Growth hormone effect on body composition of children born small for gestational age: a systematic review

Kühl, Adriana M.; Tortorella, Catiuscie C.S.; Almeida, Claudia C.B.; Gomes Dias, Marcia R.M.; Pereira, Rosana M.

doi:10.1016/j.jped.2022.11.010

Acessibilidade / Reportar erro

Brasil

Español English

sumário « anterior atual seguinte »

Sumário

Review article • J. Pediatr. (Rio J.) 99 (3) • May-Jun 2023 • https://doi.org/10.1016/j.jped.2022.11.010 copy

Growth hormone effect on body composition of children born small for gestational age: a systematic review

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

Objective

The present study aimed to evaluate the effects of GH treatment on the body composition of children born with SGA.

Methods

This study is a systematic review of the literature. CINAHL, Embase; Medline/Pubmed, Scopus and Web of Science were searched from inception to March 2022.

Results

Four studies met the inclusion criteria, with an intervention time of 1 to 3 years, using doses from 0.03 to 0.07 mg/kg/day of GH. Bone densitometry by dual-energy X-ray absorptiometry (DXA) with whole-body scans was the most used method to assess body composition. Most studies (n= 3) had SGA children as a control group with the same characteristics as the case group; the mean age was similar between the groups (minimum of 5.1 ± 1.4 years and maximum of 6.7 ± 1 0.8 years) and all participants had an average height ≤ -3DP. The Lean Mass (LM) and Fat Mass (FM) outcomes of the studies were not presented in a standardized manner; thus, they cannot be compared. There was a significant increase in LM in the group treated with GH in relation to the pre-treatment period and in comparison, to the untreated control group. Three studies showed a significant decrease in FM at the end of the intervention period, and in two studies, this decrease occurred in the control group.

Conclusions

Despite the differences in the presentation of results and in the evaluation periods, the results of the studies showed that growth hormone favors the gain and maintenance of lean mass, and it also affects fat mass reduction and redistribution.

Keywords
Infant, small for gestational age; Growth hormone; Body composition; Systematic review

First author (year)	Country	Study type	Inclusion criteria	Dose (mg/kg/dia)	Intervention's time (anos)	Evaluation method
Leger et al. (1998)	France	Randomized clinical trial	Birth weight <3rd percentile; Normal peak GH secretion	0,07	3	MRI
Boonstra et al. (2006)	Netherlands	Randomized clinical trial	Birth length <−2 SD for gestational age; Uncomplicated neonatal period; Chronological age (CA) between 3.00 and 7.99 years at start of the study; Height SDS for CA <−2.0 (Dutch,1985); Height velocity SDS for CA≤0; Pre-pubertal; Normal liver, kidney and thyroid function.	0,03	1	DXA
Willemsen et al. (2007)	Netherlands	Randomized clinical trial	Birth length <−2 SD for gestational age; Uncomplicated neonatal period; Chronological age (CA) between 3.00 and 7.99 years at start of the study; Height SDS for CA <−2.0 (Fredriks et al., 2000); Height velocity SDS for CA≤0; Pre-pubertal; Normal liver, kidney and thyroid function.	0,03	3	DXA
Schepper et al. (2008)	Belgium	Randomized clinical trial	Birth weight, length, or both <−2 SD for gestational age; Current height<−2SD; Height velocity <1SD; Chronological age (CA) between 3 and 8 years at study start.	0,07	2	DXA

First author (year)	N	N Group		N Group and sex				Mean age (SD) (y)	Mean age (SD) (y) Group		Mean height (SD/SDS)	Mean height (SDS) Group
		GHG	CG	GH		CG			GHG	CG		GHG	CG
		GHG	CG	M	F	M	F		GHG	CG		GHG	CG
Leger et al. (1998)	21	14	7	8	6	-	-	6,1 ± 1,9	6,1 ± 1,9	6,7 ± 1,8	−3,6 ± 0,8SD	−3,6 ± 0,8	0,1 ± 1,1
Boonstra et al. (2006)	88	62	26	26	36	16	10	-	5,9 ± 1,6	5,9 ± 1,5	−3,1SDS	−2,9 ± 0,7	−3,1 ± 0,5
Willemsen et al. (2007)	25	16	9	7	9	6	3	-	6,1 ± 1,5	5,9 ± 1,7	−3,0 ± 0,7SDS	−3,0 ± 0,7	−3,2 ± 0,5
Schepper et al. (2008)	25	11	14	-	-	-	-	5,1 ± 1,5	5,1 ± 1,6	5,1 ± 1,4	−3 ± 0,7SDS	−3,3 ± 0,7	−3,2 ± 1,0

				Intervention Time (years)
First author (year)	Measured area	Daily dose (mg\/kg)	Measured unit	Pretreatment	1	2	3	p^# # p value for changes over period.	p^* ⁎ p value in relation to the control group.
Leger et al. (1998)	Thigh	0,07	% change	-	31,2 ± 2,6	18,1 ± 1,8	8,9 ± 1,6	<0,01^a a second year vs. third year.	<0,0001^c c after one year of treatment.
Boonstra et al. (2006)	Full body	0,03	SDS	−2,7 ± 0,5	−1,8 ± 0,5	-	-	<0,001^b b at the end of intervention.	<0,001
Willemsen et al. (2007)	Full body	0,03	SDS-age	−2,0 ± 0,3	−1,4 ± 0,4	−1,1 ± 0,5	−1,1 ± 0,5	<0,001^b b at the end of intervention.	<0,001
			SDS-height	0,5 ± 2,1	0,2 ± 1,3	−0,1 ± 0,9	−0,3 ± 0,9	NS^b b at the end of intervention.	<0,01
Schepper et al. (2008)	Full body	0,07	Kg	10 ± 3	13,2 ± 3,4	15.5 ± 3,4	-	<0,0001^b b at the end of intervention.	<0,0001
			%	78 ± 4	82 ± 3	82 ± 3		<0,05^b b at the end of intervention.	<0.05

				Intervention Time (years)
First author (year)	Measured área	Daily dose (mg\/kg)	Measured unit	Pretreatment	1	2	3	p^# # p value for changes over period.	p^* ⁎ p value in relation to the control group.
Leger et al. (1998)	Thigh	0,07	% change	-	−16,4±3,4	24,4±7,7	7,6±6,3	0,001^a a first year vs. pretreatment.	NS
Boonstra et al. (2006)	Full body	0,03	SDS	−1,4 ± 0,5	−1,6 ± 0,5	-	-	NS^b b at the end of intervention.	0,03
Willemsen et al. (2007)	Full body	0,03	SDS-age	−1,0 ± 0,8	−1,7 ± 0,8	−1,4 ± 0,8	−1,5 ± 0,7	<0,01^b b at the end of intervention.	NS
			SDS-height	−1,3 ± 1,3	−2,1 ± 1,1	−1,6 ± 1,0	−1,7 ± 1,0	<0,01^a a first year vs. pretreatment.	NS
Schepper et al. (2008)	Full body	0,07	Kg	2,3 ± 0,5	2,4 ± 0,7	2,9 ± 1	-	NS^b b at the end of intervention.	NS
			%	19 ± 4	15 ± 3	15 ± 2	-	<0,05^b b at the end of intervention.	<0,05

Methodological Quality Assessment	Leger et al., 1998	Boonstra et al., 2006	Willemsen et al., 2007	Schepper et al., 2008
True randomization to treatment groups	Unclear	Low	Low	Unclear
Allocation to treatment groups was concealed	Unclear	Unclear	Unclear	Unclear
Treatment groups were similar at the baseline	High	Low	Low	Low
Blinding of participants	Unclear	High	High	Unclear
Blinding of those delivering the treatment	Unclear	High	High	Unclear
Blinding of assessors	Unclear	High	High	Unclear
Treatment groups were treated identically other than the intervention of interest	Low	Low	Low	Low
The follow-up was complete and if not, were differences between groups in terms of their follow up adequately described and analyzed	Low	High	Low	Low
Participants were analyzed in the groups in which they were randomized	Low	Low	Low	Low
Outcomes were measured in the same way between groups	High	Low	Low	Low
Outcomes were measured in a reliable way	Unclear	Unclear	Unclear	Low
Appropriate statistical analysis was used	Low	Low	Low	Low
Appropriate study design and deviations from the standard RCT design were considered in the conduct and analysis of the study	High	Low	Low	Low

Sociedade Brasileira de Pediatria Av. Carlos Gomes, 328 cj. 304, 90480-000 Porto Alegre RS Brazil, Tel.: +55 51 3328-9520 - Porto Alegre - RS - Brazil
E-mail: jped@jped.com.br

Acompanhe os números deste periódico no seu leitor de RSS

[1] ⁎ Corresponding author. E-mail: amasiero@unicentro.br (A.M. Kühl).

P (population)	Children born small for gestational age (SGA), prepubertal at the start of the treatment.
I (intervention)	Treatment with GH as a single therapy, given subcutaneously, regardless of the administered dose, for at least 1 year.
C (comparator)	Comparison of the group that received GH with an untreated control group, in at least two moments;
O (outcomes)	Lean mass (LM) and total fat mass (FM) expressed as kilograms (kg), standard deviation score (SDS), and percentage (%) at the study start and after the observation period.