Modification of serum fatty acids in preterm infants by parenteral lipids and enteral docosahexaenoic acid/arachidonic acid: A secondary analysis of the Mega Donna Mega trial.

BACKGROUND & AIM: Preterm infants risk deficits of long-chain polyunsaturated fatty acids (LCPUFAs) that may contribute to morbidities and hamper neurodevelopment. We aimed to determine longitudinal serum fatty acid profiles in preterm infants and how the profiles are affected by enteral and parenteral lipid sources. METHODS: Cohort study analyzing fatty acid data from the Mega Donna Mega study, a randomized control trial with infants born <28 weeks of gestation (n = 204) receiving standard nutrition or daily enteral lipid supplementation with arachidonic acid (AA):docosahexaenoic acid (DHA) (100:50 mg/kg/day). Infants received an intravenous lipid emulsion containing olive oil:soybean oil (4:1). Infants were followed from birth to postmenstrual age 40 weeks. Levels of 31 different fatty acids from serum phospholipids were determined by GC-MS and reported in relative (mol%) and absolute concentration (µmol l-1) units. RESULTS: Higher parenteral lipid administration resulted in lower serum proportion of AA and DHA relative to other fatty acids during the first 13 weeks of life (p < 0.001 for the 25th vs the 75th percentile). The enteral AA:DHA supplement increased the target fatty acids with little impact on other fatty acids. The absolute concentration of total phospholipid fatty acids changed rapidly in the first weeks of life, peaking at day 3, median (Q1-Q3) 4452 (3645-5466) µmol l-1, and was positively correlated to the intake of parenteral lipids. Overall, infants displayed common fatty acid trajectories over the study period. However, remarkable differences in fatty acid patterns were observed depending on whether levels were expressed in relative or absolute units. For example, the relative levels of many LCPUFAs, including DHA and AA, declined rapidly after birth while their absolute concentrations increased in the first week of life. For DHA, absolute levels were significantly higher compared to cord blood from day 1 until postnatal week 16 (p < 0.001). For AA, absolute postnatal levels were lower compared to cord blood from week 4 throughout the study period (p < 0.05). CONCLUSIONS: Our data show that parenteral lipids aggravate the postnatal loss of LCPUFAs seen in preterm infants and that serum AA available for accretion is below that in utero. Further research is needed to establish optimal postnatal fatty acid supplementation and profiles in extremely preterm infants to promote development and long-term health. CLINICAL TRIAL REGISTRY: ClinicalTrials.gov, identifier: NCT03201588.

Mother's Own Milk and Its Relationship to Growth and Morbidity in a Population-based Cohort of Extremely Preterm Infants.

OBJECTIVES: The aim of the study was to evaluate the relationships between intake of mother's own milk (MOM), compared with intake of pasteurized donor milk (DM), and postnatal growth, incidence of retinopathy of prematurity (ROP) and bronchopulmonary dysplasia (BPD), in extremely preterm infants. METHODS: Swedish population-based cohort of surviving extremely preterm infants born 2004 to 2007. Exposure to MOM and DM was investigated from birth until 32 weeks postmenstrual age (PMA) in 453 infants. Primary outcome variables were change in z-score (Δ) from birth to 32 weeks PMA for weight, length, and head circumference (HC). Secondary outcomes were incidence of ROP and BPD. Mixed models adjusting for confounders were used to investigate the association between exposures and outcomes. RESULTS: Infants' mean gestational age (GA) was 25.4 weeks. Unadjusted, MOM (per 10 mL ·â€Škg-1 ·â€Šday-1) was associated with Δweight and ΔHC with beta estimates of 0.03 z-score units (95% CI, 0.02-0.04, P < 0.001) and 0.03 z-score units (95% CI, 0.01-0.05, P = 0.003), respectively. After adjustment for predefined confounders, the association remained significant for Δweight and ΔHC. A similar pattern was found between Δweight and each 10% increase of MOM. Unadjusted, a higher intake of MOM (mL ·â€Škg-1 ·â€Šday-1) was significantly associated to a lower probability of any ROP and severe ROP; however, these associations did not remain in the adjusted analyses. No associations were found between MOM (mL ·â€Škg-1 ·â€Šday-1) and BPD. Moreover, no associations were found between DM and growth or morbidity outcomes. CONCLUSIONS: An increased intake of MOM, as opposed to DM (and not formula feeding), was associated with improved postnatal weight gain and HC growth from birth until 32 weeks PMA in extremely preterm infants. Interventions aiming at increasing early intake of unpasteurized MOM for extremely preterm infants should be encouraged.

Effect of Enteral Lipid Supplement on Severe Retinopathy of Prematurity: A Randomized Clinical Trial.

Importance: Lack of arachidonic acid (AA) and docosahexaenoic acid (DHA) after extremely preterm birth may contribute to preterm morbidity, including retinopathy of prematurity (ROP). Objective: To determine whether enteral supplementation with fatty acids from birth to 40 weeks' postmenstrual age reduces ROP in extremely preterm infants. Design, Setting, and Participants: The Mega Donna Mega trial, a randomized clinical trial, was a multicenter study performed at 3 university hospitals in Sweden from December 15, 2016, to December 15, 2019. The screening pediatric ophthalmologists were masked to patient groupings. A total of 209 infants born at less than 28 weeks' gestation were tested for eligibility, and 206 infants were included. Efficacy analyses were performed on as-randomized groups on the intention-to-treat population and on the per-protocol population using as-treated groups. Statistical analyses were performed from February to April 2020. Interventions: Infants received either supplementation with an enteral oil providing AA (100 mg/kg/d) and DHA (50 mg/kg/d) (AA:DHA group) or no supplementation within 3 days after birth until 40 weeks' postmenstrual age. Main Outcomes and Measures: The primary outcome was severe ROP (stage 3 and/or type 1). The secondary outcomes were AA and DHA serum levels and rates of other complications of preterm birth. Results: A total of 101 infants (58 boys [57.4%]; mean [SD] gestational age, 25.5 [1.5] weeks) were included in the AA:DHA group, and 105 infants (59 boys [56.2%]; mean [SD] gestational age, 25.5 [1.4] weeks) were included in the control group. Treatment with AA and DHA reduced severe ROP compared with the standard of care (16 of 101 [15.8%] in the AA:DHA group vs 35 of 105 [33.3%] in the control group; adjusted relative risk, 0.50 [95% CI, 0.28-0.91]; P = .02). The AA:DHA group had significantly higher fractions of AA and DHA in serum phospholipids compared with controls (overall mean difference in AA:DHA group, 0.82 mol% [95% CI, 0.46-1.18 mol%]; P < .001; overall mean difference in control group, 0.13 mol% [95% CI, 0.01-0.24 mol%]; P = .03). There were no significant differences between the AA:DHA group and the control group in the rates of bronchopulmonary dysplasia (48 of 101 [47.5%] vs 48 of 105 [45.7%]) and of any grade of intraventricular hemorrhage (43 of 101 [42.6%] vs 42 of 105 [40.0%]). In the AA:DHA group and control group, respectively, sepsis occurred in 42 of 101 infants (41.6%) and 53 of 105 infants (50.5%), serious adverse events occurred in 26 of 101 infants (25.7%) and 26 of 105 infants (24.8%), and 16 of 101 infants (15.8%) and 13 of 106 infants (12.3%) died. Conclusions and Relevance: This study found that, compared with standard of care, enteral AA:DHA supplementation lowered the risk of severe ROP by 50% and showed overall higher serum levels of both AA and DHA. Enteral lipid supplementation with AA:DHA is a novel preventive strategy to decrease severe ROP in extremely preterm infants. Trial Registration: ClinicalTrials.gov Identifier: NCT03201588.

Serum choline in extremely preterm infants declines with increasing parenteral nutrition.

PURPOSE: Choline is an essential nutrient for fetal and infant growth and development. Parenteral nutrition used in neonatal care lack free choline but contain small amounts of lipid-bound choline in the form of phosphatidylcholine (PC). Here, we examined the longitudinal development of serum free choline and metabolically related compounds betaine and methionine in extremely preterm infants and how the concentrations were affected by the proportion of parenteral fluids the infants received during the first 28 postnatal days (PNDs). METHODS: This prospective study included 87 infants born at gestational age (GA) < 28 weeks. Infant serum samples were collected PND 1, 7, 14, and 28, and at postmenstrual age (PMA) 32, 36, and 40 weeks. The serum concentrations of free choline, betaine, and methionine were determined by 1H NMR spectroscopy. RESULTS: The median (25th-75th percentile) serum concentrations of free choline, betaine, and methionine were 33.7 (26.2-41.2), 71.2 (53.2-100.8), and 25.6 (16.4-35.3) µM, respectively, at PND 1. The choline concentration decreased rapidly between PND one and PND seven [18.4 (14.1-26.4) µM], and then increased over the next 90 days, though never reaching PND one levels. There was a negative correlation between a high intake of parenteral fluids and serum-free choline. CONCLUSION: Circulating free choline in extremely preterm infants is negatively affected by the proportion of parenteral fluids administered. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT02760472, April 29, 2016, retrospectively registered.

Unpasteurised maternal breast milk is positively associated with growth outcomes in extremely preterm infants.

AIM: Extrauterine growth restriction is common among extremely preterm infants. We explored whether intake of unpasteurised maternal milk (MM) and pasteurised donor milk (DM) was associated with longitudinal growth outcomes and neonatal morbidities in extremely preterm infants. METHODS: Observational study of 90 preterm infants born between 2013 and 2015 in Gothenburg, Sweden. Data were prospectively collected on nutritional and breast milk intakes during the first 28 days. RESULTS: Ninety infants (39 girls and 51 boys) with a median gestational age of 25.3 (22.7-27.9) weeks were evaluated. MM intake (mL/kg/d) correlated positively with almost all z-scores for weight, length and head circumference at 28 postnatal days and at postmenstrual age (PMA) 32 and 36 weeks. After multivariable adjustment, MM intake and weight z-score at 28 postnatal days and at PMA 32 and 36 weeks remained significantly associated. Infants consuming ≥80% MM had more favourable weight z-scores at PMA 32 and 36 weeks. Intake of DM did not correlate with any growth outcomes. Infants without retinopathy of prematurity had a significantly higher intake of MM (mL/kg/d). CONCLUSION: Unpasteurised MM was positively associated with longitudinal growth outcomes. Motivating mothers to provide their infants with their own milk after preterm birth should be emphasised.

Review shows that donor milk does not promote the growth and development of preterm infants as well as maternal milk.

AIM: This nonsystematic review examined differences in the composition of raw maternal breastmilk and pasteurised donor milk and possible health effects on preterm infants. METHODS: We searched PubMed up to July 2018 for studies published in English that focused on four comparisons as follows: raw maternal milk versus donor milk, human milk before and after Holder pasteurisation, milk from mothers who delivered preterm and at term and milk collected during early and late lactation. We also searched for possible effects of the milk components, as well as the effects of maternal and donor milk on preterm infants' health. RESULTS: Raw maternal milk contained factors involved in antioxidant and anti-inflammatory defence, gut microbiome establishment and the maturation of immune defences, food tolerability and metabolism. Many of these factors were reduced or abolished in processed donor milk. Both maternal milk and donor milk have been associated with a reduced incidence of necrotising enterocolitis. High-dose feeding with maternal milk during the neonatal period reportedly reduced the risk of other morbidities and promoted growth and neurodevelopment. CONCLUSION: Many of the components in raw maternal breastmilk were lacking in pasteurised donor milk, which was inferior in promoting the growth and development of very preterm infants.