antenatal steroids for lung maturation

1. Steroids in Pregnancy
Dr Anuj Sharma
MBBS, MS, DNB

5. RDS
• Also known as
• Hyaline Membrane Disease
• Neonatal Respiratory Distress Syndrome
• Common breathing disorder that affects newborns
• Most often in preterm babies
• Lungs are not able to make enough surfactant
• Surfactant - substance that keeps the lungs fully expanded so that newborns can breathe in air
once they are born
• Ganong’s Review of Medical Physiology

6. Surfactant
DPPC
62%
Neutral lipids
13%
Other
phospholipids
10%
Proteins
8%
Phosphatidylglycer
ol
5% Carbohydrate
2%
Surfactant
• A lipid surface-tension-lowering agent
• a mixture of
• In spherical structures like the alveoli
• Pressure = 2Tension/radius
• In absence of Surfactant
• Surface tension in the alveoli tends to collapse the alveoli
• This creates positive pressure in the alveoli, attempting to push the air out
• Guytons Textbook of Medical Physiology

7. • Produced by type II alveolar epithelial cells
• Following secretion, phospholipids of surfactant line up in alveoli with their hydrophobic fatty acid
tails facing alveolar lumen
• Surfactant molecules move further apart as alveoli enlarge during inspiration- surface tension
increases
• Surface tension decreases when they move closer together during expiration
• Ganong’s Review of Medical Physiology
Surfactant

8. Mechanism of Action
• Antenatal administration accelerate development of type 2 pneumocytes
• Induction of type 2 pneumocytes increases surfactant production by inducing production of
surfactant proteins and enzymes necessary for phospholipid synthesis
• Other effects
• Induction of pulmonary beta-receptors - play a role in surfactant release & absorption of alveolar fluid
when stimulated
• Induction of fetal lung antioxidant enzymes
• Upregulation of gene expression for the epithelial Na+ channel - important for absorption of lung fluid
after birth
• Ganong’s Review of Medical Physiology

9. Effect Of Antenatal Steroids On Fetal Lungs
• Increased surfactant release
• Improved surfactant treatment responses
• Improved surfactant dosage-response curve
• Decreased inactivation of surfactant
• Decreased incidence of respiratory distress syndrome
• Decreased mortality
Creasy and Resnik’s Maternal-Fetal Medicine

10. Clinical Impact ACOG RCOG Govt of India WHO
Reduction in RDS 34% 44% 34% 35%
Reduction in Neonatal Death 31% 31% 31% 32%
Reduction in IVH 46% 46% 46% 46%
Reduction in NE 54% Reduced Risk 54% 54%
• Antenatal corticosteroids in preterm birth significantly reduced incidences of
• Respiratory support
• Intensive care admissions
• Systemic Infection
Clinical Impact

11. Definitions

12. Recommendations
• At risk for Preterm delivery
• 20 0/7 to 22 6/7 POG - Not recommended
• 23 0/7 to 23 6/7 POG - May be considered if delivery eminent in next
7 days
• 24 0/7 to 34 6/7 - Recommended
• 34 0/7 to 36 6/7 - Recommended if delivery eminent in next 7
day & not received a previous course
ACOG Committee Opinion No 713 Aug 2017

13. Recommendations
• At risk for Preterm delivery
• 20 0/7 to 22 6/7 POG - Not recommended
• 23 0/7 to 23 6/7 POG - May be considered if at risk for
preterm delivery
• 24 0/7 to 34 6/7 - Single course Recommended
• Elective LSCS prior to 38 6/7 - Recommended

14. Recommendations
• At risk for Preterm delivery
• < 24 weeks POG - May be considered if at risk for
preterm delivery
• 24 0/7 to 34 6/7 - Single course Recommended
• 34 0/7 to 36 6/7 - Recommended if delivery eminent in next
7 day & not received a previous course
• Elective LSCS prior to 38 6/7- Recommended

15. • Single Rescue Course
• Single repeat course of steroids be considered in women
• Who are less than 34 0/7 weeks of gestation who are at risk of preterm delivery within
7 days
• & 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
• Rescue course of corticosteroids with PROM is controversial
Recommendations
• ACOG Committee Opinion Number 713 August 2017

16. Efficacy
• How long after administration is a course of antenatal corticosteroids most effective
• 24 hrs after and up to 7 days after completion
• Treatment with corticosteroids for < 24 hrs is still associated with significant reduction in
neonatal morbidity and mortality
• First dose to be administered even if the ability to give second dose is unlikely, based on
clinical scenario
• No role of “accelerated dosing”
Green top Guideline No.7 October 2010
ACOG Committee Opinion No 713 Aug 2017
Good clinical practice advice: Antenatal Corticosteroids for fetal lung maturation , FIGO 2019

17. Special scenarios
• Setting of PPROM
• Single dose is not associated with increased risks of maternal/neonatal infection regardless PoG
• Rescue dose – Controversial
• Not indicated in women diagnosed with clinical chorioamnionitis
Guidelines ACOG RCOG FIGO
Recommended YES

18. • Setting of Multiple Gestation
Special scenarios
Guidelines ACOG RCOG FIGO
Recommended YES

19. Special scenarios
• Gestational Diabetes Mellitus
• Not a contraindication to antenatal corticosteroid treatment
• Women with impaired glucose tolerance or diabetes receiving fetal steroids should have additional
insulin
• Should be accompanied by interventions to optimize maternal blood glucose control
Guidelines ACOG RCOG FIGO
Recommended YES

20. Special scenarios
• Fetal Growth Restriction
• Single use benefit of steroids in FGR babies outweighs the possible adverse effects
• Multiple doses causes small decrement in fetal weight
Guidelines ACOG RCOG FIGO
Recommended YES
Guidelines ACOG RCOG FIGO
Recommended - Yes Yes

22. • No evidence of long-term harm
• No evidence of neurocognitive deficiency
• In the context of maternal critical care steroids are not contraindicated, even in the setting of
sepsis
Long-term outcome/Risk/Add Consideration
ACOG Committee Opinion Number 713 August 2017

23. • Inj Dexamethasone 4mg/ml • Inj Betamethasone 4mg/ml
CORTICOSTEROIDS

24. Dexamethasone Vs Betamethasone
• Dexamethasone & Betamethasone are the fluorinated steroids most commonly used for Steroid
Exhibition
DEXAMETHASONE BETAMETHASONE
Available as Dexamethasone Phosphate (Dex-PO4) Equal parts-
Betamethasone phosphate (Beta-PO4) +
Betamethasone acetate (Beta-Ac)
Short acting Beta-PO4 short life/ Beta-Ac long life
4 doses of 6 mg each, 12 hrs apart, total dose 24 mg 2 doses 24 hrs apart of 12 mg each total dose of 24
mg
Readily available, cheaper, good efficacy, safe Available preparation - Betamethasone phosphate
Costlier
Use of Antenatal corticosteroids in preterm labour Operational Guidelines June 2014, MoHFW, GOI

25. Dexamethasone Vs Betamethasone
• Since only short acting Beta-PO4 is available dosing is similar to Dex-PO4 but
cost is more
INJ DEXAMETHASONE IS RECOMMEND BY GOI
Use of Antenatal corticosteroids in preterm labour Operational Guidelines June 2014, MoHFW, GOI

26. Role of Tocolysis
• Tocolysis for Steroids is recommended if PoG > 24 wks up to 34 wks after excluding risk factors like frank
infection, pre-eclampsia and diabetes
• Tocolysis not recommended in an attempt to delay delivery in order to administer antenatal corticosteroids
in the late preterm period
ACOG Committee Opinion Number 713 August 2017
Use of Antenatal corticosteroids in preterm labour Operational Guidelines June 2014, MoHFW, GOI

27. Other Corticosteroids
• Prednisolone
• Lipophilic so it can cross the placenta
• But its fetal uptake is limited by active retrograde transport by P-glycoprotein of placenta
• Its conversion to inactive metabolites by placental 11beta-hydroxysteroid dehydrogenase type
2 present in placenta
• Hydrocortisone
• Elevated circulating Estrogen levels in Pregnancy induce CBG production
• More Hydrocortisone is bound to CBG
• Its conversion to inactive metabolites by placental 11beta-hydroxysteroid dehydrogenase type
2 present in placenta
The Goodman and Gilman Manual of Pharmacology and Therapeutics

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