Table of Contents 21-2

Psychological Benefits of Growth Hormone in Children Born Small for Gestational Age

Approximately 10% of children born small for gestational age (SGA) fail to show catch-up growth and remain short. SGA children are also at risk for cognitive deficits, poor academic performance, and increased psychosocial problems. Beginning in 1991, as part of a multicenter, double-blind, growth hormone (GH) dose-response study, investigators examined growth, intellectual function, and psychosocial adaptation in 79 SGA children without evidence of catch-up growth. Intelligence quotient (IQ) was estimated using 2 subtests (Block Design and Vocabulary) of the Dutch versions of the Wechsler Intelligence Scale for Children (WISC-R) and the Wechsler Adult Intelligence Scale (WAIS). Behavioral and emotional functioning was assessed by the parent-report Child Behavior Checklist (CBCL) and Young Adult Behavior Checklist (YABS). Self-esteem was evaluated using the Self-Perception Profile. After 2 years of GH treatment, relative height increased significantly (70% within 2 SDs of the general population), as did scores on several intellectual and psychosocial variables. The current report summarizes psychological outcomes after 8 years of GH treatment (n=53, 73% of the original cohort remaining in the study). Forty-eight children (91%) achieved a height within 2 SDs of the general population. Age-standardized Block Design scores also rose significantly from baseline to within population norms. Extrapolating from this single subtest to the full scale IQ, SGA participants showed a mean increase of 7 IQ points. In contrast, the change over time in Vocabulary subtest scores was not statistically significant. A significant decline in parent-reported Externalizing and Total Behavior Problem scores to within population norms (indicating improved adjustment) was observed, and these declines were inversely related to change in height SD. In contrast, Internalizing scale scores did not significantly change, remaining comparable to norms at all time points. (The Externalizing and Internalizing scales reflect the distinction between aggressive, antisocial, and undercontrolled behavior fearful versus inhibited, and overcontrolled behavior.) Self-esteem scores rose to a significantly higher level than norms in the first 2 years of the study and remained stable thereafter. GH-dose (1 vs 2 mg/m²/d, or approximately 0.035 or 0.07 mg/kg/d) was unrelated to change in IQ, psychosocial adaptation, or self-esteem measures. Also, with the exception of Externalizing and Total Behavior Problem scores, increase in height SD was unrelated to outcomes. Cognitive test scores improved independently of changes in head circumference, although the latter remained significantly positively associated with cognitive performance prior to, and over the course of, treatment.

van Pareren YK, Duivenvoorden HJ, Slijper FSM, Koot HM, Hokken-Koelega ACS. Intelligence and psychosocial functioning during long-term growth hormone therapy in children born small for gestational age. J Clin Endocrinol Metab. 2004;89:5295–5302.

Editor’s Comment: This study presents the intriguing possibility that, in addition to substantial improvements in height SD, GH treatment raises IQ and self-esteem, and reduces behavior problems in individuals born SGA. Caution in interpretation of the findings is warranted, particularly in regard to change in IQ which might create unwarranted expectations. Although it is noted that those who refused to participate in the study were no different auxologically at the start of the trial from those who participated, it is no less important to have reported whether the refusers and those who dropped out were different in psychological variables or family of origin socioeconomic status. A bias toward better functioning subjects participating at the 8-year follow-up would influence outcomes. Because the study design did not include a placebo group, it is not possible to conclude that GH, per se, was responsible for changes in psychological outcome variables. Parents’ expectations for improved psychological adjustment with GH-mediated increases in height represent an alternative interpretation for reduced parent-reported behavior problems. Unfortunately, the investigators’ efforts in conducting a well-designed study of GH on growth was not matched in the choice of methods on the psychological side. Short forms of the WISC-R and WAIS were used to estimate IQ. It is a statistical given that any short form will be less reliable than the full battery. Furthermore, the investigators extrapolated from a single subtest belonging to one IQ domain (Perceptual Organization) to the full scale IQ, a dubious practice,¹ and particularly so in light of the finding that performance on the other subtest remained stable. Finally, parents served as the sole informants regarding participants’ behavior. Given that the average correlation between the reports of parents and their children on the behavior checklists are quite modest,² the protocol should have incorporated self reports. Regression to the mean could serve as an alternative explanation for the decline in Externalizing and Total Behavior Problems. In sum, firm conclusions regarding the cognitive, behavioral, and self-concept benefits of GH in SGA await replication that would employ a comprehensive neuropsychological evaluation and multi-informant behavioral assessment.

David E. Sandberg, PhD

Reference - (linked to )

1. Herrera-Graf M, Dipert ZJ, Hinton RN. Exploring the effective use of the Vocabulary/Block Design short form with a special school population. Educational & Psychological Measurement. 1996;56:522–528.
2. Achenbach TM, McConaughy SH, Howell CT. Child/adolescent behavioral and emotional problems: Implications of cross-informant correlations for situational specificity. Psychological Bulletin. 1987;101:213–232.