Extremely preterm infants are at high risk for retinopathy of prematurity (ROP), a potentially blinding disease characterized by abnormalities in retinal vascularization. Whereas animal studies ...revealed that n-3 polyunsaturated fatty acids (PUFAs) may be of benefit in preventing ROP, human studies conducted on preterm infants during the 1
weeks of life showed no association between blood n-3 PUFA bioavailability and ROP incidence and/or severity, probably because of the influence of nutrition on the lipid status of infants. In the OmegaROP prospective cohort study, we characterized the erythrocyte concentrations of PUFAs in preterm infants aged less than 29 weeks gestational age (GA) without any nutritional influence. We show that GA is positively associated with the erythrocyte n-6 to n-3 PUFA ratio, and particularly with the ratio of arachidonic acid (AA) to docosahexaenoic acid (DHA), in infants with ROP. A time-dependent accumulation of AA at the expense of DHA seems to occur in utero in erythrocytes of preterm infants who will develop ROP, thus reinforcing previous data on the beneficial properties of DHA on this disease. In addition, preliminary data on maternal erythrocyte membrane lipid concentrations suggest modifications in placental transfer of fatty acids. Documenting the erythrocyte AA to DHA ratio at birth in larger cohorts might be useful to set up new prognostic factors for ROP.
N-3 polyunsaturated fatty acids (PUFAs) may prevent retinal vascular abnormalities observed in oxygen-induced retinopathy, a model of retinopathy of prematurity (ROP). In the OmegaROP prospective ...cohort study, we showed that preterm infants who will develop ROP accumulate the n-6 PUFA arachidonic acid (ARA) at the expense of the n-3 PUFA docosahexaenoic acid (DHA) in erythrocytes with advancing gestational age (GA). As mice lacking plasmalogens ―That are specific phospholipids considered as reservoirs of n-6 and n-3 PUFAs― Display a ROP-like phenotype, the aim of this study was to determine whether plasmalogens are responsible for the changes observed in subjects from the OmegaROP study. Accordingly, preterm infants aged less than 29 weeks GA were recruited at birth in the Neonatal Intensive Care Unit of University Hospital Dijon, France. Blood was sampled very early after birth to avoid any nutritional influence on its lipid composition. The lipid composition of erythrocytes and the structure of phospholipids including plasmalogens were determined by global lipidomics using liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS). LC-HRMS data confirmed our previous observations by showing a negative association between the erythrocyte content in phospholipid esterified to n-6 PUFAs and GA in infants without ROP (rho = −0.485,
p
= 0.013 and rho = −0.477,
p
= 0.015 for ethanolamine and choline total phospholipids, respectively). Phosphatidylcholine (PtdCho) and phosphatidylethanolamine (PtdEtn) species with ARA, namely PtdCho16:0/20:4 (rho = −0.511,
p
< 0.01) and PtdEtn18:1/20:4 (rho = −0.479,
p
= 0.015), were the major contributors to the relationship observed. On the contrary, preterm infants developing ROP displayed negative association between PtdEtn species with n-3 PUFAs and GA (rho = −0.380,
p
= 0.034). They were also characterized by a positive association between GA and the ratio of ethanolamine plasmalogens (PlsEtn) with n-6 PUFA to PlsEtn with n-3 PUFAs (rho = 0.420,
p
= 0.029), as well as the ratio of PlsEtn with ARA to PlsEtn with DHA (rho = 0.843,
p
= 0.011). Altogether, these data confirm the potential accumulation of n-6 PUFAs with advancing GA in erythrocytes of infants developing ROP. These changes may be partly due to plasmalogens.
Recent guidelines for preterm parenteral nutrition (PN) recommend an earlier and higher intake of amino acids (AA) and energy to avoid postnatal catabolism and approximate normal fetal growth. Few ...investigations explored how early PN may affect electrolyte and water homeostasis. We performed a prospective observational trial to assess the effect of nutrient intake on electrolyte homeostasis and balance.
During 16 months, all infants ≤32 weeks were eligible. In the first week of life, we recorded the following daily: electrolytes (plasma and 8-h urine collection), nutritional intake, urine output, body weight, and we calculated sodium (Na) and potassium (K) balance. Infants were divided, for analysis, into three groups of AA intake: low <1.5 g/kg/day (LAA), medium 1.5-2 g/kg/day (MAA) and high >2 g/kg/day (HAA).
A total of 154 infants were included. HAA group presented lower weight loss. Na balance was influenced by urine output and postnatal age, with little contribution of nutrition. Kalemia and K balance were mainly influenced by AA intake. K balance differed among groups: LAA, -2.3 mmol/kg/week; MAA, 1.1 mmol/kg/week; and HAA 2.6 mmol/kg/week (P<0.0001). In the HAA group, plasma and urine K were significantly lower and non-oliguric hyperkalemia was reduced.
Na homeostasis was very slightly modified by early nutrition, suggesting that a negative Na balance is obligatory after birth. We showed that AA intake strongly affects K balance, minimize hyperkalemia and reduces weight loss. As K balance is strictly linked to cellular metabolism, we speculate that early nutrition may inhibit cellular catabolism and reduce the contraction of intracellular water compartment.
Obtaining a rapid etiological diagnosis for infants with early-onset rare diseases remains a major challenge. These diseases often have a severe presentation and unknown prognosis, and the genetic ...causes are very heterogeneous. In a French hospital network, we assessed the feasibility of performing accelerated trio-genome sequencing (GS) with limited additional costs by integrating urgent requests into the routine workflow. In addition to evaluating our capacity for such an approach, this prospective multicentre pilot study was designed to identify pitfalls encountered during its implementation. Over 14 months, we included newborns and infants hospitalized in neonatal or paediatric intensive care units with probable genetic disease and in urgent need for etiological diagnosis to guide medical care. The duration of each step and the pitfalls were recorded. We analysed any deviation from the planned schedule and identified obstacles. Trio-GS was performed for 37 individuals, leading to a molecular diagnosis in 18/37 (49%), and 21/37 (57%) after reanalysis. Corrective measures and protocol adaptations resulted in a median duration of 42 days from blood sampling to report. Accelerated trio-GS is undeniably valuable for individuals in an urgent care context. Such a circuit should coexist with a rapid or ultra-rapid circuit, which, although more expensive, can be used in particularly urgent cases. The drop in GS costs should result in its generalized use for diagnostic purposes and lead to a reduction of the costs of rapid GS.
Perinatal arterial ischemic stroke (PAIS) is a common cause of hemiplegic cerebral palsy in children. The diagnosis of PAIS is based on cerebral imaging. The objective of our study was to determine ...prenatal risk factors associated with PAIS.
A retrospective case-control study was nested in the whole population of Burgundy, France, from January 2000 to December 2007. Case patients were confirmed by review of brain imaging and medical records. Three control subjects per case were randomly selected from the study population by sex, term, place, and year of birth.
PAIS was confirmed in 32 patients and its incidence was one per 4400 live births. In comparison to control subjects, clinical conditions significantly associated to cases were gestational diabetes (16.1% versus 4.2%; P=0.04), fetal heart rate abnormalities (35.5% versus 10.9%; P=0.001), and meconium-stained liquor (40% versus 12%; P<0.001). At the limit of statistical significance were found maternal smoking before (39.3% versus 22.9%; P=0.08) and during pregnancy (32.1% versus 16.7%; P=0.07), cord abnormalities (29% versus 14.1%; P=0.06), and cesarean delivery (28.1% versus 14.6%; P=0.08). In the multivariate analysis, maternal smoking during pregnancy (OR, 3.1; 95% CI, 1.1-8.8; P=0.04) was the only risk factor significantly associated with PAIS.
This study is the first to identify maternal smoking during pregnancy as an independent prenatal risk factor of PAIS. Additional prospective studies are needed to confirm this result and to investigate the role of maternal smoking in fetal and neonatal thrombogenesis.
Les thrombus intracardiaques sont rares chez les nouveau-nés prématurés. L’incidence des thromboses sur cathéters veineux ombilicaux (CVO) est estimée entre 2,5 à 9 %. Pour autant, il a été constaté ...dans l’unité de réanimation néonatale de notre centre trois cas de thrombus intracardiaque ces deux dernières années. Rétrospectivement, tous ces enfants avaient reçu une transfusion sur leur CVO. Il se pose donc la question de l’imputabilité des transfusions sur CVO dans la survenue de thrombus intracardiaque.
Hospitalisation d’un prématuré de 27 SA, 585g. Devant une hypotension artérielle, nécessité de pose d’un CVO 4 Fr à j0. Survenue d’une thrombopénie secondaire au retard de croissance intra-utérin motivant la réalisation d’une transfusion plaquettaire. Survenue d’une erreur de calcul par l’EFS de la quantité de plaquettes à transfuser et non décelée par l’infirmière qui a donc transfusé 3 fois la dose prescrite soit 34mL/kg. Découverte fortuite d’un thrombus intracardiaque lors d’une échographie cardiaque réalisée dans le cadre d’une tachycardie persistante à 4jours de vie. Devant ce thrombus, mise en place d’un traitement par héparine à doses curatives suivie de l’ablation du CVO 48heures après. Chez ce patient qui présentait déjà des facteurs de risque de thrombose (prématurité extrême, retard de croissance intra-utérin, alimentation parentérale concomitante à la transfusion), la transfusion plaquettaire sur cathéter veineux central a été un élément supplémentaire ayant pu favoriser la survenue d’un thrombus et plus spécifiquement un thrombus intracardiaque dans notre cas.
La survenue d’une thrombose est un événement indésirable grave d’autant plus que son traitement curatif (héparine) est un facteur de risque majeur d’hémorragie intraventriculaire chez les nouveau-nés prématurés. Il paraît donc légitime de préférer une transfusion plaquettaire sur une voie veineuse périphérique que sur une voie veineuse centrale.