Comparison of various betamimetics on preterm labor, survival and development of the child

Abstract

During the past 5 yr inhibition of preterm labor by use of .beta.-sympathomimetics has been common practice. The initial use of compounds with mixed .beta.1 and .beta.2 effect has gradually been replaced by more selective .beta.2 compounds. Interest has been mainly focused upon the elicited prolongation of pregnancy, possible fetal or maternal metabolic disturbances and the acute influence on fetal heart rate. Only few reports mention the possibility of long-term effects in children of treated mothers. In the present study the efficacy of 3 different .beta.-sympathomimetics on premature labor was studied and the children followed for 18 mo. after delivery. Patients (79) were treated with either isoxsuprine (25), ritodrine (29) or terbutaline (25). The following criteria were demanded for entering the study: length of gestation 25 or 35 wk, uterine contractions of at least 10 per h (cardiotocogram registered), cervix not dilated more than 4 cm and no rupture of the membranes. In each group the patients were treated primarily with an i.v. infusion followed by oral administration of the respective compound. The treatment was considered successful if prolongation of pregnancy exceeded 7 days. The failure group (pregnancy prolongation < 7 days) was somewhat smaller in the terbutaline group compared to both the isoxsuprine and the ritodrine groups. The prolongation of pregnancy was shorter for isoxsuprine (.hivin.x [mean] 17.4 days) compared to ritodrine (.hivin.x 31.2 days) and terbutaline (.hivin.x 35.0 days). The children were carefully supervised by pediatricians during the 1st wk of life and thereafter scheduled for a special check up at 5, 10 and 18 mo. after delivery. A tendency towards a higher degree of light for gestational age in all 3 groups was found, but this was not statistically significant. At 18 mo. the surviving children did not differ significantly from the normal weight at this age; thus no retarded growth rate at 18 mo. of age was found. Ten children (12%) died during the neonatal period, while 5 children (6%) died beyond the neonatal period, 2 of them unexpectedly and suddenly. Two children had signs of psychomotor disturbances at 18 mo. of age, both belonging to the group treated with ritodrine. The present study confirms earlier reports demonstrating that more selective .beta.2 compounds are most potent in inhibiting premature labor. From the long-term evaluation of children of treated mothers a remarkably high incidence of complications occurred (7-8%). In this connection it is worthwhile to keep in mind the findings of myocardial necrosis reported after isoproteronol treatment to rats and the reports concerning in vitro degeneration in human fetal heart after fenoterol treatment. Treatment with .beta.-sympathomimetics should be restricted to carefully selected groups, since long-term adverse effects on children of treated mothers at present cannot be excluded.