Silver-Russell Syndrome & Small for Gestational Age : Long-term health perspectives

For over 25 years, our research group and others have been investigating children born small for gestational age (SGA) with persistent short stature, and the efficacy and safety of biosynthetic growth hormone treatment (GH) in these children. One of the causes of short SGA is Silver-Russell syndrome (SRS). This doctoral thesis presents the response to, and safety of GH treatment, and describes pubertal progression and metabolic health in patients with SRS. Because being born with a lower birth weight leads to an increased risk for age-associated diseases, health in later life has been a concern in patients born SGA. In the second part of this thesis, we present data on parameters associated with health in later life, such as telomere length and bone mineral density, and the effects of GH treatment on these parameters

Effects of size at birth, childhood growth patterns and growth hormone treatment on leukocyte telomere length

__Background__ Small size at birth and rapid growth in early life are associated with increased risk of cardiovascular disease in later life. Short children born small for gestational age (SGA) are treated with growth hormone (GH), inducing catch-up in length. Leukocyte telomere length (LTL) is a marker of biological age and shorter LTL is associated with increased risk of cardiovascular disease. __Objectives__ To investigate whether LTL is influenced by birth size, childhood growth and long-term GH treatment. __Methods__ We analyzed LTL in 545 young adults with differences in birth size and childhood growth patterns. Previously GH-treated young adults born SGA (SGA-GH) were compared to untreated short SGA (SGA-S), SGA with spontaneous catch-up to a normal body size (SGA-CU), and appropriate for gestational age with a normal body size (AGA-NS). LTL was measured using a quantitative PCR assay. __Results__ We found a positive association between birth length and LTL (p = 0.04), and a trend towards a positive association between birth weight and LTL (p = 0.08), after adjustments for gender, age, gestational age and adult body size. Weight gain during infancy and childhood and fat mass percentage were not as

Bone Mineral Density After Cessation of GH Treatment in Young Adults Born SGA: A 5-Year Longitudinal Study

Context: Short children born small for gestational age (SGA) have below-average bone mineral density (BMD). Growth hormone (GH) treatment improves height and BMD in short SGA children. Longitudinal data on BMD in adults born SGA, after GH cessation (GH-stop), are lacking.Objective: To determine BMD in young adults born SGA during 5 years after GH-stop.Methods: In 173 GH-treated adults born SGA (SGA-GH), BMD of total body (BMDTB) and bone mineral apparent density of lumbar spine (BMADLS) were measured longitudinally at adult height (AH) and 6 months, 2 years, and 5 years thereafter. At 5 years after GH-stop (age 21 years), data were compared with 45 untreated short SGA adults (SGA-S), 59 SGA adults with spontaneous catch-up (SGA-CU), and 81 adults born appropriate for gestational age (AGA).Results: At GH-stop (mean age 16.4 years), estimated mean (standard error) BMDTB standard deviation score (SDS) was -0.40 (0.1) in males and -0.51 (0.1) in females, followed by a trend toward a decrease of BMDTB in males to -0.59 (0.1) at 5 years after GH-stop (P = 0.06), whereas it remained stable in females [-0.57 (0.1); P = 0.33]. At GH-stop, BMADLS SDS was -0.01 (0.1) in males and -0.29 (0.1) in females, followed by a decrease in males and females to -0.38 and -0.55, respectively, at 5 years after GH-stop (P < 0.001). At 5 years after GH-stop, BMDTB and BMADLS in SGA-GH were similar compared with SGA-S, SGA-CU, and AGA.Conclusion: After GH-stop, there is a gradual decline of BMADLS, but at the age of 21 years, BMDTB and BMADLS are similar as in untreated short SGA adults