Introduction
Preterm birth (PTB) is a worldwide challenge and a major public health problem1. PTB leads to short and long-term consequences for newborns and families, including cerebral palsy, blindness, and neurodevelopment problems2.
In women with multiple gestations, nowadays seen more often due to assisted reproductive treatments and due to a rising maternal age, the prevalence of PTB is increased. In the presence of a mid-gestation short uterine cervix, an independent predictor for prematurity, the rate of spontaneous PTB in twins <32 weeks increases exponentially as shorter is the cervical length measure3,4. For women with a singleton pregnancy, progesterone is useful to reduce PTB <34 weeks in women with a previous PTB or mid-trimester short cervix (vaginal progesterone vs no treatment RR 0.78; CI 0.68 to 0.90)5. Other preventative interventions include cerclage and cervical pessary with good efficacy. When considering only multiple gestations, interventions such as progesterone, cerclage or cervical pessary are also possible options to decrease PTB.
In fact, the uncertainty of evidence can be related to small sample sizes and different study designs and outcomes. Recently, a network meta-analysis (NMA) looking for effective treatments for preventing PTB in women with multiple gestations did not show a significant effect in reducing the rate of PTB or perinatal morbidity in twins, either when these interventions are applied to an unselected population of twins or in pregnancies with a short cervix6. One issue is that this NMA did not assess the integrity of the included studies, which is worrisome as some studies recently have been retracted7 it has recently become more clear that . Also, the P5 trial8 (n = 71 twins) and PESSAREONE study9 (n = 310) have been recently published, which warrants new updates for the evidence.
The aim of this study is to perform a systematic review and NMA evaluating the effectiveness of progesterone, cerclage and cervical pessary and their combination as possible treatments for preventing PTB in multiple gestations according to cervical length. We specifically tried to assess the trustworthiness of the underlying studies.