Fetal Weight Research Articles

Impacts of tolylfluanid on implantation and placental development: Disruption of mitochondrial function and implantation-related gene expression in vitro and in vivo

Tolylfluanid is a widely used pesticide and antifouling agent in agricultural and marine industries and is recognized as a potential endocrine disruptor. However, the toxicological effects of tolylfluanid on the placenta development was not elucidated. This study used trophoblastic cell (HTR-8/SVneo cell) and endometrial cell (T HESCs) lines as in vitro model and mouse models as in vivo model to investigate the toxic effects of tolylfluanid on implantation-associated cell and placenta development during early pregnancy. Experimental results indicated that both cell lines exhibited reduced viability upon tolylfluanid exposure. Various in vitro experiments were conducted at <1 mg/L concentration. The results indicate that tolylfluanid can arrest cell cycle and induce apoptosis in endometrial and trophoblastic cells, abnormally regulate Ca2+ homeostasis and MAPK signaling pathways, and disrupt mitochondrial function. In vivo experiments, subchronic tolylfluanid exposure to mouse during puberty and pregnancy period impaired placenta development, resulting in reduced fetal and placental weight, abnormal placental structures, and altered gene expression. Specifically, a decrease in the ratio of labyrinth/junctional zones and changes in placenta gene expression patterns after tolylfluanid exposure were similar to characters of adverse pregnancy outcomes such as preeclampsia and fetal growth restriction (FGR). This study suggests that tolylfluanid exposure may have negative outcomes on female reproduction, and highlights the need for stricter regulation and monitoring of tolylfluanid use to protect women's reproductive health. This is the first study indicating the adverse effects of tolylfluanid on implantation and placental development during pregnancy.

Prenatal developmental toxicity studies of allyl alcohol in rats and rabbits

Allyl alcohol (C3H6O; prop-2-en-1-ol; CAS RN 107-18-6; EINECS 203-470-7) is used as an intermediate/monomer in polymerization reactions producing chemicals/optical resins or as a coupling/cross-linking agent for unsaturated polyester and alkyd resins. Human exposure to allyl alcohol (AA) is restricted to workplace manufacturing facilities where it is used in enclosed systems, which limits release and impact on environmental receptors. To address regulatory questions about possible developmental toxicity, two OECD Guideline studies were conducted. A rat developmental toxicity study found fetal and maternal toxicity, in the form of resorptions and decreased body weight and food consumption, but no teratogenic effects. A rabbit developmental toxicity study was subsequently conducted upon request by the European Chemical Agency in 2011 under the REACH program and likewise reported maternal toxicity in the form of reductions in body weight gain and food consumption, but neither fetal toxicity or teratogenic effects. The results of both studies are presented and compared in this paper. Based on our review of the collective results of these studies, AA is considered non-teratogenic, yet does elicit increased post-implantation loss and reduced fetal body weight, possibly resulting from concomitant maternal toxicity. Based on the results of these studies, a maternal and developmental toxicity No Observed Adverse Effect Level of 10 mg/kg/day was apparent for both species.

Evaluation of the Screening Performance of Ultrasonographic Abdominal Circumference and Estimated Fetal Weight in Predicting Small for Gestational age Newborns

OBJECTIVES: We aimed to evaluate the screening performance of estimated fetal weight (EFW) and abdominal circumference (AC) measurements in predicting newborns with birth weight (BW) less than the 10th percentile for birth age (BW &lt;10p). STUDY DESIGN: Three hundred thirty-one pregnant women who met the inclusion and exclusion criteria were included in the study. The groups were divided into two groups: those diagnosed with FGR (FGR group) and those not diagnosed (non-FGR)after the 32nd week of gestation. Demographic and obstetric histories, ultrasonographic and clinical features, and neonatal outcomes of the groups were recorded, and comparisons between the groups were conducted. The screening performances of AC and EFW were compared for predicting newborns with BW&lt;10p and assessing neonatal outcomes. RESULTS: AC or EFW measures below 10% (AC&lt;10p or EFW&lt;10p) demonstrated the highest screening performance for BW&lt;10p, with 91.7% sensitivity and 91% specificity. AC&lt;10p demonstrated the highest performance in predicting neonatal intensive care unit (NICU) admission, with 75.9% sensitivity and 89.1% specificity. For neonates with a 5-minute APGAR score of less than 7, AC&lt;10p or EFW&lt;10p had 88.2% sensitivity and 69.7% specificity. CONCLUSION: This study shows that AC and EFW measurements can be used together or separately to predict newborns who are small for their gestational age (SGA). Using values below 10% of either AC or EFW together gives the best results in terms of sensitivity and specificity.

Predictive value of Vitamin D levels in pregnant women on gestational length and neonatal weight in China: a population-based retrospective study

BackgroundVitamin D deficiency, a common occurrence among pregnant women, is an emerging public health concern worldwide. According to research, prenatal vitamin D deficiency is associated with various complications. This study assessed the vitamin D status of pregnant women in Yanbian, Jilin Province, as well as the correlation and predictive value of their vitamin D levels in relation to gestational length (weeks) and fetal weight, aiming to provide a basis for clinical diagnosis and treatment.MethodsWe conducted a population-based retrospective study involving 510 pregnant women from August 2019 to October 2022. Blood samples were collected at 16–20 weeks of gestation for the detection of serum vitamin D levels. Statistical analyses were performed using SPSS 28.0 and R 4.1.0 software. Multifactorial logistic regression analysis was employed to establish whether each variable was a risk factor for deliveries at ≤ 38 gestational weeks and low fetal weight. These results were used to construct a risk prediction model, and the model’s predictive efficacy was evaluated. Results or differences with p < 0.05 were considered statistically significant.ResultsMultifactorial logistic regression analysis revealed that vitamin D ≤ 14.7 ng/mL(OR: 1.611; 95% CI: 1.120–2.318; P = 0.010), Bone Mineral Density (BMD) T-value ≤-1(OR: 1.540; 95%CI: 1.067–2.223; P = 0.021), and gestational hypertension(OR: 7.173; 95% CI: 1.482–34.724; P = 0.014) were the independent risk factors for deliveries at ≤ 38 gestational weeks. Additionally, vitamin D ≤ 14.7 ng/mL(OR: 1.610; 95%CI: 1.123–2.307; P = 0.009), BMD T-value ≤ -1(OR: 1.560; 95%CI: 1.085–2.243; P = 0.016), and gestational hypertension(OR: 4.262; 95% CI: 1.058–17.167; P = 0.041) were the independent risk factors for low fetal weight (< 3400 g).ConclusionThis study revealed that low vitamin D levels are an independent risk factor for a short gestational length and low fetal weight. Prenatal low BMD T-value and comorbid hypertensive disorders were also found to increase the risk of a short gestational length and low fetal weight.

Baicalin ameliorates heat stress-induced hepatic injury and intestinal microecology dysbiosis in late gestational mice

Heat stress (HS) disrupts intestinal microbiota, glycolipid metabolism, and hepatic mitochondrial function in late gestational mice. Baicalin (BAI), a Chinese herbal medicine known for its heat-clearing and anti-inflammatory properties, has shown promise in modulating intestinal microecology and mitigating inflammation in various organs. This study investigates whether baicalin attenuates HS-induced intestinal microbial dysbiosis and liver damage in pregnant mice during late gestation. Twenty-four pregnant mice were randomly assigned to four groups, including thermoneutral (TN) (24 ± 1 ℃), HS (35 ± 1 ℃), HS+BAI200 (oral gavaged with 200 mg/kg BW of BAI), and HS+BAI400 (oral gavaged with 400 mg/kg BW of BAI). 400 mg/kg BAI treatment markedly decreased the rectal temperature and increased fetal weight in HS pregnant mice. Furthermore, 400 mg/kg BAI administration effectively ameliorated HS-induced hepatic damage and lipid disorders, reducing HSP70, AST, and ALT levels while increasing TG concentration. Notably, it activated a network of genes involved in lipid synthesis, including fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC), and oxidation, such as peroxisome proliferator-activated receptor alpha (PPARα), carnitine palmityl transferase 1 beta (CPT1β). Moreover, BAI intervention restored the intestinal morphology and barrier function, evidenced by increased intestinal villus height, the ratio of villus height to crypt depth, and colonic goblet cells numbers. 400 mg/kg of BAI treatment up-regulated the expression of tight junction proteins, such as claudin-1 and Zonula Occludens-1 (ZO-1), in the jejunum and ileum, counteracting HS-induced downregulation. High-throughput sequencing showed that BAI treatment altered cecal microbial composition, increasing the relative abundance of beneficial Bacteroidota and decreasing Deferribacterota, Turicibacter, and Akkermansia. Spearman’s correlation analysis highlighted significant correlations between differential cecal microbiota and physiological indexes. In conclusion, BAI administration alleviated adverse impacts in heat-exposed mice during late gestation, improving maternal physiological parameters, and ameliorating hepatic damage with altered cecal microbial composition. The findings suggest that BAI may regulate the gut-liver axis by modulating intestinal morphology, microecology, and hepatic function.

Prenatal organophosphate pesticide exposure and sex-specific estimated Fetal size.

Prenatal organophosphate (OP) pesticide exposure may be associated with reduced fetal growth, although studies are limited and have mixed results. We investigated associations between prenatal OP pesticide exposure and fetal size and modification by fetal sex. Maternal urinary concentrations of dialkyl phosphate (DAP) metabolites were measured at three time points. Fetal biometrics were obtained from ultrasounds in the second (n=773) and third (n=535) trimesters. Associations between pregnancy-averaged ΣDAP and fetal biometry z-scores were determined through multiple linear regression. Modification by sex was investigated through stratification and interaction. In the second trimester, one ln-unit increase in ΣDAP was associated with lower estimated fetal weight (-0.15 SD; 95% CI: -0.29, -0.01), head circumference (-0.11 SD; CI: -0.22, 0.01), biparietal diameter (-0.14 SD; CI: -0.27, -0.01), and abdominal circumference (-0.12 SD; CI: -0.26, 0.01) in females. In the third trimester, one ln-unit increase in ΣDAP was associated with lower head circumference (-0.14 SD; CI: -0.28, 0.00) and biparietal diameter (-0.12 SD; CI: -0.26, 0.03) in males. Our results suggest that prenatal OP pesticide exposure is negatively associated with fetal growth in a sex-specific manner, with associations present for females in mid-gestation and males in late gestation.

Third-Trimester Ultrasound Diagnosis of Large for Gestational Age and Risk of Cesarean Delivery.

Determine if knowledge of a third-trimester ultrasound diagnosis of large for gestational age (LGA) independently increases the risk of cesarean delivery (CD). Historical cohort comparing CD rate among patients diagnosed with an LGA fetus on a clinically indicated ultrasound from January 2017 to July 2021 with those without an LGA diagnosis at 34 weeks or later. LGA was defined as an ultrasound-estimated fetal weight greater than or equal to the 90th percentile for the gestational age. Univariate analysis was performed to identify significant confounding variables and was utilized as covariates for binary regression with CD rate as the primary outcome, and adjusted odds ratios (AOR) with 95% confidence intervals (CI) were calculated. Nulliparous term singleton vertex (NTSV) and multiparous CD rates were also compared. There were 447 patients diagnosed with an LGA fetus and 1971 patients without an LGA diagnosis on third-trimester ultrasound. The positive predictive value of LGA diagnosis was 50.1% and the false positive rate was 10.6%. Patients with a diagnosis of LGA had higher AOR of CD (OR 2.11, 95% CI 1.56-2.83), and higher AOR of NTSV CD (OR 1.88, 95% CI 1.14-3.13) compared with those without an LGA diagnosis. There was no difference in the rates of non-medically indicated CD, multiparous primary CD, and attempted and successful TOLAC. Our results suggest third-trimester ultrasound diagnosis of LGA independently increases odds of CD, specifically among nulliparous patients, and the potential bias may be one factor contributing to excessive CDs and NTSV CDs.

Omega-3 reverses the metabolic and epigenetically regulated placental phenotype acquired from preconceptional and peri-conceptional exposure to air pollutants

Air pollution is detrimental to pregnancy adversely affecting maternal and child health. Our objective was to unravel epigenetic mechanisms mediating the effect of preconception, periconception, and gestational exposure to inhaled air pollutants (AP) upon the maternal and placental-fetal phenotype and explore the benefit of an omega-3 rich dietary intervention. To this end, we investigated intranasal instilled AP during 8 weeks of preconception, periconception, and gestation (G; D0 to 18) upon GD16-19 maternal mouse metabolic status, placental nutrient transporters, placental-fetal size, and placental morphology. Prepregnant mice were glucose intolerant and insulin resistant, while pregnant mice were glucose intolerant but displayed no major placental macro-nutrient transporter changes, except for an increase in CD36. Placentas revealed inflammatory cellular infiltration with cellular edema, necrosis, hemorrhage, and an increase in fetal body weight. Upon examination of placental genome-wide epigenetic processes of DNA sequence specific 5′-hydroxymethylation (5′-hmC) and 5′-methylation (5′-mC) upon RNA sequenced gene expression profiles, revealed changes in key metabolic, inflammatory, transcriptional, and cellular processing genes and pathways. An omega-3 rich anti-inflammatory diet from preconception (8 weeks) through periconception and gestation (GD0-18), ameliorated all these maternal and placental-fetal adverse effects. We conclude that preconceptional, periconceptional and gestational exposures to AP incite a maternal inflammatory response resulting in features of pre-existing maternal diabetes mellitus with injury to the placental-fetal unit. DNA 5′-mC more than 5′-hmC mediated AP induced maternal inflammatory and metabolic dysregulation which together alter placental gene expression and phenotype. A dietary intervention partially reversing these adversities provides possibilities for a novel nutrigenomic therapeutic strategy.

Ultrasonic Estimation of Fetal Weight: Are Averaged Triplicate Measurements More Accurate Than Single Measurements?

To assess whether, and to what extent, performing triplicate measurements can improve accuracy of estimation of fetal weight (EFW) compared to single measurements. This was a prospective study conducted at a single medical center. A total of 100 term parturients with an anticipated delivery within 72 hours were recruited for EFW measurements. All examinations were done with adherence to the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG) guidelines. EFW was calculated using the Hadlock formula. Triplicate measurements from three different images were obtained for each parameter and the averaged values were used for clinical purposes. EFW calculated using average measurements was compared to EFW calculated using the first measurements. There was a small but significant improvement in EFW when using averaged measurements compared to single measurements (mean improvement 34 ± 105 g, P = .002). Deviance from birthweight in single measurements was significantly higher compared to averaged measurements (median deviance 198 versus 148 g, respectively, P = .005). This difference was more pronounced when assessing the 75th centile (348 versus 282 g, respectively). Using triplicate measurements instead of single measurements when performing EFW confers a small, but statistically significant, improvement to EFW accuracy. Using triplicate measurements for assessing EFW should be thus considered, especially in cases suspected of growth disorders.

Prediction of intrapartum fetal compromise at the end of pregnancy; is Doppler, and not weight, that matters

Despite the fact that labor depends on too many interacting factors and no parameter can fully predict its outcome, fetal cerebral Doppler has emerged as the most reliable tool for prediction, in contrast with fetal weight, which performs significantly worse in the last weeks of pregnancy. The importance of the cerebral Doppler follows the inverse pathway of fetal weight increasing its performance in the last weeks of pregnancy and reaching its highest ability prior to labor. A combination of cerebral flow, fetal weight, and selected clinical information may obtain moderate predictions of labor outcome, provided the interval to labor is not long.

Transcriptomic Signatures of the Foetal Liver and Late Prenatal Development in Vitrified Rabbit Embryos.

Assisted reproduction technologies (ARTs) are generally considered safe; however, emerging evidence highlights the need to evaluate potential risks in adulthood to improve safety further. ART procedures like rederivation of embryos by vitrification differ from natural conditions, causing significant disparities between in vitro and in vivo embryos, affecting foetal physiology and postnatal life. This study aims to investigate whether hepatic transcriptome and metabolome changes observed postnatally are already present in foetal livers at the end of gestation. This study compared fresh and vitrified rabbit embryos, finding differences between foetuses obtained by the transfer of fresh and vitrified embryos at 24 days of gestation. Rederived embryos had reduced foetal and liver weights and crown-rump length. However, the offspring of vitrified embryos tended to be born with higher weight, showing compensatory growth in the final week of gestation (59.2 vs. 49.8 g). RNA-Seq analysis revealed 43 differentially expressed genes (DEGs) in the foetal liver of vitrified embryos compared to the fresh group. Notably, downregulated genes included BRAT1, CYP4A7, CYP2B4, RPL23, RPL22L1, PPILAL1, A1BG, IFGGC1, LRRC57, DIPP2, UGT2B14, IRGM1, NUTF2, MPST, and PPP1R1B, while upregulated genes included ACOT8, ERICH3, UBXN2A, METTL9, ALDH3A2, DERPC-like, NR5A2-like, AP-1, COG8, INHBE, and PLA2G4C. Overall, a functional annotation of these DEGs indicated an involvement in lipid metabolism and the stress and inflammatory process or immune response. Thus, our results suggest that vitrification and embryo transfer manipulation induce an adaptive response that can be observed in the liver during the last week of gestation.

Fetal weight growth trajectories and childhood development: A population-based cohort study

This study aimed to investigate whether fetal growth trajectories (FGTs) could predict early childhood development, indicate intrauterine metabolic changes, and explore potential optimal and suboptimal FGTs. FGTs were developed by using an unsupervised machine-learning approach. Children’s neurodevelopment, anthropometry, and respiratory outcomes in the first 6 years of life were assessed at different ages. In a subgroup of participants, we conducted a metabolomics analysis of cord blood to reveal the metabolic features of FGTs. We identified 6 FGTs: early decelerating, early decelerating with late catch-up growth, early accelerating, early accelerating with late medium growth, late decelerating, and late accelerating. The early accelerating with late medium growth pattern might be the optimal FGT due to its associations with better psychomotor development, mental development, intelligence quotient, and lung function and a lower risk of behaviour and respiratory problems. Compared with the optimal FGT, early decelerating and late decelerating FGTs were associated with poor neurodevelopment and lung function, while early accelerating FGT was associated with more severe autistic symptoms, poor lung function, and increased risks of overweight/obesity. Metabolic alterations were enriched in amino acid metabolism for early decelerating and late decelerating FGTs, whereas altered metabolites were enriched in lipid metabolism for early accelerating FGT. These findings suggest that FGTs are predictors of early life development and may indicate intrauterine adaptive metabolism. The discovery of optimal and suboptimal FGTs provides potential clues for the early identification and intervention of fetal origin dysplasia or disease, but further research on related mechanisms is still needed.

IL-2 Complexed With Anti–IL-2 Antibody Expands the Maternal T-Regulatory Cell Pool and Alleviates Fetal Loss in Abortion-Prone Mice

Regulatory T (Treg) cells are essential for immune tolerance of embryo implantation and insufficient Treg cells are implicated in early pregnancy loss. An abortion-prone mouse model was utilized to evaluate the utility of IL-2 complexed with JES6-1 anti-IL-2 antibody (IL-2/JES6-1) to boost uterine Treg cells and improve reproductive success. IL-2/JES6-1 but not IL-2/IgG control administered in the peri-conception phase to CBA/J females mated with DBA/2 males elicited a >2-fold increase in the proportion of CD4+ T cells expressing FOXP3, and an increase in the ratio of FOXP3+ Treg cells to FOXP3- T conventional cells, in the uterus and its draining lymph nodes at embryo implantation that was sustained into mid-gestation. An attenuated phenotype was evident in both thymic-derived and peripheral Treg cells with elevated CTLA4, CD25, and FOXP3 indicating improved suppressive function, as well as increased proliferative marker Ki67. IL-2/JES6-1 treatment reduced fetal loss from 31% to 10%, but this was accompanied by a 6% reduction in late gestation fetal weight, despite comparable placental size and architecture. Similar effects of IL-2/JES6-1 on Treg cells and fetal growth were seen in CBA/J females with healthy pregnancies sired by BALB/c males. These findings show that expanding the uterine Treg cell pool through targeting IL-2 signaling is a strategy worthy of further investigation for mitigating immune-mediated fetal loss.

Predictive capacity of fetal pancreatic circumference for gestational diabetes mellitus.

To assess the capacity of fetal pancreatic size, before standard blood glucose testing for screening and diagnosis, to predict maternal gestational diabetes mellitus (GDM). This was a retrospective cohort study of low-risk pregnant women recruited during routine second-trimester fetal anatomical screening at 20-25 weeks' gestation at two ultrasound units in Israel between 2017 and 2020. The predictive performance of fetal pancreatic circumference ≥ 80th and ≥ 90th centiles and glucose challenge test (GCT) was examined for the outcome of GDM. The independent-samples t-test was used to compare mean pancreatic circumference centile between pregnancies with GDM and those without GDM. Diagnostic performance was evaluated with 2 × 2 contingency tables and receiver-operating-characteristics (ROC) curves. Overall, 195 women were selected for statistical analysis. Twenty-four (12.3%) women were diagnosed subsequently with GDM. The mean ± SD fetal pancreatic circumference centile was significantly higher in the GDM group compared with the non-GDM group (82.4 ± 14.6 vs 62.8 ± 27.6; P < 0.001). The pancreatic circumference centile was correlated positively with the estimated fetal weight centile (Pearson's coefficient, 0.243; P = 0.001). The 80th centile cut-off for pancreatic circumference had the highest sensitivity (70.8%) and positive predictive value (23.3%) for future maternal GDM, with the best trade-off between sensitivity and specificity achieved at the 75th centile cut-off (sensitivity, 79%; specificity, 60%). The GCT had better specificity (90.2%) and negative predictive value (97.9%) compared with both cut-offs in pancreatic circumference. The area under the ROC curve was higher for pancreatic circumference compared with GCT (0.71 vs 0.64) and only the former was statistically significant (P = 0.001). Fetal pancreatic circumference has a higher positive predictive capacity compared with GCT. Measuring pancreatic circumference can identify pregnancies at high risk for maternal GDM, thereby promoting earlier diagnosis and treatment, decreasing the time period during which the fetus is exposed to high maternal glucose levels and improving infant outcome. © 2024 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Evaluation of levamlodipine benzenesulfonate compound I for embryo-fetal developmental toxicity in SD rats and genotoxicity

In the present study, the effects of levamlodipine benzenesulfonate on the development of fertile Sprague-Dawley (SD) rats, their embryos, and littermates were assessed using an embryo-fetal developmental toxicity test. Maternal body weight reduction was observed at a dose of 20 mg/kg, but it recovered after treatment cessation. The 20 mg/kg dose group showed a skewed sex ratio in fetal rats, with a higher proportion of males. While some effects on fetal sternum development were observed at 20 mg/kg, no skeletal malformations were observed. No significant gross morphological abnormalities were detected in the dams (mothers), no significant embryotoxicity or foetotoxicity in fetal rats and no significant effects on fetal length and weight development at doses of 5 and 10 mg/kg. Genotoxicity was evaluated using a combination of the Ames test, the Chinese hamster ovary (CHO) cell chromosome aberration assay, and the ICR mouse bone marrow micronucleus test. The Ames test results indicated substantial bacteriostatic effects at doses of 500 and 5000 mg/dish, with no mutagenicity observed at doses of 0.5, 5, and 50 mg/dish. No significant effect on the aberration rate of CHO cell chromosomes was found at doses of 2.8, 5.6, and 11.2 mg/mL. In the ICR mouse micronucleus test, no micronucleus-inducing effect was observed at doses of 3.125, 6.25, and 12.5 mg/kg in each treatment group. In conclusion, under the conditions of this experiment, the no-observed-adverse-effect level (NOAEL) for developmental toxicity of levamlodipine benzenesulfonate in fertile SD rats, their embryos, and littermates was established to be 10 mg/kg/day. Levamlodipine benzenesulfonate did not exhibit significant genotoxicity.

Biomarkers of placental dysfunction. Clinical experience

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&lt;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.

The current state of the problem, clinical-pathogenetic approaches to the diagnosis and management tactics of fetal growth restriction

Fetal growth restriction is a common complication of pregnancy with a complex etiology and limited possibilities of diagnosis and treatment. The relevance of this difficult obstetric problem is determined by various published diagnostic criteria, relatively low detection rates, and limited options for prevention and treatment.Fetal growth restriction is defined as the inability of the fetus to reach its genetically determined growth potential, most often due to abnormal placentation. Forms of fetal growth restriction with early or late onset are distinguished based on the gestational age determined during prenatal ultrasound diagnosis. According to most recommendations, the 32nd week of pregnancy is set as the cut-off point for distinguishing between early and late onset fetal growth restriction.The definition underlying this classification is based on differences between these two phenotypes of fetal growth restriction in severity, natural history, Doppler findings, association with hypertensive complications, placental features, and management. It is important to distinguish two separate conditions: fetal growth restriction and small-for-gestational fetus, which differ in short-term and long-term perinatal outcomes.A fetus is defined as small for gestational age if the estimated weight or weight of the fetus at birth is below the 10th percentile. Fetal growth restriction is diagnosed if the estimated fetal weight is below the 3rd percentile or a combination of pathological blood flow in the umbilical arteries and/or uterine arteries in fetuses with an estimated weight below the 10th percentile. It can also occur in fetuses and newborns with a body weight above the 10th percentile.The need to distinguish between fetal growth restriction and small-for-gestational-age fetus is related to the fact that fetal growth restriction is the main cause of stillbirth, neonatal death, higher perinatal morbidity, as well as increased risk of diseases in adulthood.The article analyzes the approaches to differentiating fetal growth restriction from small growth retardation in terms of fetal gestation period and further increasing the accuracy of diagnosis, as well as the modern concept of pathogenesis, with an emphasis on oxidant stress as a key molecular mechanism of adverse outcomes. Appropriate interventions during pregnancy to reduce perinatal complications should include antenatal monitoring and drug therapy.

Circular RNAs mediate the regulation of maternal placental nutrient transport and fetal development by sugar-sweetened beverages

Epidemiological and experimental studies have demonstrated a strong association between maternal diet and fetal birth weight, obesity, and metabolic syndrome. We investigated the pathways and modes of action of circular RNAs (circRNAs) that mediate the regulation of maternal reproductive performance and fetal development by sugar-sweetened beverages (20 % sucrose water, SSBs) using C57BL/6J mice as a model. Results showed that SSBs significantly increased the reproductive performance (P<0.05), body weight (P<0.01), fetal birth weight (P<0.05), placental weight (P<0.01), and the expression of nutrient transporter genes in the placenta and fetal liver (P<0.05), mainly by accelerating the maternal energy metabolism during pregnancy. However, maternal serum biochemical indices, antioxidant indices, and pathological damage to the liver and placenta predicted that the mother would be at greater health risks during this period. Moreover, transcriptomics results indicated that the differentially expressed (DE) circRNAs in the placenta regulate the maternal multiple metabolic pathways and the placental nutrient transport efficiency by sponging miRNAs and forming growth factors and proteins, ultimately improving the maternal reproductive performance. In addition, we verified the reliability of the sequencing results using reverse transcription polymerase chain reaction and identified the possibility of DE circRNAs binding to nutrient transporter genes using targeting relationship prediction. Finally, we constructed a correlation network that regulates maternal placental nutrient transport based on DE circRNAs, targeted miRNAs and nutrient transport-related genes. This study will provide scientific dietary guidance for pregnant women and new research ideas for preventing and treating pregnancy complications.

Effect of White Ginger Rhizome Extract (Zingiber officinale var. amarum) on Pregnancy in Mice (Mus musculus L.) Early Post-implantation Stage

White ginger (Zingiber officinale var. Amarum) contains compounds in the antifertility group, namely flavonoids, terpenoids, and essential oils (gingerol and shogaol). Flavonoids can interfere with zygote division and implantation, while terpenoids and essential oils disrupt sperm transport and cause sperm to clot in male animals. This study aims to determine the effect of white ginger (Zingiber officinale var. Amarum) rhizome extract on the mouse (Mus musculus L.) early post-implantation stage. This research type is experimental and structured using a Completely Randomized Design (CRD) pattern. A total of 16 female mice weighing 20-30 g aged 2-3 months were divided into four treatments, namely K1 (control), K2 (0.7 mg/g BW), K3 (1.4 mg/g BW), and K4 (2.8 mg/g BW) white ginger rhizome extract. The extract is given orally at 0.5 mL/head/day on the 4th to 8th day of pregnancy. The mother's body weight is weighed every three days. On the 18th day of pregnancy, mice were sacrificed using chloroform and dissected to observe early post-implantation pregnancy parameters. Data were analyzed using Analysis of Variance (ANOVA) and Duncan's follow-up test with a confidence level of 95%. The research showed that white ginger rhizome extract significantly reduced the percentage of implantation (IM) and the percentage of live fetuses (FH), causing fetal growth to be hampered. The rate of implantation (IM) is K1 (1.8%), K2 (0.52%), K3 (0.49%). The percentage of live fetuses (FH) was K1 (1.06%), K2 (0.48%), and K3 (0.30%), while no fetus was found in K4. K3 treatment (1.4mg/g) causes fetal growth to be hampered. White ginger rhizome extract, on average, increases post-implantation mortality (KPI) and percentage of embryo resorption (ER) and reduces fetal weight. Based on the results of this study, it is concluded that white ginger extract has antifertility properties in female animals because it causes pregnancy disorders, so it is hoped that the use of white ginger in early pregnancy will be reduced.

Umbilical Vein Flows and Cardiac Size, Shape, and Ventricular Contractility in Fetuses With Estimated Weight Less-Than 10th Centile.

In a cohort of patients with estimated fetal weights (EFWs) <10th centile, we aimed 1) to compare the prevalence of abnormalities of fetal 4-chamber view (4CV) cardiac size, shape, and ventricular contractility in fetal growth restricted (FGR) and small-for-gestational-age (SGA) fetuses and 2) to compare umbilical vein flow (UVF) measurements to standard Doppler surveillance in predicting abnormalities of cardiac function. Prospective observational cohort study of fetuses with EFW <10th percentile. Measurements of size and shape used were 4CV transverse width, 4CV cardiac area, 4CV global sphericity index, and right-to-left ventricular mid-chamber width ratio. Variables of contractility used were fractional shortening change at the mid-ventricle chamber, global longitudinal strain, fractional area change, and left ventricular cardiac output. The UVF and standard Doppler surveillance including umbilical artery (UA), middle cerebral artery, and cerebroplacental ratio (CPR) were collected. Control data were from previously published studies. A total of 95 fetuses with EFWs <10th centile were included in the study. The rates of abnormalities of cardiac size and shape and ventricular contractility were all significantly elevated compared with normally grown control fetuses but similar between FGR and SGA fetuses. In a subset of 76 patients with UVF data, evaluation UVF identified more patients with any abnormality of contractility compared with UA (37.9 vs 17.2%, P = .02). The addition of UVF doubled the detection rate of ventricular contractility abnormalities. The addition of UVF should be considered in the surveillance of FGR and SGA fetuses to further stratify the severity of hypoxemia and to identify those at greater risk for future cardiovascular dysfunction.