Circadian rhythm and the neonatal intensive care unit - HERO for sepsis detection Irwin Reiss, MD PhD
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Circadian rhythm and the neonatal intensive care unit - HERO for sepsis
detection
Irwin Reiss, MD PhD
2018
Circadian physiology of metabolism Panda S, Science 2016
• Metabolites• Transcription factors• Interacting proteins• Systemic factors
McKenna HT, Reiss IKM, Martin DS J Int Care Soc 2017
Peek CB et al. Cell Metabol 2017
McKenna HT, Reiss IKM, Martin DS J Int Care Soc 2017
Normal variation from peak to trough
Lancet 2017
Circadian rhythmus in the fetus
adapted, Du Pre BC et al. Physiology 2014
Melatonin
FoodLight
ExerciseTemperature
David Barker (1938 –2013)
con WB-JLEB-JL
Gestational jet lag causes reduced weightgain and patchy baldness in offspring
• Reduced weight gain (EB>WB)• Permanently reduced body weight (EB>WB)• “Patchy” baldness (EB only)
5
10
15
20
25
30
35
2 7 12
Wei
ght
(gra
ms)
Age (weeks)
Males
DEL-LD
ADV-LD
LD-LD
WB-JL
EB-JL
control
Males
con WB-JLEB-JL
3
4
5
6
7
LD-LD DEL-LD ADV-LD
Ad
just
men
t to
ph
ase
adva
nce
(d
ays)
**
0
1
2
3
4
LD-LD DEL-LD ADV-LDA
dju
stm
ent
to p
has
e d
elay
(d
ays) **
WB jet lag
EB jet lag
WB jet lag
EB jet lag
Gestational jet lag affects time to overcome a jet lag
control EB-JLWB-JL
control EB-JLWB-JL
• Lengthened clock period (EB>WB)
• Accelerated re-entrainment
18
con WB-JLEB-JL
Ejection fraction LV
Control
Eas
tbound
Wes
tbound
0
20
40
60
%
Ejection fraction LV
EB WB
• Increased heart size (EB>WB)
• Reduced ejection volume (EB=WB)
con
EBcon WB
Gestational jet lag results in left ventricle
hypertrophy and impaired heart function
39
Gestational DEL and ADV jet-lag induces altered myocardium structure
Gestational jet-lag results in impaired heart structure
CTRL DEL ADV
con WB-JLEB-JL
Gestational jet lag (EB) results in reduced bonemass and strength
• Reduced trabecular bone mass (EB only)
• Reduced cortical bone mass (EB only)
• Reduced bone strength (EB only)
con EB WB
Work to failure
0
1
2
3
4
5
Nm
m
con EB WB
3-point bending assay
bone strength
26
DNA methylation
Vasquez-Ruiz S et al. Early Human Development 2014
Vasquez-Ruiz S et al. Early Human Development 2014
Vasquez-Ruiz S et al. Early Human Development 2014
Moshe ben Maimon ("Maimonides")
“Eat like a king in the morning, a prince at noon, and a peasant
at diner”(1135-1204)
NICU, Erasmus MC-Sophia
Blue light reduces systemic serum cytokine concentrations in humans appendicitis
Lewis AJ et al. Crit Care Med 2018
Weiss SL et al Crit Care Med 2014
“Inflammatory reflex”
Tracey KJ, Nature 2002
Fairchild KD et al. Am J Physiol integr Comp Physiol 2011
Activated vagal sensory neurons
Clin Perinatol 2010
IL-6 42251 pg/mlCRP 139 mg/lPCT 18.06 ng/ml
CRP 6 mg/LPCT 11.47 ng/mlIL-6 13488 pg/ml
CRP 54 mg/lPCT 1.5 ng/mlIL-6 149pg/ml
Mortality reduction in HeRO monitor trial (n=3003 VLBW)
p=0.04
Moorman JR et al. J Pediatrics 2011
Clin Perinatol 2010
Saria et al. Sci Trans Med 2010
Integration of early Physiological Responses Predicts later Illness Severity in Preterm Infants
J Perinatol 2013
aHRC-7d for infants who died or had severe IVH
Sullivan BA et al. J Pediatr 2016
Conclusion:
• Circardian dysrhythmia is a common afflication in the intensive care unit, both in patients and in staff
• Fetal programming of the circadian clock in the preterm infants is not known
• Only few human studies examined the effects of regulation of treatment schedule on human health and clinical outcome
• Predictive monitoring has potential for improving outcomes of ICU patients through earlier detection of acute illness such as sepsis
Acknowledgements
Inês Chaves
Chronobiology and Health(Dept. Molecular Genetics)
Jorine Roelants
Marijn Vermeulen
Vincent Jaddoe
Janine Felix
Tom Goos
Koen Joosten
Sinno Simons
Dept. Pediatrics
Joost Gribnau
Dept. Developmental Biology
Bert van der Horst
UCL, London
Daniel Martin
Helen McKenna
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