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      Methylphenidate and the Response to Growth Hormone Treatment in Short Children Born Small for Gestational Age

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          Abstract

          Background

          Growth hormone (GH) treatment has become a frequently applied growth promoting therapy in short children born small for gestational age (SGA). Children born SGA have a higher risk of developing attention deficit hyperactivity disorder (ADHD). Treatment of ADHD with methylphenidate (MP) has greatly increased in recent years, therefore more children are being treated with GH and MP simultaneously. Some studies have found an association between MP treatment and growth deceleration, but data are contradictory.

          Objective

          To explore the effects of MP treatment on growth in GH-treated short SGA children

          Methods

          Anthropometric measurements were performed in 78 GH-treated short SGA children (mean age 10.6 yr), 39 of whom were also treated with MP (SGA-GH/MP). The SGA-GH/MP group was compared to 39 SGA-GH treated subjects. They were matched for sex, age and height at start of GH, height SDS at start of MP treatment and target height SDS. Serum insulin-like growth factor-I (IGF-I) and IGF binding protein-3 (IGFBP-3) levels were yearly determined. Growth, serum IGF-I and IGFBP-3 levels during the first three years of treatment were analyzed using repeated measures regression analysis.

          Results

          The SGA-GH/MP group had a lower height gain during the first 3 years than the SGA-GH subjects, only significant between 6 and 12 months of MP treatment. After 3 years of MP treatment, the height gain was 0.2 SDS (±0.1 SD) lower in the SGA-GH/MP group (P = 0.17). Adult height was not significantly different between the SGA-GH/MP and SGA-GH group (−1.9 SDS and −1.9 SDS respectively, P = 0.46). Moreover, during the first 3 years of MP treatment IGF-I and IGFBP-3 measurements were similar in both groups.

          Conclusion

          MP has some negative effect on growth during the first years in short SGA children treated with GH, but adult height is not affected.

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          Most cited references36

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          Pharmacotherapy of attention-deficit hyperactivity disorder across the life cycle.

          To evaluate the scope of the available therapeutic armamentarium in attention-deficit hyperactivity disorder (ADHD). The literature of medication trials in ADHD was systematically reviewed, with attention to issues of psychiatric comorbidity, age, gender, and ethnic background. One hundred fifty-five controlled studies of 5,768 children, adolescents, and adults have documented the efficacy of stimulants in an estimated 70% of subjects. The literature clearly documents that stimulants not only improve abnormal behaviors of ADHD, but also self-esteem, cognition, and social and family function. However, response varied in different age groups and with certain comorbid conditions. In addition, there is an impressive body of literature documenting the efficacy of tricyclic antidepressants on ADHD in more than 1,000 subjects. Studies of alternative antidepressants, antipsychotics, antihypertensives, and other compounds were also reviewed. The available literature indicates the important role of psychopharmacological agents in the reduction of the core symptoms of ADHD and associated impairments. More research is needed on alternative pharmacological treatments and to further evaluate established therapeutics beyond school-age Caucasian boys. In addition, more research is needed on the efficacy of treatment for comorbid ADHD, use of combined medications, and the combination of medication and psychosocial treatment.
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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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              Intrauterine growth of live-born Caucasian infants at sea level: standards obtained from measurements in 7 dimensions of infants born between 25 and 44 weeks of gestation.

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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2012
                27 December 2012
                : 7
                : 12
                : e53164
                Affiliations
                [1 ]Department of Pediatrics, Subdivision of Endocrinology, Erasmus MC/Sophia Children's Hospital, Rotterdam, The Netherlands
                [2 ]Department of Biostatistics, Erasmus MC, Rotterdam, The Netherlands
                [3 ]Dutch Growth Research Foundation, Rotterdam, The Netherlands
                Tehran University of Medical Sciences, Iran (Islamic Republic of)
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: JSR AH-K. Analyzed the data: JSR MAJR AH-K. Wrote the paper: JSR. Acquisitioned and interpreted the data: JSR PEB AJL AH-K MAJR. Carefully revised the content of the article and approved the final version: MAJR PEB AJL AH-K.

                Article
                PONE-D-12-26451
                10.1371/journal.pone.0053164
                3531371
                23300884
                473ca9ee-130e-48f6-8886-b123d163b3d8
                Copyright @ 2012

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 30 August 2012
                : 26 November 2012
                Page count
                Pages: 5
                Funding
                The authors have no support or funding to report.
                Categories
                Research Article
                Biology
                Biochemistry
                Proteins
                Growth Factors
                Medicine
                Clinical Research Design
                Case-Control Studies
                Retrospective Studies
                Endocrinology
                Endocrine Physiology
                Growth Factors
                Hormones
                Insulin-like Growth Factor
                Pediatric Endocrinology
                Mental Health
                Psychology
                Behavior
                Attention (Behavior)
                Pediatrics
                Growth Retardation

                Uncategorized
                Uncategorized

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