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No cognitive defects observed in small-for-gestational age children receiving long-term hormone therapy
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In children born small for gestational age, treatment with combined growth hormone/gonadotropin-releasing hormone analogue does not appear to have any adverse long-term effects on early adulthood cognition, health-related quality of life, self-perception or problem behavior, according to findings published in the Journal of Clinical Metabolism.
“Children born small for gestational age (SGA) with a poor adult height expectation benefit from treatment with growth hormone (GH) and additional gonadotropin-releasing hormone analogue (GnRHa),” Wesley J. Goedegebuure, MD, doctoral candidate in the department of pediatrics, subdivision endocrinology, Erasmus University in Rotterdam, Netherlands, and colleagues wrote in the study’s background. “As both SGA birth and GnRHa-treatment might negatively influence cognition, [health-realted quality of life] and psychosocial functioning, we assessed these outcomes at adult height.”
Researchers identified 99 young adults born small for gestational age who participated in a Dutch randomized, dose-response study of GH use in children born small for gestational age. Birth weight and/or birth length below -2 SDS for gestational age was considered small for gestational age. Participants initiated a GH treatment regimen at age 8 years or older and continued until they reached adult height. Among the cohort 61 had 2 additional years of GnRHa treatment added to their regimen (GnRHA group), and 38 received GH treatment only (GH group). GnRHA was given in cases where height at the beginning of puberty was expected to yield an adult height less than -2.5 SDS. Upon reaching puberty, participants were randomized to treatment with either GH 1 mg or 2 mg/m2 per day. These participants completed the Weschler Adult Intelligence Scale and TNO-AZL Adults Quality of Life questionnaires when they reached adult height.
Researchers added 67 young adults born small for gestational age who participated in an interuterine growth restriction study. At age 5 to 8 years, these children began GH treatment; 19 participants received an additional 2 years of GnRHa. Upon reaching adult height, these participants completed the Self-Perception Profile of Adolescents and Child/Adolescent Behavior Checklist questionnaires.
The GnRHA group reached adult height at mean age of 17.5 years vs. 17.4 years for the GH group. Total, performance and verbal IQ scores were not significantly different between the two groups. Cognitive functioning was similar between the two groups, and within normal range, but significantly lower than that of the general population (94.84 vs. 100; P = .001).
Participants in the GnRHa group reported significantly higher health-related quality of life in terms of positive emotions vs. the GH group (76.63 vs. 66.39; P = .039). The difference persisted after adjustment for socioeconomic status (P = .028).
Compared with the general population, the GnRHA group demonstrated a significantly lower perception of cognitive function vs. the control group (87.86 vs. 78.42; P = .002), whereas the GH group demonstrated a nonsignificant trend toward lower perceived cognitive functioning (87.86 vs. 82.86). There was no significant difference in perception of cognitive function between the GnRHa and GHA groups, and the groups reported comparable levels of self-perception and problem behaviors. Health-related quality of life, self-perception and problem behavior were not correlated with adult height.
“Our study shows that 2 years of GnRHa treatment in addition to GH treatment, results in similar cognitive functioning, health-related quality of life, self-perception and problem behavior, compared to GH treatment only in young adults born SGA,” the researchers wrote. “In contrast to our hypothesis, no significant correlations were found between adult height and problem behavior and self-perception scores. Based on our results, additional GnRHa treatment could be considered at the start of puberty for GH-treated children born SGA with an [adult height] prediction below -2.5 SDS.” – by Jennifer Byrne
Disclosures: One author reports she received an independent research grant from Pfizer and Novo Nordisk Netherlands.
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