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The main etiological factor in intrauterine growth restriction (IUGR) is the impairment of the fetoplacental unit. Due to the placental endothelial disintegrity and vascular permeability disruptions, endocan has been an interesting molecule to search for associations with IUGR. The aim of this study was to investigate the umbilical cord blood endocan concentrations in IUGR pregnancies.

Abstract Background Intrauterine growth restriction (IUGR) is defined as a fetus that fails to achieve its genetically determined growth potential. The exact molecular mechanisms of placental insufficiency IUGR pathogenesis are a little known. Our goal was to identify key genes and gene co-expression modules related to placental insufficiency IUGR. Methods We used weighted gene co-expression network analysis (WGCNA) and protein-protein interaction (PPI) network analysis to examine the IUGR dataset GSE114691 from NCBI Gene Expression Omnibus. Core modules and hub nodes of the protein-protein interaction network were identified. A gene network was constructed and genes were classified by WGCNA into different modules. The validation of potential key genes was carried out using additional datasets (GSE12216 and GSE24129). Results We identified in GSE114691 539 down regulated genes and 751 up regulated genes in placental tissues characteristic of placental insufficiency IUGR compared with non-IUGR, and defined 76 genes as hub nodes in the protein-protein interaction network. Genes in the key modules of the WGCNA network were most closely associated with placental insufficiency IUGR and significantly enriched in biological process such as cellular metabolic process and macromolecule metabolic process. We identified as key genes TGFB1, LEP, ENG, ITGA5, STAT5A, LYN, GATA3, FPR1, TGFB2, CEBPB, KLF4, FLT1, and PNPLA2. The RNA expression levels of ENG and LEP, as biomarkers, were validated. Conclusion A holistic gene expression profile of placental insufficiency IUGR has been generated and the key genes ENG and LEP has potential to serve as circulating diagnosis biomarkers and therapeutic targets for placental insufficiency IUGR.

PROBLEM:Premature birth complicates 10%-12% of deliveries. Infection and inflammation are the most common etiologies and are associated with increased offspring morbidity and mortality. We hypothesize that lipopolysaccharide (LPS)-induced maternal inflammation causes direct placenta injury and subsequent injury to the fetal intestine. METHOD OF STUDY:Pregnant C57Bl6 mice were injected intraperitoneally on day 15.5 with 100 μg/kg LPS or saline. Maternal serum, amniotic fluid, placental samples, and ileal samples of offspring were obtained assessed for inflammation and/or injury. Maternal placental ultrasounds were performed. Placental DNA was isolated for microbiome analysis. RESULTS:Maternal injection with LPS caused elevated IL-1β, IL-10, IL-6, KC-GRO, and TNF. Placental tissue showed increased IL-1β, IL-6, and KC-GRO and decreased IL-10, but no changes were observed in amniotic fluid. Placental histology demonstrated LPS-induced increases in mineralization and necrosis, but no difference in placental blood flow. Most placentas had no detectable microbiome. Exposure to maternal LPS induced significant injury to the ilea of the offspring. CONCLUSION:Lipopolysaccharide causes a maternal inflammatory response that is mirrored in the placenta. Placental histology demonstrates structural changes; however, placental blood flow is preserved. LPS also induces an indirect intestinal injury in the offspring that lasts beyond the neonatal period.

Background : Fetal growth restriction caused by placental insufficiency is associated with increased risk of poor neurodevelopment, even in the absence of specific perinatal brain injury. Placental insufficiency leads to chronic hypoxaemia that may alter cerebral tissue organisation and maturation. Objective: The aim of this study was to assess the effects fetal growth restriction and fetal haemodynamic abnormalities have on brain volumes and white matter microstructure at early school age. Materials and methods: This study examined 32 children born with fetal growth restriction at 24 to 40 gestational weeks, and 27 gestational age-matched children, who were appropriate for gestational age. All children underwent magnetic resonance imaging (MRI) at the age of 8–10 years. Cerebral volumes were analysed, and tract-based spatial statistics and atlas-based analysis of white matter were performed on 17 children born with fetal growth restriction and 14 children with birth weight appropriate for gestational age. Results: Children born with fetal growth restriction demonstrated smaller total intracranial volumes compared to children with normal fetal growth, whereas no significant differences in grey or white matter volumes were detected. On atlas-based analysis of white matter, children born with fetal growth restriction demonstrated higher mean and radial diffusivity values in large white matter tracts when compared to children with normal fetal growth. Conclusion: Children ages 8–10 years old born with fetal growth restriction demonstrated significant changes in white matter microstructure compared to children who were appropriate for gestational age, even though no differences in grey and white matter volumes were detected. Poor fetal growth may impact white matter maturation and lead to neurodevelopmental impairment later in life. [ABSTRACT FROM AUTHOR]

Placental insufficiency affects about 10% of pregnancies and can lead to pre-eclampsia, fetal growth restriction, and preterm birth. Despite significant advances in early prediction and prevention of preterm pre-eclampsia with aspirin, the effects of prophylaxis on fetal growth restriction are less certain, and the rates of late-onset pre-eclampsia are not influenced by aspirin treatment. Pregnancies complicated by placental insufficiency are characterized by increased oxidative stress, and recent studies suggest that melatonin has antioxidant properties and contributes to maintaining placental homeostasis. We aimed to systematically review the available literature about melatonin in pregnancies complicated by placental insufficiency, specifically preeclampsia and fetal growth restriction, exploring three different aspects: 1) maternal melatonin levels; 2) expression and activity of melatonin placental receptors; 3) effects of maternal melatonin administration. PubMed (Medline) and Scopus were searched until December 2020. Identified studies were screened and assessed independently by two authors. Data were extracted and compiled in qualitative evidence synthesis. The circadian pattern of melatonin secretion seems to be altered in pregnancies complicated by placental insufficiency reflected by lower production of melatonin, with consequent lower systemic and placental concentrations and lower expression of melatonin receptors, thus reducing the local release of the indole and its autocrine function. Small intervention studies also suggest that treatment is safe and may lead to prolongation of pregnancy and better outcomes, but double-blind, randomized placebo-controlled trials are lacking. [ABSTRACT FROM AUTHOR]

Copyright of Revista Peruana de Investigación Materno Perinatal is the property of Peruvian Journal of Maternal Perinatal Research / Revista Peruana de Investigacion Materno Perinatal and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Purpose: A growing body of evidence accumulate pointing to sex-specific differences in placental adaptation to pregnancy complications. We aimed to study if there is a difference in placental histopathology lesions, between female and male fetuses in pregnancies complicated with preeclampsia. Methods: The medical files of all patients with preeclampsia, were reviewed. Placental lesions were classified to lesions related to maternal or fetal malperfusion lesions (MVM, FVM), vascular and villous changes, and inflammatory lesions. Comparison was performed between the male and the female groups. Results: The study included 441 preeclamptic patients. Women in the male preeclampsia group (n = 225) had higher rate of chronic hypertension (p = 0.05) and diabetes mellitus (p < 0.005), while women in the female preeclampsia group (n = 216) had higher rate of thrombophilia. There were no between groups differences in neonatal outcome or placental histopathology lesions. The early preeclampsia cohort included 91 patients. Placentas from the female early preeclampsia group (n = 44) had more vascular changes related to MVM lesions (decidual arteriopathy), as compared to the male early preeclampsia group (n = 47), 50% vs. 25%, p = 0.01. Conclusions: Higher rate of placental MVM lesions in the female as compared to male group correspond with sex-specific difference of placental pathophysiological adaptation, in early preeclampsia. [ABSTRACT FROM AUTHOR]

Simple Summary: Based on human medicine, Neonatal Encephalopathy is the term used by equine clinicians for newborn foals which develop a variety of non-infectious neurological signs in the immediate postpartum period. It has become the preferred term because it does not imply a specific underlying etiology or pathophysiology, as hypoxia and ischemia may not be recognized in all cases. Understanding the underlying pathophysiology is important in formulating a rational approach to diagnosis. Our aim is to clinically characterize a population of foals spontaneously affected by Neonatal Encephalopathy and to evaluate the levels of trophic factors, such as nerve growth factor and vascular epithelial growth factor, and thyroid hormones obtained at birth/admission from a population of affected foals and in the first 72 h of life/hospitalization, as well as the expression of trophic factors in the placenta of mares that delivered foals affected by Neonatal Encephalopathy. The less pronounced decrease of the two trophic factors compared to healthy foals, their close relationship with thyroid hormones over time, and the dysregulation of trophic factor expression in placental tissues, could be key regulators in the mechanisms of equine Neonatal Encephalopathy. Neonatal Encephalopathy (NE) may be caused by hypoxic ischemic insults or inflammatory insults and modified by innate protective or excitatory mechanisms. Understanding the underlying pathophysiology is important in formulating a rational approach to diagnosis. The preliminary aim was to clinically characterize a population of foals spontaneously affected by NE. The study aimed to: (i) evaluate nerve growth factor (NGF) and vascular endothelial growth factor (VEGF) levels in plasma samples obtained in the affected population at parturition from the mare's jugular vein, umbilical cord vein and foal's jugular vein, as well as in amniotic fluid; (ii) evaluate the NGF and VEGF content in the plasma of foals affected by NE during the first 72 h of life/hospitalization; (iii) evaluate NGF and VEGF levels at birth/admission in relation to selected mare's and foal's clinical parameters; (iv) evaluate the relationship between the two trophic factors and thyroid hormone levels (TT3 and TT4) in the first 72 h of life/hospitalization; and (v) assess the mRNA expression of NGF, VEGF and brain-derived neurotrophic factor (BDNF), and their cell surface receptors, in the placenta of mares that delivered foals affected by NE. Thirteen affected foals born from mares hospitalized for peripartum monitoring (group NE) and twenty affected foals hospitalized after birth (group exNE) were included in the study. Dosage of NGF and VEGF levels was performed using commercial ELISA kits, whereas NGF, VEGF, and BDNF placental gene expression was performed using a semi-quantitative real-time PCR. In group NE, NGF levels decreased significantly from T0 to T24 (p = 0.0447) and VEGF levels decreased significantly from T0 to T72 (p = 0.0234), whereas in group exNE, only NGF levels decreased significantly from T0 to T24 (p = 0.0304). Compared to healthy foals, a significant reduction of TT3 levels was observed in both NE (T24, p = 0.0066; T72 p = 0.0003) and exNE (T0, p = 0.0082; T24, p < 0.0001; T72, p < 0.0001) groups, whereas a significant reduction of TT4 levels was observed only in exNE group (T0, p = 0.0003; T24, p = 0.0010; T72, p = 0.0110). In group NE, NGF levels were positively correlated with both TT3 (p = 0.0475; r = 0.3424) and TT4 levels (p = 0.0063; r = 0.4589). In the placenta, a reduced expression of NGF in the allantois (p = 0.0033) and a reduced expression of BDNF in the amnion (p = 0.0498) were observed. The less pronounced decrease of the two trophic factors compared to healthy foals, their relationship with thyroid hormones over time, and the reduced expression of NGF and BDNF in placental tissues of mares that delivered affected foals, could be key regulators in the mechanisms of equine NE. [ABSTRACT FROM AUTHOR]

Background: Although there is a biological basis for it, there is scarce evidence on the effect of heparin in ameliorating placental insufficiency and maximizing gestational age at delivery among fetal growth restriction (FGR) pregnancies., Objective: To explore the effectiveness of treatment using low molecular weight heparin (LMWH) at a prophylactic dose started at the time of diagnosis in prolonging gestation in pregnancies with early-onset fetal growth restriction (FGR)., Study Design: This was a phase III, multicenter, triple-blind, parallel-arm randomized clinical trial conducted in two university hospitals in Spain. Singleton pregnancies qualifying for early-onset placental FGR according to the adapted Delphi consensus (20 +0 -31 +6 weeks at diagnosis with umbilical artery Doppler with absent/reversed diastolic flow; or estimated fetal weight <10th percentile plus pulsatility index (PI) of umbilical artery Doppler >95th percentile; or estimated fetal weight <10th percentile plus mean PI of uterine artery Doppler >95th) were randomized to receive either subcutaneous treatment with bemiparin 3500 IU/0.2 mL/day or a placebo from inclusion at diagnosis to the time of delivery. The primary outcomes were prolongation of pregnancy from inclusion to live birth (days) and gestational age at live birth (days)., Results: 49 patients were included (23 in the LMWH group and 26 in the placebo group). In the LMWH group, the median prolongation of pregnancy was 42 days, while in the placebo group it was 41.5 days (median difference 0.5 days [95% CI -22.7 to 6.3] (p=0.667) and in the LMWH group, the median gestational age at delivery was 35.1 weeks, while in the placebo group, it was 34.6 weeks (median difference 0.5 weeks [95% CI -3.4 to 1.2] (p=0.639)., Conclusion: The use of prophylactic dose LMWH started at the time of diagnosis does not prolong pregnancy in individuals with early-onset fetal restriction., (Copyright © 2024. Published by Elsevier Inc.)

Background: Fetal Growth Restriction (FGR), often due to placental insufficiency, poses significant risks to perinatal outcomes. This review evaluates the efficacy of pentaerythritol tetranitrate (PETN), a nitric oxide donor, in preventing FGR., Methods: A systematic review and meta-analysis was conducted by searching PubMed, Embase, and CENTRAL up to July 2024. The inclusion criteria focused on randomized controlled trials comparing PETN to placebo in FGR prevention. Key outcomes were incidences of FGR, perinatal mortality, neonatal mortality, and intrauterine fetal demise (IUFD). Other outcomes were classified as maternal, fetal, neonatal and safety outcomes. We used Cochrane RoB 2.0 tool to assess risk of bias, and GRADE criteria for evidence quality., Results: Two eligible studies encompassing 417 pregnant women at risk of FGR were included. PETN did not significantly reduce incidence of FGR (RR 0.83, 95 % CI 0.66-1.04, 2 trials, 417 participants, low certainty) or perinatal mortality (RR 0.64, 95 % CI 0.26-1.58, 2 trials, 417 participants, very low certainty) compared to placebo. None of the studies reported neonatal mortality or IUFD. However, PETN treatment was associated with a reduction in preterm birth (RR 0.74, 95 % CI 0.58-0.93, 2 trials, 417 participants, moderate certainty). Other outcomes were similar between the groups., Conclusion: While PETN does not significantly impact FGR rates or perinatal mortality, it is associated with a reduction in preterm birth, suggesting potential benefits in high-risk pregnancies. Larger trials are necessary to substantiate these findings and clarify the role of PETN in FGR prevention., Competing Interests: The authors declare that they have no conflicts of interest or financial relationship with any organization.The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

The etiology of fetal growth restriction (FGR) is multifactorial, although many cases involve placental insufficiency. Placental insufficiency is associated with inadequate trophoblast invasion resulting in high resistance to blood flow, decreased availability of nutrients, and increased hypoxia. We have developed a non-viral, polymer-based nanoparticle that facilitates delivery and transient gene expression of human insulin-like 1 growth factor ( hIGF1 ) in trophoblast for the treatment of placenta insufficiency and FGR. Using the established guinea pig maternal nutrient restriction (MNR) model of placental insufficiency, the aim of the study was to identify novel pathways in the sub-placenta/decidua that provide insight into the underlying mechanism driving placental insufficiency, and may be corrected with hIGF1 nanoparticle treatment. Pregnant guinea pigs underwent ultrasound-guided sham or hIGF1 nanoparticle treatment at mid-pregnancy, and sub-placenta/decidua tissue was collected 5 days later. Transcriptome analysis was performed using RNA Sequencing on the Illumina platform. The MNR sub-placenta/decidua demonstrated fewer maternal spiral arteries lined by trophoblast, shallower trophoblast invasion and downregulation of genelists involved in the regulation of cell migration. hIGF1 nanoparticle treatment resulted in marked changes to transporter activity in the MNR + hIGF1 sub-placenta/decidua when compared to sham MNR. Under normal growth conditions however, hIGF1 nanoparticle treatment decreased genelists enriched for kinase signaling pathways and increased genelists enriched for proteolysis indicative of homeostasis. Overall, this study identified changes to the sub-placenta/decidua transcriptome that likely result in inadequate trophoblast invasion and increases our understanding of pathways that hIGF1 nanoparticle treatment acts on in order to restore or maintain appropriate placenta function.

Benjamin Bhunu, Isabel Riccio, Suttira Intapad Department of Pharmacology, Tulane University School of Medicine, New Orleans, LA, 70112, USACorrespondence: Suttira IntapadDepartment of Pharmacology, Tulane University School of Medicine, 1430 Tulane Avenue, #8683, New Orleans, LA, 70112-2699, USATel +1 504-988-9924Email sintapad@tulane.eduAbstract: In recent decades, both clinical and animal studies have shown that fetal growth restriction (FGR), caused by exposure to adverse uterine environments, is a risk factor for hypertension as well as for a variety of adult diseases. This observation has shaped and informed the now widely accepted theory of developmental origins of health and disease (DOHaD). There is a plethora of evidence supporting the association of FGR with increased risk of adult hypertension; however, the underlying mechanisms responsible for this correlation remain unclear. This review aims to explain the current advances in the field of fetal programming of hypertension and a brief narration of the underlying mechanisms that may link FGR to increased risk of adult hypertension. We explain the theory of DOHaD and then provide evidence from both clinical and basic science research which support the theory of fetal programming of adult hypertension. In addition, we have explored the underlying mechanisms that may link FGR to an increased risk of adult hypertension. These mechanisms include epigenetic changes, metabolic disorders, vascular dysfunction, neurohormonal impairment, and alterations in renal physiology and function. We further describe sex differences seen in the developmental origins of hypertension and provide insights into the opportunities and challenges present in this field.Keywords: hypertension, FGR, placental insufficiency, LBW

The aim of this research was to study the pathomorphological changes in the placenta in case of coronavirus disease (COVID-19) in the anamnesis during different periods of gestation. Materials and methods. 53 placentas of women with the coronavirus disease (COVID-19) (RNA determination of the SARS-CoV-2) during the pregnancy were studied. The material was divided into the following groups: 1 and 2 – placentas in cases with a negative PCR test in full-term newborns who were born in satisfactory condition and high Apgar score. Group 1 (n = 29) – mother’s history of COVID-19 at 34–39 weeks of gestation; group 2 (n = 17) – mother’s history of COVID-19 at 23-33 weeks of gestation; 3 (n = 7) – placenta in case of antenatal fetal death. Results. Statistically significant differences were revealed between study groups: chorioamnionitis prevailed in group 1 (in 28 cases (96.6 %); confidence interval (CI): 86.4–100.0 %; P1-2 = 0.004); in groups 2 and 3 – arteriosclerosis (in 13 cases (76.5 %); CI: 52.2– 93.9 %; P1-2 = 0.0003 and in 7 cases (100 %); CI: 75.7–100.0 %; P1-3 = 0.001; respectively). COVID-19 was diagnosed in group 1 from 34 to 39 weeks of gestation (median 36.5), group 2 from 23 to 33 weeks (median 28.0), in group 3 from 13 to 32 weeks with a median of 24.5. Antenatal fetal death was observed between 14 and 41 weeks (median 31.4). Conclusions. Pathomorphological changes in the placenta in the coronavirus disease COVID-19 depended on the duration of the post-COVID interval (the time interval from the diagnosis of COVID-19 and the moment of delivery), due to the sequential change in the phases of the inflammatory process: alteration, exudation and proliferation, followed by fibrosis. The formation of acute placental insufficiency in coronavirus disease COVID-19, diagnosed up to 1–6 weeks to delivery, is associated with the development of severe disorders of circulation and acute exudative inflammatory reactions of varying severity. The formation of chronic placental insufficiency is associated with the proliferative stage of inflammation. These changes lead to the development of fibrosis in the wall of arterioles and intervillous space. The most significant structural changes in the placenta, leading to placental insufficiency, were observed in group 2 – at the time of infection in the period from 23–33 weeks of pregnancy. Coronavirus disease COVID-19 in the mother in the second trimester of pregnancy is a risk factor for perinatal losses, which are caused by the changes in the placenta described above with an increase in the duration of the post-COVID interval.

Genetic variation shapes placental development and function, which has long been known to impact fetal growth and pregnancy outcomes such as miscarriage or maternal pre-eclampsia. Early epidemiology studies provided evidence of a strong heritable component to these conditions with both maternal and fetal-placental genetic factors contributing. Subsequently, cytogenetic studies of the placenta and the advent of prenatal diagnosis to detect chromosomal abnormalities provided direct evidence of the importance of spontaneously arising genetic variation in the placenta, such as trisomy and uniparental disomy, drawing inferences that remain relevant to this day. Candidate gene approaches highlighted the role of genetic variation in genes influencing immune interactions at the maternal-fetal interface and angiogenic factors. More recently, the emergence of molecular techniques and in particular high-throughput technologies such as Single-Nucleotide Polymorphism (SNP) arrays, has facilitated the discovery of copy number variation and study of SNP associations with conditions related to placental insufficiency. This review integrates past and more recent knowledge to provide important insights into the role of placental function on fetal and perinatal health, as well as into the mechanisms leading to genetic variation during development.

Background: The clinical inability to correctly identify late fetal growth restriction (FGR) within a group of fetuses who are identified as small for gestational age (SGA) is an everyday problem for all obstetrician-gynecologists. This leads to substantial overtreatment of healthy small fetuses but also inadequate detection of the growth-restricted fetuses that may benefit from timely delivery. Redistribution of the fetal circulation, signaled by an abnormal ratio of the Doppler velocity flow profiles of the umbilical artery and the middle cerebral artery, more specifically an increased umbilicocerebral ratio (UCR) (or its inverse: a decreased cerebroplacental ratio (CPR)), is an adaptation to chronic hypoxemia and nutritional scarcity with long-term consequences in survivors. The relevance of an abnormal UCR has been signaled extensively, and there is a general consensus that it is a signal of FGR, independent of size, with a strong association with poor outcomes. Yet, in the current literature, no comparisons of a monitoring-delivery strategy based on unfavorable UCR have been published. The objective of the Doppler Ratio In fetal Growth restriction Intervention Trial At (near) Term (DRIGITAT) is to evaluate if the timing of the delivery based on an abnormal UCR in late preterm fetuses identified as SGA improves neurodevelopmental outcomes at 2 years of age.Methods: The DRIGITAT study is a national multicenter cohort study of women with singleton pregnancies between 32 and 37 weeks of gestation identified as SGA, with a nested randomized controlled trial (RCT) in case of an abnormal UCR (> 0.8). Recruiting centers are in The Netherlands. In the nested RCT, women are randomized to either immediate induction of labor or expectant management from 34 weeks in case of severely abnormal size (EFW or FAC < p3) and from 36 weeks in case of mildly abnormal size (EFW or FAC p3-p10). The primary outcome measure is the 7-point average difference in the composite cognitive score (CCS) and composite motor score (CMS) on the Bayley-3 at 2 years. Secondary outcome measures include a composite outcome of neonatal morbidity, perinatal mortality, mode of delivery, maternal quality of life, costs, and predictive value of serum biomarkers. Analyses will be by intention to treat. The required sample size is determined for the nested RCT as 185 patients.Discussion: This study will provide insight into the diagnostic efficacy of UCR measurement in the evaluation of SGA fetuses in order to differentiate the healthy SGA fetus from the growth-restricted fetus and to determine if a fetus with abnormal UCR benefits from early delivery.Trial Registration: Healthcare Evaluation Netherlands NTR6663 . Registered on 14 August 2017. [ABSTRACT FROM AUTHOR]

Introduction: Abnormalities in placental function can lead to fetal growth restriction (FGR), but there is no consensus on their evaluation. Using blood oxygen level-dependent magnetic resonance imaging (BOLD MRI), we compared placental oxygenation between FGR cases and previously reported normal pregnancies.Methods: Eight singleton pregnant women (>32 weeks of gestation) diagnosed with fetal growth failure during pregnancy were recruited. BOLD MRI was consecutively performed under normoxia (21% O2), hyperoxia (100% O2), and normoxia for 4 min each. Each placental time-activity curve was evaluated to calculate the peak score (peakΔR2*) and the time from the start of maternal oxygen administration to the time of peakΔR2* (time to peakΔR2*). In six of the eight FGR cases, placental FGR-related pathological findings were evaluated after delivery.Results: The parameter peakΔR2* was significantly decreased in the FGR group (8 ± 3 vs 6 ± 1, p < 0.001), but there was no significant difference in time to peakΔR2* (458 ± 74 s vs 468 ± 57 s, p = 0.750). The findings in the six FGR cases assessed for placental pathologies included chorangiosis in two cases, avascular chorions in two cases, placental infarction in two cases, and syncytial knot formation in one case.Discussion: The peakΔR2* values were lower in the FGR group than in the normal pregnancy group. This suggests that oxygenation of the placenta is decreased in the FGR group compared to the normal group, and this may be related to FGR. Placental pathology also revealed findings possibly related to FGR, suggesting that low peakΔR2* values in the FGR group may reflect placental dysfunction. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Tepecik Education & Research Hospital / İzmir Tepecik Eğitim ve Araştırma Hastanesi Dergisi is the property of Logos Medical Publishing and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Epidemiological and animal experimental studies suggest an association between gestational cholestasis and intrauterine growth restriction (IUGR). Here, we explored the mechanism through which gestational cholestasis induced IUGR. To establish gestational cholestasis model, pregnant mice were subcutaneously injected with 17α‐Ethynylestradiol (E2) on gestational day 13 (GD13)–GD17. Some pregnant mice were intraperitoneally injected with 4μ8C on GD13–GD17. The results found that the apoptosis of trophoblast cells was elevated in placentas of mice with gestational cholestasis and in deoxycholic acid (DCA)‐treated human trophoblast cell lines and primary mouse trophoblast cells. Correspondingly, the levels of placental cleaved caspase‐3 and Bax were increased, while placental Bcl2 level was decreased in mice with gestational cholestasis and in DCA‐treated trophoblast cells. Further analysis found that placental IRE1α pathway was activated in mice with gestational cholestasis and in DCA‐treated trophoblast cells. Interestingly, 4μ8C, an IRE1α RNase inhibitor, significantly inhibited caspase‐3 activity and apoptosis of trophoblast cells in vivo and in vitro. Importantly, 4μ8C rescued gestational cholestasis‐induced placental insufficiency and IUGR. Furthermore, a case–control study demonstrated that placental IRE1α and caspase‐3 pathways were activated in cholestasis cases. Our results provide evidence that gestational cholestasis induces placental insufficiency and IUGR may be via triggering IRE1α‐mediated apoptosis of placental trophoblast cells. [ABSTRACT FROM AUTHOR]

We aimed to examine the contribution of splenic artery (SA) Doppler parameters in the detection of foetuses with late-onset foetal growth restriction (LO-FGR) and to evaluate its power in predicting adverse perinatal outcomes. Within the study's scope, 52 cases in the LO-FGR group and 92 cases in the control group were evaluated. The criteria determined in the Delphi procedure by an international consensus were used to define the LO-FGR. Middle cerebral artery (MCA) pulsatility index (PI) and SA PI were significantly lower in the LO-FGR group (p:.002, p<.001, respectively). Likewise, cerebroplacental ratio (CPR) was significantly lower in the LO-FGR group (p<.001). Decreased CPR and decreased SA PI were significantly and positively associated with an increased likelihood of exhibiting adverse obstetric outcome (p<.001, p:.012, respectively). The receiver operating characteristic (ROC) curve analysis showed that the optimal cut-off value for SA PI was 1.41 to predict LO-FGR with 70.7% sensitivity and 61.5% specificity (AUC = 0.684; 95% CI, 0.594–0.774). What is already known on this subject? The main clinical difficulty in late-onset foetal growth restriction (LO-FGR) is the detection of the disease. Whatdothe results of this study add? The splenic artery (SA) pulsatility index (PI) may contribute to both diagnostic and the prediction of adverse perinatal outcomes in LO-FGR cases. Our results showed that the SA PI value, as well as cerebroplacental ratio (CPR), can be a useful parameter in predicting negative outcomes. What are the implications of these findings for clinical practice and/orfurther research? Various degrees of uteroplacental insufficiency in foetuses with LO-FGR may be associated with abnormalities in SA Doppler velocimetry. Splenic artery Doppler velocimetry can be used for the clinical management of LO-FGR. [ABSTRACT FROM AUTHOR]

Background and Purpose: Preeclampsia, characterized by hypertension, proteinuria and restriction of fetal growth, is one of the leading causes of maternal and perinatal mortality. So far, there is no effective pharmacological therapy for preeclampsia. The present study was conducted to investigate the effects of supplementation with l‐citrulline in Dahl salt‐sensitive rats, a model of superimposed preeclampsia. Experimental Approach Parental Dahl salt‐sensitive rats were treated with l‐citrulline (2.5 g·L−1 in drinking water) from the day of mating to the end of lactation period. Blood pressure was monitored throughout pregnancy and markers of preeclampsia were assessed. Endothelial function of the pregnant Dahl salt‐sensitive rats was assessed by wire myograph. Key Results: In Dahl salt‐sensitive rats, l‐citrulline supplementation significantly reduced maternal blood pressure, proteinuria and levels of circulating soluble fms‐like tyrosine kinase 1. l‐Citrulline improved maternal endothelial function by augmenting the production of nitric oxide in the aorta and improving endothelium‐derived hyperpolarizing factor‐mediated vasorelaxation in resistance arteries. l‐Citrulline supplementation improved placental insufficiency and fetal growth, which were associated with an enhancement of angiogenesis and reduction of fibrosis and senescence in the placentas. In addition, l‐citrulline down‐regulated genes involved in the TLR4 and NF‐κB signalling pathways. Conclusion and Implications: This study shows that l‐citrulline supplementation reduced gestational hypertension and improved placentation and fetal growth in a rat model of superimposed preeclampsia. l‐Citrulline supplementation may provide an effective and safe therapeutic strategy for preeclampsia that benefits both the mother and the fetus. [ABSTRACT FROM AUTHOR]

Placental insufficiency (PI) lowers fetal oxygen and glucose concentrations, which disrupts glucose-insulin homeostasis and promotes fetal growth restriction (FGR). To date, prenatal treatments for FGR have not attempted to correct the oxygen and glucose supply simultaneously. Therefore, we investigated whether a 5-day correction of oxygen and glucose concentrations in PI-FGR fetuses would normalize insulin secretion and glucose metabolism. Experiments were performed in near-term FGR fetal sheep with maternal hyperthermia-induced PI. Fetal arterial oxygen tension was increased to normal levels by increasing the maternal inspired oxygen fraction and glucose was infused into FGR fetuses (FGR-OG). FGR-OG fetuses were compared with maternal air insufflated, saline-infused fetuses (FGR-AS) and control fetuses. Prior to treatment, FGR fetuses were hypoxemic and hypoglycemic and had reduced glucose-stimulated insulin secretion (GSIS). During treatment, oxygen, glucose, and insulin concentrations increased, and norepinephrine concentrations decreased in FGR-OG fetuses, whereas FGR-AS fetuses were unaffected. On treatment day 4, glucose fluxes were measured with euglycemic and hyperinsulinemic-euglycemic clamps. During both clamps, rates of glucose utilization and production were greater in FGR-AS than FGR-OG fetuses, while glucose fluxes in FGR-OG fetuses were not different than control rates. After 5 days of treatment, GSIS increased in FGR-OG fetuses to control levels and their ex vivo islet GSIS was greater than FGR-AS islets. Despite normalization in fetal characteristics, GSIS, and glucose fluxes, FGR-OG and FGR-AS fetuses weighed less than controls. These findings show that sustained, simultaneous correction of oxygen and glucose normalized GSIS and whole-body glucose fluxes in PI-FGR fetuses after the onset of FGR. [ABSTRACT FROM AUTHOR]

Diabetes mellitus in pregnant women is one of the topical problems of modern medicine. Recently, there has been an increase in cases of type 2 diabetes, especially an increase in the frequency of early onset in children and adolescents, respectively, in the fertile age, in a few years; they will enter with the burden of pathology. This is particularly problematic and important during pregnancy, since type 1 and type 2 diabetes are accompanied by a high risk of adverse obstetric and perinatal complications, which are detected in most women with type 1 and type 2 diabetes. The purpose of this review was to assess the role of vascular endothelial dysfunction and subclinical inflammation in the genesis of placental insufficiency causing the development of a number of pregnancy complications in diabetes mellitus, to search for biological markers of these processes, which may reveal some pathogenetic mechanisms for the formation and diagnosis of these disorders.The review shows changes in the content of a number of biological markers, primarily such as pro-inflammatory cytokines (IL-1, TNFα, IL-6); CRP, for certain pregnancy complications in diabetes mellitus women. It is the imbalance of cytokines that very often determines the development of gestational complications and disrupts immunological tolerance in the mother-placenta-fetus system. The degree of severity of angiogenesis processes depends on the level of hyperglycemia, manifestations of subclinical inflammation and is reflected in the increase in the VEGF expression level and its receptors in terminal and stem villi of the placenta.Thus, the review shows the role of endothelial dysfunction and subclinical inflammation in the development of obstetric and perinatal complications in diabetes mellitus patients, which is indicated by the changes in a range of proinflammatory cytokines and other biologically active markers.

Epithelial membrane protein-2 (EMP2) is a tetraspan protein predicted to regulate placental development. Highly expressed in secretory endometrium and trophectoderm cells, previous studies suggest that it may regulate implantation by orchestrating the surface expression of integrins and other membrane proteins. In order to test the role of EMP2 in pregnancy, mice lacking EMP2 (Emp2-/- ) were generated. Emp2-/- females are fertile but have reduced litter sizes when carrying Emp2-/- but not Emp2+/- fetuses. Placentas of Emp2-/- fetuses exhibit dysregulation in pathways related to neoangiogenesis, coagulation, and oxidative stress, and have increased fibrin deposition and altered vasculature. Given that these findings often occur due to placental insufficiency resulting in an oxygen-poor environment, the expression of hypoxia-inducible factor-1 alpha (HIF-1α) was examined. Placentas from Emp2-/- fetuses had increased total HIF-1α expression in large part through an increase in uterine NK (uNK) cells, demonstrating a unique interplay between uNK cells and trophoblasts modulated through EMP2. To determine if these results translated to human pregnancy, placentas from normal, term deliveries or those complicated by placental insufficiency resulting in intrauterine growth restriction (IUGR) were stained for EMP2. EMP2 was significantly reduced in both villous and extravillous trophoblast populations in IUGR placentas. Experiments in vitro using human trophoblast cells lines indicate that EMP2 modulates angiogenesis by altering HIF-1α expression. Our results reveal a novel role for EMP2 in regulating trophoblast function and vascular development in mice and humans, and suggest that it may be a new biomarker for placental insufficiency. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Impairments in placental development can adversely affect pregnancy outcomes. The bioactive nutrient choline may mitigate some of these impairments, as suggested by data in humans, animals, and human trophoblasts. Herein, we investigated the effects of maternal choline supplementation (MCS) on parameters of fetal growth in a Dlx3+/- (distal-less homeobox 3) mouse model of placental insufficiency. Dlx3+/- female mice were assigned to 1X (control), 2X, or 4X choline intake levels during gestation. Dams were sacrificed at embryonic days E10.5, 12.5, 15.5, and 18.5. At E10.5, placental weight, embryo weight, and placental efficiency were higher in 4X versus 1X choline. Higher concentrations of hepatic and placental betaine were detected in 4X versus 1X choline, and placental betaine was positively associated with embryo weight. Placental mRNA expression of Igf1 was downregulated by 4X (versus 1X) choline at E10.5. No differences in fetal growth parameters were detected at E12.5 and 15.5, whereas a small but significant reduction in fetal weight was detected at E18.5 in 4X versus 1X choline. MCS improved fetal growth during early pregnancy in the Dlx3+/- mice with the compensatory downregulation of Igf1 to slow growth as gestation progressed. Placental betaine may be responsible for the growth-promoting effects of choline.

Abstract Background Routine assessment in (near) term pregnancy is often inaccurate for the identification of fetuses who are mild to moderately compromised due to placental insufficiency and are at risk of adverse outcomes, especially when fetal size is seemingly within normal range for gestational age. Although biometric measurements and cardiotocography are frequently used, it is known that these techniques have low sensitivity and specificity. In clinical practice this diagnostic uncertainty results in considerable ‘over treatment’ of women with healthy fetuses whilst truly compromised fetuses remain unidentified. The CPR is the ratio of the umbilical artery pulsatility index over the middle cerebral artery pulsatility index. A low CPR reflects fetal redistribution and is thought to be indicative of placental insufficiency independent of actual fetal size, and a marker of adverse outcomes. Its utility as an indicator for delivery in women with reduced fetal movements (RFM) is unknown. The aim of this study is to assess whether expedited delivery of women with RFM identified as high risk on the basis of a low CPR improves neonatal outcomes. Secondary aims include childhood outcomes, maternal obstetric outcomes, and the predictive value of biomarkers for adverse outcomes. Methods International multicentre cluster randomised trial of women with singleton pregnancies with RFM at term, randomised to either an open or concealed arm. Only women with an estimated fetal weight ≥ 10th centile, a fetus in cephalic presentation and normal cardiotocograph are eligible and after informed consent the CPR will be measured. Expedited delivery is recommended in women with a low CPR in the open arm. Women in the concealed arm will not have their CPR results revealed and will receive routine clinical care. The intended sample size based on the primary outcome is 2160 patients. The primary outcome is a composite of: stillbirth, neonatal mortality, Apgar score

Introduction. Currently, the most implemented approach to the study of the mechanisms of the formation of obstetric complications (in particular, fetal growth restriction syndrome and fetoplacental insufficiency, FPI) is the identification of disease associations with DNA polymorphisms of candidate genes or their protein products. Particular attention is paid to the genes of the endothelial system, which play a role in the development of thrombophilia. Patients and methods. The study involved 50 pregnant women aged 20 to 45 years, including 40 patients with FPI and 10 patients without FPI. All pregnant women underwent general clinical, instrumental, biochemical and molecular genetic studies. The object and subject of research for molecular genetic studies were DNA samples of pregnant women and the FGB gene polymorphism (rs1695) IIe 105 Val. Results. The results of a comparative analysis of the frequencies of distribution of alleles and genotypes of IIe 105 Val polymorphism of the FGB fibrinolysis gene among 80 DNA samples in 40 pregnant women in 87.5% of cases revealed the presence of the normal allele G and in 12.5% of cases — the presence of the allele A (χ2=0.1; р=0.8; OR=1.2; 95%CI 0.306-4.983). Meanwhile, in the control group in 10 pregnant women without FPI, the frequency of the normal allele G of the FGB gene was 85%, while the frequency of the A mutant allele IIe 105 Val of the FGB gene amounted to 15%. The study of the genetic structure of this marker revealed a tendency to an increase in the expected mutation in the main group of pregnant women with FPI in relation to the group without FPI (10% and 2.25%, respectively). Conclusion. FGB fibrinolysis gene polymorphism (rs1695) IIe 105 Val is relatively widespread among pregnant women in Uzbekistan, and its clinical significance requires further studies.

Objective: the study aimed to reveal the daily periodicity of labor, the nature of melatonin metabolism, and the outcome of childbirth in women with a physiological and complicated pregnancy, depending on the sex of the fetus.Materials and methods: to study the chronophysiological characteristics of birth outcomes depending on fetal sex, 1 980 birth histories and stories of newborns were analyzed. The neonates were born between January 1 and December 31, 2016, in a maternity ward of the Federal State Budgetary Educational Institution of Higher Education “RostGMU” of the Ministry of Health of Russia. Melatonin production was identified by the level of urinary excretion of 6-sulfatoxymelatonin (6-SM) (its main metabolite) examining the morning portion of the urine of women by the ELISA method (at 8 am 3 ml of urine were collected in Eppendorf tube).Results: it was revealed that fetal sex modulated the activity of the central regulatory mechanisms responsible for the daily period functional processes in the female body and the initiation of labor. The largest number of spontaneous births by male fetuses occurred in the early evening before midnight when daily illumination was decreased, while the birth of girls was observed more often in the period from midnight to early morning. At the same time, mothers of boys had lower production of melatonin compared to that of girls’ mothers.Conclusions. The peculiarities of labor and birth complications associated with the sex of the fetus were identified.

Placental insufficiency is associated with reduced oxygen and nutrient supply to the fetus, which may result in fetal growth restriction (FGR). In an attempt to cope with the hostile intrauterine environment, FGR fetuses respond through metabolic, endocrine, vascular, cardiac, behavioral, hematological, and immunological adaptive mechanisms. However, permanent sequelae may result from such adaptive mechanisms. In this review, we describe the mechanisms of fetal adaptation to the hostile intrauterine environment in FGR of uteroplacental origin and detail their pathophysiology and potential implications for the extrauterine life of the individual. [ABSTRACT FROM AUTHOR]

Introduction: Multiple pregnancies are at increased risk of placental-related complications. The aim of the study was to investigate the prevalence and cumulative incidence of placental-related complications in twin pregnancies undergoing a late selective termination, compared to matched singleton and twin controls.Methods: A retrospective case-control study of post-selective late termination (≥20 weeks of gestation) singletons performed between 2009 and 2020 at a single tertiary center. Each post-termination pregnancy was matched to 2 singleton and 2 dichorionic twin pregnancies for: mode of conception, maternal age group and parity. The prevalence of composite placental related outcome was determined and compared. Kaplan-Meier curves were constructed, and log rank test was performed to compare the cumulative incidence of placental complications among groups.Results: Included were 90 post-selective termination pregnancies and 360 matched singletons and twins. These were subdivided according to trimester at procedure: 1) late 2nd trimester (N = 43, 20-27.6 weeks); 2) 3rd trimester (N = 47, ≥28 weeks). Placental-related complications presented earlier in the 3rd trimester selective termination group compared to singletons (median 35.5 vs median 37.4 weeks of gestation, P = 0.01). The cumulative incidence of placental-related complications in twins and post-selective termination singletons rose significantly earlier compared to singletons (P < 0.0001). A late 2nd trimester selective termination resulted in a comparable gestational age and cumulative incidence of placental-related complications as singletons.Discussion: Compared to singletons, the cumulative incidence of placental complications rises significantly earlier in post-third trimester selective termination singleton pregnancies. While a late 2nd trimester selective termination results in a cumulative incidence comparable to singletons. [ABSTRACT FROM AUTHOR]

Introduction: Fetoplacental Doppler is considered to be a key tool for the diagnosis of placenta-mediated fetal growth restriction(FGR). We aimed to determine the diagnostic accuracy of fetoplacental Doppler for specific placental diseases.Methods: A retrospective cohort study of all women with a singleton pregnancy and an antenatal diagnosis of SGA fetus(estimated fetal weight <10th centile for gestational age), who underwent fetoplacental Doppler assessment within 2 weeks before birth. Primary exposure was any abnormal Doppler result, defined as an abnormal umbilical artery(UA) Doppler, middle cerebral artery(MCA) Doppler, cerebroplacental-ratio(CPR), or umbilico-cerebral ratio(UCR). Study outcomes were abnormal placental pathology: maternal vascular malperfusion(MVM), villitis of unknown etiology(VUE), or fetal vascular malperfusion(FVM).Results: A total of 558 women with a singleton SGA fetus were included, of whom 239(42.8%) had an abnormal fetoplacental Doppler findings. UA Doppler had the lowest detection rate for abnormal placental pathology. MCA Doppler exhibited a significantly higher detection rate for all types of pathology. CPR and UCR exhibited highest detection rates for all types of placental pathology, however, were also associated with the highest false positive rate. The combination of fetoplacental Doppler with the severity of SGA and maternal hypertensive status achieved a high negative predictive value MVM lesions(97%). In contrast, fetoplacental Doppler did not improve the negative predictive value for non-MVM pathology(VUE or FVM).Discussion: Among SGA fetuses, the combination of UA and MCA Doppler is highly accurate in ruling out FGR due to MVM placental pathology, but is of limited value in excluding FGR due to underlying non-MVM pathologies. [ABSTRACT FROM AUTHOR]

Stillbirth is a recently recognized complication of COVID-19 in pregnant women. Other congenitally transmitted infections from viruses, bacteria and parasites can cause stillbirth by infecting fetal organs following transplacental transmission of the agent from the maternal bloodstream. However, recent research on pregnant women with COVID-19 having stillbirths indicates that there is another mechanism of stillbirth that can occur in placentas infected with SARS-CoV-2. In these cases, viral infection of the placenta results in SARS-CoV-2 placentitis, a combination of concurrent destructive findings that include increased fibrin deposition which typically reaches the level of massive perivillous fibrin deposition, chronic histiocytic intervillositis and trophoblast necrosis. These three pathological lesions, in some cases together with placental hemorrhage, thrombohematomas and villitis, result in severe and diffuse placental parenchymal destruction. This pathology can involve greater than one-half of the placental volume, averaging 77% in the largest study of 68 cases, effectively rendering the placenta incapable of performing its function of oxygenating the fetus. This destructive placental process can lead to stillbirth and neonatal death via malperfusion and placental insufficiency which is independent of fetal infection. Fetal autopsies show no evidence that direct infection of fetal organs is contributory. Because all mothers examined have been unvaccinated, maternal vaccination may prevent viremia and consequent placental infection. [ABSTRACT FROM AUTHOR]

Abstract Background Coronavirus disease 2019 (COVID-19), the global pandemic that has spread throughout the world, is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Given the limited scientific evidence on the manifestations and potential impact of this virus on pregnancy, we decided to report this case. Case presentation The patient was a 38 year-old Iranian woman with a triplet pregnancy and a history of primary infertility, as well as hypothyroidism and gestational diabetes. She was hospitalized at 29 weeks and 2 days gestational age due to elevated liver enzymes, and finally, based on a probable diagnosis of gestational cholestasis, she was treated with ursodeoxycholic acid. On the first day of hospitalization, sonography was performed, which showed that biophysical scores and amniotic fluid were normal in all three fetuses, with normal Doppler findings in two fetuses and increased umbilical artery resistance (pulsatility index [PI] > 95%) in one fetus. On day 4 of hospitalization, she developed fever, cough and myalgia, and her COVID-19 test was positive. Despite mild maternal symptoms, exacerbated placental insufficiency occurred in two of the fetuses leading to the rapid development of absent umbilical artery end-diastolic flow. Finally, 6 days later, the patient underwent cesarean section due to rapid exacerbation of placental insufficiency and declining biophysical score in two of the fetuses. Nasopharyngeal swab COVID-19 tests were negative for the first and third babies and positive for the second baby. The first and third babies died 3 and 13 days after birth, respectively, due to collapsed white lung and sepsis. The second baby was discharged in good general condition. The mother was discharged 3 days after cesarean section. She had no fever at the time of discharge and was also in good general condition. Conclusions This was a complicated triplet pregnancy, in which, after maternal infection with COVID-19, despite mild maternal symptoms, exacerbated placental insufficiency occurred in two of the fetuses, and the third fetus had a positive COVID-19 test after birth. Therefore, in cases of pregnancy with COVID-19 infection, in addition to managing the mother, it seems that physicians would be wise to also give special attention to the possibility of acute placental insufficiency and subsequent fetal hypoxia, and also the probability of vertical transmission.

Abstract Background Fetal growth restriction (FGR) due to placental insufficiency is a major risk factor for stillbirth. While small-for-gestational-age (SGA; weight 30 centiles between 20 and 36 weeks were associated with two–threefold increased relative risks of these indicators of placental insufficiency, while low 20–28-week growth velocities were not. Conclusions Reduced growth velocity between 20 and 36 weeks among AGA fetuses is associated with antenatal, intrapartum and postnatal indicators of placental insufficiency. These fetuses potentially represent an important, under-recognised cohort at increased risk of stillbirth. Encouragingly, this novel fetal assessment would require only one additional ultrasound to current routine care, and adds to the potential benefits of routine 36-week ultrasound.

BackgroundData is still lacking about the expediency of umbilical cord milking (UCM) in preterm neonates born to mothers with placental insufficiency (PI).ObjectiveTo study the effect of UCM in preterm neonates who had ante-natal evidence of placental insufficiency on peripheral blood cluster of differentiation 34 (CD34) percentage, hematological indices, and clinical outcomes.MethodsPreterm neonates,

Objective: Chronic hypertension (CHTN) causes vascular damage and resistance in the pregnant person and malperfusion in the placenta which may worsen the endothelial dysfunction of hypertensive disorders of pregnancy (HDP). These conditions frequently co-exist. A cumulative effect has been inconsistently demonstrated in prior studies, and it is unclear how co-existing hypertensive conditions affect pregnancy outcomes. We sought to examine maternal and neonatal outcomes in pregnancies affected by co-existing CHTN and HDP and compare these outcomes to those of pregnancies which were unaffected or affected by either condition alone., Methods: This is a retrospective cohort study of singleton deliveries at a single institution 1 October 2013 to 1 October 2021. Data were extracted from the electronic medical record using standardized definitions and billing and diagnosis codes. Pregnant people with no evidence of hypertensive condition were compared to those with CHTN only, HDP only, and co-existing CHTN and HDP. Demographics, baseline clinical data, and use of aspirin or antihypertensive medications were assessed. Maternal outcomes included cesarean delivery, critical range blood pressure, intensive care unit (ICU) admission, and death. Neonatal outcomes included preterm birth <37 weeks' gestation, small for gestational age (SGA) birthweight, ICU admission, and a morbidity composite. Bivariate tests of association were performed using Chi-square test. Crude and adjusted odds ratios (aORs) were calculated using logistic regression for three maternal and four neonatal outcomes. Descriptive statistics and multivariable analyses were performed., Results: Of 40,840 eligible people, 1451 (3.6%) had CHTN only; 5213 (12.8%) had HDP only; and 1890 (4.6%) had co-existing CHTN and HDP. Though odds of adverse maternal and neonatal outcomes were significantly increased for all hypertensive groups relative to the unaffected referent group, co-existing CHTN and HDP had the highest odds of cesarean delivery (aOR 1.60; 95% confidence interval (CI) 1.45-1.77), critical blood pressure (OR 41.54; 95% CI 35.96-47.99), maternal ICU admission or death (aOR 3.52; 95% CI 2.65-4.67), preterm birth (aOR 2.76; 95% CI 2.41-3.16), and SGA birthweight (aOR 1.61; 95% CI 1.39-1.87)., Conclusions: Hypertensive disorders of pregnancy in the setting of CHTN are associated with the highest odds of serious consequences on the pregnant person and neonate independent of maternal comorbidities and prematurity. Antihypertensive medication use lowers the odds of some adverse outcomes. Patients should be informed of heightened risks, but optimal management remains unclear.

At birth, the mammalian myocardium switches from using carbohydrates as the primary energy substrate to free fatty acids as the primary fuel. Thus, a compromised switch could jeopardize normal heart function in the neonate. Placental embolization in sheep is a reliable model of intrauterine growth restriction (IUGR). It leads to suppression of both proliferation and terminal differentiation of cardiomyocytes. We hypothesized that the expression of genes regulating cardiac fatty acid metabolism would be similarly suppressed in IUGR, leading to compromised processing of lipids. Following 10 days of umbilicoplacental embolization in fetal sheep, IUGR fetuses had elevated circulating long‐chain fatty acylcarnitines compared with controls (C14: CTRL 0.012 ± 0.005 nmol/ml vs. IUGR 0.018 ± 0.005 nmol/ml, P < 0.05; C18: CTRL 0.027 ± 0.009 nmol/mol vs. IUGR 0.043 ± 0.024 nmol/mol, P < 0.05, n = 12 control, n = 12 IUGR) indicative of impaired fatty acid metabolism. Uptake studies using fluorescently tagged BODIPY‐C12‐saturated free fatty acid in live, isolated cardiomyocytes showed lipid droplet area and number were not different between control and IUGR cells. mRNA levels of sarcolemmal fatty acid transporters (CD36, FATP6), acylation enzymes (ACSL1, ACSL3), mitochondrial transporter (CPT1), β‐oxidation enzymes (LCAD, HADH, ACAT1), tricarboxylic acid cycle enzyme (IDH), esterification enzymes (PAP, DGAT) and regulator of the lipid droplet formation (BSCL2) gene were all suppressed in IUGR myocardium (P < 0.05). However, protein levels for these regulatory genes were not different between groups. This discordance between mRNA and protein levels in the stressed myocardium suggests an adaptive protection of key myocardial enzymes under conditions of placental insufficiency. Key points: The fetal heart relies on carbohydrates in utero and must be prepared to metabolize fatty acids after birth but the effects of compromised fetal growth on the maturation of this metabolic system are unknown.Plasma fatty acylcarnitines are elevated in intrauterine growth‐restricted (IUGR) fetuses compared with control fetuses, indicative of impaired fatty acid metabolism in fetal organs.Fatty acid uptake and storage are not different in IUGR cardiomyocytes compared with controls.mRNA levels of genes regulating fatty acid transporter and metabolic enzymes are suppressed in the IUGR myocardium compared with controls, while protein levels remain unchanged.Mismatches in gene and protein expression, and increased circulating fatty acylcarnitines may have long‐term implications for offspring heart metabolism and adult health in IUGR individuals. This requires further investigation. [ABSTRACT FROM AUTHOR]

Preeclampsia is defined as hypertension arising after 20 weeks of gestational age with proteinuria or other signs of end-organ damage and is an important cause of maternal and perinatal morbidity and mortality, particularly when of early onset. Although a significant amount of research has been dedicated in identifying preventive measures for preeclampsia, the incidence of the condition has been relatively unchanged in the last decades. This could be attributed to the fact that the underlying pathophysiology of preeclampsia is not entirely understood. There is increasing evidence suggesting that suboptimal trophoblastic invasion leads to an imbalance of angiogenic and antiangiogenic proteins, ultimately causing widespread inflammation and endothelial damage, increased platelet aggregation, and thrombotic events with placental infarcts. Aspirin at doses below 300 mg selectively and irreversibly inactivates the cyclooxygenase-1 enzyme, suppressing the production of prostaglandins and thromboxane and inhibiting inflammation and platelet aggregation. Such an effect has led to the hypothesis that aspirin could be useful for preventing preeclampsia. The first possible link between the use of aspirin and the prevention of preeclampsia was suggested by a case report published in 1978, followed by the first randomized controlled trial published in 1985. Since then, numerous randomized trials have been published, reporting the safety of the use of aspirin in pregnancy and the inconsistent effects of aspirin on the rates of preeclampsia. These inconsistencies, however, can be largely explained by a high degree of heterogeneity regarding the selection of trial participants, baseline risk of the included women, dosage of aspirin, gestational age of prophylaxis initiation, and preeclampsia definition. An individual patient data meta-analysis has indicated a modest 10% reduction in preeclampsia rates with the use of aspirin, but later meta-analyses of aggregate data have revealed a dose-response effect of aspirin on preeclampsia rates, which is maximized when the medication is initiated before 16 weeks of gestational age. Recently, the Aspirin for Evidence-Based Preeclampsia Prevention trial has revealed that aspirin at a daily dosage of 150 mg, initiated before 16 weeks of gestational age, and given at night to a high-risk population, identified by a combined first trimester screening test, reduces the incidence of preterm preeclampsia by 62%. A secondary analysis of the Aspirin for Evidence-Based Preeclampsia Prevention trial data also indicated a reduction in the length of stay in the neonatal intensive care unit by 68% compared with placebo, mainly because of a reduction in births before 32 weeks of gestational age with preeclampsia. The beneficial effect of aspirin has been found to be similar in subgroups according to different maternal characteristics, except for the presence of chronic hypertension, where no beneficial effect is evident. In addition, the effect size of aspirin has been found to be more pronounced in women with good compliance to treatment. In general, randomized trials are underpowered to investigate the treatment effect of aspirin on the rates of other placental-associated adverse outcomes such as fetal growth restriction and stillbirth. This article summarizes the evidence around aspirin for the prevention of preeclampsia and its complications. [ABSTRACT FROM AUTHOR]

Background: Intrauterine growth restriction (IUGR) is defined as a fetus that fails to achieve its genetically determined growth potential. The exact molecular mechanisms of placental insufficiency IUGR pathogenesis are a little known. Our goal was to identify key genes and gene co-expression modules related to placental insufficiency IUGR.Methods: We used weighted gene co-expression network analysis (WGCNA) and protein-protein interaction (PPI) network analysis to examine the IUGR dataset GSE114691 from NCBI Gene Expression Omnibus. Core modules and hub nodes of the protein-protein interaction network were identified. A gene network was constructed and genes were classified by WGCNA into different modules. The validation of potential key genes was carried out using additional datasets (GSE12216 and GSE24129).Results: We identified in GSE114691 539 down regulated genes and 751 up regulated genes in placental tissues characteristic of placental insufficiency IUGR compared with non-IUGR, and defined 76 genes as hub nodes in the protein-protein interaction network. Genes in the key modules of the WGCNA network were most closely associated with placental insufficiency IUGR and significantly enriched in biological process such as cellular metabolic process and macromolecule metabolic process. We identified as key genes TGFB1, LEP, ENG, ITGA5, STAT5A, LYN, GATA3, FPR1, TGFB2, CEBPB, KLF4, FLT1, and PNPLA2. The RNA expression levels of ENG and LEP, as biomarkers, were validated.Conclusion: A holistic gene expression profile of placental insufficiency IUGR has been generated and the key genes ENG and LEP has potential to serve as circulating diagnosis biomarkers and therapeutic targets for placental insufficiency IUGR. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to establish whether the increased fetal pulmonary venous pulsatility index (PVPI) in late pregnancy can independently predict small for gestational age (SGA) and to verify its cut point value and efficacy. Method: The PVPI was measured in women with singleton pregnancies between 25 and 39 gestational weeks. Maternal hypertension and diabetes, estimated fetal weight (EFW) and percentile of the corresponding weeks of pregnancy (USG_PER), gestational weeks at delivery, and birth weight and percentile of the corresponding weeks of pregnancy (BABY_PER) were reviewed. To assess whether PVPI was independently correlated with BABY_PER, Pearson's correlation analysis was performed. The cut point value of PVPI for the prediction of SGA was established using a receiver operating characteristic (ROC) curve. Results: A total of 129 mothers were included in this study. Both USG_PER and PVPI were significantly related to SGA, independently (P <.001 and P =.004, respectively). The cut point value of PVPI was found to be 1.13. The AUCs of PVPI and USG_PER were not significantly different (P =.624). The sensitivity of PVPI was 70.27%, and the specificity was 92.39%. Conclusion: PVPI could predict SGA independently, and the efficacy was comparable to EFW during pregnancy. [ABSTRACT FROM AUTHOR]

Abstract Background Traditionally, the placental functional integrity is suggested by indirect ultrasound measurements like fetal growth, amniotic fluid index, and uterine and umbilical artery Doppler indices. Only recently the elasticity of the placenta is studied as a measure of placental consistency and biomechanical prosperities and may reflect the placental function. Shear wave velocity is the quantitative parameter of the shear wave elastography. A high-risk pregnancy is a situation which puts the mother, the fetus, or both at greater risk than a normal pregnancy. Results The shear wave velocity (SWV) showed no significant difference between the placenta of normal pregnancies in the second and third trimesters (0.85 ± 0.43 m/s and 0.89 ± 0.57 m/s, respectively). The placenta of patients with preeclampsia/eclampsia had high SWV in the second and third trimesters (2.13 ± 1.48 m/s and 2.23 ± 1.48 m/s) with a highly significant difference from the normal placenta (P < 0.001). The placentas with abnormal location (placenta previa) and penetration (placenta accreta) had higher SWV than the placenta of normal pregnancies. The mean SWV for placenta previa was 1.1 ± 0.74 m/s and 1.3 ± 0.81 m/s in the second and third trimesters, respectively, with a mildly significant difference with the normal placenta. The placenta accreta shows high mean SWV in the second and third trimesters (1.6 ± 0.65 m/s and 1.961.6 ± 0.65, respectively) which differed significantly (P < 0.001) from SWV in the normal placenta in the second and third trimesters. Conclusion Shear wave velocity measurement as the quantitative parameter of acoustic radiation force impulse (ARFI) elastography reflects the placental elasticity in normal and high-risk pregnancies. The SWV increases in conditions like hypertension, preeclampsia, maternal renal disease, and diabetes and reflects the structural and biomechanical abnormalities in such diseases. High shear wave velocity correlates with the incidence of growth restriction and abnormal Doppler parameters especially in the hypertensive disease. The virtual touch quantification (VTQ) can be used as a complementary diagnostic and prognostic tool in high-risk pregnancy.

Resumen: Introducción: El estudio del doppler fetal permite identificar la etiología placentaria y clasificar su gravedad en aquellos neonatos pequeños para la edad gestacional. Existen estudios que relacionan estos datos doppler con alteraciones en el flujo intestinal del recién nacido, pero su relación con los datos de oximetría intestinal ha sido poco estudiada. Objetivo: Evaluar si existe relación entre los datos doppler prenatales y los datos de oximetría abdominal en los niños pequeños para su edad gestacional. Material y métodos: Estudio prospectivo observacional en neonatos > 32 semanas con un peso al nacer 32 weeks with a birth weight

The aim of the study was to determine whether early-onset and late-onset fetal growth restriction (FGR) differentially affects the blood–brain barrier integrity. Furthermore, the purpose of the study was to investigate the relationship between the blood–brain barrier breakdown and neurological disorders in FGR newborns. To evaluate the serum tight junction (TJ) proteins and the placental TJ proteins expression, an ELISA method was used. A significant difference in serum OCLN concentrations was noticed in pregnancies complicated by the early-onset FGR, in relation to the intraventricular hemorrhage (IVH) occurrence in newborns. No significant differences in concentrations of the NR1 subunit of the N-methyl-d-aspartate receptor (NR1), nucleoside diphosphate kinase A (NME1), S100 calcium-binding protein B (S100B), occludin (OCLN), claudin-5 (CLN5), zonula occludens-1 (zo-1), the CLN5/zo-1 ratio, and the placental expression of OCLN, CLN5, claudin-4 (CLN4), zo-1 were noticed between groups. The early-onset FGR was associated with a higher release of NME1 into the maternal circulation in relation to the brain-sparing effect and premature delivery. Additionally, in late-onset FGR, the higher release of the S100B into the maternal serum in regard to fetal distress was observed. Furthermore, there was a higher release of zo-1 into the maternal circulation in relation to newborns’ moderate acidosis in late-onset FGR. Blood–brain barrier disintegration is not dependent on pregnancy advancement at the time of FGR diagnosis. NME1 may serve as a biomarker useful in the prediction of fetal circulatory centralization and extremely low birth weight in pregnancies complicated by the early-onset FGR. Moreover, the serum zo-1 concentration may have prognostic value for moderate neonatal acidosis in late-onset FGR pregnancies.