Maternal constraint of fetal growth and its consequences.

The major non-genetic factor determining the size of the fetus at term is maternal constraint. This term refers to a set of poorly defined processes by which maternal and uteroplacental factors act to limit the growth of the fetus, presumably by limiting nutrient availability and/or the metabolic-hormonal drive to grow. Maternal constraint can be divided into supply-limited constraint (e.g. maternal size) and demand-driven constraint (e.g. twinning). Maternal constraint acts in all pregnancies, but is greater in some situations, particularly those involving young maternal age, small maternal size, nulliparous and multiple pregnancies. Maternal constraint is an important physiological cause of the variation in birth size, but is not without longer-term consequences. There is increasing evidence that maternal constraint is an important factor in determining the increased risk of adult diseases in those who have poor fetal growth due to pathophysiological factors. The evidence is reviewed and placed in the context of discussing the evolutionary significance of maternal constraint. The role of predictive adaptive responses as the basis of programming, and the effects of maternal constraint on these responses are discussed. Changing demography means that maternal constraint must increasingly be considered as a significant factor in determining the pattern of disease.