Adverse outcomes and maternal complications in pregnant women with severe-critical COVID-19: a tertiary center experience.

OBJECTIVES: This study aimed to present perinatal outcomes, clinical challenges, and basic ICU management in pregnant women with severe-critical COVID-19 at our tertiary referral center. METHODS: In this prospective cohort study, patients were divided into two groups, whether they survived or not. Clinical characteristics, obstetric and neonatal outcomes, initial laboratory test results and radiologic imaging findings, arterial blood gas parameters at ICU admission, and ICU complications and interventions were compared between groups. RESULTS: 157 of the patients survived, and 34 of the patients died. Asthma was the leading health problem among the non-survivors. Fifty-eight patients were intubated, and 24 of them were weaned off and discharged healthfully. Of the 10 patients who underwent ECMO, only 1 survived (p<0.001). Preterm labor was the most common pregnancy complication. Maternal deterioration was the most common indication for a cesarean section. Higher neutrophil-to-lymphocyte-ratio (NLR) values, the need for prone positioning, and the occurrence of an ICU complication were important parameters that influenced maternal mortality (p<0.05). CONCLUSIONS: Overweight pregnant women and pregnant women with comorbidities, especially asthma, may have a higher risk of mortality related to COVID-19. A worsening maternal health condition can lead to increased rates of cesarean delivery and iatrogenic prematurity.

The influence of COVID-19 pandemic on intrauterine fetal demise and possible vertical transmission of SARS-CoV-2.

OBJECTIVE: The impact of COVID-19 on intrauterine fetal demise (IUFD) and vertical transmission of the SARS-CoV-2 from the mother to the fetus are crucial issues of the COVID-19 pandemic. In the current study, we aimed to detect the pandemic's influence on the IUFD and evaluate the vertical transmission of the SARS-CoV-2 through analysis of placental tissues collected from PCR positive women with IUFD above 20 weeks of gestation. MATERIALS AND METHODS: The pregnant women above 20 weeks of gestation and had a fetus intrauterine demised during pandemic were included in the study. The pregnant women screened for COVID-19. Vertical transmission searched from placental tissues of COVID-19 positive women by RT-PCR tests for the presence of SARS-CoV-2 RNA. The number of IUFD before the pandemic and during the pandemic compared to assess the influence of the COVID-19 pandemic on the IUFD ratio. RESULTS: Among 138 pregnant women with IUFD, 100 of them could screen for COVID-19 status. RT-PCR test results of 6 of the screened pregnant women were positive for SARS-CoV-2. Placental tissues of these six women were analyzed, and one test result was positive for SARS-CoV-2 RNA. The IUFD ratio was significantly increased during the pandemic. CONCLUSION: It is clear that COVID-19 increases the IUFD ratio. Previous data for vertical transmission of SARS-CoV-2 during the second trimester is limited. We present the third case of literature that has positive placental results for SARS-CoV-2 RNA in the second trimester of pregnancy.

Comparison of maternal serum NRG-4 levels in healthy and preeclamptic pregnancies

Objective: The new adipokine, neuregulin-4 (NRG-4), acts as a signaling protein and plays a role in lipogenesis, inflammatory events and atherosclerosis. The aim was to investigate maternal levels of NRG-4 in preeclampsia (PE) disease. Material and Methods: Pregnant women with PE, divided into severe and mild PE, and gestational age-matched healthy pregnant women, as a control group, were recruited. NRG-4 levels were measured using an ELISA. NRG-4 levels in the groups and the relation between NRG-4 and clinical and laboratory parameters were analyzed. Results: There were 41 women in the PE group, 11 (26.8%) in the severe and 30 (73.2%) in the mild subgroups and 41 controls. There were no significant differences between the groups in terms of maternal age, gravidity, parity, abortion, gestational week at the time of blood sampling, levels of hemoglobin, platelet count, alanine and aspartate transaminases (p=0.067, p=0.819, p=0.957, p=0.503, p=0.054, p=0.217, p=0.306, and p=0.270 respectively). The PE group had higher body mass index, nitrogen urea and creatinine values, and diastolic and systolic blood pressure (p=0.005, p<0.001, p<0.001, p<0.001, and p<0.001 respectively). In addition, earlier gestational week at delivery, lower birth weight and Apgar scores at 1 and 5 minutes and the occurrence of non-reassuring fetal heart rate tracing were found in the PE group (p=0.010, p=0.004, p=0.005, p=0.005, and p=0.026 respectively). There were no significant differences between the groups in terms of NRG-4 (p=0.611). No correlation was identified between clinical parameters examined and NRG-4 levels (p=0.722). Conclusion: No association was found between NRG-4 concentrations and PE patients, regardless of severity of PE, compared to healthy pregnancies. Future longitudinal studies are needed to confirm this lack of association in PE.

Cardiotocographic features in COVID-19 infected pregnant women.

OBJECTIVES: We aimed to evaluate the cardiotocograph (CTG) traces of 224 women infected with novel coronavirus 2019 (COVID-19) and analyze whether changes in the CTG traces are related to the severity of COVID-19. METHODS: We designed a prospective cohort study. Two-hundred and twenty-four women who had a single pregnancy of 32 weeks or more, and tested positive for SARS-CoV-2 were included. Clinical diagnosis and classifications were made according to the Chinese management guideline for COVID-19 (version 6.0). Patients were classified into categories as mild, moderate, severe and the CTG traces were observed comparing the hospital admission with the third day of positivity. RESULTS: There was no statistically significant relationship between COVID-19 severity and CTG category, variability, tachycardia, bradycardia, acceleration, deceleration, and uterine contractility, Apgar 1st and 5th min. CONCLUSIONS: Maternal COVID-19 infection can cause changes that can be observed in CTG. Regardless of the severity of the disease, COVID-19 infection is associated with changes in CTG. The increase in the baseline is the most obvious change.

Fetal epicardial fat thickness in fetal growth restriction; effects on fetal heart function and relationship with the severity of disease.

OBJECTIVE: To investigate fetal epicardial fat thickness (EFT) value in fetal growth restriction (FGR) and its relationship with clinical parameters, fetal modified myocardial index (Mod-MPI), and the Doppler parameters. MATERIAL METHODS: Eighty-five pregnant women, with 30 diagnosed with FGR and 55 healthy pregnant women as control group participated in this prospective case-control study. FGR group was divided into 2 subgroups as early (n = 9) and late FGR (n = 21) groups. Demographic data were taken from the medical records. Amnion fluid value, fetal biometric measurements, and Doppler parameters were obtained. Fetal EFT and fetal Mod-MPI were measured by using the echocardiographic methods. The correlation tests were performed to assess the association between EFT and clinical and ultrasonographic parameters. p < .05 was interpreted as statistically significant. RESULTS: EFT value was found statistically lower in the early and late FGR groups than the control group (p = .003). Higher umbilical artery pulsatility index (PI) and lower cerebroplacental ratio (CPR) values were found in the early and late FGR (p < .001, p = .001). The optimal EFT cutoff level to predict FGR disease was measured as 1.25 with 63.3% specificity and 77.4% sensitivity. Lower ejection time (ET) and higher Mod-MPI and isovolumetric contraction time (ICT) values were found in the group FGR with absent UAEDF than in the group FGR with no absent UAEDF (p = .001, p < .000, p < .000, respectively). Correlation tests showed statistically negative and weak correlations among EFT, umbilical artery PI, and mean Ut A-PI (p = .019, p = .019). Positive correlations were found in regard to gestational age, EFW, and EFT (p = .002, p < .000). CONCLUSION: Our study showed that the measurement of EFT may contribute to predicting the diagnosis of FGR. Moreover, lower EFT values can be related to the severity of FGR. Future randomized control studies are needed to understand the effects and pathways of fetal EFT on fetal cardiac function.

Impact of vitamin D on the course of COVID-19 during pregnancy: A case control study.

OBJECTIVE: We aimed to evaluate the vitamin D status of pregnant women with COVID-19, and the association between vitamin D level and severity of COVID-19. METHODS: In this case control study, 159 women with a single pregnancy and tested positive for SARS-CoV-2, and randomly selected 332 healthy pregnant women with similar gestational ages were included. COVID-19 patients were classified as mild, moderate, and severe. Vitamin D deficiency was defined as 25-hydroxycholecalciferol <20 ng/mL (50 nmol/L), and 25-OH D vitamin <10 ng/mL was defined as severe vitamin D deficiency, also 25-OH D vitamin level between 20-29 ng/mL (525-725 nmol/L) was defined as vitamin D insufficiency. RESULTS: Vitamin D levels of the pregnant women in the COVID-19 group (12.46) were lower than the control group (18.76). 25-OH D vitamin levels of those in the mild COVID-19 category (13.69) were significantly higher than those in the moderate/severe category (9.06). In terms of taking vitamin D supplementation, there was no statistically significant difference between the groups. However, it was observed that all of those who had severe COVID-19 were the patients who did not take vitamin D supplementation. CONCLUSION: The vitamin D levels are low in pregnant women with COVID-19. Also, there is a significant difference regarding to vitamin D level and COVID-19 severity in pregnant women. Maintenance of adequate vitamin D level can be useful as an approach for the prevention of an aggressive course of the inflammation induced by this novel coronavirus in pregnant women.

Vertical transmission of SARS-CoV-2: A prospective cross-sectional study from a tertiary center.

The aim was to investigate the association of the delivery mode and vertical transmission of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) through the samples of vaginal secretions, placenta, cord blood, or amniotic fluid as well as the neonatal outcomes. This cross-sectional study presents an analysis of prospectively gathered data collected at a single tertiary hospital. Sixty-three pregnant women with confirmed coronavirus disease 2019 (COVID-19) participated in the study. Vertical transmission of SARS-CoV-2 was analyzed with reverse transcriptase-polymerase chain reaction (RT-PCR) tests and blood tests for immunoglobulin G (IgG)-immunoglobulin M (IgM) antibodies. All patients were in the mild or moderate category for COVID-19. Only one placental sample and two of the vaginal secretion samples were positive for SARS-CoV-2. Except for one, all positive samples were obtained from patients who gave birth by cesarean. All cord blood and amniotic fluid samples were negative for SARS-CoV-2. Two newborns were screened positive for COVID-19 IgG-IgM within 24 h after delivery, but the RT-PCR tests were negative. A positive RT-PCR result was detected in a neof a mother whose placenta, cord blood, amniotic fluid, and vaginal secretions samples were negative. He died due to pulmonary hemorrhage on the 11th day of life. In conclusion, we demonstrated that SARS-CoV-2 can be detectable in the placenta or vaginal secretions of pregnant women. Detection of the virus in the placenta or vaginal secretions may not be associated with neonatal infection. Vaginal delivery may not increase the incidence of neonatal infection, and cesarean may not prevent vertical transmission. The decision regarding the mode of delivery should be based on obstetric indications and COVID-19 severity.

Is GDF-15 level associated with gestational diabetes mellitus and adverse perinatal outcomes?

OBJECTIVE: Growth differentiation factor-15 (GDF-15), the new member of transforming growth factor (TGF)-beta family, is released as a response of oxidative stress, inflammation and tissue injury. We aimed to determine GDF-15 levels in patients with Gestational Diabetes Mellitus (GDM) and the relation between GDF-15 and adverse perinatal outcomes. MATERIALS AND METHODS: Forty pregnant women with GDM (receiving diet and insulin therapy) and forty healthy pregnant women as control group participated in this current study. GDF- 15 levels were analyzed by enzyme-linked immunosorbent assess kit. RESULTS: The median serum GDF-15 level was measured higher in patients with GDM, and it was statistically meaningful (p: 0.000). Logistic regression analysis indicated that with the increase of GDF-15 level, the risk of GDM diseases increases as well. (P: 0.001, OR = 1.009; 95% CI = 1.003-1.014). There were no differences between GDF-15 levels and perinatal outcomes. CONCLUSION: We concluded that higher GDF-15 levels are related to GDM in the third trimester. The optimal GDF-15 cut-off value was measured as 326 pg/ml for the diagnosis of GDM with 70% sensitivity and 60% specificity in our study. Further studies are needed to show the significance of GDF-15 as a biomarker for the disease.

Turkish reference ranges for the left fetal modified myocardial performance index.

BACKGROUND: This study aimed to assess fetal cardiac left ventricular function in healthy pregnant women by calculating the modified myocardial performance index (Mod-MPI) and to construct reference ranges for the Turkish population. METHODS: One-hundred-two randomly selected healthy singleton pregnant women ranging between 25 and 39 gestational weeks were included in the study. Left fetal Mod-MPI was measured for each pregnant woman. Women with chronic systemic diseases or fetuses with chromosomal or structural abnormalities were excluded from the study. Mitral valve (MV) and aortic valve (AoV) clicks were used as landmarks to define the following time periods that were used to calculate the Mod-MPI: isovolumetric contraction time (ICT), isovolumetric relaxation time (IRT), and ejection time (ET). RESULTS: The mean Mod-MPI was 0.42±0.10. The mean IRT, ICT, and ET were 43.5±10.2, 27.27±8.1, and 170.5±16.9, respectively. A significant correlation was found between Mod-MPI and gestational age, umbilical artery systolic/diastolic (UA S/D) ratio and the middle cerebral artery pulsatility index (MCA PI) values (r=0.199, p=0.047, r=-0.328, p=0.001, and r=-0.0349, p=0.001, respectively) Conclusions. The current study`s results will be a reference for future studies, especially studies investigating pathological conditions that impact fetal cardiac function.

Does having a high-risk pregnancy influence anxiety level during the COVID-19 pandemic?

OBJECTIVE: We aimed to analyze the changing level of anxiety during COVID-19 pandemic in pregnant women, with and without high-risk indicators separately, in a tertiary care center serving also for COVID-19 patients, in the capital of Turkey. STUDY DESIGN: We designed a case-control and cross-sectional study using surveys. The Spielberger State-Trait Anxiety Scale questionnaire (STAI-T) and Beck Anxiety Inventory (BAI) which were validated in Turkish were given to outpatient women with high-risk pregnancies as study group and normal pregnancies as control group. A total of 446 women were recruited. RESULTS: There was a statistically significant difference between those with and without high-risk pregnancy in terms of Trait-State Anxiety scores with COVID-19 pandemic (p < 0.05). We found an increased prevalence of anxiety during COVID-19 pandemic in high-risk pregnant women comparing to pregnancies with no risk factors (p < 0.05). There was a statistically significant difference between the education level in high-risk pregnant women in terms of anxiety scores (p < 0.05), Beck Anxiety score was highest in high school graduates (42.75). While the level of Trait Anxiety was the highest with pandemic in those with high-risk pregnancy with threatened preterm labor and preterm ruptures of membranes (58.0), those with thrombophilia were the lowest (50.88). The State Anxiety level and Beck Anxiety Score of those with maternal systemic disease were the highest (53.32 and 45.53), while those with thrombophilia were the lowest (46.96 and 40.08). The scores of Trait Anxiety (56.38), State Anxiety (52.14), Beck Anxiety (43.94) were statistically higher during the pandemic in those hospitalized at least once (p < 0.05). CONCLUSION: High-risk pregnant women require routine anxiety and depression screening and psychosocial support during the COVID-19 pandemic. High-risk pregnancy patients have comorbid conditions most of the time, hence they not only at more risk for getting infected, but also have higher anxiety scores because of the stress caused by COVID-19 pandemic.

Vitamin D deficiency in adolescent pregnancy and obstetric outcomes.

OBJECTIVE: The aim of this study was to evaluate the rates of vitamin D deficiency in adolescent pregnants and its influence on the obstetric outcomes. MATERIALS AND METHODS: A total of 300 singleton pregnant women aged between 14 and 20 years, were divided into three groups according to their gestational weeks (100 pregnant adolescents from each trimester). Randomly selected 300 singleton pregnant women older than 20 years of age with the similar gestational ages were designed as the control group at the same time period. We divided serum 25(OH)D levels into three categories deficiency, inadequacy and adequate levels according to the Endocrine Society guidelines. Serum 25(OH)D levels were also evaluated according to age, seasons and gestational periods. Adverse obstetric outcomes were recorded. RESULTS: Overall, 86% of the subjects were found to have deficient 25(OH)D levels (<20 ng/ml). The levels indicated an inadequate state in 72 subjects (12%) and only 12 (2%) women had adequate 25 (OH) D levels. Among adult pregnant women the rates of deficient, inadequate and adequate levels were 88.3%, 11%, and 0.7% respectively. Among adolescent pregnant women these rates were 83.7%, 13%, and 3.3% respectively. The lowest 25(OH)D levels occurred during the winter while the highest levels were detected during the summer in both groups. Calcidiol, 25(OH)D, was a significant predictor for preterm delivery (AUC = 0,909; p < 0,001) and also for SGA (AUC = 0,915; p < 0,001). Maternal age was another significant predictor for SGA (AUC = 0,787; p < 0,001) and preterm delivery (AUC = 0,785; p < 0,001). CONCLUSION: We found a high incidence of 25(OH)D deficiency in Turkish pregnant women. Adolescent age and low 25(OH)D levels are significant risk factors for PTD and SGA. Effective prophylaxis programs for vitamin D deficieny and/or fortification of foods with vitamin D are essential in pregnant women especially in the winter season.

Utility of the modified myocardial performance index in growth-restricted fetuses.

OBJECTIVES: The modified myocardial performance index (Mod-MPI) can be used to assess myocardial function. Fetal growth restriction can affect fetal myocardial function, thereby altering the Mod-MPI. The results of previous studies on the utility of the Mod-MPI in growth-restricted fetuses are conflicting. The aim of this study was to calculate the left modified-MPI in growth-restricted fetuses and to compare the results with those of healthy fetuses. METHODS: This was a prospective cross-sectional case-control study. In total, 40 women with growth-restricted fetuses and 40 women with fetuses of normal weight (controls) at 29-39 gestational weeks were enrolled in the study. An experienced obstetrician calculated the Mod-MPI for each fetus. Women with systemic diseases or fetuses with chromosomal/structural abnormalities were excluded from the study. The results of Mod-MPI measurements of the two groups were compared. RESULTS: The mean single deepest vertical pocket (SDVP) of amniotic fluid, estimated fetal weight (EFW), and isovolumetric relaxation time (IRT) was significantly lower in the fetal growth restriction (FGR) group as compared with these parameters in the control group (P < .05). The uterine artery (UtA) pulsatility index (PI) was significantly higher in the FGR group as compared with that in the control group (P < .05). There were six cases of absent end-diastolic flow (AED) in the FGR group. There were no statistically significant between-group differences in the Mod-MPI, isovolumetric contraction time (ICT), and ejection time (ET) (P > .05). There was also no statistically significant correlation between the Mod-MPI in the fetuses with AED and the control group for Mod-MPI (P > .05). CONCLUSION: The utility of the Mod-MPI in FGR remains unclear. Future studies with larger populations are needed to determine the utility of the Mod-MPI as a predictor of cardiac compromise in FGR.

The Relationship between Z-Protein Level and other Parameters in Pregnant Women with Intrauterine Growth Retardation in Third Trimester.

BACKGROUND: Protein Z is a glycoprotein which acts as an anticoagulant factor. A deficiency of protein Z is associated with thrombotic events and adverse obstetric outcomes. The association between protein Z deficiency and adverse obstetric outcomes has previously been demonstrated in several studies. However, none of them have investigated each complication independently. The aim of this study was to evaluate serum levels of protein Z in pregnancies complicated by intrauterine growth restriction (IUGR). METHODS: Pregnant and nonpregnant healthy women between the ages of 18 and 40 years were included in the study. There were three groups: One: Study group: pregnant women with IUGR fetuses; Two: Control group 1: pregnant women with normal fetuses; Three: Control group 2: nonpregnant, healthy women. Plasma protein levels of protein Z, protein S, and protein C were measured for each group. RESULTS: Women with IUGR had significantly higher mean plasma concentrations of protein Z compared to women with normal pregnancies. This is in contrast to previous studies. CONCLUSIONS: The results of this study indicate that the association between protein Z levels and IUGR is still controversial.

Can Variable Plasma Volume Alterations Affect the Efficiency of the First Trimester Screening Test?

BACKGROUND: The aim of this study was to assess the effect of plasma volume alteration determined by hematocrit on biochemical parameters of the first trimester screening test. METHODS: Enrolled in this study were 1,424 pregnant women in their first trimester who underwent a first trimester screening test. Fetal Nuchal Trancluciency measurement was obtained by ultrasonographic evaluation. Blood samples were taken for complete blood count, serum free ß-HCG, and PAPP-A between 11 and 14 weeks of gestation. The effect of plasma volume alteration on the screening test was evaluated. Mean corpuscular volume was used to rule out possible iron deficiency anemia. RESULTS: There were 59 women with combined risk > 1/270. Of these 59 women, there were 21 false positive results (1.5%). Serum Htc significantly predicted the false positive cases (AUC: 0.839, p < 0.001). The optimal cutoff value was obtained at a value of 30.2% with 85% sensitivity and 75% specificity. CONCLUSIONS: Our study suggests that the degree of plasma alterations may affect the serum levels of the biochemical components of the first trimester screening test for aneuploidy, thereby leading to false positive test results.

The Diagnostic Role of Vitamin D and Cathelicidin Levels in Pelvic Inflammatory Disease.

BACKGROUND: The aim of this study was to evaluate the effect of 25-hydroxyvitamin D [25(OH)D] and cathelicidin levels on pelvic inflammatory disease [PID] in reproductive aged women. METHODS: A total of 81 reproductive aged women, 43 with PID and 38 without PID, were included in the study. Five millilitres of venous blood were collected from subjects and controls for complete hemogram and serum for CRP, IL-6, 25(OH)D and cathelicidin. RESULTS: There were significant differences between the study group and the control group for 25(OH)D (study group, 47.3 ± 2.01 ng/mL, control group, 28.38 ± 1.35 ng/mL, p = 0.001), for cathelicidin (study group, 165.56 ± 65.92 ng/mL, control group, 10.34 ± 6.48 ng/mL, p = 0.001). There was a positive correlation between 25(OH)D, cathelicidin, and other markers (WBC, CRP, and IL-6). Receiver operator curve analysis showed that the best cutoff value for 25(OH)D was 34.25 ng/mL, sensitivity 88%, and specificity 89%, and for cathelicidin 15 ng/mL, sensitivity 91%, specificity 90%. CONCLUSIONS: 25(OH)D and cathelicidin can be used as acute phase reactants like conventional markers in PID. Future studies are needed to understand the roles of these molecules in both diagnosis and follow-up of infectious situations.