Preterm labor: diagnosis and treatment - Problem-Oriented Diagnosis

Author: Beverly A. Von Der Pool
Date: May 15, 1998

Unfortunately, the incidence of premature birth has not decreased during the past 40 years. In the United States, preterm delivery affects approximately one in 10 births and is the cause of at least 75 percent of neonatal deaths, excluding those related to congenital malformations.[1]

Preterm. labor is defined as labor that occurs before completion of the 37th week of gestation. Currently, physicians must diagnose and manage preterm. labor amid substantial controversy over the effectiveness of preventive and therapeutic modalities. This article proposes an approach to the diagnosis and treatment of preterm labor that concurs with the guidelines recently established by the American College of Obstetricians and Gynecologists (ACOG).[2]

Etiology and Epidemiology

In most cases, the cause of preterm labor is not diagnosed, and the etiology is likely to be multifactorial. The clinical factors associated with preterm. labor are listed in Table 1. In 25 percent of preterm births, labor is induced for various maternal and fetal medical indications; approximately 30 percent of preterm, births are associated with premature rupture of the membranes (PROM). Preterm birth can potentially be prevented in less than one half of the mothers who present in labor earlier than 37 weeks of gestation.[3] Consequently, family physicians should identify all women in early preterm labor or at risk for preterm labor.

TABLE 1 Clinical Factors Associated with Preterm Labor

Maternal factors

Low socioeconomic status

Nonwhite race

Maternal age [is less than or equal to] 18 or

[is greater than or equal to] 40 years

Low prepregnancy weight


Substance abuse

Maternal history

Previous history of preterm delivery

Previous history of a second-trimester abortion

Uterine factors

Uterine volume increased

Uterine anomalies



Because family physicians often have the advantage of seeing a patient before conception, they may be able to influence some of the maternal factors associated with preterm labor. All women, especially those under 18 or over 40 years of age, should be offered education and/or intervention for family planning, smoking, substance abuse, poor nutrition, sexually transmitted diseases and adverse work conditions that could harm a fetus. Prenatal care should also be provided in underserved rural and urban areas to women at high risk for preterm birth. Furthermore, pregnancy outcome can be optimized by the treatment of preexisting medical conditions, such as hypertension and diabetes.

Uterine malformations that predispose a patient to preterm labor include a bicornate or unicorn uterus, and uterine fibroids, particularly submucosal and subplacental fibroids. Women who are diagnosed with uterine malformations before conception may be given the option of birth control or surgery, if applicable. Cervical incompetence from trauma or exposure to diethylstilbestrol can lead to painless cervical dilation and preterm labor. Both of these conditions may respond to the placement of a cerclage; however, no controlled trials have been conducted to support this approach.

Infections of the genitourinary tract are an important and treatable factor associated with preterm labor. Women with Neisseria gonorrhoeae, Chlamydia trachomatis, Treponema pallidum, Trichomonas vaginalis, Gardnerella vaginalis or group B streptococci infections have higher rates of preterm births. Although cause and effect have not yet been conclusively defined, diagnosis and treatment of these infections are necessary to prevent perinatal transmission.[4]

A maternal history of one or more second-trimester abortions or a previous history of preterm labor also increases the risk of subsequent preterm labor. Women with such a history should be given the option of effective family planning.

Markers of Preterm Labor and Delivery

A number of studies have attempted to identify clinical and biochemical markers of preterm labor and delivery associated with overall poor predictive values (Tables 2 and 3).[5-17] The most promising of these markers is the presence of fetal fibronectin in cervicovaginal secretions, which, if positive (defined as greater than 50 ng per mL) after 20 weeks of gestation, indicates decidual disruption.[14] In 1995, the U.S. Food and Drug Administration labeled fetal fibronectin enzymatic immunoassay for use as a screening test for preterm labor. In symptomatic patients, fetal fibronectin has an excellent sensitivity (69 to 93 percent)[14-17] and a negative predictive value as high as 99.7 percent (or, in other words, a one in 333 chance of delivery within one week of a negative test result).[15] The positive predictive value (PPV), that is, the ability to predict that a patient with a positive test result will have a preterm delivery, is as high as 83 percent in symptomatic patients. In the future, the greatest value of the test may be to identify a symptomatic patient with a negative test result who may then be followed without drug intervention.

TABLE 2Ability of Biochemical Markers to Predict Preterm Labor(*)Marker Test Sensitivity (%)Fibronectin Cervical or 69 to 93 vaginal[14-17]Cytokine Serum[5,16] 50 (Interleukin-6) Amniotic fluid[15] 52Estradiol-17[Beta] Serum[6] 12Estriol Salivary[7] 71Progesterone Serum[6] 6 to 35Marker Specificity (%) PPV(%) NPV(%)Fibronectin 72 to 86 13 to 83 81 to 99Cytokine 73 to 85 47 to 57 67 to 86 (Interleukin-6) 100 100 79Estradiol-17[Beta] 71 to 76 12 to 14 --Estriol 77 27 77Progesterone 67 to 69 7 to 32 --

PPV = positive predictive value; NPV = negative predictive value.

(*) --Values are a summary of ranges noted in the cited articles.

Information from references 5, 6 and 7, and 14 through 17.

TABLE 3Ability of Clinical Markers to Predict Preterm Labor(*)Marker Test Sensitivity (%)Risk scoring systems Risk factors[8,9] 88 to 92Assessment of Manual 8 to 64 cervical length examination[10,15,17] Ultrasound examination[11,12] 76 to 100Monitoring of Patient-perceived[13] NS uterine activity Tocodynamometry[10,15,17] 18 to 58Vaginal bleeding Pelvic examination[15,17] 8 to 36Marker Specificity(%) PPV(%) NPV(%)Risk scoring systems 23 to 30 94 to 98 41 to 76Assessment of 68 to 96 7 to 32 89 to 94 cervical length 55 to 59 55-75 93 to 100Monitoring of NS NS NS uterine activity 45 to 94 7 to 20 82 to 94Vaginal bleeding 89 to 95 21 to 82 82 to 97

PPV = positive predictive value; NPV = negative predictive value; NS = not significant (P < 0.05).

(*) --Values are a summary of ranges noted in the cited articles.

Information from references 8 through 13, and 15 through 17.

Fetal fibronectin is not a useful screening test in unselected populations (PPV: 13 to 36 percent).[18] At the present time, general use of the test cannot be recommended because of its cost (approximately $215), a lack of accessible laboratories performing the test and insufficient data to justify a clinical advantage.

Prevention of Preterm Delivery

Although prospective, randomized studies conducted in the United States have not shown that educating patients at high risk for preterm labor and health care personnel caring for them decreases the incidence of preterm births, studies in France have shown a decrease in preterm births following implementation of an education program for preterm labor.[19] Until further studies resolve the discord, family physicians who provide obstetric care should include risk identification and education regarding the signs and symptoms of preterm labor in routine prenatal care. Although bed rest and decreased activity have not been shown to decrease the rate of preterm birth in high-risk pregnancies, decreased activity is reasonable if the woman experiences increased uterine contractions with activity. Because the data do not clearly show benefits of monitoring uterine activity at home, it is not recommended at this time for the prevention of preterm delivery.[20]

[2.] American College of Obstetricians and Gynecologists, Preterm labor, Technical bulletin no. 206. Washington, D.C.: ACOG, 1995.

[3.] Goldenberg RL, Davis RO, Copper RL, Corliss DK, Andrews JB, Carpenter AH. The Alabama preterm birth prevention project. Obstet Gynecol 1990; 75:933-9.

[4.] Romero R, Mazor M, Munoz H, Gomez R, Galasso M, Sherer DM. The preterm labor syndrome. Ann N Y Acad Sci 1994;734:414-29.

[5.] Inglis SR, Jeremias J, Kuno K, Lescale K, Peeper Q, Chervenak FA, et al. Detection of tumor necrosis factor-alpha, interleukin-6, and fetal fibronectin in the lower genital tract during pregnancy: relation to outcome. Am J Obstet Gynecol 1994; 171:5-10.

[6.] Block BS, Liggins GC, Creasy RK. Preterm delivery is not predicted by serial plasma estradiol or progesterone concentration measurements. Am J Obstet Gynecol 1984;150:716-22.

[7.] McGregor JA, Jackson GM, Lachelin GC, Goodwin TM, Artal R, Hastings C, et al. Salivary estriol as risk assessment for preterm labor: a prospective trial. Am J Obstet Gynecol 1995;173:1337-42.

[8.] Holbrook RH Jr, Laros RK Jr, Creasy RK. Evaluation of risk-scoring system for prediction of preterm labor. Am J Perinatol 1989;6:62-8.

[9.] Creasy RK, Gummer BA, Liggins GC. System for predicting spontaneous preterm birth. Obstet Gynecol 1980;55:692-5.

[10.] Copper RL, Goldenberg RL, Dubard MB, Hauth JC, Cutter GR. Cervical examination and tocodynamometry at 28 weeks' gestation: prediction of spontaneous preterm birth. Am J Obstet Gynecol 1995;172(2 Pt 1):666-71.

[11.] Andersen HF, Nugent CE, Wanty SD, Hayashi RH. Prediction of risk for preterm delivery by ultrasonographic measurement of cervical length. Am J Obstet Gynecol 1990;163:859-67.

[12.] Iams JD, Paraskos J, Landon MB, Teteris JN, Johnson FF. Cervical sonography in preterm labor. Obstet Gynecol 1994;84:40-6.

[13.] Copper RL, Goldenberg RL, Davis RO, Cutter GR, DuBard MB, Corliss DK, et al. Warning symptoms, uterine contractions, and cervical examination findings in women at risk of preterm delivery. Am J Obstet Gynecol 1990; 162:748-54.

[14.] Lockwood CJ, Senyei A, Dische MR, Casal D, Shah KID, Thung SN, et al. Fetal fibronectin in cervical and vaginal secretions as a predictor of preterm delivery. N Engl J Med 1991;325:669-74.

[15.] Iams JD, Casal D, McGregor JA, Goodwin TM, Kreaden US, Lowensohn R, et al. Fetal fibronectin improves the accuracy of diagnosis of preterm labor. Am J Obstet Gynecol 1995;173:141-5.

[16.] Morrison JC, Allbert JR, McLaughlin BN, Whitworth NS, Roberts WE, Martin RW. Oncofetal fibronectin in patients with false labor as a predictor of preterm delivery. Am J Obstet Gynecol 1993;168:538-42,

[17.] Peaceman AM, Andrews WW, Thorp JM, Cliver SP, Lukes A, Iams JD, et al. Fetal fibronectin as a predictor of preterm birth in patients with symptoms: a multicenter trial. Am J Obstet Gynecol 1997;177:13-8.

[18.] Goldenberg RL, Mercer BM, Meis PJ, Copper RL, Das A, McNellis D. The preterm prediction study: fetal fibronectin testing and spontaneous preterm birth. Obstet Gynecol 1996;87(5 Pt 1):643-8.

[19.] Papiernik E. Prevention of preterm labour and delivery. Baillieres Clin Obstet Gynaecol 1993:7:499-521.

[20.] American College of Obstetricians and Gynecologists. Home uterine activity monitoring. Committee opinion no. 172. Washington, D.C.: ACOG, 1996.

[21.] Canadian Preterm Labor Investigators Group. Treatment of preterm labor with the beta-adrenergic agonist ritodrine. N Engl J Med 1992;327:308-12.

[22.] Creasy RK, Herron MA. Prevention of preterm birth. Semin Perinatol 1981;5:295-302.

[23.] Eschenbach DA. Bacterial vaginosis and anaerobes in obstetric-gynecologic infection. Clin Infect Dis 1993;16(Suppl 4):S282-7.

[24.] McCoy MC, Katz VL, Kuller JA, Killam AP, Livengood CH 3d. Bacterial vaginosis in pregnancy: an approach for the 1990s. Obstet Gynecol Surv 1995;50:482-8.

[25.] Romero R, Jimenez C, Lohda AK, Nores J, Hanaoka S, Avila C, et al. Amniotic fluid glucose concentration: a rapid and simple method for the detection of intraamniotic infection in preterm labor. Am J Obstet Gynecol 1990; 163:968-74.

[26.] King JF, Grant A, Keirse MJ, Chalmers I. Betamimetics in preterm labour: an overview of the randomized controlled trials. Br J Obstet Gynecol 1988;95:211-22.

[27.] Beall MH, Edgar BW, Paul RH, Smith-Wallace T. A comparison of ritodrine, terbutaline, and magnesium sulfate for the suppression of preterm labor. Am J Obstet Gynecol 1985;153:854-9.

[28.] Miller JM Jr, Keane MW, Horger EO 3d. A comparison of magnesium sulfate and terbutaline for the arrest of premature labor. A preliminary report. J Reprod Med 1982;27:348-51.

[29.] Effect of corticosteroids for fetal maturation on perinatal outcomes. NIH Consens Statement 1994 Feb 28 - Mar 2;12(2):1-18.

[30.] McCombs J. Update on tocolytic therapy. Ann Pharmacother 1995;29:515-22.

[31.] Shubert PJ. Atosiban. Clin Obstet Gynecol 1995; 38:722-4.

[32.] Goodwin TM, Paul R, Silver H, Spellacy W, Parsons M, Chez R, et al. The effect of the oxytocin antagonist atosiban on preterm uterine activity in the human. Am J Obstet Gynecol 1994; 170:474-8.

[33.] Macones GA, Berlin M, Berlin JA. Efficacy of oral beta-agonist maintenance therapy in preterm labor: a meta-analysis. Obstet Gynecol 1995;85:313-7.

[34.] Barden TP, Peter JB, Merkatz IR. Ritodrine hydrochloride: a betamimetic agent for use in preterm labor. I. Pharmacology, clinical history; administration, side effects and safety. Obstet Gynecol 1980;56:1-6.

[35.] Besinger RE, Niebyl JR, Keyes WG, Johnson TR. Randomized comparative trial of indomethacin and ritodrine for the long-term treatment of preterm labor. Am J Obstet Gynecol. 1991;164:981-6.

[36.] Morales WJ, Madhav H. Efficacy and safety of indomethacin compared with magnesium sulfate in the management of preterm labor: a randomized study. Am J Obstet Gynecol 1993; 169:97-102.

[37.] Meyer WR, Randall HW, Graves WL. Nifedipine versus ritodrine for suppressing preterm labor. J Reprod Med 1990;35:649-53.

[38.] Pettibone DJ, Clineschmidt BV, Kishel MT, Lis EV, Reiss DR, Woyden CJ, et al. Identification of an orally active, nonpepticlyl oxytocin antagonist. J Pharmacol Exp Ther 1993;264:308-14.

[39.] McGregor JA, French JI, Reller LB, Todd JK, Makowski EL. Adjunctive erythromycin treatment for idiopathic preterm labor: results of a randomized, double blind, placebo-controlled trial. Am J Obstet Gynecol 1986,-154:98-103.

Each year members of a different family practice department develop articles for "Problem-Oriented Diagnosis." This series is coordinated by the Department of Family and Community Medicine at the University of Alabama at Birmingham. Guest editors of the series are T. Michael Harrington, M.D., and Myra A. Crawford, Ph.D.

BEVERLY A. VON DER POOL, M.D., is an assistant professor and director of family medicine predoctoral education and family-centered maternal care programs in the Department of Family and Community Medicine at the University of Alabama School of Medicine, Birmingham. Dr. Von Der Pool received a medical degree from the University of California, San Francisco, School of Medicine, and completed a residency in family medicine at Providence Medical Center, a hospital affiliated with the University of Washington in Seattle.

Address correspondence to Beverly A. Von Der Pool, M.D., Department of Family and Community Medicine, University of Alabama School of Medicine, 930 South 20th St., Room 309, Birmingham, AL 35294-2042. Reprints are not available from the author.

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