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Weekly intra-amniotic IGF-1 treatment increases growth of growth-restricted ovine fetuses and up-regulates placental amino acid transporters.

ABSTRACT: Frequent treatment of the growth-restricted (IUGR) ovine fetus with intra-amniotic IGF-1 increases fetal growth. We aimed to determine whether increased growth was maintained with an extended dosing interval and to examine possible mechanisms. Pregnant ewes were allocated to three groups: Control, and two IUGR groups (induced by placental embolization) treated with weekly intra-amniotic injections of either saline (IUGR) or 360 µg IGF-1 (IGF1). IUGR fetuses were hypoxic, hyperuremic, hypoglycemic, and grew more slowly than controls. Placental glucose uptake and SLC2A1 (GLUT2) mRNA levels decreased in IUGR fetuses, but SLC2A3 (GLUT3) and SLC2A4 (GLUT4) levels were unaffected. IGF-1 treatment increased fetal growth rate, did not alter uterine blood flow or placental glucose uptake, and increased placental SLC2A1 and SLC2A4 (but not SLC2A3) mRNA levels compared with saline-treated IUGR animals. Following IGF-1 treatment, placental mRNA levels of isoforms of the system A, y(+), and L amino acid transporters increased 1.3 to 5.0 fold, while the ratio of phosphorylated-mTOR to total mTOR also tended to increase. Weekly intra-amniotic IGF-1 treatment provides a promising avenue for intra-uterine treatment of IUGR babies, and may act via increased fetal substrate supply, up-regulating placental transporters for neutral, cationic, and branched-chain amino acids, possibly via increased activation of the mTOR pathway.

SUBMITTER: Wali JA

PROVIDER: S-EPMC3358268 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Weekly intra-amniotic IGF-1 treatment increases growth of growth-restricted ovine fetuses and up-regulates placental amino acid transporters.

Wali Jibran A JA de Boo Hendrina A HA Derraik José G B JG Phua Hui Hui HH Oliver Mark H MH Bloomfield Frank H FH Harding Jane E JE

PloS one 20120522 5

Frequent treatment of the growth-restricted (IUGR) ovine fetus with intra-amniotic IGF-1 increases fetal growth. We aimed to determine whether increased growth was maintained with an extended dosing interval and to examine possible mechanisms. Pregnant ewes were allocated to three groups: Control, and two IUGR groups (induced by placental embolization) treated with weekly intra-amniotic injections of either saline (IUGR) or 360 µg IGF-1 (IGF1). IUGR fetuses were hypoxic, hyperuremic, hypoglycemi ...[more]

PMID: 22629469

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Project description:BackgroundStillbirth, defined as foetal death ≥20 weeks' gestation, is associated with poor foetal growth and is often attributed to placental abnormalities, which are also associated with poor foetal growth. Evaluating inter-relationships between placental abnormalities, poor foetal growth, and stillbirth may improve our understanding of the underlying mechanisms for some causes of stillbirth.ObjectiveOur primary objective was to determine whether poor foetal growth, operationalised as small for gestational age (SGA), mediates the relationship between placental abnormalities and stillbirth.MethodsWe used data from the Stillbirth Collaborative Research Network study, a population-based case-control study conducted from 2006-2008. Our analysis included 266 stillbirths and 1135 livebirths. We evaluated associations of stillbirth with five types of placental characteristics (developmental disorders, maternal and foetal inflammatory responses, and maternal and foetal circulatory disorders) and examined mediation of these relationships by SGA. We also assessed exposure-mediator interaction. Models were adjusted for maternal age, race/ethnicity, education, body mass index, parity, and smoking status.ResultsAll five placental abnormalities were more prevalent in cases than controls. After adjustment for potential confounders, maternal inflammatory response (odds ratio [OR] 2.58, 95% confidence interval [CI] 1.77, 3.75), maternal circulatory disorders OR 4.14, 95% CI 2.93, 5.84, and foetal circulatory disorders OR 4.58, 95% CI 3.11, 6.74 were strongly associated with stillbirth, and the relationships did not appear to be mediated by SGA status. Associations for developmental disorders and foetal inflammatory response diverged for SGA and non-SGA births, and strong associations were only observed when SGA was not present.ConclusionsFoetal growth did not mediate the relationships between placental abnormalities and stillbirth. The relationships of stillbirth with maternal and foetal circulatory disorders and maternal inflammatory response appear to be independent of poor foetal growth, while developmental disorders and foetal inflammatory response likely interact with foetal growth to affect stillbirth risk.

Project description:BACKGROUND:Intrauterine growth restriction is defined as a fetal weight below the 10th percentile for a given gestational age and can be identified using umbilical artery Doppler velocimetry which is a non-invasive technique. The objective of this study was to determine the perinatal outcome of growth-restricted fetuses with abnormal umbilical artery Doppler study compared to those with normal umbilical artery Doppler waveforms at a tertiary referral hospital in Ethiopia. METHODS:A prospective cohort study was conducted among pregnant mothers with fetal growth restriction admitted for labour and delivery from September 2018-February 2019. The data were entered and analyzed using SPSS version 23. After conducting descriptive analysis, exploring the entire data, and checking for, statistical associations between abnormal umbilical artery Doppler and outcome variables, multiple logistic regression was conducted to control for confounders. RESULTS:A total of 170 pregnant mothers complicated with growth-restricted fetuses were included in the study, among which 133 were with normal umbilical artery Doppler studies and 37 were with abnormal umbilical artery Doppler studies. Four (3%) of normal and 9(24.3%) of abnormal umbilical artery Doppler studies ended in perinatal death-value = 0.001. Twenty (15%) of normal and 24(64.9%) of abnormal umbilical artery Doppler study neonates required neonatal intensive care admission-value = 0.002. Growth restricted fetuses complicated with abnormal Doppler were two times more likely to require neonatal intensive care unit admissions compared to growth-restricted fetuses with normal umbilical artery Doppler flow, P-value 0.002, (OR = 2.059,95%CI 1.449-2.926). Growth restricted fetuses complicated with abnormal Doppler were four times more likely to end in early neonatal death compared to growth-restricted fetuses with normal umbilical artery Doppler flow, P-value 0.001, (OR = 4.136, 95%CI 3.423-4.998). However, the study is unmatched and there is a possibility of gestational age confounding the result and should be seen with the context of preterm morbidity and mortality. CONCLUSION:The abnormal umbilical artery Doppler waveform is associated with cesarean section delivery, neonatal intensive care unit admission, respiratory distress syndrome, neonatal sepsis, neonatal hyperbilirubinemia, and early neonatal death compared to normal umbilical artery Doppler flow.

Dataset Information

Weekly intra-amniotic IGF-1 treatment increases growth of growth-restricted ovine fetuses and up-regulates placental amino acid transporters.

Publications

Weekly intra-amniotic IGF-1 treatment increases growth of growth-restricted ovine fetuses and up-regulates placental amino acid transporters.

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