Intrauterine growth retardation - The role of insulin-like growth factors in the regulation of fetal growth

Fetal growth retardation and preterm delivery remain the most important risk factors contributing to perinatal mortality and morbidity. Furthermore, as shown in recent follow-up studies, IUGR children often suffer from retarded somatic and psychomotor development, i.e. poor speech development, deficient audio-visual perception, poor fine- and coarse-motor skills and abnormal social behaviour, as well as slow growth. The incidence of IUGR ranges from 3-10% in industrial countries, depending on definition of the term. Symmetric and asymmetric IUGR can be differentiated by evaluation of etiological factors and the time of onset of IUGR. Detection of IUGR requires meticulous prenatal care and observation, including early determination of gestational age by ultrasound examination, and close monitoring of fetal growth throughout pregnancy. Doppler ultrasound investigation of the fetal circulation is an important means of monitoring the growth-retarded fetus. There is still no screening method for IUGR. Fetal growth in utero is determined by several factors. The question of how it is regulated has been intensively researched. It is now well established that insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) as well as growth hormone (GH) and human placental lactogen (HPL) play an important role in the regulation of fetal growth in utero. IGFs and IGFBPs are detectable in fetal, maternal and placental tissues from early pregnancy onwards. Levels of IGF-I and IGF-II in the fetal circulation increase during pregnancy, and, at term, levels of IGF-I are directly related to birthweight. The main binding proteins for IGFs in the human fetus are IGFBP-1 and IGFBP-2. Fetal levels of circulating ICF-I are reduced in cases of IUGR, while fetal levels of IGFBP-1 and IGFBP-2 are increased. Maternal levels of IGFBP-1 are elevated in IUGR. Recent studies have attempted to elucidate feedback mechanisms underlying IUGR at the molecular-biological level. Our long-term aim is to find a way to treat IUGR in utero. In view of the early- and late morbidity of children affected by this condition, this remains an urgent task.