Circadian Rhythm, Infant Sleep Problems, Neurodevelopment
Conditions
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
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.
Detailed description
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.
Interventions
OTHERChronobiologically Timed Feeding of Expressed Breast Milk
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.
OTHERUsual Feeding Practice (Untimed Expressed Breast Milk)
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.
Sponsors
Luzerner Kantonsspital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
0 Days to 1 Months
Healthy volunteers
Yes
Inclusion criteria
* 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
Exclusion criteria
* 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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Sleep consolidation (longest nocturnal sleep bout) | At 6 months of age | Measured by actigraphy |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Sleep fragmentation | At 2, 4, 6, 12, and 24 months | Assessed by actigraphy and sleep-wake diaries |
| Circadian rhythm development (day-night activity ratios and circadian function index) | At 2, 4, 6, 12, and 24 months | Assessed by actigraphy |
| Parent-reported sleep outcomes | At 2, 4, 6, 12, and 24 months | Assessed using the Brief Infant Sleep Questionnaire (BISQ) |
| Melatonin circadian profiles | At 2, 4, 6, 12, and 24 months | In breast milk and infant stool |
| Intestinal microbiota composition | At 2, 4, 6, 12, and 24 months | Assessed by shotgun metagenomic sequencing |
| Infection rates | At 2, 4, 6, 12, and 24 months | Clinically diagnosed infections (including otitis media and lower respiratory tract infections), assessed via medical records and parental report |
| Neurodevelopmental outcomes | 24 months | Bayley Scales of Infant and Toddler Development (Bayley-III) |
Countries
Switzerland
Contacts
CONTACTPetra Zimmermann, MD, PhD
Outcome results
None listed