Updates, controversies and current evidence of use of antenatal steroids in prematurity

2. Update on Antenatal Steroids
Dr Padmesh V, DM Neonatology

3. Agenda for the talk
• 1. History of Antenatal Steroids
• 2. Effects of Antenatal Steroids
• 3. The recommendations
• 4. The controversies
• 5. The Verdict

4. Agenda for the talk
• 1. History of Antenatal Steroids
• 2. Effects of Antenatal Steroids
• 3. The recommendations
• 4. The controversies
• 5. The Verdict

5. • THE HISTORY:
• Dr Liggins believed that it was the fetus and not the
mother that was responsible for the timing of labor.
• Fetuses lacking an intact hypothalamic-pituitary-adrenal axis
(such as those with anencephaly or hypothalamic lesions) fail to
go into labor at term.

6. • Dr. Liggins began infusing sheep with
corticosteroids to see what effect it had on the
timing of labor.

7. • Dr. Liggins also infused the fetuses of sheep with
corticosteroids to see what effect it had on the
timing of labor.

8. • Dexamethasone had no effect when administered to
pregnant ewes. But caused premature delivery when
infused into foetal lambs.

9. • A sheep infused with corticosteroids had delivered overnight.
• The lamb was so premature that it should not have survived, but
it was alive and breathing!

12. Agenda for the talk
• 1. History of Antenatal Steroids
• 2. Effects of Antenatal Steroids
• 3. The recommendations
• 4. The controversies
• 5. The Verdict

13. Agenda for the talk
• 1. History of Antenatal Steroids
• 2. Effects of Antenatal Steroids
• 3. The recommendations
• 4. The controversies
• 5. The Verdict

14. • EFFECTS OF ACS:
27 studies (11,272 randomised women and 11,925 neonates) from 20 countries.
Ten trials (4422 randomised women) took place in lower- or middle-resource
settings.
Evidence is robust, regardless of resource setting (high, middle or low).
Issue 12, 2020

15. • EFFECTS OF ACS:
• Antenatal corticosteroids reduce the risk of:
-perinatal death (risk ratio (RR) 0.85, 95% (CI) 0.77 to 0.93 )
-neonatal death (RR 0.78, 95% CI 0.70 to 0.87)
-respiratory distress syndrome (RR 0.71, 95% CI 0.65 to 0.78)

16. • EFFECTS OF ACS:
• Antenatal corticosteroids probably reduce
- IVH (RR 0.58, 95% CI 0.45 to 0.75)
- Developmental delay in childhood
(RR 0.51, 95% CI 0.27 to 0.97)

17. • EFFECTS OF ACS:
• Maternal outcomes
• Antenatal corticosteroids probably result in little to no
difference in
-Maternal death (RR 1.19, 95% CI 0.36to 3.89),
-Chorioamnionitis (RR 0.86, 95% CI 0.69 to 1.08),
-Endometritis (RR 1.14, 95% CI 0.82 to 1.58)

18. Agenda for the talk
• 1. History of Antenatal Steroids
• 2. Effects of Antenatal Steroids
• 3. The recommendations
• 4. The controversies
• 5. The Verdict

19. Agenda for the talk
• 1. History of Antenatal Steroids
• 2. Effects of Antenatal Steroids
• 3. The recommendations
• 4. The controversies
• 5. The Verdict

20. The recommendations:

21. The recommendations:

22. • OPERATIONAL GUIDELINES:
• Single course of injection of Dexamethasone to
be administered to women with preterm labour
(between 24 and 34 weeks of gestation) at all
levels of health facilities in the public as well as
the private sector.

23. • OPERATIONAL GUIDELINES:
• Single course of injection of Dexamethasone to
be administered to women with preterm labour
(between 24 and 34 weeks of gestation) at all
levels of health facilities in the public as well as
the private sector.

24. • OPERATIONAL GUIDELINES:

25. • OPERATIONAL GUIDELINES:

26. • OPERATIONAL GUIDELINES:

27. • OPERATIONAL GUIDELINES:
• Maternal diabetes,
• Pre-eclampsia
• Hypertension
NOT
contraindications
for using antenatal
steroids

28. • OPERATIONAL GUIDELINES:
• Repeat course of antenatal steroids is not
recommended.

29. The recommendations:

30. • A single course of corticosteroids is recommended for
pregnant women between 24 0/7 weeks and 33 6/7
weeks of gestation who are at risk of preterm delivery
within 7 days, including for those with ruptured
membranes and multiple gestations.
The recommendations:

31. • A single course of betamethasone is recommended for
pregnant women between 34 0/7 weeks and 36 6/7
weeks of gestation at risk of preterm birth within 7
days, and who have not received a previous course of
antenatal corticosteroids.
The recommendations:

32. • A single repeat course of antenatal corticosteroids should
be considered in women who are less than 34 0/7 weeks
of gestation who are at risk of preterm delivery within 7
days, and whose prior course of antenatal corticosteroids
was administered more than 14 days previously.
• Rescue course corticosteroids could be provided as early as 7 days
from the prior dose, if indicated by the clinical scenario.
The recommendations:

33. Agenda for the talk
• 1. History of Antenatal Steroids
• 2. Effects of Antenatal Steroids
• 3. The recommendations
• 4. The controversies
• 5. The Verdict

34. Agenda for the talk
• 1. History of Antenatal Steroids
• 2. Effects of Antenatal Steroids
• 3. The recommendations
• 4. The controversies
• 5. The Verdict

35. • CONTROVERSIES:
• 1. TIMING BEFORE DELIVERY
• Efficacy is incomplete <24 hours from administration of
the first dose and appears to decline after seven days.
• Neonatal benefits begin to accrue within a few hours of
ACS administration.
24
hrs
7 days

36. • CONTROVERSIES:
• 2. MULTIPLE GESTATIONS
• International guidelines recommend administering same
dose of antenatal corticosteroids, similar to that of a
singleton pregnancy.
(Though there are limitations in the published data.)

37. • CONTROVERSIES:
• 3. PERIVIABILITY
• Between 20-24 weeks of pregnancy  Not viable.
• Born between 24-28 weeks  the chances of survival is
less and should be decided on case to case basis
• Born after 28 weeks  every effort should be made to
ensure the child survives.

38. • CONTROVERSIES:
• 3. PERIVIABILITY
• Pregnancies <22+0 weeks are generally not considered
candidates for ACS as there are only a few primitive
alveoli at this gestational age on which the drug can exert
an effect.

39. • CONTROVERSIES:
• 4. PPROM
• A single course of corticosteroids is recommended for
pregnant women between 24 0/7 weeks and 33 6/7
weeks of gestation who are at risk of preterm delivery
within 7 days, including for those with ruptured
membranes.
• Whether to administer a repeat or rescue course of
corticosteroids with preterm prelabor rupture of
membranes (PROM) is controversial, and there is
insufficient evidence to make a recommendation for or
against.

40. • CONTROVERSIES:
• 5. WHICH STEROID?
Dexamethasone Sodium Phosphate

41. • Betamethasone sodium phosphate is soluble, so
it is rapidly absorbed.
• Betamethasone acetate is only slightly soluble
and, therefore, provides sustained activity.

44. • CONTROVERSIES:
• 6. WHY NOT OTHER STEROIDS?
• The other steroids are extensively metabolized by
the placental enzyme 11 beta-hydroxysteroid
dehydrogenase type 2 (HSD-11β Type 2) - so they
have low fetal impact.
HSD-11β Type 2

45. • CONTROVERSIES:
• 7. MATERNAL DIABETES
• Not a contraindication.
• However, secondary hyperglycemia must be
closely monitored.

46. • CONTROVERSIES:
• 8. LATE PRETERM (> 34 WEEKS GESTATION )
• In contrast to pregnancies upto 33+6 weeks,
where consensus exists about ACS administration,
the use of ACS at ≥34+0 weeks is controversial.

47. • CONTROVERSIES:
• 8. LATE PRETERM (> 34 WEEKS GESTATION )
• Reasons behind controversy:
• Absence of a survival benefit,
• Less absolute respiratory benefit due to the lower
risk of serious respiratory problems at this
gestational age,
• Greater concern about potential long-term harm.

48. • CONTROVERSIES:
• 8. LATE PRETERM (> 34 WEEKS GESTATION )
Antenatal Late Preterm Steroids (ALPS)

49. • CONTROVERSIES:
• 8. LATE PRETERM (> 34 WEEKS GESTATION )
• Antenatal Late Preterm Steroids (ALPS)
• Singleton pregnancy at 34 weeks 0 days to 36 weeks 5 days of
gestation who were at high risk for delivery.
• The primary outcome was a composite measure of
respiratory morbidity, stillbirth and neonatal mortality
within 72 hours of birth.
• Administration of betamethasone to women at risk for late
preterm delivery significantly reduced the rate of neonatal
respiratory complications.
• There was a significantly increased rate of neonatal
hypoglycaemia.

50. • CONTROVERSIES:
• 8. LATE PRETERM (> 34 WEEKS GESTATION )
• ACOG: A single course of betamethasone is
recommended for pregnant women between 34 0/7
weeks and 36 6/7 weeks of gestation at risk of preterm
birth within 7 days, and who have not received a previous
course of antenatal corticosteroids.
• National Institute for Health and Care Excellence
(NICE) guideline recommends considering ACS for
women between 34+0 and 35+6 weeks of gestation who
are in suspected, diagnosed, or established preterm
labor; are having a planned preterm birth; or have
preterm prelabor rupture of membranes

51. • CONTROVERSIES:
• 8. LATE PRETERM (> 34 WEEKS GESTATION )
• The World Health Organization ACTION-II (Antenatal
CorTicosteroids for Improving Outcomes in preterm
Newborns) Trial
• Safety and efficacy of dexamethasone when given to women at
imminent risk of late preterm birth, at 34 weeks 0 days to 36 weeks
0 days

52. • CONTROVERSIES:
• 9. USE OF RESCUE (SALVAGE, BOOSTER) ACS
• The Australasian Collaborative Trial of Repeat Doses of
Steroids (ACTORDS).
• Investigated 982 women who remained at risk of preterm
birth prior to 32 weeks' gestation, more than 7 days after
receiving the first course of antenatal corticosteroids.
• There was a statistically significant decrease in respiratory
distress syndrome, use of oxygen therapy and duration of
mechanical ventilation in the treatment group.
• Reports regarding the long-term outcomes following
exposure to repeat doses of steroids are conflicting.

53. • CONTROVERSIES:
• 9. USE OF RESCUE (SALVAGE, BOOSTER) ACS

54. • CONTROVERSIES:
• 9. USE OF RESCUE (SALVAGE, BOOSTER) ACS
• ACOG: A single repeat course of antenatal corticosteroids
should be considered in women who are less than 34 0/7
weeks of gestation who are at risk of preterm
delivery within 7 days, and whose prior course of
antenatal corticosteroids was administered more than 7-
14 days previously.

55. • CONTROVERSIES:
• 10. PRIOR TO ELECTIVE CESAREAN
• ASTECS (Antenatal Steroids for Term Elective Caesarean
Section) TRIAL

56. • CONTROVERSIES:
• 10. PRIOR TO ELECTIVE CESAREAN
• ACOG : No recommendation
• RCOG : No recommendation
• WHO : Not recommended
• FIGO Working group: Consider between 37-39 wk if
there is clinical reason for early birth.

57. • CONTROVERSIES:
• 11. MATERNAL SIDE EFFECTS
• Most pregnant women tolerate a single course of ACS without
difficulty.
• 2017 systematic review of randomized trials: treatment did not
increase the risk of chorioamnionitis or endometritis .
• Betamethasone and dexamethasone have low mineralocorticoid
activity compared with other corticosteroids- therefore,
hypertension is not a contraindication to therapy.
• Transient hyperglycemia occurs in many women.

58. • CONTROVERSIES:
• 12. STEROID IN COVID MOTHERS
American Journal of Perinatology

59. Agenda for the talk
• 1. History of Antenatal Steroids
• 2. Effects of Antenatal Steroids
• 3. The recommendations
• 4. The controversies
• 5. The Verdict

60. Agenda for the talk
• 1. History of Antenatal Steroids
• 2. Effects of Antenatal Steroids
• 3. The recommendations
• 4. The controversies
• 5. The Verdict

61. • SIMPLIFIED VERDICT:
• 1. GESTATIONAL AGE:
• A single course of corticosteroids is recommended
for pregnant women between 24 0/7 weeks and
33 6/7 weeks of gestation who are at risk of
preterm delivery within 7 days.

62. • SIMPLIFIED VERDICT:
• 2. LATE PRETERM:
• A single course of corticosteroids is recommended for
pregnant women between 34 0/7 weeks and 36 6/7
weeks of gestation at risk of preterm birth within 7
days, and who have not received a previous course of
antenatal corticosteroids.

63. • SIMPLIFIED VERDICT:
• 3. REPEAT DOSE:
• A single repeat course of antenatal corticosteroids should
be considered in women who are less than 34 0/7 weeks
of gestation who are at risk of preterm delivery within 7
days, and whose prior course of antenatal corticosteroids
was administered more than 7-14 days previously.

64. • SIMPLIFIED VERDICT:
• 4. PRIOR TO ELECTIVE LSCS:
• Do not routinely administer prior to elective LSCS.

65. • SIMPLIFIED VERDICT:
• 5. WHICH STEROID: