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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Conflicting Cholesterol Guidelines –Massive Undertreatment or Massive Overtreatment?

A fascinating article (Gooding HC et al. JAMA Pediatr doi:10.1001/jamapediatrics.2015.0168) studies a cross-sectional analysis of the National Health and Nutrition Examination Survery (NHANES) population and determines the frequency of the need for statin therapy for hyperlipidemia based on two separate guidelines.

  • 2011 Integrated Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescents of the National Heart, Lung, and Blood Institute (Pediatrics 2011; 128 (sup 5): S213-S256) PEDS RECS
  • 2013 Guidelines on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults from the American College of Cardiology and American Heart Association (Circulation 2014: 129 (25) (supl 2) S1-S45) ADULT GUIDELINES

Specifically, the design of the study focused on 17-21 year olds in which the guidelines had overlapping recommendations. While the NHANES population involved only 6338 patients, this representative sample was used to calculate the likelihood of statin therapy more broadly among the US population of 20.4 million in this age group.

Key Findings:

  • Among the cohort of 6338, 2.5% would qualify for statin treatment using PEDS RECS compared with 0.4% under ADULT GUIDELINES.
  • This finding extrapolates to 483,500 patients nationwide compared with 78,200, respectively.  This is a difference of more than 400,000 and reflects a 6-fold difference.

Why the discrepancy?

  • ADULT GUIDELINES recommend use of statins only if LDL-C is >190. PEDS RECS extend to as low as 130 or 160 if additional risk factors (highly prevalent) are present, including hypertension, obesity, and smoking.
  • ADULT GUIDELINES are based on randomized clinical trials, though “they advocate for physician’s judgement in areas where the evidence base is insufficient.” PEDS RECS use extrapolated evidence for lifetime risk of coronary vascular disease.

Bottomline: While these guidelines highlight differences among 17-21 year olds, the decision regarding statin therapy extends across the age spectrum in terms of whether a low or high threshold should be in place.  Also, it is unfortunate that the additional modifiable risk factors (smoking, hypertension, and obesity) are so prevalent as to create this divergence in approach.

Related references:

  • NEJM 2015; 372: 1489-99. Alirocumab, a monoclonal antibody that inhibits PCSK9, lowered LDL 62% in patients receiving maximal statin therapy. Randomized, placebo-controlled study with 2341 patients.
  • NEJM 205; 372: 1500-09. Evolocumab, a monoclonal antibody that inhibits PCSK9, lowered LDL 61% in two open-label randomized trials (n=4465).

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