Effects of recombinant growth hormone (GH) replacement and psychomotor and cognitive stimulation in the neurodevelopment of GH-deficient (GHD) children with cerebral palsy: a pilot study

Figures & data

Table 1 Main characteristics of the patients studied

Patient	Age (years)	Gender	PC cause	Radiologic findings	Motor impairment	GMFCS level
1	3	M	Perinatal hypoxia	PVL; plagiocephaly; corpus callosum hypoplasia; macrocephaly	PI	III
2	4	F	Perinatal hypoxia	PVL	PI	I
3	5,4	F	Perinatal hypoxia	PVL	PI	I
4	4,8	M	Postsurgical iatrogenic injury	Decreased activity and volume in PO cortex; bilateral PO ischemia; diffuse cerebral edema	Spastic TP	V
5	3,5	M	Perinatal hypoxia	PVL; bilateral parietal pachygyria; hydrocephalus; microcephaly	Flaccid TP	V
6	3,1	M	Premature twins; single umbilical artery	PVL; plagiocephaly; polymicrogyria	Spastic TP	V
7	3	F	Premature twins	PVL; right occipital cortex and bilateral frontal cortex ischemic injuries	Distonic TP	V
8	3	M	Prematurity	PVL; microcephaly	PI	III
9	3,2	M	Perinatal hypoxia	PVL	Distonic TP	V
10	5,7	F	Postsurgical iatrogenic injury	PVL; diffuse multicystic leukoencephalopathy; focal hemorrhage in right brain hemisphere and cerebellar hemispheres deep white matter; microcephaly	Distonic TP	V
11	6,7	M	Postvaccine iatrogenic injury	PVL	PI	I

Abbreviations: GMFCS, Gross Motor Function Classification System; F, female; M, male; PC, cerebral palsy; PI, psychomotor impairment; PO, parieto-occipital; PVl, periventricular leucomalacia; TP, tetraplegia.

Figure 1 Study timing.

Notes: Arrowheads: assessments by using the BDIST carried out: 2 months before commencing GH treatment (1), just before the beginning of the treatment (2) and after 2 months of GH treatment (3).

Table 2 Main plasma chemistry parameters analyzed

Patient	GH peak	TC		TG		G		IGF-1		IGFBP3
		Pre	Post	Pre	Post	Pre	Post	Pre	Post	Pre	Post
1	4.5	205	182	75	74	82	75	34.2	89	2.33	3.1
2	6.3	181	169	102	65	89	73	28.1	256	1.7	2.9
3	2.8	194	171	41	37	70	77	53	200	3.61	4.3
4	5.3	175	168	125	104	76	85	67.2	103.3	2.5	3.8
5	1.5	225	165	186	85	72	77	25	69.5	2.2	3.6
6	6.9	193	166	125	97	75	83	31	75	1.8	3.03
7	3.4	215	171	157	110	81	79	35	125	2.1	3.1
8	4.7	186	155	114	65	92	84	69.5	89.5	3	4.2
9	7.1	177	165	145	75	74	72	25	78	1.4	1.76
10	5.2	191	164	165	108	84	96	78	162	2.9	4.06
11	4.8	187	155	128	90	74	101	67	225	1.96	3.03
Mean (SD)	4.77 (1.71)	193.54 (15.69)	166.45 (7.51)	123.90 (41.16)	82.72 (22.25)	79 (7.15)	82 (9.27)	46.63 (20.49)	133.84 (66.41)	2.31 (0.64)	3.35 (0.73)
SS		0.003***		0.003***		ns		0.003***		0.003***

Note:

*** P < 0.01 (Wilcoxon signed-rank test).

Abbreviations: GH peak, peak growth hormone (ng/mL) after insulin-induced hypoglycemia; TC, plasma total cholesterol (mg/dL); TG, plasma triglycerides (mg/dL); G, plasma glucose (mg/dL); IGF-1, plasma insulin-like growth factor (ng/mL); IGFBP3, plasma insulin-like growth factor binding protein 3 (μg/mL); SD, standard deviation of the mean; SS, statistical significance; ns, not significant; pre, pretreatment; post, post-treatment.

Figure 2 Clinical data from the BDIST during pre-treatment and treatment periods.

Notes: A) Pre-treatment period; (B) Treatment period. Horizontal axis: the different domains of the BDIS T and total score of it (TOTAL) are described. Vertical axis: score achived. Notice that different scales are used for (A) and (B). A) means and SD of the mean before (white bars) and after (grey bars) for each specific assessment. B) means and SD of the mean before (white bars) and after (grey bars) treatment period for each specific assessment. Statistical significance was calculated by comparing the data from the BDIST before and after the pre-treatment period (A) and the treatment period (B) (Wilcoxon signed-rank test). **P < 0.02 and ***P < 0.01.

Figure 3 Comparison of improvements during pre-treatment and treatment periods.

Notes: The horizontal axis shows the different domains of the BDIST and the total (TOTAL) score of the test. The vertical axis shows the percentage improvements observed during the pre-treatment period (white bars) and treatment period (grey bars) over baseline values for each specific assessment (mean + SD). Statistical significance was calculated by comparing the improvements relative to baseline from the BDIST during pre-treatment periods (Wilcoxon signed-rank test). **P < 0.02 and ***P < 0.01.

Table 3 Results obtained from the Battelle Developmental Inventory Screening Test (BDIST)

BDIST	Pretreatment period mean (months) (SD)	After treatment period mean (months) (SD)	Statistical significance from improvements during the treatment period (Wilcoxon)	Improvement mean relative to baseline during the pretreatment period (%) (SD)	Improvement mean relative to baseline during the treatment period (%) (SD)	Statistical significance from the comparison of improvements during the pretreatment and treatment periods (Wilcoxon)
Personal/social	16.36 (9.71)	21.64 (10.22)	0.003***	1.01 (3.35)	46.26 (46.54)	0.003***
Adaptive	11.73 (6.45)	16.73 (8.84)	0.005***	1.38 (3.25)	36.49 (31.57)	0.008***
Gross motor	9.18 (9.32)	12.64 (12.29)	0.008***	3.63 (10.05)	65.91 (84.29)	0.008***
Fine motor	10.45 (8.26)	14.36 (11.35)	0.018**	0.43 (1.43)	39.91 (62.18)	0.018**
Total motor	9.18 (8.61)	12.36 (11.03)	0.007***	0.47 (1.58)	52.31 (59.18)	0.008***
Receptive communication	13.36 (8.06)	20.55 (8.41)	0.003***	1.51 (5.02)	73.67 (60.73)	0.003***
Expressive communication	11 (10.14)	13.55 (10.78)	0.018**	1.01 (3.35)	50 (98.69)	0.018**
Total communication	11.91 (8.81)	15.45 (9.66)	0.003***	3.18 (7.83)	43.24 (51.51)	0.006***
Cognitive	14.36 (9.36)	22.09 (12.46)	0.003***	0.9 (3.01)	70.95 (56.26)	0.003***
Total score	12.91 (8.51)	17.73 (10.46)	0.003***	2.61 (6.13)	51.2 (51.34)	0.004***

Notes: The first column shows the different domains involved in the BDIST. The third column shows the statistical significance from data obtained in the BDIST during the treatment period (Wilcoxon signed-rank test). The fourth, fifth, and sixth columns show, respectively, the mean improvement relative to baseline during pretreatment period, treatment period and the statistical significance obtained after comparing these 2 values (Wilcoxon signed-rank test) (

** P < 0.02 and

*** P < 0.01).