A new study in the Lancet is a multi-center RCT of the use of a cervical pessary to reduce preterm delivery in twin pregnancies.
I must say this sounded a bit unlikely to me, but it turns out there just might be something to it. First, however, the major finding, which was that overall there was no effect on the primary outcome, a composite of poor perinatal outcomes ‘stillbirth, periventricular leucomalacia of grade 2 or worse, severe respiratory distress syndrome of grade 2 or worse, bronchopulmonary dysplasia, intraventricular haemorrhage of grade 2B or worse, necrotising enterocolitis, proven sepsis, and neonatal death within 6 weeks after the expected term date.’
Women were randomized at between 12 and 20 weeks gestation if they had a multiple pregnancy. The pessaires were then inserted and the pregnancy followed. The only frequent complication was a vaginal discharge. The combined outcome was 13% with the pessary and 14% without.
If I say ‘there might just be something in this approach’: it is based on a subgroup analysis, which should always make you skeptical.
There were also 2 significant changes in study design during the trial. 1. They increased the sample size, because they re-considered the analysis and how they were going to account for the twining (only 2% were triplets). 2. They changed the cutoff for the subgroup analysis based on cervical length, as they had too few mothers with a length below 25 mm (the initial cutoff), so they changed the threshold to the 25% percentile, which turned out to be 38mm. This was apparently done before they looked at the results, just based on the numbers of short cervices.
It was this subgroup analysis that was significantly different. The interaction term for the effect of cervical length on the outcome was p=0.01. This was mostly due to more deaths in the controls with short cervix, (and fewer in the controls with longer cervix, but non-significant). So there were 17 baby deaths in the short-cervix controls and 3 in the pessary group. This seems to be due to a shift in the gestational age at delivery of these pregnancies, with fewer extremely preterm <28 weeks (4% compared to 16%) and fewer very preterm, <32 weeks (14% vs 29%).
This is clearly not conclusive evidence, being based on a subgroup analysis, and relatively small numbers of extremely preterm deliveries in this subgroup (n=12 total pregnancies that ended before 28 weeks). But it does suggest that another trial specifically targeting multiples with a short cervix should be considered.
Currently there really isn’t anything else that works. As I have discussed before on this blog, progesterone doesn’t seem to work in multiple pregnancy with short cervix.
Also there is previous work in singleton pregnancies, randomized to receive a pessary at 18 to 22 weeks if the cervical length was under 25 mm, in which preterm delivery (the primary outcome was delivery before 34 weeks) was much lower with the pessary use (7% vs 28%). This reduction was associated with fewer VLBW babies, and fewer complications of prematurity. This is starting to look a little consistent, and the effect size is substantial enough to warrant further studies.
I was intrigued to see what these things looked like, and the 2012 Lancet article has a photo and a diagram, which I reproduce below. There is also an ultrasound picture if you want to go see that.
This is what it looks like:
And this is where you put it:
This positioning is described in the figure legend thusly: The smaller diameter of the pessary is fitted around the cervix and the larger diameter faces the pelvic floor, thus rotating the cervix to the posterior vaginal wall and correcting the cervical angle.
How might this work? Well that really isn’t clear, it would be nice to know a bit more about mechanisms, so that better designs could be developed for the future, but for the moment, it is as the editorial in the lancet put it ‘a glimmer of hope‘.