- Email: [email protected]
10 Acute blood pressure variability response to antihypertensive drugs in an experimental model of preeclampsia
Abstracts / Pregnancy Hypertension: An International Journal of Women’s Cardiovascular Health 6 (2016) 137–177
Results: A total of 550 participants from the PROGNOSIS validation cohort were included in this analysis (median age 31 years; median pre-pregnancy body mass index 26.2 kg/m2; median systolic blood pressure 128.0 mmHg; median gestation week 31w + 3d; 79 (14%) were current smokers; 418 (76%) were white/Caucasian). Of these, 98 (18%) developed preeclampsia/HELLP syndrome at some point during their pregnancy: 15 (3%) within one week; 41 (7%) within two weeks; 60 (11%) within three weeks; and 71 (13%) within four weeks. The NPV to rule out preeclampsia in women with sFlt-1/ PlGF values of 38 and below within two, three and four weeks of testing was 97.9% (95% confidence interval [CI]: 96.0–99.0), 95.7% (95% CI: 93.3–97.5), and 94.3% (95% CI: 91.7–96.3), respectively (Table). Conclusions: This post-hoc analysis of PROGNOSIS shows that sFlt-1/PlGF ratios of 38 and below could rule out preeclampsia for up to four weeks after testing with high NPV in women with suspicion of the syndrome.
Table. NPV using the sFlt-1/PlGF ratio cut-off value of 38 to rule out preeclampsia within one, two, three, and four weeks after testing % (95% CI) Within 1 week NPV
Within 2 weeks Within 3 weeks Within 4 weeks
99.3 (97.9–99.9) 97.9 (96.0–99.0) 95.7 (93.3–97.5) 94.3 (91.7–96.3)
Sensitivity 80.0 (51.9–95.7) 78.0 (62.4–89.4) 70.0 (56.8–81.2) 66.2 (54.0–77.0) Specificity 78.3 (74.6–81.7) 81.1 (77.5–84.4) 82.4 (78.8–85.7) 83.1 (79.4–86.3)
doi:10.1016/j.preghy.2016.08.009
Clinical science 9 Pregnancy and chronic hypertension: Nifedipine vs labetalol as antihypertensive treatment (the panda study) Anti-hypertensive medications Louise Webster a, Jenny Myers b, Catherine Nelson-piercy a, Ingrid Watt-Coote c, Cornelia Wiesender d, Paul T. Seed a, Lucy C. Chappell a (a King’s College London, London, United Kingdom, b University of Manchester, Manchester, United Kingdom, c St. George’s University of London, London, United Kingdom, d Leicester Royal Infirmary, Leicester, United Kingdom) Introduction: Chronic hypertension complicates around 3% of all pregnancies and is associated with adverse maternal and perinatal outcome. The optimal antihypertensive treatment(s) for pregnancy complicated by chronic hypertension is uncertain. Choice of antihypertensive outside pregnancy depends on ethnicity. It is unclear if ethnicity impacts on the efficacy of antihypertensive treatment during pregnancy. Objectives: To perform a feasibility study to inform a randomised controlled trial in women with chronic hypertension in pregnancy, comparing nifedipine and labetalol for control of chronic hypertension in pregnancy, with additional assessment of the impact of ethnicity on efficacy of each treatment. Method: Pregnant women with chronic hypertension were enrolled between August 2014 and October 2015 at four UK centres, with the last woman delivering in April 2016. Participants were randomised to nifedipine or labetalol as antihypertensive treatment between 12 + 0 and 27 + 6 weeks’ gestation using a minimisation protocol. Demographic, serial longitudinal antenatal blood pressure
141
readings, and maternal/perinatal outcome data were collected and analysed. Results: 114 women were randomised to antihypertensive treatment (67% of those screened and eligible). Average monthly recruitment varied from 1.2 to 3.7 participants per centre. 54% (n = 62) of those recruited were of black ethnicity. 98% (n = 112) completed the study (1 withdrawal, 1 lost to follow-up). 12 participants (10.5%) (five in the nifedipine arm and seven in the labetalol arm) discontinued their assigned intervention due to side effects of the treatment and switched to alternative medication. Four women (3.6%) had a second trimester miscarriage and two women (1.8%) underwent termination of pregnancy (one with superimposed pre-eclampsia at 16 weeks’ gestation and one with a fetus with sickle cell disease on amniocentesis). Of the women whose pregnancies continued beyond 24 weeks’ gestation, 25% (n = 27) were diagnosed with superimposed pre-eclampsia; 27% (n = 29) of babies were delivered before 37 weeks’ gestation, 35% (n = 38) of birthweights were less than the 10th percentile, 17% (n = 20) of birthweights were less than the 3rd percentile and there were two stillbirths (1.9%). Conclusion: This study confirms good recruitment to a trial comparing commonly used antihypertensive agents for the treatment of chronic hypertension in pregnancy. In addition, the high incidence of adverse maternal and perinatal outcomes is highlighted within this cohort. Further exploration of the antenatal blood pressure profiles and maternal/perinatal outcomes within each treatment group is planned to assess efficacy. doi:10.1016/j.preghy.2016.08.010
Basic science 10 Acute blood pressure variability response to antihypertensive drugs in an experimental model of preeclampsia Suzanne Pears a, Paul Pilowsky b, Shikha Aggarwal c, Neroli Sunderland d, Shirlene Lim b, Katrina Chau a, Scott Heffernan d, Robert Ogle e, Jim Iliopoulos f, John Thompson g, Alicia Dennis h, Annemarie Hennessy c, Angela Makris c (a School of Medicine, b University of Sydney, Sydney, Australia, Heart Research c Institute, Sydney, Australia, School of Medicine, Western d Sydney University, Sydney, Australia, Royal Prince Alfred e Hospital, Sydney, Australia, Department of Obstetrics, Royal f Prince Alfred Hospital, Sydney, Australia, Department of Vascular Surgery, Liverpool Hospital, Sydney, Australia, g Department of Surgery, Royal Prince Alfred Hospital, Sydney, Australia, h The Royal Women’s Hospital, Melbourne, Australia) Introduction: Increased blood pressure (BP), especially sudden, unexpected and severe rises in women with preeclampsia considerably increases the risk of peripartum complications. A specific quantitative criterion for diagnosing labile blood pressure does not exist and minimal evidence is available to guide therapeutic decisions. Objectives: To assess the effect of antihypertensives commonly used to manage hypertension in pregnant women on blood pressure lability at rest in an experimental model of preeclampsia (EPE). Methods: EPE was established in Papio hamadryas (n = 6) by surgically ligating the non-dominant uterine branch artery to reduce perfusion by 30–40%. EPE was confirmed by assessing proteinuria (urine protein:creatinine ratio mmol/L), BP changes (intra-arterial radiotelemetry) and soluble fms-like tyrosine kinase receptor-1 (sFLT-1) (ELISA). BP readings were collected every 20 s before and
142
Abstracts / Pregnancy Hypertension: An International Journal of Women’s Cardiovascular Health 6 (2016) 137–177
after antihypertensive treatment. Equipotent doses of labetalol, methyldopa and hydralazine were given. Lability was defined by SD1 and SD2 values as measures of shortterm variability (STV) and long-term variability (LTV) respectively. These values were generated using Poincaré plots (Spike2 v8.06). Prism GraphPad6 v6.05 was used for parametric testing, data expressed as mean ± SEM and significance set at p < 0.05. The Sydney Local Heath District Animal Welfare Committee approved this project. Results: All animals developed EPE, demonstrated by systolic BP rise of 7.1 mmHg (p < 0.05), diastolic BP rise of 6.8 mmHg (p < 0.05) and an increase in proteinuria of 32.2 mg/mmol (p < 0.05) compared to baseline. sFlt-1 levels increased significantly: prior to EPE (1998 ± 544 pg/mL, p < 0.05) and after 2 weeks of EPE (4463 ± 1249 pg/mL, p < 0.05). There was a significantly different effect of these three drugs on systolic BP variability (p < 0.05). Labetalol demonstrated the greatest systolic STV (1.173 ± 0.101). Post hoc analysis showed greatest difference in STV with labetalol as compared to hydralazine (0.15, CI 0.003–0.290, p = 0.03). Diastolic STV was not significantly affected. The three drugs did not significantly affect systolic or diastolic LTV. Conclusions: Systolic STV was affected by drug choice but not diastolic STV or LTV in EPE. doi:10.1016/j.preghy.2016.08.011
Basic science 11 Fetomaternal and peripheral immune status in preeclamptic and normotensive oocyte donation cases Immune and inflammatory mechanisms Shigeru Saito a, Yasushi Nakabayashi a, Akitoshi Nakashima b,c, Tomoko Adachi d, Masao Nakabayashi d (a Department of Obstetrics and Gynecology, University of Toyama, Toyama, b Japan, Dept. of Obstetrics and Gynecology, University of Toyama, Japan, c Dept. of Obstetrics and Gynecology, Aiiku H, Toyama, Japan, d Department of Obstetrics and Gynecology, Aiiku Hospital, Tokyo, Japan) Oocyte donation (OD) is a high risk for preeclampsia because a fetus is a complete allograft to the maternal host. However the differences of immune status between preeclamptic OD cases and normotensive OD cases have not been clarified. Objectives: To clarify the immunological differences between preeclamptic OD cases and normotensive OD cases. Methods: Deciduel CD3+Tcells, CD4+Tcells, CD8+Tcells, Foxp3 +Treg cells CD56+NK cells and CD68+ macrophage were evaluated by immunohistochemistry. Peripheral blood effector Treg cells were evaluated by flow cytometry in 5 preeclamptic OD cases and 16 normotensive OD cases. Results: The populations of CD3+ T cells, CD4+ T cells, CD8+ T cells, Foxp3+ Treg cells, CD56+ NK cells and CD68+ macrophage in placental bed biopsy samples of OD cases were significantly lower compare to those in normal pregnancy subjects. Those levels in preeclamptic OD cases were similar to those in normotensive OD cases. Same findings were observed in preeclamptic cases in natural
conception. Vascular remodeling of spiral arteries was very poor in OD cases regardless of the presence of preeclampsia. These findings were quite similar to those in preeclampsia of natural conception. Peripheral blood-effector Treg cells was significantly decreased in preeclampsia, but these levels in OD pregnancies were not changed in preeclamptic OD cases and normotensive OD cases. Conclusion: Poor vascular remodeling and some of the immunological changes were observed in uncomplicated OD pregnancy, but we have not yet identified the crucial factors that lead to preeclampsia in OD pregnancy. doi:10.1016/j.preghy.2016.08.012
Basic science 12 Difference in blood flow velocity of spiral arteries in placental syndrome-compared to healthy pregnancies Placenta and decidua Veronique Schiffer, Ghislaine Gruiskens, Chahinda Ghossein, Marc Spaanderman, Salwan Al-Nasiry (Maastricht UMC, Maastricht, Netherlands) Objectives: Directly measuring the spiral arteries instead of the uterine arteries could better reflect the pathological process underlying placenta insufficiency related diseases collectively known as placenta syndrome (PS). The purpose of this study is to examine if the blood flow velocity of spiral arteries in placenta syndromepregnancies is higher compared to healthy pregnancies and can be affected by location of spiral arteries. Methods: A cross sectional study was conducted in woman between 24 and 42 weeks of gestation reporting at the department of obstetrics in the MUMC+. Using a Voluson E8TM abdominal transducer with predefined settings, spiral artery flow velocity indices were measured in women with PS (preeclampsia, preterm delivery, pregnancy induced hypertension and intra uterine growth restriction) and compared to women with uncomplicated pregnancies. Results: Spiral artery Dopplers were successfully obtained in 32 PS- and 14 control pregnancies. Both groups were comparable in characteristics, except for diastolic blood pressure (73.4 ± 12.1 vs. 62 ± 6.8 mmHg, p = 0.02). Mean peak systolic velocity (PSV) in spiral arteries showed a linear decrease with advancing gestational age in both groups (0.94 ± 0.5 cm/s/week), but was significant higher in PSgroup (32.5 ± 8.7 cm/s) compared to control group (24.5 ± 7.1 cm/s, p = 0.03). As expected, the mean PSV of the centrally localized spiral arteries was lower compared to the peripherally localized spiral arteries in the control group (24.5 ± 7.1 cm/s vs. 34.1 ± 14.6 cm/s, p = 0.14). No such difference was found in the PS-group (34.3 ± 8.7 vs. 34.6 ± 23.4 cm/s, p = 0.87). Conclusions: Mean blood flow velocity of spiral arteries in placental syndrome pregnancies is higher compared to healthy pregnancies, suggesting that inadequate conversion of the spiral arteries can lead to placental syndrome. These promising findings need to be tested in a prospective cohort to determine the predictive value of spiral artery Dopplers in high risk pregnancies. doi:10.1016/j.preghy.2016.08.013
Results: A total of 550 participants from the PROGNOSIS validation cohort were included in this analysis (median age 31 years; median pre-pregnancy body mass index 26.2 kg/m2; median systolic blood pressure 128.0 mmHg; median gestation week 31w + 3d; 79 (14%) were current smokers; 418 (76%) were white/Caucasian). Of these, 98 (18%) developed preeclampsia/HELLP syndrome at some point during their pregnancy: 15 (3%) within one week; 41 (7%) within two weeks; 60 (11%) within three weeks; and 71 (13%) within four weeks. The NPV to rule out preeclampsia in women with sFlt-1/ PlGF values of 38 and below within two, three and four weeks of testing was 97.9% (95% confidence interval [CI]: 96.0–99.0), 95.7% (95% CI: 93.3–97.5), and 94.3% (95% CI: 91.7–96.3), respectively (Table). Conclusions: This post-hoc analysis of PROGNOSIS shows that sFlt-1/PlGF ratios of 38 and below could rule out preeclampsia for up to four weeks after testing with high NPV in women with suspicion of the syndrome.
Table. NPV using the sFlt-1/PlGF ratio cut-off value of 38 to rule out preeclampsia within one, two, three, and four weeks after testing % (95% CI) Within 1 week NPV
Within 2 weeks Within 3 weeks Within 4 weeks
99.3 (97.9–99.9) 97.9 (96.0–99.0) 95.7 (93.3–97.5) 94.3 (91.7–96.3)
Sensitivity 80.0 (51.9–95.7) 78.0 (62.4–89.4) 70.0 (56.8–81.2) 66.2 (54.0–77.0) Specificity 78.3 (74.6–81.7) 81.1 (77.5–84.4) 82.4 (78.8–85.7) 83.1 (79.4–86.3)
doi:10.1016/j.preghy.2016.08.009
Clinical science 9 Pregnancy and chronic hypertension: Nifedipine vs labetalol as antihypertensive treatment (the panda study) Anti-hypertensive medications Louise Webster a, Jenny Myers b, Catherine Nelson-piercy a, Ingrid Watt-Coote c, Cornelia Wiesender d, Paul T. Seed a, Lucy C. Chappell a (a King’s College London, London, United Kingdom, b University of Manchester, Manchester, United Kingdom, c St. George’s University of London, London, United Kingdom, d Leicester Royal Infirmary, Leicester, United Kingdom) Introduction: Chronic hypertension complicates around 3% of all pregnancies and is associated with adverse maternal and perinatal outcome. The optimal antihypertensive treatment(s) for pregnancy complicated by chronic hypertension is uncertain. Choice of antihypertensive outside pregnancy depends on ethnicity. It is unclear if ethnicity impacts on the efficacy of antihypertensive treatment during pregnancy. Objectives: To perform a feasibility study to inform a randomised controlled trial in women with chronic hypertension in pregnancy, comparing nifedipine and labetalol for control of chronic hypertension in pregnancy, with additional assessment of the impact of ethnicity on efficacy of each treatment. Method: Pregnant women with chronic hypertension were enrolled between August 2014 and October 2015 at four UK centres, with the last woman delivering in April 2016. Participants were randomised to nifedipine or labetalol as antihypertensive treatment between 12 + 0 and 27 + 6 weeks’ gestation using a minimisation protocol. Demographic, serial longitudinal antenatal blood pressure
141
readings, and maternal/perinatal outcome data were collected and analysed. Results: 114 women were randomised to antihypertensive treatment (67% of those screened and eligible). Average monthly recruitment varied from 1.2 to 3.7 participants per centre. 54% (n = 62) of those recruited were of black ethnicity. 98% (n = 112) completed the study (1 withdrawal, 1 lost to follow-up). 12 participants (10.5%) (five in the nifedipine arm and seven in the labetalol arm) discontinued their assigned intervention due to side effects of the treatment and switched to alternative medication. Four women (3.6%) had a second trimester miscarriage and two women (1.8%) underwent termination of pregnancy (one with superimposed pre-eclampsia at 16 weeks’ gestation and one with a fetus with sickle cell disease on amniocentesis). Of the women whose pregnancies continued beyond 24 weeks’ gestation, 25% (n = 27) were diagnosed with superimposed pre-eclampsia; 27% (n = 29) of babies were delivered before 37 weeks’ gestation, 35% (n = 38) of birthweights were less than the 10th percentile, 17% (n = 20) of birthweights were less than the 3rd percentile and there were two stillbirths (1.9%). Conclusion: This study confirms good recruitment to a trial comparing commonly used antihypertensive agents for the treatment of chronic hypertension in pregnancy. In addition, the high incidence of adverse maternal and perinatal outcomes is highlighted within this cohort. Further exploration of the antenatal blood pressure profiles and maternal/perinatal outcomes within each treatment group is planned to assess efficacy. doi:10.1016/j.preghy.2016.08.010
Basic science 10 Acute blood pressure variability response to antihypertensive drugs in an experimental model of preeclampsia Suzanne Pears a, Paul Pilowsky b, Shikha Aggarwal c, Neroli Sunderland d, Shirlene Lim b, Katrina Chau a, Scott Heffernan d, Robert Ogle e, Jim Iliopoulos f, John Thompson g, Alicia Dennis h, Annemarie Hennessy c, Angela Makris c (a School of Medicine, b University of Sydney, Sydney, Australia, Heart Research c Institute, Sydney, Australia, School of Medicine, Western d Sydney University, Sydney, Australia, Royal Prince Alfred e Hospital, Sydney, Australia, Department of Obstetrics, Royal f Prince Alfred Hospital, Sydney, Australia, Department of Vascular Surgery, Liverpool Hospital, Sydney, Australia, g Department of Surgery, Royal Prince Alfred Hospital, Sydney, Australia, h The Royal Women’s Hospital, Melbourne, Australia) Introduction: Increased blood pressure (BP), especially sudden, unexpected and severe rises in women with preeclampsia considerably increases the risk of peripartum complications. A specific quantitative criterion for diagnosing labile blood pressure does not exist and minimal evidence is available to guide therapeutic decisions. Objectives: To assess the effect of antihypertensives commonly used to manage hypertension in pregnant women on blood pressure lability at rest in an experimental model of preeclampsia (EPE). Methods: EPE was established in Papio hamadryas (n = 6) by surgically ligating the non-dominant uterine branch artery to reduce perfusion by 30–40%. EPE was confirmed by assessing proteinuria (urine protein:creatinine ratio mmol/L), BP changes (intra-arterial radiotelemetry) and soluble fms-like tyrosine kinase receptor-1 (sFLT-1) (ELISA). BP readings were collected every 20 s before and
142
Abstracts / Pregnancy Hypertension: An International Journal of Women’s Cardiovascular Health 6 (2016) 137–177
after antihypertensive treatment. Equipotent doses of labetalol, methyldopa and hydralazine were given. Lability was defined by SD1 and SD2 values as measures of shortterm variability (STV) and long-term variability (LTV) respectively. These values were generated using Poincaré plots (Spike2 v8.06). Prism GraphPad6 v6.05 was used for parametric testing, data expressed as mean ± SEM and significance set at p < 0.05. The Sydney Local Heath District Animal Welfare Committee approved this project. Results: All animals developed EPE, demonstrated by systolic BP rise of 7.1 mmHg (p < 0.05), diastolic BP rise of 6.8 mmHg (p < 0.05) and an increase in proteinuria of 32.2 mg/mmol (p < 0.05) compared to baseline. sFlt-1 levels increased significantly: prior to EPE (1998 ± 544 pg/mL, p < 0.05) and after 2 weeks of EPE (4463 ± 1249 pg/mL, p < 0.05). There was a significantly different effect of these three drugs on systolic BP variability (p < 0.05). Labetalol demonstrated the greatest systolic STV (1.173 ± 0.101). Post hoc analysis showed greatest difference in STV with labetalol as compared to hydralazine (0.15, CI 0.003–0.290, p = 0.03). Diastolic STV was not significantly affected. The three drugs did not significantly affect systolic or diastolic LTV. Conclusions: Systolic STV was affected by drug choice but not diastolic STV or LTV in EPE. doi:10.1016/j.preghy.2016.08.011
Basic science 11 Fetomaternal and peripheral immune status in preeclamptic and normotensive oocyte donation cases Immune and inflammatory mechanisms Shigeru Saito a, Yasushi Nakabayashi a, Akitoshi Nakashima b,c, Tomoko Adachi d, Masao Nakabayashi d (a Department of Obstetrics and Gynecology, University of Toyama, Toyama, b Japan, Dept. of Obstetrics and Gynecology, University of Toyama, Japan, c Dept. of Obstetrics and Gynecology, Aiiku H, Toyama, Japan, d Department of Obstetrics and Gynecology, Aiiku Hospital, Tokyo, Japan) Oocyte donation (OD) is a high risk for preeclampsia because a fetus is a complete allograft to the maternal host. However the differences of immune status between preeclamptic OD cases and normotensive OD cases have not been clarified. Objectives: To clarify the immunological differences between preeclamptic OD cases and normotensive OD cases. Methods: Deciduel CD3+Tcells, CD4+Tcells, CD8+Tcells, Foxp3 +Treg cells CD56+NK cells and CD68+ macrophage were evaluated by immunohistochemistry. Peripheral blood effector Treg cells were evaluated by flow cytometry in 5 preeclamptic OD cases and 16 normotensive OD cases. Results: The populations of CD3+ T cells, CD4+ T cells, CD8+ T cells, Foxp3+ Treg cells, CD56+ NK cells and CD68+ macrophage in placental bed biopsy samples of OD cases were significantly lower compare to those in normal pregnancy subjects. Those levels in preeclamptic OD cases were similar to those in normotensive OD cases. Same findings were observed in preeclamptic cases in natural
conception. Vascular remodeling of spiral arteries was very poor in OD cases regardless of the presence of preeclampsia. These findings were quite similar to those in preeclampsia of natural conception. Peripheral blood-effector Treg cells was significantly decreased in preeclampsia, but these levels in OD pregnancies were not changed in preeclamptic OD cases and normotensive OD cases. Conclusion: Poor vascular remodeling and some of the immunological changes were observed in uncomplicated OD pregnancy, but we have not yet identified the crucial factors that lead to preeclampsia in OD pregnancy. doi:10.1016/j.preghy.2016.08.012
Basic science 12 Difference in blood flow velocity of spiral arteries in placental syndrome-compared to healthy pregnancies Placenta and decidua Veronique Schiffer, Ghislaine Gruiskens, Chahinda Ghossein, Marc Spaanderman, Salwan Al-Nasiry (Maastricht UMC, Maastricht, Netherlands) Objectives: Directly measuring the spiral arteries instead of the uterine arteries could better reflect the pathological process underlying placenta insufficiency related diseases collectively known as placenta syndrome (PS). The purpose of this study is to examine if the blood flow velocity of spiral arteries in placenta syndromepregnancies is higher compared to healthy pregnancies and can be affected by location of spiral arteries. Methods: A cross sectional study was conducted in woman between 24 and 42 weeks of gestation reporting at the department of obstetrics in the MUMC+. Using a Voluson E8TM abdominal transducer with predefined settings, spiral artery flow velocity indices were measured in women with PS (preeclampsia, preterm delivery, pregnancy induced hypertension and intra uterine growth restriction) and compared to women with uncomplicated pregnancies. Results: Spiral artery Dopplers were successfully obtained in 32 PS- and 14 control pregnancies. Both groups were comparable in characteristics, except for diastolic blood pressure (73.4 ± 12.1 vs. 62 ± 6.8 mmHg, p = 0.02). Mean peak systolic velocity (PSV) in spiral arteries showed a linear decrease with advancing gestational age in both groups (0.94 ± 0.5 cm/s/week), but was significant higher in PSgroup (32.5 ± 8.7 cm/s) compared to control group (24.5 ± 7.1 cm/s, p = 0.03). As expected, the mean PSV of the centrally localized spiral arteries was lower compared to the peripherally localized spiral arteries in the control group (24.5 ± 7.1 cm/s vs. 34.1 ± 14.6 cm/s, p = 0.14). No such difference was found in the PS-group (34.3 ± 8.7 vs. 34.6 ± 23.4 cm/s, p = 0.87). Conclusions: Mean blood flow velocity of spiral arteries in placental syndrome pregnancies is higher compared to healthy pregnancies, suggesting that inadequate conversion of the spiral arteries can lead to placental syndrome. These promising findings need to be tested in a prospective cohort to determine the predictive value of spiral artery Dopplers in high risk pregnancies. doi:10.1016/j.preghy.2016.08.013