No association between routinely recorded infections in early life and subsequent risk of childhood-onset Type 1 diabetes: a matched case-control study using the UK General Practice Research Database

Aims To determine whether children with infections in early life (recorded routinely in general practice) have a reduced risk of Type 1 diabetes, as would be expected from the hygiene hypothesis.

Worldwide childhood type 1 diabetes incidence - what can we learn from epidemiology?

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.

Secular trends, disease maps and ecological analyses of the incidence of childhood onset type 1 diabetes in Northern Ireland, 1989-2003

Aims To investigate secular trends in the incidence of Type 1 diabetes in Northern Ireland over the period 1989-2003. To highlight geographical variations in the incidence of Type 1 diabetes by producing disease maps and to compare incidence rates by relevant area characteristics.

Variation and trends in incidence of childhood diabetes in Europe

Background To study the epidemiology of childhood-onset type 1 insulin-dependent diabetes in Europe, the EURODIAB collaborative group established in 1988 prospective geographically-defined registers of new cases diagnosed under 15 years of age. This report is based on 16 362 cases registered during the period 1989-94 by 44 centres representing most European countries and Israel and covering a population of about 28 million children.

Trends in the incidence of childhood-onset diabetes in Europe 1989-1998

Aims/hypothesis. To study the epidemiology of childhood-onset (Type 1) insulin-dependent diabetes mellitus in Europe., the EURODIAB collaborative group in 1988 established prospective, geographically-defined registers of all children diagnosed with Type I diabetes under 15 years of age. This report is based on 24423 children, registered by 36 centres, with complete participation during the period 1989-1998 and representing most European countries with a population coverage of approximately 20 million children.

Infections and vaccinations as risk factors for childhood type I (insulin-dependent) diabetes mellitus: a multicentre case-control investigation.

AIMS/HYPOTHESIS: To determine if vaccinations and infections are associated with the subsequent risk of Type I (insulin-dependent) diabetes mellitus in childhood. METHOD: Seven centres in Europe with access to population-based registers of children with Type I diabetes diagnosed under 15 years of age participated in a case-control study of environmental risk factors. Control children were chosen at random in each centre either from population registers or from schools and policlinics. Data on maternal and neonatal infections, common childhood infections and vaccinations were obtained for 900 cases and 2302 control children from hospital and clinic records and from parental responses to a questionnaire or interview. RESULTS: Infections early in the child's life noted in the hospital record were found to be associated with an increased risk of diabetes, although the odds ratio of 1.61 (95% confidence limits 1.11, 2.33) was significant only after adjustment for confounding variables. None of the common childhood infectious diseases was found to be associated with diabetes and neither was there evidence that any common childhood vaccination modified the risk of diabetes. Pre-school day-care attendance, a proxy measure for total infectious disease exposure in early childhood, was found, however, to be inversely associated with diabetes, with a pooled odds ratio of 0.59 (95% confidence limits 0.46, 0.76) after adjustment for confounding variables. CONCLUSION/INTERPRETATION: It seems likely that the explanation for these contrasting findings of an increased risk associated with perinatal infections coupled with a protective effect of pre-school day care lies in the age-dependent modifying influence of infections on the developing immune system.

Early Childhood Development of Late-Preterm Infants: A Systematic Review

CONTEXT: Late-preterm infants (LPIs) born at 34 to 36 weeks' gestation are increasingly regarded as being at risk for adverse developmental outcomes. To date, the early childhood development of LPIs has not been systematically considered.

OBJECTIVE: To undertake a broad examination of literature relating to early childhood development at the ages of 1 to 7 years of LPIs born at 34 to 36 weeks' gestation.

METHODS: We conducted a systematic review of early childhood outcomes in LPIs by using 9 electronic databases (January 1980 to March 2010). Bibliographies were reviewed. After examination of abstracts, ineligible studies were excluded. A specifically designed data-extraction form was used. The methodologic quality of included studies was assessed by using well-documented quality-appraisal guidelines.

RESULTS: Of 4581 studies, 10 (3 prospective and 7 retrospective cohort) were included. Studies were heterogeneous, and poorer outcomes were reported among LPIs in relation to neurodevelopmental disabilities, educational ability, early-intervention requirements, medical disabilities, and physical growth in comparison to term-born children. No identified study used healthy nonadmitted LPIs as a comparison group for admitted LPIs.

CONCLUSIONS: Evidence suggests that LPIs are at increased risk of adverse developmental outcomes and academic difficulties up to 7 years of age in comparison to term infants. An infant control group matched for gestational age has not been used; thus, for LPIs, the effect of neonatal admission on longer-term outcomes has not been fully explored. Systematic measurement of early childhood outcomes is lacking, and focused long-term follow-up studies are needed to investigate early childhood development after late-preterm birth. Pediatrics 2011;127:1111-1124

Birth order and childhood type 1 diabetes risk: A pooled analysis of 31 observational studies

Background: The incidence rates of childhood onset type 1 diabetes are almost universally increasing across the globe but the aetiology of the disease remains largely unknown. We investigated whether birth order is associated with the risk of childhood diabetes by performing a pooled analysis of previous studies. Methods: Relevant studies published before January 2010 were identified from MEDLINE, Web of Science and EMBASE. Authors of studies provided individual patient data or conducted pre-specified analyses. Meta-analysis techniques were used to derive combined odds ratios (ORs), before and after adjustment for confounders, and investigate heterogeneity. Results: Data were available for 6 cohort and 25 case-control studies, including 11 955 cases of type 1 diabetes. Overall, there was no evidence of an association prior to adjustment for confounders. After adjustment for maternal age at birth and other confounders, a reduction in the risk of diabetes in second-or later born children became apparent [fully adjusted OR=0.90 95% confidence interval (CI) 0.83-0.98; P=0.02] but this association varied markedly between studies (I 2=67%). An a priori subgroup analysis showed that the association was stronger and more consistent in children <5years of age (n=25 studies, maternal age adjusted OR=0.84 95% CI 0.75, 0.93; I 2=23%). Conclusion: Although the association varied between studies, there was some evidence of a lower risk of childhood onset type 1 diabetes with increasing birth order, particularly in children aged <5 years. This finding could reflect increased exposure to infections in early life in later born children. Published by Oxford University Press on behalf of the International Epidemiological Association © The Author 2010; all rights reserved.

Childhood Trauma and Hippocampal and Amygdalar Volumes in First-Episode Psychosis

Objective: A history of childhood trauma is common in individuals who later develop psychosis. Similar neuroanatomical abnormalities are observed in people who have been exposed to childhood trauma and people with psychosis. However, the relationship between childhood trauma and such abnormalities in psychosis has not been investigated. This study aimed to explore the association between the experience of childhood trauma and hippocampal and amygdalar volumes in a first-episode psychosis (FEP) population. Methods: The study employed an observational retrospective design. Twenty-one individuals, who had previously undergone magnetic resonance imaging procedures as part of the longitudinal Northern Ireland First-Episode Psychosis Study, completed measures assessing traumatic experiences and were included in the analysis. Data were subject to correlation analyses (rand rob). Potential confounding variables (age at FEP and delay to scan from recruitment) were selected a priori for inclusion in multiple regression analyses. Results: There was a high prevalence of lifetime (95%) and childhood (76%) trauma in the sample. The experience of childhood trauma was a significant predictor of left hippocampal volume, although age at FEP also significantly contributed to this model. There was no significant association between predictor variables and right hippocampal volume. The experience of childhood trauma was a significant predictor of right and total amygdalar volumes and the hippocampal/amygdalar complex volume as a whole. Conclusions: The findings indicate that childhood trauma is associated with neuroanatomical measures in FEP. Future research controlling for childhood traumatic experiences may contribute to explaining brain morphology in people with psychosis.