Cervical cerclage placement decreases local levels of proinflammatory cytokines in patients with cervical insufficiency.

BACKGROUND: Cervical insufficiency is characterized by premature, progressive dilation and shortening of the cervix during pregnancy. If left unattended, this can lead to the prolapse and rupture of the amniotic membrane, which usually results in midtrimester pregnancy loss or preterm birth. Previous studies have shown that proinflammatory cytokines such as interleukin-1ß, interleukin-6, interleukin-8, and tumor necrosis factor alpha are up-regulated in normal parturition but are also associated with preterm birth. Studies evaluating such markers in patients with cervical insufficiency have evaluated only their diagnostic potential. Even fewer studies have studied them within the context of cerclage surgery. OBJECTIVES(S): The objective of the study was to evaluate the impact of local and systemic inflammatory markers on the pathogenesis of cervical insufficiency and the effect of cerclage surgery on the local immune microenvironment of women with cervical insufficiency. STUDY DESIGN: We recruited 28 pregnant women (12-20 weeks' gestation) diagnosed with insufficiency and referred for cerclage surgery and 19 gestational age-matched normal pregnant women as controls. Serum and cervicovaginal fluid samples were collected before and after cerclage surgery and during a routine checkup for normal women and analyzed using a targeted 13-plex proinflammatory cytokine assay. RESULTS: Before surgery, patients with cervical insufficiency had higher levels of interleukin-1ß, interleukin-6, interleukin-12, monocyte chemoattractant protein-1 and tumor necrosis factor alpha in cervicovaginal fluid compared to controls, but after surgery, these differences disappeared. No differences were found in serum of insufficiency versus control women. In patients with insufficiency, the levels of interleukin-1ß, interleukin-6, interleukin-8, monocyte chemoattractant protein-1, and interferon gamma in cervicovaginal fluid declined significantly after cerclage compared with before intervention, but these changes were not detected in serum. CONCLUSION: Compared with normal women, patients with cervical insufficiency have elevated levels of proinflammatory cytokines in cervicovaginal fluid but not in serum, suggesting a dysregulation of the local immune environment. Cerclage intervention led to a significant decline in these proinflammatory cytokines, suggesting that cerclage may help reduce local inflammation in cervical insufficiency.

Coxsackievirus Group B Infections during Pregnancy: An Updated Literature Review.

Coxsackievirus group B (CVB), a member of the Picornaviridae family and enterovirus genus, poses risks during pregnancy due to its potential to cause severe fetal and neonatal infections. Transmission primarily occurs through fecal-oral routes, with infections peaking mostly in warmer months. Vertical transmission to the fetus can lead to conditions such as myocarditis, encephalitis, and systemic neonatal disease, presenting clinically as severe myocardial syndromes and neurological deficits. Diagnostic challenges include detecting asymptomatic maternal infections and conducting in utero assessments using advanced techniques like RT-PCR from amniotic fluid samples. Morbidity and mortality associated with congenital CVB infections are notable, linked to preterm delivery, fetal growth restriction, and potential long-term health impacts such as type 1 diabetes mellitus and structural cardiac anomalies. Current treatments are limited to supportive care, with emerging therapies showing promise but requiring further study for efficacy in utero. Preventive measures focus on infection control and hygiene to mitigate transmission risks, which are crucial especially during pregnancy. Future research should aim to fill knowledge gaps in epidemiology, improve diagnostic capabilities, and develop targeted interventions to enhance maternal and fetal outcomes.

Vulvovaginitis in pregnant women.

• The balanced vaginal microbiome is the main factor defending the vaginal environment against infections. Lactobacilli play a key role in this regard, maintaining the vaginal pH within the normal range (3.8 to 4.5). •Hormonal and immune adaptations resulting from pregnancy influence changes in the vaginal microbiome during pregnancy. •An altered vaginal microbiome predisposes to human immunodeficiency virus (HIV) infection. •Bacterial vaginosis is the main clinical expression of an imbalanced vaginal microbiome. •Vulvovaginal candidiasis depends more on the host's conditions than on the etiological agent. •Trichomonas vaginalis is a protozoan transmitted during sexual intercourse. •The use of probiotics is not approved for use in pregnant women.

The effect of body mass index on maternal and perinatal outcomes in COVID-19 infection during pregnancy and postpartum: Secondary analysis from the REBRACO cohort study.

OBJECTIVES: To compare maternal and perinatal outcomes among women with obesity, overweight, and normal body mass index, associated with COVID-19 infection during pregnancy and postpartum. METHOD: Prospective Cohort Study, within the REBRACO (Brazilian Network of COVID-19 in Pregnancy) multicenter initiative. Confirmed positive cases of SARS-CoV-2 were included, and women categorized into three groups according to their pre-pregnancy BMI: obesity (BMI ≥ 30), overweight (BMI <30 but >25), and normal BMI. Sociodemographic, clinical, and obstetric characteristics and different maternal and perinatal outcomes were compared, and a multiple regression analysis was performed to investigate factors independently associated with adverse maternal and perinatal outcomes. RESULTS: Two hundred eighty-nine women positive for SARS-CoV-2 infection were considered, and 202 had available data on maternal BMI for the current analysis. Overall, 72 (35.6%)obese, 68 (33.6%) overweight, and 60 (29.7%) normal BMI. Obesity was associated with increased adverse clinical outcomes including sepsis (P = 0.02), acute respiratory distress syndrome (P = 0.002), and the need for mechanical ventilation (P = 0.044). Considering perinatal outcomes, a multiple regression model confirmed obesity as an independent factor associated with adverse results (adjusted odds ratio 3.73, 95% CI 1.54-9.08). CONCLUSION: Obesity and overweight were associated with worse clinical outcomes, severe/critical COVID-19, and adverse perinatal outcomes.

The experience of pregnant women and their families who were infected with covid-19 before vaccination: A qualitative approach within a multicenter study in Brazil.

BACKGROUND: Pregnant and postpartum women infected by COVID-19 are at increased risk of adverse outcomes, including negative effects on their mental health. Brazilian maternal mortality rate due to COVID-19 is 2.5 times higher than overall mortality rates. This study aimed to understand how pregnant/postpartum women experienced the COVID-19 suspicion/investigation or confirmed infection in different Brazilian cities, the pandemic's consequences to women and their families, and their needs to improve maternal health services during public health emergencies. METHODS: We conducted a qualitative study with 27 women with COVID-19 and 6 of their family members, as part of a multicenter study among 15 maternity hospitals in Brazil. We applied in-depth interviews through telephone calls when women received the diagnostic or had a suspect infection and after 60 days. Another semi-structured interview was applied to their close family members. The interviews were considered through thematic analysis. RESULTS: From the thematic content analysis three major themes emerged from the first and second interviews: (Cucinotta and Vanelli, 2020) assistance received by the woman and newborn in the medical services; (World Health Organization (WHO) 2021) stigma/fear of contamination from health workers and from family and friends reported by the women; (Allotey et al., 2020) the COVID-19 pandemic impact. CONCLUSION: Before the availability of the COVID-19 vaccine, pregnant women experienced fear of death, hospitalization, quarantine, loss of family members, and financial repercussions, resulting in physical, psychological, and socioeconomic impacts on these women's lives.

A new model based on artificial intelligence to screening preterm birth.

OBJECTIVE: The objective of this study is to create a new screening for spontaneous preterm birth (sPTB) based on artificial intelligence (AI). METHODS: This study included 524 singleton pregnancies from 18th to 24th-week gestation after transvaginal ultrasound cervical length (CL) analyzes for screening sPTB < 35 weeks. AI model was created based on the stacking-based ensemble learning method (SBELM) by the neural network, gathering CL < 25 mm, multivariate unadjusted logistic regression (LR), and the best AI algorithm. Receiver Operating Characteristics (ROC) curve to predict sPTB < 35 weeks and area under the curve (AUC), sensitivity, specificity, accuracy, predictive positive and negative values were performed to evaluate CL < 25 mm, LR, the best algorithms of AI and SBELM. RESULTS: The most relevant variables presented by LR were cervical funneling, index straight CL/internal angle inside the cervix (≤ 0.200), previous PTB < 37 weeks, previous curettage, no antibiotic treatment during pregnancy, and weight (≤ 58 kg), no smoking, and CL < 30.9 mm. Fixing 10% of false positive rate, CL < 25 mm and SBELM present, respectively: AUC of 0.318 and 0.808; sensitivity of 33.3% and 47,3%; specificity of 91.8 and 92.8%; positive predictive value of 23.1 and 32.7%; negative predictive value of 94.9 and 96.0%. This machine learning presented high statistical significance when compared to CL < 25 mm after T-test (p < .00001). CONCLUSION: AI applied to clinical and ultrasonographic variables could be a viable option for screening of sPTB < 35 weeks, improving the performance of short cervix, with a low false-positive rate.

Brazilian Black Women are at Higher Risk for COVID-19 Complications: An Analysis of REBRACO, a National Cohort.

OBJECTIVE: To evaluate the impact of the race (Black versus non-Black) on maternal and perinatal outcomes of pregnant women with COVID-19 in Brazil. METHODS: This is a subanalysis of REBRACO, a Brazilian multicenter cohort study designed to evaluate the impact of COVID-19 on pregnant women. From February 2020 until February 2021, 15 maternity hospitals in Brazil collected data on women with respiratory symptoms. We selected all women with a positive test for COVID-19; then, we divided them into two groups: Black and non-Black women. Finally, we compared, between groups, sociodemographic, maternal, and perinatal outcomes. We obtained the frequency of events in each group and compared them using X2 test; p-values < 0.05 were considered significant. We also estimated the odds ratio (OR) and confidence intervals (CI). RESULTS: 729 symptomatic women were included in the study; of those, 285 were positive for COVID-19, 120 (42.1%) were Black, and 165 (57.9%) were non-Black. Black women had worse education (p = 0.037). The timing of access to the health system was similar between both groups, with 26.3% being included with seven or more days of symptoms. Severe acute respiratory syndrome (OR 2.22 CI 1.17-4.21), intensive care unit admission (OR 2.00 CI 1.07-3.74), and desaturation at admission (OR 3.72 CI 1.41-9.84) were more likely to occur among Black women. Maternal death was higher among Black women (7.8% vs. 2.6%, p = 0.048). Perinatal outcomes were similar between both groups. CONCLUSION: Brazilian Black women were more likely to die due to the consequences of COVID-19.

OBJETIVO: Avaliar o impacto da raça (negra versus não negra) nos desfechos maternos e perinatais de gestantes com COVID-19 no Brasil. MéTODOS: Esta é uma subanálise da REBRACO, um estudo de coorte multicêntrico brasileiro desenhado para avaliar o impacto da COVID-19 em mulheres grávidas. De fevereiro de 2020 a fevereiro de 2021, 15 maternidades do Brasil coletaram dados de mulheres com sintomas respiratórios. Selecionamos todas as mulheres com teste positivo para COVID-19; em seguida, as dividimos em dois grupos: mulheres negras e não negras. Finalmente, comparamos, entre os grupos, os resultados sociodemográficos, maternos e perinatais. Obtivemos a frequência dos eventos em cada grupo e comparamos usando o teste X2; Valores de p < 0,05 foram considerados significativos. Também estimamos o odds ratio (OR) e os intervalos de confiança (IC). RESULTADOS: 729 mulheres sintomáticas foram incluídas no estudo; desses, 285 foram positivos para COVID-19, 120 (42,1%) eram negros e 165 (57,9%) não eram negros. As mulheres negras apresentaram pior escolaridade (p = 0,037). O tempo de acesso ao sistema de saúde foi semelhante entre os dois grupos, com 26,3% incluídos com sete ou mais dias de sintomas. Síndrome respiratória aguda grave (OR 2,22 CI 1,17­4,21), admissão em unidade de terapia intensiva (OR 2,00 CI 1,07­3,74) e dessaturação na admissão (OR 3,72 CI 1,41­9,84) foram mais prováveis de ocorrer entre mulheres negras. A mortalidade materna foi maior entre as negras (7,8% vs. 2,6%, p = 0,048). Os resultados perinatais foram semelhantes entre os dois grupos. CONCLUSãO: Mulheres negras brasileiras tiveram maior probabilidade de morrer devido às consequências da COVID-19.

Preeclampsia among women with COVID-19 during pregnancy and its impact on maternal and perinatal outcomes: Results from a national multicenter study on COVID in Brazil, the REBRACO initiative.

OBJECTIVE: To evaluate the prevalence of preeclampsia among cases of COVID-19 infection during pregnancy and the association between both conditions, in a multicenter cohort of Brazilian women with respiratory symptoms. STUDY DESIGN: Ancillary analysis of the Brazilian Network of COVID-19 in Obstetrics (REBRACO) study. We performed a nested case-control analysis selecting all women with COVID-19 and compared outcomes between women with and without PE. MAIN OUTCOMES: Maternal, gestational, and clinical characteristics and perinatal outcomes. MEASURES: Prevalence ratio (PR) and its 95%CI for each of the predictors and outcomes. RESULTS: A total of 203 women were included: 21 (10.3%) in PE group and 182 (89.7%) in non-PE group. Preeclampsia was not different among women with and without COVID-19 (10.3% vs 13.1%, p-value = 0.41), neither complication such as eclampsia and HELLP syndrome. Chronic hypertension (33.4%) (p < 0.01) and obesity (60.0%) (p = 0.03) were the most frequent comorbidities in PE group, and they were significantly more frequent in this group. Women with PE had more cesarean section (RR 5.54 [1.33 - 23.14]) and their neonates were more frequently admitted to neonatal intensive care unit (PR 2.46[1.06 - 5.69]), most likely due to preterm-birth-related complications. CONCLUSION: The prevalence of PE among women with COVID-19 infection during pregnancy was around 10%; women with COVID-19 and a history of chronic hypertension or obesity are more likely to have preeclampsia. Cesarean section is increased among women with PE and COVID-19, with increased rates of neonatal admission to intensive care units, mostly due to prematurity.

The COVID-19 pandemic in Brazilian pregnant and postpartum women: results from the REBRACO prospective cohort study.

Brazil presented a very high number of maternal deaths and evident delays in healthcare. We aimed at evaluating the characteristics of SARS-CoV-2 infection and associated outcomes in the obstetric population. We conducted a prospective cohort study in 15 Brazilian centers including symptomatic pregnant or postpartum women with suspected COVID-19 from Feb/2020 to Feb/2021. Women were followed from suspected infection until the end of pregnancy. We analyzed maternal characteristics and pregnancy outcomes associated with confirmed COVID-19 infection and SARS, determining unadjusted risk ratios. In total, 729 symptomatic women with suspected COVID-19 were initially included. Among those investigated for COVID-19, 51.3% (n = 289) were confirmed COVID-19 and 48% (n = 270) were negative. Initially (before May 15th), only 52.9% of the suspected cases were tested and it was the period with the highest proportion of ICU admission and maternal deaths. Non-white ethnicity (RR 1.78 [1.04-3.04]), primary schooling or less (RR 2.16 [1.21-3.87]), being overweight (RR 4.34 [1.04-19.01]) or obese (RR 6.55 [1.57-27.37]), having public prenatal care (RR 2.16 [1.01-4.68]), planned pregnancies (RR 2.09 [1.15-3.78]), onset of infection in postpartum period (RR 6.00 [1.37-26.26]), chronic hypertension (RR 2.15 [1.37-4.10]), pre-existing diabetes (RR 3.20 [1.37-7.46]), asthma (RR 2.22 [1.14-4.34]), and anaemia (RR 3.15 [1.14-8.71]) were associated with higher risk for SARS. The availability of tests and maternal outcomes varied throughout the pandemic period of the study; the beginning was the most challenging period, with worse outcomes. Socially vulnerable, postpartum and previously ill women were more likely to present SARS related to COVID-19.

Brazilian network of COVID-19 during pregnancy (REBRACO: a multicentre study protocol).

INTRODUCTION: The aim of this study was to evaluate the clinical, epidemiological and laboratory aspects of SARS-CoV-2 infection during pregnancy and postpartum in 16 maternity hospitals. METHODS AND ANALYSIS: A prospective multicentre study, with five axes. First, the prevalence of SARS-CoV-2 infection among women admitted for childbirth will be described in a cross-sectional study. Second, maternal and perinatal outcomes will be assessed in a prospective cohort study including pregnant or postpartum women with suspected COVID-19. Third, a cohort of positive COVID-19 cases with sampling of a variety of biological material. Histopathological and viral analysis of biological maternal and neonatal samples will be performed, and the assessment of nutritional variables to evaluate the association between vitamin D and severity of infection. Fourth, a monitoring and evaluation committee to collect relevant healthcare information and plan actions in centres facing the pandemic. Furthermore, qualitative studies will be performed to study pregnant women, their families and health professionals. Fifth, an ecological study will monitor the number of live births, stillbirths and other outcomes to explore any trend among the periods before, during and after the pandemic. Data will systematically be collected in an electronic platform following standardised operational procedures. For quantitative study components, an appropriate statistical approach will be used for each analysis. For qualitative data, in-depth interviews recorded in audio will be transcribed, checking the text obtained with the recording. Subsequently, thematic analysis with the aid of the NVivo programme will be performed. ETHICS AND DISSEMINATION: Ethical approval was obtained (letters of approval numbers 4.047.168, 4.179.679 and 4.083.988). All women will be fully informed to sign the consent form before enrolment in the study. Findings will be disseminated through peer-reviewed journals and scientific conferences.

Brazilian Black Women are at Higher Risk for COVID-19 Complications: An Analysis of REBRACO, a National Cohort / Mulheres negras brasileiras correm maior risco de complicações da COVID-19: uma análise do REBRACO, uma coorte nacional

Abstract Objective To evaluate the impact of the race (Black versus non-Black) on maternal and perinatal outcomes of pregnant women with COVID-19 in Brazil. Methods This is a subanalysis of REBRACO, a Brazilian multicenter cohort study designed to evaluate the impact of COVID-19 on pregnant women. From February2020 until February 2021, 15 maternity hospitals in Brazil collected data on women with respiratory symptoms. We selected all women with a positive test for COVID-19; then, we divided them into two groups: Black and non-Black women. Finally, we compared, between groups, sociodemographic, maternal, and perinatal outcomes. We obtained the frequency of events in each group and compared them using X2 test; p-values < 0.05 were considered significant. We also estimated the odds ratio (OR) and confidence intervals (CI). Results 729 symptomatic women were included in the study; of those, 285 were positive for COVID-19, 120 (42.1%) were Black, and 165 (57.9%) were non-Black. Black women had worse education (p = 0.037). The timing of access to the health system was similar between both groups, with 26.3% being included with seven or more days of symptoms. Severe acute respiratory syndrome (OR 2.22 CI 1.17-4.21), intensive care unit admission (OR 2.00 CI 1.07-3.74), and desaturation at admission (OR 3.72 CI 1.41-9.84) were more likely to occur among Black women. Maternal death was higher among Black women (7.8% vs. 2.6%, p = 0.048). Perinatal outcomes were similar between both groups. Conclusion Brazilian Black women were more likely to die due to the consequences of COVID-19.

Resumo Objetivo Avaliar o impacto da raça (negra versus não negra) nos desfechos maternos e perinatais de gestantes com COVID-19 no Brasil. Métodos Esta é uma subanálise da REBRACO, um estudo de coorte multicêntrico brasileiro desenhado para avaliar o impacto da COVID-19 em mulheres grávidas. De fevereiro de 2020 a fevereiro de 2021, 15 maternidades do Brasil coletaram dados de mulheres com sintomas respiratórios. Selecionamos todas as mulheres com teste positivo para COVID-19; em seguida, as dividimos em dois grupos: mulheres negras e não negras. Finalmente, comparamos, entre os grupos, os resultados sociodemográficos, maternos e perinatais. Obtivemos a frequência dos eventos em cada grupo e comparamos usando o teste X2; Valores de p <0,05 foram considerados significativos. Também estimamos o odds ratio (OR) e os intervalos de confiança (IC). Resultados 729 mulheres sintomáticas foram incluídas no estudo; desses, 285 foram positivos para COVID-19, 120 (42,1%) eram negros e 165 (57,9%) não eram negros. As mulheres negras apresentaram pior escolaridade (p = 0,037). O tempo de acesso ao sistema de saúde foi semelhante entre os dois grupos, com 26,3% incluídos com sete ou mais dias de sintomas. Síndrome respiratória aguda grave (OR 2,22 CI 1,17-4,21), admissão em unidade de terapia intensiva (OR 2,00 CI 1,07-3,74) e dessaturação na admissão (OR 3,72 CI 1,41-9,84) foram mais prováveis de ocorrer entre mulheres negras. A mortalidade materna foi maior entre as negras (7,8% vs. 2,6%, p = 0,048). Os resultados perinatais foram semelhantes entre os dois grupos. Conclusão Mulheres negras brasileiras tiveram maior probabilidade de morrer devido às consequências da COVID-19.

Thrombophilic mutations and polymorphisms, alone or in combination, and recurrent spontaneous abortion.

Generally, recurrent spontaneous abortions (RSAs) have no identifiable cause; yet, vascular alterations during pregnancy may be associated with pregnancy loss. Therefore, we evaluated the association between thrombophilic mutations and RSAs. This case-control study was conducted in 112 patients who had RSAs and 98 health control women. Genomic DNA was extracted from whole blood, and polymorphism genotyping was conducted using polymerase chain reaction. The following 6 genetic variants were analyzed: factor V Leiden, prothrombin mutation, methylenetetrahydrofolate reductase C677T and A1298C, plasminogen activator inhibitor type 1 (4G>5G), and factor XIII G103T (V34L). No correlations were found in any of the investigated polymorphisms. Moreover, 35.0% of cases and 25.5% of controls had at least 2 mutations in combination, and 4.8% of cases and 5.1% of controls had 3, but these combinations were not associated with additional risk. In conclusion, we found no association between the polymorphisms studied and the occurrence of RSAs.

FAS and FAS-L genotype and expression in patients with recurrent pregnancy loss.

We assessed FAS and FAS-L gene polymorphisms and messenger RNA (mRNA) levels in patients with recurrent pregnancy loss (RPL). This case-control study compared 129 women with RPL with 235 healthy multiparous women (control group). Genomic DNA and total mRNA were extracted from whole blood, and polymorphisms genotyping was performed by polymerase chain reaction (PCR). Messenger RNA expression levels were analyzed by real-time PCR. Data were analyzed by chi-square and Fisher exact tests; P < .05 was considered significant. There were no significant differences in the FAS (670 A/G) genotype or allelic frequencies between the RPL and control groups. We found significant differences in the FAS-L (844 C/T) genotype and allelic frequencies between women with RPL and controls. Patients with RPL had significantly higher FAS-L expression. Our data suggest that FAS-L gene polymorphism is associated with increased susceptibility to RPL. Moreover, women with RPL seem to abnormally express FAS-FAS-L molecules.

Video laparoscopic intervention for an interstitial pregnancy after failure of clinical treatment.

CONTEXT: Interstitial pregnancy is a rare form of ectopic pregnancy for which the best therapeutic course of action has yet to be determined. Surgical intervention entails a high risk of hemorrhage due to the great vascularization of the cornual region of the uterus. Case descriptions facilitate the analysis of results and aid clinicians in determining the most appropriate course of action in these situations. CASE REPORT: In a patient with an ultrasound diagnosis of interstitial pregnancy, clinical treatment using methotrexate was chosen. However, after one week, there was a marked decline in the serum level of the ß subunit of chorionic gonadotropin hormone, although an ultrasound examination revealed embryonic cardiac activity. A second dose of the chemotherapy was administered. Embryonic cardiac activity persisted 48 hours later. Video laparoscopy was performed to achieve right-side cornual resection, which resulted in satisfactory resolution of the case.

Polymorphisms in VEGF, progesterone receptor and IL-1 receptor genes in women with recurrent spontaneous abortion.

Hormonal, inflammatory and vascular alterations during pregnancy are thought to be involved in pregnancy loss. The role of progesterone, the actions of which involve cytokines and vascular endothelial growth factor (VEGF), has been thoroughly studied. Genetic factors are involved in modulation of these molecules, and several genes have been associated with recurrent spontaneous abortion (RSA), as well other obstetric conditions. Here we investigate the relationship between RSA and gene polymorphisms of the progesterone receptor (PROGINS), interleukin-1 receptor 1 (PstI) and vascular endothelial growth factor (VEGF) (-634, 936). This case-controlled study comprised a total of 89 women with idiopathic RSA and a control group of 191 women with at least two successful pregnancies and no miscarriages. Genomic DNA was extracted from whole blood, and polymorphism genotyping was conducted by digesting PCR products with specific restriction endonucleases. No correlations were found in any of the investigated polymorphisms, even among dominant, co-dominant and additive inheritance models and alleles. Our results support the hypothesis that these specific gene polymorphisms are not the major determinant of pregnancy success. Although we did not find any correlations, the investigation of these and other polymorphisms remains a challenge in the evaluation of RSA.