Louis David

Vitamin D supplementation during pregnancy: Effect on neonatal calcium homeostasis

We assessed whether modification of vitamin D nutritional status during the last trimester of pregnancy affects maternal and neonatal calcium homeostasis. At the end of the first trimester, 40 pregnant women were randomly assigned to either of two groups, and blood taken to assess the basal values of Ca, Pi, Mg, iPTH, 25-OHD, and 1,25(OH)2D. From the sixth month on, group 1 (+D) received 1000 IU vitamin D3 daily; group 2 (-D) served as control. At the time of delivery, maternal serum 25-OHD was higher in the +D group (P less than 0.0005). Ca, Pi, iPTH, and 1,25(OH)2D were not affected. At term, venous cord 25-OHD levels were also higher in the +D group (P less than 0.0005), and 1,25(OH)2D levels slightly lower (P less than 0.05), but neither Ca, Pi, nor iPTH differed between the two groups. Serum CaT dropped significantly (P less than 0.002) at 4 days of age in the infants from both groups, although to a lesser extent in these from the +D group (P less than 0.05). Circulating iPTH increased in both groups. Serum 25-OHD remained low in the -D group, and dropped slightly in the +D group; 1,25(OH)2D remained stable during the first 4 days of life in the -D group, and increased in the +D group (P less than 0.001). Our data demonstrate the importance of providing adequate maternal vitamin D stores to ensure better perinatal handling of calcium. This is of particular importance for populations at risk for hypovitaminosis D.

Recurrent nephrotic syndrome after transplantation: Early treatment with plasmaphaeresis and cyclophosphamide

Steroid-resistant nephrotic syndrome (NS) with focal glomerulosclerosis (FGS) and its recurrence after transplantation are mainly seen in children. The recurrence rate approximates 30% and the graft loss is about half this. Several therapeutic regimens have been proposed, giving conflicting results. In an attempt to remove a putative circulating factor and inhibit its production by lymphocytes, three patients with biopsy-proven FGS in the native kidney were included in a prospective uncontrolled trial using early plasmaphaeresis followed by substitutive immunoglobulins in association with methylprednisolone pulses and cyclophosphamide instead of azathioprine over a 2-month period. The patients were girls, aged 6.5, 13.3 and 15.8 years, who received a cadaveric transplant; concomitant immunosuppression included prednisone and cyclosporine A. All three patients exhibited early recurrence of the NS and were treated 5–10 days after the onset of proteinuria. Rapid and sustained remission was achieved in all patients within 12–24 days on therapy. One patient experienced a late acute but steroid-sensitive rejection episode; another suffered from septic ankle arthritis as a complication of reinforced immunosuppression. The latter girl had a second late recurrence of proteinuria that was controlled within 7 weeks. With a 18-to 27-month follow-up, all three patients have normal renal function, normal blood pressure and no proteinuria. We conclude that intensive therapy using plasmaphaeresis, steroid pulses and cyclophosphamide over a 2-month period can induce complete remission in children with early recurrence of NS after transplantation.

High-dose albuterol by metered-dose inhaler plus a spacer device versus nebulization in preschool children with recurrent wheezing: A double-blind, randomized equivalence trial.

Inhaled albuterol is the most frequently used bronchodilator for acute wheezing, and nebulization is the standard mode of delivery in hospital setting. However, recent guidelines consider spacer devices as an easier to use, and cost-saving alternative and recommend the high-dose metered-dose inhaler bronchodilator. Objective. To demonstrate clinical equivalence between a spacer device and a nebulizer for albuterol administration. Design. Randomized, double-blind, parallel group equivalence trial. Setting. Pediatric emergency wards at 2 tertiary teaching hospitals. Patients. Sixty-four 12- to 60-month-old children with acute recurrent wheezing (32 per group). Interventions. Albuterol was administered through the spacer device (50 μg/kg) or through the nebulizer (150 μg/kg) and repeated 3 times at 20-minute intervals. Parents completed a questionnaire. Outcome Measures. Pulmonary index, hospitalization, ease of use, acceptability, and pulse oximetry saturation. Results. The 90% confidence interval of the difference between treatment groups for the median absolute changes in pulmonary index values between T0 and T60 was [−1; +1] and was included in the equivalence interval [−1.5; +1.5]. Clinical improvement increased with time. Less than 10% of the children (3 in each group) required hospitalization (2 in each group attributable to treatment failure). Parents considered administration of albuterol using the spacer device easier (94%) and better accepted by their children (62%). Conclusions. The efficacy of albuterol administered using the spacer device was equivalent to that of the nebulizer. Given its high tolerance, repeated 50-μg/kg doses of albuterol administered through the spacer device should be considered in hospital emergency departments as first-line therapy for wheezing.

Vitamin D metabolism in preterm infants: Serum calcitriol values during the first five days of life†

To ascertain the activity of the vitamin D biosynthetic pathway, the serum concentration of 1,25-dihydroxyvitamin D (calcitriol) was measured in 16 preterm infants (32 to 37 weeks of gestation) at 1 to 2 and 120 hours of age. Half of the subjects received a daily oral supplement of 2,100 IU of vitamin D3 during the five-day study period. In the first two hours of life, all subjects were hypocalcemic (8.2 +/- 0.2 mg/dl) and 14 subjects had low concentrations of 25-hydroxyvitamin D (calcidiol, 8 +/- 1 ng/ml). The latter finding probably reflects a mild degree of vitamin D deficiency in the mothers of our subjects. Calcitriol concentrations (42 +/- 3 pg/ml) were comparable to those of older children. At 120 hours of age, the control group had no significant change in calcitriol values, whereas the group supplemented with D3 had a more than threefold increase. There was a positive correlation between the circulating concentrations of calcidiol and calcitriol over the period of the study. The data show that, after 32 weeks of gestation, renal 25-hydroxyvitamin D-1 alpha-hydroxylase activity is present, with the rate of calcitriol synthesis being apparently substrate limited. Early neonatal hypocalcemia is therefore unlikely to be caused by an impairment of vitamin D activation.

Evolution of secondary hyperparathyroidism after renal transplantation.

Abstract Renal osteodystrophy is an important problem in children with chronic renal failure, leading to skeletal deformities. The most-frequent type of renal osteodystrophy is secondary hyperparathyroidism, and the main factors contributing to the pathogenesis of this condition are completely or partially corrected after successful renal transplantation. The present paper reviews data on the evolution of secondary hyperparathyroidism after transplantation. Studies in both adults and children suggest that secondary hyperparathyroidism and increased bone remodelling activity may persist months after transplantation. The severity of secondary hyperparathyroidism prior to transplantation, the duration of dialysis, and the development of nodular and/or monoclonal hyperplasia of parathyroid glands are the most-important factors that determine the phenomenon. Important issues, which still need to be answered, are the possible roles of growth factors, cytokines, VDR gene polymorphism (B/b allele), and type of immunosuppressive regimen in the skeletal abnormalities observed.

Early Oral Administration of Vitamin D and its Metabolites in Premature Neonates. Effect on Mineral Homeostasis

Summary: For five days, three groups of six premature infants each were fed human milk and given a daily dosage of one of the following: vitamin D3 (30 μg), 25-OH D3 (10 μg) and 1,25-OH D3 (0.5 μg). The infants in the groups were matched for gestational age and birthweight. Administration of 25-OH D3 or 1,25-(OH)2 D3 did not significantly modify the course of early neonatal hypocalcemia as compared with infants receiving vitamin D3. Mean plasma Ca ± S.D. (mg/100 ml) decreased to nadir values at 48 hr (D3: 5.7 ± 1.2; 25 OH D3: 6.8 ± 0.9; 1,25-(OH)2 D3: 6.7 ± 1.1). A progressive increase toward normal values was seen at 120 and 168 hr in the three groups. Mean plasma immunoreactive parathyroid hormone ± S.D. (μ Eq/ml) followed an opposite pattern with peak values at 48 hr (D3: 231 ± 137; 25-OH D3: 281 ± 138; 1,25-(OH)2 D3:211 ± 149). Mean plasma ± S.D. 25-OH D values (ng/ ml) were low at 1.2 hr (8.7 ± 4.8) n: 16) and increased significantly after 7 days of D3 (18.2 ± 4.2 P < 0.001) and 25-OH D3 administration (46 ± 10.3 P < 0.001)/ Mean plasma iCT ± S.D. (pg/ml) reached peak values at 24 hr (D3: 457 ± 186; 25-OH D3: 415 ± 121; 1,25-(OH)2 D3: 443 ± 183). These data suggest that the various forms of vitamin D are well absorbed in preterm infants and that administration of vitamin D metabolites during the first days of life is not warranted for the prophylaxis of early neonatal hypocalcemia.Speculation: A defect in vitamin D metabolism is considered to be a possible pathogenetic factor in early hypocalcemia in premature infants. Since our data indicate adequate intestinal absorption and liver hydroxylation of vitamin D3 with no obvious effect on the D metabolites, it is speculated that the biotransformation pathway of vitamin D3 is operative in preterm infants after 32 wk of gestation.

Body composition in children with renal disease: use of dual energy X-ray absorptiometry

Dual energy X-ray absorptiometry (DEXA) is a non-invasive accurate method which estimates bone mineral content and density (BMD), as well as fat (FM) and lean (LM) body mass. This method was used in control children in order to establish normal values for BMD of lumbar spine and whole body composition {logistic curves, general equation E=k+K/[1+αexp(-βA)]}. In children with chronic renal failure (CRF), LM correlated with the urinary excretion of creatinine (r=0.97,P=0.0001) independently from glomerular filtration rate. However, the assessment of LM by DEXA must take into account the hydration level, since there is a positive correlation between fluid loss and reduction in LM in children on hemodialysis (r=0.98,P=0.0001). After renal transplantation, a significant loss of BMD (median −9.2%), was observed at 6 months which returned to 95% of pretransplant values by the end of the 1 st year. Maximal changes in LM and FM occurred during the first 3 months (−7.8% and +7.2%, respectively) and may be due to steroids; these should be influenced by physical activity since FM correlated inversely with maximal oxygen consumption (r=0.69P=0.0001). Recombinant growth hormone treatment could also increase LM and decrease FM, as shown in 9 patients. DEXA appears therefore to be a reliable method for evaluating therapeutic interventions affecting nutritional status in children with CRF.

Undescended testis: comparison of two protocols of treatment with human chorionic gonadotropin. Effect on testicular descent and hormonal response.

A randomized study of two protocols of human chorionic gonadotropin (hCG) treatment was performed in 183 prepubertal boys between 7 months and 12 years of age: protocol I, in which the boys were given 7 injections of 1,500 IU every other day, and protocol II consisting of 4 injections of 100 IU/kg at 4- to 5-day intervals. In both protocols, by the end of the test, testosterone had risen significantly to values within the normal adult male range. However, the amplitude of the rise was slightly but significantly lower using protocol II (4.08 +/- 2.07 ng/ml) than protocol I (5.16 +/- 2.73 ng/ml). It would thus appear that repetition of the hCG injection at intervals of less than 4 days is unnecessary, and that a total stimulation period of 2-3 weeks is sufficient. Although not correlated with testosterone levels, the success rates for treatment were similar in both protocols and comparable to rates reported in the literature.

Takayasu arteritis in children

Takayasu arteritis (TA) is a large vessel vasculitis that usually affects young female patients during the second and third decades of life, but has been reported in children as young as 24 months of age. Aim of this report was to describe four children (two girls) with TA, as well as summarizing main published studies. The mean age at presentation of our cases was 11 years (range 8–15). Three patients were Caucasians and one Asian. Arterial hypertension was the commonest mode of presentation followed by systemic symptoms. Other related symptoms were due to ischemia and consisted of abdomen, chest, and limb pain. An abdominal bruit was noted in only one patient. Inflammation markers were always abnormal. Angiography was performed in all cases; left subclavian artery and common carotid artery were more frequently involved. Renal artery stenosis was observed in two patients. One boy was diagnosed as having an associated immune deficiency (Wiskott-Aldrich syndrome). Treatment modalities included prednisone (n = 4), methotrexate (n = 3), and mycophenolate mofetil (MMF) (n = 1). Surgery was required in two patients. Follow-up ranged from 3 to 10 years since diagnosis. In three cases antihypertensive drugs and methotrexate were stopped, and prednisone was reduced to 7.5 mg/day.

familial infantile nephrotic syndrome with ocular abnormalities

Two siblings born from consanguineous parents experienced infantile nephrotic syndrome with ocular and neurological abnormalities; the boy also had a micropenis; both patients died before age 1 year. An initial renal biopsy followed by a two-step binephrectomy allowed good histological assessment of disease progression in one patient. The progression of the lesions was characterized by mesangial involvement, then an extensive extracapillary proliferation and tubular dilatations with a high mitotic activity of the epithelium and nuclei of unequal size. The main features involved major ultrastructural changes of the glomerular basement membrane. These two patients may represent a new disease entity or a severe form of diffuse mesangial sclerosis, with autosomal recessive inheritance.