When Do Day-Night Circadian Rhythms Really Start for Infants?

Patient Presentation
A 4-day-old male came to clinic for his first well child check after discharge. Although he would awake to feed every 2-2.5 hours, his mother said that he would not latch well and would come off the breast often. She felt that when he did latch well, he would rhythmically suck and she could see his ear moving and see milk in his mouth afterwards. He was urinating 4-5 times/day and was stooling small amounts 5 or more times/day. His mother appeared somewhat disheveled and easily broke into tears saying that “I haven’t slept at all.” The father said that he was trying to help but the mother was very concerned about the feeding and wasn’t sleeping much. The past medical history showed a full term male with uneventful pregnancy or delivery who was discharged on day 2 of life. The family history was non-contributory.

The pertinent physical exam showed a somewhat sleepy infant who would awaken and root. His weight was 3258 grams which was 8% decreased from his birthweight and 2% decreased from his discharge weight. He was mildly jaundiced to the abdomen but the rest of his examination was normal. The work-up of a transcutaneous bilirubin showed a level of 10.2 mg/dL.

The diagnosis of a term male was made and breastfeeding support to help with the infant’s latch was given to the mother by a lactation nurse in the clinic. The pediatrician emphasized that both parents needed to rest and try to sleep when the baby slept. Other family members were available close by to also support the family. “It’s going to be a while before he knows day from night, so you are going to need to sleep or rest as much as you can when he does and leave some of the household chores to other people. Let them take care of you,” he advised. The patient’s clinical course at his next appointment in 2 days showed that the infant’s weight had increased by 30 grams. He was latching better although not perfectly and appeared more contented after eating. He was less jaundiced also. The mother also looked better and said that she had been trying to sleep as she could. They also gave the baby a bottle once at night so that she could sleep for about 4 hours. “It’s going a little better but he still has his days and nights mixed up,” she said.

The earth rotates on its axis approximately every 24 hours with corresponding changes in ambient light occurring over that time period. Circadian systems have evolved in almost all living organisms to adapt to the changes in environmental light conditions and include sleep-wake cycles and changes in daily hormone production. In mammals , “[c]ircadian clocks resident in nearly every, if not all, mammalian cells…” and have been detected in embryonic stem cells. The circadian timing system has 3 major components – a central biological clock, input pathways and output pathways.

The central biological clock in the suprachiasmatic nuclei (SCN) isin the anterior hypothalamus just above the optic chiasm. There are peripheral biological clocks such as the liver also but they play less importance. The SCN oscillations (or rhythmic changes) are about 24 hours in length, but not exactly and stimulation is needed daily to reset the SCN and prevent it from drifting or freely running out of phase.

Input pathways are mainly from light which strikes the retina sending messages directly to the SCN or from the retina to the retinohypothalmic tract and then to the SCN. Output pathways are to the hypothalamus and other nonhypothalamic sites that regulate the daily changes of several hormones including melatonin and cortisol, which are two of the most important hormonal circadian regulators. Melatonin is produced in the pineal gland. Melatonin is the main hormone that regulates the daily resetting of the SCN and appears to be a main hormone for circadian rhythm entrainment for neonates and infants.

Primate studies have found that the SCN develops during gestational days 27-48, and metabolic activity is present by the end of gestation. The main SCN day-night settings appear to be set by the end of gestation but need to be entrained after birth. Entrainment appears to be mainly regulated by light cycles in neonates but feeding activities and temperature also appear to play a part of the entrainment. Other maternal time-of-day cues may also play a part.

Learning Point
For term human neonates there are few day-night rhythms detected. Infant activities are evenly distributed over the 24 hour cycle. However by 1-2 months of age, awake activities are consolidating more during daytime hours and by 3 months of age daytime sleeping decreases further with more sleep occurring at night. Day-night melatonin production is detectable by 12 weeks of age and by 3-6 months circadian cortisol variations are seen.

Questions for Further Discussion
1. What are some of the health problems related to inadequate sleep? To review click here.
2. How do circadian rhythms differ for preterm infants relative to full term infants?
3. Does taking melatonin help with jet lag?
4. What are SIDS prevention techniques?

Related Cases

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Evidence-based medicine information on this topic can be found at SearchingPediatrics.com, the National Guideline Clearinghouse and the Cochrane Database of Systematic Reviews.

Information prescriptions for patients can be found at MedlinePlus for this topic: Sleep Disorders

To view current news articles on this topic check Google News.

To view images related to this topic check Google Images.

To view videos related to this topic check YouTube Videos.

Rivkees SA. Emergence and influences of circadian rhythmicity in infants. Clin Perinatol. 2004 Jun;31(2):217-28, v-vi.

Feldman R. The development of regulatory functions from birth to 5 years: insights from premature infants. Child Dev. 2009 Mar-Apr;80(2):544-61.

Christ E, Korf HW, von Gall C. When does it start ticking? Ontogenetic development of the mammalian circadian system. Prog Brain Res. 2012;199:105-18.

Sumova A, Sladek M, Polidarova L, Novakova M, Houdek P. Circadian system from conception till adulthood. Prog Brain Res. 2012;199:83-103.

Donna M. D’Alessandro, MD
Professor of Pediatrics, University of Iowa Children’s Hospital