scholarly journals Isolated Hypomethylation of IGF2 Associated with Severe Hypoglycemia Responsive to Growth Hormone Treatment

Diagnostics ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 749
Author(s):  
Sarah C. Grünert ◽  
Uta Matysiak ◽  
Franka Hodde ◽  
Gunda Ruzaike ◽  
Ekkehart Lausch ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Intrauterine Growth Restriction ◽  
Severe Hypoglycemia ◽  
Hormone Treatment ◽  
Postnatal Growth ◽  
Growth Restriction ◽  
Poor Growth ◽  
Feeding Difficulties ◽  
Intrauterine Growth ◽  
Pathogenic Variants

Hypomethylation of H19 and IGF2 can cause Silver–Russell syndrome (SRS), a clinically and genetically heterogeneous condition characterized by intrauterine growth restriction, poor postnatal growth, relative macrocephaly, craniofacial abnormalities, body asymmetry, hypoglycemia and feeding difficulties. Isolated hypomethylation of IGF2 has been reported in single cases of SRS as well. Here, we report on a 19-month-old patient who presented with two episodes of hypoglycemic seizures. No intrauterine growth restriction was observed, the patient did not present with SRS-typical facial features, and postnatal growth in the first months of life was along the lower normal percentiles. Exome sequencing did not reveal any likely pathogenic variants explaining the phenotype; however, hypomethylation studies revealed isolated hypomethylation of IGF2, while the methylation of H19 appeared normal. Hypoglycemia responded well to growth hormone therapy, and the boy showed good catch-up growth. Our case demonstrates that SRS and isolated IGF2 hypomethylation should be considered early in the diagnosis of recurrent hypoglycemia in childhood, especially in combination with small gestational age and poor growth.

Hepatic IGF1 DNA methylation is influenced by gender but not by intrauterine growth restriction in the young lamb

2015 ◽  
Vol 6 (6) ◽  
pp. 558-572 ◽  
Author(s):  
D. J. Carr ◽  
J. S. Milne ◽  
R. P. Aitken ◽  
C. L. Adam ◽  
J. M. Wallace
Keyword(s):  
Dna Methylation ◽  
Growth Hormone ◽  
Sexual Dimorphism ◽  
Mrna Expression ◽  
Intrauterine Growth Restriction ◽  
Messenger Rna ◽  
Methylation Status ◽  
Growth Restriction ◽  
Intrauterine Growth ◽  
Increased Risk

Intrauterine growth restriction (IUGR) and postnatal catch-up growth confer an increased risk of adult-onset disease. Overnourishment of adolescent ewes generates IUGR in ∼50% of lambs, which subsequently exhibit increased fractional growth rates. We investigated putative epigenetic changes underlying this early postnatal phenotype by quantifying gene-specific methylation at cytosine:guanine (CpG) dinucleotides. Hepatic DNA/RNA was extracted from IUGR [eight male (M)/nine female (F)] and normal birth weight (12 M/9 F) lambs. Polymerase chain reaction was performed using primers targeting CpG islands in 10 genes: insulin, growth hormone, insulin-like growth factor (IGF)1, IGF2, H19, insulin receptor, growth hormone receptor, IGF receptors 1 and 2, and the glucocorticoid receptor. Using pyrosequencing, methylation status was determined by quantifying cytosine:thymine ratios at 57 CpG sites. Messenger RNA (mRNA) expression of IGF system genes and plasma IGF1/insulin were determined. DNA methylation was independent of IUGR status but sexual dimorphism in IGF1 methylation was evident (M<F, P=0.008). IGF1 mRNA:18S and plasma IGF1 were M>F (both P<0.001). IGF1 mRNA expression correlated negatively with IGF1 methylation (r=−0.507, P=0.002) and positively with plasma IGF1 (r=0.884, P<0.001). Carcass and empty body weights were greater in males (P=0.002–0.014) and this gender difference in early body conformation was mirrored by sexual dimorphism in hepatic IGF1 DNA methylation, mRNA expression and plasma IGF1 concentrations.

scholarly journals Postnatal Growth after Intrauterine Growth Restriction Alters Central Leptin Signal and Energy Homeostasis

PLoS ONE ◽  
2012 ◽  
Vol 7 (1) ◽  
pp. e30616 ◽  
Author(s):  
Bérengère Coupé ◽  
Isabelle Grit ◽  
Philippe Hulin ◽  
Gwenaëlle Randuineau ◽  
Patricia Parnet
Keyword(s):  
Intrauterine Growth Restriction ◽  
Energy Homeostasis ◽  
Postnatal Growth ◽  
Growth Restriction ◽  
Intrauterine Growth

scholarly journals Prenatal intrauterine growth restriction and risk of retinopathy of prematurity

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Alison Chu ◽  
Yasmeen Dhindsa ◽  
Myung Shin Sim ◽  
Marie Altendahl ◽  
Irena Tsui
Keyword(s):  
Gestational Age ◽  
Retinopathy Of Prematurity ◽  
Intrauterine Growth Restriction ◽  
Growth Failure ◽  
Postnatal Growth ◽  
Growth Patterns ◽  
Growth Restriction ◽  
Intrauterine Growth ◽  
Prenatal Growth ◽  
Postnatal Growth Failure

Abstract Low birthweight and decreased postnatal weight gain are known predictors of worse retinopathy of prematurity (ROP) but the role of prenatal growth patterns in ROP remains inconclusive. To distinguish small for gestational age (SGA) from intrauterine growth restriction (IUGR) as independent predictors of ROP, we performed a retrospective cohort study of patients who received ROP screening examinations at a level IV neonatal intensive care unit over a 7-year period. Data on IUGR and SGA status, worst stage of and need for treatment for ROP, and postnatal growth was obtained. 343 infants were included for analysis (mean gestational age = 28.6 weeks and birth weight = 1138.2 g). IUGR infants were more likely to have a worse stage of ROP and treatment-requiring ROP (both p < 0.0001) compared to non-IUGR infants. IUGR infants were more likely to be older at worst stage of ROP (p < 0.0001) and to develop postnatal growth failure (p = 0.01) than non-IUGR infants. Independent of postnatal growth failure status, IUGR infants had a 4–5 × increased risk of needing ROP treatment (p < 0.001) compared to non-IUGR infants. SGA versus appropriate for gestational age infants did not demonstrate differences in retinopathy outcomes, age at worst ROP stage, or postnatal growth failure. These findings emphasize the importance of prenatal growth on ROP development.

scholarly journals Effect of intrauterine growth restriction on weight and cellularity of gastrointestinal tract in postnatal lambs

2008 ◽  
Vol 88 (1) ◽  
pp. 107-112 ◽  
Author(s):  
Feng Gao ◽  
Xianzhi Hou ◽  
Yingchun Liu
Keyword(s):  
Gastrointestinal Tract ◽  
Dna Content ◽  
Intrauterine Growth Restriction ◽  
Late Pregnancy ◽  
Postnatal Growth ◽  
Growth Restriction ◽  
Control Group ◽  
Intrauterine Growth ◽  
Significant Difference ◽  
Restricted Group

This study investigated the effect of intrauterine growth restriction (IUGR) during late pregnancy on weight and cellularity of the gastrointestinal tract (GIT) in postnatal lambs. Twenty-three Mongolian lambs were entered into the study. Their dams were mated at a synchronized estrus and divided into three groups offered 0.175 MJ ME kg-0.75 d-1 (Restricted Group 1, RG1), 0.33 MJ ME kg-0.75 d-1 (Restricted Group 2, RG2) and Control Group (CG, ad libitum access to feed) during their late pregnancy (90 d), respectively. The lambs were slaughtered at birth (neonatal lambs) and at 28 wk of age. The neonatal abomasum weight, jejunum weight and length, abomasum and jejunum DNA content, and the reticulum protein:DNA ratio were lower for RG1 than those of CG (P < 0.05). At 28 wk of age, there were no significant difference in the weights and lengths of jejunum and the weight of abomasum in the lambs among RG1, RG2 and CG (P > 0.05). However, the rumen and omasum weight, and omasum DNA content were lower for RG1 than for CG (P < 0.05). For the jejunum, the protein:DNA ratios in RG2 were significantly higher than those of CG (P < 0.05). These changes in the weight and cellularity of the GIT may have significant implications on postnatal growth and health. Key words: Intrauterine growth restriction, postnatal lambs, gastrointestinal tract, weight, cellularity

scholarly journals Intrauterine Growth Restriction: Hungry for an Answer

Physiology ◽  
2016 ◽  
Vol 31 (2) ◽  
pp. 131-146 ◽  
Author(s):  
Sherin U. Devaskar ◽  
Alison Chu
Keyword(s):  
Intrauterine Growth Restriction ◽  
Epigenetic Modification ◽  
Growth Restriction ◽  
Cardiometabolic Disease ◽  
Lifestyle Modifications ◽  
Poor Growth ◽  
Public Health Burden ◽  
Metabolic Phenotypes ◽  
Intrauterine Growth ◽  
Significant Public Health

Intrauterine growth restriction (IUGR) has been defined in several ways, but in general describes a condition in which the fetus exhibits poor growth in utero. This complication of pregnancy poses a significant public health burden as well as increased morbidity and mortality for the offspring. In human IUGR, alteration in fetal glucose and insulin homeostasis occurs in an effort to conserve energy and survive at the expense of fetal growth in an environment of inadequate nutrient provision. Several animal models of IUGR have been utilized to study the effects of IUGR on fetal glucose handling, as well as the postnatal reprogramming of energy metabolite handling, which may be unmasked in adulthood as a maladaptive propensity for cardiometabolic disease. This developmental programming may be mediated in part by epigenetic modification of essential regulators of glucose homeostasis. Several pharmacological therapies and nonpharmacological lifestyle modifications have shown early promise in mitigating the risk for or severity of adult metabolic phenotypes but still require further study of unanticipated and/or untoward side effects.

Treatment of intrauterine growth restriction with maternal growth hormone supplementation in sheep

2008 ◽  
Vol 199 (5) ◽  
pp. 559.e1-559.e9 ◽  
Author(s):  
Hendrina A. de Boo ◽  
Simona C. Eremia ◽  
Frank H. Bloomfield ◽  
Mark H. Oliver ◽  
Jane E. Harding
Keyword(s):  
Growth Hormone ◽  
Intrauterine Growth Restriction ◽  
Growth Restriction ◽  
Intrauterine Growth

scholarly journals Intrauterine Growth Restriction: New Insight from the Metabolomic Approach

Metabolites ◽  
2019 ◽  
Vol 9 (11) ◽  
pp. 267 ◽  
Author(s):  
Elena Priante ◽  
Giovanna Verlato ◽  
Giuseppe Giordano ◽  
Matteo Stocchero ◽  
Silvia Visentin ◽  
...  
Keyword(s):  
Intrauterine Growth Restriction ◽  
Postnatal Growth ◽  
Growth Restriction ◽  
Clinical Aspects ◽  
Intrauterine Growth ◽  
Thrifty Phenotype ◽  
Thrifty Phenotype Hypothesis ◽  
Uterine Environment ◽  
Short And Long Term

Recognizing intrauterine growth restriction (IUGR) is a matter of great concern because this condition can significantly affect the newborn’s short- and long-term health. Ever since the first suggestion of the “thrifty phenotype hypothesis” in the last decade of the 20th century, a number of studies have confirmed the association between low birth weight and cardiometabolic syndrome later in life. During intrauterine life, the growth-restricted fetus makes a number of hemodynamic, metabolic, and hormonal adjustments to cope with the adverse uterine environment, and these changes may become permanent and irreversible. Despite advances in our knowledge of IUGR newborns, biomarkers capable of identifying this condition early on, and stratifying its severity both pre- and postnatally, are still lacking. We are also still unsure about these babies’ trajectory of postnatal growth and their specific nutritional requirements with a view to preventing, or at least limiting, long-term complications. In this setting, untargeted metabolomics—a relatively new field of ‘-omics’ research—can be a good way to investigate the metabolic perturbations typically associated with IUGR. The aim of this narrative review is to provide a general overview of the pathophysiological and clinical aspects of IUGR, focusing on evidence emerging from metabolomic studies. Though still only preliminary, the reports emerging so far suggest an “early” pattern of glucose intolerance, insulin resistance, catabolite accumulation, and altered amino acid metabolism in IUGR neonates. Further, larger studies are needed to confirm these results and judge their applicability to clinical practice.

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