Reduced growth in fetal life together with accelerated growth in childhood results in an ~50% greater risk of coronary heart disease in adult life. It is unclear why changes in growth patterns in early life lead to a vulnerability to cardiovascular disease. IGF1 acts via the IGF1 receptor (IGF1R) both in vivo and in vitro to increase the size of cardiomyocytes but when IGF1R is blocked in vitro, addition of IGF2 results in an increase in the size of cardiomyocytes. The adaptation of the fetal heart to a period of reduced substrate supply has critical consequences for heart health in later life because at birth, the human heart contains most of the cardiomyocytes it will have for life. We have found that heart mass was maintained relative to fetal body mass, but that there was a relative increase in the size of binucleated cardiomyocytes in the heart of the IUGR sheep fetus. In addition, the low birth weight lamb has increased relative left ventricular weight at 21d of age. We propose that in response to a poor substrate supply in the fetus, the IGF1R signalling pathway plays a protective role in the heart. We also suggest that once up-regulated, the IGF2R signalling pathway mediates cardiomyocyte hypertrophy. This is a novel and significant hypothesis as it places the IGF2R, rather than the IGF1R, signalling pathway as a key mechanism underlying the changes in heart cell growth in utero which may contribute to a later vulnerability of the heart to pathological hypertrophy.