[Show abstract][Hide abstract] ABSTRACT: Aims/hypothesis:
We investigated the impact of type 1 diabetes on educational achievements in compulsory and upper secondary school, as well as potential long-lasting effects.
Altogether 2,485 individuals with type 1 diabetes, diagnosed at the age of <15 years and born in 1972-1978, were selected from the Swedish Childhood Diabetes Register, which was linked to national population registers including the Swedish Education Register. For each individual, four controls from the general population, matched for year of birth and residence at the time of diagnosis, were selected by Statistics Sweden (n = 9,940). We analysed the impact of diabetes on final school grades at 16 years (compulsory school) and 19 years (upper secondary school) and on participation in the labour market at 29 years using linear, logistic, ordered logistic and quantile regression analyses, controlling for demographics and socioeconomic background.
Diabetes had a negative effect on mean final grades (scale of 1-5) in compulsory school (-0.07, p < 0.001) and theoretical programmes in upper secondary school (-0.07, p = 0.001). Children with early-onset diabetes (0-4 years) suffered a greater disadvantage as a result of the disease (-0.15, p = 0.001 in compulsory school). The strongest effect was seen in the lowest deciles of the conditional distribution on mean final grades. At age 29, individuals with diabetes were less likely to be gainfully employed (OR 0.82, 95% CI 0.73, 0.91).
The small but significant negative effect of type 1 diabetes on schooling could affect opportunities for further education and career development. Attention must be paid in school to the special needs of children with diabetes.
[Show abstract][Hide abstract] ABSTRACT: Mood disorders, including depression, are suggested to be prevalent in persons with type 1 diabetes and may negatively affect self-management and glycaemic control and increase the risk of diabetic complications. The aim of this study was to analyse the prevalence of antidepressant (AD) use in adults with childhood onset type 1 diabetes and to compare risk determinants for AD prescription among diabetic patients and a group of matched controls.
Young adults ≥ 18 years on 1 January 2006 with type 1 diabetes (n = 7,411) were retrieved from the population-based Swedish Childhood Diabetes Registry (SCDR) and compared with 30,043 age- and community-matched controls. Individual level data were collected from the Swedish National Drug Register (NDR), the Hospital Discharge Register (HDR) and the Labor Market Research database (LMR).
ADs were prescribed to 9.5% and 6.8% of the type 1 diabetes and control subjects, respectively. Female sex, having received economic or other social support, or having a disability pension were the factors with the strongest association with AD prescription in both groups. Type 1 diabetes was associated with a 44% (OR 1.44, 95% CI 1.32, 1.58) higher risk of being prescribed ADs in crude analysis. When adjusting for potential confounders including sex, age and various socioeconomic risk factors, this risk increase was statistically non-significant (OR 1.11, 95% CI 0.99, 1.21).
The risk factor patterns for AD use are similar among type 1 diabetic patients and controls, and socioeconomic risk factors, rather than the diabetes per se, contribute to the increased risk of AD use in young adults with type 1 diabetes.
[Show abstract][Hide abstract] ABSTRACT: The incidence of type 1 diabetes in children younger than 15 years is increasing. Prediction of future incidence of this disease will enable adequate fund allocation for delivery of care to be planned. We aimed to establish 15-year incidence trends for childhood type 1 diabetes in European centres, and thereby predict the future burden of childhood diabetes in Europe.
20 population-based EURODIAB registers in 17 countries registered 29 311 new cases of type 1 diabetes, diagnosed in children before their 15th birthday during a 15-year period, 1989-2003. Age-specific log linear rates of increase were estimated in five geographical regions, and used in conjunction with published incidence rates and population projections to predict numbers of new cases throughout Europe in 2005, 2010, 2015, and 2020.
Ascertainment was better than 90% in most registers. All but two registers showed significant yearly increases in incidence, ranging from 0.6% to 9.3%. The overall annual increase was 3.9% (95% CI 3.6-4.2), and the increases in the age groups 0-4 years, 5-9 years, and 10-14 years were 5.4% (4.8-6.1), 4.3% (3.8-4.8), and 2.9% (2.5-3.3), respectively. The number of new cases in Europe in 2005 is estimated as 15 000, divided between the 0-4 year, 5-9 year, and 10-14 year age-groups in the ratio 24%, 35%, and 41%, respectively. In 2020, the predicted number of new cases is 24 400, with a doubling in numbers in children younger than 5 years and a more even distribution across age-groups than at present (29%, 37%, and 34%, respectively). Prevalence under age 15 years is predicted to rise from 94 000 in 2005, to 160 000 in 2020.
If present trends continue, doubling of new cases of type 1 diabetes in European children younger than 5 years is predicted between 2005 and 2020, and prevalent cases younger than 15 years will rise by 70%. Adequate health-care resources to meet these children's needs should be made available.
European Community Concerted Action Program.
The Lancet 07/2009; 373(9680):2027-33. DOI:10.1016/S0140-6736(09)60568-7 · 45.22 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To study the cumulative incidence of hospitalization for severe diabetic vascular complications in childhood onset type 1 diabetes patients with special regards to age at onset and gender.
The Swedish Childhood Diabetes Register (SCDR) was linked to the Swedish Hospital Discharge Register up to 31 December 2004. The following diagnoses were traced: diabetic kidney disease, myocardial infarction, stroke, lower limb arterial disease and diabetes with multiple complications. Cox proportional hazards survival method was applied with the following covariates: maternal age, birthweight deviation from gestational week standard, age at onset and gender.
Until 31 December 9974 children had been followed for at least 10 years corresponding to 141 839 person years at risk and 103 (7.3 per 1000 person years) had been hospitalized at least once at the maximum duration of follow-up of 26 years. Diabetic kidney disease was the most common cause of hospitalization and 63 patients had more than one diabetic complication. Female gender (RR=2.02, 95% CI=1.05-3.89) and age at onset of diabetes (RR=1.37, 95% CI=1.20-1.56) were significant risk factors for severe complication.
Hospitalization for severe diabetic complications at a maximum follow-up of 26 years is rather low in Sweden. There is a higher hospitalization rate among females than among males, and also among patients diagnosed with diabetes after 10 years of age than among patients diagnosed before the age of 10 years.
[Show abstract][Hide abstract] ABSTRACT: : HLA DQA1*0301-DQB1*0302 (DQ8) and DQA1*0501-DQB1*0201 (DQ2) are positively and DQA1*0102-DQB1*0602 (DQ6) negatively associated with IDDM. In DQA1*0301-DQB1*0302 (DQ8)-positive patients, susceptibility is also mediated by DRB1*0401. The aim of the study was to determine the association between HLA-DR4 and DQ and the presence of GAD65, ICA512, and insulin autoantibodies as well as ICA in 425 Swedish children with IDDM and 367 controls in the age group of 0–15 years. We found that ICA512 autoantibodies were associated primarily with DRB1*0401 and not with DQA1*0301-DQB1*0302 (DQ8). No such hierarchy could be demonstrated for insulin autoantibodies, which were associated with both DQA1*0301-DQB1*0302 (DQ8) and DRB1*0401. GAD65 autoantibodies, known to be closely associated with DQA1*0501-DQB1*0201 (DQ2)-DRB1*0301 haplotype, also showed no preferential association with DQA1*0301-DQB1*0302 (DQ8) versus DRB1*04. These results suggest that the immune response to different β-cell autoantigens may be mediated via HLA class II molecules from different loci. Design of the antigen-specific immuno-intervention trials should take into account these HLA-DR and DQ subtype associations.
[Show abstract][Hide abstract] ABSTRACT: A questionnaire measuring food frequency was validated against 7-day records of food intake in a group of 30 children, 2–16 years of age. Special emphasis was given to the ability of the questionnaire to estimate frequency of intake of foods of particular interest in diabetes mel-litus. Fifteen children had insulin-dependent diabetes; 15 were healthy. Comparison of the two methods regarding frequency of foods with high content of sucrose, protein, fat, fibres, nitrite or vitamin C showed a correlation of 0.52–0.76. The frequency of intake of some staple foods was often overestimated by the questionnaire, while the frequency of meat, sausage and some sweet snacks was underestimated. The use of the questionnaire to identify high or low consumers of the mentioned nutrients showed a rather low sensitivity (0.38–0.50), but a high specificity (0.86–1.0) when compared with results of the 7-day record. In our limited sample of subjects no systematic differences were found comparing sexes or diabetic and healthy children. A food frequency questionnaire may, in spite of some important reservations, be a useful tool for screening purposes when more time-consuming and resource-demanding methods cannot be used.
[Show abstract][Hide abstract] ABSTRACT: This is a prospective study of the incidence of insulin-dependent diabetes mellitus (IDDM) in children 0–14 years of age, including all newly diagnosed cases in the whole of Sweden from July 1, 1977 until June 90, 1980. All 45 Swedish departments of paediatrics participated. During the three-year-period studied, 1108 Swedish children, 0–14 years of age had their onset of diabetes. That means around 369 new diabetics yearly in the age groups studied. The mean yearly incidences in the years 1977–80 were 22.6, 22.8 and 22.6 per 100000 children, respectively. Mean prevalence on June 30, 1980 was 1.48 per 1000 children 0–14 years with a wide range of 0.71-2.65. The age distribution at onset showed a gradual increase and peak incidences at 11 years of age for the girls and 4 and 13 years of age for the boys. There was a consistently higher incidence for boys in the younger age groups during the three-year-period studied. Peak incidences of new cases were reached in January, March and July through October for the age groups 5–9 and 10–14 years of age. No such seasonal variation was seen for children 0–4 years of age. The cumulative incidence of IDDM at 14 years of age was 3.2 per 1000 for the boys and 2.9 per 1000 for the girls. The degree of ascertainment in this study was 93.4 %.
[Show abstract][Hide abstract] ABSTRACT: The aims of this study were to provide a contemporary picture of mortality and causes of death in Europe following a diagnosis of type 1 diabetes made before the 15th birthday, and to examine excess mortality by country for possible links to incidence level or national prosperity.
Thirteen population-based EURODIAB registers in 12 countries followed-up 28,887 children diagnosed since 1989, either by record linkage to population registers or through contact with doctors providing care.
There were 141 deaths in the cohort during 219,061 person-years of follow-up compared with 69.1 deaths expected from national mortality rates, a standardised mortality ratio (SMR) of 2.0 (95% CI 1.7-2.4). The SMR varied from 0 to 4.7 between countries, but showed little relationship with the country's incidence rate or gross domestic product (US$ per capita). The SMR did not change significantly with attained age, calendar period or time since diagnosis. The female SMR (2.7; 95% CI 2.0-3.5) was greater than the male SMR (1.8; 95% CI 1.4-2.2), although absolute numbers of excess deaths were similar in the two sexes. One-third of deaths were classified as directly attributable to diabetes (many with mention of ketoacidosis) and half were unrelated to diabetes. There was a non-significant excess of accidental/violent deaths (48 observed vs 40.7 expected; SMR 1.2; 95% CI 0.9-1.6) but little excess in suicides (11 observed, 10.2 expected; SMR 1.1; 95% CI 0.5-1.9).
Before the onset of late complications, significant excess mortality existed following the diagnosis of type 1 diabetes in childhood, even in recent years. Variation between countries in this excess could not be explained.
[Show abstract][Hide abstract] ABSTRACT: Type 1 diabetes is the most common form of diabetes in most part of the world, although reliable data are still unavailable in several countries. Wide variations exist between the incidence rates of different populations, incidence is lowest in China and Venezuela (0.1 per 100,000 per year) and highest in Finland and Sardinia (37 per 100,000 per year). In most populations girls and boys are equally affected. In general, the incidence increases with age, the incidence peak is at puberty. After the pubertal years, the incidence rate significantly drops in young women, but remains relatively high in young adult males up to the age 29-35 years. Prospective national and large international registries (DIAMOND and EURODIAB) demonstrated an increasing trend in incidence in most regions of the world over the last few decades and increases seem to be the highest in the youngest age group. Analytical epidemiological studies have identified environmental risk factors operating early in life which might have contributed to the increasing trend in incidence. These include enteroviral infections in pregnant women, older maternal age (39-42 years), preeclampsia, cesarean section delivery, increased birthweight, early introduction of cow's milk proteins and an increased rate of postnatal growth (weight and height). Optimal vitamin D supplementation during early life has been shown to be protective. Some of these environmental risk factors such as viruses may initiate autoimmunity toward the beta cell, other exposures may put on overload on the already affected beta cell and thus accelerate the disease process.
[Show abstract][Hide abstract] ABSTRACT: To study, at a population level, school performance when leaving compulsory school of Swedish children whose mothers had diabetes during pregnancy compared with a reference population.
We linked the Swedish Medical Birth Register with the Swedish School Mark Register, which contains school marks for all children in Sweden when leaving compulsory school. A total of 6,397 children were identified whose mothers had a diagnosis of diabetes during pregnancy in the years 1973 to 1986. Data on these children were compared with 1,300,683 children whose mothers had no diagnosis of diabetes during pregnancy. Risks were estimated as odd ratios (ORs) after adjustment for year of birth, maternal age, parity and educational level of the mother.
The children's average numerical school marks (for children leaving school between 1988 and 1997) were statistically significantly lower among children born to mothers with diabetes in pregnancy compared with reference children (3.13 +/- 0.01 vs 3.23, p < 0.001). The effect was similar among boys and girls. There was also an effect of maternal diabetes during pregnancy on the risk of the child not completing compulsory school (OR 1.25; 95% CI 1.10-1.43, and after exclusion of infants with certain perinatal characteristics an OR of 1.25; 95% CI 1.02-1.53). When sports and the core subjects mathematics, English and Swedish were studied, there were increased risks of having scores below pass level and decreased probabilities of having scores above pass level for children of mothers with diabetes during pregnancy.
Children of mothers with diabetes during pregnancy performed slightly but significantly less well than reference children when leaving compulsory school at about 16 years old; this was also seen after adjustment for some putative perinatal and social confounders.
[Show abstract][Hide abstract] ABSTRACT: Aims/hypothesisWe examined the school marks of diabetic children in Sweden at the time of leaving compulsory education. Marks were examined
in comparison with non-diabetic children and with special regard to age at onset of diabetes.
Subjects and methodsThe study involved 5,159 children who developed diabetes between 1 July 1977 and 1 July 2000, and 1,330,968 non-diabetic children.
We linked the nationwide Swedish Childhood Diabetes Register to the Swedish School-Mark Register, which contains school marks
for all children in Sweden at the time of leaving compulsory education (usually at 16years old). Adjustment was made for
potential confounders such as year of birth, maternal age, parity and educational level.
ResultsThe mean of all numerical school marks for diabetic children was slightly but statistically significantly lower than those
of the referent children (3.15 ± 0.01 [mean + SD] vs 3.23, p < 0.001). The lowest mean score was among children with diabetes diagnosis before the age of 2years (2.97 ± 0.09 vs 3.08–3.17
in the older age groups, p = 0.10). When individual subjects were studied (sports, mathematics, English and Swedish), a more complex picture emerged.
In four subjects (mathematics, English, Swedish and sports) the risk of a diabetic child not getting a school mark or not
passing was increased; in sports and English the diabetic children had significantly reduced odds of getting a high mark.
Conclusions/interpretationDespite a well-developed diabetes care system, we have not succeeded in preventing the disease from affecting school achievements.
Among children with a young age at onset and therefore longer duration, the negative effects tend to be greater.
[Show abstract][Hide abstract] ABSTRACT: The intercellular adhesion molecule-1 (ICAM-1) gene is located on chromosome 19p13, which is linked to Type 1 diabetes (T1D). ICAM-1 expression is related to development of T1D and diabetic nephropathy. The present study aims to evaluate the genetic influence of ICAM-1 gene polymorphisms on the development of T1D and diabetic nephropathy.
Five valid single nucleotide polymorphisms (SNPs) were genotyped in 432 T1D patients (196 patients had diabetic nephropathy) and 187 non-diabetic control subjects by using dynamic allele-specific hybridization (DASH) and pyrosequencing.
SNPs rs281432(C/G) and rs5498 E469K(A/G) had high heterozygous indexes. They were significantly associated with T1D [P = 0.026, OR = 1.644 (95% CI 1.138-2.376) and P < 0.001, OR = 2.456 (1.588-3.8)]. Frequencies of the C allele in SNP rs281432(C/G) and the A allele in SNP rs5498 E469K(A/G) increased stepwise from non-diabetic control subjects to T1D patients without diabetic nephropathy and T1D patients with diabetic nephropathy. Further analysis for these two SNPs indicated that T1D patients had increased frequency of the common haplotype C-A, in comparison with non-diabetic control subjects (38.1 vs. 32.1%, P = 0.035).
The present study provided evidence that SNPs rs281432(C/G) and rs5498 E469K(A/G) in the ICAM-1 gene confer susceptibility to the development of T1D and might also be associated with diabetic nephropathy in Swedish Caucasians.
Diabetic Medicine 11/2006; 23(10):1093-9. DOI:10.1111/j.1464-5491.2006.01948.x · 3.12 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Aims To examine incidence and trends of Type 1 diabetes worldwide for the period 1990-1999. Methods The incidence of Type 1 diabetes (per 100 000/year) was analysed in children aged <= 14 years from 114 populations in 112 centres in 57 countries. Trends in the incidence of Type 1 diabetes were analysed by fitting Poisson regression models to the dataset. Results A total of 43 013 cases were diagnosed in the study populations of 84 million children. The age-adjusted incidence of Type 1 diabetes among 112 centres (114 populations) varied from 0.1 per 100 000/year in China and Venezuela to 40.9 per 100 000/year in Finland. The average annual increase in incidence calculated from 103 centres was 2.8% (95% CI 2.4-3.2%). During the years 1990-1994, this increase was 2.4% (95% CI 1.3-3.4%) and during the second study period of 1995-1999 it was slightly higher at 3.4% (95% CI 2.7-4.3%). The trends estimated for continents showed statistically significant increases all over the world (4.0% in Asia, 3.2% in Europe and 5.3% in North America), except in Central America and the West Indies where the trend was a decrease of 3.6%. Only among the European populations did the trend in incidence diminish with age. Conclusions The rising incidence of Type 1 diabetes globally suggests the need for continuous monitoring of incidence by using standardized methods in order to plan or assess prevention strategies.
Diabetic Medicine 08/2006; 23(8):857-866. DOI:10.1111/j.1464-5491.2006.01925.x · 3.12 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Overload of the beta cell, mediated by a variety of mechanisms, may sensitise it to immune damage and apoptosis, and thus accelerate ongoing autoimmune processes leading to its destruction. Environmental risk determinants that may exert such overload effects include insulin resistance due to excess fat cell accumulation, and increased insulin requirement due to a high growth rate, physical stress (infection, inflammation) or psychological stress. The increasing incidence of childhood diabetes, and the shift to younger age at onset, is unlikely to be driven by environmental risk factors that have been associated with initiation of autoimmunity, e.g. virus infections or early infant feeding. Risk factors that may accelerate beta cell destruction have shown a steady increase in the population, and are more plausible causes of such a pattern of change. Child growth, weight and birthweight are well-established estimates of community wealth and increase in most countries of Europe. Overfeeding of children early in life leads to both accelerated growth and weight, and even a moderate excess of child growth, not necessarily associated with obesity, is associated with risk of type 1 diabetes. New, safe and effective immune-modulating drugs for possible arrest of the autoimmune process may become available in time, but in the interim these accelerating factors may be targeted. Public health programmes for pregnant mothers and young families, aiming at changing overfeeding and the sedentary lifestyle of the children would be preferable to other alternatives. Interventions such as these would be safe and could potentially influence future risks of type 1 and type 2 diabetes and other major threats to adult health.
[Show abstract][Hide abstract] ABSTRACT: To compare the time trend of childhood type 1 diabetes over an 18-y period in Lithuania and Sweden--countries with different incidence levels and different socio-economic conditions.
Percent average incidence change per year between 1983 and 2000, based on 8031 Swedish and 1100 Lithuanian cases in the age group 0-14 y, was calculated using Poisson regression.
Average age- and sex-standardized incidence/100 000/y was 28.9 (95% CI: 28.2-29.5) in Sweden and 7.5 (95% CI: 7.1-8.0) in Lithuania. Between 1983 and 2000, the average increase per year was 2.2% in Sweden (95% CI: 1.7-2.6) and 2.3% in Lithuania (95% CI: 1.1-3.5), but the latter trend depended on an increase during the last few years of the period, and only for girls. In Sweden, incidence increased significantly in all age groups, but more so in the younger groups (3.0%, 2.2% and 1.7% per year in 0-4, 5-9 and 10-14-y age groups, respectively), while in Lithuania a significant increase was found only in the 10-14-y age group (3.0%). In Sweden, a trend towards a younger age at diagnosis was indicated for both boys and girls when comparing 1983-1991 and 1992-2000, whereas in Lithuania, the changes in age distribution over time were small, with an opposite tendency for boys.
Incidence variability over time differed considerably in the two countries in the region of the Baltic Sea, suggesting a complex effect of environmental risk factors, some of which may be associated with wealth and socio-economic conditions.
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVE - To confirm that early growth is associated with type 1 diabetes risk in European children and elucidate any role of infant feeding. RESEARCH DESIGN AND METHODS- Five centers participated, each with a population-based register of type 1 diabetes diagnosed at <15 years of age. Control subjects were randomly chosen from population registers, schools, or polyclinics. Growth data were obtained from routine records and infant feeding information from parental questionnaire or interview. Patient/control subject differences in mean standard deviation score (SDS) were obtained for each center and pooled. Odds ratios (ORs) were pooled by the Mantel-Haenszel method, and logistic regression was used to adjust for confounders. RESULTS- Growth data were available for 499 patients and 1,337 control subjects. Height and weight SDS were significantly increased among patients from I month after birth, the maximum differences of 0.32 (95% Cl 0.14-0.50) and 0.41 (0.26-0.55), respectively, occurring between 1 and 2 years of age. Significant excesses in BMI SDS were observed from 6 months of age, with the largest difference of 0.27 (0.10, 0.44) evident between 1 and 2 years. Breastfeeding was associated with reduced disease risk, OR 0.75 (0.58-0.96). Introduction of cow's milk, formula, or solid foods before 3 months was not associated with significant risk elevation. CONCLUSION -Increased early growth is associated with disease risk in various European populations. Any role of infant feeding in this association remains unclear.
Diabetes Care 10/2002; 25(10):1755-1760. DOI:10.2337/diacare.25.10.1755 · 8.42 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To analyse the incidence of Type I (insulin-dependent) diabetes mellitus in the 0-34 years age group in Sweden 1983-1998.
Incidence and cumulative incidence per 100 000 and Poisson regression analysis of age-period effects was carried out using 11 751 cases from two nation-wide prospective registers.
Incidence (95%-CI) was 21.4 (20.8-21.9) in men and 17.1 (16.6-17.5) in women between 0 and 34 years of age. In boys aged 0-14 and girls aged 0-12 years the incidence increased over time, but it tended to decrease at older age groups, especially in men. Average cumulative incidence at 35 years was 748 in men and 598 in women. Cumulative incidence in men was rather stable during four 4-year periods (736, 732, 762, 756), while in women it varied more (592, 542, 617, 631). In males aged 0-34 years, the incidence did not vary between the 4-year periods ( p=0.63), but time changes among the 3-year age groups differed ( p<0.001). In females the incidence between the periods varied ( p<0.001), being lower in 1987-1990 compared to 1983-1986, but time changes in the age groups did not differ ( p=0.08). For both sexes median age at diagnosis was higher in 1983-1986 than in 1995-1998 ( p<0.001) (15.0 and 12.5 years in males; 11.9 and 10.4 in females, respectively).
During a 16-year period the incidence of Type I diabetes did not increase in the 0-34 years age group in Sweden, while median age at diagnosis decreased. A shift to younger age at diagnosis seems to explain the increasing incidence of childhood Type I diabetes.
[Show abstract][Hide abstract] ABSTRACT: IDDM is positively associated with HLA-DQA1*0301-DQB1*0302 (DQ8) and DQA1*0501-DQB1*0201 (DQ2) and negatively associated with DQA1*0102-DQB1*0602 (DQ6). The aim of the present study was to analyze the importance of several polymorphic residues and domains of DQalpha and DQbeta, in addition to residue 52 DQalpha and residue 57 DQbeta, with regard to susceptibility or resistance in new-onset 0- to 15-year-old Swedish children with IDDM (n = 425) and matched controls (n = 367). HLA genotyping identified several polymorphic residues of the DQalpha and DQbeta to be either positively or negatively associated with IDDM, including Arg 52 DQalpha and Asp 57 DQbeta. Leu 69 DQalpha was positively (OR 7.02, P < 0.0001), Ala 69 DQalpha was negatively (OR 0.22, P < 0.0001), Gln 47 DQalpha was positively (OR 5.8, P < 0.0001), Cys 47 DQalpha was positively (OR 2.2, P < 0.0001), Lys 47 DQalpha was negatively (OR 0.47, P < 0.005), and Arg 47 DQalpha was negatively (OR 0.22, P < 0.005) associated with IDDM. Similarly, residues at 11, 18, 45, 48, 50, 53, 55, 61, 64, 66, 76, and 80 were either positively or negatively associated with IDDM. Likewise, for DQbeta, Leu 53 DQbeta was positively (OR 11.01, P < 0.0001), Gln 53 DQbeta was negatively (OR 0.22, P < 0.0005), Arg 70 DQbeta was positively (OR 11.01, P < 0.0001), and Gly 70 DQbeta was negatively (OR 0.19, P < 0.0001) associated like other residues at 71, 74, 84, 85, 86, 89, and 90 DQbeta with IDDM. Certain domains in the DQalpha, RFTIL (at DQalpha positions 52, 61, 64, 66, and 69), were present in 95% of patients compared to 69% of controls (OR 9.01, P(c) < 0.0001), and DQbeta domain GR (at DQbeta positions 45 and 70) was present in 95% of patients and 68% of controls (OR 8.68, P < 0.0001), which correlated better than the individual amino acid residues with IDDM. A combination of the DQalpha and DQbeta chain domains was present in 94% of patients compared to 60% of controls (OR 10.6, P < 0.001). In conclusion, domains in the DQalpha, DQbeta, or both in the DQ molecule explain susceptibility or resistance to IDDM better than individual amino acid residues of DQA1 and DQB1.
Annals of the New York Academy of Sciences 04/2002; 958(1):362-75. DOI:10.1111/j.1749-6632.2002.tb03006.x · 4.38 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: There is an absence of population-based long-term studies on the risk of neurological sequelae in children born after in-vitro fertilisation (IVF). Our aim was to compare the frequency of such problems between IVF-born children and controls.
We did a population-based retrospective cohort study in which we compared development of neurological problems in 5680 children born after IVF, with 11360 matched controls. For 2060 twins born after IVF, a second set of controls (n=4120), all twins, were selected. We obtained data on neurological problems from the records of the Swedish habilitation centres.
Children born after IVF are more likely to need habilitation services than controls (odds ratio 1.7, 95% CI 1.3-2.2). For singletons, the risk was 1.4 (1.0-2.1). The most common neurological diagnosis was cerebral palsy, for which children born after IVF had an increased risk of 3.7(2.0-6.6), and IVF singletons of 2.8 (1.3-5.8). Suspected developmental delay was increased four-fold (1.9-8.3) in children born after IVF. Twins born after IVF did not differ from control twins with respect to risk of neurological sequelae. Low-birthweight and premature infants were more likely to need habilitation than fullterm babies. Maternal age did not affect risk.
Our study suggests that children born after IVF have an increased risk of developing neurological problems, especially cerebral palsy. These risks are largely due to the high frequency of twin pregnancies, low birthweight, and prematurity among babies born after IVF. To limit these risks, we recommend that only one embryo should be transferred during IVF.
The Lancet 03/2002; 359(9305):461-5. DOI:10.1016/S0140-6736(02)07674-2 · 45.22 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To investigate whether factors in the fetal or neonatal period influence the risk of later development of coeliac disease we conducted a population-based register study. The Swedish Medical Birth Register was linked with the Hospital Discharge Register and identified 3392 singleton infants born in the period 1987-97 who developed coeliac disease. Perinatal data for these children were compared with all children born in these years. Exposure variables: Maternal age, parity and smoking habits in early pregnancy, preeclampsia, pregnancy duration and birthweight, birthweight by gestational week, Apgar score, neonatal icterus, neonatal infections, maternal-fetal blood group incompatibility, exchange transfusion, phototherapy. Odds ratios and test-based confidence intervals were calculated. Analyses were made with stratification for year of birth and other risk factors. The risk of developing coeliac disease decreased with maternal age and was lower in first-born than in second-born children. Maternal smoking in early pregnancy was a weak risk factor, as was low birthweight. The most evident risk factors were being exposed to neonatal infections (OR = 1.52, confidence limits 1.19: 1.95) and being small for gestational age (OR = 1.45, confidence limits 1.20; 1.75). These risk factors were independent of each other. Conclusions: We have demonstrated that the intrauterine environment, mainly as mirrored by a low birthweight for gestational age and, independently, neonatal infection diagnosis, is associated with the risk of developing coeliac disease, supporting the idea of a multifactorial aetiology of the disease.