Carbohydrate and Energy Composition of Preterm Human Milk: A Systematic Review and Meta-Analysis

Preterm human milk (HM) is a major source of carbohydrates (CHO), primarily lactose, which contribute to energy intake and support growth and neurodevelopment. This systematic review and meta-analyses quantified total CHO, lactose, and energy content in preterm HM. EBSCO Health Source - Nursing/Academic Edition and MEDLINE with Full Text), PubMed, and Scopus were searched through July 2023 for studies reporting nutrient composition in preterm HM (< 37 weeks gestation) from countries with a Human Development Index >0.8 to reduce potential heterogeneity that may influence HM composition. Cross-sectional, case control (n > 1), prospective cohort, and randomized controlled trials published in English were included. Two reviewers independently screened titles and abstracts. Of the studies meeting inclusion criteria, this meta-analysis included articles that reported total CHO, lactose, and energy content in preterm HM. Random effects models estimated pooled mean amounts of total CHO, lactose, and energy across studies. Heterogeneity was estimated using I² and publication bias using Begg's rank correlation test. Repeated measures were aggregated. Of 884 identified articles, 53 studies reported total CHO, lactose, and energy. Mean [95% CI] total CHO was 6.74 [6.41, 7.07] g/100 mL with the lowest concentration in colostrum (6.30 [6.13, 6.48] g/100 mL). Total CHO was similar for transition (6.83 [6.60, 7.06] g/100 mL) and mature (6.80 [6.45, 7.14] g/100 mL) HM. Lactose followed a comparable pattern, with an overall mean of 6.33 [6.02, 6.64] g/100 mL. Mean energy content was 68.13 [65.92, 70.33] kcal/100 mL; colostrum had the lowest, while transition and mature were similar. Stratified analyses by analytical method and milk type were also conducted. This systematic review provides updated pooled estimates of total CHO and lactose concentrations and energy in preterm HM, and highlights substantial variability related to study design, analytical methods, and data reporting. REGISTRY NUMBER IN PROSPERO: CRD42023445191 STATEMENT OF SIGNIFICANCE: The current manuscript advances the field of preterm human milk (HM) nutrition by providing up-to-date estimates of total CHO, lactose, and energy in colostrum, transition, and mature preterm HM. These values fulfill a critical need for practitioners and researchers to more accurately understand the nutritional needs of preterm infants, as well as any supplementary nutrition that may be necessary for appropriate growth and development.