New Horizons in Short Children Born Small for Gestational Age

Abstract

Children born small for gestational age (SGA) comprise a heterogeneous group due to the varied nature of the cause. Approximately 85–90% have catch-up growth within the first 4 postnatal years, while the remainder remain short. In later life, children born SGA have an increased risk to develop metabolic abnormalities, including visceral adiposity, insulin resistance, and cardiovascular problems, and may have impaired pubertal onset and growth. The third “360° European Meeting on Growth and Endocrine Disorders” in Rome, Italy, in February 2018, funded by Merck KGaA, Germany, included a session that examined aspects of short children born SGA, with three presentations followed by a discussion period, on which this report is based. Children born SGA who remain short are eligible for GH treatment, which is an approved indication. GH treatment increases linear growth and can also improve some metabolic abnormalities. After stopping GH at near-adult height, metabolic parameters normalize, but pharmacological effects on lean body mass and fat mass are lost; continued monitoring of body composition and metabolic changes may be necessary. Guidelines have been published on diagnosis and management of children with Silver-Russell syndrome, who comprise a specific group of those born SGA; these children rarely have catch-up growth and GH treatment initiation as early as possible is recommended. Early and moderate pubertal growth spurt can occur in children born SGA, including those with Silver-Russell syndrome, and reduce adult height. Treatments that delay puberty, specifically metformin and gonadotropin releasing hormone analogs in combination with GH, have been proposed, but are used off-label, currently lack replication of data, and require further studies of efficacy and safety.

Pubertal timing in children with Silver Russell syndrome compared to those born small for gestational age

“…It is known that children who are born small for gestational age (SGA), including those with SRS, tend to have earlier and rapidly progressing puberty, with faster bone maturation and a shorter period of pubertal peak height velocity, associated with metabolic abnormalities such as visceral adiposity ( 12 – 15 ). According to the available literature, onset of puberty in SRS is usually within the normal range (8–13 years in girls and 9–14 years in boys) but at the younger end of the spectrum ( 2 , 12 , 15 , 16 ). SRS children (particularly those with 11p15LOM) can experience an early and rapidly progressive adrenarche in comparison with non-SRS SGA children ( 2 , 12 , 16 , 17 ).…”

“…According to the available literature, onset of puberty in SRS is usually within the normal range (8–13 years in girls and 9–14 years in boys) but at the younger end of the spectrum ( 2 , 12 , 15 , 16 ). SRS children (particularly those with 11p15LOM) can experience an early and rapidly progressive adrenarche in comparison with non-SRS SGA children ( 2 , 12 , 16 , 17 ). In a retrospective study including 62 subjects with clinical diagnosis of SRS, Binder et al.…”

Should Skeletal Maturation Be Manipulated for Extra Height Gain?

“…My interpretation of the available data goes a step further than the one taken by the International Consortium (“it is appropriate to consider the potential advantages and disadvantages of treatment with GH and GnRHa in this population”) and contrasts with a recent opposite view ( 62 ). I believe that there is sufficient evidence that co-treatment with a GnRHa for 2-3 years does increase AH in rhGH treated short SGA-born children if height SDS is <-2.5 at pubertal onset.…”

First Year Metabolic and Hormonal Behavior Define two Different Populations of SGA Newborn for Weight or Height

“…The GH IGF axis is fundamental to mediate fetal and early postnatal growth [ 12 ]. Accordingly, lower IGF-1, IGF-2, and IGF binding protein-3 (IGFBP-3) levels are detected during fetal life in SGA compared with appropriate-for-gestational-age (AGA) children [ 5 , 13 ]. In addition, SGA children who reached catchup growth show normal GH–IGF-1 axis early in postnatal, whereas GH deficiency and/or GH resistance could be detected in those children with persistent short stature [ 5 ].…”

“…In addition, SGA children who reached catchup growth show normal GH–IGF-1 axis early in postnatal, whereas GH deficiency and/or GH resistance could be detected in those children with persistent short stature [ 5 ]. Several studies evaluated IGF-1 and IGFBP-3 growth factors pre- and postnatally in SGA children, although confounding results have been reached so far, mainly because of the heterogeneous SGA classification and definition [ 13-15 ].…”