First Year of Life Antibiotics and Celiac Disease

Briefly noted:

A recent study (SD Sander et al. Gastroenterol 2019; 156: 2217-29) found an association between antibiotics in the first year of life and celiac disease.

The authors “collected medical information on 1.7 million children, including 3346 with a diagnosis of celiac disease” using nationwide register-based cohorts from Norway and Denmark.

Key finding:

  • “Exposure to systematic antibiotics in the first year of life was positively associated with diagnosed celiac disease,” pooled odds ratio 1.26.  Furthermore, there was a dose-dependent relationship with increasing number of exposures increasing the risk of celiac disease.

My take: The increase in prevalence of celiac disease over that past few decades is likely related to changes in our environment.  These changes affect nearly everyone, but some are more susceptible to immune-related disease that may be triggered by these environmental changes.  This study shows that early exposure to antibiotics is likely to be one of the environmental factors that increase the risk of celiac disease.

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Early Life Events and the Development of Inflammatory Bowel Disease

Full Text via AGA Journal Link: Events Within the First Year of Life, but Not the Neonatal Period, Affect Risk for Later Development of Inflammatory Bowel Diseases

A recent study (CN Bernstein et al. Gastroenterol 2019; 156: 2190-7; editorial 2124) delves into the topic of early life risk factors for the development of IBD. In the background, the author note that in 2018, 267,983 Canadians (0.73%) were estimated to be living with IBD and there is a forecast that this will increase to 402,853 by 2030.

This study used a Manitoba database and examined the records of individuals diagnosed with between 1984-2010. In addition, they correlated this data with individual data of the postnatal period between 1970-2010. From this database, they analyzed 825 individuals with IBD and 5999 matched controls.

Key Findings:

  • The strongest risk factor for the development of IBD was a maternal diagnosis of IBD with an odds ratio (OR) of 4.53; the OR was higher for CD at 5.98 compared to OR of 2.71 for UC
  • Infections in the first year of life was associated with an OR of 3.06 for IBD diagnosed before age 10 years, and OR of 1.63 for IBD diagnosis before age 20 years.  Only infections in the first year of life were correlated with IBD as infections during the first 3 years of life were not associated with a significant increased risk.
  • While infections in the first year of life were associated with an increase risk of IBD, the authors could not demonstrate that individuals who developed IBD had more infections than unaffected sibling controls (though they did have more infections than the entire control cohort).
  • Highest socioeconomic quintile, also, had an increased OR of 1.35.
  • Gastrointestinal illnesses (like abdominal pain) were not found to be associated with the later development of IBD.

It is unclear whether infections in early life increase the risk of IBD or whether other factors like antibiotics contribute to the higher rate of IBD.  The authors did not find more immunodeficiency disorders in the IBD cohort compared to controls.

My take: This study identified genetic risk as substantially greater than specific environmental risks.  However, the increasing incidence of IBD suggests that environmental factors are quite significant, as genetic risk factors are less likely to change enough to account for the changes in epidemiology.  As such, there are a few explanations:

  1. There are other unidentified environment risk factors
  2. Some individuals are more susceptible to the changes that have occurred in the environment; that is, their environmental exposures are not significantly different from their peers but are significantly different than individuals from 20, 40, 60 and 100 years ago.

From AGA Journal link

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Highest Reported Prevalence Rates for Eosinophilic Esophagits

A recent retrospective study (J Robson et al. Clin Gastroenterol Hepatol 2019; 17: 107-14) utilized a pathology database encompassing the vast majority of Utah pediatric cases to determine the incidence and prevalence of eosinophilic esophagitis (EoE) from 2011 to 2016.

The authors determined cases of EoE by looking for symptomatic children with isolated esophageal eosinophilia (more that 14 eos/hpf) in the absence of other comorbid conditions.

Key findings:

  • 1060 children met the criteria for a new diagnosis of EoE
  • Average annual incidence of EoE was 24 per 100,000 children; this is nearly double the previously reported rate 12.8 per 100,000 from Hamilton County, Ohio in 2003.
  • Prevalence of EoE was 118 per 100,000 children

The authors speculate on several factors that produced this increased incidence rate –all related to EoE risk factors:

  • Predominant non-Hispanic White population
  • High rates of atopy
  • Increased capture rate of their database
  • Also, the authors did NOT exclude PPI-responsive esophageal eosinophilia (which is a subtype of EoE and not a different disease

The authors note that “there is reason to believe that this [high incidence rate] is a conservative estimate:”

  • ~2% of pathology reports had 10-14 eos/hpf.  Further review of these cases would likely have identified some which have exceeded the >14 threshold
  • Some pediatric EoE cases are diagnosed by adult gastroenterologists who did not use the pathology databases

My take: This study shows high rates of EoE but comes as no surprise.  And, there are likely a large number of individuals with mild EoE which has not been diagnosed.  In my experience, families and physicians often overlook altered eating habits as related solely to behavior.  Useful questions to uncover dysphagia include the following: how long does it take your child to eat? does your child have to drink a lot of liquids when eating? does food get stuck frequently?

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Global Prevalence of Celiac Disease

Briefly noted: P Singh et al. Clin Gastroenterol Hepatol 2018; 16: 823-36. After a systemic review which selected 96 articles from a pool of 3843 published between 1991 through 2016, the authors determined a pooled global prevalence of 1.4% in 275,818 individuals based on seroprevalence (positive TTG or EMA).  Biopsy-confirmed celiac disease was noted in 0.7% in 138,792 individuals.

In their study, biopsy-proven disease was most prevalent in Argentina, Egypt, Hungary, Finland, Sweden, New Zealand, and India.

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Northern Latitudes -Higher Prevalence of Celiac Disease and Gluten Avoidance

A recent study (A Unalp-Arida et al. Gastroenterol 2017; 152: 1922-32) examines the relationship of latitude and the prevalence of celiac disease and gluten avoidance.

Using the NHANES 2009-2014 survey with 22,277 participants (6 years and older), the authors identified persons with celiac disease (based on serology) along with those who avoided gluten without a diagnosis of celiac disease.

Key findings:

  • 0.7% of participants had celiac disease and 1.1% avoided gluten without celiac disease
  • Celiac disease was more common among individuals who lived at latitudes of above 35 degrees and more common with higher socioeconomic status. Figure 2 map provides latitude lines. In the eastern U.S. the Georgia-Tennessee border corresponds to this latitude line and in the western U.S. the southern tip of Nevada lies on this line.
  • From 35 degrees to 39 degrees the odds ratio was 3.2, whereas the odds ratio was 5.4 for those above 40 degrees.  These odds ratios were independent of race, ethnicity, socioeconomic status and body mass index.
  • Similarly, the prevalence of gluten avoidance without celiac disease was twice as common among persons living north of 40 degrees compared with those residing at latitudes <35 degrees.
  • The findings on latitude were heavily influenced by the increased rate of celiac and gluten avoidance in the Northeast region (more so than in the West)

In their discussion, the authors note that “a North-South gradient in disease occurrence in genetically similar populations has been shown in studies of autoimmune diseases, including inflammatory bowel disease, multiple sclerosis, and rheumatoid arthritis.” Potential environmental factors could include lack of sunshine/vitamin D deficiency, hygiene, and infections.  A study comparing similar populations in Finland and Russia suggested a lower economic status/less hygiene increased the risk of celiac disease despite similar gluten exposure.  The authors note that there was NOT an increased risk in Northern Sweden compared to Southern Sweden.  In fact, this study of children found a higher rate of celiac disease in Southern Sweden (Arch Dis Child 2016; 101: 1114-18).

My take: This is another intriguing study regarding celiac disease epidemiology which strongly points to environmental factors accounting for marked variation in celiac disease prevalence.

More information on this topic from AGA Blog: Do More People Have Celiac Disease in the North vs the South?

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More IBD Cases Than Ever in Young Canadian Children

Summary of recent article (Link to full study: Benchimol EI, et al. Am J Gastroenterol. 2017;doi:10.1038/ajg.2017.97) by Healio Gastroenterology: IBD incidence rapidly increasing in young Canadian children

An excerpt:

To evaluate the recent incidence, prevalence and trends in childhood-onset IBD in Canada, Benchimol and colleagues used health administrative data from five provinces to identify children aged younger than 16 years who were diagnosed with IBD between 1999 and 2010. During this period, 3,462 children were diagnosed with Crohn’s disease, 1,382 with ulcerative colitis and 279 with unclassifiable IBD, for an overall IBD incidence of 9.68 (95% CI, 9.11-10.25) per 100,000 children.

Throughout the study period, the annual percentage change in overall IBD incidence remained statistically stable, increasing by just 2.06% per year, but the incidence increased significantly among children aged younger than 5 years, rising by 7.19% per year.

Further, the annual percentage change in the prevalence of IBD increased significantly throughout the study period (4.56%), and at the end of the study period IBD prevalence was 38.25 (95% CI, 35.78-40.73) per 100,000 children.

The investigators noted their findings confirmed the predominant form of pediatric-onset IBD was Crohn’s disease, and that more boys were affected than girls.

My take: While Canada has high prevalence of IBD, I expect that there will be similar trends in epidemiology in multiple regions in young children.  When one looks at the increases in IBD prevalence over the last 100 years (see previous post) and the emergence of IBD in non-Western countries, it is quite alarming.

Also, last week a blog post discussed hepatic problems associated with IBD (Liver problems with IBD): here is full article text link: Hepatic Issues and Complications Associated with IBD

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Achalasia -Updated Epidemiology

In this new era of high resolution manometry, there is an increasing incidence of achalasia.

Briefly noted:

JA Duffield et al. Clin Gastroenterol Hepatol 2017; 15: 360-5. In this study from South Australia, using a large database (2004-2013), the annual incidence of achalasia was between 2.3 and 2.8 per 100,000 persons. Mean age at diagnosis was 62 years.

S Samo et al. Clin Gastroenterol Hepatol 2017; 15: 366-73. In a similar study from Chicago, the authors estimated that the yearly city-wide incidence averaged 1.07 per 100,000; however the average in the neighborhood closest to the hospital (and possibly with better case capture) was 2.92 per 100,000.

My take: These studies identified incidence rates that are about double the rates that were reported prior to the availability of high resolution manometry.

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