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Tocolysis after preterm premature rupture of membranes and neonatal outcome: a propensity-score analysis
Elsa Lorthe1, François Goffinet2, Stéphane Marret3
1Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche 1153, Obstetrical, Perinatal, and Pediatric Epidemiology Research Team (Epopé), Center for Epidemiology and Statistics, Sorbonne Paris Cité, and Département Hospitalo-Universitaire Risks in Pregnancy, Paris Descartes University, Paris, France; Sorbonne Universités, Université Pierre and Marie Curie, Institut de Formation Doctorale, Paris, France.
Background:
There are conflicting results regarding tocolysis in cases of preterm premature rupture of membranes. Delaying delivery may reduce neonatal morbidity because of prematurity and allow for prenatal corticosteroids and, if necessary, in utero transfer. However, that may increase the risks of maternofetal infection and its adverse consequences.
Objective:
The objective of the study was to investigate whether tocolytic therapy in cases of preterm premature rupture of membranes is associated with improved neonatal or obstetric outcomes.
Study Design:
Etude Epidémiologique sur les Petits Ages Gestationnels 2 is a French national prospective, population-based cohort study of preterm births that occurred in 546 maternity units in 2011. Inclusion criteria in this analysis were women with preterm premature rupture of membranes at 24-32 weeks' gestation and singleton gestations. Outcomes were survival to discharge without severe morbidity, latency prolonged by ≥48 hours and histological chorioamnionitis. Uterine contractions at admission, individual and obstetric characteristics, and neonatal outcomes were compared by tocolytic treatment or not. Propensity scores and inverse probability of treatment weighting for each woman were used to minimize indication bias in estimating the association of tocolytic therapy with outcomes.
Results:
The study population consisted of 803 women; 596 (73.4%) received tocolysis. Women with and without tocolysis did not differ in neonatal survival without severe morbidity (86.7% vs 83.9%, P = .39), latency prolonged by ≥48 hours (75.1% vs 77.4%, P = .59), or histological chorioamnionitis (50.0% vs 47.6%, P = .73). After applying propensity scores and assigning inverse probability of treatment weighting, tocolysis was not associated with improved survival without severe morbidity as compared with no tocolysis (odds ratio, 1.01 [95% confidence interval, 0.94-1.09], latency prolonged by ≥48 hours (1.03 [95% confidence interval, 0.95-1.11]), or histological chorioamnionitis (1.03 [95% confidence interval, 0.92-1.17]). There was no association between the initial tocolytic drug used (oxytocin receptor antagonists or calcium-channel blockers vs no tocolysis) and the 3 outcomes. Sensitivity analyses of women with preterm premature rupture of membranes at 26-31 weeks' gestation, women who delivered at least 12 hours after rupture of membranes, women with direct admission after the rupture of membranes and the presence or absence of contractions gave similar results.
Conclusion:
Tocolysis in cases of preterm premature rupture of membranes is not associated with improved obstetric or neonatal outcomes; its clinical benefit remains unproven.