Dominique Haumont

Plasma lipid and plasma lipoprotein concentrations in low birth weight infants given parenteral nutrition with twenty or ten percent lipid emulsion.

Because 10% and 20% intravenously administered lipid emulsions (intralipid preparations) differ in their phospholipid/triglyceride ratio (0.12 and 0.06, respectively), 28 low birth weight infants requiring parenteral nutrition for at least 1 week were selected at random to receive either emulsion to determine the effects on plasma lipids and lipoproteins. Triglyceride intake was progressively increased to reach 2 gm/kg per day between days 4 and 7. During that period, all plasma lipids in samples taken 6 hours after infusion were higher in the 10% intralipid group. In comparison with day 0 values, triglyceride concentrations decreased (63 +/- 7 to 45 +/- 4 mg/dl; p less than 0.05) in the 20% group. Cholesterol levels increased in both groups, but the rise was more than twofold higher in the 10% group. Phospholipid increase was approximately 25% in the 20% group but more than 125% in patients receiving the 10% emulsion (p less than 0.005). The changes in plasma cholesterol and phospholipid levels were almost entirely in low-density lipoproteins. After 7 days, eight infants from each group were given the alternate emulsion, which resulted in a reversal of lipid patterns in each patient. We conclude that the higher phospholipid intake in 10% than in 20% intralipid is associated with higher plasma triglyceride concentrations and leads to accumulation of cholesterol and phospholipids in low-density lipoproteins. Emulsions with lower phospholipid content may be preferable for low birth weight infants and perhaps other patient populations with impaired removal of parenteral fat emulsions.

Effect of liposomal content of lipid emulsions on plasma lipid concentrations in low birth weight infants receiving parenteral nutrition

We studied the effects of phospholipid liposomes present in intravenously administered lipid emulsions on plasma lipid levels in preterm infants given 10% and 20% lipid emulsions. Twenty premature infants (birth weight 1454 +/- 54 gm) on a parenteral nutrition regimen received up to 4 gm triglycerides per kilogram per day in a 20% lipid emulsion for 2 weeks, and then received the 10% emulsion at 2 gm triglycerides per kilogram per day, which delivered the same total phospholipid load but twice the amount of liposomes. Triglyceride, total cholesterol, and phospholipid concentrations increased significantly when the infants were given 2 gm triglycerides per kilogram per day in the 10% emulsion rather than 4 gm/kg per day in the 20% emulsion (44 +/- 4 to 57 +/- 5 mg/dl, 134 +/- 6 to 162 +/- 9 mg/dl, and 204 +/- 8 to 251 +/- 10 mg/dl, respectively). Lipoprotein analysis indicated the presence of lipoprotein X-like particles in the low-density lipoprotein fraction and an increase of the intermediate-density lipoprotein fraction in infants who received the 10% emulsion. The presence of excess phospholipids in the 10% emulsion was associated with greater plasma lipid alterations. Therefore the use of 20% rather than 10% emulsion allows for more efficient triglyceride clearance, even at a higher triglyceride intake. Administration of emulsions that are relatively poor in phospholipid liposomes may allow delivery of > 2 gm triglycerides per kilogram per day to low birth weight infants.

Parental involvement and kangaroo care in European neonatal intensive care units: A policy survey in eight countries

Objective: To compare, in a large representative sample of European neonatal intensive care units, the policies and practices regarding parental involvement and holding babies in the kangaroo care position as well as differences in the tasks mothers and fathers are allowed to carry out. Design: Prospective multicenter survey. Setting: Neonatal intensive care units in eight European countries (Belgium, Denmark, France, Italy, The Netherlands, Spain, Sweden, and the United Kingdom). Patients: Patients were not involved in this study. Interventions: None. Measurements and Main Results: A structured questionnaire was mailed to 362 units (response rate 78%); only units with ≥50 very-low-birth-weight annual admissions were considered for this study. Facilities for parents such as reclining chairs near the babies’ cots, beds, and a dedicated room were common, but less so in Italy and Spain. All units in Sweden, Denmark, the United Kingdom, and Belgium reported encouraging parental participation in the care of the babies, whereas policies were more restrictive in Italy (80% of units), France (73%), and Spain (41%). Holding babies in the kangaroo care position was widespread. However, in the United Kingdom, France, Italy, and Spain, many units applied restrictions regarding its frequency (sometimes or on parents request only, rather than routinely), method (conventional rather than skin-to-skin), and clinical conditions (especially mechanical ventilation and presence of umbilical lines) that would prevent its practice. In these countries, fathers were routinely offered kangaroo care less frequently than mothers (p < .001) and less often it was skin-to-skin (p < .0001). Conclusions: This study showed that, although the majority of units in all countries reported a policy of encouraging both parents to take part in the care of their babies, the intensity and ways of involvement as well as the role played by mothers and fathers varied within and between countries.

New developments in fat emulsions.

In Western countries, the transport of triacylglycerols by plasma triacylglycerol-rich lipoproteins (chylomicra and very-low-density lipoproteins (VLDL)) accounts for approximately 100 g lipids/d and represents a major pathway in the delivery of energy to tissues. Fat emulsions have been developed to resemble endogenous chylomicra (Wretlind, 1981). However, if the particle size of emulsion droplets is within the range of chylomicra, significant differences in composition can be found between both types of particles; indeed, no cholesteryl ester is dissolved in the triacylglycerol core of artificial particles and no apoprotein is present on their surface; their phospholipid content is higher than that of chylomicra. this difference being particularly marked in 10% emulsions. In fact, it is possible by ultracentrifugation in saline (9 g sodium chlorideA) for 30 min to demonstrate that fat emulsions are made up of not one but two different particle populations: one consisting of triacylglycerol-rich particles and the other of phospholipids. These phospholipid-rich particles, which resemble liposomes, are present in a much greater proportion in 10% than in 20% emulsions. They have a number of important metabolic features which have been recently reviewed (Carpentier, 1989). Their elimination from the plasma is much slower than that of infused triacylglycerols. High concentrations of liposomal particles substantially delay the clearance of triacylglycerols (Carpentier et al. 1987) and form phospholipid-free cholesterol complexes which accumulate in the low-density-lipoprotein (LDL) density range (Griffin et al. 1979: Untracht, 1982). Preterm neonates appear to be particularly sensitive to the presence of a high liposomal content in the emulsions. When infused at a dose of 2 g triacylglycerols/ kg per d in the parenteral regimen of low-birth-weight infants, 10% emulsion induces high plasma levels of phospholipids, free cholesterol and triacylglycerols (Haumont et al. 1989a). These effects can be substantially reduced by the use of 20% emulsions which even allow increases of parenteral lipid intake (Haumont er al. 1989h). The triacylglycerol fatty acid pattern of lipid emulsions also markedly differs from that of endogenous lipoproteins. For many years, soya-bean oil and to a lesser extent safflower oil have been used as sources of triacylglycerols. They contain exclusively long-chain triacylglycerols (LCT) and a majority of polyunsaturated fatty acids. More recently, a new emulsion has been developed, which provides an equal ponderal proportion of medium (mainly octanoate)and long-chain fatty acids, both being present in the triacylglycerol core. In vitro studies have demonstrated medium-chain triacylglycerol (MCT) emulsions to be a better substrate than LCT emulsions for hydrolysis by lipoprotein lipase and hepatic lipase. This is, at least partly, due to the much greater solubility of MCT v. LCT into phospholipid bilayers, which makes them more available for the endothelial bound

Interactions between exogenous fat and plasma/lipoproteins

Fat emulsions are essentially composed of triglycerides and phospholipids. Their elimination from the plasma--which is generally rapid--is influenced by the amount and the composition of both these components. During their short stay in the vascular compartment, exogenous particles undergo major compositional changes. They acquire various apolipoproteins--namely C-II, C-III, E and A-IV--by transfer from HDL. They also acquire esterified cholesterol from HDL and LDL and transfer exogenous triglycerides and phospholipids to these endogenous lipoproteins. These exchanges are affected by the type of triglyceride fatty acids and the amount of phospholipids present in fat emulsions, as well as by the infusion rate. Some 10% of emulsions--with a high phospholipid: triglyceride ratio--contain a huge phospholipid excess which can be isolated as a separate fraction from the triglyceride-rich particles. These phospholipids markedly interfere with the metabolism of cholesterol and the plasma lipoprotein profile.

Modifications of Surfactant Phospholipid Pattern in Premature Infants Treated with Curosurf: Clinical and Dietary Correlations

Neonatal respiratory distress syndrome (RDS) is characterized by an immature surfactant phospholipid pattern. We aimed to study the evolution of surfactant phospholipids over a 6-day period, before and after surfactant replacement therapy with Curosurf, and to investigate possible interactions with exogenous phospholipids administered during total parenteral nutrition (TPN). Seventeen premature infants with RDS were randomly assigned to receive TPN with lipids or without (glucose group). Both groups showed a similar evolution of the surfactant phospholipids. At day 6, the surfactant composition had changed towards a mature human surfactant pattern except for phosphatidylglycerol which remained low (1%), compensated for by a high phosphatidylinositol and phosphatidylserine proportion (13.3%), Phospholipid subcomponents in plasma remained unchanged in both groups. Plasma total cholesterol (151 +/- 18 vs. 113 +/- 6 mg/dl, p less than 0.05) and cholesteryl esters (172 +/- 20 vs. 113 +/- 9 mg/dl, p less than 0.01) were higher in the glucose than in the lipid group. Total calorie intake was significantly higher in the lipid group (85 +/- 4 vs. 64 +/- 6 kcal/kg.day, p less than 0.01).

Relationship Between some Clinical and Biological Factors and Incipient Diabetic Retinopathy Diagnosed by Fluorescein Angiography

We conducted several studies to determine the influence of some clinical and biological findings on the occurrence of diabetic retinopathy in children and adolescents, as detected by retinal fluorescein angiography. In our experience this method doubles the frequency of diagnosis of incipient retinopathy, showing fluorescein leakage that may occur before specific lesions. 1,2

NIDCAP and developmental care: a European perspective.

The systematic review by Ohlsson and Jacobs on the NIDCAP approach concluded that there is no evidence that NIDCAP improves long-term neurodevelopmental or short-term medical outcome.1 Despite their conclusion, “Because NIDCAP was not effective in reducing adverse outcomes, performing cost-effectiveness analyses became redundant,” they report that NIDCAP is associated with a better daily weight gain, a shorter hospitalization, and an increase in Bayley Scale of Infant Development scores at 9 months. Developmental care and environmental strategies emerged in response to the background of the potential harmful effects of traditional NICU settings. When neonatal intensive care …

Sharing Data to Accelerate Medicine Development and Improve Neonatal Care: Data Standards and Harmonized Definitions

T he development and testing of the majority of medicine prescribed for newborn infants has been inadequate, with multiple barriers despite multiple legislative initiatives to encourage studies. One impediment is our current limited capacity to share standardized data that would facilitate the evaluation of the effectiveness and risks of medicine given to newborn infants. Neonatal drug development requires data sharing and in this commentary, we will discuss the importance and feasibility of defining standards for definitions when sharing neonatal data in a context that meets the needs of multiple stakeholders. There are many reasons to share data about effectiveness and risks of neonatal drug therapy. Baseline data across large and diverse populations can inform the development of clinical trials to ensure they have adequate power to detect relevant effects. The results of studies can be compared in meta-analyses. Multiple trials allow for the evaluation of generalizability across a range of settings. Placebo arms can be pooled to assess background rates of serious morbidities and other adverse events. Databases can contribute to the evaluation of a medicine across the entire pipeline of development through to postmarketing studies to monitor safety and efficacy. There is increasing recognition of the value of “real-world data,” but this approach needs efficient data sharing and reliable parameters for linkage. The problems that arise when information is shared in the absence of standardized ways to define events have been highlighted in recent publications. For example, the iNeo collaborators identified 13 different definitions of bronchopulmonary dysplasia (BPD) in 628 papers; see also Steinhorn et al. A comparison of outcomes for infants of very low birth weight across 8 databases in high-resource settings (Canada, United Kingdom, Sweden, Spain, Switzerland, Israel, Australia/New Zealand, and Japan) found that the incidence of a composite outcome comprising death, severe cerebral ultrasound scan abnormalities, BPD, and treated retinopathy of prematurity ranged between 26% and 42% with significant variation among sites. These differences may well be attributable to inconsistencies in components of data and denominators (such as number of recorded births, number of admissions to neonatal units, criteria for a live birth). Variation in how clinicians interpret seemingly similar conditions as well as factors not generally recorded, such as differences in service delivery and staff numbers and skill-mix, also must be considered. Finding a way to address such variation in data capture, as has been achieved in some databases, would unlock an valuable resource. Thus, data sharing requires data standards, defined as “a set of rules on how a particular type of data should be structured, defined, formatted, or exchanged between computer systems.” The definition of data standards in neonatology has been difficult because data sharing has not been prioritized sufficiently across stakeholders, there are limited drivers for consensus across multiple perspectives and continents, and the biological variation caused by the combination of ontogeny and multiple comorbidities impedes discussion. The methodology for the development of data standards has been engineered by organizations such as the Clinical Data Interchange Standards Consortium (CDISC), which develops data standards that meet the specifications of regulatory agencies for use in clinical trials. One family of CDISC standards that meet regulatory specifications relates to “foundational standards” about how data captured by all clinical trials can be recorded and presented from protocol through to reporting and

Contents Vol. 93, 2008

S. Andersson, Helsinki E. Bancalari, Miami, Fla. G. Buonocore, Siena W.A. Carlo, Birmingham, Ala. V.P. Carnielli, Ancona W.J. Cashore, Providence, R.I. I.A. Choonara, Derby T. Curstedt, Stockholm O. Dammann, Boston, Mass. C. Dani, Florence B. Darlow, Christchurch P. Gluckman, Auckland M. Hallman, Oulu B. Jonsson, Stockholm S.E. Juul, Seattle, Wash. A. Llanos, Santiago R.J. Martin, Cleveland, Ohio C.J. Morley, Melbourne J. Neu, Gainesville, Fla. P.C. Ng, Hong Kong M. Obladen, Berlin A.G.S. Philip, Palo Alto, Calif. M. Post, Toronto E. Saliba, Tours O.D. Saugstad, Oslo B. Schmidt, Hamilton E. Shinwell, Rehovot J. Smith, Cape Town B. Sun, Shanghai H. Togari, Nagoya F. van Bel, Utrecht N. Vain, Buenos Aires M. Vento Torres, Valencia M. Weindling, Liverpool J.A. Widness, Iowa City, Iowa Fetal and Neonatal Research