“Preterm labor can no longer be considered a single disease…(it) is the clinical expression of different pathologic insults to the feto-maternal unit.” Roberto Romero, 1993
It is clear that there are a variety of initiating factors that can lead to preterm labor, but it is equally likely that in many cases, there is an end-stage “final common pathway” to the process that results from ‘activation’ of the placental bed and fetal membranes to initiate uterine contractions, cervical ripening, and rupture of membranes. If we are to logically approach the management of preterm labor and delivery, we must methodically dissect the correlates, identify those most amenable to intervention, and then attempt a multidisciplinary approach to reduce/interrupt their contributions to the “final common pathway.”
For the sake of simplicity, when I discuss preterm labor (or recurrent pregnancy loss) with patients, I like to lump certain risk factors into broad categories. I also make it very clear at the outset of the discussion, that there may well be overlap (and questions as to “which came first, the chicken or the egg”) in terms of how these different factors ultimately result in preterm labor and delivery.
The first category I usually discuss is uterine abnormalities. I break this down into structural abnormalities and abnormalities of volume. Structural abnormalities include congenital abnormalities of the uterus (Mullerian abnormalities) such as bicornuate (double) or septate (divided) uteri, cervical incompetence, and common neoplasms (growths) such as uterine fibroids (leiomyomata) and polyps. Mullerian abnormalities can result in a smaller uterine cavity, fewer suitable implantation sites, and cervical incompetence, which frequently accompanies septate uteri. Uterine fibroids can distort and/or decrease the volume of the uterine cavity, compromise implantation or growth of the placenta, and if located in proximity to the cervix, distort the internal cervical opening (os) sufficiently to cause cervical incompetence as well. Endometrial polyps, and also submucosal (just under the inner uterine lining) and pedunculated fibroids (on a stalk and protruding into the uterine cavity), can in some instances act like an IUD, by preventing implantation, or provide a site of chronic inflammation or infection that can play a large role in the “final common pathway” to preterm labor and delivery. Although structural abnormalities of the uterus account for probably no more than 5-10% cases of PTB, the reason I discuss them first is they can be easily diagnosed and are amenable to surgical interventions between pregnancies (and during pregnancy in the case of cervical incompetence) that can play a significant role, if successful, in reducing the risk of PTB.
Under the subcategory of abnormalities of uterine volume, I usually discuss factors that cause the uterus to enlarge more quickly and to a greater extent than would ordinarily occur during a normal pregnancy. (Stretching of the uterine muscle, before it can accommodate to distention, results in contractions and these, accompanied by ‘volume overload,’ put a lot of stress on the uterus at its weakest point, the cervix). Included in this category are multifetal gestations and polyhydramnios (too much amniotic fluid). These factors tend to be of greatest concern in women who are pregnant for the first time or who have a small uterine cavity for any of the reasons mentioned above. Although at least 50% of polyhydramnios is “idiopathic” (i.e., we aren’t smart enough to figure out why it’s there), it is also common with diabetes and with fetal conditions that prevent recycling of amniotic fluid. Amniotic fluid is produced constantly and to maintain a ‘balance’ requires fetal swallowing and a patent gastrointestinal tract. Neuromuscular disorders, chromosomal abnormalities, and/or structural abnormalities of the esophagus, stomach, and bowel that either prevent swallowing or passage of fluid through small bowel to the colon where it can be reabsorbed into the fetal circulation (and the excess then passed across the placenta to the mother for disposal) can result in too much fluid. Multifetal pregnancies, above and beyond the excess volume (and rapid uterine distention) related to the growth of two or more babies, placentas, and fluid, can also be accompanied by polyhydramnios for any of the reasons previously noted, such as diabetes and fetal anomalies, and also as the result of a condition that is specific to monochorionic multiple gestations, “twin-to-twin transfusion sequence.” Let’s save that discussion for another day!
The next broad category I usually discuss is factors that are associated with increased uterine contractions during pregnancy. The uterus is largely composed of smooth muscle (like the bladder, gastrointestinal tract, and blood vessels). Smooth muscle has an innate tendency to contract spontaneously, and that tendency is increased when it is stretched. During normal pregnancy, it is not unusual for the uterus to have irregular, noncoordinated (involving only small portions of the uterus) contractions, beginning in early second trimester. Many factors, especially the hormone progesterone, produced in early pregnancy by the corpus luteum (site of the egg production in the ovary) and then by the placenta in large quantities, help to keep the uterus ‘quiet,’ down-regulating the anatomical/physiological changes (neurologic and muscular connections and communication) that usually do not develop until late in pregnancy and that facilitate the coordinated uterine contractions (the entire uterus contracting at once) that are necessary for labor.
Some women tend to contract more than others during pregnancy. In general, women who contract more, or have a higher frequency of ‘coordinated uterine contractions’ earlier in pregnancy, are at somewhat greater risk for PTB than women who don’t. Reasons some women spontaneously contract more (or contract more effectively when they shouldn’t be) are not clear. In the absence of extenuating factors, genetic predisposition may play a role here. Do they make less progesterone or other endogenous tocolytic (smooth muscle relaxing) substances? Are they less sensitive to these substances? Do they make larger amounts of factors that promote the neuromuscular connections that lead to coordinated uterine activity? Or, are they more sensitive to these latter substances than ‘normal’ women? We know that certain ‘environmental’ factors can increase uterine activity, including stress (psychological and physical), tobacco products, cocaine, and methamphetamine. It is likely that poor nutritional status, deficiencies of certainvitamins such as folic acid, and maternal anemia may contribute as well for reasons that are also not clear. This category of conditions, potentially, also lends itself to intervention for PTB prevention, but is much more challenging because both medical and social support services often need to work in concert to truly address the multiplicity of issues that can lead to increased uterine activity.
We will continue this discussion in a subsequent post. Until then, see ya’….