Background: The iodine supply of the population in Berlin has normalized during the last 5 years. Therefore autoimmune thyroiditis has become the most important differential diagnosis in children and adolescents with goiter. Objective: The aim of the present study was to define the prevalence of anti-thyroid peroxidase (TPO) antibodies and autoimmune thyroiditis in children and adolescents with a normalized iodine intake. Design: To enable the measurement of antibodies to thyroid peroxidase (anti-TPO-Ab) in a large cohort, a method to determine anti-TPO-Ab in dried filter paper blood spots was established. In co-operation with pediatricians the antibody prevalence was assessed and data regarding thyroid size, echostructure and the medical history concerning iodine intake and familial thyroid diseases were collected. Methods: 660 children and adolescents participated in the study; urinary iodine, TSH and TPO-Ab were measured and an ultrasound of the thyroid gland was performed. Results: The sensitivity of the newly established filter paper assay was 91.8% and specificity was 100%. The results confirmed the improved iodine supply, with a median urinary iodine concentration of 139 mg iodine/g creatinine. The prevalence of anti-TPO-Ab was 3.4% with a female to male ratio of 2.7:1. Conclusion: The prevalence of anti-TPO-Ab is lower or equal to data reported from other iodine sufficient areas. Data from a moderate iodine deficiency in schoolchildren range from 0.0 to 7.3%. Using the new filter paper method field studies can be implemented to monitor the effect of changes in iodine nutrition on thyroid autoimmunity. Furthermore, this study on the prevalence of anti-TPO-Ab in a cohort of healthy children and adolescents in an iodine replete area can serve as reference data for future investigations and for the comparison with other groups of patients with increased risks for thyroid autoimmunity.
Antiepileptic drugs taken by pregnant epileptic women are known human teratogens. They may also cause pharmacological side effects in the newborn, i.e. sedation and or withdrawal symptoms. We examined the relationship between the maternal antiepileptic therapy, neonatal behaviour and later neurological functions in infancy. The study comprised 40 children exposed in utero to a single antiepileptic drug (phenobarbitone, phenytoin, valproic acid). Valproic-acid-exposed children were the highest compromised, except for apathy, which was most profound in phenobarbitone-exposed neonates. Valproic acid serum concentrations at birth correlated with the degree of neonatal hyper-excitability and neurological dysfunction when children were re-examined 6 years later. We suggest that valproic acid may not only cause malformations but also cerebral dysfunction immediate and long term.
Fourteen epileptic women treated with primidone, either alone or in combination with other antiepileptic drugs, were studied prospectively during their pregnancy. Plasma levels of primidone and its metabolites were monitored and correlated to findings in the offspring. Maternal serum concentrations of primidone and metabolites were generally low during pregnancy. The levels of its main metabolites--phenobarbital and PEMA--were found to drop within the first month of pregnancy in two cases. The plasma concentrations remained low until birth and rose sharply thereafter. The phenobarbital/primidone ratio (mean 0.84) and PEMA/primidone ratio (mean 0.56) in pregnant patients were found to be lower than in non-pregnant patients, except when primidone was given in combination with phenytoin in which case the expected phenobarbital/primidone (mean 2.5) and PEMA/primidone (mean 1.5) ratios were found. A ventricular septal defect was found in one of the offspring of the fourteen mothers and five children had microcephaly. There was a high incidence of poor somatic development with dystrophy (n=3) and short stature (n=2). Head circumferences (n=8), lengths (n=4) and/or weights (n=8) were below the 10th percentile in a number of children. Four children showed marked facial dysmorphy. Our preliminary data suggest that primidone intake during pregnancy may be important in the pathogenesis of minor anomalies and in the induction of poor somatic development.
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