Marek Pietryga

Threshold values of maternal blood glucose in early diabetic pregnancy--prediction of fetal malformations.

Background.  The prevention of congenital malformations in the newborns of diabetic mothers still constitutes one of the main problems in this group of patients.

Abnormal uterine Doppler is related to vasculopathy in pregestational diabetes mellitus

Background— The aim of the study was to evaluate the relation between maternal placental Doppler velocimetry, levels of the maternal glucose, and clinical signs of vasculopathy in pregnancy complicated by pregestational diabetes mellitus. Methods and Results— A retrospective study of 155 pregestational diabetic women between the 22nd and 40th weeks of pregnancy, categorized in White classification as B, 49; C, 40; D, 22; R, 20; F, 5; and RIF, 19. Cases in classes R, F, and R/F were defined as having vasculopathy. Doppler velocimetry of umbilical and uterine arteries was evaluated for vascular impedance, both in terms of pulsatility index (PI) for both arteries and a notch in early diastole in the uterine arteries. The last examination before delivery was used for analysis. Increased umbilical artery PI was seen in 19 and a uterine artery abnormality in 45 cases. There was a correlation between levels of HbAlc and increased vascular impedance in the uterine and umbilical arteries. Signs of increased uterine artery vascular impedances were significantly related to pregestational vasculopathy. In cases of small-for-gestational-age newborn infants, PI was significantly increased in uterine and umbilical arteries. Furthermore, PI in macrosomic fetuses was significantly lower than in normal infants. Abnormal uterine artery Doppler was also strongly related to adverse outcome. Conclusions— Abnormal uterine artery Doppler is related to pregestational vasculopathy and adverse outcome of pregnancy. The results suggest that the uterine arteries are affected in women with clinical signs of pregestational vasculopathy. This may influence placental perfusion and fetal well-being.

Fetal and maternal Doppler velocimetry and cytokines in high-risk pregnancy

Abstract Objective: Fetal hypoxia and preterm delivery are reported to be strongly associated with brain damage and neurodevelopmental delay. Doppler signs of fetal brain sparing have been described during chronic hypoxia, but whether they are related to brain damage is unknown. The aim of this study was to evaluate if markers of tissue injury, i.e., tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) are related to signs of increased perinatal vascular impedance and/or fetal brain sparing in high-risk pregnancies. Study design: TNF-α and IL-6 levels were evaluated in maternal blood serum of 67 high-risk pregnancies. Serum samples were taken at the time of umbilical, middle cerebral artery and uterine artery Doppler velocimetry examination. The values for TNF-α and IL-6 were correlated with reference median values obtained with gestational age in the form of a Z-score. Results: TNF-α levels showed values within the normal range in only four cases. IL-6 values were found normal in 14 cases. The Z-score for mean middle cerebral artery pulsatility index (PI) showed a significant correlation to TNF-α and IL-6 levels, P<0.0001 and P<0.003, respectively. This might suggest a strong correlation between signs of fetal brain sparing and increased maternal serum TNF-α and IL-6 levels. Abnormal uterine artery PI and the presence of a “notch” were also highly significantly related to TNF-α and IL-6 levels, which were nearly two-fold higher compared to normal uterine artery blood flow and the absence of a “notch”. Abnormal cerebro/placental ratios showed significant correlations to TNF-α and IL-6 levels. Conclusion: The present results suggest a strong correlation between levels of TNF-α and IL-6 not only for signs of fetal brain sparing, but also for uteroplacental blood flow. This finding supports the role of tissue injury in cases of fetal brain sparing, but whether this is a reflection of brain damage or secondary to placental pathology needs further evaluation.

Maternal serum placental growth factor and fetal SGA in pregnancy complicated by type 1 diabetes mellitus

Abstract Aim: To analyze the role of maternal placental growth factor (PlGF) in the prediction of small for gestational age (SGA) birth weight in pregnancy complicated by type 1 diabetes mellitus (T1DM). Methods: A prospective observational study on 59 normotensive T1DM pregnant women, assessing maternal PlGF concentrations between the 10th–14th and 22nd–25th weeks of gestation. Results: Number of SGA vs. non-SGA newborns was 11 (18.6%) vs. 48 (81.4%), respectively. First trimester PlGF serum concentrations (pg/mL) were similar between SGA vs. non-SGA groups [data given as median (interquartile range)]: 65.5 (35.58–159.20) vs. 68.23 (11.59–150.03), respectively; P=0.44. A trend for lower PlGF concentrations was observed in the second trimester in the SGA vs. non-SGA group: 63.34 (12.79–119.16) vs. 116.75 (33.93–235.82); P=0.07. In the SGA group, PlGF concentrations did not differ between the first and the second trimester: 65.5 (35.58–159.20) vs. 63.34 (12.79–119.16), respectively; P=0.36. In the non-SGA group, PlGF concentrations were significantly higher at the gestational age of 22–25 weeks compared to 10–14 weeks [116.75 (33.93–235.82) vs. 68.23 (11.59–150.03); P=0.03). Conclusions: Decreased PlGF serum concentration in mid-pregnancy, as well as a lack of physiological increase in PlGF levels between early and mid-gestation, may precede development of SGA in women with T1DM.

Concentration of chemokines in peripheral blood in first trimester of diabetic pregnancy

Background. Several types of regulators (i.e. chemokines and metalloproteinases) are considered to play a crucial role in pregnancy by local modulation of the immune system at the level of peripheral leukocytes. The aim of this study was to determine whether changes in chemokines (interferon‐gamma‐inducible protein (IP‐10), monocyte chemotactic peptide‐1 (MCP‐1), cytokines regulated upon activation normal T cell expressed and secreted (RANTES) and matrix metalloproteinase‐9 (MMP‐9)) concentrations in diabetic patients could affect the course of pregnancy. Methods. The study group consisted of 65 diabetics in the first trimester of pregnancy. Some 47 pregnancies were successfully continued to delivery, 18 were terminated with spontaneous miscarriages. Twenty healthy women matched for gestational age served as a control group. Results. Glycated haemoglobin (HbA1C), vascular complications and lipoproteins (cholesterol, HDL‐cholesterol, low density lipoprotein (LDL)‐cholesterol and triglicerides) concentrations in maternal blood did not influence the chemokines concentrations. Lower RANTES level and higher MMP‐9 concentrations were found in diabetic women. MCP‐1 and RANTES levels differed significantly between pregnancies with good and poor perinatal outcome. A logistic regression model revealed that not only duration of diabetes, age of patients, HbA1C and insulin requirements, but also MMP‐9, RANTES, MCP‐1 and LDL‐cholesterol levels seem to be involved in first trimester metabolism. Conclusions. Our results suggest the possible role of chemokines in early pregnancy development, especially in well‐controlled diabetic patients, when hyperglycaemia is unlikely to be the main reason for an unfavourable outcome. Our results show that MCP‐1 and RANTES might serve as predictive factors for an unfavourable outcome in diabetic pregnancy, whereas MMP‐9 seems to be a marker of immunological changes related to mild hyperglycaemia. However, the open question of how the modulation of chemokines concentrations might be applied to prevent miscarriage in diabetic patients remains.

OC204: Placental Doppler velocimetry in pregnancies complicated by pre‐gestation diabetes mellitus

Introduction: Cerebral hypoxic and ischaemic changes have been implicated in the aetiology of the characteristic seizures that signify the end-progression of pre-eclampsia. Until recently, neuronal dysfunction secondary to ischaemic causes or functional impairment has been difficult to study in adult humans due to the relative inaccessibility of the cerebral circulation. Doppler ultrasound now provides a means of assessing the normalcy of blood flow velocity, and has demonstrated consistency in the evaluation of severe vascular stenosis 1. Differences in systemic peripheral resistance between normotensive and preeclamptic pregnant women have also been demonstrated using calibrated carotid pulse tracings 2. Objective: To measure peak Carotid blood volume flow in a group of prospective mothers at high-risk of pregnancy hypertension and preeclampsia following uterine artery Doppler screening. Methods: Carotid artery velocimetric and blood volume flow profiles were evaluated using standardised techniques in 31 pregnant women at 24–28 weeks gestation. Results: Blood volume flow measurement showed a 75% sensitivity for elevated blood pressure in later pregnancy, 60% sensitivity for the development of preeclampsia and 100% sensitivity for preterm preeclampsia. Conclusion: The measurement of blood volume flow in the Carotid circulation in high-risk pregnant women merits further investigation as a second-tier screening test for pregnancy hypertension and preeclampsia.

Chorionic thickness and PlGF concentrations as early predictors of small-for-gestational age birth weight in a low risk population

OBJECTIVES SGA is associated with higher incidence of postnatal complications, including suboptimal neurodevelopment and increased cardiovascular risk. Screening for SGA, carried out at 11-13 (+ 6d) gestational weeks enables to reduce or completely eliminate the above mentioned complications. The aim of this study was to assess the correlation between chorionic thickness, concentration of PIGF protein and foetal birth weight in a single low-risk pregnancy. MATERIAL AND METHODS The study included 76 patients at 11-13 (+ 6d) gestational weeks, monitored throughout preg-nancy. Ultrasound examinations identified the location and thickness of the chorion by measuring it in its central part at its widest point in a sagittal section. Additionally, at each visit venous blood was collected to determine the level of PlGF, PAPP-A, and BhCG. RESULTS A significant positive correlation (r = 0.37) was found between the foetal weight and chorionic thickness. This correlation was affected by the location of the chorion and a significant negative correlation was observed between the level of PLGF, FHR, weight and length of the newborn. Maternal early-pregnancy BMI did not affect neonatal weight and body length, FHR, chorionic thickness, and the levels of PlGF, PAPP-A, and BhCG. CONCLUSIONS The preliminary analysis indicates an association between chorionic thickness assessed during ultrasound at 11-13 (+ 6d) gestational weeks, PIGF levels assayed at the same time and birth weight. Increasing chorion thickness was accompanied by increasing foetal birth weight. PlGF level showed an inversely proportional effect on the foetal weight. This correlation was significant for the posterior location of the chorion.

Selected oxidative stress biomarkers in antenatal diagnosis as 11–14 gestational weeks

Abstract The primary objective in modern obstetrics and prenatal diagnosis is to predict risks of congenital abnormalities. The aim of the research was to assess the correlation between selected oxidative stress biomarkers with the risk of foetal chromosomal aberration evaluated at the first trimester screening. A series of studies show that balanced free radical activity and oxidative homeostasis are essential for proper bodily growth and function. Reactive oxygen species (ROS) may be one of the factors associated with disruption of cell cycle and tissue development, thus leading to developmental abnormalities. Thats why its so important to examine connection between level of oxidative stress and congenital abnormalities. Using ultrasonography examinations between 11–13+6d gestational weeks combined with serum levels of pregnancy associated plasma protein A and human chorionic gonadotropin and spectrophotometric analysis of oxidative stress markers such as glutathione (GSH), S‐transferase, S‐nitrosothiols (RSNO), trolox equivalent antioxidant capacity (TEAC), protein and nitrites we tried to find correlation between birth defects and oxidative stress status. In conclusion, our analysis suggests that elevated maternal serum levels of protein, S‐transferase and TEAC as well as decreased maternal serum levels of GSH and protein correlated with the risk of chromosomal aberrations and congenital developmental defects in a foetus. Graphical abstract Figure. No Caption available. HighlightsValuable early prenatal diagnosis of congenital malformations is necessary nowadays.The importance of discovering new opportunities for non‐invasive prenatal screening.Prenatal test were performed on 76 pregnant women.Patients were divided into groups with high and low risks of chromosomal aberrations.Measurement of oxidative stress using liquid chromatography‐tandem mass spectrometry.Levels of elected oxidative stress markers could be significant for foetal diagnosis.

OC51: Chorion volume measurements in 3D‐USG between the 10th and 14th week of gestation in normal pregnancy

Results: Four variables (patient age, EGA by LMP, endometrial thickness and βHCG) were found to be significant in the prediction of normal IUP (ROC curve c = 0.86 and Hosmer–Lemeshow Chisquare analysis P = 0.74). As the patient’s age, EGA and βHCG increased, the likelihood of a normal IUP decreased. As the endometrial thickness increased, the more likely the outcome of a normal IUP. For each millimeter increase in endometrial thickness, the odds increased by 27% that the patient would have a normal IUP. With the use of this model, the outcome of 89.1% of all subjects was correctly identified.

P11.01: Diagnostic accuracy of IOTA ADNEX and IOTA LR2 model compared with subjective assessment ( SA) in differentiating benign and malignant ovarian masses

Objectives The aim of this research was to systematically examine the placenta in congenital anomalies. Methods: The placental pathological section was examined in 217 cases with congenital fetal anomalies including 87 cases with congenital heart diseases, 41 cases facial abnormalities, genitourinary abnormalities, 62 cases with neurologic abnormalities. Results: Placental infarction or villus degeneration was observed in 4 cases and chorangiosis was found in 12 cases with congenital heart diseases corresponding to the overall placental disease rate being 16.1%; chorangiosis was observed in 5 cases with facial abnormalities corresponding to the placental disease rate being 12.1%; chorangiosis was found in 2 cases with genitourinary abnormalities corresponding to the placental disease rate being 7.4%. In addition, chorangiosis was observed in 10 cases with neurologic abnormalities corresponding to the placental disease rate being 14.5%. Conclusions: Relative to other system abnormalities the placental disease rate was more higher in cases with congenital fetal heart anomalies.