Enteral Docosahexaenoic Acid and Retinopathy of Prematurity: A Randomized Clinical Trial.

BACKGROUND: Retinopathy of prematurity (ROP) is a disorder of the retina of low-birth-weight preterm infants that potentially leads to blindness. Docosahexaenoic acid (DHA), is protective in experimental models, but its administration as part of parenteral nutrition has shown inconsistent results. We test the effect of enteral DHA to prevent ROP and/or severity and to reduce hospital stay. METHODS: This was a double-blind parallel clinical trial. Preterm infants (n = 110; 55 per group) with birth weight <1500 g but ≥1000 g were recruited in a neonatal intensive care unit. Infants were randomized to receive 75 mg of DHA/kg/d (DHA group) or high oleic sunflower oil (control group) for 14 days by enteral feeding. The effect of DHA was evaluated on any stage of ROP, severe ROP (stage ≥3) incidence, and hospital stay. Groups were compared with relative risk (RR) and 95% confidence interval (CI), Fisher's exact test, Student's t-test, or Mann-Whitney U-test, as appropriate. Logistic regression was applied to adjust for confounders. RESULTS: There was no difference between the DHA and control groups in ROP risk (RR for DHA = 0.79; 95% CI, 0.49-1.27; P = 0.33). However, patients who received DHA showed lower risk for stage 3 ROP (RR for DHA = 0.66; 95% CI, 0.44-0.99; P = 0.03). After adjusting for confounders, this decreased risk remained significant (adjusted odds ratio = 0.10; 95% CI, 0.011-0.886; P = 0.04). Hospital stay was similar between groups. CONCLUSION: Enteral DHA may reduce the incidence of stage 3 ROP.

Enteral Docosahexaenoic Acid Reduces Analgesic Administration in Neonates Undergoing Cardiovascular Surgery.

BACKGROUND: Neonates undergoing surgery require analgesic medication to ameliorate acute pain. These medications produce negative side effects. Docosahexaenoic acid (DHA) has an antinociceptive effect in animals, but this has not been evaluated in human neonates. We evaluated the DHA effect on cumulative dose and duration of analgesics administered to neonates undergoing cardiovascular surgery. METHODS: A secondary analysis was performed with data from a clinical trial, in which enteral DHA was administered perioperatively compared with sunflower oil (SO). Present study assessed the antinociceptive effect of DHA by measuring the cumulative dose and duration of analgesics administered during postoperative stay in a neonatal intensive care unit. Multivariate linear regression models were performed. RESULTS: Seventeen neonates received DHA and 18 received SO in the control group. Compared with the control group, the DHA group received lower cumulative dose (14.6 ± 2.2 vs. 25.2 ± 4.8 µg/kg, p = 0.029) and shorter duration of buprenorphine (2 days (1-8) vs. 4.5 days (1-12); p = 0.053). After adjusting for confounders, the DHA group received significantly lesser buprenorphine (ß = -27 µg/kg, p = 0.028; R2 model = 0.90) for shorter duration (ß = -9 days, p = 0.003; R2 model = 0.94). No differences in fentanyl or ketorolac were detected. CONCLUSIONS: Buprenorphine administration was reduced in neonates who received DHA, suggesting that DHA likely has analgesic effects.

Beneficial Effects of Enteral Docosahexaenoic Acid on the Markers of Inflammation and Clinical Outcomes of Neonates Undergoing Cardiovascular Surgery: An Intervention Study.

BACKGROUND: Neonates undergoing surgery are at risk for uncontrolled inflammatory response and adverse clinical outcomes. Docosahexaenoic acid (DHA) ameliorates inflammation, improving clinical outcomes. However, its effect has not been evaluated in neonates undergoing surgery. We evaluated the effect of DHA on markers of inflammation and clinical outcomes in neonates undergoing surgery. METHODS: A double-blind clinical trial evaluated the effect of enteral DHA (DHA group) versus sunflower oil (SO group) perioperatively administered in neonates scheduled for cardiovascular surgery. Inflammation was evaluated by percentage of cells+ for cytokines and CD69 in mononuclear cells at baseline, 24 h and 7 days post surgery. Clinical outcomes measured were sepsis, organ dysfunctions (ODs), length of stay in intensive care and bleeding. Repeated measures analysis of variance and logistic regression were applied. RESULTS: Sixteen neonates received DHA and 18 received SO. Cells+ from neonates in the DHA group showed an early increase in receptor antagonist of interleukin (IL)-1+ (IL-1ra+) and IL-10+ and a late decrease in IL-6+. IL-1ß+ and IL-10+ changes were different between groups. After adjusting for confounders, less cells from DHA group were IL-1ß+, IL-6+, IL-1ra+ and IL-10+. DHA group presented less sepsis, ODs and shorter stay, but no difference in CD69+CD4+ cells or bleeding between groups. CONCLUSIONS: Administration of enteral DHA ameliorates markers of inflammation and improves clinical outcomes in surgical neonates.

Ácido docosahexaenoico y ácido araquidónico en neonatos: ¿el aporte que reciben es suficiente para cubrir sus necesidades? / Docosahexaenoic acid in neonates: do they receive enough to reach their needs?

Se describen las bases fisiológicas de la acción de los ácidos grasos poliinsaturados de las familias n-6 y n-3, así como de sus productos finales: el ácido araquidónico y el ácido docosahexaenoico, respectivamente, para identificar su importancia durante la etapa fetal en las funciones estructurales críticas al llegar a las 40 semanas de gestación. El déficit de los ácidos grasos poliinsaturados se relaciona con patologías en los niños pretérmino que no lograron la acreción adecuada, como la retinopatía del prematuro, la enterocolitis necrosante o la displasia broncopulmonar, entre otras. Se analizan los trabajos que evalúan el efecto del suplemento con diferentes concentraciones de ácidos grasos poliinsaturados sobre funciones neurológicas y visuales y crecimiento en los recién nacidos. Se abordan las necesidades de ácido docosahexaenoico y ácido araquidónico en esta etapa de la vida, y se comparan con el aporte que se puede lograr mediante la alimentación con leche humana y con las diferentes fórmulas para recién nacidos pretérmino, término y lactantes. Dado que el niño pretérmino nace con deficiencias tisulares pero con requerimientos aumentados de estos ácidos grasos, parece ser insuficiente el aporte con las fórmulas suplementadas comerciales actuales. La recomendación final es la alimentación de los niños con leche humana, ofreciendo a la madre sugerencias de consumo de fuentes con alto contenido de ácido docosahexaenoico, sobre todo si su hijo fue pretérmino.

In this article we discuss the physiological bases of polyunsaturated fatty acids (PUFAs) from n-6 and n-3 families and their end products: arachidonic acid (AA) and docosahexaenoic acid (DHA), respectively, to identify their importance in the fetal stage such as critical structural functions at 40 weeks of gestation. PUFA deficit is related to pathologies in preterm infants who did not achieve adequate accretion such as retinopathy of prematurity (ROP), necrotizing enterocolitis (NEC), and bronchopulmonary dysplasia (BPD), among others. In addition, studies evaluating the effect of supplementation with different concentrations of PUFAs on neurological and visual function and growth in neonates are analyzed. We also address the needs of DHA and AA at this stage of life and compare the enteral intake achieved by human milk feeding and the different formulas for preterm and term infants. DHA concentration in breast milk is highly variable and its contribution may be insufficient in neonates. Preterm infant formulas can meet international recommendations of DHA and AA issued by different organizations but, due to preterm birth, these infants have scarce tissue reserves but increased requirements for these fatty acids. Thus, enteral intake using current supplemental formula feeding appears to be insufficient. The final recommendation is to feed neonates with human milk by offering information to mothers regarding food sources with high DHA content, especially in the case of preterm babies.

Validation of a prognostic index in the critically ill newborn / Validación de un índice pronóstico en el recién nacido en estado crítico

Objetivo. Elaborar y validar un modelo pronóstico para evaluar a los pacientes que ingresan a una Unidad de Cuidados Intensivos Neonatales (UCIN). Diseño. Casos y controles anidado en una cohorte. Lugar. UCIN de dos hospitales de tercer nivel y uno de segundo nivel. Pacientes. El estudio se realizó en dos fases (elaboración y validación del modelo respectivamente). En la primera fase se estudiaron 336 recién nacidos, 112 casos (pacientes fallecidos en la UCIN) y 224 controles (pacientes egresados vivos de la UCIN). En la segunda fase se incluyeron 300 pacientes, 100 casos y 200 controles. Mediciones. A cada uno de los pacientes que ingresaron al estudio se les determinaron los factores perinatales, clínicos, paraclínicos, y de co-morbilidad dentro de las primeras 12 horas de haber ingresado. Las variables que mostraron significancia estadística en el análisis bivariado se llevaron a un modelo de regresión logística. Resultados. Las variables que constituyeron el modelo pronóstico fueron edad gestacional x peso al nacer, paO2/FiO2 x saturación de O2, paro cardiaco, malformaciones congénitas mayores, septicemia y exceso de base. En la cohorte de elaboración la sensibilidad del modelo fue 70 por ciento y la especificidad 91 por ciento. En la cohorte de validación la sensibilidad fue 68 por ciento y la especificidad 92 por ciento, el valor predictivo positivo 80 por ciento, el valor predictivo negativo 85 por ciento y la frecuencia de clasificación correcta 84 por ciento. Conclusiones. El índice pronóstico de mortalidad neonatal desarrollado en este estudio demostró ser útil para la evaluación de la mortalidad hospitalaria en recién nacidos críticamente enfermos que ingresan a una UCIN.