Development of systemic lupus erythematosus in a patient with selective complete C1q deficiency

 A 7-year-old male with recurrent erythematous and desquamated skin lesions and respiratory infections was diagnosed as selective complete C1q deficiency following detailed studies of the complement system. His asymptomatic sister also had selective complete C1q deficiency. During a follow up period of 3 years, his skin lesions persisted, he suffered from recurrent bronchopneumonias and glomerulonephritis developed. Renal function deteriorated with the appearance of anti-DNA antibodies. Renal biopsy was consistent with systemic lupus erythematosus. The patient was treated with immunosuppressive drugs, but died of renal failure. It is postulated that in this patient defective clearance of antigen-antibody complexes by the reticulo- endothelial system resulted in progressive renal disease as observed in other complement deficiencies. A retrospective molecular study disclosed a point mutation in the ClqA chain gene in a heterozygous state in parents and two siblings; in a homozygous state in the asymptomatic sister. The reason why some individuals with this defect are asymptomatic is not known at present. Diagnosis of heterozygotes by molecular studies is extremely important to give genetic counselling to the family. Conclusion Patients with recurrent infections, ery-thematous desquamative skin lesions, malar rash and oral mucosal involvement should be screened for complement Clq deficiency. Received: 29 March 1996 / Accepted: 1 August 1996     

Seasonal variation in childhood asthma hospitalisations in Finland, 1972–1992

All hospital treatment periods caused by asthma in children under 15 years in Finland during 1972–1992 were examined. The data were obtained from the Hospital Discharge Register, covering all hospitalisations in Finland. A total of 59,624 asthma related treatment periods were recorded. The monthly variation in hospitalisations peaked in May (35.6% above the trend) and in autumn and early winter (41.3% above the trend in October), whereas the monthly variations were low in late winter and in summer. The overall profile of seasonal variation was similar in both sexes, although admissions were lower for boys than for girls in winter and higher in autumn. The average monthly deviation was highest in the age group 0–4 years in May, 42.8% above the trend, and highest in the age group 5–9 years in October, 53.9% above the trend. Closer examination of the seasonal variation gives indirect information on possible trigger factors for acute asthma. Conclusion A clear seasonal variation could be obser ved in childhood asthma hospital admissions, together with age and sex-related differences in this seasonality. Preventive treatment for asthma should be used effectively in order to avoid acute attacks leading to hospitalisation in children who are allergic to birch pollen and also at times of viral respiratory infections. Received: 14 May 1996 / Accepted: 26 September 1996     

Generalized metaphyseal modification with cone-shaped epiphyses following long-term administration of 13-cis-retinoic acid

We report on a 6-year-old girl with short stature which developed following the administration of 13-cis-retinoic acid (a synthetic derivative of vitamin A or retinoid) for 40 months as adjunct chemotherapy for neuroblastoma. Radiographic examination suggested osteophyte formation in the cervical spine, which is the most common skeletal manifestation of retinoid toxicity [10, 11]. In addition, severe metaphyseal cupping with a cone-shaped epiphysis primarily affecting rapidly growing long bones was found, which represented impaired enchondral ossification. This epi-metaphyseal alteration, though unusually severe, was reminiscent of the premature epiphyseal closure which has been described as an adverse effect of 13-cis-retinoic acid [10–12]. Other minor skeletal changes included posterior scalloping of the vertebral bodies and increased interpediculate distances, which were related to a widened spinal canal found on CT. A literature search disclosed several primary skeletal dysplasias with superficial radiological similarities to those of the present patient. However, these entities showed significant clinical and radiological differences from our patient. Conclusion The precise cause of the generalized skeletal alteration in the present patient remained unknown, but it conceivably resulted from the administration of 13-cis-retinoid acid. Received: 4 June 1996 / Accepted: 24 September 1996     

Pseudohypo-aldosteronism and cholelithiasis: coincidence or pathogenetic correlation?

Cholelithiasis is being documented with increasing frequency in the paediatric age group. Causes of gallstone formation in infants and neonates seem to differ from those in older children and adolescents. Two infants with pseudohypo-aldosteronism and cholelithiasis are reported. Salt-wasting and dehydration in pseudohypo-aldosteronism are suggested to be the pathogenetic mechanisms leading to gallstone formation possibly beginning in fetal life. The diagnosis of pseudohypo-aldosteronism may be missed, when salt-wasting is transitional. Cholelithiasis may go undetected when asymptomatic. ConclusionPseudohypo-aldosteronism should be con sidered in infants with cholelithiasis even without ob vious salt-wasting signs. Routine ultrasonographic screening for gallstones should be performed in pa tients with pseudohypo-aldosteronism. Received: 15 March 1996 / Accepted: 21 August 1996     

Final height and puberty in 40 patients after antileukaemic treatment during childhood

Endocrine dysfunction and damage of the epiphysial growth plates have been reported as late effects of antileukaemic treatment during childhood. It is a common opinion that cranial irradiation (CI) is the most important factor for blunted growth. Accordingly, recent therapeutic strategies in acute lymphoblastic leukaemia (ALL) avoid cranial irradiation. Here we analysed longitudinal data on growth and puberty of 54 children in first complete remission, who were treated with 18 Gy CI or not submitted to radiotherapy. Two chemotherapeutic protocols were compared which were similar during the induction period but differed in the intensity of maintenance therapy. In cranial irradiated patients both in males and females the pubertal growth spurt started at a mean age of 1.2 years (SD: 0.93 years) earlier than controls. Age at diagnosis and age at pubertal growth spurt were significantly correlated (r = 0.35, P = 0.017). Similarly, menarche occurred at a mean age (n = 22) of 12.1 years and was correlated with the age at start of therapy in girls who were treated with 18 Gy CI (r = 0.61, P = 0.01). Adult height was reached spontaneously in 30 patients treated during prepubertal age and in 10 treated shortly before or during puberty. In all prepubertal patients treated for 2–3 years with intensive maintenance therapy blunted growth resulted in a significant loss of −1.85 H-SDS (median, P = 0.0051) compared to height at diagnosis. However, if continuation treatment used only methotrexate and 6-mercaptopurine (i.e. BFM protocol) final height equalled projected adult height, despite 18 Gy CI. Conclusions (1) multiagent chemotherapy is of major impact for growth and puberty; (2) 18 Gy cranial irradiation is below the critical dosage responsible for blunted growth; (3) loss in potential growth might be prevented by current CT strategies; (4) onset of puberty depends on age when antileukaemic therapy is applied. Received: 22 April 1996 / Accepted: 24 September 1996     

Paediatric thrombo-embolism: the influence of non-genetic factors and the role of activated protein C resistance and protein C deficiency

 In many children, the pathogenesis of thrombo-embolism remains unexplained. This study examines the role of non-genetic risk factors in 37 children with venous or arterial thrombosis. Included were 17 patients with portal vein thrombosis following umbilical vein catheterisation, 6 with portal vein thrombosis and an uneventful neonatal period, 4 with deep vein␣thrombosis, 4 with renal vein thrombosis after kidney transplantation, 1 haemodialysis patient with thromboses of arteriovenous shunts, and 5 with arterial thromboses at various sites. In 25 of these 37 patients (68%) exogenic risk factors and particularly vascular manipulations (24/37) were related to the thrombotic event. Resistance to activated protein C was identified in 5 patients and protein C deficiency in 2 (7/37; 19%). This prevalence was significantly higher than that of the control group (14/243; 5.8%; χ², P < 0.008). Conclusion Our data show that non-genetic and particular iatrogenic risk factors can often be identified in children with thrombosis, but activated protein C resistance and protein C deficiency are significant genetic risk factors in this age group. Received: 23 April 1996 / Accepted: 1 August 1996     

A retrospective epidemiological study of bacterial meningitis in an urban area in Belgium

In order to obtain epidemiological data on the incidence of bacterial meningitis (BM) before the systematic introduction of vaccination against Haemophilus influenzae type b, a retrospective study of 124 children with proven BM was performed in an urban area in Belgium. N. meningitidis was the most prevalent cause, followed by H. influenzae and S. pneumoniae. Over a period of 6 years the incidence of BM increased ten fold, mainly due to an increase in N. meningitidis. The median age of the children with BM was 17 months and 35% of those with H. influenzae were younger than 1 year. Significant risk factors for BM as a whole were: age under 1 year, male gender, non-Caucasian descent and winter time. These findings may have implications for future vaccination policy in Belgium. Conclusion Future vaccination schemes in Belgium should take into account that N. meningitis was the prevalent cause of bacterial meningitis and that certain factors increase the risk for developing bacterial meningitis. Received: 26 February 1996 / Accepted: 14 October 1996     

Serum concentration of granulocyte colony stimulating factor in term and preterm infants

We measured serum granulocyte colony stimulating factor (GCSF) concentration and absolute neutrophil count in four groups of infants: (1) 15 healthy term newborn infants; (2) 21 healthy preterm newborn infants, with mean (SD) birth weight 1583 (533) g, and gestational age 32.0 (3.8) weeks; (3) 5 infected newborn infants; (4) 22 6-month-old control infants. Median (range) serum GCSF concentration was 132.2 (41.5–176.0) pg/ml in term infants, 51.5 (1.8–175.7) pg/ml in preterm infants and 138.9 (54.1–449.8) pg/ml in 6-month-old control infants, with a significant reduction in preterm infants, as compared to term and control infants. GCSF levels were significantly higher in the infected infants, as compared to healthy neonates. Conclusion A significant positive relationship was found in term and preterm infants between serum GCSF concentration and gestational age or birth weight. No relationship was found between serum GCSF concen tration and neutrophil count. The low GCSF baseline levels may contribute to the increased incidence and severity of infection in preterm infants. Received: 17 May 1996 and in revised form: 20 July 1996 / Accepted: 29 July 1996     

Antenatal ambroxol treatment does not prevent the respiratory distress syndrome in premature infants

The effectiveness of ambroxol in the prevention of neonatal respiratory distress syndrome and in reducing the need for intermittent mandatory ventilation and oxygen therapy was studied in 88 mothers whose infants was born between 24 and 34 weeks of gestation and who were randomized either for treatment with ambroxol (group A = 42) or served as control (group B = 46). There were no significant differences in the mean gestational age, birth weight or Apgar score between the two groups. We found no significant differences in occurrence of respiratory distress syndrome (55% vs 45%), in support by intermittent mandatory ventilation (71% vs 72%) or oxygen therapy (74% vs 75%) at 12 h of age between groups A and B. Conclusion This study does not suggest the efficacy of antenatal ambroxol treatment both for the prevention of neonatal respiratory distress syndrome and for the reduction of its severity. Received: 12 October 1995 and in revised form: 30 August 1996 / Accepted: 10 September 1996     

Study of the bronchodilating effect of three doses of nebulized oxitropium bromide in asthmatic preschool children using the forced oscillation technique

The aim of this study was to evaluate the bronchodilating capacity of nebulized oxitropium bromide (OB) in preschool asthmatic children and to determine an appropriate dose for usage in this age group. The trial enrolled 20 patients with moderate to severe stable asthma aged between 3.2 and 6.2 years (mean 4.7). Applying a placebo controlled, double-blind design, the effect of placebo was compared with three different doses of OB (375, 750 and 1500 μg) and with 400 μg fenoterol. The three different doses of OB resulted in a highly significant bronchodilation within 15 min after administration. The observed bronchodilation was comparable between the three doses during the first 2 h. However, after 4 h the lowest dose was significantly less powerful than the highest dose. Compared to the additional bronchodilation induced by fenoterol, no difference was found with the degree of bronchodilation of OB which occurred during the first 2 h. Furthermore, <%b>after 4 h only the lowest dose of OB was significantly less powerful than fenoterol assessed 10 min following a single 400 μg dose. Conclusion Oxitropium bromide is a potent and long-acting bronchodilator in preschool children at a dose of 750 μg and 1500 μg. No side-effects were observed. The exact duration of action remains uncertain, but even 4␣h after inhaling 750 or 1500 μg of OB no additive bronchodilation induced by fenoterol could be observed. Received: 2 April 1996 and in revised form: 20 August 1996 / Accepted: 12 September 1996     

The effect of blood transfusion on oxygenation in premature ventilated neonates

The effect of blood transfusion to maintain a preset packed cell volume (PCV) level in preterm ventilated infants has been investigated. Fifty infants, median gestational age 26 (range 23–33) weeks and postnatal age 4 (1–29) days, transfused a median of 15 ml/kg of blood in response to a PCV ≤ 40% were retrospectively identified and their medical records reviewed to determine the change in PCV and haemoglobin resulting from the transfusions. In addition, their mean airway pressure (MAP) was noted and, as an index of oxygenation, their oxygenation index (OI), alveolar/arterial oxygen gradient (AaDO₂) and arterial/alveolar (a/A) ratio calculated 12 h, 6 h and immediately prior to the transfusion and immediately post, 12, 18 and 24 h after the transfusion. The transfusion improved the PCV and haemoglobin (P < 0.0001). No significant changes in MAP or level of oxygenation were experienced in the 12 h prior to the transfusion. Post transfusion, despite no significant change in MAP, the AaDO₂ OI and a/A ratios compared to immediately prior to the transfusion were significantly better at 12, 18 and 24 h. Conclusion It is useful to transfuse ventilated preterm infants to maintain their PCV above a preset level. Received: 8 March 1996 / Accepted: 1 July 1996     

Respiratory control in children with Prader-Willi syndrome

  Physiological parameters of infants and children with Prader-Willi syndrome were examined in order to clarify whether there were indicators of disturbed respiratory control mechanisms in the pre-obesity stage of the syndrome. From January 1993 to March 1995 in eight patients with Prader-Willi syndrome (five boys, three girls, aged 6 weeks – 12.5 years),␣polysomnography was performed and compared with 28 children matched for gestational age, sex, birth weight and age at sleep study. The recordings included thoracic and abdominal breathing movements, nasal airflow, tcPO₂, tcPCO₂, oxygen saturation, EEG, EOG and ECG. Respiratory responses to hypercapnia during quiet sleep were obtained from five Prader-Willi patients and ten peers. The Prader-Willi group showed an increased number of apnoeas per hour of sleep, a decreased nadir of oxygen saturation, increased maximum of the instantaneous heart rate and decreased respiratory responses to hypercapnia during quiet sleep. Conclusion These findings indicate a primary dis‐turbance of central respiratory control in patients with Prader-Willi syndrome which may be worsened by the development of obesity. Received: 26 January 1996 / Accepted: 21 July 1996     

Fatty acid composition of human milk during the 1st month after term and preterm delivery

The fatty acid composition of human breast milk was determined longitudinally after term and preterm delivery by high resolution gas liquid chromatography. Milk samples were obtained at days 5, 10, 20 and 30 after term (n = 38) or preterm (n = 19) delivery. The saturated fatty acids C10:0 and C12:0 and the polyunsaturates linoleic acid (C18:2ω-6) and α-linolenic acid (C18:3ω-3) increased significantly from day 5 to day 10, whereas arachidonic acid (C20:4ω-6), total ω-6 long-chain polyunsaturates (LCP), docosahexaenoic acid (C22:6ω3) and total ω-3 LCP decreased significantly. Term and preterm milk did not differ in percentage content of linoleic acid, α-linolenic acid and LCP at any time point. Preterm milk contained significantly more medium and intermediate chain fatty acids (C10:0, C12:0 and C14:0) than term milk on days 5 (12.28 vs 9.78%; P > 0.05), 10 (16.25 vs 12.62%; P > 0.05) and 20 (17.29 vs 13.47%; P > 0.005). Conclusion The milk of mothers of preterm infants is not better suited to meet the high LCP requirements of their infants during the first weeks after birth. The slightly higher proportion of medium and intermediate chain fatty acids in preterm milk during the 1st month after birth might be advantageous for the fat and calcium absorption of preterm infants. Received: 22 February 1996 / Accepted: 1 August 1996     

Final height outcome in girls with Turner syndrome treated with a combination of low dose oestrogen and oxandrolone

Final stature in girls with Turner syndrome treated with combination of low dose oestrogen and oxandrolone. Nineteen prepubertal girls with Turner syndrome (mean age 10.9 years, range, 8.9–14.2 years) were randomly assigned to receive either oxandrolone (0.05 mg/kg/day) or ethinyloestradiol (40 ng/kg/day) for 1 year. Subsequently the alternate therapy was added and the combination given until attainment of final height. Ethinyloestradiol was gradually increased at the age of 12.5 years in order to induce secondary sexual characteristics. The duration of treatment was a mean of 5.2 years (range, 3–7 years) when the 1st year of monotherapy was included. Therapy produced a sustained acceleration in growth rate for a duration of 4 years and eventually has resulted in an increment of mean adult height of 3 cm relative to pre-treatment projected height with mean values of 146.5 cm versus 143.5 cm respectively. The moderate side-effects observed did not cause any of the girls to discontinue treatment. Nevertheless, amelioration of adult height appears to be modest, notably in comparison to published data of growth hormone treatment and 4 girls had a decrease in final height prediction. Conclusion Combination of low dose of oxandrolone and oestrogen may have a moderate but positive impact on final height in girls with Turner syndrome. However, some girls do worse than predicted in term of final height using this regimen. Oestrogen therapy started at low dose around the age of 10 years and increased gradually at approximately 12.5 years to induce secondary sexual characteristics does not have a deleterious effect on adult height in Turner syndrome. In summary, low dose oxandrolone-oestrogen treatment was found to accelerate the tempo of growth in girls with Turner syndrome, but did not appear to have a consistent effect on final height. Received: 22 July 1996 / Accepted: 22 October 1996     

Blood transfusion

To study the relationship between blood transfusion, iron load and retinopathy of prematurity (ROP), we performed a prospective observational cohort study in a level III neonatal intensive care unit. During a 24-month period, data on the volume of blood transfused during the first 6 weeks of life and on the incidence of ROP were collected in all surviving very low birth weight infants (n = 114 median birth weight␣1130␣g, range 520–1500 g). Associations between these data and values for serum iron, transferrin and ferritin measured at weekly intervals were analysed in a nested case-control design by logistic regression. There was a significant association between the volume of blood transfused and the incidence of ROP. After adjustment for gestational age at birth, duration of oxygen therapy FiO₂> 0.3) and duration of mechanical ventilation, the relative risk of developing ROP was 6.4 (95% CI 1.2–33.4) for infants who had received 16–45 ml/kg, and 12.3 (1.6–92.5) for those who had received more than 45 ml/kg of blood (reference, 0–15 ml/kg). In contrast, there was no independent relationship between ROP and any of the parameters on iron metabolism analysed. Conclusion This study confirms the role of blood transfusions as an independent risk factor for ROP. This relationship, however, does not appear to be mediated via an increased iron load. Received: 5 September 1996 and in revised form: 17 October 1996 / Accepted: 26 October 1996     

The Marshall-Smith syndrome: a review of the laryngeal complications

The Marshall-Smith syndrome is characterised by a triad of facial dysmorphism, failure to thrive and accelerated osseous maturation. We report a further case of this rare syndrome with the unusual but previously reported complication of laryngeal hypoplasia and review the associated laryngeal anomalies that have been reported to date. Conclusion Severe airway obstruction due to congenital anomalies must be excluded in any dysmorphic child presenting with respiratory distress at birth. Rapid airway assessment will enable early and appropriate intervention and may be important when deciding on the long-term plan for the infant. Received: 28 March 1996 and in revised form: 13 November 1996 / Accepted: 13 November 1996     

Congenital microgastria, growth hormone deficiency and diabetes insipidus

 Microgastria is a rare malformation of the stomach always associated with variable patterns of malformations of the lung, heart, aortic arch, skeleton, and central nervous system. Many cases present with asplenia and hepatic symmetry as well as intestinal malrotation. We report a first case of a 4.5-year-old girl with congenital microgastria in association with growth hormone deficiency, diabetes insipidus, brachyoesophagus, hernia of the diaphragm, gastro-oesophageal reflux, intestinal malrotation, enlarged symmetrical liver, asplenia, as well as mental and statomotor retardation. Conclusion Congenital microgastria is always asso‐ciated with malformations of other organs. Patients at any age presenting one of the symptoms: failure to thrive, vomiting, asplenia, midline defects and parts of the VACTERL association should be carefully examined to exclude microgastria. Received: 20 November 1994 / Accepted: 1 July 1996     

A critical appraisal of current management practices for infant regurgitation – recommendations of a working party

Regurgitation is a common manifestation in infants below the age of 1 year and a frequent reason of counselling of general practitioners and paediatricians. Current management starts with postural and dietary measures, followed by antacids and prokinetics. Recent issues such as an increased risk of sudden infant death in the prone sleeping position and persistent occult gastro-oesophageal reflux in a subset of infants receiving milk thickeners or thickened “anti-regurgitation formula” challenge the established approach. Therefore, the clinical practices for management of infant regurgitation have been critically evaluated with respect to their efficacy, safety and practical implications. The updated recommendations reached by the working party on the management of infant regurgitation contain five phases: (1A) parental reassurance; (1B) milk-thick ening agents; (2) prokinetics; (3) positional therapy as an adjuvant therapy; (4A) H2-blockers; (4B) proton pump inhibitors; (5) surgery. Received: 26 July 1996 / Accepted: 22 November 1996     

Assessment of late results of surgery in talipes equino-varus: a reliability study

The variability of a method for clinical and functional assessment of the long-term results of surgical correction of idiopathic congenital talipes equino varus was studied in ten boys and four girls (average age: 19.1 (SD 2.3 years); 22 affected feet) with radiographical evidence of fusion of the foot and ankle ossification centres. Patients were measured twice, 1 week–1 month apart, by the same investigator and were assessed twice on each visit. Assessment included anthropometry, functional assessment and subjective functional evaluation. Calf circumference, skinfold thickness, foot length and width were highly reproducible. Foot length was not significantly influenced by the operation whereas calf circumference, skinfold thickness and foot width were. Although highly reproducible, hopping was not significantly affected by operation. Active and passive range of motion were significantly different. Each was highly reproducible and both were significantly affected by the operation. Patients reported a high and highly reproducible (within two points) functional level. Conclusion An assistant-administered functional questionnaire together with measurement of active and passive range of motion allows easy, valid and reproducible assessment of long-term results of surgery for idiopathic congenital talipes equino-varus␣correc-tion. A significant effect of the number and type of operation was evidenced. Received: 1 July 1996 and in revised form: 8 October 1996 / Accepted: 15 October 1996     

The effect of obesity, age, puberty and gender on resting metabolic rate in children and adolescents

During puberty fat-free mass (FFM) and fat mass (FM) change quickly and these changes are influenced by sex and obesity. Since it is not completely known how these changes affect resting metabolic rate (RMR), the aim of the present study was to investigate the effect of body composition, age, sex and pubertal development of postabsorptive RMR in 9.5- to 16.5-year-old obese and non-obese children. Postabsorptive RMR was measured in a sample of 371 pre- and postpubertal children comprising 193 males (116 non-obese and 77 obese) and 178 females (119 non-obese and 59 obese). RMR was assessed by indirect calorimetry using a ventilated hood system for 45 min after an overnight fast. Body composition (FFM and FM) was estimated from skinfold measurements. The mean (± SD) RMR was significantly (P < 0.001) lower in non-obese (males: 5600 ± 972 kJ/24h; females: 5112 ± 632 kJ/24h) than in obese (males: 7223 ± 1220 kJ/24h; females: 6665 ± 1106 kJ/24h) children. This difference became non-significant when RMR was adjusted for body composition (FFM + FM). However, the difference between the genders still remained significant (control male: 6118 ± 507, control female: 5652 ± 507, P < 0.001; obese male: 6256 ± 507, obese female: 5818 ± 507 kJ/24h, P < 0.001). The main determinant of RMR was FFM. In the whole cohort, FFM explained 79.8% of the variation in RMR, followed by age, gender and FM adding further 3.8%, 1.1% and 0.8% to the predictability of RMR, respectively. No significant contribution for study group (obese, non-obese), pubertal stage, or fat distribution was found in the regression for RMR. The adjusted value of RMR (for FFM and FM) slightly, but significantly (P < 0.01) decreased between the age of 10–16 years, demonstrating the important effect of age on RMR. Conclusions The resting metabolic rate of obese and control children is not different when adjusted for body composition. The main determinant of RMR is the fat-free mass, however, age, gender and fat mass are also significant factors. Pubertal development and fat distribution do not influence RMR independently from the changes in body composition. Received: 4 March 1996 / Accepted: 21 August 1996