Sex-Specific Neurodevelopmental Outcomes Among Offspring of Mothers With SARS-CoV-2 Infection During Pregnancy

JAMA Network Open, Год журнала: 2023, Номер 6(3), С. e234415 - e234415

Опубликована: Март 23, 2023

Importance Prior studies using large registries have suggested a modest increase in risk for neurodevelopmental diagnoses among children of mothers with immune activation during pregnancy, and such may be sex-specific. Objective To determine whether utero exposure to SARS-CoV-2 is associated sex-specific disorders up 18 months after birth, compared unexposed offspring born or prior the COVID-19 pandemic period. Design, Setting, Participants This retrospective cohort study included live all who delivered between January 1 December 31, 2018 (born followed before pandemic), March 2019 1, 2020, May 2021 pandemic). Offspring were at any 8 hospitals across 2 health systems Massachusetts. Exposures Polymerase chain reaction evidence maternal infection pregnancy. Main Outcomes Measures Electronic record documentation International Statistical Classification Diseases Related Health Problems, Tenth Revision diagnostic codes corresponding disorders. Results The 355 births (9399 boys [51.2%]), including 883 (4.8%) positivity 1809 Asian individuals (9.9%), 1635 Black (8.9%), 12 718 White (69.3%), 1714 (9.3%) other race (American Indian Alaska Native, Native Hawaiian Pacific Islander, more than race); 2617 (14.3%) Hispanic ethnicity. Mean age was 33.0 (IQR, 30.0-36.0) years. In adjusted regression models accounting race, ethnicity, insurance status, hospital type (academic center vs community), age, preterm statistically significant elevation male (adjusted OR, 1.94 [95% CI 1.12-3.17]; P = .01) but not female 0.89 CI, 0.39-1.76]; .77). Similar effects identified matched analyses lieu regression. At months, observed 1.42 0.92-2.11]; .10). Conclusions Relevance this utero, greater magnitude following birth. As infection, substantially larger cohorts longer follow-up will required reliably estimate refute risk.

Язык: Английский

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Respiratory distress in SARS-CoV-2 exposed uninfected neonates followed in the COVID Outcomes in Mother-Infant Pairs (COMP) Study

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Янв. 24, 2024

Abstract Respiratory distress (RD) has been reported in SARS-CoV-2 exposed uninfected (SEU) term neonates. Prior studies suggest that prenatal exposure to Coronavirus Disease 19 (COVID-19) may activate an inflammatory cascade the newborn airway. In this study, we examine relationship between maternal COVID-19 vaccination and neonatal RD using a longitudinal cohort of mother-infant pairs Los Angeles, CA. Two-hundred twenty-one mothers with laboratory confirmed during pregnancy 227 fetuses are enrolled our study. Maternal disease severity variables were defined based on current accepted clinical criteria. To explore multifactorial associations parameters infant RD, utilize multivariable logistic regression model proteomic sub-analysis propose pathway for development following utero SARS-CoV-2. Unusually high rates observed SEU infants (17%). The odds ratio is 3.06 (95% CI:1.08-10.21) neonates born unvaccinated individuals versus those vaccinated prior infection. Proteomic analysis reveals robust response associated ciliary dysregulation enhanced IgE production among RD. against reduces frequency

Язык: Английский

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Sensing of SARS-CoV-2 by pDCs and their subsequent production of IFN-I contribute to macrophage-induced cytokine storm during COVID-19

Science Immunology, Год журнала: 2022, Номер 7(75)

Опубликована: Сен. 9, 2022

Lung-infiltrating macrophages create a marked inflammatory milieu in subset of patients with COVID-19 by producing cytokine storm, which correlates increased lethality. However, these are largely not infected SARS-CoV-2, so the mechanism underlying their activation lung is unclear. Type I interferons (IFN-I) contribute to protecting host against SARS-CoV-2 but may also have some deleterious effect, and source IFN-I lungs well defined. Plasmacytoid dendritic cells (pDCs), key cell type involved antiviral responses, can produce response SARS-CoV-2. We observed infiltration pDCs SARS-CoV-2–infected patients, correlated strong signaling macrophages. In severe COVID-19, expressed robust signature, persistent at single-cell level. Hence, we uncoupling kinetics associated storm that were dominant IFN-α–producing virus blood, whereas produced IFN-α only when physical contact epithelial cells. showed pDCs, after sensing TLR7, mediated changes both transcriptional epigenetic levels, favored hyperactivation environmental stimuli. Together, data indicate priming result from leading macrophage COVID-19.

Язык: Английский

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COVID-19 and pregnancy: clinical outcomes; mechanisms, and vaccine efficacy

Translational research, Год журнала: 2022, Номер 251, С. 84 - 95

Опубликована: Авг. 12, 2022

Язык: Английский

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Maternal immune activation and role of placenta in the prenatal programming of neurodevelopmental disorders

Neuronal Signaling, Год журнала: 2023, Номер 7(2)

Опубликована: Май 17, 2023

Maternal infection during pregnancy, leading to maternal immune activation (mIA) and cytokine release, increases the offspring risk of developing a variety neurodevelopmental disorders (NDDs), including schizophrenia. Animal models have provided evidence support these mechanistic links, with placental inflammatory responses dysregulation function implicated. This leads changes in fetal brain balance altered epigenetic regulation key pathways. The prenatal timing such mIA-evoked changes, accompanying developmental an

Язык: Английский

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The immune landscape of fetal chorionic villous tissue in term placenta

Frontiers in Immunology, Год журнала: 2025, Номер 15

Опубликована: Янв. 13, 2025

Introduction The immune compartment within fetal chorionic villi is comprised of Hofbauer cells (HBC) and invading placenta-associated maternal monocytes macrophages (PAMM). Recent studies have characterized the transcriptional profile first trimester (T1) placenta; however, phenotypic functional diversity villous at term (T3) remain poorly understood. Methods To address this knowledge gap, from human tissues obtained full-term, uncomplicated pregnancies were deeply phenotyped using a combination flow cytometry, single-cell RNA sequencing (scRNA-seq, CITE-seq) chromatin accessibility profiling (snATAC-seq). Results Our results indicate that, relative to trimester, frequency (HBC, proliferating HBC) significantly reduced, whereas that infiltrating monocytes/macrophages (PAMM1b, PAMM1a, PAMM2, MAC_1) increased in T3. PAMM1b HBCs exhibit most phagocytic capacity highlighting their regulatory role tissue homeostasis late pregnancy. profiles resident subsets heightened activation state T1, likely support labor parturition. Additionally, we provide one insights into myeloid term. We next stratified our findings by pre-pregnancy BMI since pregravid obesity associated with several adverse pregnancy outcomes. Pregravid inflammatory gene expression, particularly among HBC PAMM1a subsets, but dampened expression antimicrobial genes, supporting tolerant-like phenotype cells. report decline abundance accompanied an increase macrophages, which aligns reports pathologies obesity. Finally, given shared yolk-sac origin microglia, leveraged vitro model umbilical cord blood-derived microglia investigate impact on neurodevelopment. reveal markers albeit Discussion Overall, study highlights adaptations gestational age obesity, as well insight towards dysfunction possibly underlying poor neurodevelopmental outcomes offspring women

Язык: Английский

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A placental model of SARS-CoV-2 infection reveals ACE2-dependent susceptibility and differentiation impairment in syncytiotrophoblasts

Nature Cell Biology, Год журнала: 2023, Номер 25(8), С. 1223 - 1234

Опубликована: Июль 13, 2023

Abstract SARS-CoV-2 infection causes COVID-19. Several clinical reports have linked COVID-19 during pregnancy to negative birth outcomes and placentitis. However, the pathophysiological mechanisms underpinning placentation early are not clear. Here, shed light on this, we used induced trophoblast stem cells generate an in vitro placenta model. We identified that syncytiotrophoblasts could be infected through angiotensin-converting enzyme 2 (ACE2). Using a co-culture model of vertical transmission, confirmed ability virus infect previous endometrial cell infection. further demonstrated transcriptional changes led impairment cellular processes, reduced secretion HCG hormone morphological vital for syncytiotrophoblast function. Furthermore, different antibody strategies antiviral drugs restore these impairments. In summary, established scalable tractable platform study placental types highlighted its use studying protect placenta.

Язык: Английский

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Accelerated Longitudinal Weight Gain Among Infants With In Utero COVID-19 Exposure

The Journal of Clinical Endocrinology & Metabolism, Год журнала: 2023, Номер 108(10), С. 2579 - 2588

Опубликована: Март 29, 2023

Abstract Context Since the initial outbreak of coronavirus disease 2019 (COVID-19), a novel population children with in utero exposure to maternal infection has emerged whose health outcomes are largely unknown. Objective To compare longitudinal growth trajectories among infants vs without COVID-19 exposure. Methods We conducted cohort study leveraging prospectively enrolled perinatal biorepository 149 and 127 unexposed controls. Weight, length, body mass index (BMI) were abstracted from records at 0, 2, 6, 12 months standardized using World Health Organization charts. Analyses adjusted for age, ethnicity, parity, insurance, BMI as well infant sex, birthdate, breastfeeding. Results Infants controls exhibited differential weight BMI, but not z-score over first year life (study group × time interaction, P < .0001 BMI). born mothers prenatal had lower birth (effect size: −0.35, 95% CI −0.66 −0.03) greater gain 0.53, 0.06 0.99). Birth mediated significant proportion relationship between postnatal (estimate ± SE, 32 14%, = .02). Conclusion accelerated life, which may be harbingers downstream cardiometabolic pathology. Further studies needed delineate sequelae this emerging global population.

Язык: Английский

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SARS-CoV-2 niches in human placenta revealed by spatial transcriptomics

Med, Год журнала: 2023, Номер 4(9), С. 612 - 634.e4

Опубликована: Июль 8, 2023

BackgroundFunctional placental niches are presumed to spatially separate maternal-fetal antigens and restrict the vertical transmission of pathogens. We hypothesized a high-resolution map transcription could provide direct evidence for niche microenvironments with unique functions profiles.MethodsWe utilized Visium Spatial Transcriptomics paired H&E staining generate 17,927 spatial transcriptomes. By integrating these transcriptomes 273,944 single-cell single-nuclei transcriptomes, we generated an atlas composed at least 22 subpopulations in maternal decidua, fetal chorionic villi, chorioamniotic membranes.FindingsComparisons placentae from uninfected healthy controls (n = 4) COVID-19 asymptomatic symptomatic 5) infected participants demonstrated that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection syncytiotrophoblasts occurred both presence absence clinical disease. With transcriptomics, found limit SARS-CoV-2 was 1/7,000 cells, without detectable viral transcripts were unperturbed. In contrast, high transcript levels associated significant upregulation pro-inflammatory cytokines interferon-stimulated genes, altered metallopeptidase signaling (TIMP1), coordinated shifts macrophage polarization, histiocytic intervillositis, perivillous fibrin deposition. Fetal sex differences gene expression responses limited, confirmed mapping limited decidua males.ConclusionsHigh-resolution transcriptomics resolution revealed dynamic coordinate clinically evident disease.FundingThis work supported by NIH (R01HD091731 T32-HD098069), NSF (2208903), Burroughs Welcome Fund March Dimes Preterm Birth Research Initiatives, Career Development Award American Society Gene Cell Therapy.

Язык: Английский

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Systematic review and synthesis of stillbirths and late miscarriages following SARS-CoV-2 infections

American Journal of Obstetrics and Gynecology, Год журнала: 2023, Номер 229(2), С. 118 - 128

Опубликована: Янв. 25, 2023

Язык: Английский

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