The Development of Circadian Rhythms in Human Infants

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2.1.1 Expression of interest contact on postnatal ward ................................... 60 2.1.2 Recruitment visits in the home .............................................................. 61 2.1.3 Home monitoring visits .......................................................................... 63 2.1.4 Further monitoring information required ............................................... 65 2.2 Infant temperature monitoring ...................................................................... 66 2.3 Collection of urine samples ........................................................................... 69 2.4 Estimation of creatinine ................................................................................ 70 2.5 Estimation of urinary melatonin .................................................................... 71 2.6 Estimation of urinary cortisol ........................................................................ 72 2.7 Use of Actiwatch for activity-rest measurement ........................................... 72 2.8 Gene expression measurement ...................................................................... 74 2.8.1 RNA preparation and cDNA synthesis .................................................. 75 2.8.2 Quantitative PCR (qPCR) ...................................................................... 75 2.9 Supplementary questionnaires ....................................................................... 78 2.10 Analysis ......................................................................................................... 78 2.11 Statistical methods ......................................................................................... 79 3 RESULTS .............................................................................................85 3.1 Recruited subjects and participant families .................................................. 85 3.1.1 Infant Recruitment ................................................................................. 85 3.1.2 Summary of demographic data .............................................................. 87 3.1.3 Socioeconomic demographics of participant families ........................... 91 3.2 Summary of Data Collected .......................................................................... 95 4 RESULTS .............................................................................................99 4.1 Core body temperature monitoring ............................................................... 99 4.2 Summary of development of core body temperature during night time sleep …………………………………………………………………………….100 4.3 Changes in core body temperature with sleep relative to postnatal age ...... 102 4.3.1 Thermal Environment during night time sleep for infants ................... 112 5 RESULTS ...........................................................................................116 5.1 Analysis of urinary melatonin in infants ..................................................... 116 5.1.1 Changes to melatonin secretion relative to postnatal age .................... 118 5.1.2 Emergence of diurnal rhythm for melatonin secretion ........................ 121 5.1.3 Melatonin secretion relative to temperature maturation stage ............. 124 5.1.4 Relationship between night and day time log melatonin ..................... 128 6 RESULTS ...........................................................................................131 6.1 Analysis of urinary cortisol ......................................................................... 131 6.1.1 Changes to cortisol secretion relative to postnatal age ........................ 132 6.1.2 Emergence of diurnal rhythm for cortisol secretion ............................ 135 6.1.3 Cortisol secretion relative to temperature maturation stage ................ 138 6.1.4 Relationship between night and day time log cortisol ......................... 143 7 RESULTS ...........................................................................................146 II
7.1 Analysis of infant sleep measurements ....................................................... 146 7.2 Description of mean sleep parameters for 35 infants .................................. 149 7.3 Development of infant sleep relative to temperature maturation stage ....... 151 7.3.1 Care giver dependent infant sleep parameters ..................................... 151 7.3.2 Non care giver dependent infant sleep parameters .............................. 156 8 RESULTS ...........................................................................................166 8.1 Analysis of buccal swabs in infants ............................................................ 166 8.2 Description of peripheral gene expression in human infants ...................... 169 8.2.1 Description of peripheral gene data from first case infant ................... 170 8.2.2 Description of peripheral gene data from second case infant .............. 172 9 RESULTS ...........................................................................................185 9.1 Factors affecting physiological maturation in human infants ..................... 185 9.1.1 Factors affecting infant night time sleep .............................................. 186 9.1.2 Factors affecting overnight deep body temperature in infants ............. 188 9.1.3 Factors affecting the secretion of night time melatonin ....................... 189 9.1.4 Factors affecting cortisol secretion in infants ...................................... 194 10 RESULTS ...........................................................................................197 10.1 Circadian rhythms – investigation of temporal relationships ...................... 197 11 DISCUSSION.......................................................................................204 11.1 Physiological development - age related changes in core body temperature during night time sleep ........................................................................................... 207 11.2 Pattern of melatonin secretion and how it relates to age and temperature maturation .............................................................................................................. 210 11.3 Pattern of cortisol secretion and how it relates to age and temperature maturation .............................................................................................................. 212 11.4 Pattern of sleep and how it relates to age and temperature maturation ....... 216 11.5 Factors affecting physiological development (in temperature, melatonin, cortisol and infant sleep) ........................................................................................ 220 11.6 Ordering of physiological events in postnatal months ................................ 224 11.7 Measurement of peripheral gene expression and changes with age ............ 228 11.8 Choice of physiological measurements in human infants ........................... 230 III
Page 1 and 2: The Development of Circadian Rhythm
Page 3: Table of Contents LIST OF FIGURES .
Page 7 and 8: List of Figures Figure 1.1 - Diagra
Page 9 and 10: List of Tables Table 3.1 - Descript
Page 11 and 12: 1 Introduction Happiness is not a m
Page 13 and 14: Each of these independently is impo
Page 15 and 16: There is general agreement, that al
Page 17 and 18: Summary 1. Development encompasses
Page 19 and 20: Figure 1.1 - Diagram illustrating c
Page 21 and 22: A phase shift is used to describe a
Page 23 and 24: 1.4 Ontogeny in Human Infants Well
Page 25 and 26: 1.5.2 Circadian Rhythms in Temperat
Page 27 and 28: 1.5.4 Factors affecting Temperature
Page 29 and 30: 1.6 Melatonin (Reviewed in Cardinal
Page 31 and 32: mechanism by which this occurs is n
Page 33 and 34: It is at this time that infant slee
Page 35 and 36: 1.7 Cortisol Cortisol is a hormone,
Page 37 and 38: 1.7.3 Circadian pattern of Cortisol
Page 39 and 40: In a separate study, Weerth et al u
Page 41 and 42: Summary 1. Cortisol is crucial to a
Page 43 and 44: NREM sleep has 4 stages. It occupie
Page 45 and 46: 1.8.1 Functions of Sleep The functi
Page 47 and 48: 1.8.3 Ontogeny of Sleep in Infants
Page 49 and 50: Sleep can clearly be used as marker
Page 51 and 52: For the purpose of this study, the
Page 53 and 54: Summary 1. Sleep is defined by lack
Page 55 and 56:
Overall the SCN generates signals (
Page 57 and 58:
Figure 1.2 - The mammalian circadia
Page 59 and 60:
1.9.3 Molecular Components of the C
Page 61 and 62:
Figure 1.3 - Mechanisms from SCN to
Page 63 and 64:
1.9.7 Melatonin and Clock Melatonin
Page 65 and 66:
The links between the central clock
Page 67 and 68:
Chapter 2 Methods
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There were strict inclusion and exc
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This personal contact on the postna
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2.1.3 Home monitoring visits The fi
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2.1.4 Further monitoring informatio
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Core body temperature was taken sim
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2.3 Collection of urine samples Pai
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were read against air at 429 nm aft
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allowed the display and comprehensi
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2.8.1 RNA preparation and cDNA synt
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In total three methods were trialle
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2.11 Statistical methods For compar
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test that each infant‟s height an
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Power calculation Sample size: Fift
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3 Results 3.1 Recruited subjects an
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predominantly affluent areas of the
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Birth history and past medical hist
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3.1.3 Socioeconomic demographics of
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her best friend losing her battle w
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Sleep environment of infants All mo
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Summary 1. This study had higher ra
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4 Results 4.1 Core body temperature
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Degrees Celsius 36.70 36.60 36.50 3
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11-13 weeks There is no significant
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Core body temperature (degrees Cels
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Number of infants 10 8 6 4 2 0 7 8
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Mean minimum rectal temperature in
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Mean minimum rectal temperature in
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Figure 4.7 shows the changes in the
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Chapter 5 Result
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4 or 6 hourly samples. Circadian rh
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Figure 5.1 - Distribution of mean n
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5.1.2 Emergence of diurnal rhythm f
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Figure 5.3 - Histogram showing dist
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Figure 5.4 - Changes in night time
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Night-day difference in melatonin s
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Summary 1. There is an increase in
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6 Results DESCRIPTION OF THE URINAR
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Page 145 and 146:
6.1.2 Emergence of diurnal rhythm f
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Figure 6.3 - Histogram showing dist
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Cortisol values were corrected to a
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6.1.4 Relationship between night an
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Chapter 7 Results
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Mean Length of Sleep/ Wake Bouts Th
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Sleep parameters were recorded as m
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7.3 Development of infant sleep rel
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Figure 7.2 - Changes in infant slee
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Figure 7.4 - Changes in percentage
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Figure 7.5 - Changes in infant frag
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Figure 7.7 - Changes in number of m
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Figure 7.9 - Changes in the percent
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Sleep efficiency (%) 100.0 90.0 80.
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Chapter 8 Results
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Considering only those weeks of mea
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8.2 Description of peripheral gene
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18:30 hours 0.9927; 01:00 ours 1.01
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The weeks after temperature maturat
Page 185 and 186:
Further peripheral gene graphical r
Page 187 and 188:
Raw data points are represented by
Page 189 and 190:
H3f3b/Gap H3f3b/Gap H3f3b/Gap H3f3b
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8.3 Detailed gene expression analys
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Summary 1. H3f3b was selected as ge
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9 Results FACTORS AFFECTING SLEEP A
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Care and infant related factors �
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Table 9.3 - Effect of family occupa
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* Class 7 used as reference group
Page 203 and 204:
Table 9.6 - Effect of measured infa
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Summary: 1. A mature physiological
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10 Results 10.1 Circadian rhythms -
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value of above 0.5 for R squared wa
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Table 10.1 - Temporal relationship
Page 213 and 214:
Chapter 11 Discussion
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� What if any are the factors whi
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11.1 Physiological development - ag
Page 219 and 220:
There are other proven factors whic
Page 221 and 222:
drawbacks of the spread of data - a
Page 223 and 224:
presented in table 6.1 do not have
Page 225 and 226:
separate methods were applied to th
Page 227 and 228:
significant. Sleep latency was cons
Page 229 and 230:
The function of sleep in developmen
Page 231 and 232:
Melatonin secretion was higher on n
Page 233 and 234:
In this study sleeping in the same
Page 235 and 236:
Timing of sleep maturation was diff
Page 237 and 238:
systematic, ordered developmental p
Page 239 and 240:
individual gene plots that provide
Page 241 and 242:
temperature recording devices adapt
Page 243 and 244:
Both melatonin and cortisol rhythms
Page 245 and 246:
Extension of this period of monitor
Page 247 and 248:
Second, we demonstrated the gene of
Page 249 and 250:
Cortisol and melatonin Slope based
Page 251 and 252:
Summary and Future work This study
Page 253 and 254:
� Maximise technique for measurin
Page 255 and 256:
“There is a science of infant car
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References
Page 259 and 260:
Bajanowski, T., Vege, Å., Byard, R
Page 261 and 262:
Chamley, C.A., Carson P, Randall D,
Page 263 and 264:
Frank, M.G., Heller, H.C., 2003. Th
Page 265 and 266:
intrahypothalamic administration of
Page 267 and 268:
Mirmiran, M. & Ariagno, R.L., 2000.
Page 269 and 270:
Rawson, D., Petersen, S.A., Wailoo,
Page 271 and 272:
Stokkan, K.A., Yamazaki, S., Tei, H
Page 273 and 274:
Winter, J.S.D., 1985. The adrenal c
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The Development of Circadian Rhythms in Human Infants

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