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We know that tocolytic agents effectively inhibit uterine contractions, but the evidence for improved perinatal outcomes is much less clear. Why is this so, and what are the implications for your patients?
Tocolysis could be said to "work," for example, if it improves maternal quality of life, decreases the number and duration of triage evaluations,2 or allows outpatient management after resolving an acute episode of preterm labor. Many perinatologists, however, would hesitate to say that tocolysis "works" if they could not demonstrate changes in neonatal mortality or morbidity. Unfortunately, available tocolytics have not produced a clear improvement in perinatal outcomes.
The discrepancy between the ability of tocolytics to inhibit uterine contractions and their apparent inability to improve neonatal outcomes remains a mystery. Possible explanations for this paradox include:
Does tocolysis address the underlying causes of preterm labor?
Intuitively, the relationship between uterine contractions and preterm birth should be straightforward: Uterine contractions progressively dilate the cervix and eventually expel the fetus from the uterus if they are not inhibited pharmacologically. This is the principle underlying the use of tocolytic medications. It has become clear, however, that contractions are merely the end organ response to the process of parturition.
STOPPING CONTRACTIONS probably does little to modify the mechanisms leading to preterm labor. This process-characterized by increases in gap junctions, oxytocin receptors, and contractile efficiency-may be initiated by many factors, including intrauterine infections (IUI), decidual hemorrhage, uterine overdistension, or fetal or maternal stress.3 Tocolytic agents do not alter any of these stimuli. If the myometrial response to a parturitional stimulus is blocked pharmacologically while the underlying pathologic process is allowed to progress, myometrial inhibition will likely fail.
If tocolysis cannot address the underlying cause of preterm labor, the risk of artificially maintaining the fetus in a uterus where a pathologic process, especially IUI, is present may outweigh the risks of prematurity itself. For this reason, tocolysis is generally not recommended in the presence of overt IUI. (An exception may be intrauterine Listeria infection, which can be treated effectively with antibiotics.)
Many women in preterm labor do not exhibit overt clinical evidence of IUI, yet may have subclinical infection.4 Gomez and colleagues demonstrated an association between increasing rates of positive amniotic fluid cultures and decreasing gestational age and cervical length among patients in preterm labor.4 Tocolysis in such patients might maintain the fetus in an infected environment from which it would have otherwise been expelled. Even if the fetus does not become infected directly, intrauterine exposure to inflammatory cytokines may have detrimental effects, a phenomenon known as the Fetal Inflammatory Response Syndrome. 5 Cytokines have been linked to cerebral palsy,6 bronchopulmonary dysplasia,7 and other disorders.