62 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 Fetal monitoring in pre-eclampsia
women from 5 to 8 years postpartum was also analyzed for AT1- Nicola Fratelli (Department of Obstetrics and Gynaecology,
AA. Non-parametric statistics were used and P < 0.05 was considered University of Brescia, Italy)
statistically significant.
Results: Preeclamptic women had a significantly higher incidence Early onset preeclampsia is often associated with fetal growth
of AT1-AA than controls (57% vs 22%, P = 0.03). Acute atherosis did restriction. Management with immediate delivery leads to high
not correlate with AT1-AA. At 5–8 years postpartum, 2 of 10 women neonatal mortality and morbidity rates and prolonged hospitaliza-
had circulating AT1-AA. Both these had previously a diagnosis of tion in the neonatal intensive care unit because of the association
preeclampsia, without acute atherosis. of growth restriction and prematurity. The intervals to delivery,
Conclusions: Preeclamptic women have high rates of AT1-AA, but perinatal death and severe morbidity are related to the presence
AT1-AA have no general correlation to acute atherosis. AT1-AA and severity of maternal hypertensive conditions [1]. In selected
may persist after preeclampsia, and their association with future car- women with early onset preeclampsia below 32 0/7 weeks of ges-
diovascular risk is unknown. tation, in absence of severe maternal conditions requiring immedi-
ate delivery, expectant management monitoring fetal wellbeing
References including ductus venosus flow pattern evaluation and safety-net
delivery indication of very low short term fetal heart rate varia-
[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
tion and/or recurrent decelerations, increases infant survival with-
definition, Placenta (2016) 37 (2016) 26–33. out neurological impairment at two years [2]. In non severe
[2] N.K. Harsem, A.C. Staff, L. He, B. Roald, The decidual suction method: a new way hypertensive disorders at 34+0/7–37+0/7 weeks of gestation, imme-
of collecting decidual tissue for functional and morphological studies, Acta
diate delivery significantly increases the risk of neonatal respira-
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, tory distress syndrome, without a significan decrease in the
Hypertension (2007) 49 (3) (2007) 604–611. already small risk of adverse maternal outcomes. Therefore, rou-
tine immediate delivery does not seem justified in these cases
doi:10.1016/j.preghy.2016.10.019 and a strategy of expectant monitoring until the clinical situation
deteriorates can be considered [3].

Validation of predictive models for pre-eclampsia References

Federico Prefumo (Department of Obstetrics and Gynaecology,
[1] C. Lees, N. Marlow, B. Arabin, C.M. Bilardo, et al, Perinatal morbidity and
University of Brescia, Italy) 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.
Prediction model are frequently proposed for use in obstetrics. It [2] C.C. Lees, N. Marlow, A. van Wassenaer-Leemhuis, et al, 2 year
is recommended that they undergo internal and external validation. neurodevelopmental and intermediate perinatal outcomes in infantswith very
The latter involves determining external validity or generalizability preterm fetal growth restriction (TRUFFLE): a randomised trial, Lancet (2015)
385 (2015) 2162–2172.
of the prognostic model, ideally by independent investigators in a [3] K. Broekhuijsen, G.J. van Baaren, M.G. van Pampus, et al, Immediate delivery
hospital or population different from those where the model was ini- versus expectant monitoring for hypertensive disorders of pregnancy between
tially established. Moreover, when the performance of a model is 34 and 37 weeks of gestation (HYPITAT-II): an open-label,randomised
controlled trial, Lancet (2015) 385 (2015) 2492–2501.
reported, not only its discrimination power (e.g. sensitivity, speci-
ficity, receiver-operating characteristics curves) should be assessed,
doi:10.1016/j.preghy.2016.10.021
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 valida- Cardiovascular origins of Preeclampsia
tion. Calibration was only assessed for 12% of the models. Another Basky Thilaganathan (Feto-Maternal Medicine, St Georges
systematic review assessed models predicting the risk of pre- University Hospital NHS Foundation Trust, UK)
eclampsia in the first trimester, including uterine artery Doppler
Preeclampsia is the leading cause of maternal mortality in indus-
among independent variables [2]. In 22% of the models, the number
trialized countries, accounting for 42% of maternal deaths and 25% of
of events per variable was fewer than the commonly recommended
overall neonatal morbidity. The definition of the disease is seemingly
value of 10 events per predictor; this proportion increased to 94% in
straightforward: the new onset of hypertension and proteinuria after
models for early pre-eclampsia. Treatment and handling of missing
20 weeks of gestation. However, it is well known that the simplicity
data were not reported in 97% of the models. Only 8% of the models
of this arbitrary definition does not reflect the complexity of the
reported validation. In conclusion, predictive models for pre-
multisystem disorder. It has been shown recently that angiogenic
eclampsia have variable methodological quality and frequently lack
and antiangiogenic factors have the highest accuracy in predicting
validations studies. Therefore, they should be introduced with cau-
pregnancy complications associated with preeclampsia in singletons
tion into clinical practice.
and twins presenting with signs and symptoms for preeclampsia in
the second and third trimester. Despite these advances, the patho-
References
physiology of preeclampsia is still largely unresolved, being labelled
[1] C.E. Kleinrouweler, F.M. Cheong-See, G.S. Collins, A. Kwee, S. Thangaratinam, K. a ‘‘disease of theories”. According to the two-stage theory of
S. Khan, B.W. Mol, E. Pajkrt, K.G. Moons, E. Schuit, Prognostic models in preeclampsia, the maternal syndrome, hypertension and proteinuria,
obstetrics: available, but far from applicable, Am. J. Obstet. Gynecol. (2016) 214
constitutes the end-stage of a pathogenetic cascade beginning in the
(2016) 79–90.e36.
[2] V.B. Brunelli, F. Prefumo, Quality of first trimester risk prediction models for first trimester. The initial pathognomonic lesion, a failure in tro-
pre-eclampsia: a systematic review, BJOG (2015) 122 (2015) 904–914. phoblast invasion, is localized in the placenta. It has been proposed
that placental dysfunction disorders such as early onset PE comprise
doi:10.1016/j.preghy.2016.10.020 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 63

first has been dubbed as ‘‘fetal” preeclampsia. We propose that this Even though the administration of Cardio Aspirin (ASA) seems
dichotomy is rather simplistic. efficient in decreasing the PET rate in high risk patients, it is uncer-
It has been shown previously that women with a history of tain whether the same prophylaxis is effective in ‘‘low risk” patients
preeclampsia have an increased for cardiovascular diseases in later identified at ‘‘high risk” of early onset PET at first trimester CST.
life. The prevalence of hypertension in women with previous ASPRE (ASpirin for evidence-based PREeclampsia prevention –
preeclampsia is approximately 50% at an average of 14 years after ASPRE – study) is the acronym of an ongoing Randomized
pregnancy, which is 3–4 times the risk found in women without Controlled Trial investigating the effectiveness of low-dose Aspirin
preeclampsia. Large epidemiologic studies have shown that the in the prevention of early onset PET in high risk patients identified
onset of the disease constitutes an important factor of cardiovascular at first trimester CST. Results from this study are warranted in order
mortality in later life. From public health perspective, cardiovascular to provide further insights in prevention strategies for PET.
disease due to preeclampsia constitutes a major burden. Recent
studies focussing on the role of maternal cardiovascular adaptation doi:10.1016/j.preghy.2016.10.023
to pregnancy might potentially change our perception of the mater-
nal cardiovascular changes in normal pregnancy. Triggered by the
known fact that women with a history of preeclampsia have a higher Of mice and women: Statins as a potential treatment to prevent
incidence of cardiovascular morbidity and mortality in later life, preeclampsia in antiphospholipid syndrome.
prospective studies have been initiated to further elucidate the role Guillermina Girardi (King’s College London, United Kingdom)
of cardiac function in hypertensive pregnancy diseases. The results
of these studies have shed a light on firstly the extent of cardiovas- Pregnancy complications in antiphospholipid syndrome APS have
cular dysfunction in pregnancy and secondly the impact on long- been associated with placental insufficiency. While in vitro and
term cardiovascular morbidity in later life. But most of all, thirdly, ex vivo studies suggest that the placenta is the main target organ
these new data haven given insights in the cardiovascular adapta- in obstetric APS, in vivo data was missing. Using 111In labelled
tions to pregnancy and thus the etiology of preeclampsia. antiphospholipid antibodies (aPL) and single photon emission com-
In this talk, the recent understandings of maternal cardiovascular puted tomography we identified the placenta as the main organ tar-
adaptation to pregnancy and its failure in preeclampsia are to be get in a new mouse model of obstetric APS that closely resembles the
reviewed. The recent findings of our group on cardiac function in clinical scenario. The cause of placental insufficiency in APS was
preeclampsia have confirmed and improved existing literature on attributed to the procoagulant effects of aPL antibodies. However,
cardiovascular adaptation of the maternal organism to pregnancy. we demonstrated that APS is a proinflammatory syndrome. Based
With the introduction of up to date methods such as Tissue on our previous findings on the crucial role of complement activa-
Doppler as well as the normalization of indices according to cardio- tion in placental mal perfusion in APS, we developed an MRI-based
logical standards, we were able to clarify the central role of cardiac method in which anti-complement C3-targeted ultrasmall super-
dysfunction for the pathogenesis of preeclampsia. paramagnetic iron oxide (USPIO) nanoparticles were used for the
noninvasive detection of complement activation in placenta in utero.
doi:10.1016/j.preghy.2016.10.022 C3 deposition was detected in the placenta using this novel method,
confirming the role of inflammation in obstetric APS. Management of
obstetric APS is based on attenuating the procoagulant state. In
many cases, however, there is no evidence of decidual thrombosis
Role of the first trimester combined screening test in the pre-
and instead inflammatory signs are present. Current treatment fails
diction of early onset preeclampsia
in a significant number of pregnancies- raising the need to explore
Tullio Ghi, Andrea Dalla’sta, Alice Suprani, Letizia Galli, Tiziana
other therapies to improve obstetrical outcome. Based on our pre-
Frusca (Obstetrics and Gynecology Unit, University of Parma,
clinical studies in which pravastatin prevented adverse pregnancy
Parma, Italy)
outcomes in mouse models of preeclampsia and APS we performed
Although first trimester combined screening test (CST) has been translational studies in women. Our aim was to investigate the clin-
originally implemented for the screening of chromosomal anomalies, ical use of pravastatin in APS women refractory to classical treat-
more recent evidences have shown its role in the estimation of the ment LDA+LMWH that developed PE and/or severe IUGR. Eleven
risk of preeclampsia (PET). pregnant women with APS that developed PE or severe IUGR despite
Pathophysiological basis of PET are related to impaired tro- conventional antithrombotic therapy were treated with pravastatin
phoblastic invasion of the maternal spiral arteries occurring during (20mg/day) when signs of placental insufficiency (PE, IUGR) were
the process of placentation as early as 9 weeks of gestation, which observed. After pravastatin addition, placental blood flow and
in normal conditions leads to the conversion of uterine vessels into maternal symptoms of PE improved significantly leading to live birth
low resistance reservoirs allowing feto/maternal blood exchange. in 100% of the patients. The beneficial effects of pravastatin were
Uterine artery pulsatility index (PI) is inversely related to the observed as early as 10 days, with a mean response time of
extent of trophoblastic invasion of the spiral arteries. Impaired pla- 14.08 ± 3.25. Pregnancies survived 14 weeks [IQR 12–15] in patients
centation is featured by an abnormal functional and biochemical cotreated with pravastatin. In this group. all babies were born close
environment which consists in increase in uterine artery PI, increase to term and alive and are now healthy while the neonates in the
in antiangiogenetic and proinflammatory factors – i.e. sEng, sFLT1, group that did not receive pravastatin experienced still births, pre-
AFP, Inhibin-A, AFP – and reduction in angiogenetic and mitogenic term birth, were admitted at NICU and some of tem showed devel-
factors - i.e. PlGF, PAPP-A, PP13. These biomarkers are responsible opmental abnormalities. Our study indicates that the addition of
for a subclinical syncitiotrophoblastic injury in the first trimester pravastatin at the time of onset of PE or severe IUGR to conventional
and PET arising before 34 weeks of gestation. Combined assessment treatment is worthy of further assessment in the management of
of maternal history and characteristics together with the above men- women with APS and preeclampsia. RCT should be organized to con-
tioned biomarkers and uterine artery Doppler in the first trimester firm these observations.
has shown high specificity in the detection of women at risk to
develop early onset PET. doi:10.1016/j.preghy.2016.10.024