ANTENATAL CORTICOSTEROIDS - legacymfm.org CORTICOSTEROIDS website … · ^A single rescue course of...

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ANTENATAL CORTICOSTEROIDS WHO, WHEN, WHY (PROBABLY NOT WHAT AND WHERE)

Transcript of ANTENATAL CORTICOSTEROIDS - legacymfm.org CORTICOSTEROIDS website … · ^A single rescue course of...

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ANTENATAL CORTICOSTEROIDS

WHO, WHEN, WHY

(PROBABLY NOT WHAT AND WHERE)

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ACS• Been used for years and years

• Initially demonstrated to be efficacious in reducing incidence and severity of RDS

• Classic study by Liggins/Howie 1972

• Mostly demonstrated benefit in 28-34 weeks

• No benefit in infants born after 34 weeks

– Wrong conclusion (?)

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ACS• Incidence of RDS was so low in the control

group that unable to demonstrate benefit in those over 34 weeks

• Similar argument in < 28 weeks

– Incidence was so high in that group that initially not thought be beneficial

• Study by Garite, et al demonstrated large reduction in IVH but not RDS

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ACSMECHANISM OF ACTION

• Accelerate development of type 1 and 2 pneumocytes to improve lung mechanics and increase production of surfactant

• Alter fluid dynamics to improve fluid reabsorption

• Stabilize circulatory cells to reduce fragility so lower IVH rate and incidence of NEC

• Effects last 7 days

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ACS• Now it is pretty clear that ACS

– Reduce incidence/severity of RDS

– Reduce incidence/severity of IVH

– Reduce NEC

– Improve overall morbidity and mortality in babies from 24-34 weeks

• What about outside these parameters?

– More to come

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ACSOUTCOMES DATA

REDUCTION RR

RDS 0.66 (0.59-0.73)

IVH 0.54 (0.43-0.69)

NEC 0.46 (0.29-0.74)

Mortality 0.69 (0.58-0.81)

Infection/sepsis 0.56 (0.38-0.85)

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ACSEFFICACY BASED ON EGA

• Meta-analysis showed significant improvement in all measures when given between 26-34 weeks

• 2016 meta-analysis demonstrated improvement in all measures at 23&24 weeks

• Trend toward improved outcome at 22 weeks

• Limited to no data supporting steroids prior to 22 weeks

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REMEMBER THE DAYS OFREPEAT STEROIDS?

• Steroids thought to last 1 week

• Very concerned about RDS and stuff

• Repeat steroids seemed harmless

• Some patients might get weekly steroid shots from 24-34 weeks if high risk

• Follow up data for this was concerning

• PMR increased after 3 course

• Decreased brain size, postnatal growth delay and many other problems???

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HOW LONG IS THE BENEFIT?

• Retrospective chart review

• 197 infants received steroids

– 98 delivered within 7 days

– 99 delivered after 7 days

• Matched for everything

– Race Payer mix

– Gender Route of delivery

– EGA at delivery Birth weight

Peaceman et al AJOG 2005;193:1165-9

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HOW LONG IS THE BENEFIT?

Delivery

< 7 days

Delivery

> 7 days

P

Ventilation or CPAP

> 24 hours

63% 81% < 0.01

Surfactant use 39% 47% .28

O2 at 28 days 23% 22% .92

NEC, IVH, or sepsis 31% 28% .56

Length of stay 34 days 38 days .80

Peaceman et al AJOG 2005;193:1165-9

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FINALLY, THE MEAT:WHAT ABOUT A REPEAT DOSE?

• Now, 4 randomized controlled trials in the literature looking at this– Guinn 2001 (N = 502)– Wapner 2006 (N= 556)***– Crowther 2006 (N= 1047)– Garite 2009 (N= 437)

• All suggest a modest reduction in RDS

• No improvement in other morbidities or in mortality– *** non-significant increase in CP at age 2

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IMPACT OF A ‘RESCUE COURSE’ OF STEROIDS

• Multi-center randomized placebo trial

• 437 patients– 223 in repeat group

– 214 in single course

• Included multiple gestations (N = 141)

• 25 to 33 weeks

• Randomized if– Received 1st course > 14 days earlier

– High likelihood of delivering in next 7 days

Garite et al AJOG 2009;200:248.e1-248.e9

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IMPACT OF A ‘RESCUE COURSE’OF STEROIDS

• No difference in demographics

• Significant reduction in

– Composite morbidity (44% vs 66%)

– RDS (41% vs 61%)

– Surfactant use (38% vs 55%)

– Ventilation (38% vs 53%)

• No difference in mortality or other significant morbidities

Garite et al AJOG 2009;200:248.e1-248.e9

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WHAT DID ACOG SAY?

“A single rescue course of antenatal corticosteroids may be considered if the antecedent treatment was given more than 2 weeks prior, the gestational age is less than 32 6/7 weeks, and the women are judged by the clinician to be likely to give birth within the next week. However, regularly scheduled repeat courses or multiple courses (more than two) are not recommended. Further research regarding the risks and benefits, optimal dose, and timing of a single rescue course of steroid treatment is needed”

ACOG Committee Opinion Feb 2011

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The following recommendations and conclusionsare based on good and consistent scientific evidence(Level A):

A single course of corticosteroids is recommendedfor pregnant women between 24 weeks and 34 weeksof gestation, and may be considered for pregnantwomen starting at 23 weeks of gestation, who are atrisk of preterm delivery within 7 days.

The following recommendations and conclusionsare based on limited and inconsistent scientificevidence (Level B):

A single repeat course of antenatal corticosteroidsshould be considered in women whose prior courseof antenatal corticosteroids was administered at least7 days previously and who remain at risk of pretermbirth before 34 weeks of gestation.

PRACTICE BULLETIN SUMMARYNumber 159, January 2016

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WHAT ABOUT LATE PRETERMERS(34-37 WEEKS)

• This group can still have significant issues with oxygen requirements

• Less problems with NEC or IVH

• PMR is not significantly different from 34 up to a term gestation

• Requiring oxygen does effect feeding, length of stay, bonding…..

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NICU ADMISSIONS2000 - 2003

Oshiro et al. Obstet Gynecol 2009, 113:804-811

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TIMING OF ELECTIVE REPEAT CESAREAN SECTION AND NEONATAL

OUTCOMES

Tita AT, et al NEJM 2009;360:111

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TIMING OF ELECTIVE REPEAT CESAREAN SECTION AND NEONATAL

OUTCOMES

Tita AT, et al NEJM 2009;360:111

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FETAL BRAIN STUFF

• Cortex volume increases 50% between 34-40 weeks

• Brain volume increases 15 cc/week from 29-41 weeks

• Myelinated white matter increases 5 fold from 35-41 weeks

• Frontal lobe is the last to develop

– Impulses Judgement

– Problems solving Socialization

– Planning Executing behavior

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STUDY PROTOCOL

• No prior steroid exposure

• Between 34 0/7 and 36 5/7 weeks

• In active labor, 3 cm dilated or felt to be high risk to deliver within 7 days

• Excluded multiples, diabetics, fetal anomalies

• No alteration in OB care (no tocolysis, induce PPROM after 12 hours or so….)

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CONCLUSIONS

• Some select late preterm deliveries, the neonate will benefit from steroids

• The risk is mostly composite respiratory issues, specifically TTN

• The benefit, though statistically significant is really not clinically relevant (?)

• Definitely more hypoglycemia and possibly maternal infection in steroid group

• Most neonatal problems had a 50% reduction but the control was usuall 10% or less

• It is a slippery slope to start on!!!!!!!!

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QUESTIONS?

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WHAT IS VIABILITY?

• Tough question!!!!

• A lot depends on

– Religious/cultural beliefs

– Definition of living vs. being alive

– Where you deliver and access to various services

– Legal obligations

– Other co-morbidities (anomalies, multiple gestations, fetal growth….

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WHAT IS VIABILITY?

This has changed as technology has changed!

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Baby Patrick, born at 34 weeks. Weight: 4 lbs 10 oz. Died from RDS at 39 hours of life

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WHAT IS VIABILITY?

• So in the 1960’s, it was in the early 3rd

trimester

• When I was a resident (just a few short years ago) it was about 28 weeks

• Now it is 26, 25, 24, 23, 22, 21……?

• Here is what some national organizations say

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SUMMARY OF SURVIVAL

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SUMMARY OF SURVIVAL

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WEEKS

AT

BIRTH

SURVIVAL

RATE(Literature

Survey)

VON 2003

SURVIVAL

RATE

PSVMC

SURVIVAL

RATE

1996-2003

SEVERE

NEUROLOGIC

DISABILITY*

(Literature

Survey)

MODERATE

NEUROLOGIC

DISABILITY#

(Literature

Survey)

<23 ~5% 8% 0% ??? ???

23 0/7 to 23 6/7 ~15% 32% 10% ~ 30-35% ~20–30%

24 0/7 to 24 6/7 ~ 40% 58% 68% ~ 25-30% ~20–30%

25 0/7 to 25 6/7 ~ 60% 76% 74% ~20-25% ~20–30%

26 0/7 to

26 6/7 ~75% 83% 83% ~15-20% ~ 20%

* Severe Disability = Mental Development IQ <70 or >2 S.D. below the mean, and/or Cerebral Palsy, and/or Blind,

and/or Deaf

# Moderate Disability = Mental Development IQ 70-84 or 1-2 S.D. below the mean. Moderate disorders of motor skills,

vision, hearing, academic achievement, social performance, and/or behavior included in some

follow-up references.

Northwest Newborn Numbers

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ACOG/SMFM BEST PRACTICE RECOMMENDATIONS

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OVERALL SUMMARY

• Steroids are a good thing in appropriate doses and at the right time

• Timing is everything and hard to guess when someone is going to deliver

• Clearly steroids are beneficial from 23-34 weeks (probably 35 too)

• One repeat dose of steroids is probably reasonable prior to 34 weeks

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OVERALL SUMMARY

• I believe it is important to appropriately time your first dose (cervical length, fFN…) so we don’t get in the dilemma of repeat dosing

• Steroids before an indicated c-section under 37 weeks will reduce respiratory complications in the neonate

• I’m sure the pendulum will continue to swing

• WATCH OUT FOR IT!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!

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