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

Обзор

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.

Подробное описание

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.

Вмешательства

• Другое Chronobiologically 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.
• Другое Usual 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.

Первичные конечные точки

• Sleep consolidation (longest nocturnal sleep bout) [Срок оценки: At 6 months of age]

Вторичные конечные точки (7)

• Sleep fragmentation [Срок оценки: At 2, 4, 6, 12, and 24 months]
• Circadian rhythm development (day-night activity ratios and circadian function index) [Срок оценки: At 2, 4, 6, 12, and 24 months]
• Parent-reported sleep outcomes [Срок оценки: At 2, 4, 6, 12, and 24 months]
• Melatonin circadian profiles [Срок оценки: At 2, 4, 6, 12, and 24 months]
• Intestinal microbiota composition [Срок оценки: At 2, 4, 6, 12, and 24 months]
• Infection rates [Срок оценки: At 2, 4, 6, 12, and 24 months]
• Neurodevelopmental outcomes [Срок оценки: 24 months]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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)

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Простое слепое

Основная цель

Другое

Центры проведения

Швейцария · 1 центр

• Kantonsspital Luzern, Universität Luzern — Lucerne

Идентификаторы

NCT: NCT07533578 · 2026-

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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