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This International Consensus Guideline was developed by experts in the field of small for gestational age (SGA) of 10 pediatric endocrine societies worldwide. A consensus meeting was held and 1300 articles formed the basis for discussions. All experts voted about the strengths of the recommendations. The guideline gives new and clinically relevant insights into the etiology of short stature after SGA birth, including novel knowledge about (epi)genetic causes. Further, it presents long-term consequences of SGA birth and also reviews new treatment options, including treatment with gonadotropin-releasing hormone agonist (GnRHa) in addition to growth hormone (GH) treatment, as well as the metabolic and cardiovascular health of young adults born SGA after cessation of childhood GH treatment in comparison with appropriate control groups. To diagnose SGA, accurate anthropometry and use of national growth charts are recommended. Follow-up in early life is warranted and neurodevelopment evaluation in those at risk. Excessive postnatal weight gain should be avoided, as this is associated with an unfavorable cardiometabolic health profile in adulthood. Children born SGA with persistent short stature < −2.5 SDS at age 2 years or < −2 SDS at 3 to 4 years of age, should be referred for diagnostic workup. In case of dysmorphic features, major malformations, microcephaly, developmental delay, intellectual disability, and/or signs of skeletal dysplasia, genetic testing should be considered. Treatment with 0.033 to 0.067 mg GH/kg/day is recommended in case of persistent short stature at age of 3 to 4 years. Adding GnRHa treatment could be considered when short adult height is expected at pubertal onset. All young adults born SGA require counseling to adopt a healthy lifestyle.

Accelerated gain in fat mass (FM) in early life increases the risk for adult diseases. Longitudinal data on infant body composition are crucial for clinical and research use, but very difficult to obtain due to limited measurement tools and unsuccessful measurements between age 6–24 months. We compared FM% by dual-energy X-ray absorptiometry (DXA), with cushion to reduce movement artifacts, with FM% by air-displacement plethysmography (ADP) and evaluated the reliability of this cushion during DXA by comparing FM% with and without cushion. Subsequently, we constructed sex-specific longitudinal body composition charts from 1–24 months. In 692 healthy, term-born infants (Sophia Pluto Cohort), FM% was measured by ADP from 1–6 months and DXA with cushion from 6–24 months. At 6 months, FM% was measured in triplicate by ADP and DXA with and without cushion(n = 278), later on in smaller numbers. At 6 months, mean FM% by DXA with cushion was 24.1 and by ADP 25.0, mean difference of 0.9% (Bland–Altman p = 0.321, no proportional bias). Mean FM% by DXA without cushion was 12.5% higher compared to ADP (Bland–Altman p

Background: Growth hormone treatment increases glomerular filtration rate (GFR), as serum IGF-I stimulates the renin-angiotensin system. Infants born with a low birth weight have a smaller number of nephrons, which cause a lower GFR, a higher blood pressure and a higher albumin-to-creatinine ratio in early adulthood. Method: A total of 261 young adults born SGA, previously treated with growth hormone (SGA-GH), were longitudinally followed. Glomerular filtration rate, based on serum creatinine levels, was determined at cessation of GH treatment and at 6 months, 2 years and 5 years thereafter. Glomerular filtration rate, blood pressure and urinary albumin-to-creatinine ratio at 5 years after cessation of GH were compared with untreated age-matched controls (56 untreated short subjects born SGA [SGA-S], 118 subjects born SGA with spontaneous catch-up growth [SGA-CU], 135 subjects born appropriate for gestational age [AGA]). Results: Glomerular filtration rate decreased significantly only during the first 6 months after cessation of GH treatment, while remaining well within the normal range (124.6 vs 120.2 mL/min/1.73 m2, P

Background In children born small for gestational age (SGA) with persistent short stature, 2 years of gonadotropin-releasing hormone analogue (GnRHa), in addition to long-term growth hormone (GH) treatment, can improve adult height. We assessed safety on metabolic and bone health of GnRHa/GH treatment during 5 years after cessation of GH. Methods A total of 363 young adults born SGA, previously treated with combined GnRHa/GH or GH-only, were followed for 5 years after attainment of adult height at GH cessation and 2 and 5 years thereafter. Data at 5 years after GH cessation, at age 21 years, were also compared with 145 age-matched adults born appropriate for gestational age (AGA). Frequently sampled intravenous glucose tolerance (FSIGT) tests were used to assess insulin sensitivity, acute insulin response, and β-cell function. Body composition and bone mineral density (BMD) was determined by dual-energy x-ray absorptiometry (DXA) scans. Findings In the GnRHa/GH and GH-only groups, fat mass increased during the 5 years after GH cessation, but the changes in FSIGT results, body composition, blood pressure, serum lipid levels, and BMD were similar in both groups. At age 21 years, the GnRHa/GH group had similar fat mass, FSIGT results, blood pressure, serum lipid levels and BMD-total body as the GH-only group and the AGA control group, a higher BMD-lumbar spine and lower lean body mass than the AGA control group. Interpretation This study during 5 years after GH cessation shows that addition of 2 years of GnRHa treatment to long-term GH treatment of children short in stature born SGA has no unfavorable effects on metabolic and bone health in early adulthood. Clinical trial registration ISRCTN96883876, ISRCTN65230311 and ISRCTN18062389.

Objective Adults with Prader–Willi syndrome (PWS) are at increased risk of developing age-associated diseases early in life and, like in premature aging syndromes, aging might be accelerated. We investigated leukocyte telomere length (LTL), a marker of biological age, in young adults with PWS and compared LTL to healthy young adults of similar age. As all young adults with PWS were treated with growth hormone (GH), we also compared LTL in PWS subjects to GH-treated young adults born short for gestational age (SGA). Design Cross-sectional study in age-matched young adults; 47 with PWS, 135 healthy, and 75 born SGA. Measurements LTL measured by quantitative polymerase chain reaction, expressed as telomere/single copy gene ratio. Results Median (interquartile range) LTL was 2.6 (2.4–2.8) at a median (interquartile range) age of 19.2 (17.7–21.3) years in PWS, 3.1 (2.9–3.5) in healthy young adults and 3.1 (2.8–3.4) in the SGA group. Median LTL in PWS was significantly lower compared to both control groups (P < .01). In PWS, a lower LTL tended to be associated with a lower total IQ (r = 0.35, P = .08). There was no association between LTL and duration of GH treatment, cumulative GH dose, or several risk factors for type 2 diabetes mellitus or cardiovascular disease. Conclusions Young adults with PWS have significantly shorter median LTL compared to age-matched healthy young adults and GH-treated young adults born SGA. The shorter telomeres might play a role in the premature aging in PWS, independent of GH. Longitudinal research is needed to determine the influence of LTL on aging in PWS.

Accelerated gain in fat mass (FM) in early life increases the risk for adult diseases. Longitudinal data on infant body composition are crucial for clinical and research use, but very difficult to obtain due to limited measurement tools and unsuccessful measurements between age 6-24 months. We compared FM% by dual-energy X-ray absorptiometry (DXA), with cushion to reduce movement artifacts, with FM% by air-displacement plethysmography (ADP) and evaluated the reliability of this cushion during DXA by comparing FM% with and without cushion. Subsequently, we constructed sex-specific longitudinal body composition charts from 1-24 months.In 692 healthy, term-born infants (Sophia Pluto Cohort), FM% was measured by ADP from 1-6 months and DXA with cushion from 6-24 months. At 6 months, FM% was measured in triplicate by ADP and DXA with and without cushion(n = 278), later on in smaller numbers.At 6 months, mean FM% by DXA with cushion was 24.1 and by ADP 25.0, mean difference of 0.9% (Bland-Altman p = 0.321, no proportional bias). Mean FM% by DXA without cushion was 12.5% higher compared to ADP (Bland-Altman p 0.001). DXA without cushion showed higher mean FM% compared to DXA with cushion (+11.6%, p 0.001) at 6 months. Longitudinally, FM% increased between 1-6 months and decreased from 6-24 months(both p 0.001).In infants, DXA scan with cushion limits movement artifacts and shows reliable FM%, comparable to ADP. This allowed us to construct longitudinal body composition charts until 24 months. Our study shows that FM% increases from 1-6 months and gradually declines until 24 months.

Introduction:Treatment with aromatase inhibitors (AI) is a potential novel treatment in patients with congenital adrenal hyperplasia (CAH) and advanced bone age (BA), to increase near adult height (NAH). Not much is known about the efficacy of AI treatment in CAH and how AI treatment will influence the management of corticosteroid treatment. Case Presentation:At the age of 6 years and 3 months, a boy with salt-losing CAH presented with a BA 7 years in advance. Treatment with an AI (exemestane) was initiated to decelerate bone maturation. We continued the standard dosage of corticosteroid treatment. Precocious puberty was treated with 4 years of gonadotropin-releasing hormone agonist, while AI treatment was continued until attainment of NAH. His NAH 177.7 cm (–0.8 SDS) was considerably higher than his predicted adult height of 151.3 cm (–4.6 SDS) at the start of AI treatment. The higher serum androgen levels during AI treatment did not result in short adult stature. Discussion/Conclusion:This report shows that AI treatment can adequately decelerate bone maturation, causing predicted adult height to increase significantly in patients of CAH with accelerated bone maturation. We suggest continuing the same corticosteroid dosage during AI treatment and accepting higher serum androgen levels.

ContextPercutaneous epiphysiodesis (PE) around the knee to reduce predicted excessive final height. Studies until now included small numbers of patients and short follow-up periods.Objective and designThis Dutch multicentre, long-term, retrospective, follow-up study aimed to assess adult height (AH), complications, knee function and patient satisfaction after PE. The primary hypothesis was that PE around the knee in constitutionally tall boys and girls is an effective treatment for reducing final height with low complication rates and a high level of patient satisfaction.Participants77 treated adolescents and 60 comparisons.InterventionPercutaneous epiphysiodesis.OutcomeAH, complications, knee function, satisfaction.ResultsIn the PE-treated group, final height was 7.0 cm (±6.3 cm) lower than predicted in boys and 5.9 cm (±3.7 cm) lower than predicted in girls. Short-term complications in file search were seen in 5.1% (three infections, one temporary nerve injury), one requiring reoperation. Long-term complications in file search were seen in 2.6% (axis deformity 1.3%, prominent head of fibula 1.3%). No significant difference in knee function was found between treated cases and comparisons. Satisfaction was high in both the comparison and PE groups; most patients in the PE group recommended PE as the treatment for close relatives with tall stature.ConclusionPE is safe and effective in children with predicted excessive AH. There was no difference in patient satisfaction between the PE and comparison group. Careful and detailed counselling is needed before embarking on treatment.