Volume 164 l\"urnber 1. Part 2

II EFFECT OF VARYING MILIEU ON PLACENTAL GLUCOSE METABOLISM. FJ Frieden, MD, MR Brown, MS: SA Ordorica, MD, DIxBergman, MD, IA Hoskins, MD, S Ramanathan, MD, BK Young, MD. Departments of OB/GYN and Anesthesiology, NYU Medical Center, New York, NY.

In vitro metabolism in the term human pla­centa was studied using fragments of fresh pla­cental tissue incubated with and without glu­cose in varying oxygen environments and in the presence of different concentrations of medica­tions given to parturients (insulin, ritodrine, magnesium, AZT). Net production of lactate and pyruvate was determined with spectrophotometric assays. Statistical analysis was performed with ANOVA and Student's t-test. Lactate production was independent of glucose and oxygen. Pyruvate production was significantly increased in hy­peroxic conditions, while there was no signif­icant change due to glucose. There were no effects on lactate or pyruvate production for any concentration of any medication studied, from therapeutic to toxic range. In all exper­imental settings, lactate production far ex­ceeded that of pyruvate. The term human placen­ta appears to function with a primarily anaero­bic metabolism of glucose. Furthermore, the four medications investigated appear to have no direct effect on placental glucose metabolism.

.2 GLYBURIDE IS INSIGNIFICANTLY TRANSPORTED TO THE FETAL CIRCULATION BY THE HUMAN PLACENTA IN VITRO. xByron Elhott. Oded Langer. xSteve Schenker. xRaymond Johnson. Depts O1f7(;YN and Medicine. The Univ of TX H S C. at San Antonio. TX.

Tight glycemic control reduces maternal and fetal morbidity in pregnant diabetics. and this goal is presently achieved by Insuhn andlor diet therapy No data eXists regarding the safety of the oral hypoglycemic agents (eg. glybundel dUring pregnancy. The recirculating single cotyledon placenta model was used to characterize the maternal to fetal transport of H3-glyburide in term placentas perfused immediately following delivery C14-antipyrine was used as a standard reference for simple diffusion during these perfusions. Serial samples were taken from both the maternal and fetal reservoirs during each 4-hour perfusion and transport was calculated using liquid scintillation spectrometry. The identity of Isotope with parent compound was confirmed by HPLC

nglml Glyburide 1000

750

500

250

-.... • • • • Transport@2 hr=O 62%

Glyburide/Antip"yrine transport ratio (8J 2 hr=0.07

• •

a a 60 120 180 240 Minutes Additionally. the fetal to maternal transport was similarly tested Yielding a greater transport rate of 2.1 % at 2 hrs with a glyburide/antipyrlne transport ratio of 0.15 Minimal fetal concentrations of glyburide were achieved dUring these experiments with maternal levels 5 times pharmacologic concentrations This data suggests that insignificant fetal concentrations would occur at pharmacologic maternal levels.

SPO Abstracts 247

13 ANTIBIOTIC PROPHYLAXIS IN PRETERM PREMATURE RUPTURE OF THE MEMBRANES: A PROSPECTIVE RANDOMIZED

DOUBLE BLIND TRIAL OF 220 PATIENTS. Mercer B.', Moretti M', Rogers R " S,bai B. U .T. MemphiS

Prophylactic antimicrobial therapy has been proposed to prolong latency and reduce infectious complicatlons for women suffering pretcrm premature mem­branerupture (PROM). Methods: Between March 1989 and August 1990. 220 women admitted wah PROM before 35 weeks (mean 30.1) without progressive labor. active infection. or fetal distress. were randomized. Patients received oral E-Mycin 333 (N=106) or an indistinguishable placebo (N=114) every 8 hours from admission to delivery. Management included immediate hospitalization. endocervical cultures for Neisseria Gonorrhea. Chlamydia, and Group B streptococcus. Amniotic fluid analyses for gram stain. culture and pulmonary maturity were performed if poSSible. Patients were followed for maternal infection and fetal compromise. Results: Life-Table analysis and Wilcoxon Rank Sum tests identified significant prOlongation of latency from PROM to dehvery (p=O.04), admission to delivery (p=0.05) and randomization to deli very (p=O.02) with E-mycin therapy. E-mycin was associated With a lower delIvery rate during the first 7 days (see Table). This effcct was primarily seen ill those destined to develop chorioamniomtis (p=0.OO3). Of patients subsequemly de­velopmg infection. 68% ofE-Mycin patients were undelivered after 48 hours of therapy (vs. 36%-placebo, p=0.006). No reduction in the illcidences of chorioamniorutis, neonatal sepsis or other perinatal complIcations were IdentI­fied. No Increase in adverse neonatal outcomes was Identified with E-Mycm.

Days from randomization 1 2 3 4 5 6 7

. I Placebo 72 50 35 26 21 19 18 % Undehvered E-Mvcin 83 65 54 46 36 29 27

P-Value = .052 .017 .003 .007 .007 .058 .056

Conclusions: Oral E-mycin is effective in prolonging the latency to delivery following preterm PROM. This effect is seen during the crucial first 48 hours. Chorioamnionitis is delayed but not prevented with this therapy

14 NEUTROPHIL ACTIVATING PEPTIDE·l/INTERLEUKIN-8 AND INTRAAMNIOTIC INFECTION. Robello ~omero, M.D .. Mosh9c Mazor

L M.D., Cecili~ Avila, M.D., Muoslav Ceska,

Ph.D., Ivan indley, Ph,D. Department of Ob/Gyn, Yale University School of Medicine, New Haven, cr and Sandoz Research Institute Vienna, Austria.

The neutrophil is the cell most frequently recruited to the amniotic cavity and fetal membranes during the course of intrauterine infections. The stimulus responsi51e for neutrophil accumulation at these sites has not been determined. Neutrophil activating factor/interleukin-S (NAP-lIlL-S) is a novel (;)'tokine, produced by a wide variety or cells and capable of inducing neutrophil chemotaxis and activation (degranulation, respiratory burst, etc.). The purpose of this study was to determine whether NAP-l-/lI:'-S is present in the amniotIc fluid (AP) of women with intraamniotic infection. Materials and Methods: Amniotic fluid was retrieved by transabdominal amniocentesis from 71 women classified into tlie following groups: midtrimester (n = 14), term without labor (n = 15) and preterm labor with intact membranes (n = 42). Fluid was cultured for aerobic and anaerobic bacteri~ Mycoplasma hominis and Ureaplasma urealyticum. NAP-lIlL-1S PWas measured with a senSitive and specific immunoassay validated for human AP (sensitivity = 1 ngtm!). Results: Nor­mal AF from women in the second and thud trimesters did not contain detectable NAP-lIlL-S «2 ngfml). Among women with preterm labor, those with intraamniotic infectIOns had sig­nificantly higher AP concentrations of NAP-1IlL-S than those with negative AF cultures (median = 70 nldm!, range = 1.5 ngiml to 203.6 nglml vs. median = 0 ngimf, range = 0 to 62 ngiml; p < 0.00lJ, There was a correlation between the absolute neutrophil count in AF and the level ofNAP-1IlL-S (Spearman r = 0.6, P < 0.(01). All patients with histologic chonoamnionitis had detectable AF NAP-1IlL-S. Conclusions: 1) NAP-1IlL-8 is not a physiologic comp'onent of AP in the second and third trimesters. 2) Microliial invasion of the amniotic cavity and placental chonoamnionitis are associated with dramatic levels of NAP-1IlL-8. 3) NAP-1IlL-8 may serve as a diagnostic test for the detection of intraamniotic infection.