Pre-pregnancy body mass index in mothers, birth weight and the risk of type I diabetes in their offspring: A dose-response meta-analysis of cohort studies.

BACKGROUND The incidence of type I diabetes among children has increased significantly and the relationship between maternal pre-pregnancy Body Mass Index (BMI), Birth weight and risk of Type 1 diabetes in children (T1DMC) is controversial. OBJECTIVE This dose-response meta-analysis was performed to investigate the association between maternal Pre-Pregnancy Body-Mass Index, Birth Weight and the Risk of Childhood Type I Diabetes. SEARCH STRATEGY A comprehensive systematic search was conducted in MEDLINE/PubMed, SCOPUS, Cochrane, and Web of Science databases from inception to April 2019. Key search terms included "body mass index" OR "Birth weight" AND "Type 1 diabetes". SELECTION CRITERIA Peer-reviewed studies that reporting association between BMI or birth weight and type I diabetes in a retrospective or prospective study by appropriate estimates such as the hazard ratio (HR), risk ratio (RR), or odds ratio (OR) and the corresponding 95 % confidence intervals (CI). DATA COLLECTION AND ANALYSIS MOOSE guidelines were followed. Data were extracted by 2 researchers, independently. Combined hazard ratios (HRs) was evaluated by DerSimonian and Laird Random-effects model. RESULTS Two studies continuing four arms with 1,209,122 participants were eligible for pre-pregnancy BMI section meta-analysis and six studies were eligible for inclusion, providing 10,340,036 participants for birth weight section meta-analysis. Pooled results demonstrated a significant association between obesity and risk of T1DMC (HR: 1.30, 95 % CI: 1.16-1.46, I2 = 7%). The combined HR (95 % CI) showed lower risk of T1DMC in low birth weight infants (HR: 0.78, 95 % CI: 0.69-0.88, I2 = 0%) and higher risk of T1DMC in the high birth weight infants versus the normal category of birth weight (HR: 1.08, 95 % CI: 1.00-1.17, I2 = 31 %). There was a significant non-linear association between birth weight and risk of T1DMC in children (Coef =-0.00032, p = 0.001). CONCLUSIONS AND RELEVANCE This systematic review and meta-analysis identified high maternal BMI and High birth weight (HBW) increase risk of childhood T1DMC.