Size at birth has been associated repeatedly with increased risk of cardiovascular morbidity and mortality later in life. However, there is accumulating evidence to suggest an association between ...being born small for gestational age (SGA) and increased risk of lower intelligence, poor academic performance, low social competence and behavioural problems, compared with individuals born appropriate for gestational age. Crude neurological handicaps, such as cerebral palsy, are extremely rare in children born SGA at term. Such handicaps are more common in very premature children. However, there does appear to be an increase in the risk for non-severe neurological dysfunction in individuals born SGA. Intellectual performance is evaluated in young children in several different ways, including standardized tests such as Weschler's Intelligence Scale – Revised, and teachers and parents' reports. In adulthood, indirect variables such as education and occupation are used in addition to standardized tests. It may be possible to modify the effects of SGA on intellectual development by breast feeding the baby for more than 6 months. Nutrient-enriched formula does not have any advantages when it comes to intellectual development, and induces a risk of rapid weight gain and eventually overweight. Growth hormone treatment may also have some effect on intelligence quotient.
We have studied the occurrence of enterovirus (EV)-RNA at the onset of childhood type 1 diabetes in all 24 new cases of childhood type 1 diabetes during 1 year in Uppsala county, Sweden. We also ...studied 24 matched control subjects and 20 siblings of the patients. RNA was isolated from peripheral blood mononuclear cells and EV-RNA detected by RT-PCR. Primers (groups A and B) corresponding to conserved regions in the 5' noncoding region (NCR) of EV were used in the PCRs, and the amplicons were sequenced. By the use of group A primers, EV-RNA was found in 12 (50%) of the 24 type 1 diabetic children, 5 (26%) of 19 siblings, and none of the control subjects. Both patients and siblings showed a higher frequency of EV-RNA compared with the control subjects. The group B primers detected EV-RNA in all three groups but did not show statistically significant differences between the groups. The EV-RNA positivity with the group B primers was 11 (46%) of 24 in the type 1 diabetic children, 11 (58%) of 19 in the siblings, and 7 (29%) of 24 in the control subjects. The significant difference between groups seen with the group A primers but not with the group B primers might indicate the existence of diabetogenic EV strains. The phylogenetic analysis of the PCR products revealed clustering of the sequences from patients and siblings into five major branches when the group A PCR primers were used. With the group B primers, the sequences from patients, siblings, and control subjects formed three major branches in the phylogenetic tree, where 6 of the 7 control subjects clustered together in a sub-branch of CBV-4/VD2921. Seven of the type 1 diabetic children clustered together in another sub-branch of CBV-4/VD2921. Five of the type 1 diabetic children formed a branch together with the CBV-4/E2 strain, four clustered together with CBV-5, and one formed a branch with echovirus serotype. The presence of EV-RNA in the blood cells of most newly diagnosed type 1 diabetic children supports the hypothesis that a viral infection acts as an exogenous factor. In addition, sequencing of the PCR amplicons from the type 1 diabetic children, their siblings, and matched control subjects might reveal differences related to diabetogenic properties of such a virus.
We sought to study whether the association between being born small for gestational age and risk for low intellectual performance was modified by gestational age.
A population-based cohort study was ...conducted of 352,125 boys who were born between 28 and 43 completed weeks of gestation from 1973 to 1981 in Sweden. Risk for low intellectual performance at military conscription, estimated as odds ratios with 95% confidence intervals was measured.
Compared with men who were born preterm (28-36 weeks) and had normal birth weight for gestational age, men who were born preterm and had a very low birth weight for gestational age were not at increased risk for low intellectual performance. In contrast, men who were born preterm with a very short birth length or a very small head circumference for gestational age faced a near doubled risk for low intellectual performance compared with their appropriate peers. Among men who were born at term (37-41 weeks), risk for low intellectual performance was increased among those with very or moderately small birth weight, birth length, or head circumference for gestational age.
During early stages of gestation, growth in length and head circumference may be more important for intellectual development than weight increase. Future studies on size at birth and intellectual performance should consider also including anthropometric measurements other than birth weight.
Background The aim was to identify determinants (biomedical and social characteristics of children and their parents) of cystatin C levels in healthy children drawn from a population sample. Study ...Design Cross-sectional study. Setting & Participants 425 pairs of consecutive full siblings born 1987-1995 in Uppsala were identified using the Swedish Medical Birth Registry and invited with their parents for examination in 2000-2001. Outcome Serum cystatin C level was log-transformed and analyzed using random-effects models. Measurements The examination in parents and children consisted of a nonfasting blood sample, anthropometry, and questionnaires about lifestyle and socioeconomic position. Tanner stage was used for assessment of pubertal status. Results In age-, height-, and body mass index–adjusted analyses, cystatin C level increased by 2.6% (95% CI, 0.3%-4.8%) higher in Tanner stage 2 vs 1 girls, and 1.6% (95%CI, 0.2%-3.1%) lower in boys than girls. For every 10% increase in maternal cystatin C level, offspring cystatin C level increased by 3.0% (95% CI, 2.2%-3.8%); the equivalent effect for paternal cystatin C level was 2.1% (95% CI, 1.3%-2.9%). Lower maternal education was associated with a 2.4% (95% CI, 0.3%-4.6%) higher cystatin C level in their offspring. Limitations Cross-sectional study design, missing cystatin C values for subset of parents, lack of urinary measurements, no gold-standard measurement of glomerular filtration rate. Conclusions There are intergenerational associations of cystatin C level in families in line with previous reports of heritability of kidney disease. Lower maternal education is associated with higher cystatin C levels in their children. Further studies of healthy children are needed to explore the biological mechanisms for these findings. If cystatin C is measured, these studies will need to record pubertal stages.
Short stature and excess weight in adulthood are both associated with an increased risk of health problems. In a population-based investigation, data on birth length, birth weight, and gestational ...age for males born in Sweden in 1976 were used to predict the risk of being short or overweight in adulthood. The Swedish Birth Register was used to identify singleton males, born to Nordic mothers, who were without malformations and alive at 18 y of age. After individual record linkage between the Birth Register and the Swedish Conscript Register, information about height and weight at 18-21 y was obtained for 90% (n = 39901) of the birth cohort. Logistic regression analyses were used to estimate the risk of being short or overweight at conscription. The odds ratio (OR) was used to estimate relative risk. At conscription, mean height (+/-SD) was 179.5+/-6.6 cm, mean weight 72.1+/-11.2 kg, and mean body mass index 22.3+/-3.1 kg/m2. The risk of short adult stature (<166.3 cm) was associated with being short for gestational age (OR = 5.9), having a low birth weight for gestational age (OR = 1.7), and being born at a gestational age below 32 wk (OR = 2.6). The risk of being overweight (body mass index > +2 SD) was primarily associated with a high ponderal index (> +2 SD; OR = 1.8). In conclusion, anthropometric birth data are better predictors of short stature than of being overweight in adulthood. Among anthropometric data at birth, birth length is the most important predictor of adult height.
Enterovirus (EV) infections have been implicated in the development of type 1 diabetes. (T1D). They may cause β-cell destruction either by cytolytic infection of the cells or indirectly by triggering ...the autoimmune response. Virus was isolated from a woman at diagnosis of T1D (Tuvemo 1) and in addition, virus was isolated from her son at diagnosis of T1D at the same day (Tuvemo 2). None of the isolates could initially be serotyped by conventional methods. The Tuvemo 1 virus was genotyped and after sub-cultivation it was also serotyped as Coxsackievirus B5. The mother revealed antibodies against GAD65. The boy and the father both revealed a significant increase in neutralization antibody titre against two strains of CBV-4, clearly indicating a recent or ongoing EV infection. In addition, the brother showed such a titre rise against another CBV-4 strain (E2) and against a CBV-5 strain (4429). These results show that the whole family had a proven EV infection at the time of T1D diagnosis of the mother and the 10-years-old boy, indicating that the infection might cause or accelerate the T1D.
The problems of central precocious puberty (CPP) are serious enough to the patient to deserve treatment. There is a general consensus among paediatric endocrinologists that the treatment of true CPP ...(i.e., in children young enough to have a formal diagnosis) is indicated in many cases. In children with modestly early puberty who are not fulfilling the diagnostic criteria, this is not the case. The treatment of choice is a gonadotropin-releasing hormone (GnRH) analogue. Prolonged analogues are more effective than short-acting ones and, most importantly, independent of patient compliance. Data on agonists have accumulated over two decades and evidence of effects is rich in girls but sparse in boys. GnRH agonists are generally effective and safe drugs; the suppression of puberty is reversible and there is much information on GnRH agonists for the treatment of CPP showing very few adverse effects and the effects on final height are well documented in girls < 6 years of age. There is some (but not highly convincing) evidence for their effect on final height for those of 6 - 8 years of age and there is no evidence for an increase in final height after the age of 8 years in girls. If a decision to have treatment is taken, treatment should start immediately as a possible benefit is less probable if the start of treatment is delayed. When treatment should be stopped is a matter of controversy. Combination with growth hormone increases final height, but the clinical relevance can be discussed as well as the health economy aspects. The limits of indications are still to be defined.
Aim
This study measured autoantibodies against tissue transglutaminase (anti‐tTG) to detect untreated coeliac disease in children with type 1 diabetes and their siblings.
Methods
Anti‐tTG was ...measured in prospectively collected sera from 169 children at the onset of diabetes, 88 of their siblings and 96 matched control children. Coeliac disease was confirmed with a small intestinal biopsy.
Results
Coeliac disease was diagnosed in five children before diabetes onset. A further 12 children were diagnosed after diabetes onset, without any gastrointestinal symptoms, and 11 of these had anti‐tTG at the onset of diabetes, with the remaining child showing seroconversion within 6 months. Hence, all the children with both diseases had anti‐tTG at or before diabetes diagnosis, and the prevalence of coeliac disease was 10.1%. Moreover, 6.8% of the siblings and 3.1% of the control children had elevated levels of anti‐tTG. None of the siblings reported any coeliac‐related symptoms, despite being positive for anti‐tTG, and coeliac disease has so far been biopsy confirmed in 4.5%.
Conclusion
Silent coeliac disease is over‐represented in children with type 1 diabetes and their siblings. All diabetes children and their siblings should be tested and followed for the presence of anti‐tTG and coeliac disease.
To test whether short stature in young men without malformations or chronic childhood diseases is associated with intellectual and physical performance and morbidity, a large cohort of apparently ...healthy 18-year-old Swedish men was analysed. The original cohort consisted of all men born in 1976 and conscripted in 1994 (n = 38, 900). After exclusion due to growth-affecting disorders or missing data, 32,887 subjects were available for analysis. Short conscripts (height below or equal to -2 SD scores) demonstrated increased overall morbidity compared with taller conscripts (above -2 SD scores). Specifically, short conscripts had more psychiatric and musculoskeletal diagnoses and were more often considered psychologically unsuitable for military service. Mean intellectual performance increased continuously with height; the mean 'standard nine' score was 4.22 for the short men and 5.17 for the rest (p < 0. 001). Short conscripts scored less well than taller conscripts in assessment of psychological functioning during mental stress, and were evaluated as less suitable for leadership positions. Maximal working capacity per kilogramme body weight correlated negatively with height (p < 0.001). In conclusion, short stature was associated with increased morbidity and psychological problems and with lower mean intellectual performance. To what extent this association is direct or indirect needs further evaluation.
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