Thiopurines are negatively associated with anthropometric parameters in pediatric Crohn’s disease

Table 1 Demographics, Tanner stage, disease location, and medications

Item	n (%)
Race
Asian	12 (14.6)
East Asian	6
South Asian	6
Black/African American	1 (1.2)
Other	4 (4.9)
White	65 (79.3)
Ethnicity
Hispanic or Latino	7 (8.5)
Not Hispanic or Latino	75 (91.5)
Tanner stage
1	8 (9.8)
2	15 (18.3)
3	16 (19.5)
4	24 (29.3)
5	19 (23.2)
Disease location
Esophagus or stomach	9 (11)
Small bowel, no colon	12 (14.6)
Colon, no small bowel	17 (20.7)
Small bowel and colon	53 (64.6)
Perianal disease	49 (59.8)
Medication
Adalimumab	4 (4.9)
5-Aminosalicylates	50 (61.0)
Antibiotics	14 (17.1)
Azathioprine/6-Mercaptopurine	44 (53.7)
Infliximab	20 (24.4)
Methotrexate	7 (8.5)
Steroids ever	55 (67.1)

Table 2 Summary of anthropometric parameters

Variable (n)	Mean ± SD	Range	Percent with z-scores > 2 (%)	Percent with z-scores < -2 (%)
Mid-arm circumference-CA-z-score n = 82	-0.64 ± 1.39	-5.03 to 2.88	2	17
Mid-arm circumference-BA-z-score n = 49	-0.54 ± 1.30	-2.86 to 2.50	2	16
Subscapular skinfold-CA-z-score n = 81	0.59 ± 0.83	-1.56 to 2.31	3	0
Subscapular skinfold-BA-z-score n = 48	0.64 ± 0.87	-1.17 to 2.27	4	0
Triceps-CA-z-score n = 81	1.02 ± 0.74	-0.88 to 2.79	11	0
Triceps-BA-z-score n = 49	1.10 ± 0.72	-1.17 to 2.47	8	0
Height-CA-z-score n = 82	-0.30 ± 1.02	-2.74 to 2.34	1	6
Height-BA-z-score n = 49	0.17 ± 1.12	-3.29 to 2.53	4	2
Weight CA-z-score n = 82	-0.17 ± 1.10	-3.49 to 2.20	4	5
Weight BA-z-score n = 49	0.11 ± 0.91	-2.52 to 1.97	0	2
BMI-CA-z-score n = 82	-0.07 ± 1.04	-2.78 to 2.17	4	4
BMI BA-z-score n = 49	0.05 ± 0.86	-2.58 to 2.09	2	2

BA z-score: z score based on bone age; BMI: Body mass index; CA z-score: z score based on chronological age.

Table 3 Significant associations between medications/serum biomarkers and anthropometric parameters [z-scores based on chronological age (n = 82)] - unadjusted analyses

Variable	Mid-arm circumference CA-z-scores	Subscapular skinfold CA-z-scores	Weight CA-z-scores	BMI CA-z-scores
Adalimumab		0.901 (0.08, 1.72)2 0.0333		1.09 (0.05, 2.13) 0.04
Azathioprine	-0.65 (-1.25, -0.05) 0.033	-0.5 (-0.85, -0.14) 0.006	-0.7 (-1.16, -0.23) 0.004	-0.56 (-1.004, -0.12) 0.014
Methotrexate		0.75 (0.06, 1.43) 0.032
ESR	-0.024 (-0.05, -0.002) 0.036		-0.03 (-0.05, -0.02) 0.0003	-0.02 (-0.04, -0.006) 0.009
Hemoglobin			0.19 (0.04, 0.34) 0.015

¹Regression coefficient for unadjusted analyses [i.e., one medication or serum biomarker (independent variable) per model and no adjustment for potential confounding];

²(95% confidence interval);

³P-value. BMI: Body mass index; CA z-score: z score based on chronological age; ESR: Erythrocyte sedimentation rate.

Table 4 Significant associations between medications/serum biomarkers and anthropometric parameters [z-scores based on chronological age (n = 82)] - adjusted analyses

Variable	Mid-arm circumference CA-z-scores	Subscapular skinfold CA-z-scores	Weight CA-z-scores	BMI CA-z-scores
Adalimumab		1.021 (0.18, 1.86)2 0.0183		1.17 (0.13, 2.21) 0.029
Azathioprine	-0.64 (-1.26, -0.02) 0.045	-0.47 (-0.83, -0.10) 0.014	-0.73 (-1.17, -0.29) 0.002	-0.58 (-1.03, -0.12) 0.013
Methotrexate		0.81 (0.10, 1.53) 0.027
ESR			-0.03 (-0.05, -0.01) 0.01	-0.03 (-0.05, -0.004) 0.024

¹Regression coefficient for adjusted analyses [i.e., one medication or serum biomarker (independent variable) per model and CA at study visit, sex, CRP, albumin, ESR and hemoglobin are included in the model to adjust for potential confounding];

²(95% confidence interval);

³P-value. BMI: Body mass index; CA z-score: z score based on chronological age; CRP: C-reactive protein; ESR: Erythrocyte sedimentation rate.

Table 5 Significant associations between serum biomarkers and anthropometric parameters [z-scores based on bone age (n = 49)] - unadjusted analyses

Variable	Mid-arm circumference BA-z-scores	Subscapular skinfoldBA-z-scores	Triceps skinfoldBA-z-scores	WeightBA-z-scores	BMIBA-z-scores
WBC	-0.191 (-0.36, -0.02)2 0.0293	-0.12 (-0.24, -0.01) 0.04		-0.16 (-0.28, -0.04) 0.008
ESR				-0.03 (-0.04, -0.01) 0.003	-0.02 (-0.03, -0.001) 0.037
CRP			-0.03 (-0.07, -0.0001) 0.049	-0.06 (-0.10, -0.02) 0.008
Albumin				0.73 (0.28, 1.18) 0.002
IGF-1 BA-z-scores				0.2 (0.01, 0.38) 0.039

¹Regression Coefficient for Unadjusted Analyses [i.e., one serum biomarker (independent variable) per model and no adjustment for potential confounding];

²(95% confidence interval);

³P-value. BA z-score: z score based on bone age; BMI: Body mass index; WBC: White blood cell; ESR: Erythrocyte sedimentation rate; IGF-1: Insulin-like growth factor-1; CRP: C-reactive protein.

Table 6 Significant associations between medications/serum biomarkers and height z-scores by sex (based on chronological age (female n = 35; male n = 47)) - unadjusted analyses

Variable	Height CA z-scores	Point estimate1	95%CI	P value
Infliximab	Females	0.65	0.04, 1.25	0.038
CRP	Males	-0.04	-0.079, -0.002	0.039
ESR	Males	-0.03	-0.051, -0.011	0.003
Hemoglobin	Males	0.23	0.04, 0.42	0.018
Platelets	Males	-0.004	-0.006, -0.001	0.005

¹Regression coefficient for unadjusted analyses [i.e., one medication or serum biomarker (independent variable) per model and no adjustment for potential confounding]. CA z-score: z score based on chronological age; CRP: C-reactive protein; ESR: Erythrocyte sedimentation rate.

Table 7 Significant associations between serum biomarkers and height z-scores [based on bone age (n = 49)] - unadjusted analyses

Variable	Height BA-z-scores	Point estimate1	95%CI	P value
Albumin	Males and females	0.8	0.22, 1.36	0.008
CRP	Males and females	-0.06	-0.11, -0.006	0.03
ESR	Males and females	-0.02	-0.05, -0.003	0.029
IGF-1 BA-z-scores	Males and females	0.26	0.03, 0.48	0.025

¹Regression coefficient for unadjusted analyses [i.e., one serum biomarker (independent variable) per model and no adjustment for potential confounding]. BA z-score: z score based on bone age; BMI: Body mass index; ESR: Erythrocyte sedimentation rate; IGF-1: Insulin-like growth factor-1; CRP: C-reactive protein.