[Tocolysis, use of beta-sympatomimetics for threatening preterm delivery: a critical review]

Abstract

Use of beta-sympatomimetics for threatening preterm delivery: a critical review. Preterm birth is the principal cause of perinatal and neonatal mortality and morbidity. Over the past 40 years, numerous treatments have been tested and used to try to inhibit preterm labor. This literature review is limited to the published studies of beta-adrenergic agonists (beta-sympathomimetics). Among 36 articles that have examined the treatment of acute phase preterm labor by intravenous beta-sympathomimetic administration, 26 are clinical studies with severe biases that make them unacceptable for analysis: non-randomized clinical trials, retrospective studies or retrospective control groups, inadequate recording of pregnancy outcome, exclusion of patients after randomization, confounding factors due to the use of multiple therapeutic agents, inadequate study power.Of the 10 acceptable placebo-controlled trials, seven, including the largest (the Canadian Preterm Labor Investigators' Group, with 708 women), found that beta-sympathomimetics were not better than placebo in prolonging pregnancy or reducing neonatal morbidity. Only three studies found that they were superior to placebo. These agents cause numerous maternal side effects that may be life-threatening, because beta-adrenergic receptors are present in many organs. The cardiovascular system is the most severely affected, but side effects also concern the pancreas, kidneys, intestines, and liver. beta-Sympathomimetics cross the placenta rapidly. Fetuses probably respond in the same way their mothers do to stimulation of their beta-adrenergic receptors. Nonetheless, data from the controlled clinical trials show no difference in neonatal mortality or severe morbidity between children born to mothers treated with beta-sympathomimetics and those born to mothers in control groups. The efficacy of preventive treatment by oral or subcutaneous administration of beta-sympathomimetics has also been assessed: a meta-analysis and 2 large randomized placebo-controlled trials have showed that oral maintenance treatment offers no advantages over placebo during the latency phase or for the recurrence rate of preterm labor and the rate of preterm delivery. A single - and smaller - placebo-controlled study found that oral maintenance treatment with ritodrine was beneficial. Treatment trials of subcutaneous administration of beta-sympathomimetics have been performed with a portable subcutaneous pump. Ten studies of this method have been reported, but only two were randomized trials. They found no significant difference in either the mean time until delivery or neonatal morbidity.