Do low-risk nulliparous women with abnormal uterine artery Doppler in the third trimester have poorer perinatal outcomes? A longitudinal prospective study on uterine artery Doppler in low-risk nulliparous women and correlation with pregnancy outcomes

Objective: To evaluate uterine artery (UtA) Doppler over the course of pregnancy in low-risk nulliparous women and to analyze whether an abnormal uterine artery pulsatility index (UtA-PI) at a 32–34 week’ scan implies poorer perinatal outcomes.

Methods: An observational prospective study was carried out including 616 low-risk nulliparous women. Women with any of the following were excluded: fetal abnormalities, multiple pregnancy, and heparin, metformin or hypotensive treatment. Maternal characteristics, mean arterial pressure measurements and UtA Doppler findings were recorded longitudinally.

Results: Complete pregnancy data were available for 489/616 women (79.3%). Of these, 385 women had a normal UtA-PI throughout pregnancy (Group 0), while 50 (10.1%) had an UtA-PI?>?95th percentile in the first or the second trimester that normalized in the third trimester (Group 1), and 56 (11.4%) had an abnormal UtA-PI in the third trimester (Group 2). We found that the rate of pre-eclampsia (PE) was higher in Group 2 (7/56 versus 4/435, p?=?0.003) as was the rate of intrauterine growth restriction (IUGR) (6/56 versus 14/435, p?=?0.02).

Conclusions: Low-risk nulliparous women with abnormal UtA Doppler findings in the third trimester are at a higher risk of developing PE and having a baby with IUGR.     

Relationship between Doppler findings and fetal brain apparent diffusion coefficient in early-onset intra-uterine growth restriction*

Objective: The aim of the study is to assess the relationship between uteroplacental Doppler sonography findings and cerebral diffusion measured by diffusion-weighted magnetic resonance imaging (DWI) in fetuses with early-onset intrauterine growth restriction (IUGR).

Materials and methods: The study included 54 pregnant women with fetal IUGR and 15 healthy controls (n: 15). Fetuses with IUGR were classified into four groups based on Doppler findings: group 1 (n?=?12), umbilical artery (UA) pulsatility index (PI)?>?95pc; group 2 (n?=?11), UA PI >95?pc and middle cerebral artery PI?n?=?21), absent end-diastolic (A-EDF) in UA; group 4 (n?=?10), reversed EDF in UA. After Doppler evaluation, DWI was performed in all patients within hours. The groups were compared with respect to apparent diffusion coefficient (ADC) levels.

Findings: In cases with fetal IUGR, significant decreases were detected in ADC values of periatrial white matter (PAWM) (p?=?.01), frontal white matter (FWM) (p?=?.038), thalamus (p?=?.004), and basal ganglia (p?=?.013) compared to controls. In Doppler subgroup analysis adjusted for gestational age, ADC values of FWM, thalami, and pons were significantly lower in group 4 than control group (p?=?.02, p?=?.02, and p?=?.037, respectively). In PAWM, ADC values were significantly lower in group 4 than control and Group 1 (p?=?.004). No significant differences with regard to ADC values in basal ganglia, cerebellum was found between Doppler groups and control.

Conclusions: In fetuses with IUGR, ADC values as measured by DWI decreases. The critical Doppler finding that is associated with reduced diffusion in some brain areas (FWM, PAWM, thalami, pons) is reverse end-diastolic flow in umbilical artery. Further prospective studies with larger sample size are needed to introduce cerebral ADC values in the management of IUGR     

Effect of aspirin in prevention of adverse pregnancy outcome in women with elevated alpha-fetoprotein

Abstract

Background: To evaluate the effect of low-dose aspirin in prevention of adverse pregnancy outcomes (APO) in women with second trimester alpha-fetoprotein (AFP) >2.5 multiple of median (MOM) and to compare aspirin effect on women with normal and abnormal uterine artery (UtA) Doppler. The primary outcome was the adverse pregnancy outcome.

Methods: This randomized controlled trial was conducted in singleton pregnant women, who had unexplained AFP >2.5 MOM and gestational age between 15 and 18 weeks of gestation. They were assigned randomly to receive either aspirin (N?=?65) or control (N?=?68). UtA Doppler velocimetry studies were performed at the time of targeted ultrasonographic exam.

Results: Two groups were comparable regarding the maternal characteristics. The frequency of APO in aspirin and control groups were 26.1% versus 44.1% (p?=?0.045), the frequency of preterm delivery before 34 weeks were 3.2% versus 22.0% in aspirin and control group, p?=?0.001. Other outcomes were similar in both groups. The frequency of adverse outcomes in women with abnormal UtA Doppler was 39.1% in aspirin and 60.0% in control group, p?=?0.556.

Conclusion: Low-dose aspirin reduces APO and delivery before 34 weeks of gestation in pregnant women with unexplained elevated AFP.     

Perinatal sclerostin concentrations in abnormal fetal growth: the impact of gestational diabetes

Objective: To prospectively evaluate maternal and cord blood concentrations of sclerostin – an osteocyte-secreted factor, inhibiting osteoblast differentiation and bone formation and associated with adverse metabolism – in pregnancies with normal and abnormal fetal growth.

Methods: Plasma sclerostin concentrations were determined by ELISA in 80 maternal and 80?cord blood samples from asymmetric intrauterine-growth-restricted (IUGR, n?=?30), large-for-gestational-age (LGA, n?=?30), and appropriate-for-gestational-age (AGA, n?=?20) singleton full-term pregnancies. Fourteen out of 30 mothers with LGA offspring presented with gestational diabetes mellitus (GDM).

Results: Maternal and fetal sclerostin concentrations did not differ among LGA, IUGR, and AGA groups. Fetal concentrations were higher than maternal. In LGA group, maternal concentrations were elevated in cases of GDM (b?=?13.009, 95%CI 1.425–24.593, p?=?.029). In a combined group and the IUGR group, maternal concentrations were elevated in older mothers (b?=?0.788, 95%CI 0.190–1.385, p?=?.010, and b?=?0.740, 95%CI 0.042–1.438, p?=?.039, respectively).

Conclusions: Maternal and fetal sclerostin concentrations may not be differentially regulated in pregnancies complicated by abnormal fetal growth. Circulating maternal levels are higher in cases of GDM, probably implying reduced bone formation. Sclerostin up-regulation with aging may be one of the molecular pathways responsible for the observed age-related decline in bone synthesis, leading to accelerated bone loss in humans.     

Added value of cerebro-placental ratio and uterine artery Doppler at routine third trimester screening as a predictor of SGA and FGR in non-selected pregnancies

Objectives: The objective of this study is to determine the added value of cerebroplacental ratio (CPR) and uterine Doppler velocimetry at third trimester scan in an unselected obstetric population to predict smallness and growth restriction.

Methods: We constructed a prospective cohort study of women with singleton pregnancies attended for routine third trimester screening (32⁺⁰–34⁺⁶ weeks). Fetal biometry and fetal–maternal Doppler ultrasound examinations were performed by certified sonographers. The CPR was calculated as a ratio of the middle cerebral artery to the umbilical artery pulsatility indices. Both attending professionals and patients were blinded to the results, except in cases of estimated fetal weight Results: A total of 1030 pregnancies were included. The mean gestational age at scan was 33 weeks (SD 0.6). The addition of CPR and uterine Doppler to maternal characteristics plus EFW improved the explained uncertainty of the predicting models for SGA (15 versus 10%, p?p?=?.03). However, the addition of CPR and uterine Doppler to maternal characteristics plus EFW only marginally improved the detection rates for SGA (38 versus 34% for a 10% of false positives) and did not change the predictive performance for FGR.

Conclusions: The added value of CPR and uterine Doppler at 33 weeks of gestation for detecting defective growth is poor.     

Assessment of human placental perfusion by intravoxel incoherent motion MR imaging

Purpose: To provide functional information on the human placenta, including perfusion, and diffusion, with no contrast agent injection, and to study correlations between intravoxel incoherent motion (IVIM) placental parameters and fetal growth.

Materials and methods: MRI was performed in women undergoing legal termination of pregnancy at 17–34 weeks, including a 4-b-value and 11-b-value DW sequences. The apparent diffusion coefficient (ADC), the restricted diffusion coefficient (D), the pseudoperfusion coefficient (D*), and the perfusion fraction (f) were calculated. Their relationships with gestational age, Z-scores for fetal and placental weight were evaluated by means of regression analysis. Logistic regression analysis was used to assess the ability of IVIM parameters to predict/detect intrauterine growth retardation (SGA).

Results: Fifty-five pregnant women, including nine cases of SGA (16%), were included in the study. The ADC (n?=?55) showed a quadratic correlation with gestational age (p?p?=?.02). Mean ADC values were significantly different between normally growing and SGA fetuses (2.37?±?0.25 versus 2.29?±?0.33 10^?3.mm².s^?1, p=.048). The perfusion fraction f (n?=?23) showed a quadratic correlation with gestational age (p?=?.017) and a linear correlation with the fetal weight Z???score (p?=?.008). Mean f values differed significantly between normally growing and SGA fetuses (42.55?±?9.30% versus 27.94?±?8.76%, p?=?.002). The receiver operating characteristics (ROC) curve for f to predict SGA was produced (area under the ROC curve?=?0.9).

Conclusions: The observed association between f and fetal weight suggests that fMRI could be suitable for studying placental insufficiency and for identifying risk of SGA.

Trial registration: ClinicalTrials.gov identifier: NCT01092949.     

Utero-placental perfusion Doppler indices in growth restricted fetuses: effect of sildenafil citrate

Objective: To assess efficacy and tolerability of sildenafil citrate on utero-placental blood flow and fetal growth in pregnancies complicated by fetal growth restriction (FGR).

Methods: From March 2015, a randomized controlled trial of 54 patients at 24?weeks or more complicated by FGR and abnormal Doppler indices were randomly allocated 1:1 into an intervention arm (receive sildenafil citrate, 50?mg) or a control arm (receive placebo). The primary outcomes were changes occurred in the Doppler parameters 2?h following drug administration.

Results: Baseline characteristics were similar between groups. Significant difference was observed in the Delta uterine and umbilical Doppler indices among sildenafil group as compared to placebo group (p?p?=?0.979). Sildenafil was also associated with pregnancy prolongation (p?=?.0001), increased gestational age at delivery (p?=?.004), improved neonatal weight (p?=?.0001), and less admission to neonatal intensive care unit (p?=?.03). No adverse effects reported in both treatment arms.

Conclusion: Sildenafil citrate, by its vasodilator effect, can improve utero-placental blood flow in pregnancies complicated by FGR and abnormal Doppler.

Clinical Trial.gov Registry: NCT02362399     

Association between uterine artery Doppler blood flow changes and arterial wall elasticity in pregnant women

Introduction: Uterine artery (UtA) Doppler velocimetry changes and increased arterial stiffness are associated with preeclampsia. We aimed to investigate the relation between UtA velocimetry changes and arterial stiffness in pregnant women.

Methods: Doppler velocimetry and photoplethysmographic digital pulse wave analysis (DPA) were performed in 173 pregnant women in the second or the third trimester, where UtA Doppler pulsatility index (PI), diastolic notching, and UtA score (UAS) combining notching and high PI were calculated. DPA stiffness parameters representing large arteries were ejection elasticity index (EEI) and b/a, small arteries dicrotic index (DI) and d/a, and global stiffness the aging index (AI).

Results: One hundred and thirty women had normal Doppler and 43 had diastolic notching, of whom nine had high PI. DI indicated increased stiffness in small arteries when notching was present (p?=?0.044) and showed a significant but weak correlation to UAS (p?=?0.025, tau 0.12). EEI and b/a indicated increased large artery stiffness (p?≤0.014), d/a small artery stiffness (p = 0.023), and AI a systemic stiffness (p = 0.040) when high PI.

Conclusion: High UtA PI was associated with increased systemic arterial stiffness, whereas notching was related to increased stiffness in small arteries only. This indicates pathophysiological differences between the two Doppler parameters.     

Can flavonoid-rich chocolate modulate arterial elasticity and pathological uterine artery Doppler blood flow in pregnant women? A pilot study

Introduction: Dark chocolate has shown beneficial effects on cardiovascular health and might also modulate hypertensive complications in pregnancy and uteroplacental blood flow. Increased uteroplacental resistance is associated with systemic arterial stiffness. We aimed to investigate the short-term effect of flavonoid-rich chocolate on arterial stiffness and Doppler blood flow velocimetry indexes in pregnant women with compromised uteroplacental blood flow.

Methods: Doppler blood flow velocimetry and digital pulse wave analysis (DPA) were performed in 25 women pregnant in the second and third trimesters with uterine artery (UtA) score (UAS) 3–4, before and after 3 days of ingestion of chocolate with high flavonoid and antioxidant contents. UtA pulsatility index (PI), UtA diastolic notching, UAS (semiquantitative measure of PI and notching combined), and umbilical artery PI were calculated, and DPA variables representing central and peripheral maternal arteries were recorded.

Results: Mean UtA PI (p?=?.049) and UAS (p?=?.025) significantly decreased after chocolate consumption. There were no significant changes in UtA diastolic notching or any DPA indexes of arterial stiffness/vascular tone.

Conclusion: Chocolate may have beneficial effects on the uteroplacental circulation, but in this pilot study, we could not demonstrate effects on arterial vascular tone as assessed by DPA.     

Influence of gestational age and fetal heart rate on the fetal mechanical PR interval

Objective: The fetal mechanical PR interval obtained via pulsed Doppler has previously been demonstrated to correlate with electrocardiographic PR interval measured in the neonate. We sought to further analyze the influence of fetal heart rate and gestational age upon the fetal mechanical PR interval.

Methods: We searched our database for mechanical PR intervals, which were obtained during fetal echocardiography performed in our antenatal diagnostic unit. We included fetuses with a normal cardiac structural survey. The mechanical PR interval is measured from the A wave of the mitral valve to the beginning of ventricular systole corresponding to the opening of the aortic valve. Linear regression curves were generated to examine the correlation of mechanical PR interval with gestational age and fetal heart rate. Analysis of variance was used to compare the mean variation across three gestational age groups: 17–21.9 weeks (n?=?24), 22–25.9 weeks (n?=?52) and 26–38 weeks (n?=?20).

Results: Mechanical PR intervals were measured in 96 fetuses with normal fetal echocardiography. The mechanical PR interval was 123.9?±?10.3?ms (mean?±?SD), with a range of 90–150?ms. Linear regression curves correlating mechanical PR interval with fetal heart rate and gestational age demonstrated a flat slope with R²?=?0.016, p?=?0.22 and R²?=?0.0004, p?=?0.85, respectively. The mechanical PR interval measured over the three gestational ages was as follows (mean?±?SD): 122.3?±?10.5?ms for 17–21.9 weeks; 125.0?±?9.6?ms for 22–25.9 weeks; and 123.1?±?11.9?ms for 26–38 weeks. Analysis of variance revealed no difference among the mechanical PR interval means measured over the three gestational age groups (p?=?0.53).

Conclusions: Fetal mechanical PR interval ranges from 90 to 150?ms in fetuses with sonographically normal fetal cardiac structure and rate. The mechanical PR interval appears to be independent of gestational age and fetal heart rate.     

Analysis of correlations between the placental expression of glucose transporters GLUT-1, GLUT-4 and GLUT-9 and selected maternal and fetal parameters in pregnancies complicated by diabetes mellitus

Purpose: The aim of the study was to analyze the correlations between the expression of glucose transporters GLUT-1, GLUT-4, and GLUT-9 in human term placenta and selected maternal and fetal parameters in pregnancies complicated by diabetes mellitus (DM).

Materials and methods: Placental samples were obtained from healthy control (n?=?25) and diabetic pregnancies, including diet-controlled gestational diabetes mellitus (GDMG1) (n?=?16), insulin-controlled gestational diabetes mellitus (GDMG2) (n?=?6), and pregestational DM (PGDM) (n?=?6). Computer-assisted quantitative morphometry of stained placental sections was performed to determine the expression of selected glucose transporter proteins. For the purposes of correlation analysis, the following parameters were selected: type of diabetes, gestational age, maternal prepregnancy body mass index (BMI), gestational weight gain, third trimester glycated hemoglobin concentration, placental weight, fetal birth weight (FBW) as well as ultrasonographic indicators of fetal adiposity, including subscapular (SSFM), abdominal (AFM), and midthigh (MTFM) fat mass measurements.

Results: In the PGDM group, the analysis demonstrated positive correlations between the placental expression of GLUT-1, GLUT-4, and GLUT-9 and FBW, AFM, and SSFM measurements (p?p?p?p?Conclusions: The study results revealed that placental expression of GLUT-1, GLUT-4, and GLUT-9 may be involved in the intensification of the fetal growth in pregnancies complicated by GDM/PGDM.     

Effects of smoking and preeclampsia on birth weight for gestational age

Objective: A counterintuitive interaction between smoking during pregnancy and preeclampsia on birth weight for gestational age (BWGA) outcomes was recently reported. In this report, we examine the relationship between these factors in a well-documented study population with exposure data on trimester of maternal smoking.

Methods: Preeclamptic (n?=?238), gestational hypertensive (n?=?219), and normotensive women (n?=?342) were selected from live-births to nulliparous Iowa women. Disease status was verified by medical chart review, and smoking exposure was assessed by self-report. Fetal growth was assessed as z-score of BWGA. Multiple linear regression was used to test for the association of maternal smoking and preeclampsia with BWGA z-score.

Results: There was no interaction between smoking with preeclampsia or gestational hypertension on fetal growth. BWGA z-scores were significantly lower among women with preeclampsia and those who smoked any time during pregnancy (β?=??0.33, p?=?<0.0001 and β?=??0.25, p?=?0.05) compared to normotensive and non-smoking women, respectively. Infants of women with gestational hypertension were comparable in size to infants born to normotensive women.

Conclusions: Women who developed preeclampsia and those who smoked during pregnancy delivered infants that were significantly smaller than infants of women who did not develop preeclampsia and non-smoking women, respectively.     

Maternal serum laeverin (aminopeptidase Q) measured in the first trimester of pregnancy does not predict preeclampsia

Objective: The aim of this study was to compare the laeverin level in maternal serum from first trimester (11–14 weeks) of pregnancy between normal pregnancies and pregnancies that later developed preeclampsia (PE).

Material and methods: This was a case-cohort study. The laeverin concentration was measured in cases with preterm PE (n?=?55), term PE (n?=?95), and a reference group of randomly selected women with normal pregnancy outcome (n?=?200) in stored serum samples collected from the double-test as part of the combined first trimester trisomy 21 screening program. The samples were thawed and analyzed for laeverin. The median gestational age at blood sampling was 77 days (range 57–96 days). Multiple regression analysis was performed to establish a normal median. Concentrations were converted to multiples of the median (MoM) and groups were compared using the Mann–Whitney U-test.

Results: In the reference group, laeverin was significantly correlated with gestational age (r?=?0.18, p?=?.01) and its concentration ranged from 41–393 µg/L. No significant differences in the median laeverin MoM were found between the reference group (1.01 MoM) and cases with preterm PE (0.98 MoM) or term PE (0.96 MoM).

Conclusions: First trimester maternal serum laeverin level cannot be used to predict preeclampsia.     

Maternal cardiovascular profiling in the first trimester of pregnancies complicated with gestation-induced hypertension or fetal growth retardation: a pilot study

Abstract

Objective: In this study, we determine whether maternal cardiovascular (CV) profiling can detect first trimester differences between women with uncomplicated pregnancies (UP) and those who will develop gestational hypertensive disorders (GHD) or normotensive fetal growth retardation (FGR).

Methods: Cardiac, arterial, and venous function were evaluated in 242 pregnant women around 12 weeks of gestation, using impedance cardiography (ICG) and combined electrocardiogram – Doppler ultrasonography. After postnatal determination of gestational outcome, first trimester measurements were compared between groups using Mann–Whitney U test for continuous data or Fisher’s Exact test for categorical variables (SPSS 20.0).

Results: Compared to UP, first trimester aortic flow velocity index [71?±?0.96 versus 61?±?4.91 1/1000/s (p?=?0.016)], acceleration index [133?±?2.25 versus 106?±?11.26 1/100/s² (p?=?0.023)] and Heather index [23.1?±?0.35 versus 19.2?±?1.70?Ω/s² (p?=?0.019)] were lower in GHD pregnancies, and first trimester stroke volume [77?±?1.16 versus 67?±?3.97?ml (p?=?0.033)] and cardiac output [7.3?±?0.10 versus 6.2?±?0.31?l/min (p?=?0.025)] were lower in FGR pregnancies.

Conclusions: Maternal CV function in the first trimester of pregnancy differs between UP and those destined to develop GHD or FGR. This can be assessed with non-invasive maternal CV profiling, opening perspectives for the application of this technique in early gestational screening for GHD and FGR.     

First and second trimester screening for large for gestational age infants

Abstract

Objectives: To find the best early predictor model for fetal growth and large for gestational age (LGA) infants considering clinical, ultrasonographic and biochemical variables.

Method: In 2097 singleton pregnancies at first trimester, we evaluated maternal characteristics, PAPP-A and ß-HCG proteins, fetal nuchal translucency thickness and uterine artery pulsatility index (UtA-PI). At second trimester fetal ultrasound biometry and UtA-PI were then measured. The relationships between birth weight and LGA and maternal characteristics, first and second trimester variables, and all variables combined, were studied. The performance of screening was determined by receiver operating characteristic curves analysis.

Results: Stepwise regression analysis showed that in the prediction of birthweight percentile there were significant contributions from all maternal factors, PAPP-A and Ut-A PI in the first trimester, and fetal biometric variables in the second trimester. Maternal charateristics combined with PAPP-A, β-hCG, fetal NT and uterine artery PI identified 30.2 % LGA (FPR 10%). The combined model reached a sensitivity of 41.2% (FPR 10%) and 56.2% (FPR 20%).

Conclusions: Sensitivity of the screening for LGA improves significantly after addition of second trimester ultrasound measurements to first trimester variables and maternal characteristics.     

Identification of patients at risk for preeclampsia with the use of uterine artery Doppler velocimetry and copeptin

Purpose: To investigate the relationship between maternal copeptin levels and uterine artery Doppler examination and progress of preeclampsia.

Materials and methods: A cross-sectional study was designed with women those were screened at 20?+?0 – 24+ 6 weeks’ gestation between May 2014 and August 2014. The obstetric records of all normotensive women were examined. Uterine artery Doppler velocimetry results and serum copeptin levels were measured. The patients were divided into two groups according to normal (n?=?67) and abnormal uterine artery Doppler (n?=?21) findings.

Results: Maternal age was significantly lower in group 1 (n?=?21, 23.9%) than in group 2 (n=?67, 76.1%) (p?p?=?0.002).

Conclusions: Copeptin levels are significantly higher in patients who develop preeclampsia.     

Perinatal outcomes in uncomplicated late preterm pregnancies with borderline oligohydramnios

Purpose: The purpose of this study is to determine the adverse perinatal outcomes in uncomplicated late preterm pregnancies with borderline oligohydramnios.

Methods: A total of 430 pregnant women with an uncomplicated singleton pregnancy at a gestational age of 34?+?0–36?+?6 weeks were included. Borderline oligohydramnios was defined as an amniotic fluid index (AFI) of 5.1–8?cm, which was measured using the four-quadrant technique. Adverse perinatal outcomes were compared between the borderline and normal AFI groups.

Results: Approximately 107 of the 430 pregnant women were borderline AFI, and 323 were normal AFI. The demographic and obstetric characteristics were similar in both groups. Delivery <37 weeks, cesarean delivery for non-reassuring fetal heart-rate testing, meconium-stained amniotic fluid, Apgar 5?min <7, transient tachypnea of the newborn, respiratory distress syndrome, neonatal intensive care unit, and hyperbilirubinemia were not statistically different between the groups (p?=?.054, p?=?.134, p?=?.749, p?=?0.858, p?=?.703, p?=?.320, p?=?.185, and p?=?.996, respectively). Although gestational age was full-term, induction of labor rates were significantly higher in the borderline AFI group (p?=?.040). In addition, fetal renal artery pulsatility index pulsatility index (PI) was significantly lower in the borderline AFI group than in the normal AFI group (p?=?.014).

Conclusion: Our results indicated that borderline AFI was not a risk for adverse perinatal outcomes in uncomplicated, late preterm pregnancies.     

Prenatal diagnosis of chromosomal polymorphisms: most commonly observed polymorphism on Chromosome 9 have associations with low PAPP-A values*

Introduction: To identify the prevalence and types of fetal chromosomal polymorphisms in pregnant women and to examine possible associations with screening test parameters.

Materials and methods: Fetal chromosomal polymorphism rate was investigated in pregnant women who had been implemented for invasive prenatal test in a tertiary reference center in Thrace Region of Turkey. Fetal chromosomal polymorphisms were determined and their effects on screening tests’ parameters were investigated. Possible differences in the first and second-trimester screening test parameters between women; with fetal chromosomal polymorphism who had screening test results (Group 1) and those with a normal karyotype (Group 2) were evaluated.

Results: Fetal chromosomal polymorphism prevalence was 5.3% (n?=?101). The most common polymorphisms were identified on chromosome 9, 1, and 16 [54.5% (n?=?55); 8.9% (n?=?9), and 6.9% (n?=?7), respectively]. The most common polymorphic variant was 9qh+ (n?=?23; 22.8%). Among the screening test parameters, significantly lower pregnancy-associated plasma protein-A (PAPP-A) (p?=?.028) and higher unconjugated estriol (uE3) (p?=?.019) values were found in Group 1. In patients having fetuses with polymorphic variants on chromosome 9, a significantly lower PAPP-A values were observed compared to women with other fetal polymorphic variants (p?=?.048) or women having fetuses with normal karyotype (p?=?.007).

Conclusions: Lower PAPP-A and higher uE3 levels were observed in women having fetuses with chromosomal polymorphisms, which might affect screening test results. Lower PAPP-A levels were apparent in women having fetuses with polymorphism on chromosome 9.     

The agonistic autoantibodies to the angiotensin II type 1 receptor in pregnancies complicated by hypertensive disorders

Introduction: The etiology and pathogenesis of pregnancy-related hypertensive disorders is complex and multifactorial. The aim of our study is the investigation of the differences in the autoantibodies against angiotensin II type 1 receptor (AT1-AA) titers among pregnant patients with chronic hypertension, gestational hypertension, and preeclampsia compared to the healthy pregnant women.

Patients and methods: We created three study groups (preeclampsia [n?=?16], chronic hypertension [n?=?13], gestational hypertension [n?=?17]) and the control group consisting of 17 healthy pregnant women. Every compared group was matched for mother’s age, parity, prepregnancy BMI, and gestational age at time of recruitment into study. The autoantibodies titer were assessed using commercially available ELISA kit.

Results: We found a statistically higher AT1-AA titer in the group of patients with gestational hypertension (GH) and preeclampsia (PE) compared to healthy normotensive pregnant women (median 9.6 versus 7.8?ng/ml, p?=?.01 and 10.9?ng/ml versus 7.8?ng/ml, p?=?.02, respectively). There was no correlation between blood pressure values and AT1-AA titer in any group. We found no correlation in group with preeclampsia between urinary protein excretion and AT1-AA titer (p?=?.23, R?=?0.32).

Conclusions: We assume that pregnancy-related hypertensive disorders might be autoimmune diseases and AT1-AA contribute to the pathophysiology of the disease. Our study may have some therapeutic implications and shows the necessity of new research into the mechanisms involved in the production of AT1-AA. Such investigations might enable to inhibit the formation of these autoantibodies or elaborate another method for AT1-AA removal.