Obstetrics and Gynaecology

at a Glance

Fourth EditionErrol R. Norwitz, John O. Schorge

Case Studies

Case 6: Preterm labor

A 28-year-old G5P2 is admitted to your office at 28 weeks’ gestation with regular painful uterine contractions every 3 minutes. Bimanual examination shows her cervix to be long and closed.

  • 1. How is preterm labor defined? Is this patient in preterm labor?

    Correct answer: Labor is a clinical diagnosis that includes two elements: (1) regular phasic uterine contractions increasing in frequency and intensity, and (2) progressive cervical effacement and dilation. Preterm (premature) labor refers to labor occurring before 37 weeks’ gestation. It is not possible to make a diagnosis of preterm labor in this patient, because – although she is experiencing regular uterine contractions – her cervix is long and closed.

  • 2. What are the causes of preterm birth?

    Correct answer: Of preterm births 20% are iatrogenic, meaning that obstetric care providers recommend delivery for either maternal or fetal indications, including pre-eclampsia, placenta previa, placental abruption, and diabetes. The remainder are due to preterm labor, which represents a syndrome rather than a diagnosis because the etiologies are varied. The major causes of preterm labor include intra-amniotic infection/inflammation (20–30%) and preterm premature rupture of membranes (PROM; 30%). Of preterm labors 30–50% have no known cause and are regarded as spontaneous (idiopathic) preterm labors.

  • 3. This patient has had three prior spontaneous preterm deliveries at 28–31 weeks’ gestation and is very concerned that this pregnancy too will end prematurely. What tests are available to screen for preterm labor?

    Correct answer: This woman is at high risk of preterm delivery. Screening tests currently available for the prediction of preterm birth fall into four broad categories:

    • (a) Home uterine activity monitoring. Although uterine contractions are a prerequisite for preterm labor, home uterine activity monitoring does not reduce the incidence of preterm birth and, as such, is not recommended.
    • (b) Risk factor scoring. A number of risk factors for preterm labor have been identified (listed below). However, reliance on risk factor scoring alone will fail to identify over 50% of pregnancies that deliver preterm (low sensitivity) and most women designated “at risk” will deliver at term (low positive predictive value [PPV]).

      Risk factors for preterm labor
      • Prior preterm birth
      • African-American race
      • Age <18 or >40 years
      • Poor nutrition
      • Anemia
      • Low pre-pregnancy weight
      • Low socioeconomic status
      • Absent prenatal care
      • Bacteriuria/urinary tract infection
      • Genital and/or gingival disease
      • Cigarette smoking
      • Cervical injury or anomaly
      • Uterine anomaly or fibroids
      • Excessive uterine activity
      • Premature cervical dilation (>21 cm) and/or effacement (>80%)
      • Overdistended uterus (twins, polyhydramnios)
      • ? Vaginal bleeding
      • ?? Strenuous work
      • ?? High personal stress
    • (c) Assessment of cervical maturation. Transvaginal ultrasound is the “gold standard” for the measurement of cervical length. A strong inverse correlation exists between residual cervical length and preterm birth. The mean cervical length at 22–24 weeks’ gestation is 3.5 cm (10th to 90th percentile: 2.5–4.5 cm). A cervical length of ≤1.5 cm at 22–24 weeks occurs in <2% of low-risk women, but is predictive of delivery before 28 and 32 weeks in 60% and 90% of cases, respectively.
    • (d) Biochemical/endocrine markers. A number of biochemical/endocrine markers have been associated with preterm delivery, including, but not limited to, activin, inhibin, follistatin, fibronectin, collagenase, progesterone, and estradiol-17β. To date, only fetal fibronectin (fFN) is established and approved by the US Food and Drug Administration (FDA) as a screening test for preterm birth. Elevated levels of fFN (>50 ng/mL) in cervicovaginal secretions at 22–34 weeks are associated with premature birth, although the PPV of a positive fFN test at 22–24 weeks, for spontaneous preterm birth before 28 weeks and 37 weeks, is only 13% and 36%, respectively. The primary value of this test therefore lies in its negative predictive value (NPV): 99.9% of patients with a negative fFN test will not deliver within 7 days and 98% will still be pregnant in 14 days. Fortunately, 80% of high-risk symptomatic patients will have a negative fFN.
  • 4. The patient continues to contract. A repeat cervical examination 4 hours later shows her cervix to be 4 cm dilated and 90% effaced. You make a diagnosis of preterm labor and are considering initiating tocolytic therapy. Are there any contraindications to tocolysis?

    Correct answer: In many instances, premature labor represents a necessary escape of the fetus from a hostile intrauterine environment. As such, aggressive intervention to stop labor in such cases may be counterproductive. Absolute contraindications to tocolytic therapy include non-reassuring fetal testing (previously referred to as “fetal distress”), chorioamnionitis, intrauterine fetal demise, a lethal fetal structural anomaly or chromosomal defect (such as trisomy 13 or 18), and any maternal condition precluding expectant management (such as severe pre-eclampsia). Relative contraindications include unexplained vaginal bleeding, preterm PROM, and a favorable gestational age (commonly defined as >34 weeks).

  • 5. Should you recommend strict bed rest and aggressive intravenous hydration?

    Correct answer: Bed rest is recommended in 20% of all pregnancies with an estimated cost of >US$250 million per year in the USA alone. There is no proven benefit to bed rest in women at risk for preterm labor. Intravenous hydration is also commonly recommended, but without proven benefit.

  • 6. Is antibiotic administration recommended? If so, what is the indication and for how long should treatment be continued?

    Correct answer: There are two reasons to administer antibiotics to women at imminent risk of preterm birth:

    • (a) Antibiotics to prevent preterm birth. Broad-spectrum antibiotic administration in the setting of preterm PROM <34 weeks’ gestation has been shown to prolong latency, delay preterm birth, and improve short-term perinatal outcome. However, there is no consistent evidence of prolonged latency in the setting of preterm labor with intact membranes. As such, antibiotics for this indication are not recommended.
    • (b) Chemoprophylaxis against group B β-hemolytic streptococcal (GBS) infection. Premature neonates are at increased risk of early onset neonatal GBS sepsis. As such, all women at imminent risk of preterm delivery should receive intrapartum GBS chemoprophylaxis. If such a woman has had a negative GBS perineal culture within the previous 5 weeks, GBS prophylaxis can be withheld. In this case, a perineal GBS culture should be sent and GBS chemoprophylaxis initiated immediately (intravenous penicillin 5 mU loading dose followed by 2.5 mU 4-hourly until delivery). If the episode of preterm labor stabilizes and continued expectant management is recommended, then GBS chemoprophylaxis can be stopped and restarted in labor, depending on the result of GBS culture.
  • 7. You are considering starting a tocolytic agent. What is the goal of tocolysis? What tocolytic agents are available and which are most effective?

    Correct answer: Pharmacologic tocolytic therapy has been the cornerstone of modern management for preterm labor. However, there are no reliable and consistent data that any tocolytic agent can delay delivery for longer than 24–48 hours. As such, the goal of tocolysis is to delay delivery for 48 hours to allow administration of a full course of antenatal corticosteroids and the patient to be transferred to a tertiary care center. A number of agents are now available for short-term tocolysis (listed below).

    No single tocolytic agent has a clear therapeutic advantage. As such, the side-effect profile of each of the drugs will often determine which to use in a given clinical setting. Nifedipine (a calcium channel blocker) or magnesium sulfate is commonly used as a first-line agent in the USA, whereas oxytocin receptor antagonists (such as atosiban) are used more commonly in Europe. Magnesium sulfate has the added advantage of being neuroprotective in infants born <32 weeks’ gestation. Prostaglandin synthesis inhibitors (such as indometacin), although very effective in delaying preterm birth, have been associated with a number of serious neonatal complications, especially if given shortly before delivery. The only agent that is FDA approved in the USA for the treatment of preterm labor is the β-adrenergic agonist, ritodrine hydrochloride; unfortunately, this drug is no longer marketed in North America because it is too dangerous to administer to pregnant women.

    Options for short-term tocolytic therapy

    Tocolytic agent

    Route of administration (dosage)

    Efficacy*

    Magnesium sulfate

    IV (4–6 g bolus, then 2–3 g/h infusion)


    Effective

    β-Adrenergic agonists:




    – Terbutaline sulfate

    – Ritodrine hydrochloride

    IV (2 μg/min infusion, maximum 80 μg/min)

    SC (0.25 mg every 20 min)

    Effective



    IV (50 μg/min infusion, maximum 350 μg/min)

    Effective



    IM (5–10 mg every 2–4 h)

    Effective

    Prostaglandin inhibitors:




    – Indometacin

    Oral (25–50 mg every 4–6 h)

    Rectal (100 mg every 12 h)

    Effective

    Calcium channel blockers:




    – Nifedipine

    Oral (20–30 mg every 4–8 h)


    Effective

    Oxytocin antagonists:




    – Atosiban

    IV (1 μmol/L per min infusion, maximum 32 μmol/L per min)


    Effective

    Others:




    – Ethanol

    (historical interest only)



    – Nitroglycerin

    TD (10–50 mg daily)

    IV (100 μg bolus, 1–10μg/kg per min infusion)

    Effective

    Unproven

    Unproven

    * Efficacy is defined as proven benefit in delaying delivery by 24–48 hours compared with placebo or standard control. IM, intramuscular; IV, intravenous; SC, subcutaneous; TD, three times daily.

  • 8. Is there a place for progesterone to prevent preterm birth?

    Correct answer: There is increasing evidence that progesterone supplementation – not treatment – from 16–20 weeks through 34–36 weeks may reduce the rate of preterm birth and improve short-term perinatal outcome in some high-risk women, specifically women with a history of a prior unexplained preterm birth and women with cervical shortening (<1.5 cm at 22–24 weeks). Recent studies suggest that multiple pregnancies are not likely to benefit from progesterone supplementation. Note that this is progesterone prophylaxis in women at high risk, not treatment with progesterone in women who present in preterm labor.

See Chapters 57 and 42.

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