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Background Pregnant patients with Marfan's syndrome (MFS) are at an increased risk for adverse aortic outcomes. While beta-blockers are used to slow aortic root dilatation in nonpregnant MFS patients, the benefit of such therapy in pregnant MFS patients remains controversial. The purpose of this study was to investigate the effect of beta-blockers on aortic root dilatation during pregnancy in MFS patients. Methods This was a longitudinal single-center retrospective cohort study of females with MFS who completed a pregnancy between 2004 and 2020. Clinical, fetal, and echocardiographic data were compared in patients on- versus off-beta-blockers during pregnancy. Results A total of 20 pregnancies completed by 19 patients were evaluated. Beta-blocker therapy was initiated or continued in 13 (65%) of the 20 pregnancies. Pregnancies on-beta-blocker therapy experienced less aortic growth compared with those off-beta-blockers (0.10 [interquartile range, IQR: 0.10–0.20] vs. 0.30 cm [IQR: 0.25–0.35]; p = 0.03). Using univariate linear regression, maximum systolic blood pressures (SBP), increase in SBP, and absence of beta-blocker use in pregnancy were found to be significantly associated with greater increase in aortic diameter during pregnancy. There were no differences in rates of fetal growth restriction between pregnancies on- versus off-beta-blockers. Conclusion This is the first study that we are aware of to evaluate changes in aortic dimensions in MFS pregnancies stratified by beta-blocker use. Beta-blocker therapy was found to be associated with less aortic root growth during pregnancy in MFS patients.

Background: While the incidence of pregnancy has increased among individuals with adult CHD, little has been described about considerations and experiences of patients with adult CHD regarding pregnancy. Objective: We aimed to explore patients’ motivations, concerns, and decision-making processes regarding pregnancy. Methods: In April 2019–January 2020, we conducted in-depth telephone interviews with patients (n = 25) with simple, moderate, or complex adult CHD, who received prenatal care at the University of Washington during 2010–2019 and experienced a live birth. Transcripts were analysed using thematic analysis. Results: Participants described motivations for pregnancy as both internal desires (motherhood, marriage fulfillment, biological connection, fetal personhood, self-efficacy) and external drivers (family or community), as well as concerns for the health and survival of themselves and the fetus. Factors that enabled their decision to maintain a pregnancy included having a desire that outweighed their perceived risk, using available data to guide their decision, planning for contingencies and knowing their beliefs about termination, plus having a trusted healthcare team, social support, and resources. Factors that led to insurmountable risk in subsequent pregnancies included desire having been fulfilled by the first pregnancy, compounding risk with age and additional pregnancies, new responsibility to an existing child, and reduced healthcare team and social support. Conclusions: Understanding individuals’ motivations and concerns, and how they weigh their decisions to become or remain pregnant, can help clinicians better support patients with adult CHD considering pregnancy. Clinician education on patient experiences is warranted.

OBJECTIVE: Aberrant DNA methylation is an early event in carcinogenesis which could be leveraged to detect ovarian cancer (OC) in plasma. METHODS: DNA from frozen OC tissues, benign fallopian tube epithelium (FTE), and buffy coats from cancer-free women underwent reduced representation bisulfite sequencing (RRBS) to identify OC MDMs. Candidate MDM selection was based on receiver operating characteristic (ROC) discrimination, methylation fold change, and low background methylation among controls. Blinded biological validation was performed using methylated specific PCR on DNA extracted from independent OC and FTE FFPE tissues. MDMs were tested using Target Enrichment Long-probe Quantitative Amplified Signal (TELQAS) assays in pre-treatment plasma from women newly diagnosed with OC and population-sampled healthy women. A random forest modeling analysis was performed to generate predictive probability of disease; results were 500-fold in silico cross-validated. RESULTS: Thirty-three MDMs showed marked methylation fold changes (10 to >1000) across all OC subtypes vs FTE. Eleven MDMs (GPRIN1, CDO1, SRC, SIM2, AGRN, FAIM2, CELF2, RIPPLY3, GYPC, CAPN2, BCAT1) were tested on plasma from 91 women with OC (73 (80%) high-grade serous (HGS)) and 91 without OC; the cross-validated 11-MDM panel highly discriminated OC from controls (96% (95% CI, 89–99%) specificity; 79% (69–87%) sensitivity, and AUC 0.91 (0.86 – 0.96)). Among the 5 stage I/II HGS OCs included, all were correctly identified. CONCLUSIONS: Whole methylome sequencing, stringent filtering criteria, and biological validation yielded candidate MDMs for OC that performed with high sensitivity and specificity in plasma. Larger plasma-based OC MDM studies, including testing of pre-diagnostic specimens, are warranted.

Pregnancy-associated aortic dissection (AD) is a rare event, with an incidence of 0.0004% per pregnancy. The work of the Aortic Dissection Collaborative identified pregnancy-associated AD as a high-priority topic, despite its rarity. The Pregnancy Working Group, which included physicians and patient stakeholders, performed a systematic literature review of pregnancy-associated AD from 1960 to 2021 and identified 6,333 articles through PubMed, OVID MEDLINE, Cochrane, Embase, CINAHL and Web of Science. The inclusion criterion was AD in pregnant populations and exclusion criteria were case reports, conference abstracts, and languages other than English. Assessment of full-text articles for eligibility after removal of duplicates from all databases yielded 68 articles to be included in the final review. Topics included were timing of AD in pregnancy, type of AD, and management considerations of pregnancy-associated AD. The Pregnancy Working Group identified gaps in knowledge and future areas of research for pregnancy-associated AD, including clinical management, mental health outcomes post AD, reproductive and genetic counseling, and contraception after AD. Future collaborative projects could be a multicenter, international registry for all pregnancy-associated AD to refine the risk factors, best practice and management of AD in pregnancy. In addition, future mixed methodology studies may be useful to explore social, mental, and emotional factors related to pregnancy-associated AD and to determine support groups' effect on anxiety and depression related to these events in the pregnancy and postpartum period.

As the COVID-19 pandemic progresses, widespread community transmission of SARS-CoV-2 has ushered in a volatile era of viral immune evasion rather than the much-heralded stability of “endemicity” or “herd immunity.” At this point, an array of viral variants has rendered essentially all monoclonal antibody therapeutics obsolete and strongly undermined the impact of vaccinal immunity on SARS-CoV-2 transmission. In this work, we demonstrate that antigenic drift resulting in evasion of pre-existing immunity is highly evolutionarily favored and likely to cause waves of short-term transmission. In the long-term, invading variants that induce weak cross-immunity against pre-existing strains may co-circulate with those pre-existing strains. This would result in the formation of serotypes that increase disease burden, complicate SARS-CoV-2 control and raise the potential for increases in viral virulence. Less durable immunity does not drive positive selection as a trait, but such strains may transmit at high levels if they establish. Overall, our results draw attention to the importance of inter-strain cross-immunity as a driver of transmission trends and the importance of early immune evasion data to predict the trajectory of the pandemic.

Background: Because adverse events are more common than in the general population, pregnancy is a high-risk experience for some patients with adult congenital heart disease (ACHD). Guidelines for pregnancy are based on published literature, informed by adverse clinical outcomes with less priority given to patients' lived experiences. This study aims to describe ACHD patients' expectations for and experiences with pregnancy, including factors that influenced patients’ perceived quality of care.” Methods: We conducted a qualitative study of 25 patients who received care between 2010 and 2019. Purposive sampling was used to gain diversity in ACHD lesion complexity, race, age at pregnancy, and marital status. Semi-structured telephone interview data were analyzed using thematic analysis. Results: Mean age at pregnancy was 29 years (range 15–41 years), and 84% had more than one completed pregnancy. ACHD was simple in six participants (24%), moderate in 11 (44%), and complex in eight (32%). Participants' perceptions of pregnancy care were influenced by their experiences in four domains: 1) their existing expectations, derived from prior clinicians' counsel and from observations of others' pregnancies; 2) clinicians' ability and willingness to partner with the patient to address their individual needs, including pre-pregnancy testing, pregnancy education, and planning for birth and delivery; 3) clinicians' recommendations that account for logistical reality and patients’ unique life situations; and 4) the importance of clinician confidence and communication in providing care for patients with ACHD. Conclusion: To achieve positive pregnancy outcomes, ACHD patients favor partnerships with clinicians centered on education, realistic recommendations, and good communication.

The association between prenatal phthalate exposure and late preterm birth (LPTB) is unclear. We examined singleton pregnancies (2006–2011) from a racially and socioeconomically diverse sample of women in the CANDLE cohort of the ECHO-PATHWAYS Consortium. Urine collected in the second and third trimester was analyzed for 14 phthalate metabolites. Multivariate logistic and linear regressions were performed for LPTB, defined as delivery 34–37 weeks, and gestational week, respectively. Models were controlled for socio-demographics, behavioral factors, clinical measurements, medical history, and phthalates in the other trimester. Effect modification by race and pregnancy stress, indicated by intimate partner violence (IPV), was investigated. We conducted a secondary analysis in women with spontaneous preterm labor. The rate of LPTB among 1408 women (61% Black, 32% White) was 6.7%. There was no evidence of decreased gestational age (GA) in association with any phthalate metabolite. Each two-fold increase in third trimester mono-benzyl phthalate (MBzP) was associated with 0.08 weeks longer gestational age (95% CI: 0.03, 0.12). When restricting to women with spontaneous labor, second trimester mono-n-butyl phthalate (MBP) was associated with 54% higher odds (95% CI: 2%, 132%) of LPTB. Associations were not modified by maternal race or IPV exposure. In conclusion, we observed mixed evidence concerning our hypothesis that prenatal phthalate exposure increases risk of LPTB, though secondary analyses suggest increased risk of spontaneous LPTB associated with MBP, which is consistent with a recent pooled analysis of 16 cohorts.