- Email: [email protected]
[249-POS]
Abstracts / Pregnancy Hypertension: An International Journal of Women’s Cardiovascular Health 5 (2015) 53–156
settings. Performance of the fullPIERS model using the miniPIERS dataset was assessed based on discrimination (AUC ROC), calibration (agreement between predicted and observed outcomes) and risk stratification (classification accuracy). Results: 14% of 757 women in the mini-PIERS dataset suffered an adverse maternal outcome within 48 h of admission. The fullPIERS model had moderate discriminative ability (AUC ROC 0.77, 95%CI 0.72–0.82). Upon baseline adjustment of the intercept to account for the difference in outcome prevalence, there was neither improvement in discrimination nor calibration of the model. The model was then recalibrated by (1) updating the intercept and, (2) updating both the intercept and the slope to account for differences in Case-Mix between the two cohorts. Both modifications had no effect on model discrimination but resulted in improved calibration and classification accuracy (Table 1). Conclusions: The fullPIERS model may not be ideal for maternal risk prediction in low-resourced setting due to differences in outcome prevalence and clinical practice.
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women was evaluated in the second year of life with the Bayley Scales of Infant and Toddler Development Third Edition (Bayley-III Screening). Results: The mean age of pregnant women was 25.8 years and the mean gestational age of 23.6 weeks review. The average pulsatility index of the uterine artery was 0.89 and 1.47 for the 95th percentile. Evaluation of children, showed no increased risk associated with delay in pulsatility index of uterine artery greater than or equal to the 95th percentile development (cognitive performance: RR 0.76, 95% CI 0.3–1.96, receptive communication: RR 1.17, 95% CI 0.46– 3.01, expressive communication: RR 0.66, 95% CI 0 0.67–1, 36, fine motor: RR 1.26, 95% CI 0.5–3.27, gross motor: RR 1.14 95% CI 0.44–2.94). Conclusions: The high flow resistance of the uterine artery in the second quarter, without deleting other perinatal factors, cannot be considered as a risk factor for the delay in child development. Additional studies should be performed excluding the perinatal risk factors such as prematurity that may adversely affect psychomotor performance of children.
Table 1. Risk stratification of adverse maternal outcome within 48 h for the Recalibrated intercept and slope. Group #
Prediction score range
Number of women (%)
Confidence Interval
Number of women with outcome (%)
True positive rate (%)
False positive rate (%)
1 2 3 4 5 6 7 Total
0–0.99 % 1–2.4% 2.5– 4.9% 5.0–9.9% 10–19% 20–29% P30%
6 (0.8%) 24 (3.2%) 115 (15.9%) 253 (33.4%) 225 (29.7%) 61 (8.1%) 73 (9.6%) 757
0.32–1.8% 2.1–4.8% 12.8–17.9% 30.1–36.9% 26.5–33.1% 6.3–10.3% 7.7–12.0%
1 (16.7%) [CI 0.88–63.5%] 1 (4.2%) [CI 0.22–23.1%] 3 (2.6%) [CI 0.68–8.0%] 16 (6.3%) [CI 3.77–10.26%] 33 (14.7%) [CI 10.45–20.13%] 12(19.7%) [CI 11.0–32.22%] 43(58.9%) [CI 46.77–70.09%] 109 (14.4%) [CI 12.0–17.2%]
– 99% 98% 95% 81% 50% 39%
– 99% 96% 78% 42% 12% 4.6%
Disclosures: U. Ukah: None. doi:10.1016/j.preghy.2014.10.253
Disclosures: M.M. Okido: None. L.B. Martins: None. T.V. Bertagnolli: None. M.A. Barbieri: None. H. Bettiol: None. V.C. Cardoso: None. R.C. Cavalli: None. doi:10.1016/j.preghy.2014.10.254
[248-POS] [249-POS] Relationship of uterine artery flow in the second trimester of pregnancy with the neurodevelopment of children in the second year of life – A cohort study Marcos M. Okido, Luiz Augusto B. Martins, Tawana V. Bertagnolli, Marco A. Barbieri, Heloisa Bettiol, Viviane C. Cardoso, Ricardo C. Cavalli (Ribeirão Preto Medical School – University of São Paulo, Ribeirão Preto, São Paulo, Brazil) Objectives: The association between increased resistance to flow in the uterine artery and adverse pregnancy outcomes has been demonstrated, but there are no studies evaluating their relationship with outcomes after birth. Our aim was to evaluate the relationship of the pulsatility index of the uterine artery in the second trimester of pregnancy with the neurodevelopment of children in the second year of life. Methods: A cohort study was performed involving 1370 women with singleton pregnancies. Pulsatility index of the uterine artery between 20 and 25 weeks was obtained. The psychomotor development of the children of these
Proteolytic activation of the epithelial sodium channel ENaC in preeclampsia examined with urinary exosomes Maria Ravn Nielsen a, Mie Rytz a, Britta FrederiksenMøller a, Per Svenningsen a, Rikke M. Zachar a, Jan Stener Jørgensen b, Boye Lagerbon Jensen a (a Institute of Molecular Medicine, Cardiovascular and Renal Research, University of Southern Denmark, Odense, Denmark, b Odense University Hospital, Odense, Denmark) Objectives: Increased activity of the epithelial sodium channel (ENaC) in the kidneys may explain the coupling between proteinuria, edema, suppressed aldosterone and hypertension in preeclampsia. Preeclamptic women excrete plasminogen-plasmin in urine. In vitro, plasmin increases the activity of ENaC by proteolytic cleavage of the c-subunit ectodomain and release of a 43-aminoacid inhibitory tract from the channel.
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Abstracts / Pregnancy Hypertension: An International Journal of Women’s Cardiovascular Health 5 (2015) 53–156
Exosomes are membrane vesicles released into the urine from apical membranes of the kidney epithelial cells. Objectives: (1) To investigate if the proteolytic state of the ENaC c-subnit can be studied in urine exosomes from pregnant women. (2) To investigate if the ENaC c-subunit ectodomain is abnormally activated by proteolysis in preeclamptic women. Methods: 100 mL spot urine samples from 14 preeclamptic women, 17 pregnant women and 9 non-pregnant women were collected with protease inhibitors. Plasmin/plasminogen was measured. Exosomes were recovered by ultracentrifugation at 220,000g at 4 °C for 100 min. The exosome fraction was used for western blotting with a newly developed monoclonal antibody, mAb3C7, directed against the ‘‘inhibitory’’ tract in c-ENaC. Aquaporin-2 (AQP2) was used as a positive control for the presence of collecting duct membrane. Results: Urine plasmin-plasminogen/creatinine ratio was increased in the preeclampsia group (p < 0.001). Plasma aldosterone was increased in pregnancy compared to nonpregnant women (p < 0.001). Creatinine-normalized urine exosome fractions were positive for AQP2. No intact, fulllength ENaC c-subunit was detected in the exosome fractions. In some samples the inhibitory tract was not detected while AQP2 was. Others displayed bands corresponding to ENaC cleaved by furin and/or by prostasin/plasmin, but with no systematic difference between normal pregnancy and preeclampsia Conclusions: It is possible to examine collecting duct transport proteins in urine exosome from pregnant women including c-ENaC, 2) Urine exosome fraction displays a variable pattern of c-ENaC signal with a predominance of cleaved forms in both normal and preeclamptic women. Disclosures: M.R. Nielsen: None. M. Rytz: None. B. Frederiksen-Møller: None. P. Svenningsen: None. R.M. Zachar: None. J.S. Jørgensen: None. B.L. Jensen: None. doi:10.1016/j.preghy.2014.10.255
[250-POS] Pregnancy outcomes of massively obese hypertensive gravidas David G. Chaffin Jr., Jessica Granger (Marshall University, Huntington, WV, USA) Objectives: The obesity epidemic is of increasing obstetrical concern as these women are more likely to be hypertensive prior to pregnancy and experience adverse outcomes. The purpose of this study was to examine the perinatal outcomes of conventionally managed massively obese gravidas with preexisting hypertension to management guided by hemodynamics obtained from impedance cardiography. Methods: The Cabell–Huntington Hospital maternal and neonatal charts of all patients hemodynamically evaluated using impedance cardiography weighing 300 lbs (136 kg) or more (58 study patients) were reviewed; controls were the most recently delivered 90 patients of similar weight with (n = 17) and without (n = 73) preexisting hypertension.
Differences demographic, pregnancy and delivery data were assessed by one-way ANOVA for continuous variables and Chi-square analysis for categorical data. Results: There was no difference in age, weight, or BMI or route of delivery. Although delivering at term, the treated infants delivered 12 days earlier. There was no difference in the mean birth weight percentile and rates of IUGR and macrosomia were similar. Conventionally treated hypertensive massively obese gravidas spent more days in the hospital as did their infants, possibly because the incidence of severe preeclampsia was higher (23% vs 6%) than in those whose antihypertensive therapy was hemodynamically directed. Conclusions: Obesity is a known risk factor for hypertensive disorders of pregnancy; in obese women with preexisting hypertension the risk is markedly higher. In massively obese women with preexisting hypertension, hemodynamically-guided treatment results in fewer cases of severe preeclampsia and fewer maternal and neonatal hospital days. Disclosures: D.G. Chaffin: Commercial Interest: MIST, LLC. J. Granger: None. doi:10.1016/j.preghy.2014.10.256
[251-POS] Risk of eclampsia compared to number of prenatal visits Elizabeth T. Greeley a, Kathryn L. Terry b, Jeffrey V. Spencer c (a North Shore University Hospital, Manhasset, NY, USA, b Brigham and Women’s Hospital, Boston, MA, USA, c The Center for Maternal Fetal Medicine, Annapolis, MD, USA) Objectives: To compare the relative risk of eclampsia and frequency of prenatal visits. Methods: We evaluated the risk of gestational hypertension with the number of prenatal visits in 4,247,694 delivered women included in the CDC 2008 Vital Stats dataset. The incidence of eclampsia among subgroups of women defined by their number of prenatal visits was calculated. Relative risks were determined for each subgroup by comparing the incidence of eclampsia in each subgroup compared to those women with 13–14 visits (reference group). These groups were (1) no visits, (2) 1–2 visits, (3) 3–4 visits, (4) 5–6 visits, (5) 7–8 visits, (6) 9–10 visits, (7) 11–12 visits, (8) 13–14 visits {reference group}, (9) 15–16 visits, (10) 17–18 visits, (11) 19 or more visits. Results: The relative risk of eclampsia increased as the number of prenatal visits decreased, with the highest risk among those women who had no prenatal visits (RR = 2.16, 95% CI = 1.90–2.45). The relative risk of eclampsia also increased as the number of prenatal visits increased above 13–14 visits. The highest risk was for those women with 19 or more visits (RR = 2.34, 95%, CI = 2.13–2.58). Conclusions: Fewer prenatal visits may be associated with a higher risk of eclampsia. This may be due to iatrogenic preterm delivery or poor patient compliance. Eclampsia may also be associated with an increased number of prenatal visits. This may be due to close monitoring of a high risk patient.
settings. Performance of the fullPIERS model using the miniPIERS dataset was assessed based on discrimination (AUC ROC), calibration (agreement between predicted and observed outcomes) and risk stratification (classification accuracy). Results: 14% of 757 women in the mini-PIERS dataset suffered an adverse maternal outcome within 48 h of admission. The fullPIERS model had moderate discriminative ability (AUC ROC 0.77, 95%CI 0.72–0.82). Upon baseline adjustment of the intercept to account for the difference in outcome prevalence, there was neither improvement in discrimination nor calibration of the model. The model was then recalibrated by (1) updating the intercept and, (2) updating both the intercept and the slope to account for differences in Case-Mix between the two cohorts. Both modifications had no effect on model discrimination but resulted in improved calibration and classification accuracy (Table 1). Conclusions: The fullPIERS model may not be ideal for maternal risk prediction in low-resourced setting due to differences in outcome prevalence and clinical practice.
125
women was evaluated in the second year of life with the Bayley Scales of Infant and Toddler Development Third Edition (Bayley-III Screening). Results: The mean age of pregnant women was 25.8 years and the mean gestational age of 23.6 weeks review. The average pulsatility index of the uterine artery was 0.89 and 1.47 for the 95th percentile. Evaluation of children, showed no increased risk associated with delay in pulsatility index of uterine artery greater than or equal to the 95th percentile development (cognitive performance: RR 0.76, 95% CI 0.3–1.96, receptive communication: RR 1.17, 95% CI 0.46– 3.01, expressive communication: RR 0.66, 95% CI 0 0.67–1, 36, fine motor: RR 1.26, 95% CI 0.5–3.27, gross motor: RR 1.14 95% CI 0.44–2.94). Conclusions: The high flow resistance of the uterine artery in the second quarter, without deleting other perinatal factors, cannot be considered as a risk factor for the delay in child development. Additional studies should be performed excluding the perinatal risk factors such as prematurity that may adversely affect psychomotor performance of children.
Table 1. Risk stratification of adverse maternal outcome within 48 h for the Recalibrated intercept and slope. Group #
Prediction score range
Number of women (%)
Confidence Interval
Number of women with outcome (%)
True positive rate (%)
False positive rate (%)
1 2 3 4 5 6 7 Total
0–0.99 % 1–2.4% 2.5– 4.9% 5.0–9.9% 10–19% 20–29% P30%
6 (0.8%) 24 (3.2%) 115 (15.9%) 253 (33.4%) 225 (29.7%) 61 (8.1%) 73 (9.6%) 757
0.32–1.8% 2.1–4.8% 12.8–17.9% 30.1–36.9% 26.5–33.1% 6.3–10.3% 7.7–12.0%
1 (16.7%) [CI 0.88–63.5%] 1 (4.2%) [CI 0.22–23.1%] 3 (2.6%) [CI 0.68–8.0%] 16 (6.3%) [CI 3.77–10.26%] 33 (14.7%) [CI 10.45–20.13%] 12(19.7%) [CI 11.0–32.22%] 43(58.9%) [CI 46.77–70.09%] 109 (14.4%) [CI 12.0–17.2%]
– 99% 98% 95% 81% 50% 39%
– 99% 96% 78% 42% 12% 4.6%
Disclosures: U. Ukah: None. doi:10.1016/j.preghy.2014.10.253
Disclosures: M.M. Okido: None. L.B. Martins: None. T.V. Bertagnolli: None. M.A. Barbieri: None. H. Bettiol: None. V.C. Cardoso: None. R.C. Cavalli: None. doi:10.1016/j.preghy.2014.10.254
[248-POS] [249-POS] Relationship of uterine artery flow in the second trimester of pregnancy with the neurodevelopment of children in the second year of life – A cohort study Marcos M. Okido, Luiz Augusto B. Martins, Tawana V. Bertagnolli, Marco A. Barbieri, Heloisa Bettiol, Viviane C. Cardoso, Ricardo C. Cavalli (Ribeirão Preto Medical School – University of São Paulo, Ribeirão Preto, São Paulo, Brazil) Objectives: The association between increased resistance to flow in the uterine artery and adverse pregnancy outcomes has been demonstrated, but there are no studies evaluating their relationship with outcomes after birth. Our aim was to evaluate the relationship of the pulsatility index of the uterine artery in the second trimester of pregnancy with the neurodevelopment of children in the second year of life. Methods: A cohort study was performed involving 1370 women with singleton pregnancies. Pulsatility index of the uterine artery between 20 and 25 weeks was obtained. The psychomotor development of the children of these
Proteolytic activation of the epithelial sodium channel ENaC in preeclampsia examined with urinary exosomes Maria Ravn Nielsen a, Mie Rytz a, Britta FrederiksenMøller a, Per Svenningsen a, Rikke M. Zachar a, Jan Stener Jørgensen b, Boye Lagerbon Jensen a (a Institute of Molecular Medicine, Cardiovascular and Renal Research, University of Southern Denmark, Odense, Denmark, b Odense University Hospital, Odense, Denmark) Objectives: Increased activity of the epithelial sodium channel (ENaC) in the kidneys may explain the coupling between proteinuria, edema, suppressed aldosterone and hypertension in preeclampsia. Preeclamptic women excrete plasminogen-plasmin in urine. In vitro, plasmin increases the activity of ENaC by proteolytic cleavage of the c-subunit ectodomain and release of a 43-aminoacid inhibitory tract from the channel.
126
Abstracts / Pregnancy Hypertension: An International Journal of Women’s Cardiovascular Health 5 (2015) 53–156
Exosomes are membrane vesicles released into the urine from apical membranes of the kidney epithelial cells. Objectives: (1) To investigate if the proteolytic state of the ENaC c-subnit can be studied in urine exosomes from pregnant women. (2) To investigate if the ENaC c-subunit ectodomain is abnormally activated by proteolysis in preeclamptic women. Methods: 100 mL spot urine samples from 14 preeclamptic women, 17 pregnant women and 9 non-pregnant women were collected with protease inhibitors. Plasmin/plasminogen was measured. Exosomes were recovered by ultracentrifugation at 220,000g at 4 °C for 100 min. The exosome fraction was used for western blotting with a newly developed monoclonal antibody, mAb3C7, directed against the ‘‘inhibitory’’ tract in c-ENaC. Aquaporin-2 (AQP2) was used as a positive control for the presence of collecting duct membrane. Results: Urine plasmin-plasminogen/creatinine ratio was increased in the preeclampsia group (p < 0.001). Plasma aldosterone was increased in pregnancy compared to nonpregnant women (p < 0.001). Creatinine-normalized urine exosome fractions were positive for AQP2. No intact, fulllength ENaC c-subunit was detected in the exosome fractions. In some samples the inhibitory tract was not detected while AQP2 was. Others displayed bands corresponding to ENaC cleaved by furin and/or by prostasin/plasmin, but with no systematic difference between normal pregnancy and preeclampsia Conclusions: It is possible to examine collecting duct transport proteins in urine exosome from pregnant women including c-ENaC, 2) Urine exosome fraction displays a variable pattern of c-ENaC signal with a predominance of cleaved forms in both normal and preeclamptic women. Disclosures: M.R. Nielsen: None. M. Rytz: None. B. Frederiksen-Møller: None. P. Svenningsen: None. R.M. Zachar: None. J.S. Jørgensen: None. B.L. Jensen: None. doi:10.1016/j.preghy.2014.10.255
[250-POS] Pregnancy outcomes of massively obese hypertensive gravidas David G. Chaffin Jr., Jessica Granger (Marshall University, Huntington, WV, USA) Objectives: The obesity epidemic is of increasing obstetrical concern as these women are more likely to be hypertensive prior to pregnancy and experience adverse outcomes. The purpose of this study was to examine the perinatal outcomes of conventionally managed massively obese gravidas with preexisting hypertension to management guided by hemodynamics obtained from impedance cardiography. Methods: The Cabell–Huntington Hospital maternal and neonatal charts of all patients hemodynamically evaluated using impedance cardiography weighing 300 lbs (136 kg) or more (58 study patients) were reviewed; controls were the most recently delivered 90 patients of similar weight with (n = 17) and without (n = 73) preexisting hypertension.
Differences demographic, pregnancy and delivery data were assessed by one-way ANOVA for continuous variables and Chi-square analysis for categorical data. Results: There was no difference in age, weight, or BMI or route of delivery. Although delivering at term, the treated infants delivered 12 days earlier. There was no difference in the mean birth weight percentile and rates of IUGR and macrosomia were similar. Conventionally treated hypertensive massively obese gravidas spent more days in the hospital as did their infants, possibly because the incidence of severe preeclampsia was higher (23% vs 6%) than in those whose antihypertensive therapy was hemodynamically directed. Conclusions: Obesity is a known risk factor for hypertensive disorders of pregnancy; in obese women with preexisting hypertension the risk is markedly higher. In massively obese women with preexisting hypertension, hemodynamically-guided treatment results in fewer cases of severe preeclampsia and fewer maternal and neonatal hospital days. Disclosures: D.G. Chaffin: Commercial Interest: MIST, LLC. J. Granger: None. doi:10.1016/j.preghy.2014.10.256
[251-POS] Risk of eclampsia compared to number of prenatal visits Elizabeth T. Greeley a, Kathryn L. Terry b, Jeffrey V. Spencer c (a North Shore University Hospital, Manhasset, NY, USA, b Brigham and Women’s Hospital, Boston, MA, USA, c The Center for Maternal Fetal Medicine, Annapolis, MD, USA) Objectives: To compare the relative risk of eclampsia and frequency of prenatal visits. Methods: We evaluated the risk of gestational hypertension with the number of prenatal visits in 4,247,694 delivered women included in the CDC 2008 Vital Stats dataset. The incidence of eclampsia among subgroups of women defined by their number of prenatal visits was calculated. Relative risks were determined for each subgroup by comparing the incidence of eclampsia in each subgroup compared to those women with 13–14 visits (reference group). These groups were (1) no visits, (2) 1–2 visits, (3) 3–4 visits, (4) 5–6 visits, (5) 7–8 visits, (6) 9–10 visits, (7) 11–12 visits, (8) 13–14 visits {reference group}, (9) 15–16 visits, (10) 17–18 visits, (11) 19 or more visits. Results: The relative risk of eclampsia increased as the number of prenatal visits decreased, with the highest risk among those women who had no prenatal visits (RR = 2.16, 95% CI = 1.90–2.45). The relative risk of eclampsia also increased as the number of prenatal visits increased above 13–14 visits. The highest risk was for those women with 19 or more visits (RR = 2.34, 95%, CI = 2.13–2.58). Conclusions: Fewer prenatal visits may be associated with a higher risk of eclampsia. This may be due to iatrogenic preterm delivery or poor patient compliance. Eclampsia may also be associated with an increased number of prenatal visits. This may be due to close monitoring of a high risk patient.