Intrauterine deaths - an unsolved problem in Polish perinatology.

OBJECTIVES: The Polish criteria for "intrauterine death" include fetal demise after 22 weeks of gestation, weighing > 500 g and body length at least 25 cm, when the gestational age is unknown. The rate of fetal death in Poland in 2015 is 3:10,000. In 2020, 1,231 stillbirths were registered. MATERIAL AND METHODS: An analysis using 142,662 births in the period between 2015-2020 in 11 living in Poland. The first subgroup was admitted as patients > 22 to the beginning of the 30th week of pregnancy (n = 229), and the second from the 30th week of pregnancy inclusively (n = 179). In the case of women from both subgroups, there was a risk of preterm delivery close to hospitalization. RESULTS: It was found that stillbirth in 41% of women in the first pregnancy. For the patient, stillbirth was also the first in his life. The average stillbirth weight was 1487 g, the average body length was 40 cm. Among fetuses up to 30 weeks, male fetuses are born more often, in subgroup II, the sex of the child was usually female. Most fetal deaths occur in mothers < 15 and > 45 years of age. CONCLUSIONS: According to the Polish results of the origin of full-term fetuses > 30 weeks of gestation for death in the concomitant antenatal, such as placental-umbilical and fetal hypoxia, acute intrapartum effects rarely, and moreover < 30 Hbd fetal growth restriction (FGR), occurring placental-umbilical, acute intrapartum often.

Evidence of Placental Aging in Late SGA, Fetal Growth Restriction and Stillbirth-A Systematic Review.

During pregnancy, the placenta undergoes a natural aging process, which is considered normal. However, it has been hypothesized that an abnormally accelerated and premature aging of the placenta may contribute to placenta-related health issues. Placental senescence has been linked to several obstetric complications, including abnormal fetal growth, preeclampsia, preterm birth, and stillbirth, with stillbirth being the most challenging. A systematic search was conducted on Pubmed, Embase, and Scopus databases. Twenty-two full-text articles were identified for the final synthesis. Of these, 15 presented original research and 7 presented narrative reviews. There is a paucity of evidence in the literature on the role of placental aging in late small for gestational age (SGA), fetal growth restriction (FGR), and stillbirth. For future research, guidelines for both planning and reporting research must be implemented. The inclusion criteria should include clear differentiation between early and late SGA and FGR. As for stillbirths, only those with no other known cause of stillbirth should be included in the studies. This means excluding stillbirths due to congenital defects, infections, placental abruption, and maternal conditions affecting feto-maternal hemodynamics.

Atypical Preeclampsia before 20 Weeks of Gestation-A Systematic Review.

This systematic review was conducted to gather evidence of preeclampsia occurring before the 20th week of gestation, additionally considering the role of PLGF and sFlt-1 in the development of the disease. In the three cases of preeclampsia before the 20th week of gestation presented in the authors' material, all pregnancies ended up with IUFD, and the SFlt-1/PLGF ratios were significantly elevated in all women. Eligible publications were identified with searches in the PubMed, Embase, Scopus, and Web of Science databases. No date or language restrictions were made. All original peer-reviewed scientific reports were included. A total of 30 publications were included in the final report, including case reports and case series. No other publication types regarding this issue were identified. In the literature, 34 cases of preeclampsia with onset occurring before the 20th week of gestation were identified, for a final total of 37 cases. Live births were reported in 5 cases (10.52%), and there were 9 intrauterine fetal demises (24.32%), and 23 terminations of pregnancy (62.16%). Preeclampsia before the 20th week of gestation is rare but can occur. We collected all available evidence regarding this phenomenon, with 37 cases reported worldwide. We call for large-scale cohort or register-based studies to establish revised definitions or develop new ones regarding the currently unrecognized very early onset preeclampsia.

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.

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.

Diagnosis of placental insufficiency independently of clinical presentations using sFlt-1/PLGF ratio, including SGA patients.

INTRODUCTION: Angiogenic markers (sFLt1 and PlGF) are altered in preeclampsia and related placental insufficiency syndromes. The utility of these markers in various types of placental insufficiency is still not well known. AIMS: We analyzed blood specimens from 918 women with suspected or confirmed preeclampsia, HELLP syndrome, abruptio placenta, SGA, gestational hypertension for angiogenic markers - sFLT1, PlGF, sFlT1/PlGF ratios and studied them at various gestational windows. RESULTS: sFlt-1/PLGF ratio shows high sensitivity and specificity in all placental insufficiency cases independent of clinical forms below 34 weeks (AUC 0.964 respectively 0.834 34-37 weeks' and 0.843 >37 weeks). In preeclampsia or HELLP, they maintain a high specificity and sensitivity also after 34 weeks of gestation. SGA prior to 34 weeks' gestation displayed severe placental angiogenesis disorders, with their share amounting to 78%. After 34 weeks, this share dropped to only slightly above 50%, and after the 37th week, a mere 38%. CONCLUSIONS: Placental angiogenesis markers may be useful in diagnosing many forms of placental ischemia syndromes, particularly when the disease presents early in gestation. In late-onset SGA cases, assessment of the diagnostic value of angiogenesis markers requires further analysis.

Molecular Pathways of Cellular Senescence and Placental Aging in Late Fetal Growth Restriction and Stillbirth.

Abnormally accelerated, premature placental senescence plays a crucial role in the genesis of pregnancy pathologies. Abnormal growth in the third trimester can present as small for gestational age fetuses or fetal growth restriction. One differs from the other by the presence of signs of placental insufficiency and the risk of stillbirth. The majority of stillbirths occur in normally grown fetuses and are classified as "unexplained", which often leads to conclusions that they were unpreventable. The main characteristic of aging is a gradual decline in the function of cells, tissues, and organs. These changes result in the accumulation of senescent cells in mitotic tissues. These cells begin the aging process that disrupts tissues' normal functions by affecting neighboring cells, degrading the extracellular matrix, and reducing tissues' regeneration capacity. Different degrees of abnormal placentation result in the severity of fetal growth restriction and its sequelae, including fetal death. This review aims to present the current knowledge and identify future research directions to understand better placental aging in late fetal growth restriction and unexplained stillbirth. We hypothesized that the final diagnosis of placental insufficiency can be made only using markers of placental senescence.

The crown-rump length measurement - ISUOG criteria and clinical practice.

OBJECTIVES: Significance of the crown-rump length (CRL) measurement criteria in the assessments of gestational age and actual precision in daily clinical practice. MATERIAL AND METHODS: We recruited 806 pregnant women with singleton pregnancy and history of regular menstrual periods.We analysed retrospectively CRL measurements obtained during routine first trimester scan performed between 11 + 0 and 13 + 6 weeks gestation. Gestational age was calculated using both the last menstrual period (LMP) and the CRL. The images of the CRL measurements were assessed by the expert. The visual analysis of the images in terms of meeting the five criteria recommended by the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG) was performed. Statistical analysis were used to assess how the above-mentioned criteria influenced calculation of the gestational age. RESULTS: The study showed 323 out of 806 of the CRL measurements (40.1%) were qualified by a specialist as accurate, 279 (34.6%) as inaccurate, and 204 (25.3%) as inaccurate, but not changing the duration of a pregnancy. With the application in the assessment of the five criteria of the ISOUG 217 (26.9%), the following results of qualification were obtained: accurate - fulfilled ≥ 4, inaccurate 341 (42.3%) - fulfilled ≤ 2, whereas inaccurate, but not changing the duration of a pregnancy 248 (30.8%) - 3 criteria fulfilled. We found that only the neutralof the fetus demonstrated a significant corellation with the assessment of the duration of a gestation. CONCLUSIONS: a) the accurate audit of the CRL measurements is recommended; b) neutral position of the fetus is the most important criterion out of 5.

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.

A Common Profile of Disordered Angiogenic Factor Production and the Exacerbation of Inflammation in Early Preeclampsia, Late Preeclampsia, and Intrauterine Growth Restriction.

Preeclampsia and intrauterine growth restriction are two separate disease entities that, according to numerous reports, share the same pathogenesis. In both, angiogenesis disorders and generalized inflammation are the dominant symptoms. In this study, we hypothesized that both diseases demonstrate the same profile in early preeclampsia, late preeclampsia, and intrauterine growth restriction patients, with the only difference being the degree of exacerbation of lesions. One hundred sixty-seven patients were enrolled in the study and divided into four groups: early preeclampsia, late preeclampsia, and intrauterine growth restriction groups, and one control group. Concentrations of the angiogenesis and inflammatory markers soluble fms-like tyrosine kinase receptor 1, placental growth factor, high-sensitivity C-reactive protein, and interleukin-6 were determined, and the behavior of these markers and correlations among them were studied. Higher concentrations of soluble fms-like tyrosine kinase receptor 1, high-sensitivity C-reactive protein, and interleukin-6 and a lower concentration of placental growth factor were observed in the study groups compared with the control group. No differences in concentrations of the studied markers were found among the study groups but significant correlations were observed. The higher values for the angiogenesis and inflammatory markers both in preeclampsia patients and patients with intrauterine growth restriction of placental origin compared with the control group suggest the existence of the same underlying disorders in the development of these pathologies. The observed mutual correlations for disordered angiogenesis and inflammatory markers are suggestive of a mutual relationship between these processes in the development of pathologies evolving secondary to placental ischemia. The same lesion profile was observed for both preeclampsia and 'placental' intrauterine growth restriction patients, which could be used in developing common diagnostic criteria for pregnant patients.