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Preeclampsia and subsequent risk of cancer
SMFM Abstracts S35 79
INTEGRATED FETAL TESTING IS THE MOST ACCURATE PREDICTOR OF PERINATAL OUTCOME IN INTRAUTERINE GROWTH RESTRICTION (IUGR) AHMET BASCHAT1, MICHELLE KUSH1, ANITA MANOGURA1, DOLORES MOYANO2, SIFA TURAN2, UTE GERMER3, CHRISTOPH BERG4, AMARNATH BHIDE5, DICK OEPKES6, BASKARAN THILAGANATHAN5, HENRY GALAN7, SARAH BOWER2, KYPROS NICOLAIDES2, ULRICH GEMBRUCH8, CHRISTOPHER HARMAN1, 1University of Maryland, Obstetrics, Gynecology and Reproductive Sciences, Baltimore, Maryland, 2 King’s College Hospital, London, United Kingdom, 3Medical University Lubeck, Obstetrics & Gynecology, Lubeck, Germany, 4Friedrich Wilhelm University, Obstetrics & Prenatal Medicine, Bonn, Germany, 5St. George’s Hospital Medical School, Fetal Medicine Unit, London, United Kingdom, 6 Leiden University, Leiden, Ontario, Netherlands, 7University of Colorado Health Sciences Center, Obstetrics and Gynecology, Denver, Colorado, 8 Medical University Lu¨beck, Obstetrics & Gynecology, Bonn, Germany OBJECTIVE: Biophysical profile scoring (BPS) and arterial and venous multivessel Doppler each test fetal behavioral and cardiovascular responses to compromised placental function. We aimed to study if integration of two testing modaIities improves prediction of critical perinatal outcomes in IUGR fetuses. STUDY DESIGN: Fetuses with IUGR (Abdominal Circumference !5%ile, elevated umbilical artery (UA) Doppler) were studied in a multicenter collaboration. UA end-diastolic velocity (EDV), middle cerebral artery brain sparing, abnormal ductus venosus Doppler (DV-RAV) and BPS were compared for their ability to predict stillbirth (SB), neonatal death (NND), birth acidemia, low 5 minute Apgar, and major neonatal morbidity (intraventricular hemorrhage OGrade 2, bronchopulmonary dysplasia, necrotizing enterocolitis). Integration of the two testing modalities was modelled to provide the best outcome prediction. RESULTS: In 534 IUGR fetuses, there were 38 stillborn, 32 neonatal deaths (PNM 13.1%). Low Apgar and birth acidemia occured in 7.3% and 9.6% respectively. In survivors, 67 (14.8%) had major morbidity. Prediction of PNM by single abnormal parameter ranged from Odds Ratios of 2.1 for brain sparing and fetal tone, to 14.6 for DV-RAV. However, DV-RAV was present in only 22 of deaths. No single parameter correctly predicted more than 2/3 of PNM. This pattern was repeated for all individual outcomes. The analysis was repeated for combined test domains. Combining DV index, UA-EDV, amniotic fluid volume, fetal movement, and fetal breathing (in declining order of statistical contribution), produced highest predictive accuracy for both normal and abnormal outcomes. Eighteen of twenty possible test domains (nine normal and nine abnormal parameters) provided enhanced outcome specifictity. CONCLUSION: Optimal prediction of critical perinatal outcome in IUGR requires combined evaluation of fetal cardiovacular and behavioral responses. For the clinincian, the combination of umbilical and venous Doppler with the four ultrasound parameters of BPS, can provide this optimal assessment.
81
MATERNAL-FETAL MEDICINE SPECIALIST DENSITY IS INVERSELY ASSOCIATED ROGER NEWMAN1, WITH PERINATAL MORTALITY SCOTT SULLIVAN (F)1, KATHRYN MENARD2, 1Medical University of South Carolina, Obstetrics and Gynecology, Charleston, South Carolina, 2Medical University of South Carolina, Department of Medicine, Charleston, South Carolina OBJECTIVE: To determine the relationship between state specific maternalfetal medicine specialist density and perinatal mortality using national databases. Models incorporating provider density, population density and state demographic characteristics were constructed to examine perinatal risk. STUDY DESIGN: State specific perinatal mortality data including rates of fetal, neonatal and infant death for 2001-2 was obtained from the March of Dimes Peri-Stats databases and the Department of Health and Human Services Centers for Disease Control and Prevention. Practitioner distribution data from that same period was obtained from the respective professional organizations. Demographic information including rates of hypertension, diabetes, prenatal care, poverty, smoking, teenage and advanced maternal age pregnancy, and minority status for individual states was gathered from the 2000 Census Bureau data. Geographic density mapping was performed. Spearman correlations and multiple linear and Poisson regression modeling were used for statistical analysis. RESULTS: The median rates of fetal, neonatal and infant deaths were 6.2, 4.8 and 7 per 1000 live births respectively. Maternal-fetal medicine specialist density was significantly and inversely correlated with fetal death (p!.003), neonatal death (p!.02) and infant death (p!.002). Multivariable regression analysis confirmed the inverse associations with fetal death (p!.001) and infant death (p!.02) while controlling for population density and demographic risk factors. In addition general obstetric provider density was found to be inversely associated with fetal death in the model (p!.01). CONCLUSION: Models including adverse perinatal outcomes, provider densities, population densities and state specific demographics confirmed that the density of maternal-fetal medicine specialists was inversely associated with fetal death and infant death. General obstetric provider density was found to be inversely and independently associated with fetal death.
80
LONG TERM EFFECTS OF PREMATURITY: RESULTS FROM THE MEDICAL BIRTH REGISTRY OF NORWAY GEETA K. SWAMY1, TRULS OSTBYE2, ROLV SKJAERVEN3, 1 Duke University, Obstetrics & Gynecology, Durham, North Carolina, 2 Duke University, Dept of Community and Family Medicine, Durham, North Carolina, 3University of Bergen, Section for Epidemiology & Medical Statistics, Bergen, Norway OBJECTIVE: To determine long term effects of preterm birth—survival, reproduction, and preterm birth in the next generation STUDY DESIGN: Using the Medical Birth Registry of Norway, 610,258 men and 577,801 women born from 1967-1988 were analyzed. Mortality was determined through 2003. Subjects were grouped by gender and gestational age (22-27 weeks (wks), 28-32 wks, 33-36 wks, and 37-42 wks). We evaluated parental characteristics and the risk of perinatal, infant, early childhood (1-6 years (y)), late childhood (6-13 y), and adolescent (13-18 y) mortality. For subjects born from 1967-1978, we evaluated reproductive and birth outcomes in next-generation offspring for the same subgroups. Using 37-42 wks as the reference group, odds ratios (OR) with 95% confidence intervals (CI) were calculated. RESULTS: Subjects born preterm were more likely to have parents who were unmarried, had lower education, and mothers with diabetes or preeclampsia. As expected, preterm subjects had considerably higher perinatal and infant mortality. This increased risk of mortality persisted through adolescence. For 22-27 wks, the OR for early and late childhood deaths among males were 6.1 [2.5, 14.7] and 6.4 [2.0, 19.8], respectively. For females, the OR for early childhood deaths was 8.8 [3.6-21.3]. No late childhood deaths occurred among females. For 28-32 wks, the OR for early and late childhood deaths in males were 2.5 [1.7, 3.6] and 1.9 [1.1, 3.4], respectively. For females, the OR=2.1 [1.2, 3.7] and 0.9 [0.3, 2.9], respectively. Reproduction was significantly diminished for surviving men and women born at 22-27 wks, OR=0.48 [0.39, 0.60] and 0.52 [0.43, 0.62], respectively. For 28-32 wks, OR=0.75 [0.7, 0.8] for men and 0.81 [0.75, 0.86] for women. Among those who reproduced, there was no difference in the mean number of offspring. Only females were at increased risk for producing preterm offspring. CONCLUSION: Preterm birth is associated with diminished short- and longterm survival and reproductive ability. Women born preterm are at risk for delivering their offspring preterm.
82
PREECLAMPSIA AND SUBSEQUENT RISK OF CANCER KJERSTI AAGAARD-TILLERY (F)1, CALLA HOLMGREN1, YVETTE LACOURSIERE1, ALISON FRASER2, GERI MINEAU3, MICHAEL VARNER1, 1University of Utah, Obstetrics and Gynecology, Salt Lake City, Utah, 2University of Utah-Huntsman Cancer Institute, Population Sciences, Salt Lake City, Utah, 3University of Utah-Huntsman Cancer Institute, Oncological Sciences, Salt Lake City, Utah OBJECTIVE: It is suggested that endothelial progenitors play a primary role in the initiation of angiogenesis during normal and neoplastic tissue growth. Prospective evidence has shown that circulating anti-angiogenic factors are elevated prior to the clinical onset of preeclampsia (PRE); this is accompanied by low serum concentrations of their proangiogenic soluble counterparts. These observations led us to hypothesize that preeclamptic women may have a reduced risk of developing cancer later in life. STUDY DESIGN: We employed the Utah Population Database, a unique resource of linked datasets containing over 8 million records. Cases were initially selected among all women giving birth in Utah from 1947-1999 and identified with preeclampsia or eclampsia. A comparison cohort of controls were matched 3:1 on maternal age and birth year. Subjects were then linked to the Utah Cancer Registry in order to ascertain diagnoses of all cancers in the interval 1966-1999. RESULTS: We identified 17,432 cases and 52,296 controls available for linked analyses. Mean birthweight (2842 vs 3105 gms, p!0.000), number of previous live births (1.1 vs 1.5, p!0.000), and incidence of multiples (1.04 vs 0.99, p!0.000) all differed significantly among cases when compared to controls. By contrast, neither maternal (25.42 vs 25.43 years) nor paternal (27.4 vs 27.5 years) age significantly differed. Pearson Chi-squared analyses revealed a lower risk of cancer among women whose pregancies were affected by PRE (4.6% vs 5.1%, p=0.012); a trend towards less invasive disease was similarly observed (OR 0.92, 95% CI 0.76,1.11). The offspring of PRE women were not significantly different in their risk of developing cancer than were offspring of controls (0.7% vs 0.6%, p=0.454). These findings were confirmed in stratified analyses. CONCLUSION: We demonstrate that women whose pregnancies are affected by preeclampsia have a decreased risk of cancer through their lifetime.
INTEGRATED FETAL TESTING IS THE MOST ACCURATE PREDICTOR OF PERINATAL OUTCOME IN INTRAUTERINE GROWTH RESTRICTION (IUGR) AHMET BASCHAT1, MICHELLE KUSH1, ANITA MANOGURA1, DOLORES MOYANO2, SIFA TURAN2, UTE GERMER3, CHRISTOPH BERG4, AMARNATH BHIDE5, DICK OEPKES6, BASKARAN THILAGANATHAN5, HENRY GALAN7, SARAH BOWER2, KYPROS NICOLAIDES2, ULRICH GEMBRUCH8, CHRISTOPHER HARMAN1, 1University of Maryland, Obstetrics, Gynecology and Reproductive Sciences, Baltimore, Maryland, 2 King’s College Hospital, London, United Kingdom, 3Medical University Lubeck, Obstetrics & Gynecology, Lubeck, Germany, 4Friedrich Wilhelm University, Obstetrics & Prenatal Medicine, Bonn, Germany, 5St. George’s Hospital Medical School, Fetal Medicine Unit, London, United Kingdom, 6 Leiden University, Leiden, Ontario, Netherlands, 7University of Colorado Health Sciences Center, Obstetrics and Gynecology, Denver, Colorado, 8 Medical University Lu¨beck, Obstetrics & Gynecology, Bonn, Germany OBJECTIVE: Biophysical profile scoring (BPS) and arterial and venous multivessel Doppler each test fetal behavioral and cardiovascular responses to compromised placental function. We aimed to study if integration of two testing modaIities improves prediction of critical perinatal outcomes in IUGR fetuses. STUDY DESIGN: Fetuses with IUGR (Abdominal Circumference !5%ile, elevated umbilical artery (UA) Doppler) were studied in a multicenter collaboration. UA end-diastolic velocity (EDV), middle cerebral artery brain sparing, abnormal ductus venosus Doppler (DV-RAV) and BPS were compared for their ability to predict stillbirth (SB), neonatal death (NND), birth acidemia, low 5 minute Apgar, and major neonatal morbidity (intraventricular hemorrhage OGrade 2, bronchopulmonary dysplasia, necrotizing enterocolitis). Integration of the two testing modalities was modelled to provide the best outcome prediction. RESULTS: In 534 IUGR fetuses, there were 38 stillborn, 32 neonatal deaths (PNM 13.1%). Low Apgar and birth acidemia occured in 7.3% and 9.6% respectively. In survivors, 67 (14.8%) had major morbidity. Prediction of PNM by single abnormal parameter ranged from Odds Ratios of 2.1 for brain sparing and fetal tone, to 14.6 for DV-RAV. However, DV-RAV was present in only 22 of deaths. No single parameter correctly predicted more than 2/3 of PNM. This pattern was repeated for all individual outcomes. The analysis was repeated for combined test domains. Combining DV index, UA-EDV, amniotic fluid volume, fetal movement, and fetal breathing (in declining order of statistical contribution), produced highest predictive accuracy for both normal and abnormal outcomes. Eighteen of twenty possible test domains (nine normal and nine abnormal parameters) provided enhanced outcome specifictity. CONCLUSION: Optimal prediction of critical perinatal outcome in IUGR requires combined evaluation of fetal cardiovacular and behavioral responses. For the clinincian, the combination of umbilical and venous Doppler with the four ultrasound parameters of BPS, can provide this optimal assessment.
81
MATERNAL-FETAL MEDICINE SPECIALIST DENSITY IS INVERSELY ASSOCIATED ROGER NEWMAN1, WITH PERINATAL MORTALITY SCOTT SULLIVAN (F)1, KATHRYN MENARD2, 1Medical University of South Carolina, Obstetrics and Gynecology, Charleston, South Carolina, 2Medical University of South Carolina, Department of Medicine, Charleston, South Carolina OBJECTIVE: To determine the relationship between state specific maternalfetal medicine specialist density and perinatal mortality using national databases. Models incorporating provider density, population density and state demographic characteristics were constructed to examine perinatal risk. STUDY DESIGN: State specific perinatal mortality data including rates of fetal, neonatal and infant death for 2001-2 was obtained from the March of Dimes Peri-Stats databases and the Department of Health and Human Services Centers for Disease Control and Prevention. Practitioner distribution data from that same period was obtained from the respective professional organizations. Demographic information including rates of hypertension, diabetes, prenatal care, poverty, smoking, teenage and advanced maternal age pregnancy, and minority status for individual states was gathered from the 2000 Census Bureau data. Geographic density mapping was performed. Spearman correlations and multiple linear and Poisson regression modeling were used for statistical analysis. RESULTS: The median rates of fetal, neonatal and infant deaths were 6.2, 4.8 and 7 per 1000 live births respectively. Maternal-fetal medicine specialist density was significantly and inversely correlated with fetal death (p!.003), neonatal death (p!.02) and infant death (p!.002). Multivariable regression analysis confirmed the inverse associations with fetal death (p!.001) and infant death (p!.02) while controlling for population density and demographic risk factors. In addition general obstetric provider density was found to be inversely associated with fetal death in the model (p!.01). CONCLUSION: Models including adverse perinatal outcomes, provider densities, population densities and state specific demographics confirmed that the density of maternal-fetal medicine specialists was inversely associated with fetal death and infant death. General obstetric provider density was found to be inversely and independently associated with fetal death.
80
LONG TERM EFFECTS OF PREMATURITY: RESULTS FROM THE MEDICAL BIRTH REGISTRY OF NORWAY GEETA K. SWAMY1, TRULS OSTBYE2, ROLV SKJAERVEN3, 1 Duke University, Obstetrics & Gynecology, Durham, North Carolina, 2 Duke University, Dept of Community and Family Medicine, Durham, North Carolina, 3University of Bergen, Section for Epidemiology & Medical Statistics, Bergen, Norway OBJECTIVE: To determine long term effects of preterm birth—survival, reproduction, and preterm birth in the next generation STUDY DESIGN: Using the Medical Birth Registry of Norway, 610,258 men and 577,801 women born from 1967-1988 were analyzed. Mortality was determined through 2003. Subjects were grouped by gender and gestational age (22-27 weeks (wks), 28-32 wks, 33-36 wks, and 37-42 wks). We evaluated parental characteristics and the risk of perinatal, infant, early childhood (1-6 years (y)), late childhood (6-13 y), and adolescent (13-18 y) mortality. For subjects born from 1967-1978, we evaluated reproductive and birth outcomes in next-generation offspring for the same subgroups. Using 37-42 wks as the reference group, odds ratios (OR) with 95% confidence intervals (CI) were calculated. RESULTS: Subjects born preterm were more likely to have parents who were unmarried, had lower education, and mothers with diabetes or preeclampsia. As expected, preterm subjects had considerably higher perinatal and infant mortality. This increased risk of mortality persisted through adolescence. For 22-27 wks, the OR for early and late childhood deaths among males were 6.1 [2.5, 14.7] and 6.4 [2.0, 19.8], respectively. For females, the OR for early childhood deaths was 8.8 [3.6-21.3]. No late childhood deaths occurred among females. For 28-32 wks, the OR for early and late childhood deaths in males were 2.5 [1.7, 3.6] and 1.9 [1.1, 3.4], respectively. For females, the OR=2.1 [1.2, 3.7] and 0.9 [0.3, 2.9], respectively. Reproduction was significantly diminished for surviving men and women born at 22-27 wks, OR=0.48 [0.39, 0.60] and 0.52 [0.43, 0.62], respectively. For 28-32 wks, OR=0.75 [0.7, 0.8] for men and 0.81 [0.75, 0.86] for women. Among those who reproduced, there was no difference in the mean number of offspring. Only females were at increased risk for producing preterm offspring. CONCLUSION: Preterm birth is associated with diminished short- and longterm survival and reproductive ability. Women born preterm are at risk for delivering their offspring preterm.
82
PREECLAMPSIA AND SUBSEQUENT RISK OF CANCER KJERSTI AAGAARD-TILLERY (F)1, CALLA HOLMGREN1, YVETTE LACOURSIERE1, ALISON FRASER2, GERI MINEAU3, MICHAEL VARNER1, 1University of Utah, Obstetrics and Gynecology, Salt Lake City, Utah, 2University of Utah-Huntsman Cancer Institute, Population Sciences, Salt Lake City, Utah, 3University of Utah-Huntsman Cancer Institute, Oncological Sciences, Salt Lake City, Utah OBJECTIVE: It is suggested that endothelial progenitors play a primary role in the initiation of angiogenesis during normal and neoplastic tissue growth. Prospective evidence has shown that circulating anti-angiogenic factors are elevated prior to the clinical onset of preeclampsia (PRE); this is accompanied by low serum concentrations of their proangiogenic soluble counterparts. These observations led us to hypothesize that preeclamptic women may have a reduced risk of developing cancer later in life. STUDY DESIGN: We employed the Utah Population Database, a unique resource of linked datasets containing over 8 million records. Cases were initially selected among all women giving birth in Utah from 1947-1999 and identified with preeclampsia or eclampsia. A comparison cohort of controls were matched 3:1 on maternal age and birth year. Subjects were then linked to the Utah Cancer Registry in order to ascertain diagnoses of all cancers in the interval 1966-1999. RESULTS: We identified 17,432 cases and 52,296 controls available for linked analyses. Mean birthweight (2842 vs 3105 gms, p!0.000), number of previous live births (1.1 vs 1.5, p!0.000), and incidence of multiples (1.04 vs 0.99, p!0.000) all differed significantly among cases when compared to controls. By contrast, neither maternal (25.42 vs 25.43 years) nor paternal (27.4 vs 27.5 years) age significantly differed. Pearson Chi-squared analyses revealed a lower risk of cancer among women whose pregancies were affected by PRE (4.6% vs 5.1%, p=0.012); a trend towards less invasive disease was similarly observed (OR 0.92, 95% CI 0.76,1.11). The offspring of PRE women were not significantly different in their risk of developing cancer than were offspring of controls (0.7% vs 0.6%, p=0.454). These findings were confirmed in stratified analyses. CONCLUSION: We demonstrate that women whose pregnancies are affected by preeclampsia have a decreased risk of cancer through their lifetime.