Epigenetic and Transcriptomic Programming of HSC Quiescence Signaling in Large for Gestational Age Neonates.
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ABSTRACT:
SUBMITTER: Pelletier A
PROVIDER: S-EPMC9267056 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Objective: To investigate the impact of fetal growth restriction (FGR) on hormonal regulation of post-natal growth and glucose metabolism [via insulin and growth hormone (GH)/Insulin-like Growth factor 1 (IGF1) axis pathways] in small for gestational age (SGA) neonates. Methods: We conducted a monocentric observational prospective comparative study on 73 singleton babies born with a weight inferior to 2,000 g. We analyzed auxological (weight, height and head circumference), and hormonal (GH, IGF1, and insulin plasma concentrations) data comparing SGA and appropriate for gestational age (AGA) neonates, between day 1 and 60. Results: One third (23/73) of the neonates were SGA. Twenty-five percent (18/73) required insulin for idiopathic hyperglycemia of prematurity and were smaller in weight and head circumference at discharge. In the SGA group compared with the AGA group, GH plasma concentrations were higher at day 3 (70.1 vs. 38.0 mIU/L) and IGF1 plasma concentrations were higher at day 10 (29.0 vs. 18.7 ng/ml). Conclusions: SGA neonates displayed resistance to GH and IGF1, concomitant to insulin resistance. This could partially explain the initial defective catch-up growth and, later in life, the higher prevalence of metabolic syndrome in this population.
| S-EPMC8382944 | biostudies-literature
Project description:Adverse environmental conditions faced by an individual early during its life, such as gestational hypoxia, can have a profound influence on the risk of diseases, such as neurological disorders, in later life. Clinical and preclinical studies suggest that epigenetic programming of gene expression patterns in response to maternal stress have a crucial role in the fetal origins of neurological diseases. Herein, we summarize recent studies regarding the role of epigenetic mechanisms in the developmental programming of neurological diseases in offspring, primarily focusing on DNA methylation/demethylation and miRNAs. Such information could increase our understanding of the fetal origins of adult diseases and help develop effective prevention and intervention against neurological diseases.
| S-EPMC4262616 | biostudies-literature
Project description:Lipidome-wide metabolites may be useful biomarkers of pregnancy outcomes. We sought to characterize maternal lipidomic signatures associated with preterm birth and neonatal anthropometric parameters. Plasma samples were collected 24-28 weeks gestation, and lipidomic profiling was quantified using high-performance liquid chromatography tandem mass spectrometry. Lipid metabolites were analyzed individually and as whole lipid classes and subgroups based on degree of hydrocarbon chain saturation. Associations were estimated using linear and logistic regression. After false discovery adjustment (q < 0.15), four plasmenyl-phosphatidylethanolamines and three free fatty acids associated with increased risk for spontaneous preterm birth. Five phosphatidylinositols, two phosphatidylglycerols, and one phosphatidic acid were associated with large for gestational age neonates. The saturated plasmenyl-phosphatidylethanolamines held the association with increased risk for spontaneous preterm birth. Both the mono- and poly-unsaturated free fatty acids held the association for increased risk for spontaneous preterm birth. Mono- and poly-unsaturated phosphatidylinositols were associated with large for gestational age neonates. Whole lipid classes (plasmenyl-phophatidylcholines and plasmenyl-phosphatidylethanolamines) were associated with increased risk for large for gestational age at delivery. This study provides evidence that finer omics-scale analysis of the maternal lipidome may be more informative biomarkers of pregnancy outcomes compared to whole class level lipid analysis.
| S-EPMC8046995 | biostudies-literature
Project description:OBJECTIVE:To compare fetal heart rate (FHR) patterns during the last hour of labor between small-for-gestational-age (SGA; birth weight less than the 10th percentile for gestational age) and appropriate-for-gestational-age (AGA; birth weight at the 10-90th percentile) neonates at 36 weeks of gestation or greater. We also compared the rate of cesarean delivery and composite neonatal morbidity among SGA and AGA newborns. METHODS:This is a secondary analysis of a randomized trial of intrapartum fetal electrocardiographic ST-segment analysis. We excluded women with chorioamnionitis, insufficient duration of FHR tracing in the hour before delivery, and anomalous newborns. Fetal heart rate patterns were categorized by computerized pattern recognition software (PeriCALM Patterns). Composite neonatal morbidity was defined as any of the following: intrapartum fetal death, Apgar score 3 or less at 5 minutes, cord artery pH 7.05 or less, base deficit 12 mmol/L or greater, neonatal seizure, intubation at delivery, neonatal encephalopathy, and neonatal death. Logistic regression was used to evaluate the association between FHR patterns and SGA adjusted for magnesium sulfate exposure and stage of labor. RESULTS:Of the 11,108 women randomized, 85% (n=9,402) met inclusion criteria, of whom 9% were SGA. In the last hour, the likelihood of accelerations was significantly lower among SGA than AGA neonates (72.4% vs 66.8%; P=.001). Variable decelerations lasting greater than 60 seconds, with depth greater than 60 beats per minute (bpm) or nadir less than 60 bpm, were significantly more common with SGA than AGA (all P<.001). The rate of late decelerations, prolonged decelerations, or bradycardia were similar between SGA and AGA (all P>.05). Cesarean delivery for fetal indications was significantly more common with SGA (7.0%) than AGA (4.0%; P<.001). The composite neonatal morbidity was 1.4% among SGA and 1.0% among AGA (odds ratio 1.40, 95% CI 0.74-2.64). CONCLUSION:Although the FHR patterns in the last hour of labor differ among SGA and AGA neonates, as does the rate of cesarean delivery, the composite neonatal morbidity was similar.
| S-EPMC6247114 | biostudies-other
Project description:To compare morbidity among small-for-gestational-age (SGA; birth weight less than the 10th percentile for gestational age), appropriate-for-gestational-age (AGA; birth weight 10th to 90th percentile; reference group), and large-for-gestational-age (LGA; birth weight greater than the 90th percentile) neonates in apparently uncomplicated pregnancies at term (37 weeks of gestation or greater).This secondary analysis, derived from an observational obstetric cohort of 115,502 deliveries, included women with apparently uncomplicated pregnancies of nonanomalous singletons who had confirmatory ultrasound dating no later than the second trimester and who delivered between 37 0/7 and 42 6/7 weeks of gestation. We used two different composite neonatal morbidity outcomes: hypoxic composite neonatal morbidity for SGA and traumatic composite neonatal morbidity for LGA neonates. Log Poisson relative risks (RRs) with 95% CIs adjusted for potential confounding factors (nulliparity, body mass index, insurance status, and neonatal sex) were calculated.Among the 63,436 women who met our inclusion criteria, SGA occurred in 7.9% (n=4,983) and LGA in 8.3% (n=5,253). Hypoxic composite neonatal morbidity was significantly higher in SGA (1.1%) compared with AGA (0.7%; adjusted RR 1.44, 95% CI 1.07-1.93) but similar between LGA (0.6%) and AGA (adjusted RR 0.84, 95% CI 0.58-1.22). Traumatic composite neonatal morbidity was significantly higher in LGA (1.9%) than AGA (1.0%; adjusted RR 1.88, 95% CI 1.51-2.34) but similar in SGA (1.3%) compared with AGA (adjusted RR 1.28, 95% CI 0.98-1.67).Among women with uncomplicated pregnancies, hypoxic composite neonatal morbidity is more common with SGA neonates and traumatic-composite neonatal morbidity is more common with LGA neonates.
| S-EPMC5578445 | biostudies-literature
Project description:BackgroundOur understanding of the normative concentrations of urine biomarkers in premature neonates is limited.MethodsWe evaluated urine from 750 extremely low gestational age (GA) neonates without severe acute kidney injury (AKI) to determine how GA affects ten different urine biomarkers at birth and over the first 30 postnatal days. Then, we investigated if the urine biomarkers changed over time at 27, 30, and 34 weeks postmenstrual age (PMA). Next, we evaluated the impact of sex on urine biomarker concentrations at birth and over time. Finally, we evaluated if urine biomarkers were impacted by treatment with erythropoietin (Epo).ResultsWe found that all ten biomarker concentrations differ at birth by GA and that some urine biomarker concentrations increase, while others decrease over time. At 27 weeks PMA, 7/10 urine biomarkers differed by GA. By 30 weeks PMA, 5/10 differed, and by 34 weeks PMA, only osteopontin differed by GA. About half of the biomarker concentrations differed by sex, and 4/10 showed different rates of change over time between males vs. females. We found no differences in urine biomarkers by treatment group.ConclusionsThe temporal patterns, GA, and sex differences need to be considered in urine AKI biomarker analyses.ImpactUrine biomarker concentrations differ by GA at birth. Some urine biomarkers increase, while others decrease, over the first 30 postnatal days. Most urine biomarkers differ by GA at 27 weeks PMA, but are similar by 34 weeks PMA. Some urine biomarkers vary by sex in premature neonates. Urine biomarkers did not differ between neonates randomized to placebo vs. Epo.
| S-EPMC9149147 | biostudies-literature
Project description:BackgroundInfants being born Large-for-gestational-age (LGA) are prone to developing cardiometabolic disease. However, the underlying mechanisms remain unclear.ResultsClinical investigation showed that children born LGA had significantly higher serum level of total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-c), and insulin, ratio of TC/high-density lipoprotein-cholesterol (HDL-c) compared to children born appropriate for gestational age (AGA). Birth weight (BW) was positively correlated to TC, LDL-c, and the ratio of TC/HDL in serum. Genome-wide DNA methylation analyzed in umbilical cord blood of controls and macrosomia cases. We identified 3459 methylation variable positions (MVPs) achieving genome-wide significance (adjusted P-value < 0.05) with methylation differences of ≥ 5%. A total of 327 MVPs were filtered by methylation differences of ≥ 7% located within an island, which mapped to 213 genes. Function analysis using Ingenuity Pathway Analysis showed 16 genes enriched in "cardiovascular disease". Four genes included contributed to hyperlipidemia.Materials and methodsFifty-eight children aged 3-6 years born LGA and 123 subjects born AGA were enrolled. Anthropometric parameters and blood pressure (BP) were measured, and metabolic assessment was performed in all subjects. Genome-wide DNA methylation in umbilical blood was assayed by the 450K BeadChip in six AGA and six macrosomia newborns.ConclusionsOur data indicate that excess birth weight may increase the risk of lipid dysfunction in children aged 3-6 years. It might through reprogramming a group of genes correlated to cardiovascular disease. The genes identified in this study might be potential biomarker for cardiometabolic disease.
| S-EPMC5349931 | biostudies-literature
Project description:The intestinal microbiota is an important contributor to the health of preterm infants, and may be destabilized by a number of environmental factors and treatment modalities. How to promote the development of a healthy microbiota in preterm infants is largely unknown. We collected fecal samples from 45 breastfed preterm very low birth weight (birth weight < 1500 g) infants from birth until 60 days postnatal age to characterize the intestinal microbiota development during the first weeks of life in preterm infants. Fecal microbiota composition was determined by 16S rRNA amplicon sequencing. The main driver of microbiota development was gestational age; antibiotic use had strong but temporary effects and birth mode had little influence. Microbiota development proceeded in four phases indicated by the dominance of Staphylococcus, Enterococcus, Enterobacter, and finally Bifidobacterium. The Enterococcus phase was only observed among the extremely premature infants and appeared to delay the microbiota succession. The results indicate that hospitalized preterm infants receiving breast milk may develop a normal microbiota resembling that of term infants.
| S-EPMC5802739 | biostudies-literature
Project description:Small for gestational age (SGA) newborns are often born from hypertensive pregnancies. This study aimed to compare the systemic metabolism of cortisol (F) in pregnancies with SGA and appropriate for gestational age (AGA) infants, considering both the normotensive (NT) and hypertensive patients. We hypothesized that the disturbances in systemic metabolism of F in pre-eclampsia (PE) might be attributed not to hypertension only, but to SGA. The study included 117 pregnants in the third trimester, divided into groups: NT pregnancy and SGA neonate (SGA-NT); NT pregnancy and AGA neonate (AGA-NT; controls), and respective groups with PE: SGA-PE and AGA-PE. We assessed the glucocorticoid balance with the function of enzymes involved in systemic metabolism of F: 11?-hydroxysteroid dehydrogenase type 1 and 2 (11?-HSD1 and 11?-HSD2), 5?- and 5?-reductase. The enzymes' functions were estimated with the levels of F, cortisone (E), and their metabolites in plasma or urine, which we measured with HPLC-FLD and HPLC-MS/MS. The plasma F/E and urinary free F/E (UFF/UFE) ratios correlated significantly only in patients with the normal function of 5?- and 5?-reductase. The increased function of 11?-HSD2 was noted in all pre-eclamptic pregnancies. Increased function of 5?- and 5?-reductase was specific only for SGA-PE pregnancies, and the function of 5?-reductase was dependent on fetal sex. The SGA-NT pregnancies with male fetuses trended towards the higher function of renal 11?-HSD2 and 5?-reductase; SGA-NT pregnancies with female fetuses lacked any systemic glucocorticoid imbalance. In conclusion, systemic metabolism of F is the most intensive in pre-eclamptic pregnancies complicated by SGA with female fetuses. Our study supports the hypothesis about the different origins of PE and idiopathic intrauterine growth restriction and suggests the sex-specific mechanisms responsible for fetal growth restriction.
| S-EPMC6884581 | biostudies-literature
Project description:Prematurity predisposes to cardiovascular disease; however the underlying mechanisms remain elusive. Disturbance of the endothelial glycocalyx (EG), an important regulator of vessel function, is thought to contribute to vascular pathology. Here, we studied the EG with respect to gestational and postnatal age in preterm and term neonates. The Perfused Boundary Region (PBR), an inverse measure of glycocalyx thickness, was measured postnatally in 85 term and 39 preterm neonates. Preterm neonates were further analyzed in two subgroups i.e., neonates born < 30 weeks gestational age (group A) and neonates born ≥ 30 weeks (group B). In preterm neonates, weekly follow-up measurements were performed if possible. PBR differed significantly between preterm and term neonates with lowest values representing largest EG dimension in extremely premature infants possibly reflecting its importance in fetal vascular development. Linear regression revealed a dependence of PBR on both, gestational age and postnatal age. Furthermore, hematocrit predicted longitudinal PBR changes. PBR measured in group A at a corrected age of > 30 weeks was significantly higher than in group B at birth, pointing towards an alteration of intrinsic maturational effects by extrinsic factors. These changes might contribute to the increased cardiovascular risk associated with extreme prematurity.
| S-EPMC7862677 | biostudies-literature