The ALPS Trial
/The #OBGynInternChallenge is back! Enrollment will open Monday 4/18. Check out www.obgyninternchallenge.com/enroll.
Here’s the RoshReview Question of the Week:
A 21-year-old G1P0 woman at 36w2d gestation presents to L&D with preterm contractions. Which of the following is an indication for giving antenatal corticosteroids?
Check out the links above for the correct answer, and get more details on the group discount deal with RoshReview QBanks for CREOG and ABOG exam studying!
THE ALPS Study
Actual Title: Antenatal Betamethasone for Women at Risk for Late Preterm Delivery
ALPS = Antenatal Late Preterm Steroids
Some general background information
Who did the study and who published it?
Another study done by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, MFMU
Published in the NEJM in 2016
Why was the study done?
Antenatal corticosteroids were widely used up to 34 weeks prior to this study
Decided after consensus conference held by the National Institutes of Health in 1994 - strong evidence that corticosteroids reduce adverse neonatal outcomes (death, RDS, and other morbidities)
Recommendation not given after 34 weeks because it was thought that babies usually do well after 34 weeks
However, it became clear later that infants born in the late preterm period still have increased neonatal and childhood risks compared to term infants
8% of all deliveries occur in the late preterm time period
Question we want answered:
Does administration of betamethasone to women likely to deliver in the late preterm period (defined as 34w0d - 36w6d) decrease respiratory and other neonatal morbidities?
Methods
Who participated and when?
Done at 17 university-based clinical centers participating in the MFMU Network
Recruitment began in October 2010 - February 2015
Eligibility criteria:
Live singleton pregnancy 34w0d- 36w5d
High probability of delivery in the late preterm period
Preterm labor with intact membranes, at least 3 cm dilated or 75% effaced or
Spontaneous rupture of membranes
If neither applied, expected preterm delivery for any other indication via IOL or CS between 24h - 7 days after planned randomization
Ineligible if:
Expected to deliver in <12 hours for any reason
ROM with more than 6 contractions/hour or cervical dilation of 3 cm or more unless pit was withheld for at least 12 hours (but other induction agents were allowed)
Chorioamnionitis
Cervical dilation 8 cm or more
Evidence of non-reassuring fetal status requiring immediate delivery
Previously received steroids for fetal lung maturity in pregnancy
Candidate for stress dose steroids
Contraindication to betamethasone
Pre-gestational diabetes
Known major fetal anomaly
How was the study done?
After subjects were consented, they were allocated in 1:1 ratio to either course of 12 mg of BMZ (2 doses 24 hours apart) or placebo
Stratified by clinical site and gestational age categories (34-35 weeks vs. 36 weeks)
Double-blind (neither study participant nor investigator knew if BMZ or placebo)
Rest of labor/delivery managed per indication
What outcomes did they look for?
Primary outcome
Composite endpoint for need for respiratory support by 72 hours of age consisting of:
CPAP or HFNC for at least 2 consecutive hours
O2 requirement with FiO2 of at least 30% for at least 4 continuous hours
ECMO or mechanical ventilation
Stillbirth and neonatal death before 72 hours were also included in both composite outcomes as they could be competing events
Subgroup analysis for primary outcome and severe respiratory morbidity for 34-35 vs 36 weeks gestation, indication for trial entry, planned CS vs planned VD, sex, and race/ethnicity
Secondary outcomes
Neonatal: many, but included severe respiratory morbidity; TTN, apnea, bronchopulmonary dysplasia, need for surfacntat, hypoglycemia, resuscitation, feeding difficulty, IVH, sepsis, death before discharge, etc.
What were the results
Who did they recruit?
Out of 24,538 screening, 2831 eligible were consented and randomized
1429 got betamethasone
Only 860 (60%) got both doses
1402 got placebo - only 826 (59%) got both doses
Reason those did not get a second dose: 95% delivered before 24 hours
What were their outcomes?
No stillbirths or neonatal deaths within 72 hours
4 women lost to follow up (0.14%)
Primary outcome:
Occurred less frequently in the BMZ group than placebo
11.6% vs. 14.4% RR 0.8, 95% CI 0.66-0.97, p = 0.02
Number needed treat to prevent one case was 35
Unchanged in post-hoc analyses
None of the subgroup analysis were significant
Secondary outcome
Severe respiratory morbidity composite outcome also significantly reduced in BMZ compared to placebo
8.1 vs. 12.1%, RR 0.67, 95% CI 0.53-0.84, P<0.001
NNT 25
Rate of TTN, need for resuscitation, and BPD were significantly less frequent in BMZ group
No significant difference in chorio or endometritis
Other findings of note:
Significant difference in hypoglycemia of glucose <40
343 (24.0%) vs 209 (14.9%) - those that got BMZ more likely to have hypoglycemia, P<0.001
What was the impact?
Found that BMZ even up to 36w5d for initial can decrease respiratory morbidity
Consistent with previous data from the ASTECs trial (Antenatal STeroids for Term Cesarean Section)
This did find dec NICU admission for respiratory distress
So babies in the UK do get steroids at term for CS not in labor!
There is a recommendation from ACOG now to give single course of steroids to pregnant patients between 34w0d-36w6d at risk of preterm delivery within 7 days who have not previously received steroids