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Chairman Hyde, and members of the Committee. My name is Jean A. Wright, MD., MBA. I am an Associate Professor of Pediatrics and Anesthesia at Emory University School of Medicine in Atlanta. I am also an Associate Professor at the Emory Center for Clinical Evaluation Sciences. I am board certified in Pediatrics, Anesthesia, and in both sub- boards of Critical Care Medicine. I have been a faculty member and a practicing physician since 1983.
I appreciate the invitation to testify before the Committee on the topic of the effects of anesthesia administered to a mother during a partial birth abortion. I understand that this committee was considering legislation which would ban ūpartial birth abortionsū, and that this is the second hearing on this topic. I will focus my testimony on the ability of the fetus to feel and respond to pain during this procedure, and on the effects of the anesthetic upon the fetus while administered to the mother.
My testimony will be divided into three parts. 1) The developmental aspects of pain in the fetus; 2) The increased sensitivity of preterm infants to pain compared to term or older infants; and 3) the effects of maternally administered anesthetics to blunt or alter the effect of this pain.
1. Evidence of the development of a pain system in neonates
Very preterm neonates have the neuroanatomic substrate and functional physiologic and chemical processes responsible for mediating pain or noxious stimuli (known as nociception). [Fitzgerald and Anand]. [Refer to Chart from NEJM, 1987].
Anatomic studies have shown that the density of 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.
Traditionally, lack of myelination has been proposed as an index of immaturity in the neonatal nervous system and used frequently to support the arguement that neonates and infants are not capable of pain perception. Nociceptive impulses in adults can be carried by unmyelinated or thinly myelinated fibers. Gilles has shown that nerve tracts associated with nociception in the spinal cord and brain stem are completely myelinated up to the thalamus by 30 weeks of gestation.
Several types of observations speak for the functional maturity of the cerebral cortex in the fetus and neonate. First are reports of fetal and enonatal EEG patterns, including cortical components of visual and auditory evolked potentials, that have been recorded in preterm babies of less than 30 weeks gestation. Well defined periods of sleep and wakefulness are present in utero from 28 weeks gestation onward.
2. Increased sensivity to pain in preterm infants.
Contrary to previous teaching, current data indicate that preterm neonates have a greater sensitivity than term neonates or older age groups. This is evidenced in at least 5 key indicators. I will review these from the most basic science, to that which reflects clinical practice.
Cutaneous Flexor Reflex - has a lower threshold in preterm neonates than in term neonates or adults [Fitzgerald; Woolf]. The study of this reflexe has been used to establish when connection between the skin and the spinal cord are first made in the fetus, and they have ben used to study the maturation of secending motor pathways. This reflex has been shown in man to parallel pain perception exactly in terms of threshold, peak intensity, and sensitivity to analgesics.
Neurotransmitter development in the dorsal horn of the spinal cord - has demonstrated the early and abundant expression of putative neurotransmitters mediating nociception (subsdtance 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, Norepi, Dopamine) were expressed postnatally, [Anand & Carr] implying poorly developed gate control mechanisms for pain in preterm infants
Opioid receptor labelling in the fetal brain stem - demonstrated very high densitites in supraspinal centers associated with sensory perception [Kinney]. These inhibitory opioid receptors may protect developing neuronal systems from constant over stimulation, given the underdeveloped gate control mechanism in the dorsal horn of the spinal cord.
Other data suggests more opioid receptors in the preterm infant brain and spinal cord....
The magnitude of endocrine-metabolic and other stress responses - to invasive procedures or surgical operations was much greater in neonates as compared to adults; with neonatal catacholamine and metabolic responses up 3 - 5 x those of adult patients undergoing similar types of surgery [Anand]. Pain in the fetus and neonate can be measure in two dimensions. Pain and surgical stress are demonstrated by a coordinated outpouring of pitutitary, adrenal, and pancreatic hormones. Secondly, cardiovascular responses, such as dysrhythmias or poor cardiac output, may signal pain.
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 patient ductuus arteriousus were given nitrous oxide and curare, with or without the addition of intravenous fentanyl. The hormonal responses of neonates receiving nitrous oxide alon were associated with signifiannt increases in blood glucoe, lactate, and pyruvate; these were prevented in neonates given therapeutic doses of fentanyl. 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.
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 [Yaster; Greeley & de Bruijn].
Developmental changes occur in the expression of pain which differentiate preterm from term or older infants; however, these findings illustrate a communicational specificity and not changes in pain threshold during development [Johnston]. The studies cited above indicate a lower pain threshold in preterm neonates, and the occurrence of further decreases in pian following exposure to a painful stimulus or experience [Fitzgerald].
3. Effects of Anesthesia on the fetus
Obstetrical anesthesia has become a very safe practice, with over 50,000 women a year receiving an anesthetic during the time of their pregnancy. This is in addition to those who receive an anesthetic at the time of delivery.
Local anesthetics do not have an affect on the fetus. By their nature, their affect is to the nerves and tissues around the injection site, and miniscule amounts enter the motherūs circulation, and even less reaches the fetus.
The administration of intravenous sedation/anesthesia has minimal effects on the unborn due to two mechanism: The motherūs liver clears much of the drug, and secondly, the drug must cross from the motherūs blood stream into the placenta before reaching the fetus. Since the fetus has more opioid receptors, scientific reasoning postulates that it takes a higher dose of opioid to saturate the increased number of receptors, and achieve a therapeutic response.