Ischemic heart disease in pregnancy: a practical approach to management.

Ischemic heart disease is a crucial issue during pregnancy. The term is composed of both preexisting conditions and acute coronary syndrome in pregnancy, including pregnancy-associated myocardial infarction, which can have a significant effect on maternal and fetal outcomes. This review provides a complete guide to managing ischemic heart disease in pregnant women, emphasizing the importance of multidisciplinary care and individualized treatment strategies. Cardiovascular disease, particularly ischemic heart disease, is now the leading cause of maternal mortality worldwide. Pregnancy introduces unique physiological changes that increase the risk of acute myocardial infarction, with pregnancy-associated myocardial infarction cases often associated with factors, such as advanced maternal age, chronic hypertension, and preexisting cardiovascular conditions. This review distinguishes between preexisting ischemic heart disease and pregnancy-associated myocardial infarction. It will emphasize the various etiologies of pregnancy-associated myocardial infarction, including coronary atherosclerosis and plaque rupture presenting as ST-elevation myocardial infarction, non-ST-elevation myocardial infarction, and other nonatherosclerotic causes, including spontaneous coronary artery dissection, vasospasm, and embolism. Our study discusses the practical management of ischemic heart disease in pregnancy, with a focus on preconception counseling, risk assessment, and tailored antenatal planning for women with preexisting ischemic heart disease. Moreover, this document focuses on the challenges of diagnosing cardiovascular disease, especially when presented with nonclassical risk factors and presentation. It provides insight into the appropriate diagnostic testing methods, such as electrocardiogram, cardiac biomarkers, and echocardiography. In addition, the review covers various treatment strategies, from medical management to more invasive procedures, including coronary angiography, percutaneous coronary intervention, and coronary artery bypass graft. Special attention is given to medication safety during pregnancy, including anticoagulation, beta-blockers, and antiplatelet agents. The complexities of delivery planning in women with ischemic heart disease are discussed, advocating for a multidisciplinary team-based approach and careful consideration of the timing and mode of delivery. Furthermore, the roles of breastfeeding and postpartum care are explored, emphasizing the long-term benefits and the suitability of various medications during lactation. Lastly, this review provides crucial insights into the management of ischemic heart disease in pregnancy, stressing the need for heightened awareness, prompt diagnosis, and tailored management to optimize maternal and fetal health outcomes.

Outcomes in Pregnant Adolescent Patients Infected With SARS-CoV-2.

BACKGROUND: Pregnant patients with coronavirus disease 2019 (COVID-19) are at risk for adverse pregnancy outcomes. Although clinical outcomes for pregnant adults have been reported, the impact of COVID-19 on adolescents is lacking. We sought to evaluate obstetric outcomes of pregnant adolescents infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and compare them with uninfected adolescent controls. METHODS: Retrospective cohort study of pregnant adolescents (14-19 years) who had a positive polymerase chain reaction test for SARS-CoV-2 from April 2020 to December 2020 at Inova Health System Hospitals. Controls included pregnant adolescents who tested negative. The primary outcome was a composite of preeclampsia, preterm delivery, cesarean delivery, fetal growth restriction and stillbirth. Secondary outcomes included maternal and neonatal morbidity. RESULTS: Forty-eight pregnant adolescents who tested positive for SARS-CoV-2 were compared with 394 controls. Infected adolescents were more likely to be Hispanic (91.67% vs. 12.18%; risk ratio [RR] 41.85 [95% CI: 15.43-113.5]) and uninsured (50% vs. 7.87%; RR 7.04 [95% CI: 4.31-11.49]. Nearly 80% of infected adolescents remained asymptomatic, whereas one-third of symptomatic adolescents progressed to severe or critical COVID-19. The primary composite outcome was more prevalent in infected adolescents compared with noninfected controls (41.67% vs. 25.38%; adjusted RR 2.65 [95% CI: 1.19-5.93]). Maternal morbidity was more prevalent in infected adolescents (6.25% vs. 0.76%; adjusted RR 9.53 [95% CI: 3.83-23.71]). Primary and secondary maternal outcomes were more prevalent in younger adolescents and those with higher severity of COVID-19. Maternal SARS-CoV-2 infection was not associated with neonatal morbidity. CONCLUSIONS: Pregnant adolescents infected with SARS-CoV-2 are more likely to have adverse obstetric outcomes and maternal morbidity compared with noninfected pregnant adolescents.

Evaluation of first trimester ultrasound fetal biometry ratios femur length/biparietal diameter, femur length/abdominal circumference and femur length/foot for the screening of skeletal dysplasia.

OBJECTIVE: Skeletal dysplasia is usually apparent in the second trimester. First trimester femur-length/biparietal diameter (FL/BPD), FL/abdominal circumference (AC) and FL/foot for the screening of skeletal dysplasia were evalauted. METHOD: Case-control study: pregnancies with molecular confirmation of skeletal dysplasia undergoing nuchal translucency (January_2007-December_2021). Controls included pregnancies without fetal abnormalities. Performance of FL/BPD, FL/AC and FL/foot was evaluated by receiver operating characteristic curves. RESULTS: Twenty-eight skeletal dysplasia cases were identified; 17 (60.71%) corresponded to lethal types. Compared to 184 controls, cases had a lower median FL/BPD (0.34 [IQR 0.30-0.38] vs. 0.44 [IQR 0.39-0.48]; p < 0.001), FL/AC (0.13 [IQR 0.09-0.15] vs. 0.15 [IQR 0.13-0.16]; p = 0.001) and FL/foot (0.84 [IQR 0.76-0.91] vs. 1.01 [IQR 0.94-1.11]; p < 0.001). FL/BPD and FL/foot ratios had a superior area under the curve (0.846 and 0.853, respectively) than FL/AC (0.64). The probability of diagnosing skeletal dysplasia increased at least 9-fold if FL/BPD <0.376 (OR 26.05, 95% CI 9.79-69.3; p < 0.001) and 14-fold if FL/foot <0.891 (OR 39.46, 95% CI 14.17-109.9; p < 0.001). Low FL/BPD and FL/foot were associated significantly with lethal types compared to viable skeletal dysplasia. CONCLUSIONS: First trimester FL/BPD and FL/foot may be of clinical utility in the detection of skeletal dysplasia especially when there is another suspicious sonographic sign or when there is a relevant family history before overt second trimester sonographic markers become apparent.

Molecular-level analysis of the serum antibody repertoire in young adults before and after seasonal influenza vaccination.

Molecular understanding of serological immunity to influenza has been confounded by the complexity of the polyclonal antibody response in humans. Here we used high-resolution proteomics analysis of immunoglobulin (referred to as Ig-seq) coupled with high-throughput sequencing of transcripts encoding B cell receptors (BCR-seq) to quantitatively determine the antibody repertoire at the individual clonotype level in the sera of young adults before and after vaccination with trivalent seasonal influenza vaccine. The serum repertoire comprised between 40 and 147 clonotypes that were specific to each of the three monovalent components of the trivalent influenza vaccine, with boosted pre-existing clonotypes accounting for ∼60% of the response. An unexpectedly high fraction of serum antibodies recognized both the H1 and H3 monovalent vaccines. Recombinant versions of these H1 + H3 cross-reactive antibodies showed broad binding to hemagglutinins (HAs) from previously circulating virus strains; several of these antibodies, which were prevalent in the serum of multiple donors, recognized the same conserved epitope in the HA head domain. Although the HA-head-specific H1 + H3 antibodies did not show neutralization activity in vitro, they protected mice against infection with the H1N1 and H3N2 virus strains when administered before or after challenge. Collectively, our data reveal unanticipated insights regarding the serological response to influenza vaccination and raise questions about the added benefits of using a quadrivalent vaccine instead of a trivalent vaccine.

Identification and characterization of the constituent human serum antibodies elicited by vaccination.

Most vaccines confer protection via the elicitation of serum antibodies, yet more than 100 y after the discovery of antibodies, the molecular composition of the human serum antibody repertoire to an antigen remains unknown. Using high-resolution liquid chromatography tandem MS proteomic analyses of serum antibodies coupled with next-generation sequencing of the V gene repertoire in peripheral B cells, we have delineated the human serum IgG and B-cell receptor repertoires following tetanus toxoid (TT) booster vaccination. We show that the TT(+) serum IgG repertoire comprises ∼100 antibody clonotypes, with three clonotypes accounting for >40% of the response. All 13 recombinant IgGs examined bound to vaccine antigen with Kd ∼ 10(-8)-10(-10) M. Five of 13 IgGs recognized the same linear epitope on TT, occluding the binding site used by the toxin for cell entry, suggesting a possible explanation for the mechanism of protection conferred by the vaccine. Importantly, only a small fraction (<5%) of peripheral blood plasmablast clonotypes (CD3(-)CD14(-)CD19(+)CD27(++)CD38(++)CD20(-)TT(+)) at the peak of the response (day 7), and an even smaller fraction of memory B cells, were found to encode antibodies that could be detected in the serological memory response 9 mo postvaccination. This suggests that only a small fraction of responding peripheral B cells give rise to the bone marrow long-lived plasma cells responsible for the production of biologically relevant amounts of vaccine-specific antibodies (near or above the Kd). Collectively, our results reveal the nature and dynamics of the serological response to vaccination with direct implications for vaccine design and evaluation.

Molecular deconvolution of the monoclonal antibodies that comprise the polyclonal serum response.

We have developed and validated a methodology for determining the antibody composition of the polyclonal serum response after immunization. Pepsin-digested serum IgGs were subjected to standard antigen-affinity chromatography, and resulting elution, wash, and flow-through fractions were analyzed by bottom-up, liquid chromatography-high-resolution tandem mass spectrometry. Identification of individual monoclonal antibodies required the generation of a database of IgG variable gene (V-gene) sequences constructed by NextGen sequencing of mature B cells. Antibody V-gene sequences are characterized by short complementarity determining regions (CDRs) of high diversity adjacent to framework regions shared across thousands of IgGs, greatly complicating the identification of antigen-specific IgGs from proteomically observed peptides. By mapping peptides marking unique V(H) CDRH3 sequences, we identified a set of V-genes heavily enriched in the affinity chromatography elution, constituting the serum polyclonal response. After booster immunization in a rabbit, we find that the antigen-specific serum immune response is oligoclonal, comprising antibodies encoding 34 different CDRH3s that group into 30 distinct antibody V(H) clonotypes. Of these 34 CDRH3s, 12 account for ∼60% of the antigen-specific CDRH3 peptide mass spectral counts. For comparison, antibodies with 18 different CDRH3s (12 clonotypes) were represented in the antigen-specific IgG fraction from an unimmunized rabbit that fortuitously displayed a moderate titer for BSA. Proteomically identified antibodies were synthesized and shown to display subnanomolar affinities. The ability to deconvolute the polyclonal serum response is likely to be of key importance for analyzing antibody responses after vaccination and for more completely understanding adaptive immune responses in health and disease.