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.