Clinical Review

Predicting and preventing preterm birth

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Preterm delivery seems likely, and the nearest tertiary care nursery is 90 minutes away. What should you do?


 

References

Patricia’S Case

A 25-year-old primigravida with an intrauterine pregnancy at 26 weeks presents with contractions of moderate intensity every 4 minutes, intact membranes, and minimal vaginal bleeding. On digital exam, her cervix is soft, 50% effaced, and closed. Estimated fetal weight is 775 g.

You are at a Level I hospital in a rural community, 90 minutes from a tertiary nursery. What steps should you take first?

Tocolytics and antibiotics are the first steps. They may help to maximize the benefits of secondary strategies such as antenatal corticosteroids during transport to a tertiary care facility. In addition, assessment of fetal fibronectin levels and use of endovaginal ultrasound can supplement clinical judgment and improve prediction of outcomes. Their excellent negative predictive value can spare many women unnecessary and potentially harmful treatments.

This article discusses these measures in the context of an actual case.

The value of “secondary prevention”

Giving corticosteroids to enhance fetal lung and brain maturity and transporting the mother to a tertiary care center may not prevent preterm delivery, but they can mitigate some of the damage and are supported by the evidence.

Corticosteroids. Given the clear evidence of their efficacy, steroids should be administered once preterm birth appears likely. I would give steroids before maternal transport.

Betamethasone is preferable to dexamethasone, which may be toxic to the fetal central nervous system. However, dexamethasone is preferable to no therapy.

Contraindications to corticosteroids include systemic maternal or fetal infections and maternal endocrinopathies such as Cushing’s disease or poorly controlled diabetes.

Transport to tertiary care. A neonatal intensive care unit clearly benefits tiny babies. Clinicians should be aware of the pediatric capacity of their community hospitals and maintain a referral relationship with the nearest tertiary care centers. Conversely, clinicians on the receiving end of maternal transports should make every effort to expedite these referrals.

Is Local Care Too Risky?

Patricia and her family strongly prefer that she undergo treatment in her own community, if at all possible.

Signs and symptoms of preterm labor are poor predictors of preterm birth. Although most symptomatic women deliver at term, even the most clinically astute physician cannot predict when a symptomatic patient will deliver.

INTEGRATING EVIDENCE AND EXPERIENCE

Which tocolytic is most effective?

Berkman ND, Thorp JM Jr, Lohr KN, et al. Tocolytic treatment for the management of preterm labor: a review of the evidence. Am J Obstet Gynecol. 2003;188:1648–1659.

No single drug is best. In this metaanalysis, magnesium, β-mimetics, calcium channel blockers, and nonsteroidal anti-inflammatory drugs (NSAIDs) performed about the same at prolonging the interval between onset of preterm labor and actual birth, compared with placebo or no treatment. Ethanol was less effective and “inappropriate.” Tocolytics are given to stop contractions (first-line therapy) and to maintain quiescence after an acute episode (maintenance therapy).

To determine the most effective tocolytic, we analyzed 16 studies of first-line therapy and 8 involving maintenance therapy, using the above 5 drug classes.

How 5 drugs compare

Estimated odds ratios suggest that, when used as first-line therapy, all the drugs except ethanol are about the same. Odds ratios ranged from 1.622 for β-mimetics to 2.485 for calcium channel blockers. (The odds ratio for NSAIDs was based on only 1 study.)

When we tested whether β-mimetics, calcium channel blockers, and magnesium sulfate had the same effects, compared with placebo, the results suggested that they do not. However, the body of literature was not large enough to establish this conclusively.

Overall, β-mimetics appear to lack superiority over the other drugs as first-line therapy and cause more maternal harms, while ethanol is “inappropriate” and no longer in use.

As maintenance therapy, none of the drugs appeared to have any benefit.

Maternal and fetal harms

We defined harms as “clinical markers and events that the authors of individual studies considered as adverse events or side effects.”

Among maternal harms were serious cardiac side effects, including arrhythmias, heart failure, and chest pain, linked to β-mimetics. Minor cardiovascular harms were also higher among women given β-mimetics. In addition, calcium channel blockers appeared to increase the risk of minor cardiovascular harms, but not as much as the β-mimetics.

Overall, maternal cardiac, metabolic, and psychologic harms were more prevalent among women taking β-mimetics. This may be due, at least in part, to the fact that studies of β-mimetics tended to look for these effects more than other studies did.

As for short-term fetal harms, we found “little consistent evidence” of them in the infants of women receiving these drugs, and the studies lacked sufficient data to evaluate potential long-term harms.

What later analyses found

After 1999, the cutoff year of our review, several relatively large studies showed the oxytocin antagonist atosiban to be effective as acute7,8and maintenance8 therapy, with a favorable side effect profile. Another trial9 compared 2 doses of magnesium (2 and 5 g per hour); the higher dose acted more quickly but with more side effects. These and other studies do not alter our conclusions about the effectiveness of tocolytic therapy—or the specifics of the 5 drugs studied.

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