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Validation of predictive models for pre-eclampsia
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Abstracts / Pregnancy Hypertension: An International Journal of Women’s Cardiovascular Health 7 (2017) 56–64
pled with receptor-specific antagonists [3]. Blood from 10 of the women from 5 to 8 years postpartum was also analyzed for AT1AA. Non-parametric statistics were used and P < 0.05 was considered statistically significant. Results: Preeclamptic women had a significantly higher incidence of AT1-AA than controls (57% vs 22%, P = 0.03). Acute atherosis did not correlate with AT1-AA. At 5–8 years postpartum, 2 of 10 women had circulating AT1-AA. Both these had previously a diagnosis of preeclampsia, without acute atherosis. Conclusions: Preeclamptic women have high rates of AT1-AA, but AT1-AA have no general correlation to acute atherosis. AT1-AA may persist after preeclampsia, and their association with future cardiovascular risk is unknown. References [1] P. Alnaes-Katjavivi, F. Lyall, B. Roald, C.W. Redman, A.C. Staff, Acute atherosis in vacuum suction biopsies of decidua basalis: An evidence based research definition, Placenta (2016) 37 (2016) 26–33. [2] N.K. Harsem, A.C. Staff, L. He, B. Roald, The decidual suction method: a new way of collecting decidual tissue for functional and morphological studies, Acta Obstet. Gynecol. Scand. (2004) 83 (8) (2004) 724–730. [3] F. Herse, R. Dechend, N.K. Harsem, G. Wallukat, J. Janke, F. Qadri, et al, Hypertension (2007) 49 (3) (2007) 604–611. doi:10.1016/j.preghy.2016.10.019
Validation of predictive models for pre-eclampsia Federico Prefumo (Department of Obstetrics and Gynaecology, University of Brescia, Italy) Prediction model are frequently proposed for use in obstetrics. It is recommended that they undergo internal and external validation. The latter involves determining external validity or generalizability of the prognostic model, ideally by independent investigators in a hospital or population different from those where the model was initially established. Moreover, when the performance of a model is reported, not only its discrimination power (e.g. sensitivity, specificity, receiver-operating characteristics curves) should be assessed, but also its calibration i.e. the agreement between predicted and observed outcomes. In a recent systematic review [1], it was found that only 20% of published predictive models for pre-eclampsia were internally validated, and even less (7%) underwent external validation. Calibration was only assessed for 12% of the models. Another systematic review assessed models predicting the risk of preeclampsia in the first trimester, including uterine artery Doppler among independent variables [2]. In 22% of the models, the number of events per variable was fewer than the commonly recommended value of 10 events per predictor; this proportion increased to 94% in models for early pre-eclampsia. Treatment and handling of missing data were not reported in 97% of the models. Only 8% of the models reported validation. In conclusion, predictive models for preeclampsia have variable methodological quality and frequently lack validations studies. Therefore, they should be introduced with caution into clinical practice. References [1] C.E. Kleinrouweler, F.M. Cheong-See, G.S. Collins, A. Kwee, S. Thangaratinam, K. S. Khan, B.W. Mol, E. Pajkrt, K.G. Moons, E. Schuit, Prognostic models in obstetrics: available, but far from applicable, Am. J. Obstet. Gynecol. (2016) 214 (2016) 79–90.e36. [2] V.B. Brunelli, F. Prefumo, Quality of first trimester risk prediction models for pre-eclampsia: a systematic review, BJOG (2015) 122 (2015) 904–914. doi:10.1016/j.preghy.2016.10.020
Fetal monitoring in pre-eclampsia Nicola Fratelli (Department of Obstetrics and Gynaecology, University of Brescia, Italy) Early onset preeclampsia is often associated with fetal growth restriction. Management with immediate delivery leads to high neonatal mortality and morbidity rates and prolonged hospitalization in the neonatal intensive care unit because of the association of growth restriction and prematurity. The intervals to delivery, perinatal death and severe morbidity are related to the presence and severity of maternal hypertensive conditions [1]. In selected women with early onset preeclampsia below 32 0/7 weeks of gestation, in absence of severe maternal conditions requiring immediate delivery, expectant management monitoring fetal wellbeing including ductus venosus flow pattern evaluation and safety-net delivery indication of very low short term fetal heart rate variation and/or recurrent decelerations, increases infant survival without neurological impairment at two years [2]. In non severe hypertensive disorders at 34+0/7–37+0/7 weeks of gestation, immediate delivery significantly increases the risk of neonatal respiratory distress syndrome, without a significan decrease in the already small risk of adverse maternal outcomes. Therefore, routine immediate delivery does not seem justified in these cases and a strategy of expectant monitoring until the clinical situation deteriorates can be considered [3]. References [1] C. Lees, N. Marlow, B. Arabin, C.M. Bilardo, et al, Perinatal morbidity and mortality in early-onset fetal growth restriction: cohort outcomes of the trial of randomized umbilical and fetal flow in Europe (TRUFFLE), Ultrasound Obstet. Gynecol. (2013) 42 (2013) 400–408. [2] C.C. Lees, N. Marlow, A. van Wassenaer-Leemhuis, et al, 2 year neurodevelopmental and intermediate perinatal outcomes in infantswith very preterm fetal growth restriction (TRUFFLE): a randomised trial, Lancet (2015) 385 (2015) 2162–2172. [3] K. Broekhuijsen, G.J. van Baaren, M.G. van Pampus, et al, Immediate delivery versus expectant monitoring for hypertensive disorders of pregnancy between 34 and 37 weeks of gestation (HYPITAT-II): an open-label,randomised controlled trial, Lancet (2015) 385 (2015) 2492–2501. doi:10.1016/j.preghy.2016.10.021
Cardiovascular origins of Preeclampsia Basky Thilaganathan (Feto-Maternal Medicine, University Hospital NHS Foundation Trust, UK)
St
Georges
Preeclampsia is the leading cause of maternal mortality in industrialized countries, accounting for 42% of maternal deaths and 25% of overall neonatal morbidity. The definition of the disease is seemingly straightforward: the new onset of hypertension and proteinuria after 20 weeks of gestation. However, it is well known that the simplicity of this arbitrary definition does not reflect the complexity of the multisystem disorder. It has been shown recently that angiogenic and antiangiogenic factors have the highest accuracy in predicting pregnancy complications associated with preeclampsia in singletons and twins presenting with signs and symptoms for preeclampsia in the second and third trimester. Despite these advances, the pathophysiology of preeclampsia is still largely unresolved, being labelled a ‘‘disease of theories”. According to the two-stage theory of preeclampsia, the maternal syndrome, hypertension and proteinuria, constitutes the end-stage of a pathogenetic cascade beginning in the first trimester. The initial pathognomonic lesion, a failure in trophoblast invasion, is localized in the placenta. It has been proposed that placental dysfunction disorders such as early onset PE comprise a disease entity, which is more or less distinct from late onset PE.26 The latter has been attributed as ‘‘maternal” preeclampsia, while the
Abstracts / Pregnancy Hypertension: An International Journal of Women’s Cardiovascular Health 7 (2017) 56–64
pled with receptor-specific antagonists [3]. Blood from 10 of the women from 5 to 8 years postpartum was also analyzed for AT1AA. Non-parametric statistics were used and P < 0.05 was considered statistically significant. Results: Preeclamptic women had a significantly higher incidence of AT1-AA than controls (57% vs 22%, P = 0.03). Acute atherosis did not correlate with AT1-AA. At 5–8 years postpartum, 2 of 10 women had circulating AT1-AA. Both these had previously a diagnosis of preeclampsia, without acute atherosis. Conclusions: Preeclamptic women have high rates of AT1-AA, but AT1-AA have no general correlation to acute atherosis. AT1-AA may persist after preeclampsia, and their association with future cardiovascular risk is unknown. References [1] P. Alnaes-Katjavivi, F. Lyall, B. Roald, C.W. Redman, A.C. Staff, Acute atherosis in vacuum suction biopsies of decidua basalis: An evidence based research definition, Placenta (2016) 37 (2016) 26–33. [2] N.K. Harsem, A.C. Staff, L. He, B. Roald, The decidual suction method: a new way of collecting decidual tissue for functional and morphological studies, Acta Obstet. Gynecol. Scand. (2004) 83 (8) (2004) 724–730. [3] F. Herse, R. Dechend, N.K. Harsem, G. Wallukat, J. Janke, F. Qadri, et al, Hypertension (2007) 49 (3) (2007) 604–611. doi:10.1016/j.preghy.2016.10.019
Validation of predictive models for pre-eclampsia Federico Prefumo (Department of Obstetrics and Gynaecology, University of Brescia, Italy) Prediction model are frequently proposed for use in obstetrics. It is recommended that they undergo internal and external validation. The latter involves determining external validity or generalizability of the prognostic model, ideally by independent investigators in a hospital or population different from those where the model was initially established. Moreover, when the performance of a model is reported, not only its discrimination power (e.g. sensitivity, specificity, receiver-operating characteristics curves) should be assessed, but also its calibration i.e. the agreement between predicted and observed outcomes. In a recent systematic review [1], it was found that only 20% of published predictive models for pre-eclampsia were internally validated, and even less (7%) underwent external validation. Calibration was only assessed for 12% of the models. Another systematic review assessed models predicting the risk of preeclampsia in the first trimester, including uterine artery Doppler among independent variables [2]. In 22% of the models, the number of events per variable was fewer than the commonly recommended value of 10 events per predictor; this proportion increased to 94% in models for early pre-eclampsia. Treatment and handling of missing data were not reported in 97% of the models. Only 8% of the models reported validation. In conclusion, predictive models for preeclampsia have variable methodological quality and frequently lack validations studies. Therefore, they should be introduced with caution into clinical practice. References [1] C.E. Kleinrouweler, F.M. Cheong-See, G.S. Collins, A. Kwee, S. Thangaratinam, K. S. Khan, B.W. Mol, E. Pajkrt, K.G. Moons, E. Schuit, Prognostic models in obstetrics: available, but far from applicable, Am. J. Obstet. Gynecol. (2016) 214 (2016) 79–90.e36. [2] V.B. Brunelli, F. Prefumo, Quality of first trimester risk prediction models for pre-eclampsia: a systematic review, BJOG (2015) 122 (2015) 904–914. doi:10.1016/j.preghy.2016.10.020
Fetal monitoring in pre-eclampsia Nicola Fratelli (Department of Obstetrics and Gynaecology, University of Brescia, Italy) Early onset preeclampsia is often associated with fetal growth restriction. Management with immediate delivery leads to high neonatal mortality and morbidity rates and prolonged hospitalization in the neonatal intensive care unit because of the association of growth restriction and prematurity. The intervals to delivery, perinatal death and severe morbidity are related to the presence and severity of maternal hypertensive conditions [1]. In selected women with early onset preeclampsia below 32 0/7 weeks of gestation, in absence of severe maternal conditions requiring immediate delivery, expectant management monitoring fetal wellbeing including ductus venosus flow pattern evaluation and safety-net delivery indication of very low short term fetal heart rate variation and/or recurrent decelerations, increases infant survival without neurological impairment at two years [2]. In non severe hypertensive disorders at 34+0/7–37+0/7 weeks of gestation, immediate delivery significantly increases the risk of neonatal respiratory distress syndrome, without a significan decrease in the already small risk of adverse maternal outcomes. Therefore, routine immediate delivery does not seem justified in these cases and a strategy of expectant monitoring until the clinical situation deteriorates can be considered [3]. References [1] C. Lees, N. Marlow, B. Arabin, C.M. Bilardo, et al, Perinatal morbidity and mortality in early-onset fetal growth restriction: cohort outcomes of the trial of randomized umbilical and fetal flow in Europe (TRUFFLE), Ultrasound Obstet. Gynecol. (2013) 42 (2013) 400–408. [2] C.C. Lees, N. Marlow, A. van Wassenaer-Leemhuis, et al, 2 year neurodevelopmental and intermediate perinatal outcomes in infantswith very preterm fetal growth restriction (TRUFFLE): a randomised trial, Lancet (2015) 385 (2015) 2162–2172. [3] K. Broekhuijsen, G.J. van Baaren, M.G. van Pampus, et al, Immediate delivery versus expectant monitoring for hypertensive disorders of pregnancy between 34 and 37 weeks of gestation (HYPITAT-II): an open-label,randomised controlled trial, Lancet (2015) 385 (2015) 2492–2501. doi:10.1016/j.preghy.2016.10.021
Cardiovascular origins of Preeclampsia Basky Thilaganathan (Feto-Maternal Medicine, University Hospital NHS Foundation Trust, UK)
St
Georges
Preeclampsia is the leading cause of maternal mortality in industrialized countries, accounting for 42% of maternal deaths and 25% of overall neonatal morbidity. The definition of the disease is seemingly straightforward: the new onset of hypertension and proteinuria after 20 weeks of gestation. However, it is well known that the simplicity of this arbitrary definition does not reflect the complexity of the multisystem disorder. It has been shown recently that angiogenic and antiangiogenic factors have the highest accuracy in predicting pregnancy complications associated with preeclampsia in singletons and twins presenting with signs and symptoms for preeclampsia in the second and third trimester. Despite these advances, the pathophysiology of preeclampsia is still largely unresolved, being labelled a ‘‘disease of theories”. According to the two-stage theory of preeclampsia, the maternal syndrome, hypertension and proteinuria, constitutes the end-stage of a pathogenetic cascade beginning in the first trimester. The initial pathognomonic lesion, a failure in trophoblast invasion, is localized in the placenta. It has been proposed that placental dysfunction disorders such as early onset PE comprise a disease entity, which is more or less distinct from late onset PE.26 The latter has been attributed as ‘‘maternal” preeclampsia, while the