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      Adult Height after Growth Hormone Treatment at Pubertal Onset in Short Adolescents Born Small for Gestational Age: Results from a Belgian Registry-Based Study

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          Abstract

          Objectives

          Information on the efficacy of GH treatment in short SGA children starting their treatment in adolescence is limited. Therefore, adult height (AH), total height gain, and pubertal height gain were evaluated in short SGA children who started GH treatment at pubertal onset.

          Patient and Methods

          Growth data of 47 short SGA adolescents (22 boys) who started GH treatment at pubertal onset (PUB group) were compared with results from 27 short SGA patients (11 boys) who started GH therapy at least 1 year before pubertal onset (PrePUB group).

          Results

          The PUB group achieved a mean (±SD) total height gain of 0.8 ± 0.7 SDS and an AH of −2.5 ± 0.7 SDS after 4.1 ± 1.1 years of GH treatment with a dosage of 41.8 ± 8.4  μg/kg/day. These results were comparable with those in the PrePUB group, which was treated for a longer duration (5.8 ± 2.1 years), resulting in a total height gain of 1.1 ± 0.7 SDS and an AH of −2.1 ± 1.0 SDS. Multiple regression analysis showed a significantly lower height gain in pubertal patients, females, and patients weighing less at start of GH treatment. An AH above −2 SDS and above the parent-specific lower limit of height was, respectively, reached in 28% and 70% of PUB and 44% and 67% of PrePUB patients (NS). AH SDS was positively correlated with the height SDS at start of GH.

          Conclusions

          Short SGA adolescents starting GH therapy at an early pubertal stage have a modest and variable height gain. A normal AH can be expected in one third of the patients, especially in those with a smaller height deficit at onset of GH treatment.

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          Most cited references22

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          References for growth and pubertal development from birth to 21 years in Flanders, Belgium.

          Due to the secular trend in length and height, growth references need to be updated regularly. Reference charts that were until recently used in Belgium are based on samples collected more than 30 years ago, and references for body mass index (BMI) and pubertal development have not been established before. To establish contemporary cross-sectional reference charts for height, weight, BMI, head circumference, and pubertal development from birth to 21 years of age, based on a representative sample of children from Flanders, Belgium. 15 989 healthy subjects of Belgian origin, 0-25 years of age, were measured in 2002-2004. Growth curves were fitted with the LMS method, and percentiles for the pubertal development were estimated with generalized additive models on status quo data from 8690 subjects aged 6-22 years of age. A positive secular trend in height and weight is observed in children above 5 years of age. Adult median height has increased by 1.2 cm/decade in boys and 0.8 cm/decade in girls; median weight by 0.9 kg/decade in boys, and 1.0 kg/decade in girls, and the weight distribution became more skewed. The BMI curve is comparable to that of other populations, except for higher percentiles. This reflects the increasing prevalence of overweight and obesity. Median age at menarche (13.0 years) has not advanced any more over the past 50 years. Median ages at menarche and B2 in girls and G2 or T4 in boys are comparable to other West European estimates, but approximately 10% enter G2/T4 before 9 years of age. The ongoing secular trend in height and weight makes growth charts previously used in Belgium obsolete. New representative charts for growth and pubertal development are introduced. For weight monitoring, it is advised that the now-available BMI growth charts are used.
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            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.

            The GH dose-response effect of long-term continuous GH treatment on adult height (AH) was evaluated in 54 short children born small for gestational age (SGA) who were participating in a randomized, double-blind, dose-response trial. Patients were randomly and blindly assigned to treatment with either 3 IU (group A) or 6 IU (group B) GH/m(2).d ( approximately 0.033 or 0.067 mg/kg.d, respectively). The mean (+/-SD) birth length was -3.6 (1.4), the age at the start of the study was 8.1 (1.9) yr, and the height SD score (SDS) at the start of the study -3.0 (0.7). Seventeen of the 54 children were partially GH deficient (stimulated GH peak, 10-20 mU/liter). Fifteen non-GH-treated, non-GH-deficient, short children born SGA, with similar inclusion criteria, served as controls [mean (+/-SD) birth length, -3.3 (1.2); age at start, 7.8 (1.7) yr; height SDS at start, -2.6 (0.5)]. GH treatment resulted in an AH above -2 SDS in 85% of the children after a mean (+/-SD) GH treatment period of 7.8 (1.7) yr. The mean (SD) AH SDS was -1.1 (0.7) for group A and -0.9 (0.8) for group B, resulting from a mean (+/-SD) gain in height SDS of 1.8 (0.7) for group A and 2.1 (0.8) for group B. No significant differences between groups A and B were found for AH SDS (mean difference, 0.3 SDS; 95% confidence interval, -0.2, 0.6; P > 0.2) and gain in height SDS (mean difference, 0.3 SDS; 95% confidence interval, -0.1, 0.7; P > 0.1). When corrected for target height, the mean corrected AH SDS was -0.2 (0.8) for group A and -0.4 (0.9) for group B. The mean (+/-SD) AH SDS of the control group [-2.3 (0.7)] was significantly lower than that of the GH-treated group (P < 0.001). Multiple regression analysis indicated the following predictive variables for AH SDS: target height SDS, height SDS, and chronological age minus bone age (years) at the start of the study. GH dose had no significant effect. In conclusion, long-term continuous GH treatment in short children born SGA without signs of persistent catch-up growth leads to a normalization of AH, even with a GH dose of 3 IU/m(2).d ( approximately 0.033 mg/kg.d).
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              Final height in short children born small for gestational age treated with growth hormone.

              The aim of this observational study was to assess the long-term growth responses to GH treatment of children born small for gestational age (SGA). GH treatment was begun before puberty and continued to final height (FH). Seventy-seven short (height SD score below -2) prepubertal children born SGA (below -2 SD for birth weight and/or birth length), with a broad range of GH secretory capacity, were treated with GH in a daily dose of 33 microg/kg (0.1 U/kg), beginning before the onset of puberty. We observed a difference between adult and pretreatment projected height of 1.3 SD (9 cm) for the entire group. Among the children treated for >2 y before puberty, this mean gain (i.e. difference) in final height was 1.7 SD, whereas the mean gain was 0.9 SD among those in whom treatment was begun <2 y before puberty. Better catch-up growth was observed in the younger (r=-0.56, p<0.0001), shorter (r=-0.49, p<0.0001), and lighter (r=-0.46, p<0.0001) subjects. We conclude that GH treatment improves the final height of short children born SGA. The height gain attained before the onset of puberty is maintained to final height. The younger, shorter, and lighter the child at the start of GH treatment, the better the response. Moreover, most of these SGA individuals treated with GH reach their target height.
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                Author and article information

                Contributors
                Journal
                Int J Endocrinol
                Int J Endocrinol
                IJE
                International Journal of Endocrinology
                Hindawi
                1687-8337
                1687-8345
                2018
                3 April 2018
                : 2018
                : 6421243
                Affiliations
                1The Belgian Society for Pediatric Endocrinology and Diabetology (BESPEED), Bruxelles, Belgium
                2Division of Pediatric Endocrinology, Université catholique de Louvain, CHU UCL Namur, Yvoir, Belgium
                3Division of Pediatric Endocrinology, Hôpital Universitaire des Enfants Reine Fabiola (HUDERF), Bruxelles, Belgium
                4Division of Pediatric Endocrinology, UZ Antwerpen, Antwerpen, Belgium
                5Division of Pediatric Endocrinology, CHU-Notre-Dame des Bruyères, Chênée, Belgium
                6Division of Pediatric Endocrinology, Cliniques Universitaires Saint-Luc, Bruxelles, Belgium
                7Division of Pediatric Endocrinology, Jessa Ziekenhuis, Hasselt, Belgium
                8Division of Pediatric Endocrinology, UZ Leuven, Leuven, Belgium
                9Division of Pediatric Endocrinology, UZ Gent, Gent, Belgium
                10Department of Public Health and Primary Care, KU Leuven, Leuven, Belgium
                11Division of Pediatric Endocrinology, UZ Brussel, Brussel, Belgium
                Author notes

                Academic Editor: Donatella Capalbo

                Author information
                http://orcid.org/0000-0003-1598-7998
                http://orcid.org/0000-0002-2999-0250
                Article
                10.1155/2018/6421243
                5903317
                29849621
                f853abb2-fc83-47e3-9736-01203ec62d57
                Copyright © 2018 M. Thomas et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 19 October 2017
                : 17 January 2018
                : 6 February 2018
                Categories
                Clinical Study

                Endocrinology & Diabetes
                Endocrinology & Diabetes

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