PMID- 29604064
OWN - NLM
STAT- MEDLINE
DCOM- 20191125
LR  - 20240214
IS  - 1469-7793 (Electronic)
IS  - 0022-3751 (Print)
IS  - 0022-3751 (Linking)
VI  - 596
IP  - 23
DP  - 2018 Dec
TI  - Altered autonomic control of heart rate variability in the chronically hypoxic 
      fetus.
PG  - 6105-6119
LID - 10.1113/JP275659 [doi]
AB  - KEY POINTS: Fetal heart rate variability (FHRV) has long been recognised as a 
      powerful predictor of fetal wellbeing, and a decrease in FHRV is associated with 
      fetal compromise. However, the mechanisms by which FHRV is reduced in the 
      chronically hypoxic fetus have yet to be established. The sympathetic and 
      parasympathetic influences on heart rate mature at different rates throughout 
      fetal life, and can be assessed by time domain and power spectral analysis of 
      FHRV. In this study of chronically instrumented fetal sheep in late gestation, we 
      analysed FHRV daily over a 16 day period towards term, and compared changes 
      between fetuses of control and chronically hypoxic pregnancy. We show that FHRV 
      in sheep is reduced by chronic hypoxia, predominantly due to dysregulation of the 
      sympathetic control of the fetal heart rate. This presents a potential mechanism 
      by which a reduction in indices of FHRV predicts fetuses at increased risk of 
      neonatal morbidity and mortality in humans. Reduction in overall FHRV may 
      therefore provide a biomarker that autonomic dysregulation of fetal heart rate 
      control has taken place in a fetus where uteroplacental dysfunction is suspected. 
      ABSTRACT: Although fetal heart rate variability (FHRV) has long been recognised 
      as a powerful predictor of fetal wellbeing, the mechanisms by which it is reduced 
      in the chronically hypoxic fetus have yet to be established. In particular, the 
      physiological mechanism underlying the reduction of short term variation (STV) in 
      fetal compromise remains unclear. In this study, we present a longitudinal study 
      of the development of autonomic control of FHRV, assessed by indirect indices, 
      time domain and power spectral analysis, in normoxic and chronically hypoxic, 
      chronically catheterised, singleton fetal sheep over the last third of gestation. 
      We used isobaric chambers able to maintain pregnant sheep for prolonged periods 
      in hypoxic conditions (stable fetal femoral arterial PO2 10-12 mmHg), and a 
      customised wireless data acquisition system to record beat-to-beat variation in 
      the fetal heart rate. We determined in vivo longitudinal changes in overall FHRV 
      and the sympathetic and parasympathetic contribution to FHRV in hypoxic (n = 6) 
      and normoxic (n = 6) ovine fetuses with advancing gestational age. Normoxic 
      fetuses show gestational age-related increases in overall indices of FHRV, and in 
      the sympathetic nervous system contribution to FHRV (P < 0.001). Conversely, 
      gestational age-related increases in overall FHRV were impaired by exposure to 
      chronic hypoxia, and there was evidence of suppression of the sympathetic nervous 
      system control of FHRV after 72 h of exposure to hypoxia (P < 0.001). This 
      demonstrates that exposure to late gestation isolated chronic fetal hypoxia has 
      the potential to alter the development of the autonomic nervous system control of 
      FHRV in sheep. This presents a potential mechanism by which a reduction in 
      indices of FHRV in human fetuses affected by uteroplacental dysfunction can 
      predict fetuses at increased risk.
CI  - (c) 2018 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd 
      on behalf of The Physiological Society.
FAU - Shaw, C J
AU  - Shaw CJ
AUID- ORCID: 0000-0002-8002-2976
AD  - Department of Physiology, Development and Neuroscience, University of Cambridge, 
      Cambridge, UK.
AD  - Institute of Reproductive and Developmental Biology, Imperial College London, 
      London, UK.
FAU - Allison, B J
AU  - Allison BJ
AUID- ORCID: 0000-0002-1060-513X
AD  - Department of Physiology, Development and Neuroscience, University of Cambridge, 
      Cambridge, UK.
FAU - Itani, N
AU  - Itani N
AUID- ORCID: 0000-0001-6171-1349
AD  - Department of Physiology, Development and Neuroscience, University of Cambridge, 
      Cambridge, UK.
FAU - Botting, K J
AU  - Botting KJ
AUID- ORCID: 0000-0003-4290-9821
AD  - Department of Physiology, Development and Neuroscience, University of Cambridge, 
      Cambridge, UK.
AD  - Cambridge Cardiovascular Research Initiative, Addenbrooke's Hospital, Cambridge, 
      UK.
FAU - Niu, Y
AU  - Niu Y
AUID- ORCID: 0000-0002-8843-9952
AD  - Department of Physiology, Development and Neuroscience, University of Cambridge, 
      Cambridge, UK.
AD  - Cambridge Cardiovascular Research Initiative, Addenbrooke's Hospital, Cambridge, 
      UK.
FAU - Lees, C C
AU  - Lees CC
AUID- ORCID: 0000-0002-2104-5561
AD  - Institute of Reproductive and Developmental Biology, Imperial College London, 
      London, UK.
AD  - Department of Obstetrics and Gynaecology, University Hospitals Leuven, Leuven, 
      Belgium.
FAU - Giussani, D A
AU  - Giussani DA
AUID- ORCID: 0000-0002-1308-1204
AD  - Department of Physiology, Development and Neuroscience, University of Cambridge, 
      Cambridge, UK.
AD  - Cambridge Cardiovascular Research Initiative, Addenbrooke's Hospital, Cambridge, 
      UK.
LA  - eng
GR  - RG/17/8/32924/BHF_/British Heart Foundation/United Kingdom
GR  - RG/06/006/22028/BHF_/British Heart Foundation/United Kingdom
GR  - RG/11/16/29260/BHF_/British Heart Foundation/United Kingdom
GR  - BB/E002668/1/BB_/Biotechnology and Biological Sciences Research Council/United 
      Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180429
PL  - England
TA  - J Physiol
JT  - The Journal of physiology
JID - 0266262
SB  - IM
CIN - J Physiol. 2018 Dec;596(23):5507-5508. PMID: 29774552
MH  - Animals
MH  - Autonomic Nervous System/physiopathology
MH  - Female
MH  - *Heart Rate, Fetal
MH  - Hypoxia/*physiopathology
MH  - Pregnancy
MH  - Sheep
MH  - Sympathetic Nervous System/physiopathology
PMC - PMC6265555
OTO - NOTNLM
OT  - Fetal Growth Restriction
OT  - Fetal heart rate
OT  - Fetal heart rate variability
OT  - Intrauterine hypoxia
OT  - Sympathetic nervous system
EDAT- 2018/04/01 06:00
MHDA- 2019/11/26 06:00
PMCR- 2018/04/29
CRDT- 2018/04/01 06:00
PHST- 2017/11/30 00:00 [received]
PHST- 2018/03/19 00:00 [accepted]
PHST- 2018/04/01 06:00 [pubmed]
PHST- 2019/11/26 06:00 [medline]
PHST- 2018/04/01 06:00 [entrez]
PHST- 2018/04/29 00:00 [pmc-release]
AID - TJP12943 [pii]
AID - 10.1113/JP275659 [doi]
PST - ppublish
SO  - J Physiol. 2018 Dec;596(23):6105-6119. doi: 10.1113/JP275659. Epub 2018 Apr 29.