Pregnancy-related Events Research Articles

Pregnancy and inherited cardiomyopathies: insights from specialized care

Abstract Background Pregnancy and postpartum represent periods of increased risk of cardiovascular complications. Management of women with modified World Health Organization (mWHO) class II–III, III, and IV during pregnancy and around delivery should be conducted at an expert centre by a multidisciplinary team. Purpose Our objective was to analyze the impact of pregnancy on cardiomyopathy outcomes in a centre specialized in inherited cardiovascular conditions in the United Kingdom. Methods All women with cardiomyopathy referred due to pregnancy to our centre between 2016 and 2023 were retrospectively analyzed. Demographic, clinical, obstetric, genetic, electrocardiographic, and multimodal imaging variables were collected. Results Between 2016 and 2023, follow-up and delivery planning were initiated for 86 pregnancies in women with cardiomyopathies referred to our centre, resulting in 81 live births and 5 miscarriages, all in the first trimester. Among the full-term pregnancies, 17 (21%) were in patients in mWHO class I or II, 22 (27.2%) in II-III, 34 (42%) in III, and 8 (9.8%) in IV. The distribution of cardiomyopathy types among different mWHO classification is represented in Table 1. Women in mWHO class ≥ II-III had more pregnancy-related events than patients in mWHO I or II [28 (34.6%) vs 1 (1.2%); p = 0.004]. The most common complication in the first group was supraventricular tachycardia in 11 pregnancies (13.6%), followed by gestational diabetes in 9 (11.1%), left ventricular ejection fraction impairment in 4 (4.9%), preeclampsia in 3 (3.7%), and 1 (1.2%) ventricular tachycardia. One patient in the second group developed gestational diabetes. The distribution of the type of delivery among different mWHO classification is represented in Table 2. Only one patient with hypertrophic cardiomyopathy in mWHO II-III who underwent a caesarean section presented a post-delivery complication related to retroperitoneal haematoma, with no statistical significative differences between the groups (p = 0.604). 100% of the patients survived pregnancy and postpartum period. Conclusions Pregnant women with cardiomyopathy face an increased risk of adverse events. Despite the presence of cardiovascular and obstetric complications, careful monitoring at a specialized centre leads to favourable outcomes particularly concerning mortality rates for both the mother and fetus. This highlights the importance of a comprehensive risk assessment and meticulous pregnancy and delivery planning to ensure optimal maternal and fetal health.Table 1.Cardiomyopathy and mWHOTable 2.Type of delivery and mWHO

Pregnancy Recommendations Solely Based on Preclinical Evidence Should Be Integrated with Real-World Evidence: A Disproportionality Analysis of Certolizumab and Other TNF-Alpha Inhibitors Used in Pregnant Patients with Psoriasis.

Treatment for pregnant women with psoriasis is limited by the lack of information typically related to clinical trials. While anti-tumor necrosis factor (TNF) drugs offer therapeutic benefits, their safety during pregnancy is a concern. Notably, certolizumab is comparatively safer than adalimumab, etanercept, infliximab, and golimumab according to the current recommendations. Thus, this study aimed to conduct a pharmacovigilance comparative analysis of maternal and neonatal outcomes associated with certolizumab versus other anti-TNF drugs by using data from EudraVigilance. A descriptive analysis was performed of Individual Case Safety Reports (ICSRs) associated with an anti-TNF drug and related to the pregnant patients with psoriasis from 2009 and 2023, focusing our analysis on the specific pregnancy outcomes and fetal/neonatal disorders. The most common pregnancy-related adverse event was spontaneous abortion, predominantly related to adalimumab and certolizumab. Certolizumab was also reported in cases of caesarean section, gestational diabetes, abortion, fetal death, fetal distress syndrome, pre-eclampsia, and premature separation of placenta. Generally, the findings from our study depicted a safety profile that overlapped for each anti-TNF drug, both in maternal/neonatal outcomes and other adverse events, suggesting no substantial differences between treatments. We advocate for further investigations before making concrete recommendations.

Vaginal Microbiome and Pregnancy Complications: A Review.

Background/Objectives: There are indications that the microbial composition of the maternal mucosal surfaces is associated with adverse events during pregnancy. The aim of this review is to investigate the link between vaginal microbiome alterations and gestational complication risk. Methods: This comprehensive literature review was performed using Medline and Scopus databases. The following search algorithm was used, "Pregnancy Complications" [Mesh] AND (Vagin*), and after the literature screening, 44 studies were included in the final review. Results: The studies that were included investigated the association between vaginal microbial composition and preterm birth, miscarriage, preeclampsia, ectopic pregnancy, gestational diabetes mellitus, chorioamnionitis, and preterm premature rupture of membranes. In most of the studies, it was well established that increased microbial diversity is associated with these conditions. Also, the depletion of Lactobacillus species is linked to most of the gestational complications, while the increased relative abundance and especially Lactobacillus crispatus may exert a protective effect in favor of the pregnant woman. Several pathogenic taxa including Gardnerella, Prevotella, Sneathia, Bacterial Vaginosis-Associated Bacteria-2, Atopobium, and Megasphera seem to be correlated to higher maternal morbidity. Conclusions: Vaginal microbiome aberrations seem to have an association with pregnancy-related adverse events, but more high-quality homogenous studies are necessary to reliably verify this link.

Health Service Use and Costs During Pregnancy Among Privately Insured Individuals With Congenital Heart Disease

Individuals with congenital heart disease (CHD) are increasingly reaching childbearing age, are more prone to adverse pregnancy events, and uncommonly undergo recommended cardiac evaluations. Data to better understand resource allocation and financial planning are lacking. To examine health care use and costs for patients with CHD during pregnancy. This retrospective cohort study was performed from January 1, 2010, to December 31, 2016, using Merative MarketScan commercial insurance data. Participants included patients with CHD and those without CHD matched 1:1 by age, sex, and insurance enrollment year. Pregnancy claims were identified for all participants. Data were analyzed from September 2022 to March 2024. Baseline characteristics (age, US region, delivery year, insurance type) and pregnancy-related events (obstetric, cardiac, and noncardiac conditions; birth outcomes; and cesarean delivery). Health service use (outpatient physician, nonphysician, emergency department, prescription drugs, and admissions) and costs (total and out-of-pocket costs adjusted for inflation to represent 2024 US dollars). A total of 11 703 pregnancies (mean [SD] maternal age, 31.5 [5.4] years) were studied, with 2267 pregnancies in 1785 patients with CHD (492 pregnancies in patients with severe CHD and 1775 in patients with nonsevere CHD) and 9436 pregnancies in 7720 patients without CHD. Compared with patients without CHD, pregnancies in patients with CHD were associated with significantly higher health care use (standardized mean difference [SMD] range, 0.16-1.46) and cost (SMD range, 0.14-0.55) except for out-of-pocket inpatient and ED costs. After adjustment for covariates, having CHD was independently associated with higher total (adjusted cost ratio, 1.70; 95% CI, 1.57-1.84) and out-of-pocket (adjusted cost ratio, 1.40; 95% CI, 1.22-1.58) costs. The adjusted mean total costs per pregnancy were $15 971 (95% CI, $15 480-$16 461) for patients without CHD, $24 290 (95% CI, $22 773-$25 806) for patients with any CHD, $26 308 (95% CI, $22 788-$29 828) for patients with severe CHD, and $23 750 (95% CI, $22 110-$25 390) for patients with nonsevere CHD. Patients with vs without CHD incurred $8319 and $700 higher total and out-of-pocket costs per pregnancy, respectively. This study provides novel, clinically relevant estimates for the cardio-obstetric team, patients with CHD, payers, and policymakers regarding health care and financial planning. These estimates can be used to carefully plan for and advocate for the comprehensive resources needed to care for patients with CHD.

Prenatal arsenite exposure alters maternal cardiac remodeling during late pregnancy

Exposure to inorganic arsenic through drinking water is widespread and has been linked to many chronic diseases, including cardiovascular disease. Arsenic exposure has been shown to alter hypertrophic signaling in the adult heart, as well as in utero offspring development. However, the effect of arsenic on maternal cardiac remodeling during pregnancy has not been studied. As such, there is a need to understand how environmental exposure contributes to adverse pregnancy-related cardiovascular events. This study seeks to understand the impact of trivalent inorganic arsenic exposure during gestation on maternal cardiac remodeling in late pregnancy, as well as offspring outcomes. C57BL/6 J mice were exposed to 0 (control), 100 or 1000 μg/L sodium arsenite (NaAsO2) beginning at embryonic day (E) 2.5 and continuing through E17.5. Maternal heart function and size were assessed via transthoracic echocardiography, gravimetric measurement, and histology. Transcript levels of hypertrophic markers were probed via qRT-PCR and confirmed by western blot. Offspring outcomes were assessed through echocardiography and gravimetric measurement. We found that maternal heart size was smaller and transcript levels of Esr1 (estrogen receptor alpha), Pgrmc1 (progesterone receptor membrane component 1) and Pgrmc2 (progesterone receptor membrane component 2) reduced during late pregnancy with exposure to 1000 μg/L iAs vs. non-exposed pregnant controls. Both 100 and 1000 μg/L iAs also reduced transcription of Nppa (atrial natriuretic peptide). Akt protein expression was also significantly reduced after 1000 μg/L iAs exposure in the maternal heart with no change in activating phosphorylation. This significant abrogation of maternal cardiac hypertrophy suggests that arsenic exposure during pregnancy can potentially contribute to cardiovascular disease. Taken together, our findings further underscore the importance of reducing arsenic exposure during pregnancy and indicate that more research is needed to assess the impact of arsenic and other environmental exposures on the maternal heart and adverse pregnancy events.

Pregnancy-related cardiovascular events in marfan syndrome

Abstract Background Some studies have suggested an increased risk of aortic dissection (AoDis) during pregnancy and higher rate of cardiovascular (CV) events on the long-term in Marfan syndrome (MFS) patients. Purpose To analyse the rate of CV events during pregnancy and follow up in our cohort of MFS patients. Methods We prospectively collected data of a cohort of women with MFS that attended our dedicated clinic between the years 2000-2021. This included demographics, clinical characteristics and pregnancy. CV events were defined as AoDis, urgent AoSurg or CV death. Patients with a previous event before the first pregnancy were excluded. Results We identified 148 women with a mean age at last follow up of 40±16 years and a mean follow up of 11 years (IQR 25-75: 4-17 years). Sixty-nine patients fell pregnant (130 pregnancies, median 2, range 1-4 pregnancies, age at delivery 29±5y) and 79 were never pregnant. Amongst the 69 ever pregnant patients, 2 patients had a type A AoDis during pregnancy (one was unaware of the MFS diagnosis; the other was under follow up with a pre-pregnancy aortic root of 34mm/Z-score 1.5 and at third trimester of 36 mm/Z-score 2.2). No maternal deaths were recorded. Pregnancy related rate of CV events was 2.9% and 1.5% in women with known MFS diagnosis before pregnancy. Ever-pregnant patients were older at diagnosis (32±17y vs 20±14y, p<0,001) and at the end of follow up (49±14y vs 33±13, p<0,001) compared to never-pregnant patients. Ectopia lentis was significantly higher in never-pregnant patients (45.3% vs 25%, p=0.03). There were no statistically significant differences in time of follow up or other clinical features of MFS. Only 36% of the ever-pregnant cohort were diagnosed before pregnancy. During follow up, 14 patients from the ever-pregnant group and 16 patients from the never-pregnant group underwent prophylactic AoSurg (p=0,72). Never-pregnant patients were younger at age of elective AoSurg (35±14y vs 45±13y, p=0.031). Eleven (7.4%) patients experienced a CV event (7 type A and 4 type B AoDis), 7 in the ever-pregnant group and 4 in the never pregnant group (p=0.09). Age at CV event was similar in the ever-pregnant and never-pregnant groups (48±11y vs 40±8y, p=0.26) In the ever-pregnant group, 3 patients experienced ³2 CV events during follow up compared to none in the never-pregnant group (p=0.1). Conclusion In our cohort of ever pregnant MFS patients, 2.9% of patients experienced a pregnancy related CV event. On the long term, never-pregnant patients were younger at age of elective AoSurg but there were no differences between the groups in prophylactic AoSurg or CV events.

Assessment of antenatal care satisfaction amongst postpartum women at the University College Hospital, Ibadan, Nigeria

BackgroundMaternal mortality is unacceptably high especially in developing countries. About 287,000 women died during and following pregnancy and childbirth in 2020. The vast majority of these deaths (95 %) occurred in low and lower middle countries in 2020 and most could have been prevented. Every day in 2020, approximately 800 women died from preventable causes related to pregnancy and childbirth. Utilization of antenatal visit has been shown to improve birth outcome as well as the maternal outcome during pregnancy-related events, giving a positive impact when the visit frequency and care are adequate while satisfaction has equally been an important outcome measures of quality of care. In order to improve feto-maternal outcome and turn the tide against maternal deaths, it is expedient to assess the satisfaction of women who had experienced antenatal care with the aim of identifying areas requiring additional attention. ObjectiveThis study aimed to assess the level of antenatal care satisfaction of postpartum women and factors associated with satisfaction at the University College Hospital (UCH), Ibadan and their future intention for subsequent utilization of antenatal care. MethodsA descriptive cross-sectional study of 261 women in the postnatal ward using simple random sampling technique was conducted with an interviewer-administered structured questionnaire. Items in the questionnaire included sociodemographic and obstetric variables, assessment of quality of amenities, waiting time and level of satisfaction. Data was entered, cleaned and analyzed by computer using the Statistical Package for Social Sciences Version 23.0 (SPSS, IBM). The variables were summarized using frequencies, proportions, means and standard deviation. Chi Square was used for test of significance with the p-value set at P < 0.05. ResultsOf the 261 participants 176 (67.5 % percent) were aged 25–34 years; majority (244,93.5 %) had tertiary education while (189, 72.4 %) were skilled workers or professionals. Most of the women (243, 93.2 %) were Para 1–3 and the pregnancy was planned (80.8 %) while financing was mostly out of pocket (60.9 %). Only one-third of the participants has at least eight (8) antenatal contacts. In overall rating, most women (90.0 %) were satisfied with the antenatal care services received. The highest rating of satisfaction was with the competence of the service providers (90.4 %) especially with the care given to them and their unborn babies (90.4 %). The parity, distance of their home from antenatal clinic, number of antenatal contacts, number of health education sessions attended, total time spent, attitude of health workers, cost of services and desire to register again at the facility were statistically associated with patient’s satisfaction. Also, the number of antenatal visits was statistically associated with the fetal outcome. ConclusionThere is a high overall level of satisfaction with antenatal services among postpartum women in UCH. It is important to encourage women to register early to ensure they have adequate number of antenatal contacts and also participate in the health education sessions.

Belgian medication exposure during pregnancy (BeMeP), a new nationwide linked database: Linkage methods and prevalence of medication use.

This study aimed to describe the implementation of a new retrospective Belgian national cohort of pregnant women, the Belgian Medication Exposure during Pregnancy (BeMeP). We linked the national dispensing data to birth and death certificates and hospital stay data for a 7-year period between 2010 and 2016 for the first time in Belgium. We presented the characteristics of pregnancy events associated with the mothers enrolled in the linkage study. Next, we constructed a cohort of pregnancies and compared some characteristics computed using the BeMeP database with the national statistics. Finally, we described the use of medications during pregnancy based on the first level of the Anatomical Therapeutic Chemical (ATC) classification. We included 630 457 pregnant women with 900 024 pregnancy-related events (843 780 livebirths, 1937 stillbirths, 6402 ectopic events, and 47 905 abortions) linked to medication exposure information. Overall, 96.3% of live births and 83.5% of stillbirths (national statistics as reference) were captured from the BeMeP. During pregnancy, excluding the week of birth, 78.9% of live birth pregnancies and 79.6% of stillbirth pregnancies were exposed to at least one medication. The most frequently dispensed medications were anti-infectives (ATC code J = 50.2%) for live births and for stillbirths (44.0%). We linked information on pregnancies, all reimbursed medications dispensed by community pharmacists, all medications dispensed during hospitalization, sociodemographic status, and infant health to create the BeMeP database. The database represents a valuable potential resource for studying exposure-outcome associations for medication use during pregnancy.

Pregnancy-related adverse events associated with statins: a real-world pharmacovigilance study of the FDA Adverse Event Reporting System (FAERS)

ABSTRACT Background Statins, previously rated as pregnancy category X agents, were contraindicated during pregnancy due to the teratogenic effects observed in animal studies. However, it is still controversial whether statins have detrimental impact on pregnant women or not, and some studies even suggest a potential benefit of statin use against pregnancy complications. The aim of this study was to explore whether maternal exposure to statins is associated with increased rates of pregnancy-related adverse events (AEs), including abortion, abortion spontaneous, preterm birth, low birth weight, stillbirth/fetal death, and fetal complications. Research design and methods Data from 1 January 2004 to 30 June 2022 were extracted through the U.S. FDA Adverse Event Reporting System (FAERS) database, to conduct disproportionality analysis and Bayesian analysis by reporting odds ratio (ROR) and Bayesian confidence propagation neural network (BCPNN) algorithms. To identify the potential risks of pregnancy-related AEs, each statin was compared to all the other drugs, all the other statins, and the reference drugs (fenofibrate and evolocumab). Results A total of 477 cases involving pregnancy-related AEs associated with stains were submitted to the FAERS database by healthcare professionals. No obvious disproportionate association of abortion, abortion spontaneous, or stillbirth/fetal death was identified for all statins during gestation. In comparison with all the other drugs, lovastatin showed an increased risk of fetal complications (ROR = 2.45, 95% CI, 1.22–4.95; IC025 = 0.63), and pravastatin demonstrated increased risks of preterm birth (ROR = 4.89, 95% CI, 3.65–6.54; IC025 = 1.69) and low birth weight (ROR = 9.60, 95% CI, 5.56–16.56; IC025 = 1.88). Similar results were found when compared lovastatin or pravastatin with fenofibrate. Furthermore, statins were associated with higher proportion of fetal complications and preterm birth when comparing with evolocumab. Conclusions Statins did not increase the risk of pregnancy-related AEs, including abortion, abortion spontaneous, or stillbirth/fetal death. However, we did find significant disproportionality signals for preterm birth and low birth weight associated with pravastatin, and lovastatin was related to a higher proportion of fetal complications. The results in this study may provide evidence on the safety of statins during pregnancy, which need to be verified in further investigations.

Large-Scale Data Harmonization Across Prospective Studies.

The Preconception Period Analysis of Risks and Exposures Influencing Health and Development (PrePARED) Consortium creates a novel resource for addressing preconception health by merging data from numerous cohort studies. In this paper, we describe our data harmonization methods and results. Individual-level data from 12 prospective studies were pooled. The crosswalk-cataloging-harmonization procedure was used. The index pregnancy was defined as the first postbaseline pregnancy lasting more than 20 weeks. We assessed heterogeneity across studies by comparing preconception characteristics in different types of studies. The pooled data set included 114,762 women, and 25,531 (22%) reported at least 1 pregnancy of more than 20 weeks' gestation during the study period. Babies from the index pregnancies were delivered between 1976 and 2021 (median,2008), at a mean maternal age of 29.7(standard deviation, 4.6) years. Before the index pregnancy, 60% of women were nulligravid, 58% had a college degree or more, and 37% were overweight or obese. Other harmonized variables included race/ethnicity, household income, substance use, chronic conditions, and perinatal outcomes. Participants from pregnancy-planning studies had more education and were healthier. The prevalence of preexisting medical conditions did not vary substantially based on whether studies relied on self-reported data. Use of harmonized data presents opportunities to study uncommon preconception risk factors and pregnancy-related events. This harmonization effort laid the groundwork for future analyses and additional data harmonization.

COVID-19 and Cerebrovascular Disease

COVID-19 has been associated with numerous neurological complications, with acute cerebrovascular disease being one of the most devastating complications. Ischemic stroke is the most common cerebrovascular complication of COVID-19, affecting between 1 and 6% of all patients. Underlying mechanisms for COVID-related ischemic strokes are thought to be due to vasculopathy, endotheliopathy, direct invasion of the arterial wall, and platelet activation. Other COVID-19-associated cerebrovascular complications include hemorrhagic stroke, cerebral microbleeds, posterior reversible encephalopathy syndrome, reversible cerebral vasoconstriction syndrome, cerebral venous sinus thrombosis, and subarachnoid hemorrhage. This article discusses the incidence of these cerebrovascular complications, risk factors, management strategies, prognosis and future research directions, as well as considerations in pregnancy-related cerebrovascular events in the setting of COVID-19.

Safety of hepatitis E vaccination for pregnancy: a post-hoc analysis of a randomized, double-blind, controlled phase 3 clinical trial

ABSTRACT Special attention has been paid to Hepatitis E (HE) prophylaxis for pregnant women due to poor prognosis of HE in this population. We conducted a post-hoc analysis based on the randomized, double-blind, HE vaccine (Hecolin)-controlled phase 3 clinical trial of human papillomavirus (HPV) vaccine (Cecolin) conducted in China. Eligible healthy women aged 18–45 years were randomly assigned to receive three doses of Cecolin or Hecolin and were followed up for 66 months. All the pregnancy-related events throughout the study period were closely followed up. The incidences of adverse events, pregnancy complications, and adverse pregnancy outcomes were analysed based on the vaccine group, maternal age, and interval between vaccination and pregnancy onset. During the study period, 1263 Hecolin receivers and 1260 Cecolin receivers reported 1684 and 1660 pregnancies, respectively. The participants in the two vaccine groups showed similar maternal and neonatal safety profiles, regardless of maternal age. Among the 140 women who were inadvertently vaccinated during pregnancy, the incidences of adverse reactions had no statistical difference between the two groups (31.8% vs 35.1%, p = 0.6782). The proximal exposure to HE vaccination was not associated with a significantly higher risk of abnormal foetal loss (OR 0.80, 95% CI 0.38–1.70) or neonatal abnormality (OR 2.46, 95% CI 0.74–8.18) than that to HPV vaccination, as did distal exposure. Significant difference was not noted between pregnancies with proximal and distal exposure to HE vaccination. Conclusively, HE vaccination during or shortly before pregnancy is not associated with increased risks for both the pregnant women and pregnancy outcomes.

IL-6 and IL-8: An Overview of Their Roles in Healthy and Pathological Pregnancies

Interleukin-6 (IL-6) is an acknowledged inflammatory cytokine with a pleiotropic action, mediating innate and adaptive immunity and multiple physiological processes, including protective and regenerative ones. IL-8 is a pro-inflammatory CXC chemokine with a primary function in attracting and activating neutrophils, but also implicated in a variety of other cellular processes. These two ILs are abundantly expressed at the feto-maternal interface over the course of a pregnancy and have been shown to participate in numerous pregnancy-related events. In this review, we summarize the literature data regarding their role in healthy and pathological pregnancies. The general information related to IL-6 and IL-8 functions is followed by an overview of their overall expression in cycling endometrium and at the feto-maternal interface. Further, we provide an overview of their involvement in pregnancy establishment and parturition. Finally, the implication of IL-6 and IL-8 in pregnancy-associated pathological conditions, such as pregnancy loss, preeclampsia, gestational diabetes mellitus and infection/inflammation is discussed.

The influence of COVID-19 infection-associated immune response on the female reproductive system†.

Coronavirus disease 2019 (COVID-19) is a multi-system disease that has led to a pandemic with unprecedented ramifications. The pandemic has challenged scientists for the past 2 years and brought back previously abandoned research topics. COVID-19 infection causes a myriad of symptoms ranging from mild flu-like symptoms to severe illness requiring hospitalization. Case reports showed multiple systemic effects of COVID-19 infection, including acute respiratory distress syndrome, fibrosis, colitis, thyroiditis, demyelinating syndromes, and mania, indicating that COVID-19 can affect most human body systems. Unsurprisingly, a major concern for women all over the globe is whether a COVID-19 infection has any long-term effects on their menstrual cycle, fertility, or pregnancy. Published data have suggested an effect on the reproductive health, and we hypothesize that the reported reproductive adverse effects are due to the robust immune reaction against COVID-19 and the associated cytokine storm. While the COVID-19 receptor (angiotensin converting enzyme, ACE2) is expressed in the ovaries, uterus, vagina, and placenta, we hypothesize that it plays a less important role in the adverse effects on the reproductive system. Cytokines and glucocorticoids act on the hypothalamo-pituitary gonadal axis, arachidonic acid pathways, and the uterus, which leads to menstrual disturbances and pregnancy-related adverse events such as preterm labor and miscarriages. This hypothesis is further supported by the apparent lack of long-term effects on the reproductive health in females, indicating that when the cytokine storm and its effects are dampened, the reproductive health of women is no longer affected.

Blurring the Lines Between Life and Death — Ethical and Psychological Considerations in Posthumous Conception

ART practitioners routinely offer embryo and oocyte/sperm cryopreservation services to patients and couples who are interested in future family building. Unfortunately, some patients, whether due to disease or accident, die after cryopreserving their genetic material. In the event of a patient’s death, their partner or other family members may desire to use those materials to achieve pregnancy. However, posthumous reproduction (reproductive attempts after the death of a partner) has resulted in a number of ethical issues regarding pre-death consent from the deceased patient and ambiguous legal and social status for the resulting child(ren). Multiple psychological issues also arise during the course of posthumous reproduction. This includes decision making in the context of grieving the death of a loved one, family disagreements about posthumous reproduction, and coping with potential pregnancy-related adverse events. Further, it is unknown what if any psychological burden posthumously conceived children or their family members will bear as the child grows. From an ethical standpoint, it is often unclear as to who should have rights to these gametes or embryos as pre-death consent forms have often not been completed. Because of the psychological and ethical concerns regarding posthumous reproduction many practitioners have concerns about facilitating such treatment. This presentation will address the psychological and ethical issues in posthumous reproduction and will provide direction to providers for how to address these issues with surviving loved ones.

Thrombophilia Impact on Treatment Decisions, Subsequent Venous or Arterial Thrombosis and Pregnancy-Related Morbidity: A Retrospective Single-Center Cohort Study.

(1) Background: Thrombophilia testing utility has remained controversial since its clinical introduction, because data on its influence on treatment decisions are limited. (2) Methods: We conducted a single-center retrospective cohort study of 3550 unselected patients referred for thrombophilia consultation at the Bern University Hospital in Switzerland from January 2010 to October 2020. We studied the influence of thrombophilia testing results on treatment decisions and evaluated the association between thrombophilia and thromboembolic and pregnancy-related morbidity events after testing up to 03/2021. (3) Results: In 1192/3550 patients (34%), at least one case of thrombophilia was found and 366 (10%) had high-risk thrombophilia. A total of 211/3550 (6%) work-ups (111/826 (13%) with low-risk thrombophilia and 100/366 (27%) with high-risk thrombophilia) led to an appropriate decision to extend or initiate anticoagulation, and 189 (5%) negative results led to the withholding of anticoagulation therapy inappropriately. A total of 2492 patients (69%) were followed up for >30 days, with a median follow-up of 49 months (range, 1–183 months). Patients with high-risk thrombophilia had a higher risk of subsequent venous thromboembolic events and pregnancy-related morbidity compared to those without thrombophilia. (4) Conclusions: Our study demonstrated the limited usefulness of thrombophilia work-up in clinical decision-making. High-risk thrombophilia was associated with subsequent venous thromboembolism and pregnancy-related morbidity.

Facilitating safety evaluation in maternal immunization trials: a retrospective cohort study to assess pregnancy outcomes and events of interest in low-risk pregnancies in England

BackgroundMaternal characteristics like medical history and health-related risk factors can influence the incidence of pregnancy outcomes and pregnancy-related events of interest (EIs). Data on the incidence of these endpoints in low-risk pregnant women are needed for appropriate external safety comparisons in maternal immunization trials. To address this need, this study estimated the incidence proportions of pregnancy outcomes and pregnancy-related EIs in different pregnancy cohorts (including low-risk pregnancies) in England, contained in the Clinical Practice Research Datalink (CPRD) Pregnancy Register linked to Hospital Episode Statistics (HES) between 2005 and 2017.MethodsThe incidence proportions of 7 pregnancy outcomes and 15 EIs were calculated for: (1) all pregnancies (AP) represented in the CPRD Pregnancy Register linked to HES (AP cohort; N = 298 155), (2) all pregnancies with a gestational age (GA) ≥ 24 weeks (AP24+ cohort; N = 208 328), and (3) low-risk pregnancies (LR cohort; N = 137 932) with a GA ≥ 24 weeks and no diagnosis of predefined high-risk medical conditions until 24 weeks GA.ResultsMiscarriage was the most common adverse pregnancy outcome in the AP cohort (1 379.5 per 10 000 pregnancies) but could not be assessed in the other cohorts because these only included pregnancies with a GA ≥ 24 weeks, and miscarriages with GA ≥ 24 weeks were reclassified as stillbirths. Preterm delivery (< 37 weeks GA) was the most common adverse pregnancy outcome in the AP24+ and LR cohorts (742.9 and 680.0 per 10 000 pregnancies, respectively). Focusing on the cohorts with a GA ≥ 24 weeks, the most common pregnancy-related EIs in the AP24+ and LR cohorts were fetal/perinatal distress or asphyxia (1 824.3 and 1 833.0 per 10 000 pregnancies), vaginal/intrauterine hemorrhage (799.2 and 729.0 per 10 000 pregnancies), and labor protraction/arrest disorders (752.4 and 774.5 per 10 000 pregnancies).ConclusionsThis study generated incidence proportions of pregnancy outcomes and pregnancy-related EIs from the CPRD for different pregnancy cohorts, including low-risk pregnancies. The reported incidence proportions of pregnancy outcomes and pregnancy-related EIs are largely consistent with external estimates. These results may facilitate the interpretation of safety data from maternal immunization trials and the safety monitoring of maternal vaccines. They may also be of interest for any intervention studied in populations of pregnant women.

“It’s a lot of pain you’ve got to hide”: a qualitative study of the journey of fathers facing traumatic pregnancy and childbirth

BackgroundThis study aims to explore the emotional and behavioural responses and coping strategies of fathers or expectant fathers who faced a significant traumatic event during a partner's pregnancy, labour, or the postpartum period.MethodsThis prospective qualitative study of 24 fathers was conducted at a public teaching hospital in Brisbane, Australia. ‘Traumatic pregnancy’ was defined as a pregnancy complicated by life-threatening or severe risk to the mother and the fetus, termination of pregnancy, intrauterine fetal death or stillbirth. Semi-structured interviews of participants were conducted 3-4 months after the traumatic event. An initial qualitative analysis with automatic coding was performed using Leximancer and later followed by a six-phase manual thematic analysis.ResultsA pregnancy-related traumatic event had significant mental and physical impacts on fathers. Participants' reactions and coping strategies were varied and influenced by their background history, pre-existing vulnerabilities, and the gap between expectation and reality. Most fathers described a fluctuating state between their needs 'not being met' and 'being met'. These needs were conceptualised using Maslow’s hierarchy and Calman’s gap theory to construct a composite thematic model to depict the universal requirements of men facing a traumatic pregnancy or childbirth.ConclusionsA greater understanding of the needs of men and gaps in their care is urgently needed. A targeted effort is required to make maternity services father-inclusive. This approach may assist in preventing long term consequences on fathers, partners, and their children.

Energy balance and hippo effector activity in endometrium and corpus luteum of early pregnant ewes

The establishment of pregnancy in cows requires uterine activity regulation of the main Hippo signalling effector yes-associated protein 1 (YAP). It remains unknown (1) how YAP activity at the corpus luteum (CL) correlates with early pregnancy-related events in ruminants; and (2) if YAP activity in the uterus and CL can be affected by metabolic disorders that may lead to pregnancy failure in ruminants. To determine the effect of early pregnancy on total and phospho-YAP expression and its transcriptional activity in the CL, we compared non-pregnant vs pregnant ewes. To understand the YAP activity dysregulation with disorders that may result in pregnancy loss, we induced negative energy balance in pregnant ewes. Our main results indicate that early pregnancy alters the expression and activity patterns of YAP in the ovine CL but not in the endometrium. In addition, while our NEB-induced model fails to alter YAP activity at the endometrium level, we found that fasting during the first but not second week of pregnancy affects YAP activity in the CL of pregnant ewes. The data presented herein provide considerable insight into the activity of a signalling pathway that may be a key player in pregnancy recognition and establishment in ewes.

Pregnancy safety of COVID-19 vaccines is validated by the Vaccine Adverse Event Reporting System

Healthcare providers, vaccine manufacturers, and the public can submit reports to the CDC's Vaccine Adverse Event Reporting System (VAERS) which was created to collect reports of adverse events and reactions that occur following vaccination. Our objective was to assess the safety of COVID-19 vaccines for pregnancy-related events as reported by VAERS. This is a retrospective cohort study utilizing the United States VAERS. We included reproductive age (18-49 years old) females in this study who reported pregnancy-related events as of July 23, 2021 for the three COVID-19 vaccines available in the United States. Overall there were 1,146,536 VAERS events, of which 435,077 were COVID-19 vaccines related, 143,934 of these were reported in reproductive age women with 5,537 different symptoms. 2.7% of events (3,915/143,934) were pregnancy-related. Spontaneous abortion constituted the largest number of adverse events (0.47%: 678/143,934) There were no serious maternal sequelae reported after COVID-19 vaccinations nor was there an increase in other pregnancy-related adverse outcomes. The table shows the top 30 pregnancy-related symptoms reported. There were no significant differences in pregnancy-related issues among the 3 different COVID-19 vaccines. Our study of VAERS confirms the safety in pregnancy after COVID-19 vaccinations for each of the three different vaccines. Only 3,915 events after COVID-19 vaccines were pregnancy-related out of a total of 143,934 events among reproductive age women. The number of spontaneous abortions were in line with expected numbers, and there was no significant difference between the three vaccine manufactures. The strength of VAERS is that it is national in scope, can quickly provide an early warning of a safety problem with a vaccine, and is designed to rapidly detect unusual or unexpected patterns of adverse events, also known as “safety signals.” There were no “safety signals” for pregnancy-related events after COVID-19 vaccinations.