BEST PRACTICE GUIDELINES -  Evidence based care : Management of Preterm Labor

 

EVIDENCE BASED CARE: MANAGEMENT OF PRETERM LABOR
A compilation of recommendations from various bibliographic sources
 
INTRODUCTION


Preterm birth occurs in around 6% to 10% of birthsis the major complication of pregnancy associated with perinatal mortality and morbidity. Previous preterm delivery is a strong predictor for preterm labour, and the earlier the birth, the more likely it is to be repeated at the same gestation.


The following recommendations are based on good and consistent scientific evidence (Level A):

  • There are no clear "first-line" tocolytic drugs to manage preterm labor. Clinical circumstances and physician preferences should dictate treatment.

  • Antibiotics do not appear to prolong gestation and should be reserved for group B streptococcal prophylaxis in patients in whom delivery is imminent. There is no clear overall benefit from prophylactic antibiotic treatment for preterm labour with intact membranes on neonatal outcomes This treatment cannot therefore be currently recommended for routine practice.

  • Neither maintenance treatment with tocolytic drugs nor repeated acute tocolysis improve perinatal outcome; neither should be undertaken as a general practice.

  • Tocolytic drugs may prolong pregnancy for 2 to 7 days, which may allow for administration of steroids to improve fetal lung maturity and the consideration of maternal transport to a tertiary care facility.

The following recommendations are based on limited or inconsistent scientific evidence (Level B):

  • Cervical ultrasound examination and fetal fibronectin testing have good negative predictive value; thus, either approach or both combined may be helpful in determining which patients do not need tocolysis.

  • Amniocentesis may be used in women in preterm labor to assess fetal lung maturity and intra-amniotic infection.

  • Bed rest, hydration, and pelvic rest do not appear to improve the rate of preterm birth and should not be routinely recommended.

  • PROBIOTICS: Probiotics are defined as live micro-organisms which, when administered in an adequate amount, confer a health benefit on the host. They have been shown to displace and kill pathogens and modulate the immune response by interfering with the inflammatory cascade that leads to preterm labour and delivery. Although the use of probiotics appears to treat vaginal infections in pregnancy, there are currently insufficient data from trials to assess impact on preterm birth and its complications.

Benefits of Specific Medication

  • Antenatal corticosteroids significantly reduce the incidence and severity of neonatal respiratory distress syndrome. The incidence of intraventricular hemorrhage and necrotizing enterocolitis also are reduced by the use of antenatal corticosteroids.

  • Tocolytic drugs may prolong gestation for 2 to 7 days, which can provide time for administration of steroids and maternal transport to a facility with a neonatal intensive care unit.

  • Calcium channel Blockers: When tocolysis is indicated for women in preterm labour, calcium channel blockers are preferable to other tocolytic agents compared, to other agents. When compared with any other tocolytic agent (mainly betamimetics), calcium channel blockers reduced the number of women giving birth within seven days of receiving treatment (relative risk (RR) 0.76; 95% confidence interval (CI) 0.60 to 0.97) and prior to 34 weeks' gestation (RR 0.83; 95% CI 0.69 to 0.99). Calcium channel blockers also reduced the requirement for women to have treatment ceased for adverse drug reaction the frequency of neonatal respiratory distress syndrome, necrotising enterocolitis, intraventricular haemorrhage and neonatal jaundice

  • Oral Betamimetics: Available evidence does not support the use of oral betamimetics for maintenance therapy after threatened preterm labour.

  • Nitric Oxide donors: There is currently insufficient evidence to support the routine administration of nitric oxide donors in the treatment of threatened preterm labour

  • Magnesium Sulphate: Magnesium sulphate is ineffective at delaying birth or preventing preterm birth, and its use is associated with an increased mortality for the infant. The risk of death (fetal and paediatric) was higher for infants exposed to magnesium sulphate (RR 2.82, 95% CI 1.20-6.62, 7 trials, 727 infants). Any further trials should be of high quality large enough to assess serious morbidity and mortality, compare different dose regimens, and provide neurodevelopmental status of the child.

  • COX Inhibitors: There is insufficient information on which to base decisions about the role of COX inhibition for women in preterm labour.  

  • Screening for lower genital tract infection antenatal: There is evidence that infection screening and treatment programs in pregnant women may reduce preterm birth and preterm low birthweights.

POTENTIAL HARMS


Side Effects of Tocolytic Medication


Terbutaline

  • Maternal side effects: Cardiac or cardiopulmonary arrhythmias, pulmonary edema, myocardial ischemia, hypotension, tachycardia

  • Fetal and neonatal side effects: Fetal tachycardia, hyperinsulinemia, hyperglycemia, myocardial and septal hypertrophy, myocardial ischemia

Ritodrine

  • Maternal side effects: Metabolic hyperglycemia, hyperinsulinemia, hypokalemia, antidiuresis, altered thyroid function, physiologic tremor, palpitations, nervousness, nausea or vomiting, fever, hallucinations

  • Fetal and neonatal side effects: Neonatal tachycardia, hypoglycemia, hypocalcemia, hyperbilirubinemia, hypotension, intraventricular hemorrhage

Magnesium Sulfate

  • Maternal side effects: Flushing, lethargy, headache, muscle weakness, diplopia, dry mouth, pulmonary edema, cardiac arrest

  • Fetal and neonatal side effects: Lethargy, hypotonia, respiratory depression, demineralization with prolonged use

Calcium Channel Blockers

  • Maternal side effects: Flushing, headache, dizziness, nausea, transient hypotension. Caution should be used in patients with renal disease and hypotension when administering calcium channel blockers. In addition, concomitant use of calcium channel blockers and magnesium sulfate is potentially harmful and has resulted in cardiovascular collapse.

  • Fetal and neonatal side effects: None noted as yet

Indomethacin

  • Maternal side effects: Nausea, heartburn

  • Fetal and neonatal side effects: Constriction of ductus arteriosus, pulmonary hypertension, reversible decrease in renal function with oligohydramnios, intraventricular hemorrhage, hyperbilirubinemia, necrotizing enterocolitis

Note: Combining tocolytic drugs potentially increases maternal morbidity and should be used with caution

 

CONTRAINDICATIONS

  • Tocolysis. General contraindications for tocolysis include severe preeclampsia, placental abruption, intrauterine infection, lethal congenital or chromosomal abnormalities, advanced cervical dilatation, and evidence of fetal compromise or placental insufficiency.

  • Beta-mimetic. Contraindications include cardiac arrhythmias (for terbutaline) and poorly controlled thyroid disease and diabetes mellitus (for ritodrine).

  • Magnesium sulfate. Contraindications include myasthenia gravis.

  • Calcium channel blockers. Contraindications include cardiac disease; should not be used concomitantly with magnesium sulfate.

  • Prostaglandin synthetase inhibitors. Contraindications include significant renal or hepatic impairment (for indomethacin), active peptic ulcer disease (for ketorolac), coagulation disorders or thrombocytopenia, nonsteroidal anti-inflammatory drug (NSAID)-sensitive asthma, other sensitivity to NSAIDs (for sulindac).

Progesterone in the prevention of preterm birth


Intramuscular progesterone is associated with a reduction in the risk of preterm birth less than 37 weeks' gestation, and infant birthweight less than 2500 grams. However, other important maternal and infant outcomes have been poorly reported to date, with most outcomes reported from a single trial only (Meis 2003). It is unclear if the prolongation of gestation translates into improved maternal and longer-term infant health outcomes.


Women and their caregivers should be aware that a previous preterm labour and/or short cervix (< 15 mm at 22???26 weeks??? gestation) on transvaginal ultrasound could be used as an indication for progesterone therapy. The therapy should be started after 20 weeks??? gestation and stopped when the risk of prematurity is low. (I-A) On the basis of the data from the RCTs and meta-analysis, it is recommended that in cases where the clinician and the patient have opted for the use of progesterone the following dosages


should be used:


??? For prevention of PTL in women with history of previous PTL:
17 alpha- hydroxyprogesterone 250 mg IM weekly (IB) or
progesterone 100 mg daily vaginally. (I-A)


??? For prevention of PTL in women with short cervix of _ 15 mm
detected on transvaginal uktrasound at 22???26 weeks progesterone 200 mg daily vaginally. (I-A)


BIBLIOGRAPHIC SOURCE(S)

  • American College of Obstetricians and Gynecologists (ACOG). Management of preterm labor. Washington (DC): American College of Obstetricians and Gynecologists (ACOG); 2003 May. 9 p. (ACOG practice bulletin; no. 43). [74 references]

  • The use of progesterone for prevention of preterm birth: SOGC Technical Update No 202 January 2008

  • King J, Flenady V. Prophylactic antibiotics for inhibiting preterm labour with intact membranes. Cochrane Database of Systematic Reviews 2002, Issue 4. Art. No.: CD000246. DOI: 10.1002/14651858.CD000246

  • Othman M, Neilson JP, Alfirevic Z. Probiotics for preventing preterm labour. Cochrane Database of Systematic Reviews 2007, Issue 1. Art. No.: CD005941. DOI: 10.1002/14651858.CD005941.pub2

  • Dodd JM, Flenady V, Cincotta R, Crowther CA. Prenatal administration of progesterone for preventing preterm birth. Cochrane Database of Systematic Reviews 2006, Issue 1. Art. No.: CD004947. DOI: 10.1002/14651858.CD004947.pub2.

  • Dodd JM, Crowther CA, Dare MR, Middleton P. Oral betamimetics for maintenance therapy after threatened preterm labour. Cochrane Database of Systematic Reviews 2006, Issue 1. Art. No.: CD003927. DOI: 10.1002/14651858.CD003927.pub2.

  • Doyle LW, Crowther CA, Middleton P, Marret S. Magnesium sulphate for women at risk of preterm birth for neuroprotection of the fetus. Cochrane Database of Systematic Reviews 2007, Issue 3. Art. No.: CD004661. DOI: 10.1002/14651858.CD004661.pub2.

  • Crowther CA, Hiller JE, Doyle LW. Magnesium sulphate for preventing preterm birth in threatened preterm labour. Cochrane Database of Systematic Reviews 2002, Issue 4. Art. No.: CD001060. DOI: 10.1002/14651858.CD001060
    Stan C, Boulvain M, Hirsbrunner-Amagbaly P, Pfister R. Hydration for treatment of preterm labour. Cochrane Database of Systematic Reviews 2002, Issue 2. Art. No.: CD003096. DOI: 10.1002/14651858.CD003096

  • King J, Flenady V, Cole S, Thornton S. Cyclo-oxygenase (COX) inhibitors for treating preterm labour. Cochrane Database of Systematic Reviews 2005, Issue 2. Art. No.: CD001992. DOI: 10.1002/14651858.CD001992.pub2.

  • King JF, Flenady VJ, Papatsonis DNM, Dekker GA, Carbonne B. Calcium channel blockers for inhibiting preterm labour. Cochrane Database of Systematic Reviews 2003, Issue 1. Art. No.: CD002255. DOI: 10.1002/14651858.CD002255.

  • Sosa C, Althabe F, Beliz??n J, Bergel E. Bed rest in singleton pregnancies for preventing preterm birth. Cochrane Database of Systematic Reviews 2004, Issue 1. Art. No.: CD003581. DOI: 10.1002/14651858.CD003581.pub2.

  • Swadpanich U, Lumbiganon P, Prasertcharoensook W, Laopaiboon M. Antenatal lower genital tract infection screening and treatment programs for preventing preterm delivery. Cochrane Database of Systematic Reviews 2008, Issue 2. Art. No.: CD006178. DOI: 10.1002/14651858.CD006178.pub2.

 
     

 
         
     

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