SARS-CoV-2 Infection Increases High Risk Rate of Down Syndrome Screening Test by Reducing Alpha-Fetoprotein.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been a significant global health issue in recent years. Numerous studies indicate that COVID-19 during pregnancy is associated with an increased likelihood of pregnancy complications. Additionally, pregnancy itself is known to elevate the risk of severe SARS-CoV-2 infection. To explore the potential impact of SARS-CoV-2 infection on the probability of Down syndrome in fetuses, we conducted serological testing of Down syndrome markers in pregnant women who had contracted the virus. METHODS: Serological experiments were conducted utilizing a particle chemiluminescence test. The cohort of pregnant women was categorized into three groups: a control group with no infection, a group infected with SARS-CoV-2 Omicron within the first six weeks of gestation, and a group infected beyond the sixth week of gestation. RESULTS: In the group of individuals infected within 6 gestational weeks, the infection resulted in a decrease in alpha-fetoprotein (AFP) levels and a higher positive rate of Down syndrome screening tests (p ˂ 0.05). However, in this study, SARS-CoV-2 infection did not lead to an increase in the occurrence of Down syndrome in the fetus. The positive rate of women infected beyond 6 gestational weeks was slightly higher than the non-infected group (6.2% vs. 5.7%), but these differences were not statistically significant (p > 0.05). Within the group infected beyond 6 gestational weeks, there was, compared to the control group, a decrease in free beta human chorionic gonadotropin (ß-hCG) levels (p < 0.05). CONCLUSIONS: This study presents a novel investigation into the impact of SARS-CoV-2 infection on AFP and ß-hCG levels. It has been observed that pregnant women who contract SARS-CoV-2 may exhibit an increased likelihood of positive results in serum tests conducted for Down syndrome screening. However, it is important to note that the occurrence of Down syndrome in the developing fetus does not appear to be elevated. To validate these findings, additional research involving larger and diverse cohorts is necessary.

Association between lymphadenopathy after toxoplasmosis seroconversion in pregnancy and risk of congenital infection.

The aim of the study was to describe the pregnancy outcome of a large cohort of women with toxoplasmosis seroconversion in pregnancy and to investigate the relation between maternal lymphadenopathy and risk of congenital toxoplasmosis (CT). This was a retrospective study involving women with confirmed toxoplasmosis seroconversion in pregnancy between 2001 and 2017. Women were clinically evaluated for lymphadenopathy and classified as follows: lymphadenopathy absent (L-) or lymphadenopathy present (L+). The mothers were treated and followed-up according to local protocol, and neonates were monitored at least for 1 year in order to diagnose CT. A total of 218 women (one twin pregnancy) were included in the analysis. Pregnancy outcome was as follows: 149 (68%) of children not infected, 62 (28.3%) infected, 4 (1.8%) first trimester termination of pregnancy, 2 (0.9%) first trimester miscarriages, and 3 (1.4%) stillbirths (of which one already counted in the infected cohort). 13.8% of women were L+ , and they were nearly three times more likely to have a child with CT compared to L- women (aOR, 2.90; 95%CI, 1.28-6.58). Moreover, the result was still statistically significant when the analysis was restricted to 81 children whose mothers were clinically examined and received treatment within 5 weeks from estimated time of infection. In conclusion, there is a positive association between L+ status in pregnant women, and risk of CT also confirmed when restricting the analysis to women with early diagnosis of seroconversion and treatment. This data could be very useful in counselling pregnant women with toxoplasmosis seroconversion and lead to direct a more specific therapeutic and diagnostic protocol.

ABO blood group and risk of malaria during pregnancy: a systematic review and meta-analysis.

The association between the ABO blood group and the risk of malaria during pregnancy has not been clearly established. The present study summarised relevant knowledge and reassessed the association through meta-analysis. Articles in MEDICINE and PubMed published before 30 November 2021 were searched. Five studies satisfied the inclusion criteria and were enrolled in the meta-analysis. It was shown that primiparae with different ABO blood group, multiparae with blood group A and non-A, AB and non-AB had a comparable risk of malaria. However, multiparae with blood group B had a significantly higher risk than non-B group [odds ratio (OR) = 1.23, 95% confidence interval (CI) was 1.01 to 1.50, P = 0.04], while multiparae with blood group O had a significantly lower risk than non-O group (OR = 0.78, 95% CI was 0.63 to 0.97, P = 0.03). Therefore, the ABO blood group may not result in a different risk of malaria in primiparae. Blood group B is potentially a risk factor while blood group O is a protective factor for multiparae.

Routine screening for hepatitis C in pregnancy is cost-effective in a large urban population in Ireland: a retrospective study.

OBJECTIVE: To investigate whether risk factor-based screening in pregnancy is failing to identify women with hepatitis C virus (HCV) infection and to assess the cost-effectiveness of universal screening. DESIGN: Retrospective study and model-based economic evaluation. SETTING: Two urban tertiary referral maternity units, currently using risk factor-based screening for HCV infection. POPULATION: Pregnant women who had been tested for hepatitis B, HIV but not HCV. METHODS: Anonymised sera were tested for HCV antibody. Positive sera were tested for HCV antigen. A cost-effectiveness analysis of a change to universal screening was performed using a Markov model to simulate disease progression and Monte Carlo simulations for probabilistic sensitivity analysis. MAIN OUTCOME MEASURES: Presence of HCV antigen and cost per quality-adjusted life year (QALY). RESULTS: In all, 4655 samples were analysed. Twenty had HCV antibodies and five HCV antigen. This gives an active infection rate of 5/4655, or 0.11%, compared with a rate of 0.15% in the risk-factor group. This prevalence is 65% lower than a previous study in the same hospitals from 2001 to 2005. The calculated incremental cost-effectiveness ratio (ICER) for universal screening was €3,315 per QALY gained. CONCLUSION: This study showed that the prevalence of HCV infection in pregnant women in the Dublin region has declined by 65% over the past two decades. Risk factor-based screening misses a significant proportion of infections. A change to universal maternal screening for hepatitis C would be cost-effective in our population. TWEETABLE ABSTRACT: Universal maternal screening for hepatitis C is cost-effective in this urban Irish population.

Leaning towards Cytomegalovirus serological screening in pregnancy to prevent congenital infection: a cost-effectiveness perspective.

OBJECTIVE: To assess the cost-effectiveness of prenatal detection of congenital cytomegalovirus (cCMV) following maternal primary infection in the first trimester within standard pregnancy follow-up or involving population-based screening (serological testing at 7 and 12 weeks of gestation), with or without secondary prevention (valaciclovir) in maternal CMV primary infection. DESIGN: Cost-effectiveness study from the perspective of the French national health insurance system. SETTING: Cost-effectiveness based on previously published probability estimates and associated plausible ranges hypothetical population of 1,000,000 pregnant women. POPULATION: Hypothetical population of 1,000,000 pregnant women. METHODS: Cost-effectiveness of detecting fetal cCMV in terms of the total direct medical costs involved and associated expected outcomes. MAIN OUTCOME MEASURES: Detection rates and clinical outcomes at birth. RESULTS: Moving to a population-based approach for targeting fetal CMV infections would generate high monetary and organizational costs while increasing detection rates from 15% to 94%. This resource allocation would help implementing horizontal equity according to which individuals with similar medical needs should be treated equally. Secondary prevention with valaciclovir had a significant effect on maternal-fetal CMV transmission and clinical outcomes in newborns, with a 58% decrease of severely infected newborns for a 3.5% additional total costs. Accounting for women decision-making (amniocentesis uptake and termination of pregnancy in severe cases) did not impact the cost-effectiveness results. CONCLUSIONS: These findings could fuel thinking on the opportunity of developing clinical guidelines to rule identification of cCMV infection and administration of in-utero treatment. These findings could fuel the development of clinical guidelines on the identification of congenital CMV infection and the administration of treatment in utero. TWEETABLE ABSTRACT: CMV serological screening followed by valaciclovir prevention may prevent 58% to 71% of severe cCMV cases for 38 € per pregnancy.

Increased levels of soluble fms-like tyrosine kinase-1 are associated with adverse outcome in pregnant women with COVID-19.

OBJECTIVE: In addition to the lungs, the placenta and the endothelium can be affected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) are markers of endothelial dysfunction and could potentially serve as predictors of severe coronavirus disease 2019 (COVID-19). We aimed to investigate the association of serum concentrations of sFlt-1 and PlGF with the severity of COVID-19 in pregnancy. METHODS: This was a prospective cohort study carried out in a tertiary care hospital in Mexico City, Mexico. Symptomatic pregnant women with a positive reverse-transcription quantitative polymerase chain reaction test for SARS-CoV-2 infection who fulfilled the criteria for hospitalization were included. The primary outcome was severe pneumonia due to COVID-19. Secondary outcomes were intensive care unit (ICU) admission, viral sepsis and maternal death. sFlt-1 levels were expressed as multiples of the median (MoM). The association between sFlt-1 and each adverse outcome was explored by logistic regression analysis, adjusted for gestational age for outcomes occurring in more than five patients, and the predictive performance was assessed by receiver-operating-characteristics-curve analysis. RESULTS: Among 113 pregnant women with COVID-19, higher sFlt-1 MoM was associated with an increased probability of severe pneumonia (adjusted odds ratio (aOR), 1.817 (95% CI, 1.365-2.418)), ICU admission (aOR, 2.195 (95% CI, 1.582-3.047)), viral sepsis (aOR, 2.318 (95% CI, 1.407-3.820)) and maternal death (unadjusted OR, 5.504 (95% CI, 1.079-28.076)). At a 10% false-positive rate, sFlt-1 MoM had detection rates of 45.2%, 66.7%, 83.3% and 100% for severe COVID-19 pneumonia, ICU admission, viral sepsis and maternal death, respectively. PlGF values were similar between women with severe and those with non-severe COVID-19 pneumonia. CONCLUSION: sFlt-1 MoM is higher in pregnant women with severe COVID-19 and has the capability to predict serious adverse pregnancy events, such as severe pneumonia, ICU admission, viral sepsis and maternal death. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

A systematic review of maternal TORCH serology as a screen for suspected fetal infection.

BACKGROUND: The acronym 'TORCH' refers to well-recognised causes of perinatal infections: toxoplasmosis, rubella, cytomegalovirus (CMV) and herpes simplex virus (HSV). A TORCH serology panel is often used to test for maternal primary infection following detection of ultrasound abnormalities in pregnancy. AIM: This review aims to estimate the diagnostic yield of maternal TORCH serology in pregnancy following fetal ultrasound abnormalities. MATERIALS AND METHODS: Primary studies published since 2000 that assessed maternal TORCH serology for suspected fetal infection and included information on indications for testing, definition of positive TORCH serology results, and perinatal outcomes were included. RESULTS: Eight studies with a total of 2538 pregnancies were included. The main indications for testing were polyhydramnios, fetal growth restriction and hyperechogenic bowel. There were 26 confirmed cases of congenital CMV, of which 15 had multiple ultrasound abnormalities. There were no cases of congenital toxoplasmosis, rubella or HSV confirmed in any of the eight studies. CONCLUSIONS: The clinical utility of TORCH serology for non-specific ultrasound abnormalities such as isolated fetal growth restriction or isolated polyhydramnios is low. It is time to retire the TORCH acronym and the reflex ordering of 'TORCH' panels, as their continued use obscures, rather than illuminates, appropriate investigation for fetal ultrasound abnormalities.

Hematological changes associated with COVID-19 infection.

BACKGROUND: The unresolved COVID-19 pandemic considerably impacts the health services in Iraq and worldwide. Consecutive waves of mutated virus increased virus spread and further constrained health systems. Although molecular identification of the virus by polymerase chain reaction is the only recommended method in diagnosing COVID-19 infection, radiological, biochemical, and hematological studies are substantially important in risk stratification, patient follow-up, and outcome prediction. AIM: This narrative review summarized the hematological changes including the blood indices, coagulative indicators, and other associated biochemical laboratory markers in different stages of COVID-19 infection, highlighting the diagnostic and prognostic significance. METHODS: Literature search was conducted for multiple combinations of different hematological tests and manifestations with novel COVID-19 using the following key words: "hematological," "complete blood count," "lymphopenia," "blood indices," "markers" "platelet" OR "thrombocytopenia" AND "COVID-19," "coronavirus2019," "2019-nCoV," OR "SARS-CoV-2." Articles written in the English language and conducted on human samples between December 2019 and January 2021 were included. RESULTS: Hematological changes are not reported in asymptomatic or presymptomatic COVID-19 patients. In nonsevere cases, hematological changes are subtle, included mainly lymphocytopenia (80.4%). In severe, critically ill patients and those with cytokine storm, neutrophilia, lymphocytopenia, elevated D-dimer, prolonged PT, and reduced fibrinogen are predictors of disease progression and adverse outcome. CONCLUSION: Monitoring hematological changes in patients with COVID-19 can predict patients needing additional care and stratify the risk for severe course of the disease. More studies are required in Iraq to reflect the hematological changes in COVID-19 as compared to global data.

Evaluation of maternal serum afamin and vitamin E levels in pregnant women with COVID-19 and its association with composite adverse perinatal outcomes.

To evaluate the maternal serum afamin and vitamin E levels in pregnant women with coronavirus disease 2019 (COVID-19) and to investigate their association with composite adverse perinatal outcomes. This prospective, case-control study consisted of 60 pregnant women with COVID-19 infection and 36 age-matched pregnant women without any defined risk factors. Demographic features, laboratory test results, afamin and vitamin E levels were compared between the groups. A receiver operating characteristic (ROC) curve was used to assess the relationship of afamin and vitamin E levels in predicting composite adverse perinatal outcomes. A correlation analysis was performed between afamin and C-reactive protein (CRP) levels in pregnant women with COVID-19. The obstetric complication rate was higher in the COVID-19 group (13.3% vs. 2.8%) (p = .01). Afamin levels were higher and vitamin E levels were lower in the COVID-19 group (p = .02 and p < .001, respectively). Vitamin E levels were lower in the COVID-19 group for the all trimesters (p < .001, p < .001, and p = .004, respectively). Afamin levels were higher in the COVID-19 group for the all trimesters without reaching statistical significance (p > .05). The values in the ROC curves with the best balance of sensitivity/specificity for afamin and vitamin E were 0.424 mg/l (70.6% sensitivity, 44.3% specificity) and 3.150 µg/ml (76.5% sensitivity, 58.2% specificity), respectively. A positive moderate statistically significant correlation was found between afamin and CRP levels (r = .264, p = .009). Higher afamin and lower vitamin E levels may support the elevated oxidative stress in the etiopathogenesis of COVID-19 and the relationship with composite adverse perinatal outcomes.

Comparison of VEGF-A values between pregnant women with COVID-19 and healthy pregnancies and its association with composite adverse outcomes.

The aim is to compare VEGF-A values between pregnant women with coronavirus disease 2019 (COVID-19) and healthy controls. Furthermore, the association of inflammation parameters, disease severity, and obstetric complications with VEGF-A was investigated. This prospective case-control study was conducted on pregnant women who were admitted to Ankara City Hospital between June 14, 2020 and August 28, 2020. Pregnant women with COVID-19 (n = 95) were compared with a control group of healthy pregnant women (n = 92) with similar clinical and demographic characteristics. Demographic features, clinical characteristics, laboratory test results, VEGF-A values were compared between the groups. A correlation analysis was performed between VEGF-A levels, inflammation parameters, and clinical characteristics of the cases for pregnant women with COVID-19. VEGF-A levels were also compared between patients with composite adverse outcome and patients without any complication in the COVID-19 group. The two groups were similar except for obstetric complications (p > .05). The obstetric complication rate was higher in the COVID-19 group (p =.02). The two groups were comparable in terms of neutrophil to lymphocyte ratio and VEGF-A values. VEGF-A values were slightly different between the trimesters. A negative moderate statistically significant correlation was found between the neutrophil and VEGF-A values (r = -0.231, p =.02). VEGF-A values were similar between patients with and without composite adverse outcomes (p > .05). VEGF-A values were similar between pregnant women with COVID-19 and healthy controls.

SARS-CoV-2 in first trimester pregnancy: a cohort study.

STUDY QUESTION: Does maternal infection with severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2) in first trimester pregnancy have an impact on the fetal development as measured by nuchal translucency thickness and pregnancy loss? SUMMARY ANSWER: Nuchal translucency thickness at the first trimester scan was not significantly different in pregnant women with versus without SARS-CoV-2 infection in early pregnancy and there was no significantly increased risk of pregnancy loss in women with SARS-CoV-2 infection in the first trimester. WHAT IS KNOWN ALREADY: Pregnant women are more vulnerable to viral infections. Previous coronavirus epidemics have been associated with increased maternal morbidity, mortality and adverse obstetric outcomes. Currently, no evidence exists regarding possible effects of SARS-CoV-2 in first trimester pregnancies. STUDY DESIGN, SIZE, DURATION: Cohort study of 1019 women with a double test taken between 17 February and 23 April 2020, as a part of the combined first trimester risk assessment, and 36 women with a first trimester pregnancy loss between 14 April and 21 May 2020, prior to the double test. The study period was during the first SARS-CoV-2 epidemic wave in Denmark. PARTICIPANTS/MATERIALS, SETTING, METHODS: Cohort 1 included pregnant women with a double test taken within the study period. The excess serum from each double test was analyzed for SARS-CoV-2 antibodies. Results were correlated to the nuchal translucency thickness and the number of pregnancy losses before or at the time of the first trimester scan. Cohort 2 included women with a pregnancy loss before the gestational age for double test sample. Serum from a blood test taken the day the pregnancy loss was identified was analyzed for SARS-CoV-2 antibodies. The study was conducted at a public university hospital serving ∼12% of pregnant women and births in Denmark. All participants in the study provided written informed consent. MAIN RESULTS AND THE ROLE OF CHANCE: Eighteen (1.8%) women had SARS-CoV-2 antibodies in the serum from the double test suggestive of SARS-CoV-2 infection in early pregnancy. There was no significant difference in nuchal translucency thickness for women testing positive for previous SARS-CoV-2 infection (n = 16) versus negative (n = 966) (P = 0.62). There was no significantly increased risk of pregnancy loss for women with antibodies (n = 1) (OR 3.4, 0.08-24.3 95% CI, P = 0.27). None of the women had been hospitalized due to SARS-CoV-2 infection. None of the women with pregnancy loss prior to the double test (Cohort 2) had SARS-CoV-2 antibodies. LIMITATIONS, REASONS FOR CAUTION: These results may only apply to similar populations and to patients who do not require hospitalization due to SARS-CoV-2 infection. A limitation of the study is that only 1.8% of the study population had SARS-CoV-2 antibodies suggestive of previous infection. WIDER IMPLICATION OF THE FINDINGS: Maternal SARS-CoV-2 infection had no effect on the nuchal translucency thickness and there was no significantly increased risk of pregnancy loss for women with SARS-CoV-2 infection in first trimester pregnancy. Evidence concerning COVID-19 in pregnancy is still limited. These data indicate that infection with SARS-CoV-2 in not hospitalized women does not pose a significant threat in first trimester pregnancies. Follow-up studies are needed to establish any risk to a fetus exposed to maternal SARS-CoV-2 infection. STUDY FUNDING/COMPETING INTEREST(S): Prof. H.S.N. and colleagues received a grant from the Danish Ministry of Research and Education for research of COVID-19 among pregnant women. The Danish government was not involved in the study design, data collection, analysis, interpretation of data, writing of the report or decision to submit the paper for publication. A.I., J.O.-L., J.B.-R., D.M.S., J.E.-F. and E.R.H. received funding from a Novo Nordisk Foundation (NNF) Young Investigator Grant (NNF15OC0016662) and a Danish National Science Foundation Center Grant (6110-00344B). A.I. received a Novo Scholarship. J.O.-L. is funded by an NNF Pregraduate Fellowship (NNF19OC0058982). D.W. is funded by the NNF (NNF18SA0034956, NNF14CC0001, NNF17OC0027594). A.M.K. is funded by a grant from the Rigshospitalet's research fund. H.S.N. has received speaker's fees from Ferring Pharmaceuticals, Merck Denmark A/S and Ibsa Nordic (outside the submitted work). N.l.C.F. has received a grant from Gedeon Richter (outside the submitted work). A.M.K. has received speaker's fee from Merck (outside the submitted work). The other authors did not report any potential conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

The impact of COVID-19 infection on the cytokine profile of pregnant women: A prospective case-control study.

OBJECTIVE: To compare the levels of various cytokines between pregnant women with confirmed coronavirus disease (COVID-19) infection and pregnant women without any defined risk factor. MATERIALS AND METHODS: Pregnant women with confirmed COVID-19 infection (study group)(n = 90) were prospectively compared to a gestational age-matched control group of pregnant women without any defined risk factors (n = 90). Demographic features, clinical characteristics, laboratory parameters, interferon-gamma (IFN γ), interleukin (IL-2), IL-6, IL-10, and IL-17 levels were compared between the groups. Additionally, a correlation analysis was performed in the study group for the assessment of IFN γ, IL-2, IL-6, IL-10, and IL-17 levels with disease severity and CRP levels. RESULTS: Study group had significantly higher pregnancy complication rate, erythrocyte sedimentation rate, C-reactive protein, procalcitonin, ferritin, D-dimer, lactate dehydrogenase, IFN γ, and IL-6 values (p < 0.05). On the other hand, the control group had significantly higher hemoglobin, leukocyte, platelet, lymphocyte, IL-2, IL-10, and IL-17 values (p < 0.05). Statistically significant differences were found between the groups for IFN γ, IL-2, IL-10, and IL-17 values between the trimesters (p < 0.05). Statistically significant positive correlations were found for IFN γ and IL-6 with disease severity (r = 0.41 and p < 0.001 for IFN γ and r = 0.58 and p < 0.001 for IL-6). On the other hand, a moderate negative correlation for IL-2 and a weak negative correlation for IL-10 were present (r = -0.62 and p < 0.001 for IL-2 and r = -0.19 and p = 0.01 for IL-10). A statistically significant positive moderate correlation was found between IL-6 and CRP (r = 0.40 and p < 0.001) CONCLUSION: COVID-19 infection seems to have an impact on the cytokine profile of pregnant women varying according to pregnancy trimesters and cytokine levels seem to be correlated with disease severity.

Immunity and coagulation and fibrinolytic processes may reduce the risk of severe illness in pregnant women with coronavirus disease 2019.

BACKGROUND: There are specific physiological features regarding the immunity and coagulation among pregnant women, which may play important roles in the development of coronavirus disease 2019. OBJECTIVE: This study aimed to determine the key factors associated with the deterioration of patients with coronavirus disease 2019 and the differentiating clinical characteristics of pregnant women with coronavirus disease 2019 to interfere with the progression of coronavirus disease 2019. STUDY DESIGN: A retrospective study of 539 Chinese Han adult patients with coronavirus disease 2019 was conducted, of which 36 cases were pregnant women. In addition, 36 pregnant women without coronavirus disease 2019 were recruited as the control. The characteristics of severe and critical illnesses, which were differentiated from mild and moderate illnesses in patients with coronavirus disease 2019, were analyzed using a machine learning algorithm. In addition, major differences between pregnant women with coronavirus disease 2019 and age-matched nonpregnant women with severe or critical coronavirus disease 2019, paired with pregnant women without coronavirus disease 2019, were explored to identify specific physiological features of pregnant women with coronavirus disease 2019. RESULTS: For the total patient population, the lymphocyte, CD3+, CD4+, CD8+, CD19+, and CD16+CD56+ cell counts were significantly lower, and white blood cell count, neutrophil count, and neutrophil-to-lymphocyte ratio were higher in those with severe or critical illness than those with mild or moderate illness (P<.001). The plasma levels of interleukin-6, interleukin-10, and interleukin-6-to-interleukin-10 ratio were significantly increased in patients with critical illness compared with patients with mild, moderate, and severe illnesses (P<.001). The above immunologic coclusters achieved an area under the receiver operating characteristic curve of 0.801 (95% confidence interval, 0.764-0.838), and its combined model with the coagulation and fibrinolysis indices (prothrombin time, D-dimer) achieved an area under the receiver operating characteristic curve of 0.815 (95% confidence interval, 0.779-0.851) using the random forest regression model to predict severe or critical illness. For pregnant women with coronavirus disease 2019, none had preexisting diseases. Compared with nonpregnant women with mild or moderate coronavirus disease 2019, pregnant women with coronavirus disease 2019 displayed increased white blood cell count, neutrophil count, neutrophil-to-lymphocyte ratio, and levels of D-dimer and fibrinogen, along with decreased lymphocyte and interleukin-4 levels (P<.05). Although they presented similar changes of immunologic markers of lymphocyte; white blood cell count; neutrophil-to-lymphocyte ratio; CD3+, CD4+, CD8+, and CD16+CD56+ cell counts; and interleukin-6-to-interleukin-10 ratio, compared with nonpregnant women with severe or critical coronavirus disease 2019, none of the pregnant women with coronavirus disease 2019 deteriorated into severe or critical illness. There was no significant difference in white blood cell count, lymphocyte count, neutrophil count, neutrophil-to-lymphocyte ratio, immunologic markers, or coagulation and fibrinolysis markers between pregnant women with coronavirus disease 2019 and pregnant women without coronavirus disease 2019. As for the discrepancy of pathophysiological features between pregnant women with coronavirus disease 2019 and nonpregnant women with severe or critical coronavirus disease 2019, the immunologic markers achieved an area under the receiver operating characteristic curve of 0.875 (95% confidence interval, 0.773-0.977), and its combined model with coagulation and fibrinolysis indices achieved an area under the receiver operating characteristic curve of 0.931 (95% confidence interval, 0.850-1.000). CONCLUSION: Immune dysregulation was identified as a crucial feature of patients with coronavirus disease 2019, which developed severe or critical illness, and pregnant women with coronavirus disease 2019 presented with similar immune responses but rarer incidences of severe or critical illness. Immune dysregulation is related to the risks of deterioration into severe or critical illness. The specific coagulation and fibrinolysis systems of pregnancy may reduce the risk of pregnant women with coronavirus disease 2019 without preexisting disease from developing severe illness.

COVID-19 vaccination in pregnant and lactating diabetic women.

AIM: To discuss available information on the opportunity for pregnant women affected by diabetes/obesity to receive COVID-19 vaccine. DATA SYNTHESIS: Pregnant women with SARS-CoV-2 (COVID-19) infection are at high risk for severe acute respiratory syndrome and adverse outcomes. Pregnant women with severe COVID-19 present increased rates of preterm delivery (<37 gestational weeks), cesarean delivery and neonatal admissions to the intensive care unit. Comorbidity such as diabetes (pregestational or gestational) or obesity further increased maternal and fetal complications. It is known that diabetic or obese patients with COVID-19 present an unfavorable course and a worse prognosis, with a direct association between worse outcome and suboptimal glycol-metabolic control or body mass index (BMI) levels. Critical COVID-19 infection prevention is important for both mother and fetus. Vaccination during pregnancy is a common practice. Vaccines against COVID-19 are distributed across the world with some population considered to have a priority. Since pregnant women are excluded from clinical trials very little information are available on safety and efficacy of COVD-19 vaccines during pregnancy. However, it is well known the concept of passive immunization of the newborn obtained with transplacental passage of protective antibodies into the fetal/neonatal circulation after maternal infection or vaccination. Moreover, it has been reported that COVID-19 vaccine-induced IgG pass to the neonates through breastmilk. Therefore, maternal vaccination can protect mother, fetus and baby. CONCLUSIONS: After an individual risk/benefit evaluation pregnant and lactating women should be counselled to receive COVID-19 vaccines.

Circulating angiogenic factors and HIV among pregnant women in Zambia: a nested case-control study.

BACKGROUND: Maternal HIV increases the risk of adverse birth outcomes including preterm birth, fetal growth restriction, and stillbirth, but the biological mechanism(s) underlying this increased risk are not well understood. We hypothesized that maternal HIV may lead to adverse birth outcomes through an imbalance in angiogenic factors involved in the vascular endothelial growth factor (VEGF) signaling pathway. METHODS: In a case-control study nested within an ongoing cohort in Zambia, our primary outcomes were serum concentrations of VEGF-A, soluble endoglin (sEng), placental growth factor (PlGF), and soluble fms-like tyrosine kinase-1 (sFLT-1). These were measured in 57 women with HIV (cases) and 57 women without HIV (controls) before 16 gestational weeks. We used the Wilcoxon rank-sum and linear regression controlling for maternal body mass index (BMI) and parity to assess the difference in biomarker concentrations between cases and controls. We also used logistic regression to test for associations between biomarker concentration and adverse pregnancy outcomes (preeclampsia, preterm birth, small for gestational age, stillbirth, and a composite of preterm birth or stillbirth). RESULTS: Compared to controls, women with HIV had significantly lower median concentrations of PlGF (7.6 vs 10.2 pg/mL, p = 0.02) and sFLT-1 (1647.9 vs 2055.6 pg/mL, p = 0.04), but these findings were not confirmed in adjusted analysis. PlGF concentration was lower among women who delivered preterm compared to those who delivered at term (6.7 vs 9.6 pg/mL, p = 0.03) and among those who experienced the composite adverse birth outcome (6.2 vs 9.8 pg/mL, p = 0.02). Median sFLT-1 concentration was lower among participants with the composite outcome (1621.0 vs 1945.9 pg/mL, p = 0.04), but the association was not significant in adjusted analysis. sEng was not associated with either adverse birth outcomes or HIV. VEGF-A was undetectable by Luminex in all specimens. CONCLUSIONS: We present preliminary findings that HIV is associated with a shift in the VEGF signaling pathway in early pregnancy, although adjusted analyses were inconclusive. We confirm an association between angiogenic biomarkers and adverse birth outcomes in our population. Larger studies are needed to further elucidate the role of HIV on placental angiogenesis and adverse birth outcomes.

Biomarkers for a histological chorioamnionitis diagnosis in pregnant women with or without group B streptococcus infection: a case-control study.

BACKGROUND: Chorioamnionitis may cause serious perinatal and neonatal adverse outcomes, and group B streptococcus (GBS) is one of the most common bacteria isolated from human chorioamnionitis. The present study analyzed the impact of GBS infection and histological chorioamnionitis (HCA) on pregnancy outcomes and the diagnostic value of various biomarkers. METHODS: Pregnant women were grouped according to GBS infection and HCA detection. Perinatal and neonatal adverse outcomes were recorded with a follow-up period of 6 weeks. The white blood cell count (WBC), neutrophil ratio, and C-reactive protein (CRP) level from peripheral blood and soluble intercellular adhesion molecule-1 (sICAM-1), interleukin 8 (IL-8), and tumor necrosis factor α (TNF-α) levels from cord blood were assessed. RESULTS: A total of 371 pregnant women were included. Pregnant women with GBS infection or HCA had a higher risk of pathological jaundice and premature rupture of membranes and higher levels of sICAM-1, IL-8, and TNF-α in umbilical cord blood. Univariate and multivariate regression analysis revealed that sICMA-1, IL-8, TNF-α, WBC, and CRP were significantly related to an increased HCA risk. For all included pregnant women, TNF-α had the largest receiver operating characteristic (ROC) area (area: 0.841; 95% CI: 0.778-0.904) of the biomarkers analyzed. TNF-α still had the largest area under the ROC curve (area: 0.898; 95% CI: 0.814-0.982) for non-GBS-infected pregnant women, who also exhibited a higher neutrophil ratio (area: 0.815; 95% CI: 0.645-0.985) and WBC (area: 0.849; 95% CI: 0.72-0.978), but all biomarkers had lower value in the diagnosis of HCA in GBS-infected pregnant women. CONCLUSION: GBS infection and HCA correlated with several perinatal and neonatal adverse outcomes. TNF-α in cord blood and WBCs in peripheral blood had diagnostic value for HCA in non-GBS-infected pregnant women but not GBS-infected pregnant women.

Comparison of hematological parameters and perinatal outcomes between COVID-19 pregnancies and healthy pregnancy cohort.

OBJECTIVES: To evaluate the relationship between Coronavirus Disease 2019 (COVID-19) in pregnancy and adverse perinatal outcomes. The secondary aim is to analyze the diagnostic value of hematologic parameters in COVID-19 complicated pregnancies. METHODS: The current study is conducted in a high volume tertiary obstetrics center burdened by COVID-19 pandemics, in Turkey. In this cohort study, perinatal outcomes and complete blood count indices performed at the time of admission of 39 pregnancies (Study group) complicated by COVID-19 were compared with 69 uncomplicated pregnancies (Control group). RESULTS: There was no significant difference between the obstetric and neonatal outcomes of pregnancies with COVID-19 compared to data of healthy pregnancies, except the increased C-section rate (p=0.026). Monocyte count, red cell distribution width (RDW), neutrophil/lymphocyte ratio (NLR), and monocyte/lymphocyte ratio (MLR) were significantly increased (p<0.0001, p=0.009, p=0.043, p<0.0001, respectively) whereas the MPV and plateletcrit were significantly decreased (p=0.001, p=0.008) in pregnants with COVID-19. ROC analysis revealed that the optimal cut-off value for MLR was 0.354 which indicated 96.7% specificity and 59.5% sensitivity in diagnosis of pregnant women with COVID-19. A strong positive correlation was found between the MLR and the presence of cough symptom (r=41.4, p=<0.0001). CONCLUSIONS: The study revealed that, pregnancies complicated by COVID-19 is not related with adverse perinatal outcomes. MLR may serve as a supportive diagnostic parameter together with the Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) in assessment of COVID-19 in pregnant cohort.

A considerable asymptomatic proportion and thromboembolism risk of pregnant women with COVID-19 infection in Wuhan, China.

OBJECTIVES: The coronavirus disease 2019 (COVID-19) had become a worldwide pandemic, however, information is limited on the asymptomatic proportion and thromboembolism risk of pregnant women with infection. METHODS: All 32 pregnant women with COVID-19 who were admitted to the hospital in Wuhan during the outbreak from January 20 to March 18, 2020, were retrospectively reviewed for the clinical records, laboratory tests, chest CT scans, and neonatal outcomes. RESULTS: There were 17 of the 32 patients (53%) with no subjective symptoms before admission, and 13 (41%) remained asymptomatic throughout hospitalization. There were 28 patients (88%) showing typical radiographic evidence of pneumonia on chest CT. The patients with COVID-19 were found in an increased risk of thromboembolism with much higher D-dimer levels than uninfected pregnant women. One neonate with asphyxia and positive immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies was reported. CONCLUSIONS: The considerable asymptomatic proportion of pregnant women with COVID-19 indicates symptom-based screening would miss a number of cases. Chest CT could provide a useful screening resource during the COVID-19epidemic outbreak. Anticoagulation therapy for the postpartum patients may be helpful for good prognosis. The findings provide important information for the hospital isolation, control strategies and clinical therapy.

COVID-19 pandemic effect on early pregnancy: are miscarriage rates altered, in asymptomatic women?

PURPOSE: To evaluate the effect of the COVID-19 pandemic state on early, first-trimester pregnancies. METHODS: A retrospective cohort study conducted at a university-affiliated fertility center in Montreal, Quebec, since the COVID-19 shut down, March 13 until May 6, 2020. Included: all women who came for a first-trimester viability scan during the study period (Study group) and between March 1, 2019 and May 17, 2019, approximately one year prior (Control). The study population denied symptoms of COVID-19. We reviewed all first trimester scans. Early first-trimester pregnancy outcomes (Viable pregnancy, arrested pregnancy including biochemical pregnancy loss and miscarriage, and ectopic pregnancy) were measured as total number and percentage. A multivariate analysis was performed to control for other potentially significant variables, as was a power analysis supporting sample size. RESULTS: 113 women came for a first-trimester viability scan in the study period, and 172 in the control period (5-11 weeks gestational age), mean maternal age 36.5 ± 4.5 and 37.2 ± 5.4 years (p = 0.28). Viable clinical pregnancy rate was not different between the two groups (76.1 vs. 80.2% in the pandemic and pre-pandemic groups p = 0.41). No significant difference was seen in the total number of arrested pregnancies (defined as the sum of biochemical, 1st trimester miscarriages, and blighted ova) (22.1 vs. 16.9% p = 0.32), or in each type of miscarriage. CONCLUSION: The COVID-19 pandemic environment does not seem to affect early first-trimester miscarriage rates in asymptomatic patients.

Serum levels of vasoactive factors in HIV-infected pre-eclamptic women on HAART.

In South Africa, pre-eclampsia (PE) and human immunodeficiency virus (HIV) infection are major causes of pregnancy-related deaths. This study aimed to measure serum levels of endothelin-1 (ET-1), endothelial nitric oxide synthase (eNOS), soluble fms-like tyrosine kinase 1 (sFlt-1), soluble endoglin (sEng) and placental growth factor (PlGF) in HIV-infected highly active antiretroviral therapy (HAART)-treated and HIV-uninfected PE and normotensive women to ascertain if HIV/HAART alters their concentrations. Mean sFlt-1 levels were significantly up-regulated in the PE (HIV-uninfected 4.39 ± 1.29; HIV-infected 5.10 ± 1.10 ng/ml) compared to normotensive women (HIV-uninfected 2.59 ± 0.83; HIV-infected 2.20 ± 0.85 ng/ml). Mean PlGF levels were significantly lower in HIV-uninfected PE vs. HIV-infected normotensive women (29.69 ± 4.47 pg/ml vs. 32.86 ± 6.46 pg/ml; p = .002). In conclusion, PE women with HIV exhibited significantly low serum PlGF, ET-1 and eNOS levels. Infection with HIV may have further increased the sFlt-1 levels.IMPACT STATEMENTWhat is already known on this subject? In PE, the numerous identified local and circulating bioactive factors differed in concentrations when compared to normal pregnancy.What do the results of this study add? PE women with HIV exhibited significantly low serum PlGF, ET-1 and eNOS levels as well as increased levels of sFlt-1.What are the implications of these findings for clinical practice and/or further research? Understanding the link between PE, HIV and HAART during pregnancy will improve prognosis, management and treatment strategies for women clinically.