Black lung persistent pulmonary hypertension of the newborn

Discussion

In this study we documented black lung PPHN in 10 term or near term infants who had respiratory, cardiac, and echocardiographic manifestations of PPHN. In addition, all these babies had severe hypoxemia without respiratory distress and with normal “well aerated lungs” demonstrated on chest x-rays. Therefore, these infants were labeled as black lung PPHN. Neonatal PPHN is rare and known to affect 1 or 2 infants per 1000 live births.1,2 Typically, neonatologists face cases of PPHN secondary to underlying lung pathology with severe respiratory failure that requires intubation and mechanical ventilation. If left untreated, PPHN may lead to death. In this case series, we report persistent pulmonary hypertension of the newborn in 10 infants who had normally aerated black lungs. All cases were term and near term with mean gestational age of 37.6 ± 2, which may rule out the risk of surfactant insufficiency, leading to PPHN in preterm infants.4 Antenatal exposure to non-steroidal anti-inflammatory medication and serotonin reuptake inhibitor causing premature closure of PDA was reported as a cause of PPHN.5

In such a series, only 4 out of 10 mothers had received aspirin during pregnancy, but no evidence of premature duct closure was observed. Chambers et al5 have demonstrated that non-steroidal anti-inflammatory drugs, such as ibuprofen and naproxen are frequently found in meconium of infants suffering from PPHN (even with a negative maternal history).5

Furthermore, concentration of the drugs in the meconium correlated with the incidence and severity of idiopathic PPHN. The meconium drug levels were not measured in this series due to the lack of this facility. All cases were presented with cyanosis and low oxygen saturation, along with 3 out of 10 mild or no respiratory distress, as well as mild metabolic acidosis in 6 out of 10 with a mean PH of 7.16, raising the possibility of right out flow obstruction groups of cyanotic congenital heart lesion. However, this possibility was excluded by echocardiographic findings in our patients.

Real-time echocardiography combined with Doppler flow studies remain to be gold standards for diagnosing PPHN demonstrating an increase in pulmonary pressure more than mean systemic blood pressure and right-to-left shunting across a patent foramen oval and a ductus arteriosus with Tricuspid insufficiency. Evan et al6 reported a same range of results in term of neonates with hypoxic respiratory findings.

The other striking findings reported by Evan et al6 indicated no correlation between pulmonary blood pressure level and the degree of hypoxemia. There was no significant relation observed during the mode of delivery, Apgar score, gender, and birth weight in this series. Unlike infants with idiopathic PPHN, all our patients had risk factors and underline diagnoses. Forty percent of our patients have DS. This agrees with the findings of the prospective study of a birth cohort of children with DS born between 2003 and 2006 in the Netherlands, which reported an incidence of 5.2% of PPHN in DS, that was significantly higher than the general population (p<0.001).7 Similarly, another retrospective study8 conducted in Columbus children hospital, Ohio State, concluded that DS has 10 times increase incidence of PPHN as compared with historical controls of pediatric population regardless of baseline demographics.8 Similar to previous studies on PPHN in DS, we demonstrated that our patients with DS had translucent well aerated lungs. Four of our patients in this cohort were infants of diabetic mothers who had no other predisposing factors for PPHN, such as birth asphyxia or meconium aspiration. However, all these 4 neonates were male infants born by elective cesarean section, that had been reported by Hernandez-Diaz et al9 as independent factors associated with an elevated risk of persistent pulmonary hypertension of the newborn.

Various other risk factors were known to influence susceptibility of the high-altitude city on post natal pulmonary vascular adaptation. It may lead to PPHN and defect in oxygenation. This effect had been documented in literature with some ethnic groups and in animal studies.10,11 The prognosis of our patients was excellent, as 9 cases responded to oral sildenafil. This has also been proved in the previous literature to be a standard therapy for PPHN.12,13 The dose ranged from 0.3-1 mg/kg/dose every 6-8 hours. Our patients weaned from oxygen supply over 10 to 14 days with no major side effects. Only one infant in our cohort required INO together with mechanical ventilation. Inhaled nitric oxide is considered as a standard of care for infants with severe PPHN. However, this intervention requires well equipped neonatal unit with well trained staff. This may not be widely available in a big country such as in the Kingdom of Saudi Arabia. The limitations of this study include its retrospective nature and the relative small number of infants included.

In conclusion, the main risk factors included down syndrome and infants of diabetic mothers, especially male infants born through cesarean section. This study offered an insight into the etiology and predisposing factors to black lung PPHN in Saudi patients. The prognosis of our cohort was excellent with the use of oral sildenafil. Therefore, this study provides further evidence that the use of sildenafil in infants with black lung PPHN is effective and may be tried especially when inhaled nitric oxide is not available.