Circadian-Synchronized Breast Milk Feeding and Sleep in Preterm Infants: A Multicenter Randomized Controlled Trial

Official title

Effect of Circadian-Synchronized Breast Milk Feeding on Sleep in Preterm Infants: A Multicenter Randomized Controlled Trial

Overview

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.

Interventions

• Behavioral Circadian-Synchronized Breast Milk Feeding
  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
• Behavioral Routine Breast Milk Feeding
  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.

Primary outcome measures

• Active Sleep to Quiet Sleep Ratio (AS:QS Ratio) at 37 Weeks of Corrected Gestational Age [Time frame: During a 12-hour monitoring period at 37 weeks of corrected gestational age]

Secondary outcome measures (3)

• Proportion of Each Sleep State During the Total Monitoring Period [Time frame: 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 [Time frame: During a 12-hour monitoring period at 37 weeks of corrected gestational age]
• Heart Rate Variability (HRV) Parameters During the Total Monitoring Period [Time frame: During a 12-hour monitoring period at 37 weeks of corrected gestational age]

Eligibility criteria

Inclusion criteria

• Preterm infants born between 28 weeks and 36 weeks plus 6 days of gestation.
• Infants who have reached full enteral feeding.
• Written informed consent signed by a legal guardian.

Exclusion criteria

• Need for 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 congenital neurologic or chromosomal abnormalities.
• Presence of congenital gastrointestinal malformations or anorectal malformations.
• Conditions affecting digestion or absorption, such as diarrhea, intestinal obstruction, or necrotizing enterocolitis.
• Critical illnesses such as patent ductus arteriosus, neonatal sepsis, neutropenia, or coagulation disorders.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Supportive care

Study locations

China · 6 centers

• Fujian Children's Hospital — Fuzhou
• Nantong First People's Hospital — Nantong
• Nantong Maternal and Child Health Hospital — Nantong
• Children's Hospital of Soochow University — Shanghai
• Zhangjiagang First People's Hospital — Zhangjiagang
• Shanghai Children's Medical Center Affiliated to Shanghai Jiao Tong University School of M — Shanghai

Publications

• 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 36474114
• 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 36894247
• 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 32759654
• 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 40195944

Identifiers

NCT: NCT07645677 · SCMCIRB-K2026077-1

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗