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      A Comparison of Different Definitions of Growth Response in Short Prepubertal Children Treated with Growth Hormone

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          Abstract

          Background: How to define poor growth response in the management of short growth hormone (GH)-treated children is controversial. Aim: Assess various criteria of poor response. Subjects and Methods: Short GH-treated prepubertal children [n = 456; height (Ht) SD score (SDS) ≤–2] with idiopathic GH deficiency (IGHD, n = 173), idiopathic short stature (ISS, n = 37), small for gestational age (SGA, n = 54), organic GHD (OGHD, n = 40), Turner syndrome (TS, n = 43), skeletal dysplasia (n = 15), other diseases (n = 46) or syndromes (n = 48) were evaluated in this retrospective multicenter study. Median age at GH start was 6.3 years and Ht SDS –3.2. Results: Median [25–75 percentile] first-year gain in Ht SDS was 0.65 (0.40–0.90) and height velocity (HtV) 8.67 (7.51–9.90) cm/year. Almost 50% of IGHD children fulfilled at least one criterion for poor responders. In 28% of IGHD children, Ht SDS gain was <0.5 and they had lower increases in median IGF-I SDS than those with Ht SDS >0.5. Only IGHD patients with peak stimulated growth hormone level <3 µg/l responded better than those with ISS. A higher proportion of children with TS, skeletal dysplasia or born SGA had Ht SDS gain <0.5. Conclusion: Many children respond poorly to GH therapy. Recommendations defining a criterion may help in managing short stature patients.

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          Consensus statement on the diagnosis and treatment of children with idiopathic short stature: a summary of the Growth Hormone Research Society, the Lawson Wilkins Pediatric Endocrine Society, and the European Society for Paediatric Endocrinology Workshop.

          P. Cohen, A Rogol, C L Deal … (2008)
          Our objective was to summarize important advances in the management of children with idiopathic short stature (ISS). Participants were 32 invited leaders in the field. Evidence was obtained by extensive literature review and from clinical experience. Participants reviewed discussion summaries, voted, and reached a majority decision on each document section. ISS is defined auxologically by a height below -2 sd score (SDS) without findings of disease as evident by a complete evaluation by a pediatric endocrinologist including stimulated GH levels. Magnetic resonance imaging is not necessary in patients with ISS. ISS may be a risk factor for psychosocial problems, but true psychopathology is rare. In the United States and seven other countries, the regulatory authorities approved GH treatment (at doses up to 53 microg/kg.d) for children shorter than -2.25 SDS, whereas in other countries, lower cutoffs are proposed. Aromatase inhibition increases predicted adult height in males with ISS, but adult-height data are not available. Psychological counseling is worthwhile to consider instead of or as an adjunct to hormone treatment. The predicted height may be inaccurate and is not an absolute criterion for GH treatment decisions. The shorter the child, the more consideration should be given to GH. Successful first-year response to GH treatment includes an increase in height SDS of more than 0.3-0.5. The mean increase in adult height in children with ISS attributable to GH therapy (average duration of 4-7 yr) is 3.5-7.5 cm. Responses are highly variable. IGF-I levels may be helpful in assessing compliance and GH sensitivity; levels that are consistently elevated (>2.5 SDS) should prompt consideration of GH dose reduction. GH therapy for children with ISS has a similar safety profile to other GH indications.
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            Continuous growth reference from 24th week of gestation to 24 months by gender

            Aimon Niklasson, Kerstin Albertsson-Wikland (2008)
            Background Growth charts and child growth assessment have become prime global instruments in child health practice over the 30 years. An updated, continuous growth standard that bridges size at birth values with postnatal growth values can improve child growth screening and monitoring. Methods This novel growth chart was constructed from two sources of information. Size at birth (weight, length and head circumference) reference values were updated based on information of normal deliveries (i.e. singleton live births without severe congenital malformation, with healthy mothers and born vaginally) from the Swedish Medical Birth Registry, 1990–1999 (n = 810393). Weight was evaluated using logarithmic transformation as for postnatal weight. Standard deviations were estimated from data within the empirical mean ± 1.0 SD for each gestational week and gender. These values were smoothed by empirical curve-fitting together with values from our recently published postnatal growth reference including 3650 longitudinally followed children from birth to final height [9]. Timescale and weight axes were made logarithmic in order to magnify the early time part of the graph. Results This study presents the first continuous gender specific growth chart from birth irrespective of gestational age at birth until 2 years of age for weight, length and head circumference. Birth weight at 40 weeks of gestation increased approximately 100 gram and length increased only 1 mm compared with earlier Swedish reference from 1977–81. The curve is now less S-shaped as compared with earlier curves and compared with 4 curves from other countries and with more constant variation over the whole range. Conclusion Our values picture the unrestricted pattern of growth improving the detection of a deviating growth pattern, when the growth of an individual infant is plotted on the charts. Especially for very preterm infants age corrected growth can be more easily evaluated although it must be recognized that the early comparison is with what is estimated as normal growth in uterus. The reference values are useful in child health care systems for population screening, but also in research or in the clinic for evaluating various growth promoting interventions – either nutritional, surgical or therapeutic – that might affect a child in early life.
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              Prediction of response to growth hormone treatment in short children born small for gestational age: analysis of data from KIGS (Pharmacia International Growth Database).

              D. Price, Michael B. Ranke, H Reiter … (2002)
              A model was developed that allows physicians to individualize GH treatment in children born short for gestational age (SGA) who fail to show spontaneous catch-up growth. Data from children (n = 613) in a large pharmacoepidemiological survey, the KIGS (Pharmacia International Growth Database), or who had participated in clinical trials were used to develop the model. Another group of similar children (n = 68) from KIGS was used for validation. In the first year of GH treatment, the growth response correlated positively with GH dose, weight at the start of GH treatment, and midparental height SD score and negatively with age at treatment start. Using this model, 52% of the variability of the growth response could be explained, with a mean error SD of 1.3 cm. GH dose was the most important response predictor (35% of variability), followed by age at treatment start. The second year growth response was best predicted by a three-parameter model (height velocity in yr 1 of treatment, age at start of treatment, and GH dose), which accounted for 34% of the variability, with an error SD of 1.1 cm. The first year response to GH treatment was the most important predictor of the second year response, accounting for 29% of the variability. No statistically significant differences between the predicted and observed growth responses were found when the models were applied to the validation groups. In conclusion, using simple variables, we have developed a model that can be used in clinical practice to adjust the GH dose to achieve the desired growth response in patients born SGA. Furthermore, this model can be used to provide patients with a realistic expectation of treatment and may help to identify compliance problems or other underlying causes of treatment failure.
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                Author and article information

                Journal
                Journal ID (publisher-id): HRP
                Journal ID (nlm-ta): Horm Res Paediatr
                Journal ID (doi): 10.1159/issn.1663-2818
                Title: Hormone Research in Paediatrics
                Publisher: S. Karger AG
                ISSN (Print): 1663-2818
                ISSN (Electronic): 1663-2826
                Publication date Subscription-year: 2011
                Publication date (Print): May 2011
                Publication date (Electronic): 12 January 2011
                Volume: 75
                Issue: 5
                Pages: 335-345
                Affiliations
                aDepartment of Women’s and Children’s Health, Karolinska Institute and University Hospital, Stockholm, Sweden; bDepartment of Clinical Medicine, Section for Pediatrics, University of Bergen, Norway; cDepartment of Pediatrics, Sahlgrenska Academy, University of Gothenburg, Sweden; dDepartment of Pediatrics, Kuopio University Hospital, Kuopio, Finland; eDepartment of Women’s and Children’s Health, University of Uppsala, Sweden; fDepartment of Growth and Reproduction, University of Copenhagen, Denmark; gDepartment of Clinical Science, Umeå University, Umeå, Sweden; hDepartment of Pediatrics and Adolescence, University of Oulu, Finland; iInstitut Produits Synthèse (IPSEN) AB, Kista, Sweden
                Author notes
                *Peter Bang, MD, PhD, MSci, Pediatric Endocrinology Unit Q2:08, Department of Women’s and Children’s Health, Karolinska Institute and University Hospital, SE–17176 Stockholm (Sweden), Tel. +46 851 777 314, Fax +46 851 775 128, E-Mail peter.bang@ki.se
                Article
                Publisher ID: 322878 Other ID: Horm Res Paediatr 2011;75:335–345
                DOI: 10.1159/000322878
                PubMed ID: 21228552
                SO-VID: dcae9acc-3b68-4e1e-aebc-8ebdad76babf
                Copyright © © 2011 S. Karger AG, Basel
                License:

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                Date received : 30 June 2010
                Date accepted : 11 April 2010
                Page count
                Figures: 5, Tables: 2, Pages: 11
                Categories
                Subject: Original Paper

                ScienceOpen disciplines: Endocrinology & Diabetes,Neurology,Nutrition & Dietetics,Sexual medicine,Internal medicine,Pharmacology & Pharmaceutical medicine
                Keywords: Turner syndrome,Skeletal dysplasia,Growth prediction,Growth hormone therapy,Growth response,Height velocity,Growth hormone deficiency,Organic growth hormone deficiency,Small for gestational age,Idiopathic short stature
                Data availability:
                ScienceOpen disciplines: Endocrinology & Diabetes, Neurology, Nutrition & Dietetics, Sexual medicine, Internal medicine, Pharmacology & Pharmaceutical medicine
                Keywords: Turner syndrome, Skeletal dysplasia, Growth prediction, Growth hormone therapy, Growth response, Height velocity, Growth hormone deficiency, Organic growth hormone deficiency, Small for gestational age, Idiopathic short stature

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