Maternal virus infections in pregnancy and type 1 diabetes in their offspring: Systematic review and meta‐analysis of observational studies

Abstract

Virus infections are implicated in the development of type 1 diabetes based on epidemiological, clinical, in vitro cell-based and molecular studies, and animal models. We reviewed the association between virus infections in pregnant women and development of islet autoimmunity or type 1 diabetes in their offspring. We performed a systematic review and meta-analysis, analysed using random effects models, of human studies from Medline and EMBASE without language restriction. Inclusion criteria were as follows: cohort and case-control studies measuring viral nucleic acid in blood, stool, urine, or tissue, or serological tests for viruses, in pregnant women whose offspring developed islet autoimmunity and/or type 1 diabetes. All studies required sufficient data to calculate odds ratios and 95% confidence intervals. The 10 studies (4 case control, 6 nested-case control) that met the eligibility criteria included 2992 participants (953 offspring, 2039 mothers), with varying study design. The 2 outcomes examined were islet autoimmunity (n = 466) and type 1 diabetes (n = 2526). Meta-analysis showed a significant association between virus infection during pregnancy and clinical type 1 diabetes during childhood (odds ratio 2·16, 95% CI 1·22-3·80; P = 0·008; heterogeneity X = 1·65, I = 40%), but no association with islet autoimmunity (1·45, 0·63-3·31; P = 0·38; X = 1·34, I = 25%). The increased risk of type 1 diabetes following maternal virus infection is consistent with viraemia involving the fetus during pregnancy and suggests a potential causative link between antenatal infection and type 1 diabetes. Larger prospective birth studies with more frequent sampling, and pathogenesis studies, are required to more clearly establish an aetiological link.

T lymphocytes and cytotoxic astrocyte blebs correlate across autism brains

“…T1D is initiated and possibly sustained by viral infections. 25 Although histologic evidence of typical CNS viral infections and immunohistochemical staining for herpes simplex virus 1 (HSV1), HSV2, varicella zoster virus, cytomegalovirus, and JC virus were negative (not shown), a potential role of infection in initiating or sustaining this T-lymphocyte immune response in ASD remains an important consideration.…”

ISPAD Clinical Practice Consensus Guidelines 2018: Stages of type 1 diabetes in children and adolescents

“…Congenital rubella is a long standing recognized environmental trigger. 32,33 Other putative exposures are enterovirus infections during pregnancy and childhood, 34,35 and the introduction of multiple foreign antigens in the infant diet. [36][37][38] In at-risk children, concurrent breast milk feeding at the time of cereal introduction may be protective.…”

The influence of maternal body mass index, maternal diabetes mellitus, and maternal smoking during pregnancy on the risk of childhood‐onset type 1 diabetes mellitus in the offspring: Systematic review and meta‐analysis of observational studies

“…The following search terms were used to identify relevant publications: (type 1 diabetes mellitus OR insulin-dependent diabetes mellitus) AND (cohort OR case-control) AND (childhood OR offspring OR early-onset OR children OR adolescence OR adolescent). In addition to database searches, we also performed a full text review of the studies included in several meta-analyses [6][7][8][9][10][11][12][13][14][15][16][17] investigating the influence of maternal, perinatal, and early childhood factors on the risk of childhood-onset T1DM to identify relevant studies that were missed during database searches.…”