Fetal Growth Restriction Group Research Articles

Ultrasound assessment of insular development in adequate-for-gestational-age fetuses and fetuses with early-onset fetal growth restriction using 3D-ICRV technology.

This study aimed to evaluate the growth trajectory of the insula in adequate-for-gestational-age (AGA) and early-onset fetal growth restriction (FGR) fetuses and analyze the difference between the two groups using three-dimensional inversion crytal and realistic vue technique (3D-ICRV). Singleton pregnant women, with a gestational age ranging from 20 to 32+6 weeks, who underwent routine examinations at Shandong Maternal and Child Care Hospital between March 2023 and December 2023 were included. The participants were divided into two groups: the FGR and AGA fetuses. Three-dimensional volumes were obtained using transabdominal ultrasound in the transverse section of the fetal hypothalamus based on different gestational ages. 3D-ICRV rendering technology was used for 3D imaging of the fetal insula. Volumes with a clear display of the insula were selected. We observed the morphology of the insula, and measured the area and circumference of the insula. By evaluating the growth trajectory of the insula in AGA and FGR fetuses, differences in insular development between the two groups were compared. Overall, 203 participants were included in this study, with 164 and 39 in the AGA and FGR groups, respectively. The 3D volumes were successfully acquired, and the area and circumference of the insula were measured using 3D-ICRV imaging technology. We found that as gestational age increased, the area and circumference of the insula gradually increased and showed positive correlations with the gestational age, with no significant changes in morphology. The growth rate of insular area and insular circumference in the FGR group is slower than that in the AGA group (insular area: 0.15 vs 0.19 cm2 / week, insular circumference: 0.25 vs 0.28 cm / week). The area and circumference of the insula in the FGR group were significantly different from those in the AGA group (insular area: p = 0.003, insular circumference: p = 0.004). The measured values of the insula using 3D-ICRV identify the differences in insular development between the FGR and AGA fetuses. The findings of this study have important implications for the prenatal evaluation of cortical development and maturity in FGR fetuses and further clinical consultation and management.

Elevated 12,13-diHOME level in maternal and umbilical cord blood complicated with preeclampsia.

Preeclampsia (PE) is a condition in pregnancy characterized by hypertension and proteinuria, thus leading to severe complications for both mother and fetus, including fetal growth restriction (FGR). However, there are still unclear aspects regarding the pathogenesis, prevention, and treatments. This study aimed to elucidate the characteristics of lipid metabolism in maternal and umbilical cord plasma complicated with PE using liquid chromatography-mass spectrometry (LC-MS). The study included singleton pregnant women at Osaka Metropolitan University Hospital from March 2023 to February 2024. PE was diagnosed based on new-onset hypertension after 20 weeks of gestation and other symptoms such as proteinuria and organ dysfunction. FGR was defined by ultrasound measurements below -1.5 standard deviation (SD). Plasma samples were collected from maternal and umbilical cord blood within 24 hours before delivery. Lipid metabolites were comprehensively analyzed using LC-MS, and the lipokine 12,13-diHOME, identified as elevated in the comprehensive analysis, was quantified. Immunohistochemistry was conducted on placental samples to assess soluble epoxide hydrolase (sEH) expression. The study involved 31 participants, with 20 in the control group and 11 in the PE group. A comprehensive analysis of maternal plasma samples identified a significant increase in 12,13-diHOME levels in the PE group compared to the control group. Quantification of 12,13-diHOME showed a significant increase in maternal plasma, umbilical venous plasma, and umbilical arterial plasma in the PE group compared to the control group (p = 0.007, p = 0.008, p = 0.005). PE with FGR showed significantly higher 12,13-diHOME concentrations in the umbilical arterial/venous ratio compared to the PE without FGR group (p = 0.03). Negative correlations were observed between 12,13-diHOME levels and birth weight in the PE group. Immunohistochemistry did not show significant differences in the sEH expression between the groups. This study demonstrated that 12,13-diHOME levels were significantly elevated in maternal and umbilical cord blood in PE patients, particularly in PE with FGR. Elevated 12,13-diHOME may reflect the progression of placental ischemia due to PE pathogenesis. This lipid metabolite could serve as a marker for the severity of preeclampsia, thus providing new insights into perinatal lipidomics and the potential role of 12,13-diHOME in PE.

Evaluation of Anterior and Middle Brain Structures With Cerebrovascular Flow in Fetuses With Fetal Growth Restriction: A Prospective Study.

To investigate the adaptation of the anterior cerebral artery (ACA) in fetuses with fetal growth restriction (FGR) and assess if forebrain and midbrain structures are affected by vascular adaptations. A prospective case-control study involving normally developed fetuses and those with late-onset FGR (estimated fetal weight < 3rd percentile and/or abdominal circumference < 3rd percentile). Doppler indices of the middle cerebral artery (MCA), ACA and umbilical artery (UA) were determined between 32 + 0 and 37 + 0 weeks. Neurosonography assessed the depth of the insula, the sylvian fissure, and the antero-posterior diameter of the frontal lobes (FAPD). The cerebral-placental ratio (CPR) and cerebro-placental-uterine ratio (CPUR) were lower in FGR cases. ACA PI percentile values were significantly lower in the FGR group (p = 0.020). Sylvian fissure depth was significantly lower in FGR fetuses. The ACA may be the first cranial vascular structure affected in fetuses with FGR. This may be related to the impact on postnatal cognitive functions in FGR patients. NCT06215690.

New Marker in the Umbilical Cord Blood of Fetuses with Fetal Growth Restriction: Serum Sortilin-1 Level

Objective: To determine the role of sortilin in the pathogenesis of fetal growth restriction (FGR) by examining serum sortilin levels in fetal cord blood. Methods: This prospective case-control study was conducted at Ankara Etlik City Hospital between July 2023 and January 2024. Group 1 included 44 pregnant women with late FGR; Group 2 included 44 healthy pregnant women as controls. Results: Umbilical cord blood sortilin levels were significantly higher in the FGR group [2.96 (2.43–4.01)] compared to the control group [2.12 (1.74–3.18)] (p = 0.001). Sortilin levels negatively correlated with APGAR scores at 1 min (r=-0.281, p = 0.008) and 5 min (r=-0.292, p = 0.006). A sortilin threshold of 2.58 ng/ml predicted composite adverse neonatal outcomes with 66.7% sensitivity, 53.1% specificity, and an AUC of 0.652 (95% CI: 0.529–0.775, p = 0.031). Conclusion: This study showed that sortilin levels, which are indicators of oxidation, were higher in the cord blood of newborns with late FGR.

Ultrasound shear wave elastography of the placenta: a potential tool for early detection of fetal growth restriction

BackgroundSonographic placental elastography has recently been employed as a non-invasive tool to investigate the structural alterations associated with various conditions such as pre-eclampsia, gestational diabetes and fetal growth restriction (FGR). The study was conducted based on the hypothesis that the placental elasticity might differ with varying severity of FGR and with that of appropriate for gestational age (AGA) pregnancies. MethodsThis study involved 121 pregnant women, with 54 in the normal group and 67 in the FGR group, which was defined as the fetal weight below the 10th percentile for gestational age. The FGR pregnancies were sub grouped into different stages based on the presence and extent of Doppler abnormalities. Shear-wave elastography was carried out to investigate the placental elasticity values, which were compared using the Kruskal-Wallis test. A P value of ≤0.05 was considered significant. ResultsThe placental elasticity differed significantly between pregnancies with and without FGR and among the different stages of FGR. There was a significant difference in PE (kPa) and SWV (m/s) among groups, with a p-value of 0.000001. PE and SWV in FGR pregnancies were significantly higher compared to AGA as a whole using t-test with p values of <0.0001. Doppler indices of umbilical, uterine and fetal middle cerebral arteries also correlated significantly with these. ConclusionThe study suggests that placental elasticity values reflect structural alterations associated with FGR and could serve as a valuable tool in the early detection and staging of this condition.

Study of Ultrasonographic Changes of the Adrenal Gland in Growth Restricted Fetus

Background: Fetuses with Fetal Growth Restriction (FGR) are at increased risk of chronic intra-uterine hypoxia, due to increased secretion of corticosterone from the fetal adrenal glands. This plays a major role in the cardiovascular and circulatory adaptation of FGR fetuses. These modifications are untimely identified by sonographic imaging. Objective: To study the association between ultrasound features of the adrenal gland and growth restriction in the fetus. Methods: A total of 104 pregnant women (52 FGR pregnancies and 52 controls) were evaluated between 28 and 36 weeks of gestation. All the study participants underwent transabdominal ultrasonography to measure bilateral fetal adrenal gland volume and fetal zone volume, corrected for gestational age. They were followed up until delivery. The two groups were compared to analyze the perinatal outcome in relation to ultrasonographic changes in the adrenal gland. Results: The adrenal gland measurements were significantly larger in fetuses with FGR as compared to the control group. FGR group had a larger corrected adrenal gland volume(cAGV) and fetal zone and adrenal gland (FZ/AG)ratio A statistically significant correlation was found between the two groups regarding gestational age at delivery, birth weight, APGAR score, and NICU admissions. Perinatal morbidity was found to be higher among women diagnosed with FGR, i.e., 14 (53.84%). Conclusion: Fetal adrenal gland size measurement is important to identify FGR fetuses that are vulnerable to hypoxia. It helps the obstetrician prepare for effective in-utero management to reduce perinatal morbidity and mortality.

Comprehensive evaluation of fetal renal ultrasound parameters for fetal growth restriction

ObjectiveThis study aims to investigate variances in renal ultrasound parameters between fetuses experiencing fetal growth restriction (FGR) and those with normal intrauterine development, with the intent to offer actionable insights for clinical management. MethodForty-five pregnant women diagnosed with FGR between 28 and 36 weeks of gestation, who underwent examination at Wenzhou People's Hospital from September 2021 to June 2023, constituted the FGR group. Concurrently, 65 pregnant women with normal intrauterine development at matching gestational weeks formed the control group. Renal ultrasound parameters, encompassing renal artery peak systolic velocity (PSV), end diastolic velocity (EDV), time averaged maximum velocity (TAMX), resistive indices (S/D, PI, RI), ratios of renal volume to gestational age (RV/WEEK) and estimated fetal weight (RV/EFW), vascular indices (VI, FI, VFI), were compared between the two groups. All parameters represented the mean values of bilateral kidneys. ResultIn the FGR group, fetal renal artery PSV (37.71 ± 9.93 cm/s), EDV (6.19 ± 1.50 cm/s), TAMX (15.10 ± 3.83 cm/s), RV/WEEK (0.45 ± 0.12), RV/EFW (7.53 ± 3.24), VI (22.19 ± 15.00), and VFI (5.53 ± 3.63) were significantly lower compared to the control group (PSV: 47.11 ± 11.24 cm/s, EDV: 7.13 ± 2.00 cm/s, TAMX: 17.85 ± 3.85 cm/s, RV/WEEK: 0.66 ± 0.19, RV/EFW:9.20 ± 3.17, VI: 28.67 ± 14.72, VFI: 7.40 ± 3.68). Conversely, fetal renal artery resistive indices (S/D: 9.09 ± 2.58, PI: 2.71 ± 0.56, RI: 0.92 ± 0.04) in the FGR group were notably higher than those in the control group (S/D: 6.22 ± 1.93, PI: 2.20 ± 0.73, RI: 0.87 ± 0.04), with statistical significance (P < 0.05). No significant difference was found in renal FI between the FGR group (26.78 ± 6.59) and the control group (26.89 ± 5.82) (P > 0.05). Receiver operating characteristic (ROC) curve analysis revealed higher diagnostic efficacy for RV/WEEK and RI among individual indicators, while combined parameter application yielded the highest diagnostic efficiency. ConclusionUtilizing a comprehensive evaluation of fetal kidney ultrasound parameters with multiple indices facilitates early screening and diagnosis of FGR fetuses, thereby aiding clinical decision-making and enhancing newborn birth outcomes.

Fetal epicardial fat thickness and modified myocardial performance index in late-onset fetal growth restriction.

In our study, we aimed to investigate the value of fetal epicardial fat thickness (EFT) and modified myocardial performance index (mod-MPI) in fetal growth restriction (FGR) that develops after the 32nd week of gestation. Fifty-six pregnant women who met the inclusion and exclusion criteria were included in the study and were divided into two groups: pregnancies diagnosed with FGR after the 32nd week of gestation (FGR group) and those without (control group). Demographic and obstetric histories, ultrasonographic and clinical characteristics, fetal EFT and mod-MPI values, and neonatal outcomes of the groups were recorded, and comparisons were made between the groups. Additionally, the diagnostic performance of fetal EFT value in late FGR was investigated. The FGR group had fetal EFT that was statistically significantly lower (1.11 ± 0.21 vs. 1.34 ± 0.23, p = 0.001). The FGR group had a significantly lower isovolumetric contraction time (ICT) (31.04 ± 6.88 vs. 35.14 ± 7.58, p = 0.048). The two groups' isovolumetric relaxation time (IRT), ejection time (ET), and mod-MPI values (p values 0.871, 0.55, and 0.750, respectively) were comparable. Receiver operating characteristic (ROC) analysis at a cutoff of 1.2 revealed 76.1% sensitivity and 74.2% specificity, respectively, for the diagnostic performance of the fetal EFT value in late-onset FGR. There was a positive predictive value (PPV) and negative predictive value (NPV) of 64.0% and 83.8%, respectively. We found that fetal EFT was significantly lower in FGR and may be useful in diagnosing FGR. However, we observed that mode-MPI did not change in FGR.

Alterations in maternal cardiovascular parameters and their impact on uterine and fetal circulation in hypertensive pregnancies and fetal growth restriction

ObjectiveTo examine potential alterations in maternal cardiovascular parameters in hypertensive pregnancies with or without fetal growth restriction (FGR) in comparison to uncomplicated normotensive pregnancies, and to determine the correlation between maternal cardiovascular parameters and changes in umbilical and uterine artery circulation. Materials and methodsThis study enrolled 73 pregnant women starting from the 20th week of gestation, categorized into three groups: hypertensive conditions (pregnancy-induced hypertension, preeclampsia or eclampsia, n = 30), hypertensive conditions with FGR (n = 8) and a control group of healthy normotensive pregnant women (n = 35). All participants underwent echocardiography to assess cardiac output and calculate peripheral vascular resistance. Additionally, fetal biometric measurements and Doppler ultrasound examinations of the uterine and umbilical artery were performed. The results were standardized into gestational age-adjusted z-scores. ResultsThe mean pulsatility index (PI) of the uterine artery (1.36, p < 0.001) and umbilical artery PI z-scores (1.32, p < 0.001) showed significant increases in the hypertensive conditions + FGR group. Maternal cardiac output z-scores were notably lower in both the hypertensive + FGR group (−2.62, p = 0.001) and the hypertensive group (−2.49, p < 0.001). Peripheral vascular resistance was significantly elevated in the hypertensive + FGR group (7.43, p < 0.001) and the hypertensive group (6.06, p < 0.001). There was a positive correlation between maternal peripheral vascular resistance and uterine artery PI (R2 = 0.172; p = 0.0004), and a negative correlation between cardiac output and uterine artery PI (R2 = 0.067; p = 0.031). However, significant correlation between maternal cardiovascular parameters and umbilical artery PI was not identified. ConclusionsMaternal cardiac output exhibits a significant decrease whereas peripheral vascular resistance increases in hypertensive pregnancies, irrespective of the presence of FGR. Both uterine and umbilical artery PI notably increase when hypertensive pregnancies are accompanied by FGR. A positive correlation exists between maternal peripheral vascular resistance and uterine artery PI, as well as a negative correlation between maternal cardiac output and uterine artery PI. However, changes in maternal cardiovascular parameters do not exhibit significant correlations with umbilical artery PI.

The spectrum of infections identified in pregnant women with different types of fetal growth restriction

BACKGROUND: Bacterial, viral and protozoal infections can cause miscarriage, antenatal death, congenital organ abnormalities or other limited consequences depending on the pathogen. The role of infection processes identified during pregnancy on placental pathology and fetal growth restriction. AIM: The aim of this study was to conduct a comparative analysis of infections identified in pregnant women with different types of fetal growth restriction, as well as to assess a potential impact of identified infections on the outcomes of fetal growth restriction in newborns in the same groups. MATERIALS AND METHODS: We performed a retrospective analysis of outcomes for 394 pregnant women with an established diagnosis of fetal growth restriction, who had given birth from 2018 to 2022 in the Perinatal Center of the Arkhangelsk Regional Clinical Hospital. Maternal and neonatal case histories were obtained using a continuous sampling method. Considering the transition to new criteria for establishing the diagnosis of fetal growth restriction in Russia, we formed four study groups, of which only 139 cases met the Delphi criteria of clinical guidelines by Russian Society of Obstetricians and Gynecologists, 2021. In the selected groups, we analyzed the results of microscopic and microbiological tests of various localizations in mothers during antepartum examination, as well as postpartum examination of the placenta and culture tests in newborns in their relation to adverse outcomes. RESULTS: A high prevalence (25–70.4%) of positive bacteriological findings was revealed in all of the study groups. The frequency was highest in the group of pregnant women with fetal growth restriction before 32 weeks (90–92%). Combined infections (two or more localizations) were noted in 59.2% of pregnant women in groups with early fetal growth restriction compared to 23.3% in late fetal growth restriction groups. In all cases, we observed a direct relationship between the severity of fetal growth restriction and the prevalence of infections. The range of infections identified during routine examination of pregnant women is quite limited; Candida spp. (from 40.8% in the control group to 75% in the comparison group), Escherichia coli (from 22.9 to 33.3%, respectively), and Chlamydia trachomatis (from 4.5 to 23.5%, respectively) being identified most commonly. In a morphological study of the placenta, infectious and inflammatory lesions were the most significant and ranged from 100 to 81.4% of cases in groups with early and late fetal growth restriction, respectively, with signs of hematogenous transmission prevailed. When analyzing infectious lesions in fetuses, we have found the presence of three and more localizations of the infectious process in 90 to 45% of cases with a fatal outcome for early and late fetal growth restriction, respectively. In the control groups, similar rates were 40 and 15.8%. When assessing the distribution of various types of infectious process in newborns, Candida spp., Escherichia coli, and Enterococcus faecalis also took the lead in all cases. However, the percentage of the same etiology of maternal and neonatal infections turned out to be very low (from 0 to 31% for individual pathogens), which makes it difficult to apply preventive treatment during pregnancy. CONCLUSIONS: Authors identified indirect but numerous signs of significant involvement of infectious processes in the development of fetal growth restriction, especially its early type, as well as the influence of infections on the outcomes for such newborns. In most cases, infectious processes during pregnancy are subclinical. Current screening of pregnant women is insufficient to identify high-risk groups. Examination of pregnant women for infections carried out by culture tests provide low-component and, most likely, incomplete information.

The placental blood perfusion and LINC00473-mediated promotion of trophoblast apoptosis in fetal growth restriction

This study aimed to investigate placental microblood flow perfusion in fetal growth restriction (FGR) both pre- and post-delivery, and explore the influence of LINC00473 and its downstream targets on FGR progression in trophoblast cells. Placental vascular distribution, placental vascular index (VIMV), CD34 expression, and histological changes were compared between control and FGR groups. FGR-related differentially expressed genes (DEGs) were analyzed and validated by quantitative real-time polymerase chain reaction (qPCR) and immunohistochemistry (IHC) in placentae. In vitro experiments examined the regulatory relationships among LINC00473, miR-5189-5p, and StAR, followed by investigations into their impacts on cell proliferation and apoptosis. FGR placentae exhibited irregular shapes, uneven parenchymal echo, stromal dysplasia, ischemic infarction, and variable degrees of thickening in some cases. FGR samples showed less prominent mother vessel lakes, significantly lower VIMV, and decreased CD34 expression. Hematoxylin & eosin (H&E) staining revealed placental fibrosis, fibrin adhesion, infarction, and interstitial dysplasia in FGR. LINC00473, miR-5189-5p, and StAR were identified as DEG, with qPCR demonstrating a significant increase in LINC00473 and a decrease in miR-5189-5p in FGR, while both qPCR and IHC indicated a significant increase in StAR expression. LINC00473 served as an endogenous sponge against miR-5189-5p in human HTR-8/SV neo cells, and StAR expression was regulated by both LINC00473 and miR-5189-5p. Dysregulation of these genes affected cell proliferation and apoptosis. Pathological changes in the placenta are significant contributors to FGR, with placental microblood flow potentially serving as an indicator for monitoring its progression. LINC00473 and its downstream targets may modulate trophoblasts proliferation and apoptosis, thus influencing the onset of FGR, suggesting novel avenues for diagnosis and treatment.

Immunohistochemical localization of HCA1 receptor in placenta in presence of fetal growth restriction

IntroductionGlucose metabolism produces lactate and hydrogen ions in an anaerobic environment. Fetuses with intrauterine growth restriction are considered to become progressively lactacidemic as well as hypoxic. Roles of lactate in the placenta in the presence of fetal growth restriction (FGR) remain to be clarified. MethodsImmunohistochemical localization of lactate-related substances, such as a receptor for lactate (hydroxy-carboxylic acid 1 receptor (HCA1 receptor/GPR81)), monocarboxylate transporters (MCTs) for lactate, lactate dehydrogenases (LDHs), and proteins expressed in syncytiotrophoblasts or cytotrophoblasts was examined in placentas of appropriate weight for gestational age (AGA) fetus and those showing FGR. ResultsImmunoreactivity for the HCA1 receptor was present in the cytoplasm of some trophoblasts, predominantly localized to their basal (fetus-facing) side, and was frequently colocalized with that for E-cadherin or serine peptidase inhibitor, Kunitz type 1 (SPINT1), a marker protein of cytotrophoblasts. Immunoreactivity for MCT1 and MCT4 was present on the basal and the microvillous (maternal-facing) membranes of trophoblasts in both groups, respectively. Clear immunoreactivity for LDHA and LDHB was also observed in the cytoplasm of trophoblasts, mainly localized to their basal side. However, there were no significant differences in immunohistochemically stained areas of lactate-related substances between AGA and late-onset FGR groups. On the other hand, there were correlations between coefficients of the presence of chorioamnionitis and the values of LDHB and E-cadherin. DiscussionImmunohistochemical localization of the HCA1 receptor was predominantly observed in the cytoplasm located on the basal side of trophoblasts, suggesting a role of lactate in human placental development, including syncytialization.

Prediction of severe preeclampsia and intrauterine growth restriction based on serum placental exosome miR-520a-5p levels during the first-trimester.

To assess the predictive capabilities of serum exosomal levels of micro-RNA-520a-5p (miR-520a-5p) concerning the occurrence of severe preeclampsia (sPE) and fetal growth restriction (FGR) during the first trimester of pregnancy. During the period spanning from October 2020 to October 2021, serum samples were procured from the first trimester and subsequently preserved by freezing at -80 ℃. These samples were obtained from 105 pregnant women in a nested case-control study. This cohort consisted of individuals who later developed sPE (sPE group, n = 35) and FGR (FGR group, n = 35) during the third trimester. Additionally, 35 women with normal blood pressure were denoted as normal pregnancy group. Serum samples from the first trimester were retrieved from all groups for further analysis after thawing. Exosomes were extracted from the serum samples collected during the first trimester and examined using transmission electron microscopy, western blot, and nanoparticle tracking analysis. Additionally, the determination of their placental origin was also established during the course of the study. Exosome miR-520a-5p levels were measured using real-time quantitative polymerase chain reaction assays, primarily involving quantitative reverse transcription polymerase chain reactions. Fetal placental tissues from the 3 groups were collected shortly after birth, and miR-520a-5p expression was measured using real-time quantitative polymerase chain reaction. Serum placental exosomes and fetal placental tissues were compared for miR-520a-5p levels. Placental trophoblasts were identified as the source of serum exosomes in all 3 groups. It was found that serum placental exosomes exhibited lower levels of miR-520a-5p in both the sPE and FGR groups when compared to the normal pregnancy group. This finding was consistent with observations made in postpartum placental tissues. The predictive accuracy for sPE using miR-520a-5p levels in serum placental exosomes during the first trimester was notably higher (area under the receiver operating characteristic curve = 0.806, P <.05) compared to the prediction of FGR (area under the receiver operating characteristic curve = 0.628, P <.05). Placenta-derived exosomes can be extracted from maternal serum during the first trimester of pregnancy and miR-520a-5p detected from the exosomes. The downregulation of miR-520a-5p serves as a more predictive indicator for the subsequent development of sPE compared to predicting FGR.

Associations of serum D-dimer and glycosylated hemoglobin levels with third-trimester fetal growth restriction in gestational diabetes mellitus.

Gestational diabetes mellitus (GDM) is a special type of diabetes that commonly occurs in women during pregnancy and involves impaired glucose tolerance and abnormal glucose metabolism; GDM is diagnosed for the first time during pregnancy and can affect fetal growth and development. To investigate the associations of serum D-dimer (D-D) and glycosylated hemoglobin (HbA1c) levels with third-trimester fetal growth restriction (FGR) in GDM patients. The clinical data of 164 pregnant women who were diagnosed with GDM and delivered at the Obstetrics and Gynecology Hospital of Fudan University from January 2021 to January 2023 were analyzed retrospectively. Among these women, 63 whose fetuses had FGR were included in the FGR group, and 101 women whose fetuses had normal body weights were included in the normal body weight group (normal group). Fasting venous blood samples were collected from the elbow at 28-30 wk gestation and 1-3 d before delivery to measure serum D-D and HbA1c levels for comparative analysis. The diagnostic value of serum D-D and HbA1c levels for FGR was evaluated by receiver operating characteristic analysis, and the influencing factors of third-trimester FGR in GDM patients were analyzed by logistic regression. Serum fasting blood glucose, fasting insulin, D-D and HbA1c levels were significantly greater in the FGR group than in the normal group, while the homeostasis model assessment of insulin resistance values were lower (P < 0.05). Regarding the diagnosis of FGR based on serum D-D and HbA1c levels, the areas under the curves (AUCs) were 0.826 and 0.848, the cutoff values were 3.04 mg/L and 5.80%, the sensitivities were 81.0% and 79.4%, and the specificities were 88.1% and 87.1%, respectively. The AUC of serum D-D plus HbA1c levels for diagnosing FGR was 0.928, and the sensitivity and specificity were 84.1% and 91.1%, respectively. High D-D and HbA1c levels were risk factors for third-trimester FGR in GDM patients (P < 0.05). D-D and HbA1c levels can indicate the occurrence of FGR in GDM patients in the third trimester of pregnancy to some extent, and their combination can be used as an important index for the early prediction of FGR.

The genetics and clinical outcomes in 151 cases of fetal growth restriction: A Chinese single-center study

ObjectiveTo determine the detection rate of chromosomal abnormalities and pregnancy outcomes in fetuses with intrauterine growth restriction.Study designA total of 151 fetal samples with intrauterine growth restriction were divided into the isolated fetal growth restriction (FGR) group, FGR group with structural malformation, and FGR group with non-structural malformation, according to ultrasound abnormalities. The enrolled patients were divided into an early onset FGR group (<32 weeks) and a late-onset FGR group (≥32 weeks). Chromosomal karyotype and microarray analyses were performed and pregnancy outcomes were monitored.ResultsThe karyotypes of 122 patients were analyzed. Four patients exhibited abnormal chromosome numbers or structures. Variations in copy number were detected in 151 cases; 19 cases were found to have chromosomal abnormalities, with a positivity rate of 12.6 %. There was one trisomy in 18 cases, one trisomy in 21 cases, eight pathogenic copy number variations (CNVs), and nine CNVs of unknown clinical significance. The detection rate of FGR combined with structural malformation was significantly higher than that of isolated FGR group. The detection rate of FGR with structural malformations was significantly higher than that with non-structural malformations. The positive detection rate in the FGR group was similar to that in the FGR group with non-structural malformations, with no statistical significance. Chromosomal abnormalities were detected in 17 patients with early onset FGR, with a positivity rate of 13.8 %. Two cases of chromosomal abnormalities were detected in the late-onset FGR group, with a positive rate of 7.1 %, with no statistical significance. A total of 151 fetuses with FGR were followed up for pregnancy outcomes, resulting in 36 cases of pregnancy termination and 13 cases of loss to follow-up. Among the 102 delivered fetuses, six exhibited delayed growth and development, one presented with hypospadias, and another failed the hearing screening. The remaining 94 fetuses demonstrated normal growth and development.ConclusionsThis study confirms the value of CNV detection in fetuses and dynamic ultrasound monitoring for fetuses with intrauterine growth restriction.

Long-term neurological outcomes of offspring misdiagnosed with fetal growth restriction.

Fetal growth restriction (FGR) is a major determinant of adverse short- and long-term perinatal outcomes. The current definition of FGR (estimated fetal weight measurement < 10th percentile) may lead, at times, to a false diagnosis of fetuses that are eventually born appropriate for gestational age (AGA). Our objective was to investigate the potential association between a misdiagnosis of antepartum fetal growth restriction and long-term neurological outcomes in offspring. A population-based cohort analysis was performed including deliveries between the years 1991-2020 in a tertiary medical center. We compared neurological hospitalization during childhood among AGA infants falsely diagnosed as FGR versus AGA infants without a false FGR diagnosis. A Kaplan-Meier survival curve was used to assess cumulative morbidity and a Cox proportional hazards model was employed to control for confounders. During the study period, 324,620 AGA infants met the inclusion criteria; 3249 of them were falsely classified as FGR. These offspring had higher rates of hospitalizations due to various neurological conditions, as compared to those without an FGR diagnosis (OR 1.431, 95% CI 1.278-1.608; P < 0.001). In addition, cumulative hospitalization incidence was elevated in the FGR group (log-rank P-value < 0.001). When controlling for confounders, a false FGR diagnosis remained independently associated with long-term neurological morbidities (adjusted HR 1.086, 95% CI 1.003-1.177, P = 0.043). Misdiagnosis of FGR in the antepartum period is associated with an increased risk for offspring long-term neurological morbidities.

The significance of Syndecan 1, a new marker for endothelial dysfunction, in cases of fetal growth retardation.

In the current study we aimed to investigate Syndecan 1 (SDC1) levels in pregnant women diagnosed with fetal growth restriction (FGR) and the relationship between SDC1 levels and clinical and doppler parameters in FGR cases associated with endothelial dysfunction, angiogenesis and uteroplacental insufficiency METHOD OF STUDY: A total of 90 pregnant women included in the study, (45 with FGR, 45 healthy control) matched by week of gestation and maternal age. Venous blood samples were collected and plasma concentrations of SDC1 were determined by a specific immunoassay. Doppler examination was performed to evaluate the relationship between the SDC1 levels and placental blood supply. Doppler parameters; meanUtA-PI(p <.001), CPR (p=.002) and CPUR (p <.001) were different between the groups, however MCA PI, umbilical artery PI and umbilical artery S/D were not (p>.05). While gestational age at delivery, birth weight, APGAR score at 1 and 5 min were significantly lower (all, p <.001) in the study group, non-reassure fetal heart rate tracing (p=.09) and NICU admission (p=.02) were significantly higher. SDC 1 level was 2,00±1,47ng/mL and 2,34±1,12ng/mL in the FGR and control groups, respectively (p=.008). In the study group SDC 1 level was 1,69±2,00 in those with gestational age below 32weeks and 2,13±1,18 in those with gestational age above 32weeks and there was a statistically significant difference between the groups (p=.015). Plasma SDC 1 concentration of 2,1850ng/mL or less had a sensitivity of 70%, a specificity of 72%, area under the ROC curve.65 (p<.005). Low maternal plasma SDC1 level may be associated with placental insufficiency and FGR. Low levels of SDC1 may be helpful as a predictor for the development of FGR during gestation.

Maternal serum vasohibin-1 and vasohibin-2 concentrations in pregnant women diagnosed with late fetal growth restriction or small for gestational age fetus

Aims: Vasohibin 1, a member of the vasohibin family, is an inhibitor of angiogenesis, while vasohibin 2 stimulates angiogenesis. Placental expressions of vasohibins and their relationship with preeclampsia have been investigated, but their effects on intrauterine fetal growth are unknown. In this context, we aimed to investigate the concentrations of vasohibin 1 and 2 in the serum of pregnant women diagnosed with late fetal growth restriction (FGR) or small for gestational age (SGA) in the third trimester. Methods: This prospective non-interventional cohort study was conducted on 81 pregnant women, 26 of whom were diagnosed with late FGR, 28 were SGA, and 27 were healthy controls. Three groups were compared in terms of serum vasohibin 1 and 2 concentrations in the third trimester. Results: Three groups were similar in terms of demographic characteristics and gestational age at blood sampling for vasohibin 1 and 2 (p &lt; 0.05). The median vasohibin 1 concentration was determined as 1227.41 ng/mL in the late FGR group, 1311.15 ng/mL in the SGA group, and 1391.38 ng/mL in the control group (p = 0.139). The median vasohibin 2 concentration was determined as 11.24 ng/mL in the late FGR group, 11.86 ng/mL in the SGA group, and 14.34 ng/mL in the control group (p = 0.198). Conclusion: Serum vasohibin 1 and 2 concentrations were found to be similar in pregnant women diagnosed with late FGR and SGA and pregnant women with AGA fetuses. Vasohibin 1 and 2 are involved in the regulation of placental angiogenesis, but their roles in intrauterine fetal growth remain unclear.

The associations between maternal and fetal exposure to endocrine-disrupting chemicals and asymmetric fetal growth restriction: a prospective cohort study.

Recent evidence has revealed associations between endocrine-disrupting chemicals (EDCs) and placental insufficiency due to altered placental growth, syncytialization, and trophoblast invasion. However, no epidemiologic study has reported associations between exposure to EDCs and asymmetric fetal growth restriction (FGR) caused by placenta insufficiency. The aim of this study was to evaluate the association between EDC exposure and asymmetric FGR. This was a prospective cohort study including women admitted for delivery to the Maternal Fetal Center at Seoul St. Mary's Hospital between October 2021 and October 2022. Maternal urine and cord blood samples were collected, and the levels of bisphenol-A (BPA), monoethyl phthalates, and perfluorooctanoic acid in each specimen were analyzed. We investigated linear and non-linear associations between the levels of EDCs and fetal growth parameters, including the head circumference (HC)/abdominal circumference (AC) ratio as an asymmetric parameter. The levels of EDCs were compared between fetuses with and without asymmetric FGR. Of the EDCs, only the fetal levels of BPA showed a linear association with the HC/AC ratio after adjusting for confounding variables (β = 0.003, p < 0.05). When comparing the normal growth and asymmetric FGR groups, the asymmetric FGR group showed significantly higher maternal and fetal BPA levels compared to the normal growth group (maternal urine BPA, 3.99 μg/g creatinine vs. 1.71 μg/g creatinine [p < 0.05]; cord blood BPA, 1.96 μg/L vs. -0.86 μg/L [p < 0.05]). In conclusion, fetal exposure levels of BPA show linear associations with asymmetric fetal growth patterns. High maternal and fetal exposure to BPA might be associated with asymmetric FGR.

Potential Association of Gut Microbial Metabolism and Circulating mRNA Based on Multiomics Sequencing Analysis in Fetal Growth Restriction.

Fetal growth restriction (FGR) is a significant contributor to negative pregnancy and postnatal developmental outcomes. Currently, the exact pathological mechanism of FGR remains unknown. This study aims to utilize multiomics sequencing technology to investigate potential relationships among mRNA, gut microbiota, and metabolism in order to establish a theoretical foundation for diagnosing and understanding the molecular mechanisms underlying FGR. In this study, 11 healthy pregnant women and nine pregnant women with FGR were divided into Control group and FGR group based on the health status. Umbilical cord blood, maternal serum, feces, and placental tissue samples were collected during delivery. RNA sequencing, 16S rRNA sequencing, and metabolomics methods were applied to analyze changes in umbilical cord blood circulating mRNA, fecal microbiota, and metabolites. RT-qPCR, ELISA, or western blot were used to detect the expression of top 5 differential circulating mRNA in neonatal cord blood, maternal serum, or placental tissue samples. Correlation between differential circulating mRNA, microbiota, and metabolites was analyzed by the Spearman coefficient. The top 5 mRNA genes in FGR were altered with the downregulation of TRIM34, DEFA3, DEFA1B, DEFA1, and QPC, and the upregulation of CHPT1, SMOX, FAM83A, GDF15, and NAPG in newborn umbilical cord blood, maternal serum, and placental tissue. The abundance of Bacteroides, Akkermansia, Eubacterium_coprostanoligenes_group, Phascolarctobacterium, Parasutterella, Odoribacter, Lachnospiraceae_UCG_010, and Dielma were significantly enriched in the FGR group. Metabolites such as aspartic acid, methionine, alanine, L-tryptophan, 3-methyl-2-oxovalerate, and ketoleucine showed notable functional alterations. Spearman correlation analysis indicated that metabolites like methionine and alanine, microbiota (Tyzzerella), and circulating mRNA (TRIM34, SMOX, FAM83A, NAPG) might play a role as mediators in the communication between the gut and circulatory system interaction in FGR. Metabolites (METHIONINE, alanine) as well as microbiota (Tyzzerella) and circulating mRNA (TRIM34, SMOX, FAM83A, NAPG) were possible mediators that communicated the interaction between the gut and circulatory systems in FGR.