Randomized Controlled Trial of Early Docosahexaenoic Acid and Arachidonic Acid Enteral Supplementation in Very Low Birth Weight Infants.

OBJECTIVE: To determine feasibility of providing a concentrated emulsified long-chain polyunsaturated fatty acids (LCPUFA) supplement to very low birth weight infants, and to evaluate blood LCPUFA concentrations at 2 and 8 weeks of study supplementation. STUDY DESIGN: This prospective, randomized, double-blind, placebo-controlled trial randomized infants to receive (1) LCPUFA-120 (a supplement of 40 mg/kg/day docosahexaenoic acid [DHA] and 80 mg/kg/day arachidonic acid [ARA]; DHA:ARA at 1:2 ratio), (2) LCPUFA-360 (a supplement of 120 mg/kg/day DHA and 240 mg/kg/day ARA), or (3) sunflower oil (placebo control). Infants received supplement daily for 8 weeks or until discharge, whichever came first. Whole blood LCPUFA levels (wt%; g/100 g) were measured at baseline, 2 weeks, and 8 weeks. RESULTS: Infants were 28 weeks of gestation (IQR, 27-30 weeks of gestation) and weighed 1040 g (IQR, 910-1245 g). At 2 weeks, the change in blood DHA (wt%) from baseline differed significantly among groups (sunflower oil, n = 6; -0.63 [IQR, -0.96 to -0.55]; LCPUFA-120: n = 12; -0.14 [IQR, -0.72 to -0.26]; LCPUFA-360, n = 12; 0.46 [IQR, 0.17-0.81]; P = .002 across groups). Change in blood ARA (wt%) also differed by group (sunflower oil: -2.2 [IQR, -3.9 to -1.7]; LCPUFA-120: 0.1 [IQR, -2.1 to 1.1] vs LCPUFA-360: 2.9 IQR, 1.5 to 4.5]; P = .0002). Change from baseline to 8 weeks significantly differed between groups for DHA (P = .02) and ARA (P = .003). CONCLUSIONS: Enteral LCPUFA supplementation supported higher blood DHA by 2 weeks. LCPUFA supplementation at 360 mg of combined DHA and ARA is likely necessary to reduce declines as well as allow increases in whole blood concentrations in the first 8 weeks of life. TRIAL REGISTRATION: Clinicaltrials.gov: NCT03192839.

Energy and Protein Intake During the Transition from Parenteral to Enteral Nutrition in Infants of Very Low Birth Weight.

OBJECTIVE: To evaluate the association between nutrition delivery practices and energy and protein intake during the transition from parenteral to enteral nutrition in infants of very low birth weight (VLBW). STUDY DESIGN: This was a retrospective analysis of 115 infants who were VLBW from a regional neonatal intensive care unit. Changes in energy and protein intake were estimated during transition phase 1 (0% enteral); phase 2 (>0, ≤33.3% enteral); phase 3 (>33.3, ≤66.7% enteral); phase 4 (>66.7, <100% enteral); and phase 5 (100% enteral). Associations between energy and protein intake were determined for each phase for parenteral nutrition, intravenous lipids, central line, feeding fortification, fluid restriction, and excess non-nutritive fluid intake. RESULTS: In phases 2 and 3, infants receiving feeding fortification received less protein than infants who were unfortified (-1.1 and -0.3 g/kg/d, respectively; P < .001). However, this negative association was not observed after adjusting for relevant nutrition delivery practices. Despite greater enteral protein intake during phases 2 and 3 (0.3 and 0.8 g/kg/d, respectively; P < .001), infants with early fortification received less parenteral protein than infants who were unfortified (-1.4 and -1.1 g/kg/d, respectively; P < .001). Similar patterns were observed for energy intake. Protein intake declined during phases 3 and 4. CONCLUSIONS: Infants paradoxically received less protein and energy on days with early fortification, suggesting that clinicians may lack easily accessible data to detect the association between nutrition delivery practices and overall nutrition in infants who are VLBW.

Docosahexaenoic and arachidonic acid levels in extremely low birth weight infants with prolonged exposure to intravenous lipids.

OBJECTIVE: To report changes in red blood cell long-chain polyunsaturated fatty acids levels in extremely low birth weight (ELBW) infants relative to duration of intravenous lipid emulsion. STUDY DESIGN: Serial blood samples were collected from 26 ELBW infants during the first 2 months of life in the neonatal intensive care unit using a prospective cohort study design. The primary outcome was the change in long-chain polyunsaturated fatty acids levels over the study period relative to a duration of intravenous lipid emulsion of either ≤ 28 days or >28 days. Secondary outcomes included parenteral and enteral nutritional exposures as well as prematurity-associated morbidities. Longitudinal regression estimated changes in fatty acid levels between the 2 exposure groups. RESULTS: Infants with >28 days intravenous lipid emulsion had 36 more days of intravenous lipid emulsion than did those with ≤ 28 days (P < .001). Docosahexaenoic acid significantly decreased over time in all infants and decreased significantly more in infants exposed to intravenous lipid emulsion for >28 days (P = .03). Arachidonic acid significantly decreased over the study period but the decrease was not related to intravenous lipid emulsion duration. Linoleic and α-linolenic acids had significantly larger increases over time in those with longer exposure to intravenous lipid emulsion (P < .01). CONCLUSION: Docosahexaenoic acid status of ELBW infants declined significantly in the first 2 months of life and the decline was significantly greater in those exposed to intravenous lipid emulsion >28 days compared with those exposed ≤ 28 days.

Parenteral nutrition-associated cholestasis in small for gestational age infants.

OBJECTIVE: To identify small for gestational age (SGA) as an independent risk factor for parenteral nutrition-associated cholestasis (PNAC). STUDY DESIGN: In a case-control study, records of infants treated in the neonatal intensive care unit from 1994 through 2003 with gestational ages (GA) < 34 weeks and exposure to parenteral nutrition (PN) > or = 7 days were reviewed. The primary outcome was the incidence of cholestasis in infants who were SGA. Secondary outcomes included PN duration, age at full enteral nutrition (FEN) and incidence of late-onset sepsis, necrotizing enterocolitis (NEC) and bronchopulmonary dysplasia (BPD). Analysis was by t test, logistic regression, and chi2 analysis. RESULTS: Cases (n = 79) and control subjects (n = 152) had similar birth weights and GA (963 +/- 465 g versus 1090 +/- 463 g; 27 +/- 2 weeks versus 27 +/- 2 weeks; [mean +/- SD]). Of the infants who were SGA, 58% developed cholestasis (OR = 3.3, P < .01). Infants with cholestasis achieved FEN later (43 +/- 25 days versus 23 +/- 11 days) and had higher rates of sepsis (80% versus 34%), NEC (51% versus 7%), and BPD (65% versus 25%; P < .01). Of infants with cholestasis, infants who were SGA received fewer days of PN than infants who were appropriate for GA (49 +/- 24 days versus 68 +/- 36 days, P = .024). CONCLUSION: Being SGA is an independent risk factor for PNAC. Infants who are SGA require less PN for cholestasis to develop.