Managing Preterm Labor in Multiple Gestations

Studies are underway that may provide us with more guidance in the use of this agent. However, no evidence exists that it is safe and efficacious in multiple gestation pregnancies, so I suggest its use be reserved for patients in clinical trials.

Antibiotics

It is tantalizing to believe antibiotics would be helpful in preventing or treating preterm labor. Many researchers theorize that intrauterine infection or fetal infection may be responsible for preterm labor, particularly in pregnancies that are not complicated by multiple fetuses. However, the data do not show that antibiotic treatment is any more efficacious than placebo in prolonging pregnancy or preventing preterm delivery.

Tocolytics

The use of tocolytics to decrease or halt preterm labor is controversial in multiple gestations as well as in singleton pregnancies because the drugs pose risks to the mother and, in some cases, to the fetus. However, the available data support the position that tocolytic agents work for a short period—about 48 hours, although Roger B. Newman, M.D., and colleagues have shown that some multiple gestations can be prolonged for more than 7 days (Am. J. Obstet. Gynecol. 1989;161:547–55; “Multifetal Pregnancy: A Handbook for Care of the Pregnant Patient” [Philadelphia: Lippincott Williams & Wilkins, 2000]).

Each tocolytic agent carries its own benefits, risks, contraindications, and adverse effects profile. Numerous sources are available for this information; for quick reference; I recently published a summary in chart form (Clin. Obstet. Gynecol. 2004;47:216–26). Keep in mind that women with multiple gestations have an elevated risk of cardiovascular complications, such as pulmonary edema resulting from anemia, lower colloid oncotic pressure, and higher blood volume.

I would take a middle-of-the-road approach in choosing an agent or agents for tocolysis. For example, oral terbutaline, oral calcium channel blockers, and oral Indocin have been well-studied and widely used, with varying levels of success.

John P. Elliott, M.D., and Tari Radin, Ph.D., studied a small number of high-order multiple gestations and found similar levels of serum magnesium in triplets and quadruplets and in singleton pregnancies after the administration of magnesium sulfate for tocolysis (J. Reprod. Med. 1995;40:450–2). However, they concluded that higher levels of magnesium sulfate are needed in multiple gestations to inhibit labor. They suggested administration at infusion rates of 4–5 g/h in triplet and quadruplet pregnancies.

Research on combination tocolytic therapy has produced conflicting results. Most of the studies on this topic are dated, limited in scope, and not specifically focused on multiple gestations. Some concerns, however, have been raised. For example, magnesium sulfate administered in conjunction with nifedipine can result in significant neuromuscular blockage and a subsequent marked hypotensive effect.

My recommendation is to administer combination tocolytic therapy only with great caution, using agents such as intravenous magnesium sulfate with oral terbutaline or indomethacin. The mother and fetus also should be monitored closely by professionals well-versed in side effects linked to this form of therapy.

Should tocolytic therapy be maintained after successful cessation of labor? A careful reading of the available evidence suggests the answer is no. In well-designed studies, maintenance tocolytic therapy has reduced neither preterm deliveries nor perinatal morbidity or mortality.

Corticosteroids

Corticosteroids are among the few noncontroversial agents for use during preterm labor. These agents—which clearly reduce the incidence and severity of neonatal respiratory distress syndrome, intraventricular hemorrhage, necrotizing enterocolitis, and neonatal mortality—should be administered to any patient in preterm labor at 24–34 weeks, using the same regimen as in singleton gestations.

The accepted corticosteroid treatment consists of two intramuscular doses of betamethasone or four intramuscular doses of dexamethasone.

In higher-order gestations, Dr. Elliott and Dr. Radin have observed that beta-methasone can increase uterine contractions and advance labor in patients with frequent contractions. They therefore recommend that corticosteroids be reserved in these pregnancies for patients having fewer than three contractions per hour (Obstet. Gynecol. 1995;85:250–54). Uterine activity in higher-order gestations should be closely monitored following the administration of corticosteroids.

It once was suggested that multiple courses of prenatal corticosteroids might be of benefit. This recommendation is no longer made, because there is no good evidence for enhanced efficacy and because repeated doses are associated with clear risks, including decreased fetal growth and reduced birth weight.

Adjunctive Treatments

Isolated studies have suggested a role in preterm labor for such interventions as vaginal lever pessaries, blood transfusions, and cerclage. None of these have been put to rigorous scientific scrutiny. Cerclage obviously has no role in patients who do not have an incompetent cervix, or in such specific cases as the previable delivery of one dichorionic twin when a delayed-interval delivery of the second twin is desired.