Predicting and preventing preterm birth

2 useful markers

In the 1990s, 2 biologic markers were discovered that improve the precision of preterm birth risk assessment:

• fetal fibronectin (fFN) and
  
• endovaginal sonography (EVUSD).¹
  

Use of EVUSD enables measurement of the cervix from the internal to external os. Cervices shorten before spontaneous birth.

These 2 tests, when positive (fFN detected or cervical length

I use a negative test to identify women who do not require further treatment or evaluation. If a patient has a negative fFN or EVUSD, I would not transport her to a tertiary care center. In fact, I would probably discharge her home with close follow-up.

3 concerns about the tests

Clinicians tend to have some concerns about incorporating these tests into their routines:

• How reliable is negative predictive value? Arguably, these tests perform better than clinical judgment and can spare many women unnecessary treatments.² No test is perfect, however. These bio-markers should be adjuncts to—not replacements for—clinical wisdom.
  
• What about false results? With fFN, a proper collection kit with plastic tube and Dacron swab is critical because the molecule will adhere to glass or cotton, creating a false-negative result. A false-positive result can occur after recent coitus or a digital cervical exam; therefore, collect fFN specimens before checking the cervix. With EVUSD, the examinations require a moderate amount of skill.
  
• Which biomarker is best? Both fFN and EVUSD make independent and separate contributions to the prediction of preterm birth. Therefore, I use both.
  

Start Tocolysis And Antibiotics?

Patricia’s fFN and EVUSD tests are both positive. Should you start tocolysis and antibiotic therapy prior to transfer?

Metaanalysis suggests tocolysis, and antibiotics extend the interval between symptom onset and delivery.¹The length of this prolongation can be measured in days, and no evidence suggests that prolonged pharmacotherapy has any benefit.

I would initiate both therapies while waiting for the mother to be moved to a tertiary center, even though neither therapy has been shown to improve perinatal outcome.

Tocolysis. We could find no differences among tocolytic drugs.³ Serious side effects are rare, but nuisance cardiovascular symptoms are frequent. Sympathomimetic drugs lead to lethargy, and magnesium is associated with malaise. Magnesium requires intravenous access and should be given only via infusion pump by trained personnel. That often means a nurse must accompany the patient to the Level III hospital.

Thus, for logistical reasons, I favor nonsteroidal anti-inflammatory drugs, of which indomethacin is the most widely studied. Indomethacin can be given by mouth or rectum, with minimal side effects. Harm to the fetus is rare if the drug is used acutely for only 48 to 72 hours (the maximum duration of any potential benefit).

Antibiotics. Current protocols calling for betalactam antibiotic therapy as prophylaxis against early-onset neonatal sepsis in preterm births have led to almost universal use of antibiotics among these patients. Our metaanalysis did not demonstrate superior pregnancy prolongation with any other regimen, so the one for group B strep prophylaxis provides a double benefit.⁴ As with tocolytics, there is no role for maintenance therapy.

When Contractions Cease

Patricia is transferred and completes her steroid therapy. Her symptoms and contractions cease. After a few days of observation and no cervical changes, she is discharged home. She asks about home therapies, work, activities, and sex.

Since our metaanalysis of tocolysis studies showed no efficacy for maintenance regimens, I do not recommend them except in this rare situation: when a woman has so much uterine activity without cervical change that she is unable to rest or complete her daily activities. In this case I would favor “as needed” doses of a β-mimetic drug by mouth.

Although home uterine activity monitors and subcutaneous tocolytic pumps are available, evidence suggests they are ineffective.¹I seldom, if ever, use these devices.

Despite the almost universal recommendation that women at risk of preterm birth avoid physical and sexual activity, we lack evidence that bed rest or abstinence prolong pregnancy or prevent preterm birth.

Is sex allowed? When we studied both physical activity and sexuality in asymptomatic women at midpregnancy, neither was associated with spontaneous preterm birth.^5,6 Therefore, I do not recommend restricting activity or sexual intercourse. Instead, I encourage women to carefully assess uterine activity. If certain behaviors appear to increase contractions, those behaviors should be limited.

Counsel her to trust her instincts. It is important to encourage the patient to trust her own instincts, so that an overzealous employer or partner cannot coerce or cajole her to do something that violates her internal sense of well-being.