**3. Tocolysis in multiple gestation**

regarding the mean of cervical length which is lower in UNIFESP pessary plus progesterone group than El-refaie's groups, which cause higher risk to SPB to pessary group; so but the

Considering the birthweight of twins not selected by cervix (n = 32), the mean weight of the biggest twin was 2.492 ± 643 g, and of the smallest twin, it was 2.195 ± 665 g; in comparison, in the twin group with short cervix treated by pessary plus progesterone (n = 24), the weight of the biggest one was 2.148 ± 434 g (p = 0.028), and of the smallest twin, it was 2.037 ± 425 g (p = 0.327), presenting a statistically significant difference between the groups for the biggest newborn, but no statistic difference for the smallest one. This result allows the conclusion that for the most vulnerable newborn (smallest one), the use of the cervical pessary was sufficient to modify the statistic difference expected, by cervical length difference, and in accordance

Furthermore, the use of the cervical pessary did not influence the weight difference between the fetuses. For the group not selected by cervix, the mean difference was 12 ± 6%; for the

This small difference demonstrates clear similarity between treated high-risk cases and cases of habitual twin pregnancy without involvement or diagnosis of complication factors in the

This study is according to a prospective, multicenter, randomized clinical trial conducted in Spain (PECEP-Twin). The primary outcome was SPB before 34 weeks of gestation. Neonatal morbidity and mortality were also evaluated. Cervical length was measured in

**Figure 1.** Comparison of percentage of SPB per gestational age between twin pregnancy from El-refaie's trial with short cervix (expectant and progesterone group) and UNIFESP twin pregnancy treated by pessary plus progesterone for short

performance is better for pessary, despite high risk mentioned (**Figure 1**).

group of twins with short cervix, the difference was 11 ± 2% (p = 0.375).

with the difference registered between taller twins.

cervix and UNIFESP controls without selection by cervix.

prenatal routine (**Table 2**).

194 Multiple Pregnancy - New Challenges

2287 women.

When an acute preterm labor is detected, it is possible to use tocolytic drugs to reduce uterine activity, and this is considered part of tertiary prevention. However, the diagnosis of preterm labor is not always simple, being generally defined as painful and regular contractions leading to cervical changes after the 20th week and before the 37th week of pregnancy.

The main goal of tocolysis is not to prevent preterm delivery, once the effectiveness for it is not proven [33]. However, tocolytic drugs can postpone delivery in 48 hours to 7 days, which is essential to manage antenatal corticosteroids to accelerate fetal pulmonary maturation and to transfer the patients to a tertiary care center when necessary [34, 35].

Tocolytic drugs should be administered when there is a clear benefit to the newborn, once the majority of these drugs has side effects to the mother and, sometimes, also to the fetus. So, it can be used from viability (23–24 weeks of pregnancy) until the 34th week, as most guideline recommendations propose. In special cases, they can also be used before viability, for example, in patients after an intra-abdominal surgery, when the cause of preterm labor is self-limited [34, 36, 37].

Contraindications for tocolytics include lethal fetal anomaly, preterm premature rupture of membranes, chorioamnionitis, severe preeclampsia and eclampsia, maternal hemorrhage with hemodynamic instability, suspected placental abruption, intrauterine fetal demise, and compromised fetal status [34].

Nowadays, the main drugs used in tocolysis are beta-agonists (as terbutaline), calcium channel blockers (as nifedipine), cyclooxygenase inhibitors (as indomethacin), and oxytocin receptor antagonist (as atosiban), as exposed in **Table 3**.

The ACOG recommends as first-line treatment in acute preterm labor in multiple pregnancy calcium channel blockers and cyclooxygenase inhibitors due to fewer side effects of these drugs [7]. In UNIFESP, the preference is for calcium channel blockers and oxytocin receptor antagonists.
