Growth and Metabolism in Children Born Small for Gestational Age

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Key points

  • Growth hormone (GH) treatment effectively induces catch-up growth and improves adult height in most short children born small for gestational age (SGA).

  • During GH treatment, fat mass, insulin sensitivity, and blood pressure decrease, whereas lean body mass increases; favorable changes occur in lipid levels.

  • GH-induced lower insulin sensitivity is reversible after GH treatment and 6.5 years thereafter it is similar in GH-treated and untreated short SGA adolescents.

  • At 6.5 years after GH treatment,

Small for gestational age

Small for gestational age (SGA) accounts for approximately 20% of all cases of short stature.2 SGA refers to the size of an infant at birth. It is defined as a birth length and/or weight of at least 2 standard deviation scores (SDS) below the mean for gestational age and gender.3 The etiology of SGA consists of a broad spectrum of maternal, environmental, placental, and fetal factors, but in a significant proportion of cases the reason for being born SGA remains unclear. By definition, 2.3% of

Effects of growth hormone treatment in children born small for gestational age

An overview of the main effects of GH treatment is shown in Table 2.

Metabolic and endocrine consequences in adults born small for gestational age

Low birth weight is associated with metabolic and cardiovascular adult diseases in late adulthood.30, 31

Combining growth hormone treatment with gonadotropin-releasing hormone analog treatment

Data have shown that children born SGA with an expected AH less than −2 SDS at start of puberty can benefit from additional GnRHa treatment to delay puberty for 2 years.11 Recently, it has been shown that combined GH/GnRHa treatment results in a similar body composition, insulin sensitivity, blood pressure, and lipid levels at AH as treatment with GH only.42, 43 Additional GnRHa treatment for 2 years can therefore be considered in pubertal SGA children with a poor AH expectation.

Summary

Short stature is one of the most common conditions presented to pediatric endocrinologists. SGA accounts for approximately 20% of all cases of short stature. Most children born SGA show spontaneous catch-up growth to a normal weight and height above −2 SDS; however, 10% remain short and can be treated with GH to improve AH. GH treatment is effective in inducing catch-up growth and improving AH. It also has positive effects on several risk factors for type 2 diabetes and cardiovascular disease.

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      A majority of previous studies have reported that maternal exposure to ambient air pollution around pregnancy was associated with increased risks of adverse birth outcomes, such as stillbirth, preterm birth (PTB), small for gestational age (SGA), low birth weight (LBW) and large for gestational age (LGA) (Chen et al., 2020; Melody et al., 2020; Yuan et al., 2019; Zhao et al., 2018). Adverse birth outcomes can not only have a severe impact on the normal development of childhood but also increase risks of diabetes, cardiovascular disease, chronic respiratory disease, metabolic system disease and neurobehavioral problems in adulthood, imposing a huge economic burden on society (Aarnoudse-Moens et al., 2009; Caudri et al., 2007; Levine et al., 2015; Norman and M, 2013; Rundle et al., 2012; Saigal and Doyle, 2008; Trasande et al., 2016; van der Steen and Hokken-Koelega, 2016). However, to the best of our knowledge, no study has explored the durational effects of sustained maternal exposure to high-level air pollution on adverse birth outcomes, though increasing epidemiological studies demonstrated that single days of high ambient air pollution could increase risks of adverse birth outcomes (Guo et al., 2019; Li et al., 2019).

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      If this treatment produces antibodies against GH arresting growth, rhIGF1 could be employed. In children born Small for Gestational Age that remain short, rhGH improves adult height [87,88]. Furthermore, some children with Silver-Russell syndrome have also been treated with rhGH, with good results [17].

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      When corrected for mid-parental target height the overall height gains were slightly less: 1.46 SDS (9.2 cm) in those children born SGA and treated with rhGH and 0.4 SDS (2.5 cm) compared to those who did not receive rhGH therapy. In addition to promoting longitudinal growth, rhGH treatment of short children born SGA also favorably affects body composition, blood pressure and lipid metabolism [67–69]. Several factors are associated with GH response including age and height at start of therapy, mid-parental height and dose [10].

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    Disclosure Statement: A.C.S. Hokken-Koelega received unrestricted research grants from Novo Nordisk and Pfizer for investigator initiated growth hormone studies in short children born SGA. M. van der Steen has nothing to disclose.

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