The Vexing Problem of Preterm Birth Prevention

Abstract

Preterm birth (delivery before 37 weeks of gestation) is a significant risk factor for maternal and perinatal mortality. Despite intensive efforts to develop preventive and treatment interventions intended to delay delivery until term, preterm birth continues to be one of the most important problems facing contemporary obstetrics. The incidence of preterm birth remains stubbornly high, hovering around 10% to 11% of all pregnancies in the United States, with numerous and often overlapping etiologies, including preterm rupture of amniotic membranes, cervical insufficiency, decidual hemorrhage, multiple gestation, infection, and maternal stress. 1 Interventions to reduce preterm birth have been studied in different at-risk populations, including those with a prior preterm birth or a short (<25 mm) cervix in the current pregnancy. For patients with a short cervix, interventions that have been studied include supplemental vaginal progesterone, cervical cerclage, and cervical pessary. Despite these interventions, the overall rate of preterm birth and obstetric outcomes has remained largely unchanged. Thus far, only the field of neonatology can quantify significantly improved perinatal outcomes. 2,3 In the past, small pilot studies of tocolytic agents, home uterine activity monitoring, intramuscular progesterone, and screening for preterm birth risk factors have shown effectiveness at delaying delivery until term. However, results of larger, adequately powered studies of these interventions have been mixed and meta-analyses inconclusive or disputed. [4][5][6][7] The lack of large, rigorously conducted trials limits evidence-based obstetric interventions. When small studies have shown benefit, the intervention may be widely accepted and used clinically (eg, electronic fetal monitoring) before subsequent larger studies with appropriate power and more rigorous study designs conclusively show no benefit. This paradigm has led to significant financial costs to patients and health care systems without benefit. Perhaps this tension in seeking to find an intervention to prevent preterm birth is best exemplified by the use of intramuscular 17α-hydroxyprogesterone caproate, the approval of which was recently revoked by the US Food and Drug Administration. 8-10 Additionally, these well-intentioned interventions may potentially harm pregnant people and their fetuses (eg, β-mimetic tocolytic agents). 11 Given this history of unsuccessful obstetric interventions, one can understand the enthusiasm of the obstetric community for new treatments that could decrease the rate of preterm birth. Thus, the development of an intravaginal pessary that could prevent preterm birth in at-risk individu-