NCT07645677

Brief Summary

This clinical trial aims to find out whether a circadian-synchronized breast milk feeding approach can help improve sleep in preterm infants in the neonatal intensive care unit (NICU). The study mainly aims to answer the following questions: Can this feeding approach improve sleep in preterm infants? Can this feeding approach help preterm infants develop more regular sleep patterns compared with routine breast milk feeding? Researchers will compare a feeding approach that tries to match the time when breast milk was expressed with the time when the baby is fed, with routine breast milk feeding, to see whether this method can improve sleep in preterm infants. Participants will: Be randomly assigned to 1 of 2 groups: circadian-synchronized breast milk feeding or routine breast milk feeding. Receive the assigned feeding approach for at least 2 weeks during the study. Have one 12-hour continuous sleep monitoring session at 37 weeks of corrected age. Have changes in different sleep states recorded and analyzed during the study, so that sleep patterns can be compared between the 2 groups.

Trial Health

63
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
120

participants targeted

Target at P50-P75 for not_applicable

Timeline
14mo left

Started Jun 2026

Geographic Reach
1 country

6 active sites

Status
not yet recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress3%
Jun 2026Aug 2027

Study Start

First participant enrolled

June 1, 2026

Completed
8 days until next milestone

First Submitted

Initial submission to the registry

June 9, 2026

Completed
3 days until next milestone

First Posted

Study publicly available on registry

June 12, 2026

Completed
12 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2027

Expected
2 months until next milestone

Study Completion

Last participant's last visit for all outcomes

August 1, 2027

Last Updated

June 12, 2026

Status Verified

June 1, 2026

Enrollment Period

1 year

First QC Date

June 9, 2026

Last Update Submit

June 9, 2026

Conditions

Preterm InfantSleep

Keywords

Breast Milk FeedingCircadian RhythmChrononutritionNICUPreterm InfantSleep

Outcome Measures

Primary Outcomes (1)

  • Active Sleep to Quiet Sleep Ratio (AS:QS Ratio) at 37 Weeks of Corrected Gestational Age

    The primary outcome is the ratio of active sleep (AS) to quiet sleep (QS) across the entire monitoring period at 37 weeks of corrected gestational age. Active sleep is one of the 2 main neonatal sleep states and is considered the precursor of rapid eye movement (REM) sleep. Sleep data will be collected during a 12-hour monitoring period using a wearable EEG patch combined with a sleep mat. The EEG device uses a single-channel, three-electrode configuration and supports synchronized acquisition of EEG and pulse wave signals. All monitoring data will be preprocessed, scored, and exported using a standardized data processing workflow.

    During a 12-hour monitoring period at 37 weeks of corrected gestational age

Secondary Outcomes (3)

  • Proportion of Each Sleep State During the Total Monitoring Period

    During a 12-hour monitoring period at 37 weeks of corrected gestational age

  • Number of Complete AS-QS-Arousal Sleep Cycles During the Total Monitoring Period

    During a 12-hour monitoring period at 37 weeks of corrected gestational age

  • Heart Rate Variability (HRV) Parameters During the Total Monitoring Period

    During a 12-hour monitoring period at 37 weeks of corrected gestational age

Other Outcomes (1)

  • Gut Microbiota Composition in Stool Samples

    At enrollment and on the same day as the 12-hour sleep monitoring period at 37 weeks of corrected gestational age

Study Arms (2)

Routine Breast Milk Feeding

ACTIVE COMPARATOR

Preterm infants in this group will receive routine breast milk feeding according to standard NICU practice. Expressed breast milk will be prepared and administered without matching the time of milk expression to the time of feeding.

Behavioral: Routine Breast Milk Feeding

Circadian-Synchronized Breast Milk Feeding

EXPERIMENTAL

Preterm infants in this group will receive circadian-synchronized breast milk feeding in the NICU. Expressed breast milk will be classified and labeled according to the time of milk expression into 4 time periods: morning (06:00-12:00), afternoon (12:00-18:00), evening (18:00-24:00), and late night/early morning (00:00-06:00). During the study, breast milk collected within each predefined time period will be used preferentially for feedings scheduled within the corresponding time period. This feeding approach is intended to keep the timing information in breast milk as consistent as possible with the infant's feeding time and will continue for at least 2 weeks during the study.

Behavioral: Circadian-Synchronized Breast Milk Feeding

Interventions

Routine Breast Milk FeedingBEHAVIORAL

In this intervention, preterm infants will receive routine breast milk feeding according to standard NICU practice. Expressed breast milk will be prepared and administered without matching the time of milk expression to the time of feeding.

Routine Breast Milk Feeding
Circadian-Synchronized Breast Milk FeedingBEHAVIORAL

In this intervention, expressed breast milk will be classified and labeled according to the time of milk expression into 4 predefined periods: morning (06:00-12:00), afternoon (12:00-18:00), evening (18:00-24:00), and late night/early morning (00:00-06:00). During the study, breast milk collected within each predefined time period will be used preferentially for feedings scheduled within the corresponding time period. This intervention is designed to keep the timing information in breast milk as consistent as possible with the infant's feeding time and will be implemented for at least 2 weeks.

Circadian-Synchronized Breast Milk Feeding

Eligibility Criteria

Age0 Days+
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • Preterm infants born between 28 and 36 weeks of gestation Have reached full enteral feeding Written informed consent signed by a legal guardian

You may not qualify if:

  • Need invasive respiratory support, such as endotracheal intubation Use of sedatives or other medications that may affect the central nervous system or sleep rhythm
  • Presence of diseases or abnormalities that may affect normal feeding or sleep behavior, including:
  • Congenital anomalies, such as neurologic or chromosomal abnormalities Congenital gastrointestinal malformations or anorectal malformations Conditions affecting digestion or absorption, such as diarrhea, intestinal obstruction, or necrotizing enterocolitis (NEC) Critical illnesses such as patent ductus arteriosus (PDA), neonatal sepsis, neutropenia, or coagulation disorders

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (6)

Fujian Children's Hospital

Fuzhou, Fujian, 350014, China

Location

Nantong First People's Hospital

Nantong, Jiangsu, 226001, China

Location

Nantong Maternal and Child Health Hospital

Nantong, Jiangsu, 226018, China

Location

Children's Hospital of Soochow University

Shanghai, Jiangsu, 215025, China

Location

Zhangjiagang First People's Hospital

Zhangjiagang, Jiangsu, 215600, China

Location

Shanghai Children's Medical Center Affiliated to Shanghai Jiao Tong University School of Medicine

Shanghai, Shanghai Municipality, 200127, China

Location

Related Publications (4)

  • Ryan MAJ, Mathieson SR, Livingstone V, O'Sullivan MP, Dempsey EM, Boylan GB. Sleep state organisation of moderate to late preterm infants in the neonatal unit. Pediatr Res. 2023 Feb;93(3):595-603. doi: 10.1038/s41390-022-02319-x. Epub 2022 Dec 6.

    PMID: 36474114BACKGROUND

  • Wang W, Huang L, Zhang X, Lin L, Chen X, Zhong C, Chen R, Wu M, Yang S, Tu M, Cao X, Tan T, Zhu W, Liu J, Zhang H, Yang S, Li N, Yang X, Hao L, Yang R, Yang N. Association of Breastfeeding Practices During the First 3 Months with Infant Sleep Trajectories: A Prospective Cohort Study. J Nutr. 2023 Feb;153(2):562-568. doi: 10.1016/j.tjnut.2022.12.018. Epub 2022 Dec 26.

    PMID: 36894247BACKGROUND

  • Italianer MF, Naninck EFG, Roelants JA, van der Horst GTJ, Reiss IKM, Goudoever JBV, Joosten KFM, Chaves I, Vermeulen MJ. Circadian Variation in Human Milk Composition, a Systematic Review. Nutrients. 2020 Aug 4;12(8):2328. doi: 10.3390/nu12082328.

    PMID: 32759654BACKGROUND

  • Temizsoy E, Uysal G, Karadag N. The Effect of a Chronobiological Feeding Model on Growth Parameters and Length of Hospitalization in Preterm Infants: A Randomized Controlled Study. Breastfeed Med. 2025 Jun;20(6):432-440. doi: 10.1089/bfm.2024.0221. Epub 2025 Apr 8.

    PMID: 40195944BACKGROUND

MeSH Terms

Conditions

Premature Birth

Condition Hierarchy (Ancestors)

Obstetric Labor, PrematureObstetric Labor ComplicationsPregnancy ComplicationsFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital Diseases

Central Study Contacts

Biyu Shen, PhD

CONTACT

+86 13862937317shenbiyu@126.com

Qiuyue Zhai, MS

CONTACT

+86 136817343072319957509@qq.com

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
Purpose
SUPPORTIVE CARE
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Principal Investigator

Study Record Dates

First Submitted

June 9, 2026

First Posted

June 12, 2026

Study Start

June 1, 2026

Primary Completion (Estimated)

June 1, 2027

Study Completion (Estimated)

August 1, 2027

Last Updated

June 12, 2026

Record last verified: 2026-06

Locations

CN(6)