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During pregnancy, most maternal organ systems increase in function or size. This is indeed also the case for cardiovascular function and maternal haemodynamics. Most systems show enormous changes that put a serious strain on these systems. Gestational complications develop when an organ system is unable to meet the increased physiological demands of pregnancy. Pregnancy can be considered as the ultimate stress test for these organ systems. Preeclampsia may be considered as a derangement of the hemodynamic and cardiovascular system during pregnancy. Delivery eventually solves the problem but this is only a transient relief. During later life the hemodynamic and cardiovascular system again derails when aging has its toll. Cardiovascular morbidity and mortality is greatly increased after pregnancies complicated by gestational complications. This is not only true for preeclampsia and other hypertensive disorders in pregnancy but also for other gestational complications like preterm delivery, gestational diabetes, fetal growth restriction and placental abruption. Excessive weights gain and weight retention postpartum also pose risks for maternal health in later life. Gestational complications have to be acknowledged by health care providers as a risk factor for later cardiovascular disease. The care of women after previous gestational complications has to be focused on prevention and early detection of signs of cardiovascular deterioration. Specific prevention programs are needed for this group of future patients.

Maternal hemodynamics varies in different clinical phenotypes of preeclampsia: early placental damage associated with fetal growth restriction; maternal cardiovascular risk factors most frequently associated with appropriate feto-placental growth. We compared maternal hemodynamic profile during pregnancy and at 6–12 months postpartum in women affected by Hypertensive Disorder of Pregnancy (HDP), associated with two different feto-placental growth patterns. 89 patients from 24 weeks to term were enrolled in this prospective observational study: 24 HDP with appropriate for gestational age fetus (HDP-AGAf), 27 HDP with intrauterine growth restriction (HDP-IUGR), 16 normotensive women with severe IUGR (s-IUGR), 22 controls. Diagnosis of HDP was made according to the ISSHP criteria, with the exclusion of chronic hypertension. s-IUGR was defined as abdominal circumference 2SD. Maternal echocardiography was performed by a cardiologist blinded to clinical diagnosis, at recruitment and at 6–12 months postpartum. During pregnancy, HDP-IUGR showed significantly lower heart rate (HR), lower cardiac output (CO) and increased total vascular resistances (TVR), compared to controls. s-IUGR presented significantly lower CO and increased TVR, compared to controls. These profiles remained relatively unchanged at 6–12 months postpartum. HDP-AGAf showed increased CO as in control pregnancies, but significantly higher TVR; this group also presented significantly increased left ventricular mass (LVM) and relative wall thickness (RWT), and a reduced E/A ratio, indicating an impaired myocardial relaxation. In post-partum we observed persistently increased MAP values, due to high TVR, in spite of a return to normal HR and CO values. Our hypothesis, that prioritizes the feto-placental phenotype, allowed us to observe a significantly poor cardiovascular adaptation to pregnancy metabolic demands in HDP-IUGR and s-IUGR. This was profoundly different from uneventful pregnancies, characterized by increased HR and CO and low TVR. HDP-AGAf presented similar increase in HR and CO as in controls, but at the cost of diastolic function impairment and of left ventricle remodeling. In postpartum, HR and CO returned to normal, but TVR and MAP remained higher.

Introduction Visual symptoms are present in about 25% of women with pre-eclampsia (PE). The origin of these visual disturbances is localized in either the neurological or ophthalmic pathway. The exact causative factors of these disturbances have not been elucidated yet. Cerebral edema may affect the visual cortex, which can even lead to cortical blindness. The occipital cortex seems to be more susceptible for preeclampsia related breakthrough of the cerebral autoregulation. Because the vertebrobasilar system is less innervated with sympathetic nerves, this part of the brain is less capable to regulate cerebral blood flow with rising blood pressure. Objectives The objective of the study was to describe the neurophysiological changes by means of visual evoked potentials (VEPs) in patients with PE. A VEP measures the functional integrity of the visual pathway from retina to the occipital cortex of the brain. Our hypothesis is that women with PE have a longer VEP latency and lower amplitude compared to normotensive pregnant women. Methods From October 2005 till July 2008 a prospective study was performed. Normotensive pregnant women were recruited at the outpatient clinic from a gestational age of 12 weeks. They underwent clinical and neurophysiological measurements at 5 different time points: at a gestational age of 12–14 weeks, 26–28 weeks, 32–34 weeks, 36–40 weeks and 6–8 weeks postpartum. Women PE were recruited at the moment of diagnosis and investigated during pregnancy and 6-8 weeks postpartum. The visual evoked potentials were measured using a checkerboard pattern (Viking 4 device). Results VEP measurements of 29 normotensive controls, 15 mild PE and 34 severe PE were performed. The absolute values of the mean latency and amplitude were not significantly different between the groups. When compared to normative values of a group of women in the age of 20–59 year in the normotensive controls a higher proportion of women in the severe PE group had a latency time >107 (left eye: controls 31.0%, mild PE 41.7%, severe PE 52.9%, p = 0.215; right eye: controls 10.3% , mild PE 26.7%, severe PE 38.2%, p = 0.041). Conclusion This study showed that a higher percentage of women with PE had a longer latency. We are now studying the association between the VEP results and the cerebral blood flow measured with transcranial Doppler in these women.

Introduction Severe early onset preeclampsia (PE) is a rare pregnancy disorder with a high maternal and neonatal mortality and morbidity. At an extremely premature gestational age, severe preeclampsia is rare. It causes a distinctive dilemma, as foetal and maternal interests conflict. Prolongation of pregnancy (expectant management) may improve foetal prognosis on one hand, but increases maternal risks of severe morbidity and mortality on the other hand. Objectives To compare maternal and neonatal outcomes of immediate delivery or expectant management in women with severe, early onset preeclampsia before 26 weeks’ gestation. Methods We conducted a nationwide retrospective cohort study. We included women diagnosed with severe preeclampsia, who delivered between 22 and 26 weeks’ gestation in all tertiary perinatal care centres in the Netherlands between 2008 and 2014. Patients were identified through computerized hospital databases. We collected data using the medical records. Maternal complications, neonatal mortality and neonatal complications were the primary outcomes. Results We studied 133 women, of whom 99 (74%) were managed expectantly, while 34 women (26%) were treated with immediate delivery. Time interval between admittance and delivery was 4 days longer in the expectant group (6 versus 2 days, 95%CI 2.45–5.55). Expectant management was less often associated with perinatal death than immediate delivery (50% versus 88%; OR: 0.079, 95%CI: 0.02–0.37), but no differences were found for maternal (69% versus 68%; OR: 3.1, 95%CI: 0.22–44) or neonatal complications (81% versus 80%; OR: 3.3, 95%CI: 0.068–159). In 46 reported ongoing subsequent pregnancies, 17 (37%) women had recurrent preeclampsia. While no evident trend over time can be found in management or neonatal survival over the study period, a peak appears in caesarean section rate in 2011 and the occurrence of maternal complications seem to decrease. Conclusion In women with severe, early onset preeclampsia, expectant care was often applied in the Netherlands. The maternal complication rate is high. Therefore, women need to be counselled carefully, weighing expectant care versus high perinatal mortality in case of immediate delivery.

Objectives Severe preeclampsia presents as a multi-organ disorder, affecting the liver, kidney, brain, and clotting system. In the brain, this sometimes leads to complications, such as eclamptic seizures and stroke. A disturbed autoregulatory response of the brain to blood pressure changes and endothelial cell dysfunction may be causative factors. Currently, no clinically useful biomarker is available to investigate the integrity of the blood–brain barrier in preeclamptic patients. Our objective was to identify new biomarkers in cerebrospinal fluid for cerebrovascular involvement in preeclampsia. Methods A case-control study was conducted among preeclamptic and normotensive pregnant women undergoing a caesarean section or a cervical cerclage procedure. During spinal anesthesia, 1 mL of cerebrospinal fluid was collected. The samples were analyzed using a nano-LC-Orbitrap mass spectrometer. Results Cerebrospinal fluid samples of 43 pre-eclamptic patients and 55 normotensive controls were obtained. Free hemoglobin was identified in the cerebrospinal fluid of patients and controls. Eight proteins were upregulated and 17 were downregulated in women with preeclampsia. The alpha-1-microglobulin/bikunin precursor was the most distinctive protein we identified. This protein is a precursor of a heme-binding protein that counteracts the damaging effects of free hemoglobin. Table. Upregulated proteins in cerebrospinal fluid of patients with preeclampsia. ∗ Protein (accession number) #Peptides P -value θ (%) P -value〈0.05 (%) θ Peptides changed in the same direction (%) 1. Alpha-1-microglobulin/bikunin precursor (P02760) 10 100 100 100 2. Alpha-1-acid glycoprotein 1 (P02763) 12 58 67 83 3. Alpha-1-antichymotrypsin (P01011) 17 53 71 93 4. Retinol-binding protein 4 (P02753) 11 45 55 89 5. Insulin-like growth factor 2 (P01344) 3 33 100 100 6. Lumican (P51884) 3 33 67 100 7. Histidine-rich glycoprotein (P04196) 9 33 56 91 8. Alpha-1B-glycoprotein (P04217) 13 31 69 82 ∗ Selection criteria of statistically significant differentially abundant proteins were: >3 peptides identified, >30% with a P -value of 50% with a P -value of 75% of the peptides changed in the same direction. θ t -Test comparison between the groups. Conclusions We identified new potential biomarkers for cerebral involvement in preeclampsia. The presence of free hemoglobin in the cerebrospinal fluid of patients and controls is quite remarkable, when compared with cerebrospinal fluid of nonpregnant subjects. This could possibly be explained by a modulated blood-brain barrier permeability during pregnancy. This suggests that pregnancy makes the brain more vulnerable to hypertension-related brain complications. Whether this finding is a key to cerebrovascular involvement in preeclampsia needs to be further elucidated. Disclosures C.B. van den Berg: None. J.J. Duvekot: None. C. Guzel: None. T.G. de Leeuw: None. T.M. Luider: None. E.A. Steegers: None. H. Versendaal: None. M.P. Stoop: None.

Objectives The diagnosis acute fatty liver of pregnancy (AFLP) is made by the clinical presentation in combination with the laboratory abnormalities. It is often difficult to distinguish AFLP from HELLP syndrome, a complication of severe preeclampsia. Transient elastography (TE, FibroScan®, EchoSense, Paris) measures tissue elasticity as an indirect parameter for tissue fibrosis, and is frequently used in hepatology for non-invasive assessment of fibrosis. To obtain reference data for TE in hypertensive disorders of pregnancy and AFLP. Methods We conducted a prospective case–control study. Included were patients with severe preeclampsia and HELLP syndrome and AFLP between 24 and 40 weeks of gestational age. A reference group of normotensive pregnant women served as controls. Results We identified 3 cases of AFLP and 25 patients with severe preeclampsia and HELLP syndrome. All cases were matched with normotensive pregnant women. Liver stiffness expressed in kPa was significantly higher in AFLP patients than in patients with severe preeclampsia and HELLP syndrome. Normotensive pregnant women had lower values (See figure). Conclusions Transient elastography of the liver forms a new and discriminating measure to rule out AFLP in hypertensive patients. Disclosures J. Duvekot: None. C. Verveer: None. L. Neven: None. R.D. Man: None. E.A. Steegers: None. H.L. Janssen: None. R.J. Knegt: None.

Objectives The contribution of thrombophilia to the etiology of preeclampsia is becoming less apparent. Previous case-control studies has shown possible associations between thrombophilia and preeclampsia, but later published prospective studies could not reproduce these associations. Whether the phenotypes of preeclampsia matter in these possible associations remains unclear. We wanted to test possible associations between thrombophilia and two important phenotypes of preeclampsia: with/without HELLP and with/without IUGR. Methods A retrospective cohort was formed of women who delivered between 1985 and 2010 in the Erasmus medical center, Rotterdam, The Netherlands, who were diagnosed with preeclampsia and were tested at least 6 weeks postpartum for thrombophilia. Tests included anti-cardiolipin antibodies (IgG and IgM), APTT lupus, APC-ratio, protein-C level (act and ag), Protein-S level (act and free), factor-V-Leiden mutation (heterozygous) and prothrombin gene mutation (heterozygous). Factor analysis with a 2-fixed axis model was used to test for associations and clustering of associations. Results 771 Women with preeclampsia were included in the cohort: 23% had no HELLP and IUGR, 27% only had IUGR, 17% only had HELLP and 33% had HELLP and IUGR. Factor-analysis showed clustering of protein-C and protein-S, as well as clustering of factor-Leiden, APC-ratio, APTT lupus and anti-cardiolipin IgM antibodies (added figure). However, the model could only explain 33% of the existing variance. Conclusions Since our model only explained one-third of the variance, we conclude that thrombophilia is poorly associated with HELLP and IUGR in preeclampsia. Combined with the absence of associations in previous prospective studies, this finding confirms that contribution of thrombophilia to the etiology of preeclampsia is limited. Therefore, testing for thrombophilia after preeclampsia should not be standard practice. Disclosures D. Berks: None. W. Visser: None. M.P. De Maat: None. E.A. Steegers: None. H.J. Duvekot: None.

Objectives A pregnancy complicated by preeclampsia (PE), intra-uterine growth restriction (IUGR) or gestation diabetes (GD) is a maternal predictor for future cardiovascular disease. Lifestyle changes may well lower this risk. The Pro-Active study was designed to evaluate a postpartum lifestyle intervention program after complicated pregnancy. Methods From 2007 to 2012 women with PE, IUGR or GD were invited to participate. Women with known pre-existent pathology were excluded. At inclusion (6 mos postpartum) and closure (13 mos postpartum) measurements and lifestyle questionnaires were obtained. A non-randomized cohort (Erasmus MC, Rotterdam, n = 144) was offered a web based health check and 3 counseling sessions with a behavioral expert. The control cohort (Amphia Hospital, Breda, n = 62) was not. Primary outcome measure was weight reduction. The effect of lifestyle intervention was estimated, using linear regression on measurement changes, adjusted for changes in controls, measurement at inclusion and demographic variables. Results The figure shows crude changes. Regression analysis showed that lifestyle intervention significantly reduced weight by 1.7 kg (95%CI 0.4–3.1), waist-hip ratio by 0.05 (95%CI 0.03–0.06) and total fats core by 2.9 gr/d (95%CI 1.5–4.3). No significant effects were seen on systolic and diastolic blood pressure, LDL-, HDL- and total cholesterol, triglycerides, fasting glucose, HOMA2-score, smoking and exercise. Conclusions This study, although limited in design, is the first to study effects of a postpartum lifestyle intervention after complicated pregnancy. We showed some promising effects of postpartum lifestyle intervention on body constitution and fat intake. Randomized controlled trials should be conducted with more participants and a longer period of follow-up to test the lasting. We recommend mentioning the possible beneficial effects of lifestyle intervention after a pregnancy complicated by PE, IUGR or GD. Disclosures D. Berks: None. M. Hoedjes: None. H. Raat: None. H.J. Duvekot: None. E.A. Steegers: None.

Objectives To ascertain the incidence and demographic data of TOP for hypertensive disorders at the limits of fetal viability. Methods We conducted a retrospective cohort study. All terminations for hypertensive disorders between 2000 and 2009 in the ten Dutch tertiary care centers with a gestational age between 22 and 28 weeks were included. In all cases the fetus was judged to be non-viable, either because of the low gestational age or because of the effects of the maternal condition on the fetus. There was no intention to intervene for fetal indications. Results During the study period TOP for hypertensive disorders occurred in 0.8 promille (131/163.052) of all deliveries in these 10 centers, of which there were 126 singleton and five twin pregnancies. 94 women were nulliparous and 37 multiparous. The main indication for TOP was HELLP syndrome. General history revealed hypertension in 24 women (18.3%). History was unremarkable in 98 cases (75%). The mean gestational age at admission was 166 days ± 9.6 days (GA 23+5), and at delivery this was 173 days ± 9.7 days (GA 24 + 5 weeks). The mean birth weight was 472 ± 123 g (70% Conclusions In 10 years there we identified 131 cases of TOP for hypertensive disorders prior to fetal viability in The Dutch tertiary care centers. Ninety-eight women (75%) had no preexisting maternal disease. Table 1. Indications for termination of pregnancy. N = number. Indication N (%) HELLP syndrome 80 (61.1) Preeclampsia 40 (30.5) Eclampsia 7 (5.3) Refractory hypertension 4 (3) Disclosures L. van Eerden: None.

Introduction Women with a history of preeclampsia have an increased risk of developing cardiovascular disease (CVD) later in life. 24-hour ambulatory blood pressure measurement is considered to be the gold-standard for diagnosing hypertension. Data on 24-hour ambulatory blood pressure measurement in women with a history of preeclampsia are scarce. Objectives To evaluate hypertension in previously severe preeclamptic women, 24-hour ambulatory blood pressure measurements were performed one year after delivery as part of our cardiovascular risk follow-up program. Results Since 2011 213 women were included in this program. 24-hour ambulatory blood pressure measurement was performed in 90 out of 121 women (74%) who completed follow-up one year after delivery. Systolic blood pressure was 121 mm Hg (median; range 96-157) and diastolic blood pressure 78 mm Hg (median; range 62–114). Twenty-three women (26.0%) used antihypertensive medication one year postpartum. Blood pressure levels were not significantly different between women with and without medication. Five women (5/67, 7.5%) of those not using antihypertensives, were diagnosed as having hypertension by this measurement. Conclusion These data show that 30% of these previously severe preeclamptic women have persisting hypertension one year postpartum. These data stress the importance of close monitoring of blood pressure in these women.

Introduction Women with a pregnancy complicated by preeclampsia, intra-uterine growth restriction and/or gestational diabetes are at increased risk of future cardiovascular and metabolic disease. Lifestyle intervention may help these women to effectively lower these risks. Objectives To test if offering lifestyle intervention after a complicated pregnancy significantly improves saturated fat-intake and exercise (primary objectives) and/or smoking habits (secondary objective). Methods The Pro-Active study ( P ostpartum Ro tterdam A ppraisal of C ardiovascular health and T ailored I nter ve ntion) is a feasibility study to develop and evaluate a postpartum lifestyle intervention program. In a prospective case-control setting we tested the effect of the lifestyle intervention. Women were included between April 2007 and August 2009. They were eligible if ⩾18 years old at time of inclusion, being able to understand and speak the Dutch language and not having pre-existing conditions that could interfere with the lifestyle intervention. Cases were offered lifestyle intervention by a trained counsellor between 6 and 10 months postpartum. During 3 private sessions, mainly exercise and fat-intake and to some extend smoking habits were discussed and aims were made to improve lifestyle. Controls did not receive these sessions, but were not restricted to improve lifestyle on their own. Lifestyle habits were scored at 6 and 13 months postpartum. For saturated fat-intake we used the Maastricht Fatlist. For exercise we used the International Physical Activity Questionnaire (IPAQ). For smoking habits we used a short version of the questionnaire of STIVORO (the Dutch anti-smoking association). We also performed a formative evaluation of the intervention program. Results During our study 1121 women gave birth after a complicated pregnancy. 490 Women were eligible for the study of which 240 women (49%) gave informed consent to participate. 56 Women (23%) were lost-to-follow-up, leaving 186 women for the analysis. Between 6 and 13 months postpartum saturated fat-intake was significantly reduced by 3.6 g/day (95% > CI 1.8–5.4) in cases compared to controls. Exercise was improved in cases compared to controls, but it did not reach significance (277 MET’s (-2699–3254)). Although smoking decreased from 14.5% to 10.4% in cases, it was not significant and comparable to the decrease in controls (15.0% to 8.4%). The formative evaluation showed that the most important motivator to improve lifestyle was the increased risk of future cardiovascular and metabolic disease (70%) and the increased risk for recurrence in a next pregnancy (57%). Main barriers were an already busy life (40%), distance (35%) and duration (38%) of travelling to the hospital and to early postpartum to pay attention to lifestyle (26%). Conclusion Lifestyle intervention after complicated pregnancy may be effective in improving saturated fat-intake. Other interventions, specially aimed at postpartum women, are needed to improve exercise and smoking habits. More research is needed to develop lifestyle intervention program specifically aimed at these women. New possibilities of multimedia are promising.

Introduction: Large population studies have observed an increased risk for cardiovascular disease in later life for former preeclamptic women: 1.8 fold for (non)fatal stroke and 2.2 fold for (non)fatal ischemic heart disease. Since the absolute 10-year cardiovascular risk is low, primary postpartum lifestyle intervention is suggested. However, how effective lifestyle intervention after preeclampsia may be in lowering the cardiovascular risk, is not yet known. This study aimed to estimate the potential benefit of primary lifestyle intervention after preeclampsia to lower cardiovascular risk. Material and methods: Pubmed and Cochrane were first searched for studies that compared postpartum cardiovascular parameters, like blood pressure and BMI, of former preeclamptic women to non-preeclamptic women. Second, Pubmed and Cochrane were searched for studies, that reported the effect of lifestyle intervention on cardiovascular parameters. Studies that reported on women between 25 and 45 years of age were selected for further use. For each cardiovascular parameter a consensus based realistic effect and 90%-confidence interval were calculated. With these results the cardiovascular parameters for a virtual population of former preeclamptic women after lifestyle intervention were estimated and compared to non-preeclamptic women. For each parameter the median and 90%-confidence interval of the difference was calculated. These results were put into existing risk prediction models to estimate the remaining odds-ratio for cardiovascular disease in former preeclamptic women after lifestyle intervention. Results: The first search resulted in 10 studies ranging from 6 months to 19 years postpartum. The second search resulted in 17 studies. In former preeclamptic women the remaining odds-ratio of cardiovascular disease after lifestyle intervention for (non)fatal stroke was estimated at 1.52 (90%-CI 1.11-2.44) and for (non)fatal ischemic heart disease at 1.81 (90%-CI 1.53-2.10). Discussion: Although in former preeclamptic women lifestyle intervention decreases cardiovascular risk, they still remain at an increased risk for remote cardiovascular disease.