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Background: Preterm birth is the leading cause of neonatal morbidity and mortality. The recurrence rate of spontaneous preterm birth is high, and additional preventive measures are required. Our objective was to assess the effectiveness of low-dose aspirin compared to placebo in the prevention of preterm birth in women with a previous spontaneous preterm birth., Methods and Findings: We performed a parallel multicentre, randomised, double-blinded, placebo-controlled trial (the APRIL study). The study was performed in 8 tertiary and 26 secondary care hospitals in the Netherlands. We included women with a singleton pregnancy and a history of spontaneous preterm birth of a singleton between 22 and 37 weeks. Participants were randomly assigned to aspirin 80 mg daily or placebo initiated between 8 and 16 weeks of gestation and continued until 36 weeks or delivery. Randomisation was computer generated, with allocation concealment by using sequentially numbered medication containers. Participants, their healthcare providers, and researchers were blinded for treatment allocation. The primary outcome was preterm birth <37 weeks of gestation. Secondary outcomes included a composite of poor neonatal outcome (bronchopulmonary dysplasia, periventricular leukomalacia > grade 1, intraventricular hemorrhage > grade 2, necrotising enterocolitis > stage 1, retinopathy of prematurity, culture proven sepsis, or perinatal death). Analyses were performed by intention to treat. From May 31, 2016 to June 13, 2019, 406 women were randomised to aspirin (n = 204) or placebo (n = 202). A total of 387 women (81.1% of white ethnic origin, mean age 32.5 ± SD 3.8) were included in the final analysis: 194 women were allocated to aspirin and 193 to placebo. Preterm birth <37 weeks occurred in 41 (21.2%) women in the aspirin group and 49 (25.4%) in the placebo group (relative risk (RR) 0.83, 95% confidence interval (CI) 0.58 to 1.20, p = 0.32). In women with ≥80% medication adherence, preterm birth occurred in 24 (19.2%) versus 30 (24.8%) women (RR 0.77, 95% CI 0.48 to 1.25, p = 0.29). The rate of the composite of poor neonatal outcome was 4.6% (n = 9) versus 2.6% (n = 5) (RR 1.79, 95% CI 0.61 to 5.25, p = 0.29). Among all randomised women, serious adverse events occurred in 11 out of 204 (5.4%) women allocated to aspirin and 11 out of 202 (5.4%) women allocated to placebo. None of these serious adverse events was considered to be associated with treatment allocation. The main study limitation is the underpowered sample size due to the lower than expected preterm birth rates., Conclusions: In this study, we observed that low-dose aspirin did not significantly reduce the preterm birth rate in women with a previous spontaneous preterm birth. However, a modest reduction of preterm birth with aspirin cannot be ruled out. Further research is required to determine a possible beneficial effect of low-dose aspirin for women with a previous spontaneous preterm birth., Trial Registration: Dutch Trial Register (NL5553, NTR5675) https://www.trialregister.nl/trial/5553., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: BM reported an Investigator grant from the National Health and Medical Research Council (NHMRC; grant no. GNT1176437); receipt of research funding from Guerbet; and is a former advisory board member at ObsEva. All other authors do not report any relevant financial activities outside the submitted work.

Objective: To elucidate patients' knowledge and counseling perspective on aspirin reducing the risk of hypertensive disorders of pregnancy (HDP)., Methods: A quantitative survey was performed including women who are members of the patient orgasnization Dutch HELLP Foundation due to a history of HDP., Results: Awareness of the risk-reducing effect of aspirin on HDP was present in 51.9% of the 189 women. The majority was informed by their gynecologist (89.8%) and preferred to be informed by a gynecologist (79.4%), at the postpartum checkup (42.3%) or in the consecutive pregnancy (30.7%), both orally and written (62.4%)., Conclusion: Half of the women with a history of HDP were aware of the risk-reducing effect of aspirin in a consecutive pregnancy.

Objectives: The objective of this study is to investigate possible changes in aspirin resistance during and after pregnancy over time., Study Design: A longitudinal cohort study in obstetric high risk women with an indication for aspirin usage during pregnancy to prevent placenta mediated pregnancy complications., Main Outcome Measures: Aspirin resistance measured in the first, second and third trimester of pregnancy and at least three months postpartum by four complementary test: PFA-200, VerifyNow®, Chronolog light transmission aggregometry (Chronolog LTA) and serum thromboxane B 2 (TxB 2 ) level measurements. Correlation between the devices was investigated., Results: In total, 23 pregnant women participated in the present study. Aspirin resistance according to the PFA-200, VerifyNow®, Chronolog LTA and serum TxB 2 , was 30.4%, 17.4%, 26.1% and 23.8% respectively. Resistance by any device was 69.6%. Aspirin resistance measured by the VerifyNow®, Chronolog LTA, serum TxB 2 and aspirin resistance by any device during pregnancy was demonstrated more frequently than aspirin resistance after pregnancy. Correlation between the different devices was weak., Conclusion: Aspirin resistance was found in a considerable part of the participants. Considerable variation between participants, within participants over time and between the different devices was found. Prevalence of aspirin resistance during pregnancy differs from after pregnancy. More research on aspirin resistance and clinical obstetric outcome is needed., (Copyright © 2019 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.)

Background: Preterm birth (birth before 37 weeks of gestation) is a major problem in obstetrics and affects an estimated 15 million pregnancies worldwide annually. A history of previous preterm birth is the strongest risk factor for preterm birth, and recurrent spontaneous preterm birth affects more than 2.5 million pregnancies each year. A recent meta-analysis showed possible benefits of the use of low dose aspirin in the prevention of recurrent spontaneous preterm birth. We will assess the (cost-)effectiveness of low dose aspirin in comparison with placebo in the prevention of recurrent spontaneous preterm birth in a randomized clinical trial., Methods/design: Women with a singleton pregnancy and a history of spontaneous preterm birth in a singleton pregnancy (22-37 weeks of gestation) will be asked to participate in a multicenter, randomized, double blinded, placebo controlled trial. Women will be randomized to low dose aspirin (80 mg once daily) or placebo, initiated from 8 to 16 weeks up to maximal 36 weeks of gestation. The primary outcome measure will be preterm birth, defined as birth at a gestational age (GA) < 37 weeks. Secondary outcomes will be a composite of adverse neonatal outcome and maternal outcomes, including subgroups of prematurity, as well as intrauterine growth restriction (IUGR) and costs from a healthcare perspective. Preterm birth will be analyzed as a group, as well as separately for spontaneous or indicated onset. Analysis will be performed by intention to treat. In total, 406 pregnant women have to be randomized to show a reduction of 35% in preterm birth from 36 to 23%. If aspirin is effective in preventing preterm birth, we expect that there will be cost savings, because of the low costs of aspirin. To evaluate this, a cost-effectiveness analysis will be performed comparing preventive treatment with aspirin with placebo., Discussion: This trial will provide evidence as to whether or not low dose aspirin is (cost-) effective in reducing recurrence of spontaneous preterm birth., Trial Registration: Clinical trial registration number of the Dutch Trial Register: NTR 5675 . EudraCT-registration number: 2015-003220-31.

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 B 2 (TXB 2 ). An independent t-test, Mann-Whitney U test, Fisher's Exact test and Chi 2 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 TXB 2 . 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., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

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.

Objective: To evaluate the implementation of low-dose aspirin in pregnancy for the prevention of utero-placental complications among gynecologists in the Netherlands between 2016 and 2021. In this timeframe, a national guideline about aspirin in pregnancy was introduced by the Dutch Society of Obstetrics and Gynecology. Materials and methods: A national online survey among Dutch gynecologists and residents was performed. An online questionnaire was distributed among the members of the Dutch Society of Obstetrics and Gynecology in April 2016 and April 2021. Main outcome measure was the proportion of gynecologists indicating prescription of aspirin in pregnancy for high and moderate risk indications. Results: In 2016, 133 respondents completed the survey, and in 2021 231. For all indications mentioned in the guideline there was an increase in prescribing aspirin in 2021 in comparison to 2016. More specifically, the percentage of gynecologists prescribing aspirin for a history of preeclampsia before 34 weeks, between 34 and 37 weeks and at term increased from respectively 94% to 100%, 39% to 98%, and 15% to 97%. Consultant obstetricians and respondents working in an university hospital did not more often indicate the prescription of aspirin for tertiary care indications in 2021. Future use of a prediction model was suggested in the narrative comments. Conclusion: Implementation of aspirin in pregnancy among Dutch gynecologists substantially improved after a five year timeframe in which the national guideline on aspirin during pregnancy was introduced and trials confirming the effect of aspirin were published. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the long-term effects of antenatal aspirin exposure on child health and neurodevelopmental outcome beyond the perinatal period.Study Design: PubMed, Embase.com, the Cochrane Library and Web of Science were systematically searched from inception through 5 November 2020. We performed a cited-reference search and ClinicalTrials.gov was searched on 20 October 2020 to identify trial results that were not reported elsewhere. We included randomized controlled trials reporting on health-related outcomes in children (aged > 28 days) exposed to aspirin versus placebo or no treatment during pregnancy. Studies with any dose or duration of aspirin use were included. We excluded studies evaluating other antiplatelet agents or non-steroidal inflammatory drugs. Two authors independently performed study selection, data extraction and quality assessment. Quality assessment was performed using the Cochrane RoB2 tool for the original randomized controlled trials and the QUIPS for the follow-up studies. Results are presented as relative risks (RR) with 95% confidence intervals (95%CI).Results: The search yielded 6,907 unique records. Two studies were included, containing 4,168 children at age 12 months and 5,153 children at 18 months. Children were exposed to aspirin 50-60 mg versus placebo or no treatment. At 12 months, post-neonatal mortality was lower after allocation to aspirin (0.2% versus 0.5%; RR 0.28, 95%CI 0.08-0.99) in a single study. At 18 months, fewer children were found to have (gross and fine) motor problems (RR 0.49, 95%CI 0.26-0.91) after antenatal aspirin exposure in one study. No differences were found in mortality rate; the proportion of children with a short stature or low weight; or respiratory, hearing or visual problems at 18 months. Both included studies had a high risk of bias.Conclusion: The two included studies showed evidence of potential benefit of antenatal low-dose aspirin on mortality and neurodevelopment up to the age of 18 months. Our findings support the current application of low-dose aspirin in pregnant women at risk for preeclampsia and fetal growth restriction. However, further follow-up research of children who were exposed to low-dose aspirin during pregnancy is of utmost importance to exclude potential long-term harm. [ABSTRACT FROM AUTHOR]