Metabolic Mechanisms Induced by Enteral DHA and ARA Supplementation in Preterm Infants

Metabolic Mechanisms Induced by Enteral Docosahexaenoic Acid (DHA) and Arachidonic Acid (ARA) Supplementation in Preterm Infants

A comprehensive analysis of the impact of exogenous enteral DHA and ARA supplementation on lipid metabolism including the production of downstream derived mediators and how this impacts important biological pathways such as metabolism, inflammation, and organogenic factors.

Infants will be randomized to receive the combined enteral DHA/ARA supplement within the first 48 hours after birth to 36 weeks postmenstrual age. The randomization procedure will follow a stratified permuted block scheme to fulfill two goals: (1) randomize infants into one of four arms and (2) ensure an adequate sample size within each week of gestational age. Preterm infants will be randomized using random permuted blocks within each of the 5 birth gestational age strata. When treatment assignment is open and sample size is not overtly large, a block randomization procedure with randomly chosen block sizes can maintain treatment assignment balance and reduce the potential for selection bias. This approach will also ensure that preterm infants of all eligible gestational ages at birth are approximately equally represented in each of 4 arms of the trial, thus ensuring that important comorbidities and standard of care applicable to infants of different gestational ages at birth are also approximately equally distributed across the study arms. There is no placebo for this study. There is no blinding in this study. Consent will also be obtained from the mother of the infant, as they will be asked to provide milk samples if they're breastfeeding their infant, and maternal medical history and demographical data will be recorded.

There will be four arms of the trial encompassing the period from enrollment to 36 weeks' postmenstrual age: (a) DHA/ARA supplement throughout the duration of the protocol, "d-on"; (b) no DHA/ARA supplement throughout the duration of the protocol, "d-off"; (c) a cross-over arm of DHA/ARA supplement from enrollment to 31 6/7 weeks post-menstrual age (PMA) then no supplement from 32 to 36 weeks' PMA, "x- on/off"; and (d) a cross-over arm of no DHA/ARA supplement till 31 6/7 weeks' then long-chain polyunsaturated fatty acids (LCPUFA) supplement from 32 to 36 weeks PMA, "x-off/on".

DHA/ARA supplement from enrollment to 31 6/7 weeks post-menstrual age (PMA) then no supplement from 32 to 36 weeks' PMA, "x- on/off"

No DHA/ARA supplement till 31 6/7 weeks' then long-chain polyunsaturated fatty acids (LCPUFA) supplement from 32 to 36 weeks PMA, "x-off/on"

Dosage: 60 mg/kg/day of DHA and 120 mg/kg/day of ARA. Route of administration: enteral tube or by oral syringe

Biomarker reflective of system development and function will be measured. There are no specific levels since there is no normative data in neonates.

Biomarker reflective of system development and function will be measured. There are no specific levels since there is no normative data in neonates.

Biomarker reflective of system development and function will be measured. There are no specific levels since there is no normative data in neonates.

Inclusion Criteria: born between 25 0/7 and 29 6/7 weeks of gestation less than 48 hours of age at first lipid dose (The cohort is defined by gestational age rather than birth weight to avoid an over-represented sample of growth-restricted infants in birth weight defined cohorts.) Exclusion Criteria: serious congenital anomalies conditions at birth that will require surgery prior to discharge imminent death such that withdrawal of intensive care support is anticipated within the first 72 hours after birth

Deidentified data will be shared with the funding body, NIH, summary results will be shared in ClinicalTrials.gov