Maternal mental health: a key area for future research among women with congenital heart disease.

In this viewpoint, we respond to the recently published national priorities for research in congenital heart disease (CHD) among adults, established through the James Lind Alliance Priority Setting Partnership, with specific attention to priority 3 (mental health) and priority 5 (maternal health). Our recent policy impact project explored how maternal mental health is currently addressed in adult congenital heart disease (ACHD) services in the National Health Service, identified gaps and discussed possible ways forward. Our multidisciplinary discussion groups, which included women with lived experience of CHD and pregnancy, cardiology and obstetrics clinicians and medical anthropologists, found that while pregnancy and the postnatal period increase the mental health challenges faced by women with CHD, current services are not yet equipped to address them. Based on this work, we welcome the prioritisation of both mental health and maternal health in ACHD, and suggest that future research should focus on the overlaps between these two priority areas.

Altered cardiac and vascular stiffness in pregnancy after a hypertensive pregnancy.

Hypertensive disorders of pregnancy are an important cause of morbidity and mortality, impacting on both maternal and fetal wellbeing. Affected women are at higher risk of future cardiovascular morbidity and mortality. Our study objective was to assess differences in cardiovascular function in pregnant women previously affected by gestational hypertension or preeclampsia. Pregnant women diagnosed with gestational hypertension or preeclampsia in a previous pregnancy were recruited at the start of a subsequent pregnancy and compared to healthy pregnant and non-pregnant controls. All patients underwent pulse wave analysis and echocardiography. Indexes of echocardiography-derived arterial and left ventricular elastance were calculated. In our study women with prior hypertension (n = 25) were more likely to have blood pressure in the 120-139/80-99 mmHg (prehypertension) range. Women with previous hypertension in pregnancy had increased late diastolic transmitral flow velocities (A wave) and increased augmentation index. Women without prior hypertension (n = 50) demonstrated more compliance (reduced EaI and Ees) compared to the non-pregnant controls (n = 40). This adaptation was not seen in pregnancy with prior hypertension, where increased arterial stiffness was observed. In conclusion we have shown increased prevalence of prehypertension and increased arterial stiffness in pregnant women previously affected by gestational hypertensive disease. An increased atrial component to ventricular filling reflects altered diastolic function after hypertensive pregnancy. These women are at increased future cardiovascular risk due to altered cardiac and vascular function and require effective risk mitigation.

Monocytes are increased in pregnancy after gestational hypertensive disease.

Monocytes derive from bone marrow and circulate in the blood. They phagocytose, produce cytokines and present antigens. Individual monocyte subsets play distinct roles in the pathogenesis of cardiovascular disease, but their implications in gestational hypertensive disease are unclear. Our objective was to examine the difference in monocyte subsets between pregnant women with or without previous hypertension in pregnancy. Women were enrolled in a prospective observational study in which monoclonal antibodies against cell surface receptors were used to detect monocytes in the peripheral blood by flow cytometry. We compared 17 pregnant women with previous hypertension in pregnancy (Group 1) and 42 pregnant women without previous gestational hypertensive disease (Group 2) with 27 healthy, non-pregnant controls (Group 3). The pregnant women were studied at 13 ± 1 weeks gestation. Monocyte subsets were quantified by flow cytometry: Mon1 (CD14++CD16-CCR2+), Mon2 (CD14++CD16+CCR2+), Mon3 (CD14+CD16+CCR2-), their aggregates with platelets and expression of the surface markers. The groups were well-matched for age, body mass index and ethnicity (P > 0.05 for all). Mon1 counts were higher in women with a history of gestational hypertension or preeclampsia compared to other groups (Group 1 = 441 per µl (376-512); Group 2 = 357 (309-457); Group 3 = 323 (277-397); P < 0.001). Mon3 was higher in both groups of pregnant women compared to non-pregnant controls (Group 1 = 51 (38-62); Group 2 = 38 (29-58); Group 3 = 26 (20-40), P = 0.002). Increased monocytes in women with a previous hypertensive pregnancy generates a hypothesis that these cells may link hypertension in pregnancy, chronic inflammation and future cardiovascular risk.

The prenatal exome - a door to prenatal diagnostics?

Introduction: Prenatal exome sequencing (ES) allows parents the opportunity to obtain arapid molecular diagnosis of monogenic etiology when their fetus is found to have structural anomalies detected on prenatal ultrasound. Such information can improve antenatal and neonatal counseling, decision-making and management, and expand reproductive options in subsequent pregnancies.Areas covered: This review appraises the evidence, from acomprehensive search of bibliographic databases, for the introduction of ES into the fetal medicine care pathway when investigating congenital malformations. The perspectives of clinical geneticists, clinical scientists, fetal medicine specialists, and patients are explored in relation to the novel investigation and the benefits and challenges of its use in ongoing pregnancies with particular reference to UK medical practice.Expert opinion: ES provides agenetic diagnosis for more than 1 in 10 fetuses with structural differences on ultrasound and normal conventional tests (karyotype or chromosomal microarray) in carefully selected cases. The diagnostic rate increases for certain phenotypes and can range between 6% and 80% where conventional cytogenetics have not detected adiagnosis. Expert oversight is required to ensure that patients receive high-quality, evidence-based care and accurate counseling, supported by amultidisciplinary team familiar with the test and its implications.

Medical therapy to attenuate fetal anaemia in severe maternal red cell alloimmunisation.

Haemolytic disease of the fetus and newborn (HDFN) remains an important cause of fetal mortality with potential neonatal and longer-term morbidity. HDFN is caused by maternal red cell alloimmunisation, with IgG antibodies crossing the placenta to destroy fetal erythroid cells expressing the involved antigen. Intrauterine fetal blood transfusion is the therapy of choice for severe fetal anaemia. Despite a strong evidence base and technical advances, invasive fetal therapy carries risk of miscarriage and preterm birth. Procedure-related risks are increased when invasive, in utero transfusion is instituted prior to 22 weeks to treat severe early-onset fetal anaemia. This review focuses upon this cohort of HDFN and discusses intravenous immunoglobin (IVIg) and novel monoclonal antibody (M281, nipocalimab) treatments which, if started at the end of the first trimester, may attenuate the transplacental passage and fetal effects of IgG antibodies. Such therapy has the ability to improve fetal survival in this severe presentation of HDFN when early in utero transfusion may be required and may have wider implications for the perinatal management in general.

Red cell alloimmunization: A 2020 update.

Management of maternal red cell alloimmunization has been revolutionized over the last 60 years. Advances in the prevention, screening, diagnosis, and treatment of alloimmune-induced fetal anemia make this condition an exemplar for contemporary practice in fetal therapy. Since survival is now an expectation, attention has turned to optimization of long-term outcomes following an alloimmunized pregnancy. In this review, the current management of red cell alloimmunization is described. Current research and future directions are discussed with particular emphasis on later life outcomes after alloimmune fetal anemia.

Updated guidance for the management of twin and triplet pregnancies from the National Institute for Health and Care Excellence guidance, UK: What's new that may improve perinatal outcomes?

In September 2019, NICE published updated guidance on the management of multiple pregnancy (NG 137). Many of the previous recommendations for care are upheld but there have been important changes: increased frequency of combined ultrasound/specialist antenatal care appointments for pregnancies containing a monochorionic placenta (twins and triplets), increased frequency of ultrasound monitoring in all triplet pregnancies, changes in the definition of selective growth restriction and its subsequent referral pathways, the introduction of some monitoring for twin (or triplet) anemia polycythemia sequence in monochorionic pregnancies (albeit in complex pregnancies or at an advanced stage), and a recommended timing of birth for any pregnancy with monoamniotic fetuses. New recommendations have been made for mode of delivery, fetal monitoring in labor, maternal analgesia, and the prevention of postpartum hemorrhage. The absence of any recommendation relating to the prevention of preterm birth is notable. The basis and implications of the updates that may improve perinatal outcomes are discussed.

Echocardiographic Structure and Function in Hypertensive Disorders of Pregnancy: A Systematic Review.

BACKGROUND: Echocardiography is commonly used to direct the management of hypertensive disorders in medical patients, but its application in pregnancy is unclear. Our objective was to define the use of echocardiography in pregnancies complicated by gestational hypertension (GH) and preeclampsia. METHODS AND RESULTS: We performed a systematic review of articles using an electronic search of databases from inception to March 2015, prospectively registered with PROSPERO (CRD42015015700). Eligible studies included pregnant women with GH or preeclampsia, evaluating left ventricular structure and function using echocardiography. The search strategy identified 36 studies, including 745 women with GH and 815 women with preeclampsia. The populations were heterogeneous with respect to clinical characteristics, parity, and risk of bias. Increased vascular resistance and left ventricular mass were the most consistent findings in GH and preeclampsia. Differentiating features from normal pregnancy were left ventricular wall thickness of ≥1.0 cm, exaggerated reduction in E/A, and lateral e' of <14 cm/s. There was disagreement between studies with regard to cardiac output because of the timing of echocardiography, although reduced stroke volume was an indicator of adverse prognosis. Diastolic dysfunction and left ventricular remodeling are most marked in severe and early-onset preeclampsia, but are also markers of preeclampsia before clinical manifestation, and are associated with adverse outcomes. CONCLUSIONS: Echocardiography is a valuable tool to stratify risk and can guide management and counseling in the preclinical and clinical phases of GH and preeclampsia. Changes in cardiac function and morphology are recognizable at an asymptomatic early stage and correlate with disease severity and adverse outcomes.