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
2015 ◽  
Vol 6 (6) ◽  
pp. 558-572 ◽  
Author(s):  
D. J. Carr ◽  
J. S. Milne ◽  
R. P. Aitken ◽  
C. L. Adam ◽  
J. M. Wallace

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.


Diagnostics ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 749
Author(s):  
Sarah C. Grünert ◽  
Uta Matysiak ◽  
Franka Hodde ◽  
Gunda Ruzaike ◽  
Ekkehart Lausch ◽  
...  

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.


2019 ◽  
Vol 10 (1) ◽  
pp. 21-28
Author(s):  
Kristina F. Islamova ◽  
Alexandra V. Kaplina ◽  
Nina N. Shabalova ◽  
Elena V. Plotnikova ◽  
Kseniya A. Medinskaya

Relevance of the research. Intrauterine growth restriction in children is associated with an increased risk of insulin resistance and non-insulin-dependent diabetes mellitus later in life. The influence of type of intrauterine growth restriction and the mechanisms of insulin resistance are still unknown; the role of catch-up growth in this process is controversial. The aim of the study was to identify insulin resistance in children with different types of intrauterine growth restriction and to analyze the role of catch-up growth in this process. Materials and methods. The research involved 95 newborns, which were divided into groups based on birth weight and length: 60 newborns with intrauterine growth restriction (group I – 31 with asymmetrical intrauterine growth restriction; group II – 29 with symmetrical intrauterine growth restriction) and control group (group III) – 35 newborns without intrauterine growth restriction. Children also were divided into groups according to the presence of catch-up growth to 3 months old. The levels of insulin, insulin-like growth factor-1, growth hormone were measured in cord blood at birth and in blood serum at 3 months old. Glucose levels were measured in serum and insulin resistance index “the homeostasis model assessment of insulin resistance” (HOMA-IR) was calculated in children at 3 months. Results. The children with intrauterine growth restrictioncompared to control group had significantly lower levels of insulin-like growth factor-1 in cord blood. The differences between types of intrauterine growth restrictionhave been observed: children with symmetrical intrauterine growth restriction had higher levels of growth hormone, insulin and HOMA-IR then in asymmetrical one. Correlations between insulin and glucose in children with symmetrical intrauterine growth restriction were absent unlike to asymmetrical intrauterine growth restriction (+0.61). The negative role of catch-up growth in insulin resistance development has been defined: it was related to hyperinsulinemia and increased the frequency of insulin resistance in children either in asymmetrical or in symmetrical intrauterine growth restriction, but more in symmetrical one. Conclusion. Children with symmetrical intrauterine growth restriction especially with catch-up growth are at the highest risk of metabolic syndrome development in later life and require increased monitoring by pediatricians and endocrinologists.


2019 ◽  
pp. 50-54
Author(s):  
V.O. Golyanovskiy ◽  
◽  
Ye.O. Didyk ◽  

Pregnant women with intrauterine growth restriction (IUGR) have an increased risk of adverse perinatal and long-term complications compared with the birth of children with normal body weight. Thus, IUGR is one of the main challenges for the global health system, especially in poor and developing countries. Morpho-functional studies of the placentas help in determining the causes of IUGR, and therefore, timely prevent complications in pregnant women with IUGR. The objective: The purpose of this study is to investigate various morphometric and pathomorphological changes in the placenta, including inflammatory, in cases of IUGR, and to establish a correlation of these results with the etiology and complications for the fetus. Materials and methods. In the current study, 54 placentas of the fetuses with IUGR (the main group) were compared with 50 placentas of the fetuses with normal development (control group). The criteria for the inclusion of IUGR were gestational age more than 30 weeks and all fetuses with a weight less than 10th percentile for this period of pregnancy. The placenta material was studied pathomorphologically with laboratory screening for infection and inflammation. Similarly, the results were determined for placentas of the fetuses with normal development compared to placentas with IUGR. Results. The placenta study showed the presence of calcification in the case of IUGR, as well as in the case of prolonged pregnancy. However, calcification of the placenta in the case of IUGR was more progressive compared with placenta in the normal pregnancy. In addition, the presence of intrauterine infection and inflammation was observed, which could also lead to an adverse outcome for the further progression of pregnancy with IUGR. Conclusion. A comparative macro- and microscopic pathomorphological study of the placentas in the two groups has shown a significant increase in the pathological changes in all the anatomical structures of the fetuses with IUGR. Key words: Intrauterine growth restriction (IUGR), fetal weight, pathomorphological changes of the placenta.


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