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Circadian rhythm development in preterm infants. The role of postnatal versus postmenstrual age
R B Govindan1, Nickie N Andescavage2, Sudeepta Basu2
1The Zickler Family Prenatal Pediatrics Institute, Children's National Hospital, Washington, DC, USA; The Developing Brain Institute, Children's National Hospital, Washington, DC, USA; Department of Pediatrics, The George Washington University School of Medicine, Washington, DC, USA.
Insights
Preterm infants
Area of Science:
- Neonatal physiology
- Developmental biology
- Chronobiology
Background:
- Neonatal intensive care units (NICUs) may disrupt the natural development of circadian rhythms in premature infants.
- Understanding circadian rhythm maturation is crucial for optimizing infant care and long-term health outcomes.
Purpose of the Study:
- To investigate the development of circadian rhythms in preterm infants throughout their NICU stay.
- To differentiate the influence of postmenstrual age (PMA) versus postnatal age (PNA) on circadian rhythm maturation.
Main Methods:
- Continuous heart rate monitoring was used to assess circadian rhythms via cosine fit analysis.
- Circadian rhythm amplitudes were analyzed weekly in relation to PMA and PNA using linear mixed-effects models.
- Grand averages of daily circadian rhythms were computed for specific PMA and PNA groups.
Main Results:
- Both PMA and PNA were significantly associated with increased circadian rhythm amplitude.
- Early in development (≤31 weeks PMA, ≤30 days PNA), circadian rhythms peaked at night.
- Circadian rhythm amplitude was highest in infants >35 weeks PMA and >60 days PNA, indicating maturation.
Conclusions:
- Circadian rhythm maturation progresses with increasing gestational and postnatal age in preterm infants.
- The initial reversed circadian phase may be an adaptation to the extrauterine environment, requiring further investigation.
Background, Aims:
Circadian rhythm maturation may be disturbed in premature infants undergoing neonatal intensive care. We used continuous heart rate recordings across the entire neonatal intensive care period to study circadian rhythm development in preterm infants and to evaluate the roles of postmenstrual (PMA) versus postnatal age (PNA).
Materials And Methods:
The circadian rhythm was calculated using a cosine fit of heart rate. The circadian rhythm amplitudes were averaged weekly and studied relative to PMA and PNA using the linear mixed effects models, adjusting for clinical variables that could affect the heart rate. The daily circadian rhythms were used to create grand averages for PMA groups: ≤31, 32-35, and > 35 weeks, and for PNA groups: ≤30, 31-60, and > 60 days.
Results:
Sixty-six infants were evaluated as part of an ongoing prospective study with gestational ages between 23 and 36 weeks. The PMA (1.47 × 10-2 beats per minute (bpm)/week, P = 2.07 × 10-8) and PNA (1.87 × 10-2 bpm/day; P = 1.86 × 10-6) were significantly associated with the circadian rhythm amplitude independent of covariates. Infants ≤31 weeks' PMA and ≤30 days PNA, the phase of circadian rhythm amplitude grand averages showed a peak at night and a nadir during the day. Hereafter the circadian rhythm phase reversed to that established for mature individuals. The highest circadian rhythm amplitudes present >35 weeks' PMA and > 60 days PNA.
Conclusions:
Our results indicate circadian rhythm matures with advancing gestation. The reversed circadian rhythm phase during the early postnatal period could be due to premature exposure to the ex-utero environment and warrant further study.
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