FETAL PAIN. NEW ADVANCES

Autor: Carlo V. Bellieni

ÍNDICE

1. Abstract
2. Introduction
3. Evidence of fetal pain
4. Some objections
5. The fetus as a patient: analgesia
6. Conclusion
7. Table 1

References

 

1. Abstract.

 Fetuses can feel pain since when their nociceptive system has achieved an adequate development. Recent advances in fetal physiology and imaging show that the fetus’ nervous system is ready from the half of the pregnancy (about 20-22 weeks from conception) to feel pain and to respond to it. This has important clinical and legal consequences.

 

 

2. Introduction

 

Can a fetus feel pain? When it was impossible to observe the fetus, or to perform thorough analyses of his/her reactions, this question could have no answer. But in the last few years, some observations have permitted to add details and information on this topic. Four-D-Ultrasound images have given useful data, and physiology advances have shown that the connections of peripheral receptors with the fetal cortex are more precocious than previously supposed, but also that the spino-thalamic connection (a connection with a precocious and deep brain centre) is sufficient to experience pain.

This has a special clinical impact. First, because fetal surgery has moved its first steps (1-5), and now it is evident that in the case of fetal pain analgesia should be provided; second, because fetal pain gives a further evidence of the moral gravity of voluntary abortion, though the absence of pain would not make it less inacceptable.

Here I will highlight some of the main points of this discussion.

3. Evidence of fetal pain.

A         Anatomy and physiology The human brain can receive pain stimuli from the half of pregnancy. To this aim, some structures are needed: pain receptors, nerves that transport the stimulus to the thalamus (with the possibility that they have an insulating layer called myelin), neurotransmitters that permit that the stimulus passes from a neuron to another, and a central integration. The central integration is provided by the brain cortex, whose transitory first step is represented by the subplate; but also the thalamus can integrate pain. Table 1 shows the timetable of appearance of the different structures necessary to the sentience of pain (6-11).

B          Neurophysiology Is fetal brain active? Fetal magnetoencephalography has been used to effectively record fetal auditory and visual evoked responses and spontaneous brain activity of cortical origin from 27 weeks (12) and at 26-28 weeks GA, evoked potentials may be recorded from somatosensory, visual, auditory and frontal cortices (13). Near infrared spectroscopy with preterm infants, has demonstrated localized somatosensory cortical responses in premature newborn infants from 24 weeks, following painful heel lance and venepuncture (14). Fetal brain blood circulation undergoes sudden changes during fetal painful procedures (15).

C         Images Four-D images of the fetus have also been reported to show fetuses ‘crying’ after external stimuli (16) and having blink-startle reflex at 30 weeks of gestational age after an unpleasant stimulus (17). Infants delivered at 26–31 weeks show coordinated facial expressions in response to heel prick although these are immature compared to older infants (18).

D         Hormons Transfusions performed in utero provoke an increase of stress hormones since 19 weeks of postgestational age, if performed through the skin, where nociceptive receptors are present, but not if performed through the umbilical cord, where these receptors are absent (19-21).

E         Evidence of neonatal pain Newborns feel pain: this is a well established evidence. Thus, there is no reason to doubt that a fetus of the same level of development of a prematurely born baby can feel pain. Some fetuses arrive to the term of pregnancy (40 weeks), i.e. they are more developed of some newborns born at 25, 26 weeks, whose pain sensation is out of doubt and who receive analgesia for surgery.

4. Some objections

Some studies (22-24), object that these evidences cannot be considered evidences of pain, basing their objections upon two main arguments.

The first is the absence of cortical involvement in pain processing before 24 weeks GA; this would mean an absence of consciousness and, according with these authors, an absence of pain perception. Nevertheless, several studies (25) highlight the clinical evidence for perception mediated by subcortical centers (namely the thalamus): infants and children with hydranencephaly, despite total or near-total absence of the cortex, possess some form of discriminative awareness  (26), and the subplate vicariates the definitive cortex in those critical development weeks.

The second argument is the supposed continuous state of fetal sleep throughout pregnancy, that would inhibit pain perception, even beyond the 24th week GA. Nonetheless, Van de Pas (27) described states F3 (calm wake) and F4 (active wake) up to 21% of daytime in term fetuses, and even the state F5 (crying) is described in a fetus (16). Moreover, a great difference exists between sedation and sleep: during pregnancy fetuses sleep, but sleep does not annihilate the possibility of experiencing pain.

5. The fetus as a patient: analgesia

Fetal surgery has recently made rapid progresses (1-5). Now it is possible to treat some mechanical anomalies before birth, and this in some cases has brought clear advantages to the babies, who have not to wait birth to be cured. Fetal surgery is used in fetuses with congenital diaphragmatic hernia, in whom lung growth is triggered by percutaneous tracheal occlusion. It can also be used to treat urinary obstructions. Many fetal interventions remain investigational, but randomised trials have established the role of in utero surgery for a number of conditions, making fetal surgery a clinical reality. Even non-lethal conditions, such as myelomeningocele repair, can be considered an indication (5).

During fetal surgery, the fetus undergoes several potentially painful procedures, and direct analgesics should be administered to him/her. Mother’s anesthesia is not sufficient to overcome pain during surgery (during C-sections performed with general mother’s anesthesia, babies are often born awake), then (28-30) direct analgesia is provided to the fetus.

6. Conclusion

A sufficient evidence exist to admit that during surgery fetuses from 20-22 weeks of gestational age undergo pain during potentially painful maneuvers. Some authors agree with this limit (31-33).

This evidence has some important legal consequences: in fact, some US States subordinate the possibility of legal abortion to the exclusion of the possibility of fetal pain. In early 2010, the Nebraska state legislature passed a new abortion restricting law asserting a new, compelling state interest in preventing fetal pain. Idaho law, passed during the 2011 Legislature, bans abortions once a fetus has reached 20 weeks on the belief that fetuses begin to feel pain at that stage. Idaho was one of five states along with Kansas, Alabama, Indiana and Oklahoma that enacted bans modeled after a fetal pain bill passed in Nebraska in 2010.

Being painful, does not add “per se” moral gravity to the voluntary abortion, that is always the deliberate suppression of a living prenatal baby. Nevertheless, it makes the injustice more evident.

7. Table 1

Structure

Appearance

(weeks of gestational age)

Myelination (the formation of a sort of insulation of each nerve from the outer environment)

 

12-14

   

Substance P (a transmitter of pain impulse)

8-10

     

Connections between pain receptors and the thalamus (The thalamus is the structure where most nociceptive or pleasant stimuli are decoded)

   

20

 

Direct thalamocortical fibers (the fibers that connect the thalamus with the cortex)

     

23

Subplate (a waiting compartment for growing cortical afferents. Its cells are involved in the establishment of pioneering cortical efferent projections and transient fetal circuitry)

 

13

   

Brain cortex

   

20

 

REFERENCES

  1. Williams H. Questioning the rationale and conduct of the management of myelomeningocele study. Med Hypotheses. 2011 Apr 29. [Epub ahead of print]
  2. Hartmann KE, McPheeters ML, Chescheir NC, Gillam-Krakauer M, McKoy JN, Jerome R, Sathe NA, Meints L, Walsh WF. Evidence to Inform Decisions About Maternal-Fetal Surgery: Technical Brief. Obstet Gynecol. 2011May;117(5):1191-1204.
  3. Ruano R. Fetal surgery for severe lower urinary tract obstruction. Prenat Diagn. 2011 Mar 17. doi: 10.1002/pd.2736. [Epub ahead of print]
  4. Deprest JA, Nicolaides K, Gratacos E. Fetal surgery for congenital diaphragmatic hernia is back from never gone. Fetal Diagn Ther. 2011;29(1):6-17.
  5. Simpson JL, Greene MF. Fetal surgery for myelomeningocele? New Engl Journal Med. 2011 Mar 17; 364(11):1076-7.
  6. Weidenheim KM, Bodhireddy SR, Rashbaum WK, Lyman WD. Temporal and spatial expression of major myelin proteins in the human foetal spinal cord during the second trimester. J Neuropathol Exp Neurol 1996;55:734– 45
  7. Zecevic N, Andjelkovic A, Matthieu JM, Tosic M. Myelin basic protein immunoreactivity in the human embryonic CNS. Dev Brain Res 1998;105:97–108
  8. Fitzgerald M. Neurobiology of fetal and neonatal pain. In Wall PD & Melzack R (eds) Textbook of Pain. London: Churchill Livingstone, 1994, pp 153
  9. Cousins MJ: Cousins and Bridenbaugh's Neural Blockade in Clinical Anesthesia and Pain Medicine. Lippincott Williams & Wilkins, 2008
  10. Lowery CL, Hardman MP, Manning N, Hall RW, Anand KJ, Clancy B. Neurodevelopmental changes of fetal pain. Semin Perinatol. 2007 Oct;31(5):275-82
  11. Kostovic I, Rakic P. Developmental history of the transient subplate zone in the visual and somatosensory cortex of the macaque monkey and human brain. J Comp Neurol. 1990;297:441-470.
  12. Govindan RB, Wilson JD, Preissl H, Murphy P, Lowery CL, Eswaran H. An objective assessment of fetal and neonatal auditory evoked responses. Neuroimage. 2008 Nov 15;43(3):521-7
  13. Vanhatalo S, Lauronen L. Neonatal SEP – back to bedside with basic science. Semin Fetal Neonatal Med 2006; 11: 464–70
  14. Bartocci M, Bergqvist LL, Lagercrantz H, Anand KJ. Pain activates cortical areas in the preterm newborn brain. Pain 2006;122:109–17.
  15. Teixeira JM, Glover V, Fisk NM. Acute cerebral redistribution in response to invasive procedures in the human fetus. Am J Obstet Gynecol. 1999 Oct; 181(4):1018-25.
  16. Gingras JL, Mitchell EA, Grattan KE. Fetal homologue of infant crying. Arch Dis ChildFetal Neonatal Ed. 2005 Sep;90(5):F415-8.
  17. Bellieni CV, Severi F, Bocchi C, Caparelli N, Bagnoli F, Buonocore G, Petraglia F. Blink-startle reflex habituation in 30-34-week low-risk fetuses. J Perinat Med. 2005;33(1):33-7
  18. Johnston CC, Stevens BJ, Franck LS, Jack A, Stremler R, Platt R. Factors explaining lack of response to heel stick in preterm newborns. J Obstet Gynecol Neonat Nurs 1999;28:587–94
  19. Gitau R, Fisk NM, Glover V. Human fetal and maternal corticotrophin releasing hormone responses to acute stress. Arch Dis Child Fetal Neonatal Ed. 2004 Jan; 89(1):F29-32.
  20. Fisk NM, Gitau R, Teixeira JM, Giannakoulopoulos X, Cameron AD, Glover VA. Effect of direct fetal opioid analgesia on fetal hormonal and hemodynamic stress response to intrauterine needling. Anesthesiology. 2001 Oct;95(4):828-35.
  21. Giannakoulopoulos X, Teixeira J, Fisk N, Glover V. Human fetal and maternal noradrenaline responses to invasive procedures. Pediatr Res. 1999 Apr;45(4 Pt 1):494-9.
  22. Mellor DJ, Diesch TJ, Gunn AJ, Bennet L. The importance of 'awareness' for understanding fetal pain. Brain Res Brain Res Rev. 2005 Nov;49(3):455-71
  23. Derbyshire SW. Fetal pain: do we know enough to do the right thing? Reprod HealthMatters. 2008 May;16(31 Suppl):117-26.
  24. Lee SJ, Ralston HJ, Drey EA, Partridge JC, Rosen MA. Fetal pain: a systematic multidisciplinary review of the evidence. JAMA. 2005 Aug 24;294(8):947-54.
  25. Denton DA, McKinley MJ, Farrell M, Egan GF. The role of primordial emotions in the evolutionary origin of consciousness. Conscious Cogn. 2009 Jun;18(2):500-14.
  26. Merker B: Consciousness without a cerebral cortex: A challenge for neuroscience and medicine. Behavioral and Brain Sciences, 2007;30:63-81
  27. van de Pas M, Nijhuis JG, Jongsma HW. Fetal behaviour in uncomplicated pregnancies after 41 weeks of gestation. Early Hum Dev. 1994 Dec 16;40(1):29-38
  28. Strümper D, Durieux ME, Gogarten W, Van Aken H, Hartleb K, Marcus MA. Fetal plasma concentrations after intraamniotic sufentanil in chronically instrumented pregnant sheep. Anesthesiology. 2003 Jun;98(6):1400-6
  29. Gaiser RR, Kurth CD. Anesthetic considerations for fetal surgery. Semin Perinatol1999;23:507e14
  30. Sutton LN: Fetal surgery for neural tube defects. Best Pract Rres Clin Obstet Gynecol2008;22(1):175-88
  31. Glover V. The fetus may feel pain from 20 weeks. Conscience. 2004-2005;25(3):35-7
  32. Bellieni CV, Buonocore G. Is Fetal Pain A Real Evidence? J Matern Fetal Neonatal Med. 2011 Oct 25.
  33. Lowery CL, Hardman MP, Manning N, Hall RW, Anand KJ, Clancy B. Neurodevelopmental changes of fetal pain. Semin Perinatol. 2007 Oct;31(5):275-82.

¿Cómo citar esta voz?

Sugerimos el siguiente modo de citar, que contiene los datos editoriales necesarios para la atribución de la obra a sus autores y su consulta, tal y como se encontraba en la red en el momento en que fue consultada:

Bellieni, Carlo, FETAL PAIN. NEW ADVANCES, en García, José Juan (director): Enciclopedia de Bioética.

Última modificación: Monday, 6 de July de 2020, 13:26