Physical outcome and school performance of very-low-birthweight infants treated with minimal handling and early nasal CPAP

Aim: To describe physical outcome and school performance in a cohort of very-low-birthweight infants treated with early nasal continuous positive airway pressure (NCPAP)/minimal handling regimen with permissive hypercapnia, in comparison to siblings of normal birthweight. Material and methods: Neonatal and follow-up data from 213 very-low-birthweight infants from 1983-1988 were registered and a questionnaire concerning school achievements was sent to the families of survivors and siblings attending school. Results: Mortality was 22%. Of the survivors, 4% had moderate-severe and 9% mild sequelae. Eighty-seven per cent of VLBW children and 95% of their siblings attended regular school. Average or above-average achievement was accomplished by 33 (65%) of the VLBW children and 34 (74%) of the siblings in mathematics, and 35 (69%) and 32 (68%), respectively, in reading/spelling. None of these differences reached statistical significance. However, the performance ratings correlated significantly with socio-economic conditions.

Conclusion: In this study of infants treated with a regimen of early NCPAP/minimal handling, we found a relatively low incidence of handicaps and impairments. Nearly 90% attended ordinary schools, with near-average performances in mathematics and reading/spelling, which were not statistically different to their siblings. The overall results indicate that these infants fare at least as well as survivors after conventional treatment.     

Effect of a six-month training programme on the physical capacities of Romanian schoolchildren

Aim: To analyse the effects of a training programme on the motor performance of Romanian schoolchildren. Methods: A total of 178 boys (9.5±0.8 y, 34±9 kg, 137.6±8 cm) and 192 girls (9.6±0.4 y, 32.7±7.6 kg, 136.9±7.5 cm) were randomly selected for the training group (TG) (n=198, 109 girls, 89 boys) and control group (CG) (n=172, 83 girls, 89 boys). The TG completed a 6-mo extracurricular training programme (two 50-min sessions per week) involving moderate-intensity impact exercises. At baseline and at follow-up, the EUROFIT tests were administered, and body composition, skeletal maturation and BMI were calculated. Results: At baseline there were no differences in physical characteristics between TG and CG. With the exception of cardiorespiratory endurance, both groups improved motor performances at follow-up. However, for TG boys the improvement was greater than for CG boys in the plate-tapping (+37.2%), sit-up (+20.4%), standing broad-jump (+13%) and shuttle-run tests (+3.8%). TG girls improved more than CG girls only in the standing broad-jump (+18.8%) and shuttle-run (+8.5%) tests.

Conclusion: Boys and girls in trained groups demonstrated greater increases in some tests of motor performance compared to their untrained peers. Two extra sessions of physical education per week were sufficient to elicit improvements in a number of components of motor fitness.     

Prevalence of germline mutations in the TSH receptor gene as a cause of juvenile thyrotoxicosis

Aim: To ascertain the prevalence of germline mutations in the TSH receptor gene as a cause of juvenile thyrotoxicosis (JT) in non-autoimmune patients. TSH receptor gene mutations are not seen in autoimmune-active patients. Methods: In a nationwide study on JT, 123 patients were re-examined 10 y (range 4 to 21 y) after diagnosis. Two patients with toxic adenoma were excluded. In 25 patients, no TPO, TG or TSH-R antibodies were found. In 17 patients, DNA material was available for TSH receptor gene analysis. The entire TSH receptor gene was sequenced in five patients. TSH receptor “hot spots” for mutations in exon 9 and 10 were sequenced in the remaining 12 patients. Results: A TSH receptor gene germline mutation was identified in only one patient of a total number of 121 patients with JT, of which 17 patients were presumed to have non-autoimmune JT by the lack of thyroid autoantibodies.

Conclusion: In Denmark the prevalence of germline mutations in the TSH receptor gene is one in 121 patients with JT (0.8%; 95% CI: 0.02-4.6%) and one in 17 patients with presumed non-autoimmune JT (6%; 95% CI: 5.88% (0.15-28.69)).     

Attitudes and feelings towards menstruation and womanhood in girls at menarche

Aim: To elucidate early adolescent girls' attitudes, thoughts and feelings towards menstruation and their bodies. Methods: 309 12-y-old girls answered questionnaires. One part of the questionnaire dealt with thoughts and feelings towards menstruation. The other part dealt with thoughts and feelings towards menstruation and sex and ability to communicate on aspects of womanhood. Results: Postmenarcheal girls were less positive towards menstruation than premenarcheal girls (p=1×10^-6). Many girls (43%) did not reaffirm the statement “I like my body” and almost one quarter stated being teased for their appearance. Many of the girls claimed that they had been called “cunt” (38%) or “whore” (46%). If called “cunt” or “whore”, 17% stated that they felt alone, 76% felt anger and 50% were offended. Mothers were those with whom girls could most easily “chat” about their period. Sixty-seven per cent received information about menstruation from school nurses.

Conclusion: Wanting to be an adult and liking that their body develops seem to be associated with a more positive feeling towards menstruation. Furthermore, mothers' timing and ability to communicate attitudes towards menstruation and the body are as important as those in a girl's immediate environment.     

The Milan Project: a newborn hearing screening programme

Aim: Since 1997 a newborn hearing screening programme has been implemented by the U.O. Neurologia-Neurofisiopatologia and Dipartimento di Neonatologia of the Istituti Clinici di Perfezionamento ICP in Milan for both babies with no risk and those at risk of hearing impairment. This programme was named the Milan Project. Methods: The protocol for no-risk babies consisted of three stages: in the first two stages, newborns were tested with transient click-evoked otoacoustic emissions (TEOAE), in the third one with conventional auditory brainstem responses (ABR). The first TEOAE test was performed by 36 h of age, before discharge, the second one after 15-30 d in case of referral, and the third one, by ABR, for those babies who failed the second TEOAE stage. Newborns at audiological risk were submitted to conventional ABR before the third month of corrected age. Some of this latter population was also submitted to the TEOAE test. The entire tested population (no-risk babies and newborns at audiological risk) consisted of 19 777 babies: 19 290 without risk (“no risk”) and 487 at risk (“at risk”). Results: During the course of the Milan Project, hearing impairment (ABR threshold equal to or greater than 40 dB nHL) was identified in 63 newborns (19 from the no-risk and 44 from the at-risk population), with a prevalence of 0.32%. Bilateral hearing impairment (BHI) was found in 33 newborns (10 from the no-risk and 23 from the at-risk population), corresponding to 0.17%. Among infants with bilateral hearing impairment, 30.3% had no risk factors. The prevalence of hearing impairment was determined on days 15-30 after birth.

Conclusions: The results show that the implementation of a hospital-based, universal neonatal hearing screening programme for babies with and without audiological risk is feasible and effective. The effectiveness of the programme has increased as a function of the years since its inception, with a strong decrease in the referral rate. Further improvement is obtained if the TEOAE measurements are repeated in cases of referral scoring before discharge.     

The natural history of idiopathic toe-walking: a long-term follow-up of fourteen conservatively treated children

Aim: To determine the long-term results after conservative treatment (physiotherapy, casting, orthoses, or a combination of these) of idiopathic toe-walking (ITW). Methods: Tiptoe-walking is diagnosed as idiopathic (habitual) if no signs of neurological, orthopaedic, or psychiatric disease are detected. The diagnosis is one of exclusion. Sixteen former patients with ITW, all now at least 13 y old, were asked to participate in a follow-up investigation 7-21 y after being first diagnosed. Two cases were excluded because heel-cord lengthening had been performed later on in other hospitals. The remaining 14 patients completed a questionnaire. Eleven patients consented to a clinical examination, during which they were videotaped and their active and passive ankle-joint dorsiflexion measured. These data were compared with the assessment at the initial evaluation. In one instance, the toe-walking ceased after conservative treatment (plaster cast). In all other cases the toe-walking pattern recurred. Results: At follow-up three patients showed some toe-walking when they were unobtrusively observed. When videotaped, they did not toe-walk, although a distinct heel-strike was missing. The remaining eight patients all walked with a heel-strike. Two patients had slight symptoms possibly related to toe-walking. No fixed contracture was present at the first evaluation, and none was found at follow-up. There was no systematic change in ankle-joint dorsiflexion from initial assessment to follow-up examination.

Conclusion: Non-surgical treatment of ITW does not have a lasting effect and the long-term results in this study are considered to reflect the natural history, i.e. the toe-walking pattern eventually resolves spontaneously in the majority of children. Surgical treatment of ITW should be reserved for the few cases with a fixed ankle-joint contracture.     

Survival after surgery for congenital heart defects: Does reduced early mortality predict improved long‐term survival?

Aim: The objectives of this study were 1) to compare early mortality (first 30 d after surgery) and long-term survival between two cohorts of patients operated on for congenital cardiac defects, and 2) to evaluate the impact of possible changes in early mortality on long-term survival. Methods: 945 patients with congenital cardiac defects, born in 1990-1999 and operated on in the same period were examined in a retrospective cohort study. The patients were divided into three groups: “univentricular cardiac defects”, “severe cardiac defects” and “less severe cardiac defects”. The study population was divided into two cohorts: group 1 included patients born and operated on in 1990-1994; group 2 included patients born and operated on in 1995-1999. The survival patterns in the two groups were compared. Results: For all patients, except those with univentricular cardiac defects, early mortality (30 d after surgery) was reduced. Among patients with severe cardiac defects, early mortality was reduced from 18.6% in group 1 to 2.9% in group 2. Among patients with less severe cardiac defects, early mortality was reduced from 6.2% to 1.9%. The improved outcome was maintained during the following 5 y. Overall relative risk of death during follow-up was reduced to 0.31 (95% CI: 0.15-0.56) for patients with severe cardiac defects, and to 0.53 (95% CI: 0.31-0.93) for patients with less severe cardiac defects born and operated on in 1995-1999.

Conclusion: Early mortality has been substantially reduced in congenital heart defect patients, and corresponds with significantly improved long-term survival.     

Early detection of podiatric anomalies in children with Down syndrome

Aims: To verify the importance of podiatric evaluation in patients with Down syndrome for the early diagnosis and treatment of minor orthopaedic problems. Methods: Case-control study of 50 children affected by Down syndrome (aged 4-10 y) without major orthopaedic malformations compared to 100 healthy children. A complete podiatric examination was performed on all patients and controls. Results: Children with Down syndrome showed several orthopaedic anomalies including bony deformity of the forefoot (90%), flat foot (60%), isolated calcaneal valgus (24%), knee valgus (22%) and pronated flat foot (16%). These abnormalities were responsible for postural alterations as confirmed by baropodometric examination.

Conclusion: The data demonstrated a greater incidence of minor orthopaedic alterations and suggest the necessity of regular podiatric examinations in the follow-up of this syndrome.     

Prospective evaluation of late effects after childhood cancer therapy with a follow-up over 9 years

Intensive multimodality treatment has led to a remarkable improvement of prognosis in paediatric cancer patients, however, a great number of long-term survivors suffer from considerable tumour- or treatment-related late effects. Between January 1990 and December 1998, 223 consecutive survivors of childhood malignancies entered a prospective follow-up study designed to evaluate the frequency and severity of tumour- and/or therapy-related long-term sequelae. After cessation of therapy and subsequently once a year, all patients underwent a detailed examination programme including physical examination, laboratory tests, abdominal sonography, echocardiography, electrocardiography, electroencephalography, spirometry, audiometry, ophthalmological examination and endocrine stimulation tests. Median follow-up was 5 years (range 0.4 to 9.6 years). A total of 167 patients (75%) had at least one chronic medical problem of whom 80 needed permanent medical support. The organ systems most frequently affected were the nervous system in 39%, the endocrine system in 32%, the ears/eyes in 22%, the kidneys in 17%, and the liver in 12% of the patients. Some late effects (endocrine deficits, hearing loss, tubulopathy) were primarily diagnosed only several years after the end of oncological therapy. Conclusion The results of this study indicate that a considerable number of former paediatric cancer patients suffer from remarkable long-term side-effects. Since life quality is an important parameter of cancer survival, careful follow-up of long-term survivors is mandatory with the aim to reduce or even abrogate possible side-effects at the earliest time. Received: 8 December 1999 and in revised form: 1 March 2000 / Accepted: 31 March 2000     

Ten years' experience of enzyme infusion therapy of Norrbottnian (type 3) Gaucher disease

Aim: To study the long-term effects of enzyme replacement therapy on the neurological signs of chronic neuronopathic Gaucher disease and to evaluate some biochemical parameters for monitoring the treatment. Methods: Eight patients from the Norrbottnian cohort were followed during 10 y of treatment. They were followed with regular clinical observations, biochemical tests and psychometric testing. Results: After the start of treatment, their general well-being improved and was stable during the follow-up. In three of the patients there were some indications of slow neurological deterioration. The mean results of psychometric testing did not decrease. Glucosylceramide and chitotriosidase levels were useful in monitoring the treatment. The chemokine CCL18 also seems to be a useful parameter for future monitoring.

Conclusions: Enzyme replacement therapy seems to slow down further neurological and mental deterioration in mild chronic neuronopathic (type 3) Gaucher disease.     

Multiple-step polyclonal versus one-step monoclonal enzyme immunoassay in the detection of Helicobacter pylori antigen in the stools of children

Objective: Evaluation of a polyclonal and a monoclonal Helicobacter pylori stool antigen test (HpSAT) for the detection of Helicobacter pylori (HP) infection in children. Methods: 43 children underwent a ¹³C-urea breath test (¹³C UBT) and a HpSAT for the detection of HP. A child was considered HP positive if the ¹³C UBT was positive. Two HpSATs were tested: the “Premier Platinum HpSA” test (PP HpSAT) (polyclonal enzyme immunoassay) and the “ImmunoCard STAT! HpSA” test (ICS HpSAT) (one-step immunochromatographic assay). Results: The mean age of the children was 8.9 y (range 3.5-17.5 y). Of the 43 children, 18 (41.9%) were HP positive and 25 (58.1%) were HP negative. The PP HpSAT showed a sensitivity of 94.4% and a specificity of 100.0%. With the ICS HpSAT, equivocal results occurred in 5/42 (11.9%) of the tests due to a problem with the visual interpretation of the change in colour of the test-line. The ICS HpSAT had a sensitivity of 100.0% and a specificity of 76.0% when the test was considered positive in case of any change of colour of the test-line, which is the correct practice according to the manufacturer. The ICS HpSAT had a sensitivity of 100.0% and a specificity of 96.0% when the test was considered positive only in case of a “significant change of colour” of the test-line.

Conclusion: Compared to the ¹³C UBT, the PP HpSAT shows a comparably good sensitivity and specificity, the ICS HpSAT has a comparably good sensitivity but lower specificity due to a high percentage of equivocal results when the test is used according to the manufacturer's instructions, and the ICS HpSAT has a comparably good sensitivity and specificity when a weakly positive test is considered negative for the diagnosis of HP infection in children. The ICS HpSAT is easy to perform with results available within 10 min, and is therefore of particular interest in ambulatory medicine.     

Exploration of health status, healthcare utilization, and health service expectations among Taiwanese adolescents

There have been few reports about adolescent experiences with and expectations of health service utilization in an Asian societal setting. The aim of this study is to analyze the use of healthcare services in relation to health status and explore adolescents' preferences for youth-friendly service among Taiwanese high school students. A cross-sectional questionnaire-based survey was conducted on Taiwanese adolescents aged 12–18 years in 2010. We invited participants to rate their health status, report their previous healthcare service use, and rank their health service preferences. We used logistic regression analysis to investigate the association between self-rated health status and healthcare utilization and used nonparametric analysis to compare health service preferences among sociodemographic subgroups. A total of 4,907students (97.2 % response rate) returned valid questionnaires for analysis. Poor health status and chronic illness were most salient factors independently associated with frequent healthcare service use. Only 40 % of respondents reported having a regular doctor, and pediatrics (57.7 %) was the most commonly identified professional source of medical care. A great majority (86.2 %) of respondents made clinical visits with parents. For characteristics of youth-friendly clinician, the top-ranked items included competency and patience, while having helpful and friendly personnel was highlighted for clinical setting. Conclusion: Family participation is critical in healthcare for adolescents in Asian cultures. Health service use is significantly influenced by health status and chronic illness in the general health insurance system. Understanding these background influences on expectations for healthcare may help to create youth-friendly health services that are more culturally appropriate.     

Improved final height with long-term growth hormone treatment in Noonan syndrome

Aim: To assess whether children with Noonan syndrome on long-term growth hormone (GH) therapy improve their final height to near mid-parental height. Methods: Twenty-five prepubertal children (13 girls) with Noonan syndrome (NS) were studied. A single clinician made the diagnosis based on clinical criteria. GH treatment started at an age ranging from 3.1 to 13.8 y and was continued for at least 2 y. Improvement or “gain” in final height (FH) was defined as either the difference between adult height SD scores (SDS) and pre-treatment height SDS (the childhood component of the Swedish reference) or height SDS compared to the Noonan reference. Results: Ten children received a GH dose of 33 μg/kg/d (mean age at start 7.7±2.1 y, mean age at stop 17.6±1.7 y) and 15 received a dose of 66 μg/kg/d (mean age at start 8.6±3.3 y, mean age at stop 18.4±2.1 y). Eighteen out of 25 patients reached FH. A substantial improvement in FH of 1.7 SDS, equivalent to 10.4 cm compared to pre-treatment height, was observed. No significant difference was seen between the two GH doses. Females gained a mean height of 9.8 cm and males 1-13 cm (FH 174.5±7.8 cm vs mean adult height of 162.5±5.4 cm for males with NS) at final height. Moreover, 60% reached a mid-parental height of±1 SD.

Conclusion: GH treatment improves final height in patients with Noonan syndrome, with a mean gain of 1.7 SDS. The prepubertal height gain is maintained to final height and the children achieve a height close to their mid-parental height.     

Oral anticoagulant treatment in children based on monitoring at home

Aim: To evaluate the feasibility of home monitoring of oral anticoagulant treatment (OAT) in paediatric patients. Methods: A total of 19 paediatric patients received OAT and then monitored their treatment at home with CoaguChek®. Data on their International Normalized Ratio (INR) values were collected retrospectively from hospital records and from the notes kept by the families. The families of the patients were also asked to fill in a questionnaire. Results: No thrombotic or haemorrhagic complications occurred during a total amount of 44.7 follow-up years. INR: the proportion of INR values measured at home falling within the therapeutic range for the given patient varied from 33 to 86% (median 69%). The questionnaire: all respondents were satisfied with home monitoring, and 63% felt that a major advantage of home monitoring was that there was no need to perform venipuncture. While 47% of the respondents reported no disadvantages of home monitoring, 42% reported that they occasionally lacked confidence in their ability to conduct OAT correctly at home.

Conclusion: Home monitoring of OAT is feasible and reasonably reliable in paediatric patients. However, it is crucial that healthcare professionals supervise the treatment and the families are provided with detailed and precise instructions on how to act in a variety of clinical situations.     

Children with chronic conditions in a paediatric emergency department

Aim: To describe the use of a paediatric emergency department by children with chronic conditions. Material and methods: We prospectively indexed all the children seen in our emergency department during 1 y to describe the population of children with chronic conditions, and to compare it with the general paediatric population. Results: There were 11 483 patient visits, of which 11% were by chronically ill children. Six subspeciality areas accounted for the vast majority of the chronic conditions seen: neurology (30%), cardiology (18%), pulmonology (18%), nephro-urology (16%), haemato-oncology (9%) and endocrinology (4%). Admission rate to the hospital was significantly higher for chronically ill patients (38% vs 23%). Among chief complaints, fever, respiratory distress, headache and seizures were overrepresented in chronically ill children. The chief complaint was related to the child's chronic condition in 51% of the visits. In both chronically and non-chronically ill patients, the majority of final diagnoses were related to infection (57% and 65%, respectively). Among diagnoses, bacterial infections, seizures, vasovagal syncopes and asthma were overrepresented in chronically ill children.

Conclusion: From the analysis of our data, we conclude that children with chronic conditions account for a tenth of all visits to a paediatric emergency department. The paediatric emergency physicians provide an important service to both the children with chronic conditions and the subspecialists who care for them.     

Effects of sociodemographic factors on adherence to breastfeeding and other important infant dietary recommendations

Aim: To examine in an affluent and healthy population the association between sociodemographic factors and the adherence to key infant dietary recommendations. Methods: In a longitudinal prospective study, healthy newborns were selected randomly in maternity wards around Iceland and their diet recorded every month for one year (n=124). In addition, a 48-hour-weighed-record, including information on added sugar, fruits, vegetables and the use of A and D vitamin drops was completed by 91 (73%) mothers at 9 and 12 months. Information about the mothers' education, smoking, age, parity, and family income was collected (n=98; 79%). Results: Regression analyses, including sociodemographic factors, showed exclusive breastfeeding to be positively associated with more education (P=0.022) and non-smoking (P=0.013) explaining 22% of the variance, and total breastfeeding (exclusive + partial) with non-smoking (P=0.006). Multiple regression also showed children's intake of added sugar from 9-12 months to be positively associated with mother's smoking (P=0.022) and negatively with age (P = 0.026), explaining 30% of variance. Sociodemographic factors were associated with children's fruit and vegetable consumption but not with the administration of AD-vitamin drops. However, when tested for significance between groups, younger mothers with fewer children seemed less likely to give AD-vitamin drops.

Conclusions: In a group of mothers getting regular antenatal care and giving birth to healthy infants, sociodemographic factors can predict which mothers need special guidance concerning recommendations about diet in infancy. These were mothers with less education, who smoked, were younger and were having their first or second child.     

Trends in the epidemiology of neonatal sepsis of vertical transmission in the era of group B streptococcal prevention

Aim: To assess trends in the epidemiology of culture-proven and clinical neonatal sepsis of vertical transmission in the era of intrapartum antibiotic prophylaxis. Methods: Since 1995, the neonatal services of 28 acute-care teaching hospitals in Spain (“Grupo de Hospitales Castrillo”) have been involved in the prospective surveillance of neonatal infection of vertical transmission. We here report the comparison of the incidence for the periods 1996-1997 and 2000-2001, and look separately at two groups of hospitals according to the time at which the official hospital policy to provide intrapartum antibiotic prophylaxis for group B Streptococcus (GBS) prevention was adopted. In 16 hospitals the policy was adopted in 1999 and in 10 before 1998 (nine hospitals in 1996, one in 1997). Results: The incidence of proven sepsis decreased significantly by 22% and 54% in the hospitals that started prophylaxis in 1999 and before 1998, respectively. The incidence of GBS sepsis also declined significantly by 36.4% and 65.4% in both groups of hospitals, respectively. Significant variations in the incidence of clinical vertical sepsis as well as in the incidence of sepsis caused by Haemophilus influenzae and Klebsiella were not found. Sepsis caused by Escherichia coli increased in the hospitals with prophylaxis from 1999 and decreased in those that began prophylaxis before 1998, in which the mortality rate of proven and clinical sepsis also decreased significantly by 58.6%.

Conclusions: There was a substantial decline in the incidence of proven vertical sepsis, with a significant reduction of GBS sepsis, although decreases were more marked when antibiotic prophylaxis was started before 1998. In this group of hospitals, there was also a decrease in the mortality rate. Fluctuations in the incidence of E. coli infection suggest the need for continuing epidemiological surveillance.     

Using radioligand-binding assays to measure tissue transglutaminase autoantibodies in young children

Aim: To measure autoantibodies against tissue transglutaminase (tTG) in young children prospectively screened for coeliac disease (CD). Methods: In total, 652 children aged 2.9 (2.5-4.2) y were analysed for IgA-tTG and IgG-tTG with radioligand-binding assays and IgA endomysial antibodies (EMA) by indirect immunofluorescence. Antibody-positive children were retested after 1.2 (range 0.2-1.9) y. Intestinal biopsy was performed on children with persistently high antibody levels. Results: In total, 3.2% (95% CI: 1.9-4.6%) of the 652 children were positive for at least one antibody at baseline: 2.5% (95% CI: 1.3-3.7%) for IgA-tTG, 1.7% (95% CI: 0.7-2.7%) for IgG-tTG and 2.9% (95% CI: 1.6-4.2%) for IgA-EMA, respectively. Ten children were positive for all three antibodies, five for both IgA-tTG and EMA, four for EMA only, one for IgA-tTG and another for IgG-tTG. IgA-EMA titres correlated with IgA-tTG levels (r = 0.73, p = 0.0003). At follow-up, seven of 20 children remained positive for all three antibodies, three for IgA-tTG only, one for both IgA-tTG and EMA, one for IgA-tTG and IgG-tTG, and the remaining child refused further participation. Three biopsies showed villous atrophy, two increased intraepithelial lymphocytes and two normal findings. Biopsy was not performed in four children with low or declining tTG antibody levels at follow-up and in one child who declined. CD was evident in 0.5% (95% CI: 0.0-1.0%) (3/652).

Conclusion: This study revealed a high number of young children positive for tTG antibodies as well as EMA, but the majority showed declining levels in both antibodies over time. We suggest using radioligand-binding assays for quantitative measurement of tTG antibodies when change in antibody levels is studied in young children.     

Somatic factors at 8 years of age in children with recurrent use of antibiotics in early infancy

Aim: To examine the influence of recurrent therapy with antibiotics (RTA) in infancy on children's somatic factors at 8 y of age. Methods: Subject selection was based on stratified randomized cluster sampling. Altogether 1287 infants were potential participants in the follow-up study. Children with ≥6 courses of antibiotics (100 children) during their first 18 mo of life and children with no (62%) or ≤2 courses (38%) of antibiotics participated in a clinical examination in a case-control setting (100 matched controls) at the age of 8 y. Results: The children with RTA continued to have more infections and had had more courses of antibiotics compared to controls during the follow-up. There was no clinically significant difference in the somatic and dental status at the age of 8 between the two groups. The parents of the children with RTA reported significantly more often recurrent infections than the parents of the controls.

Conclusions: The children with recurrent therapy with antibiotics in early childhood also continue to be prescribed more antibiotics in later childhood when compared to those who received no or few antibiotics in infancy. However, recurrent infections and medications do not seem to have a marked effect on the somatic and dental status of these children at 8 y of age.     

Thiamine-responsive megaloblastic anaemia syndrome: long-term follow-up and mutation analysis of seven families

Aim: Thiamine-responsive megaloblastic anaemia syndrome (TRMA) is the association of diabetes mellitus, anaemia and deafness, due to mutations in SLC19A2, encoding a thiamine transporter protein. This is a unique monogenic form of vitamin-dependent diabetes for which there is limited long-term data. We aimed to study genotype-phenotype relationships and long-term follow-up in our cohort. Methods: We have studied 13 patients from seven families and have follow-up data for a median of 9 y (2-30 y). Results: All patients originated from Kashmir or Punjab, and presented with non-immune, insulin-deficient diabetes mellitus, sensorineural deafness and a variable anaemia in the first 5 y of life, the anaemia progressing to megaloblastic and sideroblastic changes in the bone marrow. The anaemia and diabetes mellitus responded to oral thiamine hydrochloride 25 mg/d, but during puberty thiamine supplements became ineffective, and almost all patients require insulin therapy and regular blood transfusions in adulthood. All patients are homozygous for mutations in the SLC19A2 gene. We have identified a novel missense mutation (T158R) that was excluded in 100 control alleles.

Conclusion: Diabetes in this syndrome is due to an insulin insufficiency that initially responds to thiamine supplements; however, most patients become fully insulin dependent after puberty. A mutation screening strategy is feasible and likely to identify mutations in almost all cases.