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JOGC

No. 364-Antenatal Corticosteroid Therapy for Improving Neonatal Outcomes

      Abstract

      Objective

      To assess the benefits and risks of antenatal corticosteroid therapy for women at risk of preterm birth or undergoing pre-labour Caesarean section at term and to make recommendations for improving neonatal and long-term outcomes.

      Options

      To administer or withhold antenatal corticosteroid therapy for women at high risk of preterm birth or women undergoing pre-labour Caesarean section at term.

      Outcomes

      Perinatal morbidity, including respiratory distress syndrome, intraventricular hemorrhage, bronchopulmonary dysplasia, infection, hypoglycemia, somatic and brain growth, and neurodevelopment; perinatal mortality; and maternal morbidity, including infection and adrenal suppression.

      Intended Users

      Maternity care providers including midwives, family physicians, and obstetricians.

      Target Population

      Pregnant women.

      Evidence

      Medline, PubMed, Embase, and the Cochrane Library were searched from inception to September 2017. Medical Subject Heading (MeSH) terms and key words related to pregnancy, prematurity, corticosteroids, and perinatal and neonatal mortality and morbidity were used. Statements from professional organizations including that of the National Institutes of Health, the American College of Obstetricians and Gynecologists, the Society for Maternal Fetal Medicine, the Royal College of Obstetricians and Gynaecologists, and the Canadian Pediatric Society were reviewed for additional references. Randomized controlled trials conducted in pregnant women evaluating antenatal corticosteroid therapy and previous systematic reviews on the topic were eligible. Evidence from systematic reviews of non-experimental (cohort) studies was also eligible.

      Validation Methods

      This Committee Opinion has been reviewed and approved by the Maternal-Fetal Medicine Committee of the SOGC and approved by SOGC Council.

      Benefits, Harms, and/or Costs

      A course of antenatal corticosteroid therapy administered within 7 days of delivery significantly reduces perinatal morbidity/mortality associated with preterm birth between 24 + 0 and 34 + 6 weeks gestation. When antenatal corticosteroid therapy is given more than 7 days prior to delivery or after 34 + 6 weeks gestation, the adverse effects may outweigh the benefits. Evidence on long-term effects is scarce, and potential neurodevelopment harms are unquantified in cases of late preterm, term, and repeated exposure to antenatal corticosteroid therapy.

      Guideline Update

      Evidence will be reviewed 5 years after publication to evaluate the need for a complete or partial update of the guideline. If important evidence is published prior to the 5-year time point, an update will be issued to reflect new knowledge and recommendations.

      Sponsors

      The guideline was developed with resources provided by the Society of Obstetricians and Gynaecologists of Canada with support from the Canadian Institutes of Health Research (APR-126338).

      Summary Statements

      • 1.
        Trials enrolling pregnant women from 24 + 0 to 34 + 6 weeks gestation at high risk of preterm birth show that antenatal corticosteroid therapy significantly reduces perinatal death, respiratory distress syndrome, and intraventricular hemorrhage (Moderate).
      • 2.
        Evidence from cohort studies shows a significant reduction in perinatal mortality among infants exposed to antenatal corticosteroid therapy at less than 24 weeks gestation (Low).
      • 3.
        Antenatal corticosteroid therapy administered to women at risk of preterm delivery between 34 + 0 and 36 + 5 weeks gestation decreases neonatal respiratory morbidity (Moderate).
      • 4.
        There is an increased risk of neonatal hypoglycemia among infants exposed to antenatal corticosteroid therapy at 34 + 0 to 36 + 5 weeks gestation (Moderate).
      • 5.
        Administration of antenatal corticosteroid therapy decreases respiratory distress syndrome and need for mechanical ventilation in infants of women undergoing elective pre-labour Caesarean delivery at term (Moderate).
      • 6.
        Limited evidence is available on long-term outcomes following antenatal corticosteroid therapy in cases of elective pre-labour Caesarean delivery at term gestation. However, there are concerns regarding the cognitive functioning of children exposed to antenatal corticosteroid therapy prior to elective Caesarean section at term gestation (Low).
      • 7.
        Betamethasone has been more commonly used in studies evaluating the effect of antenatal corticosteroid therapy. In indirect comparisons, betamethasone shows greater reductions in chorioamnionitis, respiratory distress syndrome, and chronic lung disease compared with dexamethasone. In direct comparisons, dexamethasone is associated with a greater reduction in intraventricular hemorrhage and lower length of neonatal intensive care unit stay compared with betamethasone. Effects on other outcomes are generally similar (Low).
      • 8.
        The likelihood of preterm delivery and also the gestational age need to be carefully considered when contemplating the use of antenatal corticosteroid therapy among pregnant women. The efficacy of such therapy is highest when the course is given 24 hours to 7 days prior to delivery. Administration more than 7 days before delivery leads to reduced benefit and potentially unnecessary adverse effects (Low).
      • 9.
        Repeated courses of antenatal corticosteroid therapy are associated with a reduction in respiratory distress syndrome, mechanical ventilation, and use of surfactant (Moderate).
      • 10.
        Birth weights and head circumferences are decreased in infants exposed to multiple courses compared with those exposed to a single course of antenatal corticosteroid therapy (High).
      • 11.
        There is limited evidence on the long-term effects of repeated courses of antenatal corticosteroid therapy. Follow-up from a large trial indicated higher risks of neurosensory disability and of a composite of death or severe disability (neuromotor, neurosensitive, neurocognitive) in children exposed to multiple courses of antenatal corticosteroid therapy and born at term (Moderate).
      • 12.
        Few trials of antenatal corticosteroid therapy in multifetal pregnancies are available. Subgroup analyses show that effects of antenatal corticosteroid therapy are not different between multifetal pregnancies and singleton pregnancies (Low).
      • 13.
        Evidence from cohort studies shows benefits of antenatal corticosteroid therapy are greater in multifetal pregnancies when antenatal corticosteroid therapy is administered within 7 days prior to delivery (Low).
      • 14.
        Evidence on the effects of antenatal corticosteroid therapy in diabetic women is scarce, and no comparative study has been conducted in this subpopulation (Low).
      • 15.
        Antenatal corticosteroid therapy leads to an increase in maternal blood glucose levels up to 1 week after the initiation of the first dose (Low).
      • 16.
        There is an absence of evidence on the effects of antenatal corticosteroid therapy among women with obesity, and no comparative study has been conducted in this subpopulation (Low).
      • 17.
        Responsiveness of growth-restricted fetuses to antenatal corticosteroid therapy remains largely unknown (Low).
      • 18.
        A lower frequency of major brain lesions, but a higher frequency of body size below the 10th centile at school age is observed in cohort studies of small for gestational age infants exposed to antenatal corticosteroid therapy (Low).
      • 19.
        Antenatal corticosteroid therapy may induce transient variations in fetal body movements including a potential reduction in fetal movements in the first 3 days following therapy initiation (Low).

      Recommendations

      Gestational Age Considerations
      • 1.
        One course of antenatal corticosteroid therapy should be routinely administered to women at 24 + 0 to 34 + 6 weeks gestation who are at high risk for preterm delivery within the next 7 days (Strong, Moderate).
      • 2.
        Women between 22 + 0 weeks and 23 + 6 weeks gestation at high risk of preterm birth within the next 7 days should be provided with a multidisciplinary consultation regarding the high likelihood for severe perinatal morbidity and mortality and associated maternal morbidity. Antenatal corticosteroid therapy may be considered if early intensive care is requested and planned (Conditional, Low).
      • 3.
        The balance of risks and benefits does not support routine administration of antenatal corticosteroid therapy for women at 35 + 0 to 35 + 6 weeks gestation who are at high risk for preterm birth in the next 7 days (Conditional, Moderate).
      • 4.
        Antenatal corticosteroid therapy should not be routinely administered to women at 36 + 0 to 36 + 6 weeks gestation who are at risk for preterm delivery (Conditional, Moderate).
      • 5.
        Antenatal corticosteroid therapy may be administered between 35 + 0 and 36 + 6 weeks gestation in select clinical situations after risks and benefits are discussed with the woman and the pediatric care provider(s) (Conditional, Moderate).
      • 6.
        Elective pre-labour Caesarean section should be performed at or after 39 + 0 weeks gestation to minimize respiratory morbidity (Strong, Low).
      • 7.
        Antenatal corticosteroid therapy should not be routinely administered to women undergoing pre-labour Caesarean section at term gestation (including at 37 and 38 weeks gestation) (Strong, Low).
      Agents, Dosage, Regimen, and Target Timing
      • 8.
        When antenatal corticosteroid therapy is indicated, women should receive a course of antenatal corticosteroid therapy (i.e., either 2 doses of betamethasone 12 mg given by intramuscular injection 24 hours apart or 4 doses of dexamethasone 6 mg given by intramuscular injection 12 hours apart) (Strong, Moderate).
      • 9.
        Antenatal corticosteroid therapy should be administered to women requiring medically indicated delivery only when the plan to proceed with delivery within 7 days has been finalized and gestational age criteria for antenatal corticosteroid therapy are met (Strong, Low).
      • 10.
        Antenatal corticosteroid therapy should be routinely administered to women in spontaneous preterm labour characterized by regular uterine contractions associated with significant cervical dilation or significant cervical change on repeated examination when gestational age criteria for antenatal corticosteroid therapy are met.
        Regular contractions in the absence of cervical dilation/change, or a short cervical length in the absence of regular contractions, are not indications for antenatal corticosteroid therapy (Strong, Low).
      • 11.
        Antenatal corticosteroid therapy should be routinely administered at the time of diagnosis to women with preterm premature rupture of membranes, when gestational age criteria are met (Strong, Low).
      • 12.
        Antenatal corticosteroid therapy should be administered to women with significant antepartum hemorrhage when the risk of delivery within 7 days is high and the gestational age criteria for such therapy are met (Strong, Low).
      • 13.
        Antenatal corticosteroid therapy should be administered to asymptomatic patients with vasa previa or placenta previa when the risk of delivery within 7 days is high and the gestational age criteria are met (Strong, Low).
      • 14.
        In cases where the diagnosis of preterm labour has not been firmly established (i.e., no documented cervical change and dilatation <3 cm), and the woman is being transferred to a higher level of care for further assessment, antenatal corticosteroid therapy should not be administered prior to transfer (Strong, Low).
      • 15.
        If the risk of preterm delivery decreases significantly following administration of the first dose of antenatal corticosteroid therapy, cancellation of the second dose of corticosteroids should be considered. If the second dose is cancelled and a high risk of preterm birth arises subsequently at less than 34 + 6 weeks gestation, 1 dose or 1 course of antenatal corticosteroid therapy should be considered, depending on gestational age and the duration since the first dose (Strong, Low).
      • 16.
        If the woman remains undelivered beyond 7 days after the first antenatal corticosteroids course, the balance of risks and benefits does not support further routine administration of antenatal corticosteroid therapy even if the risk of preterm delivery increases subsequently. The gestational age and the time interval since the first course of antenatal corticosteroid therapy (at least 14 days) should be taken into account when considering a rescue course. A single rescue course of antenatal corticosteroid therapy may be administered after risks and benefits are discussed with the woman (Conditional, Moderate).
      Subpopulations and Special Consideration
      • 17.
        Antenatal corticosteroid therapy should be administered according to the same indications and in the same gestational age range to women with twin or higher-order multifetal pregnancies as for singleton pregnancies (Conditional, Low).
      • 18.
        Antenatal corticosteroid therapy should not be administered to women with multifetal pregnancies in the absence of a high risk of preterm birth within the next 7 days (Conditional, Low).
      • 19.
        Antenatal corticosteroid therapy should be administered to diabetic women at the same dosage, according to the same indications, and in the same gestational age range as that recommended for non-diabetic women (Conditional, Low).
      • 20.
        Close attention should be paid to control of maternal blood glucose among women with diabetes in the days following antenatal corticosteroid therapy because of anticipated elevations in maternal blood glucose levels (Strong, Low).
      • 21.
        Because of the transient elevation of blood glucose levels induced by corticosteroids, gestational diabetes screening should be delayed for a minimum of 1 week following antenatal corticosteroid therapy (Strong, Low).
      • 22.
        Antenatal corticosteroid therapy should be administered to women with obesity at the same dosage as that recommended for women without obesity (according to the same indications and in the same gestational age range) because there is insufficient evidence to guide dosage adjustments by maternal weight (Conditional, Low).
      • 23.
        There is insufficient evidence to withhold routine antenatal corticosteroid therapy in cases of suspected fetal growth restriction with a high risk of preterm birth. Antenatal corticosteroid therapy should be administered according to the same indications and in the same gestational age range as in normal pregnancies after risks and benefits are discussed with the woman (Conditional, Low).
      • 24.
        Antenatal corticosteroid therapy should not be administered to women with suspected fetal growth restriction at the time of diagnosis unless there is a high risk of preterm birth within the next 7 days (Conditional, Low).
      • 25.
        Women should be informed of the potential for a transient reduction in fetal movements and advised to consult with their health care professional if this occurs (Strong, Low).

      Key Words

      Abbreviations:

      ACS (Antenatal corticosteroid therapy), ALPS (Antenatal Late Preterm Steroids), ASTECS (Antenatal Steroids for Term Caesarean Section), CI (confidence interval), MACS (Multiple Courses of Antenatal Corticosteroids for Preterm Birth Study), OR (odds ratio), RDS (respiratory distress syndrome), RR (risk ratio)
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