Recurrent postmenopausal bleeding: Pathological findings and predictive factors. A multicenter, prospective, observational study.

INTRODUCTION: Recurrent postmenopausal bleeding (PMB) occurs in 6%-25% of postmenopausal women who have experienced a previous episode of PMB. The question of whether recurrent PMB leads to a higher risk of endometrial cancer (EC) in comparison to a single episode of PMB is, however, controversial. Furthermore, little is known about predictive factors for recurrent PMB. MATERIAL AND METHODS: A multicenter prospective cohort study was conducted over a 5-year period in four hospitals in the Netherlands. Women with PMB undergoing endometrial sampling and aged 40 years and older were included. Occurrence of recurrent PMB was retrospectively determined. Primary outcomes included (1) the incidence of recurrent PMB and (2) differences in pathological findings between patients with a single episode vs recurrent PMB. Secondary outcomes included (1) the association between diagnosis of benign polyps at first PMB and pathological findings at recurrent PMB and (2) factors predictive for recurrent PMB. RESULTS: A total of 437 women with PMB were included, of whom 360 were at risk of recurrent PMB. With a median follow-up of 61 months (IQR (Interquartile range) 44-73), 26.4% experienced recurrent PMB. Patients with recurrent PMB were more often diagnosed with benign polyps (34.7% vs. 25.1%, p-value 0.015) and less frequently with a malignancy (5.3% vs. 17.8%, p-value 0.015), compared to patients with a single episode of PMB. Benign polyps at initial PMB were not associated with a (pre)malignancy at recurrence (OR 4.16, 95% CI 0.75-23.03). Predictive factors for recurrent PMB included use of hormone replacement therapy (HRT) (OR 3.32, 95% CI 1.64-6.72), and benign polyps at initial PMB (OR 1.80, 95% CI 1.07-3.04). CONCLUSIONS: Recurrent PMB is common in women with a previous episode of PMB. Compared to patients with a single episode of PMB, patients with recurrent PMB and benign histological outcomes at accurate workup during their first episode were less often diagnosed with malignancies and more frequently with benign polyps. Benign polyps at first PMB are predictive for recurrent PMB, but not for a higher risk of (pre)malignancy.

Long-term quality of life after obstetric intensive care unit admission: A cross-sectional cohort study.

OBJECTIVE: To assess the long-term quality of life (QoL) after obstetric Intensive Care Unit (ICU) admission. DESIGN: Cross-sectional survey study. SETTING: Tertiary care centre. POPULATION: Women admitted to the level 3 ICU during pregnancy or ≤6 weeks postpartum, between 2000 and 2015. METHODS: Quality of life measures were compared with the population reference values. Associations with baseline ICU parameters were assessed with multivariable linear regression. Patient-reported outcome and experience measures (PROMs/PREMs) were described. MAIN OUTCOME MEASURES: Quality of life according to the Linear Analogous Scale (LAS), the Satisfaction with Life Scale (SWLS) and the SF-36 questionnaire; PROMs/PREMs using the Pregnancy and Childbirth outcome set of the International Consortium for Health Outcomes Measurement. RESULTS: Of all 265 obstetric ICU admissions, 230 were eligible and 94 (41%) were included (median follow-up time 14 years). The LAS (75.7 versus 78.7, p = 0.077) and SWLS (25.2 versus 26, p = 0.176) sum scores were not different from the population reference values. The SF-36 subdomains bodily pain (55.3 versus 73.9), general health (58.2 versus 73.9) and vitality (56.9 versus 69.1) were lower than the reference values (all p < 0.001). PROMs/PREMs were low in 46.2% for pain, 15.1% for depression, 11.8% for satisfaction with care and 52.7% for healthcare responsiveness. An indirect obstetric ICU admission diagnosis was independently associated with a reduced physical health score (B -1.7, 95% confidence interval [CI] -3.4 to -0.1) and severe neonatal morbidity with a reduced mental health score (B -6.6, 95% CI -11.3 to -1.8). CONCLUSION: Obstetric ICU admission is associated with reductions in long-term physical health QoL and in some patients with mental health QoL. We suggest multidisciplinary rehabilitation and long-term psychosocial support.

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.

ACE Inhibitor and Angiotensin Receptor Blocker Use During Pregnancy: Data from the ESC Registry Of Pregnancy and Cardiac Disease (ROPAC).

Angiotensin-converting enzyme inhibitors (ACE-Is) and angiotensin receptor blockers (ARBs) are not recommended during the second and third trimester because of the significant risk of congenital anomalies associated with their use. However, data are scarce, especially regarding their use in the first trimester and about the impact of stopping just before pregnancy. Our study illustrates the profile of the women who used ACE-Is or ARBs during pregnancy and evaluates the impact on perinatal outcomes. The Registry of Pregnancy and Cardiac Disease is a prospective, global registry of pregnancies in women with structural heart disease. Outcomes were compared between women who used ACE-Is or ARBs and those who did not. Multivariable regression analysis was performed to assess the effect of ACE-I or ARB use on the occurrence of congenital anomalies. ACE-Is (n = 35) and/or ARBs (n = 8) were used in 42 (0.7%) of the 5,739 Registry of Pregnancy and Cardiac Disease pregnancies. Women who used ACE-Is or ARBs more often came from a low-or-middle-income country (57% vs 40%, p = 0.021), had chronic hypertension (31% vs 6%, p <0.001), or a left ventricular ejection fraction <40% (33% vs 4%, p <0.001). In the multivariable analysis, ACE-I use during the first trimester was associated with an increased risk of congenital anomaly (odds ratio 3.2, 95% confidence interval 1.0 to 9.6). Therefore, ACE-Is should be avoided during pregnancy, also in the first trimester, because of a higher risk of congenital anomalies. However, there is no need to stop long before pregnancy. Preconception counseling is crucial to discuss the potential risks of these medications, to evaluate the clinical condition and, if possible, to change or stop the medication.

Diuretics in pregnancy: Data from the ESC Registry of Pregnancy and Cardiac disease (ROPAC).

AIMS: Data on diuretic use in pregnancy are limited and inconsistent, and consequently it remains unclear whether they can be used safely. Our study aims to evaluate the perinatal outcomes after in-utero diuretic exposure. METHODS AND RESULTS: The Registry Of Pregnancy And Cardiac disease (ROPAC) is a prospective, global registry of pregnancies in women with heart disease. Outcomes were compared between women who used diuretics during pregnancy versus those who did not. Multivariable regression analysis was used to assess the impact of diuretic use on the occurrence of congenital anomalies and foetal growth. Diuretics were used in 382 (6.7%) of the 5739 ROPAC pregnancies, most often furosemide (86%). Age >35 years (odds ratio [OR] 1.5, 95% confidence interval [CI] 1.2-2.0), other cardiac medication use (OR 5.4, 95% CI 4.2-6.9), signs of heart failure (OR 1.7, 95% CI 1.2-2.2), estimated left ventricular ejection fraction <40% (OR 2.9, 95% CI 2.0-4.2), New York Heart Association class >II (OR 3.4, 95% CI 2.3-5.1), valvular heart disease (OR 6.3, 95% CI 4.7-8.3) and cardiomyopathy (OR 3.9, 95% CI 2.6-5.7) were associated with diuretic use during pregnancy. In multivariable analysis, diuretic use during the first trimester was not significantly associated with foetal or neonatal congenital anomalies (OR 1.3, 95% CI 0.7-2.6), and diuretic use during pregnancy was also not significantly associated with small for gestational age (OR 1.4, 95% CI 1.0-1.9). CONCLUSIONS: Our study does not conclusively establish an association between diuretic use during pregnancy and adverse foetal outcomes. Given these findings, it is essential to assess the risk-benefit ratio on an individual basis to guide clinical decisions.

Pregnancy in women with congenital heart disease: a focus on management and preventing the risk of complications.

INTRODUCTION: Congenital heart disease (CHD) is the most common cardiac disorder in pregnancy in the western world (around 80%). Due to improvements in surgical interventions more women with CHD are surviving to adulthood and choosing to become pregnant. AREAS COVERED: Preconception counseling, antenatal management of CHDs and strategies to prevent maternal and fetal complications.Preconception counseling should start early, before the transition to adult care and be offered to both men and women. It should include the choice of contraception, lifestyle modifications, pre-pregnancy optimization of cardiac state, the chance of the child inheriting a similar cardiac lesion, the risks to the mother, and long-term prognosis. Pregnancy induces marked physiological changes in the cardiovascular system that may precipitate cardiac complications. Risk stratification is based on the underlying cardiac disease and data from studies including CARPREG, ZAHARA, and ROPAC. EXPERT OPINION: Women with left to right shunts, regurgitant lesions, and most corrected CHDs are at lower risk and can be managed in secondary care. Complex CHD, including systemic right ventricle need expert counseling in a tertiary center. Those with severe stenotic lesions, pulmonary artery hypertension, and Eisenmenger's syndrome should avoid pregnancy, be given effective contraception and managed in a tertiary center if pregnancy does happen.

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.

Pregnancy outcomes in women with Ebstein's anomaly: data from the Registry of Pregnancy And Cardiac disease (ROPAC).

OBJECTIVE: Ebstein's anomaly is a rare congenital cardiac condition and data regarding pregnancy outcomes in this patient group are scarce. We evaluated the maternal and perinatal risks of pregnancy in 81 women with Ebstein's anomaly. METHODS: The Registry of Pregnancy and Cardiac disease is a prospective global registry of pregnancies in women with structural cardiac disease. Pregnancy outcomes in women with Ebstein's anomaly were examined. The primary outcome was the occurrence of a major adverse cardiac event (MACE) defined as maternal mortality, heart failure, arrhythmia, thromboembolic event or endocarditis. Secondary endpoints were obstetric and perinatal outcomes and the influence of pregnancy on tricuspid valve regurgitation as well as right atrial and ventricular dimensions. RESULTS: In the 81 women with Ebstein's anomaly (mean age 29.7±6.1 years, 46.9% nulliparous), MACE occurred in 8 (9.9%) pregnancies, mostly heart failure (n=6). There were no maternal deaths. Prepregnancy signs of heart failure were predictive for MACE. Almost half of the women were delivered by caesarean section (45.7%) and preterm delivery occurred in 24.7%. Neonatal mortality was 2.5% and 4.9% of the infants had congenital heart disease. In the subgroup in which prepregnancy and postpregnancy data were available, there was no difference in tricuspid valve regurgitation grade or right atrial and ventricular dimensions before and after pregnancy. CONCLUSIONS: Most women with Ebstein's anomaly tolerate pregnancy well, but women with prepregnancy signs of heart failure are at higher risk for MACE during pregnancy and should be counselled accordingly.