Evaluation of The Relationship between Cell-Free DNA Fetal Fraction of The Circulatory System and Fetal and Maternal Pregnancy Prognosis: A Prospective Study.

BACKGROUND: Non-invasive prenatal testing (NIPT), sometimes called noninvasive prenatal screening (NIPS), is a non-invasive prenatal genetic test using cell-free DNA in maternal blood. This method is used to diagnose fetal aneuploidy disorders such as Down syndrome (trisomy 21), Edwards syndrome (trisomy 18) and Patau syndrome (trisomy 13), which causes disability disorders or significant postpartum defects. The aim of this study was to investigate the relationship between high and low fetal fraction (FF) and prognosis of maternal pregnancy. MATERIALS AND METHODS: In this prospective study, after obtaining informed consent, 10 ml of blood was collected from 450 mothers with singleton pregnancies with gestational age above 11 weeks (11-16) at the request of NIPT for cell-free DNA BCT test. After obtaining the test results, maternal and embryonic results were evaluated based on the amount of non-cellular DNA FF. Data analysis was performed by using SPSS software version 21 and independent t test, chi-square statistical tests. RESULTS: Based on test results, 20.5% of women were nulli par. The mean FF index in the studied women was 8.3% with a standard deviation of 4.6. The minimum and maximum values were 0 and 27, respectively. The frequency of normal, low and high FFs was 73.2, 17.3 and 9.5%, respectively. CONCLUSION: High FF has fewer risks to the mother and fetus than low FF. The use of FF level (high or low) can help us determining the prognosis of pregnancy and using it to better manage the pregnancy.

Anxiety and Uterine Artery Doppler Flow in A Population of Pregnant Women of High Risk Down Syndrome Fetus: A Prospective Cohort Study.

BACKGROUND: Fetal exposure to maternal anxiety is associated with low birth weight and maternal stress may be led to constriction of uterine arteries. This study compared the relation of anxiety and uterine artery doppler flow indices in pregnant women with the high and low-risk of Down syndrome. MATERIALS AND METHODS: This prospective cohort study was conducted among pregnant women in the second trimester that were classified as having a high or low risk according to their prenatal aneuploidy screening outcome. The high risk group underwent amniocentesis. Anxiety was initially assessed using the Spielberger State-Anxiety Inventory (STAI) and uterine artery blood flow indices were evaluated 2 times for the both groups. For the high-risk group first: immediately before amniocentesis and second: after two weeks follow up, when receiving the karyotype results and for the low-risk group in the first admission and two weeks later. RESULTS: Totally, 375 pregnant women participated in our study that sorted into 2 risk populations based on the aneuploidy screening test, low-risk=176 and high-risk women=199. The high-risk group for Down syndrome amniocentesis showed abnormal results in the 23 cases (23/199). The mean state (P=0.003) and trait (P=0.033) of the Anxiety Inventory scores were significantly different between the groups. Baseline uterine artery indices were no significant difference between the groups. Baseline Uterine artery indices in the high-risk group was significantly different with follow-up (in both positive-amniocentesis and negative amniocentesis sub-groups) indices. Also, there was a weak and significant correlation in the uterine resistance index and STAI scores (P=0.008, r=0.137) during the follow-up period. CONCLUSION: All pregnant women experienced high level anxiety, especially in the high-risk group that may reduce after confirmation of prenatal aneuploidy screening test and also affects the Doppler indices. For all pregnant women; Stress management and emotional support training is recommended before and during pregnancy.

The association between fetal renal artery indices in late pregnancy and birth weight in gestational diabetes mellitus: A cohort study.

Background: Estimation of the fetal birth weight and diagnosis of small for gestational age in the fetuses of women with gestational diabetes mellitus (GDM) are currently imprecise. Objective: We aimed to evaluate the association between fetal renal artery Doppler indices and neonatal birth weight in women with GDM in late pregnancy. Materials and Methods: This cohort study recruited 246 pregnant women from Shariati Hospital in Tehran, Iran, in two GDM and healthy control groups. Participants underwent weekly Doppler ultrasounds in the late pregnancy period (37-40 wk) to determine the Doppler indices of the umbilical artery, middle cerebral, and renal arteries. Fetal growth indices including biparietal diameter, abdominal circumference, head circumference, and femur length were also recorded and compared between the two groups. Results: Fetal growth indices and estimated fetal weight were not significantly different between the two groups. Neonatal birth weight was significantly higher in the GDM group (p < 0.01). The GDM group had significantly higher renal artery indices (resistance index: p = 0.01, pulsatility index [PI]: p = 0.03, and systolic/diastolic ratio [S/D]: p = 0.01) compared to the control group. Also, there was an inverse linear correlation between umbilical indices and birth weight (PI: p = 0.01, S/D: p < 0.01), and between renal artery indices and birth weight (resistance index: p = 0.02, PI: p = 0.01, and S/D: p = 0.03). In the control group, only umbilical artery PI had an inverse linear correlation with birth weight (p = 0.03) and there was no correlation between renal artery indices and birth weight. Conclusion: Using Doppler hemodynamic indices of the renal artery in late pregnancy in women with GDM can be helpful for early detection of hypoxic fetuses, who are at risk of being small for gestational age or having intrauterine growth restriction, even when of normal weight.

The effect of vaginal progesterone on Doppler findings in increased uterine artery resistance.

OBJECTIVE: The present study aimed to evaluate the effect of vaginal progesterone on Doppler finding in increased uterine artery resistance compared with aspirin. MATERIALS AND METHODS: This study is a double-blind randomized clinical trial that was conducted on 140 pregnant women with increased uterine artery resistance who were referred to the Shariati hospital (Tehran, Iran) in 2017-2018. Patients were randomized to 1 of the 3 treatment groups - group A: tablet aspirin 80 mg; group B: vaginal suppository progesterone; and group C: control group without any intervention. Low-risk pregnant women at the gestational age of 16-20 weeks, were assessed by the uterine artery Doppler. In the presence of increased resistance of the uterine artery, patients were randomly assigned to one of the three above mentioned groups. RESULTS: The results of paired t-tests for right uterine artery pulsatility index (RUA.PI), right uterine artery resistance index (RUA.RI), left uterine artery PI (LUA.PI), and left uterine artery RI (LUA.RI) before and after of intervention in the three groups were statistically significant. Also, the one-way analysis of variance (ANOVA) results for comparison between three groups showed that before the intervention only means of RUA.PI has a significant difference between three groups (p = .025), but means of all variables after intervention shows a significant difference (p < .001). CONCLUSION: The findings showed that the use of vaginal progesterone suppressed the resistance of uterine artery compared to aspirin.

Coronavirus diseases and pregnancy: COVID-19,SARS, and MERS.

Around the end of December 2019, a new beta-coronavirus from Wuhan City, Hubei Province, China began to spread rapidly. The new virus, called SARS-CoV-2, which could be transmitted through respiratory droplets, had a range of mild to severe symptoms, from simple cold in some cases to death in others. The disease caused by SARS-CoV-2 was named COVID-19 by WHO and has so far killed more people than SARS and MERS. Following the widespread global outbreak of COVID-19, with more than 132758 confirmed cases and 4955 deaths worldwide, the World Health Organization declared COVID-19 a pandemic disease in January 2020. Earlier studies on viral pneumonia epidemics has shown that pregnant women are at greater risk than others. During pregnancy, the pregnant woman is more prone to infectious diseases. Research on both SARS-CoV and MERS-CoV, which are pathologically similar to SARS-CoV-2, has shown that being infected with these viruses during pregnancy increases the risk of maternal death, stillbirth, intrauterine growth retardation and, preterm delivery. With the exponential increase in cases of COVID-19 throughout the world, there is a need to understand the effects of SARS-CoV-2 on the health of pregnant women, through extrapolation of earlier studies that have been conducted on pregnant women infected with SARS-CoV, and MERS-CoV. There is an urgent need to understand the chance of vertical transmission of SARS-CoV-2 from mother to fetus and the possibility of the virus crossing the placental barrier. Additionally, since some viral diseases and antiviral drugs may have a negative impact on the mother and fetus, in which case, pregnant women need special attention for the prevention, diagnosis, and treatment of COVID-19.

Evaluation of the predictive value of fetal Doppler ultrasound for neonatal outcome from the 36th week of pregnancy.

BACKGROUND: Early prediction of adverse neonatal outcome would be possible by Doppler impedance indices of middle cerebral artery (MCA), umbilical artery (UmA), and descending aortal artery (AO) that result in decrease neonatal morbidity and mortality rate. The aim of the present study was a determination of optimal value for the ratio of MCA to descending aorta blood flow (MCA/AO) impedance indices and its comparison with the ratio of MCA to UmA (MCA/UmA) impedance indices and their relationship with neonatal outcome. MATERIALS AND METHODS: This was a prospective cohort study on 212 pregnant women with gestational age 36 weeks or more, in three hospitals in Tehran, from April 2012 to April 2013. We investigated AO, MCA, and UmA impedance indices Doppler ultrasound every 2 weeks till delivery. The mother was monitored for adverse pregnancy outcome (hypertension [HTN], fetal growth retardation, and other maternal complications) then infant birth weight, cord blood of pH, and Neonatal Intensive Care Unit (NICU) admission during the first 24 h after delivery were assessed. Finally, we investigated relationships between Doppler indices and neonatal outcomes include neonatal body weight (NBW), cord blood of pH, and NICU admission. RESULTS: MCA/AO resistance index (RI) and MCA/AO pulsatile index (PI) showed an area under the receiver operating characteristics curve (area under the curve) of 0.905 (95% confidence interval (CI): 0.850, 0.959) and 0.818 (95% CI: 0.679, 0.956), respectively. The cutoff values for pH (≥7.2 vs. <7.2) based on MCA/AO RI and MCA/AO PI indices were 0.951 (sensitivity, 80% and specificity, 86%) and 0.853 (sensitivity, 91% and specificity, 83%), respectively. The cutoff value for NBW (≥2500 vs. <2500 g) based on MCA/UmA PI index was 1.467 (sensitivity, 73% and specificity, 63%). The cutoff value of NICU admission of child based on MCA/AO PI index was 1.114 (sensitivity, 73% and specificity, 54%). CONCLUSION: In the end of third-trimester pregnancies with the assessment of MCA and AO artery Doppler ultrasonography, it is possible to prevent many cases of neonatal acidosis caused by prenatal asphyxia as well as inappropriate interventions which are applied on mother. If MCA/AO PI was <0.85, the fetus needs to be evaluated further because it is at risk for acidosis.

Association of maternal and umbilical cord blood leptin concentrations and abnormal color Doppler indices of umbilical artery with fetal growth restriction.

BACKGROUND: Fetal growth restriction (FGR) is a condition with heterogeneous pathophysiology which characterized by fetal weight less than the tenth percentile for gestational age. Several factors have impact on maternal, placental and fetal due to growth restriction. OBJECTIVE: The aim of this study was to investigate the relationship between levels of leptin in the cord, and serum leptin of mothers also abnormal color Doppler indices of umbilical artery with fetal growth restriction. MATERIALS AND METHODS: This is a cross sectional study conducted in Isfahan, Iran, 2015-2016. We recruited 40 women with singleton pregnancies complicated by fetal growth restriction (Group I) and 40 pregnant women with normal fetal growth (Group II) with matched age. Maternal serum and umbilical artery leptin levels were determined with Enzyme-Linked immunosorben method. Also, color Doppler ultrasound of umbilical artery was performed. RESULTS: Mean maternal and fetal leptin levels were lower in the FGR group compared to the normal group (36.58±(20.99) and 7.42 ±(4.08)vs. 47.32±(22.50) and 30.49±(14.50) respectively). Also, mean fetal leptin level was lower in the group with abnormal color Doppler sonographic indices compared to the normal group (7. 40 ±(4.10)vs 27.06±(15.80), respectively). CONCLUSION: This study indicated that maternal and fetal leptin levels are correlated with FGR originating from damaged placental function; also fetal leptin level can indicate changes in color Doppler sonographic indices.

Is preterm placental calcification related to adverse maternal and foetal outcome?

This prospective cohort study aimed to evaluate the role of premature placental calcification in adverse pregnancy outcomes and identify its associated potential risk factors. We consecutively enrolled 293 women who presented to three academic medical centres from September 2011 to March 2013. Participants underwent transabdominal sonographies between 28-36 weeks of gestation in an attempt to determine placental maturity. We compared maternal and foetal outcomes between two groups of women, those with grade III placenta (n = 69) and those without grade III placenta (n = 224). Passive smoking was the only predictor of early placental calcification. There were more abnormal Doppler, low birth weight (LBW) and caesarean section (CS) deliveries observed in the preterm calcification group. No definite relationship existed between maternal hypertension (HTN), diabetes and other medical diseases with placental calcification. In conclusion, umbilical artery (UA) resistance index (RI) and absent or reversed end-diastolic velocity (AREDV) were observed more often in preterm placental calcification. Serious antepartum follow-up should be advised for these mothers. Impact Statement • Placental calcification is a physiological phenomenon but normally, a grade III placenta is not frequently found until 36 weeks of gestation (so is called preterm placental calcification - PPC). There is currently a lack of consistent evidence on the clinical significance of PPC and pregnancy outcome. The present study was designed to evaluate the role of PPC in adverse pregnancy outcomes. • In our study, although none of the pregnant women were smokers, we found that passive smoking was the only predictor of PPC. Abnormal umbilical artery Doppler waveforms considerably and absent end diastolic velocity pattern significantly were observed more often in the PPC group. • We observed that PPC can be a landmark for high-risk pregnancy and an alarm sign for placental dysfunction. So, close antepartum follow up should be advised for these mothers. Regular and frequent foetal wellbeing tests should be done to prevent pregnancy complications. Certainly larger and more extensive study can provide more valid results.