Safety and efficacy of new drugs in preterm labor

The pathophysiological events that trigger spontaneous preterm birth (SPB) are largely unknown but include decidual hemorrhage (abruption), mechanical factors (uterine overdistention or cervical incompetence) and hormonal changes (perhaps mediated by fetal or maternal stress). In addition, several cervicovaginal infections have been associated with preterm labor. SPB is the leading cause of perinatal mortality and long-term morbidity, including neurodevelopmental handicap, cerebral palsy, seizure disorders, blindness, deafness and non-neurological disorders, such as bronchopulmonary dysplasia and retinopathy of prematurity. Delaying delivery may reduce the rate of long-term morbidity by facilitating the maturation of developing organs and systems. The benefits of administration of antepartum glucocorticosteroids to reduce the incidence and severity of respiratory distress syndrome may be exploited by delay. Delay may also permit transfer of the fetus in utero to a center with neonatal intensive care unit facilities. If a tocolytic agent is used, betamimetics no longer seem the best choice. Alternatives, such as atosiban, appear to have comparable effectiveness in terms of delaying delivery by up to 7 days and are associated with fewer maternal and fetal adverse effects. Atosiban represents an advance in tocolytics currently available and should be considered as a first-line tocolytic for the management of SPB. Atosiban is licensed in Europe for treatment of threatened preterm labor. The recommended dosage and administration schedule for atosiban is a three-step procedure. Duration of treatment should not exceed 48 h and the total dose administered during a full course should preferably not exceed 330 mg. In the early gestational age, with or without PPROM, the use of atosiban can be prolonged for a further few days without any significant side effects. Major concerns remain regarding the use of calcium channel antagonists and nitric oxide donors: both drugs have tocolytic effects but their side effects, either maternal or fetal-neonatal, are potentially harmful and not fully known. Therefore, their use should be limited to the clinical research setting.