Ophthalmic artery Doppler in the prediction of preeclampsia.

The ophthalmic artery is an easily accessible vessel for Doppler assessment that provides information on the less accessible intracranial circulation. In women with preeclampsia, compared with normotensive pregnant women, there is a decrease in impedance to flow and an increase in velocities in the flow velocity waveforms from the ophthalmic arteries. This study aimed to report the methodology for ophthalmic artery Doppler and summarize findings from the clinical implementation of such assessment in the prediction of preeclampsia. The Embase and MEDLINE were searched from inception to November 2020 to identify studies reporting on the use of ophthalmic artery Doppler in the prediction of preeclampsia. Of note, 2 small studies in high-risk pregnancies, one at 11 to 14 weeks' gestation and another at 20 to 28 weeks' gestation, reported differences between women who developed preeclampsia, compared with unaffected pregnancies, in ophthalmic artery Doppler and suggested that this is a useful biomarker for screening for preeclampsia. Another small study in high-risk pregnancies at 18 to 23 weeks' gestation reported that there was no marked difference in ophthalmic artery Doppler indices between the preeclampsia and unaffected groups. In addition, 2 recent, large observational studies in unselected pregnancies at 19 to 23 and 35 to 37 weeks' gestation, respectively, reported that, first, it is necessary to record waveforms from both eyes to get reproducible results; second, the waveform from the ophthalmic arteries is characterized by 2 systolic peaks and the ratio of the second to the first peak systolic velocity was increased in women who developed preeclampsia; third, in the study at 19 to 23 weeks' gestation, the peak systolic velocity ratio was superior to the uterine artery pulsatility index, mean arterial pressure, serum placental growth factor, and soluble fms-like tyrosine kinase-1 as individual biomarkers in the prediction of both preterm and term preeclampsia and the peak systolic velocity ratio improved the prediction of preeclampsia provided by all the other biomarkers; and fourth, in the study at 35 to 37 weeks' gestation, the peak systolic velocity ratio improved the prediction of subsequent development of preeclampsia provided by maternal factors alone and combinations of maternal factors with mean arterial pressure, uterine artery pulsatility index, placental growth factor, and serum placental growth factor. The ophthalmic artery Doppler provides a useful biomarker for the prediction of preeclampsia.

Cross-Protection of Dengue Virus Infection against Congenital Zika Syndrome, Northeastern Brazil.

The Zika virus outbreak in Latin America resulted in congenital malformations, called congenital Zika syndrome (CZS). For unknown reasons, CZS incidence was highest in northeastern Brazil; one potential explanation is that dengue virus (DENV)-mediated immune enhancement may promote CZS development. In contrast, our analyses of historical DENV genomic data refuted the hypothesis that unique genome signatures for northeastern Brazil explain the uneven dispersion of CZS cases. To confirm our findings, we performed serotype-specific DENV neutralization tests in a case-control framework in northeastern Brazil among 29 Zika virus-seropositive mothers of neonates with CZS and 108 Zika virus-seropositive control mothers. Neutralization titers did not differ significantly between groups. In contrast, DENV seroprevalence and median number of neutralized serotypes were significantly lower among the mothers of neonates with CZS. Supported by model analyses, our results suggest that multitypic DENV infection may protect from, rather than enhance, development of CZS.

Obesity and recurrent miscarriage: A systematic review and meta-analysis.

The aim of this study is to perform a systematic review and meta-analysis on the relationship between excess weight and risk of recurrent pregnancy loss (RPL) and to highlight the common immunological mechanisms of these two conditions. The PubMed and MEDLINE databases were searched for publications in English available as of November 2017. The search terms used were 'recurrent pregnancy loss', 'body mass index' (BMI), 'overweight' and 'obesity'. For calculation of the odds ratio (OR) and 95% confidence intervals (CI) for miscarriage in different BMI groups, RevMan software was used (Review Manager, Version 5.3.5 for Windows; The Cochrane Collaboration). In total, 100 publications including the search terms were identified. Six studies were included for qualitative analysis, and two studies were included for quantitative analysis (meta-analysis). The association between excess weight and RPL was significant (OR, 1.34; 95% CI, 1.05-1.70; P = 0.02). The isolated analyses of the groups of obese and overweight women revealed an association only between obesity and RPL (OR, 1.75; 95% CI, 1.24-2.47; P = 0.001). The data available in the current literature revealed that obese women with a history of RPL have a high risk of future pregnancy losses, a risk which was not found among overweight women.

Evidence for Congenital Zika Virus Infection From Neutralizing Antibody Titers in Maternal Sera, Northeastern Brazil.

Reliable diagnosis of congenital Zika virus (ZIKV) infection is challenging. Here, we assessed ZIKV-specific neutralizing antibodies in 28 mothers of children with microcephaly (cases) and 122 controls from northeastern Brazil using plaque reduction neutralization tests. ZIKV-specific antibody titers were significantly higher in cases than in controls (t test, P < .0001). We identified a putative case of congenital Zika syndrome retrospectively by unusually high ZIKV-specific antibody titers. High ZIKV-specific antibody titers in cases were unrelated to prior dengue virus infection. Our data suggest a strong immunological stimulus from prolonged placental or transplacental ZIKV shedding and potential utility of maternal antibody titers to corroborate congenital ZIKV infection.

Lymphocyte immunotherapy in the treatment of recurrent miscarriage: systematic review and meta-analysis.

PURPOSE: Recurrent miscarriage (RM) affects up to 2-3% of couples of reproductive age. There are several causes for this condition, including immunologic. The embryo is considered an allograft, subject to the rejection mechanisms of the maternal immune system. Immunotherapy involving immunization with lymphocytes is considered in cases of idiopathic RM. However, there is still no consensus regarding the efficacy and safety of this therapy. METHODS: This systematic review and meta-analysis evaluated the data available in the literature regarding the efficacy and safety of the use of immunotherapy with lymphocytes in couples with history of RM. Searches in PubMed/Medline, SCOPUS, and Cochrane Library databases were conducted, using the following keywords: "recurrent miscarriage," "lymphocyte immunotherapy," and "meta-analysis." Statistical analyses were performed using Review Manager 5.3 (RevMan), version 5.3. RESULTS: Six published meta-analysis were retrieved; two found no improvements in the rate of live births after the use of immunization with lymphocytes in the treatment of RM, and four found a beneficial effect of the use of immunotherapy with lymphocytes in cases of RM, with significant improvements in the rate of live births. CONCLUSION: Data available in the literature supports the efficacy and safety of immunotherapy with lymphocytes in cases of RM without an identified cause.

Ultrasonographic evaluation of the fetal thymic-thoracic ratio and its association with conotruncal heart defects.

OBJECTIVE: To evaluate the thymic-thoracic ratio (TT ratio) on fetal ultrasound and its association with conotruncal heart defects. METHODS: A case control study was carried out to retrospectively assess the TT ratio on fetal echocardiograms performed between 19 and 39 weeks of gestation, showing congenital heart defects, from January to December 2018. The control group was comprised of fetuses with no echocardiogram evidence of congenital cardiac malformations. Cases of multiple pregnancies and patients where the TT ratio could not be established have been excluded. RESULTS: A total of 338 pregnancies have been analysed. Fifty-two pregnancies were diagnosed with fetal heart defects (15%), 17 of which showed conotruncal heart defects (32.7%). The TT ratio in normal fetuses (286 pregnancies) increased with gestational age, and had an average of 0.43 ± 0.06. Compared to the control group (normal fetuses), fetuses with conotruncal heart defects had significantly lower mean TT ratio (0.33 ± 0.07). Those that were diagnosed with nonconotruncal heart defects did not show any statistically significant difference in the TT ratios compared with the control group (0.40 ± 0.09 vs. 0.43 ± 0.06, respectively). CONCLUSION: The TT ratio was significantly lower in fetuses with conotruncal heart defects compared with both the control group (normal fetuses) and the fetuses with nonconotruncal heart defects.

Prevalence of sarcopenia using different methods in patients with non-alcoholic fatty liver disease.

BACKGROUND: Sarcopenia is a clinical condition associated with several liver diseases and it includes non-alcoholic fatty liver disease (NAFLD) in its broad spectrum as steatosis, steatohepatitis and fibrosis. However, the criteria to define sarcopenia are diverse, and even those established in consensus have been discussed regarding their performance in making an accurate diagnosis. AIM: To evaluate the prevalence of sarcopenia, using different methods, in patients with NAFLD, and its association with clinical-anthropometric parameters. METHODS: This was an observational study of outpatients with NAFLD. Sarcopenia was defined by the European Working Group Consensus on Sarcopenia in Older People of 2010 (EWGSOP1) and 2018 (EWGSOP2). The skeletal muscle index was used to estimate muscle mass, handgrip strength was assessed using the dynamometer and physical performance by walking a distance of four meters at usual walking speed. The non-invasive fibrosis scores, fibrosis-4 (FIB-4) index and Aspartate aminotransferase to platelet ratio index (APRI), were used to assess the absence and presence of fibrosis. RESULTS: Fifty-seven individuals with NAFLD were evaluated, the mean age (SD) was 52.7 (11.3) years and 75.4% were female. Fibrosis assessed by FIB-4 and APRI was observed in 3.7% and 16.6% of patients with NAFLD, respectively. The diagnosis of sarcopenia was identified only by EWGSOP1 in 3.5% of NAFLD patients, and the prevalence of probable/pre-sarcopenia was higher using the EWGSOP2 consensus at 26.3%, when compared to 1.8% with EWGSOP1. Sarcopenia defined by EWGSOP1, was associated with grade I steatosis, but without overweight (P < 0.05). An association between sarcopenia and fibrosis was not observed (P > 0.05). EWGSOP2 showed a greater number of patients with probable sarcopenia, and who were overweight (12 (80.0%)), with a higher degree of steatosis [11 (73.3%) and presence of fibrosis (1 (6.7%), FIB-4 and 3 (20.0%), APRI] compared to EWGSOP1 [1 (100%), 0 (0.0%), 0 (0.0%), FIB-4 and 0 (0.0%), APRI, respectively]. CONCLUSION: The present study showed that sarcopenia in NAFLD was not predominant in patients without fibrosis, by both diagnostic methods. In addition, the prevalence of probable sarcopenia also depends on the method applied.

Unequal burden of Zika-associated microcephaly among populations with public and private healthcare in Salvador, Brazil.

OBJECTIVES: To describe the differences in clinical presentation and relative disease burden of congenital Zika syndrome (CZS)-associated microcephaly at 2 large hospitals in Salvador, Brazil that serve patients of different socioeconomic status (SES). METHODS: Clinical and serologic data were collected prospectively from pregnant women and their infants, who delivered at 2 study centers during the 2015-2016 Zika virus (ZIKV) epidemic in Salvador, Brazil. RESULTS: Pregnant women from Salvador, Brazil delivering in a low SES hospital had 3 times higher ZIKV exposure rate than women at a high SES hospital. However, different SES hospitals had similar prevalence of infants with CZS-associated microcephaly (10% vs 6%, p = 0.16) after controlling for ZIKV exposure in their mothers. CONCLUSIONS: Our study supports the positive association between low SES, high maternal ZIKV exposure, and high rates of CZS-associated microcephaly.

Lymphocyte immunotherapy in recurrent miscarriage and recurrent implantation failure.

PROBLEM: Lymphocyte immunotherapy (LIT) emerged in the early 1980s as a new therapeutic proposal for couples with a history of recurrent miscarriages (RM). However, in the early 2000s, the effectiveness of LIT was questioned. Recently, meta-analyses have observed the effectiveness and safety of LIT in treating couples with RM. Some studies evaluated the use of LIT in recurrent implantation failure (RIF) in in vitro fertilization cycles. METHODS: This systematic and narrative review evaluated the data available in the literature regarding the efficacy and safety of the use of LIT. Searches in PubMed/Medline, Embase, and Cochrane Library databases were conducted, using the following keywords: "recurrent miscarriage," "lymphocyte immunotherapy," and "recurrent implantation failure". RESULTS: This review describes the historical aspects of LIT and discusses its protocols, mechanisms of action, side effects, complications, and current evidence of the effectiveness in cases of reproductive failure. It also discusses the use of LIT during the COVID-19 pandemic and new immunological therapies. CONCLUSION: In the vast majority of studies, the use of LIT for RM couples has shown an improvement in pregnancy outcomes. The most of the current studies that support the evidence are quasi-experimental, with few randomized, double-blind studies (Level of evidence III). However, the current evidence are not convincing for the use of LIT in RIF patients.

Maternal immune responses and obstetrical outcomes of pregnant women with COVID-19 and possible health risks of offspring.

Coronavirus disease 2019 (COVID-19) pandemic has spread rapidly across the world. The vast majority of patients with COVID-19 manifest mild to moderate symptoms but may progress to severe cases or even mortalities. Young adults of reproductive age are the most affected population by SARS-CoV-2 infection. However, there is no consensus yet if pregnancy contributes to the severity of COVID-19. Initial studies of pregnant women have found that COVID-19 significantly increases the risk of preterm birth, intrauterine growth restriction, and low birth weight, which have been associated with non-communicable diseases in offspring. Besides, maternal viral infections with or without vertical transmission have been allied with neurological and behavioral disorders of the offspring. In this review, obstetrical outcomes of women with COVID-19 and possible risks for their offspring are discussed by reviewing maternal immune responses to COVID-19 based on the current evidence. Structural and systemic follow-up of offspring who are exposed to SARS-CoV-2 in-utero is suggested.

COVID-19 and miscarriage: From immunopathological mechanisms to actual clinical evidence.

The association between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the first half of pregnancy and pregnancy loss is still unknown. Infections by other coronaviruses, such as severe acute respiratory syndrome coronavirus (SARS-CoV) and the Middle East respiratory syndrome coronavirus (MERS-CoV), appear to increase the risk of miscarriage. The purpose of this study is to assess whether SARS-CoV-2 infection increases the risk of miscarriage. Firstly, a narrative review of the literature on animal and human studies was performed to analyze the immunopathological mechanisms of SARS-CoV-2 infection during preconception and early pregnancy, by which it may increase the risk of miscarriage. Secondly, a systematic review/meta-analysis of studies was conducted to assess the prevalence of miscarriage in COVID-19 patients diagnosed during pregnancy. Meta-analysis of proportions was used to combine data, and pooled proportions were reported. Seventeen case series and observational studies and 10 prevalence meta-analyses were selected for the review. The estimate of the overall miscarriage rate in pregnant women with COVID-19 was 15.3 % (95 % CI 10.94-20.59) and 23.1 (95 % CI 13.17-34.95) using fixed and random effect models, respectively. Based on the data in the current literature, the miscarriage rate (<22 weeks gestation) in women with SARS-CoV-2 infection is in the range of normal population. Well-designed studies are urgently needed to determine whether SARS-CoV-2 infection increases the risk of miscarriage during periconception and early pregnancy.

Accuracy of the mid-trimester ultrasound scan in the detection of fetal congenital anomalies in a reference center in Northeastern Brazil.

OBJECTIVE: To assess the performance of a basic mid-trimester fetal ultrasound scan protocol for the diagnosis of congenital anomalies by calculating its accuracy, sensitivity, and specificity. METHODS: This longitudinal cohort study involved singleton pregnant women recruited at the mid-trimester fetal ultrasound scan through the postnatal evaluation of congenital anomalies. Pregnant women who underwent a routine mid-trimester ultrasound scan for fetal abnormalities at 20-24 weeks of gestation were enrolled in this study. After childbirth, we searched their medical records on gestational outcomes and neonatal examination records, as well as complementary medical examinations, to assess the ultrasound performance in diagnosing congenital malformations. RESULTS: We included 967 pregnant women in the study population, and prenatal ultrasound scans detected congenital abnormalities in 67 fetuses (6.9%). Among newborns, 54 (5.6%) were postnatally diagnosed with malformations. The overall sensitivity and specificity of the mid-trimester ultrasound scan for congenital malformation detection were 61.1% and 96.3%, respectively, with an accuracy of 94.3% (p < .05). CONCLUSION: The mid-trimester ultrasound scan had good accuracy in the detection of congenital malformations, although the overall sensitivity does not support it as the only screening test for anomalies throughout pregnancy.

Anthropometric clinical indicators of visceral adiposity as predictors of nonalcoholic fatty liver disease.

OBJECTIVE: This study aims to evaluate the role of anthropometric clinical indicators of visceral adiposity as predictors of NAFLD, identifying the cutoff points based on gender. METHODS: This was a cross-sectional study conducted in patients with or without NAFLD. Waist circumference (WC), body mass index (BMI), waist-to-height ratio (WHtR), Conicity Index (C Index), and lipid accumulation product (LAP) were evaluated. RESULTS: A total of 107 individuals were evaluated, of which 46.7% were diagnosed with NAFLD. Individuals with NAFLD presented higher values of WC, BMI, C Index, LAP, and WHtR when compared with those without NAFLD (p<0.05). For the total sample, the indicators WC, BMI, WHtR, LAP, and C Index had an area under the receiver operator characteristic curve (AUC) above 0.87, with no difference in the prediction of NAFLD in both sexes. WHtR (AUC=0.934) was the indicator of visceral adiposity with the best discriminatory power for NAFLD, followed by LAP (0.919), WC (0.912), C Index (0.907), and BMI (0.877). CONCLUSIONS: The anthropometric clinical indicators of visceral adiposity showed high performance, especially the WHtR indicator, as NAFLD predictors.

Muscle mass and cellular membrane integrity assessment in patients with nonalcoholic fatty liver disease.

OBJECTIVE: To evaluate the association between muscle mass depletion and compromising of the cell membrane integrity and clinical-anthropometric characteristics in patients with nonalcoholic fatty liver disease. METHODS: This observational study evaluated waist circumference, body mass index, and waist-to-height ratio in patients with nonalcoholic fatty liver disease. Skeletal mass index corrected by weight and impairment of cell membrane integrity were assessed using bioelectrical impedance analysis. RESULTS: In 56 patients, muscle mass depletion was observed in 62.5% and cell membrane impairment in 28.6%. The metabolic syndrome and elevated aspartate aminotransferase were the only clinical factors associated with mass depletion (p<0.05). The linear regression analysis showed association between skeletal mass index and waist-to-height ratio and waist circumference, after adjustments (p<0.05). The phase angle value was not different between those with and without mass depletion, and also it did not have correlation with skeletal mass index and clinical parameters (p>0.05). CONCLUSIONS: The prevalence of mass depletion and cell membrane impairment was higher in patients with nonalcoholic fatty liver disease. The muscle mass depletion was associated with central obesity, aspartate aminotransferase elevated, and metabolic syndrome; however, the phase angle is not associated with clinical and anthropometric data.

Intrauterine perfusion immunotherapies in recurrent implantation failures: Systematic review.

Studies have investigated the gestational outcomes of new immunological therapies in the treatment of patients with recurrent implantation failure (RIF) in assisted reproductive technology (ART). The objective of this article is to assess the current state of evidence available in the literature on intrauterine perfusion immunotherapies in women undergoing ART treatments. By considering the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA), the authors performed systematic review by searching the databases of PubMed/MEDLINE and Scopus using the following key words: "recurrent implantation failure," "intrauterine infusion," "Platelet-Rich Plasma (PRP)," "Peripheral Blood Mononuclear Cells (PBMC)," "Granulocyte Colony-Stimulating Factor (G-CSF)," and "Human Chorionic Gonadotropin (hCG)." The authors analyzed the indications and the impact of new immunological therapies with intrauterine infusions on the pregnancy outcomes of patients undergoing ART. PRP, PBMC, G-CSF, and hCG were the four most used immunological therapies with intrauterine infusion. These new therapies appear to improve the results of ART treatments in cases of RIF. However, the small number of studies does not allow definitive conclusions about the effectiveness of these therapies.

Seroprevalence and factors associated with Human Immunodeficiency virus, Human T lymphotropic virus and Hepatitis B/C infections in parturient women of Salvador - Bahia, Brazil.

BACKGROUND: The heterogeneity in detection rates of Human immunodeficiency virus, (HIV), Human T lymphotropic virus (HTLV) and Hepatitis B and C infections among pregnant women and the continuous exposure to risk factors limits the adoption of preventive and control actions. OBJECTIVE: To evaluate the HIV, HTLV, Hepatitis B and C seroprevalence rates, and associated risk factors in parturient women in Salvador, Brazil. METHODS: This was a cross-sectional study in 2099 parturient women attended in two public maternity hospitals in Salvador, Brazil. One blood sample was drawn for serological screening and socio-demographic, obstetric and clinical data were collected. RESULTS: HIV seroprevalence rate was 1.5% (of which 0.6% were new cases); seroprevalence rates for HTLV, HBV, and HCV were 0.4%, 0.4%, and 0.1%, respectively. Univariate analysis showed a significant association between socio-demographic and behavioral factors with retroviral infections, while viral hepatitis was mainly associated with parenteral exposure. In a multivariate analysis, multiple sexual partners (OR 3.3; 95% CI: 1.1-9.2), history of sexual/domestic violence (OR 2.8; 95% CI: 1.1-6.9), syphilis co-infection (OR 2.6; 95% CI: 1.0-6.9), use of alcohol or drugs (OR 2.5; 95% CI: 1.2-5.5), and low schooling level (OR 2.3; 95% CI: 1.1-4.9) were independent risk factors for HIV infection. History of stillbirth and low birth weight infants was significantly associated with HTLV positive status, showing a negative impact on gestation. CONCLUSIONS: The seroprevalence rates for HIV, HCV, HBV, and HTLV were similar to that found in previous studies in other Brazilian regions. The high individual, socioeconomic, and social vulnerability detected in seropositive parturient women indicates the need to improve coverage and effectiveveness of STDs control with prevention, detection and monitoring strategies, focusing in pregnant women exposed to high biopsychosocial risk.

Antinuclear antibodies and recurrent miscarriage: Systematic review and meta-analysis.

Studies have investigated the relationship between antinuclear antibodies (ANA) and recurrent miscarriage (RM). The objective of this paper is to evaluate the presence of ANA as a risk factor for spontaneous abortion in patients with RM. By considering the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analysis, the authors performed systematic review and meta-analysis by searching the databases of PubMed/Medline and SCOPUS. Review Manager, Version 5.3 performed the statistical analysis. Binary variables were analyzed by odds ratio (ORs) and 95% confidence interval (CI). The subgroup analysis compared the effect of different ANA titers. The authors analyzed the ANA patterns of immunofluorescence staining. Seven case-control studies were selected. The frequency of positive ANA was statistically higher in the RM group (20.6%, 288/1400) as compared to the control group (6.7%, 72/1080). The meta-analysis of the positive ANA showed a statistical difference between the two groups (OR 3.30, 95% CI 1.41-7.73; I2  = 87%, P = .006). Studies have revealed different frequencies of ANA patterns of immunofluorescence. This meta-analysis suggested that positive ANA might increase the risk of RM. However, it was not possible to conclude which ANA pattern of immunofluorescence staining is more frequent in the RM group.