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Maternal Creatine Supplementation during Pregnancy Prevents Long-Term Changes in Diaphragm Muscle Structure and Function after Birth Asphyxia.

ABSTRACT: Using a model of birth asphyxia, we previously reported significant structural and functional deficits in the diaphragm muscle in spiny mice, deficits that are prevented by supplementing the maternal diet with 5% creatine from mid-pregnancy. The long-term effects of this exposure are unknown. Pregnant spiny mice were fed control or 5% creatine-supplemented diet for the second half of pregnancy, and fetuses were delivered by caesarean section with or without 7.5 min of in-utero asphyxia. Surviving pups were raised by a cross-foster dam until 33±2 days of age when they were euthanized to obtain the diaphragm muscle for ex-vivo study of twitch tension and muscle fatigue, and for structural and enzymatic analyses. Functional analysis of the diaphragm revealed no differences in single twitch contractile parameters between any groups. However, muscle fatigue, induced by stimulation of diaphragm strips with a train of pulses (330 ms train/sec, 40 Hz) for 300 sec, was significantly greater for asphyxia pups compared with controls (p<0.05), and this did not occur in diaphragms of creatine + asphyxia pups. Birth asphyxia resulted in a significant increase in the proportion of glycolytic, fast-twitch fibres and a reduction in oxidative capacity of Type I and IIb fibres in male offspring, as well as reduced cross-sectional area of all muscle fibre types (Type I, IIa, IIb/d) in both males and females at 33 days of age. None of these changes were observed in creatine + asphyxia animals. Thus, the changes in diaphragm fatigue and structure induced by birth asphyxia persist long-term but are prevented by maternal creatine supplementation.

SUBMITTER: LaRosa DA

PROVIDER: S-EPMC4773130 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Maternal Creatine Supplementation during Pregnancy Prevents Long-Term Changes in Diaphragm Muscle Structure and Function after Birth Asphyxia.

LaRosa Domenic A DA Ellery Stacey J SJ Parkington Helena C HC Snow Rod J RJ Walker David W DW Dickinson Hayley H

PloS one 20160301 3

Using a model of birth asphyxia, we previously reported significant structural and functional deficits in the diaphragm muscle in spiny mice, deficits that are prevented by supplementing the maternal diet with 5% creatine from mid-pregnancy. The long-term effects of this exposure are unknown. Pregnant spiny mice were fed control or 5% creatine-supplemented diet for the second half of pregnancy, and fetuses were delivered by caesarean section with or without 7.5 min of in-utero asphyxia. Survivin ...[more]

PMID: 26930669

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Project description:OBJECTIVES/BACKGROUND: Given the widespread prevalence of micronutrient deficiencies in developing countries, supplementation with multiple micronutrients rather than iron-folate alone, could be of potential benefit to the mother and the fetus. These benefits could relate to prevention of maternal complications and reduction in other adverse pregnancy outcomes such as small-for-gestational age (SGA) births, low birth weight, stillbirths, perinatal and neonatal mortality. This review evaluates the evidence of the impact of multiple micronutrient supplements during pregnancy, in comparison with standard iron-folate supplements, on specific maternal and pregnancy outcomes of relevance to the Lives Saved Tool (LiST). DATA SOURCES/REVIEW METHODS: A systematic review of randomized controlled trials was conducted. Search engines used were PubMed, the Cochrane Library, the WHO regional databases and hand search of bibliographies. A standardized data abstraction and Child Health Epidemiology Reference (CHERG) adaptation of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) technique were used for data abstraction and overall quality of evidence. Meta-analyses were performed to calculate summary estimates of utility to the LiST model for the specified outcome of incidence of SGA births. We also evaluated the potential impact of multiple micronutrients on neonatal mortality according to the proportion of deliveries occurring in facilities (using a threshold of 60% to indicate functionality of health systems for skilled births). RESULTS: We included 17 studies for detailed data abstraction. There was no significant benefit of multiple micronutrients as compared to iron folate on maternal anemia in third trimester [Relative risk (RR) = 1.03; 95% confidence interval (CI): 0.87 - 1.22 (random model)]. Our analysis, however, showed a significant reduction in SGA by 9% [RR = 0.91; 95% CI: 0.86 - 0.96 (fixed model)]. In the fixed model, the SGA outcome remained significant only in women with mean body mass index (BMI) ? 22 kg/m2. There was an increased risk of neonatal mortality in studies with majority of births at home [RR = 1.47, 95% CI: 1.13-1.92]; such an effect was not evident where ? 60% of births occurred in facility settings [RR = 0.94, 95% CI: 0.81-1.09]. Overall there was no increase in the risk of neonatal mortality [RR = 1.05, 95% CI: 0.92 - 1.19 (fixed model)]. CONCLUSION: This review provides evidence of a significant benefit of MMN supplementation during pregnancy on reducing SGA births as compared to iron-folate, with no significant increase in the risk of neonatal mortality in populations where skilled birth care is available and majority of births take place in facilities. Given comparability of impacts on maternal anemia, the decision to replace iron-folate with multiple micronutrients during pregnancy may be taken in the context of available services in health systems and birth outcomes monitored.

Project description:BackgroundMaternal overweight and obesity are associated with increased risks of birth-asphyxia-related outcomes, but the mechanisms are unclear. If a change of exposure (i.e., maternal body mass index [BMI]) over time influences risks, this would be consistent with a causal relationship between maternal BMI and offspring risks. Our objective was to investigate associations between changes in maternal BMI between consecutive pregnancies and risks of birth-asphyxia-related outcomes in the second offspring born at term.Methods and findingsThis study was a prospective population-based cohort study that included 526,435 second-born term (?37 wk) infants of mothers with two consecutive live singleton term births in Sweden between January 1992 and December 2012. We estimated associations between the difference in maternal BMI between the first and second pregnancy and risks of low Apgar score (0-6) at 5 min, neonatal seizures, and meconium aspiration in the second-born offspring. Odds ratios (ORs) were adjusted for BMI at first pregnancy, maternal height, maternal age at second delivery, smoking, education, mother´s country of birth, inter-pregnancy interval, and year of second delivery. Analyses were also stratified by BMI (<25 versus ?25 kg/m2) in the first pregnancy. Risks of low Apgar score, neonatal seizures, and meconium aspiration increased with inter-pregnancy weight gain. Compared with offspring of mothers with stable weight (BMI change of -1 to <1 kg/m2), the adjusted OR for a low Apgar score in the offspring of mothers with a BMI change of 4 kg/m2 or more was 1.33 (95% CI 1.12-1.58). The corresponding risks for neonatal seizures and meconium aspiration were 1.42 (95% CI 1.00-2.02) and 1.78 (95% CI 1.19-2.68), respectively. The increased risk of neonatal seizures related to weight gain appeared to be restricted to mothers with BMI < 25 kg/m2 in the first pregnancy. A study limitation was the lack of data on the effects of obstetric interventions and neonatal resuscitation efforts.ConclusionsRisks of birth-asphyxia-related outcomes increased with maternal weight gain between pregnancies. Preventing weight gain before and in between pregnancies may improve neonatal health.

Project description:In a double-blind, crossover, randomized and placebo-controlled trial; 28 men and women ingested a placebo (PLA), 3 g of creatine nitrate (CNL), and 6 g of creatine nitrate (CNH) for 6 days. Participants repeated the experiment with the alternate supplements after a 7-day washout. Hemodynamic responses to a postural challenge, fasting blood samples, and bench press, leg press, and cycling time trial performance and recovery were assessed. Data were analyzed by univariate, multivariate, and repeated measures general linear models (GLM). No significant differences were found among treatments for hemodynamic responses, clinical blood markers or self-reported side effects. After 5 days of supplementation, one repetition maximum (1RM) bench press improved significantly for CNH (mean change, 95% CI; 6.1 [3.5, 8.7] kg) but not PLA (0.7 [-1.6, 3.0] kg or CNL (2.0 [-0.9, 4.9] kg, CNH, p = 0.01). CNH participants also tended to experience an attenuated loss in 1RM strength during the recovery performance tests following supplementation on day 5 (PLA: -9.3 [-13.5, -5.0], CNL: -9.3 [-13.5, -5.1], CNH: -3.9 [-6.6, -1.2] kg, p = 0.07). After 5 days, pre-supplementation 1RM leg press values increased significantly, only with CNH (24.7 [8.8, 40.6] kg, but not PLA (13.9 [-15.7, 43.5] or CNL (14.6 [-0.5, 29.7]). Further, post-supplementation 1RM leg press recovery did not decrease significantly for CNH (-13.3 [-31.9, 5.3], but did for PLA (-30.5 [-53.4, -7.7] and CNL (-29.0 [-49.5, -8.4]). CNL treatment promoted an increase in bench press repetitions at 70% of 1RM during recovery on day 5 (PLA: 0.4 [-0.8, 1.6], CNL: 0.9 [0.35, 1.5], CNH: 0.5 [-0.2, 0.3], p = 0.56), greater leg press endurance prior to supplementation on day 5 (PLA: -0.2 [-1.6, 1.2], CNL: 0.9 [0.2, 1.6], CNH: 0.2 [-0.5, 0.9], p = 0.25) and greater leg press endurance during recovery on day 5 (PLA: -0.03 [-1.2, 1.1], CNL: 1.1 [0.3, 1.9], CNH: 0.4 [-0.4, 1.2], p = 0.23). Cycling time trial performance (4 km) was not affected. Results indicate that creatine nitrate supplementation, up to a 6 g dose, for 6 days, appears to be safe and provide some ergogenic benefit.

Dataset Information

Maternal Creatine Supplementation during Pregnancy Prevents Long-Term Changes in Diaphragm Muscle Structure and Function after Birth Asphyxia.

Publications

Maternal Creatine Supplementation during Pregnancy Prevents Long-Term Changes in Diaphragm Muscle Structure and Function after Birth Asphyxia.

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