Chrononutrition in Preterm Infants: a Randomised Controlled Trial of Time-matched Breast Milk Feeding and Its Effects on Sleep and Circadian Development

NCT07533578 | Not Yet Recruiting DMC

• 1 other identifier: 2026-
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

This study investigates whether the timing of feeding expressed breast milk influences infant sleep and circadian (day-night) development in preterm infants. In early life, infants produce very little of the hormone melatonin, which plays a key role in regulating sleep and circadian rhythms. Breast milk naturally contains melatonin, and its levels vary across the day, with higher concentrations at night. This variation may provide important biological signals that help infants develop healthy sleep-wake patterns. However, expressed breast milk is often fed without considering the time it was expressed. This may disrupt the transfer of circadian signals from mother to infant. The aim of this randomised controlled trial is to determine whether feeding expressed breast milk according to the time of expression (e.g. giving night-time milk at night) improves sleep consolidation and circadian development compared with usual feeding practices. A total of 200 preterm infants born between 32+0 and 36+6 weeks' gestation who are receiving expressed breast milk will be enrolled and randomly assigned to one of two groups: Intervention group: preterm infants receive expressed breast milk matched to the time of day it was expressed (day, evening or night) Control group: preterm infants receive expressed breast milk without regard to timing (usual practice) The main outcome is sleep consolidation at 6 months of age, measured objectively using actigraphy (a small wearable device that records sleep and activity). Additional outcomes include sleep patterns over time, circadian development, melatonin exposure, gut microbiota composition, and clinical outcomes such as infections and neurodevelopment. The intervention does not involve any medication and uses the infant's usual nutrition. Risks are minimal and mainly relate to the additional effort required for milk labelling and timing. This study will provide evidence on whether a simple, low-risk change in feeding practice can support infant sleep and early-life circadian development, with potential benefits for child health and family well-being.

Conditions

Infant Sleep Problems; Circadian Rhythm; Neurodevelopment

Keywords

Chrononutrition; Breast Milk; Circadian Rhythm; Circadian Development; Infant Sleep; Sleep Consolidation; Melatonin; Infant Microbiome; Gut Microbiota; Chronobiology; Sleep-Wake Cycle; Actigraphy; Randomized Controlled Trial

Outcome Measures

Primary Outcomes (1)

• Sleep consolidation (longest nocturnal sleep bout)

  Measured by actigraphy

  At 6 months of age

Secondary Outcomes (7)

• Sleep fragmentation

  At 2, 4, 6, 12, and 24 months

• Circadian rhythm development (day-night activity ratios and circadian function index)

  At 2, 4, 6, 12, and 24 months

• Parent-reported sleep outcomes

  At 2, 4, 6, 12, and 24 months

• Melatonin circadian profiles

  At 2, 4, 6, 12, and 24 months

• Intestinal microbiota composition

  At 2, 4, 6, 12, and 24 months

Study Arms (2)

Chronobiologically Timed Feeding of Expressed Breast Milk

EXPERIMENTAL

Infants receive expressed breast milk that is administered according to the time of expression (day, evening, or night), aligning feeding with circadian timing.

Other: Chronobiologically Timed Feeding of Expressed Breast Milk

Usual Feeding Practice (Untimed Expressed Breast Milk)

ACTIVE COMPARATOR

Infants receive expressed breast milk without regard to the time of expression (standard care).

Other: Usual Feeding Practice (Untimed Expressed Breast Milk)

Interventions

Chronobiologically Timed Feeding of Expressed Breast Milk OTHER

Expressed breast milk is labelled at the time of expression and categorised into predefined time windows: Day milk: 06:00-17:59 Evening milk: 18:00-21:59 Night milk: 22:00-05:59 Infants are fed milk corresponding to the appropriate time-of-day window to align feeding with circadian rhythms. Caregivers receive standardised training, and adherence is monitored using feeding logs.

Chronobiologically Timed Feeding of Expressed Breast Milk

Usual Feeding Practice (Untimed Expressed Breast Milk) OTHER

Expressed breast milk is fed without consideration of the time of expression. Milk handling, storage, and preparation follow standard procedures. No modification of milk composition or additional substances are introduced.

Usual Feeding Practice (Untimed Expressed Breast Milk)

Eligibility Criteria

• Age: 0 Days - 1 Month
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• Preterm infants born between 32+0 and 36+6 weeks' gestation
• Age ≤ 1 month at enrolment
• Infants routinely receiving expressed breast milk (fully or partially breastfed)
• Written informed consent obtained from parent(s) or legal representative(s)
• Ability of caregivers to comply with study procedures including milk labelling and feeding according to study allocation

You may not qualify if:

• Prenatal exposure to illicit drugs (e.g. cannabis, cocaine, heroin, opiates) or significant alcohol exposure
• Major congenital malformations or congenital infections
• Significant underlying disease (excluding transient neonatal conditions such as feeding difficulties, hyperbilirubinaemia, hypoglycaemia, anaemia, respiratory distress syndrome, or apnoea-bradycardia syndrome)

Sponsors & Collaborators

• Luzerner Kantonsspital: lead

Study Sites (1)

Kantonsspital Luzern, Universität Luzern

Lucerne, Switzerland

Location

Central Study Contacts

Petra Zimmermann, MD, PhD

CONTACT

+4141 205 82 69; petra.zimmermann@luks.ch

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 10, 2026
• First Posted: April 16, 2026
• Study Start (Estimated): October 1, 2026
• Primary Completion (Estimated): September 30, 2030
• Study Completion (Estimated): December 30, 2031
• Last Updated: April 16, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF, ANALYTIC CODE
• Time Frame: Clinically diagnosed infections (including otitis media and lower respiratory tract infections), assessed via medical records and parental report.

Locations

CH (1)