventilator management and echocardiographic evidence of pulmonary hypertension. Associated diagnoses included meconium aspiration syndrome (3 patients), sepsis (3 patients), and congenital diaphragmatic hernia (2 patients). Infants were initially treated with inhaled nitric oxide at 20 ppm for 4 hours and then at 6 ppm for 20 hours. In all infants, oxygenation promptly improved (arterial/alveolar oxygen ratio, 0.077 +/- 0.016 at baseline vs 0.193 +/- 0.030 at 4 hours; p < 0.001) without a decrease in systemic blood pressure. Sustained improvement in oxygenation was achieved in eight patients treated with inhaled nitric oxide for 24 hours at 6 ppm (arterial/alveolar oxygen ratio, 0.270 +/- 0.053 at 24 hours; p < 0.001 vs baseline). One patient with overwhelming sepsis had an initial improvement of oxygenation with nitric oxide but required ECMO for multiorgan and cardiac dysfunction. We conclude that low doses of nitric oxide cause sustained clinical improvement in severe PPHN and may reduce the need for ECMO. However, immediate availability of ECMO is important in selected cases of PPHN complicated by severe systemic hemodynamic collapse.