Could they alter the effectiveness of progesterone?

Last week I looked at the idea that putting a plastic ring around that part of the cervix that protrudes into the vagina could prevent preterm birth (click here); it didn’t make much sense. Today I consider the idea that how we diagnose women at risk of preterm birth affects whether treatment works. The two tests are cervical length scanning and vaginal fetal fibronectin (fFN) measurement.

As preterm labour approaches, the uterus contracts, pulling and shortening the cervix – so called effacement. Although cervical length measurement by ultrasound is tricky, and there are false positives, it’s a reasonable test for predicting preterm birth (click here).

fFN, a protein made by the fetus, lies between the membranes and the uterus, holding them together. Normally it is absent from vaginal secretions, but as the cervix effaces the membranes shear off the lower part of the uterus, and fFN leaks into the vagina.  Again some false positives but a reasonable test (click here).

Each test is a different way to measure the same thing, the process of cervical effacement that precedes labour.  It may be that, depending on the cut-off values – length of cervix, level of fFN – one is slightly better than the other, but they are based on the same process and identify the same women, those at risk of preterm birth because the cervix is effacing.

It would be strange if treatment for preterm labour worked when the risk had been diagnosed one way, but not the other.  Imagine if streptomycin cured tuberculosis diagnosed by X ray, but not diagnosed by m. tubercle in sputum! Or if anti-hypertensive drugs prevented strokes when high blood pressure had been measured directly, but not when it had been inferred by retinal fundoscopy! If tests identify the same disease, treatment will work equally well whichever test is used.

But some enthusiasts claim that progesterone works when the risk of preterm birth is based on an ultrasound detected short cervix, but not on a vaginal fFN test. They argue as follows:

The best quality trials are overall negative, and dividing them up by singletons or twins, or by progestagen type, doesn’t identify a subgroup where the drug works.  But apparently it does work for the subgroup of women who joined trials on the basis of a short cervix diagnosed by vaginal scan. Many secondary meta-analyses make this claim (e.g. click here, here, and here), such that some people advocate universal cervical length screening followed by treatment with progesterone (click here).

But progesterone doesn’t work, it might even be harmful, for women judged at risk of preterm birth on the basis of a positive vaginal fFN test. Does that really make biological sense? It doesn’t to me.

Jim Thornton