1. ANTENATAL STEROIDS Dr. Somendra Shukla Neonatologist & Pediatrician
2. Mechanism of Action of Antenatal Corticosteroids
3. Antenatal Corticosteroids How do corticosteroids work? Increase the amount of lung surfactant (+/-) Decrease the inflammatory process from trauma Decrease vascular permeability Increase tissue compliance & thus lung volume Improve the response to surfactant that is present Enhance the clearance of lung water
4. A. Respiratory Action Antenatal corticosteroid therapy leads to architectural and biochemical changes that improve both lung mechanics and gas exchange. These changes are primarily the result of accelerated morphologic development of type 1 and type 2 pneumocytes. Type 1 pneumocytes are responsible for gas exchange in the alveoli, while type 2 pneumocytes are responsible for production and secretion of surfactant. Antenatal corticosteroids also alter production of surfactant binding proteins and enhance fetal lung antioxidant enzymes. However, for these changes to occur the lungs need to have reached a stage of development that is biologically responsive to corticosteroids.
5. B. Circulatory Action Antenatal corticosteroid therapy improves circulatory stability in preterm neonates, resulting in less intraventricular hemorrhage and necrotizing enterocolitis.
6. Betamethasone Vs Dexamethasone Betamethasone half life 72 hours with a larger volume of distribution Dexamethasone half life 60 hours Both freely cross the placenta Differ by a single methyl group
7. Betamethasone Vs Dexamethasone Baud et al. NEJM 1999 Less PVL with betamethasone vs. dexamethasone or untreated controls Van Marter et al. Pediatrics 1990 Less BPD with betamethasone vs. other corticosteroids Lee et al. Pediatrics 2008 less impaired neurodevelopment at 18 to 22 months in betamethasone group over dexamethasone Betamethasone fewer dosages and less time to complete Elimian et al. Obstet Gynecol 2007 Less IVH with dexamethasone vs. betamethasone
8. Antenatal Corticosteroids Dosing Schedule What steroid should be used and what should the injection schedule be? Betamethasone 12 mg IM x 2 doses Q 24 hours or Dexamethasone 6 mg IM x 4 doses Q 12 hours But if felt to be needed Betamethasone 12 mg IM x 2 doses Q 12 hours can be administered
9. Rationale for Repeating antenatal corticosteroids
10. Rationale for Repeating antenatal corticosteroids The biologic rationale for repeating antenatal corticosteroid therapy is based upon the observation that biochemical stimulation of surfactant production appears to be reversible in cell culture models i.e. surfactant protein mRNA levels decline to control levels after cortisol is removed. However, other beneficial effects, such as cytostructural maturation, persist after steroid exposure is withdrawn.
11. Advantages & Disadvantages of Repeated Antenatal Corticosteroids
12. Advantages Repeated doses are associated with better neonatal lung function than single course of corticosteroids, particularly among infants delivered before 32 weeks of gestation. Also, less need for mechanical ventilation, continuous positive airway pressure, and surfactant use. There was also a reduction in the frequency of pneumothorax. However, there is NO SIGNIFICANT BENEFIT in reduction of severe respiratory distress syndrome, grade III or IV intraventricular hemorrhage, chronic lung disease or periventricular leukomalacia.
13. Disadvantages Repeated doses are associated with lower birth weight than the single course, and appear to cause IUGR. However, it was found that repeating a SINGLE RESCUE DOSE or COURSE, does not affect fetal growth. Some studies reported increased incidence of cerebral palsy. Regarding late term effects, some studies showed affection of neurological development in early childhood.
14. Disadvantages In animals: studies have shown decreased brain size, altered nerve growth, a delayed rate of myelination, altered retinal development, a decrease in the number of neurons and a dose- dependent degeneration of neurons in the hippocampus. Also it may be associated with increased incidence of hypertension.
15. ANS Evidence Based Guidelines: Repeat Courses Weekly repetitive courses of antenatal steroids are no longer recommended because of concerns for fetal head and somatic growth. The effect is generally seen after >=3 courses or >=4 courses. The 2000 NIH Consensus Conference reaffirmed the 1994 Consensus recommendations and further stated that repeat courses of corticosteroids should not be used routinely, but should be reserved for patients enrolled in randomized controlled trials.
16. ANS Evidence Based Guidelines: Repeat Courses In mothers likely to deliver beyond 2 weeks from the primary course and before 34 weeks gestation, a single rescue course of antenatal corticosteroids appears to provide additional benefit. The same medication regimens would be utilized. Rescue course of ANS simply means the administration of a second course to patients whose pregnancies continue more than a week or 2 from their original course and only in whom, in the judgment of the clinician, delivery has again become likely.
17. ANS Evidence Based Guidelines: Rescue Courses Research has shown that choosing to administer a rescue course of antenatal corticosteroids in pregnant women treated initially >2 weeks prior, and who are judged by the clinician to be likely to deliver within the next week and before 34 weeks gestation, is a beneficial approach that significantly decreases respiratory complications of prematurity and is without apparent immediate or short-term adverse effects to the mother or infant.
18. Antenatal Corticosteroids ACOG Committee Opinion # 475 Feb 2011 ACOG (overall) supports the conclusions of the 1994 & 2000 NIH consensus conferences All women at risk for PTD from 24 to 34 weeks gestation (or 24 to < 32 weeks with PPROM) are candidates for a single course of corticosteroids A single repeat rescue course may be considered if the gestational age is < 32 6/7 weeks, it has been more than 2 weeks from the prior treatment, and delivery is likely within the next 7 days
19. Antenatal Corticosteroids ACOG Committee Opinion # 475 Feb 2011 For PPROM 32 to 33 6/7 weeks treatment is ?? but may be beneficial in cases with documented pulmonary immaturity Regularly scheduled courses (more than 2) are not recommended Betamethasone 12mg IM x 2 doses Q24 hours (24 hour treatment time) Dexamethasone 6mg IM x 4 doses Q12 hours (36 hour treatment time)
20. Antenatal Corticosteroids ACOG and AAP Joint Statement 2007 Antenatal Corticosteroid Administration ACOG Practice Bulletin # 127-June 2012 Management of Preterm Labor ACOG Practice Bulletin #139-October 2013 Management of PPROM All state administering a single course of corticosteroids for 240/7 to < 34 weeks gestation
21. ANS - Repeat Courses: References Antenatal Corticosteroids Revisited: Repeat Courses. NIH Consensus Statement 2000; 17(2): 1-10. Antenatal corticosteroid therapy for fetal maturation. ACOG Committee Opinion No. 273. Obstet Gynecol 2002; 99: 871-873. Wapner RJ, Sorokin Y, Thom EA, Johnson F, Dudley DJ, Spong CY, et al. Single versus weekly courses of antenatal corticosteroids: Evaluation of safety and efficacy. Am J Obstet Gynecol 2006; 195(3): 633-42. Crowther CA, Harding JE. Repeat doses of prenatal corticosteroids for women at risk of preterm birth for preventing neonatal respiratory disease. Cochrane Database of Systematic Reviews 2007, Issue 3. Art No.: CD003935. DOI: 10.1002/14651858.CD003935.pub2.
22. ANS Evidence Based Guidelines: Timing All fetuses between 24 and 34 weeks gestation at risk of preterm delivery should be considered candidates for antenatal treatment with corticosteroids. There are no recommendations concerning routine early treatment with antenatal corticosteroids. In selected situations beyond 34 weeks gestational age with an indicated delivery (e.g., placenta previa, prior uterine rupture) in the presence of an immature fetal lung profile, treatment with antenatal corticosteroids can be effective. The same medication regimens would be utilized.
23. Corticosteroids after 34 weeks gestation Haas et al. 2012 retrospective study of 110 cases with a FLM between 340/7 and 370/7 weeks gestation where 69 received corticosteroids and 41 did not Rate of RDS, TTN, hypoglycemia, NICU admission and hyperbilirubinemia were the same
24. Corticosteroids after 34 weeks gestation Feitosa Porto et al. 2011 randomized trial of antenatal corticosteroids in late preterm infants 320 patients between 34 & 36 weeks randomized to betamethasone or placebo 2008 to 2010 43 discharged / 2 SB / 2 excluded total 47 lost 143 steroid group 2 cases RDS 130 in placebo group 1 case RDS No benefit seen
25. Corticosteroids after 34 weeks gestation Stutchfield et al. 2005 Antenatal Steroids for Term Elective Cesarean Section (ASTECS) 942 patients for C-section randomized to betamethasone or regular care 1995 to 2002 467 treated 11 (2.4%) to NICU for RDS 475 controls 24 (5.1%) to NICU for RDS P = 0.02
26. RATIONALE 3 out of 4 preterm delivery b/w 34-37 wks Incidence of RDS 34 wks --- 50% 35 wks --- 15% 36 wks --- 8%
27. MECHANISM OF ACTION No role of surfactant deficiency Helps in fluid reabsorption Via E- Na channel TTNB
28. Recommendation Not recommended routinely Not received prior steroid Not in cases with prior labor delivery Indication 34- 35+6 wks Elective LSCS without prior labor
29. ACTECS (Antenatal Steroid for Term Elective Cesarean section) After 37 wks- 39 wks No significant redu