Use of tocolytics – what is the benefit of gaining 48 hours for the fetus?

Professor Gian Carlo Di Renzo
Centre of Perinatal and Reproductive Medicine
University of Perugia
Perugia, Italy

Biography
Professor Di Renzo has been the Professor of Obstetrics and Gynaecology, Prenatal Medicine and the Head of the Perinatal and Reproductive Centre at the University of Perugia since 2000 and has recently been appointed the Chairman of the Section of Obstetrics and Gynaecology and Dean of the Faculty of Obstetrics and Midwifery, as well as Chairman of the Department of Obstetrics and Gynaecology. His research interests include prostaglandins and parturition, amniotic fluid, fetal lung maturity, childbirth organisations, fetal monitoring, preterm labour and obstetric and gynaecological endocrinology. Professor Di Renzo is a member of several key European and international societies and is Editor-in-chief of the Journal of Maternal-Fetal and Neonatal Medicine and has editorships with a number of major journals in obstetrics and gynaecology.

[return to top of page]

Abstract
Tocolysis is the first therapeutic tool for the management of threatened preterm labour. The primary aims of tocolytic therapy are to delay delivery to allow the administration of a complete course of antepartum glucocorticoids (GC) in order to reduce the incidence and severity of idiopathic respiratory distress syndrome (RDS) and to arrange an in-utero transfer to a centre with neonatal intensive care unit facilities. The secondary aim of tocolytic therapy is to delay delivery to reduce the perinatal mortality and morbidity associated with severe prematurity.

A single course of GC to pregnant women, at risk of preterm delivery within 7 days, should be administered between 24 and 34 weeks’ gestation. A meta-analysis of 18 randomized trials has demonstrated that antenatal corticosteroids significantly reduce the occurrence of neonatal RDS (OR 0.53, 95% CI, 0.44 - 0.63) and neonatal death (OR 0.6, 95% CI, 0.48 - 0.75). Furthermore, there was a significant reduction of intraventricular hemorrhage (IVH) diagnosed both at autopsy (OR 0.29, 95% CI, 0.14 - 0.61) and by ultrasound (OR 0.48, 95% CI, 0.32 - 0.72). One single course of antenatal GC may also reduce periventricular leukomalacia (PVL) and cerebral palsy.

Betamethasone and dexamethasone are the two most widely used GC for antenatal prophylaxis, but there are no randomized controlled studies comparing these agents with respect to efficacy. Even though betamethasone seems to affect fetal heart rate variation and fetal movements more than dexamethasone, it seems to offer several advantages.

A combination of drugs (namely betamethasone, aminophylline, magnesium sulphate) has recently been found to significantly reduce severe IVH in preterm newborns before the 30 th week of gestation. The administration of this regimen is administered for 48 hours, as for antepartum GC alone.

As soon as the diagnosis has been accomplished, it is recommended that neonatologists involved in management decisions are informed to ensure that a neonatal intensive care cot is available on site or that an in-utero transfer to a centre with intensive care unit facilities may be arranged.

In absence of clear evidence that tocolytic drugs improve outcome following preterm labour, it is reasonable not to use them. The women who are more likely to benefit from tocolysis are those who are still very preterm, those needing transfer to a hospital that can provide neonatal intensive care or those who have not yet completed a full course of corticosteroids to promote fetal lung maturation. For these women, tocolytic drugs should be taken into account.

[return to top of page]