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.