Aberrant Fetal Clock

The idea that preterm delivery is due to an aberrant fetal clock is one theory that has been around for a long time, according to some participants. This theory developed because the fetus stimulates the onset of normal labor, probably through endocrine and paracrine mechanisms, but also through mechanical stimulation, said James Roberts of Magee-Women’s Research Institute. As discussed Chapter 2, as the fetus grows there is an increase in uterine size. The uterus is usually able to accommodate the growing fetus as long as progesterone is present. A recognized cause of preterm birth is, in fact, uterine distension with multiple gestations, or polyhydramnios. In this case, the symptom certainly occurs earlier, and we have an aberration of that particular component of the clock starting labor. However, Roberts cautioned that most people would not agree that the majority of preterm labor is just term labor occurring early. He suggested that we currently do not know enough about preterm labor to assume any hypothesis.

Abnormal Implantation

Implantation occurs approximately five days after fertilization. In order to supply the placenta and ultimately the fetus, a number of changes in the vascular system of the uterus occur. In the normal pregnancy, there is striking remodeling of the vessels that supply the intravillous space, resulting in a marked increase in luminal diameter and the loss of smooth muscle and elastic components of the vessel wall. The endothelial lining is replaced at least in part by trophoblastic cells that have been modified to express a vascular phenotype.

Roberts noted that under certain conditions, this normal remodeling and the subsequent increase in blood supply to the placenta do not occur—for example, in preeclampsia, growth restriction, and one-third of preterm birth. This suggests that preterm birth may be one of a number of implantation diseases, and these various conditions may have a number of similarities. For example, abnormal implantation is more likely to occur in a first pregnancy. In a recent study, Roberts found an additional link between preterm birth and preeclampsia. The iron storage protein ferritin—a measure of serum iron levels—is linked to both acute and chronic infections. In both preeclamptic pregnancy and preterm birth, ferritin is increased in the blood of these women long before they deliver preterm. This suggests an increase in inflammatory activation in early delivery and preeclampsia (see cytokines below).

Preterm Birth and Infection

In the 1980s and 1990s researchers suggested that subclinical infections in either the choriodecidual space or the amniotic cavity may lead to preterm birth. Interestingly, according to Robert Goldenberg, up to 80 percent of early preterm



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