Lipid Metabolism in the Neonate

I neonati nel reparto di terapia intensiva neonatale, specialmente quelli nati pretermine e con basso peso alla nascita, possono aver bisogno di nutrizione enterale e parenterale (NP) con lipidi. I lipidi forniti con la dieta sono essenziali per raggiungere i requisiti nutrizionali ed energetici necessari per una corretta crescita. Uno stato di malnutrizione nella vita post-natale e una scarsa crescita intra-ospedaliera sono state associate ad un ritardo di crescita a lungo termine e del neurosviluppo. Questa tesi descrive studi sul metabolismo lipidico di neonati alimentati per via enterale e parenterale. I nostri dati suggeriscono che la placenta umana limita la disponibilità di fitosteroli (steroli di origine naturale presenti in prodotti derivati da piante come gli oli vegetali) al feto. Il metabolismo dei fitosteroli nel neonato pretermine in NP è ridotto rispetto a quello del neonato a termine e dell’adulto: più bassa esterificazione e lenta eliminazione dal torrente sanguigno. La difficoltà di metabolizzare i fitosteroli è marcatamente ridotta in caso di colestasi. L’assunzione orale/enterale di alimenti con elevato contenuto di fitosteroli (es. formule per l’infanzia a base di oli vegetali) è associata ad alti livelli di fitosteroli plasmatici nei neonati pretermine e a termine. Una dieta con basso contenuto di fitosteroli è preferibile per i neonati. L’olio di pesce assunto per via intravenosa non influenza negativamente la crescita ponderale dei pretermine. Le emulsioni con olio di pesce sembrano essere sicure anche se il loro effetto sulla crescita di organi come cervello e polmoni richiede ulteriori studi. L’ipertrigliceridemia è associata ad una riduzione degli apporti dei lipidi intravenosi ma non a ridotta crescita e neurosviluppo nei pretermine. Le dosi raccomandate di lipidi intravenosi potrebbero essere in eccesso rispetto a quelle necessarie per una corretta crescita. I benefici di lipidi extra in caso di ipertrigliceridemia restano da chiarireInfants admitted to neonatal intensive care unit, especially those born prematurely and with low birth weight, may require enteral and parenteral nutrition (PN) with lipids. Dietary lipids are essential for infants to achieve nutrient and energy requirements to ensure an adequate growth. Early life malnutrition and poor in-hospital growth have been associated with later impaired long-term growth and neurodevelopment. This thesis describes a number of investigations on lipid metabolism in enterally and parenterally fed infants. Our data suggest that human placenta tends to limit the availability of phytosterols (naturally occurring sterols found in plant-derived products, such as vegetable oils) to the foetus. Phytosterol metabolism in preterm infants on routine PN with vegetable oils is reduced in comparison with term infants and adults: lowest esterification and slow elimination from the bloodstream. In case of cholestasis, the ability of preterm infants to manage phytosterols in intravenous (IV) lipid emulsions (LE) is markedly low. A high enteral phytosterol intake as it occurs in infant milk formula-fed infants results in elevated plasma phytosterol levels both in preterm and term infants. A low phytosterol diet should be preferred for infants. We found that IV fish oil does not negatively affect weight gain in small preterm infants. New generation IV LE containing fish oil appear to be safe for preterm infants but their effect on organ growth (such as brain and lungs) deserves further studies. In a case-control study, we found that hypertriglyceridemia (HiTG) affects IV LE intakes in small preterm infants on routine PN. We did not find any association between HiTG and reduced growth and poorer neurodevelopment. The recommended doses of IV LE may still be in excess compared to those effectively required for adequate growth and metabolism of small preterm infants. The benefits of the extra IV LE during HiTG remain to be clarified

DHA turnover in pregnant women using the natural abundance variation of 13C: a pilot study

The importance of DHA to support fetal development and maternal health is well established. In this study, we applied the natural abundance approach to determine the contribution of 200 mg/d of DHA supplement to the plasma DHA pool in nineteen healthy pregnant women. Women received DHA, from week 20 until delivery, from an algal source (n 13, Algae group) or from fish oil (n 6, Fish group) with slightly different content of C-13. We measured plasma phospholipids DHA C-13:C-12 ratio (reported as delta C-13) prior to supplementation (T0), after 10 (T1) and 90 days (T2) and prior to delivery (T3). The delta C-13 of DHA in algae and fish supplements were -15 center dot 8 (sd 0 center dot 2) mUr and -25 center dot 3 (sd 0 center dot 2) mUr (P < 0 center dot 001). DHA delta C-13 in the Algae group increased from -27 center dot 7 (sd 1 center dot 6) mUr (T0) to -21 center dot 9 (sd 2 center dot 2) mUr (T3) (P < 0 center dot 001), whereas there were not significant changes in the Fish group (-27 center dot 8 (sd 0 center dot 9) mUr at T0 and -27 center dot 3 (sd 1 center dot 1) mUr at T3, P = 0 center dot 09). In the Algae group, 200 mg/d of DHA contributed to the plasma phospholipid pool by a median value of 53 % (31-75 % minimum and maximum). This estimation was not possible in the Fish group. Our results demonstrate the feasibility of assessing the contribution of DHA from an algal source to the plasma DHA pool in pregnant women by the natural abundance approach. Plasma delta C-13 DHA did not change when consuming DHA of fish origin, with almost the same delta C-13 value of that of the pre-supplementation plasma delta C-13 DHA

A novel deuterium-based model for measurement of exogenous surfactant using deuterium-depleted water

: Stable isotope tracers, like 13 C, can be used for the measurement of the partition between the endogenous and exogenous pulmonary disaturated-phosphatidylcholine (DSPC). Deuterium labeling methods are still not fully explored. Our aim was to investigate the feasibility of using deuterium-depleted water (DDW) and deuterium-enriched water (DEW) to measure endogenous and exogenous pulmonary DSPC in a rabbit model of surfactant depletion. Data obtained from the 13 C dilution method were used as a reference. We studied 9 adult rabbits: 4 drank DDW and 5 DEW for 5 days. Lung surfactant depletion was induced at Day 5 by repeated saline bronchoalveolar lavages (BAL), which were stored as a pool (BAL pool). After endogenous surfactant depletion, rabbits received exogenous surfactant followed by a second BAL depletion procedure (End-Experiment Pool). DSPC quantity, and palmitic acid (PA)-DSPC 2 H/1 H (δ2 H) and 13 C/12 C ratios (δ13 C) of exogenous surfactant batches and of BAL pools were measured by High-Resolution Mass Spectrometry. The amount of exogenous surfactant recovered from the lungs ranged from 45% to 81% and, it was highly correlated with those obtained with the use of the 13 C (r = 0.9844, p < 0.0001). We demonstrated that commercially available purified DDW and even low doses of DEW can be used to modify the deuterium background of endogenous surfactants with the purpose of measuring the contribution of exogenous surfactants to the endogenous alveolar surfactant pool

Is low cerebral near infrared spectroscopy oximetry associated with neurodevelopment of preterm infants without brain injury?

Objectives To evaluate the association between low regional cerebral oxygen saturation (rScO2) and neurodevelopment in preterm infants classified as no brain injury (NBI). Methods We retrospectively reviewed data of rScO2 monitoring during the first 3 days of life of infants with a gestational age (GA)&lt;28 weeks or birth weight (BW)&lt;1,000 g, with and without brain injury (BI). BI was defined as intraventricular haemorrhage, cystic periventricular leukomalacia or cerebellar haemorrhage. Univariate and multivariate analyses were used to study the association of rScO2&lt;55% for more than 10 h in the first 3 days of life ((NIRS10H)) and the 24 months neurodevelopment. Results Of the 185 patients who met the inclusion criteria, 31% were classified as BI infants and 69% NBI. BI compared to NBI infants had a significantly lower GA and a higher incidence of complications of prematurity. Mean rScO2 in the first 72 h of life was significantly lower in BI than NBI. (NIRS10H) in NBI patients was negatively associated with neurodevelopmental scores both at the univariate and multivariate analysis (p&lt;0.05). NBI infants with (NIRS10H) were found to have lower systemic oxygenation than their counterparts with rScO2Conclusions (NIRS10H) in NBI small preterm infants was found to be an independent predictor of neurodevelopment at 24 months and it was associated with low systemic saturation values

Amniotic Membrane-Derived Mesenchymal Cells and Their Conditioned Media: Potential Candidates for Uterine Regenerative Therapy in the Horse

<div><p>Amniotic membrane-derived mesenchymal cells (AMCs) are considered suitable candidates for a variety of cell-based applications. In view of cell therapy application in uterine pathologies, we studied AMCs in comparison to cells isolated from the endometrium of mares at diestrus (EDCs) being the endometrium during diestrus and early pregnancy similar from a hormonal standpoint. In particular, we demonstrated that amnion tissue fragments (AM) shares the same transcriptional profile with endometrial tissue fragments (ED), expressing genes involved in early pregnancy (<i>AbdB-like Hoxa</i> genes), pre-implantantion conceptus development (<i>Erα, PR</i>, <i>PGRMC1</i> and <i>mPR</i>) and their regulators (<i>Wnt7a</i>, <i>Wnt4a</i>). Soon after the isolation, only AMCs express <i>Wnt4a</i> and <i>Wnt7a</i>. Interestingly, the expression levels of prostaglandin-endoperoxide synthase 2 (<i>PTGS2</i>) were found greater in AM and AMCs than their endometrial counterparts thus confirming the role of AMCs as mediators of inflammation. The expression of nuclear progesterone receptor (PR), membrane-bound intracellular progesterone receptor component 1 (<i>PGRMC1</i>) and membrane-bound intracellular progesterone receptor (<i>mPR</i>), known to lead to improved endometrial receptivity, was maintained in AMCs over 5 passages <i>in vitro</i> when the media was supplemented with progesterone. To further explore the potential of AMCs in endometrial regeneration, their capacity to support resident cell proliferation was assessed by co-culturing them with EDCs in a transwell system or culturing in the presence of AMC-conditioned medium (AMC-CM). A significant increase in EDC proliferation rate exhibited the crucial role of soluble factors as mediators of stem cells action. The present investigation revealed that AMCs, as well as their derived conditioned media, have the potential to improve endometrial cell replenishment when low proliferation is associated to pregnancy failure. These findings make AMCs suitable candidates for the treatment of endometrosis in mares.</p></div

Surfactant Components and Tracheal Aspirate Inflammatory Markers in Preterm Infants with Respiratory Distress Syndrome

In 93 preterm infants ≤32 weeks of gestational age and 12 control infants, epithelial lining fluid disaturated-phosphatidylcholine, surfactant protein A and B, albumin, and myeloperoxidase activity were assessed after intubation and before exogenous surfactant administration. We found that disaturated-phosphatidylcholine, surfactant protein B, and myeloperoxidase were significantly higher in preterms with chorioamnionitis

The maternal-fetal gradient of free and esterified phytosterols at the time of delivery in humans

Background: High dietary intakes of phytosterols (Phyto), such as those consumed by vegans and vegetarians, are not recommended for cholesterol-lowering in pregnant women (PW) because the safety of their use during pregnancy has not been fully established [1]. Information on Phyto in pregnancy is very limited. Objective: To characterize the maternal-fetal gradient of free and esterified Phyto at the time of delivery in humans. Design: PW who had a term delivery at the Obstetrics and Gynecology Unit of the University Hospital of Padua (Padua, Italy), between November 2016 and March 2017, participated in the study. Fatty acids (FA), cholesterol (Chol), Chol metabolites (7-dehydrocholesterol, 7-DHChol; lathosterol, Latho; 7\u3b1-hydroxycholesterol, 7\u3b1-OHChol), and Phyto (campesterol, Camp; stigmasterol, Stigma; sitosterol, Sito) were measured in both maternal (MB) and cord blood (CB) at the time of delivery. Non-pregnant adult volunteers (Ref-NA) served as a reference. Results: Thirty-four term PW and 12 Ref-NA signed informed consent and were studied. Plasma total Phyto concentrations in CB were up to 20-fold lower than in MB (p < 0.05). Positive and significant correlations were found between total Phyto of MB-CB pairs (p < 0.01), and between total FA and Camp of MB (p < 0.05). Interestingly, free Chol to Chol ester ratio of CB did not differ from that of MB, and free Phyto to Phyto ester ratios were higher in CB than in MB (p < 0.001). No differences were found between Phyto concentrations of MB and Ref-NA. However, free Chol to Chol ester ratio, and free Phyto to Phyto ester ratios were higher in MB than in Ref-NA (p < 0.05). Chol synthesis, as indicated by 7-DHChol to 7\u3b1-OHChol, Latho to 7\u3b1-OHChol, and Latho to Sito ratios, was greatest in CB and lowest in Ref-NA. Conclusion: Our data suggest that free Phyto cross the human placenta more easily than Phyto ester. An elevated Stigma to Chol ratio in CB than in MB was also described for the first time. The impact of these findings on the neonatal outcomes remains to be elucidated