What Is Known
- The role of obesity in adults with Crohn disease is unclear, with some reports suggesting worsened disease course, whereas other reports suggest no impact.
- Little is known about the role of obesity in children with Crohn disease.
What Is New
- In this cohort of children with newly diagnosed Crohn disease, obesity appears to have no impact on Crohn disease course at 1 year.
- Further study is warranted to evaluate longer-term impact of obesity in pediatric Crohn disease.
Obesity among children is a growing challenge in the United States with approximately 15% of children being overweight and an additional 17% being obese, defined by age-specific growth charts (1,2). Although obesity is typically considered a proinflammatory state, the impact of obesity on immune-mediated diseases, such as Crohn disease (CD), is not entirely clear (3,4). Limited data in adult patients show conflicting impact of obesity on inflammatory bowel disease (IBD), with some studies suggesting increased disease flares and complications, whereas other studies show no impact or even reduced need for surgery in obese patients with IBD (5–9). Literature on obesity in pediatric IBD is even more limited, with very few reports directly addressing this issue. The aim of the present study was to use a large multicenter cohort of children with newly diagnosed CD to evaluate the impact of obese and overweight status on IBD-related outcomes.
METHODS
Study Design
We performed a retrospective cohort study of children with newly diagnosed CD enrolled in the ImproveCareNow (ICN) Network from September 2006 to October 2014. The ICN Network includes prospectively collected data regarding demographic factors, IBD phenotype, IBD disease course, treatment course, and disease-related outcomes. Data are entered into the ICN database by clinicians or research personnel. For the present analysis, we included patients with a first visit within 90 days of CD diagnosis and at least 1 follow-up visit within 12 to 18 months after diagnosis. All children with age >2 years (24 months) and <21 years (252 months) were included. Patients were excluded if weight, height, sex, or birthdate were missing at baseline or 1-year follow-up. Underweight children, as defined by body mass index (BMI) <10th percentile at baseline or 1-year follow-up, were also excluded.
Exposure Variables (Overweight/Obese Status)
Using BMI at the initial visit, patients were categorized into obese, overweight, and normal-weight groups. For children ages 2 to 20 years, the Centers for Disease Control and Prevention age- and sex-specific nomograms were used to categorize patients by weight status. Obesity was defined as BMI ≥95th percentile and overweight was defined as BMI between 85th and 94th percentile for given age and sex. Normal weight was defined as 10th to 84th percentile. For patients ages 20 years, traditional BMI cut points were used: normal weight BMI 18.5 to 24.9, overweight BMI 25.0 to 29.9, obese BMI ≥30.0 (10).
Outcome Variables
The primary outcome was the number of visits in clinical remission during 1-year follow-up based on physician global assessment (PGA). The visit closest to 1 year from diagnosis (and after a minimum of 365 days since diagnosis) was used to assess additional secondary outcomes. Secondary outcomes assessed include disease activity by short Pediatric Crohn Disease Activity Index (sPCDAI), nutritional status (satisfactory, at risk, in failure), growth status (satisfactory, at risk, in failure), serologic markers of disease (sedimentation rate, hematocrit, albumin), and medication treatment differences.
Statistical Analysis
Obese and overweight patients were evaluated as separate groups with normal-weight patients as the reference group. The t test or nonparametric Kruskal-Wallis rank sum test were used to look at differences in continuous variables. Pearson Chi square test or Fisher test was used to evaluate bivariate outcomes by weight group (obese vs normal; overweight vs normal). Missing data variables were omitted from the analysis (pairwise deletion). All statistical analyses were performed using R 3.0.1 (11).
The study was approved by the Nationwide Children's Hospital Institutional Review Board.
RESULTS
A total of 898 children with newly diagnosed CD were included in the analysis. Table 1 shows demographic and clinical characteristics between normal weight, overweight, and obese patients at baseline. The majority of children were normal weight (n = 768, 85.5%), whereas smaller numbers were overweight (n = 87, 9.7%) or obese (n = 43, 4.7%). Children with obesity had a younger age at CD diagnosis compared to normal-weight children (11.4 vs 12.9 years, P = 0.016). Compared to normal-weight children, children with obesity also had higher percentage of Medicaid insurance (35% vs 12%) and lower percentage of commercial insurance (47% vs 74%), P < 0.001. Other demographic characteristics, including sex and race, were similar between groups. CD phenotype and behavior at diagnosis were also similar between obese, overweight, and normal-weight children.
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TABLE 1: Study cohort demographics at baseline visit
The primary outcome measure, number of visits in remission during 1 year, was similar for children with obesity (3.49 visits) compared to normal-weight children (3.98 visits, P = 0.18) and for overweight children (3.67 visits) compared to normal-weight children (P = 0.16). There was no difference in total number of visits between groups or number of visits in steroid-free remission. Other secondary outcome measures, including nutritional status, growth status, and sPCDAI, were assessed at the visit closest to 1 year. There was no difference in these secondary outcomes at 1 year (Table 2). Based on sPCDAI, numerically more children with obesity had moderate-severe disease compared to normal-weight children (20% vs 11%) and fewer children with obesity had inactive disease compared to normal-weight children (60% vs 72%). These trends were, however, not statistically significant (P = 0.33). Medication use, including use of steroids, immune suppressants, or biologics, was similar between obese, overweight, and normal-weight children at 1 year. Serum hematocrit was statistically higher for children with obesity at 1 year compared with normal-weight children (39.5 vs 37.8). Other laboratory measurements, including sedimentation rate and albumin, were, however, similar between groups (Table 2).
TABLE 2: Crohn disease outcomes at 1-year follow-up
Some children did change weight category from baseline through the 1 year of follow-up. Among children who were normal weight at baseline, 66 children increased to overweight (9% of the normal weight cohort) and 16 children (2%) increased to obese at 1-year follow-up. Among children who were obese at baseline, 7 children (16%) decreased to overweight and 5 children (12%) decreased to normal weight. There was more movement in the group of children who were overweight at baseline. Amongst these overweight children, 22 children (25%) increased to the obese category and 28 children (32%) decreased to normal weight.
For most data fields shown in Tables 1 and 2, the proportion of missing data was small (<10% missing). Notable exceptions include Paris Classification, in which approximately 45% of children had missing data, and sPCDAI, in which 35% of children had missing data. The proportion of missing data was similar between normal-weight, overweight, and obese children.
DISCUSSION
Obesity is a growing health challenge in adults and children. The impact of obesity on CD is poorly characterized, particularly in children. Our present study looks at children with newly diagnosed CD and shows no impact of obesity or overweight status on CD outcomes at 1 year from diagnosis.
Research on the impact of obesity on CD outcomes is limited. Literature in the adult setting shows conflicting impact of obesity on IBD course. Early reports seemed to indicate higher rates of perianal disease, active disease flares, and shorter time to first surgery amongst obese or overweight adults with CD (5,6). These studies were, however, somewhat limited by their retrospective design and relatively small numbers. A more recent retrospective cohort study of almost 1500 patients showed no association between BMI and IBD outcomes, including steroid use, anti-TNF use, hospitalization, or IBD-related surgery (7). A retrospective cohort by Flores et al (9), included approximately 600 adult patients and showed lower rates of steroid use, anti-TNF use, hospitalization, and IBD-related surgery amongst obese adults with IBD. The authors concluded that obesity may be a marker of less severe disease.
Literature in the pediatric setting is even more limited. A 2014 study used the Kids’ inpatient database to analyze more than 12,000 hospital admissions of children with IBD and demonstrated no impact of obesity on rate of perforation, hemorrhage, complex fistula, or need for surgery (12). This study was, however, limited to the hospitalized IBD population and focused only on in-hospital outcomes. In addition, only 1.3% of admissions had a code for obesity, raising concern for potential undercoding in the dataset. A 2011 study performed a cross-sectional analysis of overweight and obese children enrolled in ICN. That study showed that prior IBD-related surgery was associated with overweight or obese status, suggesting a worsened disease course for these children (13). The cross-sectional design of that study limited conclusions about causality and no weight-based differences in other clinical characteristics, including PGA, medication use, or disease phenotype, were observed.
Although our data show no signs of differing disease course at 1 year for obese compared with normal-weight children, it is possible that obesity may have a delayed effect on CD outcomes that manifests several years later. Moreover, some children with a normal weight at the time of diagnosis may develop obesity later in their disease course. Indeed, 11% of children in our cohort progressed from normal weight at baseline to overweight or obese at 1-year follow-up. It is unclear whether this subsequent obesity would have an impact on CD course, and this would be an interesting area to investigate in future studies.
A key difference between our study and prior pediatric and adult studies was our use of an inception cohort including assessment of baseline weight status within 90 days of diagnosis. In prior studies, obesity status was generally assessed several years into the patient's disease course. Because CD can lead to malnutrition and weight loss, categorizing obesity after several years of disease may in fact just be a measure of disease severity, as suggested by Flores et al. There are additional strengths of our study. In particular, the ICN Network is a large, multicenter cohort with robust data on clinical measures, disease activity indices, medication data, and laboratory data. Secondly, we were able to simulate an inception cohort by including only children with newly diagnosed CD.
Nonetheless, there are some key limitations. Our study only captures height/weight data within 90 days of diagnosis. Hence, the characterization of weight status could be affected by weight loss before diagnosis (resulting in potential bias toward worse outcomes for normal-weight children). Conversely, weight status could be affected by steroid use at the time of diagnosis which could bias toward worse outcomes for overweight or obese children. Also, for some data fields, most notably the sPCDAI, there was substantial proportion of missing data (∼35% missing for sPCDAI). The proportion of missing data was, however, similar across normal weight, overweight, and obese children suggesting that missing data may have been random rather related to obesity status.
In conclusion, this multicenter cohort study shows no impact of obesity or overweight status on CD outcomes at 1 year after diagnosis, as measured by multiple clinical endpoints. Longer-term studies would be beneficial to see whether obesity has an impact on CD outcomes later in the disease course.
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