In April of this year the ALPS trial results were published in the New England Journal of Medicine (Antenatal Betamethasone for Women at Risk for Late Preterm Delivery) and I took the time to review the paper at the time Antenatal Steroids After 34 weeks. Believe the hype? In the analysis I focused on an issue which was relevant at the time, being a shortage of betamethasone. In a situation when the drug of choice is in short supply I argued that while the benefits of giving steroid to women at risk of delivery between 34 0/7 to 36 6/7 weeks was there, if I had to choose (as I did at the time) I would save the doses for those at highest risk of adverse outcome. Since the blog post though a couple of things have come out in the literature that I believe are worth sharing as it could truly influence practice.
The American College of Obstetricians and Gynecologists, moved by the results of the ALPS trial issued the following recommendations (shortened in places).
- Betamethasone may be considered in women with a singleton pregnancy between 34 0/7 and 36 6/7 weeks gestation at imminent risk of preterm birth within 7 days.
- Monitoring of late preterms for hypoglycemia (already being done)
- Do not give in the setting of chorioamnionitis.
- Tocolysis or delayed delivery for maternal indications should not be done in order to to allow for administration of late preterm antenatal corticosteroids.
- Do not provide if the pregnancy was already exposed to antenatal corticosteroids.
The exclusions above such as twins and triplets, diabetic pregnancies and previous receipt of steroids were included since the study had not included these patients. As the ACOG states in the summary, they will be reviewing such indications in the future and providing recommendations. I would imagine that if I were in a US based practice then this post might seem like old news since many centres would have started doing this. Given that the readers of this blog are based in many different countries around the globe and at least in Canada this has not become commonplace I thought it would be worth the update!
Antenatal corticosteroids for maturity of term or near term fetuses: systematic review and meta-analysis of randomized controlled trials
I posted the abstract for this review on my Facebook page the other day and it certainly garnered a lot of interest. Some of my readers indicated the practice is already underway. I was curious what a systematic review would reveal about the topic since the ACOG was so moved by the ALPS study in particular. Perusing through the Society of Obstetricians and Gynecologists of Canada (SOGC) I can’t find any commentary on this topic and certainly there are no new clinical practice guidelines since the ALPS study landed on my desktop.
Here are the pooled results from 6 trials:
- Lower risk of RDS (relative risk 0.74, 95% confidence interval 0.61 to 0.91)
- Mild RDS (0.67, 0.46 to 0.96)
- Moderate RDS (0.39, 0.18 to 0.89)
- Severe RDS (0.55, 0.33 to 0.91)
- Transient tachypnea of the newborn (0.56, 0.37 to 0.86)
- Shorter stay on a neonatal intensive care unit (−7.64 days, −7.65 to −7.64)
So across the board patients who receive antenatal steroids after 34 weeks still continue to see a benefit but looked at a different way the real benefit of the intervention is easier to see and that is through looking at the number needed to treat (NNT). For those of you who are not familiar with this analysis, this looks at how many patients one would need to treat in order to avoid the outcome in 1 patient.
For the outcomes above as an example the NNT for RDS overall is about 59 while for TTN 31 patients. Severe RDS which is less common after 34 weeks you might expect to require more patients to treat to help 1 avoid the outcome and you would be correct. That number is 118 patients. It is interesting to look at the impact of steroids in pregnancies below 34 weeks (taken from the Cochrane review on the subject) as the NNT there is 23! If you were to break these benefits down from 23-27 weeks though where the risk of RDS is quite high the NNT would be even lower. Steroids help, no question to reduce neonatal complications but as you can see even when there is a reduction in risk for various outcomes, the number of women you need to treat to get one good outcome is quite different.
Some Discussion With Obstetrics Is Needed Here
As you read through this post you may find yourself saying “Who cares? if there is a benefit at all most moms would say give me the steroids!” The issue here has to do with long term outcome. To put it simply, we don’t know for this type of patient. We know clearly that for patients at high risk of adverse outcomes eg. 24 week infant, the reduction in risks of infection, NEC, PDA, BPD etc from receiving antenatal steroids translates into many long term benefits. What about the patient who say is 35 weeks and would have none of those risks? Yes we are avoiding some short term outcomes that let’s be honest can be scary for a new parent but what are we trading this benefit for. The concern comes from what we know about steroids impact on the developing brain. Steroids lead to a developmental arrest but in very preterm infants there is no doubt that the protective effect on all of these other outcomes more than offsets whatever impact there is there. Incidentally I wrote about this once before and the section of interest appears at the end of the relevant post Not just for preemies anymore? Antenatal steroids for elective c-sections at term. In the absence of these other conditions could there be a long term impact in babies 34 – 36 6/7? My suspicion is that the answer is no but discussion is needed here especially in the absence of an endorsement by our Canadian SOGC. Having said all that I expect the future will indeed see an expansion of the program but then I do hope that someone takes the time to follow such children up so we have the answer once and for all.