Perinatal risk factors for type 1 diabetes revisited : a population-based register study

Aims/hypothesis Single-centre studies and meta-analyses have found diverging results as to which early life factors affect the risk of type 1 diabetes during childhood. We wanted to use a large, nationwide, prospective database to further clarify and analyse the associations between perinatal factors and the subsequent risk for childhood-onset type 1 diabetes using a case- control design. Methods The Swedish Childhood Diabetes Register was linked to the Swedish Medical Birth Register and National Patient Register, and 14,949 cases with type 1 diabetes onset at ages 0–14 years were compared with 55,712 matched controls born from the start of the Medical Birth Register in 1973 to 2013. After excluding confounders (i.e. children multiple births, those whose mother had maternal diabetes and those with a non-Nordic mother), we used conditional logistic regression analyses to determine risk factors for childhood-onset type 1 diabetes. We used WHO ICD codes for child and maternal diagnoses. Results In multivariate analysis, there were small but statistically significant associations between higher birthweight z score (OR1.08, 95% CI 1.06, 1.10), delivery by Caesarean section (OR 1.08, 95% CI 1.02, 1.15), premature rupture of membranes (OR 1.08, 95%CI 1.01, 1.16) and maternal urinary tract infection during pregnancy (OR 1.39, 95%CI 1.04, 1.86) and the subsequent risk of childhood-onset type 1 diabetes. Birth before 32 weeks of gestation was associated with a lower risk of childhood-onset type 1 diabetes compared with full-term infants (OR 0.54, 95%CI 0.38, 0.76), whereas birth between 32 and 36 weeks' gestation was associated with a higher risk (OR 1.24, 95% CI 1.14, 1.35). In subgroup analyses (birth years 1992–2013), maternal obesity was independently associated with subsequent type 1 diabetes in the children (OR 1.27, 95% CI 1.15, 1.41) and rendered the association with Caesarean section non-significant. In contrast to previous studies, we found no association of childhood-onset type 1 diabetes with maternal–child blood-group incompatibility, maternal pre-eclampsia, perinatal infections or treatment of the newborn with phototherapy for neonatal jaundice. The proportion of children with neonatal jaundice was significantly higher in the 1973–1982 birth cohort compared with later cohorts. Conclusions/interpretation Perinatal factors make small but statistically significant contributions to the overall risk of childhoodonset type 1 diabetes. Some of these risk factors, such as maternal obesity, may be amendable with improved antenatal care. Better perinatal practices may have affected some previously noted risk factors over time

Fetal and perinatal risk factors for inflammatory bowel disease

Aim: To study the influence of specific factors and events during pregnancy and the perinatal period on the risk of children developing inflammatory bowel disease. Methods: Population-based national register study. Linkage between the Swedish Medical Birth Register and the Swedish Hospital Discharge Register during the period 1987 to 2000 identified 455 singleton infants who later developed inflammatory bowel disease. Data for these children were compared with data for all children born in Sweden during the same period. Results: Smoking during early pregnancy reduced the risk of inflammatory bowel disease ( odds ratio ( OR) 0.71, 95% CI 0.55-0.91). For ulcerative colitis the odds ratio was 0.70 ( 95% CI 0.56-0.86), and for Crohn's disease 0.73 ( 95% CI 0.58 - 0.94). Infections during the neonatal period seemed to increase the risk of inflammatory bowel disease ( OR 17.6, 95% CI 3.6 - 51.6), but the number of observed events was small. The other factors examined did not influence the risk of inflammatory bowel disease. Conclusion: Maternal smoking during early pregnancy reduces the risk for the child to be hospitalized with a diagnosis of inflammatory bowel disease. Severe neonatal infections may increase the risk. Thus, some exposures during the fetal and neonatal period seem to affect the risk of inflammatory bowel disease later in life

Confirmed association between neonatal phototherapy or neonatal icterus and risk of childhood asthma

We have previously demonstrated an association between neonatal phototherapy and/or neonatal icterus and risk of hospitalization for childhood asthma. This study included children who were prescribed anti-asthmatic medication on a population basis to study exposures during the foetal and neonatal period and risk of childhood asthma. The Swedish Medical Birth Register was linked to the Swedish Prescribed Drug Register. Perinatal data for singleton children who were prescribed anti-asthmatic medication (n = 61 256) were compared with corresponding data for all singleton children born in Sweden from 1 January 1990 to 30 June 2003 and surviving to 1 July 2005 (n = 1 338 319). Mantel-Haenszel's odds ratios were calculated after adjustment for various known confounders. Being the first-born child, maternal age above 44 yr, involuntary childlessness for more than 1 yr, maternal smoking during pregnancy, maternal diabetes mellitus of any kind, pre-eclampsia, caesarean section, and instrumental vaginal delivery were all associated with an increased prescription of anti-asthmatic medication during childhood. Preterm birth, low birth weight, being small for gestational age, respiratory problems, mechanical ventilation, and sepsis and/or pneumonia were also associated with increased drug prescriptions. Neonatal phototherapy and/or icterus were risk determinants for children who developed asthma before the age of 12. After controlling for confounders, the odds ratio for phototherapy and/or icterus remained at 1.30 (95% confidence interval 1.16-1.47). In conclusion, this large population-based study confirms an association between some maternal and perinatal factors and childhood asthma, including neonatal phototherapy and/or icterus

The incidence of childhood-onset type 1 diabetes, time trends and association with the population composition in Sweden : a 40 year follow-up

Aims/hypothesis: During the 1980s and 1990s, the incidence of childhood-onset type 1 diabetes more than doubled in Sweden,followed by a plateau. In the present 40 year follow-up,we investigated if the incidence remained stable and whether this could be explained by increased migration from countries reporting lower incidences. Methods: We used 23,143 incident cases of childhood-onset type 1 diabetes reported between 1978 and 2019 to the nationwide, population-based Swedish Childhood Diabetes Registry and population data from Statistics Sweden. Generalised additive models and ANOVA were applied to analyse the effects of onset age, sex, time trends and parental country of birth and interaction effects between these factors. Results: The flattening of the incidence increase seems to remain over the period 2005–2019. When comparing the incidence of type 1 diabetes for all children in Sweden with that for children with both parents born in Sweden, the trends were parallel but at ahigher level for the latter. A comparison of the incidence trends between individuals with Swedish backgrounds (high diabetestrait) and Asian backgrounds (low diabetes trait) showed that the Asian subpopulation had a stable increase in incidence overtime. Conclusions/interpretation: In Sweden, the increase in incidence of childhood-onset type 1 diabetes in the late 20th century has been approaching a more stable albeit high level over the last two decades. Increased immigration from countries with lower incidences of childhood-onset type 1 diabetes does not provide a complete explanation for the observed levelling off

Childhood Health and Labor Market Outcomes in the Case of Type 1 Diabetes

This study investigates the impact of childhood health on labor market outcomes. We used type 1 diabetes as an instrument of health because its cause is multifactorial and it is triggered by a complex combination of genetic and environmental components; its incidence is low and unforeseeable for the individual; and its onset may be considered an exogenous health shock. Using data from the Swedish Childhood Diabetes Register and national registers on education, employment, and earnings for 2,485 individuals born in 1972–1978 and diagnosed with type 1 diabetes at <15 years old, we found that childhood health impacts on labor market outcomes. The results also imply that causality in the often observed correlation between health and socioeconomic status is partly explained by a gradient that runs from health to earnings, rather than the other way around, which has important implications for policy to reduce socioeconomic-related health inequality

Risk of cancer in young and middle-aged adults with childhood-onset type 1 diabetes in Sweden - A prospective cohort study

Aims/hypothesis: In persons with type 1 diabetes, the risk of cancer remains controversial. We wanted to examine the excess risk of cancer in a large population-based cohort diagnosed with type 1 diabetes before 15 years of age. Study population and methods: From 1 July 1977 to 31 December 2013, we prospectively and on a national scale included 18,724 persons (53% men) with childhood-onset type 1 diabetes. For each person with type 1 diabetes, we selected four referents, matched for the date at birth and municipality of living at the time when the case developed diabetes. Cases and referents were linked to national registers of cancer and of the cause of death. Results: A total of 125 persons (61% women) with diabetes had 135 different cancers, all diagnosed after the diabetes diagnosis. The median duration from diabetes diagnosis to first cancer diagnosis was 19 years (interquartile range 10-26). The median age at cancer diagnosis in the diabetes group was 28 years (interquartile range 20-35). The overall standardized incidence ratio (95%), using the Swedish general population as referents for women with diabetes was 1.28 (1.02, 1.58) and when comparing women with diabetes with matched referents, we found a hazard ratio of 1.42 (1.10, 1.85). No elevated risk was seen for men. Cancers of the breast and testis were the most common types in women and men respectively. Conclusions: Women with childhood-onset type 1 diabetes had a small but significantly elevated risk of cancer. No such tendency was seen for men. The reason behind this is unclear

Incidence of Type 1 Diabetes in Sweden Among Individuals Aged 0–34 Years, 1983–2007:An analysis of time trends

OBJECTIVE: To clarify whether the increase in childhood type 1 diabetes is mirrored by a decrease in older age-groups, resulting in younger age at diagnosis. RESEARCH DESIGN AND METHODS: We used data from two prospective research registers, the Swedish Childhood Diabetes Register, which included case subjects aged 0–14.9 years at diagnosis, and the Diabetes in Sweden Study, which included case subjects aged 15–34.9 years at diagnosis, covering birth cohorts between 1948 and 2007. The total database included 20,249 individuals with diabetes diagnosed between 1983 and 2007. Incidence rates over time were analyzed using Poisson regression models. RESULTS: The overall yearly incidence rose to a peak of 42.3 per 100,000 person-years in male subjects aged 10–14 years and to a peak of 37.1 per 100,000 person-years in female subjects aged 5–9 years and decreased thereafter. There was a significant increase by calendar year in both sexes in the three age-groups <15 years; however, there were significant decreases in the older age-groups (25- to 29-years and 30- to 34-years age-groups). Poisson regression analyses showed that a cohort effect seemed to dominate over a time-period effect. CONCLUSIONS: Twenty-five years of prospective nationwide incidence registration demonstrates a clear shift to younger age at onset rather than a uniform increase in incidence rates across all age-groups. The dominance of cohort effects over period effects suggests that exposures affecting young children may be responsible for the increasing incidence in the younger age-groups

Why childhood-onset type 1 diabetes impacts labour market outcomes : a mediation analysis

Aims/hypothesis: Previous studies show a negative effect of type 1 diabetes on labour market outcomes such as employment and earnings later in life. However, little is known about the mechanisms underlying these effects. This study aims to analyse the mediating role of adult health, education, occupation and family formation. Methods: A total of 4179 individuals from the Swedish Childhood Diabetes Register and 16,983 individuals forming a population control group born between 1962 and 1979 were followed between 30 and 50 years of age. The total effect of having type 1 diabetes was broken down into a direct effect and an indirect (mediating) effect using statistical mediation analysis. We also analysed whether type 1 diabetes has different effects on labour market outcome between the sexes and across socioeconomic status. Results: Childhood-onset type 1 diabetes had a negative impact on employment (OR 0.68 [95% CI 0.62, 0.76] and OR 0.76 [95% CI 0.67, 0.86]) and earnings (−6%, p &lt; 0.001 and −8%, p &lt; 0.001) for women and men, respectively. Each of the mediators studied contributed to the total effect with adult health and occupational field accounting for the largest part. However, some of the effect could not be attributed to any of the mediators studied and was therefore likely related to other characteristics of the disease that hamper career opportunities. The effect of type 1 diabetes on employment and earnings did not vary significantly according to socioeconomic status of the family (parental education and earnings). Conclusions/interpretation: A large part of the effect of type 1 diabetes on the labour market is attributed to adult health but there are other important mediating factors that need to be considered to reduce this negative effect