title: Effects of growth hormone treatment on cognitive function and head circumference in children born small for gestational age.
abstract: 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 [ approximately 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.
authors.affiliation: Department of Paediatrics, Division of Endocrinology, Sophia Children's Hospital/Erasmus University Medical Centre, Rotterdam, The Netherlands. a.hokken@erasmusmc.nl
authors.forename: Anita
authors.initials: A
authors.lastname: Hokken-Koelega
authors.forename: Yvonne
authors.initials: Y
authors.lastname: van Pareren
authors.forename: Nicolette
authors.initials: N
authors.lastname: Arends
mesh_terms: D002648:Child; D002675:Child, Preschool; D003071:Cognition / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006257:Head / Q000254:growth & development; D019382:Human Growth Hormone / Q000008:administration & dosage*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007236:Infant, Small for Gestational Age / Q000254:growth & development; D008297:Male; D011340:Problem Solving / Q000187:drug effects*; D012189:Retrospective Studies; D012649:Self Concept; D013065:Speech Intelligibility / Q000187:drug effects*
chemical_list: D019382:Human Growth Hormone