Oral citrulline supplementation in pregnancies with preeclampsia: a multicenter, randomized, double-blind clinical trial.

Background: Preeclampsia (PE) contributes to maternal and fetal mortality and morbidity. Supplementation with L-arginine, the precursor of nitric oxide, has not proven effective, possibly due to extensive arginine catabolism in the splanchnic bed. Citrulline is converted by the kidney to L-arginine.

Dietary Arginine Supplementation during Gestation and Lactation Increases Milk Yield and Mammary Lipogenesis in Rats.

Background: Arginine, an essential amino acid during the reproductive period, has been shown to enhance lactation performances in livestock. Whether it could help mothers with breastfeeding difficulties is not known.

Objectives: This study aimed to determine whether dietary arginine supplementation would enhance milk production in rat dams nursing large 12-pup litters and, if so, what mechanisms are involved.

Breast milk protein content at week 3 after birth and neurodevelopmental outcome in preterm infants fed fortified breast milk.

Background: Feeding supplemented mother milk during hospital stay improves neurodevelopment in preterm infants. Yet the composition of mother milk varies widely between subjects. The relationship between this variation and outcome is unknown.

Fenugreek Stimulates the Expression of Genes Involved in Milk Synthesis and Milk Flow through Modulation of Insulin/GH/IGF-1 Axis and Oxytocin Secretion.

We previously demonstrated galactagogue effect of fenugreek in a rat model of lactation challenge, foreshadowing its use in women's breastfeeding management. To assess longitudinal molecular mechanisms involved in milk synthesis/secretion in dams submitted to fenugreek supplementation, inguinal mammary, pituitary glands and plasma were isolated in forty-three rats nursing large 12 pups-litters and assigned to either a control (CTL) or a fenugreek-supplemented (FEN) diet during lactation. RT-PCR were performed at days 12 and 18 of lactation (L12 and L18) and the first day of involution (Inv1) to measure the relative expression of genes related to both milk synthesis and its regulation in the mammary gland and lactogenic hormones in the pituitary gland.

Moderate High Caloric Maternal Diet Impacts Dam Breast Milk Metabotype and Offspring Lipidome in a Sex-Specific Manner.

Lactation is a critical period during which maternal sub- or over-nutrition affect milk composition and offspring development that can have lasting health effects. The consequences of moderate high-fat, high-simple carbohydrate diet (WD) consumption by rat dams, during gestation and lactation, on milk composition and offspring blood lipidome and its growth, at weaning, were investigated by using a comprehensive lipidomic study on mass-spectrometric platform combined to targeted fatty- and free amino-acids analysis. This holistic approach allowed clear-cut differences in mature milk-lipidomic signature according to maternal diet with a similar content of protein, lactose and leptin.

Correction: Alexandre-Gouabau et al. "Comprehensive Preterm Breast Milk Metabotype Associated with Optimal Infant Early Growth Pattern", , 2019, , 528.

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Simultaneous exploration of nutrients and pollutants in human milk and their impact on preterm infant growth: An integrative cross-platform approach.

Early nutritional management including fortified human breastmilk is currently recommended to fulfil the energy demands and counterbalance risks associated to preterm birth. However, little is known about the potential adverse effects of exposure to persistent organic pollutants (POPs) carried in human milk on preterm infant growth. We conducted a pilot study proving the application of an integrative analytical approach based on mass spectrometry (MS) coupled to advanced statistical models, favouring the comprehensive molecular profiling to support the identification of multiple biomarkers.

Impact of Fenugreek on Milk Production in Rodent Models of Lactation Challenge.

Fenugreek, a herbal remedy, has long been used as galactologue to help mothers likely to stop breastfeeding because of perceived insufficient milk production. However, few studies highlight the efficacy of fenugreek in enhancing milk production. The aims of our study were to determine whether fenugreek increased milk yield in rodent models of lactation challenge and if so, to verify the lack of adverse effects on dam and offspring metabolism.

Comprehensive Preterm Breast Milk Metabotype Associated with Optimal Infant Early Growth Pattern.

Early nutrition impacts preterm infant early growth rate and brain development but can have long lasting effects as well. Although human milk is the gold standard for feeding new born full-term and preterm infants, little is known about the effects of its bioactive compounds on breastfed preterm infants' growth outcomes. This study aims to determine whether breast milk metabolome, glycome, lipidome, and free-amino acids profiles analyzed by liquid chromatography-mass spectrometry had any impact on the early growth pattern of preterm infants.

Maternal protein restriction during lactation induces early and lasting plasma metabolomic and hepatic lipidomic signatures of the offspring in a rodent programming model.

Perinatal undernutrition affects not only fetal and neonatal growth but also adult health outcome, as suggested by the metabolic imprinting concept. However, the exact mechanisms underlying offspring metabolic adaptations are not yet fully understood. Specifically, it remains unclear whether the gestation or the lactation is the more vulnerable period to modify offspring metabolic flexibility.

Breast Milk Lipidome Is Associated with Early Growth Trajectory in Preterm Infants.

Human milk is recommended for feeding preterm infants. The current pilot study aims to determine whether breast-milk lipidome had any impact on the early growth-pattern of preterm infants fed their own mother's milk. A prospective-monocentric-observational birth-cohort was established, enrolling 138 preterm infants, who received their own mother's breast-milk throughout hospital stay.

Use of water turnover method to measure mother's milk flow in a rat model: Application to dams receiving a low protein diet during gestation and lactation.

Assessment of milk production is of utmost relevance for pediatricians and scientists interested in early life nutrition. The weight-suckle-weight (WSW) method, which consists of weighing babies before and after they suckle their mother, uses the difference in body weight as an estimate of milk intake. However, this is prone to many sources of error.

Neonatal Citrulline Supplementation and Later Exposure to a High Fructose Diet in Rats Born with a Low Birth Weight: A Preliminary Report.

A low birth weight (LBW) leads to a higher risk of metabolic syndrome in adulthood. Literature suggests that citrulline supplementation in adulthood prevents the effect of a high fructose diet on energy metabolism. Whether neonatal citrulline supplementation would alter early growth or energy metabolism in the long-term in rats with LBW is unknown.

Higher concentrations of branched-chain amino acids in breast milk of obese mothers.

Objective: Nutrition during fetal life and early childhood is thought to play a crucial role in the risk for developing metabolic syndrome and cardiovascular diseases in the future adult and branched-chain amino acids (BCAA) intake may play a role in the development of obesity. The aim of this study was to compare the breast milk amino acid profiles of obese and normal weight (control) breast-feeding mothers.

Methods: Fifty obese and 50 control breast-feeding mothers were enrolled.

Calibration Adjustment of the Mid-infrared Analyzer for an Accurate Determination of the Macronutrient Composition of Human Milk.

Background: Human milk composition analysis seems essential to adapt human milk fortification for preterm neonates. The Miris human milk analyzer (HMA), based on mid-infrared methodology, is convenient for a unique determination of macronutrients. However, HMA measurements are not totally comparable with reference methods (RMs).

Perinatal protein restriction affects milk free amino acid and fatty acid profile in lactating rats: potential role on pup growth and metabolic status.

Perinatal undernutrition affects not only fetal and neonatal growth but also adult health outcome, as suggested by the metabolic imprinting concept. Although maternal milk is the only channel through which nutrients are transferred from mother to offspring during the postnatal period, the impact of maternal undernutrition on milk composition is poorly understood. The present study investigates, in a rat model of nutritional programming, the effects of feeding an isocaloric, low-protein diet throughout gestation and lactation on milk composition and its possible consequences on offspring's growth and metabolic status.

Effect of pre- and postnatal growth and post-weaning activity on glucose metabolism in the offspring.

Maternal caloric restriction during late gestation reduces birth weight, but whether long-term adverse metabolic outcomes of intra-uterine growth retardation (IUGR) are dependent on either accelerated postnatal growth or exposure to an obesogenic environment after weaning is not established. We induced IUGR in twin-pregnant sheep using a 40% maternal caloric restriction commencing from 110 days of gestation until term (∼147 days), compared with mothers fed to 100% of requirements. Offspring were reared either as singletons to accelerate postnatal growth or as twins to achieve standard growth.

Time window-dependent effect of perinatal maternal protein restriction on insulin sensitivity and energy substrate oxidation in adult male offspring.

Epidemiological and experimental evidence suggests that a suboptimal environment during perinatal life programs offspring susceptibility to the development of metabolic syndrome and Type 2 diabetes. We hypothesized that the lasting impact of perinatal protein deprivation on mitochondrial fuel oxidation and insulin sensitivity would depend on the time window of exposure. To improve our understanding of underlying mechanisms, an integrative approach was used, combining the assessment of insulin sensitivity and untargeted mass spectrometry-based metabolomics in the offspring.

Use of UPLC-ESI-MS/MS to quantitate free amino acid concentrations in micro-samples of mammalian milk.

Although free amino acids (FAA) account for a small fraction of total nitrogen in mammalian milk, they are more abundant in human milk than in most formulas, and may serve as a readily available source of amino acids for protein synthesis, as well as fulfill specific physiologic roles. We used reversed phase Ultra Performance Liquid Chromatography (UPLC) coupled to electrospray ionization tandem mass spectrometry (ESI-MS/MS) technique for FAA profiling in milks from three species (human, rat and cow) with a simple and rapid sample preparation. The derivatization procedure chosen, combined with UPLC-ESI-MS/MS allowed the quantitation of 21 FAA using labeled amino acids (Internal Standards) over a 10 min run time in micro-samples of mammalian milk (50 μL).

Relative contribution of foetal and post-natal nutritional periods on feeding regulation in adult rats.

Aim: The aim of this study was to assess the contribution of both foetal and/or post-natal nutritional periods on feeding regulation in adult rats.

Methods: Body weight gain, adipose tissue development, food preferences and feeding pattern under regular chow or Western diets were characterized on four experimental groups of rats: pups born from protein-restricted dams (R) and weaned by control (RC) or R dams (RR) and pups born from control dams weaned by C (CC) or R dams (CR).

Results: Rats born with intrauterine growth restriction (IUGR) and fed a Western diet at adulthood appeared predisposed to body weight gain and more fat accretion, whereas CR rats, despite their preference for high-fat diet and their hyperphagia for Western diet, did not show significant increase in fat tissue.

Maternal and cord blood LC-HRMS metabolomics reveal alterations in energy and polyamine metabolism, and oxidative stress in very-low birth weight infants.

To assess the global effect of preterm birth on fetal metabolism and maternal-fetal nutrient transfer, we used a mass spectrometric-based chemical phenotyping approach on cord blood obtained at the time of birth. We sampled umbilical venous, umbilical arterial, and maternal blood from mothers delivering very-low birth weight (VLBW, with a median gestational age and weight of 29 weeks, and 1210 g, respectively) premature or full-term (FT) neonates. In VLBW group, we observed a significant elevation in the levels and maternal-fetal gradients of butyryl-, isovaleryl-, hexanoyl- and octanoyl-carnitines, suggesting enhanced short- and medium chain fatty acid β-oxidation in human preterm feto-placental unit.

1H-NMR-based metabolic profiling of maternal and umbilical cord blood indicates altered materno-foetal nutrient exchange in preterm infants.

Background: Adequate foetal growth is primarily determined by nutrient availability, which is dependent on placental nutrient transport and foetal metabolism. We have used (1)H nuclear magnetic resonance (NMR) spectroscopy to probe the metabolic adaptations associated with premature birth.

Methodology: The metabolic profile in (1)H NMR spectra of plasma taken immediately after birth from umbilical vein, umbilical artery and maternal blood were recorded for mothers delivering very-low-birth-weight (VLBW) or normo-ponderal full-term (FT) neonates.

Offspring metabolomic response to maternal protein restriction in a rat model of intrauterine growth restriction (IUGR).

Intrauterine growth restriction (IUGR), along with postnatal growth trajectory, is closely linked with metabolic diseases and obesity at adulthood. The present study reports the time-dependent metabolomic response of male offspring of rat dams exposed to maternal adequate protein diet during pregnancy and lactation (CC) or protein deprivation during pregnancy only (IUGR with rapid catch-up growth, RC) or through pregnancy and lactation (IUGR with slow postnatal growth, RR). Plasma LC-HRMS metabolomic fingerprints for 8 male rats per group, combined with multivariate statistical analysis (PLS-DA and HCA), were used to study the impact of IUGR and postnatal growth velocity on the offspring metabolism in early life (until weaning) and once they reached adulthood (8 months).

Postnatal growth velocity modulates alterations of proteins involved in metabolism and neuronal plasticity in neonatal hypothalamus in rats born with intrauterine growth restriction.

Intrauterine growth restriction (IUGR) due to maternal protein restriction is associated in rats with an alteration in hypothalamic centers involved in feeding behaviour. In order to gain insight into the mechanism of perinatal maternal undernutrition in the brain, we used proteomics approach to identify hypothalamic proteins that are altered in their expression following protein restriction in utero. We used an animal model in which restriction of the protein intake of pregnant rats (8% vs.