Developmental effects on sleep-wake patterns in infants receiving a cow's milk-based infant formula with an added prebiotic blend: a Randomized Controlled Trial

Pediatr Res. 2021 Apr;89(5):1222-1231. doi: 10.1038/s41390-020-1044-x. Epub 2020 Jul 2.

Abstract

Background: Few studies have evaluated nutritive effects of prebiotics on infant behavior state, physiology, or metabolic status.

Methods: In this double-blind randomized study, infants (n = 161) received cow's milk-based infant formula (Control) or similar formula with an added prebiotic blend (polydextrose and galactooligosaccharides [PDX/GOS]) from 14-35 to 112 days of age. Infant wake behavior (crying/fussing, awake/content) and 24-h sleep-wake actograms were analyzed (Baseline, Days 70 and 112). Salivary cortisol was immunoassayed (Days 70 and 112). In a subset, exploratory stool 16S ribosomal RNA-sequencing was analyzed (Baseline, Day 112).

Results: One hundred and thirty-one infants completed the study. Average duration of crying/fussing episodes was similar at Baseline, significantly shorter for PDX/GOS vs. Control at Day 70, and the trajectory continued at Day 112. Latency to first and second nap was significantly longer for PDX/GOS vs. Control at Day 112. Cortisol awakening response was demonstrated at Days 70 and 112. Significant stool microbiome beta-diversity and individual taxa abundance differences were observed in the PDX/GOS group.

Conclusions: Results indicate faster consolidation of daytime waking state in infants receiving prebiotics and support home-based actigraphy to assess early sleep-wake patterns. A prebiotic effect on wake organization is consistent with influence on the gut-brain axis and warrants further investigation.

Impact: Few studies have evaluated nutritive effects of prebiotics on infant behavior state, cortisol awakening response, sleep-wake entrainment, and gut microbiome. Faster consolidation of daytime waking state was demonstrated in infants receiving a prebiotic blend in infant formula through ~4 months of age. Shorter episodes of crying were demonstrated at ~2 months of age (time point corresponding to age/developmental range associated with peak crying) in infants receiving formula with added prebiotics. Results support home-based actigraphy as a suitable method to assess early sleep-wake patterns. Prebiotic effect on wake organization is consistent with influence on the gut-brain axis and warrants further investigation.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actigraphy
  • Animals
  • Brain-Gut Axis
  • Cattle
  • Double-Blind Method
  • Feces
  • Female
  • Galactose / analysis
  • Gastrointestinal Microbiome
  • Glucans / chemistry
  • Humans
  • Hydrocortisone / metabolism
  • Infant
  • Infant Formula
  • Infant, Newborn
  • Male
  • Milk / chemistry*
  • Oligosaccharides / chemistry
  • Prebiotics
  • Prospective Studies
  • Saliva / metabolism
  • Sleep*
  • Wakefulness*

Substances

  • Glucans
  • Oligosaccharides
  • Prebiotics
  • polydextrose
  • Hydrocortisone
  • Galactose