15
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      Two-Year Data from a Long-Term Phase IV Study of Recombinant Human Growth Hormone in Short Children Born Small for Gestational Age

      research-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Introduction

          This ongoing, prospective, open-label, non-comparative, multicenter phase IV study is evaluating the safety and efficacy of recombinant human growth hormone (rhGH; Omnitrope ®, Sandoz GmbH) in short children born small for gestational age (SGA). Here we report data from patients who have completed 2 years’ treatment.

          Methods

          Eligibility criteria included prepubertal children born SGA with growth disturbances defined as current height standard deviation score (HSDS) <−2.5 and parental adjusted SDS <−1; birth weight and/or length <−2 SDS; and failure of catch-up growth [height velocity (HV) SDS <0 during the last year] by 4 years of age or later. The primary study objective is to assess the long-term effect of Omnitrope treatment on the development of diabetes in short children born SGA. Secondary objectives include evaluation of efficacy, incidence and severity of adverse events (AEs), occurrence of malignancies during treatment, and detection of anti-rhGH antibodies during treatment.

          Results

          In total, 278 children have been enrolled and received study medication; 249 have completed 2 years of treatment. No child has developed diabetes mellitus during the first 2 years; no fasting glucose or 2-h oral glucose tolerance test value exceeded the pre-defined limits of >126 or >200 mg/dL, respectively. No adverse alterations in body mass were noted. Treatment-emergent AEs were experienced by 211 (76.2%) children; most of these were of mild-to-moderate intensity (99.3%) and considered unrelated to study medication (97.6%). Treatment with Omnitrope was effective; mean HSDS was −3.39 at baseline, −2.57 at 1 year and −2.15 at 2 years of treatment. Mean HVSDS (peak-centered) also improved, from −2.13 at baseline to +4.16 at 1 year and +2.23 at 2 years.

          Conclusion

          In this second interim analysis, short children born SGA were safely and effectively treated with rhGH (Omnitrope), and 2 years’ treatment had no major adverse impact on carbohydrate metabolism or body mass.

          Funding

          Sandoz.

          Electronic supplementary material

          The online version of this article (doi:10.1007/s12325-016-0301-1) contains supplementary material, which is available to authorized users.

          Related collections

          Most cited references13

          • Record: found
          • Abstract: found
          • Article: not found

          Fetal nutrition and cardiovascular disease in adult life.

          Babies who are small at birth or during infancy have increased rates of cardiovascular disease and non-insulin-dependent diabetes as adults. Some of these babies have low birthweights, some are small in relation to the size of their placentas, some are thin at birth, and some are short at birth and fail to gain weight in infancy. This paper shows how fetal undernutrition at different stages of gestation can be linked to these patterns of early growth. The fetuses' adaptations to undernutrition are associated with changes in the concentrations of fetal and placental hormones. Persisting changes in the levels of hormone secretion, and in the sensitivity of tissues to them, may link fetal undernutrition with abnormal structure, function, and disease in adult life.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: found
            Is Open Access

            Continuous growth reference from 24th week of gestation to 24 months by gender

            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.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Patterns of growth among children who later develop type 2 diabetes or its risk factors.

              We studied fetal and childhood growth patterns that are associated with IGT and type 2 diabetes in adult life. We examined clinically 2,003 subjects born in Helsinki between 1934 and 1944. They had on average 11 measurements of height and weight between birth and 2 years of age, and seven measurements between 2 and 11 years of age. Glucose tolerance in adult life was assessed by a 75-g oral glucose tolerance test. We identified 311 subjects with type 2 diabetes and 496 with IGT. Both IGT and type 2 diabetes were associated with low birthweight (p < 0.0001 adjusting for current BMI). The risk of these conditions was increased by low weight gain between birth and 2 years. A 1 SD increase in weight at 2 years was associated with an odds ratio for either type 2 diabetes or IGT of 0.76 (95% CI 0.69-0.84). This effect was greatest in people who had low birthweight. Low growth in the first 6 months after birth was a critical period for the development of insulin resistance in later life; other critical periods were associated with slow fetal growth and rapid increase in BMI between age 2 and 11 years. Low weight gain during infancy increases the risk of IGT and type 2 diabetes. The effect is greater in people who had low birthweight. The first 6 months after birth may be the most critical period for growth, in relation to development of glucose intolerance.
                Bookmark

                Author and article information

                Contributors
                ellen.schuck@sandoz.com
                Journal
                Adv Ther
                Adv Ther
                Advances in Therapy
                Springer Healthcare (Cheshire )
                0741-238X
                1865-8652
                17 February 2016
                17 February 2016
                2016
                : 33
                : 423-434
                Affiliations
                [ ]Department of Endocrinology, von Haunersches Kinderspital, University Hospital Munich, Munich, Germany
                [ ]Department of Paediatric Endocrinology and Diabetology, Pomeranian Medical University, Szczecin, Poland
                [ ]Department of Diabetology and Endocrinology, Medical University of Gdansk, Gdańsk, Poland
                [ ]Clinic of Endocrinology and Diabetology, Children’s Memorial Health Institute, Warsaw, Poland
                [ ]Faculty of Medicine and Health Sciences UJK, Kielce, Poland
                [ ]“Alfred Russescu” Institute for Mother and Child Care, Bucharest, Romania
                [ ]HEXAL AG, Holzkirchen, Germany
                Article
                301
                10.1007/s12325-016-0301-1
                4833801
                26886776
                6fb34dbe-eb5f-4c01-9882-a4cffbf49784
                © The Author(s) 2016
                History
                : 14 December 2015
                Funding
                Funded by: Sandoz International GmbH
                Categories
                Original Research
                Custom metadata
                © Springer Healthcare 2016

                endocrinology,omnitrope,recombinant human growth hormone,small for gestational age,somatropin

                Comments

                Comment on this article