Advances in the Understanding of Fetal Pain

Ten Questions On Fetal Pain

1. Can an unborn baby feel pain?
   Up until recently, few people ever asked, “does the baby feel pain during the abortion? or how early can a fetus feel pain?” The science is available now to answer those questions.
2. When is an unborn infant viable? Don’t all abortions just affect infants who could not live outside the womb?
   Viability is certainly much earlier than was ever thought possible in 1973. As medical science pushes the frontier of fetal viability to 23 weeks, and perhaps sooner with the advent of artificial wombs and placental support—there is a possibility that a definition of viability based upon gestational age will soon be irrelevant.
3. What is the earliest sign of pain perception?
   Unborn infants have pain receptors on their face by 7 weeks of development, and over their entire body by the 20th week of gestation in the same or greater density than adults.
4. How do we know those pain receptors are really transmitting a pain signal?
   EEGs have recorded the response to noxious stimuli as early as 26 weeks.
5. How do we know pain is perceived the same in preborn infants as in adults?
   The same way that children and adults respond to pain with changes in their hormones, the 20–35 week preborn infants also respond.
6. How does the threshold for pain differ from adults?
   It takes less of a noxious stimulus to create pain in the unborn child.
7. Over time, adults with chronic pain learn ways to cope. Can the unborn cope?
   The fibers and substances needed to feel pain are present; but the mechanisms needed to modulate and tone down the response to pain are poorly developed.
8. Do the preborn and newborns feel more or less pain than adults?
   Newborns not only feel pain; they react to pain with 3–5 times the response of adults.
9. How do we know the pain impacts the baby in a substantial way?
   The response to pain is not inconsequential. Infants who were not treated for their pain during operations had worse clinical outcomes.
10. Since Fetal Surgery centers provide anesthesia for the preborn, should pain to the unborn child be a consideration in an abortion?
    If a preborn child requires anesthesia for fetal surgery, then shouldn’t the logical extension be that children undergoing abortion also feel pain—and would have the same requirements for anesthesia?

Introduction

Why is the development of pain in the fetus and newborn important?

In the last 30 years, the fields of developmental neurobiology, perinatology, neonatology, pediatric anesthesia and pediatric surgery have exploded with knowledge. That knowledge has radically impacted how we care for the unborn infant, and the infant born prematurely. However this knowledge has lagged behind in permeating the clinical care involved in abortion, particularly in the abortion of the late-term fetus.

Up until recently, few people ever asked, “does the baby feel pain during the abortion? How early can a fetus feel pain?” The science is available now to answer those questions.

Improvements In Neonatology

Improvements in neonatology push for a new definition of viability for the premature infant.

In 1973 neonatology was in its infancy as a science and as a practice. The understanding of the physiology of the preterm infant, the equipment, medications, physicians, and specialized units available to care for them were present but limited. By contrast, today there are thousands of neonatologists, hundreds of Neonatal Intensive Care units, and breaking discoveries in the world and womb of the developing fetus and neonate. Artificial surfactant, liquid ventilation, ECMO, and other heroic technologies support the infants who would have not survived in 1973. Specific textbooks, journals, fellowship training programs, and scientific conferences abound focused solely on the care of the premature infant.

Compare that to 1973, when the Supreme Court discussion focused heavily on the issue of fetal viability. At that time, the common understanding was that infants born before 28 weeks could not survive. And there was no expectation that the date of viability would be pushed back earlier than 28 weeks. Today that age of viability has not only been pushed back beyond 28 weeks, but even to 23 and 24 weeks.

The number of children that are born and survive at 23–28 weeks gestation is common enough now that the term Micro-premie has been coined to describe them and an additional body of neonatal science is focused upon them.

So when is an unborn infant viable?

Certainly much earlier than was ever thought possible in 1973.

More importantly, as medical science pushes the frontier of fetal viability to 23 weeks, and perhaps earlier with the advent of artificial wombs and placental support—there is a possibility that a definition of viability based upon gestational age will soon be irrelevant.

Understanding Pain Perception

Research in anesthesia provides a better understanding of the development of pain perception.

Pain is a subjective phenomenon for every one—adults, children, and the unborn. It includes the perception of noxious stimuli, remembering the event, and the processing of the event in a series of hormonal and physiologic responses. Therefore, evaluating the perception of pain is difficult in all human subjects. But identifying the structures, processes and measuring the response to noxious stimuli is increasingly done in all age groups.

Drs. Anand and Fitzgerald have demonstrated that very preterm neonates have the neuro-anatomic substrate and functional physiologic and chemical processes in the brain required for mediating pain or noxious stimuli, known as nociception. The pain receptors needed to feel pain on the skin are referred to as cutaneous nociceptive nerve endings. Recent anatomic studies have shown that the density of these cutaneous nociceptive nerve endings in the late fetus and newborn infant may equal or exceed that of adult skin. Early studies by Hooker showed that cutaneous sensory perception appears in the perioral area of the human fetus in the seventh week of gestation and gradually spreads to all cutaneous and mucous surfaces by 20 weeks.

Unborn infants have pain receptors on their face by seven weeks of development, and over their entire body by the 20th week of gestation in same or greater density than adults.

Several types of observations speak for the functional maturity of the cerebral cortex in the fetus and neonate. First, fetal and neonatal EEG patterns (which include cortical components of visual and auditory evoked potentials) have been recorded in preterm babies of less than 28 weeks gestation. Second, cortical evoked potentials from somatosensory stimuli (touch, pain, heat, and cold) were also recently documented in preterm neonates from 26 weeks gestation.

Evoked potentials and EEGs have recorded the response to noxious stimuli as early as 26–28 weeks.

A study of intrauterine blood sampling and blood transfusions in fetuses between 20 and 34 weeks of gestation showed that hormonal responses to the needle sticks were consistent with the fetal perception of pain and were correlated with the duration of the painful stimulus.

Infants Respond To Pain

The preborn 20–34 week infant responds to pain with changes in stress hormones in the same manner as children and adults.

Ultrasonographic findings report specific fetal movements in response to needle punctures in utero. When neonates are born prematurely at 23 weeks gestation, they demonstrate highly specific and well-coordinated physiologic and behavioral responses to pain—similar to those seen in full-term neonates, older infants, and small children. The responses of these prematurely born infants gives us a window in the world of preborn, validating outside the uterus what they were capable of manifesting inside the uterus.

Contrary to previous teaching, current data indicate that preterm neonates have greater pain sensitivity than term neonates or older age children and adults.

Several lines of scientific evidence support this concept.

The study of the cutaneous flexor reflex has been used to establish when connections between the skin and the spinal cord are first made in the fetus. It has also been used to study the maturation of ascending motor pathways. This reflex has been shown in man to parallel pain perception exactly in terms of threshold, peak intensity, and sensitivity to analgesics. This reflex has a lower threshold in premature neonates (and thus unborn infants) than in full term newborns or adults.

Unborn Child Is More Sensitive To Pain

It takes less of a noxious stimulus to create pain in the unborn child.

Neurotransmitter development in the dorsal horn of the spinal cord involves the early and abundant expression of the neurotransmitters mediating nociception (substance P, L-glutamate, VIP, CGRP) and increased somatosensory excitability in the premature spinal cord. In contrast, the neurotransmitters contained in descending inhibitory fibers from supraspinal centers (5-HT, Norepinephrine, Dopamine) were expressed after birth, implying poorly developed gate control mechanisms for pain in preterm infants.

Opioid receptor labeling in the brain stem of fetuses at 19-21 weeks gestation demonstrate very high densities in supraspinal centers associated with sensory perception. These inhibitory opioid receptors may be the only protection for the developing neuronal systems from constant over-stimulation, given the overall underdeveloped gate control mechanism in the dorsal horn of the spinal cord.

Pain Defense Is Underdeveloped

The fibers and substances needed to feel pain are present, but the mechanisms needed to modulate and tone down the response to pain are poorly developed.

The practice of Pediatric Surgery and Pediatric Anesthesia has shown us how preborn and preterm infants respond to pain.

The magnitude of hormonal and physiologic responses to invasive procedures or surgical operations is much greater in neonates as compared to adults. Pain in the fetus and neonate can be measured in two dimensions. Pain and surgical stress are demonstrated by a coordinated outpouring of pituitary, adrenal, and pancreatic hormones. Secondly, cardiovascular responses, such as increases in blood pressure, heart rate, dysrhythmias, or poor cardiac output may signal pain. Anand demonstrated that newborns generate a catacholamine and metabolic responses up to 3–5 times those of adult patients undergoing similar types of surgery.

Pharmacokinetic studies of anesthetic drugs have shown higher plasma concentrations were required to maintain effective surgical anesthesia in preterm neonates as compared to old age groups. The studies cited above indicate a lower pain threshold in preterm neonates, and the occurrence of further decreases in pain threshold following exposure to a painful stimulus or experience.

Newborns Feel Pain More Intensely

Newborns not only feel pain; they react to pain with 3–5 times the response of adults. They require higher doses of anesthesia during surgery, and repeated exposure to pain lowers the threshold to pain even more.

The effects of anesthesia on the neonatal stress responses are important and may contribute to the effects of stress suppression on postoperative clinical outcome. In a randomized controlled trial, preterm babies undergoing ligation of the patent ductus arteriosus were given nitrous oxide, with or without the addition of an intravenous pain medication (fentanyl). The hormonal responses of neonates receiving nitrous oxide alone were associated with significant increases in blood glucose, lactate, and pyruvate. These biochemical changes were prevented in neonates given the therapeutic doses of the pain medication. This study went on to show that aggressive anesthesia not only decreased the stress responses of neonates undergoing surgery but also improved their postoperative clinical outcome.

Research Shows Consequences Of No Pain Treatment

The response to pain is not insignificant nor inconsequential. Infants who were not treated for their pain had more stress responses and worse clinical outcomes.

In the early 1970’s, many preterm infants were considered too ill and too frail to tolerate the anesthesia required for their needed surgery. Even by the early 1980’s, preterm infants still received minimal anesthesia in the operating room and the neonatal intensive care unit. Two landmark articles by Anand in 1987 challenged this assumption and changed the practice of pediatric anesthesia.

Lastly, exciting surgical advances at places like the Fetal Surgery Center at the University of California allow for the surgeon to partially remove the fetus through an incision in the womb, repair the congenital defect and slip the pre-viable infant back into the womb. These procedures challenge us to reconsider the outcome and viability of many preterm infants including those with serious congenital defects. Anesthesia for the preborn child is a planned part of these surgical procedures, and every effort is made to prevent the preborn child from experiencing noxious stimuli with the hormonal and physiologic changes that accompany the surgery.

Abortion And Anesthesia

If a preborn child requires anesthesia for fetal surgery, then shouldn’t children undergoing abortion have the same requirements for anesthesia?

Fletcher, in the editorial that accompanied Anand’s study, comments that….

unless a neonatologist had made a concerted effort to study the topic of pain, a subject that has not until now been in the forefront of concern in neonatal care, he or she would not have had easy access to more of the information in the Anand study.

She highlights that among the 201 references, only 20 occurred in medical journals that might have been part of a neonatologist’s regular reading. She further states that “Good often comes from bad,” thereby encouraging the readers to learn from their earlier misunderstandings. Her succinct statement could be applied to the topic of fetal pain today.

Anand and Hickey concluded in “Pain and Its Effects in the Human Neonate and Fetus”…

[C]urrent knowledge suggest that human considerations should apply as forcefully to the care of neonates and young, nonverbal infants as they do to children and adults in similar painful and stressful situations.

Selected Bibliography

• Anand KJS, Hickey PR. Pain and its effect in the human neonate and fetus. New Engl J Med 317:1321-1329.
• Anand KJS, Aynsley-Green A. Metabolic and endocrine effects of surgical litigation of patent ductus arteriosus in the human preterm neonate: Are there implications for further improvement of postoperative outcome? Mod Probl Paediatr 1985; 23:143-57.
• Torres F, Anderson C. The normal EEG of the human newborn. J Clin Neurophysiol 1985; 2:89-103.
• Hickey PR, Hansen DD, Wessel DL, Lang P, Jonas RA, Elixson EM. Blunting of stress responses in the pulmonary circulation of infants by fentanyl. Anesth Analg 1985; 64:1137-42.
• Anand KJS, Brown JM, Causon RC, Christofides ND, Bloom SR, Aynsley-Green A. Can the human neonate mount an endocrine and metabolic response to surgery? J Pediatr Surg 1985; 20:41-8.
• Fitzgerald M, Shaw A, MacIntosh N. The postnatal development of the cutaneous flexor reflex: a comparative study in premature infants and newborn rat pups. Dev Med Child Neuro.
• Berry FA, Gregory GA. Do premature infants require anesthesia for surgery? Anesthesiology 1987; 67: 291-3.
• Yaster M. Analgesia and anesthesia in neonates. J Pediatr 1987; 111: 394-6.

Note: This paper, prepared in April 2002, is not an official ethical statement of the Christian Medical Association but rather an informational resource. Nothing written here is to be construed as necessarily reflecting the views of the Emory School of Medicine or its affiliates.

This article first appeared in Theology Matters, Vol. 9, No. 3 (May/Jun 2003).