False-positive results in neonatal screening for cystic fibrosis based on a three-stage protocol (IRT/DNA/IRT): Should we adjust IRT cut-off to ethnic origin?

Since 1979, newborn screening for cystic fibrosis (CF) has been possible by measuring immunoreactive tryspinogen (IRT) in blood spots. In France, a programme based on a three-stage strategy (IRT/DNA/IRT) started in 2002. In the Rhône-Alpes area, the positive screening rate (i.e. the proportion of samples sent for genotyping) observed after the first IRT measurement was higher than the expected rate (0.65% versus 0.50%), without a greater CF incidence. We hypothesized that the IRT reference range could differ according to the ethnic origin of the newborns. 35 141 newborns were studied and divided into two groups: European ethnic group 26 324 (75%) and North African ethnic group 8817 (25%). 243 positive newborns were identified: 146 (60%) in the European ethnic group and 97 (40%) in the North African ethnic group. Three CF patients and 11 unaffected heterozygotes were found in the European group, but no mutations were found in the North African group. Mean IRT values and the percentage of IRT values over the cut-off were significantly higher in the North African group than in the European group (mean IRT = 21.17 microg/L and 19.74 microg/L, p < 0.0001; %IRT > cut-off = 1.1% and 0.5%, respectively). For the positive screened newborns, term and IRT mean were comparable, whereas birth weight was higher in the North African ethnic group. These results lead us to conclude that (i) newborns from families of North African origin have higher IRT values and (ii) most of the positive screened newborns in this population could be considered as 'false positives'. These conclusions could explain, in part, the large variations seen in the positive screening rate in the French CF neonatal screening and raise the question whether it is relevant to adapt cut-off to ethnic origin of the newborns.

A 5-year (1990-1994) neuroblastoma screening feasibility study in France. Methodology and preliminary observations.

INTRODUCTION: Following the pioneering Japanese experience, several European and North American groups implemented pilot studies on screening infants for neuroblastoma, considering the possibility of demonstrating a decrease in mortality rate. In France, a 5-year (1990-1994) feasibility study on neuroblastoma screening at the age of 4 months was initiated in the Rhône district (1.5 M inhabitants, 26,000 births per year). METHODS: Vanillylmandelic (VMA) and homovanillic (HVA) acids were measured by HPLC, and creatinine (Cr) by the Jaffé's kinetic method on Technicon RA-XT. VMA and HVA were expressed as microgram/mg of Cr. The method was assessed with both a daily intra-laboratory control and a sample of urine obtained from a national quality control organism. RESULTS AND DISCUSSION: The overall participation rate for the 5-year period was 82.2%. Out of 105,293 infants tested from 128,126 births, 12 NB cases were discovered with screening (screened cases) and 1 case was discovered with a late performed test (at 13 months of age). Six neuroblastomas were found clinically before the age of 4 m. Two cases were missed because the parents did not perform the test. Three children with normal tests at screening were false-negative cases: two of them were found secreting at diagnosis, while one remained non-secretory at diagnosis and later on. Otherwise, thirty-five false-positive tests were found. Biochemical observations are discussed. It is too early to reach clinical conclusions from this screening program on neuroblastomas as it is presently being followed up.

[Wilms tumor and Bloom syndrome]. / Tumeur de Wilms et syndrome de Bloom.

UNLABELLED: Bloom syndrome is characterized by growth failure, skin anomalies with sun sensitivity, minor anatomic defects, excessive chromosomic fragility and usually severe immune deficiency. The chromosome fragility predisposes these children to the development of hematologic malignancies and solid tumors. CASE REPORT: Morgan, a 4-year-old boy with Bloom syndrome, developed a Wilms tumor. Chemotherapy was poorly tolerated. Two years later, the child died from an uncontrolled progressive disease. CONCLUSION: This is the fourth reported case of Wilms tumor occurring in a child with Bloom syndrome. This possibility requires repeated abdominal ultrasonography in such patients.

[Determination of apolipoproteins B in children: use in the screening of atherogenic risk and influence of diet]. / Dosage des apoprotéines B chez l'enfant: utilisation pour le dépistage du risque athérogène et influence de la diététique.

The determination of plasma concentrations of apolipoproteins B (apo B) among 390 children (age 2-18 years) and the study of their antecedents showed that the prevalence of family histories of ischaemic cardiovascular diseases was higher among children whose apo B reached or exceeded 1.20 g/l. A low cholesterol diet was prescribed for children whose apo B levels were equal to or higher than 1.20 g/l. Two years later 45 of them were re-examined: they showed decreased apo B levels and a significant relationship between the magnitude of the decrease and the dietetic score related to the observance of the diet.

[A new case of acute lymphoblastic leukemia with Philadelphia chromosome in the child (author's transl)]. / Un nouveau cas de leucémie aiguë lymphoblastique de l'enfant avec chromosome Philadelphie.

The systematic study of the medullary karyotype in the course of haemopathies has led us to a new case of Philadelphia chromosome in an acute lymphoblastic leukemia. This was a case of a 13 year old child. Is this a particular class of haemopathy? Do such observations put a question on the dual theory of the origins of blood germ cells? The elaborate medullary karyotype in the course of haemopathy may solve this problem. A rigorously nosological classification is essential for appraising the therapeutic plan chosen and making a pronosis.

[Supplementary intravenous alimentation in the premature infant weighing less than 1,500 grams]. / Alimentation intraveineuse supplementaire chez le premature de moins de 1 500 g

The effects of a 10% glucose solution and of a fructose plus 1.4% casein hydrolysate solution have been comparatively evaluated in infants with birth weights under 1 500 g. Children fed with glucose solution only are used as matched controls. Children fed with protein hydrolysate associated with fructose have a weight loss lower than those of the control-group. However, the time necessary to regain the birth weight is similar in both groups. The biologic data which were studied (glucosemia, calcemia, acid-base balance, clotting factors) are statistically identical in both groups. Neither of the groups showed hyperglucosemia. The survival rate is similar in both groups; caloric and proteic supplementation does not change the death rate.