Is Long-Term Tocolysis Effective for Threatened Premature Labour?

Abstract

There is some controversy regarding the optimum duration of tocolysis. This retrospective multicentre study was performed to evaluate whether long-term (> 2 days) tocolysis is effective in treating threatened premature labour. A total of 1147 eligible patients were grouped according to whether or not tocolytics were given, and according to route of administration and whether or not ritodrine (the standard tocolytic regimen in Japan) or other tocolytic was given. They were then further stratified into three subgroups, using the Baumgarten and Gruber tocolysis index (TI), to assess the efficacy of tocolysis treatment according to the risk of premature labour. Prolongation of gestation was significantly longer in patients treated with tocolytics for > 2 days compared with the unmedicated, bed-rest group. In women receiving tocolysis, the mean duration of prolonged gestation was 2.2 times longer in the intermediate-risk TI group and 3.1 times longer in the high-risk TI group compared with the unmedicated group. In the patients who received tocolysis, IV ritodrine was used in 86% of cases and was considered safe and effective for prolonging gestation in cases of threatened premature labour.

Inflammatory and infectious risk factors are associated with the response to tocolysis in patients with preterm labor

“…Although a decrease in PTD rates is highly desirable from medical and socioeconomic perspectives, there is not yet a globally or locally established standard treatment for preterm labor [10]. The use of short-term (52 days) tocolysis allows to the maximal effect of parenteral steroids administered to the mother, enabling the transfer to a center with a neonatal intensive care unit.…”

Assessment of side effects of generic injectable ritodrine hydrochloride products

“…By stimulating β2 adrenergic receptors and antagonizing prostaglandin production in a dose-dependent manner, ritodrine hydrochloride exerts a relaxing effect on uterine muscles, and has been an indispensable drug in daily obstetrics treatment since its approval and sale in 1986. Especially in Japan, ritodrine has been used to prolong pregnancy as much as possible, 6) while in most western countries, it is restrictively and temporarily used to maintain pregnancy for a period less than 48 hours, which is long enough to allow women to be transferred to tertiary care or to complete a course of antenatal corticosteroids for the maturation of fetal lungs. 7) In many countries including Japan, a DPC-based fixed payment system for hospitalization costs has been introduced to the health insurance system, which prioritizes economic efficiency.…”

Concentration of Sulfate and Glucuronide Conjugates of Ritodrine in Twin Pregnancy

“…14,15) Ritodrine, a highly selective β 2 agonist, used in Japan for the treatment of threatened premature labor to prolong pregnancy until full term birth at week 37 with long-term continual infusion. 1) But, in Europe and the United States, the use of ritodrine to prevent labor is limited to 48 h to avoid the side effects caused by the β 2 agonistic effects of ritodrine outside the uterus. 15,16) However, because substantial brain development of the fetus occurs during the 2nd and 3rd trimester, neonates born between the gestational ages of 22-25 weeks are highly susceptible to brain damage.…”

“…1) Pulmonary edema has been reported as one of the serious side effects of overdoses of ritodrine when used in combination with adrenocorticosteroids in multiple pregnancies. 1) Although ritodrine has been shown to provide significant control for births within 48 h, there are reports that it provides no improvement in the perinatal prognosis or newborn mortality. 2,3) The use of ritodrine has recently been restricted in Europe because of its maternal side effects.…”

“…4) However, because fetal development is considered important, ritodrine continues to be used in Japan following a policy of long-term tocolysis for the purpose of extending the gestational age. 1) The most important perinatal problem in multiple pregnancies is premature labor. The risk of premature labor increases with the number of fetuses; the risk is reported to be 5.4 times greater in twin pregnancies compared to singletons.…”