471: purkinje cell protein 4 (pcp4) repression in human myometrium during preterm labor

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delivered within 7 days of BMZ administration were secondary out- comes. All data was analyzed with the Kruskal-Wallis test. RESULTS: Three hundred and fifty six patients received BMZ for PL and 247 patients for ACD. The median interval between administra- tion of BMZ and delivery was 35 days for preterm labor and 47 days for advanced 28 days (p0.0001). Compared to ACD patients, PL pa- tients were more dilated (2 vs. 1 cm, p0.0001) and more effaced (1.5 vs. 2 cm, p0.0001) at the time of BMZ administration. There was no significant difference in the median NICU length of stay between PL and ACD patients. Only patients who presented with PL and were 3.5 cm dilated or completely effaced delivered within 7 days of BMZ administration (p0.005). For ACD patients, only those who were 0.5 cm effaced or less delivered within 7 days of BMZ administration (p0.005). CONCLUSION: The interval between BMZ administration and delivery at our institution is greater than 7 days for patients who present with PL or ACD. Improvements need to be made in order to better triage patients who present with threatened PL or ACD. 471 Purkinje cell protein 4 (PCP4) repression in human myometrium during preterm labor Clifford Mason 1 , Yafeng Dong 1 , Irina A. Buhimschi 2 , Catalin S. Buhimschi 2 , Carl P. Weiner 1 1 University of Kansas Medical Center, Ob/Gyn, Kansas City, KS, 2 Yale University, Ob/Gyn & Reprod Sci., New Haven, CT OBJECTIVE: There remain wide gaps in our mechanistic knowledge of causes for preterm birth (PTB). In a comprehensive genomic analysis of myometrium from 4 groups of women (n6/group) consisting of term not in labor (TNL), preterm not in labor (PTNL), term in labor (TL), and preterm in labor (PTL), we identified for the first time that significant repression of the gene encoding purkinje cell protein 4 (PCP4, aka PEP-19), a modulator of calcium (Ca2)/calmodulin (CAM) regulated processes, occurred only in PTL. We sought to char- acterize PCP4 expression, localization, and function in human myo- metrium. STUDY DESIGN: PCP4 mRNA and protein was quantified in human myometrium from women at term and preterm with or without labor (n6 subjects/group) using Q-rtPCR and Western blot. Double stained indirect immunofluorescence was used to determine the cell- specific localization of PCP4. Myometrial smooth muscle cells were identified with an anti-desmin antibody and fibroblasts by staining for vimentin. Myometrial interstitial cells were identified by staining for de-phosphorylated connexin 43 and the sarcoplasmic reticulum by staining for the sarco-endoplasmic reticulum Ca2-ATPase pump (SERCA). RESULTS: PCP4 mRNA and protein were significantly decreased in the myometrium from PTL compared to TL, TNL, and PTNL, confirm- ing our microarray findings. PCP4 was found only at the periphery of smooth muscle bundles and localized primarily to the sarcoplasmic reticulum. CONCLUSION: PCP4 is uniquely altered in association with spontane- ous PTL. Its expression is predominantly in the sarcoplasmic reticu- lum of myometrial smooth muscle cells suggesting PCP4 may regulate myometrial intracellular Ca2 levels. We hypothesize a decrease in PCP4 either before or during PTL leads to hyperactivation of Ca2- CAM dependent enzymes. These studies promise new insights into the role of PCP4 in the regulation of myometrial contraction and may lead to the design of new approaches for controlling myometrial ac- tivity during spontaneous preterm labor. 472 Progestogen in twin pregnancies: an individual participant data meta-analysis of randomized trials E. Schuit 1 , Sarah Stock 2 , Dwight Rouse 3 , A.C. Lim 4 , Line Rode 5 , Jane Norman 6 , Anwar Nassar 7 , Vicente Serra 8 , C. Andrew Combs 9 , Patrick Rozenberg 10 , Elcin Cetingoz 11 , Christian Briery 12 , Elizabeth Thom 13 , Steve Caritis 14 , Katharina Klein 5 , Ann Tabor 5 , Johnny Awwad 7 , Ihab Usta 7 , Alfredo Perales 8 , Juan Meseguer 8 , Kimberly Maurel 9 , Thomas Garite 9 , Cetin Cam 11 , Ates Karateke 11 , John Morrison 12 , Everett Magann 12 , Rolf H.H. Groenwold 1 , Karel Moons 1 , Anneke Kwee 4 , Ben Willem Mol 4 1 University Medical Center Utrecht, Julius Center for Health Sciences and Primary Care, Utrecht, Netherlands, 2 University of Edinburgh MRC Centre for Reproductive Health, Obstetrics and Gynaecology, Edinburgh, United Kingdom, 3 NICHD MFMU Network twins trial, Providence, 4 Dutch Consortium AMPHIA trial, Netherlands, 5 Predict Group trial, Denmark, 6 Queen’s Medical Research Institute, University of Edinburgh MRC Centre for Reproductive Health, Edinburgh, United Kingdom, 7 Lebanese progestogen trial, Lebanon, 8 Spanish progestogen trial, Spain, 9 Obstetrix Medical Group twins trial, 10 French progestogen trial, France, 11 Turkish progestogen trial, Turkey, 12 Mississippi progestogen trial, 13 The George Washington University, The Biostatistics Center, Rockville, MD, 14 Magee-Womens Hospital, University of Pittsburgh, Maternal Fetal Medicine, Pittsburgh, PA OBJECTIVE: Preterm birth is the principal factor contributing to ad- verse outcomes in multiple pregnancies. RCTs of progestogen treat- ment in twin pregnancies did not show benefits in preventing preterm births, but did not have adequate power to evaluate effects on perina- tal outcome or effects among subgroups. STUDY DESIGN: We conducted an individual participant data meta- analysis of nine randomized, double-blind, placebo-controlled trials of progestogen treatment for prevention of preterm birth in twin pregnancy. The primary outcome was a composite of perinatal mor- tality and severe neonatal morbidity. Secondary outcomes included intrauterine death, a composite of intrauterine death or delivery be- fore 37, 35, 32 and 28 weeks, and time-to-delivery or death. Prespeci- fied subgroup analyses were performed for type of progestogen, monochorionicity, cervical length 25 mm, a history of spontaneous preterm birth 37 weeks, and ethnicity. RESULTS: We analyzed data from 3,304 women pregnant with 6,608 children. No statistically significant effect was seen from progestogens as compared to placebo for adverse perinatal outcome (RR 1.05; 95% CI 0.91-1.2) or any of the secondary outcomes. Separate comparisons of 17-alpha hydroxy progesterone caproate (17P) or vaginal proges- terone to placebo did not show significant differences either. In women with a cervical length 25 mm, the proportion of women with an adverse perinatal outcome was not significantly reduced: 15 (41%) versus 11 (61%) for progestogens versus placebo (RR 0.67; 95% www.AJOG.org Doppler Assessment, Fetus, Prematurity Poster Session III Supplement to JANUARY 2012 American Journal of Obstetrics & Gynecology S215

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Page 1: 471: Purkinje cell protein 4 (PCP4) repression in human myometrium during preterm labor

delivered within 7 days of BMZ administration were secondary out-comes. All data was analyzed with the Kruskal-Wallis test.RESULTS: Three hundred and fifty six patients received BMZ for PLand 247 patients for ACD. The median interval between administra-tion of BMZ and delivery was 35 days for preterm labor and 47 days foradvanced 28 days (p�0.0001). Compared to ACD patients, PL pa-tients were more dilated (2 vs. 1 cm, p�0.0001) and more effaced (1.5vs. 2 cm, p�0.0001) at the time of BMZ administration. There was nosignificant difference in the median NICU length of stay between PL

and ACD patients. Only patients who presented with PL and were3.5� cm dilated or completely effaced delivered within 7 days of BMZadministration (p�0.005). For ACD patients, only those who were 0.5cm effaced or less delivered within 7 days of BMZ administration(p�0.005).CONCLUSION: The interval between BMZ administration and deliveryat our institution is greater than 7 days for patients who present withPL or ACD. Improvements need to be made in order to better triagepatients who present with threatened PL or ACD.

471 Purkinje cell protein 4 (PCP4) repressionin human myometrium during preterm laborClifford Mason1, Yafeng Dong1, Irina A. Buhimschi2,Catalin S. Buhimschi2, Carl P. Weiner1

1University of Kansas Medical Center, Ob/Gyn, Kansas City, KS,2Yale University, Ob/Gyn & Reprod Sci., New Haven, CTOBJECTIVE: There remain wide gaps in our mechanistic knowledge ofcauses for preterm birth (PTB). In a comprehensive genomic analysisof myometrium from 4 groups of women (n�6/group) consisting ofterm not in labor (TNL), preterm not in labor (PTNL), term in labor(TL), and preterm in labor (PTL), we identified for the first time thatsignificant repression of the gene encoding purkinje cell protein 4(PCP4, aka PEP-19), a modulator of calcium (Ca2�)/calmodulin(CAM) regulated processes, occurred only in PTL. We sought to char-acterize PCP4 expression, localization, and function in human myo-metrium.STUDY DESIGN: PCP4 mRNA and protein was quantified in humanmyometrium from women at term and preterm with or without labor(n�6 subjects/group) using Q-rtPCR and Western blot. Doublestained indirect immunofluorescence was used to determine the cell-specific localization of PCP4. Myometrial smooth muscle cells wereidentified with an anti-desmin antibody and fibroblasts by staining forvimentin. Myometrial interstitial cells were identified by staining forde-phosphorylated connexin 43 and the sarcoplasmic reticulum bystaining for the sarco-endoplasmic reticulum Ca2�-ATPase pump(SERCA).RESULTS: PCP4 mRNA and protein were significantly decreased in themyometrium from PTL compared to TL, TNL, and PTNL, confirm-ing our microarray findings. PCP4 was found only at the periphery ofsmooth muscle bundles and localized primarily to the sarcoplasmicreticulum.CONCLUSION: PCP4 is uniquely altered in association with spontane-ous PTL. Its expression is predominantly in the sarcoplasmic reticu-lum of myometrial smooth muscle cells suggesting PCP4 may regulatemyometrial intracellular Ca2� levels. We hypothesize a decrease inPCP4 either before or during PTL leads to hyperactivation of Ca2�-CAM dependent enzymes. These studies promise new insights intothe role of PCP4 in the regulation of myometrial contraction and maylead to the design of new approaches for controlling myometrial ac-tivity during spontaneous preterm labor.

472 Progestogen in twin pregnancies: an individualparticipant data meta-analysis of randomized trialsE. Schuit1, Sarah Stock2, Dwight Rouse3, A.C. Lim4, Line Rode5,Jane Norman6, Anwar Nassar7, Vicente Serra8, C. AndrewCombs9, Patrick Rozenberg10, Elcin Cetingoz11, ChristianBriery12, Elizabeth Thom13, Steve Caritis14, Katharina Klein5,Ann Tabor5, Johnny Awwad7, Ihab Usta7, Alfredo Perales8, JuanMeseguer8, Kimberly Maurel9, Thomas Garite9, Cetin Cam11,Ates Karateke11, John Morrison12, Everett Magann12, Rolf H.H.Groenwold1, Karel Moons1, Anneke Kwee4, Ben Willem Mol41University Medical Center Utrecht, Julius Center for Health Sciences andPrimary Care, Utrecht, Netherlands, 2University of Edinburgh MRC Centrefor Reproductive Health, Obstetrics and Gynaecology, Edinburgh, UnitedKingdom, 3NICHD MFMU Network twins trial, Providence, 4DutchConsortium AMPHIA trial, Netherlands, 5Predict Group trial, Denmark,6Queen’s Medical Research Institute, University of Edinburgh MRCCentre for Reproductive Health, Edinburgh, United Kingdom,7Lebanese progestogen trial, Lebanon, 8Spanish progestogen trial, Spain,9Obstetrix Medical Group twins trial, 10French progestogen trial, France,11Turkish progestogen trial, Turkey, 12Mississippi progestogen trial,13The George Washington University, The Biostatistics Center,Rockville, MD, 14Magee-Womens Hospital, University ofPittsburgh, Maternal Fetal Medicine, Pittsburgh, PAOBJECTIVE: Preterm birth is the principal factor contributing to ad-verse outcomes in multiple pregnancies. RCTs of progestogen treat-ment in twin pregnancies did not show benefits in preventing pretermbirths, but did not have adequate power to evaluate effects on perina-tal outcome or effects among subgroups.STUDY DESIGN: We conducted an individual participant data meta-analysis of nine randomized, double-blind, placebo-controlled trialsof progestogen treatment for prevention of preterm birth in twinpregnancy. The primary outcome was a composite of perinatal mor-tality and severe neonatal morbidity. Secondary outcomes includedintrauterine death, a composite of intrauterine death or delivery be-fore 37, 35, 32 and 28 weeks, and time-to-delivery or death. Prespeci-fied subgroup analyses were performed for type of progestogen,monochorionicity, cervical length � 25 mm, a history of spontaneouspreterm birth � 37 weeks, and ethnicity.RESULTS: We analyzed data from 3,304 women pregnant with 6,608children. No statistically significant effect was seen from progestogensas compared to placebo for adverse perinatal outcome (RR 1.05; 95%CI 0.91-1.2) or any of the secondary outcomes. Separate comparisonsof 17-alpha hydroxy progesterone caproate (17P) or vaginal proges-terone to placebo did not show significant differences either. Inwomen with a cervical length � 25 mm, the proportion of womenwith an adverse perinatal outcome was not significantly reduced: 15(41%) versus 11 (61%) for progestogens versus placebo (RR 0.67; 95%

www.AJOG.org Doppler Assessment, Fetus, Prematurity Poster Session III

Supplement to JANUARY 2012 American Journal of Obstetrics & Gynecology S215