An Assessment of Selected Molecular and Biochemical Markers of the Folate Pathway as Potential Risk Factors for Fetal Trisomy 21 during the First Trimester of Pregnancy in the Polish Population.

Are the maternal gene variants MTHFR: c.665C>T, MTHFR: c.1286A>C, MTR: c.2756A>G, MTRR: c.66A>G, RFC1: c.80C>T and TCN2: c.776G>C and blood markers of the folate pathway important factors in assessing the risk of fetal trisomy 21 (fetal-T21)? Twenty pregnant women with a high risk and twenty with a low risk of fetal-T21 underwent prenatal examination. Selected gene variants and folate pathway markers and pregnancy-associated plasma protein A (PAPP-A) and free ß-subunit of human chorionic gonadotropin ß (free-ß-hCG) multiple of the medians (MoMs) were determined. The distributions of the alternative alleles and genotypes of the gene variants did not differ between the studied groups. There was no relationship between PAPP-A and ß-hCG MoM values and the presence of allele alternative genotype variants. The occurrence of alternative variants of the selected genes and concentrations of most of the studied folate pathway markers may not play a crucial role in the risk of fetal-T21 in pregnant women. However, the relationships between erythrocyte folate concentrations and the occurrence of alternative variants: c.665C>T MTHFR and c.776G>C TCN2, as well as the methylmalonic acid concentration and the occurrence of alternative variant c.776G>C TCN2 in pregnant women with fetal-T21, encourage further research. So far, of the biochemical markers, maternal PAPP-A and ß-hCG MoM values remain independent risk factors for fetal-T21.

Spontaneous Resolution of Congenital Dural Venous Sinus Ectasia Associated With Polymicrogyria-Case Report.

Dural venous sinus ectasia belongs to a rare group of venous sinus malformations of unknown origin and uncertain prognosis. We report the first patient with idiopathic congenital ectasia of the confluence of sinuses with thrombosis associated with bilateral polymicrogyria. It may highlight the causative relation between ischemia within the central nervous system due to torcular herophili ectasia with thrombosis in early pregnancy and the development of cortical malformations in neonates. We also highlight the role of MR neuroimaging in the diagnosis of these entities.

Can redox imbalance predict abnormal foetal development?

OBJECTIVES: Based on the current state of knowledge, elevated levels of oxidative stress markers may be considered as risk factors for pregnancy complications. The aim of the research was to assess the correlation between selected oxidative stress biomarkers with the occurrence of foetal chromosomal aberration and congenital malformations. MATERIAL AND METHODS: This retrospective research lasted for two years. The purpose was to determine serum levels of selected oxidative stress markers, including total protein (TP), glutathione (GSH), S-nitrosothiols (RSNO), nitric oxide (NO), trolox equivalent antioxidant capacity (TEAC) and glutathione S-transferase (GST) at 11-13 + 6 gestational weeks in 38 women with confirmed foetal developmental abnormalities and in 34 healthy pregnancies in order to assess their utility as predictors of abnormal foetal development. RESULTS: Serum concentrations of TP (56.90 ± 5.30 vs 69.1 ± 15.30 mg/mL), TEAC (4.93 ± 0.82 vs 5.64 ± 0.74 µM/mL) and GST (15.94 ± 4.52 vs 21.72 ± 6.81 nM/min/mg) were statistically significantly (p < 0.05) lower in the group of patients with developmental abnormalities in the fetus, whereas GSH levels (6.43 ± 1.24 vs 4.98 ± 1.88 nM/mg) were significantly higher, compared to the group of healthy fetuses. There were no differences in the concentration of these markers between chromosomal aberrations and fetal dysmorphia in subjects. A significant difference in odds ratio obtained for GSH (OR = 0.57, 95% CL: 0.40-0.80) indicates that its higher concentration can relate to reduced risk of developmental abnormalities, whereas odds ratio for TP (OR=1.11, 95% CL: 1.04-1.17), TEAC (OR = 3.54, 95% CL: 1.56-8.05) and GST (OR = 1.18, 95% CL: 1.03-1.17) indicate that their elevation may increase the risk of developmental abnormalities CONCLUSIONS: Elevated levels of TP, GST, TEAC and low GSH level may be relevant to predict congenital defects.

Association of Oxidative Stress on Pregnancy.

The pathophysiological mechanism underlying pregnancy complications such as congenital malformations, miscarriage, preeclampsia, or fetal growth restriction is not entirely known. However, the negative impact of the mother's body oxidative imbalance on the fetus and the course of gestation is increasingly discussed. This article is an integrative review of some original studies and review papers on the effects of oxidative stress on the adverse pregnancy outcomes mainly birth defects in fetuses. A systematic search for English language articles published from 2010 until 2020 was made, using MEDLINE data. Additionally, we analyzed the Cochrane and Scopus databases, discussions with experts, and a review of bibliography of articles from scientifically relevant and valuable sources. The main purposes are to assess the contribution of the existing literature of associations of oxidative stress on the etiology of the abovementioned conditions and to identify relevant information and outline existing knowledge. Furthermore, the authors aim to find any gaps in the research, thereby providing grounds for our own research. The key search terms were "oxidative stress in pregnancy," "oxidative stress and congenital malformations," and "oxidative stress and adverse pregnancy outcomes." Studies have confirmed that oxidative stress has a significant impact on pregnancy and is involved in the pathomechanism of adverse pregnancy outcomes.

Mid-trimester ultrasound parameters for predicting birth weight in low risk pregnancies vs high-risk pregnancies complicated with pre-gestational diabetes mellitus.

OBJECTIVES: The aim of the study was to assess the utility of mid-trimester ultrasound parameters in predicting birth weight in low-risk pregnancy and high-risk pregnancy complicated with pregestational diabetes mellitus. MATERIAL AND METHODS: A study group comprised 97 healthy women and 160 women with pregestational diabetes (PGDM, type 1), all in singleton pregnancy. Ultrasound examination was performed between weeks 11 and 14, and in weeks 20 and 30 of gestation, based on recommendations of the Polish Society of Gynecologists and Obstetricians, Ultrasonography Division. We also checked uterine artery blood flow parameters. RESULTS: There is a correlation between the birth weight and ultrasound-ascertained parameters, including those characterising uterine artery blood flow and foetal biometry [abdominal circumference (AC), femoral length (FL), biparietal dimension (BPD)].The biparietal dimension (BPD), head circumference (HC) abdominal circumference (AC) and pre-existing diabetes are the ultrasound predictors of LGA. The presence of an early-diastolic uterine artery blood flow waveform notching, as well as the uterine artery pulsatility index (UAPI), femoral length (FL) and hypertension in pregnancy are the ultrasound predictors of SGA. In the subset of women with pre-gestational diabetes (PGDM), there is a negative correlation between the birth weight and the uterine artery pulsatility index and early-diastolic uterine artery blood flow waveform notching. In women with pre-gestational diabetes mellitus (PGDM), femoral length (FL) is a significant predictor of LGA and in case of SGA significant predictors are uterine artery pulsatility index, artery blood flow waveform notching and femoral length (FL). CONCLUSIONS: Midtrimester ultrasound parameters with confirmed usefulness in the prediction of birth weight in low-risk pregnancy and high-risk pregnancy complicated with pregestational diabetes mellitus include: uterine artery PI, early-diastolic uterine artery blood flow waveform notching and foetal biometry.

The significance of maternal blood pregnancy-associated plasma protein A (PAPP-A) and free beta-subunit of human chorionic gonadotropin (ß-hCG) levels for the risk assessment of fetal trisomy 18 during the first prenatal testing between 11 and 13+6 weeks of pregnancy.

OBJECTIVE: The aim of the study was to evaluate the significance of the maternal blood level of pregnancy-associated plasma protein A (PAPP-A) and free beta-subunit of human chorionic gonadotropin (ß-hCG), to estimate the risk of fetal trisomy 18 and their correlation with the assessment of nuchal translucency (NT) during the first prenatal testing. MATERIAL AND METHODS: Examinations of 93 pregnant women between 11 and 13+6 weeks of pregnancy were conducted, which included determination of ß-hCG and PAPP-A concentrations in the maternal serum and ultrasound assessment of fetal nuchal translucency. Concentrations of biochemical parameters were expressed as multiples of median (MoM) for the appropriate gestational age. The risk assessment of trisomy 18 was analyzed using Astraia software. Pregnant women with a high (≥ 1:300) risk of trisomy 18 were offered a genetic amniocentesis with an examination of fetal karyotype. Twenty cases were healthy and 23 with trisomy 18. RESULTS: PAPP-A and ß-hCG MoM values < 0.3 were found in 61% cases of fetal trisomy 18. In 26% of cases, PAPP-A and ß-hCG MoM values < 0.2 were NT-independent risk factors for trisomy 18. There were no significant differences between groups with normal fetal karyotype (40%) and trisomy 18 (35%) in PAPP-A and ß-hCG MoM 0.2-0.5 range. CONCLUSIONS: Maternal free ß-hCG MoM was found to change parallelly to fetal NT widening in case of trisomy 18 diagnosis. Maternal ß-hCG and PAPP-A MoM results presented less then 0.2 might be used independently of NT widening in fetus for trisomy 18 risk evaluation. Above 0.2 for PAPP-A and ß-hCG MoMs, fetal NT measurement was an requirment.

Maternal factors, ultrasound and placental function parameters in early pregnancy as predictors of birth weight in low-risk populations and among patients with pre-gestational diabetes.

OBJECTIVES: The aim of our work was to assess the usefulness of maternal factors, ultrasound and placental function parameters during early pregnancy as predictors of birth weight in populations of healthy pregnant women and women suffering from pregestational diabetes. MATERIAL AND METHODS: A study group comprised 97 healthy women and 160 women with pregestational diabetes (PGDM, type 1), all in singleton pregnancy. Ultrasound examination was performed between weeks 11 and 14, and in weeks 20 and 30 of gestation, based on recommendations of the Polish Society of Gynecologists and Obstetricians, Ultrasonography Division. We also checked uterine artery blood flow parameters. During the first trimester consultation, all patients were surveyed and the following data were collected: age, BMI, reproductive history, comorbidities and smoking. We also collected blood samples and assessed PlGF, PAPP-A, and BhCG levels. RESULTS: Our study showed that newborn birth weight negatively correlated with mother's age, her diastolic blood pressure, PI of her uterine arteries and BhCG protein levels. Moreover, birth weight directly correlated with PlGF and PAPPA-A protein levels, and maternal early-pregnancy BMI. CONCLUSIONS: LGA diagnosis in the first trimester of pregnancy allows for selection and modification of some risk factors and closer monitoring of endangered fetuses throughout the pregnancy, with emphasis on the perinatal period. Parameters with confirmed usefulness in the prediction of birth weight in the first trimester included: maternal age, BMI, blood pressure, PAPP-A, BhCG and PlGF levels, fetal CRL and uterine artery PI.

The clinical usefulness of biochemical (free ß-hCg, PaPP-a) and ultrasound (nuchal translucency) parameters in prenatal screening of trisomy 21 in the first trimester of pregnancy.

OBJECTIVES: The aim of the study was to analyze the correlation of multiples of the normal median of PAPP-A, free ß-hCG levels and nuchal translucency values in prenatal, first trimester screening of trisomy 21 in pregnant women. MATERIAL AND METHODS: 251 pregnant women underwent antenatal screening at 11-13+6 weeks of pregnancy which was composed of the measurement of free ß-human chorionic gonadotropin (ß-hCG) and pregnancy-associated plasma protein (PAPP-A) levels in the maternal serum and an ultrasound assessment of nuchal translucency (NT). The pregnant women with a high risk of trisomy 21 (≥ 1:300) were given amniocentesis to verify fetal defects. There were 217 cases of normal fetal karyotype and 34 cases of trisomy 21. PAPP-A, ß-hCGMoM and NT values were analyzed for the predefined ranges. RESULTS: 85% cases of trisomy 21 had elevated free ß-hCGMoM (> 1.5) and only 53% of these had a PAPP-AMoM result below 0.5 (p < 0.05). Analysis of NT in selected ranges of ß-hCG (> 1.5) and PAPP-AMoM (< 0.05), which are typical for Down Syndrome values, showed that not all fetuses with Down Syndrome presented with an increased NT. Respectively 44.15% and 26.5% of fetuses presented with increased NT. Characteristic for trisomy 21, a correlation with all 1st trimester screening tests' parameters occurred in only 23.5% of cases. In 53% of cases the results were atypical. CONCLUSIONS: The PAPP-A and ß-hCG values in the selected MoM ranges did not shown a correlation to the NT measurement, therefore they are independent factors in the diagnosis of trisomy 21. Simultaneous biochemical and ultrasound testing is an indispensable condition for prenatal diagnosis of trisomy 21 in the 1st trimester of pregnancy.