First trimester origins of fetal growth impairment.

The timing of factors that lead to disorders of fetal growth have been studied for many years. Previous studies have focused on disorders of the "second wave" of trophoblast invasion of myometrial arterioles and on fetal weight gain in the third trimester. Over the last 5 years, clinical studies have shown associations between first trimester ultrasound and biochemical parameters and the risk of later adverse perinatal outcome. First trimester growth restriction is associated with an increased risk of low birth weight, low birth weight percentile for gestational age and extremely preterm birth. This may reflect a defect in early pregnancy placentation and later adverse outcome. Consistent with this hypothesis, low first trimester circulating maternal concentrations of pregnancy-associated plasma protein A, a trophoblast-derived regulator of the insulin-like growth factor system, are associated with an increased risk of later stillbirth, growth restriction, pre-term birth and pre-eclampsia. Even among healthy women having normal pregnancies, first trimester circulating concentrations of pregnancy-associated plasma protein A correlate with the timing of spontaneous labor and the eventual birth weight. These analyses suggest that in some women complications of late pregnancy have their origins in the very earliest weeks of gestation and precede first attendance for prenatal care.