274 SPO Abstracts

ONCOFEIAL FIBRONECTIN IN PATIENTS AT INCREASED RISK FOR PRETERM DELIVERY Nageotte MP, Hollenbach KA, Vanderwahl BA, Hutch KM Long Beach Memorial IJomens HospitaL University of California, Irvine

In an effort to evaluate oncofetal fibronectin (fFN) as screening test for premature birth, asymptomatic hig~ risk patients were identified and followed prospectively. Risk factors included mUltiple gestat lon, prey; aus preterm labor I prey; aus preterm birth, congenital uterine· anomaly and incompetent cervix with cerclage. Beginning at 20 weeks of gestation and repeated weeky until delivery or 37 weeks. a home visiting nurse obtained specimens of cervicQvaginal fluid from the posterior fornix. A total of 1144 specimens were obtained (mean 11.2/patient). Specimens were batched and an ELISA immunoassay for fFN was performed following delivery. A specimen was defined as positive when greater than 50 ng fFN/ml was present. S i'xty· four pat i ents del i vered at or beyond 37 weeks of gestation whiLe 38 patients delivered before 37 completed weeks. However, 6 of these preterm deliveries were induced with a resuLtant spontaneous preterm birth rate of 33.3% (32/96;. By 34 weeks of gestation 16 patients had delivered, only 1 of whom was induced (14.9%, 15/101). As a marker for delivery prior to 37 weeks, fFN had a sensitivity of 90.6%, a specificity of 44.3%, a positive predictive vaLue of 42.6% and a negative predictive value of 91.2% (OR·6.2; 95% CI 1.6·22.4; p 0.005; RR·4.0; 95% CI 1.5-9.5). For delivery prior to 34 week.s, sensitivity was 93.8%, specificity 58.8%, positive predictive value 30.0% and negative predictive vaLue 98.0% (OR 21.4; 95% CI 2.7-114.4; P = 0.0003; RR·15.3; 95% CI 3.4-68.2).

Conclusion: mark.er for pat i ents.

Oncofetal fibronectin is an excellent preterm deL ivery in asymptomatic high risk

2 NATURAl. INTERlEUKlK-l RECEPTOR ANTAGONIST BlOCKS INTERI..EUKlK-l.JNDUCED PROSTAGLANDIN PRODUCTION· BY HUMAN INTlWJTERINe TISSUES: TIlE BASIS FOR A NOIIEl APPROACH TO TIlE TREATMENT OF PRETERM LABOR IN TIlE SETTING OF INFECTION. R.Romero, W.Sepulveda: M.Mazor, C.Dinarello, M.Mitchell, Depts. of Ob-Gyn, Yale Univ. Sch. of Med., New Haven, CT; Wayne State Univ., Detroit, MI; The Unlv. of Utah, Salt Lake City, UT and Dept. of Geographic Med., Tufts Univ., Boston, MA

interleukin·l (IL-l) has been implicated in the mechanisms responsible for preterm labor (PTL) in the setting of infection. Recently; a natural IL-l receptor antagonist protoin (IRAP) has been identified. This new member of the IL-l gene family seems to have evolved to regulate the biological effects of IL·la and IL·1B (Proc Natl Acad Sci 1991;88:5232). Inhibition of IL-l-induced prostaglandin (PG) production by intrauterine tissues may have potential value in the treatment of PTL associated with infection. The purpose of these studies was 1) to determine whether IRAP is present in the amniotic fluid (AF) of women with term labor (TL) and PTL (with and without infection) and 2) to study the effects of IRAP on IL·l·induced PG biosynthesis by human amnion and chorion. Materials and Methods: AF was obtained from women with TL and PTL (n = 98). Auid was cultured for aerobic and anaerobic bacteria and Mycoplasmas. IL·la, IL·1B and IRAP AF concentrations were measured by immunoassays previously validated for human AF. The effect of IRAP on IL-l· induced PG production by amnion and chorion was studied using primary cultures. Cells were incubated with IRAP and IL·1B for 16 hrs. PGE2 released into tlie media was assayed by immunoassay. Results: 1) IRAP was present in all AF samples. 2) AF contains the highest IRAP concentrations detected in any biological fluid to date. 3) AF IRAP concentrations were not Increased in women with preterm labor and intraamniotic infection despite dramatically elevated concentrations of IL-la and IL·1B in the same fluid (PTL with negative AF cuUure: median =22 ng/ml, range = 1.6-70 vs. PTL with positive AF culture: median =38 ng/ml, range =6-70; p >0.05). 4) IRAP blocked IL-1B-induced PGE2 production by amnion and chorion in a dose-dependent manner. 5) IRAP, by itself, did not stimulate PGE2 release by amnion and chorion when used in concentrations ranging from 0.1 mg/mlto l000ng/ml. Conclusion: 1) IRAPis a physiologiC component of AF; 2) The release of IL·la and IL-IB into the AFin women with premature labor is not associated with changes in IRAP bioavailability in AF; 3) IRAP blocks IL·l·induced PG production by amnion and chorion; 4) Anti-cytokine agents may be of value in the treatment of PTL.

January 1992 Am J Obstet Gynecol

3 KETOROLAC BLOCKS RITODRINE·STlMULATED PRODUcrION OF PGF:za IN PREGNANT SHEEP. Phillip N. Rauk, Steven A. Laifer, University of Pittsburgh School of Medicine, Magee·Womens Hospital, Pittsburgh, PA

We have previously demonstrated that ritodrine infusion to pregnant sheep increases uteroplacental production of prostaglandin (PG)F:za. We have speculated that the increase in uterotonic PGF:za may contribute to the tachyphylaxis that occurs with ritodrine. We performed the following study to determine if infusion of the prostaglandin synthesis inhibitor, ketorolac, would block ritodrine-induced production of PGF:za, when the 2 agents are administered in combination to pregnant sheep. In 5 pregnant sheep (gestational ages 110-120/147), we placed catheters in the aorta, vena cava and in the uterine vein from the pregnant uterine horn. In random order on different days we infused saline, ritodrine (4 lAg/kg/min), ketorolac (1.2 lAg/kg/min), or a combination of ritodrine and ketorolac, into the venous catheter at a rate of 10 cc/min over a 4h period. Uterine venous and maternal arterial blood was sampled 60 min before and immediately before the infusion, and then at 60, 120, 180, 240 min during the infusion and assayed for PGF:za. Ritodrine significantly increased uterine venous PGF:za during the 4h infusion (mean increase at 4h 1.16 ng/ml, p<O.05). When ritodrine and ketorolac were administered in combination, there was no change in uterine venous PGF:za throughout the 4h infusion. Ketorolac completely blocked the ritodrine·induced production of PGF4a. This is the first study to show that a prostaglandin synthesis inhibitor can effectively block uteroplacental prostaglandin production stimulated by ritodrine in vivo. Based on these results, there appears to be definite physiologic advantage for tocolytic regimens that include a combination of ritodrine and a prostaglandin synthesis inhibitor.

4 CBSARBAN SBCTION POR PBTAL INDICATIONS AT THB LIMITS OP PBTAL VIABILITY (1986 TO 1991). ~ ~, Sam MOYD~ St. Louis Univeraity, St. .ary'a aealth Center, Depart •• nt of OB-GYN.

We repeated a similar aurvey of the SPO ••• ber.hip to •••••• chang •• in •• nage •• nt regarding c •• ar.~n delivery at the limita of viability. Data on 560. 1991 meabera, were compared to '0'. 1986 members. 85% of re.pondenta are attending. in MFH. 30% are strongly influenced by legal CODcerns. 70% rely more on GA than HFW for accuracy in deciding for CIS. 60% are Univ. based; 2'% Univ. affil.; and 16% non-Univ. The lower limit for initiation of cesarean delivery for fetal indicatione are aummari.ed in the table.

% RespoDse (cumulative %) Loweat GA to CIS-fetal diatress CIS-breech initiate mCUlt

22(weeka) 23 24 25 26 27 28

>28

llll llll ll!.§. illl o 0.5 0 0.2

0.' 3.'(') 0 2.7(3) 18(18) 33(37) U 2'(27) 25(43) 35(72) 22(36) 29(56) 47(90) 27(99) 46(82) 27(83) 8(98) 1(100) 7(89) 4(87)

2(100) 0.4 4(93) 2(89) 2(95) 1(90)

Do not usually CIS for breech 5% 10%

Although individualization of care prevails, the cu.ulative percentage of .embera willing to perform CIS at 24 weeks gestation for fetal indicationa haa doubled during the l.at five years.