Cromolyn sodium prophylaxis inhibits pulmonary proinflammatory cytokines in infants at high risk for bronchopulmonary dysplasia.

An imbalance of proinflammatory cytokines such as TNF-alpha, IL-1 beta, and the neutrophil chemotactic factor IL-8 and inhibitors (e.g., soluble TNF receptors and IL-1ra) in the lung during the first week of life may contribute to prolonged pulmonary inflammation and fibrosis in bronchopulmonary dysplasia (BPD). Disodium cromoglycate (DSCG) has anti-inflammatory effects in asthma, a disease with many similarities with BPD. In a prospective, randomized, blinded study, we examined whether early DSCG therapy inhibits proinflammatory cytokines in infants at risk for BPD. Twenty-six infants who were identified as high risk (> or = 75% probability) for oxygen-dependency at 28 d by a 12-h predictive score and survived 48 h were randomized to nebulized DSCG 20 mg (n = 13) or 2 cc NS (control, n = 13) every 6 h from Day 3 to Day 28. Lung lavage was collected on Day 3 (pre-study) and Day 7 and analyzed for cell count and differential and TNF-alpha, sTNFR1, sTNFR2, IL-1 beta, IL-1ra, and IL-8 concentrations. The groups' pre-study lavage cytokine concentrations were similar, but TNF-alpha and IL-8 concentrations were 3.6- and 4.9-fold lower in the DSCG group on Day 7 compared with levels in the control group. Soluble TNF receptors were unaffected by DSCG. There was a trend towards lower IL-1 beta levels in DSCG-treated infants on Day 7, but IL-1ra levels were unaffected by DSCG therapy. Three control subjects, but no DSCG-treated infants, died during the study period (p = 0.07). There were no significant differences between survivors of the two groups for oxygen-dependency at 28 d (100% control subjects; 85% DSCG). These results suggest that nebulized DSCG may exert an anti-inflammatory effect in the lungs of infants < or = 1,000 g at risk for BPD.

Symptomatic subarachnoid hemorrhage in the term newborn.

A review of the medical records of 35 term newborn infants with confirmed subarachnoid hemorrhage was undertaken to examine etiologic, clinical, laboratory, and neurodevelopmental aspects of this lesion. The most common clinical presentation was convulsive activity (69%), followed by apnea (23%), and bradycardia. Thirty-one of these infants (89%) survived, but only 16 (52%) were felt to be neurologically normal at latest evaluation. Outcomes appeared to be similar regardless of whether the presumed etiology was hypoxic-ischemic or traumatic. Six surviving infants (19%) developed post-hemorrhagic hydrocephalus, but in three of these there was a delayed presentation well beyond the neonatal period. Symptomatic subarachnoid hemorrhage in the term newborn may be a more serious event than previously believed. Close neurodevelopmental follow-up and surveillance for hydrocephalus is warranted.

Follow-up of infants treated with extracorporeal membrane oxygenation for newborn respiratory failure.

Follow-up studies were conducted to assess the medical and developmental outcome of 92 infants treated with extracorporeal membrane oxygenation at the University of Michigan. Of 118 near-term (greater than 34 weeks' gestation) infants who received extracorporeal membrane oxygenation, 103 (87%) were surviving and available for follow-up at between 1 and 7 years of age. Ninety-two of these children were seen on at least one occasion. Each visit included a history and physical examination, an evaluation by a physical therapist, and developmental testing by a pediatric psychologist. Medical outcome during year 1 found 31% of the children rehospitalized, primarily with respiratory illness. Outpatient-treated lower respiratory tract illness was seen in an additional 31% of the children. New or nonstatic neurologic problems were noted in 6% of the children. Abnormal growth during year 1 occurred in 26% of the children. At last clinic visit 16% of the children exhibited moderate-to-severe neurologic abnormalities, and 8% had moderate-to-severe cognitive delay. Sensorineural hearing loss occurred in 4% of children. Nine percent of the children were receiving speech and language therapy; screening tests showed that an additional 6% had speech and language delay. Overall, at last visit 16 (20%) of the children exhibited some type of handicap. A review of the literature on follow-up studies of non-extracorporeal membrane oxygenation-treated infants with persistent pulmonary artery hypertension produced an impairment rate of 18.5%. Outcome post-extracorporeal membrane oxygenation appears similar to that seen in less ill cohorts of infants treated with more "conventional" therapy. Long-term follow-up of all such infants remains essential.