Labour and Delivery Use of Tocolytics and Birth Outcome Yves Jacquemyn Professor of Obstetrics and Gynaecology, and Head, Department of Obstetrics and Gynaecology, Antwerp University Hospital


Abstract


Although a multitude of randomised controlled trials comparing different tocolytics in terms of maternal outcome and prolongation of pregnancy have been published, results on long-term neonatal–infant outcome are rare. After long-term tocolysis with ritodrine, an increased risk of intraventricular haemorrhage in the neonate has been reported and more behavioural problems in infants have been suggested. Indomethacin should not be given after 34 weeks due to early closure of the ductus arteriosus. In randomised controlled trials no increased risk of necrotising enterocolitis or renal failure has been demonstrated. For atosiban, no foetal or neonatal side effects have been described, but long-term follow-up is limited. Foetal and neonatal outcome is slightly better with nifedipine compared with other tocolytics. Magnesium sulphate should not be considered a tocolytic, but has now been proved to offer neuroprotection. Prolonged use (for more than five days) results in altered bone metabolism and may cause skeletal problems in the neonate. Improvements in neonatal care mean more data are required on the long-term neonatal and infant effects of tocolytics, as this will become one of the elements to consider when deciding whether or not to start a tocolytic agent.


Keywords Betamimetic, atosiban, nifedipine, tocolysis, neonatal follow-up


Disclosure: The author has no conflicts of interest to declare. Received: 31 May 2010 Accepted: 21 June 2010 Citation: European Obstetrics & Gynaecology, 2010;5:36–8 Correspondence: Yves Jacquemyn, Department of Obstetrics and Gynaecology, Antwerp University Hospital, Universitair Ziekenhuis Antwerpen, Wilrijkstraat 10, 2650 Edegem, Belgium. E: yves.jacquemyn@uza.be


When treating women in pre-term labour, most obstetricians are well aware that they are treating two patients. However, after birth one of these patients – the foetus – becomes a neonate and its care is taken over by the neonatal team. At that moment most obstetricians will continue their care for the mother only. This is one of the reasons why the long-term effects of the medication obstetricians give their patient, the foetus, are not very well known. This article provides an overview of the long-term effects of tocolytics.


Tocolytics influence the neonate but also lead to a primary difference between babies born after spontaneous pre-term birth and those born after iatrogenic pre-term birth. Bastek et al. demonstrated that infants born after spontaneous pre-term birth had less favourable outcomes at earlier gestational ages than those delivered due to pre-eclampsia at 24–28 weeks.1


However, babies born from mothers with


pre-eclampsia were more likely to stay in the neonatal intensive care unit for a longer time when they were born between 32 and 34 weeks.


Although the discussion is still ongoing regarding whether or not to use tocolytics, a recent study by the Swedish Express Group has demonstrated that for extremely pre-term infants born at


In a study on risk factors for cystic periventricular leucomalacia in pre-term infants, Bauer et al. found that the administration


36


of tocolytic agents was associated with an increased risk of periventricular leucomalacia (OR 1.8, 95% CI 1.1–3.0).3


However, they


did not provide sufficient data to differentiate between different types of tocolytic agent.


Van de Water et al. presented the long-term follow-up of newborns after tocolytic therapy.4


They presented data on patients with


pre-term labour randomised to receive either nifidipin or ritodrine. Development of the children was studied after two years of age by a parental questionnaire. Two-thirds of the children had developed normally in both groups and there were no significant differences in development found between the two groups.


Laros et al. compared the outcome of very low birthweight infants, weighing ≤1,500g exposed to beta-sympathomimetic agents (isoxsuprine, ritodrine, terbutaline or combinations) with control infants of similar birth weight at one, three and four years of age.5 Mortality was greater with terbutaline, as was the need for positive inspiratory pressure when respiratory distress syndrome was present. No other differences were found when taking time and other related confounding factors into account.


Ritodrine is well-known for its effects in pregnant women. Most clinicians know, through experience with foetal hart rate monitoring, that betamimetics induce foetal tachycardia. In a randomised trial between atosiban and ritodrine, Neri et al. performed computerised


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