Preterm birth and mid-trimester cervical length: Cervical competence

0 downloads 0 Views 72KB Size Report
preterm birth (SPTB) !34 weeks were recruited at 12 US centers for a ... 172 TIMING OF MID-TRIMESTER CERVICAL LENGTH (CL) SHORTENING IN HIGH-RISK ... RESULTS: 998 scans were performed on 367 women, 36% of whom.
SMFM Abstracts S59 171 PRETERM BIRTH AND MID-TRIMESTER CERVICAL LENGTH: CERVICAL COMPETENCE AS A CONTINUUM JOHN OWEN1, 1for the Vaginal Ultrasound Cerclage Trial Consortium, Maternal-Fetal Medicine & Biostatistics, Birmingham, Alabama OBJECTIVE: Prior reports suggest that cervical competence is best conceptualized as a biologic continuum. To test this hypothesis, we studied the relationship between past obstetric performance and mid-trimester cervical length (CL). STUDY DESIGN: Consenting women who had at least one prior spontaneous preterm birth (SPTB) !34 weeks were recruited at 12 US centers for a randomized intervention trial. Biweekly vaginal scans were scheduled, beginning at 16-19 weeks’ gestation, and continued until the earlier of 22 6/7 weeks or a CL!25 mm (the 10th percentile in a similar population). Fundal pressure-induced and spontaneous dynamic cervical shortening was assessed and used to determine the shortest observed CL at each scan. ANOVA was used to model the relationship between shortest CL observed on serial scans and the gestational age (GA) grouping of each patient´s most recent birth (GArecent) and also her earliest prior SPTB (GAearly). RESULTS: The study population comprised 359 women whose GArecent median (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, the patient´s GArecent was also her GAearly. The relationship between GArecent and CL was significant (p!.0001): women (N=53) whose GArecent was !20 weeks had a mean (SD) CL of 24.3 (9.4) mm, versus 26.7 (9.5) mm if GArecent was 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). The relationship between GAearly and CL was also significant (p=.04) but did not follow the same progressive linear trend for CL across all GA groups as did GArecent. Nevertheless, women whose GAearly was !20 weeks still had the shortest mid-trimester CL: 27.2 (11) mm of all the GA groups. CONCLUSION: There is a highly significant relationship between the GA of the most recent birth and mid-trimester CL in the next pregnancy. These data support CL as a reasonable surrogate for cervical competence and that cervical competence functions along a biologic continuum of obstetric performance.

172 TIMING OF MID-TRIMESTER CERVICAL LENGTH (CL) SHORTENING IN HIGH-RISK WOMEN JOHN OWEN1, 1for the Vaginal Ultrasound Cerclage Trial Consortium, Maternal-Fetal Medicine & Biostatisitics, Birmingham, Alabama OBJECTIVE: Prior spontaneous preterm birth (SPTB) and CL shortening are well-described risk factors for recurrent SPTB, but the mechanisms that lead to cervical change and SPTB are poorly understood. STUDY DESIGN: Consenting high-risk women, defined as at least 1 prior SPTB!34 wks, were recruited at 12 US centers and underwent q2 wk vaginal sonographic evaluations beginning at 16-19 wks and continued until either 22 6/ 7 wks or a CL!25 mm. Fundal pressure-induced and spontaneous CL shortening were used to define the (shortest) CL at each scan. Survival curves were used to compare the gestational age (GA) at CL shortening !25 mm in women whose earliest prior SPTB was !27 weeks versus 27-33 weeks’ gestation. RESULTS: 998 scans were performed on 367 women, 36% of whom developed a CL!25 mm. Of the 193 in the !27 wk group, 44% experienced CL shortening versus 28% in the 27-33 wk group (p=.002). The Kaplan-Meier survival curves below depict the natural history of CL shortening and demonstrate a significant difference (p=.001) in GA at CL shortening between the 2 groups. A Cox proportional-hazard model confirmed a hazard ratio of 1.8 (p=.001) for cervical shortening in the !27 wk group.

CONCLUSION: Women with a prior SPTB !34 weeks have an appreciable rate 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 weeks indicates significant biologic variation. Women with a prior SPTB !27 weeks shorten their cervix significantly more often and at a significantly earlier gestational age than women whose prior SPTB occurred at 27-33 weeks.

173 EFFECT OF PROGESTERONE ON NITRIC OXIDE PRODUCTION BY BACTERIASTIMULATED ENDOCERVICAL AND VAGINAL EPITHELIAL CELLS YINKA OYELESE (F)1, MORGAN PELTIER1, JOHN SMULIAN1, 1UMDNJ-Robert Wood Johnson Medical School/Robert Wood Johnson University Hospital, Obstetrics, Gynecology and Reproductive Sciences, New Brunswick, New Jersey OBJECTIVE: Progesterone (P4) administration has been proposed as a viable treatment to prevent recurrent preterm birth but the mechanism(s) by which this hormone functions is unclear. One possibility is that this hormone inhibits cervical ripening. Nitric oxide levels in the cervix are increased at term and application of Nitric oxide donors to the cervix cause cervical ripening. We hypothesized that bacterial inflammation causes genital tract cells to produce nitric oxide and that P4 inhibits this process. STUDY DESIGN: Commercially available ENDE6E7 and VK2E6E7 cell lines (human endocervical and vaginal epithelial cells transformed with human papilloma virus 16) were cultivated in serum-free medium. RAW 267 (murine macrophages) were used as a positive control for evaluating the effects of P4 on nitric oxide production. Cells were cultured on 96-well plates and treated with P4 overnight and then stimulated with various amounts of heat-killed Escherichia coli. Nitric oxide production was estimated by measuring the Nitrite concentrations in the conditioned medium colorimetrically using the Griess reagent. RESULTS: Production of Nitric oxide by endocervical cells was observed only in cultures stimulated with 108 CFU/ml bacteria but not at lower amounts of bacteria. Progesterone did not change Nitric oxide production at any of the concentrations tested (0, 10, 100, 1000, and 10,000 ng/ml). Nitric oxide production was not detected in the conditioned medium from vaginal epithelial cells cultured with or without bacteria at concentrations up to 108 CFU/ml. As expected, P4 at a high concentration (10 mg/ml) inhibited Nitric oxide production by murine macrophages stimulated with 106, 107 and 108 CFU/ml heat-killed E. coli. CONCLUSION: Heat-killed E. coli at higher concentrations stimulates Nitric oxide production by endocervical cells, but not vaginal epithelial cells. This stimulation was not inhibited by high doses of P4. Therefore, P4 does not appear to prevent preterm birth by directly inhibiting bacteria-induced Nitric oxide production by endocervical cells.

174 17-HYDROXYPROGESTERONE CAPROATE REVERSES THROMBOXANE INDUCED VASOCONSTRICTION OF THE FETOPLACENTAL ARTERIES DAMIAN PAONESSA (F)1, ANDREA SHIELDS1, JEREMY CELVER2, BOBBY HOWARD1, JENNIFER GOTKIN1, SHAD DEERING1, NATHAN HOELDTKE3, PETER NAPOLITANO1, 1Madigan Army Medical Center, OB GYN, Tacoma, Washington, 2Madigan Army Medical Center, Clinical Investigation, Tacoma, Washington, 3Tripler Army Medical Center, Honolulu, Hawaii OBJECTIVE: Progesterone therapy currently is being utilized to attempt to prevent recurrence of preterm labor. Multiple studies have suggested progesterone inhibits the inflammatory cascade. We undertook this study to determine if 17-Hydroxyprogesterone Caproate (17P) has an effect on the vasoconstrictive response of fetoplacental arteries to thromboxane. STUDY DESIGN: Two cotyledons were obtained from each of 4 placentas. A chorionic artery and vein pair were cannulated in each cotyledon. Hanks solution was infused into the chorionic artery for thirty minutes to establish baseline perfusion pressure. Thromboxane (1 nmol/L) was then continuously infused to the treatment cotyledon. Serial perfusion pressures were recorded every five minutes until vasoconstriction was detected. A bolus dose of 17P (200 nmol/L) was then administered to both cotyledons. Serial perfusion pressures were recorded over 30 minutes. A vasoconstricting dose of angiotensin II (100 nmol/L) was then administered to assess vasocontractile potential in the cotyledons. Response pressures were recorded and compared. Statistical analysis of pressure change within each arm was performed using a paired T test. Pressure differences between control and treatment were analyzed using a simple T test. A P value of !0.05 was considered significant. RESULTS: Infusion of thromboxane significantly increased the perfusion pressure in comparison to control. (60.1G13 mmHg vs. 29.5 G 8.8 mmHg) P = 0.008. 17P administration significantly lowered the perfusion pressures of the thromboxane infused vessels in comparison to pre administration. (27.3G7.1 mmHg vs. 60.1G13 mmHg) P = 0.03. 17P did not significantly alter the pressure of the control cotyledon. (30.6G8.3 mmHg vs. 30.1G7.8 mmHg) P = 0.48 There was no difference in the vasoactive response to angiotensin II between thromboxane exposed and non-exposed cotyledons. P = 0.63. CONCLUSION: 17P reverses thromboxane induced vasoconstriction in fetoplacental arteries.