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Objective: To evaluate the accuracy of combined models of maternal biophysical factors, ultrasound, and biochemical markers for predicting stillbirths. Methods: A retrospective cohort study of pregnant women undergoing first‐trimester pre‐eclampsia screening at 11–13 gestational weeks was conducted. Maternal characteristics and history, mean arterial pressure (MAP) measurement, uterine artery pulsatility index (UtA‐PI) ultrasound, maternal ophthalmic peak ratio Doppler, and placental growth factor (PlGF) serum were collected during the visit. Stillbirth was classified as placental dysfunction‐related when it occurred with pre‐eclampsia or birth weight <10th percentile. Combined prediction models were developed from significant variables in stillbirths, placental dysfunction‐related, and controls. We used the area under the receiver‐operating‐characteristics curve (AUC), sensitivity, and specificity based on a specific cutoff to evaluate the model's predictive performance by measuring the capacity to distinguish between stillbirths and live births. Results: There were 13 (0.79%) cases of stillbirth in 1643 women included in the analysis. The combination of maternal factors, MAP, UtA‐PI, and PlGF, significantly contributed to the prediction of stillbirth. This model was a good predictor for all (including controls) types of stillbirth (AUC 0.879, 95% CI: 0.799–0.959, sensitivity of 99.3%, specificity of 38.5%), and an excellent predictor for placental dysfunction‐related stillbirth (AUC 0.984, 95% CI: 0.960–1.000, sensitivity of 98.5, specificity of 85.7). Conclusion: Screening at 11–13 weeks' gestation by combining maternal factors, MAP, UtA‐PI, and PlGF, can predict a high proportion of stillbirths. Our model has good accuracy for predicting stillbirths, predominantly placental dysfunction‐related stillbirths. Synopsis: Combined screening used for pre‐eclampsia prediction is also an accurate predictor for stillbirths, especially those in association with placental dysfunction. [ABSTRACT FROM AUTHOR]

Background: Prediabetes (PD) is associated with intermediate hyperglycemia, dyslipidaemia, reduced nitric oxide (NO) bioavailability and moderate hypertension. All these factors are risk factor for preeclampsia (PE). However, the effects of the PD on placental function have not been shown. Accordingly, this study sought to investigate a possible link between maternal PD and the risk of developing PE. Methods: Pregnant female Sprague-Dawley rats (N = 18) were divided into normal, preeclamptic and prediabetic groups (n = 6 in each group) to study the effects of maternal PD on placenta function over the period of 19 days. Blood glucose and blood pressure were measured on gestational day (GND) 0, 9 and 18. Placental vascular endothelial growth factor (VEGF), placenta growth factor (PlGF) and soluble fms-like tyrosine kinase 1 (sFlt-1) mRNA expression were measured terminally. Data were analysed using ANOVA followed by the Tukey-Kramer post hoc test. Values of p < .05 were used to indicate statistical significance. Results: Maternal PD and PE significantly increased blood glucose, decrease NO concentration and increase in MAP by comparison to the normal pregnant control group. Maternal PD significantly decreased VEGF, PlGF mRNA expression with a slight increase in sFlt-1 mRNA expression comparison to the normal pregnant control group. Conclusions: Maternal PD is associated with placental dysfunction due to impaired glucose handling, endothelial dysfunction and an imbalance in angiogenic and antiangiogenic factors. Therefore, maternal PD is a risk factor of PE. [ABSTRACT FROM AUTHOR]

Gestational diabetes mellitus (GDM) presents significant risks during pregnancy, including adverse perinatal outcomes and placental dysfunction. Impaired angiogenesis, involving crucial factors like Vascular Endothelial Growth Factor (VEGF), contributes to these complications. The Nrf2/Keap1 pathway, crucial for vascular redox homeostasis, has been linked to GDM-associated angiogenesis dysregulation. This study aimed to investigate the molecular mechanisms underlying placental Nrf2 regulation, focusing on angiomiRs, key regulators of angiogenesis in GDM. Computational analysis identified miR-142-5p targeting Nrf2 mRNA. Expression levels of miR-142-5p were assessed in GDM placenta and correlated with Nrf2 expression. Experimental validation utilized human trophoblastic cell lines (BeWo) exposed to hyperglycemic conditions, assessing the effects of anti-miR-142 transfection on Nrf2 expression and angiogenic marker levels. miR-142-5p expression was significantly downregulated in GDM placenta, correlating positively with Nrf2 expression. In BeWo cells exposed to hyperglycemia, anti-miR-142 transfection notably increased Nrf2 expression alongside angiogenic marker levels, confirming the computational predictions. Our findings highlight the pivotal role of miRNAs in GDM-associated impaired angiogenesis by modulating Nrf2 expression. Understanding these molecular mechanisms provides insights into potential therapeutic targets for improving pregnancy outcomes in GDM cases. • Nrf2, its downstream targets and angiogenic factors were downregulated in GDM placenta. • Overexpression of miR-142-5p impairs angiogenesis via dysregulation of Nrf2 in GDM. • MiR-142-5p directly binding with functional domains of Nrf2 in silico. • Silencing miR-142-5p restores Nrf2 and angiogenesis expression in HG induced BeWo cells. [ABSTRACT FROM AUTHOR]

Introduction Material and Methods Results Conclusions Detection and surveillance of fetal growth restriction (FGR) is well established, but there is still room for improvement. Animal studies indicate that compromised fetuses increase adrenal blood flow. Modern ultrasound equipment allows us to measure vascular impedance in the fetal adrenal arteries despite their modest size. However, extensive anatomical variance is a challenge to standardizing measurements. We set out to improve this.We included 75 low‐risk pregnant women in a prospective cross‐sectional study aiming to develop a reliable technique to visualize and measure flow velocity in human fetal adrenal arteries. We used commercially available ultrasound equipment: a GE Voluson 10 2019 with a C2‐9 probe (GE Healthcare, Zipf, Austria), and a Philips Epiq Elite with a V9‐2 probe (Philips Medical Systems International B.V., Best, The Netherlands), exploiting the modern sensitive power Doppler modes in both scanners to visualize small vessels.Among 72 fetuses, the inferior adrenal artery was the most consistently visualized and measured artery to the gland. Doppler velocimetry was achieved in 66 (92%) participants. We found the anatomical variation described previously but were able to develop visualization strategies to identify the common arteries and use a consistent Doppler technique for the second half of pregnancy.It is possible to visualize and measure flow velocity in the adrenal arteries of human fetuses. The success rate was highest for the inferior adrenal artery making this vessel a candidate for clinical studies. [ABSTRACT FROM AUTHOR]

Gestational diabetes (GD) is a metabolic disorder characterized by glucose intolerance during pregnancy, significantly impacting maternal and fetal health. Its global prevalence is approximately 14%, with risk factors including obesity, family history of diabetes, advanced maternal age, and ethnicity, which are linked to cellular and molecular disruptions in glucose regulation and insulin resistance. GD is associated with short- and long-term complications for both the mother and the newborn. For mothers, GD increases the risk of developing type 2 diabetes, cardiovascular diseases, and metabolic syndrome. In the offspring, exposure to GD in utero predisposes them to obesity, glucose intolerance, and metabolic disorders later in life. This review aims to elucidate the complex cellular and molecular mechanisms underlying GD to inform the development of effective therapeutic strategies. A systematic review was conducted using medical subject headings (MeSH) terms related to GD's cellular and molecular pathophysiology. Inclusion criteria encompassed original studies, systematic reviews, and meta-analyses focusing on GD's impact on maternal and fetal health, adhering to PRISMA guidelines. Data extraction captured study characteristics, maternal and fetal outcomes, key findings, and conclusions. GD disrupts insulin signaling pathways, leading to impaired glucose uptake and insulin resistance. Mitochondrial dysfunction reduces ATP production and increases reactive oxygen species, exacerbating oxidative stress. Hormonal influences, chronic inflammation, and dysregulation of the mammalian target of rapamycin (mTOR) pathway further impair insulin signaling. Gut microbiota alterations, gene expression, and epigenetic modifications play significant roles in GD. Ferroptosis and placental dysfunction primarily contribute to intrauterine growth restriction. Conversely, fetal macrosomia arises from maternal hyperglycemia and subsequent fetal hyperinsulinemia, resulting in excessive fetal growth. The chronic inflammatory state and oxidative stress associated with GD exacerbate these complications, creating a hostile intrauterine environment. GD's complex pathophysiology involves multiple disruptions in insulin signaling, mitochondrial function, inflammation, and oxidative stress. Effective management requires early detection, preventive strategies, and international collaboration to standardize care and improve outcomes for mothers and babies. [ABSTRACT FROM AUTHOR]

Pregnancy is a vulnerable period of time during which pregnant people are prone to infections like COVID-19, which can increase risks for both the mother and fetus. These infections may lead to complications such as preterm birth, developmental delays, and congenital abnormalities. While COVID-19 poses additional risks like placental dysfunction and neonatal infections, studies on long-term effects remain limited. Ongoing research and monitoring are essential to understand and mitigate potential cognitive and developmental challenges in children born to mothers infected with COVID-19. This review aims to guide clinicians in managing these risks throughout childhood. Maternal COVID-19 infection during pregnancy can have significant implications for fetal development, even if the newborn is not infected at birth. The release of inflammatory cytokines may cross the placental barrier, potentially disrupting fetal brain development and increasing the risk of long-term cognitive and behavioral issues, such as ADHD or autism. Placental dysfunction, caused by inflammation or thrombosis, can lead to intrauterine growth restriction (IUGR), preterm birth, or hypoxia, affecting both neurological and respiratory health in newborns. Furthermore, a compromised fetal immune system can increase susceptibility to autoimmune conditions and infections. The early diagnosis and management of infections during pregnancy are crucial in mitigating risks to both the mother and fetus. Swift intervention can prevent complications like preterm birth and long-term developmental challenges, ensuring better health outcomes for both the mother and child. Long-term monitoring of children born to mothers infected with COVID-19 is necessary to understand the full extent of the virus's impact. This review evaluates the long-term systemic effects of maternal COVID-19 infection during pregnancy on fetuses, newborns, and children, focusing beyond vertical transmission. It highlights the broader impacts on fetal development, offering insights to help clinicians manage potential issues that may arise later in life. [ABSTRACT FROM AUTHOR]

Therapeutic plasma exchange (TPE) is a widely used treatment for numerous diseases including pregnancy-related conditions. Our prior study on 20 early-onset preeclampsia patients undergoing TPE revealed a significant extension in pregnancy duration and reduced serum levels of sFlt-1, sFlt-1/PlGF, and sEndoglin. Here, we investigated the impact of TPE on serum sB7-H4, an immunological checkpoint molecule, and placental proteins (Flt-1, Eng, B7-H4, iNOS, TNF-α) in TPE-treated early-onset preeclampsia patients (N = 12, 23 + 2–28 + 5 weeks), conventionally treated counterparts (N = 12, 23 + 5–30 weeks), and gestational age-matched controls (N = 8, 22 + 4–31 + 6 weeks). Immunoblotting, ELISA, and co-immunohistochemistry were used for biomarker analysis, including placental inflammation factors (iNOS, TNF-α). The results showed that TPE extended pregnancy by a median of 6.5 days in this cohort of early-onset preeclampsia. Serum sB7-H4, sFlt-1, and sEndoglin levels decreased, along with reduced expression of their membrane-bound proteins in placental tissue upon TPE treatment. Moreover, TPE-treated patients displayed reduced placental inflammation compared to preeclampsia patients receiving standard-of-care treatment. In conclusion, TPE may improve pregnancy outcomes in early-onset preeclampsia by lowering circulating levels of sB7-H4, sFlt-1, and sEndoglin, as well as reducing placental inflammation. This translational approach holds promise for enhancing placental function and extending gestation in high-risk pregnancies including very preterm PE or HELLP cases. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the association between placental abnormalities, placental biomarkers, and fetoplacental Dopplers in a cohort of pregnancies complicated by fetal growth restriction (FGR). We also ascertained the risk of perinatal mortality, severe neurological morbidity, and severe non-neurological morbidity by type of placental abnormality. This was a prospective cohort study. Multivariable logistic regression was used to evaluate the effect of early vs. late FGR, placental biomarkers and fetoplacental Dopplers on Maternal Vascular Malperfusion (MVM) which was the commonest placental abnormality identified. There were 161 (53.5 %) early FGR and 140 (46.5 %) late FGR cases. MVM abnormalities were present in 154 (51.2 %), VUE in 45 (14.6 %), FVM in 16 (5.3 %), DVM in 14 (4.7 %) and CHI in 4 (1.3 %) cases. The odds of MVM were higher in early compared to late FGR cohort (OR 1.89, 95%CI 1.14, 3.14, p = 0.01). Low maternal PlGF levels <100 ng/L (OR 2.34, 95%CI 1.27,4.31, p = 0.01), high sFlt-1 level (OR 2.13, 95%CI 1.35, 3.36, p = 0.001) or elevated sFlt-1/PlGF ratio (OR 3.48, 95%CI 1.36, 8.91, p = 0.01) were all associated with MVM. Increased UA PI > 95th centile (OR 2.91, 95%CI 1.71, 4.95, p=<0.001) and mean UtA PI z-score (OR 1.74, 95%CI 1.15, 2.64, p = 0.01) were associated with higher odds of MVM. Rates of severe non-neurological morbidity were highest in the MVM, FVM, and CHI cohorts (44.8 %, 50 %, and 50 % respectively). MVM was the commonest placental abnormality in FGR, particularly in early-onset disease. Low maternal PlGF levels, high sFlt-1 levels, elevated sFlt-1/PlGF ratio, and abnormal fetoplacental Dopplers were also significantly associated with MVM. MVM, FVM, and CHI abnormalities were associated with lower median birthweight, higher rates of preterm birth, operative birth for non-reassuring fetal status, and severe neonatal non-neurological morbidity. • MVM is the commonest placental abnormality in pregnancies complicated by FGR. • Early-onset FGR is more likely to have MVM abnormalities than late-onset disease. • MVM changes are associated with abnormal placental biomarkers and fetoplacental Dopplers. • Higher rates of hypertension and pre-eclampsia were seen in MVM, FVM, and CHI. • MVM, FVM, and CHI are strongly associated with adverse perinatal and pregnancy outcomes. [ABSTRACT FROM AUTHOR]

• Angiogenic biomarkers are important tools for the early prediction and diagnosis of preeclampsia. • Data from intervention trials do not support using angiogenic biomarkers for monitoring progressing of preeclampsia or deciding the timing of delivery. • There is insufficient evidence to recommend angiogenic biomarkers as an alternative to Doppler for surveillance and timing of delivery in fetal growth restriction. • Angiogenic biomarkers may have help differentiate between hypertension in chronic kidney disease from superimposed preeclampsia in pregnant women. Monitoring and timing of delivery in preterm preeclampsia and fetal growth restriction is one of the biggest challenges in Obstetrics. Finding the optimal time of delivery of these fetuses usually involves a trade-off between the severity of the disease and prematurity. So far, most clinical guidelines recommend the use of a combination between clinical, laboratory and ultrasound markers to guide the time of delivery. Angiogenic biomarkers, especially placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1), have gained significant attention in recent years for their potential role in the prediction and diagnosis of placenta-related disorders including preeclampsia and fetal growth restriction. Another potential clinical application of the angiogenic biomarkers is for the differential diagnosis of patients with chronic kidney disease, as this condition shares similar clinical features with preeclampsia. Consequently, angiogenic biomarkers have been advocated as tools for monitoring and deciding the optimal time of the delivery of fetuses affected by placental dysfunction. In this clinical opinion, we critically review the available literature on PlGF and sFlt-1 for the surveillance and time of the delivery in fetuses affected by preterm preeclampsia and fetal growth restriction. Moreover, we explore the use of angiogenic biomarkers for the differentiation between chronic kidney disease and superimposed preeclampsia. [ABSTRACT FROM AUTHOR]

Objective: To assess the utility of placental growth factor (PlGF) levels and the soluble fms‐like tyrosine kinase‐1/placental growth factor (sFlt‐1/PlGF) ratio to predict preterm birth (PTB) for infants with fetal growth restriction (FGR) and those appropriate for gestational age (AGA). Design: Prospective, observational cohort study. Setting: Tertiary maternity hospital in Australia. Population: There were 320 singleton pregnancies: 141 (44.1%) AGA, 83 (25.9%) early FGR (<32+0 weeks) and 109 (30.0%) late FGR (≥32+0 weeks). Methods: Maternal serum PlGF and sFlt‐1/PlGF ratio were measured at 4‐weekly intervals from recruitment to delivery. Low maternal PlGF levels and elevated sFlt‐1/PlGF ratio were defined as <100 ng/L and >5.78 if <28 weeks and >38 if ≥28 weeks respectively. Cox proportional hazards models were used. The analysis period was defined as the time from the first measurement of PlGF and sFlt‐1/PlGF ratio to the time of birth or censoring. Main outcome measures: The primary study outcome was overall PTB. The relative risks (RR) of birth within 1, 2 and 3 weeks and for medically indicated and spontaneous PTB were also ascertained. Results: The early FGR cohort had lower median PlGF levels (54 versus 229 ng/L, p < 0.001) and higher median sFlt‐1 levels (2774 ng/L versus 2096 ng/L, p < 0.001) and sFlt‐1/PlGF ratio higher (35 versus 10, p < 0.001). Both PlGF <100 ng/L and elevated sFlt‐1/PlGF ratio were strongly predictive for PTB as well as PTB within 1, 2 and 3 weeks of diagnosis. For both FGR and AGA groups, PlGF <100 ng/L or raised sFlt‐1/PlGF ratio were strongly associated with increased risk for medically indicated PTB. The highest RR was seen in the FGR cohort when PlGF was <100 ng/L (RR 35.20, 95% CI 11.48–175.46). Conclusions: Low maternal PlGF levels and elevated sFlt‐1/PlGF ratio are potentially useful to predict PTB in both FGR and AGA pregnancies. [ABSTRACT FROM AUTHOR]

Background Prediabetes (PD) is associated with intermediate hyperglycaemia, dyslipidaemia, reduced nitric oxide (NO) bioavailability and moderate hypertension. All these factors are risk factor for preeclampsia (PE). However, the effects of the PD on placental function have not been shown. Accordingly, this study sought to investigate a possible link between maternal PD and the risk of developing PE.Methods Pregnant female Sprague-Dawley rats (N = 18) were divided into normal, preeclamptic and prediabetic groups (n = 6 in each group) to study the effects of maternal PD on placenta function over the period of 19 days. Blood glucose and blood pressure were measured on gestational day (GND) 0, 9 and 18. Placental vascular endothelial growth factor (VEGF), placenta growth factor (PlGF) and soluble fms-like tyrosine kinase 1 (sFlt-1) mRNA expression were measured terminally. Data were analysed using ANOVA followed by the Tukey–Kramer post hoc test. Values of p

We examined 164 pregnant women who were divided into three groups. Group I included 76 pregnant women (46.4 %) with euthyroid goiter of I–II degree. Group II consisted of 63 pregnant women (38.4 %) with subclini­cal hypothyroidism and diffuse thyroid goiter of I–II degree. Group III was the controls and consisted of 25 (15.2 %) pregnant women without thyroid pathology. The placenta was studied with the characteristics of ultrasound placentography, placental maturation disorders, the area and localization were determined, and pathological changes in the placental tissue were detected. Changes in the systolic-diastolic ratio in the uterine arteries and umbilical cord arteries were assessed, the resistance index in the uterine arteries, the pulsatile index in the fetal aorta and middle cerebral artery were determined using the method of color Doppler mapping of blood flow in the mother-placenta-fetus system. Study of the echographic picture of structural changes in the placenta revealed a significant impairment of its maturation, especially in the group with euthyroidism. Ultrasound screening revealed that in every second pregnant woman with thyroid disease, the condition of the placenta did not correspond to the gestational age, there were swelling, cysts and placental infarctions, a high frequency of diffuse changes in placental tissue, and hyperechogenic inclusions in the amniotic fluid. An increase in the resistance index in the uterine arteries of pregnant women, especially those with subclinical hypothyroidism, is noteworthy. With increasing gestational age, the peripheral resistance of the placental microvasculature increases due to involutional-dystrophic changes and circulatory disorders, which allows us to develop criteria for the prognosis and diagnosis of placental dysfunction, and to prevent perinatal disorders in pregnant women with thyroid disease.

Objectives: Women with chronic rheumatic disease (CRD) are at greater risk of foetal growth restriction than their healthy peers. T2*-weighted magnetic resonance imaging of placenta (T2*P-MRI) is superior to conventional ultrasonography in predicting birth weight and works as a proxy metabolic mirror of the placental function. We aimed to compare T2*P-MRI in pregnant women with CRD and healthy controls. In addition, we aimed to investigate the correlation between T2*P-MRI and birth weight. Methods: Using a General Electric (GE) 1.5 Tesla, we consecutively performed T2*-weighted placental MRI in 10 women with CRD and 18 healthy controls at gestational week (GW)24 and GW32. We prospectively collected clinical parameters during pregnancy including birth outcome and placental weight. Results: Women with CRD had significantly lower T2*P-MRI values at GW24 than healthy controls (median T2*(IQR) 92.1 ms (81.6; 122.4) versus 118.6 ms (105.1; 129.1), p = 0.03). T2*P-MRI values at GW24 showed a significant correlation with birth weight, as the T2*P-MRI value was reduced in all four pregnancies complicated by SGA at birth. Three out of four pregnancies complicated by SGA at birth remained undetected by routine antenatal ultrasound. Conclusion: This study demonstrates reduced T2*P-MRI values and a high proportion of SGA at birth in CRD pregnancies compared to controls, suggesting an increased risk of placental dysfunction in CRD pregnancies. T2*P-MRI may have the potential to focus clinical vigilance by identifying pregnancies at risk of SGA as early as GW24. Key Points • Placenta-related causes of foetal growth restriction in women with rheumatic disease remain to be investigated. • T2*P-MRI values at gestational week 24 predicted foetuses small for gestational age at birth. • T2*P-MRI may indicate pregnant women with chronic rheumatic disease (CRD) in need of treatment optimization. [ABSTRACT FROM AUTHOR]

Introduction: To assess the rate of change in soluble fms‐like tyrosine kinase‐1/placental growth factor (sFlt‐1/PlGF) ratio and PlGF levels per week compared to a single sFlt‐1/PlGF ratio or PlGF level to predict preterm birth for pregnancies complicated by fetal growth restriction. Material and methods: A prospective cohort study of pregnancies complicated by isolated fetal growth restriction. Maternal serum PlGF levels and the sFlt‐1/PlGF ratio were measured at 4‐weekly intervals from recruitment to delivery. We investigated the utility of PlGF levels, sFlt‐1/PlGF ratio, change in PlGF levels per week or sFlt‐1/PlGF ratio per week. Cox‐proportional hazard models and Harrell's C concordance statistic were used to evaluate the effect of biomarkers on time to preterm birth. Results: The total study cohort was 158 pregnancies comprising 91 (57.6%) with fetal growth restriction and 67 (42.4%) with appropriate for gestational age controls. In the fetal growth restriction cohort, sFlt‐1/PlGF ratio and PlGF levels significantly affected time to preterm birth (Harrell's C: 0.85–0.76). The rate of increase per week of the sFlt‐1/PlGF ratio (hazard ratio [HR] 3.91, 95% confidence interval [CI]: 1.39–10.99, p = 0.01, Harrell's C: 0.74) was positively associated with preterm birth but change in PlGF levels per week was not (HR 0.65, 95% CI: 0.25–1.67, p = 0.37, Harrell's C: 0.68). Conclusions: Both a high sFlt‐1/PlGF ratio and low PlGF levels are predictive of preterm birth in women with fetal growth restriction. Although the rate of increase of the sFlt‐1/PlGF ratio predicts preterm birth, it is not superior to either a single elevated sFlt‐1/PlGF ratio or low PlGF level. [ABSTRACT FROM AUTHOR]

We examined 164 pregnant women who were divided into three groups. Group I included 76 pregnant women (46.4 %) with euthyroid goiter of I–II degree. Group II consisted of 63 pregnant women (38.4 %) with subclinical hypothyroidism and diffuse thyroid goiter of I–II degree. Group III was the controls and consisted of 25 (15.2 %) pregnant women without thyroid pathology. The placenta was studied with the characteristics of ultrasound placentography, placental maturation disorders, the area and localization were determined, and pathological changes in the placental tissue were detected. Changes in the systolic-diastolic ratio in the uterine arteries and umbilical cord arteries were assessed, the resistance index in the uterine arteries, the pulsatile index in the fetal aorta and middle cerebral artery were determined using the method of color Doppler mapping of blood flow in the mother-placenta-fetus system. Study of the echographic picture of structural changes in the placenta revealed a significant impairment of its maturation, especially in the group with euthyroidism. Ultrasound screening revealed that in every second pregnant woman with thyroid disease, the condition of the placenta did not correspond to the gestational age, there were swelling, cysts and placental infarctions, a high frequency of diffuse changes in placental tissue, and hyperechogenic inclusions in the amniotic fluid. An increase in the resistance index in the uterine arteries of pregnant women, especially those with subclinical hypothyroidism, is noteworthy. With increasing gestational age, the peripheral resistance of the placental microvasculature increases due to involutional-dystrophic changes and circulatory disorders, which allows us to develop criteria for the prognosis and diagnosis of placental dysfunction, and to prevent perinatal disorders in pregnant women with thyroid disease. [ABSTRACT FROM AUTHOR]

The objective: to determine the diagnostic value of biomarkers of placental dysfunction at different stages of gestation. Materials and methods. The research was carried out in 2015–2022 on the basis of the municipal non-commercial enterprise “Maternity House No.5” of the Odesa City Council. We analyzed the course and clinical outcomes of pregnancies in 118 women (the main group) who developed and established placental dysfunction (PD) during pregnancy at different stages of gestation. The control group included 78 healthy women whose pregnancies occurred without PD. In women of both groups the frequency of detection of risk factors for PD was assessed by analyzing the content of placental growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1) biomarkers in blood serum, Pregnancy-Associated Plasma Protein A (PAPP-A) and β-subunit of chorionic gonadotropin (hCG). Fetal growth retardation was determined by deviations of fetal metric indicators (abdominal circumference, head circumference, biparietal size, thigh length, estimated fetal weight) below the 10th percentile. Statistical processing of the obtained results was carried out using Statistica 14.0 software (TIBCO, USA). Results. Among the examined women of both groups, cases where the pregnancy occurred at the age of 30 years or more and was the first pregnancy that did not end in abortion prevailed. The average age of women in the main group was 33.4±2.3 years, the control group – 29.3±1.4 years. The main group had more women with a history of multiple abortions (odds ratio (OR)=5.6, 95% confidence interval (CI): 1.9–18.8). Disorders of the menstrual cycle in history were found in 39 (33.1%) women of the main group and in 18 (23%) women of the control group (OR=1.6, 95% CI: 0.9–3.2). Concomitant gynecological diseases were represented by uterine fibroids – in 16 (13.6%) pregnant women of the main group and in 8 (10.2%) women of the control group (OR=1.4, 95% CI: 0.6–3.4), benign ovarian tumors – in 13 (11.0%); OR=20.1, 95% CI: 1.2–343.1), mastopathy – in 19 (16.1%; OR=30.8, 95% CI: 1.8–517.6) women of the main group. A significant number of women in the main group had a hypertrophic nutritional status – the body mass index (BMI) at the time of pregnancy was on average 26.7±0.9 kg/m², women in the control group were represented by the normotrophic type (BMI – 22.2±0.3 kg/m² ), in 4 women the indicator was more 30 kg/m² . In the vast majority of pregnant women (68 persons – 57.6%) of the main group the signs of placental malperfusion were registered up to 34 weeks. In 12 (10.2%) cases a primary PD was established. The content of PIGF in women of the main group at the 20th week of pregnancy decreased to 83±4 pg/ml, which is significantly less than the reference values (≥100 pg/ml). On the other hand, in the control group the PIGF concentration was 147±8 pg/ ml (p<0.05). The sFlt-1 amount in the main group corresponded to the level of 3395±62 pg/ml. Therefore, the ratio of sFlt-1/ PlGF was equal to 40.8±0.4, which is prognostically unfavorable. The PAPP-A indicator, according to monitoring data at the 20th week of pregnancy, was 0.77±0.08 mU/l. In pregnant women with lower values in the future PD occurred earlier. As for the indicators of the β-subunit of hCG, the levels of this hormone in most cases corresponded to the normative values, amounting to an average of 4.7±0.1 IU/l in a pregnancy with a male fetus and 8133±21 IU/l in a pregnancy with a female fetus. Signs of preeclampsia were determined in 22 (18.6%) pregnant women of the main group. The value of the sFlt-1/PlGF ratio in these pregnant women exceeded 50.0. Conclusions. In the vast majority of pregnant women of the main group (68 – 57.6%) the signs of placental malperfusion were found up to 34 weeks. In 22 (18.6%) pregnant women with placental dysfunction (PD) the signs of preeclampsia were detected, the development of which increases when the sFlt-1/PlGF ratio exceeds 50, starting from the II trimester of pregnancy, which is an early biomarker of PD. [ABSTRACT FROM AUTHOR]

The objective: to assess the diagnostic value of histopathological examination of placentas in women with placenta-associated complications. Materials and methods. Placental samples from 46 patients who gave birth at the Municipal Non-Profit Enterprise «City Maternity Hospital No. 2» in 2023 were examined. A retrospective analysis of the histopathological study results was conducted. Results. The study revealed that full-term pregnancies were observed in 52.2% of patients, preterm labor in 30.4%, and prolonged pregnancies in 17.4%. The average age of the patients was 30-35 years. The placental-fetal ratio (PFR) was 0.14±0.01 for preterm labor, 0.13±0.01 for full-term pregnancies, and 0.12±0.02 for prolonged pregnancies. Pregnancy complications, by prevalence, included fetal distress (26.09%), preeclampsia (19.57%), fetal growth restriction (15.22%), antenatal fetal demise (13.04%), placental abruption (13.04%), and postpartum hemorrhage (4.35%). The most common characteristic changes in macro- and micro-preparations were: chorioamnionitis detected in 34.78% of cases, placental infarction – in 43.48% of cases, hematomas were recorded in 6.52% of cases, thromboses – in 4.35%, and hemorrhages – in 10.87%.All these changes, identified during our study, led to chronic placental dysfunction in 69.77% of cases. Conclusions. Pathological changes in the placenta can affect the normal course of pregnancy, leading to various pregnancy complications such as thromboses, hemorrhages, and preterm labor. The study confirms the necessity of timely detection and treatment of pathological processes in the placenta to prevent these complications. There is a need for comprehensive examination of women in the pregravid period, assessment of intrauterine fetal status, and consultation with relevant specialists. [ABSTRACT FROM AUTHOR]

Chronic hypertension is a major risk factor for preeclampsia (PE), associated with significant maternal and neonatal morbidity. We previously demonstrated that pregnant stroke-prone spontaneously hypertensive rats (SHRSP) display a spontaneous PE-like phenotype with distinct placental, fetal, and maternal features. Here, we hypothesized that supplementation with alpha lipoic acid (ALA), a potent antioxidant, during early pregnancy could ameliorate the PE phenotype in this model. To test this hypothesis, timed pregnancies were established using 10 to 12-week-old SHRSP females (n = 19–16/group), which were assigned to two treatment groups: ALA (injected intraperitoneally with 25 mg/kg body weight ALA on gestation day (GD1, GD8, and GD12) or control, receiving saline following the same protocol. Our analysis of maternal signs showed that ALA prevented the pregnancy-dependent maternal blood pressure rise (GD14 blood pressure control 169.3 ± 19.4 mmHg vs. 146.1 ± 13.4 mmHg, p = 0.0001) and ameliorated renal function, as noted by the increased creatinine clearance and improved glomerular histology in treated dams. Treatment also improved the fetal growth restriction (FGR) phenotype, leading to increased fetal weights (ALA 2.19 ± 0.5 g vs. control 1.98 ± 0.3 g, p = 0.0074) and decreased cephalization indexes, indicating a more symmetric fetal growth pattern. This was associated with improved placental efficiency, decreased oxidative stress marker expression on GD14, and serum soluble fms-like tyrosine kinase 1 (sFlt1) levels on GD20. In conclusion, ALA supplementation mitigated maternal signs and improved placental function and fetal growth in SHRSP pregnancies, emerging as a promising therapy in pregnancies at high risk for PE. [ABSTRACT FROM AUTHOR]

The article titled "Serum D-dimer is not predictive of placenta-mediated complications in pregnancy at high risk: The multicentric prospective cohort AngioPred study" discusses the association between serum D-dimer levels and the occurrence of placenta-mediated complications (PMC) in a high-risk pregnant population. The study, which included 200 pregnant women, found that serum D-dimer levels increased throughout pregnancy but were similar for women with PMC and those without complications. The study concluded that serum D-dimer levels were not predictive of PMC occurrence, suggesting that the origin of PMC is more related to immunity than hemostasis. This information can be useful for researchers and library patrons studying pregnancy complications. [Extracted from the article]

Background: Imbalanced angiogenesis is characteristic of normal placental maturation but it also signals placental dysfunction, underlying hypertensive disorders during pregnancy. This study aimed to investigate the relationship between angiogenic placental aging, measured by markers placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) using the new index "Multiples of a normal term placenta" (Mtp) and the duration of pregnancy. Methods: A retrospective observational study was conducted, including singleton pregnancies diagnosed or suspected of hypertensive disorders after the 20th gestational week. Mtp measures how far a single dosage of angiogenic marker deviates from the expected value in an uncomplicated full-term pregnancy (Mpt = sFlt-1/sFlt-1 reference value or PIGF/PIGF reference value). We considered the 90th, 95th, and 97.5th centiles for sFlt-1 and the 2.5th, 5th, and 10th centiles for PlGF as references. Results: The categories with longer time to delivery, regardless of gestational age, were: Mtp PlGF 10th c ≥ 2, ≥3 and Mtp sFlt-1 90th c ≤ 0.5 (median days of 9, 11, 15 days, respectively). These two categories Mtp sFlt-1 90th c ≥ 3 and Mtp sFlt-1 97.5th c ≥ 2 allow the identification of women at risk for imminent delivery within 1 day. Women who were deemed at low/medium risk based on the sFlt-1/PIGF ratio appeared to be at high risk when considering the individual values of sFlt-1 and/or PIGF. Conclusions: This new Mtp index for sFlt-1 and PlGF could be employed to assess the degree of placental aging in women with hypertensive disorders. It represents a valid tool for evaluating the risk of imminent birth, irrespective of gestational age, surpassing the current stratification based on the sFlt-1/PIGF ratio. [ABSTRACT FROM AUTHOR]

Pregnancy is a vulnerable period of time during which pregnant people are prone to infections like COVID-19, which can increase risks for both the mother and fetus. These infections may lead to complications such as preterm birth, developmental delays, and congenital abnormalities. While COVID-19 poses additional risks like placental dysfunction and neonatal infections, studies on long-term effects remain limited. Ongoing research and monitoring are essential to understand and mitigate potential cognitive and developmental challenges in children born to mothers infected with COVID-19. This review aims to guide clinicians in managing these risks throughout childhood. Maternal COVID-19 infection during pregnancy can have significant implications for fetal development, even if the newborn is not infected at birth. The release of inflammatory cytokines may cross the placental barrier, potentially disrupting fetal brain development and increasing the risk of long-term cognitive and behavioral issues, such as ADHD or autism. Placental dysfunction, caused by inflammation or thrombosis, can lead to intrauterine growth restriction (IUGR), preterm birth, or hypoxia, affecting both neurological and respiratory health in newborns. Furthermore, a compromised fetal immune system can increase susceptibility to autoimmune conditions and infections. The early diagnosis and management of infections during pregnancy are crucial in mitigating risks to both the mother and fetus. Swift intervention can prevent complications like preterm birth and long-term developmental challenges, ensuring better health outcomes for both the mother and child. Long-term monitoring of children born to mothers infected with COVID-19 is necessary to understand the full extent of the virus’s impact. This review evaluates the long-term systemic effects of maternal COVID-19 infection during pregnancy on fetuses, newborns, and children, focusing beyond vertical transmission. It highlights the broader impacts on fetal development, offering insights to help clinicians manage potential issues that may arise later in life.

Background: This study aims to assess the utility of the sFlt-1/PlGF ratio throughout pregnancy in predicting placental dysfunction and neonatal outcomes in twin pregnancies. Methods: Prospective study at a tertiary hospital. All pregnant women with a twin pregnancy who signed the informed consent were included. The sFlt-1/PlGF ratio was measured at 12, 24, and 32 weeks' gestation. Results: Seventy patients were included, and 30% developed placental dysfunction. Differences were found in the mean sFlt-1/PlGF ratios at week 32 (13.6 vs. 31.8, p = 0.007). Optimal cutoffs at 12, 24, and 32 weeks to identify patients who develop placental dysfunction were 32.5, 8.5, and 30.5, respectively, with ORs of 4.25 (1.13–20.69 95% IC; p = 0.044), 13.5 (3.07–67.90 95% IC; p = 0.001), 14.29 (3.59–66.84 95% IC; p < 0.001). The sFlt-1/PlGF ratio at 32 weeks was associated with gestational age at birth. The sFlt-1/PlGF ratio in weeks 24 and 32 had a statistically significant negative correlation with the birth weight percentile in both twins. Conclusions: The potential of the sFlt-1/PlGF ratio as a predictive tool for placental dysfunction in twin pregnancies is underscored. [ABSTRACT FROM AUTHOR]

Pregnancy with bacterial vaginosis (BV) is accompanied by a high risk of various obstetric and perinatal complications, including miscarriage, preterm birth, placental dysfunction, premature rupture of membranes, chorionamnionitis, polyhydramnios, etc. Screening for BV is carried out in the first half of pregnancy during the registration of a woman, however, taking into account the gestational age, many drugs with antimicrobial and antiseptic effects are categorically contraindicated, as they have an embryo- and fetotoxic effect. Timely detection and correction of microbiocenosis disorders of the birth canal is an extremely important element to prevent a number of obstetric and perinatal complications. A balanced approach in the treatment of vaginal dysbiosis consists in the use of modern combined antiseptic preparations for local treatment, which do not contain antibacterial components and are safe for use during pregnancy. The objective: to determine the effectiveness of the treatment of BV in primigravida women in the first half of pregnancy. Materials and methods. 126 primigravida women aged 18–35 years in the first half of pregnancy were examined during pregnancy registration. The participants were selected randomly. The main group included 36 primigravida women with a gestation period of up to 20 weeks with a diagnosis of BV according to the Amsel and Hay–Ison criteria, who were treated with a combined antiseptic drug (chlorhexidine and chlorophyllipt) – suppository vaginally twice a day, the course of treatment – 5 days. The control group included 30 primigravida women with a gestational age of up to 20 weeks with vaginal normocenosis. For all women the pH of vaginal secretions was determined, followed by microscopy of a native smear, stained according to Gram, and a cultural study was performed. Adherence to the Amsel criteria was also determined, followed by evaluation by the Hay– Ison criteria. The clinical effect was evaluated according to clinical examination data before and on the 6th day of treatment with a combined antiseptic drug (chlorhexidine and chlorophyllipt) using bacterioscopic and bacteriological methods. Results. A normal pH was observed only in every fifth part of examined pregnant woman (28 women – 22.2%), while in the rest patients the acidity of the vaginal environment was not normal. Normocenosis was observed only among 1/3 of primigravida women (37 women – 29.4%). A third of the patients were diagnosed with BV (36 women - 28.6%), every fifth pregnant woman – vulvovaginal candidiasis (28 women - 22.2%). In healthy pregnant women (control group, n=30), the main component of the microbiocenosis was Lactobacillus spp. with a small content of facultatively anaerobic microorganisms. In the main group Atopobium vaginae (38.9%), Gardnerella vaginalis (33.3%), Prevotella bivia (27.8%), Candida spp. (22.2%), as well as Lactobacillus spp. in low titers were dominated. Before the treatment all 36 pregnant women of the main group corresponded to the 3rd type according to the Hay–Ison criteria with the dominance of Gardnerella vaginalis and/or Mobiluncus morphotypes and a small number or complete absence of lactobacilli, which served as the basis for establishing the diagnosis of BV. After treatment type 1 (94.4%) was found in 34 pregnant women, and type 2 (5.6%) – in 2 pregnant women. The results of the microbiological study indicate the normalization of the content of the biotope with the predominance of Lactobacillus spp. in women of the main group, in whom the indicators were similar to the control group. Conclusions. Since pregnancy with BV is accompanied by a high risk of obstetric and perinatal complications, the premorbid background of which is laid already in the first half of pregnancy, there is an urgent need to carry out the birth canal sanitation. The drugs of choice for the BV in the first half of pregnancy are local combined agents of a wide spectrum of action. A universal antiseptic with an anti-inflammatory effect, which includes two components – chlorhexidine and chlorophyllipt, fully meets the recommendations for efficiency and safety and can be used for the BV in the first half of pregnancy. [ABSTRACT FROM AUTHOR]

Objectives: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS‐CoV‐2) virus infection in pregnancy is associated with higher incidence of placental dysfunction, referred to by a few studies as a 'preeclampsia‐like syndrome'. However, the mechanisms underpinning SARS‐CoV‐2‐induced placental malfunction are still unclear. Here, we investigated whether the transcriptional architecture of the placenta is altered in response to SARS‐CoV‐2 infection. Methods: We utilised whole‐transcriptome, digital spatial profiling, to examine gene expression patterns in placental tissues from participants who contracted SARS‐CoV‐2 in the third trimester of their pregnancy (n = 7) and those collected prior to the start of the coronavirus disease 2019 (COVID‐19) pandemic (n = 9). Results: Through comprehensive spatial transcriptomic analyses of the trophoblast and villous core stromal cell subpopulations in the placenta, we identified SARS‐CoV‐2 to promote signatures associated with hypoxia and placental dysfunction. Notably, genes associated with vasodilation (NOS3), oxidative stress (GDF15, CRH) and preeclampsia (FLT1, EGFR, KISS1, PAPPA2) were enriched with SARS‐CoV‐2. Pathways related to increased nutrient uptake, vascular tension, hypertension and inflammation were also enriched in SARS‐CoV‐2 samples compared to uninfected controls. Conclusions: Our findings demonstrate the utility of spatially resolved transcriptomic analysis in defining the underlying pathogenic mechanisms of SARS‐CoV‐2 in pregnancy, particularly its role in placental dysfunction. Furthermore, this study highlights the significance of digital spatial profiling in mapping the intricate crosstalk between trophoblasts and villous core stromal cells, thus shedding light on pathways associated with placental dysfunction in pregnancies with SARS‐CoV‐2 infection. [ABSTRACT FROM AUTHOR]

Placental dysfunction (PD) is one of the actual topics of research in the modern scientific world. Fetal growth retardation (FGR) is the leading clinical manifestation of chronic PD. Assessment of fetal growth is one of the key tasks in prenatal care. FGR is associated with an increased risk of perinatal morbidity and mortality, with long-term adverse outcomes for the child. Prenatal diagnosis of FGR is an important task for stillbirth prevention, up to 30% of cases of which are associated with this pathology or with a small-for-gestational-age fetus at the end of the III trimester. The objective: to study the influence of acetylsalicylic acid on the development of compensatory abilities of the fetus by PD. Materials and methods. 118 pregnancies with FGR and/or PD were analyzed. The women were divided into two groups: I group (67 persons) – patients with FGR and/or PD who used acetylsalicylic acid during pregnancy; II group (51 women) – pregnant women with FGR and/or PD who did not use acetylsalicylic acid during pregnancy. In all cases, the method of delivery was cesarean section due to fetal distress. Fetal distress was diagnosed using ultrasound examinations based on the following criteria: abnormal blood flow according to Doppler data (Volusun S10 ultrasound device), fetal biophysical profile indicators (Volusun S10 ultrasound device, Sonicaid Team fetal monitor) and cardiotocographic assessment of short-term variability (STV) fetal heart rate; STV > 4.5 according to the Sonicaid Team fetal monitor. Exclusion criteria: multiple pregnancy, antenatally confirmed fetal malformations. Results. The use of acetylsalicylic acid through placental regulation allows to achieve a longer gestation period before the development of fetal distress. The average gestational age before the appearance of this pathology in 50.75% of patients of the I group (34 persons) was larger – 33–36 weeks. On the other hand, 54.9% of women (28 individuals) in the II group had fetal distress earlier – at 28–32 weeks of gestation (p<0.05). Pathological blood flow in the umbilical artery or fetal biophysical profile <4 points was determined in 83.6% of cases in the I group (56 pregnant women) and in 23.5% in the II group (12 women). In women who used acetylsalicylic acid (I group) acute fetal distress diagnosed by STV was detected in 11 (16.4%) cases. In women who did not use acetylsalicylic acid (II group), distress manifested itself sharply – due to acidosis – in 39 (76.5%) cases (p<0.05). Conclusions. 1. In women who did not use acetylsalicylic acid, fetal distress manifested itself sharply – due to acidosis (STV<4.5 was recorded in 39 (76.5%) patients of the II group, while in women who used acetylsalicylic acid – in 11 pregnant women of the I group (16.4%; p<0.05). 2. Prophylactic use of acetylsalicylic acid allows to slow down the growth of placental dysfunction, which lets to the development of compensatory mechanisms and adaptation. 3. By use of acetylsalicylic acid the gestational period delivery closer to full term pregnancy. In women who used acetylsalicylic acid, most cases of fetal distress occurred at 33–36 weeks – 50.75%, while in the group that did not use acetylsalicylic acid most cases of fetal distress occurred at 28–32 weeks – in 54.9% (р<0.05). [ABSTRACT FROM AUTHOR]

Research objectives: the study examined the effect of the BsmI polymorphism of the gene encoding vitamin D receptors (A > G, rs1544410) on human placental dysfunction. Materials and methods. An observational-analytical study carried out according to the «case-control» principle. The study was conducted in two maternity hospitals in the city of Odessa, Ukraine over the same period of time. Special enzyme immunoassay and molecular genetic studies were carried out at the LLC «Diagnostic Center Evgenika» in Odessa. The intervention group included a total of 56 pregnant women aged 18 to 40 with high infectious risk and signs of placental dysfunction. The control consisted of 40 apparently healthy women with an uncomplicated pregnancy. The 25(OH)D blood level was determined by the ELISA method whereas the gene polymorphism encoding vitamin D receptors was determined by PCR. Results. The number/percentage of women with placental dysfunction in the intervention and control groups respectively, their hydroxyvitamin D levels as well as the genotypes expressed was investigated. In placental dysfunction patients, vitamin D level was significantly lower than in healthy individuals. There was a direct correlation between the placental dysfunction frequency and the A/G genotype. In vitamin D deficiency, the heterozygous A/G genotype for vitamin D receptor gene polymorphic locus increased the risk of development of placental dysfunction by 3.6 times. Conclusions. Vitamin D deficiency may increase the risk of placental dysfunction. For a more complete understanding between vitamin D receptor gene polymorphism and placental dysfunction, it is necessary to study all four vitamin D receptors polymorphisms with 25(OH)D levels correlations as well as polymorphisms of genes CYP27B1 and CYP24A1.

Abstract Yes-associated protein (YAP) is a pivotal regulator in cellular proliferation, survival, differentiation, and migration, with significant roles in embryonic development, tissue repair, and tumorigenesis. At the maternal–fetal interface, emerging evidence underscores the importance of precisely regulated YAP activity in ensuring successful pregnancy initiation and progression. However, despite the established association between YAP dysregulation and adverse pregnancy outcomes, insights into the impact of aberrant YAP levels in fetal-derived, particularly trophoblast cells, and the ensuing dysfunction at the maternal–fetal interface remain limited. This review comprehensively examines YAP expression and its regulatory mechanisms in trophoblast cells throughout pregnancy. We emphasize its integral role in placental development and maternal–fetal interactions and delve into the correlations between YAP dysregulation and pregnancy complications. A nuanced understanding of YAP's functions during pregnancy could illuminate intricate molecular mechanisms and pave the way for innovative prevention and treatment strategies for pregnancy complications. Video Abstract

Aim: to assess features of placental transcriptome in patients with complicated pregnancy course and outcome.Materials and Methods. A prospective observational comparative study in parallel groups was carried out by examining 44 patients divided into three groups: group 1 included 13 pregnant women with moderate and severe preeclampsia (PE), group 2 consisted of 12 patients with fetal growth retardation (FGR), control group included 19 clinically healthy women with uncomplicated pregnancy and delivery. All women enrolled to the study underwent a comprehensive examination, including history collection, general and obstetric-gynecological examination, laboratory and instrumental studies. Special research methods were used during the study, which included placental tissue sampling followed by analyzed expression profile of 12 microRNAs using real-time polymerase chain reaction (PCR).Results. The PCR data indicated about lack of expression for analyzed miR-210-3p, miR-320-3p, miR-1304-5p and miR-375-5p in placental tissue samples in FGR patients. No significant differences in placental miRNA levels were observed in FGR vs. PE and control group. Analysis of placenta-specific microRNAs in women with PE vs. control group showed a significantly down modulated expression level for miR-517a-3p (p = 0.025), miR-517c-3p (p = 0.036), miR-574-5p (p = 0.015) along with upregulated expression of miR-20a-5p (p = 0.046).Conclusion. The data obtained evidence that pregnancy-related complications are characterized by specific molecular changes at placental transcriptome level.

Abstract Objectives Severe Acute Respiratory Syndrome Coronavirus 2 (SARS‐CoV‐2) virus infection in pregnancy is associated with higher incidence of placental dysfunction, referred to by a few studies as a ‘preeclampsia‐like syndrome’. However, the mechanisms underpinning SARS‐CoV‐2‐induced placental malfunction are still unclear. Here, we investigated whether the transcriptional architecture of the placenta is altered in response to SARS‐CoV‐2 infection. Methods We utilised whole‐transcriptome, digital spatial profiling, to examine gene expression patterns in placental tissues from participants who contracted SARS‐CoV‐2 in the third trimester of their pregnancy (n = 7) and those collected prior to the start of the coronavirus disease 2019 (COVID‐19) pandemic (n = 9). Results Through comprehensive spatial transcriptomic analyses of the trophoblast and villous core stromal cell subpopulations in the placenta, we identified SARS‐CoV‐2 to promote signatures associated with hypoxia and placental dysfunction. Notably, genes associated with vasodilation (NOS3), oxidative stress (GDF15, CRH) and preeclampsia (FLT1, EGFR, KISS1, PAPPA2) were enriched with SARS‐CoV‐2. Pathways related to increased nutrient uptake, vascular tension, hypertension and inflammation were also enriched in SARS‐CoV‐2 samples compared to uninfected controls. Conclusions Our findings demonstrate the utility of spatially resolved transcriptomic analysis in defining the underlying pathogenic mechanisms of SARS‐CoV‐2 in pregnancy, particularly its role in placental dysfunction. Furthermore, this study highlights the significance of digital spatial profiling in mapping the intricate crosstalk between trophoblasts and villous core stromal cells, thus shedding light on pathways associated with placental dysfunction in pregnancies with SARS‐CoV‐2 infection.

Yes-associated protein (YAP) is a pivotal regulator in cellular proliferation, survival, differentiation, and migration, with significant roles in embryonic development, tissue repair, and tumorigenesis. At the maternal–fetal interface, emerging evidence underscores the importance of precisely regulated YAP activity in ensuring successful pregnancy initiation and progression. However, despite the established association between YAP dysregulation and adverse pregnancy outcomes, insights into the impact of aberrant YAP levels in fetal-derived, particularly trophoblast cells, and the ensuing dysfunction at the maternal–fetal interface remain limited. This review comprehensively examines YAP expression and its regulatory mechanisms in trophoblast cells throughout pregnancy. We emphasize its integral role in placental development and maternal–fetal interactions and delve into the correlations between YAP dysregulation and pregnancy complications. A nuanced understanding of YAP's functions during pregnancy could illuminate intricate molecular mechanisms and pave the way for innovative prevention and treatment strategies for pregnancy complications. 59X2rQyhJem7PrxahrMaVy Video Abstract [ABSTRACT FROM AUTHOR]

La survenue d'une grossesse chez une femme avec une biologie et a fortiori un syndrome des antiphospholipides (SAPL) n'est pas rare, qu'elle soit associée ou non à la présence d'une connectivite notamment un lupus systémique. Le SAPL est associé à une augmentation du risque de complications à la fois maternelles et fœtales incluant pertes fœtales, retard de croissance in utero, pré-éclampsie, prématurité, thromboses et hémorragies maternelles. La prise en charge de ces grossesses est optimisée par leur planification au cours d'une consultation préconceptionnelle associée à une prise en charge multidisciplinaire par des équipes entraînées. La faible activité d'un éventuel lupus associé, un traitement adapté aux antécédents et au profil biologique antiphospholipides ainsi qu'une surveillance régulière sont les principaux éléments permettant une issue favorable de ces grossesses à risque. Toutefois, la morbi-mortalité maternelle et fœtale reste plus importante que dans la population générale. The occurrence of pregnancy in a woman with antiphospholipid syndrome (APS) and/or antiphospholipid antibodies has become a common situation, whether or not it is associated with another connective tissue disease, in particular systemic lupus erythematosus. APS exposes to an increased risk of both maternal and fetal complications including fetal loss, in utero growth restriction, pre-eclampsia, prematurity, maternal thrombosis and hemorrhage. Improving the care of these pregnancies depends upon a systematic pregnancy planning, ideally during a preconception counseling visit and a multidisciplinary approach by teams trained in these high-risk pregnancies. Low disease activity of a possible associated lupus, appropriate medications during pregnancy adjusted to the patient's medical history and biologic antiphospholipid profile as well as a regular monitoring are the main elements allowing for a favorable outcome for these high-risk pregnancies. However, maternal and fetal morbidity and mortality remain higher than in the general population. [ABSTRACT FROM AUTHOR]

The transitory placenta develops during pregnancy and mediates the blood flow between the mother and the developing baby. Placental dysfunction, including but not limited to placenta accreta spectrum, fetal growth restriction, preeclampsia and gestational trophoblastic disease, arises from abnormal placental development and can result in significant adverse maternal and fetal health outcomes. Unfortunately, there is a lack of treatment alternatives for these disorders. Nanocarriers offer versatility, including extended circulation, organ-specific targeting and intracellular transport, finely tuning therapeutic placental interactions. This thorough review explores nanotechnological strategies for addressing placental disorders, encompassing dysfunction insights, potential drug-delivery targets and recent strides in placenta-targeted nanoparticle (NP) therapies, instilling hope for effective placental malfunction treatment. The placenta, essential for mother–baby blood exchange, may experience catastrophic abnormalities during pregnancy. Treating these issues is challenging since you must focus on the placenta while protecting the infant. Nanotechnology might be helpful in this scenario. Nanocarriers are small carriers that can transport medications to the placenta and other particular locations in the body. They can aid in the treatment of various placental issues. In our present review, we discuss nanotechnology's solutions to these issues. We discuss what goes wrong, potential therapeutic applications for nanocarriers and recent developments in their use. This might be a novel approach to treating placenta issues and maintaining the health of mothers and infants. [ABSTRACT FROM AUTHOR]

Background. Aortic isthmus retrograde blood flow in intrauterine children with growth delay and centralization of blood circulation in the late stages of placental dysfunction is associated with a high risk of perinatal death. Timely diagnosis of such condition is crucial to select further obstetric tactics and delivery time. Clinical case description. Growth delay and absent end-diastolic flow in umbilical artery and no A-wave in the venous duct were diagnosed in intrauterine child (gestational age — 36 weeks) at ultrasound study. Peripheral resistance indices in middle cerebral artery in the intrauterine child were lower than peripheral resistance indices in umbilical artery. Color Doppler imaging has revealed aortic isthmus retrograde blood flow. The woman was recommended delivery due to critical circulatory disorder in the intrauterine child. Female child was delivered via Caesarean section, child’s weight — 890 g, APGAR score — 3/4. The newborn girl died due to multi-organ failure within the first day.Conclusion. Revealing the retrograde blood flow in intrauterine child in the aortic isthmus throughout the entire ventricular diastole is an unfavorable prognostic sign of the terminal stage of cerebral blood flow disturbance associated with placental dysfunction.

Chronic hypertension is a major risk factor for preeclampsia (PE), associated with significant maternal and neonatal morbidity. We previously demonstrated that pregnant stroke-prone spontaneously hypertensive rats (SHRSP) display a spontaneous PE-like phenotype with distinct placental, fetal, and maternal features. Here, we hypothesized that supplementation with alpha lipoic acid (ALA), a potent antioxidant, during early pregnancy could ameliorate the PE phenotype in this model. To test this hypothesis, timed pregnancies were established using 10 to 12-week-old SHRSP females (n = 19–16/group), which were assigned to two treatment groups: ALA (injected intraperitoneally with 25 mg/kg body weight ALA on gestation day (GD1, GD8, and GD12) or control, receiving saline following the same protocol. Our analysis of maternal signs showed that ALA prevented the pregnancy-dependent maternal blood pressure rise (GD14 blood pressure control 169.3 ± 19.4 mmHg vs. 146.1 ± 13.4 mmHg, p = 0.0001) and ameliorated renal function, as noted by the increased creatinine clearance and improved glomerular histology in treated dams. Treatment also improved the fetal growth restriction (FGR) phenotype, leading to increased fetal weights (ALA 2.19 ± 0.5 g vs. control 1.98 ± 0.3 g, p = 0.0074) and decreased cephalization indexes, indicating a more symmetric fetal growth pattern. This was associated with improved placental efficiency, decreased oxidative stress marker expression on GD14, and serum soluble fms-like tyrosine kinase 1 (sFlt1) levels on GD20. In conclusion, ALA supplementation mitigated maternal signs and improved placental function and fetal growth in SHRSP pregnancies, emerging as a promising therapy in pregnancies at high risk for PE.

Background: Obesity and hyperlipidaemia during pregnancy increase the risk of metabolic dysfunction-associated steatotic liver disease. Our aim was to evaluate changes in the fibrinolytic system in overweight pregnant women due to metabolic dysfunction-associated steatohepatitis, compared with a control group and its impact on the development of gestational complications. Methods: Prospective cohort study included 69 overweight pregnant women with metabolic dysfunction-associated steatohepatitis and 30 healthy pregnant women (control group). All pregnants with metabolic dysfunction-associated steatohepatitis and obesity were divided into 3 subgroups: IA – 23 overweight pregnant women, IB – 25 pregnants with obesity grade 1, IC – 24 pregnant women with obesity grade 2. To evaluate the fibrinolysis system, we studied total, enzymatic and non-enzymatic fibrinolytic activity of plasma. Results: The total fibrinolytic activity of IA, IB and IC groups were, respectively, 15%, 19% and 23% lower than that of controls and the enzymatic fibrinolytic activity in overweight pregnant women with metabolic dysfunction-associated steatohepatitis of IA, IB and IC groups were, respectively 28%, 43% and 54% lower than in controls. Marked suppression of the total fibrinolytic activity and enzymatic fibrinolytic activity of the blood plasma was established in overweight pregnant women with metabolic dysfunction-associated steatohepatitis. These changes can serve as a prerequisite for the occurrence of microthrombosis with the subsequent development of placental dysfunction, fetal growth restriction and fetal distress. Conclusions: There are disorders in the system of the coagulation function with a tendency to peripheral microthrombosis, disseminated intravascular coagulation syndrome and macrothrombosis, which can be early prognostic criteria in the development of obstetric and perinatal complications in overweight pregnant women with metabolic dysfunction-associated steatohepatitis. Clinical Trial Registration: This work is a fragment of the complex research work of the Department of Obstetrics and Gynecology of I. Horbachevsky Ternopil National Medical University of the Ministry of Health of Ukraine “A comprehensive approach to symptom control, recurrent and long-term prognosis in conditions of comorbid pathology in internal medicine clinic and family doctor’s practice” (state registration number 0223U000022, 0118U000361 https://nrat.ukrintei.ua/en/searchdoc/).

Scientific research in the field of physiology and pathology of the umbilical cord is quite limited and imperfect. The purpose of the study was to evaluate the histological architecture of the pathological umbilical cord and investigate the relationship between the main parameters and placental postnatal macromorphometric characteristics, which serve as a reflection of placental dysfunction. Four groups of patients were included, each undergoing a postnatal histological and topographic examination of the umbilical cord: Wharton's jelly edema (10 samples), velamentous cord insertion (10 samples), single umbilical artery (10 samples), and physiological pregnancy (10 samples). Compared to the control group, all newborn groups exhibited changes in umbilical vessel morphology, characterized by an increased Wagenworth index and a decreased Kernohan index. The functional indices of the umbilical vessels were found to be most severely affected in cases of Wharton's jelly edema. In cases of single umbilical artery, the changes in vascular functional parameters indicated their compensatory remodeling with the highest Wagenworth and Kernohan indices of the umbilical vein. Deviation from the normal average placental weight was observed in cases of Wharton's jelly volume pathology or velamentous cord insertion. However, in the case of a single umbilical artery, there were no significant deviations in the macromorphometry of the placenta. [ABSTRACT FROM AUTHOR]

Premature birth, despite the significant achievements of perinatal medicine in recent decades, remains an urgent global and national medical and social problem, as it is the leading cause of perinatal morbidity and mortality. According to modern views, placental dysfunction can be one of the causes of premature birth, and its frequency, according to randomized studies, can be from 78 to 91%, depending on the gestational age. At the same time, the research conducted to date does not provide a clear understanding of the role of timely diagnosis and prevention of placental dysfunction in preventing premature birth. The objective: to perform clinical evaluation of the prevalence of placental dysfunction in women at risk of preterm birth and with threat of preterm birth. Materials and methods. 180 pregnant women were took part in the study. To achieve the research aim, three research groups were formed. I group – 73 pregnant women with threat of premature birth; II group – 77 pregnant women with risk factors for premature birth. Women with risk factors for premature birth were included in the study at the stage of pregnancy planning (IIA subgroup, 39 women) or from the moment of applying to a women’s outpatient clinic to monitor the course of pregnancy (IIB subgroup, 38 pregnant women). The control group included 30 pregnant women with an uncomplicated course of pregnancy. Transabdominal ultrasound examination with color Doppler mapping, determination of free estriol, progesterone and placental lactogen levels in blood serum were performed at 18–21+6 and 28–30 weeks of gestation. Results. Analysis of the prevalence of risk factors for placental dysfunction and preterm birth in patients of the studied cohort showed that in pregnant women with preterm birth (I group), the combination of risk factors was 5.2; in pregnant women who received pre-gravid training (IIA subgroup) – 3.2; in pregnant women who were included in the study in the I trimester of pregnancy (IIB subgroup) – 4.7, while in pregnant women of the control group – only 0.8 (p<0.05). The threat of early spontaneous miscarriage with the formation of a retrochorial hematoma as a clinical manifestation of primary placental dysfunction was determined in 43.8% of pregnant women whose premature delivery was carried out for medical reasons. Placenta abruption in these patients can be considered as decompensation of the primary dysfunction of the placenta with the transition to acute placental insufficiency. The formation of chronic placental dysfunction, clinically manifested by the syndrome of fetal growth retardation, was most often observed in patients whose pregnancy ended in spontaneous premature birth at 34–36+6 weeks in the presence of an untouched amnion, – 68.6% compared to births at 28–33+6 weeks of gestation – 25.9% and with childbirth at 22–37+6 weeks – 13.3%. Conclusions. Clinical manifestations of placental dysfunction were detected in 30.6% of patients with premature birth, with morphological signs in 60.4% of cases, which indicates the hidden course of placental insufficiency before the development of premature birth. Morphological signs of placental dysfunction were determined in 87.5% of cases of premature births for medical reasons and in 100.0% of cases of spontaneous births at 22–27+6 weeks of gestation (with a combination of risk factors from 2.1 to 3.0), in 66.7% – with premature births at 28–33+6 weeks of pregnancy, in 40.0% – with premature births at 34–36+6 weeks of pregnancy and only in one (5.6%) case – with term births. The frequency of fixation of morphological characteristics of placental dysfunction correlates with the frequency of early pregnancy complications, primarily with the formation of retrochorial hematomas in the first half of pregnancy. [ABSTRACT FROM AUTHOR]

The placenta is particularly susceptible to inflammation and oxidative stress, leading to placental vascular dysfunction and placental insufficiency, which is associated with fetal intrauterine growth restriction (IUGR). It is unknown whether folic acid (FA) supplementation can alleviate high-fat diet-induced IUGR in rats by improving placental function. In this study, pregnant rats were randomized into one of four diet-based groups: (1) control diet (CON), (2) control diet supplemented with FA, (3) high-fat diet (HFD), and (4) high-fat diet supplemented with FA (HFD + FA). Dams were sacrificed at gestation day 18.5 (GD18.5). The results indicated that dietary FA supplementation normalized a maternal HFD-induced decrease in fetal weight. The decrease in placental efficiency, labyrinth zone (LZ) area, blood sinusoid area, vascular density, and the levels of angiogenesis factors induced by a maternal HFD were alleviated by the addition of FA, suggesting that FA supplementation can alleviate placental vascular dysplasia. Furthermore, FA supplementation increased the protein expressions of SIRT1, inhibited NF-κB transcriptional activation, attenuated the levels of NF-κB/downstream pro-inflammatory cytokines, induced Nrf2 activation, and increased downstream target protein expression. In conclusion, we found that dietary FA supplementation during pregnancy could improve maternal HFD-induced IUGR by alleviating placental inflammation and oxidative stress, which may be associated with the regulation of SIRT1 and its mediated NF-κB and Nrf2 signaling pathways. [ABSTRACT FROM AUTHOR]

The objective: to evaluate the clinical effectiveness of L-arginine in the prevention of preeclampsia and reduction of other perinatal risks in patients with preclinical gestational endotheliopathy (GE). Materials and methods. A comparative clinical study was performed at the clinical base of the Department of Obstetrics and Gynecology N. 1 of the Vinnytsya National Pirogov Memorial Medical University. 116 pregnant women with preclinical GE (main group), which was diagnosed by laboratory and instrumental research (microalbuminuria and endothelium-dependent vasodilatation), took part in the study. The patients of the main group were divided into clinical subgroups: 31 pregnant women with GE in subgroup A received acetylsalicylic acid (ASA) at a dose of 75 mg per or per day; 33 patients with preclinical GE from subgroup B received L-arginine at a dose of 4-4.2 g per or per day; 52 pregnant women with preclinical GE who refused prophylactic treatment were included in the subgroup C. The control group involved 58 pregnant women with a physiological gestation and without GE. The clinical effectiveness of the therapy was assessed by comparing the number of cases of perinatal pathology in the I, II and III trimesters. Results. The use of L-arginine as an alternative preventive therapy for the development of preeclampsia and other perinatal pathology made possible to reduce the rate of preeclampsia significantly (RR 0.19, 95% CI: 0.05-0.77; p=0.02) and placental hyperplasia/hypoplasia (RR 0.17, 95% CI: 0.04-0.68; p=0.01), compared to patients who did not receive any preventive treatment. In pregnant women with early-onset gestational endotheliopathy who received L-arginine, placental dysfunction was not diagnosed in the II and III trimesters of pregnancy and there were no cases of fetal growth retardation. The use of L-arginine was not associated with side effects and/or adverse reactions in the proposed dose and frequency of administration and can be considered beneficial for the mother and the fetus. Conclusions. Prescribing ASA and L-arginine drugs for pregnant women with a moderate degree of perinatal risk (preclinical GE) made possible not only to prolong pregnancy, but also to prevent the development of severe perinatal pathology. A more pronounced clinical effectiveness of the course prescription of solution of L-arginine per or (daily dose of L-arginine - 4.0-4.2 g) in pregnant women with preclinical form of GE may be associated with the endotheliotropic protective effect of the drug. The appropriateness of using L-arginine during pregnancy is still debated, and further researches are needed to determine the optimal dosage, initial period for using and duration for the best prophylactic or therapeutic effect. [ABSTRACT FROM AUTHOR]

Objective: to study the effectiveness of complex therapy of placental dysfunction (PD) as a method of prevention of fetal growth retardation syndrome in pregnant women with miscarriage in the 1st trimester of pregnancy. Materials and methods. 100 pregnant women with verified PD on the background of miscarriage in the first trimester of pregnancy took part in the study. Verification criteria for PD were: a decrease in the volume of the chorion and its vascularization index by more than 15%, an increase of the resistance index in the uterine and spiral arteries during dopplerometric examination at the end of the first trimester of pregnancy. The patients were divided into groups: group I (main) – 36 pregnant women with PD who received complex treatment, group II (comparative) – 32 pregnant women with PD who were prescribed only hormonal support, III group (control) – 32 patients with the physiological course of the first trimester of pregnancy. Complex therapy in the group I included hormonal agents, venotonic drug Normoven, the drug Magnicum, and the drug Artihol. Clinical data, ultrasound fetometry, dopplerometric study of utero-fetal blood flow were used to assess the effectiveness of treatment. Results. Already in the 22–24th week of gestation there was no significant difference in the resistance index in the spiral and uterine arteries between the main and control groups (p > 0.05). Ultrasound fetometry at 32–34 weeks of gestation showed that in the first group there were 8.3% (3) fetuses small for gestational age, 15.6% (5) in the second group and 3.1% (1) in the control. The average body weight of newborns in the main group and in the comparison group differed significantly and was 2810 ± 267 and 2610 ± 175 g respectively (р < 0.05) and 3295 ± 295 g in the control group. Conclusions. Complex, pathogenetically justified, long-term treatment of PD from the early stages of pregnancy makes it possible to avoid progression of compensated and development of subcompensated stages of placental disorders. Complex therapy of PD, which includes micronized progesterone, Normoven, Artichol and Magnicum, Complex PD therapy, which includes micronized progesterone, Normoven, Artihol and Magnicum, normalizes blood flow in the mother-placenta-fetus system, normal growth and fetus development and is an effective way of preventing fetal growth retardation.

Objectives: to study the levels of the total, phosphorylated p65-subunit of the nuclear factor NF-kB, activity of p65 and the relation with the level and ratio of T-helpers type I and II in pregnant women with placental dysfunction and different clinical types of the course of preterm labor (with preterm premature rupture of membranes (pPROM) and without it). Materials and methods. The case-control study included 60 pregnant women: 40 women with placental disorders and spontaneous premature labor in the period of 24–34 weeks (group I – 20 women with premature labor and timely discharge of amniotic fluid, group II – 20 women with pPROM) and 20 women of the control group (CG) with normal timely delivery in the head position of a fetus without complications. The value of the total NF-kB p65 subunit and its phosphorylated fraction was determined in all women using ELISA in placenta lysates. On this basis the p65 subunit activity was calculated; number of T-helper I (Th1) and T-helper II (Th2) was determined using flow cytometry in a whole blood sample, with afterward calculation of the Th1/Th2 ratio. Results. Elevated levels of total p65 and its phosphorylated fraction were found in women with placental dysfunction (p < 0.01 in groups I and II compared with CG), as well as the activity p65 (p < 0.01 in group I, p = 0.04 in group II compared with CG). The difference in the Th1 value and the Th1/Th2 ratio was significantly higher in both groups (p < 0.01 in group I, p = 0.03 in group II for Th1; p < 0.01 in both groups for Th1/Th2), the number of Th2 differed significantly only in group I (p < 0.01 compared with CG). A strong positive correlation between p65 activity and Th1/Th2 was also established (r = 0.8). Conclusions. Obtained data indicates the increased NF-kB p65-subunit activity in women with placental disorders and spontaneous premature labor without pPROM, which is impact on the increase of the Th1/Th2 ratio due to the Th1 increase. This mechanism might be considered to be the leading cause of the premature birth in this group of pregnant women. However, for women with the preterm labor activity with pPROM, the difference with GC has a lower level of significance, which may indicate the existence of another leading mechanism for the initiation of premature labor in this group.

Introduction: Transplacental fetal cell transfer results in the engraftment of fetal-origin cells in the pregnant woman's body, a phenomenon termed fetal microchimerism. Increased fetal microchimerism measured decades postpartum is implicated in maternal inflammatory disease. Understanding which factors cause increased fetal microchimerism is therefore important. During pregnancy, circulating fetal microchimerism and placental dysfunction increase with increasing gestational age, particularly towards term. Placental dysfunction is reflected by changes in circulating placenta-associated markers, specifically placental growth factor (PlGF), decreased by several 100 pg/mL, soluble fms-like tyrosine kinase-1 (sFlt-1), increased by several 1000 pg/mL, and the sFlt-1/PlGF ratio, increased by several 10 (pg/mL)/(pg/mL). We investigated whether such alterations in placentaassociated markers correlate with an increase in circulating fetal-origin cells. Material and methods: We included 118 normotensive, clinically uncomplicated pregnancies (gestational age 37+1 up to 42+2 weeks' gestation) pre-delivery. PlGF and sFlt-1 (pg/mL) were measured by Elecsys® Immunoassays. We extracted DNA from maternal and fetal samples and genotyped four human leukocyte antigen loci and 17 other autosomal loci. Paternally inherited, unique fetal alleles served as polymerase chain reaction (PCR) targets for detecting fetal-origin cells in maternal buffy coat. Fetalorigin cell prevalence was assessed by logistic regression, and quantity by negative binomial regression. Statistical exposures included gestational age (weeks), PlGF (100 pg/mL), sFlt-1 (1000 pg/mL) and the sFlt-1/PlGF ratio (10 (pg/mL)/(pg/mL)). Regression models were adjusted for clinical confounders and PCR-related competing exposures. Results: Gestational age was positively correlated with fetal-origin cell quantity (DRR = 2.2, P = 0.003) and PlGF was negatively correlated with fetal-origin cell prevalence (odds ratio [OR]100 = 0.6, P = 0.003) and quantity (DRR100 = 0.7, P = 0.001). The sFlt-1 and the sFlt-1/PlGF ratios were positively correlated with fetal-origin cell prevalence (OR1000 = 1.3, P = 0.014 and OR10 = 1.2, P = 0.038, respectively), but not quantity (DRR1000 = 1.1, P = 0.600; DRR10 = 1.1, P = 0.112, respectively). Conclusions: Our results suggest that placental dysfunction as evidenced by placentaassociated marker changes, may increase fetal cell transfer. The magnitudes of change tested were based on ranges in PlGF, sFlt-1 and the sFlt-1/PlGF ratio previously demonstrated in pregnancies near and post-term, lending clinical significance to our findings. Our results were statistically significant after adjusting for confounders including gestational age, supporting our novel hypothesis that underlying placental dysfunction potentially is a driver of increased fetal microchimerism. [ABSTRACT FROM AUTHOR]

Objective: This study was conducted to analyse the medication indications of hydroxychloroquine (HCQ) and to explore the clinical characteristics and perinatal outcomes of pregnancy in women with autoimmune abnormalities. The value of HCQ against placental dysfunction–related pregnancy outcomes in people with autoimmune abnormalities was also explored. Methods: ① To collect HCQ application cases during pregnancy who were hospitalized and delivered from 2016 to 2020. The classification and distribution of HCQ indications were analysed. The characteristics of cases and pregnancy outcomes were discussed. ② To include pregnancy combined with autoimmune abnormalities population during the period. Demographic information, clinical characteristics, classification, medication time frame, and pregnancy outcomes were discussed. Results: ① There were 741 cases of HCQ use during pregnancy. Classification by drug indication was as follows: 257 cases (34.68%) had clear indications for autoimmune diseases. There were 359 controversial cases, as follows: 140 (18.89%) cases of antiphospholipid syndrome and 219 (29.55%) cases of autoantibody-positive cases who had no clear drug indication and also used HCQ during pregnancy. No indications were found for 125 cases (16.87%), without autoimmune abnormalities and empirical medication of HCQ during pregnancy. ② In 853 pregnancies with autoimmune abnormalities, women with systemic lupus erythematosus, Sjögren's syndrome, rheumatoid arthritis, and undifferentiated connective tissue disease had clear indications for HCQ. The proportions of HCQ applied during pregnancy were 86.67%, 85.71%, 73.53%, and 75.00%. The start of medication before pregnancy only accounted for 74.44%, 65.31%, 64.71%, and 43.38%. ③ Medication indicated antiphospholipid syndrome and simple autoantibody-positive cases in the controversial population. The proportions of cases in which HCQ was used during pregnancy were 74.47% (140/188) and 64.79% (219/338). Application of HCQ during pregnancy significantly reduced pre-eclampsia (19.8% vs. 8.91%, P < 0.001), early-onset pre-eclampsia (7.78% vs. 2.51%, P = 0.007), and pregnancy loss during the middle and late pregnancy stages (2.99% vs. 0.56%, P = 0.036) in this controversial population. Conclusion: Empirical, over-indicated, or even no indications usage of HCQ in pregnancy is common. The strength of standardized and specialist management are needed in populations with clear HCQ indications. HCQ-indicated controversial population should avoid overdiagnosis and guard against the potential risks of combined anticoagulation and glucocorticoid therapy. The incidence of placental dysfunction diseases in people with autoimmune abnormalities increases. HCQ application may alleviate the incidence of adverse pregnancy outcomes in this population. Key Points •The incidence of placental dysfunction diseases in people with autoimmune abnormalities increases. •Our work have discovered the unique value of HCQ in improving placental dysfunction diseases in autoimmune abnormal cases, not just in AID such as SLE, SS, UTCD, and RA. •HCQ is a potential drug option for autoimmune abnormalities to improve placental function, by providing synergistic prevention and treatment of these disorders, not just single target of antispasmodic, anti-hypertensive, and circulatory improvement. •Empirical, over-indicated, or even no indications usage of HCQ in pregnancy is common. However, the strength of standardized and specialist management are needed in populations with clear HCQ indications. [ABSTRACT FROM AUTHOR]

Introduction: Pregnancies conceived through assisted reproductive techniques (ARTs) are on the rise worldwide and have been associated with a higher risk of placental-related disease in the third trimester. Methods: A cohort was created of singleton pregnancies after assisted reproduction, admitted at our institution for delivery, between January 2020 and August 2022. Fetal growth velocity from the second trimester to delivery was compared against a gestational-age-matched group of pregnancies spontaneously conceived according to the origin of the selected oocyte (i.e., autologous vs. donated). Results: 125 singleton pregnancies conceived through ART were compared to 315 singleton spontaneous conceptions. Overall, after adjusting for possible confounders, multivariate analysis demonstrated that ART pregnancies had a significantly lower estimated fetal weight (EFW) z-velocity from the second trimester to delivery (adjusted mean difference = −0.002; p = 0.035) and a higher frequency of EFW z-velocity in the lowest decile (adjusted OR = 2.32 [95% CI, 1.15–4.68]). Also, when ART pregnancies were compared according to the type of oocyte, those conceived with donated oocytes showed a significantly lower EFW z-velocity from the second trimester to delivery (adjusted mean difference = −0.008; p = 0.001) and a higher frequency of EFW z-velocity in the lowest decile (adjusted OR = 5.33 [95% CI, 1.34–21.5]). Conclusions: Pregnancies achieved through ART exhibit a pattern of lower growth velocity across the third trimester, especially those conceived with donated oocytes. The former represents a sub-group at the highest risk of placental dysfunction that may warrant closer follow-up. [ABSTRACT FROM AUTHOR]

The risk of fetal intrauterine growth retardation (IUGR) is increased in women who have experienced acute infections, as well as in pregnant women with gynecological pathology and endocrine diseases. A woman’s lack of nutrition also makes a negative contribution to the development of IUGR. The frequency of IUGR in the population is very variable and depends on a number of reasons. In practically healthy pregnant women, IUGR is registered in 3–5% of cases, in case of complicated obstetric and gynecological diagnosis and complicated pregnancy – in 10–25%. Morphofunctional disorders in the chorion/placenta in pregnant women with COVID-19 on the background of post-covid endotheliitis are the main pathogenetic factor in the development of preeclampsia, ectopic pregnancy, antenatal fetal death, and impaired condition of the fetus and newborns. Sufficient saturation of the pregnant woman’s body with the nitric oxide donor L-arginine and L-carnitine (main cofactor of fatty acid metabolism in cells) with the improvement of microcirculation and the correction of hypovolemic disorders in the fetoplacental complex can be considered one of the real ways to prevent IUGR in women in the post-covid period. A review of the scientific literature on pathogenesis, diagnosis, impact on the life and health of a newborn with IUGR in women after COVID-19, as well as the possibilities of medical correction of placental dysfunction during pregnancy was performed. This analysis and our own clinical experience allow us to state the fact that after a coronavirus infection during pregnancy, one of the frequent and threatening for the further development of the child is the formation of placental dysfunction and IUGR. One of the ways to prevent these conditions is to saturate the woman’s body with the nitric oxide donor L-arginine from the stage of pre-gravid preparation, which will provide the opportunity for adequate angiogenesis and development of the embryo/fetus. In the case of additional risk factors, such as coronavirus disease, complex therapy blood (Rheosorbilact), in combination with a nitric oxide donor and L-carnitine as an endothelium-protective agent (Tivor-L).