17-Alpha-Hydroxyprogesterone vs. Placebo for Preventing of Recurrent Preterm Birth: A Systematic Review and Meta-Analysis of Randomized Trials

Abstract

Background: Preterm birth (PTB) is a leading cause of neonatal morbidity and mortality.Objective: To estimate the effect of 17-alpha-hydroxyprogesterone caproate (17-OHPC) compared to placebo in singleton gestations for reducing the risk of recurrent PTB and neonatal morbidity and mortality.Work Design: Systematic review and meta-analysis.Search Strategy: Searching MEDLINE, Embase, Web of Science, SCOPUS, Cochrane Library, and clinical trial registries.Selection Criteria: Randomized controlled trials of singleton gestations with a history of PTB and treated with a weekly intramuscular injection of 17-OHPC or placebo.Data Collection and Analysis: A random meta-analysis model was performed for the PTB outcomes (<32, <35, and <37 weeks) and neonatal outcomes (neonatal death, grade 3 or 4 intraventricular hemorrhage, respiratory distress syndrome, bronchopulmonary dysplasia, necrotizing enterocolitis, and sepsis). Effect estimates were measured by relative risk ratio (RR) with a 95% confidence interval (CI).Main Results: Six works were included. There were no statistically significant reductions in the PTB risk following the use of 17-OHPC at <32 weeks (RR = 0.61, 95% CI: 0.13–2.77, and I2 = 39%), <35weeks (RR = 0.60, 95% CI: 0.10–3.67, and I2 = 51%), and <37 weeks (RR = 0.68, 95% CI: 0.46–1, and I2 = 75%). Furthermore, all the neonatal outcomes were statistically similar between the two groups.Conclusion: Treatment with 17-OHPC is not associated with reducing the risk of PTB or neonatal outcomes compared to placebo.

New medicines for spontaneous preterm birth prevention and preterm labour management: landscape analysis of the medicine development pipeline

“…Assessment of cervical length requires access to transvaginal ultrasound, which is not available in all settings. Two meta-analyses from 2021 found no significant effect of injectable 17-alpha-hydroxyprogesterone caproate in preventing preterm birth, prompting the FDA, in 2022, to recommend its withdrawal from market [ 8 , 57 ]. These recent additions to the body of evidence on progesterone’s efficacy have prompted updated guidance from American College of Obstetricians and Gynecologists (ACOG) on use of progesterone in pregnant women [ 58 ].…”

Dendrimer-Based N-Acetyl Cysteine Maternal Therapy Ameliorates Placental Inflammation via Maintenance of M1/M2 Macrophage Recruitment

“…Most therapies focus on antibiotics, considering the association between inflammation and premature labor in humans. Other new treatment strategies for PTB include progesterone (Almutairi et al, 2021;Frey et al, 2021), tocolytics (Zheng et al, 2017;Jameson and Bernstein, 2019), anti-inflammatory agents (Chin et al, 2016;Xu et al, 2016;Gorasiya et al, 2018;Lee et al, 2019b) and high throughput screening (Le et al, 2020) for PTB prophylaxes (Zierden et al, 2021). In additional to the novel drugs, new drug delivery systems such as nanomedicine-based systems, help the drugs with more targeted and sustained approach.…”

Progesterone and Preterm Birth

“…A meta-analysis of similar trials found that 17-α-hydroxyprogesterone caproate injections did not significantly reduce preterm birth risk at less than 32 weeks, less than 35 weeks, or less than 37 weeks. 10 Progesterone was the standard of care for preterm birth prevention between 2003 and 2017, while concerns mounted regarding its efficacy. In 2018, scientists from the Centers for Medicare & Medicaid Innovation used mixed-methods analysis within 200 sites in 30 states documenting a significant underutilization of progesterone among Medicaid beneficiaries who were at the highest risk of recurrent preterm birth, with only 14.9% utilization among those who qualified.…”

“…In this subsequent trial, Makena did not show a decrease in preterm birth in people delivering prior to 35 weeks (11% Makena vs 12% placebo, P = .72) or prior to 37 weeks of gestation (23% Makena vs 22% placebo, P = .57). A meta-analysis of similar trials found that 17-α-hydroxyprogesterone caproate injections did not significantly reduce preterm birth risk at less than 32 weeks, less than 35 weeks, or less than 37 weeks 10…”