Low-dose Aspirin In Pregnancy Research Articles

Persistent pulmonary hypertension of the newborn infant (PPHN) due to premature closure of the ductus arteriosus (DA)

Abstract Objectives To describe the course of an infant with persistent pulmonary hypertension of the newborn (PPHN) secondary to premature closure of the ductus arteriosus (DA), a very rare phenomenon which can lead to adverse clinical outcomes. Case presentation A term infant was diagnosed with severe PPHN with echocardiographic features noted at 6 h after birth which included supra-systemic pulmonary pressures, severe isolated right ventricle (RV) hypertrophy, poor RV dysfunction and no ductal flow in the context of a structurally normal heart. There was maternal use of low-dose aspirin in pregnancy due to preeclampsia. There is a known association between use of prostaglandin synthase inhibitors such as aspirin with ductal closure leading to increased RV pressure. Treatment was commenced with positive pressure ventilation, inhaled nitric oxide (iNO) and milrinone. There was a limited response to iNO necessitating increasing the concentration of milrinone with a marked improvement in oxygenation. Following commencement of sildenafil, inhaled nitric oxide was gradually weaned and stopped in the third week and the infant extubated. The infant was discharged home on oral sildenafil at four weeks of age with no respiratory or feeding support. Echocardiographic features of raised right sided pressures persisted, but with reduced RV hypertrophy and septal flattening and improved RV function. Oral sildenafil was subsequently weaned and stopped at four months of age. Conclusions A severe form of PPHN due to premature closure of the DA requires early discussion with the cardiologist. The use of milrinone and sildenafil can lead to a favourable outcome.

572 Evaluation of implementation of an EMR-based screening tool for initiation of low-dose aspirin in pregnancy

572 Evaluation of implementation of an EMR-based screening tool for initiation of low-dose aspirin in pregnancy

Indication-based administration of low dose aspirin for the prevention of preeclampsia: A retrospective study in Northern Greece

Introduction: Preeclampsia is a multisystem progressive disorder characterized by vascular abnormalities and coagulation disorders. The administration of low-dose aspirin is recommended before 16 weeks to delay or even avoid the onset of preeclampsia, based on screening tests. This study aimed to investigate the targeted or non-targeted administration of low-dose aspirin in pregnancies, according to the indications for its administration. Material and methods: This was a retrospective cohort study from the medical records of the Third Department of Obstetrics and Gynecology, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Greece, including pregnant women that were screened for preeclampsia. The parametric or non-parametric distribution of the data was examined using the Shapiro-Wilk test. The association between the intake and the indication for aspirin intake was examined by the x2 independence test for each medical society’s guidelines. The sensitivity, specificity, and positive and negative predictive values of the different criteria were calculated and compared by applying One-Way ANOVA. All results with a p-value < 0.05 were considered statistically significant. Results: In total, 2,716 women were included in the study; a statistically significant relationship between patients’ aspirin-taking behavior and the indication for aspirin according to the FMF, ACOG and NICE criteria was found. Sensitivity was the highest based on NICE criteria (78.6%), while specificity and positive predictive value (PPV) were the highest based on FMF criteria (89.9% and 61.1%, respectively). Conclusion: Applying the FMF criteria for the use of aspirin results in its more targeted administration achieved high sensitivity, specificity and PPV. Examining the number of patients receiving low-dose aspirin in pregnancy without indication could have clinical implications, highlighting the need for better targeting of the population to which it is administered.

Evaluation of Low-Dose Aspirin to Prevent Preeclampsia in Pregnant People with Chronic Hypertension.

Our objective was to evaluate if the use of low-dose aspirin (LDA) among pregnant individuals with chronic hypertension (CHTN) reduces the rate of superimposed preeclampsia or other adverse maternal and neonatal outcomes. Our study included single-center cohort of pregnant individuals with CHTN who had a live birth after 23 weeks' gestation, between 2013 and 2018. The primary exposure was the use of LDA in pregnancy and the primary outcome was superimposed preeclampsia. LDA use was also evaluated by the timing of initiation, before or after 16 weeks' gestation. Secondary outcomes included preeclampsia subtypes (e.g., preeclampsia with severe features, early-onset disease), as well as adverse maternal and neonatal outcomes. Differences were analyzed by χ 2, Fisher's exact, or t tests, with logistic regression to adjust for confounders. Of 11,825 deliveries during the study period, 494 (4.2%) occurred in women with CHTN. Among those with CHTN, 174 (35%) were prescribed LDA, most often 81 mg daily (173 out of 174, 99%). Baseline characteristics were similar between groups, but the history of preeclampsia was more common in those prescribed LDA. The rate of superimposed preeclampsia was no different among those with CHTN-prescribed LDA compared with those who were not (36% vs. 30%, p = 0.2), even when restricting the analysis to those prescribed LDA before 16 weeks' gestation (33 vs. 30%, p = 0.2). In addition, LDA did not lead to a reduction in the rate of preeclampsia with severe features, early-onset preeclampsia, or other adverse maternal outcomes. However, the composite rate of adverse neonatal outcomes was lower in LDA users versus nonusers (4.0 vs. 13%, p = 0.002), which persisted after multivariable adjustment (adjusted odds ratio: 0.28, 95% confidence interval: 0.12-0.67). Among pregnant individuals with CHTN, LDA did not decrease the rate of superimposed preeclampsia. Further studies are warranted to validate our observed reduction in adverse neonatal outcomes and to determine if aspirin is more beneficial at dosages greater than 81 mg daily. · Superimposed preeclampsia rates are the same regardless of LDA.. · Decreased rate of adverse neonatal outcomes is seen with LDA.. · No decrease in adverse maternal outcomes is seen with LDA..

Use of Daily Low-Dose Aspirin in Pregnancy for Women at High Risk of Preeclampsia at Georgetown Public Hospital Corporation

Objective: To Determine what proportion of eligible high-risk women diagnosed with preeclampsia received low dose aspirin during antepartum care. Design & Methods: This was a retrospective chart review of all patients who delivered at Georgetown Public Hospital Corporation between September to December 2017 and were diagnosed with a hypertensive disorder in pregnancy. The primary outcome was the fraction of women diagnosed with preeclampsia, eclampsia or HELLP syndrome who met the U.S. Preventive Task Force criteria to be started on aspirin and were started on aspirin between 12 and 28 weeks of gestation. Maternal secondary outcomes included: Intensive care unit admissions, end organ injury, placental abruption and death. Neonatal secondary outcomes included: Neonatal intensive care unit admissions, fetal growth restriction, preterm births, stillbirths and neonatal death. Data was organised and analysed in Microsoft Excel 2016. Results: Of the 2,452 deliveries, 2,160 (88%) charts were found and reviewed. 14.3% were diagnosed with a hypertensive disorder in pregnancy. Of these, 37% had preeclampsia, eclampsia or HELLP syndrome. Among these, 36.8% met criteria to receive low dose aspirin antepartum but only 4.8% received aspirin. Of the secondary outcomes, one death occurred because of a haemorrhagic CVA. 42.1% of neonates were born prematurely of which 4 were stillbirths and 4 were neonatal deaths. Conclusions; The routine use of a low dose of aspirin among pregnant women who met the criteria to be started on was low. Recommendations: All women should be screened for the risk of developing preeclampsia and if needed, aspirin should be started between 12-28 weeks of gestation to get the best effects. Keywords: preeclampsia, aspirin in pregnancy, GPHC

Improved implementation of aspirin in pregnancy among Dutch gynecologists: Surveys in 2016 and 2021.

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. 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. 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. 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.

Association Between Low-Dose Aspirin and Development of Gestational Diabetes: A Systematic Review and Meta-Analysis

ObjectiveTo evaluate the association between the use of low-dose aspirin for preeclampsia prophylaxis and risks of gestational diabetes (primary outcome), neonatal hypoglycemia, macrosomia, large for gestational age, birth trauma, and shoulder dystocia (secondary outcomes). Data SourcesWe searched Ovid MEDLINE, Embase, CINAHL, and Cochrane/CENTRAL for studies published between January 1, 1989, and April 24, 2021. Study SelectionRandomized controlled trials (RCTs) or cohort studies of any size conducted in any setting were included. Data Extraction and SynthesisWe assessed risk of bias using the Cochrane Risk of Bias tool 2.0 (for RCTs) and the Newcastle-Ottawa Scale (for cohort studies). We meta-analyzed relative risks (RRs) using random-effects models. ConclusionsOur search retrieved 4441 records, of which 9 studies (6 RCTs with 1932 patients and 3 cohort studies with 313 837 patients) met inclusion criteria. We rated only 4 of the 6 RCTs and 1 of the 3 cohort studies at low risk of bias. Low-dose aspirin in pregnancy for preeclampsia prophylaxis was not associated with a greater risk of gestational diabetes (RR 1.18; 95% confidence interval 0.80–1.74). No studies reported data for the secondary outcomes. In summary, the use of low-dose aspirin does not appear associated with risk of gestational diabetes. The poor quality and small number of studies limit the interpretation of these results.

The efficacy of low-dose aspirin in pregnancy among women in malaria-endemic countries

BackgroundLow dose aspirin (LDA) is an effective strategy to reduce preterm birth. However, LDA might have differential effects globally, based on the etiology of preterm birth. In some regions, malaria in pregnancy could be an important modifier of LDA on birth outcomes and anemia.MethodsThis is a sub-study of the ASPIRIN trial, a multi-national, randomized, placebo controlled trial evaluating LDA effect on preterm birth. We enrolled a convenience sample of women in the ASPIRIN trial from the Democratic Republic of Congo (DRC), Kenya and Zambia. We used quantitative polymerase chain reaction to detect malaria. We calculated crude prevalence proportion ratios (PRs) for LDA by malaria for outcomes, and regression modelling to evaluate effect measure modification. We evaluated hemoglobin in late pregnancy based on malaria infection in early pregnancy.ResultsOne thousand four hundred forty-six women were analyzed, with a malaria prevalence of 63% in the DRC site, 38% in the Kenya site, and 6% in the Zambia site. Preterm birth occurred in 83 (LDA) and 90 (placebo) women, (PR 0.92, 95% CI 0.70, 1.22), without interaction between LDA and malaria (p = 0.75). Perinatal mortality occurred in 41 (LDA) and 43 (placebo) pregnancies, (PR 0.95, 95% CI 0.63, 1.44), with an interaction between malaria and LDA (p = 0.014). Hemoglobin was similar by malaria and LDA status.ConclusionsMalaria in early pregnancy did not modify the effects of LDA on preterm birth, but modified the effect of LDA on perinatal mortality. This effect measure modification deserves continued study as LDA is used in malaria endemic regions.

Neurodevelopmental Outcomes of Children Whose Mothers Were Randomised to Low-Dose Aspirin in Pregnancy: A Longitudinal Follow-Up Study

Neurodevelopmental Outcomes of Children Whose Mothers Were Randomised to Low-Dose Aspirin in Pregnancy: A Longitudinal Follow-Up Study

Low-dose aspirin in pregnancy: who? when? how much? and why?

The use of low dose aspirin (LDA) has become routine in prenatal care for a variety of diagnoses, most importantly in women with a history of preeclampsia and associated poor pregnancy outcomes. Although LDA is currently indicated in patients considered to be at risk for development of preeclampsia, optimal dosing, timing of treatment initiation, and persons of benefit are under investigation. Several studies have also looked at LDA treatment and its effect on other maternal and fetal outcomes. This review summarizes the current guidelines for the use of LDA, incorporating the most recent research findings, and offers possible future implications of LDA treatment. Over 10 years ago, the American College of Obstetricians and Gynecologists, the World Health Organization, and the United States Preventive Service Task Force began publishing guidelines focused on the use of LDA in pregnancy. Since the release of these guidelines, several large studies have re-evaluated the use of LDA with a focus on initiation of treatment and dosing. The combined results of these studies suggest a decreased rate of preeclampsia at aspirin doses >100 mg when treatment is initiated prior to 16 weeks of gestation. Overall, early initiation of LDA has been shown to decrease the development of preeclampsia in patients considered at increased risk. Current literature suggests increasing the recommended dose to >100 mg to optimize these risk reductions. Although LDA use seems promising for other outcomes like preterm delivery and intrauterine growth restriction, further studies to strengthen recommendations are warranted.

The Efficacy of Low-Dose Aspirin in Pregnancy Among Women in Malaria-Endemic Countries

The Efficacy of Low-Dose Aspirin in Pregnancy Among Women in Malaria-Endemic Countries

Risk factors for re-presentation for postpartum hypertension in patients without a history of hypertension or preeclampsia

Re-presentation for evaluation of hypertension following discharge after delivery is common. However, a subset of patients who re-present for evaluation of postpartum hypertension do not have a history of hypertension. Identification of those at risk may help guide postpartum management and prevent re-presentations to the hospital. This study aimed to establish risk factors for re-presentation for hypertension within 30 days of discharge after delivery in patients without a history of hypertension compared with women who did not re-present and to distinguish from risk factors for re-presentation for another reason. Subjects were identified through data extraction from a single institution between January 2012 and December 2018. We included subjects without an International Classification of Diseases, Ninth Revision or International Classification of Diseases, Tenth Revision code for (1) chronic hypertension or (2) a hypertensive disorder of pregnancy during their delivery encounter who re-presented to the hospital within 30 days. Thus, the re-presentation group was divided into the following 2 groups: those who re-presented for hypertension and those who re-presented for any other reason. Each re-presentation group was compared with the cohort of patients who delivered within the study window and did not re-present using the Student t test or Wilcoxon tests for continuous variables and chi-square or Fisher's exact tests for categorical variables. Multivariable regression was also performed on all potentially important risk factors. Factors that emerged as uniquely significant in the re-presentation group for hypertension were maternal age of ≥40 years and antenatal prescription of low-dose aspirin. Black race and body mass index of ≥30 kg/m2, although significant in both re-presentation groups, were more strongly predictive of re-presentation for hypertension. These factors remained independently significant when compared with each other in a multivariable analysis. There are identifiable risk factors for postpartum re-presentation for hypertension in patients without a history of hypertension. Upon discharge, providers may consider close blood pressure monitoring and follow-up in patients who have any of the following risk factors: age of ≥40 years, black race, body mass index of ≥30 kg/m2, or those who were prescribed low-dose aspirin in pregnancy.

Chronic Kidney Disease and Pregnancy

Women with chronic kidney disease (CKD) are at high risk for adverse outcomes in pregnancy. In the United States, pregnancy rates in women with risk factors for CKD such as obesity and advanced maternal age are increasing; thus, more pregnancies are likely to be affected by CKD. Strategies that involve coordinated multidisciplinary care to optimize preconception health, perform meticulous antenatal monitoring, and provide continued care in the postpartum "fourth trimester" appear to be most beneficial for both the mother and baby. Discussions surrounding preconception risk stratification should be individualized based on CKD stage/serum creatinine level, degree of hypertension and proteinuria, and comorbid conditions. Preparation for pregnancy should include optimization of comorbidities and medication adjustments to those compatible with pregnancy. Unless contraindicated, all women with CKD should be prescribed low-dose aspirin in pregnancy to reduce risk of preeclampsia. After delivery, women with CKD may benefit from an early postpartum visit (within 7-10days) for blood pressure check and may require serial monitoring of serum creatinine and proteinuria as appropriate. Breastfeeding is safe and can be recommended for most women with CKD. A contraceptive plan that includes patients' preferences, feasibility, medical eligibility, duration, and effectiveness of the contraceptive method should be implemented.

Impact of low‐dose aspirin on adverse perinatal outcome: meta‐analysis and meta‐regression

To perform a meta-analysis and meta-regression of randomized controlled trials (RCTs) to evaluate the impact of low-dose aspirin (LDA) on perinatal outcome, independent of its effect on pre-eclampsia (PE), preterm birth and low birth weight. An electronic search of EMBASE, PubMed, CENTRAL, PROSPERO and Google Scholar databases was performed to identify RCTs assessing the impact of LDA in pregnancy, published in English prior to May 2019, which reported perinatal outcomes of interest (placental abruption, delivery mode, low 5-min Apgar score, neonatal acidosis, neonatal intensive care unit admission, periventricular hemorrhage and perinatal death). Risk ratios (RR) and 95% CI were calculated and pooled for analysis. Analysis was stratified according to gestational age at commencement of treatment (≤ 16 weeks vs > 16 weeks) and subgroup analysis was performed to assess the impact of aspirin dose (< 100 mg vs ≥ 100 mg). Meta-regression was used to assess the impact of LDA on perinatal outcome, independent of the reduction in PE, preterm birth and low birth weight. Forty studies involving 34 807 participants were included. When LDA was commenced ≤ 16 weeks' gestation, it was associated with a significant reduction in the risk of perinatal death (RR, 0.47; 95% CI, 0.25-0.88; P= 0.02; number needed to treat, 92); however, this risk reduction was only seen when a daily dose of ≥ 100 mg was administered. If commenced > 16 weeks' gestation, LDA was associated with a significant reduction in 5-min Apgar score < 7 (RR, 0.75; 95% CI, 0.58-0.96; P= 0.02) and periventricular hemorrhage (RR, 0.68; 95% CI, 0.47-0.99; P= 0.04), but a trend towards an increase in the risk of placental abruption (RR, 1.20; 95% CI, 1.00-1.46; P= 0.06) was also noted. LDA was not associated with any significant increase in adverse events if commenced ≤ 16 weeks gestation. LDA had no effect on delivery mode, irrespective of the gestational age at which it was started. Meta-regression confirmed that the effect of LDA on perinatal death, when treatment was started ≤ 16 weeks' gestation, was independent of any reduction in the rate of PE and preterm birth. LDA improves some important perinatal outcomes, without increasing adverse events such as placental abruption or periventricular hemorrhage, and its utility, if commenced prior to 16 weeks' gestation, may be considered in a wider context beyond the prevention of PE or fetal growth restriction. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Comparative analysis of the impact on pregnancy of low-dose aspirin, low-molecular-weight heparine and combined treatment objectified by values of Doppler velocimetry

Introduction. The fact that thrombophilia is a factor involved in the pathogenesis of preeclampsia is a hypothesis supported bidirectionally by numerous contradictory results; however, it is estimated that approximately 40% of patients with preeclampsia have a thrombophilic substrate. Most valid studies do not support an association between inherited thrombophilia and preeclampsia, intrauterine growth restriction or spontaneous abortion, thus implicitly not supporting the prophylactic anticoagulant treatment with low-molecular-weight heparin (LMWH) for the prevention of the aforementioned conditions. Materials and method. We selected pregnant women with developing or spontaneous discontinued pregnancy undergoing anticoagulant or antiplatelet treatment. In the context where clear protocols for the administration of anticoagulants in pregnancy have not yet been established, we aimed to perform a comparative analysis of the clinical and anamnestic aspects on which the indication of treatment with antiplatelet, anticoagulant or the two combined in pregnancy were based and the impact on placental function by comparative analysis of the values of the Doppler measurements for the uterine, umbilical and average cerebral arteries of the patients included in the three study groups. Results. Spontaneous abortions or intrauterine fetal death in the antecedents was the main criterion for recommending antiplatelet, anticoagulant or combined treatment. In the presence of a personal history of thrombotic events, the combined treatment of LMWH and low-dose aspirin was chosen. We did not obtain a significant difference in the frequency of spontaneous pregnancy loss between the three study groups, the proportion of this condition being similar. Conclusions. The combined treatment of LMWH and low-dose aspirin in pregnancy was significantly correlated with the values of the resistance and pulsatility index of the uterine arteries closest to the normal values, with an average pulsatility index lower than 1, in particular for the left uterine artery, compared to the results obtained for the single treatment with low-dose aspirin or LMWH.

Low-Dose Aspirin for the Prevention of Preeclampsia

Preeclampsia is a hypertensive disorder specific to pregnancy that remains a significant cause of maternal and neonatal morbidity and mortality. Identification of women who are most at risk for preeclampsia is imprecise. Because of the potential negative health consequences of preeclampsia for women and newborns and the lack of effective screening mechanisms preventing preeclampsia is an important component of prenatal care. Researchers have documented that low-dose aspirin, taken daily after the first trimester, can decrease the development of preeclampsia and reduce the incidence of preterm birth and birth of small-for-gestational-age infants. This column includes an overview of low-dose aspirin in pregnancy and a review of current recommendations from leading national organizations.

Pour une prescription ciblée de l’aspirine

The use of low-dose aspirin in pregnancy should remain a highly targeted indication since its long-term safety has not been established and should be restricted to women at high risk of vascular complications. Indications for which the benefit of aspirin has been shown are women with a history of preeclampsia responsible for a premature birth before 34 weeks, those having at least two history of preeclampsia, those with an antiphospholipid syndrome and those with lupus associated with positive antiphospholipid antibodies or renal failure. In all other cases, the level of evidence of the benefit of aspirin is insufficient to recommend its routine prescription.

Risk threshold for starting low dose aspirin in pregnancy to prevent preeclampsia: an opportunity at a low cost.

BackgroundPreeclampsia (PE) increases maternal and perinatal morbidity and mortality. Based on a multitude of data from randomized clinical trials, clinical practice guidelines endorse using ASA to prevent PE in women who are “at risk.” However, data are lacking about the level of absolute risk to warrant starting ASA prophylaxis.Methods and FindingsWe present two approaches for objectively determining the minimum absolute risk for PE at which ASA prophylaxis is justified. The first is a new approach—the minimum control event rate (CERmin). The second approach uses a pre-existing concept—the minimum event rate for treatment (MERT). Here we show how the CERmin is derived, and then use the CERmin and the MERT to guide us to a reasonable risk threshold for starting a woman on ASA prophylaxis against PE based on clinical risk assessment. We suggest that eligible women need not be at “high risk” for preeclampsia to warrant ASA, but rather at some modestly elevated absolute risk of 6–10%.ConclusionsGiven its very low cost, its widespread availability, ease of administration and its safety profile, ASA is a highly attractive agent for the prevention of maternal and perinatal morbidity worldwide.

PM.43 Low Dose Aspirin in Pregnancy

IntroductionHypertensive disorders in pregnancy are associated with significant risks to both mother and baby. NICE recommends women at high risk of pre-eclampsia to be given 75 mgs of Aspirin from...

742: Pharmacodynamics of low-dose aspirin in pregnancy

742: Pharmacodynamics of low-dose aspirin in pregnancy