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Sustained maternal inflammation during the early third-trimester yields intrauterine growth restriction, impaired skeletal muscle glucose metabolism, and diminished ?-cell function in fetal sheep1,2.

ABSTRACT: Maternal inflammation causes fetal intrauterine growth restriction (IUGR), but its impact on fetal metabolism is not known. Thus, our objective was to determine the impact of sustained maternal inflammation in late gestation on fetal inflammation, skeletal muscle glucose metabolism, and insulin secretion. Pregnant ewes were injected every third day from the 100th to 112th day of gestation (term = 150 d) with saline (controls) or lipopolysaccharide (LPS) to induce maternal inflammation and IUGR (MI-IUGR). Fetal femoral blood vessels were catheterized on day 118 to assess ?-cell function on day 123, hindlimb glucose metabolic rates on day 124, and daily blood parameters from days 120 to 125. Fetal muscle was isolated on day 125 to assess ex vivo glucose metabolism. Injection of LPS increased (P < 0.05) rectal temperatures, circulating white blood cells, and plasma tumor necrosis factor ? (TNF?) concentrations in MI-IUGR ewes. Maternal leukocytes remained elevated (P < 0.05) and TNF? tended to remain elevated (P < 0.10) compared with controls almost 2 wk after the final LPS injection. Total white blood cells, monocytes, granulocytes, and TNF? were also greater (P < 0.05) in MI-IUGR fetuses than controls over this period. MI-IUGR fetuses had reduced (P < 0.05) blood O2 partial pressures and greater (P < 0.05) maternofetal O2 gradients, but blood glucose and maternofetal glucose gradients did not differ from controls. Basal and glucose-stimulated insulin secretion were reduced (P < 0.05) by 32% and 42%, respectively, in MI-IUGR fetuses. In vivo hindlimb glucose oxidation did not differ between groups under resting conditions but was 47% less (P < 0.05) in MI-IUGR fetuses than controls during hyperinsulinemia. Hindlimb glucose utilization did not differ between fetal groups. At day 125, MI-IUGR fetuses were 22% lighter (P < 0.05) than controls and tended to have greater (P < 0.10) brain/BW ratios. Ex vivo skeletal muscle glucose oxidation did not differ between groups in basal media but was less (P < 0.05) for MI-IUGR fetuses in insulin-spiked media. Glucose uptake rates and phosphorylated-to-total Akt ratios were less (P < 0.05) in muscle from MI-IUGR fetuses than controls regardless of media. We conclude that maternal inflammation leads to fetal inflammation, reduced ?-cell function, and impaired skeletal muscle glucose metabolism that persists after maternal inflammation ceases. Moreover, fetal inflammation may represent a target for improving metabolic dysfunction in IUGR fetuses.

SUBMITTER: Cadaret CN

PROVIDER: S-EPMC6915216 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Sustained maternal inflammation during the early third-trimester yields intrauterine growth restriction, impaired skeletal muscle glucose metabolism, and diminished β-cell function in fetal sheep1,2.

Cadaret Caitlin N CN Merrick Elena M EM Barnes Taylor L TL Beede Kristin A KA Posont Robert J RJ Petersen Jessica L JL Yates Dustin T DT

Journal of animal science 20191201 12

Maternal inflammation causes fetal intrauterine growth restriction (IUGR), but its impact on fetal metabolism is not known. Thus, our objective was to determine the impact of sustained maternal inflammation in late gestation on fetal inflammation, skeletal muscle glucose metabolism, and insulin secretion. Pregnant ewes were injected every third day from the 100th to 112th day of gestation (term = 150 d) with saline (controls) or lipopolysaccharide (LPS) to induce maternal inflammation and IUGR ( ...[more]

PMID: 31616931

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Project description:OBJECTIVE:To estimate the effect of inadequate maternal weight gain in the third trimester on the risk of intrauterine growth restriction (IUGR) in rural Bangladesh. METHODS:This study analyzed data from 1,463 mother-infant pairs in Matlab, Bangladesh which were available through the electronic databases of Matlab Health and Demographic Surveillance System and Matlab hospital of the International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b). All the mothers were admitted to Matlab hospital for childbirth from January 2012 to December 2014, and they had singleton live births at term. Third-trimester weight gain (kg) was calculated by subtracting the estimated weight at the end of the second trimester from the weight taken before childbirth. Inadequate third-trimester weight gain was defined as 4 kg or less irrespective of pre-gravid nutritional status. IUGR was defined as a birth weight below 2500 g in full-term newborns (LBW-Term), and a birth weight for gestational age and infant sex less than the 10th percentile (SGA-10th) and 2 standard deviations below the mean birth weight (SGA-2SD) based on the international newborn standards from the INTERGROWTH-21st project. Multivariable logistic regression models were fitted to determine the independent effect of inadequate weight gain in the third trimester on the risk of IUGR. RESULTS:A total of 824 (56.3%) women experienced inadequate weight gain in the third trimester of pregnancy. In this study, 215 (14.7%), 573 (39.2%) and 220 (15.0%) infants were born as LBW-Term, SGA-10th and SGA-2SD, respectively. In the multivariable logistic regression models, compared to adequate weight gain in the third-trimester, the odds ratios (OR) for LBW-Term, SGA-10th and SGA-2SD for inadequate weight gain were 1.8 (95% CI: 1.3, 2.5; p < 0.001), 1.4 (95% CI: 1.1, 1.8; p = 0.002) and 1.8 (95% CI: 1.3, 2.4; p = 0.001), respectively. CONCLUSIONS:Both inadequate third-trimester weight gain and IUGR are prevailing public health concerns in rural Bangladesh. Inadequate weight gain in the third trimester substantially increased the risk of IUGR. Public health programs focusing on the promotion of adequate weight gain in the third trimester of pregnancy with an ultimate aim to decrease IUGR should be implemented.

Project description:ObjectiveTo estimate the risk of adverse perinatal outcomes among women with isolated fetal growth restriction from 17 to 22 weeks of gestation.MethodsThis was a retrospective cohort study of all singleton, nonanomalous pregnancies undergoing ultrasonography to assess fetal anatomy between 17 and 22 weeks of gestation at a single center from 2010 to 2014. After excluding patients with fetal structural malformations, chromosomal abnormalities, or identified infectious etiologies, we compared perinatal outcomes between pregnancies with and without fetal growth restriction, defined as estimated fetal weight less than the 10th percentile for gestational age. Our primary outcome was small for gestational age (SGA) at birth, defined as birth weight less than the 10th percentile. Secondary outcomes included preterm delivery at less than 37 and less than 28 weeks of gestation, preeclampsia, abruption, stillbirth, neonatal death, neonatal intensive care unit admission, intraventricular hemorrhage, need for respiratory support, and necrotizing enterocolitis.ResultsOf 12,783 eligible patients, 355 (2.8%) had early second-trimester fetal growth restriction. Risk factors for growth restriction were African American race and tobacco use. Early second-trimester growth restriction was associated with a more than fivefold increase in risk of SGA at birth (36.9% compared with 9.1%, adjusted odds ratio [OR] 5.5, 95% CI 4.3-7.0), stillbirth (2.5% compared with 0.4%, OR 6.2, 95% CI 2.7-12.8), and neonatal death (1.4% compared with 0.3%, OR 5.2, 95% CI 1.6-13.5). Rates of indicated preterm birth at less than 37 weeks of gestation (7.3% compared with 3.3%, OR 2.3, 95% CI 1.5-3.5) and less than 28 weeks of gestation (2.5% compared with 0.2%, OR 10.8, 95% CI 4.5-23.4), neonatal need for respiratory support (16.9% compared with 7.8%, adjusted OR 1.6, 95% CI 1.1-2.2), and necrotizing enterocolitis (1.4% compared with 0.2%, OR 7.7, 95% CI 2.3-20.9) were also significantly higher for those with growth restriction. Rates of preeclampsia, abruption, and other neonatal outcomes were not significantly different.ConclusionAlthough fetal growth restriction in the early second trimester occurred in less than 3% of our cohort and most of those with isolated growth restriction did not have adverse outcomes, it is a strong risk factor for SGA, stillbirth, neonatal death, and indicated preterm birth.

Dataset Information

Sustained maternal inflammation during the early third-trimester yields intrauterine growth restriction, impaired skeletal muscle glucose metabolism, and diminished ?-cell function in fetal sheep1,2.

Publications

Sustained maternal inflammation during the early third-trimester yields intrauterine growth restriction, impaired skeletal muscle glucose metabolism, and diminished β-cell function in fetal sheep1,2.

Similar Datasets

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