Screening for Preeclampsia and Fetal Growth Restriction in the First Trimester in Women without Chronic Hypertension.

BACKGROUND: Nowadays, it is possible to identify a group at increased risk of preeclampsia (PE) and fetal growth restriction (FGR) using the principles of the Fetal Medicine Foundation (FMF). It has been established for several years that acetylsalicylic acid (ASA) reduces the incidence of PE and FGR in high-risk populations. This study aimed to evaluate the implementation of ASA use after the first-trimester screening in a Polish population without chronic hypertension, as well as its impact on perinatal complications. MATERIAL AND METHODS: A total of 874 patients were enrolled in the study during the first-trimester ultrasound examination. The risk of PE and FGR was assessed according to the FMF guidelines, which include the maternal history, mean arterial pressure (MAP), uterine artery pulsatility index (UtPI), pregnancy-associated plasma protein A (PAPP-A) and placental growth factor (PLGF). Among patients with a risk higher than >1:100, ASA was administered at a dose of 150 mg. Perinatal outcomes were assessed among the different groups. RESULTS: When comparing women in the high-risk group with those in the low-risk group, a statistically significantly higher risk of pregnancy complications was observed in the high-risk group. These complications included pregnancy-induced hypertension (PIH) (OR 3.6 (1.9-7)), any PE (OR 7.8 (3-20)), late-onset PE (OR 8.5 (3.3-22.4)), FGR or small for gestational age (SGA) (OR 4.8 (2.5-9.2)), and gestational diabetes mellitus type 1 (GDM1) (OR 2.4 (1.4-4.2)). The pregnancies in the high-risk group were more likely to end with a cesarean section (OR 1.9 (1.2-3.1)), while the newborns had significantly lower weights (<10 pc (OR 2.9 (1.2-6.9)), <3 pc (OR 10.2 (2.5-41.7))). CONCLUSIONS: The first-trimester screening test for PE and FGR is a necessary and effective tool in identifying high-risk pregnancies. ASA prophylaxis among high-risk patients may have the most beneficial effect. Furthermore, this screening tool may significantly reduce the incidence of early-onset PE (eo-PE).

Low-Dose Aspirin after ASPRE-More Questions Than Answers? Current International Approach after PE Screening in the First Trimester.

Preeclampsia (PE) is a multi-factorial disorder of pregnancy, and it continues to be one of the leading causes of fetal and maternal morbidity and mortality worldwide. Aspirin is universally recommended for high-risk women to reduce preeclampsia risk. The purpose of this review is to summarize the recommendations of various scientific societies on predicting preeclampsia and their indications for the inclusion of acetylsalicylic acid (ASA) prophylaxis. Fourteen guidelines were compared. The recommended dose, screening method, and gestational age at the start of the test vary depending on the recommendation. The societies are inclined to recommend using increasingly higher doses (>75 mg) of ASA, with many encouraging doses from 100 mg upward. Most societies indicate that the optimal time for implementing aspirin is prior to 16 weeks' gestation. Following the publication of the Aspirin for Evidence-Based Preeclampsia Prevention (ASPRE) trial results and other papers evaluating the Fetal Medicine Foundation (FMF) screening model, a large number of societies have changed their recommendations from those based on risk factors alone to the ones based on the risk assessment proposed by the FMF. This allows for the detection of a high-risk pregnancy population in whom aspirin will be remarkably effective in preventing preterm PE, thereby decreasing maternal and fetal morbidity.

Assessment of Cadmium (Cd) and Lead (Pb) Blood Concentration on the Risk of Endometrial Cancer.

BACKGROUND: Cadmium (Cd) and lead (Pb) are heavy metals with carcinogenic potential. Their increased concentration has been correlated with a risk of malignancies, including breast, lung, kidney, gastrointestinal, and gynecological cancers. Most of the studies have evaluated tissue heavy metal concentration. To the best of our knowledge, this is the first study to evaluate blood Cd and lead levels in different uterine pathologies and the risk of endometrial cancer. METHODS: This study included 110 patients with a histopathological diagnosis of endometrial cancer, endometrial polyps, endometrial hyperplasia, uterine myoma, and normal endometrium. The patients included in the study were assessed in terms of their endometrial cancer risk factors and blood heavy metal levels. The analysis was conducted using inductively coupled plasma optical emission spectrometry. RESULTS: There was a significant difference in the Cd and Cd/Pb ratio among the different groups of patients (p = 0.002), with higher a median Cd concentration among the endometrial cancer patients. The differences in Pb concentration were not significant (p = 0.717). There were also no differences in the Cd and Pb concentrations based on the patients' menopausal status nor BMI index. The univariate logistic regression showed a blood cadmium concentration above the median to be associated with an increased risk of endometrial cancer (OR = 5.25; 95% CI 1.56, 17.72). No significant associations were observed between the Pb concentration or Cd/Pb ratio and endometrial cancer risk. CONCLUSION: The concentration of Cd varies in patients diagnosed with different uterine pathologies. Increased blood cadmium concentration seems to be a risk factor for endometrial studies. Further research on greater populations, accounting for environmental and lifestyle heavy metal exposure, is required to validate our findings.

An Assessment of MT1A (rs11076161), MT2A (rs28366003) and MT1L (rs10636) Gene Polymorphisms and MT2 Concentration in Women with Endometrial Pathologies.

Several studies have indicated a relationship between metallothionein (MT) polymorphisms and the development of different pathologies, including neoplastic diseases. However, no studies thus far have been conducted on the influence of MT polymorphisms and the development of endometrial lesions, including endometrial cancer. This study included 140 patients with normal endometrial tissue, endometrial polyps, uterine myomas and endometrial cancer. The tissue MT2 concentration was determined using the ELISA method. MT1A, MT2A and MT1L polymorphisms were analyzed using TaqMan real-time PCR genotyping assays. We found no statistical difference between the tissue MT2 concentration in patients with EC vs. benign endometrium (p = 0.579). However, tissue MT2 concentration was significantly different between uterine fibromas and normal endometrial tissue samples (p = 0.019). Menopause status did not influence the tissue MT2 concentration (p = 0.282). There were no significant associations between the prevalence of MT1A, MT2A and MT1L polymorphisms and MT2 concentration. The age, menopausal status, and diabetes status of patients were identified as EC risk factors.

Analysis of Fecal Short-Chain Fatty Acids (SCFAs) in Healthy Children during the First Two Years of Life: An Observational Prospective Cohort Study.

Short-chain fatty acids (SCFAs) are important metabolites of the gut microbiota. The aim is to analyze the influence of perinatal factors, which can affect the gut microbiota, on the concentrations of fecal SCFAs over the first two years of life. Gas chromatography was used to analyze SCFA in a total of 456 fecal samples from 86 children. Total SCFA concentrations increased until 12 months and stabilized after that. Antibiotic treatment during pregnancy was associated with an increase in acetic acid, propionic acid and total SCFA in meconium and a decrease in the same SCFAs at 6 months. Butyric acid was increased after Caesarean delivery until 1 month. In formula-fed children, propionic acid (at 1 month) and butyric acid and total SCFA (at 12 months) were increased. Acetic and linear butyric acids and total SCFAs were also increased at 12 months in children born vaginally that were also formula-fed. Higher butyric acid was observed in children of mothers with normal pre-pregnancy weight and adequate weight gain during pregnancy. Butyric acid was also elevated in 6-month-old infants with a higher body weight (≥85th percentile). Acetic acid concentrations were significantly higher in 2-year-old females vs. males. We conclude that perinatal factors are linked to changes in fecal SCFAs and further long-term epidemiological studies are warranted.

Comparison of Laparoscopic and Open Radical Cystectomy for Muscle-Invasive Bladder Cancer.

The goal of the study was to compare laparoscopic and open radical cystectomy in treatment of muscle-invasive bladder cancer in the Department of Urology and Oncological Urology PUM in Szczecin. A total of 78 patients in the study group underwent laparoscopic cystectomy between 2016−2018, and 81 patients from the control group had open cystectomy between 2014−2016. Both groups were comparable in terms of age, stage, and concomitant diseases. The 3 year overall survival was comparable in both groups (37.7% for laparoscopy and 44.4% for open, p = 0.64). There was no difference in positive surgical margin rate. Lymph node yield during cystectomy was higher in open cystectomy (14 vs. 11.5, p = 0.001). Post-operative blood loss and transfusion rates were lower in laparoscopic cystectomy. Decrease in hemoglobin level was lower in laparoscopy (0.9 mmol/L, p < 0.001). Intraoperative transfusion rate was 11.8% in laparoscopy vs. 34.8% in open cystectomy (p = 0.002). Operation time, duration of hospitalisation, and time to full oral alimentation were comparable in both groups. Patients with BMI > 30 kg/m2 and those with pT3-T4 cancer in the laparoscopy group had less septic complications post-operatively. Patients with ASA score ≥ 3 from the laparoscopy group had fewer reoperations due to ileus. Laparoscopic cystectomy is less invasive and offers similar oncological outcomes to the open method. Patients benefit from less tissue trauma, less blood loss, and faster recovery. The presented results, as well as other publications, should encourage a wider use of this procedure in everyday urological practice.

Birth Weight < 3rd Percentile Prediction Using Additional Biochemical Markers-The Uric Acid Level and Angiogenesis Markers (sFlt-1, PlGF)-An Exploratory Study.

(1) Aim: Ultrasound is the gold standard for assessing fetal growth disorders. The relationship between high sFlt-1/PlGF scores and LBW (low birth weight) was described. In this study, we attempted to assess whether uric acid could be used as a secondary marker in estimating the pregnancy risk associated with LBW. (2) Material and methods: 665 pregnant women with a suspected or confirmed form of placental insufficiency were enrolled. In each of the patients, sFlt-1 and PlGF and uric acid levels were determined. Patients were divided into two groups according to birth weight below and above the third percentile for the given gestational age with the criteria of the neonatal definition of FGR (fetal growth restriction). (3) Results: A significant negative correlation between neonatal birth weight and the uric acid level across the entire study group was observed. We found a significant negative correlation between neonatal birth weight and the uric acid level with birth weights < 3rd percentile. (4) Conclusions: There is a significant link between the uric acid concentration and LBW in the group with placental insufficiency. Uric acid can improve the prediction of LBW. An algorithm for LBW prognosis that makes use of biophysical (ultrasound) and biochemical (uric acid level, angiogenesis markers) parameters yields better results than using these parameters separately from each other.

Analysis of the Influence of Pre-Pregnancy BMI and Weight Gain during Pregnancy on the Weight of Healthy Children during the First 2 Years of Life: A Prospective Study.

BACKGROUND: Increased pre-pregnancy maternal BMI (pBMI) and gestational weight gain (GWG) have been found to increase infants' birthweight and result in the programming of child weight and impact its later weight gain. AIM: To assess the impact of pBMI and GWG on the weight of children from birth to 2 years of age and over the duration of breastfeeding. METHODS: Single Centre observational prospective longitudinal cohort study. Data were collected from medical records, and medical history. The analysis of multiple linear and mixed models was involved. FINDINGS: 20% of females were overweight, while 13% were obese before the pregnancy. An overall model, including gender and smoking, indicated a significant impact of pBMI category on a child's birth mass (p = 0.01). The GWG category affected a child's birth weight (p = 0.018, Effect size 0.41). pBMI did not affect the breastfeeding duration. CONCLUSION: pBMI and GWG correlate with birth weight and weight in neonatal period, however they become insignificant in later childhood. Weight assessment methods among children aged up to two years of age require standardization. Maternal weight before the pregnancy nor the weight gain during the pregnancy do not influence the length of breastfeeding. The biggest limitation was the small sample size and the failure to account for weight gain per trimester of pregnancy. Further research on a larger population should be continued.

Adverse Neonatal Outcome of Pregnancies Complicated by Preeclampsia.

Despite many available treatments, infants born to preeclamptic mothers continue to pose a serious clinical problem. The present study focuses on the evaluation of infants born to preeclamptic mothers for the occurrence of early-onset complications and attempts to link the clinical status of such infants to the angiogenesis markers in maternal blood (sFlt-1, PlGF). The study included 77 newborns and their mothers diagnosed with preeclampsia. The infants were assessed for their perinatal outcomes, with an emphasis on adverse neonatal outcomes such us infections, RDS, PDA, NEC, IVH, ROP, or BPD during the hospitalization period. The cutoff point was established using the ROC curve for the occurrence of any adverse neonatal outcome and it was 204 for the sFlt-1/PlGF and 32 birth week with AOC 0.644 and 0.91, respectively. The newborns born to mothers with high ratios had longer hospitalization times and, generally, were more frequently diagnosed with any of the aforementioned adverse neonatal outcomes. Also, the neonates born prior to or at 32 wkGA with higher sFlt-1/PlGF ratios were statistically significantly more common to be diagnosed with any of the adverse neonatal outcomes compared to those with lower ratio born prior to or at 32 wkGA. The sFlt-1/PlGF ratio can be a useful tool in predicting short-term adverse neonatal outcomes. Infants born after a full 33 weeks gestation developed almost no severe neonatal complications. Appropriate screening and preventive healthcare for preeclampsia can contribute significantly to reducing the incidence of neonatal complications.

Breastfeeding Affects Concentration of Faecal Short Chain Fatty Acids During the First Year of Life: Results of the Systematic Review and Meta-Analysis.

Short chain fatty acids (SCFAs) are important metabolites of the gut microbiota. It has been shown that the microbiota and its metabolic activity in children are highly influenced by the type of diet and age. Our aim was to analyse the concentration of fecal SCFAs over two years of life and to evaluate the influence of feeding method on the content of these compounds in feces. We searched PubMed/MEDLINE/Embase/Ebsco/Cinahl/Web of Science from the database inception to 02/23/2021 without language restriction for observational studies that included an analysis of the concentration of fecal SCFAs in healthy children up to 3 years of age. The primary outcome measures-mean concentrations-were calculated. We performed a random-effects meta-analysis of outcomes for which ≥2 studies provided data. A subgroup analysis was related to the type of feeding (breast milk vs. formula vs. mixed feeding) and the time of analysis (time after birth). The initial search yielded 536 hits. We reviewed 79 full-text articles and finally included 41 studies (n = 2,457 SCFA analyses) in the meta-analysis. We found that concentrations of propionate and butyrate differed significantly in breastfed infants with respect to time after birth. In infants artificially fed up to 1 month of age, the concentration of propionic acid, butyric acid, and all other SCFAs is higher, and acetic acid is lower. At 1-3 months of age, a higher concentration of only propionic acid was observed. At the age of 3-6 months, artificial feeding leads to a higher concentration of butyric acid and the sum of SCFAs. We concluded that the type of feeding influences the content of SCFAs in feces in the first months of life. However, there is a need for long-term evaluation of the impact of the observed differences on health later in life and for standardization of analytical methods and procedures for the study of SCFAs in young children. These data will be of great help to other researchers in analyzing the relationships between fecal SCFAs and various physiologic and pathologic conditions in early life and possibly their impact on health in adulthood.

Effectiveness of Different Algorithms and Cut-off Value in Preeclampsia First Trimester Screening.

Results: For the cut-off point >1 : 150, 86 women at an increased risk of eo-PE using algorithm 1 were identified. Of these 86 patients, 83 (96%) were identified using algorithm 2, 62 (72%) using algorithm 3, and 60 (69%) using algorithm 4. In addition, it was demonstrated that between 21% and 29% of women at a low risk of eo-PE could be given acetylsalicylic acid if a screening test was used that did not account for PlGF. Conclusions: In order to provide the highest level of health care to pregnant women, it is extremely important that full screening for eo-PE should be ensured. The cheapest algorithm based only on MAP and UtPI resulted in our patients being unnecessarily exposed to complications.

First-Trimester Fetal Hepatic Artery Examination for Adverse Outcome Prediction.

OBJECTIVE: To assess whether there are differences in first-trimester fetal hepatic artery flows depending on pregnancy outcomes. METHODS: The prospective study conducted in 2012-2020 included 1841 fetuses from singleton pregnancies assessed during the routine first-trimester ultrasound examination (between 11- and 14-weeks' gestation). Also, each fetus was examined to determine their hepatic artery flows by measuring the artery's pulsatility index (HA-PI) and peak systolic velocity (HA-PSV). RESULTS: The fetuses that were classified as belonging to the adverse pregnancy outcome group (those with karyotype abnormalities and congenital heart defects) were characterized by a significantly lower HA-PI and higher HA-PSV compared to normal outcome fetuses. CONCLUSION: Hepatic artery flow assessment proved to be a very useful tool in predicting adverse pregnancy outcomes, in particular karyotype abnormalities and congenital heart defects.

PPARγ-A Factor Linking Metabolically Unhealthy Obesity with Placental Pathologies.

Obesity is a known factor in the development of preeclampsia. This paper links adipose tissue pathologies with aberrant placental development and the resulting preeclampsia. PPARγ, a transcription factor from the ligand-activated nuclear hormone receptor family, appears to be one common aspect of both pathologies. It is the master regulator of adipogenesis in humans. At the same time, its aberrantly low activity has been observed in placental pathologies. Overweight and obesity are very serious health problems worldwide. They have negative effects on the overall mortality rate. Very importantly, they are also conducive to diseases linked to impaired placental development, including preeclampsia. More and more people in Europe are suffering from overweight (35.2%) and obesity (16%) (EUROSTAT 2021 data), some of them young women planning pregnancy. As a result, we will be increasingly encountering obese pregnant women with a considerable risk of placental development disorders, including preeclampsia. An appreciation of the mechanisms shared by these two conditions may assist in their prevention and treatment. Clearly, it should not be forgotten that health education concerning the need for a proper diet and physical activity is of utmost importance here.

Analysis of Faecal Zonulin and Calprotectin Concentrations in Healthy Children During the First Two Years of Life. An Observational Prospective Cohort Study.

Factors affecting the intestinal-barrier permeability of newborns, such as body mass index (BMI), nutrition and antibiotics, are assumed to affect intestinal-barrier permeability in the first two years of life. This study assessed 100 healthy, full-term newborns to 24 months old. Faecal zonulin/calprotectin concentrations were measured at 1, 6, 12, 24 months as gut-permeability markers. Zonulin concentrations increased between 1 and 12 months (medians: 114.41, 223.7 ng/mL; respectively), whereas calprotectin concentrations decreased between one and six months (medians: 149. 29, 109.28 µg/mL); both then stabilized (24 months: 256.9 ng/mL zonulin; 59.5 µg/mL calprotectin). In individual children, high levels at one month gave high levels at older ages (correlations: calprotectin: between 1 and 6 or 12 months: correlation coefficient (R) = 0.33, statistical significance (p) = 0.0095; R = 0.28, p = 0.032; zonulin: between 1 and 24 months: R = 0.32; p = 0.022, respectively). Parameters which gave marker increases: antibiotics during pregnancy (calprotectin; six months: by 80%, p = 0.038; 12 months: by 48%, p = 0.028); vaginal birth (calprotectin: 6 months: by 140%, p = 0.005); and > 5.7 pregnancy-BMI increase (zonulin: 12 months: by 74%, p = 0.049). Conclusions: "Closure of the intestines" is spread over time and begins between the sixth and twelfth month of life. Antibiotic therapy, BMI increase > 5.7 during pregnancy and vaginal birth are associated with increased intestinal permeability during the first two years of life. Stool zonulin and calprotectin concentrations were much higher compared with previous measurements at older ages; clinical interpretation and validation are needed (no health associations found).

The temporal link between prenatal steroid therapy and labor.

Prematurity has been one of the greatest challenges faced by perinatal medicine for many years. The recommended therapy for women with threatened preterm labor at 24 to 34 weeks' gestation is a single course of glucocorticoids. The greatest benefits have been proven when labor occurs at least 24 hours, but no later than 7 days after steroid administration. Applied treatment is not without influence on neonates' development. AIM: The aim of this study is to analyze the time between the administration of a course of glucocorticoids to patients with threatened preterm labor between 24 and 34 weeks of gestation and labor. MATERIALS AND METHODS: 459 deliveries by patients between 24 and 34 weeks' gestation who had received betamethasone (two 12 mg doses) or dexamethasone (four 6 mg doses) were analyzed. Their indications for glucocorticoid therapy were divided into four categories: the signs of threatened preterm labor, premature rupture of membranes, iatrogenic prematurity and cervical incompetence. The neonates (n=530) were divided into two main groups: group 1 of those born within the first 7 days (n1=127) and group 2 of those born more than 7 days (n2=403) after the glucocorticoids therapy. Statistical analysis was performed using the Statistica 13.3 software with calculations performed using the Mann- Whitney U and χ2 tests, assuming the level of statistical significance of <0.05 (p<0.05). RESULTS: The neonates born within the first 7 days after the glucocorticoid therapy accounted for 23.96% (127 children). The average time of delay between the course of glucocorticoids and labor was 33 days, with the longest interval being 116 days. The most common indications for glucocorticoids were iatrogenic causes in group 1 (35.40%) and the signs of threatened preterm labor (67.63%) in group 2. CONCLUSIONS: The percentage of births at the recommended time after steroidotherapy (not later than 7 days) was lower than expected. The prenatal steroid therapy qualification methods, should be reanalyzed, especially when signs of preterm labor are observed.

The sFlt-1/PlGF ratio values within the <38, 38-85 and >85 brackets as compared to perinatal outcomes.

Background Soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) are used as markers of preeclampsia. The aim of this paper was to assess the correlations between the sFlt-1/PlGF ratio values within the <38, 38-85 and >85 brackets and perinatal outcomes in pregnancies that require determination of these markers. Methods A total of 927 pregnant patients between 18 and 41 weeks' gestation suspected of or confirmed with any form of placental insufficiency (preeclampsia, intrauterine growth restriction [IUGR], gestational hypertension, HELLP syndrome, placental abruption) were included in the study. In each of the patients, the sFlt-1/PlGF ratio was calculated. Patients were divided into three groups according to the sFlt-1/PlGF ratio brackets of <38, 38-85 and >85. Results Significantly worse perinatal outcomes were found in the sFlt-1/PlGF >85 group, primarily with lower cord blood pH, neonatal birth weight and shorter duration of gestation. Statistically significant correlations between the values of these markers and the abovementioned perinatal effects were found. Conclusion An sFlt-1/PlGF ratio value of >85 suggests that either preeclampsia or one of the other placental insufficiency forms may occur, which is associated with lower cord blood pH, newborn weight and earlier delivery. Determining the disordered angiogenesis markers and calculating the sFlt-1/PlGF ratio in pregnancies complicated by placental insufficiency may lead to better diagnosis, therapeutic decisions and better perinatal outcomes.

sFlt-1/PlGF and Doppler ultrasound parameters in SGA pregnancies with confirmed neonatal birth weight below 10th percentile.

We explored whether there was a relationship between the sFlt-1/PlGF ratio in early-late and late-onset SGA patients and whether it is associated with neonatal birth weight. MATERIAL/METHODS: 110 patients who were diagnosed with a fetal weight below the 10th percentile for gestational age and who at the same time delivered neonates with a birth weight below the 10th percentile for gestational age. For each of the patients sFlt-1, PlGF and the sFlt-1/PlGF ratio were studied and uterine artery (UtA) and umbilical artery (UA) Doppler were performed. RESULTS: sFlt-1/PlGF ratios and neonatal birth weight which showed significant negative correlation across the entire population studied (R = -0.46, p < 0.001). In late-onset SGA patients this negative correlation was observed, as well (R = -0.54, p < 0.001) In the group of patients with pregnancies older than 34 weeks and an sFlt-1/PlGF ratio ≥38, we observed a significantly lower neonatal birth weight when compared to the same gestational age group with an sFlt-1/PlGF ratio <38 (2045 g vs 2405 g, p < 0.001). CONCLUSION: Late-onset SGA syndromes are characterized by lower sFlt-1/PlGF ratios, which indicates a lower degree of placental function impairment. The sFlt-1/PlGF ratio can be a predictor of more significant growth disorders and a lower neonatal birth weight. The sFlt-1/PlGF ratio can be helpful in distinguishing between disordered angiogenesis-dependent and other causes of late-onset SGA cases.