A genetic and statistical study of the respiratory distress syndrome

The hospital records of 197 infants with the respiratory distress syndrome (RDS) were reviewed and the families of 111 of them subsequently contacted to obtain a family history. After correcting for bias of ascertainment, the incidence of RDS among the full sibs was found to be between 12 and 19% depending on whether the individuals diagnosed as possible RDS were counted as affected. Among the low birth weight (LBW, 2.5 kg) and/or preterm (37 weeks gestation) infants in the sibships, the incidence of RDS was 32–50%. Considering only sibs born after the probands yielded the empiric recurrence risk of 17–27% for all younger sibs and of 39–67% for LBW/preterm younger sibs. The risk for maternal half-sibs was of about the same magnitude as that for full sibs, while the risk for paternal half-sibs was minimal. Among the LBW/preterm first cousins of probands, only the infants of maternal aunts showed an RDS incidence clearly higher than that in the general population. We think these data suggest a genetically determined maternal factor predisposing the infants of certain mothers to RDS.Other significant findings include: 1) an excess of males among the probands but a normal sex ratio among the sibs of the probands; 2) a decrease in mean birth weight and mean length of gestation for not only the probands but also their sibs; 3) a decrease in the mean parental ages at the birth of the probands; 4) a relative dearth of first-born and an excess of second-born infants among the probands; 5) an increased incidence of stillbirths in the sibships; 6) an increased number of probands born by cesarean section; and 7) a twin concordance of 75%.Supported by DHEW/USPH Grants GM20130 and GM00398 from the National Institute of General Medical Science. Paper No. 1963 from the University of Wisconsin Genetics Laboratory.     

Intracerebral haemorrhages in surfactant treated neonates with severe respiratory distress syndrome: age at diagnosis,severity and risk factors

Within a randomized European multicentre trial the time of onset, severity and progression of intracerebral haemorrhages (ICH) were investigated prospectively by serial cranial ultrasonography in 343 ventilated infants with severe respiratory distress syndrome (RDS) following instillation of single or multiple doses of a natural porcine surfactant (Curosurf). In 148/343 infants (43%) ICH was diagnosed (grade I or II: 22%, grade III or IV: 21%). In 26 cases (8%) ICH was present on the ultrasound scan prior to surfactant instillation at a median age of 6h. Incidence and severity of ICH was similar after single- or multiple-dose surfactant treatment. Using a logistic regression model the following risk factors predictive of ICH were defined: low birth weight, allocation to certain hospitals, vaginal delivery, Apgar score6, rectal temperature on admission 36°C, primary anaemia, acidosis prior to treatment, RDS grade IV in pre-treatment chest films and poor response to surfactant treatmentOur study provides supportive evidence that multiple doses of Curosurf do not increase the risk for ICH as compared to single-dose administration.A preliminary report of this work was presented at 8th International Workshop on Surfactant Replacement, Oslo, Norway, May 21 1993. The study was supported by grants of the German government (BMFT 93 607 27) and the German Research Council (Deutsche Forschungsgemeinschaft He 2072: 1–2). The surfactant used in the trial was prepared ang tested in Stockholm with the skilful technical assistance of Elin Arvesen, Bim Linderholm. Eva Lundberg, Gunhild Nilsson and Petru Popa (supported by the Swedish Medical Research Council (Project No. 3351) and Oscar II:s Jubileumsfond)Dedicated to the memory of Edgar (Eddi) Laufkötter, one of the most active trial collaborators, who died under tragic circumstances on April 10, 1994.     

High-frequency oscillatory ventilation combined with intermittent mandatory ventilation in critically ill neonates: 3 years of experience

A heterogeneous group of 45 neonates with severe pulmonary disease and inadequate gas exchange on conventional intermittent mandatory ventilation (IMV) was treated with a high-frequency oscillator combined with an IMV (HFO-IMV) system (Emerson Airway Vibrator connected to a BABYBird 1 ventilator). The mean gestational age was 33 weeks (25.5–43) and mean birth weight 2.02 kg (0.66–4.24). Primary diagnoses included respiratory distress syndrome (RDS; 23), pneumonia (12), persistent fetal circulation (PFC; 6), diaphragmatic hernia/hypoplastic lungs (4). The IMV rate was reduced from 78 to 29 BPM (P0.0005), while maintaining lower partial pressure of carbon dioxide (PaCO₂) (P<0.005) and higher partial pressure of oxygen (PaO₂) (P0.0025). Active air leaks were present in 20 infants and these infants responded most favourably to HFO-IMV. HFO-IMV failed to improve ventilation in neonates with diaphragmatic hernia/hypoplastic lungs. Complications during HFO-IMV were increased pulmonary secretions (11), worsening or recurrence of pre-existing air leaks (11), or occurrence of new air leaks (10). In 4 patients death was related to major air leak complications. Twenty-four infants died, 18 of them of a respiratory cause. Twenty-one infants finally survived. We assembled a well-tolerated system to provide HFO-IMV and to successfully ventilate neonates with severe respiratory disease, who failed to respond to conventional IMV. Initiation of HFO-IMV earlier in the course of the disease in this type of infant may improve survival.Abbreviations BPM breaths per minute - FiO₂ fraction of inspired oxygen - HFI high-frequency flow interrupter - HFJ(V) high-frequency jet (ventilation) - HFO high-frequency oscillation - HFO-IMV high-frequency oscillation combined with intermittent mandatory ventilation - HFPP(V) high-frequency positive pressure (ventilation) - IMV intermittent mandatory ventilation - P(a)CO₂ partial pressure of (arterial) carbon dioxide - P(a)O₂ partial pressure of (arterial) oxygen - Paw mean airway pressure - PFC persistent fetal circulation - PIE pulmonary interstitial emphysema - PIP peak inspiratory pressure - RDS (infant) respiratory distress syndrome     

Evaluation of surfactant function at birth determined by the stable microbubble test in term and near term infants with respiratory distress

Surfactant function using the stable microbubble test (SMT) was investigated in term or near term infants with respiratory distress. Newborn infants 34 weeks gestation with an initial clinical hypothesis of transient tachypnoea of the newborn (TTN) needing supplemental oxygen and controls were included. Gastric aspirates were collected immediately after birth for SMT. The first chest X-ray films were examined by three independent radiologists and according to their interpretation the babies were divided into a TTN, a respiratory distress syndrome of the newborn (RDS), or a poorly-defined X-ray group. A total of 32 infants with respiratory distress and 32 controls with similar gestational age and birth weight were studied. The median and interquartile range (IQR) of the stable microbubble (SMB) count was significantly lower (P<0.001) for the respiratory distress group than for the control group (17; range 6–33 versus 120; range 79–275). The proportion of babies with less than 35 stable microbubbles/mm² (SMB/mm²) was significantly different for the whole respiratory distress group (24/32–75%) and for the TTN (9/13–69%), the RDS (5/5–100%), and the poorly-defined (10/12–83%) groups as compared with the controls (2/32–6%; P<0.05). A total of 24/26 babies (92%) who needed oxygen for 24 h but only 1/6 (17%) of them who needed <24 h had a bubble count of less than 35 SMB/mm² (P<0.05). Conclusion: the results suggest that deficiency or dysfunction of the surfactant system is involved in the majority of cases of respiratory distress in near term and possibly term babies. The stable microbubble test can enable clinicians to take an earlier decision to give surfactant to term or near term infants with more severe and progressive respiratory distress.Abbreviations RDS respiratory distress syndrome of the newborn - SMB stable microbubbles - SMT stable microbubble test - TTN transient tachypnoea of the newborn     

Histomorphometric Analysis of Postnatal Glomerulogenesis in Extremely Preterm Infants

Until now oligonephropathy to indicate too few nephrons has been associated with intrauterine growth restriction and experimentally induced abnormalities of renal development. The purpose of this study was to determine whether there is evidence of abnormal postnatal glomerulogenesis in extremely low birth weight preterm infants. Renal autopsy tissue was studied by computer-assisted morphometry from 56 extremely premature infants (birth weight 1000 g) and 10 fullterm infants as controls. Preterm infants were divided into two groups (short survival < 40 days vs. long survival 40 days). Each group was subdivided into those with renal failure (RF) and those with normal renal function. Forty-two of 56 preterm infants (75%) were adequate for gestational age. Glomerulogenesis as measured by radial glomerular counts (RGC) was markedly decreased in all preterm infants as compared to term controls and correlated significantly with gestational age (r = 0.87; P < 0.001). Active glomerulogenesis with basophilic S-shaped bodies was absent in longer surviving preterm and all term infants. RGC of preterm infants surviving 40 days with RF were significantly less than RGC of those with long survival and no RF (P < 0.001). Only this latter group demonstrated increased glomerular size as measured by mesangial tuft area and Bowmans capsule area compared to all other groups (P < 0.001). The kidney continues to form postnatally in preterm neonates, but glomerulogenesis ceases after 40 days. Moreover, it is further inhibited by RF. Compensatory mechanisms in longer surviving preterm infants include glomerular hypertrophy and mesangial proliferation that could lead to hyperfiltration.     

Intraesophageal pressure monitoring and the severity of respiratory distress syndrome

The intraesophageal pressure difference (P _es) was measured in 46 preterm infants, 36 with respiratory distress (RDS). It was 12.7±2.9 mm Hg (mean±SEM) in severe RDS, 9.6±3.2 mm Hg in moderate RDS, and 5.2±1.6 mm Hg in infants with mild disease, measured at the age of 8 h. These intergroup differences were highly significant (P<0.001). During the first 96 h of life the P _es decreased to 6.1±1.1 mm Hg in severe RDS and to 4.8±1.2 mm Hg in moderate RDS. These changes were also highly significant (P<0.001) when compared with respective initial values. In infants with mild disease and in healthy preterm infants, the P _es did not alter significantly during the first 96 h of life.The correlations between gastric aspirate L/S ratio and the P _es at the age of 8 h (r=-0.65, P<0.001) and at the age of 24 h (r=-0.73, P<0.001) were highly significant.It is concluded that intraesophageal pressure monitoring is a valuable tool in the intensive care evaluation of the severity of RDS.Supported by grants from the Foundation for Paediatric Research and from the Medical Research Council, Academy of Finland     

Reduction of mortality rate in premature infants by substitution of thyroid hormones

Our previous examinations had shown that 9 of 13 premature infants with severe respiratory distress had hypothyroid T4-values. On the basis of these results a prospective study was initiated. Every second neonate born after less than 37 weeks gestation or weighing less than 2200 g and admitted to our intensive care unit since Janary 1979 received a prophylactic dose of 25 g l-Thyroxine and 5 g Tri-iodothyronine daily. Five of the patients inadvertently did not receive the drug and were included in the non-treated group which thus numbered 55. Both groups were nearly identical with regard to gestational age, birth weight and Apgar score.In the treated group of 45 infants three (=6.6%) died. In the untreated group of 55 infants 16 (=29%) died. The probability that the different mortality in the two groups was due to chance alone is less than 0.5% (²-test: P<0.005). In 14 of the 55 non-treated patients transient hypothyroidism developed. Five patients with transient hypothyroidism and 2 patients with low T4-values without a TSH-increase were treated with thyroid hormone after ascertainment of their serum thyroxine levels and six survived.The analysis of the prophylactically treated cases showed that the dosage of 25 g l-Thyroxine and 5 g Tri-iodothyronine in critically ill infants (i.e., those who were mechanically ventilated or had sepsis) was rarely sufficient to produce normal serum thyroxine levels. In these children thyroxine usually rose to normal levels only when they had passed the acute stage of the disease. It therefore seems advisable to double the dose of thyroid hormone during the acute stage of the disease.     

Respiratory distress syndrome in very low birth weight infants with occasionally normal surfactant phospholipids

Lung effluent phospholipids were analysed in 120 very lwo birth weight (560–1500g) infants within 12 h from birth. The phospholipid profile accurately predicted the presence or absence of respiratory distress syndrome (RDS). However, in three of the 72 RDS cases, the phospholipids revealed no biochemical abnormality as compared to lung effluent from newborns without RDS. In RDS with normal phospholipids, only the lipid-rich fractions of the aspirate were surface active, whereas the protein-rich fraction of the aspirate inhibited the surface activity of lung effluent from normal newborns, suggesting the presence of a surfactant inhibitor. The pathogenesis and treatment of RDS with normal surfactant phospholipids may prove to be different from classical RDS.Supported by the Finnish Heart Foundation, the Paulo Foundation, and the Foundation for Pediatric Research (Finland)     

The male disadvantage in very low birthweight infants: Does it really exist?

In a nationwide collaborative study in the Netherlands, perinatal and follow up data were collected on 1338 liveborn very preterm (<32 weeks) and/or very low birth-weight (VLBW) infants (<1500g). In this group, the mortality risk was similar for both male and female infants. The handicap risk, however, was significantly greater for boys than for girls. This finding could not be explained as being due to the well-known delay in lung maturation in male infants as in idiopathic respiratory distress syndrome and need of assisted ventilation.From the collaborative study Project On Preterm and Small for gestational age infants in the Netherlands (POPS), 1983     

Serum creatinine and creatinine clearance in healthy neonates and prematures during the first 10 days of life

Normal serum creatinine (Scr) and creatinine clearance (Ccr) values during the first 10 days of life were obtained in 63 very premature (28–32 weeks of gestation), premature (33–37 weeks) and term infants (38–42 weeks). Scr fell, and Ccr rose less markedly in the very premature infants. Scr was 80 mol/l on the 1st day of life both in very premature and premature infants, and 77 mol/l in full-term neonates. After 10 days, Scr was 73, 53 and 35 mol/l respectively. There was an exponential correlation between Ccr and gestational age, indicating rapid maturation of glomerular function.Abbreviations Scr serum creatinine - Ccr creatinine clearance - GA gestational age - GFR glomerular filtration rate     

Respiratory outcome in preterm ventilated infants: importance of early respiratory system resistance

Since severity of acute respiratory distress syndrome (RDS) has been decreasing, the aetiology of long-term respiratory problems may have changed in preterm infants. We investigated whether early neonatal respiratory resistance (Rrs) and compliance (Crs) were important determinants of respiratory morbidity and lung function abnormalities during the 1st year of life in ventilated preterm infants. In 70 infants of less than 37 weeks gestation, mechanically ventilated within 24 h after birth, Rrs and Crs were assessed daily during the first 3 days of life and medians were calculated subsequently (Rrs_neo and Crs_neo). Rrs and Crs were reassessed 1 year later in 57 of 70 infants (Rrs_{1 year} and Crs_{1 year}). After correction for endotracheal tube size, increased Rrs_neo was significantly related to respiratory morbidity during the 1st year of life (OR 1.20, 95% CI 1.04 to 1.38; P =0.013), increased Rrs_{1 year} (multiplicative per kPa/l·s 1.017, 95% CI 1.000 to 1.034; P =0.045), and decreased Crs_{1 year} (multiplicative per kPa/l·s 0.986, 95% CI 0.974 to 0.998; P =0.023). Associations were not adversely affected by degree of prematurity, neonatal disease and treatment. Crs_neo did not show any significant associations. In the current surfactant era, increased Rrs_neo, and not Crs_neo was associated with poor respiratory outcome during the 1st year of life in preterm ventilated infants. Relationships were not adversely affected by measures reflecting degree of prematurity, neonatal disease, and ventilator conditions. Conclusion: our results indicate that inborn properties of the respiratory system have become increasingly important in relation to respiratory outcome instead of neonatal disease and treatment conditions.Abbreviations CLD chronic lung disease of the neonate - Crs respiratory system compliance - Crs _neo median respiratory system compliance of the first 3 days of life - Crs _{1 year} respiratory system compliance at 1 year of age - CV coefficient of variance - ERS European Respiratory Society - FiO₂ inspiratory oxygen fraction - PIP peak inspiratory pressure - RDS respiratory distress syndrome - Rrs respiratory system resistance - Rrs _neo median respiratory system resistance of the first 3 days of life - Rrs _neoC Rrs_neo corrected for endotracheal tube size - Rrs _{1 year} respiratory system resistance at 1 year of age - SBT single breath occlusion technique     

Artificial surfactant in preterm rabbits with and without respiratory distress syndrome: difference of in vitro and in vivo activities

Sixty-eight rabbit fetuses of 27 days gestation were tracheotomised, artificially ventilated, and their lung mechanics studied in a body-enclosing plethysmograph. The animals were treated by tracheal instillation of natural surfactant concentrate or large unilamellar vesicles containing dipalmitoyl-phosphatidylcholine: egg phosphatidylglycerol, 91. Both preparations were highly surface active in terms of film adsorption and surface tension-lowering potential. Before treatment, the lung mechanics were analysed to indicate the presence of respiratory distress syndrome (RDS). Controls received 0.15 M saline. Differences were found between the in vitro and in vivo activities of both preparations in some animals. In 30 preterm animals with partial lung maturity and without respiratory distress syndrome, no significant effect could be achieved with either the natural or the artificial surfactant. In 38 animals with severe RDS, the tidal volume and compliance increased markedly within 15 min of substitution of both preparations. Compliance increased to 178% of the initial value in ventilated, control animals, to 391% in animals treated with natural, and to 344% in animals treated with artificial surfactant.Abbreviations RDS respiratory distress syndrome - DPPC dipalmitoylphophatidylcholine - TV tidal volume - C_rs compliance of the respiratory system     

Prolonged ventilation of the premature newborn rabbit after treatment with natural or apoprotein-based artificial surfactant

Premature rabbit neonates (gestational age 27 days) were treated at birth with natural surfactant purified from chloroform extracts of porcine lung lipids either by acetone precipitation (Surfactant CK, n=10) or liquid gel chromatography (Curosurf, n=22). Another group of animals received artificial surfactant reconstituted from isolated low molecular weight (15 K) apoproteins and synthetic dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylglycerol (DPPG) (Aposurf, n=10). The phospholipid concentrations of the preparations were adjusted to provide the same individual dose of DPPC for each group of treated animals (3 or 4 mg). In comparison with untreated controls from the same litters, there was a 4–7-fold enhancement of lungthorax compliance in all groups of surfactant-treated animals during a 3-h period of artificial ventilation. The average initial (20 min) compliance value was lower in the Aposurf-treated group than in animals receiving natural surfactant preparations, but the difference between the groups gradually diminished and was no longer statistically significant during the 2nd and 3rd h of artificial ventilation. Judged from the fall in tidal volume during ventilation with a short expiration phase (0.17 instead of 0.75s), the apoprotein-based artificial surfactant was also less effective in stabilizing the lungs. A similar conclusion could be drawn from data on alveolar expansion in histological sections, evaluated by automated image analysis. Alveolar volume density was improved only moderately in the Aposurf-treated group (0.24 vs. 0.14; P=0.05), whereas the expected, prominent increase in this parameter was observed in both groups of natural surfactant-treated animals (0.48–0.62 vs. 0.14; P<0.001). We conclude that a physiologically active artificial surfactant can be prepared from the smaller (15 K) apoproteins, DPPC and DPPG; the in vivo effects of this preparation were clearly beneficial, yet inferior to those obtained with the same dose of natural surfactant.Abbreviations DPPC dipalmitoylphosphatidylcholine - DPPG dipalmitoylphosphatidylglycerol - RDS respiratory distress syndrome - V_v volume density - CV coefficient of variation - dV_T tidal volume reduction - K kilodalton(s)     

The long-term effect of a partial whey hydrolysate formula on the prophylaxis of atopic disease

At the age of 5 years, the prevalence of atopic manifestations was analysed in 58 formula-fed at risk infants because of a history of atopic disease in at least two first degree relatives. Infants were randomly assigned to receive either a partial whey-hydrolysate formula (n: 28) or a regular cow's milk formula (n: 30) during the first 6 months of life; thereafter, feeding was unrestricted. Only non-breastfed infants were included. The groups did not differ in risk factors or in known confounding factors possibly influencing the incidence of manifestations suggestive of atopic disease. At 6 months, the prevalence of cow's milk protein (CMP) sensitivity was significantly decreased in the hydrolysate group (7% versus 43%;P: 0.002). At the age of 12 (21% versus 53%;P: 0.029), 36 (25% versus 57%;P: 0.018) and 60 months (29% versus 60%;P: 0.016) there was still a significant difference in the number of atopic manifestations, if calculated cumulatively. There was no difference between the groups if only the new cases after the age of 6 months were considered. Eczema was less frequent in the whey-hydrolysate group, but only during the 1st year of life, suggesting a decreased prevalence of CMP sensitivity. During the first 6 months, diarrhoea of non-infectious origin occurred in 8/30 infants (27%) of the adapted formula group, and in no infant in the hydrolysate group. Colic as single manifestation was considered of allergic origin in 1/28 infants in the hydrolysate group, and in 4/30 infants in the adapted formula group. If gastro-intestinal symptoms such as diarrhoea and colic as single manifestation are not considered, the number of infants with CMP sensitivity remains only significant for the first 6 months (P: 0.004). At 12, 36 and 60 months, differences are not significant (0.106, 0.116 and 0.07, respectively). The results of this study support the hypothesis that allergy prevention is antigen specific.Conclusion If mother's milk is not available and other studies confirm these results, there might be an indication for partial hydrolysates in infants with a family history of atopy, since these formulae reduce the incidence of CMP sensitivity.     

Late anaemia in infants with rhesus haemolytic disease treated with intensive phototherapy

The purpose of the present study was to determine the incidence of late anaemia in infants with rhesus haemolytic disease (RHD) who had received intensive phototherapy. Sixty infants with RHD and with strongly positive direct Coombs' tests who had received intensive phototherapy (blue double light) were followed as out-patients with regard to development of late anaemia. Fifteen (25%) infants developed moderate anaemia and 5 (8%) severe anaemia, one of the latter requiring a blood transfusion. The incidence of late anaemia was equal in non-exchanged infants and those who required exchange transfusion. The former developed anaemia significantly earlier than the latter, and in both groups the declining Hb level caused a marked reticulocyte response which was equal in both groups. This response may explain the low incidence of anaemia in both the non-exchanged and exchanged infants. From the present study and previous investigations it can be concluded that phototherapy, especially intensive phototherapy, is of great value in the treatment of rhesus haemolytic disease.     

Surfactant treatment for respiratory distress syndrome following prolonged rupture of membranes

Surfactant replacement for respiratory distress syndrome (RDS) following very prolonged rupture of the membranes (PROM) is of uncertain value. Seven preterm babies born after PROM (median 48 days, range 22–61 days) were compared with 14 babies without PROM. All had clinical and radiological evidence of severe RDS, requiring mechanical ventilation with inspired oxygen concentrations 60%. Indices of oxygenation and compliance were compared before and serially up to 4h after surfactant treatment. Before treatment the PROM babies had more severe lung disease, based upon higher inspired oxygen concentration and mean airway pressure, and lower arterial/alveolar oxygen tension ratio and ventilator efficiency index. These indices were significantly worse in the PROM group than the comparison group at all times after treatment. The poor response of the PROM group, perhaps because of pulmonary hypoplasia, suggests that surfactant replacement may not be beneficial for RDS in these babies.     

Treatment of infants with congenital toxoplasmosis: tolerability and plasma concentrations of sulfadiazine and pyrimethamine

The aim was to study the tolerability and plasma concentrations of pyrimethamine and sulfadiazine in children treated for congenital toxoplasmosis. Infants were diagnosed through the Danish Toxoplasma Neonatal Screening Programme, based on detection of toxoplasma-specific IgM- and/or IgA-antibodies on 3 mm blood spots collected from phenylketonuria [PKU cards (Guthrie cards)]. Toxoplasma-infected children received 3 months continuous treatment with 50–100 mg/kg per day sulfadiazine in two separate administrations and 1 mg/kg per day pyrimethamine after a 1-day loading dose of 2 mg/kg, and folinic acid 7.5 mg was administered twice weekly. Blood cell counts and body weight were recorded during follow-up. The plasma concentrations of pyrimethamine and sulfadiazine were analysed in a subgroup of seven children, using high performance liquid chromatography with ultraviolet and mass spectrometric detection. Of 48 infants, 41 completed the treatment without change in schedule. Six infants had neutrophil counts below 0.5×10⁹/l, and one infant had an elevated bilirubin value. Twenty-nine children were tested by a series of neutrophil counts during treatment. The neutrophil count was 0.5×10⁹/l or lower in 4/29 (13.8%). None of the children had anaemia or thrombocytopenia. The drugs did not affect weight gain. Mean plasma drug concentrations varied between 1.3 g/ml and 2.2 g/ml for pyrimethamine and between 60 g/ml and 86 g/ml for sulfadiazine. Treatment efficacy is still a concern, since progression of eye lesions was observed in three eyes during the follow-up period. We concluded that the treatment was well tolerated in 86% (25/29) of the children. The drugs did not affect their weight gain. Drugs given in the recommended doses led to concentrations within expected therapeutic limits.     

Sociodemographic differences in the prevalence of self-reported stomach pain in school children

The study considered the prevalence of experienced stomach pain in a nationwide random sample of 2161 Icelandic 11–12 and 15–16-year-old school children. It found an 18.4% prevalence of at least weekly stomach pain and a 53.4% overall prevalence. The prevalence of stomach pain was significantly higher among younger children (P 0.001). Higher prevalence (P 0.001) of stomach pain was seen in girls in the overall sample and the gender difference was significant in both age groups. No overall class or residential differences were detected. However, the findings suggest some age-related links between social status and the experience of stomach pain. The frequency of stomach pain was moderately and significantly associated with medication use. The theoretical and clinical implications of the results are briefly discussed.     

Pharmacodynamics and pharmacokinetics of esmolol,a short-acting β-blocking agent,in children

Summary Esmolol, a short-acting intravenous cardioselective -blocking agent, was evaluated for age-dependent pharmacodynamic and pharmacokinetic features in 17 young patients (6 months to 14 years). A loading dose (500 g/kg/min) alternating with a maintenance dose (25–200 g/kg/min, titrating by 25 g/kg/min every 4 min) was infused until the heart rate or mean arterial pressure decreased 10%. Cardiac index, left ventricular shortening fraction, and systemic vascular resistance were measured at baseline, peak esmolol effect, and recovery. Serum esmolol concentrations were obtained to determine the half-life and the elimination rate constant.Esmolol reduced the heart rate, blood pressure, shortening fraction, and cardiac index in all patients, but it did not change systemic vascular resistance. Maintenance esmolol dose was 118 ±49 g/kg/min, and the half-life was 2.88±2.67 min. Blood pressure and heart rate returned to normal within 2–16 min, but cardiac index and shortening fraction took longer to recover. There were no statistically significant age-dependent pharmacodynamic effects, but blood pressure decreased prior to heart rate and cardiac index took longer to recovery in patients who weighed15kg. The pharmacokinetic profile in young patients was similar to that of older patients, but the half-life was shorter. The only side effeect was transient nausea and vomiting in one patient. Esmolol is a safe and efficacious -blocking agent in young patients.     

A new baby-spacer device for aerosolized bronchodilator administration in infants with bronchopulmonary disease

The response of salbutamol (Ventolin, Glaxo), topically administered from a metered dose inhaler (MDI) through a new baby-spacer-device (Babyhaler, Glaxo) was studied in 14 infants (8 wheezy infants, 3 infants with cystic fibrosis and 3 infants after respiratory distress syndrome), age 2.9–18.8 months. Changes in thoracic gas volume (TGV) as an estimate of pulmonary hyperinflation and changes in airway conductance (Gaw) as an estimate of bronchial obstruction were assessed by whole-body plethysmography. After baseline measurements, 1 puff of 100 g salbutamol was given repeatedly at 5 min intervals until 600 g have been inhaled and TGV and Gaw were measured after each inhalation at 5, 10, 15, 20, 25 and 30 min. Significant improvement in lung function was achieved in 57.1% of infants after 400 g and in 92.9% of infants after 600 g salbutamol. The study shows usefulness of bronchodilator treatment in infants with bronchopulmonary disease by a system with a MDI and baby-spacer-device. However a special dose-time relationship must be respected.Presented in part at the 1990 World Conference on Lung Health, May 20–24, 1990 — Boston, Massachusetts, U.S.A.