Abstract
Background
Celiac disease is a gastrointestinal disorder affecting approximately 1% of the population. Autism spectrum disorder (ASD) describes a range of developmental disorders that affects communication and behavior with no known cause. Several epidemiological studies have explored a possible connection between celiac disease and ASD.
Aims
To evaluate the association between celiac disease and ASD.
Methods
A systematic review was performed. MEDLINE and EMBASE databases were searched for observational studies reporting the co-occurrence of celiac disease and ASD between January 1st, 1946 and May 2nd, 2018. Studies reporting the prevalence of ASD within a cohort of celiac disease patients or vice versa were included. Studies were assessed for quality, heterogeneity, and overall findings.
Results
Fifteen articles investigating the association between celiac disease and ASD were identified (Table 1); thirteen studies observed cohorts of ASD patients and four studies observed cohorts of celiac disease patients. There was significant heterogeneity between studies. Statistically significant results supporting the association between ASD and celiac disease were observed in three studies that had the largest sample sizes. However, the majority of studies demonstrating no association employed invalid or unclear sampling techniques, were at risk of selection bias, or included small sample sizes.
Conclusions
This systematic review suggests there is limited evidence to support an association between ASD and celiac disease. However, several study design characteristics, rather than the non-existence of this comorbidity, may explain these findings. Further population-based studies are necessary to adequately assess the relationship between these two conditions.
| Study (Country) | Proportion of cases positive for celiac disease* or ASD** | Proportion of controls positive for celiac disease* or ASD** |
|---|---|---|
| Screening for celiac disease in patients with ASD* | ||
| Pavone 1997 (Italy) | 0/11 | 0/11 |
| Black 2002 (United Kingdom) | 0/96 | 1/449 |
| Abolfazli 2009 (Iran) | 0/34 | 0/34 |
| Lau 2013 (United States) | 0/37 | 0/76 |
| Bala 2016 (Turkey) | 0/16 | 0/27 |
| Ibrahim 2009 (United States) | 0/121 | 0/242 |
| Badalyan 2011 (Canada, United States) | 9/211 | 2/160 |
| Badalyan 2012 (Canada, United States) | 1/79 | 0/79 |
| Batista 2012 (Brazil) | 0/147 | 0.54% |
| Calderoni 2016 (Italy) | 10/382 | 29/2,616 |
| Bavykina 2018 (Russia) | 0/33 | N/A |
| Jozefczuk 2018 (Poland) | 0/77 | N/A |
| Studies screening for ASD in patients with celiac disease** | ||
| Pavone 1997 (Italy) | 0/120 | 0/20 |
| Batista 2012 (Brazil) | 2/211 | 0.90% |
| Ludvigsson 2013 (Sweden) | NR/26,955† | NR/134,076 |
| 113/26,981^ | NR/213,055 | |
| Butwicka 2017 (Sweden) | 92/10,903^ | 5,837/1,042,072 |
NR: not reported; N/A: not applicable (i.e., no control group) †diagnosis of ASD before celiac disease ^diagnosis of ASD after celiac disease
Funding Agencies
None