Severe Pulmonary Hemorrhage in the Premature Newborn Infant: Analysis of Presurfactant and Surfactant Eras

We undertook a case-control study of premature infants who developed clinically significant, severe pulmonary hemorrhage (PH) in the presurfactant and surfactant eras to learn more about the cause of severe PH and whether the pathogenesis of severe PH has changed with the advent of surfactant therapy. Severe PH was defined as an acute onset of severe endotracheal bleeding with an acute drop in hematocrit and the development of multilobar infiltrates on chest radiograph. Eleven premature infants from the presurfactant era population and 17 premature infants from the surfactant era population met the criteria for severe PH, all with gestational ages <32 weeks and birth weights <1,500 g (very low birth weight infants). These were each matched by gestational age, date of birth, birth order (for twins), and birth weight to 2 controls. The incidence of severe PH in infants of gestational age <32 weeks was similar in the two eras (1.8% in the presurfactant era and 3.0% in the surfactant era). Severe PH was not associated with maternal characteristics such as drug use or prenatal care, pregnancy complications, evidence of intrauterine anoxia, hyaline membrane disease, frequency of endotracheal suctioning, or patent ductus arteriosus. Premature infants suffering from severe PH in the presurfactant era required more delivery room resuscitation and had more severe early respiratory disease during the first 12 h of life as compared with their controls. However, these differences were not present in the group from the surfactant era. Infants with severe PH were more likely to have birth weights below the third percentile for gestation (severe intrauterine growth restriction). The proportion of infants receiving surfactant, and the number of surfactant doses used, did not differ between severe-PH infants and their controls in the surfactant era group. We conclude that severe intrauterine growth restriction represents a risk factor for severe PH in very low birth weight infants. The introduction of surfactant therapy has not altered the incidence of severe PH, even though it has apparently helped remove the severity of early lung disease as a risk factor. The physiological basis of severe PH requires further investigation.