Wheezing illness and re-hospitalization in the first two years of life after neonatal respiratory distress syndrome.

OBJECTIVES: To determine the impact of respiratory distress syndrome (RDS) on wheezing illnesses and re-hospitalizations in children as old as 2 years of age. STUDY DESIGN: We observed 2 geographically defined cohorts of children with RDS born after 26 weeks of gestation during 1990 to 1995 and 1996 to 1999 and gestationally paired control subjects. Recurrent wheezing illness and the re-hospitalizations caused by a respiratory condition were recorded. RESULTS: In the first year of life, 47 of 224 infants with RDS and 18 of 224 control subjects born in 1990 to 1995 had recurrent wheezing illness (P <.005) compared with 21 of 109 infants with RDS and 14 of 109 control subjects in the latter cohort (P=.27). A higher number of infants with RDS were readmitted to the hospital (25% versus 13%, P=.002) in the former period, and they spent more days in hospital during both periods. The frequencies of wheezing remained constant in the second year of life, but hospital admissions decreased. Siblings at home, male sex, and bronchopulmonary dysplasia were additional risk factors of wheezing illnesses. CONCLUSION: RDS increases the incidence of wheezing illnesses during the first 2 years of life. Changes in the management of RDS during the 1990s was associated with a decreased incidence of subsequent RDS-associated respiratory morbidity.

Marked variation in oxycodone pharmacokinetics in infants.

BACKGROUND: The pharmacokinetics of oxycodone (13-hydroxy-7,8-dihydrocodeinone) has been studied in adults and in children who are older than 6 months but there is no information on the disposition of oxycodone in neonates and young infants. The aim of this study was to study the pharmacokinetics of oxycodone in infants varying in age from 0 to 6 months. METHODS: Twenty-two infants undergoing surgery were given postoperatively an intravenous bolus of 0.1 mg.kg(-1) of oxycodone hydrochloride. Ten of the patients were younger than 1 week (group 1), six from 1 week to 2 months (group 2) and six from 2 to 6 months (group 3). Plasma samples were collected for the analysis of oxycodone concentrations up to 24 h. Pharmacokinetics were characterized by noncompartmental methods. RESULTS: The median (range) values for the clearance (Cl) were 9.9 (2.3-17.2), 20.1 (3.7-40.4) and 15.4 (14.8-80.2) ml.min(-1).kg(-1) in the above three groups. The values for volume of distribution at steady-state were 3.3 (1.9-4.7), 5.6 (1.3-8.5) and 3.2 (1.8-6.0) l.kg(-1) and for elimination half-life (t(1/2)) 4.4 (2.4-14.1), 3.6 (1.6-11.6) and 2.0 (0.8-3.9) h, respectively. Both Cl (r = 0.46) and half-life (r = -0.46) were correlated to the age of the patient (P < 0.05). There were 13 patients who were on mechanical ventilation at the time of oxycodone administration. None of the spontaneously breathing infants had hypoventilation which required assistance during the study. CONCLUSIONS: The values for Cl and t(1/2) varied greatly between the subjects. This variability was most pronounced in the two youngest groups. Routine dosing of oxycodone in young infants may be dangerous. The dose of oxycodone must be titrated individually.

Surfactant protein A gene locus and respiratory distress syndrome in Finnish premature twin pairs.

BACKGROUND: Surfactant protein A (SP-A) polymorphisms are associated with susceptibility to respiratory distress syndrome (RDS). According to present hypothesis the association between SP-A polymorphisms and RDS may not be applicable to the entire population of premature infants. AIM: The present study was designed to evaluate the associations between SP-A allelic variants and RDS in a population consisting of 198 premature twin pairs. METHOD: Genotype analysis of the SP-A1 and SP-A2 genes and twin zygosity definition were carried out. RESULTS: The main SP-A1 allele 6A2 (P = 0.030), genotype 6A2/6A2 (P = 0.0042) and haplotype 6A2-1A(0) (P = 0.016) were over-represented in healthy premature twin infants compared to RDS twins. The homozygous genotype 6A2/6A2 was over-represented in twin pairs of whom both were healthy compared to twins concordant for RDS (odds ratio 0.18, confidence intervals 0.06-0.6, P = 0.0016) and born between 32 and 36 weeks. 6A2/6A2 was also overrepresented in healthy twin pairs with birth weight sum higher than the median (OR 0.15, CI 0.04-0.6, P = 0.0025). CONCLUSIONS: In twins, the association between SP-A polymorphism and RDS is different from that seen in premature singleton infants. The factor associated with SP-A genotype-specific susceptibility to RDS appears to be related to the size of uterus and the length of gestation at birth.

Nitrotyrosine and NO synthases in infants with respiratory failure: influence of inhaled NO.

Inhaled nitric oxide (NO) is a selective vasodilator in pulmonary hypertension. However, the safety of inhaled NO (iNO) has not been established. Using an immunohistochemical technique, we studied the expression of NO synthase (NOS) isoforms NOS1, NOS2, NOS3, and nitrotyrosine, the marker of toxic NO-superoxide pathway, in lung specimens from autopsies. Twelve infants dying with respiratory failure had iNO up to 60 parts per million for 0.1-15 days. Twelve control infants were matched in pairs on the basis of the diagnosis, number of gestational days at birth, age at death, and whether extracorporeal perfusion was required. In addition, 5 infants who died of SIDS or nonpulmonary trauma (healthy lungs) were compared to 8 age-matched cases with respiratory failure. Immunostaining was graded by the intensity of the color deposit and the frequency in specific cells stained. Inhaled NO tended to increase NOS2 expression in bronchiolar epithelium and adjacent tissue. There were no other differences in the distribution of nitrotyrosine or NOS isoforms between iNO-treated infants and the control group with respiratory failure. All NOS isoforms were evident in the lungs studied. In severe respiratory failure, nitrotyrosine was mostly detectable in the bronchiolar epithelium and alveolar exudates, whereas in healthy lungs those sites did not contain nitrotyrosine. The alveolar tissue of infants with progressive respiratory may be affected by the NO-superoxide pathway. However, inhalation of NO was not associated with a detectable increase in oxidant stress.