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06/06/12 Antenatal use of corticosteroids in women at risk for preterm delivery
Antenatal use of corticosteroids in women at risk for preterm delivery
Disclosures
All topics are updated as new evidence becomes available and our peer review process is complete.Literature review current through: Apr 2012. | This topic last updated: may 11, 2012.
INTRODUCTION — In a landmark paper, Liggins and Howie demonstrated that antenatal corticosteroid therapy
administered to women at risk for preterm delivery (PTD) reduced the incidence of respiratory distress syndrome
(RDS) and mortality in their offspring [1]. The efficacy of antenatal corticosteroid therapy has been confirmed
subsequently by over a dozen randomized placebo-controlled trials [2-16]. The reduction in the severity and
incidence of RDS has resulted in decreased requirements for surfactant therapy, lower concentrations of
supplemental oxygen, and decreased need for prolonged mechanical ventilation in the neonatal period [17].
Premature infants exposed to antenatal corticosteroid therapy also have more circulatory stability and are less
likely to experience an intraventricular hemorrhage (IVH) or necrotizing enterocolitis than unexposed preterm
infants.
The National Institutes of Health (NIH) [17], American College of Obstetricians and Gynecologists (ACOG) [18],
Royal College of Medicine [19], and other major organizations have recommended antenatal corticosteroid
treatment for women at risk for preterm delivery prior to 34 weeks of gestation. The specific recommendations made
by the NIH are listed in the table (table 1).
This topic will review scientific evidence supporting the use of antenatal corticosteroids to improve neonatal
outcomes in women at risk for preterm delivery, pharmacological issues associated with this therapy, and other
clinical concerns from administration of antenatal corticosteroids.
MECHANISM OF ACTION — Antenatal corticosteroid therapy leads to improvement in neonatal lung function via
two mechanisms: by enhancing maturational changes in lung architecture, and by inducing lung enzymes that play
a role in biochemical maturation [20,21].
Alveoli are lined with two types of cells, the type 1 and type 2 pneumocytes. The type 1 pneumocyte is responsible
for gas exchange in the alveoli, while the type 2 pneumocyte is responsible for the production and secretion of
surfactant. Antenatal corticosteroid therapy accelerates morphologic development of both types of alveolar cells.
This is observed histologically as: flattening of epithelial cells, thinning of alveolar septa, and increased
cytodifferentiation. These changes, and others, increase maximal lung volume and compliance.
Antenatal corticosteroids also regulate enzymes in type II pneumocytes that stimulate phospholipid synthesis and
subsequent release of surfactant (figure 1). The sequence of events is as follows [22-24]: (1) free corticosteroid
enters the fetal type II pneumocyte and binds to specific intracellular corticosteroid receptors, (2) the steroid-
receptor complex then binds with corticosteroid response elements (GREs) located along the genome, (3) there is
increased transcription of certain genes and the resulting messenger ribonucleic acid (mRNA) is translated into
specific enzymatic proteins, and (4) the enzymatic proteins stimulate phospholipid synthesis.
In addition, antenatal corticosteroids alter production of surfactant binding proteins and enhance fetal lung
antioxidant enzymes. Cumulatively, the architectural and biochemical changes induced by antenatal corticosteroid
therapy improve both lung mechanics and gas exchange. For these changes to occur, however, the lungs need to
06/06/12 Antenatal use of corticosteroids in women at risk for preterm delivery
Given these benefits, we recommend antenatal corticosteroids be administered to pregnant woman at 23 to
34 weeks who are at increased risk of preterm delivery within the next seven days (Grade 1A). In our
practice, this means we restrict administration of the first course of antenatal corticosteroids to women who
rupture membranes or are receiving tocolysis for active preterm labor, or in whom delivery for maternal or fetal
indications is anticipated within the next seven days. This approach minimizes the need for salvage therapy
while allowing the vast majority of women to receive a course of antenatal corticosteroids prior to preterm
delivery. A course of antenatal corticosteroids consists of betamethasone suspension 12 mg intramuscularly
every 24 hours for two doses or four doses of 6 mg dexamethasone intramuscularly 12 hours apart. (See
'Choice of agent' above and 'Timing before delivery' above.)
The lower limit of gestational age for administration is approximately 23 weeks since only a few primitive
alveoli are present below this gestational age. Earlier administration is reasonable if aggressive neonatal
intervention is planned for a delivery prior to 23 weeks of gestation. After 34 weeks of gestation, we suggest
administration be limited to women with documented fetal pulmonary immaturity and obstetrical issues
requiring prompt delivery (Grade 2B). (See 'Gestational age at administration' above.)
The absence of consistent and long-term data precludes making an evidence-based recommendation for the
number of courses that are safe for the fetus, the appropriate time interval between courses, the optimal
dose for repeated courses of therapy, or the full ramifications of the single course approach to therapy. Given
the potential for harm from repeated courses of antenatal corticosteroid therapy:
We suggest a single course of salvage therapy only if more than two weeks have elapsed since the
initial course of antenatal corticosteroid therapy, the gestational age at administration of the initial
course was <28 weeks of gestation, the current gestational age is less than 33 weeks, AND the risk of
preterm birth has increased (eg, deterioration in the maternal or fetal status, contractions with newly
positive fetal fibronectin test result, further cervical effacement or dilatation) (Grade 2C).
We also suggest that providers who elect to give salvage therapy use one dose of 12 mg
betamethasone and limit treatment to this one additional course of antenatal corticosteroids (Grade
2C). One dose appears to be effective and may minimize complications related to steroid use. Patients
should be informed of potential adverse effects. (See 'Repeated courses of therapy' above and 'Salvage
(rescue) therapy' above.)
We recommend antenatal corticosteroids for women with preterm premature rupture of membranes (Grade
1A). We give them at 23 to 32 weeks of gestation in the absence of any clinical signs of chorioamnionitis.
Some experts will administer antenatal corticosteroids at 32 to 34 weeks if pulmonary immaturity has been
documented, although efficacy has not been proven. (See 'Preterm premature rupture of membranes' above.)
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131. Crowther CA, Doyle LW, Haslam RR, et al. Outcomes at 2 years of age after repeat doses of antenatalcorticosteroids. N Engl J Med 2007; 357:1179.
132. Murphy KE, Hannah ME, Willan AR, et al. Multiple courses of antenatal corticosteroids for preterm birth(MACS): a randomised controlled trial. Lancet 2008; 372:2143.
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134. Peltoniemi OM, Kari MA, Tammela O, et al. Randomized trial of a single repeat dose of prenatalbetamethasone treatment in imminent preterm birth. Pediatrics 2007; 119:290.
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141. Lee MJ, Davies J, Guinn D, et al. Single versus weekly courses of antenatal corticosteroids in pretermpremature rupture of membranes. Obstet Gynecol 2004; 103:274.
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Topic 6796 Version 14.0
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Recommendations for use of antenatal corticosteroids
The benefits of antenatal administration of corticosteroids to fetuses at risk of pretermdelivery vastly outweigh the potential risks. These benefits include not only a reduction inthe risk of RDS, but also a substantial reduction in mortality and IVH.
All fetuses between 24 and 34 weeks of gestation at risk of preterm delivery should beconsidered candidates for antenatal treatment with corticosteroids.
The decision to use antenatal corticosteroids should not be altered by fetal race or genderor by the availability of surfactant replacement therapy.
Patients eligible for therapy with tocolytics should also be eligible for treatment withantenatal corticosteroids.
Treatment consists of two doses of 12 mg of betamethasone given intramuscularly 24 hoursapart or four doses of 6 mg of dexamethasone given intramuscularly 12 hours apart. Optimalbenefit begins 24 hours after initiation of therapy and lasts seven days.
Because treatment with corticosteroids for less than 24 hours is still associated withsignificant reductions in neonatal mortality, RDS, and IVH, antenatal corticosteroids shouldbe given unless immediate delivery is anticipated.
In premature rupture of membranes at less than 30 to 32 weeks of gestation in the absenceof clinical chorioamnionitis, antenatal corticosteroid use is recommended because of the highrisk of IVH at these early gestational ages.
In complicated pregnancies where delivery prior to 34 weeks of gestation is likely, antenatalcorticosteroid use is recommended unless there is evidence that corticosteroids will have anadverse effect on the mother or delivery is imminent.
RDS: respiratory distress syndrome; IVH: intraventricular hemorrhage. Adapted from data in the
Report of the Consensus Development Conference on the Effect of Corticosteroids for Fetal Maturation
on Perinatal Outcomes. National Institute of Child Health and Human Development. November 1994.
NIH Publication No. 95-3784.
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