Young Adult Patient and Caregiver Perspectives on Transition Readiness in an Inflammatory Bowel Disease Clinic.

Background: When it comes to readiness to transition to an adult subspecialty clinic, perspectives between patients with inflammatory bowel disease (IBD) and their caregivers may differ and influence the ability to successfully transition. Patients with IBD have been shown to suffer from poor transfers of care. There is a need to more efficiently and accurately assess transition readiness to improve the transfer process. Methods: Patients transferring to an adult subspecialty clinic and their caregivers were each administered the Transition Readiness Assessment Questionnaire and IBD Self-Efficacy Scale-Adolescent. Differences between patient and caregiver responses and agreement among each dyad were tested. Results: There were 29 dyads of patients and caregivers who enrolled. There was no difference between patient and caregiver total scores. The average level of agreement between patients and caregivers was 78%. There was no association between patient response and their age, gender, ethnicity, age at time of transfer, age at diagnosis, or number of emergency room visits in the prior year. Conclusions: Patient-reported readiness to transition to adult care was confirmed by their caregivers using validated readiness assessment tools. As transition clinics must focus on high-yield interventions, a readiness survey of young adult patients without a survey of their caregivers may be adequate. However, as experts in each patient's journey, caregivers may be utilized when setting goals and priorities for a transition readiness program. The surveys used in this study can be used broadly to aid subspecialty clinics that are trying to improve the transition process.

Analysis of patients with Crohn's disease and intestinal obstruction: a National Inpatient Sample study.

Background: Crohn's disease (CD) predisposes patients to intestinal obstruction (IO), a severe complication. This study examined the outcomes and healthcare utilization of patients with CD and IO using data from the National Inpatient Sample (NIS). Methods: This retrospective analysis of NIS data from 2016-2020 compared hospitalized adult CD patients with and without IO. Outcomes studied include in-hospital mortality, length of stay (LOS), hospitalization charges, and the requirement for intervention, using regression models for adjustment. Results: Among the 304,149 CD patients, 27,024 had IO. These patients experienced higher in-hospital mortality (3.9% vs. 1.8% for non-IO, adjusted odds ratio [aOR] 1.78, 95% confidence interval [CI] 1.09-2.89; P=0.02), longer mean LOS (7.23 vs. 4.53 days for non-IO, P<0.001), and higher average hospitalization charges ($71,775 vs. $43,717 for non-IO, P<0.001). Additionally, they had higher odds of requiring admission to the intensive care unit (aOR 1.99, 95%CI 1.45-2.73; P<0.001), intubation (aOR 2.53, 95%CI 1.74-3.68; P<0.001), balloon dilation (aOR 1.50, 95%CI 1.132-1.98; P=0.005), or intestinal resection (aOR 2.29, 95%CI 2.11-2.49; P<0.001). Conclusions: CD patients with IO face considerable challenges, including greater mortality, longer hospital stays, and higher hospitalization costs. The need for intensive care and surgical interventions highlights the urgent need for improved management and treatment strategies to enhance outcomes for these patients.

In Situ Analyses of Placental Inflammatory Response to SARS-CoV-2 Infection in Cases of Mother-Fetus Vertical Transmission.

It has been shown that vertical transmission of the SARS-CoV-2 strain is relatively rare, and there is still limited information on the specific impact of maternal SARS-CoV-2 infection on vertical transmission. The current study focuses on a transcriptomics analysis aimed at examining differences in gene expression between placentas from mother-newborn pairs affected by COVID-19 and those from unaffected controls. Additionally, it investigates the in situ expression of molecules involved in placental inflammation. The Papa Giovanni XXIII Hospital in Bergamo, Italy, has recorded three instances of intrauterine transmission of SARS-CoV-2. The first two cases occurred early in the pandemic and involved pregnant women in their third trimester who were diagnosed with SARS-CoV-2. The third case involved an asymptomatic woman in her second trimester with a twin pregnancy, who unfortunately delivered two stillborn fetuses due to the premature rupture of membranes. Transcriptomic analysis revealed significant differences in gene expression between the placentae of COVID-19-affected mother/newborn pairs and two matched controls. The infected and control placentae were matched for gestational age. According to the Benjamani-Hochberg method, 305 genes met the criterion of an adjusted p-value of less than 0.05, and 219 genes met the criterion of less than 0.01. Up-regulated genes involved in cell signaling (e.g., CCL20, C3, MARCO) and immune response (e.g., LILRA3, CXCL10, CD48, CD86, IL1RN, IL-18R1) suggest their potential role in the inflammatory response to SARS-CoV-2. RNAscope® technology, coupled with image analysis, was utilized to quantify the surface area covered by SARS-CoV-2, ACE2, IL-1ß, IL-6, IL-8, IL-10, and TNF-α on both the maternal and fetal sides of the placenta. A non-statistically significant gradient for SARS-CoV-2 was observed, with a higher surface coverage on the fetal side (2.42 ± 3.71%) compared to the maternal side (0.74 ± 1.19%) of the placenta. Although not statistically significant, the surface area covered by ACE2 mRNA was higher on the maternal side (0.02 ± 0.04%) compared to the fetal side (0.01 ± 0.01%) of the placenta. IL-6 and IL-8 were more prevalent on the fetal side (0.03 ± 0.04% and 0.06 ± 0.08%, respectively) compared to the maternal side (0.02 ± 0.01% and 0.02 ± 0.02%, respectively). The mean surface areas of IL-1ß and IL-10 were found to be equal on both the fetal (0.04 ± 0.04% and 0.01 ± 0.01%, respectively) and maternal sides of the placenta (0.04 ± 0.05% and 0.01 ± 0.01%, respectively). The mean surface area of TNF-α was found to be equal on both the fetal and maternal sides of the placenta (0.02 ± 0.02% and 0.02 ± 0.02%, respectively). On the maternal side, ACE-2 and all examined interleukins, but not TNF-α, exhibited an inverse mRNA amount compared to SARS-CoV-2. On the fetal side, ACE-2, IL-6 and IL-8 were inversely correlated with SARS-CoV-2 (r = -0.3, r = -0.1 and r = -0.4, respectively), while IL-1ß and IL-10 showed positive correlations (r = 0.9, p = 0.005 and r = 0.5, respectively). TNF-α exhibited a positive correlation with SARS-CoV-2 on both maternal (r = 0.4) and fetal sides (r = 0.9) of the placenta. Further research is needed to evaluate the correlation between cell signaling and immune response genes in the placenta and the vertical transmission of SARS-CoV-2. Nonetheless, the current study extends our comprehension of the molecular and immunological factors involved in SARS-CoV-2 placental infection underlying maternal-fetal transmission.

Identification and multimodal characterization of a specialized epithelial cell type associated with Crohn's disease.

Crohn's disease (CD) is a complex chronic inflammatory disorder with both gastrointestinal and extra-intestinal manifestations associated immune dysregulation. Analyzing 202,359 cells from 170 specimens across 83 patients, we identify a distinct epithelial cell type in both terminal ileum and ascending colon (hereon as 'LND') with high expression of LCN2, NOS2, and DUOX2 and genes related to antimicrobial response and immunoregulation. LND cells, confirmed by in-situ RNA and protein imaging, are rare in non-IBD controls but expand in active CD, and actively interact with immune cells and specifically express IBD/CD susceptibility genes, suggesting a possible function in CD immunopathogenesis. Furthermore, we discover early and late LND subpopulations with different origins and developmental potential. A higher ratio of late-to-early LND cells correlates with better response to anti-TNF treatment. Our findings thus suggest a potential pathogenic role for LND cells in both Crohn's ileitis and colitis.

High Rates of Miscarriage and Stillbirth among Pregnant Women with Clade I Mpox (Monkeypox) Are Confirmed during 2023-2024 DR Congo Outbreak in South Kivu Province.

Mpox (monkeypox) is a neglected tropical disease that has received increased attention since the multi-nation outbreak that began in 2022. The virus is endemic in West and Central Africa, where the Democratic Republic of the Congo (DRC) is the most affected country. Clade I monkeypox virus (MPXV) infection is endemic in the DRC and has an overall case fatality rate of 10.6% among children and adults. A study conducted in Sankuru Province, DRC, from 2007 to 2011 demonstrated that 75% of pregnant women with mpox had miscarriages or stillbirth. Further analysis of a stillborn fetus showed that MPXV could infect both the placenta and fetus, causing congenital infection. No additional cases of Clade I MPXV in pregnant women were reported until a new outbreak occurred in South Kivu Province during 2023 and 2024. Eight pregnant women having Clade I MPXV infection were identified, of whom four had either miscarriages or stillbirth, representing a 50% fetal mortality rate. These reports confirm previous data from the DRC that indicate the capability of Clade I MPXV to affect the fetus, causing congenital infection and fetal loss in a high percentage of cases. In this article, we review both past and new data from the DRC on the effects of Clade I MPXV during pregnancy and discuss the association of mpox with fetal loss.

Impact of SARS-CoV-2 infection during pregnancy on the placenta and fetus.

Pregnant people and their fetuses are vulnerable to adverse health outcomes from coronavirus 2019 disease (COVID-19) due to infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 has been associated with higher rates of maternal mortality, preterm birth, and stillbirth. While SARS-CoV-2 infection of the placenta and vertical transmission is rare, this may be due to the typically longer time interval between maternal infection and testing of the placenta and neonate. Placental injury is evident in cases of SARS-CoV-2-associated stillbirth with massive perivillous fibrin deposition, chronic histiocytic intervillositis, and trophoblast necrosis. Maternal COVID-19 can also polarize fetal immunity, which may have long-term effects on neurodevelopment. Although the COVID-19 pandemic continues to evolve, the impact of emerging SARS-CoV-2 variants on placental and perinatal injury/mortality remains concerning for maternal and perinatal health. Here, we highlight the impact of COVID-19 on the placenta and fetus and remaining knowledge gaps.

Genetics and Genomics of Pulmonary Fibrosis: Charting the Molecular Landscape and Shaping Precision Medicine.

Recent genetic and genomic advancements have elucidated the complex etiology of idiopathic pulmonary fibrosis (IPF) and other progressive fibrotic interstitial lung diseases (ILDs), emphasizing the contribution of heritable factors. This state-of-the-art review synthesizes evidence on significant genetic contributors to pulmonary fibrosis (PF), including rare genetic variants and common SNPs. The MUC5B promoter variant is unusual, a common SNP that markedly elevates the risk of early and established PF. We address the utility of genetic variation in enhancing understanding of disease pathogenesis and clinical phenotypes, improving disease definitions, and informing prognosis and treatment response. Critical research gaps are highlighted, particularly the underrepresentation of non-European ancestries in PF genetic studies and the exploration of PF phenotypes beyond usual interstitial pneumonia/IPF. We discuss the role of telomere length, often critically short in PF, and its link to progression and mortality, underscoring the genetic complexity involving telomere biology genes (TERT, TERC) and others like SFTPC and MUC5B. In addition, we address the potential of gene-by-environment interactions to modulate disease manifestation, advocating for precision medicine in PF. Insights from gene expression profiling studies and multiomic analyses highlight the promise for understanding disease pathogenesis and offer new approaches to clinical care, therapeutic drug development, and biomarker discovery. Finally, we discuss the ethical, legal, and social implications of genomic research and therapies in PF, stressing the need for sound practices and informed clinical genetic discussions. Looking forward, we advocate for comprehensive genetic testing panels and polygenic risk scores to improve the management of PF and related ILDs across diverse populations.

Causes and Effects of COVID-19 Vaccine Hesitancy Among Pregnant Women and its Association with Adverse Maternal, Placental, and Perinatal Outcomes.

Populations identified to be severely affected by COVID-19, such as pregnant patients, require special consideration in vaccine counseling, access, and provider education. Maternal infection with COVID-19 poses a significant risk to the maternal-fetal dyad with known adverse placenta destruction [1-5]. Despite the widespread access and availability of vaccinations, vaccine hesitancy continues to persist and is highly prevalent in pregnant populations [6-9]. Addressing the multitude of social ecological factors surrounding vaccine hesitancy can aid in providing holistic counseling [10]. However, such factors are foremost shaped by maternal concern over possible fetal effects from vaccination. While changes in policy can help foster vaccine access and acceptance, increasing global provider education and incorporation of motivational interviewing skills are the first steps towards increasing maternal acceptance.

Efficacy and Safety of Filgotinib for the Treatment of Perianal Fistulising Crohn's Disease [DIVERGENCE 2]: A Phase 2, Randomised, Placebo-controlled Trial.

BACKGROUND AND AIMS: There is an unmet need in the treatment of perianal fistulising Crohn's disease [PFCD]. This study evaluated the efficacy and safety of the Janus kinase 1 preferential inhibitor, filgotinib, for the treatment of PFCD. METHODS: This phase 2, double-blind, multicentre trial enrolled adults with PFCD and prior treatment failure. Participants were randomised [2:2:1] to receive filgotinib 200 mg, filgotinib 100 mg, or placebo, once daily orally for up to 24 weeks. The primary endpoint was combined fistula response (reduction from baseline of at least one draining external opening determined by physical assessment, and no fluid collections >1 cm on pelvic magnetic resonance imaging [MRI]) at Week 24. RESULTS: Between April 2017 and July 2020, 106 individuals were screened and 57 were randomised. Discontinuations were lowest in the filgotinib 200 mg group (3/17 [17.6%] versus 13/25 [52.0%] for filgotinib 100 mg and 9/15 [60.0%] for placebo). The proportion of participants who achieved a combined fistula response at Week 24 was 47.1% (8/17; 90% confidence interval [CI] 26.0, 68.9%) in the filgotinib 200 mg group, 29.2% [7/24; 90% CI 14.6, 47.9%] in the filgotinib 100 mg group, and 25.0% [3/12; 90% CI 7.2, 52.7%] in the placebo group. Serious adverse events occurred more frequently with filgotinib 200 mg (5/17 [29.4%]) than with placebo (1/15 [6.7%]). There were no treatment-related serious adverse events or deaths. CONCLUSIONS: Filgotinib 200 mg was associated with numerical reductions in the number of draining perianal fistulas based on combined clinical and MRI findings compared with placebo, and was generally well tolerated [NCT03077412].

Association study of human leukocyte antigen variants and idiopathic pulmonary fibrosis.

Introduction: Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial pneumonia marked by progressive lung fibrosis and a poor prognosis. Recent studies have highlighted the potential role of infection in the pathogenesis of IPF, and a prior association of the HLA-DQB1 gene with idiopathic fibrotic interstitial pneumonia (including IPF) has been reported. Owing to the important role that the human leukocyte antigen (HLA) region plays in the immune response, here we evaluated if HLA genetic variation was associated specifically with IPF risk. Methods: We performed a meta-analysis of associations of the HLA region with IPF risk in individuals of European ancestry from seven independent case-control studies of IPF (comprising 5159 cases and 27 459 controls, including a prior study of fibrotic interstitial pneumonia). Single nucleotide polymorphisms, classical HLA alleles and amino acids were analysed and signals meeting a region-wide association threshold of p<4.5×10-4 and a posterior probability of replication >90% were considered significant. We sought to replicate the previously reported HLA-DQB1 association in the subset of studies independent of the original report. Results: The meta-analysis of all seven studies identified four significant independent single nucleotide polymorphisms associated with IPF risk. However, none met the posterior probability for replication criterion. The HLA-DQB1 association was not replicated in the independent IPF studies. Conclusion: Variation in the HLA region was not consistently associated with risk in studies of IPF. However, this does not preclude the possibility that other genomic regions linked to the immune response may be involved in the aetiology of IPF.

Demographic and Clinical Factors Associated With SARS-CoV-2 Spike 1 Antibody Response Among Vaccinated US Adults: the C4R Study.

This study investigates correlates of anti-S1 antibody response following COVID-19 vaccination in a U.S. population-based meta-cohort of adults participating in longstanding NIH-funded cohort studies. Anti-S1 antibodies were measured from dried blood spots collected between February 2021-August 2022 using Luminex-based microsphere immunoassays. Of 6245 participants, mean age was 73 years (range, 21-100), 58% were female, and 76% were non-Hispanic White. Nearly 52% of participants received the BNT162b2 vaccine and 48% received the mRNA-1273 vaccine. Lower anti-S1 antibody levels are associated with age of 65 years or older, male sex, higher body mass index, smoking, diabetes, COPD and receipt of BNT16b2 vaccine (vs mRNA-1273). Participants with a prior infection, particularly those with a history of hospitalized illness, have higher anti-S1 antibody levels. These results suggest that adults with certain socio-demographic and clinical characteristics may have less robust antibody responses to COVID-19 vaccination and could be prioritized for more frequent re-vaccination.

Genome-wide SNP-sex interaction analysis of susceptibility to idiopathic pulmonary fibrosis.

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic lung condition that is more prevalent in males than females. The reasons for this are not fully understood, with differing environmental exposures due to historically sex-biased occupations, or diagnostic bias, being possible explanations. To date, over 20 independent genetic variants have been identified to be associated with IPF susceptibility, but these have been discovered when combining males and females. Our aim was to test for the presence of sex-specific associations with IPF susceptibility and assess whether there is a need to consider sex-specific effects when evaluating genetic risk in clinical prediction models for IPF. Methods: We performed genome-wide single nucleotide polymorphism (SNP)-by-sex interaction studies of IPF risk in six independent IPF case-control studies and combined them using inverse-variance weighted fixed effect meta-analysis. In total, 4,561 cases (1,280 females and 2,281 males) and 23,500 controls (8,360 females and 14,528 males) of European genetic ancestry were analysed. We used polygenic risk scores (PRS) to assess differences in genetic risk prediction between males and females. Findings: Three independent genetic association signals were identified. All showed a consistent direction of effect across all individual IPF studies and an opposite direction of effect in IPF susceptibility between females and males. None had been previously identified in IPF susceptibility genome-wide association studies (GWAS). The predictive accuracy of the PRSs were similar between males and females, regardless of whether using combined or sex-specific GWAS results. Interpretation: We prioritised three genetic variants whose effect on IPF risk may be modified by sex, however these require further study. We found no evidence that the predictive accuracy of common SNP-based PRSs varies significantly between males and females.

The Comorbidity of Patient-Reported Crohn's Disease Activity and Depression: The Role of Health Behavior Mediators.

Background: Longitudinal research reveals a unidirectional relationship between a nonsomatic symptom of depression, a negative view of the self, and later reported Crohn's disease (CD) activity. We evaluated whether health behaviors mediated this association using a longitudinal design. Methods: We studied 3304 adult volunteers with a self-reported diagnosis of CD who completed a baseline survey that included demographics, CD activity, a symptom-specific index of depression, and measures of physical activity, smoking, and sleep quality. Crohn's disease status and the cognitive index of depression were also measured 6 and 12 months after the baseline evaluation. We specified single-mediator and multiple-mediator models to elucidate the depression-disease activity relationship. Results: Among 2395 females and 909 males, we found a significant mediation effect for activity level (P < .001) after adjusting for age, sex, and body mass index. There was no evidence that sleep quality and smoking are significant single mediators. When we considered multiple mediation models, smoking and less activity partially mediate the depression-CD association. Conclusions: Smoking and lower levels of physical activity are potential mediators of the unidirectional association between a nonsomatic symptom of depression-a negative view of the self-and patient-reported CD activity. Evaluating and treating specific symptoms of depression may reduce the frequency of CD exacerbations.

Spatially distinct molecular patterns of gene expression in idiopathic pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a heterogeneous disease that is pathologically characterized by areas of normal-appearing lung parenchyma, active fibrosis (transition zones including fibroblastic foci) and dense fibrosis. Defining transcriptional differences between these pathologically heterogeneous regions of the IPF lung is critical to understanding the distribution and extent of fibrotic lung disease and identifying potential therapeutic targets. Application of a spatial transcriptomics platform would provide more detailed spatial resolution of transcriptional signals compared to previous single cell or bulk RNA-Seq studies. METHODS: We performed spatial transcriptomics using GeoMx Nanostring Digital Spatial Profiling on formalin-fixed paraffin-embedded (FFPE) tissue from 32 IPF and 12 control subjects and identified 231 regions of interest (ROIs). We compared normal-appearing lung parenchyma and airways between IPF and controls with histologically normal lung tissue, as well as histologically distinct regions within IPF (normal-appearing lung parenchyma, transition zones containing fibroblastic foci, areas of dense fibrosis, and honeycomb epithelium metaplasia). RESULTS: We identified 254 differentially expressed genes (DEGs) between IPF and controls in histologically normal-appearing regions of lung parenchyma; pathway analysis identified disease processes such as EIF2 signaling (important for cap-dependent mRNA translation), epithelial adherens junction signaling, HIF1α signaling, and integrin signaling. Within IPF, we identified 173 DEGs between transition and normal-appearing lung parenchyma and 198 DEGs between dense fibrosis and normal lung parenchyma; pathways dysregulated in both transition and dense fibrotic areas include EIF2 signaling pathway activation (upstream of endoplasmic reticulum (ER) stress proteins ATF4 and CHOP) and wound healing signaling pathway deactivation. Through cell deconvolution of transcriptome data and immunofluorescence staining, we confirmed loss of alveolar parenchymal signals (AGER, SFTPB, SFTPC), gain of secretory cell markers (SCGB3A2, MUC5B) as well as dysregulation of the upstream regulator ATF4, in histologically normal-appearing tissue in IPF. CONCLUSIONS: Our findings demonstrate that histologically normal-appearing regions from the IPF lung are transcriptionally distinct when compared to similar lung tissue from controls with histologically normal lung tissue, and that transition zones and areas of dense fibrosis within the IPF lung demonstrate activation of ER stress and deactivation of wound healing pathways.

A Specialized Epithelial Cell Type Regulating Mucosal Immunity and Driving Human Crohn's Disease.

Crohn's disease (CD) is a complex chronic inflammatory disorder that may affect any part of gastrointestinal tract with extra-intestinal manifestations and associated immune dysregulation. To characterize heterogeneity in CD, we profiled single-cell transcriptomics of 170 samples from 65 CD patients and 18 non-inflammatory bowel disease (IBD) controls in both the terminal ileum (TI) and ascending colon (AC). Analysis of 202,359 cells identified a novel epithelial cell type in both TI and AC, featuring high expression of LCN2, NOS2, and DUOX2, and thus is named LND. LND cells, confirmed by high-resolution in-situ RNA imaging, were rarely found in non-IBD controls, but expanded significantly in active CD. Compared to other epithelial cells, genes defining LND cells were enriched in antimicrobial response and immunoregulation. Moreover, multiplexed protein imaging demonstrated that LND cell abundance was associated with immune infiltration. Cross-talk between LND and immune cells was explored by ligand-receptor interactions and further evidenced by their spatial colocalization. LND cells showed significant enrichment of expression specificity of IBD/CD susceptibility genes, revealing its role in immunopathogenesis of CD. Investigating lineage relationships of epithelial cells detected two LND cell subpopulations with different origins and developmental potential, early and late LND. The ratio of the late to early LND cells was related to anti-TNF response. These findings emphasize the pathogenic role of the specialized LND cell type in both Crohn's ileitis and Crohn's colitis and identify novel biomarkers associated with disease activity and treatment response.

Insurance Approval Delay of Biologic Therapy Dose Escalation Associated with Disease Activity in Patients with Inflammatory Bowel Disease.

BACKGROUND: Dose escalation of self-injectable biologic therapy for inflammatory bowel diseases may be required to counteract loss of response and/or low drug levels. Payors often require completion of a prior authorization (PA), which is a complex approval pathway before providing coverage. If the initial PA request is denied, clinic staff must complete a time and resource-intensive process to obtain medication approval. AIMS: This study measured time from decision to dose escalate to insurance approval and evaluated impact of approval time on disease activity. METHODS: This was a single-center retrospective analysis of adult patients with IBD prescribed an escalated dose of biologic therapy at an academic center with an integrated specialty pharmacy team from January to December 2018. Outcomes included time to insurance approval and the association between approval time and follow-up C-reactive protein (CRP) and Short Inflammatory Bowel Disease Questionnaire (SIBDQ) scores. Associations were tested using linear regression analyses. RESULTS: 220 patients were included, median age 39, 53% female, and 96% white. Overall median time from decision to dose escalate to insurance approval was 7 days [interquartile range (IQR) 1, 14]. Approval time was delayed when an appeal was required [median of 29 days (IQR 17, 43)]. Patients with a longer time to insurance approval were less likely to have CRP improvement (p = 0.019). Time to insurance approval did not significantly impact follow-up SIBDQ scores. CONCLUSION: Patients who had a longer time to insurance approval were less likely to have improvement in CRP, highlighting the negative clinical impact of a complex dose escalation process.

Congenital Mpox Syndrome (Clade I) in Stillborn Fetus after Placental Infection and Intrauterine Transmission, Democratic Republic of the Congo, 2008.

We report the autopsy pathology findings of a 21-week stillborn fetus with congenital mpox syndrome that occurred in the Democratic Republic of the Congo in 2008. The fetus acquired mpox from the mother after intrauterine transplacental monkeypox virus transmission. We confirmed monkeypox virus infection in the mother, fetus, and placenta by using a monkeypox virus-specific quantitative PCR. Subtyping of the virus was not performed, but the mother and fetus were almost certainly infected with the clade I variant that was endemic in the Democratic Republic of the Congo at the time. Risk for intrauterine infection appears to differ between virus clades, but clinicians should be aware of potential for intrauterine monkeypox virus transmission among pregnant persons during ongoing and future mpox outbreaks.