Vaginal progesterone does not decrease preterm birth risk in twin gestations, according to a recent study published in the American Journal of Obstetrics & Gynecology.
Takeaways
- The study indicates that vaginal progesterone does not reduce the risk of preterm birth in twin gestations, as compared to a placebo or no treatment.
- Preterm birth poses significant global health challenges, with approximately 15 million occurrences annually, and was the leading cause of death in newborns under 28 days in 2019.
- Twin gestations are associated with a considerably higher risk of preterm birth, with 18.4% and 22.5% of all preterm births occurring under 37-weeks' and 34-weeks' gestation, respectively, in 2020 and 2021.
- The study involved a systematic review and meta-analysis of 11 randomized control trials, encompassing 3401 women with twin gestations. The trials assessed the efficacy of vaginal progesterone in preventing preterm birth and adverse perinatal outcomes.
- The investigators concluded that based on their results, vaginal progesterone should not be recommended to women with twin gestations as an intervention for preventing preterm birth.
Approximately 15 preterm births occur worldwide annually, and preterm birth was reported as the leading cause of death in newborns aged under 28 days in 2019. Preterm birth is also associated with increased risks of bronchopulmonary dysplasia, respiratory distress syndrome, intraventricular hemorrhage, necrotizing enterocolitis, and other complications.
Twin births comprised 18.4% and 22.5%of all preterm births under 37-weeks’ and 34-weeks’ gestation respectively in 2020 and 2021, with 7-fold and 9-fold increased risk respectively for births in this range among women with twin gestation compared to those with singleton gestation. Twin gestations also experience increased risks of fetal and neonatal death.
This data indicates a need to determine an effective intervention for preventing preterm birth in twin gestations. Vaginal progesterone has been proposed, but the efficacy of this method is unclear.
To determine the efficacy of vaginal progesterone in preventing preterm birth in twin gestations, investigators performed a systematic review and meta-analysis. Randomized control trials evaluating preterm birth or adverse perinatal outcomes in asymptomatic women with a twin gestation after vaginal progesterone compared with placebo or no treatment were included in the analysis.
Exclusion criteria included evaluating vaginal progesterone in women with threatened or arrested preterm labor, second-trimester bleeding, or premature rupture of membranes, quasirandomized trials, and trials evaluating vaginal progesterone for spontaneous miscarriage.
Databases evaluated include MEDLINE, Embase, Latin American and Caribbean Health Sciences Literature, Cumulative Index to Nursing and Allied Health Literature, Cochrane Central Register of Controlled Trials, the International Clinical Trials Registry Platform, and clinical trial registries. Databases were evaluated from inception to January 31, 2023.
Preterm birth under 34-weeks’ gestations was the primary outcome of the analysis. Secondary outcomes included preterm birth under 37-, 32-, 30-, and 28-weeks’ gestation, as well as spontaneous preterm birth under 34-weeks’ gestation, fetal death, neonatal death, perinatal death, and neonatal complications.
Data extracted included publication date, title, duplicate publications, language, funding sources, trial registrations, study characteristics, participants, interventions, and outcomes. The Cochrane risk-of-bias tool was used to assess the risk of bias.
There were 3401 women with a twin gestation across 11 studies included in the final analysis. Most studies were double-blind, placebo-controlled trials, with 8 being multicenter trials and 3 single center trials. Vaginal progesterone doses across studies included 90 to 100 mg, 200 mg, 400 mg, and 600 mg. Most patients received treatment up to 34 weeks’ gestation.
Preterm birth below 34-weeks’ gestation was observed in 17.8% of patients receiving vaginal progesterone and 17.9% of patients receiving placebo or no treatment, indicating no significant difference. Similar results were found for preterm birth below 37-, 32-, 30-, and 28-weeks’ gestation with risk ratios (RRs) of 0.99, 0.85, 0.78, and 1, respectively.
Spontaneous preterm birth under 34-weeks’ gestation had an RR of 0.97. Perinatal outcomes were also not significantly impacted by vaginal progesterone.
These results indicated vaginal progesterone is not effective at preventing preterm birth and adverse perinatal outcomes in twin gestations. Investigators concluded vaginal progesterone should not be offered to women with a twin gestation to prevent preterm birth.
Reference
Conde-Agudelo A, Romero R, Rehal A, et al. Vaginal progesterone for preventing preterm birth and adverse perinatal outcomes in twin gestations: a systematic review and meta-analysis. American Journal of Obstetrics & Gynecology. 2023;229(6):599-616.E3. doi:10.1016/j.ajog.2023.05.010
