Methylmalonic acidemia presenting as persistent pulmonary hypertension of the newborn.

Persistent pulmonary hypertension of the newborn (PPHN) results from disruption of the normal fetal-neonatal circulatory transition and may be associated with meconium aspiration, group B streptococcal sepsis, pneumonia, respiratory distress syndrome, congenital diaphragmatic hernia and pulmonary hypoplasia. Seventeen percent of cases are considered idiopathic since there is no identifiable cause. Although it is recognized that acidosis and hypoxia from any cause in neonates may produce pulmonary vasoconstriction and maintain pulmonary hypertension, PPHN has not been reported in inborn errors of metabolism (IEM) associated with metabolic acidosis like methyl malonic acidemia (MMA). We report the first case in the literature of MMA presenting concomitantly with PPHN. Undiagnosed IEMs, like MMA, could represent a subset of idiopathic cases of PPHN. Infants and neonates have a limited repertoire with which to respond to an overwhelming illness. Because metabolic diseases are rare, they are considered only after excluding more common causes of neonatal distress. PPHN is therefore more likely to be attributed to meconium aspiration, sepsis, pneumonia or respiratory distress syndrome than to an IEM. The advent of expanded newborn screening has made pre-symptomatic diagnosis of several IEMs including MMA possible. However, not all IEMs are identified, and in some instances, an infant who has an IEM may become ill before the results of the newborn screen become available. Early diagnosis of IEM is crucial to prevent catastrophic consequences and the awareness of an association with PPHN would lead to an aggressive search of an underlying IEM and its management.

PGE2/TXB2 imbalance in neonatal hypoxemic respiratory failure.

BACKGROUND: An imbalance of vaso-constrictor and -dilator mediators has been implicated in the pathogenesis of the pulmonary hypertension accompanying neonatal hypoxemic respiratory failure (NHRF). AIM: To characterize plasma PGE2, TXB2 and their ratio in normal newborns and in those with NHRF. METHODS: Twenty newborns with NHRF received inhaled PGE1 (IPGE1) by jet nebulizer in doses of 25, 50, 150 and 300 ng/kg/min followed by weaning. Blood for PGE2 and TXB2 assay using EIA was available in 8 neonates with NHRF prior to IPGE1. Umbilical cord arterial samples were also obtained at delivery from 10 normal newborns to serve as controls. RESULTS: Compared to normal newborns, those with NHRF had significantly lower PGE2/TXB2 ratios after controlling for preterm gestation (< 37 weeks) and postnatal age (p < 0.05). Notably, all subjects except one in the NHRF group had a value of < 1.0 (range 0.1-1.2) compared to a value of > 1.0 in all subjects in the Control group (range 1.1-5.2). CONCLUSIONS: Lower PGE2/TXB2 ratio in subjects with NHRF compared with controls reflects a predominance of vaso-constrictor activity in these patients as the basis of pulmonary hypertension. Plasma PGE2/TXB2 ratio may have important implications for the diagnosis and treatment of NHRF.

Congenital hepatic arteriovenous malformation: an unusual cause of neonatal persistent pulmonary hypertension.

Congenital hepatic arteriovenous malformations are rare anomalies, which typically present in infancy with congestive heart failure, anemia, and hepatomegaly. Morbidity and mortality is high if the condition is not recognized and treated promptly. Hepatic arteriovenous malformation associated with persistent pulmonary hypertension of the newborn has been reported in two cases in the literature. We report a neonate who was referred for management of persistent pulmonary hypertension and was subsequently diagnosed with a large hepatic arteriovenous malformation. He underwent coil embolization following which pulmonary hypertension resolved.