Neuroimaging assessment of pediatric cerebral changes associated with SARS-CoV-2 infection during pregnancy.

Background: SARS-CoV-2 infection and perinatal neurologic outcomes are still not fully understood. However, there is recent evidence of white matter disease and impaired neurodevelopment in newborns following maternal SARS-CoV-2 infection. These appear to occur as a consequence of both direct viral effects and a systemic inflammatory response, with glial cell/myelin involvement and regional hypoxia/microvascular dysfunction. We sought to characterize the consequences of maternal and fetal inflammatory states in the central nervous system of newborns following maternal SARS-CoV-2 infection. Methods: We conducted a longitudinal prospective cohort study from June 2020 to December 2021, with follow-up of newborns born to mothers exposed or not exposed to SARS-CoV-2 infection during pregnancy. Brain analysis included data from cranial ultrasound scans (CUS) with grayscale, Doppler studies (color and spectral), and ultrasound-based brain elastography (shear-wave mode) in specific regions of interest (ROIs): deep white matter, superficial white matter, corpus callosum, basal ganglia, and cortical gray matter. Brain elastography was used to estimate brain parenchymal stiffness, which is an indirect quantifier of cerebral myelin tissue content. Results: A total of 219 single-pregnancy children were enrolled, including 201 born to mothers exposed to SARS-CoV-2 infection and 18 from unexposed controls. A neuroimaging evaluation was performed at 6 months of adjusted chronological age and revealed 18 grayscale and 21 Doppler abnormalities. Predominant findings were hyperechogenicity of deep brain white matter and basal ganglia (caudate nuclei/thalamus) and a reduction in the resistance and pulsatility indices of intracranial arterial flow. The anterior brain circulation (middle cerebral and pericallosal arteries) displayed a wider range of flow variation than the posterior circulation (basilar artery). Shear-wave US elastography analysis showed a reduction in stiffness values in the SARS-CoV-2 exposed group in all analyzed regions of interest, especially in the deep white matter elasticity coefficients (3.98 ± 0.62) compared to the control group (7.76 ± 0.77); p-value < 0.001. Conclusion: This study further characterizes pediatric structural encephalic changes associated with SARS-CoV-2 infection during pregnancy. The maternal infection has been shown to be related to cerebral deep white matter predominant involvement, with regional hyperechogenicity and reduction of elasticity coefficients, suggesting zonal impairment of myelin content. Morphologic findings may be subtle, and functional studies such as Doppler and elastography may be valuable tools to more accurately identify infants at risk of neurologic damage.

Panoramic snapshot of serum soluble mediator interplay in pregnant women with convalescent COVID-19: an exploratory study.

Introduction: SARS-CoV-2 infection during pregnancy can induce changes in the maternal immune response, with effects on pregnancy outcome and offspring. This is a cross-sectional observational study designed to characterize the immunological status of pregnant women with convalescent COVID-19 at distinct pregnancy trimesters. The study focused on providing a clear snapshot of the interplay among serum soluble mediators. Methods: A sample of 141 pregnant women from all prenatal periods (1st, 2nd and 3rd trimesters) comprised patients with convalescent SARS-CoV-2 infection at 3-20 weeks after symptoms onset (COVID, n=89) and a control group of pre-pandemic non-infected pregnant women (HC, n=52). Chemokine, pro-inflammatory/regulatory cytokine and growth factor levels were quantified by a high-throughput microbeads array. Results: In the HC group, most serum soluble mediators progressively decreased towards the 2nd and 3rd trimesters of pregnancy, while higher chemokine, cytokine and growth factor levels were observed in the COVID patient group. Serum soluble mediator signatures and heatmap analysis pointed out that the major increase observed in the COVID group related to pro-inflammatory cytokines (IL-6, TNF-α, IL-12, IFN-γ and IL-17). A larger set of biomarkers displayed an increased COVID/HC ratio towards the 2nd (3x increase) and the 3rd (3x to 15x increase) trimesters. Integrative network analysis demonstrated that HC pregnancy evolves with decreasing connectivity between pairs of serum soluble mediators towards the 3rd trimester. Although the COVID group exhibited a similar profile, the number of connections was remarkably lower throughout the pregnancy. Meanwhile, IL-1Ra, IL-10 and GM-CSF presented a preserved number of correlations (≥5 strong correlations in HC and COVID), IL-17, FGF-basic and VEGF lost connectivity throughout the pregnancy. IL-6 and CXCL8 were included in a set of acquired attributes, named COVID-selective (≥5 strong correlations in COVID and <5 in HC) observed at the 3rd pregnancy trimester. Discussion and conclusion: From an overall perspective, a pronounced increase in serum levels of soluble mediators with decreased network interplay between them demonstrated an imbalanced immune response in convalescent COVID-19 infection during pregnancy that may contribute to the management of, or indeed recovery from, late complications in the post-symptomatic phase of the SARS-CoV-2 infection in pregnant women.

Successful pregnancy after ovulation induction with human chorionic gonadotropin in a woman with selective luteinising hormone deficiency.

Selective LH deficiency has been described in several men, but only in two women who presented normal pubertal development but secondary amenorrhoea due to anovulation. Despite its rarity, this condition represents a valuable model for studying the processes regulated by FSH or LH during late folliculogenesis and ovulation in humans. A woman previously diagnosed with selective LH deficiency due to a homozygous germline splice site mutation in LHB (IVS2 + 1G→C mutation) was submitted to an individualised ovarian induction protocol, first with recombinant LH and then with highly purified urinary hCG. Ovarian follicle growth and ovulation were achieved, and a healthy baby was born after an uneventful term pregnancy. The treatment described herein demonstrates that the clinical actions of exogenous LH or hCG in inducing late-stage follicular development in women with deficient LH production or performance might be interchangeable or inevitable, once FSH-dependent early follicular growth is assured.

SARS-CoV-2/DENV co-infection: a series of cases from the Federal District, Midwestern Brazil.

BACKGROUND: Since the novel coronavirus disease outbreak, over 179.7 million people have been infected by SARS-CoV-2 worldwide, including the population living in dengue-endemic regions, particularly Latin America and Southeast Asia, raising concern about the impact of possible co-infections. METHODS: Thirteen SARS-CoV-2/DENV co-infection cases reported in Midwestern Brazil between April and September of 2020 are described. Information was gathered from hospital medical records regarding the most relevant clinical and laboratory findings, diagnostic process, therapeutic interventions, together with clinician-assessed outcomes and follow-up. RESULTS: Of the 13 cases, seven patients presented Acute Undifferentiated Febrile Syndrome and six had pre-existing co-morbidities, such as diabetes, hypertension and hypopituitarism. Two patients were pregnant. The most common symptoms and clinical signs reported at first evaluation were myalgia, fever and dyspnea. In six cases, the initial diagnosis was dengue fever, which delayed the diagnosis of concomitant infections. The most frequently applied therapeutic interventions were antibiotics and analgesics. In total, four patients were hospitalized. None of them were transferred to the intensive care unit or died. Clinical improvement was verified in all patients after a maximum of 21 days. CONCLUSIONS: The cases reported here highlight the challenges in differential diagnosis and the importance of considering concomitant infections, especially to improve clinical management and possible prevention measures. Failure to consider a SARS-CoV-2/DENV co-infection may impact both individual and community levels, especially in endemic areas.

Pregnancy Outcomes and Child Development Effects of SARS-CoV-2 Infection (PROUDEST Trial): Protocol for a Multicenter, Prospective Cohort Study.

BACKGROUND: A growing body of evidence suggests that SARS-COV-2 infection during pregnancy may affect maternal-fetal outcomes and possibly result in implications for the long-term development of SARS-CoV-2-exposed children. OBJECTIVE: The PROUDEST (Pregnancy Outcomes and Child Development Effects of SARS-CoV-2 Infection Study) is a multicenter, prospective cohort study designed to elucidate the repercussions of COVID-19 for the global health of mothers and their children. METHODS: The PROUDEST trial comprises 2 prospective, sequential substudies. The PREGNANT substudy will clinically assess the effects of SARS-CoV-2 infection on pregnancy, childbirth, and puerperium from a mechanistic standpoint to elucidate the pregnancy-related inflammatory and immunological phenomena underlying COVID-19. Pregnant women aged 18-40 years who have been exposed (proven with laboratory tests) to SARS-CoV-2 (group A; n=300) will be compared to control subjects with no laboratory evidence of in-pregnancy exposure to the virus (group B; n=300). Subjects exposed to other infections during pregnancy will be excluded. The BORN substudy is a long-term follow-up study that will assess the offspring of women who enrolled in the prior substudy. It will describe the effects of SARS-CoV-2 exposure during pregnancy on children's growth, neurodevelopment, and metabolism from birth up to 5 years of age. It includes two comparison groups; group A (exposed; n=300) comprises children born from SARS-CoV-2-exposed pregnancies, and group B (controls; n=300) comprises children born from nonexposed mothers. RESULTS: Recruitment began in July 2020, and as of January 2021, 260 pregnant women who were infected with SARS-CoV-2 during pregnancy and 160 newborns have been included in the study. Data analysis is scheduled to start after all data are collected. CONCLUSIONS: Upon completion of the study, we expect to have comprehensive data that will provide a better understanding of the effects of SARS-CoV-2 infection and related inflammatory and immunological processes on pregnancy, puerperium, and infancy. Our findings will inform clinical decisions regarding the care of SARS-CoV-2-exposed mothers and children and support the development of evidence-based public health policies. TRIAL REGISTRATION: Brazilian Register of Clinical Trials RBR65QXS2; https://ensaiosclinicos.gov.br/rg/RBR-65qxs2. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/26477.

Surgical treatment of tubal ectopic pregnancy through posterior colpotomy: experience from a Brazilian university hospital.

The objective of this study was to evaluate the feasibility of posterior colpotomy for the surgical treatment of tubal ectopic pregnancy in hemodynamically stable women. We performed a retrospective analysis of medical records obtained over a period of 18 months. Twelve cases were identified, with the following characteristics: mean gestational age, 7.7 weeks; mean serum ß-human chorionic gonadotropin level, 7,786 mIU/mL; and greater diameter of the mass, 15-69 mm. Treatment was successful in all cases. Salpingectomy was performed in 10 patients (83.3%) and salpingostomy, in 1 patient. The remaining patient only received peritoneal lavage, as the evidence of ectopic abortion with only a slightly dilated uterine tube was found during surgery. The mean surgical time was 42.5 minutes. In the analyzed cases, posterior colpotomy was found to be a feasible alternative method for the surgical treatment of tubal ectopic pregnancy in hemodynamically stable women.

Factors Associated with Malignancy in Hysteroscopically Resected Endometrial Polyps: A Systematic Review and Meta-Analysis.

In this study, we aimed to estimate the frequency of premalignant and malignant lesions in endometrial polyps, and to evaluate associated clinical and demographic factors. A literature search was performed in major databases and the gray literature using the terms polyps OR endometrial polyp AND endometrial neoplasms OR endometrial cancer OR endometrial hyperplasia OR malignan*. Studies describing the frequency of premalignant and malignant lesions in endometrial polyps and any clinical or demographic factors associated with malignant lesions extracted using hysteroscopy were considered eligible. Independent investigators selected the studies and extracted the data. A meta-analysis was performed using a random-effects model and meta-regression. We identified 37 studies (comprising 21,057 patients) of endometrial polyps. The prevalence of premalignant and malignant lesions was 3.4% (95% confidence interval [CI], 2.8-4.1; I2, 80.5%). Abnormal uterine bleeding (prevalence ratio [PR], 1.47; 95% CI, 1.27-1.69; I2, 82.4%), menopausal status (PR, 1.67; 95% CI, 1.48-1.89; I2, 78.4%), age >60 years (PR, 2.41; 95% CI, 1.84-3.16; I2, 81.5%), diabetes mellitus (PR, 1.76; 95% CI, 1.43-2.16; I2, 0.0%), systemic arterial hypertension (PR, 1.50; 95% CI, 1.20-1.88; I2, 75.9%), obesity (PR, 1.41; 95% CI:1.13-1.76; I2, 41.2%), and tamoxifen use (PR, 1.53; 95% CI, 1.06-2.21; I2, 0.0%) were associated with endometrial polyp malignancy. However, breast cancer (PR, 0.83; 95% CI, 0.44-1.57; I2, 0.0%), hormonal therapy (PR, 0.93; 95% CI, 0.67-1.30; I2, 31.7%), parity (PR, 0.87; 95% CI, 0.39-1.96; I2, 78.1%), and endometrial polyp size (PR, 1.05; 95% CI, 0.70-1.57; I2, 44.7%) were not associated with malignancy of endometrial polyps. Three of every 100 women with clinically recognized polyps, a condition associated with specific clinical and demographic factors, will harbor premalignant or malignant lesions.