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EPIDEMIOLOGY

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Definitions and Incidence

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Respiratory failure severe enough to require mechanical ventilation or other advanced respiratory support affects about 2% of all live births.1 In adult critical care, the term hypoxemic respiratory failure (HRF) defines the patient with respiratory failure and an arterial oxygen tension (PaO2) below 60 mm Hg. In neonatal intensive care, most babies with respiratory failure are preterm, while the term hypoxemic respiratory failure typically refers to the substantial subset of infants with respiratory failure that are term or near term. The term is often used interchangeably with persistent pulmonary hypertension of the newborn (PPHN), the clinical syndrome defined by the failure to achieve the normal neonatal drop in pulmonary vascular resistance (PVR) and increase in pulmonary blood flow and oxygenation. HRF or PPHN complicates a wide range of neonatal cardiopulmonary diseases and affects up to 10% of neonates who require neonatal intensive care unit (NICU) hospitalization. Timely recognition and therapy are important because of high associated rates of neonatal mortality as well as short- and long-term morbidities, including significant neurodevelopmental sequelae.

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The incidence of PPHN is not well understood. An important study from the mid-1990s estimated its prevalence at 1.9/1000 live births,2 but only included infants referred to Level III NICUs in the United States; the majority of these infants were mechanically ventilated and receiving an FiO2 (fraction of inspired oxygen) greater than 0.9. More study is needed to better understand the incidence of more moderate disease, as well as the incidence of pulmonary arterial hypertension in mildly symptomatic or even asymptomatic babies. New national initiatives to perform routine pulse oximetry screening for critical congenital heart disease may provide valuable data to address the latter.3

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General Risk Factors

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A recent case-control surveillance study sought to determine risk factors for PPHN by interviewing mothers of infants who met criteria for PPHN and matched control subjects after discharge from the hospital.4 Maternal factors that were independently associated with an elevated risk for PPHN were black or Asian maternal race, elevated body mass index (BMI) (>27), diabetes, and asthma. Neonatal risk factors included male gender, delivery by cesarean section, infants large for gestational age, and delivery before 37 weeks’ gestation or after 41 weeks.

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Genetic Risk Factors

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Unlike pulmonary hypertension, which affects adults and older children, PPHN is rarely familial, and few genetic causes have been identified. A recent single-center report described the results of rigorous genotype analysis of 88 neonates with documented PPHN.5 No differences were noted in most candidate genes, including bone morphogenetic protein receptor type II (BMPR2) and nitric oxide synthase. However, a significant association was identified in the genes for corticotropin-releasing hormone receptor 1 (CRHR1) and CRH-binding protein. Significantly increased levels of 17-hydroxyprogesterone were also noted, adding weight to the hypothesis that genetic disorders of cortisol metabolism ...

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