The neurobiological basis of fetal awareness – impact upon recommended obstetric practice.
Submitting Institutions
University College London,
Birkbeck CollegeUnit of Assessment
Biological SciencesSummary Impact Type
HealthResearch Subject Area(s)
Medical and Health Sciences: Neurosciences, Paediatrics and Reproductive Medicine
Summary of the impact
Research by Maria Fitzgerald's group in the Department of Neuroscience,
Physiology & Pharmacology has provided fundamental biological
knowledge of the development of pain pathways in the human fetus that is
recognised all over the world. As a direct result of her published
research, she co-authored a report from the Royal College of Obstetrics
and Gynaecology on clinical recommendations for practice in fetal medicine
and fetal termination. Published in March 2010, this report provides
authoritative, evidence-based recommendations for medical practitioners,
abortion advisory groups and patients, and consequently determines
clinical practice throughout the UK. The recommendations impact upon a
large number of women; in 2011 there were 196,082 abortions in England and
Wales.
Underpinning research
The research underpinning this case report stems from Fitzgerald's
studies of fetal and neonatal pain pathways which mapped the growth of
nociceptive afferent terminals into the skin and into the central nervous
system (CNS) before birth [1]. These data demonstrated that, while
peripheral nociceptors develop prenatally, their central connections and
thus their ability to transmit nociceptive information to the brain do not
develop until just before birth [2].
Subsequent research by Fitzgerald, on how pain pathways develop over the
perinatal period, has elucidated the development of central signalling
pathways, inhibitory circuits and descending brainstem control in the
maturation of pain processing in early life [e.g. 2,3].
At the same time, Fitzgerald has also pioneered the study of the
neurobiology of infant human pain processing. In the human, the extremely
premature infant is the closest model we have to the third trimester human
fetus. Her early work in this area demonstrated that premature infants
from 24 weeks gestational age (GA) can process nociceptive stimuli at
spinal and brainstem level, but in a different way from older children and
adults [4]. The research is notable for its use of quantitative
neurophysiological techniques, grounded in basic neurobiology, to study
CNS pain processing in very young preterm infants. This continues to the
present day, using cot-side techniques such as near-infra red spectroscopy
and electroencephalography (EEG) for direct brain measurement of pain
processing in extremely preterm infants [5].
Fitzgerald's work has clarified the difference between the onset of
nociceptive reflex behaviour observed in fetal life, which requires intact
circuits in the spinal cord and brainstem only, and the onset of pain
`awareness' or `experience' which requires functional cortical
connections. This is fundamental to the understanding of fetal pain.
Recent work shows a transition in the premature infant brain response
following tactile and noxious stimulation from nonspecific, evenly
dispersed neuronal bursts to modality-specific, localised, evoked
potentials between 24 weeks GA and term. The results suggest that specific
neural circuits necessary for discrimination between touch and nociception
emerge from 35-37 weeks gestation in the human brain [5].
References to the research
[3] Hathway GJ, Koch S, Low L, Fitzgerald M. The changing balance of
brainstem-spinal cord modulation of pain processing over the first weeks
of rat postnatal life. J Physiol. 2009 Jun 15;587(Pt 12):2927-35. http://dx.doi.org/10.1113/jphysiol.2008.168013
[4] Andrews K, Fitzgerald M. The cutaneous withdrawal reflex in human
neonates: sensitization, receptive fields, and the effects of
contralateral stimulation. Pain. 1994 Jan;56(1):95-101.
http://dx.doi.org/10.1016/0304-3959(94)90154-6
[5] Fabrizi L, Slater R, Worley A, Meek J, Boyd S, Olhede S, Fitzgerald
M. A shift in sensory processing that enables the developing human brain
to discriminate touch from pain. Curr Biol. 2011 Sep 27;21(18):1552-8. http://dx.doi.org/10.1016/j.cub.2011.08.010
MRC programme grant (Fitzgerald): Infant pain mechanisms — a short and
long term view; Ref: G0400572; Jan 2005-Jan 2010; £1,086,101.
Details of the impact
Elective abortion is a matter of considerable political, social and
ethical concern. The UK has one of the most liberal laws in the world,
based upon scientific and clinical rationale and a strong sense of a
woman's right to choose, rather than upon religious beliefs. After the
introduction of The Abortion Act 1967, the Act of the United Kingdom
Parliament legalising abortions by registered practitioners, and
regulating the free provision of such medical practices through the
National Health Service (NHS), the UK Government has regularly reviewed
scientific evidence related to this Act.
As a direct result of her published research, Fitzgerald was asked to
give evidence at a House of Commons Science and Technology Committee on
the scientific evidence relating to the Abortion Act of 1967 [a].
This and other evidence from different sources led to the UK Government
retaining the 24-week limit on abortion in the UK in 2007 [b].
This decision inevitably led to controversy, due to strong reactions from
pro-life religious groups, many of whom are of the opinion that fetuses
feel pain, are sentient and should not be terminated at any stage. The
Minister of State for Health therefore commissioned the Royal College of
Obstetrics and Gynaecology (RCOG) to review the scientific and clinical
evidence for fetal awareness in detail and to update their original 1997
report on this subject (to which Fitzgerald had contributed) [c].
As a direct result of her published research on fetal nervous system
development, and specifically the development of pain pathways, Fitzgerald
was invited to join the working party and was a co-author of the updated,
2010 published report, entitled `Fetal Awareness. Review of Research and
Recommendations for Practice' [d].
The intention of the report was to review the relevant science and
clinical practice relevant to the issue of fetal awareness and, in
particular, evidence published since 1997. In so doing, the report was
completely rewritten to take account not only of recent literature but
also of the evidence presented to the House of Commons Committee. The
report concluded that, since most neuroscientists believe that the cortex
is necessary for pain perception, it can be concluded that the fetus
cannot experience pain in any sense prior to 24 weeks gestation. After 24
weeks there is continuing development and elaboration of intracortical
networks such that noxious stimuli in newborn preterm infants produce
cortical responses. Such connections to the cortex are necessary for pain
experience but not sufficient, as experience of external stimuli requires
consciousness. Furthermore, there is increasing evidence that the fetus
never experiences a state of true wakefulness in utero and is kept, by the
presence of its chemical environment, in a state of continuous sleep-like
unconsciousness or sedation. This state can suppress higher cortical
activation in the presence of intrusive external stimuli. The implications
of these scientific observations for clinical practice are such that the
need for analgesia prior to intrauterine intervention, for diagnostic or
therapeutic reasons, becomes much less compelling. Indeed, in the light of
current evidence, the Working Party concluded that the use of analgesia
provided no clear benefit to the fetus. Furthermore, because of possible
risks and difficulties in administration, fetal analgesia should not be
employed where the only consideration is concern about fetal awareness or
pain [e].
The number of women affected by this report is very high: in 2010, there
were 189,574 abortions in England and Wales; in 2011 there were 196,082;
in 2012 there were 185,122 [f]. Furthermore the impact spreads
beyond the termination procedure itself to the long term physical and
mental health of affected women. The RCOG's updated guidelines were
followed by the Academy of Medical Royal Colleges' publication `Induced
abortion and mental health: a systematic review of the mental health
impact of induced abortion' [g]. The purpose of the review was to
examine the evidence of the impact of abortion upon women's mental health.
The Academy's conclusions echoed the RCOG's guidelines.
This report has set the clinical and scientific standards for medical and
allied health professions on the termination of pregnancy, and provided
scientific underpinning for the current UK abortion law. It received
considerable press attention with reaction from both pro-choice and
pro-life groups [h] and the interest of medical ethicists [i].
Sources to corroborate the impact
[a] House of Commons — Science and Technology Committee. Scientific
Developments Relating to the Abortion Act 1967. HC 1045-I, Twelfth Report
of Session 2006-07 — Volume I: Report, Together with Formal Minutes. TSO
(The Stationery Office).
http://www.publications.parliament.uk/pa/cm200607/cmselect/cmsctech/1045/1045i.pdf
[b] HM Government, Government response to the report from the House of
Commons Science and Technology Committee on the Scientific Developments
Relating to the Abortion Act 1967.
http://webarchive.nationalarchives.gov.uk/20130107105354/http://www.dh.gov.uk/prod_consum_dh/groups/dh_digitalassets/@dh/@en/documents/digitalasset/dh_086538.pdf
[c] Royal College of Obstetricians and Gynaecologists. Fetal awareness:
Report of a Working Party. London RCOG Press; 1997. Available on request.
[d] Royal College of Obstetricians and Gynaecologists. `Fetal Awareness.
Review of Research and Recommendations for Practice' . Report of a Working
Party, March 2010.
http://www.rcog.org.uk/fetal-awareness-review-research-and-recommendations-practice.
Document: http://www.rcog.org.uk/files/rcog-corp/RCOGFetalAwarenessWPR0610.pdf
[e] RCOG clinical guidelines:
http://www.rcog.org.uk/womens-health/clinical-guidance/abortion-care
http://www.rcog.org.uk/termination-pregnancy-fetal-abnormality-england-scotland-and-wales
Document: http://www.rcog.org.uk/files/rcog-corp/TerminationPregnancyReport18May2010.pdf
[f] Abortion statistics for England and Wales:
[g] Wider impacts on women's mental health: Academy of Medical Royal
Colleges report on `Induced Abortion and Mental Health'. http://www.aomrc.org.uk/publications/reports-a-guidance/doc_details/9432-induced-abortion-and-mental-health.html
[h] Examples of press reports: Telegraph and New Scientist, comments from
pro-choice groups and pro-life groups:
[i] Ethical study and RCOG ethical statement