Diagnosis and Management of Preterm Labor

James Ducey MD Staten Island University Hospital

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Making The Diagnosis

Labor is a retrospective diagnosis Once vaginal delivery has occurred we can be sure the woman was in labor There are a variety of methods we use to diagnose labor None of them are foolproof
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Clinical Factors Used to Predict Preterm Labor

Risk assessment is a concept first proposed by Papiernik (Presse Med 1969) The hope was that identification of women at increased risk to give birth early prior to the onset of labor would lead to interventions that would prevent preterm birth
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Risk Assessment
The frequency of a large # of demographic and epidemiological markers in women who did and did not give birth were compared Scoring systems to predict which women were at increased risk for preterm birth

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Economic

Poor Unemployed Father is either Not insured No access to care Not well fed

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Behavioral

Poor education Not compliant with prenatal care Substance abuse Old or young Life stresses

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Medical

Mom was small at birth Short Underweight or overweight? Chronic illnesses

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Obstetric

Previous preterm birth Multiple birth Acute infections Hypertensive disorders of pregnancy Uterine anomalies

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Risk Assessment

Creasy and co-workers have published a number of more simplified scoring systems(ObGyn 1980,1982,Birth Defects 1983) Prospective studies have reported sensitivities of 40 60% Positive predictive values between 15 30%

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History
Pain-abdominal,back,pelvic,vaginal,gas Vaginal bleeding, staining Pelvic pressure Urinary frequency Diarrhea or constipation

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History

Many normal women who deliver at term have similar symptoms Iams etal (ObGyn 1990) reported that 1/3 of the women they studied that developed preterm labor had no symptoms at all

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Physical Examination
Asymptomatic effacement and dilation of the cervix frequently occurs prior to labor It may be the first sign of labor, cervical incompetence or normal variation especially in multiparous women Buekens ( Lancet 1994) in a randomized study of over 5000 women showed no difference in outcome when cervical exam was performed at every visit
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Uterine Activity
Frequency and duration of uterine contractions can be monitored accurately in an ambulatory setting There is an increase in uterine activity in 24 hours prior to preterm labor (Katz ObGyn 1986)

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Uterine Activity

Initial studies were promising In addition to uterine activity monitoring there was a lot of nursing contact Much controversy ensued May diagnose preterm labor sooner Not clinically significant

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Biochemical Markers
Estrogen Progesterone Prostaglandins and their metabolites Activan Inhibin Collagenase Tissue inhibitors of metaloproteinases Fetal Fibronectin
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Fetal Fibronectin

Component of extra cellular matrix Lockwood (NEJM 1991) found that levels were elevated in cervicovaginal secretions in women who delivered early AHRQ published a review of the data

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Fetal Fibronectin
7 Days Sensitivity 89.4% <37 Weeks 54.7%

Specificity
PPV NPV

83.3%
22.9% 99.3%

85.6%
58.8% 83.4%

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Fetal Fibronectin AT SIUH

81 Test in 71 women

20 have delivery data

13 Negatives 8 were term 5 preterm (all 35 36 weeks) None within 7 days

7 positives 3 were term 4 preterm (all <32 weeks) 2 within 7 days

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Endovaginal Ultrasound

Cervix visualized in great detail Funneling of the internal cervical os Length of the cervix Sensitivity, specificity, positive and negative predictive values similar to fetal fibronectin

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Treatment
Surgery Pharmacological agents Behavioral changes

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Correction of Uterine Malformations

Women with defects in lateral fusion of the Mullarian ducts appear to be at increased risk for preterm labor Surgery is usually reserved only for habitual abortion

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Cervical Incompetence
History of cervical trauma or surgery Two subsequent pregnancies that terminated spontaneously in the late second or early third trimester and the loss was characterized by days of pelvic pressure followed by spontaneous rupture of the membranes and quick painless labor
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Cerclage

Has become the standard treatment Large prospective randomized study was carried out by RCOG 1992(BJOG 1993) A heterogeneous group of women felt to be at increased risk for preterm birth

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Cerclage

A very safe operation There was a significant decrease in delivery prior to 35 weeks in women who under went cerclage 25 operations to prevent 1 preterm birth

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Pharmacological Agents
Tocolytics Glucocorticoids Thyrotropin-releasing hormone Antibiotics Others

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Tocolytics
Magnesium sulfate Beta adrenergic agonists Prostaglandin inhibitors Calcium channel blockers Oxytocin-receptor antagonist Ethanol Progesterone
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Tocolytics

All these drugs seem to delay delivery 48 hours None is superior in efficacy Delay of 48 hours improves neonatal outcome when corticosteroids are used in conjunction

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Magnesium Sulfate
Maternal side effects are nausea, uncomfortable sensation of heat, weakness, pulmonary edema(1%) and respiratory arrest Fetal side effects are hypotonia and hypocalcemia

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Beta Adrenergic Agonists

Ritodrine and Terbutaline Maternal side effects include myocardial ischemia, pulmonary edema(4%), hypotension, tachycardia, hypokalemia, hyperglycemia and acidosis Fetal effects include hypotension, tachycardia, hypoglycemia and hyperbilirubinemia
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Prostaglandin Synthetase Inhibitors

Indomethacin Maternal side effects include GI upset, rash, headache and interstitial nephritis Fetal effects include oliguria, oligohydramnios, premature closure of the ductus arteriosus and pulmonary hypertension
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Calcium Channel Blockers

Nifedipine Maternal side effects include headache, nausea,flushing,hypotension,tachycardia and hepatotoxicity Fetal effects are not clear

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Oxytocin Receptor Blockers

Atosiban new drug that appears to be effective Causes nausea, headache, chest pain, arthralgias and may inhibit lactation

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Ethanol

No longer used Caused acute intoxication in the mother May be toxic to the fetus

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Progesterones
Has been used for many years to prevent miscarriage without proven efficacy Keirse (BrJObGyn 1990) found that when used routinely on initial registration resulted in a significant decrease in preterm labor and birth No effect on neonatal morbidity or mortality however
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Antenatal Steroids
Crowley etal(BrJObGyn 1990) meta-analysis of 12 controlled studies There was a significant decrease in RDS,IVH,NEC and NND NIH conference 1995 concluded that all women at risk for preterm birth between 24 and 34 weeks are candidates
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TRH
Knight etal (AJOG 1994)reported that adding TRH to corticosteroids improved fetal lung maturation Crowther etal (Lancet 1995) was unable to reproduce the results and had a high incidence of hypertension develop in treated women
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Antibiotics
Several studies have looked at the use of various drugs to treat subclinical infections and prevent neonatal sepsis Results have been inconsistent Has not gained acceptance

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Behavioral Changes
Bed rest Coitus Substance abuse Obesity

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Obesity

Will kill more Americans in the next 50 years than cancer, cigarette smoking and HIV combined

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Obesity

Schieve etal (Epid 1999) women with increased weight gain during pregnancy were at increased risk for preterm birth Rothacker etal (ADA2000) mean weight gain of women 20 30 years of age from 1992 to 1997 increased 12.1 kg

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The Future

Tocolysis will only impact on <5% of preterm birth Fetal fibronectin and/or endovaginal ultrasound needs to be used to identify objectively women for randomized studies

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The Future

Reproductive endocrinologist need to limit the # of embryos they implant Iatrogenic prematurity continues in some places despite many of our best efforts

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