Effect of maintenance tocolysis with nifedipine in established preterm labour on pregnancy prolongation and neonatal outcome.

Fifty women with singleton pregnancies between 26 and 33weeks of gestation and arrested preterm labour (PTL) after acute tocolysis were randomised by a computer generated randomisation table into an intervention group (n = 25) who received maintenance tocolysis with tablet nifedipine for 12 days or up to 34 weeks of gestation, whichever was later and a control group (n = 25). The primary outcome was achievement of term gestation and the secondary outcomes were the number of days gained till delivery and neonatal mortality and morbidity. The mean gestation at admission, cervical dilatation and effacement were similar in the two groups (30 + weeks, 2.5 cm, 60%). In the intervention group, 7/25 (28%) and in the control group, 2/25 (8%) delivered at term (p = .066) and pregnancy prolongation of 20 days (IQR 2.5-51) and 14 days (IQR 1-27.5) were achieved, respectively (p = .269). Maintenance tocolysis was given for a median of 14 days (range 3-25.5). Kaplan-Meier analysis showed no statistically significant difference in prolongation of pregnancy between the control and the intervention groups (p = .077). The median number of days of neonatal hospital stay were reduced with maintenance tocolysis, but the difference was not significant (4.0 vs 5.5; p = .608). The mean birth weight was significantly higher in the intervention group (2266 vs 1880 g, p = .044). Among women at a high risk for preterm birth (PTB) due to established PTL as evidenced by a mean cervical dilatation of 2.5 cm and a PTB rate of 92% in the control group, maintenance tocolysis did not prolong the pregnancy or reduce the neonatal hospital stay significantly. Impact statement What is already known on this subject: In women with preterm labour (PTL) the role of maintenance tocolysis following acute tocolysis to reduce recurrent PTL is uncertain. Of the six studies using nifedipine, one reported pregnancy prolongation (26.65 vs 16.14 days, p = .007), but similar perinatal outcome (Sayin et al. 2004 ). Others did not find pregnancy prolongation (Carr et al. 1999 ; Lyell et al. 2008 ; Uma et al. 2012 ; Roos et al. 2013 ; Parry et al. 2014 ). The PTB rate in the control groups ranged from 38 to 67%. A Cochrane review reported pregnancy prolongation by 5.35 days but similar neonatal outcome (RR 0.75) (Naik et al. 2013 ). A meta-analysis including five studies using progesterone and five using nifedipine concluded that progesterone, but not nifedipine, prolonged pregnancy (Ding et al. 2016 ). Thus, data on maintenance tocolysis is limited and inconclusive. What the results of this study add: In the present randomised study in 50 women with arrested PTL, 25 received maintenance tocolysis. The mean gestation at admission, cervical dilatation and effacement were similar in the two groups (30+ weeks, 2.5cm, 60%). In the intervention group, 7/25 (28%) and controls, 2/25 (8%) delivered at term (p = .066) and pregnancy prolongation of 20 days (IQR 2.5-51) and 14 days (IQR 1-27.5) were achieved, respectively (p = .269). Kaplan-Meier analysis showed no statistically significant difference in prolongation of pregnancy between the control and the intervention groups (p = .077). The median number of days of neonatal hospital stay were reduced with maintenance tocolysis but the difference was not significant (4.0 vs 5.5; p = .608). What are the implications of these findings for clinical practice and/or future research: The mean birth weight was higher in the intervention group (2266 vs 1880g, p = .044). Future studies should take cervical dilatation and the PTB rate in the control group into consideration while assessing the impact of maintenance tocolysis.