Children Born Small-for-Gestational Age: Postnatal Growth and Hormonal Status

Abstract

It is generally recognized that children born small-for-gestational age (SGA) have a 5–7 times higher risk of short stature than children born at normal size. It has been suggested that the programming of the endocrine axes occurs during critical phases of fetal development and is affected by intrauterine growth retardation. This study was undertaken to characterize the postnatal growth pattern and the final height of children born SGA, as part of a population- based study (n = 3,650), from birth to final height, and to evaluate the hormonal status in another group of prepubertal children born SGA (n = 134) without postnatal catch-up growth. The majority (88%) of ‘healthy’ full-term singleton SGA infants achieved catch-up growth during the first 2 years of life, and most of the increase in height occurred by 2 months of age. The SGA children who remained short at 2 years of age had a higher risk of short stature later in life. The risk of having a short final height (<–2 SDS) was five times higher for children with a low birth weight and seven times higher for those with a low birth length in comparison with children with a normal birth size. Moreover, about 20% of all children of short stature were born SGA. As a group, children born SGA will have a final height, expressed in SDS, as they had during the prepubertal years. This is in contrast to children, who became short postnatally. During puberty, these short children will have a mean height gain of 0.6 SDS for girls and 0.7 SDS for boys. The mean estimated secretion rate for growth hormone (GH) was lower in the short children born SGA compared with the reference groups born at an appropriate size for gestational age, of either short (p < 0.05) or normal stature (p < 0.001). Moreover, in the youngest children born SGA (2–6 years of age) a different pattern of GH secretion was found, with a high basal GH level, low peak amplitude, and high peak frequency. The majority of the children born SGA had levels of GH-binding protein within the range previously reported for normal children. However, the levels of insulin-like growth factor I (IGF-I), IGF-binding protein-3 (IGFBP-3) and leptin were significantly reduced compared with the reference values (p < 0.001, p < 0.01 and p < 0.001, respectively). In conclusion, the low spontaneous GH secretion rate and a disturbed GH secretion pattern, together with low serum levels of IGF-I, IGFBP-3 and leptin, might contribute to the reduced postnatal growth in some of the subgroup of children born SGA who remained short during childhood.

Neonatal growth and breast cancer risk in adulthood

“…The IGF system is associated with both breast cancer risk (Renehan et al, 2004;Fletcher et al, 2005;Rinaldi et al, 2006) and postnadir growth (Albertsson-Wikland et al, 1998;OgilvyStuart et al, 1998;Hikino et al, 2001;Skalkidou et al, 2003), and could therefore plausibly explain the association of postnadir growth with this risk. Our explanation of the association of immediate postnatal weight reduction with breast cancer risk invokes higher levels of pregnancy hormones, including oestrogens, on the basis of well-known properties of these hormones (Stachenfeld and Keefe, 2002;Gomella et al, 2004;Stachenfeld and Taylor, 2004).…”

“…No study, however, has investigated neonatal growth in relation to breast cancer risk, even though neonatal growth could be of particular importance, as it is strongly associated with neonatal IGF-1 levels (Albertsson-Wikland et al, 1998;Ogilvy-Stuart et al, 1998;Hikino et al, 2001;Skalkidou et al, 2003). IGF-1 levels, which could track through life, have been associated with breast cancer risk, particularly premenopausal breast cancer risk (Renehan et al, 2004;Fletcher et al, 2005;Rinaldi et al, 2006).…”

“…The decline is likely to reflect the extent of water retention by the newborn at the time of delivery, under the influence of pregnancy hormones, including oestrogens (Stachenfeld and Keefe, 2002;Gomella et al, 2004;Stachenfeld and Taylor, 2004). The rate of weight gain after the nadir is influenced by growth factors, notably the IGF system and its determinants (Albertsson-Wikland et al, 1998;Ogilvy-Stuart et al, 1998;Hikino et al, 2001;Skalkidou et al 2003).…”

Nephron Endowment and Filtration Surface Area in the Kidney after Growth Restriction of Fetal Sheep

“…A reduction in nephron number at birth could have long-lasting effects on renal function. Although IUGR infants may exhibit postnatal catch-up growth, in terms of body weight and height (4), the nephrons of the kidney can only enlarge after birth. Hence, a reduction in nephron endowment during fetal development could be causally related to the high incidence of renal disease in populations that have a high incidence of IUGR, such as the Australian Aborigines (5).…”

Pathogenesis of polycystic ovary syndrome: multifactorial assessment from the foetal stage to menopause

“…At the end of this period, the growth curves and development of these children are similar to the patterns observed in children born AGA (Albertsson-Wikland et al 1998). Compensatory growth is associated with hyperinsulinaemia, central obesity and adipose tissue dysfunction in childhood, factors that can alter the distribution of body fat and accelerate the onset of adrenarche and puberty, especially pubarche (Ibáñ ez et al 1998).…”