11,867 results on '"Intrauterine growth restriction"'
Search Results
2. Low Dose Aspirin for Preventing Intrauterine Growth Restriction and Preeclampsia in Sickle Cell Pregnancy (PIPSICKLE) (PIPSICKLE)
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- 2024
3. Treatment of Intrauterine Growth Restriction With Low Molecular Heparin. (TRACIP)
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Servicio de Asesoría a la Investigación y Logística SL
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- 2024
4. Brain serotonin and serotonin transporter expression in male and female postnatal rat offspring in response to perturbed early life dietary exposures
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Ye, Xin, Ghosh, Shubhamoy, Shin, Bo-Chul, Ganguly, Amit, Maggiotto, Liesbeth, Jacobs, Jonathan P, and Devaskar, Sherin U
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Biological Psychology ,Pharmacology and Pharmaceutical Sciences ,Biomedical and Clinical Sciences ,Psychology ,Microbiome ,Women's Health ,Mental Illness ,Dietary Supplements ,Nutrition ,Neurosciences ,Mental Health ,Brain Disorders ,Pediatric ,2.1 Biological and endogenous factors ,serotonin ,serotonin transporter ,caloric restriction ,intrauterine growth restriction ,high fat diet ,microbiome ,Cognitive Sciences ,Biological psychology - Abstract
IntroductionSerotonin (5-HT) is critical for neurodevelopment and the serotonin transporter (SERT) modulates serotonin levels. Perturbed prenatal and postnatal dietary exposures affect the developing offspring predisposing to neurobehavioral disorders in the adult. We hypothesized that the postnatal brain 5-HT-SERT imbalance associated with gut dysbiosis forms the contributing gut-brain axis dependent mechanism responsible for such ultimate phenotypes.MethodsEmploying maternal diet restricted (IUGR, n=8) and high fat+high fructose (HFhf, n=6) dietary modifications, rodent brain serotonin was assessed temporally by ELISA and SERT by quantitative Western blot analysis. Simultaneously, colonic microbiome studies were performed.ResultsAt early postnatal (P) day 2 no changes in the IUGR, but a ~24% reduction in serotonin (p = 0.00005) in the HFhf group occurred, particularly in the males (p = 0.000007) revealing a male versus female difference (p = 0.006). No such changes in SERT concentrations emerged. At late P21 the IUGR group reared on HFhf (IUGR/HFhf, (n = 4) diet revealed increased serotonin by ~53% in males (p = 0.0001) and 36% in females (p = 0.023). While only females demonstrated a ~40% decrease in serotonin (p = 0.010), the males only trended lower without a significant change within the HFhf group (p = 0.146). SERT on the other hand was no different in HFhf or IUGR/RC, with only the female IUGR/HFhf revealing a 28% decrease (p = 0.036). In colonic microbiome studies, serotonin-producing Bacteriodes increased with decreased Lactobacillus at P2, while the serotonin-producing Streptococcus species increased in IUGR/HFhf at P21. Sex-specific changes emerged in association with brain serotonin or SERT in the case of Alistipase, Anaeroplasma, Blautia, Doria, Lactococcus, Proteus, and Roseburia genera.DiscussionWe conclude that an imbalanced 5-HT-SERT axis during postnatal brain development is sex-specific and induced by maternal dietary modifications related to postnatal gut dysbiosis. We speculate that these early changes albeit transient may permanently alter critical neural maturational processes affecting circuitry formation, thereby perturbing the neuropsychiatric equipoise.
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- 2024
5. Cord Blood Adductomics Reveals Oxidative Stress Exposure Pathways of Bronchopulmonary Dysplasia
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Lin, Erika T, Bae, Yeunook, Birkett, Robert, Sharma, Abhineet M, Zhang, Runze, Fisch, Kathleen M, Funk, William, and Mestan, Karen K
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Paediatrics ,Biomedical and Clinical Sciences ,Perinatal Period - Conditions Originating in Perinatal Period ,Clinical Research ,Neonatal Respiratory Distress ,Preterm ,Low Birth Weight and Health of the Newborn ,Infant Mortality ,Pediatric ,Lung ,Prevention ,2.1 Biological and endogenous factors ,Aetiology ,2.2 Factors relating to the physical environment ,Reproductive health and childbirth ,Good Health and Well Being ,addition products ,neonate ,pre-eclampsia ,chorioamnionitis ,intrauterine growth restriction ,Biochemistry and cell biology ,Medical biochemistry and metabolomics ,Pharmacology and pharmaceutical sciences - Abstract
Fetal and neonatal exposures to perinatal oxidative stress (OS) are key mediators of bronchopulmonary dysplasia (BPD). To characterize these exposures, adductomics is an exposure science approach that captures electrophilic addition products (adducts) in blood protein. Adducts are bound to the nucleophilic cysteine loci of human serum albumin (HSA), which has a prolonged half-life. We conducted targeted and untargeted adductomics to test the hypothesis that adducts of OS vary with BPD. We studied 205 preterm infants (≤28 weeks) and 51 full-term infants from an ongoing birth cohort. Infant plasma was collected at birth (cord blood), 1-week, 1-month, and 36-weeks postmenstrual age. HSA was isolated from plasma, trypsin digested, and analyzed using high-performance liquid chromatography-mass spectrometry to quantify previously annotated (known) and unknown adducts. We identified 105 adducts in cord and postnatal blood. A total of 51 known adducts (small thiols, direct oxidation products, and reactive aldehydes) were increased with BPD. Postnatally, serial concentrations of several known OS adducts correlated directly with supplemental oxygen exposure. The application of large-scale adductomics elucidated OS-mediated pathways of BPD. This is the first study to investigate the "neonatal-perinatal exposome" and to identify oxidative stress-related exposure biomarkers that may inform antioxidant strategies to protect the health of future generations of infants.
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- 2024
6. Fetal Brain Care: Therapies for Brain Neurodevelopment in Fetal Growth Restriction
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Fundacion Clinic per a la Recerca Biomédica, Fundació Sant Joan de Déu, and Elisenda Eixarch Roca, Coordinator of Fetal Neurology Unit
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- 2024
7. Unraveling the Mfn2-Warburg effect nexus: a therapeutic strategy to combat pulmonary arterial hypertension arising from catch-up growth after IUGR.
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Yan, Lingling, Luo, Xiaofei, Hang, Chengcheng, YuWang, Zhang, Ziming, Xu, Shanshan, and Du, Lizhong
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VASCULAR remodeling , *MITOCHONDRIAL dynamics , *FETAL growth retardation , *PULMONARY arterial hypertension , *LABORATORY rats - Abstract
Background: The interplay between intrauterine and early postnatal environments has been associated with an increased risk of cardiovascular diseases in adulthood, including pulmonary arterial hypertension (PAH). While emerging evidence highlights the crucial role of mitochondrial pathology in PAH, the specific mechanisms driving fetal-originated PAH remain elusive. Methods and results: To elucidate the role of mitochondrial dynamics in the pathogenesis of fetal-originated PAH, we established a rat model of postnatal catch-up growth following intrauterine growth restriction (IUGR) to induce pulmonary arterial hypertension (PAH). RNA-seq analysis of pulmonary artery samples from the rats revealed dysregulated mitochondrial metabolic genes and pathways associated with increased pulmonary arterial pressure and pulmonary arterial remodeling in the RC group (postnatal catch-up growth following IUGR). In vitro experiments using pulmonary arterial smooth muscle cells (PASMCs) from the RC group demonstrated elevated proliferation, migration, and impaired mitochondrial functions. Notably, reduced expression of Mitofusion 2 (Mfn2), a mitochondrial outer membrane protein involved in mitochondrial fusion, was observed in the RC group. Reconstitution of Mfn2 resulted in enhanced mitochondrial fusion and improved mitochondrial functions in PASMCs of RC group, effectively reversing the Warburg effect. Importantly, Mfn2 reconstitution alleviated the PAH phenotype in the RC group rats. Conclusions: Imbalanced mitochondrial dynamics, characterized by reduced Mfn2 expression, plays a critical role in the development of fetal-originated PAH following postnatal catch-up growth after IUGR. Mfn2 emerges as a promising therapeutic strategy for managing IUGR-catch-up growth induced PAH. [ABSTRACT FROM AUTHOR]
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- 2024
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8. Is the rabbit a natural model of fetal growth restriction? Morphological and functional characterization study using diffusion-weighted MRI and stereology.
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Dap, Matthieu, Albert, Théo, Ramdhani, Ikrame, Couturier-Tarrade, Anne, Morel, Olivier, Chavatte-Palmer, Pascale, Beaumont, Marine, and Bertholdt, Charline
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Rabbits are routinely used as a natural model of fetal growth restriction (FGR); however, no studies have confirmed that rabbits have FGR. This study aimed to characterize the fetoplacental unit (FPU) in healthy pregnant rabbits using diffusion-weighted MRI and stereology. A secondary objective of the study was to describe the associations among findings from diffusion-weighted MRI (DW-MRI), fetal weight measurement and histological analysis of the placenta. Pregnant rabbits underwent DW-MRI under general anesthesia on embryonic day 28 of pregnancy. MR imaging was performed at 3.0 T. The apparent diffusion coefficient (ADC) values were calculated for the fetal brain, liver, and placenta. The placenta was analyzed by stereology (volume density of trophoblasts, the maternal blood space and fetal vessels). Each fetus and placenta were weighed. Two groups of fetuses were defined according to the position in the uterine horn (Cervix group versus Ovary group). We analyzed 20 FPUs from 5 pregnant rabbits. Fetuses and placentas were significantly lighter in the Cervix group than in the Ovary group (34.7 ± 3.7 g vs. 40.2 ± 5.4 g; p = 0.02). Volume density analysis revealed that the percentage of fetal vessels, the maternal blood space and trophoblasts was not significantly affected by the position of the fetus in the uterine horn. There was no difference in ADC values according to the position of the fetus in the uterine horn, and there was no correlation between ADC values and fetal weight. The findings of a multimodal evaluation of the placenta in a rabbit model of FGR suggested is not a natural model of fetal growth restriction. • In rabbits, the fetus closest to the ovary is heavier than the one near the cervix. • It is possible to use DW-MRI to assess placental function in rabbits. • Rabbits do not appear to be a natural model for intrauterine growth restriction. [ABSTRACT FROM AUTHOR]
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- 2024
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9. Estimating fetal weight in gastroschisis: A 10 year audit of outcomes at the National Maternity Hospital.
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O'Keeffe, Rachel, Mulligan, Karen, McParland, Peter, McAuliffe, Fionnuala M., Mahony, Rhona, Corcoran, Siobhan, O'Connor, Clare, Carroll, Stephen, and Walsh, Jennifer
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FETAL growth retardation , *FETAL development , *HUMAN abnormalities , *BIRTH weight , *ABDOMINAL wall , *GASTROSCHISIS - Abstract
Objective: To identify whether conventional methods of estimating fetal growth (Hadlock's formula), which relies heavily on abdominal circumference measurements, are accurate in fetuses with gastroschisis. Methods: A retrospective cohort study was performed between the period January 1, 2011 and December 31, 2021 in a tertiary referral maternity hospital identifying all pregnancies with a diagnosis of gastroschisis. Projected fetal weight was obtained using the formula (EFW [Hadlock's formula] + 185 g × [X/7]) where X was the number of days to delivery. Results: During the study period 41 cases were identified. The median maternal age was 25. The median BMI was 25 and 63% were primiparous women (n = 26). Median gestation at diagnosis was 21 weeks. Median gestation at delivery was 36 weeks. A total of 4.8% of mothers had a history of drug use (n = 2). The rate of maternal tobacco use was 21.9% (n = 9). A total of 4.8% of fetuses had additional congenital anomalies including amniotic band syndrome and myelomeningocele (n = 2). Estimated fetal weight (EFW) and birth weight data were available for 34 cases. A Wilcoxon signed‐rank test showed projected EFW using Hadlock's formula did not result in a statistically significant different birth weight (Z = −1.3, P = 0.169). Median projected weight and actual birth weight were 2241.35 and 2415 g respectively. Median difference was 0.64 g (95% CI: −148 to −28.5). Conclusion: Our data showed accuracy using standard formulae for EFW in fetuses with gastroschisis. Synopsis: Our study shows accuracy using standard formulae such as Hadlock's formula for estimating fetal weight in fetuses with abdominal wall defects such as gastroschisis. [ABSTRACT FROM AUTHOR]
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- 2024
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10. Anatomical and functional changes of the fetal adrenal gland in intrauterine growth restriction.
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Martinelli, Serena, Rolfo, Alessandro, Pace, Carlotta, Canu, Letizia, Nuzzo, Anna Maria, Giuffrida, Domenica, Gaglioti, Pietro, and Todros, Tullia
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SMALL for gestational age , *FETAL growth retardation , *FETAL development , *ADRENAL glands , *CORD blood - Abstract
Objective: The aim of this study was to demonstrate the establishment of adrenal sparing in intrauterine growth restricted (IUGR) human fetuses. IUGR fetuses are a subgroup of small for gestational age (SGA) fetuses that are unable to reach their own growth potential because of chronic hypoxia and undernutrition. We hypothesized that in IUGR fetuses the adrenal gland is relatively larger and secretion of noradrenaline (NA), adrenaline (A), and cortisol is increased. Study Design: This is a prospective observational study including 65 singleton pregnancies (42 IUGR and 23 controls). Using two‐dimensional ultrasound, we measured fetal adrenal diameters and adrenal/abdominal circumference (AD/AC) ratio between 25 and 37 weeks. We considered only one measurement per fetus. In 21 pregnancies we also measured NA, A, and cortisol levels in arterial and venous fetal cord blood collected at the time of delivery. Results: The AD/AC ratio was significantly higher in IUGR fetuses than in controls. Cord NA and A levels were significantly higher in IUGR fetuses than in controls. An increase in cortisol secretion in IUGR fetuses was observed but the difference was not statistically significant. Conclusions: Adrenal sparing correlates with a relative increase in adrenal measurements and function. Synopsis: The adrenal gland of intrauterine growth‐restricted fetuses is relatively larger compared with controls and its function is enhanced. [ABSTRACT FROM AUTHOR]
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- 2024
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11. Bacillus subtilis alleviates excessive apoptosis of intestinal epithelial cells in intrauterine growth restriction suckling piglets via the members of Bcl‐2 and caspase families.
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Xie, Zechen, Yun, Yang, Yu, Ge, Zhang, Xin, Zhang, Hao, Wang, Tian, and Zhang, Lili
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G protein coupled receptors , *EPITHELIAL cells , *FETAL growth retardation , *BACILLUS subtilis , *BCL-2 proteins , *TUMOR necrosis factor receptors , *CELL growth - Abstract
BACKGROUND: The intestine is a barrier resisting various stress responses. Intrauterine growth restriction (IUGR) can cause damage to the intestinal barrier via destroying the balance of intestinal epithelial cells' proliferation and apoptosis. Bacillus subtilis has been reported to regulate intestinal epithelial cells' proliferation and apoptosis. Thus, the purpose of this study was to determine if B. subtilis could regulate intestinal epithelial cells' proliferation and apoptosis in intrauterine growth restriction suckling piglets. RESULTS: Compared with the normal birth weight group, the IUGR group showed greater mean optical density values of Ki‐67‐positive cells in the ileal crypt (P < 0.05). IUGR resulted in higher ability of proliferation and apoptosis of intestinal epithelial cells, by upregulation of the messenger RNA (mRNA) or proteins expression of leucine rich repeat containing G protein coupled receptor 5, Caspase‐3, Caspase‐7, β‐catenin, cyclinD1, B‐cell lymphoma‐2 associated agonist of cell death, and BCL2 associated X (P < 0.05), and downregulation of the mRNA or protein expression of B‐cell lymphoma‐2 and B‐cell lymphoma‐2‐like 1 (P < 0.05). However, B. subtilis supplementation decreased the mRNA or proteins expression of leucine rich repeat containing G protein coupled receptor 5, SPARC related modular calcium binding 2, tumor necrosis factor receptor superfamily member 19, cyclinD1, Caspase‐7, β‐catenin, B‐cell lymphoma‐2 associated agonist of cell death, and Caspase‐3 (P < 0.05), and increased the mRNA expression of B‐cell lymphoma‐2 (P < 0.05). CONCLUSION: IUGR led to excessive apoptosis of intestinal epithelial cells, which induced compensatory proliferation. However, B. subtilis treatment prevented intestinal epithelial cells of IUGR suckling piglets from excessive apoptosis. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]
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- 2024
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12. The Beneficial Effects of Prenatal Biotin Supplementation in a Rat Model of Intrauterine Caloric Restriction to Prevent Cardiometabolic Risk in Adult Female Offspring.
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Aguilera-Méndez, Asdrubal, Figueroa-Fierros, Ian, Ruiz-Pérez, Xóchilt, Godínez-Hernández, Daniel, Saavedra-Molina, Alfredo, Rios-Chavez, Patricia, Villafaña, Santiago, Boone-Villa, Daniel, Ortega-Cuellar, Daniel, Gauthereau-Torres, Marcia Yvette, Nieto-Aguilar, Renato, and Palomera-Sanchez, Zoraya
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FETAL growth retardation , *LABORATORY rats , *LOW-calorie diet , *INSULIN resistance , *TREATMENT effectiveness , *FRUCTOSE - Abstract
Numerous studies indicate that intrauterine growth restriction (IUGR) can predispose individuals to metabolic syndrome (MetS) in adulthood. Several reports have demonstrated that pharmacological concentrations of biotin have therapeutic effects on MetS. The present study investigated the beneficial effects of prenatal biotin supplementation in a rat model of intrauterine caloric restriction to prevent cardiometabolic risk in adult female offspring fed fructose after weaning. Female rats were exposed to a control (C) diet or global caloric restriction (20%) (GCR), with biotin (GCRB) supplementation (2 mg/kg) during pregnancy. Female offspring were exposed to 20% fructose (F) in drinking water for 16 weeks after weaning (C, C/F, GCR/F, and GCRB/F). The study assessed various metabolic parameters including Lee's index, body weight, feed conversion ratio, caloric intake, glucose tolerance, insulin resistance, lipid profile, hepatic triglycerides, blood pressure, and arterial vasoconstriction. Results showed that GCR and GCRB dams had reduced weights compared to C dams. Offspring of GCRB/F and GCR/F dams had lower body weight and Lee's index than C/F offspring. Maternal biotin supplementation in the GCRB/F group significantly mitigated the adverse effects of fructose intake, including hypertriglyceridemia, hypercholesterolemia, hepatic steatosis, glucose and insulin resistance, hypertension, and arterial hyperresponsiveness. This study concludes that prenatal biotin supplementation can protect against cardiometabolic risk in adult female offspring exposed to postnatal fructose, highlighting its potential therapeutic benefits. [ABSTRACT FROM AUTHOR]
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- 2024
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13. Does atenolol use during pregnancy cause small for gestational age neonates? A meta-analysis.
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Bratton, Shauna, Taylor, Megan K., Cortez, Priscilla, Schiattarella, Antonio, Fochesato, Cecilia, and Sisti, Giovanni
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SMALL for gestational age , *FETAL growth retardation , *FETAL development , *PROPRANOLOL , *ATENOLOL - Abstract
Atenolol is a commonly used beta bloscker in non-pregnant women. Many providers are hesitant in prescribing atenolol in pregnancy because of a possible association with poor fetal growth. We aimed to assess the association between atenolol and the occurrence of small for gestational age neonates compared to other beta blockers, as described in the existing literature.We used the meta-analytic method to generate a forest plot for risk ratios (RR) of small for gestational age in patients who used atenolol vs. other beta blockers. Statistical heterogeneity was assessed with the I2 statistic.Two studies were included, with a resultant RR of 1.94 [95 % confidence interval (CI) 1.60; 2.35]. A study by Duan et al. in 2018 noted the following rate of small for gestational age for each beta blocker use: 112/638 atenolol, 590/3,357 labetalol, 35/324 metoprolol, and 50/489 propranolol. A study by Tanaka et al. in 2016 noted the following rate of small for gestational age: 8/22 for propranolol, 2/12 for metoprolol, 2/6 for atenolol, 0/5 for bisoprolol. Heterogeneity (I2) was 0 %.Our results suggested an elevated risk of small for gestational age associated with atenolol use in comparison to other beta blockers, specifically labetalol, propranolol, bisoprolol, and metoprolol. [ABSTRACT FROM AUTHOR]
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- 2024
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14. Impact of gestational diabetes mellitus on neonatal outcomes in small for gestational age infants: a multicenter retrospective study.
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Hirsch, Ayala, Peled, Tzuria, Schlesinger, Shaked, Sela, Hen Y., Grisaru-Granovsky, Sorina, and Rottenstreich, Misgav
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SMALL for gestational age , *GESTATIONAL diabetes , *INFANTS , *MECONIUM aspiration syndrome , *PREMATURE labor - Abstract
Objective: To evaluate obstetric and perinatal outcomes among small for gestational age (SGA) infants born to patients diagnosed with Gestational diabetes mellitus (GDM). Materials and methods: A multicenter retrospective cohort study between 2005 and 2021. The perinatal outcomes of SGA infants born to patients with singleton pregnancy and GDM were compared to SGA infants born to patients without GDM. The primary outcome was a composite adverse neonatal outcome. Infants with known structural/genetic abnormalities or infections were excluded. A univariate analysis was conducted followed by a multivariate analysis (adjusted odds ratio [95% confidence interval]). Results: During the study period, 11,662 patients with SGA infants met the inclusion and exclusion criteria. Of these, 417 (3.6%) SGA infants were born to patients with GDM, while 11,245 (96.4%) were born to patients without GDM. Overall, the composite adverse neonatal outcome was worse in the GDM group (53.7% vs 17.4%, p < 0.01). Specifically, adverse neonatal outcomes such as a 5 min Apgar score < 7, meconium aspiration, seizures, and hypoglycemia were independently associated with GDM among SGA infants. In addition, patients with GDM and SGA infants had higher rates of overall and spontaneous preterm birth, unplanned cesarean, and postpartum hemorrhage. In a multivariate logistic regression assessing the association between GDM and neonatal outcomes, GDM was found to be independently associated with the composite adverse neonatal outcome (aOR 4.26 [3.43–5.3]), 5 min Apgar score < 7 (aOR 2 [1.16–3.47]), meconium aspiration (aOR 4.62 [1.76–12.13]), seizures (aOR 2.85 [1.51–5.37]) and hypoglycemia (aOR 16.16 [12.79–20.41]). Conclusions: Our study demonstrates that GDM is an independent risk factor for adverse neonatal outcomes among SGA infants. This finding underscores the imperative for tailored monitoring and management strategies in those pregnancies. [ABSTRACT FROM AUTHOR]
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- 2024
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15. Transamniotic Stem Cell Therapy Modulates Uterine Natural Killer Cell Activity in the Hypoxia Model of Intrauterine Growth Restriction.
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Whitlock, Ashlyn E., Moskowitzova, Kamila, Kycia, Ina, Zurakowski, David, and Fauza, Dario O.
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FETAL growth retardation , *VASCULAR endothelial growth factors , *TUMOR necrosis factors , *MESENCHYMAL stem cells , *STEM cell treatment - Abstract
Intrauterine growth restriction (IUGR) pathophysiology is driven by abnormal uterine natural killer cell (uNK) activity leading to placental dysfunction. Transamniotic stem cell therapy (TRASCET) with mesenchymal stem cells (MSCs) can improve experimental IUGR by mechanisms not fully understood. We sought to examine TRASCET's effects in downstream products of uNKs in a model of IUGR: 15 Sprague–Dawley dams were exposed to alternating hypoxia (10.5% O2) from gestational day 15 (E15) until term (E21). Their fetuses (n = 189) were divided into four groups. One group remained untreated (n = 52), whereas three groups received volume-matched intraamniotic injections of either saline (sham, n = 44) or a suspension of amniotic fluid-derived MSCs, either in their native state (TRASCET, n = 50) or "primed" to an enhanced antiinflammatory phenotype (TRASCET-Primed, n = 43). Normal fetuses served as controls (n = 33). At term, various analyses were performed, including ELISA for surrogates of placental inflammation and uNK activity. Statistical comparisons included Bonferroni-adjusted criterion. Overall survival from hypoxia was 74% (140/189). Placental efficiency was lower in untreated and sham but normalized in both TRASCET groups (P < 0.01–0.47). Interleukin-17, a stimulator of uNKs, was elevated from normal in all groups (P < 0.01 for all). Interferon-gamma, released from activated uNKs, was elevated in all groups except sham but lower than the untreated in both TRASCET groups (P ≤ 0.01–0.06). Tumor necrosis factor-alpha, also produced by uNKs, was elevated in untreated and sham (P < 0.01 for both), but normalized by TRASCET (P = 0.05) and even lowered from normal in TRASCET-Primed (P < 0.01). Vascular endothelial growth factor, also released by uNKs, was elevated in untreated and sham but lower than normal in both TRASCET groups (P < 0.01 for all). We conclude that TRASCET with MSCs modulates the activity of placental uNKs in experimental IUGR, with distinct effects on their downstream products. This mechanistic insight may inform the development of novel strategies for the management of this disease. [ABSTRACT FROM AUTHOR]
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- 2024
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16. Clinical features associated with maternal uniparental disomy for chromosome 6.
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Li, Jing-Wen, Qian, Yan-Jie, Mao, Shao-Jia, Chao, Yun-Qi, Qin, Yi-Fang, Hu, Chen-Xi, Li, Zheng-Lan, and Zou, Chao-Chun
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FETAL growth retardation , *PRENATAL diagnosis , *GENETIC mutation , *TRISOMY , *PHENOTYPES - Abstract
Background: Maternal uniparental disomy for chromosome 6 (upd(Cajaiba MM, Witchel S, Madan-Khetarpal S, Hoover J, Hoffner L, Macpherson T, et al. Prenatal diagnosis of trisomy 6 rescue resulting in paternal UPD6 with novel placental findings. Am J Med Genet Part A. 2011;155 A(8):1996–2002.)mat) has been previously reported to cause intrauterine growth restriction (IUGR), but the specific clinical phenotype has not been defined. Based on clinical data from two new cases and patients from the literature, specific phenotypes and mechanisms will be discussed further. Case presentation: : In case 1, a maternal isodisomy mixed with a heterodisomy was found on chromosome 6, including a regional absence of heterozygosity between 6q23.3 and 6q27. In case 2, a homozygous SCUBE3 mutation and upd(Cajaiba MM, Witchel S, Madan-Khetarpal S, Hoover J, Hoffner L, Macpherson T, et al. Prenatal diagnosis of trisomy 6 rescue resulting in paternal UPD6 with novel placental findings. Am J Med Genet Part A. 2011;155 A(8):1996–2002.)mat, involving the 6p21.1-25.1 region were found. Clinical data related to upd(Cajaiba MM, Witchel S, Madan-Khetarpal S, Hoover J, Hoffner L, Macpherson T, et al. Prenatal diagnosis of trisomy 6 rescue resulting in paternal UPD6 with novel placental findings. Am J Med Genet Part A. 2011;155 A(8):1996–2002.)mat were also reviewed. Of all the 21 reported cases with upd(Cajaiba MM, Witchel S, Madan-Khetarpal S, Hoover J, Hoffner L, Macpherson T, et al. Prenatal diagnosis of trisomy 6 rescue resulting in paternal UPD6 with novel placental findings. Am J Med Genet Part A. 2011;155 A(8):1996–2002.)mat (including our 2 cases), 18 (85.7%) presented IUGR. Conclusions: The phenotypes of the two newly identified patients with upd(Cajaiba MM, Witchel S, Madan-Khetarpal S, Hoover J, Hoffner L, Macpherson T, et al. Prenatal diagnosis of trisomy 6 rescue resulting in paternal UPD6 with novel placental findings. Am J Med Genet Part A. 2011;155 A(8):1996–2002.)mat further suggest that IUGR is associated with upd(Cajaiba MM, Witchel S, Madan-Khetarpal S, Hoover J, Hoffner L, Macpherson T, et al. Prenatal diagnosis of trisomy 6 rescue resulting in paternal UPD6 with novel placental findings. Am J Med Genet Part A. 2011;155 A(8):1996–2002.)mat and case 2 is the first reported upd(Cajaiba MM, Witchel S, Madan-Khetarpal S, Hoover J, Hoffner L, Macpherson T, et al. Prenatal diagnosis of trisomy 6 rescue resulting in paternal UPD6 with novel placental findings. Am J Med Genet Part A. 2011;155 A(8):1996–2002.)mat patient with a homozygous SCUBE3 gene mutation. However, the specific phenotypes involved in upd(Cajaiba MM, Witchel S, Madan-Khetarpal S, Hoover J, Hoffner L, Macpherson T, et al. Prenatal diagnosis of trisomy 6 rescue resulting in paternal UPD6 with novel placental findings. Am J Med Genet Part A. 2011;155 A(8):1996–2002.)mat and the related mechanisms need to be further studied. [ABSTRACT FROM AUTHOR]
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- 2024
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17. Preferred lifestyle intervention characteristics and behaviour change needs of postpartum women following cardiometabolic pregnancy complications.
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Osei-Safo, Elaine K, Lim, Siew, Makama, Maureen, Chen, Mingling, Skouteris, Helen, Taylor, Frances, Harrison, Cheryce L, Hutchesson, Melinda, Bennett, Christie J, Teede, Helena, Melder, Angela, and Moran, Lisa J
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METABOLIC disorder treatment ,CROSS-sectional method ,PEARSON correlation (Statistics) ,BEHAVIOR modification ,SMALL for gestational age ,T-test (Statistics) ,RESEARCH funding ,PUERPERIUM ,QUESTIONNAIRES ,GESTATIONAL diabetes ,PREMATURE infants ,BEHAVIOR ,QUANTITATIVE research ,DESCRIPTIVE statistics ,MANN Whitney U Test ,CHI-squared test ,PREGNANCY outcomes ,EVALUATION of medical care ,HYPERTENSION in pregnancy ,MOTIVATION (Psychology) ,HEALTH behavior ,PREECLAMPSIA ,CARDIOVASCULAR diseases in pregnancy ,WOMEN'S health ,COMPARATIVE studies ,DATA analysis software ,MEDICAL needs assessment ,PATIENT participation ,DIET ,PREGNANCY - Abstract
Background: Women with cardiometabolic pregnancy complications are at increased risk of future diabetes and heart disease which can be reduced through lifestyle management postpartum. Objectives: This study aimed to explore preferred intervention characteristics and behaviour change needs of women with or without prior cardiometabolic pregnancy complications for engaging in postpartum lifestyle interventions. Design: Quantitative cross-sectional study. Methods: Online survey. Results: Overall, 473 women were included, 207 (gestational diabetes (n = 105), gestational hypertension (n = 39), preeclampsia (n = 35), preterm birth (n = 65) and small for gestational age (n = 23)) with and 266 without prior cardiometabolic pregnancy complications. Women with and without complications had similar intervention preferences, with delivery ideally by a healthcare professional with expertise in women's health, occurring during maternal child health nurse visits or online, commencing 7 weeks to 3 months post birth, with 15- to 30-min monthly sessions, lasting 1 year and including monitoring of progress and social support. Women with prior complications preferred intervention content on women's health, mental health, exercise, mother's diet and their children's health and needed to know more about how to change behaviour, have more time to do it and feel they want to do it enough to participate. There were significant differences between groups, with more women with prior cardiometabolic pregnancy complications wanting content on women's health (87.9% vs 80.8%, p = 0.037), mother's diet (72.5% vs 60.5%, p = 0.007), preventing diabetes or heart disease (43.5% vs 27.4%, p < 0.001) and exercise after birth (78.3% vs 68.0%, p = 0.014), having someone to monitor their progress (69.6% vs 58.6%, p = 0.014), needing the necessary materials (47.3% vs 37.6%, p = 0.033), triggers to prompt them (44.0% vs 31.6%, p = 0.006) and feeling they want to do it enough (73.4%, 63.2%, p = 0.018). Conclusion: These unique preferences should be considered in future postpartum lifestyle interventions to enhance engagement, improve health and reduce risk of future cardiometabolic disease in these high-risk women. [ABSTRACT FROM AUTHOR]
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- 2024
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18. Effect of Mediterranean diet or mindfulness‐based stress reduction during pregnancy on placental volume and perfusion: A subanalysis of the IMPACT BCN randomized clinical trial.
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Nakaki, Ayako, Denaro, Eugenio, Crimella, Maddalena, Castellani, Roberta, Vellvé, Kilian, Izquierdo, Nora, Basso, Annachiara, Paules, Cristina, Casas, Rosa, Benitez, Leticia, Casas, Irene, Larroya, Marta, Genero, Mariona, Castro‐Barquero, Sara, Gomez‐Gomez, Alex, Pozo, Óscar J., Vieta, Eduard, Estruch, Ramon, Nadal, Alfons, and Gratacós, Eduard
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MEDITERRANEAN diet , *MINDFULNESS , *PLACENTA , *CLINICAL trials , *PERFUSION , *FETAL development , *PREVENTION - Abstract
Introduction Material and Methods Results Conclusions The IMPACT BCN trial—a parallel‐group randomized clinical trial where 1221 pregnant women at high risk for small‐for‐gestational age (SGA) newborns were randomly allocated at 19‐ to 23‐week gestation into three groups: Mediterranean diet, Mindfulness‐based Stress reduction or non‐intervention—has demonstrated a positive effect of Mediterranean diet and Stress reduction in the prevention of SGA. However, the mechanism of action of these interventions remains still unclear. The aim of this study is to investigate the effect of Mediterranean diet and Stress reduction on placental volume and perfusion.Participants in the Mediterranean diet group received monthly individual and group educational sessions, and free provision of extra‐virgin olive oil and walnuts. Women in the Stress reduction group underwent an 8‐week Stress reduction program adapted for pregnancy, consisting of weekly 2.5‐h and one full‐day sessions. Non‐intervention group was based on usual care. Placental volume and perfusion were assessed in a subgroup of randomly selected women (n = 165) using magnetic resonance (MR) at 36‐week gestation. Small placental volume was defined as MR estimated volume <10th centile. Perfusion was assessed by intravoxel incoherent motion.While mean MR placental volume was similar among the study groups, both interventions were associated with a lower prevalence of small placental volume (3.9% Mediterranean diet and 5% stress reduction vs. 17% non‐intervention; p = 0.03 and p = 0.04, respectively). Logistic regression showed that small placental volume was significantly associated with higher risk of SGA in both study groups (OR 7.48 [1.99–28.09] in Mediterranean diet and 20.44 [5.13–81.4] in Stress reduction). Mediation analysis showed that the effect of Mediterranean diet on SGA can be decomposed by a direct effect and an indirect effect (56.6%) mediated by a small placental volume. Similarly, the effect of Stress reduction on SGA is partially mediated (45.3%) by a small placental volume. Results on placental intravoxel incoherent motion perfusion fraction and diffusion coefficient were similar among the study groups.Structured interventions during pregnancy based on Mediterranean diet or Stress reduction are associated with a lower proportion of small placentas, which is consistent with the previously observed beneficial effects of these interventions on fetal growth. [ABSTRACT FROM AUTHOR]
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- 2024
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19. Association between risk of infant death and birth‐weight z scores according to gestational age: A nationwide study using the Finnish Medical Birth Register.
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Hocquette, Alice, Pulakka, Anna, Metsälä, Johanna, Heikkilä, Katriina, Zeitlin, Jennifer, and Kajantie, Eero
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GESTATIONAL age , *VITAL records (Births, deaths, etc.) , *NEONATAL death , *INFANT mortality , *SMALL for gestational age - Abstract
Objective Methods Results Conclusion To investigate the association between infant mortality and birth weight using estimated fetal weight (EFW) versus birth‐weight charts, by gestational age (GA).This nationwide population‐based study used data from the Finnish Medical Birth Register from 2006 to 2016 on non‐malformed singleton live births at 24–41+6 weeks of gestation (N = 563 630). The outcome was death in the first year of life. Mortality risks by birth‐weight z score, defined as a continuous variable using Maršál's EFW and Sankilampi's birth‐weight charts, were assessed using generalized additive models by GA (24–27+6, 28–31+6, 32–36+6, 37–38+6, 39–41+6 weeks). We calculated z score thresholds associated with a two‐ and three‐fold increased risk of infant death compared with newborns with a birth weight between 0 and 0.675 standard deviations.The z score thresholds (with corresponding centiles in parentheses) associated with a two‐fold increase in infant mortality were: −3.43 (<0.1) at 24–27+6 weeks, −3.46 (<0.1) at 28–31+6 weeks, −1.29 (9.9) at 32–36+6 weeks, −1.18 (11.9) at 37–38+6 weeks, and − 1.34 (9.0) at 39–41+6 weeks according to the EFW chart. These values were − 2.43 (0.8), −2.62 (0.4), −1.34 (9.0), −1.37 (8.5), and − 1.43 (7.6) according to the birth‐weight chart.The association between birth weight and infant mortality varies by GA whichever chart is used, suggesting that different thresholds for the screening of growth anomalies could be used across GA to identify high‐risk newborns. [ABSTRACT FROM AUTHOR]
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- 2024
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20. Interleukins IL33/ST2 and IL1-β in Intrauterine Growth Restriction and Seropositivity of Anti- Toxoplasma gondii Antibodies.
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Franco-De León, Karen, Camarena, Eva Elizabeth, Pereira-Suárez, Ana Laura, Barrios-Prieto, Ernesto, Soto-Venegas, Andrea, Hernández-Nazara, Zamira Helena, Luna Rojas, Yithzel Guadalupe, and Galván-Ramírez, María de la Luz
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FETAL growth retardation ,RECURRENT miscarriage ,INTERLEUKIN-33 ,CONGENITAL disorders ,PEARSON correlation (Statistics) - Abstract
Toxoplasma gondii (T. gondii) is the causal agent of toxoplasmosis. It may produce severe damage in immunocompromised individuals, as well as congenital infection and intrauterine growth restriction (IUGR). Previous reports have associated interleukin IL-33 with miscarriage, fetal damage, and premature delivery due to infections with various microorganisms. However, IL-33 has not been associated with congenital toxoplasmosis. The sST2 receptor has been reported in patients who have had recurrent miscarriages. On the other hand, IL-1β was not found in acute Toxoplasma infection. Our aim was to analyze the associations between the serum levels of IL-33 and IL-1β in IUGR and toxoplasmosis during pregnancy. Eighty-four serum samples from pregnant women who had undergone 26 weeks of gestation were grouped as follows: with anti-Toxoplasma antibodies, without anti-Toxoplasma antibodies, IUGR, and the control group. IgG and IgM anti-T. gondii antibodies, as well as IL-33, ST2, and IL-1β, were determined using an ELISA assay. Statistical analyses were performed using the Pearson and Chi-square correlation coefficients, as well as the risk factors and Odds Ratios (ORs), with a confidence interval of 95% (CI 95). The results showed that 15/84 (17.8%) of cases were positive for IgG anti-Toxoplasma antibodies and 2/84 (2.38%) of cases were positive for IgM. A statistically significant difference was found between IUGR and IL-33 (p < 0.001), as well as between ST2 and IUGR (p < 0.001). In conclusion, IUGR was significantly associated with IL-33 and ST2 positivity based on the overall IUGR grade. No significant association was found between IUGR and the presence of anti-Toxoplasma antibodies. There was no association between IL-1β and IUGR. More research is needed to strengthen the utility of IL-33 and ST2 as biomarkers of IUGR. [ABSTRACT FROM AUTHOR]
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- 2024
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21. Unraveling the Mfn2-Warburg effect nexus: a therapeutic strategy to combat pulmonary arterial hypertension arising from catch-up growth after IUGR
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Lingling Yan, Xiaofei Luo, Chengcheng Hang, YuWang, Ziming Zhang, Shanshan Xu, and Lizhong Du
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Intrauterine growth restriction ,Catch-up growth ,Pulmonary hypertension ,Mfn2 ,Warburg effect ,Diseases of the respiratory system ,RC705-779 - Abstract
Abstract Background The interplay between intrauterine and early postnatal environments has been associated with an increased risk of cardiovascular diseases in adulthood, including pulmonary arterial hypertension (PAH). While emerging evidence highlights the crucial role of mitochondrial pathology in PAH, the specific mechanisms driving fetal-originated PAH remain elusive. Methods and results To elucidate the role of mitochondrial dynamics in the pathogenesis of fetal-originated PAH, we established a rat model of postnatal catch-up growth following intrauterine growth restriction (IUGR) to induce pulmonary arterial hypertension (PAH). RNA-seq analysis of pulmonary artery samples from the rats revealed dysregulated mitochondrial metabolic genes and pathways associated with increased pulmonary arterial pressure and pulmonary arterial remodeling in the RC group (postnatal catch-up growth following IUGR). In vitro experiments using pulmonary arterial smooth muscle cells (PASMCs) from the RC group demonstrated elevated proliferation, migration, and impaired mitochondrial functions. Notably, reduced expression of Mitofusion 2 (Mfn2), a mitochondrial outer membrane protein involved in mitochondrial fusion, was observed in the RC group. Reconstitution of Mfn2 resulted in enhanced mitochondrial fusion and improved mitochondrial functions in PASMCs of RC group, effectively reversing the Warburg effect. Importantly, Mfn2 reconstitution alleviated the PAH phenotype in the RC group rats. Conclusions Imbalanced mitochondrial dynamics, characterized by reduced Mfn2 expression, plays a critical role in the development of fetal-originated PAH following postnatal catch-up growth after IUGR. Mfn2 emerges as a promising therapeutic strategy for managing IUGR-catch-up growth induced PAH.
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- 2024
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22. Maternal factors in the aetiology of small-for-gestational age among term Nigerian babies
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Oluwafemi RO, Njokanma OF, Disu EA, and Ogunlesi TA
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anthropometry ,intrauterine growth restriction ,maternal illness ,nigeria ,Medicine - Abstract
Background: Babies are classified according to the relationship between birth weight and gestational age, the latter being the strongest determinant of birth weight. Small-for-gestational age (SGA) babies have birth weights less than the 10th percentile for age and sex or more than two standard deviations below the mean for age and sex. Objective: The study was carried out to investigate the maternal factors associated with the delivery of term small-for-gestational age babies in a Nigerian Hospital. Methods: In the cross-sectional survey, the anthropometric parameters of term singleton infants were related to maternal age, Parity, socio-economic class, anthropometry and medical disorders in pregnancy. Results: A total of 825 babies were surveyed within the first 24 hours of life. The mean birth weight of babies was 3233 ± 539g. The males had significantly longer mean crown-heel length and mean occipitofrontal circumference compared to females p = 0.048 and p < 0.000 respectively). The prevalence of infants with small-for-gestational age was 7.2% (5.7% and 8.8% among males and females respectively). The proportion of mothers who did not encounter significant illness in pregnancy was lowest among those who had SGA babies, followed by mothers of LGA babies and those of AGA babies in that order. With respect to maternal age, weight, height and body mass index (except inter-pregnancy interval), mothers of SGA babies had significantly lower values compared to mothers of the AGA and LGA babiesc(p < 0.03). Conclusion: This study identified age, parity, anthropometry and hypertension- related disorders as major maternal factors associated with the birth of SGA babies in Nigeria.
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- 2024
23. Clinical features associated with maternal uniparental disomy for chromosome 6
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Jing-Wen Li, Yan-Jie Qian, Shao-Jia Mao, Yun-Qi Chao, Yi-Fang Qin, Chen-Xi Hu, Zheng-Lan Li, and Chao-Chun Zou
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Failure to thrive ,Intrauterine growth restriction ,Uniparental disomy, maternal ,Chromosome 6 ,SCUBE3 ,Genetics ,QH426-470 - Abstract
Abstract Background Maternal uniparental disomy for chromosome 6 (upd(Cajaiba MM, Witchel S, Madan-Khetarpal S, Hoover J, Hoffner L, Macpherson T, et al. Prenatal diagnosis of trisomy 6 rescue resulting in paternal UPD6 with novel placental findings. Am J Med Genet Part A. 2011;155 A(8):1996–2002.)mat) has been previously reported to cause intrauterine growth restriction (IUGR), but the specific clinical phenotype has not been defined. Based on clinical data from two new cases and patients from the literature, specific phenotypes and mechanisms will be discussed further. Case presentation : In case 1, a maternal isodisomy mixed with a heterodisomy was found on chromosome 6, including a regional absence of heterozygosity between 6q23.3 and 6q27. In case 2, a homozygous SCUBE3 mutation and upd(Cajaiba MM, Witchel S, Madan-Khetarpal S, Hoover J, Hoffner L, Macpherson T, et al. Prenatal diagnosis of trisomy 6 rescue resulting in paternal UPD6 with novel placental findings. Am J Med Genet Part A. 2011;155 A(8):1996–2002.)mat, involving the 6p21.1-25.1 region were found. Clinical data related to upd(Cajaiba MM, Witchel S, Madan-Khetarpal S, Hoover J, Hoffner L, Macpherson T, et al. Prenatal diagnosis of trisomy 6 rescue resulting in paternal UPD6 with novel placental findings. Am J Med Genet Part A. 2011;155 A(8):1996–2002.)mat were also reviewed. Of all the 21 reported cases with upd(Cajaiba MM, Witchel S, Madan-Khetarpal S, Hoover J, Hoffner L, Macpherson T, et al. Prenatal diagnosis of trisomy 6 rescue resulting in paternal UPD6 with novel placental findings. Am J Med Genet Part A. 2011;155 A(8):1996–2002.)mat (including our 2 cases), 18 (85.7%) presented IUGR. Conclusions The phenotypes of the two newly identified patients with upd(Cajaiba MM, Witchel S, Madan-Khetarpal S, Hoover J, Hoffner L, Macpherson T, et al. Prenatal diagnosis of trisomy 6 rescue resulting in paternal UPD6 with novel placental findings. Am J Med Genet Part A. 2011;155 A(8):1996–2002.)mat further suggest that IUGR is associated with upd(Cajaiba MM, Witchel S, Madan-Khetarpal S, Hoover J, Hoffner L, Macpherson T, et al. Prenatal diagnosis of trisomy 6 rescue resulting in paternal UPD6 with novel placental findings. Am J Med Genet Part A. 2011;155 A(8):1996–2002.)mat and case 2 is the first reported upd(Cajaiba MM, Witchel S, Madan-Khetarpal S, Hoover J, Hoffner L, Macpherson T, et al. Prenatal diagnosis of trisomy 6 rescue resulting in paternal UPD6 with novel placental findings. Am J Med Genet Part A. 2011;155 A(8):1996–2002.)mat patient with a homozygous SCUBE3 gene mutation. However, the specific phenotypes involved in upd(Cajaiba MM, Witchel S, Madan-Khetarpal S, Hoover J, Hoffner L, Macpherson T, et al. Prenatal diagnosis of trisomy 6 rescue resulting in paternal UPD6 with novel placental findings. Am J Med Genet Part A. 2011;155 A(8):1996–2002.)mat and the related mechanisms need to be further studied.
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- 2024
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24. Maternal N-carbamylglutamate and L-arginine supplementations improve foetal jejunal oxidation resistance, integrity and immune function in malnutrition sheep during pregnancy
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Hao Zhang, Bei Zhang, Huisi Wu, Xia Zha, Mabrouk Elsabagh, Jingwen Zhao, Hongrong Wang, Mengzhi Wang, and Guihua Shu
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intrauterine growth restriction ,intestinal integrity ,l-arginine ,n-carbamylglutamate ,oxidation resistance ,Animal culture ,SF1-1100 - Abstract
The present work focused on examining the function of rumen-protected L-arginine (RP-Arg) or N-carbamylglutamate (NCG) in jejunal oxidative resistance, integrity and immune function in the ovine foetal model of intrauterine growth restriction (IUGR). Thirty-two twin-bearing Hu ewes at d 35 of gestation were randomised as 4 treatment groups (n = 8 each): Control (CON), received 100% of the recommended National Research Council (NRC) for pregnancy; Restricted (RES), received 50% of the recommended NRC for pregnancy; RES + ARG, RES ewes added with 20 g/d of RP-Arg; or RES + NCG treatment, RES ewes added with 5 g/d of NCG. Foetal jejunal samples were collected on d 110 of pregnancy and were assayed for biomarkers of oxidative damage, integrity and immune function. The villus height was elevated (p
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- 2024
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25. Covid Pandemic and War: Different Impacts on Pregnancy
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Radić, Ena, Zadro, Matilda, Hadžić, Daria, Košec, Vesna, Gall, Vesna, Pramataroff-Hamburger, Vivian, editor, and Neises-Rudolf, Mechthild, editor
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- 2024
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26. Fetal Growth Monitoring and Issues: The Intrauterine Monitoring of Middle Cerebral Artery and Its Role in Neuronal Development of the Newborn
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Visentin, Silvia, Carli, Stefania, Sartor, Federica, D’Errico, Ignazio, Cosmi, Erich, and Pani, Danilo, editor
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- 2024
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27. sFlt1/PlGF and Planned Delivery to Prevent Preeclampsia at Term. (PE37)
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Fundacion Clinic per a la Recerca Biomédica and Elisa Llurba, Professor of Obstetric and Gynecology Universitat Autònoma de Barcelona
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- 2023
28. Investigating the Structured Use of Ultrasound Scanning for Fetal Growth (OxGRIP)
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Lawrence Impey, Principal Investigator
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- 2023
29. Predicting Placental Pathologies by Ultrasound Imaging
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Mauro H. Schenone, Principal Investigator
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- 2023
30. Evaluation of Fetoplacental Oxygenation With Functional MRI in Pregnant Women (BOLD-FP)
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- 2023
31. PEPPI Study: Identification of Women at Risk for Placental Dysfunction
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PerkinElmer, Inc., Roche Diagnostics GmbH, Academy of Finland, Sigrid Jusélius Foundation, Finnish Medical Foundation, University of Oulu, and Jaana Nevalainen, Associate professor
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- 2023
32. MIRACLE of LIFE Study (MoL)
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- 2023
33. Follow-Up Study of 17-β Estradiol, Prolactin and Progesterone with the Kinetics and Prevalence of T. gondii Infection in Pregnant Women
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Yithzel Guadalupe Luna Rojas, Eva Elizabet Camarena Pulido, Laura Rocío Rodríguez-Pérez, and María de la Luz Galván-Ramírez
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toxoplasmosis ,intrauterine growth restriction ,17-β estradiol ,progesterone ,prolactin ,Biology (General) ,QH301-705.5 - Abstract
Toxoplasmosis is an infection caused by the parasite Toxoplasma gondii. One-third of the world’s population has come into contact with this parasite. In Mexico, the prevalence is between 15% and 50% in the general population and 34.9% in women with high-risk pregnancies. In pregnancy, the highest incidence of infection occurs in the third trimester and fetal damage is inversely proportional to gestational age. Maternal hormones play a fundamental role in the immune response. There are very few studies, with controversial results, on the levels of increased hormones and their relationship to the kinetics of T. gondii infections during pregnancy. The aim was to determine the serum levels of 17-β estradiol, prolactin, and progesterone, and their association with anti-T. gondii antibodies’ kinetics in pregnancy. Fifty-two pregnant patients were studied. A questionnaire with sociodemographic and clinical aspects was used. Afterward, 10 mL of venous blood was collected by venipuncture every trimester. The concentrations of 17-β estradiol, progesterone, and prolactin were measured, using the ELISA method. In addition, anti-Toxoplasma IgG and IgM antibodies were also determined in the first, second, and third trimester. The prevalence of anti-Toxoplasma IgG antibodies was 26.92% in the first and second trimester and 32.7% in the third trimester. In seropositive women, 17-β estradiol increased in the second and third trimesters of pregnancy. Progesterone increased significantly p < 0.039 in the third trimester in these women, while prolactin increased in the second trimester with a statistical significance of p < 0.021. In addition, 17-β estradiol, progesterone, and prolactin are associated with T. gondii infection during pregnancy. New studies are necessary to clarify the specific mechanisms of immune response related to these hormones during pregnancy.
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- 2024
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34. The impact of gestational weight gain on fetal and neonatal outcomes: the Araraquara Cohort Study
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Audêncio Victor, Laísla de França da Silva Teles, Isabel Oliveira Aires, Leticia Falcão de Carvalho, Liania A. Luzia, Rinaldo Artes, and Patrícia H. Rondó
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Gestational weight gain ,Pregnancy ,Fetal outcomes ,Neonatal outcomes ,Cohort study ,Intrauterine growth restriction ,Gynecology and obstetrics ,RG1-991 - Abstract
Abstract Background Gestational weight gain (GWG) is an important indicator for monitoring maternal and fetal health. Objective: To evaluate the effect of GWG outside the recommendations of the Institute of Medicine (IOM) on fetal and neonatal outcomes. Study design A prospective cohort study with 1642 pregnant women selected from 2017 to 2023, with gestational age ≤ 18 weeks and followed until delivery in the city of Araraquara, Southeast Brazil. The relationship between IOM-recommended GWG and fetal outcomes (abdominal subcutaneous tissue thickness, arm and thigh subcutaneous tissue area and intrauterine growth restriction) and neonatal outcomes (percentage of fat mass, fat-free mass, birth weight and length, ponderal index, weight adequateness for gestational age by the Intergrowth curve, prematurity, and Apgar score) were investigated. Generalized Estimating Equations were used. Results GWG below the IOM recommendations was associated with increased risks of intrauterine growth restriction (IUGR) (aOR 1.61; 95% CI: 1.14–2.27), low birth weight (aOR 2.44; 95% CI: 1.85–3.21), and prematurity (aOR 2.35; 95% CI: 1.81–3.05), and lower chance of being Large for Gestational Age (LGA) (aOR 0.38; 95% CI: 0.28–0.54), with smaller arm subcutaneous tissue area (AST) (-7.99 g; 95% CI: -8.97 to -7.02), birth length (-0.76 cm; 95% CI: -1.03 to -0.49), and neonatal fat mass percentage (-0.85%; 95% CI: -1.12 to -0.58). Conversely, exceeding GWG guidelines increased the likelihood of LGA (aOR 1.53; 95% CI: 1.20–1.96), with lower 5th-minute Apgar score (aOR 0.42; 95% CI: 0.20–0.87), and increased birth weight (90.14 g; 95% CI: 53.30 to 126.99). Conclusion Adherence to GWG recommendations is crucial, with deviations negatively impacting fetal health. Effective weight control strategies are imperative.
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- 2024
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35. Bias in the prenatal lung measurements in fetal congenital diaphragmatic hernia with intrauterine growth restriction.
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Aydın, Emrah, Khanmammadova, Narmina, Burns, Patricia, Lim, Foong-Yen, Habli, Mounira A., and Peiró, Jose Luis
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FETAL growth retardation , *HERNIA , *FETAL ultrasonic imaging , *RETROSPECTIVE studies , *DESCRIPTIVE statistics , *ODDS ratio , *LUNG volume measurements , *MEDICAL records , *ACQUISITION of data , *GESTATIONAL age , *ANTHROPOMETRY , *CONFIDENCE intervals - Abstract
The failure of a fetus to develop to its full potential due to maternal or placental factors is known as intrauterine growth restriction (IUGR). Fetal head growth is usually preserved in that situation producing a potential discordance between head and body size. Our goal is to discover if IUGR has an impact on the prenatal ultrasound measurements taken to assess pulmonary development in congenital diaphragmatic hernia (CDH). A retrospective chart review (IRB#2017-6361) was performed on all prenatally diagnosed CDH patients from 2007 to 2016. Patient demographics, fetal and neonatal anthropometric measurements, and fetal lung parameters were the main subjects of the data that were gathered. Fetal growth was assessed by the curves based on US data by Olsen et al. and by Peleg et al. Of 147 CDH patients, 19 (12.9 %) patients were diagnosed with IUGR before the 30th gestational week while there were 20 (13.6 %) patients after the 30th gestational week. Patients with IUGR and the observed-to-expected lung-to-head ratio (O/E LHR) less than 25 % had better survival rates both to discharge and date compared to non IUGR group (p=0.226, OR 2.25 95 % CI 0.60–1.08 and p=0.175, OR 2.40 95 % CI 0.66–1.17, respectively). Moreover, the ECMO need of the patients who had IUGR and O/E LHR less than 25 % was significantly less than the patients without IUGR (38.5 vs. 80.0 %, p=0.005). This study confirms that the intrauterine measurements to predict pulmonary hypoplasia in CDH patients are misleading in the presence of IUGR and cause an overestimation. [ABSTRACT FROM AUTHOR]
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- 2024
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36. First Trimester Placental Biomarkers for Pregnancy Outcomes.
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Cristodoro, Martina, Messa, Martina, Tossetta, Giovanni, Marzioni, Daniela, Dell'Avanzo, Marinella, Inversetti, Annalisa, and Di Simone, Nicoletta
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PREGNANCY outcomes , *GESTATIONAL diabetes , *FETAL growth retardation , *BIOMARKERS , *PREECLAMPSIA , *PREGNANCY , *PLACENTA - Abstract
The placenta plays a key role in several adverse obstetrical outcomes, such as preeclampsia, intrauterine growth restriction and gestational diabetes mellitus. The early identification of at-risk pregnancies could significantly improve the management, therapy and prognosis of these pregnancies, especially if these at-risk pregnancies are identified in the first trimester. The aim of this review was to summarize the possible biomarkers that can be used to diagnose early placental dysfunction and, consequently, at-risk pregnancies. We divided the biomarkers into proteins and non-proteins. Among the protein biomarkers, some are already used in clinical practice, such as the sFLT1/PLGF ratio or PAPP-A; others are not yet validated, such as HTRA1, Gal-3 and CD93. In the literature, many studies analyzed the role of several protein biomarkers, but their results are contrasting. On the other hand, some non-protein biomarkers, such as miR-125b, miR-518b and miR-628-3p, seem to be linked to an increased risk of complicated pregnancy. Thus, a first trimester heterogeneous biomarkers panel containing protein and non-protein biomarkers may be more appropriate to identify and discriminate several complications that can affect pregnancies. [ABSTRACT FROM AUTHOR]
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- 2024
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37. Mosaicism for Autosomal Trisomies: A Comprehensive Analysis of 1266 Published Cases Focusing on Maternal Age and Reproductive History.
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Kovaleva, Natalia V. and Cotter, Philip D.
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FETUS , *MATERNAL age , *REPRODUCTIVE history , *MOSAICISM , *FETAL growth retardation , *PREGNANCY outcomes - Abstract
Mosaicism for autosomal trisomy is uncommon in clinical practice. However, despite its rarity among both prenatally and postnatally diagnoses, there are a large number of characterized and published cases. Surprisingly, in contrast to regular trisomies, no attempts at systematic analyses of mosaic carriers' demographics were undertaken. This is the first study aimed to address this gap. For that, we have screened more than eight hundred publications on mosaic trisomies, reviewing data including gender and clinical status of mosaic carriers, maternal age and reproductive history. In total, 596 publications were eligible for analysis, containing data on 948 prenatal diagnoses, including true fetal mosaicism (TFM) and confined placental mosaicism (CPM), and on 318 cases of postnatally detected mosaicism (PNM). No difference was found in maternal age between normal pregnancy outcomes with appropriate birth weight and those with intrauterine growth restriction. Unexpectedly, a higher proportion of advanced maternal ages (AMA) was found in normal outcomes compared to abnormal ones (abnormal fetus or newborn) and fetal losses, 73% vs. 56% and 50%, p = 0.0015 and p = 0.0011, correspondingly. Another intriguing finding was a higher AMA proportion in mosaic carriers with concomitant uniparental disomy (UPD) for chromosomes 7, 14, 15, and 16 compared to carriers with biparental disomy (BPD) (72% vs. 58%, 92% vs. 55%, 87% vs. 78%, and 65% vs. 24%, correspondingly); overall figures were 78% vs. 48%, p = 0.0026. Analysis of reproductive histories showed a very poor reporting but almost two-fold higher rate of mothers reporting a previous fetal loss from PNM cohort (in which almost all patients were clinically abnormal) compared to mothers from the TFM and CPM cohorts (with a large proportion of normal outcomes), 30% vs. 16%, p = 0.0072. The occurrence of a previous pregnancy with a chromosome abnormality was 1 in 13 in the prenatal cohort and 1 in 16 in the postnatal cohort, which are five-fold higher compared to published studies on non-mosaic trisomies. We consider the data obtained in this study to be preliminary despite the magnitude of the literature reviewed since reporting of detailed data was mostly poor, and therefore, the studied cohorts do not represent "big data". Nevertheless, the information obtained is useful both for clinical genetic counseling and for modeling further studies. [ABSTRACT FROM AUTHOR]
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- 2024
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38. Fetal sex and the relative reactivity of human umbilical vein and arteries are key determinants in potential beneficial effects of phosphodiesterase inhibitors.
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Peyter, Anne-Christine, Beaumann, Manon, Delhaes, Flavien, Joye, Sébastien, Menétrey, Steeve, Baud, David, and Tolsa, Jean-François
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UMBILICAL arteries ,UMBILICAL veins ,PHOSPHODIESTERASE inhibitors ,FETAL growth retardation ,CYCLIC nucleotide phosphodiesterases - Abstract
Intrauterine growth restriction (IUGR) is a common complication of pregnancy. We previously demonstrated that IUGR is associated with an impaired nitric oxide (NO)-induced relaxation in the human umbilical vein (HUV) of growth-restricted females compared to appropriate for gestational age (AGA) newborns. We found that phosphodiesterase (PDE) inhibition improved NO-induced relaxation in HUV, suggesting that PDEs could represent promising targets for therapeutic intervention. This study aimed to investigate the effects of PDE inhibition on human umbilical arteries (HUAs) compared to HUV. Umbilical vessels were collected in IUGR and AGA term newborns. NO-induced relaxation was studied using isolated vessel tension experiments in the presence or absence of the nonspecific PDE inhibitor 3-isobutyl-1-methylxanthine (IBMX). PDE1B, PDE1C, PDE3A, PDE4B, and PDE5A were investigated by Western blot. NO-induced vasodilation was similar between IUGR and AGA HUAs. In HUAs precontracted with serotonin, IBMX enhanced NO-induced relaxation only in IUGR females, whereas in HUV IBMX increased NO-induced relaxation in all groups except IUGR males. In umbilical vessels preconstricted with the thromboxane A2 analog U46619, IBMX improved NO-induced relaxation in all groups to a greater extent in HUV than HUAs. However, the PDE protein content was higher in HUAs than HUV in all study groups. Therefore, the effects of PDE inhibition depend on the presence of IUGR, fetal sex, vessel type, and vasoconstrictors implicated. Despite a higher PDE protein content, HUAs are less sensitive to IBMX than HUV, which could lead to adverse effects of PDE inhibition in vivo by impairment of the fetoplacental hemodynamics. NEW & NOTEWORTHY: The effects of phosphodiesterase inhibition on the umbilical circulation depend on the presence of intrauterine growth restriction, the fetal sex, vessel type, and vasoconstrictors implicated. The human umbilical vascular tone regulation is complex and depends on the amount and activity of specific proteins but also probably on the subcellular organization mediating protein interactions. Therefore, therapeutic interventions using phosphodiesterase inhibitors to improve the placental-fetal circulation should consider fetal sex and both umbilical vein and artery reactivity. [ABSTRACT FROM AUTHOR]
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- 2024
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39. Epigenetic Modifications of White Blood Cell DNA Caused by Transient Fetal Infection with Bovine Viral Diarrhea Virus.
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Van Campen, Hana, Bishop, Jeanette V., Brink, Zella, Engle, Terry E., Gonzalez-Berrios, Carolina L., Georges, Hanah M., Kincade, Jessica N., Murtazina, Dilyara A., and Hansen, Thomas R.
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BOVINE viral diarrhea virus , *LEUCOCYTES , *HEALTH of cattle , *DNA analysis , *VIRUS diseases , *EPIGENETICS , *VIRAL antibodies - Abstract
Bovine viral diarrhea virus (BVDV) infections cause USD 1.5–2 billion in losses annually. Maternal BVDV after 150 days of gestation causes transient fetal infection (TI) in which the fetal immune response clears the virus. The impact of fetal TI BVDV infections on postnatal growth and white blood cell (WBC) methylome as an index of epigenetic modifications was examined by inoculating pregnant heifers with noncytopathic type 2 BVDV or media (sham-inoculated controls) on Day 175 of gestation to generate TI (n = 11) and control heifer calves (n = 12). Fetal infection in TI calves was confirmed by virus-neutralizing antibody titers at birth and control calves were seronegative. Both control and TI calves were negative for BVDV RNA in WBCs by RT-PCR. The mean weight of the TI calves was less than that of the controls (p < 0.05). DNA methyl seq analysis of WBC DNA demonstrated 2349 differentially methylated cytosines (p ≤ 0.05) including 1277 hypomethylated cytosines, 1072 hypermethylated cytosines, 84 differentially methylated regions based on CpGs in promoters, and 89 DMRs in islands of TI WBC DNA compared to controls. Fetal BVDV infection during late gestation resulted in epigenomic modifications predicted to affect fetal development and immune pathways, suggesting potential consequences for postnatal growth and health of TI cattle. [ABSTRACT FROM AUTHOR]
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- 2024
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40. The impact of late pregnancy dating on the detection of fetal growth restriction at term.
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Mathewlynn, Sam, Kitmiridou, Despoina, Impey, Lawrence, and Ioannou, Christos
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FETAL growth retardation , *FETAL anoxia , *PREGNANCY , *UMBILICAL arteries , *SMALL for gestational age , *DELPHI method , *ABRUPTIO placentae - Abstract
Introduction: The inaccuracy of late pregnancy dating is often discussed, and the impact on diagnosis of fetal growth restriction is a concern. However, the magnitude and direction of this effect has not previously been demonstrated. In this study, we aimed to investigate the effect of late pregnancy dating by head circumference on the detection of late onset growth restriction, compared to first trimester crown‐rump length dating. Material and methods: This was a cohort study of 14 013 pregnancies receiving obstetric care at a tertiary center over a three‐year period. Universal scans were performed at 12 weeks, including crown‐rump length; at 20 weeks including fetal biometry; and at 36 weeks, where biometry, umbilical artery doppler and cerebroplacental ratio were used to determine the incidence of fetal growth restriction according to the Delphi consensus. For the entire cohort, the gestational age was first calculated using T1 dating; and was then recalculated using head circumference at 20 weeks (T2 dating); and at 36 weeks (T3 dating). The incidence of fetal growth restriction following T2 and T3 dating was compared to T1 dating using four‐by‐four sensitivity tables. Results: When the cohort was redated from T1 to T2, the median gestation at delivery changed from 40 + 0 to 40 + 2 weeks (p < 0.001). When the cohort was redated from T1 to T3, the median gestation at delivery changed from 40 + 0 to 40 + 3 weeks (p < 0.001). T2 dating resulted in fetal growth restriction sensitivity of 80.2% with positive predictive value of 78.8% compared to T1 dating. T3 dating resulted in sensitivity of 8.6% and positive predictive value of 27.7%, respectively. The sensitivity of abnormal CPR remained high despite T2 and T3 redating; 98.0% and 89.4%, respectively. Conclusions: Although dating at 11–14 weeks is recommended, late pregnancy dating is sometimes inevitable, and this can prolong the estimated due date by an average of two to three days. One in five pregnancies which would be classified as growth restricted if the pregnancy was dated in the first trimester, will be reclassified as nongrowth restricted following dating at 20 weeks, whereas nine out of 10 pregnancies will be reclassified as non‐growth restricted with 36‐week dating. [ABSTRACT FROM AUTHOR]
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- 2024
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41. Ddx5 Targeted Epigenetic Modification of Pericytes in Pulmonary Hypertension After Intrauterine Growth Restriction.
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Hang, Chengcheng, Zu, Lu, Luo, Xiaofei, Wang, Yu, Yan, Lingling, Zhang, Ziming, Le, Kaixing, Huang, Yajie, Ye, Lixia, Ying, Yuhan, Chen, Kewei, Xu, Xuefeng, Lv, Qiannan, and Du, Lizhong
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PULMONARY hypertension ,PULMONARY arterial hypertension ,PERICYTES ,DNA helicases ,FETAL growth retardation ,RNA helicase ,EPIGENETICS ,MICRORNA - Abstract
Newborns with intrauterine growth restriction (IUGR) have a higher likelihood of developing pulmonary arterial hypertension (PAH) in adulthood. Although there is increasing evidence suggesting that pericytes play a role in regulating myofibroblast transdifferentiation and angiogenesis in malignant and cardiovascular diseases, their involvement in the pathogenesis of IUGR-related pulmonary hypertension and the underlying mechanisms remain incompletely understood. To address this issue, a study was conducted using a Sprague-Dawley rat model of IUGR-related pulmonary hypertension. Our investigation revealed increased proliferation and migration of pulmonary microvascular pericytes in IUGR-related pulmonary hypertension, accompanied by weakened endothelial–pericyte interactions. Through whole-transcriptome sequencing, Ddx5 (DEAD-box protein 5) was identified as one of the hub genes in pericytes. DDX5, a member of the RNA helicase family, plays a role in the regulation of ATP-dependent RNA helicase activities and cellular function. MicroRNAs have been implicated in the pathogenesis of PAH, and microRNA-205 (miR-205) regulates cell proliferation, migration, and angiogenesis. The results of dual-luciferase reporter assays confirmed the specific binding of miR-205 to Ddx5. Mechanistically, miR-205 negatively regulates Ddx5, leading to the degradation of β-catenin by inhibiting the phosphorylation of Gsk3β at serine 9. In vitro experiments showed the addition of miR-205 effectively ameliorated pericyte dysfunction. Furthermore, in vivo experiments demonstrated that miR-205 agomir could ameliorate pulmonary hypertension. Our findings indicated that the downregulation of miR-205 expression mediates pericyte dysfunction through the activation of Ddx5. Therefore, targeting the miR-205/Ddx5/p-Gsk3β/β-catenin axis could be a promising therapeutic approach for IUGR-related pulmonary hypertension. [ABSTRACT FROM AUTHOR]
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- 2024
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42. Impact of Pre-Gestational BMI and Gestational Weight Gain on Fetal Development Outcomes in Adolescent Pregnant Women.
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Grobeisen-Duque, Orly, Villavicencio-Carrisoza, Oscar, Mora-Vargas, Carlos Daniel, Arteaga-Lopez, Carolina Penelope, Martinez-Salazar, Maria Guadalupe, Rosas-Balan, Alejandro, León-Juárez, Moises, Villegas-Mota, Maria Isabel, Zaga-Clavellina, Veronica, Aguilera-Arreola, Ma. Guadalupe, and Helguera-Repetto, Addy Cecilia
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WEIGHT gain , *FETAL development , *PREGNANT women , *BODY mass index , *LOW birth weight - Abstract
Background. Gestational weight gain (GWG) constitutes an essential aspect of the gestational process. Due to factors such as pregestational body mass index (BMI), nutritional intake, level of physical activity, and psychological aspects, the recommended GWG may not be achieved, leading to adverse neonatal outcomes. Adolescents, due to their physiological and mental developmental stage, are at a higher risk of inappropriate GWG. Our aim is to highlight the importance of GWG in our population and to determine the correlation with perinatal outcomes. Methods. Pregnant adolescents who attended a tertiary care institution for prenatal care were included; maternal data such as preBMI and GWG were used to determine maternal and neonatal outcomes using the chi-square test and OR determination. Results. A total of 202 adolescent pregnant patients were included, comprising those with inadequate GWG (n = 70), adequate GWG (n = 85), and excessive GWG (n = 47). A statistically significant association was found between low BMI and inadequate GWG. Patients with inadequate GWG demonstrated a correlation with IUGR and low birth weight, while patients with excessive GWG gave birth to macrosomic neonates. Conclusion. We concluded that previous habits play a significant role in determining weight gain throughout pregnancy. GWG has a direct impact on neonatal growth and development. [ABSTRACT FROM AUTHOR]
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- 2024
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43. Maternal Serum Ischemia Modified Albumin Level Does Not Change In The Presence of Intrauterine Growth Restriction.
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Çetin, Orkun, Karaman, Erbil, Tolunay, Harun Egemen, Boza, Baris, Cim, Numan, Alisik, Murat, Erel, Ozcan, Şahin, Tuba Bozhüyük, Cetin, Ipek Dokurel, Yildizhan, Recep, and Şahin, Hanım Güler
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FETAL growth retardation , *PREGNANCY complications , *ALBUMINS , *PREGNANT women , *FETAL development , *PLACENTA diseases - Abstract
Maternal vascular hypoperfusion is the most common cause of fetal growth restrict ion. Maternal oxidative status features are identifiable on placental pathology, and antepartum diagnostic methods are rapidly evolving. The current study was constructed to determine the maternal oxidative status by measuring serum ischemia modified albumin (IMA) levels in pregnancies complicated with idiopathic intrauterine growth restriction (IUGR). The current study was designed as a descriptive and cohort trial. A total of 87 pregnant women; 45 healthy controls and 42 pregnancies complicated with idiopathic IUGR were included to the study population. Maternal serum IMA concentration was measured prior to the administration of any medication. The perinatal outcomes of patie nts were also recorded. Maternal serum IMA concentration in pregnancies complicated by idiopathic IUGR was higher than in healthy controls. There was no significant difference between the groups (0.54±0.04 versus 0.55±0.06 ABSU, p: 0.314). IUGR is a significant pregnancy complication. Elevated oxidative stress which leads to an ischemic microenvironment is associated with IUGR. Maternal serum IMA which is a possible marker for oxidative stress is not increase in pregnancies complicated with idiopathic IUGR. [ABSTRACT FROM AUTHOR]
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- 2024
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44. Placenta-anchored tadalafil liposomes rescues intrauterine growth restriction through continuous placental blood perfusion improvement.
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Tang, Miao, Xin, Yu, Zhao, Yunchun, Zhang, Xiao, Zhang, Meng, Sun, Dongli, Zhu, Xiaojun, Yao, Yao, Fei, Weidong, and Zheng, Caihong
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FETAL growth retardation , *LIPOSOMES , *TADALAFIL , *PLACENTAL growth factor , *WEIGHT loss , *CYCLIC guanylic acid - Abstract
Physiological or pathological hypoperfusion of the placenta is one of the main causes of intrauterine growth restriction (IUGR) which poses a significant risk to the health of the fetus and newborn. Tadalafil, a 5-type phosphodiesterase inhibitor, has previously been found to improve the symptoms of IUGR in various clinical studies. Unfortunately, its clinical utility is hindered by its limited water solubility, rapid metabolism, and lack of specific distribution in target tissues rendering tadalafil unable to maintain long-term placental perfusion. In this study, iRGD-modified tadalafil-loaded liposomes (iRGD-lipo@Tad) featuring a size of approximately 480 nm were designed to rectify the shortcomings of tadalafil. The prepared iRGD-lipo@Tad exhibited superior stability, sustained drug release capacity, and low cytotoxicity. The fluorescence study, tissue slice study, and drug biodistribution study together demonstrated the placenta-anchored ability of iRGD-modified liposomes. This was achieved by a dual approach consisting of the iRGD-mediated placenta-targeting effect and special particle size-mediated placenta resident effect. The pharmacokinetic study revealed a significant improvement in the in vivo process of tadalafil encapsulated by the iRGD-modified liposomes. In comparison to the tadalafil solution, the peak plasma concentration of iRGD-lipo@Tad was significantly increased, and the area under the curve was increased by about 7.88 times. In the pharmacodynamic study, iRGD-lipo@Tad achieved a continuous and efficient improvement of placental blood perfusion. This was achieved by decreasing the ratio of plasma soluble fms-like tyrosine kinase to placental growth factor and increasing the levels of cyclic guanosine monophosphate and nitric oxide. Consequently, iRGD-lipo@Tad resulted in a significant increase in embryo weight and a reduction in the miscarriage rate of N-Nitro-L-arginine methyl ester-induced IUGR pregnant mice without detectable toxicity. In summary, the nanotechnology-assisted therapy strategy presented here not only overcomes the limitations of tadalafil in the clinical treatment of IUGR but also offers new avenues to address the treatment of other placenta-originated diseases. In this study, a kind of placenta-anchored liposome which has the iRGD-assisted placenta-targeting effect and special particle size-mediated placenta resident effect, have been designed for achieving continuous and efficient placental blood perfusion in the treatment of intrauterine growth restriction. [Display omitted] [ABSTRACT FROM AUTHOR]
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- 2024
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45. Brain serotonin and serotonin transporter expression in male and female postnatal rat offspring in response to perturbed early life dietary exposures.
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Xin Ye, Shubhamoy Ghosh, Bo-Chul Shin, Ganguly, Amit, Maggiotto, Liesbeth, Jacobs, Jonathan P., and Devaskar, Sherin U.
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SEROTONIN transporters ,NEUROBEHAVIORAL disorders ,WESTERN immunoblotting ,HIGH-fat diet ,FETAL growth retardation - Abstract
Introduction: Serotonin (5-HT) is critical for neurodevelopment and the serotonin transporter (SERT) modulates serotonin levels. Perturbed prenatal and postnatal dietary exposures affect the developing offspring predisposing to neurobehavioral disorders in the adult. We hypothesized that the postnatal brain 5-HT-SERT imbalance associated with gut dysbiosis forms the contributing gut- brain axis dependent mechanism responsible for such ultimate phenotypes. Methods: Employing maternal diet restricted (IUGR, n=8) and high fat+high fructose (HFhf, n=6) dietary modifications, rodent brain serotonin was assessed temporally by ELISA and SERT by quantitative Western blot analysis. Simultaneously, colonic microbiome studies were performed. Results: At early postnatal (P) day 2 no changes in the IUGR, but a 24% reduction in serotonin (p = 0.00005) in the HFhf group occurred, particularly in the males (p = 0.000007) revealing a male versus female difference (p = 0.006). No such changes in SERT concentrations emerged. At late P21 the IUGR group reared on HFhf (IUGR/ HFhf, (n = 4) diet revealed increased serotonin by -53% in males (p = 0.0001) and 36% in females (p = 0.023). While only females demonstrated a -40% decrease in serotonin (p = 0.010), the males only trended lower without a significant change within the HFhf group (p = 0.146). SERT on the other hand was no different in HFhf or IUGR/RC, with only the female IUGR/HFhf revealing a 28% decrease (p = 0.036). In colonic microbiome studies, serotonin-producing Bacteriodes increased with decreased Lactobacillus at P2, while the serotonin-producing Streptococcus species increased in IUGR/HFhf at P21. Sex-specific changes emerged in association with brain serotonin or SERT in the case of Alistipase, Anaeroplasma, Blautia, Doria, Lactococcus, Proteus, and Roseburia genera. Discussion: We conclude that an imbalanced 5-HT-SERT axis during postnatal brain development is sex-specific and induced by maternal dietary modifications related to postnatal gut dysbiosis. We speculate that these early changes albeit transient may permanently alter critical neural maturational processes affecting circuitry formation, thereby perturbing the neuropsychiatric equipoise. [ABSTRACT FROM AUTHOR]
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- 2024
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46. A Second Trimester Prediction Algorithm for Early-Onset Hypertensive Disorders of Pregnancy Occurrence and Severity Based on Soluble fms-like Tyrosine Kinase 1 (sFlt-1)/Placental Growth Factor (PlGF) Ratio and Uterine Doppler Ultrasound in Women at Risk.
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Chirilă, Cristian Nicolae, Mărginean, Claudiu, Ghiga, Dana Valentina, Voidăzan, Septimiu, Chirilă, Paula Maria, and Gliga, Mirela Liana
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ULTRASONIC imaging of the uterus ,PLACENTA ,RISK assessment ,RECEIVER operating characteristic curves ,PREDICTION models ,SECOND trimester of pregnancy ,PROTEIN-tyrosine kinase inhibitors ,HYPERTENSION ,SCIENTIFIC observation ,KRUSKAL-Wallis Test ,SEVERITY of illness index ,DESCRIPTIVE statistics ,TRANSCRANIAL Doppler ultrasonography ,LONGITUDINAL method ,PREECLAMPSIA ,WOMEN'S health ,DATA analysis software ,CONFIDENCE intervals ,COMPARATIVE studies ,ALGORITHMS ,BIOMARKERS ,SENSITIVITY & specificity (Statistics) ,EVALUATION ,PREGNANCY - Abstract
Hypertensive disorders of pregnancy (HDPs) represent a significant source of severe maternal and fetal morbidity. Screening strategies relying on traditional medical history and clinical risk factors have traditionally shown relatively modest performance, mainly in the prediction of preeclampsia, displaying a sensitivity of 37% for the early-onset form and 29% for the late-onset form. The development of more accurate predictive and diagnostic models of preeclampsia in the early stages of pregnancy represents a matter of high priority. The aim of the present paper is to create an effective second trimester prediction algorithm of early-onset HDP occurrence and severity, by combining the following two biochemical markers: a soluble fms-like tyrosine kinase 1 (sFlt-1)/placental growth factor (PlGF) ratio and uterine artery Doppler ultrasound parameters, namely the pulsatility index (PI) and the resistivity index (RI), in a population of high-risk pregnant women, initially assessed through traditional risk factors. A prospective single-center observational longitudinal study was conducted, in which 100 women with singleton pregnancy and traditional clinical and medical history risk factors for preeclampsia were enrolled at 24 weeks of gestation. Shortly after study enrollment, all women had their sFlt-1 and PlGF levels and mean uterine artery PI and RI determined. All pregnancies were followed up until delivery. Receiver operating characteristic (ROC) analysis established algorithms based on cutoffs for the prediction of the later development of preeclampsia: PI 1.25 (96.15% sensitivity, 86.49% specificity), RI 0.62 (84.6% sensitivity, 89.2% specificity) and sFlt-1/PlGF ratio 59.55 (100% sensitivity, 89.2% specificity). The sFlt-1/PlGF ratio was the best predictor for preeclampsia, as it displayed the highest area under the curve (AUC) of 0.973. The prediction algorithm for the severe form of preeclampsia, complicated by fetal growth restriction leading to preterm birth, antepartum fetal demise or acute fetal distress with a cerebro-placental ratio of
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- 2024
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47. Allicin in pregnancy diets modulates steroid metabolism in pregnant sows and placental sulphate metabolism promoting placental angiogenesis and foetal development
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J. Peng, Y. Zhang, Q. Liu, Y. Tang, W. Zhang, S. Zheng, W. Huang, M. Yang, Y. He, Z. Li, L. Xie, J. Li, J. Wang, and Y. Zhou
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Hydrogen sulphide ,Intrauterine growth restriction ,Maternal ,Nutrition ,Reproductive performance ,Animal culture ,SF1-1100 - Abstract
The low-birth-weight of piglets is an important factor affecting pig enterprises. The placenta, as a key organ for material exchange between mother and foetus, directly influences the growth and development of the foetus. Allicin exhibits various biological activities, including anti-inflammatory and antioxidant properties. It may also play a crucial role in enhancing sow reproductive performance and placental angiogenesis. In this study, we used 70 lactating Landrace × Yorkshire binary heterozygous sows to explore the effect of allicin on the reproductive performance of sows and placental development. The sows were randomly assigned into the Allicin group (Allicin), which was fed with a diet containing 0.25% allicin, and the negative control group, which was fed with basal feed. The experimental period lasted for 114 d from the date of mating to the end of farrowing. The results showed that the addition of allicin to the gestation diets increased the number of total born piglets, born alive piglets, and high-birth-weight piglets, reduced peripartum oxidative stress, alleviated dysregulation of glucose-lipid metabolism in sows, and increased the levels of antioxidant markers in the placenta. Differential analysis of metabolites in maternal plasma and placenta samples by non-targeted metabolomics revealed that allicin improved cholesterol metabolism, steroid biosynthesis, and increased plasma progesterone levels in sows. Allicin promoted sulphur metabolism, cysteine and methionine metabolism in placental samples and increased the hydrogen sulphide (H2S) content in the placenta. In addition, Quantitative Real-time PCR, Western blot and immunofluorescence results showed that allicin upregulated the expression of angiogenesis-related genes, VEGF-A, FLK 1 and Ang 1, in the placenta, implying that it promoted placental angiogenesis. These results indicate that supplementing the diet of pregnant sows with allicin reduces oxidative stress, alleviates dysregulation of glucose-lipid metabolism during the periparturient period, and promotes placental angiogenesis and foetal development by increasing plasma progesterone level and placental H2S content.
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- 2024
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48. Safety and efficacy of phosphodiesterase-5 (PDE-5) inhibitors in fetal growth restriction: a systematic literature review and meta-analysis
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Ying Liu, Ella Man-Wai Un, Ying Bai, Man Keong Chan, Luo Xin Zeng, Sut Leng Lei, Junjun Li, and Carolina Oi Lam Ung
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fetal growth restriction ,phosphodiesterase-5 inhibitors ,sildenafil ,tadalafil ,intrauterine growth restriction ,Therapeutics. Pharmacology ,RM1-950 ,Pharmacy and materia medica ,RS1-441 - Abstract
Introduction: Fetal growth restriction (FGR) is associated with a higher risk of perinatal morbidity and mortality, as well as long-term health issues in newborns. Currently, there is no effective medicine for FGR. Phosphodiesterase-5 (PDE-5) inhibitors have been shown in pre-clinical studies to improve FGR. This study aimed to evaluate the latest evidence about the clinical outcomes and safety of PDE-5 inhibitors for the management of FGR.Methods: Eight databases (PubMed, Embase, Medline, Web of Science, Cochrane Library, Chinese National Knowledge Infrastructure, Chinese Biomedical Database and WangFang Database) were searched for English and Chinese articles published from the database inception to December 2023. Randomized controlled trials (RCTs) reporting the use of PDE-5 inhibitors in FGR were included. The quality of the RCTs was assessed using the Cochrane Risk of Bias Tool. Odds ratio and mean difference (MD) (95% confidence intervals) were pooled for meta-analysis.Results: From 253 retrieved publications, 16 studies involving 1,492 pregnant women met the inclusion criteria. Only sildenafil (15 RCTs) and tadalafil (1 RCT) were studied for FGR. Compared with the control group (placebo, no treatment, or other medication therapies), sildenafil increased birth weight, pregnancy prolongation and umbilical artery pulsatility indices. However, it also increased the risk of pulmonary hypertension in newborns, as well as headache and flushing/rash in mothers. There were no significant differences in gestation age, perinatal mortality or major neonatal morbidity, stillbirth, neonate death, infants admitted to neonatal intensive care unit, intraventricular hemorrhage and necrotizing enterocolitis in infants, as well as pregnancy hypertension and gastrointestinal side effects in mothers between the treatment and the control groups.Discussion: Sildenafil was the most investigated PDE-5 inhibitors for FGR. Current evidence suggests that sildenafil can improve birth weight and duration of pregnancy but at the same time increase the risk of neonatal pulmonary hypertension. It remains uncertain whether the benefits of sildenafil in FGR outweigh the risks and further high-quality RCTs are warranted.Systematic Review Registration:https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=325909
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- 2024
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49. Sexually Dimorphic Response to Hepatic Injury in Newborn Suffering from Intrauterine Growth Restriction
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Yu‐Sen Wei, Wen‐Jie Tang, Pei‐Yu Mao, Jiang‐Di Mao, Zhi‐Xiang Ni, Kang‐Wei Hou, Teresa G. Valencak, Da‐Ren Liu, Jun‐Fang Ji, and Hai‐Feng Wang
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hepatic injury ,intrauterine growth restriction ,piglet ,sexual dimorphism ,single‐cell RNA sequencing ,Science - Abstract
Abstract Intrauterine growth restriction (IUGR), when a fetus does not grow as expected, is associated with a reduction in hepatic functionality and a higher risk for chronic liver disease in adulthood. Utilizing early developmental plasticity to reverse the outcome of poor fetal programming remains an unexplored area. Focusing on the biochemical profiles of neonates and previous transcriptome findings, piglets from the same fetus are selected as models for studying IUGR. The cellular landscape of the liver is created by scRNA‐seq to reveal sex‐dependent patterns in IUGR‐induced hepatic injury. One week after birth, IUGR piglets experience hypoxic stress. IUGR females exhibit fibroblast‐driven T cell conversion into an immune‐adapted phenotype, which effectively alleviates inflammation and fosters hepatic regeneration. In contrast, males experience even more severe hepatic injury. Prolonged inflammation due to disrupted lipid metabolism hinders intercellular communication among non‐immune cells, which ultimately impairs liver regeneration even into adulthood. Additionally, Apolipoprotein A4 (APOA4) is explored as a novel biomarker by reducing hepatic triglyceride deposition as a protective response against hypoxia in IUGR males. PPARα activation can mitigate hepatic damage and meanwhile restore over‐expressed APOA4 to normal in IUGR males. The pioneering study offers valuable insights into the sexually dimorphic responses to hepatic injury during IUGR.
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- 2024
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50. SPAG7 deletion causes intrauterine growth restriction, resulting in adulthood obesity and metabolic dysfunction
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Stephen E Flaherty III, Olivier Bezy, Brianna LaCarubba Paulhus, LouJin Song, Mary Piper, Jincheng Pang, Yoson Park, Shoh Asano, Yu-Chin Lien, John D Griffin, Andrew Robertson, Alan Opsahl, Dinesh Hirenallur Shanthappa, Youngwook Ahn, Evanthia Pashos, Rebecca A Simmons, Morris J Birnbaum, and Zhidan Wu
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SPAG7 ,embryonic development ,obesity ,insulin resistance ,intrauterine growth restriction ,Medicine ,Science ,Biology (General) ,QH301-705.5 - Abstract
From a forward mutagenetic screen to discover mutations associated with obesity, we identified mutations in the Spag7 gene linked to metabolic dysfunction in mice. Here, we show that SPAG7 KO mice are born smaller and develop obesity and glucose intolerance in adulthood. This obesity does not stem from hyperphagia, but a decrease in energy expenditure. The KO animals also display reduced exercise tolerance and muscle function due to impaired mitochondrial function. Furthermore, SPAG7-deficiency in developing embryos leads to intrauterine growth restriction, brought on by placental insufficiency, likely due to abnormal development of the placental junctional zone. This insufficiency leads to loss of SPAG7-deficient fetuses in utero and reduced birth weights of those that survive. We hypothesize that a ‘thrifty phenotype’ is ingrained in SPAG7 KO animals during development that leads to adult obesity. Collectively, these results indicate that SPAG7 is essential for embryonic development and energy homeostasis later in life.
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- 2024
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