Neonatal Adverse Effects Research Articles

A comparison of terbutaline and ethanol in the treatment of preterm labor

Ninety-two women in preterm labor were randomly assigned to either terbutaline or ethanol. In women with intact membranes, terbutaline was significantly more effective than ethanol in preventing progressive cervical dilation during the first 36 hours of treatment while betamethasone was given to the mother. Additionally, pregnancy was maintained significantly longer in women with intact membranes who were treated with terbutaline (15 +/- 4 days) rather than with ethanol (10 +/- 3 days). However, only 18% of women in each treatment group maintained their pregnancy beyond 36 weeks' gestation. In women with ruptured membranes and cervical dilation less than 4 cm, terbutaline was significantly better than ethanol in maintaining pregnancy for a minimum of 36 hours. Serious maternal side effects were not observed with terbutaline or ethanol, although a majority of women also received betamethasone. Neither drug caused serious adverse neonatal effects.

The effect of flunitrazepam on reproduction in the rat. The use of cross-fostering in the evaluation of postnatal parameters in rat reproduction studies

During the course of reproduction studies in rats with flunitrazepam, a benzodiazepine derivative, a high incidence of neonatal loss at delivery and during the first 2 days of the lactation period was observed. At delivery the female rats treated with 25 mg/kg/day flunitrazepam exhibited signs of central nervous system depression and were indifferent during parturition resulting in an increased incidence of dead pups at delivery. In addition, flunitrazepam induced a peculiar voracious behavior causing some animals to cannibalize their litter shortly after dosing. A crossfostering experiment was conducted in order to determine whether the observed neonatal loss was the result of a direct toxic effect of flunitrazepam on the neonates or was secondary to aberrant maternal behavior. Cross-fostering in itself did not produce adverse neonatal effects since the survival of control neonates in litters that had been fostered was equivalent to control animals whose litters were not fostered. Treated dams nursing neonates from control litters cannibalized these apparently normal pups indicating that the observed cannibalism after delivery was due to abnormal maternal behavior. Treated neonates placed with control dams exhibited a survival rate which although much better than control pups with treated dams, was still somewhat lower than controls, suggesting that decreased viability of pups delivered from treated dams was an additional factor in the neonatal loss. The survival rate of Cesarean-delivered pups, however, from treated dams and fostered by untreated dams was not significantly different from control neonates similarly handled. This latter result demonstrated that the decreased viability of pups from treated dams appears to be the result of trauma during delivery rather than a direct toxic effect of flunitrazepam on the neonate or on the fetus in utero.

The effect of maternal medications upon the fetus and the newborn infant

Adverse neonatal effects following drug therapy in both mothers and infants are being described with increasing frequency. Any drug given to a pregnant woman and subsequently found in her blood may be expected to pass into the infant's circulation. Many substances known to be toxic when given to the infant apparently do not reach dangerous levels in the infant when given to the mother. Some medications may be without ill effects, although significant blood levels are reached. Certain types of toxic reactions have probably not yet been recognized. Chloramphenicol, for example, was used extensively in newborn infants and was responsible for many neonatal deaths before its toxicity became known. In general, drugs associated with jaundice should be avoided in the pregnant woman at parturition, as well as in the neonatal infant.Drugs with rare idiosyncrasy reactions cannot be eliminated from medical management when good indications for their use are present. In such instances, the physicians responsible for the mother and baby are expected to be aware of possible side effects, and to be prepared to diagnose and treat such complications when necessary. On the other hand, although teratogenic effects in human beings have not invariably followed the use of cancer chemotherapeutic drugs even in early pregnancy, such cytotoxic drugs are probably teratogenic and are contraindicated at least within the first trimester.