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360 SPO Abstracts

GLYBURIDE DOES NOT CROSS THE DIABETIC PLACENTA IN SIGNIFICANT AMOUNTS. Elliott, B.D., Bynum, Ox., Langer, O. Dept. Ob/Gyn, UTHSC, San Antonio, TX. OBJECTIVE: This study was undertaken to characterize the maternal to fetal transport of the oral hypoglycemic agent glyburide in diabetic human placentas, and to determine if the transport rate was significantly different from that occurring in the normal placenta. STUDY DESIGN: The recirculating single cotyledon placenta model was used to test the maternal-to-fetal transport of H3-glyburide in term placentas obtained at delivery from diabetic pregnancies. Normal term placentas served as controls, and antipyrine, a freely diffusible substance, was added to the maternal perfusate as an internal standard in all experiments. The placentas were perfused for a period of three hours with an original maternal glyburide level of 1 mcg/ml; a value five times the average peak serum level following a 5 mg oral dose. Maternal and fetal glyburide levels were measured in the serial samples by liquid scintillation spectrometry, and differences in transport between diabetics and controls were compared with the Mann-Whitney U test. RESULTS: No significant difference existed in the transport rates of glyburide between diabetics and controls.

% Transport @ 3 hr Transport Rate

(meg/hr/gm placenta) Fetal glyburide level

@ 3 hr (mcg/ml) Cotyledon Size (gm) Gestational Age (wks)

DIABETIC CONTROL 3.4 ± 1.9

0.31 ±0.22

0.09±0.04

12.7 ±2.6 37.4 ±0.6

Mean ± SO

3.6 ±1.6 0.29±0.13

0.1O±0.04

13.1 ±6.8 37.4 ±0.9

CONCLUSIONS: The oral hypoglycemic agent glyburide does not cross the diabetic placenta in significant amounts, and its transfer rate in diabetics is similar to that occurring in normal controls.

MATERNAL HYPERGLYCEMIA DOES NOT ALTER IN-VITRO PLACENTAL TRANSFER OF THE ORAL HYPOGLYCEMIC AGENT GLYBURIDE. Elliott, B.D., Bynum, Ox., Langer, O. Dept. Ob/Gyn, UTHSC, San Antonio, TX. OBJECTIVE: This study is undertaken to determine whether abnormal maternal glucose levels increase human placental transfer of glyburide, a drug which has been demonstrated not to cross the human placenta in significant amounts within the euglycemic environment. STUDY DESIGN: The non-recirculating human placenta model is used to test the clearance of H3-glyburide in term placentas obtained immediately following delivery. In each placenta, the glucose concentration in the maternal perfusate is increased in a stepped fashion at 30 minute intervals from 60 to 300 mg/dl, and infused in a continuous open fashion. Fetal perfusate glucose concentration is maintained at 100 mg/dl by continuous open infusion, and fetal and maternal perfusion flow rates are 2 mllmin and 10 mllmin, respectively. Maternal glyburide concentration is maintained at 1 mcg/ml. Perfusate samples from both the maternal and fetal placental efferant cannulas are taken at 15 minute intervals, and glyburide clearance calculated using maternal and fetal glyburide concentrations determined by liquid scintillation spectrometry. Standard Krebs-Ringers buffer with 2 gm/dl human albumin served as perfusion fluids, and the freely aiffusible marker, antipyrine is added to the maternal perfusate as an internal control. RESULTS: No significant difference exists among the placental glyburide clearances by maternal glucose level. (ANOVA, p=ns)

Maternal Glucose Level 60mg/dl

120mg/dl 180mg/dl 240mg/dl 300mg/dl

Glyburide Clearance (cc/min) 0.011 ± 0.003 0.022 ± 0.Q15 0.007 ± 0.001 0.012 ± 0.006 0.016 ± 0.009

Mean ± SEM

CONCLUSIONS: Maternal glucose level does not effect the human placental transfer of the oral hypoglycemic agent glyburide.

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January 1993 Am J Obstet Gynecol

TVlIl-TO-TVl. TBABSrUSIO. SYllDROHEI A SUBSET or THE TVl. OLIClOII'fI)IWIIIIOS/POLlB!DIWIIIIOS SEQUEBCE (TOPS). J. Bruner. R. Rosemond. Dept. Ob/Gyn. Vsnderbilt University Medicsl Center, Nashville, TN. OBJECTIVEI Msess the adequacy of currently accepted ultrasound and neonatal criteria for the diagnosis of twin-to-twin transfusion (TTT) syndrome. STUDY DESIOJII Between April, 1991 and February, 1992, nine consecutive women with twin gestation were evaluated at Vanderbilt for ultrasound findings of marked growth discordance, coexistent oligo/poly and monochorionic placenta in the second trimester. The mean gestational age at diagnosis was 19 5/7 ± 5 0/7 wko (range 13 3/7-27 6/7 wka), and mean growth discordance was 34 ± 9% (range 21-47%). Seven women underwent attempted sequential amniocentesis/ cordocentesis at 23 6/7 ± 2 4/7 wka (range 20 3/7-27 6/7 wka) to obtain amniotic fluid from each fetus for viral culture, and cord blood for CBC, reticulocyte count, anti-I, type and Coombs', karyotype, viral Ig titers, and albumi~ Type 0-negative, leucocyte-poor, washed adult &BCs were transfused into the small, oligohydramnic twin during cordocentesis, immediately following which blood aspirated from the polyhydramnic twin was tested with the Kleihauer-Betke stai~ IlESULTSI The combined procedure was successful in six (86%) of the cases attempted. True TTT was confirmed in only four cases, or 57% of those initially identified by ultrasound criteria. Hgb difference> 5 sldl was present in only one of the four cases, and in this case the recipient was anemic. Umbilical artery Doppler SID ratios demonstrated no pattern. but in five cases absent or reversed end diastolic velocities correctly predicted donor IUFD. COBCLUSIOBSI Currently accepted ultrasound and/or neonatal criteria are insufficient for the diagnosis of true TTT. Ultrasound findings of marked growth discordance, coexistent oligo/poly, and monochorionic placenta identify the twin oligohydramnios/polyhydramnios sequence (TOPS).

PLACENTAL PATHOLOGY IN DISCORDANT TWINS. A Mallozzi D LevesqueX, AM Vintzileos, JFX Egan, V Tsapanosx, CM Salafiax, Univ. of Cl' HeaHh Center, Farmington, CT and Danbury Hosp~al, Danbury, CT. OBJECTIVE: The aim of this study was to evaluate placental pathology in relation to birthweight (BW) discordance in dichorionic (DC) and monochorionic (MC) twins. STUDY DESIGN: The maternal charts and placental pathology of 147 structurally normal twin pairs with cords labelled at delivery were revieWed. The placental mass belonging to each twin was determined by measuring tho length, width and thickness in each of the 2 placental disks. Placentai weight, chorionic~y, infarction, abruption, decidual vascular pathology, villous fibrosis and hypovascular~y, chronic villitis, and intraplacental thrombi were also assessed. BW was discordant if a20%. The data were analyzed using chi square and ANOVA following log transformation of skewed discordancy values. RESULTS: Of the 147 twin pairs, 99 were DC and 48 MC. Placental weights were known for 89 DC and 35 MC twins. Of the smaller DC twins 44189 (49.4%) belonged to the larger placental mass, 32189 (3S.9%) belonged to the smaller placenta and 13189 (14.6%) had equal share of the placental mass with their larger sibling (p<O.OS). In 42199 (42.4%) the smaller DC twin had more placental lesions than the larger twin, in 38/99 (38.4%) the same number of lesions were present in both placentas and in 19199 (19.2%) the larger twin had more placental lesions. There was linear correlation between percent discordance and number of placenlallesions in the smaller twin. In DC twins 18 of the 99 (18.1%) were discordant. In 14/18 (77.8%) the smaller twin had more placental lesions than the larger twin, in 3118 (16.7%) the number of lesions were the same in both, and in 1/18 (S.6%) the larger twin had 1 more lesion than the smaller twin (p<O.OS). In MC twins, regardless of BW discordance, no differences in placental pathology were observed. CONCLUSIONS: In DC twins sign~icant BW discordance was not attributable to differences in placental mass but to a greater number of placental lesions in the smaller twin as compared to the larger twin (I><O.OS). This did not hold true for MC twins.