Total Fat and Fatty Acid Composition of Preterm Human Milk: A Systematic Review and Meta-Analysis

Preterm human milk (HM) is abundant in fat and fatty acids (FA) that contribute to overall energy intake and are vital for growth, cell integrity, and brain development. The objective of this systematic review and meta-analyses is to quantify the amount of total fat and FAs including long-chain fatty acids in preterm HM. Ebsco, PubMed, and Scopus databases were searched to July 2023 measuring total fat and FAs in preterm HM. Three reviewers, working independently, screened all titles and abstracts to identify studies meeting inclusion criteria [preterm < 37 wks; Human Development Index > 0.8; cross-sectional, case-controlled (n > 1), prospective cohort, and randomized clinical trials; English language]. Random effects models were used to estimate mean total fat and FA content across studies. Data were aggregated for studies reporting repeated measures. Heterogeneity was estimated using I 2 and publication bias using Kendall tau rank correlation coefficient. Of the 884 articles identified, a total of 69 original studies were included for the meta-analysis comprising an estimated 1871 preterm infants (gestational age range 23.2-36.6 wk). Mean [95% CI] total fat was 3.76 [3.57, 3.95] g/100 mL, which varied across colostrum (< 5 d; 3.04 [2.51, 3.57] g/100 mL), transition (5 - 14 d; 3.74 [3.47, 4.00] g/100 mL), and mature (> 14 d, 3.85 [3.61, 4.08] g/100 mL) preterm HM. The creamatocrit method provided the highest total fat composition followed by infrared, other/not specified, then gravimetric. Total mean FA content from 24 studies (895 preterm infants) also varied, where the most abundant was oleic acid (18:1n-9; 33.01% w/w FA) and palmitic acid (16:0; 22.05% w/w FA). The total mean essential FA concentrations were 13.76% w/w for 18:2 n-6 and 1.03% w/w for 18:3n-3. This systematic review provides updated estimates of total fat and FA concentrations in preterm HM, although high variability among study design and quality, analytical methodologies, and data reporting were found across studies. Registry number in PROSPERO CRD42023445191