1
56 INCREASED RECURRENCE OF PRETERM DELIVERY WITH EARLY CESSATION OF 17 ALPHA-HYDROXYPROGESTERONE CAPROATE ANDREI REBARBER 1 , LAUREN FERRARA 1 , MARY ELLEN HANLEY 2 , NIKI ISTWAN 3 , DEBBIE RHEA 3 , GARY STANZIANO 3 , DANIEL SALTZMAN 1 , 1 Mount Sinai School of Medicine, Ma- ternal Fetal Medicine, New York, New York, 2 Valley Hospital, Maternal Fe- tal Medicine, Paramus, New Jersey, 3 Matria Healthcare, Clinical Research, Marietta, Georgia OBJECTIVE: To identify the impact of early cessation of 17 alpha-hydrox- yprogesterone caproate (17P) on the incidence of recurrent spontaneous preterm birth (SPTB). STUDY DESIGN: Patients were identified retrospectively from a database of information from women receiving outpatient services for pregnancy-related conditions. Included were women with a history of PTB and current singleton gestation, enrolled for outpatient weekly IM administration of 17P beginning at 16-20.9 weeks’ gestation between 1/2004 and 5/2006. Excluded: patients with cerclage, or without complete pregnancy outcomes. The study group consisted of patients who electively terminated use of 17P prior to 32.0 weeks’ gestation with delivery occurring at O10 days from the last injection. The control group consisted of patients who received weekly 17P injections until delivery or 36 weeks’ gestation. Primary study endpoints were the rates of SPTB at !37, !35 and !32 weeks. Pair-wise differences were compared using Pearson’s or continuity-corrected c 2 , Fisher’s Exact and Mann-Whitney U tests where appropriate. RESULTS: Patients with early discontinuation of 17P were significantly more likely to experience recurrent PTB. In table, data presented as mean G SD, median (min, max), or percentage as indicated. GA=gestational age. CONCLUSION: Early cessation of 17P appears to result in an increased risk for SPTB. This was found across the complete range of prematurity including !32 weeks which is associated with the greatest neonatal morbidity and mortality. In light of our data, as in the NIHCD study, continuation of 17P until 36 weeks appears warranted. 0002-9378/$ - see front matter doi:10.1016/j.ajog.2006.10.066 57 THE ROLE OF PROTEASE ACTIVATED RECEPTOR 1 (PAR1) THROMBIN RECEPTOR POLYMORPHISMS IN RECURRENT PREGNANCY LOSS (RPL) - NOT ONLY COAGU- LATION ARON TEVET 1 , GEONA ALTARESCU 2 , EHUD MARGALIOT 3 , ARNON SAMUELOFF 4 , RACHEL BAR-SHAVIT 5 , SORINA GRANOVSKY-GRISARU 6 , 1 Shaare Zedek Medical Center, Jerusalem, Obstetrics and Gynecology, Jerusa- lem, Israel, 2 Shaare Zedek Medical Center, Genetics, Jerusalem, Israel, 3 Shaare Zedek Medical Center, Obstetrics Gynecology, Jerusalem, Israel, 4 Shaare Zedek Medical Center, Obstetrics and Gynecology, affiliated with Ben-Gurion University of the Negev, Beer-Sheva, Jerusalem, Israel, 5 Tumor Biology, Hadassah Hospital and the Hebrew University, Jerusalem, Onco- logy&Tumor Biology, Jerusalem, Israel, 6 Shaare Zedek Medical Center, Obsterics Gynecology, Jerusalem, Israel OBJECTIVE: PAR1 is implicated in hemostasis, tissue remodeling and plays a critical role in placenta establishment. PAR1 polymorphism [-1426(C/T)], which influence coagulation and adhesion molecule expression, predisposes to preterm birth. RPL has been associated with defective establishment of maternal-fetal communication. Thus, we sought to determine the relationship between PAR1 polymorphisms and RPL. STUDY DESIGN: Case-control study of 39 healthy women with idiopathic RPL (O2 consecutive spontaneous abortions) versus 98 parous women . Blood sample DNA ; PCR amplification identification of polymorphisms at 5 0 regulatory region : [-1426(C/T)], [-506 (I/D)], and IVS [-14(A/T)]. Sample size calculated for 81% power. RESULTS: We found a statistical significant difference between the study groups: the heterozygous allele state was significantly higher in the RPL group relative to controls for [-1426] (15.4% vs 5%) and for IVS [-14] (12.8% vs 1%). Both groups were similar for age, origin, education, smoking and area of residence. All women with RPL were negative for thrombophilic gene mutations (factor V, factor II , factor XIII, beta fibrinogen, MTHFR), antiphospholipid/co-factor syndrome, protein S, C, and antithrombin III deficiency; had a normal uterine shape, negative infectious screen and normal karyotypes. While the pregnancy rate was similar between the groups, the RPL group had a significantly lower live children number and higher spontaneous abortions. The wild allele frequency was comparable in both groups; few homozygous state for any PAR1 polymorphisms was seen (!2%). No difference was detected for the [-506 (I/D)] status. Thus, the carrier state for [-1426] and [-14] increased 3 and 11-fold respectively the odds for RPL. CONCLUSION: PAR1 polymorphisms [-1426(C/T)] and IVS [-14(A/T)] may be susceptibility factors affecting the risk of RPL. The concordance with the maternal predilection for heterozygocity of PAR1 [1426] polymorphism for preterm delivery is suggestive of a coagulation-independent mechanism and emphasizes that PAR1 is inimical to normal placentation. 0002-9378/$ - see front matter doi:10.1016/j.ajog.2006.10.067 58 BIRTH ORDER OF TWINS AND THE RISK OF DELIVERY RELATED PERINATAL DEATH IN ENGLAND, NORTHERN IRELAND AND WALES, 1994-2003 GORDON SMITH 1 , KATE FLEMING 2 , IAN WHITE 3 , 1 University of Cambridge, Obstetrics & Gynae- cology, Cambridge, United Kingdom, 2 Confidential Enquiry into Maternal and Child Health, London, United Kingdom, 3 MRC Biostatistics Unit, Cam- bridge, UK, Cambridge, United Kingdom OBJECTIVE: Previous studies have yielded contradictory findings on whether attempted vaginal delivery of the second twin at term is associated with an increased risk of perinatal death. We sought to determine the relationship between the birth order of twins and the risk of perinatal death due to complications during labour and delivery. STUDY DESIGN: We retrieved data from national surveys of perinatal death from England, Northern Ireland and Wales between 1994 and 2003 which included details of 5,758 perinatal deaths of twins. We studied 1,501 pregnancies where one fetus died due to an intrapartum stillbirth or neonatal death due to causes other than congenital abnormality, and the other fetus survived. We estimated the odds ratio (95% confidence intervals) of death for the second twin using conditional logistic regression. RESULTS: Birth order was not associated with the risk of death overall (odds ratio, 1.0 (95% CI 0.9 to 1.1). However, there was a highly statistically significant interaction with gestational age (P!0.001). There was no associ- ation between birth order and the risk of death among infants born prior to 36 weeks gestation but there was an increased risk of death among second twins born at term (odds ratio 2.5, 95% CI 1.8 to 3.4, P!0.001), which was stronger for deaths due to intrapartum anoxia or trauma (odds ratio 3.4, 95% CI, 2.2 to 5.4). Among term births, there was a trend (P=0.09) towards a greater risk of anoxic death of the second twin among women delivered vaginally (odds ratio 4.7, 95% CI, 1.9 to 11.3) compared with women delivered by caesarean section (odds ratio 1.8, 95% CI, 0.9 to 3.6). CONCLUSION: Second twins born at term were at increased risk of delivery- related perinatal death compared with first twins, in England, Northern Ireland and Wales between 1994 and 2003. The risk of death due to anoxia was greater than four-fold for vaginally delivered second twins. 0002-9378/$ - see front matter doi:10.1016/j.ajog.2006.10.068 S26 SMFM Abstracts

Birth order of twins and the risk of delivery related perinatal death in England, Northern Ireland and Wales, 1994-2003

Embed Size (px)

Citation preview

Page 1: Birth order of twins and the risk of delivery related perinatal death in England, Northern Ireland and Wales, 1994-2003

56 INCREASED RECURRENCE OF PRETERM DELIVERY WITH EARLY CESSATIONOF 17 ALPHA-HYDROXYPROGESTERONE CAPROATE ANDREI REBARBER1,LAUREN FERRARA1, MARY ELLEN HANLEY2, NIKI ISTWAN3, DEBBIE RHEA3,GARY STANZIANO3, DANIEL SALTZMAN1, 1Mount Sinai School of Medicine, Ma-ternal Fetal Medicine, New York, New York, 2Valley Hospital, Maternal Fe-tal Medicine, Paramus, New Jersey, 3Matria Healthcare, Clinical Research,Marietta, Georgia

OBJECTIVE: To identify the impact of early cessation of 17 alpha-hydrox-yprogesterone caproate (17P) on the incidence of recurrent spontaneouspreterm birth (SPTB).

STUDY DESIGN: Patients were identified retrospectively from a database ofinformation from women receiving outpatient services for pregnancy-relatedconditions. Included were women with a history of PTB and current singletongestation, enrolled for outpatient weekly IM administration of 17P beginningat 16-20.9 weeks’ gestation between 1/2004 and 5/2006. Excluded: patientswith cerclage, or without complete pregnancy outcomes. The study groupconsisted of patients who electively terminated use of 17P prior to 32.0 weeks’gestation with delivery occurring at O10 days from the last injection. Thecontrol group consisted of patients who received weekly 17P injections untildelivery or 36 weeks’ gestation. Primary study endpoints were the rates ofSPTB at !37, !35 and !32 weeks. Pair-wise differences were comparedusing Pearson’s or continuity-corrected c2, Fisher’s Exact and Mann-WhitneyU tests where appropriate.

RESULTS: Patients with early discontinuation of 17P were significantlymore likely to experience recurrent PTB. In table, data presented as mean GSD, median (min, max), or percentage as indicated. GA=gestational age.

CONCLUSION: Early cessation of 17P appears to result in an increased riskfor SPTB. This was found across the complete range of prematurity including!32 weeks which is associated with the greatest neonatal morbidity andmortality. In light of our data, as in the NIHCD study, continuation of 17Puntil 36 weeks appears warranted.

0002-9378/$ - see front matterdoi:10.1016/j.ajog.2006.10.066

57 THE ROLE OF PROTEASE ACTIVATED RECEPTOR 1 (PAR1) THROMBIN RECEPTORPOLYMORPHISMS IN RECURRENT PREGNANCY LOSS (RPL) - NOT ONLY COAGU-LATION ARON TEVET1, GEONA ALTARESCU2, EHUD MARGALIOT3,ARNON SAMUELOFF4, RACHEL BAR-SHAVIT5, SORINA GRANOVSKY-GRISARU6,1Shaare Zedek Medical Center, Jerusalem, Obstetrics and Gynecology, Jerusa-lem, Israel, 2Shaare Zedek Medical Center, Genetics, Jerusalem, Israel,3Shaare Zedek Medical Center, Obstetrics Gynecology, Jerusalem, Israel,4Shaare Zedek Medical Center, Obstetrics and Gynecology, affiliated withBen-Gurion University of the Negev, Beer-Sheva, Jerusalem, Israel, 5TumorBiology, Hadassah Hospital and the Hebrew University, Jerusalem, Onco-logy&Tumor Biology, Jerusalem, Israel, 6Shaare Zedek Medical Center,Obsterics Gynecology, Jerusalem, Israel

OBJECTIVE: PAR1 is implicated in hemostasis, tissue remodeling and playsa critical role in placenta establishment. PAR1 polymorphism [-1426(C/T)],which influence coagulation and adhesion molecule expression, predisposesto preterm birth. RPL has been associated with defective establishment ofmaternal-fetal communication. Thus, we sought to determine the relationshipbetween PAR1 polymorphisms and RPL.

STUDY DESIGN: Case-control study of 39 healthy women with idiopathicRPL (O2 consecutive spontaneous abortions) versus 98 parous women .Blood sample DNA ; PCR amplification identification of polymorphisms at 50

regulatory region : [-1426(C/T)], [-506 (I/D)], and IVS [-14(A/T)]. Sample sizecalculated for 81% power.

RESULTS: We found a statistical significant difference between the studygroups: the heterozygous allele state was significantly higher in the RPL grouprelative to controls for [-1426] (15.4% vs 5%) and for IVS [-14] (12.8% vs 1%).Both groups were similar for age, origin, education, smoking and area of

residence. All women with RPL were negative for thrombophilic genemutations (factor V, factor II , factor XIII, beta fibrinogen, MTHFR),antiphospholipid/co-factor syndrome, protein S, C, and antithrombin IIIdeficiency; had a normal uterine shape, negative infectious screen and normalkaryotypes. While the pregnancy rate was similar between the groups, the RPLgroup had a significantly lower live children number and higher spontaneousabortions. The wild allele frequency was comparable in both groups; fewhomozygous state for any PAR1 polymorphisms was seen (!2%). Nodifference was detected for the [-506 (I/D)] status. Thus, the carrier state for[-1426] and [-14] increased 3 and 11-fold respectively the odds for RPL.

CONCLUSION: PAR1 polymorphisms [-1426(C/T)] and IVS [-14(A/T)] maybe susceptibility factors affecting the risk of RPL. The concordance with thematernal predilection for heterozygocity of PAR1 [1426] polymorphism forpreterm delivery is suggestive of a coagulation-independent mechanism andemphasizes that PAR1 is inimical to normal placentation.

0002-9378/$ - see front matterdoi:10.1016/j.ajog.2006.10.067

S26 SMFM Abstracts

58 BIRTH ORDER OF TWINS AND THE RISK OF DELIVERY RELATED PERINATAL DEATHIN ENGLAND, NORTHERN IRELAND AND WALES, 1994-2003 GORDON SMITH1,KATE FLEMING2, IAN WHITE3, 1University of Cambridge, Obstetrics & Gynae-cology, Cambridge, United Kingdom, 2Confidential Enquiry into Maternaland Child Health, London, United Kingdom, 3MRC Biostatistics Unit, Cam-bridge, UK, Cambridge, United Kingdom

OBJECTIVE: Previous studies have yielded contradictory findings onwhether attempted vaginal delivery of the second twin at term is associatedwith an increased risk of perinatal death. We sought to determine therelationship between the birth order of twins and the risk of perinatal deathdue to complications during labour and delivery.

STUDY DESIGN: We retrieved data from national surveys of perinatal deathfrom England, Northern Ireland and Wales between 1994 and 2003 whichincluded details of 5,758 perinatal deaths of twins. We studied 1,501pregnancies where one fetus died due to an intrapartum stillbirth or neonataldeath due to causes other than congenital abnormality, and the other fetussurvived. We estimated the odds ratio (95% confidence intervals) of death forthe second twin using conditional logistic regression.

RESULTS: Birth order was not associated with the risk of death overall(odds ratio, 1.0 (95% CI 0.9 to 1.1). However, there was a highly statisticallysignificant interaction with gestational age (P!0.001). There was no associ-ation between birth order and the risk of death among infants born prior to 36weeks gestation but there was an increased risk of death among second twinsborn at term (odds ratio 2.5, 95% CI 1.8 to 3.4, P!0.001), which was strongerfor deaths due to intrapartum anoxia or trauma (odds ratio 3.4, 95% CI, 2.2 to5.4). Among term births, there was a trend (P=0.09) towards a greater risk ofanoxic death of the second twin among women delivered vaginally (odds ratio4.7, 95% CI, 1.9 to 11.3) compared with women delivered by caesarean section(odds ratio 1.8, 95% CI, 0.9 to 3.6).

CONCLUSION: Second twins born at term were at increased risk of delivery-related perinatal death compared with first twins, in England, NorthernIreland and Wales between 1994 and 2003. The risk of death due to anoxia wasgreater than four-fold for vaginally delivered second twins.

0002-9378/$ - see front matterdoi:10.1016/j.ajog.2006.10.068