Changes in Sleep Duration and Blood Pressure Across School Holiday in Teenagers
Condition: Sleep Deprivation
MeSH terms: Sleep Deprivation
Study type: Observational

Summary: 
      Our research question is: Are changes in sleep duration that occur naturally over school
      holidays associated with changes in blood pressure (BP) in sleep-deprived adolescents?

      In this study, the investigators will take advantage of changes in sleep duration that occur
      during school holidays in adolescents who are sleep deprived (>6 months' history of sleeping
      <8 hours per night during school term). The investigators will monitor the changes in
      ambulatory BP and sleep duration over a period of 3 weeks which consist of a week at school,
      followed by a week of holiday when natural sleep extension takes place, and then another week
      of school after the holiday. Sleep-wake cycle will be recorded throughout the whole study
      period with actigraphy and sleep diary. Twenty-four hour ambulatory BP monitoring will be
      performed on the same weekday during each study week, when salivary cortisol will also be
      collected. The primary outcome measure is the difference in ambulatory BP parameters between
      school term and holiday. A control group without sleep deprivation (history of sleeping >8
      hours per night) will also be studied concurrently

      It is hypothesized that changes in sleep duration are negatively associated with changes in
      BP. If this study confirms our hypothesis, sleep extension can be used as a relatively
      inexpensive and simple behavioural intervention in the management and prevention of blood
      pressure abnormalities. More importantly positive results from this project will provide
      background information on which government and local school policy can be based and altered
      for the betterment of our youths.
    

Detailed description: 
      This is a cohort study that consists of 4 visits over a 3-week study period that includes two
      periods of 7-day school attendance and one period of 7-day school holiday (Study design flow
      chart). Subjects who have undergone physical examination and completed the screening
      questionnaire, and are found to meet all the inclusion and none of the exclusion criteria
      will be recruited. The first study week will be during school days, followed by a week of
      school holiday, and the final week is when the subject returns back to school after the
      holiday. The 3 periods need not to be consecutive so as to allow more flexibility to cater
      for the subjects' schedule. All assessments however have to be completed within 60 days to
      minimize the effects of growth on BP / sleep pattern.

      Screening

      During screening examination, participants will undergo a series of anthropometric
      measurements. The body build of the subject will be assessed using standard procedures.
      Standing height (in metres) will be measured without shoes using a Harpenden Stadiometer
      (Holtain, UK). Body weight will be measured by an electronic weighing scale (Tanita BF-522,
      Japan). Waist and hip circumference (in centimetres) will also be obtained. Body mass index
      and waist circumference will be converted into z score using local reference. Blood pressure
      will be taken using the Datascope Accutorr Plus. Two measurements are taken at 1-minute
      intervals, with a third reading taken 5 minutes later if the difference between the first two
      >4 mmHg. The average of two repeatable readings (difference ≤4 mmHg) will be used. Sexual
      maturity rating will be evaluated by a validated gender specific self-assessment
      questionnaire. Subjects will have to fill in a sleep questionnaire asking about their sleep
      habits and symptoms, pediatric daytime sleepiness scale (PDSS), Epworth sleepiness scale
      (ESS), and strength and difficulties questionnaire (SDQ). Information on parental medical
      history will also be obtained from the parents using a medical history questionnaire. The
      school calendar of each participant will also be obtained.

      Collection of Data

      Sleep pattern will be monitored by actigraphy together with sleep diary throughout the whole
      study period. Twenty four-hour ambulatory BP monitoring and neurocognitive tests will be
      performed on the last day of each study week. All BP monitoring and neurocognitive tests will
      be performed during weekdays instead of weekends to avoid the possible weekend effect on
      sleep pattern and outcomes. Saliva samples will also be collected in the evening and the
      morning when the subjects are wearing the BP monitor for assessing cortisol awakening
      response.

      Actigraphy

      On day 1 of the first week of study, participants will attend our sleep laboratory to start
      actigraph recording (Actiwatch spectrum device; Phillips Respironics, Murrysville, PA; on
      their non-dominant wrist) and will be instructed on how to complete the sleep diary.
      Participants will have to wear the device until the end of the study period. Actigraphs will
      be configured to collect information in 1-minute epochs by using a medium sensitivity
      threshold, which has high sensitivity for detecting sleep compared with polysomnography.
      Self-reported bedtimes and wake times will be used to score actigraph data using established
      procedures. Variables of interest include actigraph-defined sleep period (ie, the period
      between scored sleep onset and scored final awakening), actigraph scored sleep (minutes of
      scored sleep within the actigraph-defined sleep period), wake after sleep onset (minutes of
      scored wake within the actigraph-defined sleep period), and sleep efficiency (actigraph
      scored sleep/actigraph-defined sleep period). The activity level during wakefulness will also
      be extracted as a covariate for statistical analysis, as it may affect both sleep pattern and
      BP.

      Twenty four-hour ambulatory blood pressure monitoring

      A validated oscillometric monitor (SpaceLabs 90217, SpaceLabs Medical, Redmond, Washington,
      USA) will be used. Systolic, diastolic and mean arterial BP will be measured every 30
      minutes. The exact cut-off time dividing wake and sleep BP will be defined individually
      according to actigraphy. Recordings are included in the analysis when there is a minimum of
      40 successful readings for the 24-hour period with a minimum of 1 successful reading per
      hour. Individual mean systolic, diastolic and mean arterial BP are calculated for wake and
      sleep periods. These BP data will be converted to z scores using the local "LMS" reference
      values (with reference to gender and height). Subjects will be defined as hypertensive if
      their systolic or diastolic BP is ≥95th percentile (z score ≥1.645).

      Neurocognitive tests

      Conners' Continuous Performance Test (CPT)

      CPT-II (Ver. 5.2 for Windows®) is designed as a computer game-like test for the evaluation of
      sustained attention and response inhibition for respondents aged 6 or above. Subjects are
      required to press the space bar or click the mouse whenever any letter except the letter 'X'
      appears on the computer screen. The test requires about 14 minutes to complete, and it will
      be administered in the morning in a quiet room.

      Trail-making Test Part A & B (Executive function)

      The Trail-making test is composed of two parts which assess test-takers in attention, visual
      scanning, speed of eye-hand coordination, information processing and set switching of
      executive functions. Part A required subjects to connect sequentially 25 encircled numbers
      which are randomly scattered over the test sheet. Similarly, for Part B, subjects are asked
      connect encircled numbers (1-13) and alphabets (A-L) alternately in ascending patterns, i.e.
      1-A-2-B-C. Any mistakes made throughout the test are pointed out by examiner immediately.
      Thus, the scores of the tests are the time taken to complete the task.

      Stroop Test-Victoria Version (Executive function)

      This test captures cognitive flexibility and inhibition of executive functioning by three
      successive tasks with increasing demands. It consists of three sets of stimulus cards (1)
      colored dots, (2) common words printed in same colors as dots, and (3) color words printed in
      non-corresponding colors of ink. For the first task, subjects are asked to simply name the
      color of the dots in maximum speed as possible. For the second task, subjects are asked to
      identify the color of ink each word is printed in, not to identify the word itself. For the
      third task, subjects are asked to identify the color of ink each of the color words is
      printed in, not to read the color word presented. Number of errors and time to perform the
      task are recorded for each trial. The Chinese Victoria Version of the Stroop Test is
      translated and validated by Dr. Tatia Lee and Dr. Kai Wang from the Laboratory of
      Neuropsychology, the University of Hong Kong.

      Raven's Standard Progressive Matrices Test (Nonverbal reasoning)

      The Test is a nonverbal measure of general ability that uses nonverbal stimuli including
      visual patterns and shapes to asses reasoning by analogy. It contains five sets with 12
      problems in each set. Each question is a puzzle with a missing part; subjects are asked to
      identify the most appropriate piece from six similar options. Children of age 5 years 6
      months to 8 years 5 months can do a shortened version with only Set A, B, and C to allow
      better control of test administration. Each set starts with a problem and develops a theme
      that build on previous questions and become progressively more difficult. The test is
      administered in a paper and pen format. While it is an open-ended session, most people
      complete the test in less than 40 minutes.

      Grooved Pegboard (Visual-motor coordination)

      It is a manipulative dexterity test aim at assessing visual-motor coordination. It consists
      of 25 holes with randomly positioned slots. Subjects are asked to place pegs, which have a
      key along one side, into the holes from left to right. The task is performed once with
      dominant hands and once with non-dominant hands. Subjects are advised to complete the task as
      fast as possible. Subjects from 5 years old to 8 years 12 months will use a Kiddie version of
      the test in which only the first two rows (10 pegs) of the pegboard are needed to complete.
      Time taken, number of pegs placed on the pegboard, and number of dropped pegs are recorded to
      assess the score of fine-motor coordination.

      Cortisol awakening response (CAR)

      Saliva samples will be collected with Salivette tubes for assessing the level of cortisol and
      cortisone, as a reflection of stress which on its own can influence both sleep pattern and
      BP.

      Participants will be asked to collect their saliva in the morning. Each subject will have to
      provide five saliva samples according to a fixed sampling protocol: (1) one hour before
      bedtime, (2) immediately after awakening, (3) 15 min after awakening, (4) 30 min after
      awakening, and (5) 45 min after awakening. Salivary cortisol and cortisone concentrations in
      these samples will be measured by a liquid chromatography tandem mass spectrometry method at
      the Biomedical Mass Spectrometry Unit, Department of Chemical Pathology, Prince of Wales
      Hospital. Between-batch precision performance of the method has coefficients of variation of
      <5%. The lower limits of quantitation are <0.5 nmol/l.
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Subjects will be recruited from local primary and secondary schools. We will send
        invitation letters to Principals to ask them for their help with screening questionnaire
        distribution and assessment arrangements in their school. The screening questionnaire asks
        about children sleep pattern during school terms and holidays, sleep-related symptoms (e.g.
        snoring), and medical history to see whether they are eligible to participate. Eligible
        subjects will receive the study factsheet and written informed consent form. Subjects with
        parental consent will be enrolled in our study.
      
Biospecimen description: 
      Saliva samples will be collected with Salivette tubes for assessing the level of cortisol and
      cortisone, as a reflection of stress which on its own can influence both sleep pattern and
      BP.

      Participants will be asked to collect their saliva in the morning when they are wearing the
      BP monitor. Each subject will have to provide five saliva samples according to a fixed
      sampling protocol: (1) one hour before bedtime, (2) immediately after awakening, (3) 15 min
      after awakening, (4) 30 min after awakening, and (5) 45 min after awakening.
    
Keywords: sleep duration; blood pressure; adolescents; holiday