Abstract 192: Intra-Placental Gene Transfer of Human Insulin-Like Growth Factor-1 Reprograms Fetal Predisposition to Obesity in Intra-uterine Growth Restriction

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Khaled R Omar ◽  
Helen Jones ◽  
Swathi Balaji ◽  
Young Nam ◽  
Kitcheol Kil ◽  
...  

We have shown that intra placental adenoviral mediated gene transfer of (Ad hIGF1) corrects birth weight in a new surgical mouse IUGR model. Evidence shows that IUGR offspring are predisposed to increased risk of adult diseases. We hypothesized that intraplacental Ad hIGF1 not only restores birth weight in this IUGR model but prevents adult onset obesity through fetal reprogramming Laparotomy was done at day 18 on time pregnant C57BL/6J mice, divided into 3 groups. Control: Sham operated; IUGR: birth weight <10% for gestational age; Treated: IUGR+IGF1; n= 16. Pups were delivered on day 20, cross fostered to surrogate CD1 mice, sorted by gender at 4 weeks and followed up to 24 weeks. Body weight, fat pad weight, fasting serum leptin and food consumption were measured. Data analyzed by Chi-square or ANOVA Compared to SHAM, IUGR significantly reduced birth weight, restored to normal in IUGR+IGF-1 (1.12± .1vs 0.9± .1 vs 1.09± .1 g, p= .001). At 8 weeks, IUGR achieved mean body weight equivalent to SHAM and IUGR+IGF-1. By week 21, regardless of sex, IUGR significantly increased weight (obesity) compared to sham and IUGR+IGF-1 (fig A). Total fad pad weights were significantly higher in IUGR compared to SHAM but were restored to normal in IUGR+IGF1 (fig B). IUGR significantly increased fasting serum leptin, compared to Sham and restored to normal in IUGR+IGF1 ( .6± .4vs 5.7± 1.1 vs .8± .4 pg/ug, p= .01). No difference in food consumption amongst the groups Intra placental gene transfer of Ad hIGF1 corrects birth weight in IUGR mice model and attenuates the risk of postnatal obesity, This support the concept that in utero reprogramming of fetal predisposition to obesity is a novel approch to treatment of IUGR.

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Khaled R Omar ◽  
Helen Jones ◽  
Swathi Balaji ◽  
Young Nam ◽  
Kitcheol Kil ◽  
...  

We have shown that mesenteric uterine artery ligation in mice significantly reduces fetal birth weight (IUGR) and increases risk of adult onset of hypertension and obesity, which are all reversed by adenoviral mediated hIGF1 (Ad hIGF1) intraplacental gene transfer. We hypothesized that intraplacental Ad hIGF1 in IUGR mice prevents adult onset of obesity even when challenged with environmental stress as fat diet. Laparotomy was done at day 18 on pregnant C57BL/6J mice and divided into 3 groups (n= 16). Control: Sham operated; IUGR: birth weight <10% for gestational age; Treated: IUGR+IGF-1. Pups were delivered on day 20, cross fostered to CD1 mice, sorted by gender at 4 weeks. At 8 weeks, high fat diet (45% fat) was introduced and mice were followed up to 24 weeks. Body weight, fat pad, fasting serum leptin and food consumption were measured. Data analyzed by Chi-square or ANOVA and stratified by sex Compared to sham, IUGR significantly decreases birth weight, which is restored to normal in IUGR+IGF-1(1.12± .1 vs 0.9± .1 vs 1.09± .1 g, p=0.001). Mean body weight differences among the groups persist till 8 weeks. By 14 weeks, male IUGR mice had significant weight gain(obese) compared to sham and treatment groups (fig A). Same trend was seen in female IUGR at 18 weeks. Total fad pad weights were significantly higher in IUGR compared to SHAM, restored to normal in IUGR+IGF-1 (fig B). Compared to sham, IUGR significantly increases fasting serum leptin, restored to normal in IUGR+IGF-1 (2.4±0.2 vs 7.9±1.5 vs 3.4±0.4 pg/ug, p= .01) Our results demonstrate that intraplacental gene transfer with Ad-hIGF-1 reprograms the IUGR fetus and attenuates the risk of adult onset of obesity under environmental stress


2021 ◽  
Vol 10 (4) ◽  
pp. 643
Author(s):  
Veronica Giorgione ◽  
Corey Briffa ◽  
Carolina Di Fabrizio ◽  
Rohan Bhate ◽  
Asma Khalil

Twin pregnancies are commonly assessed using singleton growth and birth weight reference charts. This practice has led to a significant number of twins labelled as small for gestational age (SGA), causing unnecessary interventions and increased risk of iatrogenic preterm birth. However, the use of twin-specific charts remains controversial. This study aims to assess whether twin-specific estimated fetal weight (EFW) and birth weight (BW) charts are more predictive of adverse outcomes compared to singleton charts. Centiles of EFW and BW were calculated using previously published singleton and twin charts. Categorical data were compared using Chi-square or McNemar tests. The study included 1740 twin pregnancies, with the following perinatal adverse outcomes recorded: perinatal death, preterm birth <34 weeks, hypertensive disorders of pregnancy (HDP) and admissions to the neonatal unit (NNU). Twin-specific charts identified prenatally and postnatally a smaller proportion of infants as SGA compared to singleton charts. However, twin charts showed a higher percentage of adverse neonatal outcomes in SGA infants than singleton charts. For example, perinatal death (SGA 7.2% vs. appropriate for gestational age (AGA) 2%, p < 0.0001), preterm birth <34 weeks (SGA 42.1% vs. AGA 16.4%, p < 0.0001), HDP (SGA 21.2% vs. AGA 13.5%, p = 0.015) and NNU admissions (SGA 69% vs. AGA 24%, p < 0.0001), when compared to singleton charts (perinatal death: SGA 2% vs. AGA 1%, p = 0.029), preterm birth <34 weeks: (SGA 20.6% vs. AGA 17.4%, p = 0.020), NNU admission: (SGA 34.5% vs. AGA 23.9%, p < 0.000). There was no significant association between HDP and SGA using the singleton charts (p = 0.696). In SGA infants, according to the twin charts, the incidence of abnormal umbilical artery Doppler was significantly more common than in SGA using the singleton chart (27.0% vs. 8.1%, p < 0.001). In conclusion, singleton charts misclassify a large number of twins as at risk of fetal growth restriction. The evidence suggests that the following twin-specific charts could reduce unnecessary medical interventions prenatally and postnatally.


Author(s):  
Aneta Weres ◽  
Joanna Baran ◽  
Ewelina Czenczek-Lewandowska ◽  
Justyna Leszczak ◽  
Artur Mazur

Background: A child’s birth parameters not only enable assessment of intrauterine growth but are also helpful in identifying children at risk of developmental defects or diseases occurring in adulthood. Studies show that children born with a body weight that is small for their gestational age (SGA) are at a greater risk of hypertension though the inverse relation between excessive birth weight and the risk of primary hypertension in children is discussed less frequently. Purpose: To assess the impact of both birth weight and length on hypertension occurring in children aged 3–15 years. Methods: A total of 1000 children attending randomly selected primary schools and kindergartens were examined. Ultimately, the analyses took into account n = 747 children aged 4–15; 52.6% boys and 47.4% girls. The children’s body height and weight were measured; their blood pressure was examined using the oscillometric method. Information on perinatal measurements was retrieved from the children’s personal health records. Results: Compared to the children with small for gestational age (SGA) birth weight, the children with appropriate for gestational age birth weight (AGA) (odds ratio (OR) 1.31; 95% confidence interval (CI) 0.64–2.65) present greater risk for primary hypertension. Infants born with excessive body weight >4000 g irrespective of gestational age, compared to infants born with normal body weight, show increased risk of primary hypertension (OR 1.19; 95% CI 0.68–2.06). Higher risk of hypertension is observed in infants born with greater body length (OR 1.03; 95% CI 0.97–1.08). Conclusions: The problem of hypertension may also affect children with birth weight appropriate for gestational age. The prevalence of hypertension in children with AGA birth weight decreases with age. Birth length can be a potential risk factor for hypertension in children and adolescents.


2013 ◽  
Vol 4 (1) ◽  
pp. 77-88
Author(s):  
Fitri

Stunting is very short state of body so that the deficit exceeded -2 SD below the median length or height. Stunting is a public health issue because it deals with an increased risk of morbidity and mortality, delayed motor development, and mental growth retardation. The general objective of research is to know the dominant factor related with stunting in infants (12-59 months) in Sumatra in 2010. This study uses cross sectional research design and quantitative method with 3126 toddlers sample. Processing and analyzing data using chi square test (bivariate) and multiple logistic regression (multivariate). The analysis showed that based on the index TB/U, stunting toddlers as much as 37.5% and 62.5% of normal. The results of chi square test showed significant relationship between stunting with birth weight, energy intake, protein intake, sex, maternal education, area of residence and economic status of families. The results of multivariate analysis showed the birth weight variable is the most dominant factor associated with stunting after being controlled with sex, area of residence and economic status of families variables.


2019 ◽  
Vol 4 (1) ◽  
pp. 44
Author(s):  
Paramitha Amelia Kusumawardani ◽  
Cholifah Cholifah Cholifah

Babies born with a body weight of less than 2500 grams or up to 2499 grams are one of the risk factors that cause death in infants, especially the perinatal period. Problems that often occur are setting the temperature that is still low and has a weak immune system and the process of forming the immune system that is not perfect so that the range of infection. Not all babies with a birth weight of less than 2,500 grams get health services using advanced technology because of financial constraints in care, geographical factors or areas of residence, transportation, and communication such as the use of incubators. The kangaroo treatment method is a method of contacting skin from skin (skin to skin) which is done directly by placing the baby on the mother's chest. The method of research carried out analytic research with a population of all mothers who have given birth either by normal or SC deliveries whose babies experience low body weight below less than 2500 grams (LBW) in SitiKhodijahSepanjang Hospital, which is the subject of research. Most of the mothers who had LBW babies had a positive attitude that was equal to 10 (66.7%) and most of the mothers carried out the kangaroo method correctly by 9 mothers (60%). This is also evidenced by the results of the Chi-Square test P = 0.005 <α = 0.05 so that H0 is rejected which means there is a relationship between the attitude of the mother and the implementation of the kangaroo method in low birth weight babies so that the community and health workers are expected to implement the kangaroo method in infants low birth weight both in health care and at home. 


2017 ◽  
Vol 8 (5) ◽  
pp. 618-625 ◽  
Author(s):  
S. Vranas ◽  
G. K. Heinemann ◽  
H. Liu ◽  
M. J. De Blasio ◽  
J. A. Owens ◽  
...  

Low birth weight is associated with increased risk of cardiovascular disease in adulthood. Intrauterine growth restriction (IUGR) hearts have fewer CMs in early postnatal life, which may impair postnatal cardiovascular function and hence, explain increased disease risk, but whether the cardiomyocyte deficit persists to adult life is unknown. We therefore studied the effects of experimentally induced placental restriction (PR) on cardiac outcomes in young adult sheep. Heart size, cardiomyocyte number, nuclearity and size were measured in control (n=5) and PR (n=5) male sheep at 1 year of age. PR lambs were 36% lighter at birth (P=0.007), had 38% faster neonatal relative growth rates (P=0.001) and had 21% lighter heart weights relative to body weight as adults (P=0.024) than control lambs. Cardiomyocyte number, nuclearity and size in the left ventricle did not differ between control and PR adults; hearts of both groups contained cardiomyocytes (CM) with between one and four nuclei. Overall, cardiomyocyte number in the adult left ventricle correlated positively with birth weight but not with adult weight. This study is the first to demonstrate that intrauterine growth directly influences the complement of CM in the adult heart. Cardiomyocyte size was not correlated with cardiomyocyte number or birth weight. Our results suggest that body weight at birth affects lifelong cardiac functional reserve. We hypothesise that decreased cardiomyocyte number of low birth weight individuals may impair their capacity to adapt to additional challenges such as obesity and ageing.


2005 ◽  
Vol 289 (1) ◽  
pp. E68-E74 ◽  
Author(s):  
Michael Koban ◽  
Kevin L. Swinson

A cluster of unique pathologies progressively develops during chronic total- or rapid eye movement-sleep deprivation (REM-SD) of rats. Two prominent and readily observed symptoms are hyperphagia and decline in body weight. For body weight to be lost despite a severalfold increase in food consumption suggests that SD elevates metabolism as the subject enters a state of negative energy balance. To test the hypothesis that mediation of this hypermetabolism involves increased gene expression of uncoupling protein-1 (UCP1), which dissipates the thermodynamic energy of the mitochondrial proton-motive force as heat instead of ATP formation in brown adipose tissue (BAT), we 1) established the time course and magnitude of change in metabolism by measuring oxygen consumption, 2) estimated change in UCP1 gene expression in BAT by RT-PCR and Western blot, and 3) assayed serum leptin because of its role in regulating energy balance and food intake. REM-SD of male Sprague-Dawley rats was enforced for 20 days with the platform (flowerpot) method, wherein muscle atonia during REM sleep causes contact with surrounding water and awakens it. By day 20, rats more than doubled food consumption while losing ∼11% of body weight; metabolism rose to 166% of baseline with substantial increases in UCP1 mRNA and immunoreactive UCP1 over controls; serum leptin decreased and remained suppressed. The decline in leptin is consistent with the hyperphagic response, and we conclude that one of the mediators of elevated metabolism during prolonged REM-SD is increased gene expression of UCP1 in BAT.


2020 ◽  
Vol 98 (12) ◽  
Author(s):  
Tom Flinn ◽  
Niki L McCarthy ◽  
Alyce M Swinbourne ◽  
Kathryn L Gatford ◽  
Alice C Weaver ◽  
...  

Abstract High preweaning mortality rates continue to limit sheep production globally, constituting a major economic and welfare concern. Greater losses in twin lambs (≥30%) compared with singletons (≥10%) are attributed primarily to lower birth weight and increased risk of intrapartum hypoxia, leading to impairment of thermoregulation, neuromotor activity, and maternal bonding behavior. Previous intensive studies demonstrated that supplementing pregnant ewes with melatonin reduced the adverse effects of fetal growth restriction and perinatal hypoxia on the neonatal brain via increased umbilical blood flow, placental efficiency, and antioxidant actions. The current study examined the effects of supplementing pregnant ewes with melatonin on lamb survival, birth weight, and behavior under intensive conditions. From gestational day (gD) 80 until parturition, pregnant singleton and twin-bearing ewes were supplemented with melatonin via a 2-mg capsule fed daily (Mel-FED, n = 61) or 18 mg subcutaneous implant (Regulin), with one implant administered at gD80 and another at gD125 (Mel-IMP, n = 60). Control ewes received no supplementation (CTL, n = 60). Ewes and lambs were monitored via video throughout parturition. Postpartum measures were taken from lambs at 4 and 24 h (live weight [LW], rectal temperature, serum immunoglobulin G, and latency to stand and suck after birth) and LW at 72 h, 7 d, marking (49.7 ± 0.2 d), and weaning (124.2 ± 0.8 d). Chi-square analysis was used to compare lamb survival between treatment groups. There were no treatment effects on singleton lamb survival. Melatonin supplementation tended to increase the proportion of twin lambs surviving from birth to weaning (Mel-FED = 85.5%; Mel-IMP = 85.9%; CTL = 72.9%; each P &lt; 0.1). Survival of first-born twins did not differ between treatment (each ~90%, P = 0.745) but within second-born twins, survival of Mel-FED was greater than CTL (81.6 vs. 57.1%, P = 0.023), and Mel-IMP (78.1%) tended to be greater than CTL (P = 0.068). Similarly, in second-born twins exposed to prolonged parturition (≥ 90 min), survival of lambs from Mel-FED ewes was greater than CTL (86.7% vs. 42.9%, P = 0.032), while Mel-IMP was intermediate (66.7%). These data suggest that the neuroprotective actions of melatonin may improve twin lamb survival by increasing tolerance of prolonged parturition and provide a sound basis for continued testing in extensively managed sheep flocks.


1970 ◽  
Vol 25 (1) ◽  
pp. 9-13
Author(s):  
S Jahan ◽  
TR Das ◽  
KB Biswas

Background and Aims: Cord blood leptin may reflect the leptinemic status of a newborn at birth more accurately than the leptin values of blood collected from other sites. The present study was undertaken to determine the relationship of cord serum leptin concentration at birth with neonatal and maternal anthropometric parameters. Materials and Methods: Blood was taken from the umbilical cord of the babies at delivery. Maternal anthropometric measurements were recorded at admission for delivery. Neonatal anthropometric measurements were recorded within 48 hours after delivery. Linear regression analysis was used to explore the relationship between cord serum leptin concentration and anthropometric parameters of the baby and the mother. Both Serum leptin and serum C-peptide levels were measured by chemiluminescence-based ELISA method. Results: The leptin concentration (ng/ml, mean±SD) in cord blood was 39.13±14.44. Cord leptin levels correlated with birth weight (r=0.673, p<0.0001), ponderal index (r=0.732, p<0.0001) but it did not correlate with maternal body mass index, gestational age (r=0.135, p=0.349) at delivery or cord serum C-peptide concentration (r=-0.049, p=0.735) or placental weight (r=0.203, p=0.157). Conclusion: There are associations between cord leptin concentration at delivery and birth weight, ponderal index (PI) of the babies but not body mass index (BMI) of the mothers. High leptin levels of the baby could represent an important feedback modulator of substrate supply and subsequently for adipose tissue status during late gestation. (J Bangladesh Coll Phys Surg 2007; 25 : 9-13)


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