Medical, psychological and intellectual development of 5-year-old children born after intracytoplasmic sperm injection.

BACKGROUND: The neurodevelopmental outcome of children born after intracytoplasmic sperm injection (ICSI) is controversial. PATIENTS AND METHODS: Thus, we compared the medical and developmental outcome at a mean age of 5 years and 6 months of 35 singletons born after an ICSI procedure performed at the Tübingen Medical Center with those of 37 naturally conceived (NC) matched control singletons born at the Tübingen Medical Center. Children with congenital anomalies which could interfere with mental development were excluded, these were reported earlier. Each child was assessed neurologically and physically. Cognitive function was assessed using the Kaufman assessment battery for children (K-ABC). Behaviour was tested using a German behavioural questionnaire for preschoolers (VBV). RESULTS: Medical and cognitive outcome, and behaviour pattern were similar in both groups. Nevertheless, there were sex-related differences in favour of ICSI children: ICSI boys had better social competence than the control boys, while ICSI girls had less emotional problems than the control girls. CONCLUSIONS: Once severe congenital anomalies were excluded, there were no differences in physical and neurodevelopmental outcome of 5-year-old ICSI children compared with controls.With regard to behaviour and emotional development, ICSI children seem to be similar or might be even more stable and socially competent than the control children. As our study is limited by the small sample size, further research is needed to confirm our results.

Increased frequency of severe major anomalies in children conceived by intracytoplasmic sperm injection.

The neurodevelopmental outcome of children born after intracytoplasmic sperm injection (ICSI) is controversial. We compared the medical and developmental outcome of 34 singletons born after ICSI (20 males, 14 females; mean ages of 18 mo and 40 mo [SD 9 mo]; range 2 y 10 mo-4 y 8 mo) with 39 case control studies (21 males, 18 females; mean ages of 18 mo and 40 mo [SD 4 mo]; range 3 y-4 y 1 mo). Each child was assessed physically and tested in three development domains (fine motor, gross motor, and language). Five children born after ICSI versus two control children (p=0.2) had major congenital anomalies (MaCAs). Four children born after ICSI versus no control children had severe MaCAs (p=0.04). These were defined as having a significant impact on development or causing chronic disease: Angelman syndrome (n=1), lissencephaly (n=1), Hanhart syndrome (n=1), and persistent hyperinsulinemic hypoglycaemia of infancy (n=1). Karyotyping in 23 children born after ICSI revealed no abnormalities. An imprinting defect was found in the child with Angelman syndrome. Results of developmental assessment were in all cases normal at the age of 18 months except for the three children with Angelman and Hanhart syndromes, and lissencephaly. At the second assessment, five more children born after ICSI and four control children showed abnormalities in one or more developmental domains. We conclude that there seems to be a higher frequency of severe major anomalies in children born after ICSI. An increased risk for imprinting defects cannot be excluded. If we exclude children with severe MaCAs, the incidence of an abnormal somatic or neurodevelopmental outcome in the fourth year of life in children born after ICSI is similar to that of spontaneously conceived children.

Coeliac disease in children with Type 1 diabetes mellitus: the effect of the gluten-free diet.

PATIENTS AND METHODS: We assessed the frequency of coeliac disease in 281 children with Type 1 diabetes and the effect of gluten-free diet (GFD) in newly diagnosed cases. Serological screening was performed using anti-gliadin and anti-endomysium antibodies. Data were obtained about clinical symptoms, height and weight-for-height. RESULTS: A small intestinal biopsy was recommended to 18 patients (6.4%) with positive serological results and 12 children agreed. Nine of them had coeliac disease. Three out of nine coeliac children complained about gastrointestinal symptoms. On a GFD, the symptoms disappeared in two patients. Iron-deficiency anaemia was present in four subjects and disappeared in the three patients who accepted the GFD. In three patients (33%), coeliac disease was asymptomatic. Height and weight-for-height were in the normal range for all patients. For well-complying patients, there was a significant increase in height standard deviation at diagnosis and on follow-up (-0.28 vs. +0.35) (P = 0.03). Changes in weight-for-height were not significant (-4.0% vs. +1.4%) (P = 0.28). There was a trend to an improvement in HbA(1c) (8.0 vs. 7.3%) (P = 0.05). CONCLUSIONS: Serological screening is effective. There is a therapeutic benefit for some screening-detected patients, but confirmatory studies are needed.

A high index of suspicion: the key to an early diagnosis of Wilson's disease in childhood.

BACKGROUND: To study the clinical features of Wilson's disease in childhood. METHODS: Retrospective review of the clinical, laboratory, and histologic features and prognosis of Wilson's disease in 26 Spanish children. RESULTS: The first medical visit, at age 9.8+/-3.4 years (range, 4-16 years), was prompted by liver dysfunction detected accidentally (61%), symptoms of liver disease (27%), family screening (8%), and extrapyramidal symptoms and personality changes (4%). There were laboratory data of hepatic failure in 27%. All copper metabolism test results (total serum copper, 24-hour urine excretion, serum ceruloplasmin) were abnormal in 62%, two in 27%, and one in 11%. All patients in whom extrahepatic involvement was found at diagnosis had severe liver disease. Histologic findings were portal fibrosis with steatosis (29%), cirrhosis (21%), portal fibrosis (17%), chronic active hepatitis (17%), and minimal changes or normality (17%). Penicillamine was administered to all but one patient. Four children underwent liver transplantation, three of them having received penicillamine for 12, 45, and 70 days. Three other patients recovered from liver failure after 1 year of treatment with penicillamine. After a follow-up of 4.5+/-3.3 years, all the children survived. Penicillamine caused severe toxicity in one patient. CONCLUSIONS: Wilson's disease in childhood is generally detected by maintaining a high suspicion of liver disease in patients who have no or nonspecific hepatic symptoms. Kayser-Fleischer ring is rare in childhood. Drug therapy is effective and well tolerated, even in some cases of hepatic insufficiency.

[Pulmonary tuberculosis in children: its age-dependent aspects]. / Tuberculosis pulmonar en el niño: características según la edad.

OBJECTIVE: The aim of this study was to investigate the clinical and radiological particularities of pulmonary tuberculosis depending on the age of the child. PATIENTS AND METHODS: The medical records of all children with pulmonary tuberculosis diagnosed between 1985 to 1996 were reviewed. They were divided into three age groups according to age: < 3 years, 3-5 year and 6-15 years. RESULTS: Of the 173 children identified, 51.4% were male. Forty percent were < 3 years if age, 33.1% between 3 and 5 years and 26.1% between 6 and 15 years old. The frequency of diagnosis derived from a case contact investigation was higher in children < 3 years of age (38.6%) and children aged 3-5 years (52.6%) than in children between 6-15 years old (21.7%, p < 0.05 for both). In the other cases, diagnosis was the result of investigation of an ill child, investigation of a child after pulmonary tuberculosis was diagnosed in a sibling and routine tuberculin skin test reactivity. An adult source of tuberculosis was identified in 68.6% of the children < 3 years old, 59.6% of children aged 3-5, but only in 37% of the children aged 6-15 years (p < 0.05 for both). The case contact was a family member in 92.7% of the children < 6 years of age and in 66.7% of children aged 6-15 years (p < 0.01). Culture of Mycobacterium tuberculosis was positive in 47.1% of children < 3 years old and 43.9% of children aged 6-15 years, but only in 27.5% of children aged 3.5 years (p < 0.05). Pulmonary parenchymal disease was more frequently found in children < 3 years (67.5%) than in children aged 6-15 years (39.4%, p < 0.05). CONCLUSIONS: Investigation of an adult source is essential when a child is diagnosed of pulmonary tuberculosis. Pulmonary tuberculosis is more intense and the source of adult contact is more frequently found in children < 3 years old.

Tolerance of pyrazinamide in short course chemotherapy for pulmonary tuberculosis in children.

BACKGROUND: This prospective study was performed to evaluate the tolerance of pyrazinamide in short course chemotherapy in children. METHODS: A total of 114 children ages 6 months to 15 years (4.5 +/- 3.4 years) with diagnosed pulmonary tuberculosis from 1985 to 1995 entered the trial. A 2-month regimen of isoniazid, rifampin and pyrazinamide, followed by rifampin and isoniazid for the remaining 4 months, was administered orally to all children. Clinical adverse effects specifically investigated were gastrointestinal disturbances, rash, signs of hepatotoxicity and arthralgias. Laboratory toxicity data (number of leukocytes, erythrocyte sedimentation rate, aspartate aminotransferase, alanine aminotransferase and serum uric acid) were collected before treatment and 1, 3 and 5 months after the beginning of chemotherapy. RESULTS: Clinical adverse effects were mild in all cases. Three children (2.6%) had fever and 5 (4.4%) had gastrointestinal disturbances. Aspartate aminotransferase and alanine aminotransferase mean values showed no differences along time and no patients had clinical signs of hepatotoxicity. Only 11 children (19.6%) showed a slight increase in alanine aminotransferase (< 194 units/l). Serum uric acid increased in 92.2% of the children compared with pretreatment values. This increase remained within the normal range in all but 9.8% of patients. There was a significant increase in uric acid mean concentrations after 1 month of therapy (from 3.7 +/- 0.7 mg/dl to 5.7 +/- 1.6 mg/dl, P < 0.05), which fell again (4.0 +/- 1.1) 1 month after pyrazinamide was stopped. There were no signs of gout or arthralgias. In no case was the treatment interrupted. CONCLUSION: The addition of pyrazinamide in chemotherapy for pulmonary tuberculosis in children was found to be safe. The slight increase in uric acid concentration during its administration had no recognized adverse consequences.