Preterm Labor and Management

Preterm Labor Problems

There are two main problems associated with preterm labor:

  1. Immature Fetal Lungs:

    • The lungs mature around 34 to 37 weeks of gestation.

    • Preterm labor often occurs before the lungs are fully mature, leading to respiratory distress syndrome (RDS) due to a lack of surfactant.

    • RDS can cause significant morbidity and mortality in preterm infants.

  2. Immature Fetal Brain:

    • Increases the risk of cerebral palsy, a group of disorders that affect a person's ability to move and maintain balance and posture.

    • Premature infants are also at higher risk for intraventricular hemorrhage (IVH), which can cause long-term neurological deficits.

Treatment Methods

Fortunately, there are methods to address these issues:

  • Corticosteroids: Used to promote lung maturity by accelerating the production of surfactant.

  • Magnesium Sulfate: Administered to reduce the risk of cerebral palsy (neuroprotection), particularly in preterm deliveries less than 32 weeks of gestation.

Corticosteroids

Role in Preterm Labor

  • Accelerate lung maturity by enhancing surfactant production and release.

    • Reduces the risk of respiratory distress syndrome (RDS).

    • Decreases the incidence of transient tachypnea of the newborn (TTN).

  • Promote vascular stability.

    • Decreases the risk of intraventricular hemorrhage (IVH).

    • Reduces the risk of necrotizing enterocolitis (NEC).

Indications for Corticosteroid Use

  1. Preterm Labor Before 34 Weeks:

    • Definitely indicated since the lungs are still maturing, and the benefits of corticosteroids outweigh the risks.

  2. Preterm Labor Between 34 Weeks and 36 Weeks Plus Six Days:

    • ACOG (American College of Obstetricians and Gynecologists) guidelines recommend corticosteroid use.

    • Caveats:

      • No chorioamnionitis (absolute contraindication) due to the risk of worsening maternal and fetal outcomes.

      • Patient should not have received a prior course of corticosteroids within 14 days, as repeated doses may not provide additional benefit and could increase risks.

      • Monitor neonates for hypoglycemia after delivery, as corticosteroids can affect glucose metabolism.

  3. Planned Cesarean Section Before 37 Weeks:

    • Administer corticosteroids regardless of the reason for the cesarean to promote fetal lung maturity.

Corticosteroid Action and Timing

  • Action begins immediately after the first dose.

  • Maximum efficacy is seen between two to seven days after the first dose.

  • For best results, wait 48 hours after the initial dose before delivery to allow sufficient time for surfactant production.

Guidelines Based on Gestational Age

  • Preterm Labor Less Than/Equal to 34 Weeks:

    • Use tocolytics to delay delivery and allow corticosteroids to reach maximum efficacy (wait at least 48 hours).

  • Preterm Labor Between 34 Weeks and 36 Weeks Plus Six Days:

    • Administer corticosteroids without tocolytics, as the lungs are already maturing, and the risks of tocolytics may outweigh the benefits.

Side Effects of Corticosteroids

  • Maternal Hyperglycemia:

    • Screen for gestational diabetes either before corticosteroid administration or five days after to avoid misinterpreting glucose levels.

    • Monitor glucose levels in the mother every 6 hours for 24 hours.

    • ACOG recommends monitoring neonate glucose levels if corticosteroids are given between 34 and 36 weeks plus six days, especially in mothers with gestational diabetes.

Corticosteroid Dosage

  • Betamethasone:

    • Two doses of 12 mg each, given intramuscularly 24 hours apart.

    • Preferred steroid worldwide due to its proven efficacy and safety profile.

  • Dexamethasone:

    • Four doses of 6 mg each, given intramuscularly every 12 hours.

    • Common in India due to lower cost, but may have slightly different efficacy compared to betamethasone.

Contraindications for Corticosteroids

  • Absolute Contraindication: Chorioamnionitis due to the risk of exacerbating the infection and worsening outcomes.

  • Diabetes and hypertension are not contraindications, but monitor glucose levels closely to manage hyperglycemia and hypertension.

Repeat Corticosteroid Injections

  • Should not be given repeatedly (rescue course) due to the risk of cerebral palsy and other adverse neurodevelopmental outcomes. A single repeat course can be considered if the patient remains at high risk of preterm delivery within 7 days and the prior course was given more than 14 days ago. Further research is needed in this area.

Tocolytics

Role of Tocolytics

  • The primary role is to buy time for corticosteroids to act (usually 48 hours).

  • Maximum use is up to 34 weeks of pregnancy and for no more than 48 hours due to increased risks and limited benefits beyond this gestational age.

First-Line Tocolytics

  • Nifedipine:

    • Generally the tocolytic of choice in India due to its safety and efficacy.

  • Indomethacin:

    • According to ACOG guidelines, it is the tocolytic of choice up to 32 weeks.

    • Between 32 to 34 weeks, nifedipine is preferred due to the risk of premature closure of the ductus arteriosus with indomethacin.

Reasons for Preference

  • Indomethacin is avoided beyond 32 weeks due to the risk of premature closure of the ductus arteriosus and oligohydramnios.

  • Oligohydramnios can occur if indomethacin is used for more than 48 hours, leading to potential fetal complications.

Second-Line Tocolytics

  • Atosiban (not FDA approved in the US)

  • Magnesium sulfate (primarily for neuroprotection, but also has tocolytic effects)

  • Beta-2 agonists (e.g., terbutaline, ritodrine)

  • Nitric oxide donors (e.g., nitroglycerin)

Important Note

  • Progesterone is not a tocolytic; it can prevent preterm birth in women with a history of preterm birth or a short cervix but does not stop active labor.

Tocolytic Details

A table format is useful here including:

  • Tocolytic name

  • Dosage

  • Maternal Side Effects

  • Fetal Side Effects

  • Contraindications

Nifedipine

  • Safest tocolytic.

  • Calcium channel blocker.

    • Loading dose: 20-30 mg orally.

    • Maintenance: 10-20 mg every 3-8 hours (maximum 180 mg/day).

  • Maternal Side Effects:

    • Flushing, headache, dizziness, hypotension (due to vasodilation).

  • Fetal Side Effects:

    • No significant fetal side effects.

  • Contraindications:

    • Hypotension, heart failure with decreased ejection fraction.

Indomethacin

  • COX inhibitor (non-specific) and antiplatelet drug.

    • Loading dose: 50-100 mg orally.

    • Maintenance: 25 mg every 4-6 hours.

  • Maternal Side Effects:

    • Nausea, gastritis, GI reflux, platelet dysfunction.

  • Fetal Side Effects:

    • Premature closure of ductus arteriosus (if used beyond 32 weeks).

    • Oligohydramnios (if used for more than 48 hours).

  • Contraindications:

    • Liver disease, kidney disease, bleeding diathesis, severe gastritis or ulcerative disease.

Beta-2 Agonists (Terbutaline)

  • Less preferred due to maternal side effects.

  • Maternal Side Effects:

    • Tremors, palpitations, tachycardia (monitor heart rate, stop if ">= 120 bpm").

    • Hyperglycemia, hypokalemia (monitor glucose and potassium levels every 4-6 hours).

    • Pulmonary edema, myocardial infarction (rare).

  • Fetal Side Effects:

    • Neonatal hypoglycemia (not very significant).

  • Contraindications:

    • Heart failure with tachycardia, diabetic patients, poorly controlled hyperthyroidism.

    • Use cautiously in pregnant females at risk of bleeding (e.g., placenta previa).

Atosiban

  • Oxytocin/vasopressin receptor antagonist.

  • Not FDA approved; not available worldwide/in India.

  • No significant maternal or fetal side effects; no contraindications.

  • Best tocolytic for heart disease patients.

Magnesium Sulfate (MgSO4)

  • Tocolytic effect at concentrations of 9-10 mEq/L, which can cause maternal side effects.

  • Maternal Side Effects:

    • Diaphoresis, slurring of speech, loss of deep tendon reflexes.

  • No significant fetal side effects.

  • Contraindications:

    • Myasthenia gravis, cardiac conduction defects, renal failure, myocardial compromise or infarction.

  • Do not use with calcium channel blockers due to the risk of respiratory depression.

  • Monitor respiratory rate, deep tendon reflexes, and urine output.

Key One-Liners on Tocolytics

  • Safest tocolytic: Nifedipine

  • Drawback of indomethacin beyond 32 weeks: Closure of ductus arteriosus

  • Tocolytic of choice in heart disease patients: Atosiban

  • Tocolytic contraindicated in diabetic patients: Beta-2 agonists

  • Tocolytic of choice in diabetic patients: Nifedipine

Absolute Contraindications to Tocolytics

These are conditions where tocolytics as a class should not be used:

  • Intrauterine fetal demise.

  • Lethal fetal anomaly on ultrasound.

  • Fetal distress (category III tracings on CTG).

  • Chorioamnionitis (corticosteroids are also contraindicated).

  • Maternal hemodynamic instability.

  • Preterm labor at or beyond 34 weeks.

  • Preterm premature rupture of membranes (PPROM) with unstable lie (increased risk of cord prolapse).

  • Cervical dilatation greater than or equal to 3 cm.

Magnesium Sulfate for Neuroprotection

  • Decreases the risk of cerebral palsy.

  • Administer when preterm labor occurs at less than 32 weeks.

    • Loading dose: 4 g IV over 20 minutes.

    • Maintenance dose: 1 g/hr IV.

    • Maximum duration: 24 hours.

  • Monitor respiratory rate and deep tendon reflexes.

  • Contraindications are the same as when used as a tocolytic.

Overall Management of Preterm Labor

Management differs based on gestational age:

Preterm Labor At or Beyond 34 Weeks vs. Less Than 34 Weeks
Initial Steps (Both Groups)

  • Admit the patient.

  • Observe for dilatation and contractions (for at least 4-6 hours).

  • Administer Group B Streptococcus (GBS) prophylaxis.

  • Take rectovaginal swab for culture.

  • Start GBS prophylaxis while awaiting culture results (48-72 hours).

  • Administer corticosteroids (to accelerate lung maturity).

Specific Interventions

Intervention

At or Beyond 34 Weeks

Less Than 34 Weeks

Tocolytics

Not indicated

Administer for 48 hours to allow corticosteroids to act.

Magnesium Sulfate

Not indicated

Administer (neuroprotective) if less than 32 weeks.

Progesterone

Not indicated (once preterm labor is established)

Not indicated (once preterm labor is established)

Induction of Labor

Not indicated

Not indicated

General Considerations

  • Monitor for 4-6 hours; if contractions subside and there is no dilatation, the patient can be sent home.

  • Assess fetal membranes (ensure they are intact).

  • Rule out abruptio placentae and fetal distress.

Group B Streptococcus (GBS) Screening

Timing

  • Screen all pregnant females between 36 weeks and 37 weeks plus six days.

  • Screen all pregnant females undergoing preterm labor.

Method

  • Rectovaginal swab (lower vagina near the introitus, rectal swab 1 cm above the anal sphincter).

  • Place swab(s) in Stuart media at room temperature and send to the lab.

Exceptions (No Screening Needed)

  • Previous history of a neonate with GBS infection.

  • GBS bacteriuria in the current pregnancy.

  • In these cases, administer GBS prophylaxis regardless of prior screening results.

GBS Prophylaxis

  • Given to prevent neonatal sepsis.

  • Administer intrapartum.

Indications for GBS Prophylaxis (International Guidelines)

  • Positive GBS screening.

  • GBS bacteriuria in the current pregnancy.

  • Previous history of a neonate affected by GBS.

  • Unknown GBS status with intrapartum fever ("> 100.4°F").

  • Preterm labor with unknown GBS status.

  • Preterm premature rupture of membranes.

  • Premature rupture of membranes for more than 18 hours.

Drug of Choice

  • Penicillin G: 5 million units loading dose, then 2.5 million units every 4 hours until delivery.

  • Alternative: Ampicillin (2 g IV initially, then 1 g IV every 4 hours until delivery).

  • If allergic to penicillin: Cefazolin (2 g IV, then 1 g IV every 8 hours).

  • In resistant cases: Vancomycin.