Diagrama de análisis del proceso de bajas Raee y otros – actual

Gersterin 1994 conducted a systematic review on literature that explored a possible link between cow milk and type 1 diabetes. Articles were excluded if they exclusively used surrogate markers for either type 1 diabetes or cow milk exposure. A total of three ecological and time-series studies, 13 case-control studies, one cohort study, and one case series were included. Meta-analysis of all included case-control studies was performed, using a fixed effect model. Both adjusted and unadjusted odds ratios were used, but there was no further analysis or discussion on potential impacts of confounding by combining unadjusted odds ratios. The methodological quality of the systematic review and meta-analysis was rated grade B, due to insufficient consideration for the potential confounding in the primary studies.

In the included time-series and ecological studies, the results showed an inverse association (geographical and temporal) between the rate/prevalence of breastfeeding and the rate/prevalence of type 1 diabetes.

The cohort study was an analysis of two groups of children born in the UK in 1958 and 1970, who were followed for 16 and 10 years, respectively. This study did not find any association between breastfeeding for less than 1 month and the risk of development of type 1 diabetes.

In the 13 case-control studies in which the neonatal feeding history of patients with type 1 diabetes and individually matched non-diabetic control subjects were compared, the results were mixed. A total of 3,708 type 1 diabetes cases and 20,340 non-diabetic controls were included. None of these studies satisfied all six methodological criteria defined by the author. Four of the 13 case-

control studies fulfilled five of six methodological criteria (e.g., inclusion of ≥75 percent of eligible diabetic patients, unbiased selection of unrelated nondiabetic control subjects, control subjects derived from the same population as diabetic subjects, an identical means of determination of infant feeding practices in both diabetic and nondiabetic groups, blind determination of early feeding history, and identification of diabetic patients from incident cases). When these four studies were combined, the overall odds ratio (adjusted odds ratios were used) for type 1 diabetes in patients exposed to less than 3 months of breastfeeding was 1.43 (95%CI 1.15 - 1.77; P=0.3 for

homogeneity). When all 13 included case-control studies were combined, the overall odds ratio (mixed crude and adjusted odds ratios were used) for type 1 diabetes in patients exposed to less than 3 months of breastfeeding was 1.37 (95%CI 1.22-1.53; P=0.11 for homogeneity).

In 1996, Norris and Scott performed a meta-analysis of infant diet and type 1 diabetes to examine further the inconsistent results reported in the literature. A total of 17 case-control studies with appropriate data for meta-analysis were included. The analysis included 4,656 type 1 diabetes cases and 16,383 non-diabetic controls. The authors abstracted case and control data for four separate exposures: breastfeeding status (ever/never), total breastfeeding duration, exposure to breast-milk substitutes, and exposure to cow milk-based substitutes. Due to the limitation of the meta-analytic technique, only unadjusted odds ratios were calculated and combined, although some primary studies had adjustments for maternal education, maternal age at birth, birth order,

household income, race/ethnicity, and/or social class. Authors performed sensitivity analyses on various characteristics of study methodological quality to explore the impacts of potential biases on the summary odds ratios. The methodological quality of this meta-analysis was rated grade B, due to insufficient consideration for the potential confounding in the primary studies.

The overall odds ratio of all included case-control studies that examined the association between never breastfed and type 1 diabetes was 1.13 (95%CI 1.04 - 1.23). Among these studies, fourteen also examined type 1 diabetes risk by months of breastfeeding duration. The duration categories in the analysis were cumulative, rather than mutually exclusive (i.e., some studies provided data on both 3-month and 6 month breastfeeding data in the same subjects). The summary odds ratios showed consistently elevated risks of type 1 diabetes associated with age at first exposure to any breast milk substitutes before 6 months of age. Since the majority of the studies reported odds ratios using a cutoff of 3 months when examining continuous exposures, this cutoff was used for the meta- analysis. The summary odds ratio for type 1 diabetes in subjects who were breastfed for less than 3 months compared with those who were breastfed for at least 3 months was 1.23 (95%CI 1.12 - 1.35).

Stratified analyses of studies by methodological and study population characteristics were performed to see whether differences in these characteristics might explain the heterogeneity. The characteristics were prevalent versus incident case-control study design, adequate versus inadequate response rates of the cases and controls, the breastfeeding prevalence in the background population, the type 1 diabetes risk in the background population, and retrospective versus concurrent infant diet assessment. All of these factors had differential impacts on the summary odds ratios for the risk of type 1 diabetes associated with infant diet exposures.

Norris and Scott concluded that their meta-analysis showed that the increased risk of type 1 diabetes associated with any of the infant diet exposures was small. According to these authors, interpretation of weak associations (i.e., an odds ratio of less than 2.0) can be problematic, since weak associations can more readily be explained by biases.

Studies Identified after the Published Systematic Reviews/Meta-