Controlled trial of dexamethasone in neonatal chronic lung disease: an 8-year follow-up of cardiopulmonary function and growth.

AIM: To evaluate the long-term effects of postnatal dexamethasone treatment in high-risk infants of very low birthweight. METHODS: The study included 16 children aged 7.8 to 9.2 y who had been born very prematurely at gestational ages of 24-29 wk and with birthweights of < 1500 g and who had participated in a randomized study of dexamethasone or placebo treatment in ventilator-dependent infants at 10 d of age. Flow-volume spirometry, impulse oscillometry, skin-prick tests and Doppler echocardiography were carried out at school age, and respiratory morbidity and overall neurological outcome evaluated. Controls were 18 non-atopic children born at term, tested for lung function. RESULTS: No significant differences were found in respiratory morbidity at school age between the dexamethasone (n = 8) and placebo (n = 8) groups. Six of the 16 children had moderate to severe neurosensory impairments, but all were able to walk without support and attended primary school. In prematurely born children, standardized height was significantly less than that in controls, but between the two study groups, no significant differences existed in somatic growth. Atopy was uncommon: skin-prick tests were positive in only one child in the placebo group. In the dexamethasone group, forced vital capacity adjusted to height was significantly higher than that in the placebo group, but impairment of basic lung function and bronchial obstruction was evident in both study groups. No hypertrophic cardiomyopathy was apparent, and non-invasive measurements of pulmonary arterial pressure did not reveal any significant difference between the study groups. CONCLUSION: In very low-birthweight children, high respiratory morbidity and neurological impairment continued until school age. Neonatal dexamethasone treatment at school age was not associated with any detectable adverse effects on somatic growth, or pulmonary or cardiac function.

Lung function measured by the oscillometric method in prematurely born children with chronic lung disease.

Premature birth is related to a chronic respiratory morbidity, which may persist until school-age. In these children, the forced oscillation technique would be suitable for evaluation of lung function even at preschool age, since it requires only minimal patient cooperation. In order to investigate the oscillometric findings related to premature birth, using the oscillation technique and conventional lung function methods 49 school-aged children born prematurely with (n=15) or without (n=34) chronic lung disease (CLD), and 18 healthy children born at full term were studied. Children with CLD had higher respiratory resistance (Rrs,5) and lower reactance (Xrs,5) than prematurely born children without CLD or healthy controls. Both Rrs,5 (r=-0.55, p<0.0001) and Xrs,5 (r=0.76, p<0.0001) were significantly associated with forced expiratory volume in one second (FEV1), the agreement with spirometry being better in Xrs,5 than in Rrs,5 (p=0.02). Rrs,5 was significantly related to airway resistance (Raw) measured by body plethysmography (r=0.63, p<0.0001), but underestimated resistance at high values of Raw. There was no significant relationship between the pulmonary diffusing capacity and the oscillometric findings. Compared to conventional methods, the oscillometric method yields concordant information on the severity of lung function deficit in children born prematurely, with or without chronic lung disease. In these children, the oscillometric findings are probably due to peripheral or more widespread airway obstruction. As conventional methods are not usually suitable for preschool children, oscillometry may serve as an alternative for early evaluation of chronic lung disease among children with premature birth in clinical or research settings.

Smith-Lemli-Opitz syndrome and other sterol disorders among Finns with developmental disabilities.

Smith-Lemli-Opitz syndrome (SLOS) is an inherited disorder of cholesterol metabolism in which 7- and 8-dehydrocholesterols are accumulated in blood and tissues. Diagnosis of SLOS and other disorders in cholesterol metabolism (eg, cerebrotendinous xanthomatosis, phytosterolemia, desmosterolosis, and X-linked dominant Conradi-Hünermann-Happle syndrome) can be performed by gas-liquid chromatographic analysis of serum sterols. To elucidate their involvement in developmental disability, we evaluated serum sterols in two study groups: developmentally disabled subjects in long-term care (N = 322) and newborns and young children (N = 49) with features of SLOS in the Finnish population of 5 million. Only 1 SLOS case (type II) was found from among the 49 children. Seven additional adult cases (type I) with a wide range of clinical features and the serum sterol abnormalities characteristic of SLOS were detected from among the developmentally disabled subjects. The frequency of SLOS in the latter group was relatively high (7 in 322). No other hereditary sterol disorders were found, but two subgroups with low serum cholesterol precursor sterols and high serum plant sterols were identified. Several subjects, including the 7 SLOS patients, used ample medication and had abnormalities in serum sterol concentrations. Thus, among the subjects taking melperone, a high serum delta8-cholestenol level suggests an interference by the drug with cholesterol synthesis. Our results emphasize the importance of analyzing the serum sterols of developmentally disabled subjects to diagnose SLOS and of finding putative undiagnosed disorders in sterol metabolism associated with these clinical conditions.