Intelligence and Psychosocial Functioning during Long-Term Growth Hormone Therapy in Children Born Small for Gestational Age

Stephen A. Sands

Departments of Pediatrics and Psychiatry, Columbia University College of Physicians and Surgeons, New York, New York 10032

Address all correspondence and requests for reprints to: Stephen A. Sands, 131 Fort Washington Avenue, Departments of Pediatrics and Psychology, Columbia University College of Physicians and Surgeons, New York, New York 10032. E-mail: ss2341{at}columbia.edu.

The study by van Pareren et al. (1) was well designed by using a randomized, double-blind approach to analyze the long-term effects of GH-dose response. The authors reference prior studies which conclude that being born small for gestational age (SGA) has been noted to be associated with lowered intelligence, poor academic performance, low social competence, and behavioral problems; however, it is important to note that these authors are among the first investigators to longitudinally analyze intellectual, social-emotional, and behavioral functioning of adolescents who have received long-term GH treatment for SGA.

Requiring and obtaining baseline assessments at the start of GH treatment, in addition to minimizing the attrition of patients over the next two follow-up assessments, represent critical components of this study’s ability to detect change over time in a cohort of patients without a significant degree of missing data. Consistently obtaining baseline and follow-up assessments of pediatric patients has proven challenging in previous studies for a variety of reasons, including a lack of insurance reimbursement, insufficient testing personnel and materials at many facilities, inconsistent referrals from medical staff, and varied interest on the part of medical personnel, parents, and patients. Consequently, compliance continues to be a major concern, negatively impacting the viability of late effects studies, which directly limits our scientific knowledge and thus the ability to design new treatment protocols that attempt to improve long-term patient functioning.

In terms of test instruments, van Pareren et al. (1) used an abbreviated approach to measuring intelligence by administering two of the 12 individual subtests from either the Wechsler Intelligence Scale for Children–Revised or the Wechsler Adult Intelligence Scale, depending on the age of the patient, which are both based on the appropriate Dutch normative population. Although the researchers selected the two subtests that demonstrate the highest correlation with overall verbal and performance IQ (vocabulary and block design subtests, respectively), these results should not be interpreted as synonymous with traditional intelligence testing results because the commonly observed variability across multiple subtests can impact the overall IQ scores, as well as provide more in-depth information regarding the individual’s cognitive strengths and weaknesses. Other researchers have alternately chosen to use published abbreviated tests of intelligence in an effort to save time in the evaluation to administer additional assessments of domains such as attention, memory, and executive functioning (2). For example, it may be interesting to determine whether or not this population demonstrated an improvement in their academic achievement, i.e. reading, spelling, and math, over time. Moreover, several test instruments have been developed that can be used to assess the impact of medical interventions on neuropsychological, social-emotional, behavioral, and health-related quality of life (3, 4, 5, 6, 7, 8, 9, 10). Specifically, normative data have been expanded in number and age range, which better enables the comparison of these SGA patients with the general "healthy" population.

Results from this current study indicate that this population showed a significant improvement on a subtest of nonverbal intelligence, whereas their performance on a subtest of verbal intelligence remained consistently within the lower limits of the average range across time. An important question that remains unanswered involves the possible explanations for this improvement in visual-perceptual functioning often mediated by the right parietal region of the brain, whereas their fund of vocabulary words and aspects of left hemispheric functioning remained at a consistent level according to their age. Because deficits in brain development can be accompanied with a smaller head circumference, the authors posit whether head circumference before GH treatment would predict IQ development during GH therapy, given the preliminary finding that IQ scores improved in short children born SGA during GH treatment. Now that GH therapy has been demonstrated to be largely effective in achieving considerable catch up in height during the 8 yr of treatment in this study, future research should continue to explore the impact of GH treatment on the neuroanatomical structures and central nervous system function.

This model of further scientific inquiry into the cognitive, emotional, and behavioral sequelae arising from successful medical treatment is currently under way, with the use of glucocorticoids (GC) as an essential component of therapy for childhood acute lymphoblastic leukemia. Specifically, prednisone has been the GC used most often in the treatment of acute lymphoblastic leukemia; however, many investigators have chosen dexamethasone over prednisone as a means to improve therapeutic efficacy. Recent studies, however, have raised concern about the potential for cognitive sequelae, given that GC exposure for prolonged periods or in high doses can impair memory functioning and reduce hippocampal volumes (11, 12, 13). Although this example focuses on the potentially harmful sequelae of medications known to be largely effective in treating a significant blood disorder and is different from the potentially positive impact that GH treatment may have on the central nervous system, the point is that psychology and pediatric medicine should continue to actively pursue collaboration on a variety of treatment protocols, such as described in this article.

To their credit, the authors’ did not rely exclusively on tests of intelligence, because they also assessed these patients’ social-emotional and behavioral functioning through the use of the Achenbach Child Behavior Checklist and the Achenbach Young Adult Checklist, depending on their age. It is important, however, to caution readers as well as future investigators against relying exclusively on parent-report questionnaires without incorporating self-report questionnaires. Specifically, the question of whether parents are good informants of their child’s social-emotional and behavioral functioning is an important one. The literature suggests that parent-child agreement is acceptable with regard to the level of physical functioning; however, there tends to be less concordance with regard to the level of emotional functioning, particularly with internalizing problems (i.e. anxiety, depression) as compared with more apparent externalizing symptoms, such as conduct problems, aggression, and hyperactivity (14, 15, 16, 17, 18, 19, 20, 21). Consequently, the incorporation of pediatric measures that use a developmentally appropriate self-report format is simultaneously recommended, as well as the incorporation of teacher-report questionnaires that would compare these children with their "normal and healthy" peers in the same classroom.

The results from this study identified that internalizing behaviors remained comparable to their Dutch peers, whereas externalizing behaviors of this SGA population significantly decreased during GH therapy. The authors suggest that these patients are engaged in less acting out behaviors perhaps as a result of increased self-esteem and acceptance by peers, which may be explained in part by the inverse relationship found between change in height and externalizing problems.

These findings are contrasted with other studies in the field which report that chronically ill children often exhibit higher levels of psychological symptoms than normal children but fewer symptoms than clinically referred children, with internalizing disorders being more common than externalizing behavioral problems in this population (22, 23). The children in this GH study have demonstrated a similar decline in externalizing behaviors, whereas their internalizing problems appear to remain within normal limits across the study. Additionally, Northam (23) states that chronic illness can undermine an adolescent’s sense of identity and independence, which in turn can compromise peer interactions. Compared with other published studies on chronic medical conditions, these SGA patients are not reported to experience significantly impaired physical functioning (24). Furthermore, van Pareren et al. (1) demonstrated a significant improvement in their self-perception, in terms of reported self-worth and capability over time during the GH treatment, particularly in the first 2 yr of therapy, on the Harter Self-Perception Profile.

Overall, this article represents an important addition to the medical literature because it is one of the first studies to longitudinally examine the intellectual, social-emotional, and behavioral functioning of children born SGA. The results are quite encouraging and warrant further collaborative investigation into the varied psychological benefits and possible deficits of long-term medical treatment for these children and adolescents.

Footnotes

Abbreviations: GC, Glucocorticoids; SGA, small for gestational age.

Received September 7, 2004.

Accepted September 7, 2004.

References

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