Preterm Labor Case File

Preterm Labor Case File

Eugene C. Toy, MD, Patti Jayne Ross, MD, Benton Baker III, MD, John C. Jennings, MD

CASE 17

A healthy 19-year-old G1P0 woman at 29 weeks’ gestation presents to the labor and delivery area complaining of intermittent abdominal pain. She denies leakage of fluid or bleeding per vagina. Her antenatal history has been unremarkable. She has been eating and drinking normally. On examination, her blood pressure (BP) is 110/70 mm Hg, heart rate (HR) is 90 beats per minute (bpm), and temperature is 99°F (37.2°C). The fetal heart rate tracing reveals a baseline heart rate of 120 bpm and a reactive pattern. Uterine contractions are occurring every 3 to 5 minutes. On pelvic examination, her cervix is 3 cm dilated, 90% effaced, and the fetal vertex is presenting at –1 station.

» What is the most likely diagnosis?

» What is your next step in management?

» What test of the vaginal fluid prior to digital examination may indicate risk for preterm delivery?

» What medication can be given to decrease the risk of neurological impairment in the baby?

ANSWER TO CASE 17:

Preterm Labor                                                         

Summary: A healthy 19-year-old G1P0 woman at 29 weeks’ gestation complains of intermittent abdominal pain. Her vital signs are normal. The fetal heart rate tracing reveals a baseline heart rate of 120 bpm and is reactive. Uterine contractions are noted every 3 to 5 minutes. Her cervix is 3 cm dilated, 90% effaced, and the fetal vertex is presenting at – 1 station.

• Most likely diagnosis: Preterm labor.
• Next step in management: Tocolysis, try to identify a cause of the preterm labor, antenatal steroids, and antibiotics for GBS prophylaxis.
• Test of vaginal fluid: Fetal fibronectin assay.
• Medication for neuroprotection: Magnesium sulfate may be given for pregnancies of <32 weeks when there is imminent delivery.

ANALYSIS

Objectives

1. Understand how to diagnose preterm labor.
2. Understand that the basic approach to preterm labor is tocolysis, identification of an etiology, steroids, and magnesium sulfate (if appropriate).
3. Know the common causes of preterm delivery.

Considerations

This 19-year-old nulliparous woman is at 29 weeks’ gestation and complains of intermittent abdominal pain. The monitor indicates uterine contractions every 3 to 5 minutes, and her cervix is dilated at 3 cm and effaced at 90%. This is sufficient to diagnose preterm labor in a nulliparous woman. If she had a previous vaginal delivery, the diagnosis may not be so clear cut. Because of the significant prematurity, many practitioners may elect to treat for preterm labor. A single examination revealing 2-cm dilation and 80% effacement in a nulliparous woman would be sufficient to diagnose preterm labor. Prior to digital examination, one should swab the posterior vaginal fornix for fetal fibronectin (fFN), which, if positive, may indicate risk of preterm birth. In contrast, a negative fFN assay is strongly associated with no delivery within 1 week. Another objective test for preterm delivery risk is transvaginal cervical length ultrasound measurements. A shortened cervix, especially with lower uterine segment changes (funneling or beaking of the amniotic cavity into the cervix), is worrisome. Tocolysis should be initiated, unless there is a contraindication (such as intra-amniotic infection or severe preeclampsia). Also, since the pregnancy is < 34 weeks’ gestation, intramuscular (IM) antenatal steroids should be given to enhance fetal pulmonary maturity. In fact, the use of antenatal corticosteroids is the single most important obstetrical intervention available that positively impacts on neonatal morbidity and survival. A careful search should also be undertaken to identify an underlying cause of preterm labor, such as urinary tract infection, cervical infection, bacterial vaginosis, generalized infection, trauma or abruption, hydramnios, or multiple gestations. Finally, intravenous (IV) antibiotics, such as penicillin, are helpful in case the tocolysis is unsuccessful to reduce the likelihood of GBS sepsis in the neonate. Last, recent studies have shown that if the pregnancy is <31 6/ 7 weeks, starting magnesium could help the neurodevelopment of the preterm baby, reducing cases of cerebral palsy in preterm infants.

APPROACH TO:

Preterm Labor                                                            

DEFINITIONS

PRETERM LABOR: Cervical change associated with uterine contractions prior to 37 complete weeks and after 20 weeks’ gestation. In a nulliparous woman, uterine contractions and a single cervical examination revealing 2-cm dilation and 80% effacement or greater are sufficient to make the diagnosis.

TOCOLYSIS: Pharmacologic agents used to delay delivery once preterm labor is diagnosed. The most commonly used agents are indomethacin, nifedipine, terbutaline, and ritodrine. Recent evidence has indicated that magnesium sulfate may be ineffective as a tocolytic agent but has been shown to decrease the risk of cerebral palsy in surviving infants if birth is anticipated before 32 weeks’ gestation.

ANTENATAL STEROIDS: Betamethasone or dexamethasone is given intramuscularly to the pregnant woman in an effort to decrease some of the complications of prematurity, particularly respiratory distress syndrome (intraventricular hemorrhage in the more extremely premature babies).

FETAL FIBRONECTIN ASSAY: A basement membrane protein that helps bind placental membranes to the decidua of the uterus. A vaginal swab is used to detect its presence. Its best utility is a negative result, which is associated with a 99% chance of not delivering within 1 week.

CERVICAL LENGTH ASSESSMENT: Transvaginal ultrasound to measure the cervical length. Cervical length of < 25 mm results in an increased risk of preterm delivery. Also an impinging of the amniotic cavity into the cervix, so-called funneling, increases the risk of preterm delivery. However, a short cervix or a positive fetal fibronectin alone should not be used exclusively to diagnose preterm labor in an acute situation, as the positive predictive value is poor.

LATE PRETERM GESTATION: Delivery that occurs between 34+0 weeks and 36+ 6 weeks. This is the subset of preterm births that are most rapidly increasing and comprises most preterm deliveries.

CLINICAL APPROACH

Preterm labor is defined as cervical change in the midst of regular uterine contractions occurring between 20 and 37 weeks’ gestation. The incidence in the United States is approximately 11% of pregnancies, and it is the cause of significant perinatal morbidity and mortality. There are many risk factors associated with preterm delivery, but the most significant one is a history of a prior spontaneous preterm birth (see Table 17– 1).

The main symptoms of preterm labor are uterine contractions and abdominal tightening. Sometimes, pelvic pressure or increased vaginal discharge may also be present. The diagnosis is established by confirming cervical change over time by the same examiner, if possible, or finding the cervix to be 2-cm dilated and 80% effaced in a nulliparous woman. Once the diagnosis has been made, an etiology should be sought. Tocolysis is considered if the gestational age is less than 34 to 35 weeks, and steroids are administered if the gestational age is < 34 weeks. The work-up for preterm labor is summarized in Table 17– 2.

Recent randomized controlled trials have suggested that magnesium sulfate is not effective as a tocolytic agent but may be useful for fetal neuroprotection. Other medications include terbutaline, ritodrine, nifedipine, and indomethacin. The speculated mechanism of action of magnesium is competitive inhibition of calcium to decrease its availability for actin–myosin interaction, thus decreasing myometrial activity (see Table 17– 3).

Nifedipine reduces intracellular calcium by inhibiting voltage-activated calcium channels. Side effects include pulmonary edema, respiratory depression, neonatal depression, and, if given for a long term, osteoporosis. Pulmonary edema is often the most serious side effect, and is seen more often with the β-agonist agents. A complication of indomethacin is closure of the ductus arteriosus, leading to severe neonatal pulmonary hypertension; oligohydramnios may also be seen.

Antenatal steroids should be given between 23 and 34 weeks’ gestation when there is no evidence of overt systemic infection. Only one course of corticosteroids is utilized. However, if 7 to 14 days or more have elapsed and the patient re-enters preterm labor and is still <34 weeks, one additional “rescue” course of corticosteroids may be considered. Repeat rescue doses are contraindicated. Antenatal corticosteroids are associated with improved neonatal survival, and lower severity and incidence of respiratory distress syndrome (RDS). In the early gestational ages, the effect is to lower the risk of intraventricular hemorrhage; at gestations >28 weeks, the primary goal is to lower the incidence of respiratory distress syndrome.

Weekly injections of 17 α-hydroxyprogesteronecaproate from 16 to 36 weeks’ gestation have been shown to help reduce the incidence of preterm birth in women at high risk. These include a history of previous spontaneous preterm delivery.

Table 17–1 • RISK FACTORS FOR PRETERM LABOR

Preterm premature rupture of membranes Multiple gestations Previous preterm labor or birth Hydramnios Uterine anomaly History of cervical cone biopsy Cocaine abuse African–American race Abdominal trauma Pyelonephritis Abdominal surgery in pregnancy

Table 17–2 • WORK-UP FOR PRETERM LABOR

History to assess for risk factors Physical examination with speculum examination to assess for ruptured membranes Serial digital cervical examinations Complete blood count Urine drug screen (especially for cocaine metabolites) Urinalysis, urine culture, and sensitivity Cervical tests for gonorrhea (possibly Chlamydia) Vaginal culture for group B streptococcus Ultrasound examination for fetal weight and fetal presentation

Table 17–3 • COMMON TOCOLYTIC AGENTS
Tocolytic Agents	Drug Class	Method of Action	Side Effects/ Complications	Contraindications
Magnesium sulfate	Minerals	Competitively inhibits calcium	Pulmonary edema, respiratory depression	Myocardial damage, heart block, diabetic coma (do not use with calcium channel blockers)
Terbutaline; Ritodrine	β-agonists	Selective for β2 receptors; relaxes smooth muscles	Pulmonary edema, increased pulse pressure, hyperglycemia, hypokalemia, and tachycardia	Arrhythmia, hypertension, seizure disorder
Nifedipine	Calcium channel blocker	Inhibits calcium ion influx into vascular smooth muscle	CHF, MI, pulmonary edema, and severe hypotension; flushing	Hypotension;
Indomethacin	NSAID	Decreased prostaglandin synthesis	Closure of fetus’ ductus arteriosus, which would lead to pulmonary hypertension, oligohydramnios	Third trimester of pregnancy due to possible effects on ductus arteriosus
17-` -hydroxyproge steronecaproate	Synthetic progesterone, hormone replacement therapy	Inhibits pituitary gonadotropin release; maintains a pregnancy	Breast pain and tenderness, dizziness, abdominal pain, intermittent bleeding	Undiagnosed vaginal bleeding

Emerging Research

The use of vaginal ultrasound to assess the cervical length and characteristics and the use of progesterone or cerclage in those patients with a short cervix are being intensively studied. The most efficacious progesterone preparation (IM injections versus vaginal gel) is unclear. Another area of research is the use of antenatal corticosteroids in pregnancies beyond 34 weeks. At the time of this writing, there is some evidence about its efficacy up to 36 weeks gestation.

COMPREHENSION QUESTIONS

17.1 A 26-year-old woman is noted to be at 29 weeks’ gestation. Her last pregnancy ended in delivery at 30 weeks’ gestation. In screening for various types of infection, which of the following is most likely to be associated with preterm delivery?

A. Herpes simplex virus

B. Candida vaginitis

C. Chlamydia cervicitis

D. Gonococcal cervicitis

E. Group B streptococcus of the vagina

17.2 A 25-year-old G1P0 woman is at 28 weeks’ gestation. She is noted to have regular uterine contractions, and her cervix is dilated at 2 cm and 80% effaced. Preterm labor is diagnosed. The physician reviews the record and notes that the patient should not have tocolytic therapy. Which one of the following is a contraindication for tocolysis?

A. Suspected placental abruption

B. Group B streptococcal bacteriuria

C. Recent laparotomy

D. Uterine fibroids

17.3 A 35-year-old G1P0 woman at 32 weeks’ gestation was seen in the obstetric (OB) triage unit the previous day with uterine contractions. On admission, the fetal heart rate is 140 bpm with accelerations and no decelerations. A fetal fibronectin assay is performed, which was positive. Over the course of the next 24 hours, the patient was examined and noted to have cervical dilation from 1 to 2 cm and effacement from 30% to 90%. A tocolytic agent is used. A repeat fetal heart rate pattern reveals a baseline of 140 bpm with moderate repetitive variable decelerations. Which of the following is the most likely tocolytic agent used?

A. Nifedipine

B. Indomethacin

C. Magnesium sulfate

D. Terbutaline

17.4 A 28-year-old woman G1P0 at 29 weeks’ gestation is treated with terbutaline for preterm labor. Her cervix had dilated to 3 cm and was 90% effaced. She also received betamethasone intramuscularly to enhance fetal lung maturity. The following day, the patient develops dyspnea, tachypnea, and an oxygen saturation level of 80%. Oxygen is given. Which of the following is the best therapeutic agent?

A. IV antibiotic therapy for probable pneumonia

B. IV heparin therapy for probable deep venous thrombosis

C. IV furosemide for probable pulmonary edema

D. Oral digoxin for probable cardiomyopathy

ANSWERS

17.1 D. Infections of various types are associated with preterm delivery. Gonococcal cervicitis is strongly associated with preterm delivery, whereas chlamydial infection is not as strongly associated. Urinary tract infections, particularly pyelonephritis, are associated with preterm delivery. Bacterial vaginosis may be linked with preterm delivery, although treatment of this condition does not seem to affect the risk.

17.2 A. Suspected abruption is a relative contraindication for tocolysis because the abruption may extend. The natural history of abruption is extension of the separation, leading to complete shearing of the placenta from the uterus. If this happens, delivery would be the best treatment with the administration of antenatal steroids to decrease the chance of respiratory distress syndrome in the preterm baby; expectant management may be exercised if the patient is stable with no active bleeding or no sign of fetal compromise since this is a premature fetus. Nevertheless, giving tocolytics would increase the chance of hemorrhage in mothers after delivery because it will be more difficult to get the uterus to contract on itself, since tocolytics also act as a uterine relaxant. Infection with Group B streptococcal bacteriuria is not a contraindication for tocolysis; however, the mother should be placed on antibiotic prophylaxis in the event that she delivers or has preterm premature rupture of membranes (PPROM). A recent laparotomy and uterine fibroid may increase the risk of preterm labor, but would not be a contraindication for administration of tocolytics, assuming that both the mother and the fetus are stable.

17.3 B. This patient has a change in her fetal heart rate tracing after tocolysis is used. Now, she has significant variable decelerations, which are caused by cord compression. A sudden worsening in the frequency and/ or severity of variable decelerations can be caused by oligohydramnios (less amniotic fluid to buffer the cord from compression), rupture of membranes, or descent of the fetal head, such as in labor, so that a nuchal cord (around the neck) may tighten. Indomethacin is associated with decreased amniotic fluid and oligohydramnios, and this is the most likely etiology.

17.4 C. In a patient on tocolytic therapy, pulmonary edema is a hazard, particularly when on β-agonists. The tachycardia that often occurs decreases the diastolic filling time, leading to increased end-diastolic pressure. Besides oxygen, IV furosemide is effective in decreasing intravascular fluid and thus decreasing hydrostatic pressure, hopefully relieving the fluid from the interstitial spaces of the lungs. Of course, the terbutaline should also be discontinued. A β-agonist therapy is associated with an increased pulse pressure, hyperglycemia, hypokalemia, and tachycardia.

    CLINICAL PEARLS    

» Dyspnea occurring in a woman with preterm labor and tocolysis is usually due to pulmonary edema. » The goal in treating preterm labor is to identify the cause, give steroids (if gestation is at 24 to 34 weeks), tocolysis, and magnesium sulfate for neuroprotection. » The most common cause of neonatal morbidity in a preterm infant is respiratory distress syndrome. » β-Agonist therapy has multiple side effects including tachycardia, widened pulse pressure, hyperglycemia, and hypokalemia. » A negative cervical fetal fibronectin assay virtually guarantees no delivery within 1 week. » Transvaginal sonography indicating a shortened cervix especially with funneling and/or beaking is suggestive of risk for preterm delivery. » Progesterone (17 OHP) injections given weekly from 16 to 36 weeks’ gestation in women with a history of prior spontaneous preterm births decreases the risk of preterm birth by one-third.

REFERENCES

American College of Obstetricians and Gynecologists. Management of preterm labor. ACOG Practice Bulletin 127. Washington, DC; 2012. 

American College of Obstetrics and Gynecologists. Prediction and prevention of preterm birth. ACOG Practice Bulletin 130. Washington, DC; 2012. 

American College of Obstetricians and Gynecologists. Use of progesterone to reduce preterm birth. ACOG Committee Opinion 419. Washington, DC; 2008. 

American College of Obstetrics and Gynecologists. Magnesium sulfate use in obstetrics. ACOG Committee Opinion 573. Washington, DC; 2013. 

American College of Obstetricians and Gynecologists. Magnesium sulfate before anticipated preterm birth for neuroprotection. Committee Opinion 455. Washington, DC; 2010. 

Cunningham FG, Leveno KJ, Bloom SL, Hauth JC, Gilstrap LC III, Wenstrom KD. Preterm birth. In: Williams Obstetrics. 22nd ed. New York, NY: McGraw-Hill; 2005:855-880. 

Hobel CJ. Obstetrical complications: preterm labor, PROM, IUGR, postterm pregnancy, and IUFD. In: Hacker NF, Gambone JC, Hobel CJ, eds. Essentials of Obstetrics and Gynecology. 5th ed. Philadelphia, PA: Saunders; 2009:146-159. 

Norwitz ER, Caughey AB. Progesterone supplementation and the prevention of preterm birth. Rev Obstetr Gynecol. 2011;4(2):60-72.

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