The fetus may feel pain from 20 weeks.

PAIN IS A SUBJECTIVE EXPERIence. The fetus cannot tell us what it is feeling, and there is no objective method for the direct measurement of pain. To address the question of pain in the fetus, one must use indirect evidence from a variety of sources, and then make an informed guess. This approach is similar to that which we use with animals. We cannot ask animals how they feel, but infer from a variety of indirect approaches including study of their behavior, anatomy and physiology.

CONSCIOUSNESS

To feel pain or suffer discomfort, one needs to be conscious, to be aware. We do not know when, if at all, consciousness starts in the fetus. The biological basis of consciousness is little understood, although at least in adult humans, the evidence suggests that it is in some way associated with electrical activity in the cerebral cortex. Susan Greenfield has explained that one should not think of consciousness as an all-or-none phenomenon but rather that it may come on like a dimmer switch. This concept of evolving consciousness could apply to the developing fetus, in whom experience is most unlikely to be similar to an adult's. Furthermore, the fetus may not have the same physical basis for conscious experience as the older human.

ANATOMY

The most important evidence for fetal pain is anatomical. For the fetus to feel pain, it is necessary for stimuli to travel around the body (nociception). This involves neural connections between peripheral receptors and the spinal cord, upward transmission via the spinal cord to the thalamus, and from there to the outer cerebral layers. The development of the human nervous system is a progressive and ascending process, with the cerebral cortex the last region to develop.

Connections from the periphery to the spinal cord are formed early, at about eight weeks; C fibers begin to grow into the spinal cord at about 10 weeks. The cerebral cortex starts to form at in weeks, although at that stage it is isolated from the rest of the brain. Cortical development starts only at about 17 weeks' gestation, but continues until long after birth. From 15 weeks, the cortex is underlain by the subplate zone, a layer of neurones below the cortex that is specific to the fetus. Synapses appear within the cortical plate from mid-gestation. The subplate zone expands considerably between 17 and 20 weeks, while from about 17 weeks, there is a shifting population of connections from the thalamus to this region. Thalamic fibres penetrate the cortical plate from 24 to 28 weeks and at this stage the full anatomical pathways necessary for nociception are in place.

Assuming that activity in the cerebral cortex or subplate zone is necessary for consciousness, then for the fetus to be conscious of an external experience these regions need to be connected with incoming nervous activity. This starts to happen at about 16 weeks and puts an early limit on when it is likely that the fetus might be aware of anything that is going on in its body or elsewhere.

The physiological evidence shows that responses in very preterm babies to visual and other stimuli (light touch, pain, pressure, temperature, and joint and muscle position sense) can be seen from as early as 24 weeks, and are well developed by 27 weeks.

BEHAVIOR

One has to be cautious about interpreting behavioral responses in terms of conscious experience, for some, at least, could be purely reflex. It is well known that animals whose cortexes have been removed for experimental purposes show a wide range of behavioral responses to noxious stimuli.

The fetus starts to make movements in response to being touched from eight weeks, and more complex movements build up, as detected by real time ultrasound, over the next few weeks. It can respond to sound from 20 weeks and discriminate between different tones from 28 weeks.

In preterm babies, who now can be kept alive from 23 weeks, one can observe behavioral responses to various clinical interventions. Such babies show a distinct pattern of behavior to painful stimuli, such as a heel prick. This includes a wide range of expressions including screwing up the eyes, opening the mouth, as well as clenching the hands and limb withdrawal, which an older baby would also show if in pain. Most nurses and mothers looking after preterm babies are convinced that they are both sentient and feel pain.

DOES ONE NEED PREVIOUS EXPERIENCE TO FEEL PAIN?

Some argue that the fetus cannot feel pain, because pain is a complex phenomenon affected by previous experience or other simultaneous occurrences. It is well known, for example, that a soldier wounded in battle often feels nothing at the time. It is also possible to sensitize the experience; people who are depressed often feel more pain than at other times. This complexity of the experience of pain in adults is not controversial. However, while suffering in adults can be affected by activity in other parts of the brain, this does not prove that in a naive being, such as the fetus, there can be no experience of pain. The fact that the sensation of pain can be affected by previous experience does not entail the conclusion that previous experience is necessary to feel pain. Such an argument would suggest that a newborn baby could not feel pain either. The view that to experience pain it is necessary to have experienced pain previously is self defeating: it would mean that there could never be a first experience of pain.

SELF CONSCIOUSNESS

It has also been suggested that consciousness implies self consciousness, and as the fetus is not self conscious it cannot be conscious either. However, consciousness does not necessarily imply self consciousness in the adult sense. All that is needed for the fetus to feel pain is that it has a simple awareness of what is going on in itself. It does not need the more complex understanding that it itself is different from the outside world.

STRESS RESPONSES

Recent research has concentrated on the stress responses of the fetus to various interventions, just as neonatal research did in the previous decade. It is important to clarify the relevance of this work to a discussion of pain. Stress responses, defined as an activation of specific hormonal and neurotransmitter systems, do not provide a direct index of pain. Although stress hormones are usually increased when a subject is experiencing pain, there are many other situations which are not painful, such as exercise, which also can increase their levels. Furthermore, production and release of stress hormones such as cortisol can be mediated by the hypothalamus, without involvement of the cortex or other higher brain regions involved in sentience.

There is now evidence that the human fetus can mount substantial stress responses. These have been shown both by examining stress hormone levels in the blood before and after invasive procedures and by examining the redistribution of blood flow within the fetus. Some of these responses have been found from as early as i6 weeks. What then is the use of measuring stress responses? In considering stress responses in relation to the question of fetal pain, the "null hypothesis" is of relevance: if there were no change in stress hormone levels, it would be very unlikely that the fetus was experiencing pain. Stress responses can also be used to give some sort of index, though imperfect, of the degree of trauma involved and further determine the effect of analgesia or anesthesia. It was the demonstration of stress responses in the newborn during surgery that precipitated the change in attitude in the medical and nursing care of newborn infants. We must emphasize, however, with both the fetus and the newborn, that a stress response, in itself, does not tell us directly what the baby is feeling.

CLINICAL IMPLICATIONS

The fetus is still often currently treated as though it feels nothing and is given no analgesia or anesthesia for potentially painful interventions. This is similar to the way in which newborn babies used to be treated until research compared neonates undergoing cardiac surgery who received deep anesthesia with those given a lighter regimen of halothane and morphine. The first-mentioned group had a much better postoperative outcome in terms of infection and mortality than the latter. Now such pain relief is routinely given to babies, not just for open surgery but for more minor procedures. However it is possible that opiate drugs may have long term adverse effects, and research is needed to determine their risk-benefit ratio for different interventions, both in the fetus and in the neonate.

TERMINATION OF PREGNANCY

Late terminations may cause pain to the fetus if they involve an invasive procedure, such as surgical dismemberment. Modification of the technique, such as preparatory occlusion of the umbilical cord, may be appropriate.

CHILD BIRTH

The experience of the baby during birth is not usually considered. It is generally assumed that as birth is a natural phenomenon, undergone for thousands of years without pain relief, that it is painless for the baby. This may not be the case.

Failure to provide adequate analgesia for preterm neonates is now considered substandard and unethical practice. There have been similar calls for fetuses to be given analgesia during invasive procedures. The opioid agonists, such as fentanyl, are the drugs most widely used for sedation and analgesia for newborns. We now have evidence that direct fentanyl administration to the fetus can blunt stress responses in utero also.

Intravenous administration of fentanyl in the mother is unsatisfactory since the rate of transfer across the placenta is slow. Larger doses may cause respiratory depression in the mother. However, not only do they cause sedation, they may also have adverse behavioral effects if delivery soon follows, impairing fetal responsiveness. General anesthesia has significant risks in pregnancy. The potential benefits of analgesia in the fetus need to be balanced against the risk of additional procedures and the potential for adverse long term drag effects.

CONCLUSION

There clearly is not enough evidence to be certain if and when the fetus starts to feel pain. By 26 weeks, the full anatomical system for nociception has been formed, an EEG shows activity in the cerebral cortex and the preterm baby of the same gestational age, if delivered, shows a complex range of pain behavior. Some have concluded that it is not possible for the fetus to be aware of events before 26 weeks gestation and not to feel pain until considerably later than that. This seems unduly certain, given the available evidence. Before 26 weeks, too little is known about the physical basis of consciousness in the fetus to be sure that it has no awareness. Given the anatomical evidence, it is possible that the fetus can feel pain from 20 weeks and is caused distress by interventions from as early as 15 or 16 weeks. This sets limits as to the earliest stage that analgesia might be considered.

It is not possible to measure pain directly in the fetus. Studies of stress responses can be used to give an index of the degree of trauma induced by different interventions and also the response to analgesia or anesthesia, but they do not indicate what the fetus actually experiences. The assessment of whether or when the fetus is likely to feel pain has to be based on an evaluation of the available anatomical and physiological--evidence. The physical system for nociception is present and functional by 26 weeks and it seems likely that the fetus is capable of feeling pain from this stage. The first neurons to link the cortex with the rest of the brain are in place from about 16 weeks' gestation. Their activation could be associated with unpleasant conscious experience, even if not pain. Thalamic fibers first penetrate the subplate zone at about 17 weeks gestation and the cortex at 20 weeks. These issues are important, not only because of immediate suffering, but also because of possible long term adverse effects of this early experience. Research in these areas is urgently required.

The 18th century philosopher, Jeremy Bentham, wrote of animals: "The question is not 'Can they reason?', nor, 'Can they talk?', but 'Can they suffer?'" This caused a change in attitude towards animals and their treatment that is still continuing today, such that in the UK, even frogs and fishes are required by Act of Parliament to be protected by anesthesia from possible suffering due to invasive procedures. Why not human beings?

This article is based on: Vivette Glover and Nicholas M Fisk, "Fetal pain: implications for research and practice," British Journal of Obstetrics and Gynaecology, 1999, Vol. 106, No. 9, pp881-6.

PROFESSOR VIVETTE GLOVER is director of the Fetal and Neonatal Stress Research Group at Imperial College, London.