Effects of antiplatelet therapy on menstrual blood loss in reproductive-aged women:a systematic review

Background: The effects of antiplatelet therapy on menstrual bleeding have not been well characterized. Objectives: To systematically review the effects of antiplatelet therapy on menstrual bleeding. Methods: A literature search was performed for studies of reproductive-aged women who received antiplatelet therapy. Characteristics of menstrual bleeding both before and after initiation of antiplatelet therapy and from comparison groups were collected. Two reviewers independently assessed the risk of bias in individual studies. Results: Thirteen studies with a total of 611 women who received antiplatelet therapy were included. Types of antiplatelet drugs used were aspirin (n = 8), aspirin and/or clopidogrel (n = 2), prasugrel (n = 1), and not specified (n = 2). Risk of bias was assessed at moderate (n = 1), serious (n = 8), critical (n = 2), and no information (n = 2). Three studies reported changes in menstrual blood loss volume. One of these showed no increase during antiplatelet therapy; the other 2 studies suggested that aspirin may increase menstrual blood loss volume. In 3 studies that assessed the duration of menstrual bleeding, up to 13% of women reported an increased duration of menstruation. In 5 studies that reported the intensity of menstrual flow, 13% to 38% of women experienced an increase in the intensity of flow. Five studies reported the prevalence of heavy menstrual bleeding in women who received antiplatelet therapy, with estimates ranging from 7% to 38%. Conclusion: There is lack of high-quality data on the effects of antiplatelet therapy on menstrual bleeding. Aspirin may increase menstrual blood loss, at least in a minority of women, whereas the effects of P2Y12 inhibitors are unknown.</p

Effects of antiplatelet therapy on menstrual blood loss in reproductive-aged women:a systematic review

Background: The effects of antiplatelet therapy on menstrual bleeding have not been well characterized. Objectives: To systematically review the effects of antiplatelet therapy on menstrual bleeding. Methods: A literature search was performed for studies of reproductive-aged women who received antiplatelet therapy. Characteristics of menstrual bleeding both before and after initiation of antiplatelet therapy and from comparison groups were collected. Two reviewers independently assessed the risk of bias in individual studies. Results: Thirteen studies with a total of 611 women who received antiplatelet therapy were included. Types of antiplatelet drugs used were aspirin (n = 8), aspirin and/or clopidogrel (n = 2), prasugrel (n = 1), and not specified (n = 2). Risk of bias was assessed at moderate (n = 1), serious (n = 8), critical (n = 2), and no information (n = 2). Three studies reported changes in menstrual blood loss volume. One of these showed no increase during antiplatelet therapy; the other 2 studies suggested that aspirin may increase menstrual blood loss volume. In 3 studies that assessed the duration of menstrual bleeding, up to 13% of women reported an increased duration of menstruation. In 5 studies that reported the intensity of menstrual flow, 13% to 38% of women experienced an increase in the intensity of flow. Five studies reported the prevalence of heavy menstrual bleeding in women who received antiplatelet therapy, with estimates ranging from 7% to 38%. Conclusion: There is lack of high-quality data on the effects of antiplatelet therapy on menstrual bleeding. Aspirin may increase menstrual blood loss, at least in a minority of women, whereas the effects of P2Y12 inhibitors are unknown.</p

Maternal, fetal, neonatal and breastmilk flecainide concentration during maternal therapy and lactation: a case report

Background: Mothers requiring the antiarrhythmic agent flecainide are often advised not to breastfeed, because of the lack of data concercing neonatal effects and flecainide plasma concentrations following maternal exposure as well as via lactation. This is the first report on combined maternal, fetal, neonatal and breastmilk flecainide concentrations in a breastfed infant of a mother requiring flecainide treatment. Case presentation: A 35-year old Gravida 2 Para 1, known with ventricular arrhythmia, was referred to our tertiary center at 35 + 4 weeks of gestation. Because of an increase of ventricular ectopy, oral metoprolol 11.9 milligrams once daily was switched to oral flecainide 87.3 milligrams twice daily. Weekly collected maternal flecainide plasma trough concentrations fell within the therapeutic range of 0.2 to 1.0 mg/L and no further clinically significant arrhythmias occurred during the study period. A healthy son was born at 39 weeks of gestation and had a normal electrocardiogram. The fetal to maternal flecainide ratio was 0.72 and at three different timepoints, the flecainide concentration was higher in breastmilk than in maternal plasma. The relative infant dose received via breastmilk compared to maternal dose was 5.6%. Neonatal plasma concentrations were not detectable, despite the flecainide passage into breastmilk. All electrocardiograms to assess the neonatal antiarrhytmic effect were normal. Conclusions: Our results assume that flecainide can be prescribed safely to lactating mothers. Quantification of drug concentrations in neonatal blood in addition to measurements in maternal and fetal blood, and breastmilk, are helpful to evaluate the effects and safety of maternal medication use during pregnancy and lactation

Patient-reported preconceptional characteristics in the prediction of recurrent preeclampsia

Objective: To develop a prediction model for recurrent preeclampsia using patient-reported preconceptional characteristics, which can be used for risk stratification of subsequent pregnancies. Study design: Retrospective cohort study using data from The Preeclampsia Registry™ of 1028 women with a history of preeclampsia and at least one subsequent pregnancy. Main outcome measures: Candidate predictors were included in a multivariable logistic regression analysis and a backward selection procedure was used to select the final predictors. Internal validation took place by internally validating the model in 500 simulated samples (bootstrapping), which provided a shrinkage factor to create the final model. This final model was evaluated for performance by a calibration plot and the area under the receiver operating curve (AUC). Missing data was handled by multiple imputation. Results: Recurrent preeclampsia occurred in 467 (45.4%) women. Predictors in the final model were: a history of migraine, first degree relative with cardiovascular disease, first degree relative with placenta-related pregnancy complication, gestational age at delivery of index pregnancy, birthweight of the previous child, history of placental abruption, multiparity, chronic hypertension, interval between index and subsequent pregnancy, paternal non-white ethnicity and maternal age. AUC of the model was 0.63 (95% CI 0.59–0.66). In a subset of women who used aspirin prior or during their subsequent pregnancy, performance of the model was similar (AUC 0.60; 95% CI 0.50–0.71). Conclusions: In this study we developed a prediction model for recurrent preeclampsia with moderate performance after internal validation. Early risk stratification of subsequent pregnancies that allows for customization of antenatal care and personalized prevention strategies, is not yet possible

Women of reproductive age in a tertiary intensive care unit: indications, outcome and the impact of pregnancy—a retrospective cohort study

Background: To evaluate the indications for admission and mortality rates of women of reproductive age admitted to a tertiary Intensive Care Unit (ICU) and to compare the outcomes of obstetric and non-obstetric admissions. Methods: A retrospective cohort study was performed, including all women aged 17–41 years admitted to a level 3 ICU in the Netherlands, between January 1, 2000 and January 1, 2016. Primary outcome was indication for admission and mortality. Mortality, length of stay (LOS), need for mechanical ventilation and APACHE II score were compared between obstetric and non-obstetric admissions. The obstetric group was further analyzed for maternal and perinatal outcomes. Results: 3461 women (median age 32 years) were included, with an overall mortality rate of 13.3%. The obstetric group consisted of 265 women (7.7%). The non-obstetric group (n = 3196) was admitted most often for cardiovascular disease (19.6%), followed by oncologic disease (15%). Mortality was the highest in women with oncologic disease (23.9%). The obstetric group had lower mortality compared to the non-obstetric group (4.9% vs. 14%, p < 0.001), despite higher APACHE II score (14 vs. 11, p < 0.001) and a higher ventilation rate (47.9% vs. 39%, p = 0.004). Major surgical or endovascular interventions, besides caesarean section, were performed in 46% of the obstetric group. Perinatal death occurred in 17.2% and of the surviving infants, 63.2% were born preterm and 45.1% required Neonatal Intensive Care Unit admission. Conclusions: Cardiovascular disease is the most important indication for admission and oncologic disease is associated with highest mortality in women of reproductive age. Obstetric patients constitute a small percentage of all ICU admissions in a tertiary ICU center. They have lower mortality rates than non-obstetric young female patients, despite a more severe initial presentation. Nevertheless lasting maternal morbidity and perinatal mortality and morbidity is frequent

Pregnancy outcomes in women with a mitral valve prosthesis: A systematic review and meta-analysis

Objectives: To evaluate the ongoing debate concerning the choice of valve prosthesis for women requiring mitral valve replacement (MVR) and who wish to conceive. Bioprostheses are associated with risk of early structural valve deterioration. Mechanical prostheses require lifelong anticoagulation and carry maternal and fetal risks. Also, the optimal anticoagulation regimen during pregnancy after MVR remains unclear. Methods: A systematic review and meta-analysis was conducted of studies reporting on pregnancy after MVR. Valve- and anticoagulation-related maternal and fetal risks during pregnancy and 30 days’ postpartum were analyzed. Results: Fifteen studies reporting 722 pregnancies were included. In total, 87.2% of pregnant women had a mechanical prosthesis and 12.5% a bioprosthesis. Maternal mortality risk was 1.33% (95% confidence interval [CI], 0.69-2.56), any hemorrhage risk 6.90% (95% CI, 3.70-12.88). Valve thrombosis risk was 4.71% (95% CI, 3.06-7.26) in patients with mechanical prostheses. 3.23% (95% CI, 1.34-7.75) of the patients with bioprostheses experienced early structural valve deterioration. Of these, the mortality was 40%. Pregnancy loss risk was 29.29% (95% CI, 19.74-43.47) with mechanical prostheses versus 13.50% (95% CI, 4.31-42.30) for bioprostheses. Switching to heparin during the first trimester demonstrated a bleeding risk of 7.78% (95% CI, 3.71-16.31) versus 4.08% (95% CI, 1.17-14.28) for women on oral anticoagulants throughout pregnancy and a valve thrombosis risk of 6.99% (95% CI, 2.08-23.51) versus 2.89% (95% CI, 1.40-5.94). Administration of anticoagulant dosages greater than 5 mg resulted in a risk of fetal adverse events of 74.24% (95% CI, 56.11-98.23) versus 8.85% (95% CI, 2.70-28.99) in ≤5 mg. Conclusions: A bioprosthesis seems the best option for women of childbearing age who are interested in future pregnancy after MVR. If mechanical valve replacement is preferred, the favorable anticoagulation regimen is continuous low-dose oral anticoagulants. Shared decision-making remains priority when choosing a prosthetic valve for young women

Pregnancy outcomes in women with a mitral valve prosthesis: A systematic review and meta-analysisCentral MessagePerspective

Objectives: To evaluate the ongoing debate concerning the choice of valve prosthesis for women requiring mitral valve replacement (MVR) and who wish to conceive. Bioprostheses are associated with risk of early structural valve deterioration. Mechanical prostheses require lifelong anticoagulation and carry maternal and fetal risks. Also, the optimal anticoagulation regimen during pregnancy after MVR remains unclear. Methods: A systematic review and meta-analysis was conducted of studies reporting on pregnancy after MVR. Valve- and anticoagulation-related maternal and fetal risks during pregnancy and 30 days’ postpartum were analyzed. Results: Fifteen studies reporting 722 pregnancies were included. In total, 87.2% of pregnant women had a mechanical prosthesis and 12.5% a bioprosthesis. Maternal mortality risk was 1.33% (95% confidence interval [CI], 0.69-2.56), any hemorrhage risk 6.90% (95% CI, 3.70-12.88). Valve thrombosis risk was 4.71% (95% CI, 3.06-7.26) in patients with mechanical prostheses. 3.23% (95% CI, 1.34-7.75) of the patients with bioprostheses experienced early structural valve deterioration. Of these, the mortality was 40%. Pregnancy loss risk was 29.29% (95% CI, 19.74-43.47) with mechanical prostheses versus 13.50% (95% CI, 4.31-42.30) for bioprostheses. Switching to heparin during the first trimester demonstrated a bleeding risk of 7.78% (95% CI, 3.71-16.31) versus 4.08% (95% CI, 1.17-14.28) for women on oral anticoagulants throughout pregnancy and a valve thrombosis risk of 6.99% (95% CI, 2.08-23.51) versus 2.89% (95% CI, 1.40-5.94). Administration of anticoagulant dosages greater than 5 mg resulted in a risk of fetal adverse events of 74.24% (95% CI, 56.11-98.23) versus 8.85% (95% CI, 2.70-28.99) in ≤5 mg. Conclusions: A bioprosthesis seems the best option for women of childbearing age who are interested in future pregnancy after MVR. If mechanical valve replacement is preferred, the favorable anticoagulation regimen is continuous low-dose oral anticoagulants. Shared decision-making remains priority when choosing a prosthetic valve for young women