Association of Vaginal Progesterone Treatment With Prevention of Recurrent Preterm Birth

Preterm birth (PTB) is the leading cause of infant morbidity and mortality worldwide. It has been suggested that vaginal progesterone (VP) treatment may reduce the recurrence of PTB.

To evaluate the association of VP treatment with prevention of recurrent PTB among patients with a singleton pregnancy.

This prospective, observational cohort study, set in a public health care system for inner-city pregnant patients, enrolled patients with prior spontaneous PTB (gestational age, ≤35 weeks) receiving VP from May 15, 2017, to May 7, 2019. Patients who delivered between 1998 and 2011 served as a referent cohort matched 3:1 for obesity, race and ethnicity, and individual specific preterm birth history. Statistical analysis was performed from August 19, 2021, to September 2, 2022.

Patients received 90 mg of vaginal progesterone, 8%, nightly, initiated between 16 weeks and 0 days and 20 weeks and 6 days of pregnancy until 36 weeks and 6 days of pregnancy or delivery.

The primary outcome was overall rate of recurrent PTB at 35 weeks or less of patients given VP compared with the 3:1 matched untreated historical controls. Secondary outcomes included assessment of PTB according to adherence (≥80% completing scheduled doses), duration of pregnancy relative to index gestational age, progesterone blood levels, and outcomes for those who declined VP.

A total of 417 patients (mean [SD] age, 30.4 [5.9] years; 64 Black patients [15.3%]; 272 [65.2%] with a body mass index of ≥30) received VP and were matched with 1251 controls (mean [SD] age, 28.8 [5.7] years; 192 Black patients [15.3%]; 816 [65.2%] with a body mass index of ≥30). The overall rate of recurrent PTB was 24.0% (100 of 417; 95% CI, 20.0%-28.4%) for the VP cohort compared with 16.8% (1394 of 8278) expected in the matched historical controls. Adherence was not associated with lower rates of recurrent PTB compared with nonadherence (odds ratio, 0.87 [95% CI, 0.51-1.41]). The mean difference between historical matched controls and those using VP was 0.2 weeks (95% CI, -1.4 to 1.0 weeks) without improvement in the interval of recurrent PTB after the implementation of VP (P = .73). Progesterone blood levels for patients who were adherent compared with those who were nonadherent were not significantly different at either 24 or 32 weeks (24 weeks: 99 ng/mL [95% CI, 85-121 ng/mL] vs 104 ng/mL [95% CI, 89-125 ng/mL]; P = .16; 32 weeks: 200 ng/mL [95% CI, 171-242 ng/mL] vs 196 ng/mL [95% CI, 155-271 ng/mL]; P = .69).

This cohort study of patients with a current singleton pregnancy suggests that VP was not associated with a reduction in recurrent PTB.