Effects of Growth Hormone Treatment on Cognitive Function and Head Circumference in Children Born Small for Gestational AgeHokken-Koelega A. · van Pareren Y. · Arends N.
Department of Paediatrics, Division of Endocrinology, Sophia Children’s Hospital/Erasmus University Medical Centre, Rotterdam, The Netherlands
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Short stature is not the only problem faced by children born small for gestational age (SGA). Being born SGA has also been associated with lowered intelligence, poor academic performance, low social competence and behavioural problems. This paper summarizes the results of a randomized, double-blind, growth hormone (GH) dose-response study (1 or 2 mg/m2/day [∼0.035 or 0.07 mg/kg/day]) on growth, intelligence quotient (IQ) and psychosocial functioning in 79 children born SGA at the start, and after 2 and 8 years of GH therapy, and addresses the associations with head circumference. Mean age at start of therapy was 7.4 years; mean duration of GH treatment was 8.0 years. In 2001, 91% of children born SGA had reached a normal height (> –2.0 standard deviation score [SDS]). Block-design s-score (Performal IQ) and Total IQ score increased (p< 0.001 for both indices) from scores significantly lower than those of Dutch peers at the start of therapy (p < 0.001) to scores that were comparable to those of Dutch peers in 2001. Vocabulary s-score (Verbal IQ) was normal at the start of therapy and remained so over time. Externalizing Problem Behaviour SDS and Total Problem Behaviour SDS improved during GH therapy (p < 0.01–0.05) to scores comparable to those of Dutch peers. Internalizing Problem Behaviour SDS was comparable to that of Dutch peers at the start of therapy and remained so, whereas Self-Perception improved from the start of GH therapy until 2001 (p < 0.001), when it reached normal scores. Head circumference SDS at the start of GH therapy and head growth during GH therapy were positively related to all IQ scores (p < 0.01), whereas neither were related to height SDS at the start of, or to its improvement during, GH therapy. A significant improvement in height and head circumference in children born SGA was seen after only 3 years of GH therapy, in contrast to randomized SGA controls. In conclusion, most children born SGA showed a normalization of height during GH therapy and, in parallel to this, a significant improvement in Performal IQ and Total IQ. In addition, problem behaviour and self-perception improved significantly. Interestingly, Performal, Verbal and Total IQ scores were positively related to head circumference, both at the start of, and during, GH therapy; head circumference increased in GH-treated children born SGA, but not in untreated SGA controls. These results are encouraging but also warrant confirmational studies and further investigations into the effects of GH on the central nervous system.
© 2005 S. Karger AG, Basel
- Hokken-Koelega ACS, De Ridder MAJ, Lemmen RJ, den Hartog H, de Muinck Keizer-Schrama S, Drop S: Children born small for gestational age: do they catch-up? Pediatr Res 1995;38:267–271.
- Karlberg J, Albertsson-Wikland K: Growth in full-term small-for-gestational-age infants: from birth to final height. Pediatr Res 1995;38:733–739.
- De Waal WJ, Hokken-Koelega ACS, Stijnen T: Endogenous and stimulated GH secretion, urinary GH excretion, and plasma IGF-I and IGF-II levels in prepubertal children with short stature after intrauterine growth retardation. Clin Endocrinol 1994;41:621–630.
- Boguszewski M, Rosberg S, Albertsson-Wikland K: Spontaneous 24-hour growth hormone profiles in prepubertal small for gestational age children. J Clin Endocrinol Metab 1995;80:2599–2606.
- McCormick MC, Workman-Daniels K, Brooks-Gunn J: The behavioral and emotional well-being of school-age children with different birth weights. Pediatrics 1996;97:18–25.
- McCarton CM, Wallace IF, Divon M, Vaughan HG: Cognitive and neurologic development of the premature, small for gestational age infant through age 6: comparison by birth weight and gestational age. Pediatrics 1996;98:1167–1178.
- Lundgren EM, Cnattingius S, Jonsson B, Tuvemo T: Intellectual and psychological performance in males born small for gestational age with and without catch-up growth. Pediatr Res 2001;50:91–96.
- Georgieff MK: Intrauterine growth retardation and subsequent somatic growth and neurodevelopment. J Pediatr 1998;133:3–5.
Van der Reijden-Lakeman EA: Growing Pains? Psychological Evaluation of Children with Short Stature after Intrauterine Growth Retardation, Before and After Two Years of Growth Hormone Treatment. Rotterdam, Erasmus University Rotterdam, 1996.
- Van Pareren YK, Duivenvoorde 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.
- Arends NJ, Boonstra VH, Hokken-Koelega ACS: Head circumference and body proportions before and during GH treatment in short children born small for gestational age (SGA). Pediatrics 2004;114:683–690.
- Fredriks AM, van Buuren S, Burgmeijer RJ, Meulmeester JF, Beuker RJ, Brugman E, Roede MJ, Verloove-Vanhorick SP, Wit JM: Continuing positive secular growth change in The Netherlands 1955–1997. Pediatr Res 2000;47:316–323.
De Bruin E, VanderSteene G, van Haasen P: WISC-R: Wechsler Intelligence Scale for Children – Revised (Dutch version), manual. Lisse, Swets & Zeitlinger BV, 1986.
Stinissen J, Willems P, Coetsier P, Hulsman W: Handleiding bij de Nederlandstalige bewerking van de Wechsler Adult Intelligence scale (W.A.I.S.). Amsterdam, Swets & Zeitlinger N.V., 1970.
- Silverstein AB: A short short form of Wechsler’s scales for screening purposes. Psychol Rep 1967;21:842.
- Silverstein AB: Validity of a new approach to the design of WAIS, WISC, and WPPSI short forms. J Consult Clin Psychol 1968;32:478–479.
Verhulst F, van der Ende J, Koot H: Manual for the CBCL/4-18. Rotterdam, Child and Adolescent Psychiatry, Sophia Children’s Hospital/University Hospital Rotterdam/Erasmus University Rotterdam, 1996.
Verhulst F, van der Ende J, Koot H: Manual for the Youth Self-Report (YSR). Rotterdam, Child and Adolescent Psychiatry, Sophia Children’s Hospital/University Hospital Rotterdam/Erasmus University Rotterdam, 1997.
Harter S: Manual of the Self-Perception Profile for Children. Denver, CO, University of Denver, 1985.
Harter S: Manual of the Self-Perception Profile for Adolescents. Denver, CO, University of Denver, 1986.
- Simis KJ, Verhulst FC, Koot HM: Body image, psychosocial functioning, and personality: how different are adolescents and young adults applying for plastic surgery? J Child Psychol Psychiatry 2001;42:669–678.
Van Dongen-Melman J, Koot H, Verhulst F: Cross-cultural validation of Harter’s self-perception profile for children in a Dutch sample. Educ Psychol Meas 1993;53:739–753.
- Van Pareren Y, Mulder P, Houdijk M, Jansen M, Reeser M, Hokken-Koelega A: Adult height after long-term, continuous growth hormone (GH) treatment in short children born small for gestational age: results of a randomized, double-blind, dose-response GH trial. J Clin Endocrinol Metab 2003;88:3584–3590.
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