Breast-feeding and childhood-onset type 1 diabetes: a pooled analysis of individual participant data from 43 observational studies.
Cardwell CR., Stene LC., Ludvigsson J., Rosenbauer J., Cinek O., Svensson J., Perez-Bravo F., Memon A., Gimeno SG., Wadsworth EJ., Strotmeyer ES., Goldacre MJ., Radon K., Chuang LM., Parslow RC., Chetwynd A., Karavanaki K., Brigis G., Pozzilli P., Urbonaite B., Schober E., Devoti G., Sipetic S., Joner G., Ionescu-Tirgoviste C., de Beaufort CE., Harrild K., Benson V., Savilahti E., Ponsonby AL., Salem M., Rabiei S., Patterson CC.
OBJECTIVE: To investigate if there is a reduced risk of type 1 diabetes in children breastfed or exclusively breastfed by performing a pooled analysis with adjustment for recognized confounders. RESEARCH DESIGN AND METHODS: Relevant studies were identified from literature searches using MEDLINE, Web of Science, and EMBASE. Authors of relevant studies were asked to provide individual participant data or conduct prespecified analyses. Meta-analysis techniques were used to combine odds ratios (ORs) and investigate heterogeneity between studies. RESULTS: Data were available from 43 studies including 9,874 patients with type 1 diabetes. Overall, there was a reduction in the risk of diabetes after exclusive breast-feeding for >2 weeks (20 studies; OR = 0.75, 95% CI 0.64-0.88), the association after exclusive breast-feeding for >3 months was weaker (30 studies; OR = 0.87, 95% CI 0.75-1.00), and no association was observed after (nonexclusive) breast-feeding for >2 weeks (28 studies; OR = 0.93, 95% CI 0.81-1.07) or >3 months (29 studies; OR = 0.88, 95% CI 0.78-1.00). These associations were all subject to marked heterogeneity (I(2) = 58, 76, 54, and 68%, respectively). In studies with lower risk of bias, the reduced risk after exclusive breast-feeding for >2 weeks remained (12 studies; OR = 0.86, 95% CI 0.75-0.99), and heterogeneity was reduced (I(2) = 0%). Adjustments for potential confounders altered these estimates very little. CONCLUSIONS: The pooled analysis suggests weak protective associations between exclusive breast-feeding and type 1 diabetes risk. However, these findings are difficult to interpret because of the marked variation in effect and possible biases (particularly recall bias) inherent in the included studies.