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.

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.

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 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 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.

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.

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.

(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.