Antenatal steroid

ANTENATAL STEROIDS

Dr. Somendra ShuklaNeonatologist & Pediatrician

Mechanism of Action of Antenatal

Corticosteroids

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

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.

B. Circulatory Action

Antenatal corticosteroid therapy improves circulatory stability in preterm neonates, resulting in less intraventricular hemorrhage and necrotizing enterocolitis.

Betamethasone Vs Dexamethasone

Betamethasone half life – 72 hours with a larger volume of distribution

Dexamethasone half life – 60 hours Both freely cross the placentaDiffer by a single methyl group

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

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 hoursor

Dexamethasone 6 mg IM x 4 doses Q 12 hours

But if felt to be neededBetamethasone 12 mg IM x 2 doses Q 12 hours can be

administered

Rationale for Repeating antenatal

corticosteroids

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.

Advantages & Disadvantages of Repeated Antenatal

Corticosteroids

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.

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.

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.

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.

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.

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.

Antenatal CorticosteroidsACOG – 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

Antenatal CorticosteroidsACOG – 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)

Antenatal Corticosteroids

ACOG and AAP Joint Statement 2007 Antenatal Corticosteroid Administration

ACOG – Practice Bulletin # 127-June 2012 Management of Preterm LaborACOG – Practice Bulletin #139-October 2013 Management of PPROM

All state administering a single course of corticosteroids for

240/7 to < 34 weeks gestation

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.

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.

Corticosteroids after34 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 notRate of RDS, TTN, hypoglycemia, NICU admission

and hyperbilirubinemia were the same


Feitosa Porto et al. 2011 – randomized trial of antenatal corticosteroids in late preterm infants320 patients between 34 & 36 weeks randomized to

betamethasone or placebo 2008 to 201043 discharged / 2 SB / 2 excluded – total 47 lost143 steroid group – 2 cases RDS130 in placebo group – 1 case RDSNo benefit seen


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 2002467 treated – 11 (2.4%) to NICU for RDS475 controls – 24 (5.1%) to NICU for RDSP = 0.02

RATIONALE

• 3 out of 4 preterm delivery b/w 34-37 wks• Incidence of RDS 34 wks --- 50% 35 wks --- 15% 36 wks --- 8%

MECHANISM OF ACTION

• No role of surfactant deficiency• Helps in fluid reabsorption• Via E- Na channel• TTNB

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

ACTECS (Antenatal Steroid for Term Elective Cesarean section)

• After 37 wks- 39 wks• No significant reduction in respiratory distress

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Antenatal steroid