ESPE Yearbook of Paediatric Endocrinology

J Clin Endocrinol Metab 2024 Dec 18;110(1):139-150. PMID: 38888175 doi: 10.1210/clinem/dgae425

Brief Summary: This study investigated the long-term health-related quality of life (HRQoL) and problem behavior in adults born small for gestational age (SGA) who were treated with growth hormone (GH) during childhood (SGA-GH), following them for 12 years after GH cessation until around age 30.

The study included 176 SGA-GH adults who had participated in Dutch GH trials for persistent short stature after being born SGA. These individuals were followed at 6 months, 2, 5, and 12 years after GH treatment ceased. At the 12-year follow-up (around age 30), 105 of the initial 176 SGA-GH adults remained. Their HRQoL and problem behavior were compared to three untreated age-matched control groups from a separate study (PROGRAM study): SGA-S: 50 adults born SGA with persistent short stature. SGA-CU: 77 adults born SGA with spontaneous catch-up growth to normal height. AGA: 99 adults born appropriate-for-gestational-age with normal height.

Main Outcome Measures:

• HRQoL was assessed using the TNO-AZL Adults Quality of Life (TAAQoL) questionnaire, which comprises 45 items across 12 subscales covering physical and emotional/social aspects of well-being. Higher scores indicate better HRQoL8.

• Problem behavior was assessed using the Adolescent Behavior Check List (ABCL), a questionnaire with 113 questions on specific problem behaviors, categorizing them into total, externalizing, and internalizing problem behavior, along with 8 subscales. Higher scores indicate more problem behavior.

• Contentment with adult height was assessed by questionnaire.

Over 12 years after GH cessation, HRQoL remained largely stable in SGA-GH adults, with some decline in specific physical and sleep-related aspects. Problem behavior, particularly externalizing, decreased. While SGA-GH adults showed similar HRQoL and problem behavior to untreated short SGA adults, they had lower HRQoL and more problem behavior than AGA adults. This suggests that the differences observed in HRQoL and internalizing problem behavior are more likely attributable to the intrinsic nature of being born SGA rather than the GH treatment itself. Although GH treatment increased adult height, adult height had only a small influence on externalizing problem behavior and no association with HRQoL or internalizing problem behavior in the final adjusted models. Non-height-related factors like chronic physical/mental conditions, lifestyle, fat mass, and education played a greater role in HRQoL and problem behavior.

The study highlights the importance of adequate counselling regarding expectations before GH treatment begins. Despite the noted differences in HRQoL and problem behavior compared to AGA adults, previous research from this group indicates that GH treatment in short SGA children is beneficial and safe, including for metabolic, cardiovascular, and cerebrovascular health up to 12 years after cessation.

References: 1. Mehl CV, Hollund IMH, Iversen JM, et al. Health-related quality of life in young adults born small for gestational age: a prospective cohort study. Health Qual Life Outcomes. 2022;20(1):49.2. Lund LK, Vik T, Lydersen S, et al. Mental health, quality of life and social relations in young adults born with low birth weight. Health Qual Life Outcomes. 2012;10(1):1-10.3. Renes JS, Willemsen RH, Mulder JC, et al. New insights into factors influencing adult height in short SGA children: results of a large multicentre growth hormone trial. Clin Endocrinol (Oxf). 2015;82(6):854-861.4. 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 Metabol. 2003;88(8): 3584-3590.