Association of Vaginal Progesterone Treatment With Prevention of Recurrent Preterm Birth

Abstract

ImportancePreterm 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.ObjectiveTo evaluate the association of VP treatment with prevention of recurrent PTB among patients with a singleton pregnancy.Design, Setting, and ParticipantsThis 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.ExposurePatients 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.Main Outcomes and MeasuresThe 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.ResultsA 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).Conclusions and RelevanceThis cohort study of patients with a current singleton pregnancy suggests that VP was not associated with a reduction in recurrent PTB.

Evaluating Vaginal Progesterone in Preventing Recurrent Preterm Birth: A Call to Action

“…Various studies have been conducted to evaluate this effectiveness in preterm birth prevention but with conflicting results and lack of consistent outcomes. Nelson et al suggest that vaginal progesterone was not associated with a reduction in risk of recurrent preterm birth; a notable feature of the study was the significantly higher rate of preterm births in those who use vaginal progesterone compared with historical controls.…”

“…The report from the recent studies on vaginal progesterone to prevent recurrent preterm birth demonstrate the critical need to investigate its effectiveness further. 2,5 The need to consistently ensure shared decision-making process in the context of its use for this purpose as recommended by ACOG is of paramount importance. This gives important opportunities for the health care workers to know the patients' preferences, and it also allows the patients to fully express their opinions and share their experiences on the treatment.…”

“…A recent study in JAMA Network Open by Nelson et al 2 investigates the association between vaginal progesterone and prevention of recurrent spontaneous preterm births. This study suggests no overall reduction in recurrent preterm birth or when evaluating for both severity and frequency of prior preterm births among participants who took vaginal progesterone compared with controls.…”

“…controls were investigated. 2 Therefore, a call to action is needed to evaluate the current practice and more research on the existing evidence. Furthermore, researchers should consider incorporating more critical checkmarks in the current use of vaginal progesterone to prevent recurrent preterm delivery while we await more benefits of its effectiveness in the near future.…”

“…Many important risk factors exist for preterm births. However, the ability of health care professionals to mitigate and prevent these risks has been traditionally challenged by the high rates of unplanned pregnancies in the US and limited access to preconception care, most commonly among populations with historically higher risks for preterm births, which were mostly participants in Nelson et al…”