Transplacental passage of diazepam during labor: Influence of uterine contractions

Abstract

The rate of transplacental passage of diazepam (DZ) has been studied in 33 cases of cephalic presentation where operative forceps delivery was indicated by intrauterine hypoxia or by prolonged second stage of labor. The drug (30 mg) was injected intravenously immediately before delivery either during uterine contractions (Group I) or in the relaxation period (Group II) according to a randomized protocol. As judged by the concentration in the newborn and the child/mother concentration ratio at 2 hr after delivery, and the concentration on the second day, the fetal exposure to the drug was probably less when the injection was timed to coincide with uterine contractions. In the group of patients given the drug in the relaxation period, the injection-delivery (I-D) interval was up to 305 sec and the 2-hr child/mother concentration ratio was close to unity in some cases. It therefore appears that the transplacental passage of DZ is rapid when the high initial concentrations in the maternal circulation coincide with favorable conditions for transfer in the relaxation period. Although sleep was induced by the injection of DZ in all of the mothers, the amounts of drug transferred during the short I-D intervals in the present study did not exert delterious effects on the newborn infants.

The effect of uterine contractions on fetal oxygen saturation

“…This will decrease oxygen transfer to the fetus. Further support of this theory comes from an experiment measuring the rate of trans‐placental passage of diazepam to the fetus (Haram et al 1978). One group of mothers was randomly allocated diazepam, injected as the uterus started to contract, and the others received it during uterine diastole.…”

Time-course of Transplacental Passage of Diazepam

“…Patients 73 patients were selected from a total of 122 cases of previously published investigations (Bakke et al, 1982, Haram andBakke, 1980;Haram et al, 1978Haram et al, , 1979 Since uterine contractions and possibly also breech delivery are associated with reduced drug transfer to the fetus (Haram et al, 1978(Haram et al, , 1979, only cases with cephalic presentation given diazepam in the relaxation phase prior to vaginal delivery and patients undergoing elective Caesarean section were included in the present study of the rate of drug 354 transfer to the fetus. Twin pregnancies and cases with severe pre-eclampsia, Rh-immunisation and diabetes mellitus where the exchange between mother and fetus could be disturbed, were excluded (Finster and Pedersen, 1979).…”

“…15 of the patients received a fixed dose of 30mg of diazepam (Valium,® Roche) administered intravenously in the relaxation phase immediately before forceps delivery (Haram et al, 1978). The remaining 58 cases were given O.3mg/kg or a fixed dose of 20mg of the drug as a sleep-inducing agent for elective Caesarean section (Bakke et al, I 981;Haram and Bakke, 1980).…”

“…In our hospital blood levels of diazepam were studied in 122 mothers and their newborn babies after a single intravenous injection of the drug for induction of sleep prior to delivery (Bakke et al, 1981;Haram and Bakke, 1980;Haram et al, 1978Haram et al, , 1979. The main purpose was to study the effect of uterine contractions, the type of presentation, and the method of delivery on fetal drug exposure and the neonatal condition.…”

Diazepam as an Induction Agent for Caesarean Section: A Clinical and Pharmacokinetic Study of Fetal Drug Exposure

“…We have previously shown that in forceps and breech deliveries with injection-delivery intervals up to 305 seconds, 30 mg of diazepam can be given intravenously to the mothers without producing sedation or respiratory depression in the newborn (Haram et al, 1978;Haram et al, 1979). Also, diazepam (20 mg) has been used as an induction agent before Caesarean section and found to be safe (Stovner and Vangen, 1974).…”