Table 3.

Crude and adjusted hazard ratios for neoplastic events overall (benign and malignant) among patients compared to matched controls.

	N	Crude HR [95% CI]	Adjusted HR [95% CI], restricted model a	Adjusted HR [95% CI], full model b
All patients	3 408	1.05 [0.95-1.15]	1.36 [1.20 -1.54]	1.28 [1.12-1.46]
Male	2 305	1.07 [0.94-1.21]	1.46 [1.24 -1.73]	1.39 [1.17-1.66]
Female	1 103	1.02 [0.88-1.18]	1.24 [1.03-1.50]	1.15 [0.94-1.41]
SGA c	672	1.19 [0.98-1.45]	1.55 [1.25-1.93]	1.47 [1.18-1.84]
male	423	1.14 [0.86-1.52]	1.63 [1.20-2.22]	1.54 [1.13-2.10]
female	249	1.17 [0.89-1.55]	1.46 [1.07-1.99]	1.39 [1.01-1.92]
GHD c	1 837	1.03 [0.91-1.16]	1.34 [1.16-1.56]	1.26 [1.07-1.48]
male	1 312	1.09 [0.93-1.28]	1.47 [1.21-1.80]	1.42 [1.15-1.75]
female	525	0.98 [0.80-1.19]	1.19 [0.94-1.50]	1.06 [0.82-1.37]
GHD (GHmax 0-4) d	485	0.96 [0.76-1.21]	1.28 [0.99-1.65]	1.19 [0.91-1.56]
male	349	1.04 [0.76-1.41]	1.46 [1.05-2.02]	1.42 [1.00-2.00]
Female	136	0.90 [0.62-1.31]	1.07 [0.72-1.59]	0.92 [0.60-1.42]
GHD (GHmax 5-9) d	1 352	1.05 [0.91-1.22]	1.37 [1.16-1.62]	1.29 [1.08-1.54]
male	963	1.12 [0.92-1.35]	1.48 [1.19-1.84]	1.42 [1.13-1.79]
female	389	1.01 [0.81-1.27]	1.24 [0.96-1.61]	1.12 [0.84-1.49]
ISS c	899	0.98 [0.81-1.18]	1.26 [1.02-1.55]	1.17 [0.93-1.47]
male	570	0.96 [0.74-1.24]	1.32 [0.99-1.77]	1.21 [0.90-1.64]
female	329	0.98 [0.74-1.28]	1.20 [0.89-1.62]	1.14 [0.81-1.60]
Duration of treatment e
0-2 years	925	0.82 [0.65-1.02]	0.93 [0.72-1.20]	0.89 [0.68-1.17]
3-6 years	1 522	1.01 [0.87-1.16]	1.29 [1.08-1.53]	1.22 [1.01-1.47]
≥7 years	961	0.93 [0.76-1.15]	1.29 [1.03-1.61]	1.23 [0.97-1.55]
P trend		0.35	0.03	0.03
Mean GH-dose e
0-29 µg/kg/d	402	1.00 [0.71-1.41]	1.26 [0.88-1.81]	1.20 [0.82-1.74]
30-39 µg/kg/d	2 383	0.89 [0.78-1.01]	1.13 [0.97-1.33]	1.09 [0.92-1.29]
40-49 µg/kg/d	337	0.97 [0.72-1.32]	1.21 [0.87-1.67]	1.13 [0.80-1.59]
≥ 50 µg/kg/d	279	1.20 [0.90-1.60]	1.49 [1.10-2.03]	1.39 [1.01-1.91]
P trend		0.19	0.30	0.53
Cumulative dose e
0-1499 mg	1 015	0.82 [0.66-1.02]	0.97 [0.76-1.23]	0.92 [0.72-1.19]
1500-2999 mg	954	1.21 [1.02-1.43]	1.43 [1.17-1.74]	1.37 [1.11-1.69]
3000-4499	902	0.76 [0.62-0.95]	1.06 [0.84-1.34]	0.98 [0.76-1.25]
≥ 4500 mg	381	0.92 [0.69-1.23]	1.39 [1.02-1.88]	1.37 [1.00-1.87]
P trend		0.62	0.18	0.22

^aRestricted model adjusted only for age at start, height at start and sex (if not stratified for sex).

^bFull model adjusted for gestational age, birth length, birth weight, age at start, height at start, parental educational level, family income and sex (if not stratified for sex).

^cSGA, Small for Gestational Age; GHD, Growth Hormone Deficiency; ISS, Idiopathic Short Stature.

^dGH_max = Growth Hormone peak level on either provocation test (mainly Arginine-Insulin Tolerance Test) or during spontaneous 12h or 24h GH secretion profiles (µg/L).

^eAnalysis with 2-year lag-period after end of treatment to avoid reversed causality (protopathic bias).