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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, Belizán 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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