Preterm labor: Diagnostic and therapeutic options are not all alike

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Applied Evidence

Preterm labor: Diagnostic and therapeutic options are not all alike

J Fam Pract. 2005 March;54(3):245-252

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References

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Treating asymptomatic bacteriuria may prevent preterm labor

Asymptomatic bacteriuria in pregnant women has also been associated with preterm birth. One review of 14 trials comparing antibiotic treatment with placebo in this patient population—though not of high quality—demonstrated decreased incidences of pyelonephritis and preterm birth or low birth weight (LOE: 1).²⁵

Treating preterm labor

The primary goal of using tocolytics in preterm labor is to prolong pregnancy for 2 to 7 days, permitting administration of corticosteroids and transfer to a tertiary care center when necessary. Recommendations for the treatment of preterm labor are summarized in Table 3 .

TABLE 3
Evaluation of proposed treatments for preterm labor

Treatment	Comment	NNT	LOE	References
Calcium channel blockers	Reduce preterm delivery, decrease neonatal morbidity, well-tolerated	11	1	26, 27
Beta-agonists	Prolong pregnancy but no beneficial effect on neonatal morbidity; maternal side effects often lead to discontinuation	N/A	1	33, 34
Magnesium sulfate	Does not prolong pregnancy; maternal side effects often lead to discontinuation	N/A	1	33, 40
Prostaglandin inhibitors	Prolong pregnancy but no beneficial effect on neonatal morbidity; increase risk of postpartum hemorrhage	N/A	1	33
Prostaglandin inhibitors		N/A	2	43
Antibiotics	No evidence to support use	N/A	1	44
Corticosteroids	Strongly recommended; decrease neonatal morbidity, well-tolerated	U	1	46
NNT, number needed to treat; LOE, level of evidence; N/A, not applicable; U, unavailable data.

Calcium channel blockers safe, effective

Calcium channel blockers (CCBs) are nonspecific smooth muscle relaxants. They prevent the influx of extracellular calcium ions into the myometrial cell, thereby exerting their tocolytic effect. Nifedipine is the most widely studied CCB in the management of preterm labor.

A systematic review of 12 randomized controlled trials including 1029 women demonstrated that CCBs significantly reduced the rate of preterm delivery within 7 days of the start of treatment and before 34 weeks gestation (LOE: 1).²⁶ Compared with betamimetics, CCBs caused fewer maternal adverse effects, and decreased the frequency of neonatal respiratory distress syndrome, necrotizing enterocolitis, intraventricular hemorrhage, and jaundice. The authors concluded that CCBs are preferable to betamimetics for tocolysis.

Calcium channel blockers have also been compared with magnesium. Eighty women at 20 to 34 weeks gestation with documented cervical change were randomized to receive nifedipine or magnesium.²⁷ No difference in tocolytic efficacy was observed between the treatments, but there were significantly fewer maternal side effects among the nifedipine-treated patients (LOE: 2).

CCBs appear not to adversely affect the human fetus.^28,29 There was no significant increase in congenital anomalies among 586 mothers who had been exposed to CCBs compared with 907 controls: 2.6% vs 2.4%, respectively (LOE: 2).³⁰ CCBs are effective at reducing the rate of preterm delivery, decreasing neonatal morbidity and mortality, and are well tolerated by both mother and baby. Although some other tocolytics (such as beta-agonists and prostaglandin inhibitors) prolong pregnancy, they have not demonstrated a beneficial effect on neonatal morbidity.

Dosing recommendations for nifedipine are a 30 mg loading dose, followed by 10 to 20 mg every 4 to 6 hours.³¹ Maternal side effects may include flushing, headache, nausea, dizziness, and transient hypotension. Neonatal side effects have not been documented. Nifedipine should not be used in conjunction with magnesium sulfate because the combination has resulted in cardiac collapse (LOE: 3).³²

Beta-agonists marginally useful

Beta-agonists increase cyclic AMP, thereby causing smooth muscle relaxation. Betamimetics are widely used as tocolytic agents. Although they have been shown to prolong pregnancy by 24 to 48 hours, they have not decreased adverse perinatal or neonatal outcomes (LOE: 1).^33,34 In addition, they have been associated with maternal side effects of palpitations, arrhythmias, nausea, tremor, chorioamnionitis, hyperglycemia, hypokalemia, and pulmonary edema. The risk of pulmonary edema increases if beta-agonists are used with magnesium sulfate.^33,35 Fetal and neonatal side effects may include tachycardia, hyperinsulinemia, and hyperglycemia.^14,35

Terbutaline is the preferred beta-agonist for preterm labor due to low cost and multiple dose forms. It may be administered subcutaneously, 0.25 mg every 30 minutes up to 1 mg in 4 hours, or by intravenous infusion, 2.5 to 10 μg per minute up to an effective maximum dose of no more than 30 μg per minute. Once stabilized, the patient is often maintained on oral terbutaline, 2.5 to 5 μg by mouth every 4 to 6 hours until term. This practice, however, has not been shown to significantly prolong pregnancy (LOE: 1).³⁶

The major benefit of terbutaline may be in the management of preterm uterine contractions without cervical changes. Among patients with premature contractions at 20 to 34 weeks, who were randomized to hydration or observation or a single subcutaneous dose of 0.25 mg of terbutaline, the shortest length of stay in triage was for the women who received the terbutaline (LOE: 1).³⁷

Magnesium sulfate: No good rationale for use

Magnesium sulfate in the management of preterm labor is controversial. Although widely used in North America, it is generally avoided in Europe, Australia, and the United Kingdom^38,39 due to the absence of clear evidence showing efficacy in the face of its adverse effect profile. Data from systematic reviews indicate it does not delay or prevent preterm birth (LOE: 1).^33,40 In addition, maternal side effects may require discontinuation of treatment. Side effects include flushing, nausea, headache, ileus, and hypocalcemia. Pulmonary edema is a serious maternal side effect and is increased when magnesium is co-administered with other tocolytic agents. Cardiac arrest is rare.^14,33 Not only does evidence suggest magnesium sulfate does not delay or prevent preterm birth, but one study suggests its use may increase infant mortality (LOE: 2).⁴¹