Prenatal treatment of intrauterine growth restriction: lessons from the sheep model

Intrauterine growth restriction (IUGR) has both immediate and long-term consequences for the affected fetus, resulting in increased perinatal morbidity and mortality, growth failure, intellectual deficits and an increased risk of adult diseases including cardiovascular disease, diabetes and stroke. Although the diagnosis is now easily made, as yet there are no treatments available for established IUGR. Postnatal interventions to increase growth have not been demonstrated to reduce long-term consequences. It is theoretically possible that intrauterine interventions might reduce both the immediate perinatal risks and also those of adverse long term outcomes. The sheep has long been used to study fetal physiology, including IUGR. This paper will discuss the various routes of administration (mother, fetus and amniotic fluid) of various interventions (nutritional, hormonal or both) that have been tested experimentally. Several interventions have been demonstrated to prevent IUGR and some show promise in reversal of established IUGR, but none yet provide a definitive treatment. It may be that a much greater understanding of the hormonal and metabolic regulation of fetal growth is necessary before a successful treatment will be found.