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Fetal growth restriction remains one of the major problems currently facing obstetricians; it contributes significantly to preterm birth rates (both iatrogenic and idiopathic), together with perinatal morbidity and mortality.1 Recent epidemiological data suggest that “prenatal programming” due to intrauterine growth restriction (IUGR) may also predispose surviving infants to diseases in adult life.2
Hepatocyte growth factor (HGF) is a ubiquitous and pluripotent cytokine with a variety of paracrine and endocrine effects that was first identified 15 years ago.3 In vitro studies have suggested that important steps in organogenesis may be mediated by HGF,4 and more recent in vivo “gene knockout” studies using mice constructs have indicated a crucial role for HGF and its receptor c-met in placental and fetal hepatic growth and development.5-7
Growth factors and intrauterine growth restriction
The development of the fetus is under multifactorial control: the inherent drive to body growth determined by the fetal genome is tempered by “epigenetic” or environmental factors that alter its expression.8 The aetiology of IUGR can therefore be divided into those factors affecting the genome itself (for example, karyotypic abnormalities such as trisomies and triploidies), and those altering its expression.
Other than fetal insulin, none of the major endocrine hormones (maternal or fetal) seems to have a direct influence on fetal growth.9 The current view is that locally synthesised macromolecules (for example, growth factors and cell adhesion molecules), acting either in an autocrine or paracrine manner, regulate embryonic organ and tissue growth. The epigenetic factors associated with IUGR must therefore in some way affect these molecules or their receptors.
Clinically, other than chromosomal abnormalities and viral infections, most IUGR is attributed to inadequate substrate supply to the fetus. This may be due to reduced availability to the placenta itself (maternal malnutrition), or to poor placental function (“placental insufficiency”). From the …