The Preterm Parturition Syndrome

Experimental distention of the uterus with a saline-filled balloon rapidly prompted regular uterine contractions in women carrying live term fetuses or dead fetuses. All were delivered within 21 hours.

Stephen Lye, Ph.D., and his group at the University of Toronto have found increased expression of oxytocin receptor, connexin 43, and the c-fos mRNA in the myometrium. Gillian Bryant-Greenwood, Ph.D., at the University of Hawaii, Honolulu, has shown that stretching of the chorioamniotic membranes in experimental models can increase the expression of interleukin-8 and also another cytokine called visfatin, which can have important effects on the integrity of the membranes.

EAR: I noticed that cervical pathology is also a potential cause of the preterm parturition syndrome. Is this the same as cervical insufficiency?

RR: Yes. Cervical insufficiency is also a cause of the preterm parturition syndrome and can result from congenital disorders, surgical trauma, trauma, or infection. Although cervical length has been touted as a predictor of preterm birth, it is important to remember that a short cervix is not always a ripe cervix. Once again, more research is needed to identify the events that occur as a result of cervical insufficiency, and the ways these affect the initiation of preterm and term labor.

EAR: What about abnormal allograft reaction?

RR: The fetoplacental unit has been called “nature's most successful transplant,” or—more accurately—a “semiallograft.” The mechanisms that bring about tolerance of this semiallograft are poorly understood. However, transplants of solid organs are tolerated through the establishment of microchimerism in the transplanted organ as well as in the host. Therefore, we consider that microchimerism in pregnancy is probably important for tolerance of the fetoplacental unit. However, I anticipate that under pathologic conditions—just as in the case of transplants—tolerance of the fetoplacental unit may break down, which in turn may lead to a unique form of rejection of the fetoplacental unit. Unraveling the mechanisms of this rejectionlike process is a fascinating challenge. However, ob.gyns. know that the frequency of adverse pregnancy outcomes is higher in mothers who have pregnancies after embryo or egg donation. Under these circumstances, the placenta and fetus are totally foreign because they do not have the normal 50% genetic endowment from the mother. The complications noticed in these pregnancies include not only preeclampsia and growth restriction, but also preterm labor.

EAR: What is the evidence that an allergic phenomenon could be associated with premature labor, and could antihistamines be a treatment for premature labor?

RR: This idea came to me after seeing the relative of an obstetrician who went into premature labor after eating shellfish to which she was allergic. Around that time, we observed that a group of women in premature labor had eosinophils in the amniotic cavity. Eosinophils are associated with an allergiclike phenomenon and are not normally present in the amniotic cavity. The evidence to support biologic plausibility was generated in our work with Dr. Robert Garfield and Dr. Egle Bytautiene. We were able to demonstrate that guinea pigs allergic to egg proteins (ovalbumin) went into premature labor when challenged with the allergen during pregnancy. Premature labor could be prevented by the administration of an antihistamine in these animals.

We have interpreted this as evidence that some patients with premature labor may have an allergiclike reaction or type I hypersensitivity reaction. The nature of the allergen may vary. However, we know that allergens can cross the placenta. For example, dust mite antigen has been demonstrated in the amniotic fluid of women in the midtrimester of pregnancy. Also, there is evidence that the fetus is able to recognize and mount an immune response to allergens in utero.

In response to your question, we have treated with antihistamines some patients who have a typical allergiclike history along with premature labor, and this has resulted in the disappearance of uterine contractions. However, these are anecdotal reports, and I would like to stress that our interest in this mechanism of disease stems from the importance of demonstrating that a common mechanism of disease, such as allergy, can be a cause of the preterm parturition syndrome. This should not be surprising, because the uterus is bestowed with mast cells, the key effector cells of an allergic response, and the uterus has all the components required to generate an allergiclike immune response.

EAR: What is the evidence and importance of hormonal dysfunction in premature parturition?

RR: Progesterone withdrawal and/or deficiency has not yet been specifically demonstrated as an initiator of spontaneous parturition in humans. However, the role of progesterone in maintaining pregnancy is unquestionable.