Department of Paediatrics; University of Cambridge
In 1991 Haig, observing the reciprocal imprinting/expression of IGF2 and IGF2R, considered whether they reflected the competing interests of mother and baby. In the ALSPAC cohort we observe maternal restraint of fetal growth particularly during primigravid pregnancies, which is related to maternal BW and associated with mitochondrial H19 and maternal transmission of H19. IGF2R is related to size at birth but its imprinting status is uncertain. In subsequent pregnancies fetal weight gain may be enhanced and linked to BW of both parents, maternal weight gain and parity. Links between paternally expressed genes regulating IGF2 expression and size at birth are strong and may include INS VNTR class III alleles. These variable influences on fetal growth have complications for postnatal development. Putative thrifty genes such as INS VNTR III have been linked to a risk of IR in childhood, PCOS and type 2 in adults. Postnatal catch up in restrained infants is influenced by common genetic variation including INS VNTR which could serve to enhance early survival, but in contemporary society increase obesity risk, insulin resistance and syndrome X. The genetic environmental interactions which affect size at birth may be more complex than first proposed, but they undoubtedly evolved to optimize maternal/fetal survival - now they also have implications for childhood growth and adult disease risk.