Preterm birth and mid-trimester cervical length: Cervical competence as a continuum

171 PRETERM BIRTH AND MID-TRIMESTER CERVICAL LENGTH: CERVICAL COMPETENCEAS A CONTINUUM JOHN OWEN1, 1for the Vaginal Ultrasound Cerclage TrialConsortium, Maternal-Fetal Medicine & Biostatistics, Birmingham, Alabama

OBJECTIVE: Prior reports suggest that cervical competence is best concep-tualized as a biologic continuum. To test this hypothesis, we studied therelationship between past obstetric performance and mid-trimester cervicallength (CL).

STUDY DESIGN: Consenting women who had at least one prior spontaneouspreterm birth (SPTB) !34 weeks were recruited at 12 US centers for arandomized intervention trial. Biweekly vaginal scans were scheduled, begin-ning at 16-19 weeks’ gestation, and continued until the earlier of 22 6/7 weeksor a CL!25 mm (the 10th percentile in a similar population). Fundalpressure-induced and spontaneous dynamic cervical shortening was assessedand used to determine the shortest observed CL at each scan. ANOVA wasused to model the relationship between shortest CL observed on serial scansand the gestational age (GA) grouping of each patient́s most recent birth(GArecent) and also her earliest prior SPTB (GAearly).

RESULTS: The study population comprised 359 women whose GArecentmedian (range) was 28.5 (17, 42) weeks and their GAearly was 26 (17, 33)weeks. Their median shortest CL was 29 (0, 60) mm. In 241 (67%) cases, thepatient́s GArecent was also her GAearly. The relationship between GArecentand CL was significant (p!.0001): women (N=53) whose GArecent was !20weeks had a mean (SD) CL of 24.3 (9.4) mm, versus 26.7 (9.5) mm if GArecentwas 21-26 weeks (N=92), 29.3 (9.9) mm if 27-32 weeks (N=103), 29.9 (11)mm if 33-35 weeks (N=27), and 33 (9.1) mm if O35 weeks (N=84). Therelationship between GAearly and CL was also significant (p=.04) but did notfollow the same progressive linear trend for CL across all GA groups as didGArecent. Nevertheless, women whose GAearly was !20 weeks still had theshortest mid-trimester CL: 27.2 (11) mm of all the GA groups.

CONCLUSION: There is a highly significant relationship between the GA ofthe most recent birth and mid-trimester CL in the next pregnancy. These datasupport CL as a reasonable surrogate for cervical competence and that cervicalcompetence functions along a biologic continuum of obstetric performance.

172 TIMING OF MID-TRIMESTER CERVICAL LENGTH (CL) SHORTENING IN HIGH-RISKWOMEN JOHN OWEN1, 1for the Vaginal Ultrasound Cerclage Trial Consortium,Maternal-Fetal Medicine & Biostatisitics, Birmingham, Alabama

OBJECTIVE: Prior spontaneous preterm birth (SPTB) and CL shorteningare well-described risk factors for recurrent SPTB, but the mechanisms thatlead to cervical change and SPTB are poorly understood.

STUDY DESIGN: Consenting high-risk women, defined as at least 1 priorSPTB!34 wks, were recruited at 12 US centers and underwent q2 wk vaginalsonographic evaluations beginning at 16-19 wks and continued until either 22 6/7 wks or a CL!25 mm. Fundal pressure-induced and spontaneous CLshortening were used to define the (shortest) CL at each scan. Survival curveswere used to compare the gestational age (GA) at CL shortening !25 mm inwomenwhose earliest prior SPTBwas!27weeks versus 27-33weeks’ gestation.

RESULTS: 998 scans were performed on 367 women, 36% of whomdeveloped a CL!25 mm. Of the 193 in the !27 wk group, 44% experiencedCL shortening versus 28% in the 27-33 wk group (p=.002). The Kaplan-Meiersurvival curves below depict the natural history of CL shortening anddemonstrate a significant difference (p=.001) in GA at CL shortening betweenthe 2 groups. A Cox proportional-hazard model confirmed a hazard ratio of1.8 (p=.001) for cervical shortening in the !27 wk group.

CONCLUSION: Women with a prior SPTB !34 weeks have an appreciablerate of mid-trimester CL shortening in a subsequent pregnancy. However, the

observation that nearly 2/3 of them do not shorten their cervix by 22 6/7 weeksindicates significant biologic variation. Women with a prior SPTB !27 weeksshorten their cervix significantly more often and at a significantly earliergestational age than women whose prior SPTB occurred at 27-33 weeks.

173 EFFECT OF PROGESTERONE ON NITRIC OXIDE PRODUCTION BY BACTERIA-STIMULATED ENDOCERVICAL AND VAGINAL EPITHELIAL CELLS YINKA OYELESE(F)1, MORGAN PELTIER1, JOHN SMULIAN1, 1UMDNJ-Robert Wood JohnsonMedical School/Robert Wood Johnson University Hospital, Obstetrics,Gynecology and Reproductive Sciences, New Brunswick, New Jersey

OBJECTIVE: Progesterone (P4) administration has been proposed as a viabletreatment to prevent recurrent preterm birth but the mechanism(s) by whichthis hormone functions is unclear. One possibility is that this hormone inhibitscervical ripening. Nitric oxide levels in the cervix are increased at term and ap-plication of Nitric oxide donors to the cervix cause cervical ripening. We hy-pothesized that bacterial inflammation causes genital tract cells to producenitric oxide and that P4 inhibits this process.

STUDY DESIGN: Commercially available ENDE6E7 and VK2E6E7 celllines (human endocervical and vaginal epithelial cells transformed with humanpapilloma virus 16) were cultivated in serum-free medium. RAW 267 (murinemacrophages) were used as a positive control for evaluating the effects of P4

on nitric oxide production. Cells were cultured on 96-well plates and treatedwith P4 overnight and then stimulated with various amounts of heat-killedEscherichia coli. Nitric oxide production was estimated by measuring theNitrite concentrations in the conditioned medium colorimetrically using theGriess reagent.

RESULTS: Production of Nitric oxide by endocervical cells was observedonly in cultures stimulated with 108 CFU/ml bacteria but not at lower amountsof bacteria. Progesterone did not change Nitric oxide production at any of theconcentrations tested (0, 10, 100, 1000, and 10,000 ng/ml). Nitric oxide pro-duction was not detected in the conditioned medium from vaginal epithelialcells cultured with or without bacteria at concentrations up to 108 CFU/ml.As expected, P4 at a high concentration (10 mg/ml) inhibited Nitric oxideproduction by murine macrophages stimulated with 106, 107 and 108 CFU/mlheat-killed E. coli.

CONCLUSION: Heat-killed E. coli at higher concentrations stimulates Nitricoxide production by endocervical cells, but not vaginal epithelial cells. Thisstimulation was not inhibited by high doses of P4. Therefore, P4 does notappear to prevent preterm birth by directly inhibiting bacteria-induced Nitricoxide production by endocervical cells.

174 17-HYDROXYPROGESTERONE CAPROATE REVERSES THROMBOXANE INDUCEDVASOCONSTRICTION OF THE FETOPLACENTAL ARTERIES DAMIAN PAONESSA (F)1,ANDREA SHIELDS1, JEREMY CELVER2, BOBBY HOWARD1, JENNIFER GOTKIN1,SHAD DEERING1, NATHAN HOELDTKE3, PETER NAPOLITANO1, 1Madigan ArmyMedical Center, OB GYN, Tacoma, Washington, 2Madigan Army MedicalCenter, Clinical Investigation, Tacoma, Washington, 3Tripler Army MedicalCenter, Honolulu, Hawaii

OBJECTIVE: Progesterone therapy currently is being utilized to attempt toprevent recurrence of preterm labor. Multiple studies have suggested proges-terone inhibits the inflammatory cascade. We undertook this study todetermine if 17-Hydroxyprogesterone Caproate (17P) has an effect on thevasoconstrictive response of fetoplacental arteries to thromboxane.

STUDY DESIGN: Two cotyledons were obtained from each of 4 placentas. Achorionic artery and vein pair were cannulated in each cotyledon. Hankssolution was infused into the chorionic artery for thirty minutes to establishbaseline perfusion pressure. Thromboxane (1 nmol/L) was then continuouslyinfused to the treatment cotyledon. Serial perfusion pressures were recordedevery five minutes until vasoconstriction was detected. A bolus dose of 17P(200 nmol/L) was then administered to both cotyledons. Serial perfusionpressures were recorded over 30 minutes. A vasoconstricting dose of angio-tensin II (100 nmol/L) was then administered to assess vasocontractilepotential in the cotyledons. Response pressures were recorded and compared.Statistical analysis of pressure change within each arm was performed using apaired T test. Pressure differences between control and treatment wereanalyzed using a simple T test. A P value of !0.05 was considered significant.

RESULTS: Infusion of thromboxane significantly increased the perfusionpressure in comparison to control. (60.1G13 mmHg vs. 29.5G 8.8 mmHg) P=0.008. 17P administration significantly lowered the perfusion pressures of thethromboxane infused vessels in comparison to pre administration. (27.3G7.1mmHgvs. 60.1G13mmHg) P=0.03. 17P did not significantly alter the pressureof the control cotyledon. (30.6G8.3mmHgvs. 30.1G7.8mmHg) P=0.48Therewas no difference in the vasoactive response to angiotensin II between throm-boxane exposed and non-exposed cotyledons. P = 0.63.

CONCLUSION: 17P reverses thromboxane induced vasoconstriction infetoplacental arteries.

SMFM Abstracts S59