Carolien N. H. Abheiden

Low-molecular-weight heparin for prevention of placenta-mediated pregnancy complications: protocol for a systematic review and individual patient data meta-analysis (AFFIRM).

BackgroundPlacenta-mediated pregnancy complications include pre-eclampsia, late pregnancy loss, placental abruption, and the small-for-gestational age newborn. They are leading causes of maternal, fetal, and neonatal morbidity and mortality in developed nations. Women who have experienced these complications are at an elevated risk of recurrence in subsequent pregnancies. However, despite decades of research no effective strategies to prevent recurrence have been identified, until recently. We completed a pooled summary-based meta-analysis that strongly suggests that low-molecular-weight heparin reduces the risk of recurrent placenta-mediated complications. The proposed individual patient data meta-analysis builds on this successful collaboration. The project is called AFFIRM, A n individual patient data meta-analysis oF low-molecular-weight heparin F or prevention of placenta-medI ated pR egnancy coMplications.Methods/DesignWe conducted a systematic review to identify randomized controlled trials with a low-molecular-weight heparin intervention for the prevention of recurrent placenta-mediated pregnancy complications. Investigators and statisticians representing eight trials met to discuss the outcomes and analysis plan for an individual patient data meta-analysis. An additional trial has since been added for a total of nine eligible trials. The primary analyses from the original trials will be replicated for quality assurance prior to recoding the data from each trial and combining it into a common dataset for analysis. Using the anonymized combined data we will conduct logistic regression and subgroup analyses aimed at identifying which women with previous pregnancy complications benefit most from treatment with low-molecular-weight heparin during pregnancy.DiscussionThe goal of the proposed individual patient data meta-analysis is a thorough estimation of treatment effects in patients with prior individual placenta-mediated pregnancy complications and exploration of which complications are specifically prevented by low-molecular-weight heparin.Systematic review registrationPROSPERO (International Prospective Registry of Systematic Reviews) 23 December 2013, CRD42013006249

Hypertensive Disorders of Pregnancy Appear Not to Be Associated with Alzheimer's Disease Later in Life

Background: After hypertensive disorders of pregnancy, more subjective cognitive complaints and white matter lesions are reported compared to women after normal pregnancies. Both have a causal relationship with Alzheimers disease (AD). Aim: To investigate if women whose pregnancy was complicated by hypertensive disorders have an increased risk of AD. Methods: A case-control study in women with AD from the Alzheimer Center of the VU University Medical Center Amsterdam and women without AD. Paper and telephone surveys were performed. Results: The response rate was 85.2%. No relation between women with (n = 104) and without AD (n = 129) reporting pregnancies complicated by hypertensive disorders (p = 0.11) was found. Women with early-onset AD reported hypertensive disorders of pregnancy more often (p = 0.02) compared to women with late-onset AD. Conclusion: A reported history of hypertensive disorders of pregnancy appears not to be associated with AD later in life.

Low-molecular-weight heparin and aspirin use in relation to pregnancy outcome in women with systemic lupus erythematosus and antiphospholipid syndrome: A cohort study

ABSTRACT Objective: To relate anticoagulant use to pregnancy complications in women with systemic lupus erythematosus (SLE) and primary antiphospholipid syndrome (APS). Methods: All ongoing pregnancies, 184, in two Dutch tertiary centers between 2000 and 2015. Results: LMWH and aspirin was prescribed in 15/109 SLE women without antiphospholipid antibodies (aPL), 5/14 with aPL, 11/13 with APS, 45/48 with primary APS. Main complications in the four treatment groups (no anticoagulant treatment, aspirin, LMWH, aspirin and LMWH) included hypertensive disorders of pregnancy (9.4%, 23.3%, 50%, 18.4%, respectively, p = 0.12) and preterm birth (16.7%, 34.3%, 75%, 36.8%, respectively, p < 0.001). Conclusion: Maternal and perinatal complications occurred frequently, despite LMWH and aspirin use.

Post-pregnancy aspirin resistance appears not to be related with recurrent hypertensive disorders of pregnancy

OBJECTIVE The FRUIT-RCT concluded that low-molecular-weight heparin added to aspirin compared to treatment with aspirin alone is beneficial in the prevention of early-onset hypertensive disorders of pregnancy (HD) in women with inheritable thrombophilia and prior HD and/or a small-for-gestational age (SGA) infant leading to delivery before 34 weeks gestation. The aim of this study is to answer the question whether aspirin resistance is associated with recurrent HD. STUDY DESIGN Women with and without recurrent HD matched for age, study arm, and chronic hypertension were invited for this follow-up study 6-16 years after they participated in the FRUIT-RCT. Aspirin resistance was tested after 10days of aspirin intake using three complementary tests: PFA-200, VerifyNow® and serum thromboxane B2 (TXB2). An independent t-test, Mann-Whitney U test, Fishers Exact test and Chi2 test were used for the statistical analyses. RESULTS Thirteen of 24 women with recurrent HD and 16 of 24 women without recurrent HD participated. The prevalence of laboratory aspirin resistance was 34.5% according to the PFA-200, 3.4% according to the VerifyNow® and 24.1% according to TXB2. The prevalence of aspirin resistance by any test was 51.7%. Aspirin resistance per individual test did not differ between women with and without recurrent HD. Aspirin resistance measured by any test occurred more frequently in women without recurrent HD (p<0.01), irrespective of low-molecular-weight heparin. CONCLUSIONS No relation could be demonstrated between recurrent HD and aspirin resistance per test, measured up to 16 years after pregnancy. On the contrary, complementary aspirin resistance measurements were encountered more frequently in women without recurrent HD.

Aspirin adherence during high-risk pregnancies, a questionnaire study

OBJECTIVE Aspirin reduces the risk of recurrent hypertensive disorders of pregnancy (HD) and fetal growth restriction (FGR). This study examined the non-adherence rates of aspirin in women with high-risk pregnancies. STUDY DESIGN All consecutive women between 24 and 36weeks gestation with an indication for aspirin use during pregnancy were invited for this study. A survey was used which included two validated questionnaires, the simplified medication adherence questionnaire (SMAQ) and the Beliefs and Behaviour Questionnaire (BBQ). MAIN OUTCOME MEASURES To determine the non-adherence rates of aspirin, and to identify the beliefs and behavior concerning aspirin. RESULTS Indications for aspirin use during pregnancy were previous HD, FGR, intrauterine fetal death or current maternal disease. Non-adherence rates according to the SMAQ and BBQ were 46.3% and 21.4% respectively. No differences in demographic background or obstetrical characteristics between adherent and non-adherent women could be demonstrated. CONCLUSIONS Adherence for aspirin in this high-risk population cannot be taken for granted. The non-adherence rates in pregnant women are comparable with the non-adherence rates for aspirin in the non-pregnant population.

OP0310 Pregnancy outcome in women with systemic lupus erythematosus, a multicenter cohort-study

Background Systemic lupus erythematosus (SLE) predominantly affects women during their fertile period. During pregnancy SLE patients are prone to pregnancy complications and may experience increased disease activity. Objectives To investigate disease activity around/during pregnancy and pregnancy complications in a European cohort according to antiphospholipid antibody (aPL) status. Additionally data on lifetime pregnancy outcomes and comparison of first and consecutive pregnancies were analyzed. Methods All ongoing pregnancies of >16 weeks gestation of SLE patients (according to the ACR revised criteria) receiving joint care from rheumatologists and gynecologists in two tertiary centers in the Netherlands between 2000–2015 were included. Disease activity (using SELENA-SLE(P)DAI around and during pregnancy), flare rate according to the SELENA- SLEDAI definitions and pregnancy complications were assessed by medical chart review. Results From 96 women (84% Caucasian) 144 pregnancies were included. Before (<6 months), during and after pregnancy (<6 months) the median SELENA-SLE(P)DAI score was 2 and mild/moderate flare rates were 6.3%, 18.8% and 13.9% respectively. Three patients developed a severe flare during pregnancy, 2 patients postpartum; all were aPL negative. Severe maternal complications (preeclampsia, eclampsia or HELLP-syndrome) occurred in 16.2% of aPL negative, 21.4% of aPL positive SLE patients, and in 30.8% of SLE patients with antiphospholipid syndrome (APS) (GEE; no significant differences between groups). HELLP-syndrome occurred in 23.1% of SLE patients with APS and in 3.1% of SLE patients without APS (Chi-Square; p<0.01). The perinatal complications intrauterine fetal death, preterm birth, small-for-gestational age and neonatal lupus occurred in 4.1%, 32.7%, 14.8%, 1.4%, respectively (GEE; no significant differences between groups). Maternal and perinatal complication rates were similar in first (18.5% and 41.4%) and consecutive (17.6% and 35.1%) pregnancies (Chi-Square; p=0.88 and p=0.44). Of all patients, 42.7% developed a complication during all of their pregnancies (obstetrical history included). Conclusions This is the first study in patients with SLE demonstrating that incidence rates of pregnancy complications do not decrease in consecutive pregnancies compared to first pregnancies, in contrast to findings in the general population. Except for HELLP-syndrome, pregnancy complications were not significant different between aPL groups. Despite overall low disease activity and the absence of aPL in the majority of patients, almost half of the patients developed a complication during their pregnancies. Disclosure of Interest B. Blomjous: None declared, C. Abheiden: None declared, S. Kroese: None declared, J. van Laar Grant/research support from: MSD, Pfizer, Roche, Eli Lilly, BMS and Crescendo, R. Derksen: None declared, I. Bultink: None declared, A. Voskuyl: None declared, A. Lely: None declared, M. de Boer: None declared, J. de Vries Grant/research support from: Pfizer, R. Fritsch-Stork: None declared

Maternal and Perinatal Outcome in Women with Systemic Lupus Erythematosus: A Retrospective Bicenter Cohort Study

Objective To investigate disease activity around and during pregnancy and pregnancy outcome in women with systemic lupus erythematosus (SLE) considering antiphospholipid antibody status. Moreover, differences between first and consecutive pregnancies were examined. Methods Pregnancies > 16 weeks gestation of SLE patients receiving joint care from rheumatologists and gynecologists in two tertiary centers in the Netherlands between 2000 and 2015 were included. Disease activity, flare rate, and pregnancy outcomes and complications were assessed. Results Ninety-six women (84% Caucasian) with 144 pregnancies were included. The median SLE(P)DAI score was 2 before, during, and after pregnancy. Flare rates were 6.3%, 20.1%, and 15.3%, respectively. Severe hypertensive disorder of pregnancy, intrauterine fetal death, preterm birth, and small-for-gestational age infants occurred in 18.1%, 4.1%, 32.7%, and 14.8%, respectively. Complication rates were similar in the first and consecutive pregnancies. Half of the women did not experience any pregnancy complication whereas 42.7% developed a complication during all pregnancies. Mean number of pregnancies was 2.4 and live births 1.7. Conclusion In this SLE population with low disease activity, pregnancy complications were present irrespective of antiphospholipid antibody status. Furthermore, there were no differences in complication rates between the first and consecutive pregnancies as seen in healthy mothers. This information is useful for patient counseling.

Cardiovascular risk factors in women with inheritable thrombophilia a decade after single or recurrent hypertensive disorder of pregnancy.

ABSTRACT Objective: To described cardiovascular risk factors in women with inheritable thrombophilia 8–19 years after early-onset hypertensive disorders of pregnancy (HD) with or without recurrent HD. Methods: Women with recurrent HD were compared with women with single HD, for physical examination and cardiovascular parameters in serum. Results: Systolic blood pressure, diastolic blood pressure, and albumin: creatinine ratio were higher in women with recurrent HD compared with women with single HD (p = 0.046, p = 0.029, and p = 0.008, respectively). In both groups 72.7% had an increased cardiovascular risk. Conclusion: Women with inheritable thrombophilia after single or recurrent HD have a high cardiovascular risk.