Linear growth impairment is a common complication of childhood-onset inflammatory bowel disease (IBD), but most patients achieve normal height as adults (1,2). We observed a similar trend in our cohort, with the majority of patients with IBD reaching their target height at mean age 19.8 years based on measured parental heights (3). Because patients with IBD often present with delayed puberty (4–6), it is plausible that they have catch-up linear growth beyond the age of expected growth cessation, 16 years for girls and 18 years for boys (7). To our knowledge, no prior studies have reported longitudinal growth patterns of young adult patients with IBD beyond anticipated cessation of growth.
Bone age is a common method for assessing skeletal maturity in relation to chronological age, and the Bayley-Pinneau method can predict adult height based on bone age and standing height without the need for recumbent length, parental heights, and Tanner staging as in the Roche-Wainer-Thissen and Tanner-Whitehouse methods (8). Others have reported that traditional methods of predicting adult height may have differing degrees of accuracy for children with growth disorders (9,10), although recent data on their accuracy in children with IBD are scarce (5,11). If the Bayley-Pinneau method can reliably predict adult height in patients with IBD, then clinicians will be able to assess patients’ growth potential and identify significant potential adult height deficit relative to family in the disease course even without parental heights, ensuring proper management. Thus, the objectives of our study were to compare heights at expected age of growth cessation (16 for girls and 18 for boys) with those obtained 2 years later, and to determine whether Bayley-Pinneau bone age–predicted adult height accurately predicts measured adult height in pediatric-onset IBD.
MATERIALS AND METHODS
We retrospectively reviewed the medical records of 475 patients, 194 boys and 281 girls, who were diagnosed as having IBD before the 16th birthday for girls and the 18th birthday for boys and had available adult stature data. These patients were diagnosed as having Crohn disease (CD), ulcerative colitis (UC), or IBD unclassified (IBDU) based on clinical, endoscopic, histopathologic, and radiographic studies (12). For each eligible patient, we collected demographic and clinical information, including date of birth, IBD type, and date of diagnosis. We also recorded height measurements obtained from a wall-mounted Holtain stadiometer in the gastroenterology and nutrition clinic at visits closest to their 16th, 18th, and 20th birthdays for female patients and the 18th and 20th birthdays for male patients. Heights were converted to standard deviation (SD) scores (z scores) using National Center for Health Statistics reference values. For those who were older than 20 years at the time of measurement, heights were converted to the same z scores calculated for sex-matched people who are 20 years old.
Where available, we also recorded all of the bone ages obtained between 9 and 17 years of age. We used the lower limit of 9 years because skeletal age correlates with the percentage of mature height approximately 86% after this age (8). For each bone age, we calculated predicted adult height with the Bayley-Pinneau method using the reference chart (8) and collected height measured on the same day or within 6 months of obtaining the bone age. The Committee on Clinical Investigation at Children's Hospital Boston approved the study protocol.
Height data were presented as mean ± SD. Two-sample and χ 2 tests were used to analyze clinical differences between groups of patients. Paired-samples t tests were used to compare longitudinal height measurements of individual subjects and to compare bone age–predicted and –measured adult heights. Statistical analyses were performed using the Statistical Package for the Social Sciences statistics version 17.0 (SPSS Inc, Chicago, IL). Statistical significance was defined as P values <0.05.
General Characteristics of Study Patients
Table 1 summarizes demographic and clinical characteristics of the study patients. Mean age at diagnosis of the 475 patients was 14.1 ± 3.1 years, and there was female preponderance. Sixty-three percent of patients had CD.
Adult Height Measurements of Patients With Pediatric-onset IBD
Compared with the general population, which has a mean adult height of 163.8 cm at the age of 16 years (7), girls with IBD were 2.7 cm shorter at the mean age of 16.5 years. Similarly, boys at the mean age of 18.4 years were 2.6 cm shorter than the general population at 18 years of age who reach a mean adult height of 176.8 cm (7) (Table 2).
Height Measurements at Expected Cessation of Growth and 2 Years Later
Two hundred fifty-eight female patients with IBD with available height measurements both at 16 and 18 years of age demonstrated no significant increase in height beyond expected age of linear growth cessation at 16 years (P = 0.189) (Table 2). Moreover, we did not observe further change at 20 years in mean height z scores of 163 female patients who had height measurements at 18 and 20 years of age. For this group of patients, height-for-age z score remained at −0.21 for both time points. Similarly, 194 male patients with height measurements both at 18 and 20 years of age did not have significant change during this interval (P = 0.105) (Table 2). As demonstrated in Fig. 1, mean height z scores of girls at age 18 years and boys at age 20 years continued to be slightly left shifted compared with the normal distribution curve.
Comparison of Bone Age–predicted and Attained Adult Heights
A total of 53 patients had at least 1 bone age measured between chronological ages 9.0 and 16.8 years (median age 14.5) as well as measured adult height at 18 and 20 years for girls and boys, respectively. In general, bone age was lower than chronological age (mean paired difference 1.16 ± 1.6 years; P < 0.001). Despite lower mean height-for-age z scores at the time of bone-age measurement (−1.17 ± 1.2), the attained adult height z scores were significantly higher (−0.63 ± 1.1; P < 0.001). Based on the Bayley-Pinneau method, bone age–predicted adult height was 2.4 cm higher than the measured adult height for boys (P = 0.017), and 1.5 cm higher than the measured adult height for girls (P = 0.060) (Fig. 2). To ensure that predicted adult height is not affected by chronological age at the time of bone-age measurement, we compared predicted heights derived from the first and second bone ages. For the 26 patients for whom we had 2 or more bone-age measurements, we found no significant difference (P = 0.323).
Our study demonstrates that patients with IBD reach adult height within normal timing for the general population because there was no significant height increase between 16 and 18 years of age for girls and 18 and 20 years of age for boys. Based on our data, patients with IBD do not seem to have significant catch-up growth beyond the expected age of linear growth cessation despite commonly associated pubertal delay (4). Although it is possible that they may continue to grow past these 2 years of observation, further significant growth is unlikely given the minimal increase seen during the 2-year interval for our 475 patients with IBD. Moreover, there was no continued growth in 163 female patients with IBD who had height measurements at both 18 and 20 years of age. Hence, catch-up growth for those with growth impairment must occur earlier in adolescence. This is further supported by lower height-for-age z scores seen at the time of bone-age measurement but significantly higher height z scores observed in adulthood. These results emphasize the importance of identifying early those with growth impairment so that appropriate treatment can be instituted before the expected time of growth cessation. Because the Bayley-Pinneau method of adult height prediction is relatively close to measured height, this adjunctive tool may be used in a clinical setting to identify those who have significant deficit from expected adult height.
To date, this is the largest study investigating longitudinal growth patterns in pediatric-onset IBD. Although there have been other studies of adult height in IBD, no prior studies have tracked measured heights of individual patients beyond the age of expected growth cessation. In addition, this is one of the few existing studies comparing bone age–predicted and –measured adult heights in patients with IBD. Prior studies in non-IBD populations suggest that the Bayley-Pinneau method of adult height prediction may be superior to other methods in children with abnormal growth patterns (9). Consistent with these results and those of Kirschner et al (5), we find that Bayley-Pinneau predictions are fairly accurate for children with IBD. Although there was a statistically significant difference between predicted and adult heights for boys, the mean difference was only 2.4 cm. The difference in girls was smaller at 1.5 cm, which was not statistically significant. Thus, adult height was on average <1 inch below that predicted. Our findings are consistent with other studies that show that this method overestimates adult height in children (especially boys) with primordial short stature and in healthy boys with height z scores <−1 (9).
A potential limitation of our study is that we did not perform subanalysis based on various clinical characteristics, because the purpose of this study was to investigate growth pattern in a large, heterogeneous IBD cohort. We did observe slightly increased linear growth among patients with CD compared with those with UC during the 2-year period; however, the difference was <1 cm (data not shown). Further study is warranted to elucidate the effect of various disease phenotypes on growth in a large IBD population. Only 11% of our total cohort had bone ages recorded, but there was no significant difference in adult height z scores between patients with and without recorded bone ages (P = 0.244). Most of our patients had bone ages measured at an older age (median age 14.5), but 74% of these patients had delayed bone age compared with chronological age.
In conclusion, children with IBD reach their adult height around the same age as their healthy peers. Our finding reinforces the importance of early detection and treatment of growth impairment, because children with IBD do not have a longer “growth window” despite experiencing delayed puberty.
We thank Richard J. Grand, MD, for reviewing this manuscript.
1. Griffiths AM, Nguyen P, Smith C, et al. Growth and clinical course of children with Crohn's disease. Gut
2. Ferguson A, Sedgwick DM. Juvenile onset inflammatory bowel disease: height and body mass index in adult life. BMJ
3. Lee JJ, Escher JC, Shuman MJ, et al. Final adult height
of children with inflammatory bowel disease is predicted by parental height and patient minimum height Z-score. Inflamm Bowel Dis
4. Ballinger AB, Savage MO, Sanderson IR. Delayed puberty associated with inflammatory bowel disease. Pediatr Res
5. Kirschner BS. Growth and development in chronic inflammatory bowel disease. Acta Paediatr Scand Suppl
6. Hildebrand H, Karlberg J, Kristiansson B. Longitudinal growth in children and adolescents with inflammatory bowel disease. J Pediatr Gastroenterol Nutr
7. Rudolph AM RC, Hostetter MK, Lister GE, et al. Rudolph's Pediatrics
. New York: McGraw-Hill; 2003.
8. Bayley N, Pinneau SR. Tables for predicting adult height
from skeletal age: revised for use with the Greulich-Pyle hand standards. J Pediatr
9. Zachmann M, Sobradillo B, Frank M, et al. Bayley-Pinneau, Roche-Wainer-Thissen, and Tanner height predictions in normal children and in patients with various pathologic conditions. J Pediatr
10. Hintz RL. Final height
prediction in constitutional growth delay. J Pediatr Endocrinol Metab
2001; 14 (suppl 6):1535–1540.
11. Markowitz J, Grancher K, Rosa J, et al. Growth failure in pediatric
inflammatory bowel disease. J Pediatr Gastroenterol Nutr
12. Bousvaros A, Antonioli DA, Colletti RB, et al. Differentiating ulcerative colitis
from Crohn disease
in children and young adults: report of a working group of the North American Society for Pediatric
Gastroenterology, Hepatology, and Nutrition and the Crohn's and Colitis Foundation of America. J Pediatr Gastroenterol Nutr