The Role of Circadian Rhythm in the Effect of Sleep Intervention on Obesity Prevention in Early Childhood

The Role of Circadian Rhythm in the Effect of Sleep Intervention on Obesity Prevention in Early Childhood

Over the last 40 years, obesity has increased dramatically among all age groups, especially in infants and young children, and became an important global public health challenge, thus early prevention is the highest priority. Emerging studies have found that infant sleep intervention is very likely to become one of the most important strategies for early obesity prevention. However, its action path is not clear, making the target of sleep intervention relatively vague. The role of circadian rhythm in human health status has received increasing attention in recent years. Both animal experiment-based studies and adult clinic-based studies have found significant effect of the circadian rhythm on obesity and other metabolic disorders. Therefore, the present research will establish a community-based 1:1 parallel multi-center randomized controlled trial of sleep intervention cohort in communities with highly rapid weight gain at the early infancy stage. Investigators will collect daily rhythm data, including sleep-wake rhythm, rest-activity rhythm, light-dark cycle, and feeding-fasting, as well as the real-world golden standard of circadian rhythm assessed by seven times saliva melatonin, to test the impact of the sleep intervention program, to determine the causal mechanism of circadian rhythm in the occurrence and  development of obesity and metabolic disorder early in life. Our study will provide a new theoretical basis for the establishment of the stable circadian rhythm for the prevention of infant obesity, which has important public health significance.

1. Research content 1.1 Study on the Reliability and Validity of Daily Circadian Rhythm of Infant and Young Child Behavior and Establishment of Circadian Circadian Rhythm Prediction Model In three study communities, 10 infants aged 4 months, 6 months, 12 months and 2 years old were recruited, with a total of 120 infants. Daily rhythms of sleep, activity, illumination and eating were collected by using portable device Actiwatch-2 and daily log book. Saliva at 7 time points (09: 00, 13: 00, 17: 00, 21: 00, 01: 00, 05: 00 and 09: 00) were collected to determine the level of melatonin as the gold standard for circadian rhythm of biological clocks under natural environment. The correlation between daily circadian rhythms and characteristics of melatonin secretion was determined. A model with high reliability was established by mathematical modeling.

   1.2 Multicenter Cohort Study of Effects of Sleep Intervention on Metabolic Function in Childhood Obesity Methods: A 1: 1 parallel multicenter randomized controlled trial was conducted to recruit 80 infants from each of the control group and the intervention group at 28 days after birth. The control group was followed up for 5 times (28 days, 2 months, 4 months, 6 months and 12 months) of evidence-based infant sleep intervention on the basis of routine child care, and followed up until 2 years old. The main outcomes were changes in BMI z at 0-6 months of age and metabolic markers of obesity at 2 years of age, such as BMI z, subcutaneous fat, body composition and blood biochemistry. On the basis of descriptive analysis, the effects of sleep intervention on infant obesity metabolism and daily rhythm were determined, and the causal mechanism of circadian rhythm, obesity metabolic index and other factors were determined by using Bayesian causal network.

   1.3 Verification of Predictive Models for Circadian Rhythms of Behavioral Clocks In the second part of the three study communities, the two groups were randomly selected 20 cases, a total of 120 infants and children.

   At 4 months, 6 months, 12 months and 2 years of age after birth, saliva samples were collected at 2 time points in addition to Actiwatch-2 and daily rhythm data, and melatonin levels were measured to validate the rhythm prediction model.

2. Research objectives

Based on the concept of early prevention, this project focuses on the role of circadian rhythms in infant sleep intervention to prevent obesity and accomplishes the following two objectives:

2.1 To determine the intensity of correlation between the daily rhythm of infants and the characteristics of melatonin secretion rhythm of gold standard.

Over mathematical modeling to establish high reliability and validity of behavioral biological clock circadian rhythm prediction model in infants and young children to verify and apply to sleep intervention multicenter cohort study.

2.2 To explore the effect of sleep intervention on infants by establishing a standard multicenter cohort of infant sleep intervention It is of great public health significance to provide high quality evidence for early prevention and control of childhood obesity and to design more pertinent prevention and control strategies.

Inclusion Criteria:

• Infants and young children: age 4 months, 6 months, 12 months, and 2 years old;
• term single birth (37-42 weeks of gestation);
• health inactive disease;
• normal Griffiths developmental assessment;
• natural vaginal delivery or social cesarean section;
• Apgar score greater than 7 at birth for 1 or 5 minute.

Exclusion Criteria:

• Infants and young children: birth weight < 2500 g;
• premature or multiple births;
• prenatal ultrasonography indicating intrauterine growth retardation;
• severe organic diseases of the baby after birth that have been hospitalized for treatment;
• congenital malformations or diseases affecting the feeding of the baby (cleft lip and palate, metabolic diseases, etc.).