Duration of intrapartum prophylaxis and concentration of penicillin G in fetal serum at delivery

Abstract

Objective: Intrapartum penicillin G prophylaxis aims to prevent early-onset group B streptococci (GBS) sepsis by interrupting vertical transmission. We examined the relationship between duration of prophylaxis and fetal serum penicillin G levels among fetuses exposed to fewer than 4 hours of prophylaxis compared with longer durations.

Methods: In this prospective cohort study, 98 laboring GBS-positive women carrying singleton gestations at 37 weeks or greater were administered 5 million units of intravenous penicillin G followed by 2.5 million units every 4 hours until delivery. Umbilical cord blood samples were collected at delivery, and penicillin G levels were measured by high-performance liquid chromatography. Intraassay and interassay coefficients of variation were less than 3%.

Results: Fetuses exposed to fewer than 4 hours of prophylaxis had higher penicillin G levels than those exposed to greater than 4 hours (P=.003). In multivariable linear regression analysis, fetal penicillin G levels were determined by duration of exposure, time since last dose, dosage, and number of doses, but not maternal body mass index. Penicillin G levels increased linearly until 1 hour (R(2)=.40) and then decreased rapidly according to a power-decay model (R(2)=.67). All subgroups analyzed were above the minimal inhibitory concentration (MIC) for GBS (0.1 micrograms/mL)(P<.002). Individual samples were 10-179-fold above the MIC. In patients receiving maintenance dosing, penicillin G did not accumulate in the cord blood and returned to baseline after each 4-hour interval.

Conclusion: Short durations of prophylaxis achieved levels significantly above the MIC, suggesting a benefit even in precipitous labors. The designation of infants exposed to fewer than 4 hours of prophylaxis as particularly at risk for GBS sepsis may be pharmacokinetically inaccurate.

Fig. 1

Blood bank and labor floor umbilical cord serum sample penicillin G concentration. Blood bank and labor floor umbilical cord serum sample penicillin G concentration measured for 18 patients. Each patient has one of each sample, and patients are organized in order of increasing penicillin G concentration, from left to right. The solid circles represent the samples obtained on the labor floor and the outlined circles represent the samples taken from the blood bank after one week of storage. Author: Figure 1 was redrawn by editorial office. Please review and indicate approval.

Fig. 2

Time after infusion of penicillin G compared with concentration in umbilical cord serum at delivery. Relation between time elapsed since initial dose of 5 million units of penicillin G and concentration of penicillin G in umbilical cord serum at the time of delivery. Author: Figure 2 was redrawn by editorial office. Please review and indicate approval.