Terbutaline and neurotoxicity in the rat model

SMFM Abstracts S63 187 CAN FETAL FIBRONECTIN BE RELIABLY SAMPLED WITHOUT SPECULUM EXAMINATION? IRENE STAFFORD1, GARY DILDY1, 1Louisiana State University Medical Center at New Orleans, Obstetrics & Gynecology, New Orleans, Louisiana OBJECTIVE: The fetal fibronectin (fFN) assay is commonly used for triaging patients at risk for preterm labor. Current recommendations include use of a vaginal speculum for specimen collection. A nonspeculum specimen collection technique would be of greater convenience for the provider and less discomfort for the patient. We performed this study to determine if fFN concentrations obtained via speculum correlate with those obtained by blind swabbing. STUDY DESIGN: Pregnant women O22 weeks of gestation who presented to the obstetrical emergency room were offered enrollment in the study. fFN was collected from each patient by blind swabbing the posterior fornix and by speculum placement. Specimens were stored at ÿ80C and fFN levels were determined by a quantitative ELISA assay. RESULTS: Thirty-five women were enrolled in the study. Four were excluded secondary to insufficient sampling or blood contamination. 30 of the 31 samples were concordant for fFN test results (96.8%). Polynomial regression analysis (y = ÿ0.0012x2 C 1.3309x ÿ 5.6643) yielded an R2 of 0.90. For the one discordant case, the specimen obtained by blind sampling was negative, while the speculum obtained sample was positive. However, the fFN negative test result was very near the cut-off of 50 ng/mL. Level of agreement as defined by the intraclass kappa was 0.87 (95% CI = 0.62-0.99). CONCLUSION: Using the standard fFN cut-off of 50 ng/mL, we found excellent agreement between cervico-vaginal fFN concentrations collected with and without speculum. These data suggest that speculum placement may not be necessary for collection of fFN test specimens.

189 MULTIPAROUS PATIENTS WHO ACQUIRE CERVICAL INCOMPETENCE: WHAT ARE THE RISK FACTORS? NISHA VYAS (F)1, JOY VINK1, ALESSANDRO GHIDINI2, JOHN PEZZULLO3, VICTORIA KORKER2, SARAH POGGI2, 1Georgetown University Hospital, Obstetrics and Gynecology, Washington, District of Columbia, 2 INOVA Alexandria Hospital, Perinatal Diagnostic Center, Alexandria, Virginia, 3Georgetown University, Pharmacology and Biostatistics, Washington, District of Columbia OBJECTIVE: Cervical incompetence (CI) can be particularly unexpected in a woman with prior term delivery. The objective of this study was to compare multiparous women with CI to those without to idenfity risk factors for the acquisition of CI after a term delivery. STUDY DESIGN: Demographic and obstetric characteristics were gathered prospectively on patients with at least one prior term delivery presenting for MFM evaluation for CI, which was defined as a midtrimester pregnancy loss with painless cervical dilation or presentation in the midtrimester with cervical length !1cm or cervical dilatation O1cm; concurrently, similar information was gathered for uncomplicated multiparous patients presenting sequentially at term for delivery. Multiparas with acquired CI (cases, N=40) were compared to multiparas with no history of CI experiencing repeat term birth (controls, N=40). RESULTS: Multiparas with CI were similar to those without in terms of maternal age, parity and BMI but differed in ethnicity (40% vs 65% African American, P=0.04). More patients with acquired CI had prior D&Cs compared with controls (68% vs 25%, P!0.001), with significance attributed to D&Cs performed after the last term birth (53% vs 18%, P!.001) but not before (P=0.4). Cases also had more prior second stage arrests than the control group (23% vs 0%, P!0.001) and a longer interdelivery interval (68G50 vs 36G25 months (P!0.001). No significant difference was noted in the number of cryo or LEEP procedures, multiple gestation, prior precipitous term or or spontaneous preterm deliveries. Logistic regression analysis identified prior D&C and interdelivery interval as independent predictors of CI. CONCLUSION: Compared to multiparas experiencing a repeat term birth, multiparas acquiring CI are more likely to have had cervical stress via prior second stage arrest or D&C subsequent to their prior term birth.

188 TERBUTALINE AND NEUROTOXICITY IN THE RAT MODEL MICHELLE TAYLOR (F)1, WILLIAM BENNETT1, JOSEPHINE WYATT-ASHMEAD2, KEDRA WALLACE1, JOHN MORRISON3, 1University of Mississippi Medical Center, Obstetrics and Gynecology, Jackson, Mississippi, 2University of Mississippi Medical Center, Pathology, Jackson, California, 3University of Mississippi Medical Center, Obstetrics & Gynecology, Jackson, Mississippi OBJECTIVE: Due to its tocolytic effects, terbutaline has been utilized as a treatment for preterm labor. Reports from one center have suggested that terbutaline, in formulations not used in humans, exhibits toxicity in the developing rat brain. We evaluated the pathologic effects of various doses of terbutaline in the developing rat brain. STUDY DESIGNTEN: litters (N = 80) of Sprague-Dawley rat pups were randomly assigned to one of five treatment groups: 1) saline, 2) low-dose (0.5 mg/kg/day) Sigma terbutaline, 3) high-dose (10 mg/kg/day) Sigma terbutaline, 4) low-dose PharMerica terbutaline, and 5) high-dose PharMerica terbutaline. On postnatal days (PND) 11-14, single subcutaneous injections were administered. On PND 15, half the pups were sacrificed and their brains harvested for detailed pathologic examination. RESULTS: No significant differences were observed between the terbutaline groups and controls. CONCLUSION: Previous reports have implicated terbutaline as a neurotoxic agent in the rat brain. Our pathologic findings do not support this assertion.

190 NEWBORN ANTHROPOMETRIC MEASUREMENTS IN TWIN PREGNANCIES EXPOSED TO MULTIPLE COURSES OF ANTENATAL STEROIDS THADDEUS WATERS1, MATTHEW HOFFMAN2, SEAN DALY3, JULIE SLOAN3, MARGARET SHERIDANPEREIRA3, 1Drexel University, Obstetrics and Gynecology, Philadelphia, Pennsylvania, 2Christiana Hospital, Newark, Delaware, 3Coombe Women’s Hospital, Dublin, Ireland OBJECTIVE: Antenatal steroids have been associated with decreased birth weights in singleton pregnancies. We sought to examine the effect of single and multiple courses of antenatal steroids on newborn weight, head circumference and birth length in twin pregnancies. STUDY DESIGN: We performed a retrospective cohort study at a tertiary care hospital. Using the hospital database, we identified all twin pregnancies admitted for threatened preterm birth O24 weeks gestation between 19951999. Data abstracted included number of steroid doses, gestational age at delivery, and neonatal anthropometric measurements. A full course of steroid therapy was defined as two doses of Dexamethasone 12 mg over 48 hours. Multiple courses were defined as two or more completed courses. We compared the neonates who received one or multiple courses of steroids to unexposed controls. Multivariate analysis was performed to asses the effect of steroid exposure on birth weight, length and head circumference and to control for gestational age. RESULTS: A total of 178 neonates were evaluated (0 courses n=64, 1 course n=70, 2C courses n=44). With progressive dosing of steroids mean birth weight decreased; although this was not significant after controlling for gestational age (1 course= C58.1 gm (p value=0.28), 2Ccourse= ÿ30.0 gm (p value=0.620). Head circumference likewise decreased with progressive doses of steroids(1 course= ÿ0.1 cm (p value=0.89), 2C courses= ÿ0.7cm (p value=!.01). No other differences in fetal anthropometric measurements could be demonstrated (see table). CONCLUSION: Repetitive steroid exposure in multiple gestations is associated with decreased head circumference in our series. Larger studies are required to confirm this finding.

Treatment group

Brain weight* Corpus callosum* Purkinje cells* EGCL** (# of (g) (m) (#) cells)*

1 2 3 4 5

1.48 G 0.03 1.39 G0.04 1.41 G0.02 1.41 G0.02 1.43 G0.02

269 G 19.2 189 G 14.8 206 G 22.3 205 G 11.0 189 G 7.9

8.2 10.2 8.4 7.9 8.9

G G G G G

1.2 0.6 0.4 0.9 0.6

3.0 3.9 4.1 2.4 3.8

G G G G G

0.3 0.3 0.3 0.5 0.3

Results: * P value O 0.05, ** Cerebellar external granular cell layer.

Newborn measurements by steroid exposure BW! 10% Dose tile (OR)

BW!5% tile (OR)

Length !10% tile (OR)

0 1

1.0 0.5 (CI-0.1 to 2.1) 1.8 (CI-0.5 to 6.2)

1.0 1.0 1.7 (CI-0.7 to 4.6) 0.9 (CI-0.1 to 6.9)

1.0 0.8 (CI-0.3 to 2.6) 2C 2.0 (CI-0.7 to 6.0)

1.3 (CII-0.5 to 3.9)

Length!3rd% tile (OR)

1.4 (CI-0.2 to 10.2)