Gluten Introduction to Infant Feeding and Risk of Celiac Disease: Systematic Review and Meta-Analysis.
OBJECTIVE
To assess the evidence regarding the effect of time of gluten introduction and breastfeeding on the risk of developing celiac disease (CD).


METHODS
We included randomized controlled trials and observational studies evaluating the proper timing for introducing gluten to the infant diet, the appropriate quantity of gluten consumption at weaning, and the effect of breastfeeding on CD risk. Studies were located through the electronic databases Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Ovid), EMBASE (Ovid), and System for Information on Grey Literature in Europe (SIGLE). Two independent authors collected the data.


RESULTS
A total of 1982 studies were identified, 15 of which were eligible for data extraction. A meta-analysis was performed on 2 randomized controlled trials, 10 cohort studies, and 1 case-control study. There was a 25% increase in CD risk with late (>6 months) vs recommended (4-6 months) gluten introduction (risk ratio [RR], 1.25; 95% CI, 1.08-1.45). There was no significant effect of breastfeeding vs no breastfeeding on CD risk (OR, 0.55; 95% CI, 0.28-1.10), with substantial heterogeneity (I(2) = 92%) among studies.


CONCLUSIONS
There is currently no evidence to support that early introduction of gluten to the infant diet increases the risk of CD; however, late introduction of gluten may be associated with increased risk of CD. More studies are needed that control for potential confounders and that evaluate environmental factors in low-risk families.
Department of Medicine, Farncombe Family Digestive Research Institute, McMaster University, Hamilton, Ontario, Canada. Electronic address: pintosm@mcmaster.ca.
María Inés
MI
Pinto-Sánchez
Department of Medicine, Farncombe Family Digestive Research Institute, McMaster University, Hamilton, Ontario, Canada.
Elena F
EF
Verdu
Colorado Center for Celiac Disease, Children's Hospital Colorado, Aurora, CO.
Edwin
E
Liu
Department of Medicine, Farncombe Family Digestive Research Institute, McMaster University, Hamilton, Ontario, Canada.
Premysl
P
Bercik
Celiac Disease Center at Columbia University, New York, NY.
Peter H
PH
Green
Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN.
Joseph A
JA
Murray
Department of Pediatrics, Section of Gastroenterology, Hepatology and Nutrition, University of Chicago, Chicago, IL.
Stefano
S
Guandalini
Department of Medicine, Farncombe Family Digestive Research Institute, McMaster University, Hamilton, Ontario, Canada.
Paul
P
Moayyedi
D001942:Breast Feeding; D002446:Celiac Disease / Q000453:epidemiology* / Q000209:etiology; D005247:Feeding Behavior; D005983:Glutens / Q000008:administration & dosage*; D006801:Humans; D007223:Infant; D064887:Observational Studies as Topic; D016032:Randomized Controlled Trials as Topic; D018570:Risk Assessment
D005983:Glutens