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Fetal pain do we know enough to do the right thing
Fetal pain do we know enough to do the right thing
Fetal pain do we know enough to do the right thing
Fetal pain do we know enough to do the right thing
Fetal pain do we know enough to do the right thing
Fetal pain do we know enough to do the right thing
Fetal pain do we know enough to do the right thing
Fetal pain do we know enough to do the right thing
Fetal pain do we know enough to do the right thing
Fetal pain do we know enough to do the right thing
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Fetal pain do we know enough to do the right thing

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Fetal pain do we know enough to do the right thing

Fetal pain do we know enough to do the right thing

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  • 1. A 2008 Reproductive Health Matters. All rights reserved. Reproductive Health Matters 2008;16(31 Supplement):117–126 0968-8080/08 $ – see front matterwww.rhm-elsevier.com PII: S 0 9 6 8 - 8 0 8 0 ( 0 8 ) 31 3 70 - 6 www.rhmjournal.org.uk Fetal Pain: Do We Know Enough to Do the Right Thing? Stuart WG Derbyshire Senior Lecturer, University of Birmingham, School of Psychology, Edgbaston, UK. E-mail: s.w.derbyshire@bham.ac.uk Abstract: Raising the possibility of fetal pain continues as a tactic to undermine support for abortion in the US and the UK. This paper examines anatomical and psychological developments in the fetus to assess the possibility of fetal pain. Neurobiological features that develop at 7, 18 and 26 weeks gestation suggest an experience of pain in utero. Pain, however, cannot be inferred from these features because they are not informative about the state of consciousness of the fetus and cannot account for the content of any presumed pain experience. We may be confident the fetus does not experience pain because unique in utero neuroinhibitors and a lack of psychological development maintain unconsciousness and prevent conscious pain experience. Before an infant can experience sensations and emotions, the elements of experience must have their own independent existence in the infant’s mind. This is achieved after birth through discoveries made in action and in patterns of adjustment and interaction with a caregiver. Recommendations about anaesthetic practice with the fetus and the newborn or young infant should not focus on pain but on outcomes with obvious, and measurable, importance. In the case of an unwanted pregnancy, the health of the woman should guide anaesthetic practice. In the case of a wanted pregnancy, the survival and long-term health of both the woman and fetus should guide anaesthetic practice. In any case, current evidence does not support efforts to inform women of the potential for fetal pain. Any policy to mitigate fetal pain could expose women to inappropriate intervention, risk and distress. A2008 Reproductive Health Matters. All rights reserved. Keywords: pain, nociception, development, infant, fetal, neuroanatomy, abortion law and policy nitrous oxide and curare.4 This finding, andT HE possibility of fetal pain continues to be raised as a tactic to undermine support for later reports,5,6 led to a major reconsideration of abortion in the US and the UK. In the US, analgesic practice on neonates. In 1992, the Newfederal legislation requiring discussion of fetal England Journal of Medicine ran an editorialpain before an abortion has been proposed and calling on clinicians to ‘‘Do the Right Thing’’recently defeated.1 In the UK, images of the fetus concluding that ‘‘it is our responsibility to treatproduced by 4-D ultrasonography have fuelled a pain in neonates and infants as effectively as wereassessment of fetal capabilities and sugges- do in other patients’’.7 Since then it has becometions that the fetus can respond emotionally and usual to assume that neonates feel pain and thiscognitively, with the implication that the current assumption has led inevitably to speculationUK abortion law should require procedures miti- that the fetus may also experience pain.8 Con-gating against fetal pain.2,3 sequently there are calls for also reconsidering This debate raises several important questions analgesic practice on fetuses and to provideabout the nature of fetal pain and proper forms pain relief for the fetus before an abortion. Theof treatment. It has been known for some time assumption of fetal pain, however, should notthat neonates receiving fentanyl anaesthesia in go unchallenged: the available evidence regard-preparation for surgery have improved clinical ing neuronal development and pain perceptionoutcomes compared with neonates receiving raise questions about whether fetal pain is 117
  • 2. SWG Derbyshire / Reproductive Health Matters 2008;16(31 Supplement):117–126possible and the appropriateness of legislation to ring out pain is developed. For this review, ato prevent fetal pain. noxious stimulus includes any sensory insult that To address whether fetal pain relief is appro- might normally cause pain in a conscious adult.priate, I propose to divide the question of fetal Free nerve endings, the ‘‘alarm buttons’’, beginpain into its two component parts: the first to develop from about seven weeks gestation andaddresses the developing neurobiology of the projections from the spinal cord, the majorfetus and the second the developmental psy- ‘‘cable’’ to the brain, can reach the thalamus (thechology of pain. With regards to neurobiology, lower ‘‘alarm’’) from seven weeks gestation.10–12there are a series of important points in fetal An intact spinothalamic projection might rea-development that may be relevant to pain sonably be viewed as the minimal necessaryprocessing. Although fetal development is con- anatomical architecture to support pain process-tinuous, new features have been observed at 7, ing. These facts place a lower limit for fetal pain18 and 26 weeks gestation and used to suggest at seven weeks gestation.an experience of pain in utero. These new At seven weeks gestation, however, the nervousfeatures are tremendously interesting and excit- system is highly immature. There is no indication ofing, but they do not tell us the fetus is expe- a laminar structure, a defining feature of maturity,riencing pain. It is here that my critique diverges in either the thalamus or the cortex.13,14 The exter-from some of the current discussion about fetal nal wall of the brain is about 1mm thick and con-pain and sentience.7–9 In my view, it is a mistake sists of an inner and outer layer with no corticalto infer subjective experience, including pain, plate from which cortical layers will later develop.from measures of anatomy, stress hormones and The cell density of the outer layer is much higherfetal movements, because this approach fails to than that of a newborn or adult but contains largeaccount for the contents of experience in gen- neurons that resemble those described in the oldereral, and of pain in particular. fetus. Thalamic fiber penetration stimulates deve- Although we normally think of pain as some- lopment and maturation of these large neuronsthing automatic and private, and therefore natural, beginning from about 12 weeks gestation. Withoutsuch a view is mistaken. Firstly, pain is dependent thalamic projections these neurons cannot be pro-on general cognitive processes that characterise cessing noxious information from the periphery.our mental lives because pain itself contains sen- The first projections from the thalamus towardssory and affective components, which we attend the cortex (the higher ‘‘alarm’’) are apparent fromto and process. Secondly, when we are in pain we 12-16 weeks gestation. By this stage, the outerremain self-located within that experience: you layer of the brain has undergone a secondary splitknow that it is you that hurts. Pain is therefore to provide for development of the outer corticaldependent on psychological developments that rim with the subplate developing below. Thesupport cognition, and self-awareness and these subplate contains several neuronal types and ispsychological developments need time to appear. a wide zone developing below the cortical plate inFetal pain is not possible because of the lack of the human fetal brain. The thalamic projectionsdevelopment necessary to support the experience. that develop from 12–16 weeks are into the sub- plate. Spinothalamic projections into the sub- plate have been described as providing a minimalThe neurobiology of the fetus: necessary anatomy for pain experience,9 butanatomical pathways this view has to account for the transient natureIt is heuristically useful to view the pain system as of the subplate and its apparent role in the mat-an alarm system. In this view, a noxious stimulus uration of functional cortical connections. Theis an event that activates free nerve endings in subplate is generally regarded as a ‘‘waiting com-the skin similar to pushing an alarm button. The partment’’ where neurons wait before migratingelectric cable from the button to the alarm is simi- and forming mature cortical connections in thelar to the connection between the nerve endings cortical plate above.15–17 This maturational pro-and the brain. Finally, the brain is similar to the cess gradually causes dissolution of the subplate.alarm ringing out pain. Whether the fetus is While it has been suggested that the subplateresponding to a noxious stimulus with pain can may be a substrate for functional and behav-then be decided in part by asking when the alarm ioural phenomenon that occur in the womb,15118
  • 3. SWG Derbyshire / Reproductive Health Matters 2008;16(31 Supplement):117–126noxious processing and pain experience clearly injury or psychologic trauma and does not includeextend beyond this timeframe. The dissolution any conscious components that may accompanyof the subplate is difficult to explain if the sub- the stress response.24 Anand’s seminal work withplate provides a mature function. Possibly, the neonates undergoing surgery demonstrated thatmaturational role of the subplate involves plac- fentanyl added to the anaesthetic regimen sig-ing neuronal connections that are already fully nificantly reduces the stress response to invasivefunctional. This speculation, however, is incon- practice.4 Specifically, plasma adrenalin, nor-sistent with what is known about cortical deve- adrenaline, glucagon, aldosterone, corticoster-lopment.15–17 A lack of functional neuronal one, 11-deoxycorticosterone and 11-deoxycortisolactivity within the subplate undermines the claim levels were significantly increased in the non-to fetal pain experience before spinothalamic fentanyl group up to 24 hours after surgery.projections arrive in the cortical plate. Reducing the normal stress response was consid- Most current theories of pain consider an ered to be responsible for the improved clinicalintact cortical system to be necessary for pain outcome of the fentanyl group who required lessexperience.18–20 In support are functional imag- post-surgical ventilator support and had reduceding studies demonstrating activation within a circulatory and metabolic complications.network of cortical regions to correlate with More recently, the stress response to invasivereported pain experience.20,21 Furthermore, cor- practice has been examined in the fetus to dem-tical activation can create the experience of pain onstrate increased cortisol and h-endorphin cir-even without actual noxious stimulation.20,22 culation following intrauterine needling of theThese observations suggest thalamic projections fetus beyond 18 weeks gestation.25 Furtherinto the cortical plate as a minimal necessary studies have demonstrated that the fetal stressanatomy for pain experience. Currently it is response includes haemodynamic changes inbelieved that these projections begin to form blood flow to protect essential organs, such asfrom 23 weeks gestation, which means the lower the brain, and blunting the stress response whenlimit of fetal pain experience might be 23 weeks. providing opioid analgesia to the fetus.26,27It remains possible, however, that thalamic pro- The changes in cortisol and h-endorphinjections into the cortical plate are developing have been interpreted as due to direct fetalbefore 23 weeks and that earlier projections might hypothalamic-pituitary-adrenal axis (HPA) acti-carry signals indicating injury or potential tissue vation. The presence of an intact HPA axis atdamage, known technically as nociception. 18 weeks gestation is a suitable conclusion, but 23–25 weeks gestation is also the time at which the HPA axis is a subcortical system and so itsthe peripheral free nerve endings and their pro- activity is not evidence for cortical awarenessjection sites within the spinal cord reach full or conscious pain perception. Stress hormonesmaturity,10 and when noxious stimulation clearly increase during surgical procedures carried outevokes haemodynamic changes in the somato- under general anaesthesia,28,29 and in brain-deadsensory cortex.23 By 26 weeks gestation the char- patients during organ harvesting,30,31 despiteacteristic layers of the thalamus and cortex are suppression of cortical activation.32becoming visible with obvious similarities to the Behavioural responses have also been used asfuture adult brain.16,17 indicators of a stress response.7,33,34 Responses The subplate reaches its developmental peak to touch begin at 7–8 weeks gestation whenat 28 weeks gestation and is followed by mas- touching the peri-oral region results in a contra-sive transfer of subplate fibers into the cortical lateral bending of the head. The palms of theplate. After that point, the cortical plate under- hands become sensitive to stroking at 10-11 weeksgoes tremendous growth – increasing in volume gestation and the rest of the body becomesby 50% between 29 weeks gestation and term.15 sensitive around 13-14 weeks gestation.35 These are spinal reflex responses, not dependent on brain activity, and thus not indicators ofThe neurobiology of the fetus: the pain experience.hormonal ‘‘stress response’’ Shortly after developing sensitivity, repeatedA stress response is characterised by the hor- skin stimulation results in hyperexcitabilitymonal and metabolic changes that follow physical and a generalised movement of all limbs. After 119
  • 4. SWG Derbyshire / Reproductive Health Matters 2008;16(31 Supplement):117–12626 weeks, this generalised movement gradually A potential function of the thalamic reticulargives way to more coordinated behavioural nucleus could be to suppress fetal arousalresponses that signal improved organisation through inhibition of thalamocortical activa-within the nervous system. Infants delivered at tion.15 Inside the womb, alertness and motion26–31 weeks, for example, show coordinated can only cause the expenditure of energy withfacial expressions in response to heel prick that little possibility of escape or other advantage.are not present in younger infants.33 Although Outside the womb, limits on behaviour becomethese later behavioural responses are not spinal detrimental to survival.cord reflexes, the responses are still unlikely to Further obstacles to equating the fetal mindinvolve higher cortical centres. An anencephalic with that of an adult or older child are the manyfetus withdraws from noxious stimulation, dem- environmental factors inherent to the wombonstrating behavioural mediation at a subcor- that distinguish the fetal and neonatal environ-tical level.36 Similarly, infants with significant ment, and have been the subject of review else-neonatal neurological injury because of a paren- where.38 The environment of the womb consistschymal brain injury respond to noxious stimula- of warmth, buoyancy and a fluid-cushioningtion with a pattern of biobehavioural reactions of tactile stimulation. The fetus and placentasimilar to infants without brain injury.37 provide a chemical environment to preserve continuous sleep-like unconsciousness and to suppress higher cortical activation in the pres-Exploring fetal ‘‘psychology’’ ence of intrusive external stimulation. The fetalWithout verbal report or other direct access to response to hypoxia and asphyxia, for example,the fetal ‘‘mind’’, inferences about what the fetus is characterised by apnea, cessation of fetalmay experience depend on interpreting sec- body movements and a shift to hypometabolicondary evidence. As discussed above, neuro- EEG states indicative of profound unconscious-anatomical pathways necessary for processing ness.38 In the newborn, similarly threateningpain, similar to those observed in adults and situations lead rapidly to full arousal, even inolder children, could be in place by 23 weeks the preterm neonate. In contrast to the bufferedgestation. The stereotypical stress response of fetal environment, the intense tactile stimula-an adult or older child reporting pain is also tion of birth, the resulting separation of theobservable in the fetus at 18 weeks gestation. neonate from the placenta as a major source ofBehavioural reactions to noxious stimulation, com- in utero neuroinhibitors, and the onset of breath-parable to the adult or older child, can be observed ing facilitate the usually rapid onset of behav-from 26 weeks gestation. These and other obser- ioural activity and wakefulness in the neonate.vations support the suggestion that the capabil- Birth marks the transition from laying downities of the fetal mind include an experience of brain tissue in the womb to organising thatpain from at least 26 weeks gestation.7,9,25 tissue with regard to the wider world outside Inferring fetal pain based on these indirect the womb.sources of evidence, however, presents notable A final obstacle to equating fetal paindifficulties. The first difficulty is to account for experience with that of an adult or older childthe many features of the fetal brain that are not is the developmental process that begins imme-similar to that of the adult and older child. The diately after birth. Theories of human develop-cell structure of the immature brain differs from ment assume the early mind has minimalthat of a mature one, and the fetal brain has content that gradually evolves into the richseveral prominent structures that are transient and effortless experience of older children andin nature. These structures likely regulate deve- adults.39–42 Although the view of a neonate as alopmental events in the womb that become blank slate, or tabula rasa, is generally rejected,unnecessary after birth. The thalamic reticular it is broadly accepted that psychological pro-nucleus, for example, appears as inconspicuous cesses have content about people, objects andin the adult human brain but is prominent in symbols, which initially exist outside thethe fetal brain. In the fetal brain, a high packing brain.43,44 To uphold that the fetal mind hasdensity of neurons characterises this reticular direct access to pain, it must first be upheld thatnucleus, which undergoes cell death after birth. the content of pain is inherent to neural tissue120
  • 5. SWG Derbyshire / Reproductive Health Matters 2008;16(31 Supplement):117–126available in the womb. That is, at some point and disease, but is a conscious experience,during fetal development, there is developing modulated by mental, emotional and sensoryneural tissue directly coding pain experience. It mechanisms, with both sensory and emotionalmust second be upheld that the developmental components. If this ‘‘multidimensionality’’ isprocess, which enriches psychological experi- the basis of conscious pain experience, can weence, does not materially alter the pain experi- apply this experience to the fetus? If the fetusence coded directly into neural tissue. lacks the neural systems that support the cog- nitive, affective and evaluative experiences necessary for pain awareness, and anywayThe content of pain remains unconscious until after birth,38 thenFew living creatures do not respond to a noxious the answer is no. Reinforcing this conclusion,stimulus, such as a pinch or a burning flame. the IASP definition further states that ‘‘pain isLight a flame next to humble fruit fly larvae, for always subjective. Each individual learns theexample, and they will bend and roll away from application of the word through experiencesthe flame.45 These responses are dependent on related to injury in early life’’.52 By this defini-the presence of specialised sensory neurons, sim- tion, the neural tissue of the fetus at any stage ofilar to the free nerve endings in humans, which development cannot support pain experience.preferentially respond to stimuli with the poten- For this reason there have been attempts totial to cause tissue damage. The larvae clearly challenge and modify the definition of pain.47have a biological apparatus to detect and respond There is good reason, however, to support theto potentially dangerous stimulation but do they definition of pain as originally constructed. Itfeel pain? allows us to define and understand pain as an If pain is the response to noxious stimulation emergent property of social awareness, ratherthen the answer is yes, the larvae feel pain. This than as a deterministic or spiritual phenomenon.definition, however, would also mean that athermostat feels pain because it responds toexcessive heat by changing its internal state. The developmental processBy this logic, rocks might also feel pain as they Without consciousness, there can be a responserespond to excessive force by shattering. Indeed, to noxious stimulation, technically referred to asinterpretations of consciousness and pain that nociception, but there cannot be pain. Thus, toview sentience or pain as an intrinsic quality understand how pain experience in particularof life or nature lead to suggestions that larvae becomes possible, it is necessary to understandand rocks have a conscious life.46,47 Such con- the origin and course of development of consciousclusions, however, seem much too permissive. experience in general. It is reasonable to assumeFurthermore, defining pain based on response that conscious function can emerge only if themay also lead to a tautological understanding of proper neural circuitry necessary to carry outpain: pain is defined in terms of a stimulus con- that function develops fully and functionally.51sidered to be painful because it elicits the pain Changes in frontal cortex activity, for example,response. Put simply, pain is defined as pain.48,49 arrive when cognitively related behaviours, such In other words, without an accurate definition as the phenomenon of stranger anxiety andof pain the conclusion whether the fetus feels improvements in memory, begin to appear.pain ends in circularity. An accurate definition Similarly the first coordinated motor movementsof pain is crucial. Definitions of pain that avoid require the further development of specialisedcircularity usually include cognition, sensation motor regions of the brain.52and affective processes, such as that provided It is also reasonable to assume that consciousby the IASP (International Association for the function emerges only with suitable psycholog-Study of Pain). The IASP have defined pain as ical content provided in a suitable environ-‘‘an unpleasant sensory and emotional expe- ment.39–44 Sensations are not something thatrience associated with actual or potential tissue we experience raw and then interpret post hoc.damage, or described in terms of such damage’’.50 The interpretation is the experience. Distin- By this definition, pain is no longer regarded as guishing sensations from thoughts from emo-merely a physical sensation of noxious stimulus tions requires a conceptual basis to allow the 121
  • 6. SWG Derbyshire / Reproductive Health Matters 2008;16(31 Supplement):117–126distinction. Neuropsychological development experience pain are things that arose within ouris more than hooking ‘‘alarms’’ to ‘‘buttons’’, it own brains by some individual biomechanisticfacilitates conscious experience. process such as neuronal maturation.39,44 For the development of neural connections This is not to deny the fetus and neonate haveand circuitry supporting conscious experience, the neural apparatus to discriminate infor-birth is a critical event. At birth and afterwards mation. Clearly, the fetus and neonate do notthere is an increase in sensory input, which con- respond to tactile stimuli in the same way astributes to neuronal organisation. Repeated they do to auditory stimuli, for example. Indeed,sensory input during this critical period of deve- this discriminatory processing is the raw mate-lopment results in generation and stabilisation rial for a primary caregiver’s assessments ofof functional brain circuits and elimination of their infant’s needs and for the interactions anddisused and unused pathways.51 This internal behavioural adjustments that will occur in theorganisation of inputs is based on sensory input forthcoming months. Innate neural and behav-that is external to the brain. ioural discrimination are part of the material for Before an infant can think about objects or developing experiential discrimination, butevents, or experience sensations and emotion, experiential discrimination is yet to developthe elements of thought must have their own and relies critically on interactions with a pri-independent existence in the infant’s mind. This mary caregiver, as described previously. For theis achieved via continued brain development fetus and neonate, these interactions are stillwith discoveries made in action and in patterns to occur.of mutual adjustment and interactions with the The experience of pain, understanding thatinfant’s caregiver. The development of repre- I am in pain, demands that we formulate thesentational memory, which allows an infant to experience as involving concepts – ‘‘sore’’,respond and learn from stored information ‘‘stabbing’’, ‘‘damage’’, ‘‘threat’’, ‘‘body’’ – that arerather than respond to material directly avail- themselves rooted in general beliefs that no fetusable, is a building block, if not a cornerstone, of could have. We can be sure the fetus does notconscious development. Representational mem- have a conceptual understanding of their sensoryory begins to emerge as the frontal cortex circumstances because there is no medium indevelops between 2 and 4 months of age. From which to hold, challenge and adjust these con-this point on there is the possibility of tagging in cepts.53 This problem extends beyond a mere lackmemory, or labeling as a ‘‘something’’, all the of language to express and individuate concep-objects, emotions and sensations that appear or tual understanding to a recognition that there isare felt. When a primary caregiver points to a no complex, segmented, mediated psychologicalspot on the body and asks,‘‘Does that hurt?’’ they self that could harbour conceptual beliefs.are providing content and enabling an internal Whether it is possible the fetus can sense adiscrimination and with it experience. This noxious event without understanding that I aminteraction thus provides for content and sym- in pain remains open to debate. There is a pro-bols that allow the infant to locate and anchor found and profoundly important difference,emotions and sensations. It is only in this way however, between knowledge about a sensationthat the infant can arrive at a particular state and sentience. The former is not merely reduc-of being within their own mind. Although pain ible to samples of the latter as there is no fact-experience is clearly individual, a process that based form of painful experience sitting insideextends beyond the individual creates pain.39,44 the stimulus waiting to erupt inside the fetus. This is likely to strike any reader as strange Over 350 years ago, Descartes demonstratedbecause it is simply not how we intuitively feel that the eye is a kind of camera obscura thatpain to be. Because pain is automatic and per- inverts entering light. Although Descartes madesonal we feel it to be both natural and private. marked steps in understanding physiology viaBut the fact that we become able to experience a mechanical interpretation of bodily existence,pain as a personal event does not mean that, in he rejected the idea that vision is merely thethe first place, we gained the ability to experi- effect of physical action in the eye and brain. Inence pain entirely on our own. Nor does it mean the Second Meditation, Descartes explains thatthat the psychological mechanisms by which we ‘‘perception is neither an act of vision, nor of122
  • 7. SWG Derbyshire / Reproductive Health Matters 2008;16(31 Supplement):117–126touch. . . but only an intuition of the mind’’.54 The survival and normal long-term neurodevelop-orderly and calculable penetration of light rays ment.55 This is in distinction to the trajectory ofthrough the camera obscura exposes the light to some policy suggestions where the primarythe reason of the mind. The senses do not dazzle concern of the paediatric health care provider isthe mind. We may be sensorily immersed but seen to be treating the stress or pain experience.56we do not drown or dissolve in sensation. Our Such an approach neglects the functional pur-intuition of ourselves as particular things with poses of physiological stress responses to noxiousparticular location and experience opens, rather stimuli, including, for instance, modulation ofthan collapses, into our senses. Consequently, inflammation. Moreover and importantly, in ateven if an unknowable sentience can logically least some cases stopping pain is not the priority;exist for the fetus, it is a mistake to suggest a rather it is preventing death and long-term com-continuum or equivalence between passive sen- plications. A primary concern of preventing painsation and active experience. and stress during paediatric health care would, By this line of reasoning alone, apart from for example, have blocked early efforts to curepersisting fetal unconsciousness, the fetus cannot childhood leukaemia because the treatments wereexperience pain. Not only do its biological exceptionally painful.57development and state of neuroinhibition prevent Several centres have now begun to performit from experiencing pain, but the post-birth open and closed fetal surgeries for conditionsconsciousness and environmental influences, such as lower urinary tract obstruction, hydro-necessary to developing pain experience, are yet thorax, cystic adenomatous malformation of theto occur. lung, congenital diaphragmatic hernia and large sacrococcygeal teratomas.58 The possibility of adverse effects on the fetus when it is undergoingClinical and policy implications: surgery dramatic neural development should temperEarlier beliefs by paediatric anaesthetists that enthusiasm for use of analgesia and anaestheticneonates and young infants could not feel pain in the fetus undergoing such procedures. Theled to an under-utilisation of analgesic medi- possibility of adverse effects on the fetal environ-cation in these populations.5,7 Before controlled ment that may disturb the conditions thattrials,4,5 however, there were reasonable con- promote normal neural development should alsocerns about intra-operative hypotension caused temper extrapolation from experiences withby the anaesthesia of infants, and about post- premature infants to the fetus. It is tempting toanaesthesia apnea and respiratory depression assume that what has been proven to be of clinicalthat might result from narcotic analgesia. There benefit in the neonate will also be of benefit inis now enough evidence that clinical benefits the fetus. However, the greater immaturity of theoutweigh risks from anaesthetic or analgesic fetus and its very different hormonal and physicalintervention during procedures on neonates and environment38 indicate that clinical trials shouldinfants, regardless of whether evidence supports be performed with fetal patients to demonstrateor denies neonatal pain. Should paediatric anaes- improved outcomes. So far, there is no evidence-thetists return to a view that the neonate and young based fetal anaesthesia or analgesia protocolinfant cannot feel pain, the clinical benefits of defined for these procedures.anaesthetic intervention will remain. A lack ofpain experience provides no ethical or practicalreason to justify returning to a regimen of lesser Clinical and policy implications: abortionanaesthetic or analgesic intervention, unless that The medical goals of survival and long-termintervention itself were shown to be harmful. normal development of the fetal patient should Accordingly, if evidence were to reveal that not influence medical decisions when theintroducing an anaesthetic or analgesic regimen patient is a pregnant woman seeking an abor-undermines clinical outcomes then a presence tion. Under these circumstances, the need forof pain experience may still be inadequate to fetal analgesia or anaesthesia can be directlymandate use of that anaesthetic or analgesic addressed via an examination of the possibilityregimen. The major clinical outcomes that are for fetal pain and the effects of fetal pain reliefimportant to neonates and their families are for the health and well-being of the pregnant 123
  • 8. SWG Derbyshire / Reproductive Health Matters 2008;16(31 Supplement):117–126woman. The case against fetal pain, as docu- not yet developed in the fetus at any gestationmented earlier, suggests that a requirement to before birth. Evidence-based approaches thatprovide fetal pain relief before abortion is not assess outcomes of greatest importance to thesupported by evidence of what is known about parents and the future of the fetal patient, sur-the neurodevelopment of systems that support vival and long-term adverse consequences,pain. Proposals to directly inject the fetus with should guide anaesthetic practice with the fetusfentanyl,26 or to provide pain relief via increased during any procedure intended to benefit thematernal administration of fentanyl and/or fetus. Current investigations of the possibilitydiazepams can be rejected. These procedures for long-term negative outcomes from injury inincrease risks to the woman and costs to the early life should eventually provide evidence-health provider, undermine the interests of the based guidance for such procedures in future.59woman, and are unnecessary for the fetus who It is important to note that an absence of fetalhas not yet reached a developmental stage that pain does not resolve the question of whetherwould support the conscious experience of pain. abortion should be legal. Debate over life, rights and the sovereignty of a woman’s body cannot be resolved with evidence of fetal immaturity thatConclusion dictate the conditions of a clinically acceptableWe can be confident the fetus does not expe- abortion. Nevertheless, current evidence does notrience pain prior to about 23 weeks gestation support efforts to inform women seeking abortionsbecause the neural circuitry for pain in the fetus of the potential for fetal pain. Any future legis-is immature. More importantly the develop- lation to mitigate fetal pain could expose women tomental processes necessary for experience are inappropriate intervention, risk and distress.References 1. The Unborn Child Pain 6. Fitzgerald M. Pain and analgesia receptive fields, and the effects Awareness Act of 2005. S. 51 in neonates. Trends in of contralateral stimulation. bhttp://frwebgate.access.gpo. Neuroscience 1987;10:344–46. Pain 1994;56:95–101. gov/cgi-bin/getdoc.cgi? 7. Rogers MC. Do the right thing: 13. Hevner RF. Development of dbname=109_cong_ pain relief in infants and connections in the human bills&docid=f:s51is.txt.pdf N. children. New England Journal visual system during fetal 2. Lee E. Late Abortion: A Review of Medicine 1992;326:55–56. mid-gestation: a DiI-tracing of the Evidence. A Briefing 8. Anand KJS, Hickey PR. Pain and study. Journal of Neuropathology Compiled by the Pro-Choice its effects in the human neonate and Experimental Neurology Forum. bwww.prochoiceforum. and fetus. New England Journal 2000;59:385–92. org.uk/pdf/PCF_late_ of Medicine 1987;317:1321–29. 14. Larroche JC. The marginal layer abortion08.pdf N. 9. Glover V, Fisk NM. Fetal pain: in the neocortex of a 7 week-old 3. Report of the Medical Research implications for research and human embryo: a light and Council Expert Group on Fetal practice. British Journal of electron microscopic study. Pain. 28 August, 2001. Obstetrics & Gynaecology Anatomy and Embryology bwww.mrc.ac.uk/pdf-fetal.pdfN. 1999;106:881–86. 1981;162:301–12. 4. Anand KJS, Sippel WG, 10. Fitzgerald M. The prenatal 15. Ulfig N, Neudorfer F, Bohl J. Aynsley-Green A. Randomised growth of fine diameter Transient structures of the trial of fentanyl anasthesia afferents into the rat spinal human fetal brain: subplate, in preterm babies undergoing cord - a transganglionic study. thalamic reticular complex, surgery: effects on the Journal of Comparative ganglionic eminence. Histology stress response. Lancet Neurology 1987;261:98–104. and Histopathology 1987;1:243–48. 11. Fitzgerald M. Cutaneous primary 2000;15:771–90. 5. Anand KJS, Hickey PR. afferent properties in the 16. Kostovic I, Judas M. Correlation Halothane-morphine compared hindlimb of the neonatal rat. between the sequential with high dose sufentanil for Journal of Physiology ingrowth of afferents and anesthesia and postoperative 1987;383:79 – 92. transient patterns of cortical analgesia in neonatal cardiac 12. Andrews KA, Fitzgerald M. The lamination in preterm infants. surgery. New England Journal cutaneous withdrawal reflex in Anatomical Record of Medicine 1992;326:1–9. human neonates: sensitization, 2002;267:1–6.124
  • 9. SWG Derbyshire / Reproductive Health Matters 2008;16(31 Supplement):117–12617. Mrzljak L, Uylings HBM, response to invasive procedures. fetal pain. Brain Research and Kostovic I, et al. Prenatal Lancet 1996;347:624. Reviews 2005;49:455–71. development of neurons in the 28. Desborough JP. The stress 39. Hobson P. The Cradle of human prefrontal cortex: I. A response to trauma and surgery. Thought: Exploring the Origins qualitative Golgi study. Journal British Journal of Anaesthesiology of Thinking. London7 of Comparative Neurology 2000;85:109–17. Macmillan, 2002. 1988;271:355–86. 29. Marana R, Margutti F, Catalano 40. Vygotsky LS. Mind in Society:18. Peyron R, Laurent B, GF, et al. Stress responses to The Development of Higher Garcia-Larrea L. Functional endoscopic surgery. Current Psychological Processes. imaging of brain responses Opinion in Obstetrics and Cambridge MA7 Harvard to pain. A review and Gynecology 2000;12:303–07. University Press, 1980. meta-analysis. Neurophysiology 30. Fitzgerald RD, Hieber C, 41. Piaget J. Language and Thought Clinics 2000;30:263–88. Schweitzer E, et al. of the Child. London719. Treede, RD, Kenshalo DR, Intraoperative catecholamine Routledge, 2001. Gracely RH, et al. The cortical release in brain-dead organ 42. Bronfenbrenner U, Ceci SJ. representation of pain. Pain donors is not suppressed by Nature-nurture reconceptualized 1999;79:105–11. administration of fentanyl. in developmental perspective:20. Derbyshire SWG, Whalley MG, European Journal of A bioecological model. Stenger VA, et al. Cerebral Anaesthesiology 2003;20: Psychological Review activation during hypnotically 952–56. 1994;101:568–86. induced and imagined pain. 31. Lopau K, Mark J, Schramm L, 43. Malik K. Man, Beast and NeuroImage 2004;23:392 – 401. et al. Hormonal changes in brain Zombie. New Brunswick721. Coghill RC, McHaffie JG, death and immune activation in Rutgers University Press, 2002. Yen YF. Neural correlates of the donor. Transplant 44. Tallis R. The Knowing Animal: interindividual differences in International 2000;1:S282–85. A Philosophical Inquiry into the subjective experience of 32. Baars BJ, Ramsoy TZ, Laureys S. Knowledge and Truth. Edinburgh7 pain. Proceedings of the Brain, conscious experience and Edinburgh University Press, 2005. National Academy of Science the observing self. Trends in 45. Goodman MB. Sensation is USA 2003;100:8538–42. Neuroscience 2003;26:671–75. painless. Trends in Neuroscience22. Craig, AD, Reiman, EM, 33. Craig KD, Whitfield MF, Grunau 2003;26:643–45. Evans, A, et al. Functional RVE, et al. Pain in the preterm 46. Chalmers DJ. Facing up to the imaging of an illusion of pain. neonate: behavioural and problem of consciousness. Nature 1996;384:258–60. physiological indices. Pain Journal of Consciousness23. Slater R, Cantarella A, Gallella 1993;52:287–99. Studies 1994;1:1–16. S, et al. Cortical pain 34. Anand KJS, Craig KD. New 47. Anand KJS, Craig KD. New responses in human infants. perspectives on the definition of perspectives on the definition of Journal of Neuroscience pain. Pain 1996;67:3–6. pain. Pain 1996;67:3–6. 2006;26:3662–66. 35. Fitzgerald M. Neurobiology of 48. Derbyshire SWG. The IASP24. Goldman RD, Koren G. Biologic fetal and neonatal pain. In: Wall P, definition captures the essence markers of pain in the Melzack R, editors. Textbook of of pain experience. Pain Forum vulnerable infant. Clinical Pain. Oxford7 Churchill 1999;8:106–09. Perinatology 2002;29:415–25. Livingstone, 1994. p.153–63. 49. Wall PD. Why the definition of25. Giannakoulopoulos X, 36. Visser GH, Laurini RN, de Vries pain is crucial. In: Wall P, Sepulveda W, Kourtis P, et al. JIP, et al. Abnormal motor Melzack R, editors. Textbook of Fetal plasma cortisol and behaviour in anencephalic Pain. Oxford7 Churchill h-endorphin response to fetuses. Early Human Livingstone, 1989. p.1–18. intrauterine needling. Lancet Development 1985;12:173–82. 50. Merskey H. The definition of 1994;344:77 – 81. 37. Oberlander TF, Grunau RE, pain. European Psychiatry26. Fisk NM, Gitau R, Teixeira JM, Fitzgerald C, et al. Does 1991;6:153–59. et al. Effect of direct fetal opioid parenchymal brain injury affect 51. Goldman-Rakic PS. Development analgesia on fetal hormonal and biobehavioral pain responses in of cortical circuitry and cognitive hemodynamic stress response very low birth weight infants at function. Child Development to intrauterine needling. 32 weeks’ postconceptional age? 1987;58:601–22. Anesthesiology 2001;95:828–35. Pediatrics 2002;110:570 – 76. 52. Chugani HT. Biological basis of27. Teixeira J, Fogliani R, 38. Mellor DJ, Diesch TJ, Gunn AJ, emotions: Brain systems and Giannakoulopoulos X, et al. et al. The importance of brain development. Pediatrics Fetal haemodynamic stress ‘awareness’ for understanding 1998;102:S1225–29. 125
  • 10. SWG Derbyshire / Reproductive Health Matters 2008;16(31 Supplement):117–12653. Tallis R. The Knowing Animal: neurodevelopmental outcomes 57. Simone JV. Fatalities during A Philosophical Inquiry into after preterm birth. British Medical remission of childhood leukaemia. Knowledge and Truth. Journal 2004;329:1390–93. Blood 1972;39:759–69. Edinburgh7 Edinburgh 56. American Academy of Pediatrics: 58. James D. Fetal Medicine. British University Press, 2005. Committee on Fetus and Newborn Medical Journal54. Descartes R. Meditations on First Committee on Drugs. Section on 1998;316:1580–83. Philosophy (1641). Translated Anesthesiology. Section on 59. Schmelzle-Lubiecki BM, by ES Haldane and GRT Ross. Surgery. Canadian Pediatric Campbell KAA, Howard RH, et al. Descartes Key Philosophical Society: Fetus and Newborn Long-term consequences of early Writings. London7 Wordsworth Committee. Prevention and infant injury and trauma upon Classics, 1997. p.139–46. management of pain and stress in somatosensory processing.55. Colvin M, McGuire W, Fowlie PW. the neonate. Pediatrics European Journal of Pain 2007;11: ABC of preterm birth: 2000;105:454–61. 799–809.Resume ´ ´ ResumenLa possibilite de la souffrance fKtale continue d’etre ´ ˆ Incrementar la posibilidad de dolor fetal continua ´utilisee comme tactique pour miner le soutien a ´ ` siendo una ta ctica para debilitar el apoyo ´ ´l’avortement aux Etats-Unis et au Royaume-Uni. para el aborto en EE.UU. y el RU. En esteCet article examine le developpement anatomique ´ artıculo se examinan los desarrollos anatomicos ´ ´et psychologique du fKtus pour e ´valuer la y psicolo gicos del feto para determinar la ´possibilite de douleur fKtale. Les caracteristiques ´ ´ posibilidad de dolor fetal. Las caracterısticas ´neurobiologiques qui se developpent a 7, 18 et 26 ´ ` neurobiologicas que se desarrollan a las 7, 18 y ´semaines de gestation suggerent une experience ` ´ 26 semanas de gestacion indican una experiencia ´de la douleur in utero. Ces caracteristiques ne´ de dolor in utero. No obstante, no se puede inferirpermettent cependant pas de prouver que cette dolor de estas caracterısticas porque no informan ´douleur existe car elles ne rendent pas compte de sobre el estado de conocimiento del feto y no sel’etat de conscience du fKtus ni du contenu d’une ´ les puede atribuir el contenido de una supuestaperception presumee de la douleur. Il semble ´ ´ experiencia de dolor. Podemos estar seguros de queassure que le fKtus ne connaıt pas la douleur ´ ˆ el feto no siente dolor porque los neuroinhibidorescar des neuro-inhibiteurs in utero uniques et unicos in utero y la falta de desarrollo psicolo ´ ´gicoun manque de developpement psychologique ´ mantienen la inconsciencia e impiden unamaintiennent l’inconscience et evitent l’experience ´ ´ experiencia consciente de dolor. Antes que unconsciente de la douleur. Pour qu’un nourrisson recien nacido pueda experimentar sensaciones y ´experimente des sensations et des emotions, les ´ ´ emociones, los elementos de la experiencia debenelements de l’experience doivent avoir leur propre´´ ´ tener su propia existencia independiente en suexistence independante dans son esprit. Cela ´ mente. Esto se logra despues del nacimiento ´s’accomplit apres la naissance par les decouvertes ` ´ mediante descubrimientos realizados en accio y ´nfaites dans l’action et les schemas d’ajustement et ´ en patrones de ajuste e interaccion con un ´d’interaction avec la personne qui s’occupe de cuidador. Las recomendaciones sobre la practica´l’enfant. Les recommandations sur la pratique de anestesica con el feto y el recien nacido o bebe no ´ ´ ´l’anesthesie du fKtus et du nouveau-ne ou du jeune ´ ´ deben centrarse en el dolor sino en los resultadosnourrisson ne doivent pas se centrer sur la douleur, con importancia obvia y mensurable. En el casomais sur des resultats d’une importance evidente, et ´ ´ de un embarazo no deseado, la salud de la mujermesurable. Pour une grossesse non desiree, la sante ´ ´ ´ deberıa guiar la practica anestesica; en el de un ´ ´ ´de la femme doit guider la pratique de l’anesthesie. ´ embarazo deseado, esta deberıa ser guiada por ´ ´Pour une grossesse desiree, c’est la survie et la sante ´ ´ ´ la supervivencia y salud a largo plazo de la mujera long terme de la femme et du fKtus qui doivent` y el feto. En todo caso, la evidencia actual nola guider. Dans tous les cas, rien dans les donnees ´ corrobora los esfuerzos por informar a lasdont nous disposons n’indique qu’il faille informer mujeres del potencial de dolor fetal. Toda polıtica ´les femmes de la possibilite de douleur fKtale. Toute ´ para mitigar el dolor fetal podrıa exponer a ´politique destinee a soulager la douleur fKtale ´ ` las mujeres a una intervencio n inadecuada, ´pourrait exposer les femmes a des interventions ` riesgo y afliccion. ´indues, des risques et des souffrances.126

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