From 23rd Annual Society for Maternal-Fetal Medicine (SMFM) Conference held in San Francisco, California - February 2003    

Do Tocolytics Really Help?

Vincenzo Berghella, MD interviewed by Hans van der Slikke, MD, PhD

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Hans van der Slikke, MD, PhD: “It is February 6th and we are at the meeting of the Maternal Fetal Medicine Society in San Francisco and next to me is Vincenzo Berghella from Jefferson’s, Philadelphia. Welcome!”

Vincenzo Berghella, MD: “Thanks, glad to be here.”

Hans van der Slikke, MD, PhD: “We’ll discuss now about prematurity, the use of tocolytics. Does giving tocolytics make any sense?”

Vincenzo Berghella, MD: “I think there are a lot of skeptics in this area and I certainly have been one for quite a while. I have reviewed the literature though extensively, and I think if anybody does that, they would be surprised to find that there are a lot of randomised, controlled trials for the different tocolytics around.

I think in general, tocolytics may be a little bit too late, so to speak, since the woman is already symptomatic and I think the real prevention of pre-term birth will come when we will eventually identify the woman before she has symptoms of pre-term labour and are able to stop whatever process has started very early on, maybe even in the first trimester or early second trimester. But, nonetheless, there will be women without risk factors who will have pre-term labour, and there I think that tocolytics have been studied and there are some interesting results, actually.”

Hans van der Slikke, MD, PhD: “Are there some good studies where, let’s say, infections are excluded as the reason and some, let’s say, pre-term labour without any causes?”

Vincenzo Berghella, MD: “Yes, there are some randomised studies of women who really, truly have pre-term labour and don’t have chorioamnionitis, don’t have other risk factors. Actually, in terms of infection, antibiotics have been studied in an evidence-based, randomised fashion, and unfortunately not been shown to decrease pre-term birth, which has been frustrating. But I think that tocolytics, some tocolytics, have been shown to be better than placebo but some have more side effects than others.”

Hans van der Slikke, MD, PhD: “In Europe, for a long time we have used betamimetics.”

Vincenzo Berghella, MD: “Yes, betamimetics are the only ones actually, even in the US, FDA-approved tocolytics. There are some studies comparing them to other tocolytics and to placebo and I think by comparing to placebo, betamimetics do actually have some preventions of pre-term birth, either short-term, two to seven days, or even up to seven weeks. The problem with those studies is that there was no use of steroids and steroids as we know truly improve nearly all outcome to women who are going to give birth to pre-term babies. But I think that they are certainly better than placebo. The interesting new information is that there are a lot of newer tocolytics coming out that may be just as effective as betamimetics but have less side effects, so, good for the baby in terms of keeping them inside mom but also not bad for the mom in terms of not causing as many side effects for the mother.”

Hans van der Slikke, MD, PhD: “Because betamimetics are very well-known for their big side effects for struggling women and they don’t want to continue . . .”

Vincenzo Berghella, MD: “Yes, it is not a drug that is well-liked and I think that not does it make them more anxious and having palpitations, but I think that they can have significant cardiac effects, even causing ischemia and then long-term problems.”

Hans van der Slikke, MD, PhD: “Next we have is nifedipine.”

Vincenzo Berghella, MD: “Nifedipine for example is being studied extensively against betamimetics and it seems to be as effective, if not more effective and again, is associated with a lot less side effects. It is a drug that can be given orally instead of through IV or subcutaneously, and so I think that it’s going to be used more and more instead of betamimetics.”

Hans van der Slikke, MD, PhD: “In Europe, we also use atosiban.”

Vincenzo Berghella, MD: “Yes, atosiban has been, I think, the research focus in terms of tocolytics in the last three to five years and the new information for example versus betamimetics says again that the side effect profile is much, much improved, you know. Probably taking atosiban is almost like taking placebo, there are very, very few side effects. But the efficacy is the same as betamimetics and this is enlisted for randomised trials so that it may be another drug that if cost-effectiveness can be looked at and proven to be beneficial, then it will really quickly replace betamimetics and I know it is happening already in Europe.”

Hans van der Slikke, MD, PhD: “Yes, that’s right.”

Vincenzo Berghella, MD: “Unfortunately in the US, there have been some older data that questions its use in terms of having a worse neonatal outcome at early gestational ages, but the study that it came from may have had biased randomisation, so that newer studies seem to confirm its safety for the foetus in unit.”

Hans van der Slikke, MD, PhD: “Thank you very much.”

Vincenzo Berghella, MD: “Thanks.”