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485: Fetal programming of adult vascular function in a preeclampsia-like animal model is gender-specific
SMFM Abstracts
www.AJOG.org 482
EARLY ONSET SEVERE PREECLAMPSIA: MODE OF DELIVERY AND NEONATAL OUTCOMES MARK ALANIS1, HULSEY THOMAS2, CHRISTOPHER ROBINSON1, MYLA EBELING2, DONNA JOHNSON1, 1Medical University of South Carolina, Department of Obstetrics and Gynecology, Charleston, South Carolina, 2Medical University of South Carolina, Department of Pediatrics, Charleston, South Carolina OBJECTIVE: Many physicians choose elective cesarean section (CS) instead of induction of labor (IOL) for patients with early onset severe preeclampsia (EOSPE), despite little evidence to support this practice. We compared the mode of delivery in women with EOSPE and analyzed associated neonatal outcomes in each arm. STUDY DESIGN: Following IRB approval, a validated research database of obstetrical and neonatal variables was used to identify women with EOSPE (24-34 weeks’ gestation) who delivered a live singleton from 1996-2006. Patients requiring immediate elective CS for non-reassuring fetal status (NRFS) or those requiring CS for the usual obstetric indications were excluded. Three groups of patients were assigned: successful IOL resulting in vaginal delivery (VD), failed-IOL resulting in CS, and elective CS. Logistic and multiple regression was used to examine differences in dichotomous outcomes and continuous variables, respectively, by delivery method controlling for gestational age. RESULTS: 582 women with EOSPE were included. 53% (n⫽310) underwent IOL, while 47% (n⫽272) had elective CS. IOL was successful in 54% (n⫽168) of cases. NRFS was present in 49% (n⫽69) of all failed IOL (n⫽142) at the time of CS. Only 16 of 62 patients ⬍ 28 weeks= were induced, and only 1 delivered vaginally. The incidences of successful IOL between 28-32 and 32-34 weeks= were 49% and 67%, respectively. When controlling for gestational age, mode of delivery was not associated with neonatal survival, necrotizing enterocolitis, respiratory distress, retinopathy of prematurity, intensive care unit admissions or length of stay (p ⬎ .05). CONCLUSION: IOL should be strongly considered beyond 28 weeks=. Larger sample sizes are required to evaluate success rates of IOL less than 28 weeks=. Additional investigation is needed to evaluate associations between mode of delivery and neonatal outcomes in women with EOSPE.
484
LEVELS OF SMOKE EXPOSURE DURING PREGNANCY AND THE INCIDENCE OF PREECLAMPSIA VANITHA JANAKIRAMAN1, MARIE GANTZ2, SHARON MAYNARD3, AYMAN EL-MOHANDES4, 1George Washington University, Department of Obstetrics and Gynecology, Washington, District of Columbia, 2Research Triangle Institute, North Carolina, 3George Washington University, Division of Renal Disease and Hypertension, District of Columbia, 4George Washington University, School of Public Health and Health Science, District of Columbia OBJECTIVE: To explore the effects of level of smoke exposure on the incidence of preeclampsia using a quantitative marker of nicotine. STUDY DESIGN: Data was analyzed from a prospective study. 1044 women were enrolled at ⬍29wks from prenatal clinics in Washington DC. A baseline interview and salivary samples were collected. Salivary cotinine (a stable nicotine metabolite) was measured using radioimmunoassay. Standardized medical record abstractions at enrollment and delivery were performed for outcome information, including presence of preeclampsia. RESULTS: 724 women with complete data were included. 18% were smokers. The incidence of preeclampsia was 6.6%. There was a lower incidence of preeclampsia among smokers (4.62% vs. 7.07%). The incidence of preeclampsia was compared between women above and below cutoffs of cotinine in 50 ng/ml increments. Exact logistic regression revealed a significant reduction in preeclampsia incidence at cotinine ⱖ200 in the unadjusted analysis and after controlling for age and parity. After adjusting for chronic hypertension, renal disease, and pregestational diabetes, the significance of this effect was reduced (see Table- “OR Adjusted” results were adjusted for age, parity, chronic hypertension, pregestational diabetes, and renal disease). There were no significant differences in preeclampsia rates using lower cutoffs for cotinine. CONCLUSION: Prior studies indicate that all smokers are protected against preeclampsia. This data suggests that women with cotinine levels of ⱖ200 have a very low risk of preeclampsia. Further studies should examine a possible threshold effect. Incidence of preeclampsia by cotinine level
0002-9378/$ - see front matter doi:10.1016/j.ajog.2007.10.555
Cotinine (ng/ml)
Pre-eclampsia
OR (95% CI)
OR adjusted (95% CI)
ⱕ50 vs ⬎50
40/584 (6.9%) vs 8/140 (5.7%) 44/620 (7.1%) vs 4/104 (3.9%) 45/642 (7.0%) vs 3/82 (3.7%) 48/667 (7.2%) vs 0/57 (0%)
0.82 (0.38–1.80)
0.92 (0.41–2.06)
0.52 (0.13–1.48)
0.60 (0.15–1.74)
0.50 (0.10–1.63)
0.59 (0.11–1.94)
0.16 (0–0.90)
0.19 (0–1.11)
ⱕ100 vs ⬎100 483
RECURRENT PREECLAMPSIA AND ADVERSE BIRTH OUTCOMES IN A POPULATIONBASED STUDY JEN JEN CHANG1, LOUIS MUGLIA2, GEORGE MACONES2, 1Saint Louis University, Community Health in Epidemiology, St. Louis, Missouri, 2Washington University in St. Louis, St. Louis, Missouri OBJECTIVE: To examine the association between recurrent preeclampsia and the risk of preterm delivery and small for gestational age. STUDY DESIGN: We conducted a population-based cohort study using birth certificate data from the Missouri maternally linked cohort from 1989 to 1997. Data from women of their first 2 singleton pregnancies with gestational age between 20 to 44 weeks (n ⫽ 6829) were analyzed. Women with concurrent medical problems such as hypertension, renal disease, or diabetes mellitus were excluded. Preterm delivery (⬍ 35 weeks) and small for gestational age were the primary outcomes of interest. Multivariate logistic regression models were fit to estimate crude and adjusted odds ratios (aOR) and 95% confidence intervals (95% CI) of the association between recurrent preeclampsia and outcomes of interest. RESULTS: Fifteen percent of study subjects experienced recurrent preeclampsia. The crude OR for small for gestational age was 2.47 (2.00, 3.05) and 3.29 (2.53, 4.27) for preterm delivery. In adjusted analysis, recurrent preeclampsia was associated with increased odds of both small for gestational age and preterm delivery by more than two folds (aOR: 2.44, 95% CI: 1.93, 3.08 and aOR: 2.72, 95% CI: 2.03, 3.63, respectively), after controlling for maternal age, race, Medicaid receipt, smoking during pregnancy, prepregnancy BMI, prenatal care, and history of previous preterm or small-for-gestational-age infant. CONCLUSION: Our study confirmed the increased risk of preterm delivery and having small-for-gestational-age infant when women experienced recurrent preeclampsia. 0002-9378/$ - see front matter doi:10.1016/j.ajog.2007.10.556
ⱕ150 vs ⬎150 ⱕ200 vs ⬎200
0002-9378/$ - see front matter doi:10.1016/j.ajog.2007.10.557
485
FETAL PROGRAMMING OF ADULT VASCULAR FUNCTION IN A PREECLAMPSIA-LIKE ANIMAL MODEL IS GENDER-SPECIFIC FANGXIAN LU, NIMA GOHARKHAY, EGLE BYTAUTIENE, ESTHER TAMAYO, PHYLLIS ORISE, GARLAND D. ANDERSON, MONICA LONGO, GEORGE R. SAADE, The University of Texas Medical Branch, Obstetrics and Gynecology, Galveston, Texas OBJECTIVE: We, and others, have shown that over-expression of sFlt-1 in pregnant rodents leads to a preeclampsia-like condition which results in altered fetal programming and hypertension in the offspring later in life. Our aim in this study was to determine the mechanisms underlying this hypertension by investigating the effect of preeclampsia on fetal programming of vascular reactivity in adult offspring. STUDY DESIGN: As previously established, CD-1 mothers at day 8 of gestation (term, day 18) were injected with an adenovirus carrying Flt (1-3) [AdFlt (1-3); 109 PFU] or carrying mFc as control virus (109 PFU), and allowed to deliver. Offspring were sacrificed at 6 months of age (n⫽10-15/group), and 2 mm segments of carotid artery were mounted in a wire myograph for isometric tension recording. Responses to KCL were determined, and concentration-response curves to acetylcholine (Ach, 10-10-10-5M), sodium nitroprusside (SNP, 10-10-10-5 M), phenylephrine (PE, 10-10-10-5M), and thromboxane A2 (TxA2, 10-10-10-6 M) were obtained. One-way ANOVA followed by Newman-Keuls post-hoc test were used for statistical analysis (significance: p⬍0.05). RESULTS: There were no significant differences in vascular responses to any of the agents used (PE, KCL, TXA2, Ach and SNP) between the female offspring born to sFlt-1 versus those born to mFc treated mothers. However, male offspring born to sFlt-1 treated mother showed significantly higher response to PE compared with control (maximum effect: 194.09 ⫾14.38 versus 114.33 ⫾ 17.33). The vasorelaxant responses to Ach and SNP were significantly lower in the male offspring sFlt-1 group compared with the control. CONCLUSION: Over-expression of sFlt-1 in the mothers leads to alterated adult vascular function only in male offspring. We speculate that the gender-specific effect of fetal programming of vascular function in this animal model of preeclampsia involves receptor- or endothelial-dependent mechanisms that are sensitive to hormonal influences, with an estrogenic milieu having a protective effect. 0002-9378/$ - see front matter doi:10.1016/j.ajog.2007.10.558
Supplement to DECEMBER 2007 American Journal of Obstetrics & Gynecology
S141
www.AJOG.org 482
EARLY ONSET SEVERE PREECLAMPSIA: MODE OF DELIVERY AND NEONATAL OUTCOMES MARK ALANIS1, HULSEY THOMAS2, CHRISTOPHER ROBINSON1, MYLA EBELING2, DONNA JOHNSON1, 1Medical University of South Carolina, Department of Obstetrics and Gynecology, Charleston, South Carolina, 2Medical University of South Carolina, Department of Pediatrics, Charleston, South Carolina OBJECTIVE: Many physicians choose elective cesarean section (CS) instead of induction of labor (IOL) for patients with early onset severe preeclampsia (EOSPE), despite little evidence to support this practice. We compared the mode of delivery in women with EOSPE and analyzed associated neonatal outcomes in each arm. STUDY DESIGN: Following IRB approval, a validated research database of obstetrical and neonatal variables was used to identify women with EOSPE (24-34 weeks’ gestation) who delivered a live singleton from 1996-2006. Patients requiring immediate elective CS for non-reassuring fetal status (NRFS) or those requiring CS for the usual obstetric indications were excluded. Three groups of patients were assigned: successful IOL resulting in vaginal delivery (VD), failed-IOL resulting in CS, and elective CS. Logistic and multiple regression was used to examine differences in dichotomous outcomes and continuous variables, respectively, by delivery method controlling for gestational age. RESULTS: 582 women with EOSPE were included. 53% (n⫽310) underwent IOL, while 47% (n⫽272) had elective CS. IOL was successful in 54% (n⫽168) of cases. NRFS was present in 49% (n⫽69) of all failed IOL (n⫽142) at the time of CS. Only 16 of 62 patients ⬍ 28 weeks= were induced, and only 1 delivered vaginally. The incidences of successful IOL between 28-32 and 32-34 weeks= were 49% and 67%, respectively. When controlling for gestational age, mode of delivery was not associated with neonatal survival, necrotizing enterocolitis, respiratory distress, retinopathy of prematurity, intensive care unit admissions or length of stay (p ⬎ .05). CONCLUSION: IOL should be strongly considered beyond 28 weeks=. Larger sample sizes are required to evaluate success rates of IOL less than 28 weeks=. Additional investigation is needed to evaluate associations between mode of delivery and neonatal outcomes in women with EOSPE.
484
LEVELS OF SMOKE EXPOSURE DURING PREGNANCY AND THE INCIDENCE OF PREECLAMPSIA VANITHA JANAKIRAMAN1, MARIE GANTZ2, SHARON MAYNARD3, AYMAN EL-MOHANDES4, 1George Washington University, Department of Obstetrics and Gynecology, Washington, District of Columbia, 2Research Triangle Institute, North Carolina, 3George Washington University, Division of Renal Disease and Hypertension, District of Columbia, 4George Washington University, School of Public Health and Health Science, District of Columbia OBJECTIVE: To explore the effects of level of smoke exposure on the incidence of preeclampsia using a quantitative marker of nicotine. STUDY DESIGN: Data was analyzed from a prospective study. 1044 women were enrolled at ⬍29wks from prenatal clinics in Washington DC. A baseline interview and salivary samples were collected. Salivary cotinine (a stable nicotine metabolite) was measured using radioimmunoassay. Standardized medical record abstractions at enrollment and delivery were performed for outcome information, including presence of preeclampsia. RESULTS: 724 women with complete data were included. 18% were smokers. The incidence of preeclampsia was 6.6%. There was a lower incidence of preeclampsia among smokers (4.62% vs. 7.07%). The incidence of preeclampsia was compared between women above and below cutoffs of cotinine in 50 ng/ml increments. Exact logistic regression revealed a significant reduction in preeclampsia incidence at cotinine ⱖ200 in the unadjusted analysis and after controlling for age and parity. After adjusting for chronic hypertension, renal disease, and pregestational diabetes, the significance of this effect was reduced (see Table- “OR Adjusted” results were adjusted for age, parity, chronic hypertension, pregestational diabetes, and renal disease). There were no significant differences in preeclampsia rates using lower cutoffs for cotinine. CONCLUSION: Prior studies indicate that all smokers are protected against preeclampsia. This data suggests that women with cotinine levels of ⱖ200 have a very low risk of preeclampsia. Further studies should examine a possible threshold effect. Incidence of preeclampsia by cotinine level
0002-9378/$ - see front matter doi:10.1016/j.ajog.2007.10.555
Cotinine (ng/ml)
Pre-eclampsia
OR (95% CI)
OR adjusted (95% CI)
ⱕ50 vs ⬎50
40/584 (6.9%) vs 8/140 (5.7%) 44/620 (7.1%) vs 4/104 (3.9%) 45/642 (7.0%) vs 3/82 (3.7%) 48/667 (7.2%) vs 0/57 (0%)
0.82 (0.38–1.80)
0.92 (0.41–2.06)
0.52 (0.13–1.48)
0.60 (0.15–1.74)
0.50 (0.10–1.63)
0.59 (0.11–1.94)
0.16 (0–0.90)
0.19 (0–1.11)
ⱕ100 vs ⬎100 483
RECURRENT PREECLAMPSIA AND ADVERSE BIRTH OUTCOMES IN A POPULATIONBASED STUDY JEN JEN CHANG1, LOUIS MUGLIA2, GEORGE MACONES2, 1Saint Louis University, Community Health in Epidemiology, St. Louis, Missouri, 2Washington University in St. Louis, St. Louis, Missouri OBJECTIVE: To examine the association between recurrent preeclampsia and the risk of preterm delivery and small for gestational age. STUDY DESIGN: We conducted a population-based cohort study using birth certificate data from the Missouri maternally linked cohort from 1989 to 1997. Data from women of their first 2 singleton pregnancies with gestational age between 20 to 44 weeks (n ⫽ 6829) were analyzed. Women with concurrent medical problems such as hypertension, renal disease, or diabetes mellitus were excluded. Preterm delivery (⬍ 35 weeks) and small for gestational age were the primary outcomes of interest. Multivariate logistic regression models were fit to estimate crude and adjusted odds ratios (aOR) and 95% confidence intervals (95% CI) of the association between recurrent preeclampsia and outcomes of interest. RESULTS: Fifteen percent of study subjects experienced recurrent preeclampsia. The crude OR for small for gestational age was 2.47 (2.00, 3.05) and 3.29 (2.53, 4.27) for preterm delivery. In adjusted analysis, recurrent preeclampsia was associated with increased odds of both small for gestational age and preterm delivery by more than two folds (aOR: 2.44, 95% CI: 1.93, 3.08 and aOR: 2.72, 95% CI: 2.03, 3.63, respectively), after controlling for maternal age, race, Medicaid receipt, smoking during pregnancy, prepregnancy BMI, prenatal care, and history of previous preterm or small-for-gestational-age infant. CONCLUSION: Our study confirmed the increased risk of preterm delivery and having small-for-gestational-age infant when women experienced recurrent preeclampsia. 0002-9378/$ - see front matter doi:10.1016/j.ajog.2007.10.556
ⱕ150 vs ⬎150 ⱕ200 vs ⬎200
0002-9378/$ - see front matter doi:10.1016/j.ajog.2007.10.557
485
FETAL PROGRAMMING OF ADULT VASCULAR FUNCTION IN A PREECLAMPSIA-LIKE ANIMAL MODEL IS GENDER-SPECIFIC FANGXIAN LU, NIMA GOHARKHAY, EGLE BYTAUTIENE, ESTHER TAMAYO, PHYLLIS ORISE, GARLAND D. ANDERSON, MONICA LONGO, GEORGE R. SAADE, The University of Texas Medical Branch, Obstetrics and Gynecology, Galveston, Texas OBJECTIVE: We, and others, have shown that over-expression of sFlt-1 in pregnant rodents leads to a preeclampsia-like condition which results in altered fetal programming and hypertension in the offspring later in life. Our aim in this study was to determine the mechanisms underlying this hypertension by investigating the effect of preeclampsia on fetal programming of vascular reactivity in adult offspring. STUDY DESIGN: As previously established, CD-1 mothers at day 8 of gestation (term, day 18) were injected with an adenovirus carrying Flt (1-3) [AdFlt (1-3); 109 PFU] or carrying mFc as control virus (109 PFU), and allowed to deliver. Offspring were sacrificed at 6 months of age (n⫽10-15/group), and 2 mm segments of carotid artery were mounted in a wire myograph for isometric tension recording. Responses to KCL were determined, and concentration-response curves to acetylcholine (Ach, 10-10-10-5M), sodium nitroprusside (SNP, 10-10-10-5 M), phenylephrine (PE, 10-10-10-5M), and thromboxane A2 (TxA2, 10-10-10-6 M) were obtained. One-way ANOVA followed by Newman-Keuls post-hoc test were used for statistical analysis (significance: p⬍0.05). RESULTS: There were no significant differences in vascular responses to any of the agents used (PE, KCL, TXA2, Ach and SNP) between the female offspring born to sFlt-1 versus those born to mFc treated mothers. However, male offspring born to sFlt-1 treated mother showed significantly higher response to PE compared with control (maximum effect: 194.09 ⫾14.38 versus 114.33 ⫾ 17.33). The vasorelaxant responses to Ach and SNP were significantly lower in the male offspring sFlt-1 group compared with the control. CONCLUSION: Over-expression of sFlt-1 in the mothers leads to alterated adult vascular function only in male offspring. We speculate that the gender-specific effect of fetal programming of vascular function in this animal model of preeclampsia involves receptor- or endothelial-dependent mechanisms that are sensitive to hormonal influences, with an estrogenic milieu having a protective effect. 0002-9378/$ - see front matter doi:10.1016/j.ajog.2007.10.558
Supplement to DECEMBER 2007 American Journal of Obstetrics & Gynecology
S141