L’utilisation des corticostéroïdes et le retard de croissance linéaire chez les enfants atteints de la maladie de Crohn

Crohn's disease (CD) is a chronic, relapsing disease of the gastrointestinal tract. In the pediatric population it is very often accompanied by growth retardation (up to 88%). CD occurs in children mainly around puberty making the impact of growth impairment vital at this crucial stage of development. One of the critical issues is whether growth delay may persist into adulthood. Literature on this has been inconsistent. With regards to potential risk factors, corticosteroids (CS), the first line of treatment in the majority of patients, have been widely implicated. Although there is considerable mechanistic evidence, clinical studies linking CS use to either temporary or permanent growth remain controversial and limited. We examined this important relationship in our present study.  The major objectives of the study were: 1. To evaluate the frequency of growth retardation in children with Crohn's disease who were administered CS and  2. To evaluate the factors associated with either temporary or permanent growth impairment in this population.  Methods: We carried out a retrospective cohort study in patients diagnosed at the gastroenterology clinics of Hospital Sainte-Justine, Montreal. Patients were children diagnosed with CD and administered CS during the entire disease course. The medical charts of the patients were prospectively examined to acquire information on: 1. Measures of height acquired at each visit to the clinic; 2. Courses of CS administered; 3. Administration of other concomitant medications; 4. Information on clinical variables such as age at diagnosis, gender, disease location and behavior at diagnosis etc. For those patients who had attained the age of 18 and who were no longer visiting the clinics, final heights were acquired by contacting them over telephone. Similarly, their parents were contacted to acquire their final heights. Z-scores for height adjusted for age and gender were estimated using the WHO 2007 classification. Children with z-scores <-1.64 were deemed temporarily growth impaired. Final adult height z-scores for the subjects were calculated using the same standards for gender-matched persons who were 17.9 years old. A z-score of <-1.64 was also used to assign individuals as permanently growth impaired. As an additional criteria, those whose final height were <8,5cm below the target height (estimated from parental heights) were deemed to be permanently growth impaired. Logistic regression analysis was carried out to examine factors associated with temporary and/or permanent growth impairment.   Results: 221 patients were included. The average age of diagnosis was 12.4 years and the average age at CS start was 12.7 years. The majority of children were male (54.3%). The majority of them where of pubertal age (62.9%). Most patients had inflammatory disease (89.1%) and ileocolonic disease location (60.2%). Concomitant medications were administered to about 88.7% of the patients. A minority of patients underwent surgery (4.1%). 19% of the patients had temporary growth impairment. Univariate analysis suggested that early age at disease diagnosis and early age at steroid administration was associated with increased risk for temporary growth impairment. Early age at administration of steroids was the only variable (in multivariate analysis) associated with increased risk for temporary impairment. Compared to children who were administered steroids after age 14, children administered steroids earlier (<11.6yr, OR: 6.9, 95% CI: 2.2-21.6, p-value: 0.001; 11.8yr-14yr, OR: 5.4, 95% CI: 1.7-17.1, p-value: 0.004) were significantly at higher risks for growth impairment.  Similarly, only 5.8% of the patients had final heights <8,5cm of the expected target height. On multivariate linear regression analysis, target height was the only variable associated with final adult height. Conclusion: Our results suggest that the frequency of permanent growth retardation in children with CD is very low. Neither temporary nor permanent growth impairment was associated with increasing CS administration, although administration of CS at an earlier age was associated with temporary growth impairment.

Keyphrases: Crohn's disease, Corticosteroids, Final adult height, Inflammatory bowel disease, Expected adult height, Z score, Growth retardation