Cervical Device Didn’t Help High-Risk Pregnancies

Cervical pessaries didn’t reduce risk of preterm birth and fetal death prior to 37 weeks gestation in high-risk singleton pregnancies, according to the randomized TOPS trial.

The intravaginal device held no advantage for nonlaboring women with a cervical length of 20 mm or less compared with usual care in rate of the primary outcome of delivery or fetal death prior to 37 weeks gestation (45.5% vs 45.6%; RR 1.00, 95% CI 0.83-1.20).

Fetal, neonatal, or infant death was actually more prevalent with use of a pessary (13.3% vs 6.8% with usual care; RR 1.94, 95% CI 1.13-3.32), reported Matthew Hoffman, MD, MPH, of ChristianaCare in Newark, Delaware, and co-authors in JAMA.

“This troubling finding has not been reported in prior pessary studies, and the precise reasons for this increased risk are not clear,” noted an accompanying editorial by Donald Dudley, MD, and Christopher Ennen, MD, both of the University of Virginia School of Medicine in Charlottesville.

“Is this the end of use of the Arabin pessary to prevent preterm birth? Perhaps,” they concluded, though noting that a trial in twin gestations is ongoing.

Until there’s more promising data, they argued, “the Arabin pessary should continue to be used only in the context of clinical trials with appropriate sample size, study design, and safety monitoring. Most likely, however, the Arabin pessary will join the ranks of intramuscular progesterone, home uterine activity monitoring, and tocolytics as yet another unsuccessful clinical intervention for the prevention of preterm birth.”

The intravaginal pessary was thought to prevent preterm birth in at-risk individuals by supporting the cervix, and the trial had a population that stood to benefit if that mechanism panned out: “These are women who not only had short cervices, but had really short cervices, meaning that they were super high risk for delivering early from that perspective. We think we found the truth by looking at a group of folks who are more at risk, unfortunately,” Hoffman told MedPage Today.

The study took place from February 2017 to November 2021 across 12 U.S. centers. In total there were 544 nonlaboring participants (average age 29.5) with a singleton pregnancy. Originally, the study sample size was designed to be 850, but researchers halted recruitment after the third interim analysis because of concern for both fetal and neonatal/infant death as well as futility.

To be eligible, individuals had to have a transvaginal ultrasound cervical length of 20 mm or less at 16 weeks’ gestation through 23 weeks and 6 days gestation. Exclusion criteria included prior spontaneous preterm birth, a cervix dilated at 3 cm or more, prolapse or rupture of the membranes, evidence of preterm labor, major fetal or müllerian anomaly, and other factors that could increase risk of preterm birth.

In a 1:1 ratio, participants were randomized to receive a cervical pessary (n=280, four of whom were not able to tolerate the pessary at insertion) or usual care (n=264). Vaginal progesterone was prescribed for nearly all participants in both groups.

Delivery or fetal death prior to 37 weeks gestation was the primary outcome. Secondary outcomes included fetal or neonatal death (from birth until 28 days of life), infant death (28 days of life to 1 year of life), duration of ventilator support and supplemental oxygen, seizures that required treatment, and small size at birth for gestational age (less than fifth percentile for gestational age).

The proportion of participants who stayed pregnant in both groups was numerically but not significantly higher in the pessary group (HR 1.9, 95% CI 0.8-4.7). Most other obstetrical outcomes were similar, except for lower likelihood of cerclage placement in the pessary group (4.7% vs 9.1%; RR 0.51, 95% CI 0.51-0.98). Additionally, 83.3% of participants had medically indicated removal of the pessary. In 23 cases, patients requested removal: 16 due to discomfort, one because of vaginal discharge, and six for no specified reason.

Dudley and Ennen pointed out that the TOPS study couldn’t decisively determine whether cervical pessary was the root cause of perinatal death. Their editorial also noted that, because nearly all women received progesterone, it was impossible to determine any interactions between progesterone and cervical pessary.

Hoffman and team acknowledged that the open-label nature of the study was a limitation, since it introduced the possibility of bias. Additionally, the participants had a shorter cervix on average than anticipated, which could have led to a higher instance of the primary outcome. They also noted that centers varied in their screening procedures.

Hoffman said future research should look into the effects of different lifestyle choices and inflammatory markers on preterm birth.

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