Effect of asymptomatic COVID-19 infection on the placenta in the third trimester of pregnancy: A prospective case-control study.

To clarify the effect of asymptomatic coronaviruse disease-2019 (COVID-19) positivity on the placenta in the third trimester of pregnancy. Materials and Methods: This prospective, case-control study included 30 pregnant women diagnosed with asymptomatic COVID-19 between April 30, 2021 and July 20, 2021 who delivered after the 34th gestational week, and a control group of 30 pregnant women without COVID-19, who delivered between April 2021 and July 2021, matched to the study group regarding age, gestational age and body mass index. Outcomes were compared in terms of demographic characteristics, serum blood outcomes, neonatal results, complications and placental histopathological findings. Results: The mean age of the study population was 28.8 years and the mean gestational week was 38.2 weeks. The C-reactive protein levels (38.2 mg/L vs 5.8 mg/L, p=0.001) and ferritin levels (266.4 µg/L and 40.5 µg/L, p=0.001) were significantly higher in the COVID-19-positive pregnant women. The lymphocyte level was significantly higher in the non-COVID-19 pregnant women (p=0.040). Mural hypertrophy was determined at a significantly higher rate in COVID-positive pregnant women (83.3% vs 30.0%, p=0.001). Multivariate regression analysis showed that only COVID-19 positivity increased the presence of mural hypertrophy in pregnant women with asymptomatic COVID-19 (4.716-fold, 95% confidence interval=1.012-22.251). Conclusion: The results of this study demonstrated that asymptomatic COVID-19 had no significant effect on pregnancy and neonatal complications. However, mural hypertrophy in the placenta was found at a significantly higher rate in pregnant women with asymptomatic COVID-19.

The role of laboratory parameters in predicting severity of COVID-19 disease in pregnant patients.

We aimed to examine the relationship between laboratory markers and the severity of the disease in pregnant women diagnosed with coronavirus disease 2019 (COVID-19). Clinical records were retrospectively reviewed for 112 pregnant women. Patients diagnosed with COVID-19 were divided into two groups as mild/moderate and severe. The relationship between predicting the severity of the disease and laboratory parameters was investigated. Neutrophil lymphocyte ratio, C-reactive protein (CRP), ferritin and aspartate aminotransferase levels were significantly higher in severe COVID-19 cases than mild/moderate cases (p = .048, p = .003, p = .015 and p = .035, respectively). CRP was found to be the most useful marker in terms of diagnostic performance with a cut off value of 10.8 (sensitivity 80%, specificity 56.1%, NPV 88.5% and PPV 40.0%). The best diagnostic performance was obtained using CRP and ferritin combined with cut-offs of 10.8 mg/L for CRP and 26.5 µg/L for ferritin. Combined CRP and ferritin showed sensitivity, specificity, negative predictive value and positive predictive value of 94.7%, 52.8%, 96.6% and 41.9%, respectively, in predicting severe COVID-19. The combination of CRP and ferritin parameters may be useful in estimating the severity of the disease in pregnant patients who were initially diagnosed with COVID-19. Impact StatementWhat is already known about this subject? Coronavirus disease 2019 (COVID-19) can rapidly develop into acute respiratory distress syndrome (ARDS) and result in serious complications in some pregnant patients. Therefore, timely diagnosis of patients is crucial. Most previous reports of COVID-19 laboratory results are based on data from the general population and limited information is available regarding pregnancy status. Although laboratory medicine makes an important contribution to clinical decision making in many infectious diseases, including COVID-19, studies to predict the severity of the disease with laboratory markers are limited and the results are contradictory.What do the results of this study add? Our study shows that C-reactive protein (CRP), neutrophil lymphocyte ratio (NLR), ferritin and aspartate aminotransferase (AST) are associated with severe disease in pregnant women diagnosed with COVID-19. In addition, the use of combined CRP and ferritin appears to have higher sensitivity and negative predictive value than using other tests alone. Furthermore, this study shows that coagulation markers are not useful in predicting disease severity in pregnancy.What are the implications of these findings for clinical practice and/or further research? Predicting the severity of COVID-19 disease in pregnancy can prevent unnecessary hospitalisations and allow the implementation of the necessary clinical approach. Further studies can focus on the clinical usefulness of these parameters in predicting severe COVID-19 in pregnancy.

An internally validated prediction model for critical COVID-19 infection and intensive care unit admission in symptomatic pregnant women.

BACKGROUND: Pregnant women are at an increased risk of mortality and morbidity owing to COVID-19. Many studies have reported on the association of COVID-19 with pregnancy-specific adverse outcomes, but prediction models utilizing large cohorts of pregnant women are still lacking for estimating the risk of maternal morbidity and other adverse events. OBJECTIVE: The main aim of this study was to develop a prediction model to quantify the risk of progression to critical COVID-19 and intensive care unit admission in pregnant women with symptomatic infection. STUDY DESIGN: This was a multicenter retrospective cohort study including 8 hospitals from 4 countries (the United Kingdom, Austria, Greece, and Turkey). The data extraction was from February 2020 until May 2021. Included were consecutive pregnant and early postpartum women (within 10 days of birth); reverse transcriptase polymerase chain reaction confirmed SARS-CoV-2 infection. The primary outcome was progression to critical illness requiring intensive care. The secondary outcomes included maternal death, preeclampsia, and stillbirth. The association between the primary outcome and 12 candidate predictors having a known association with severe COVID-19 in pregnancy was analyzed with log-binomial mixed-effects regression and reported as adjusted risk ratios. All the potential predictors were evaluated in 1 model and only the baseline factors in another. The predictive accuracy was assessed by the area under the receiver operating characteristic curves. RESULTS: Of the 793 pregnant women who were positive for SARS-CoV-2 and were symptomatic, 44 (5.5%) were admitted to intensive care, of whom 10 died (1.3%). The 'mini-COvid Maternal Intensive Therapy' model included the following demographic and clinical variables available at disease onset: maternal age (adjusted risk ratio, 1.45; 95% confidence interval, 1.07-1.95; P=.015); body mass index (adjusted risk ratio, 1.34; 95% confidence interval, 1.06-1.66; P=.010); and diagnosis in the third trimester of pregnancy (adjusted risk ratio, 3.64; 95% confidence interval, 1.78-8.46; P=.001). The optimism-adjusted area under the receiver operating characteristic curve was 0.73. The 'full-COvid Maternal Intensive Therapy' model included body mass index (adjusted risk ratio, 1.39; 95% confidence interval, 1.07-1.95; P=.015), lower respiratory symptoms (adjusted risk ratio, 5.11; 95% confidence interval, 1.81-21.4; P=.007), neutrophil to lymphocyte ratio (adjusted risk ratio, 1.62; 95% confidence interval, 1.36-1.89; P<.001); and serum C-reactive protein (adjusted risk ratio, 1.30; 95% confidence interval, 1.15-1.44; P<.001), with an optimism-adjusted area under the receiver operating characteristic curve of 0.85. Neither model showed signs of a poor fit. Categorization as high-risk by either model was associated with a shorter diagnosis to intensive care unit admission interval (log-rank test P<.001, both), higher maternal death (5.2% vs 0.2%; P<.001), and preeclampsia (5.7% vs 1.0%; P<.001). A spreadsheet calculator is available for risk estimation. CONCLUSION: At presentation with symptomatic COVID-19, pregnant and recently postpartum women can be stratified into high- and low-risk for progression to critical disease, even where resources are limited. This can support the nature and place of care. These models also highlight the independent risk for severe disease associated with obesity and should further emphasize that even in the absence of other comorbidities, vaccination is particularly important for these women. Finally, the model also provides useful information for policy makers when prioritizing national vaccination programs to quickly protect those at the highest risk of critical and fatal COVID-19.

Short-term outcomes of pregnant women with convalescent COVID-19 and factors associated with false-negative polymerase chain reaction test: A prospective cohort study.

AIM: To evaluate the clinical factors associated with false-negative RT-PCR results and to report the outcome of a cohort of pregnant women with COVID-19. METHODS: This cohort study was conducted in a tertiary referral pandemic hospital and included 56 pregnant women. A study including pregnant women with either a laboratory or clinical diagnosis for COVID-19 were included in the study. The primary outcome was clinical factors associated with false-negative RT-PCR results defined as a positive immunoglobulin M assessed by rapid testing in clinically diagnosed patients. Clinical outcomes of laboratory diagnosed patients were also reported. RESULTS: In total, 56 women with either RT-PCR or clinical COVID-19 diagnosis were included in the study. Forty-three women either had RT-PCR positivity or IgM positivity. The clinical outcome of these pregnancies was as follows: mean maternal age 27.7, immunoglobulin M positive patients 76.7%, RT-PCR positive patients 55.8%, maternal comorbidities 11.5%, complications in patients below 20 weeks 34.8%, complications in patients above 20 weeks 65.1%, elevated CRP 83.7%, lymphopenia 30.2%, time from hospital admission to final follow-up days 37 and stillbirth 8.3%. The proportion of women who tested positive for SARS-CoV-2 immunoglobulin M was 100% in the RT-PCR positive group and 56.5% in the clinical diagnosis group (P = .002). The symptom onset to RT-PCR testing interval longer than a week (risk ratio: 2.72, 95% CI: 1.14-5.40, P = .003) and presence of dyspnoea (risk ratio: 0.38, 95% CI: 0.14-0.89, P = .035) were associated with false-negative RT-PCR tests. The area under the curve of these parameters predicting false-negative RT-PCR was 0.73 (95% CI: 0.57-0.89). CONCLUSIONS: Symptomatic women with a negative RT-PCR should not be dismissed as potential COVID-19 patients, especially in the presence of prolonged symptom onset-test interval and in women without dyspnoea.

Evaluation of second-trimester maternal serum betatrophin levels and lipid and carbohydrate metabolism parameters in patients with gestational diabetes mellitus.

OBJECTIVE: We investigated the role of betatrophin in the etiopathogenesis of gestational diabetes mellitus (GDM) and its association with lipid and carbohydrate metabolism in patients with GDM and normoglycemic pregnant women. MATERIALS AND METHODS: A total of 60 patients [30 pregnant women with GDM (study group) and 30 healthy age-, body mass index-, and gestational agematched pregnant women (control group)] were included in this study. Serum betatrophin, fasting glucose, insulin, glycated hemoglobin A1c (HbA1c), and C-peptide levels, as well as lipid parameters, were measured. RESULTS: Serum betatrophin, fasting glucose, HbA1c, insulin, and C-peptide levels were significantly higher in the GDM group than in the control group (p<0.001, p=0.009, p=0.013, p<0.001, and p<0.001, respectively). Levels of triglycerides and very-low-density lipoprotein cholesterol were significantly higher in the GDM group (p=0.020 and p=0.020, respectively), but total cholesterol and LDL cholesterol levels were similar in the two groups (p=0.810 and p=0.273, respectively). Betatrophin levels in the GDM group were correlated positively with insulin levels (r=0.336, p=0.009) and the homeostatic model assessment of insulin resistance (HOMA-IR) score (r=0.269, p=0.038), and negatively with the C-peptide levels (r=-0.399, p=0.002); they were not correlated with any other glucose or lipid parameters. Multivariate stepwise linear regression analysis demonstrated that insulin levels (ß=0.134, p=0.013) and the HOMA-IR score (ß=0.112, p=0.017) were associated independently with serum betatrophin levels. CONCLUSION: These results demonstrate that serum betatrophin levels were significantly higher in pregnant women with GDM than in normoglycemic pregnant women. The levels of betatrophin were correlated significantly with insulin resistance parameters, which is a key feature of GDM pathophysiology.