KJS Anand and PR Hickey: Neonatal pain and its effects
THE NEW ENGLAND JOURNAL OF MEDICINE, Volume 317, Number 21: Pages 1321-1329,
19 November 1987.
SPenis EnlargementCIAL ARTICLE
PAIN AND ITS EFFECTS IN THE HUMAN NEONATE AND FETUS
K.J.S. ANAND, M.B.B.S., D.PHIL., AND P.R. HICKEY, M.D
From the Department of Anesthesia, Harvard Medical School, and Children's
Hospital, Boston. Address reprint requests to Dr. Anand at the Department of
Anesthesia, Children's Hospital, 300 Longwood Ave., Boston, MA 02115.
THE evaluation of pain in the human fetus and neonate is difficult because pain
is generally defined as a subjective phenomenon.1 Early studies of neurologic
development concluded that neonatal responses to painful stimuli were
decorticate in nature and that perception or localization of pain was not
present.2 Furthermore, because neonates may not have memories of painful
experiences, they were not thought capable of interpreting pain in a manner
similar to that of adults.3-5 On a theoretical basis, it was also argued that a
high threshold of painful stimuli may be adaptive in protecting infants from
pain during birth.6 These traditional views have led to a widespread belief in
the medical community that the human neonate or fetus may not be capable of
perceiving pain.7,8
Strictly speaking, nociceptive activity, rather than pain,should be
discussed with regard to the neonate, because pain is a sensation with strong
emotional associations. The focus on pain perception in neonates and confusion
over its differentiation from nociceptive activity and the accompanying
physiologic responses have obscured the mounting evidence that nociception is
important in the biology of the neonate. This is true regardless of any
philosophical view on consciousness and "pain perception" in newborns. In the
literature, terms relating to pain and nociception are used interchangeably; in
this review, no further distinction between the two will generally be made.
One result of the pervasive view of neonatal pain is that newborns are
frequently not given analgesic or anesthetic agents during invasive procedures,
including surgery.9-19 Despite recommendations to the contrary in textbooks on
pediatric anesthesiology, the clinical practice of inducing minimal or no
anesthesia in newborns, particularly if they are premature, is widespread.9-19
Unfortunately, recommendations on neonatal anesthesia are made without reference
to recent data about the development of perceptual mechanisms of pain and the
physiologic responses to nociceptive activity in preterm and full-term neonates.
Even Robinson and Gregory's landmark paper demonstrating the safety of narcotic
anesthesia in preterm neonates cites "philosophic objections" rather than any
physiologic rationale as a basis for using this technique.20 Although
methodologic and other issues related to the study of pain in neonates have been
discussed,21-23 the body of scientific evidence regarding the mechanisms and
effects of nociceptive activity in newborn infants has not been addressed
directly.
ANATOMICAL AND FUNCTIONAL REQUIREMENTS FOR PAIN Penis EnlargementRCEPTION
The neural pathways for pain may be traced from sensory receptors in the
skin to sensory areas in the cerebral cortex of newborn infants. The density of
nociceptive nerve endings in the skin of newborns is similar to or greater than
that in adult skin.24 Cutaneous sensory receptors appear in the perioral area of
the human fetus in the 7th week of gestation; they spread to the rest of the
face, the palms of the hands, and the soles of the feet by the 11th week, to the
trunk and proximal parts of the arms and legs by the 15th week, and to all
cutaneous and mucous surfaces by the 20th week.25,26 The spread of cutaneous
receptors is preceded by the development of synapses between sensory fibers and
interneurons in the dorsal horn of the spinal cord, which first appear during
the sixth week of gestation.27,28 Recent studies using electron microscopy and
immunocytochemical methods show that the development of various types of cells
in the dorsal horn (along with their laminar arrangement, synaptic
interconnections, and specific neurotransmitter vesicles) begins before 13 to 14
weeks of gestation and is completed by 30 weeks.29
Lack of myelination has been proposed as an index of the lack of maturity
in the neonatal nervous system30 and is used frequently to support the argument
that premature or full-term neonates are not capable of pain perception.9-19
However, even in the peripheral nerves of adults, nociceptive impulses are
carried through unmyelinate (C-polymodal) and thinly myelinated (A-delta)
fibers.31 Incomplete myelination merely implies a slower conduction velocity in
the nerves or central nerve tracts of neonates, which is offset completely by
the shorter interneuron and neuromuscular distances traveled by the impulse.32
Moreover, quantitative neuroanatomical data have shown that nociceptive nerve
tracts in the spinal cord and central nervous system undergo complete
myelination during the second and third trimesters of gestation. Pain pathways
to the brain stem and thalamus are completely myelinated by 30 weeks; whereas
the thalamocortical pain fibers in the posterior limb of the internal capsule
and corona radiata are myelinated by 37 weeks.33
Development of the fetal neocortex begins at 8 weeks gestation, and by 20
weeks each cortex has a full complement of 109 neurons.34 The dendritic
processes of the cortical neurons undergo profuse arborizations and develop
synaptic targets for the incoming thalamocortical fibers and intracortical
connections.35,36 The timing of the thalamocortical connection is of crucial
importance for cortical perception, since most sensory pathways to the neocortex
have synapses in the thalamus. Studies of primate and human fetuses have shown
that afferent neurons in the thalamus produce axons that arrive in the cerebrum
before mid-gestation. These fibers then "wait" just below the neocortex until
migration and dendritic arborization of cortical neurons are complete and
finally establish synaptic connections between 20 and 24 weeks of gestation
(Fig. 1).36-38
Functional maturity of the cerebral cortex is suggested by fetal and a
neonatal electroencephalographic patterns, studies of cerebral metabolism, and
the behavioral development of neonates. First, intermittent
electroencephalograpic bursts in both cerebral hemispheres are first seen at 20
weeks gestation; they become sustained at 22 weeks and bilaterally synchronous
at 26 to 27 weeks.39 By 30 weeks, the distinction between wakefulness and sleep
can be made on the basis of electroencephalo- graphic patterns.39,40 Cortical
components of visual and auditory evoked potentials have been recorded in
preterm babies (born earlier than 30 weeks of gestation),40,41 whereas olfactory
and tactile stimuli may also cause detectable changes in electroencephalograms
of neonates.40,42 Second, in vivo measurements of cerebral glucose utilization
have shown that maximal metabolic activity in located in sensory areas of the
brain in neonates (the sensorimotor cortex, thalamus, and mid brain- brain-stem
regions), further suggesting the functional maturity of these regions.43 Third,
several forms of behavior imply cortical function during fetal life.
Well-defined periods of quiet sleep, active sleep, and wakefulness occur in
utero beginning at 28 weeks of gestation.44 In addition to the specific
behavioral responses to pain described below, preterm and full-term babies have
various cognitive, coordinative, and associative capabilities in response to
visual and auditory stimuli, leaving no doubt about the presence of cortical
function.45
Several lines of evidence suggest that the complete nervous system is
active during prenatal development and that detrimental and developmental
changes in any part would affect the entire system.25,26,42,46 In studies in
animals, Ralston found that somatosensory neurons of the neocortex respond to
peripheral noxious stimuli and proposed that "it does not appear necessary to
postulate a subcortical mechanism for appreciation of pain in the fetus or
neonate."47 Thus, human newborns do have the anatomical and functional
components required for the perception of painful stimuli. Since these stimuli
may undergo selective transmission, inhibition, or modulation by various
neurotransmitters, the neurochemical mechanisms associated with pain pathways in
the fetus and newborn are considered below.
Figure 1. Schematic Diagram of the Development of Cutaneous Sensory
Perception,25
Myelination of the Pain Pathways,32 Maturation of the Fetal Neocortex,33-37 and
Electroencephalographic Patterns38-40 in the Human Fetus and Neonate.
NEUROCHEMICAL SYSTEMS ASSOCIATED WITH PAIN Penis EnlargementRCEPTION
The Tachykinin System
Various putative neurotransmitters called the tachykinins (substance P,
neurokinin A, neuromedin K, and so forth) have been identified in the central
nervous system, but only substance P has been investigated thoroughly and shown
to have a role in the transmission and control of pain impulses.48-56 Neural
elements containing substance P and its receptors appear in the dorsal-root
ganglia and dorsal horns of the spinal cord at 12 to 16 weeks of gestation.57 A
high density of substance P fibers and cells have been observed in multiple
areas of the fetal bran stem associated with pathways for pain perception and
control and visceral reactions to pain.58-63 Substance P fibers and cells have
also been found in the hypothalamus, mamillary bodies, thalamus, and cerebral
cortex of human fetuses early in the development.58 Many studies have found
higher densities of substance P and it receptors in neonates than in adults of
the same species, although the importance of this finding is unclear.61,64-68
The Endogenous Opioid System
With the demonstration of the existence of stereospecific opiate
receptors69,70 and their endogenous ligands,71 the control of pain was suggested
as a primary role for the endogenous opioid system.72 Both the enkephalinergic
and the endorphinergic systems may modulate pain transmission at spinal and
supraspinal levels.56,73 In the human fetus, however, there are no data on the
ontogeny and distribution of specific cells, fibers, and receptors (mu-, delta-,
and kappa opiate receptors) that are thought to mediate the antinociceptive
effects of exogenous and endogenous opioids.74 However, functionally mature
endorphinergic cells in fetal pituitary glands have been observed at 15 weeks of
gestation and possibly earlier.75,76 Beta-endorphin and beta-lipotropin were
found to be secreted from fetal pituitary cells at 20 weeks in response to in
vitro stimulation by corticotropin- releasing factor.77 In addition, more
production of beta-endorphin may occur in fetal and neonatal pituitary glands
than in adult glands.78-79
Endogenous opioids are released in the human fetus at birth and in
response to fetal and neonatal distress.80 Umbilical-cord plasma levels of
beta-endorphin and beta-lipotropin from healthy full-term neonates delivered
vaginally or by cesarean section have been shown to be three to five times
higher than plasma levels in resting adults.78,81 Neonates delivered vaginally
by breech presentation or vacuum extraction had further increases in
beta-endorphin levels, indication beta-endorphin secretion in response to stress
at birth.82 Plasma beta-endorphin concentrations correlated negatively with
umbilical-artery pH and partial pressure of oxygen and positively with base
deficit and partial pressure of carbon dioxide, suggesting that birth asphyxia
may be a potent stimulus to the release of endogenous opioids.81,83-87
Cerebrospinal fluid levels of beta-endorphin were also increased markedly in
newborns with apnea of prematurity,88-90 infections, or hypoxemia.83,91,92 These
elevated values may have been caused by the "stress" of illness,93 the pain
associated with these clinical conditions, or the invasive procedures required
for their treatment. However, these high levels of beta-endorphin are unlikely
to decrease anesthetic or analgesic requirements,94 because the cerebrospinal
fluid levels of beta-endorphin required to produce analgesia in human adults
have been found to be 10,000 times higher than the highest recorded levels in
neonates.95
The high levels of beta-endorphin and beta-lipotropin in cord plasma
decreased substantially by 24 hours after birth87,96 and reached adult levels by
five days, whereas the levels in the cerebrospinal fluid fell to adult values in
24 hours.87,97,98 In newborn infants of women addicted to narcotics, massive
increases in plasma concentrations of beta-endorphin, beta-lipotropin, and
metenkephalin occurred within 24 hours, with some values reaching 1000 times
those in resting adults. Markedly increased levels persisted for up to 40 days
after birth.87 However, these neonates were considered to be clinically normal,
and no behavioral effects were observed (probably because of the development of
prenatal opiate tolerance).
PHYSIOLOGIC CHANGES ASSOCIATED WITH PAIN
Cardiorespiratory Changes
Changes in cardiovascular variables, transcutaneous partial pressure of
oxygen, and palmar sweating have been observed in neonates undergoing painful
clinical procedures. In preterm and full-term neonates undergoing
circumcision99,100 or heel lancing,101-103 marked increases in the heart rate
and blood pressure occurred during and after the procedure. The magnitude of
changes in the heart rate was related to the intensity and duration of the
stimulus104 and to the individual temperaments of the babies.105 The
administration of local anesthesia to full-term neonates undergoing circumcision
prevented the changes in heart rate and blood pressure,99,100,106 whereas giving
a "pacifier" to preterm neonates during heel-stick procedures did not alter
their cardiovascular or respiratory responses to pain.101 Further studies in
newborn and older infants showed that noxious stimuli were associated with an
increase in heart rate, whereas non-noxious stimuli (which elicited the
attention or orientation of infants) caused a decrease in heart rate.22,107,108
Large fluctuations in transcutaneous partial pressure of oxygen above and
below an arbitrary "safe" range of 50 to 100 mm Hg have been observed during
various surgical procedures in neonates.109-111 Marked decreases in
transcutaneous partial pressure of oxygen also occurred during
circumcision,106,112 but such changes were prevented in neonates given local
analgesic agents.100,106,112 Tracheal intubation in awake preterm and full-term
neonates caused a significant decrease in transcutaneous partial pressure of
oxygen, together with increases in arterial blood pressure113-115 and
intracranial pressure.116 The increases in intracranial pressure with intubation
were abolished in preterm neonates who were anesthetized.117 In addition,
infants' cardiovascular responses to tracheal suctioning were abolished by
opiate-induced analgesia.118
Palmar sweating has also been validated as a physiologic measure of the
emotional state in full-term babies and has been closely related to their state
of arousal and crying activity. Substantial changes in palmar sweating were
observed in neonates undergoing heel-sticks for blood sampling, and
subsequently, a mechanical method of heel lancing proved to be less painful than
manual methods, on the basis of the amount of palmar sweating.120
Hormonal and Metabolic Changes
Hormonal and metabolic changes have been measured primarily in neonates
undergoing surgery, although there are limited data on the neonatal responses to
venipuncture and other minor procedures. Plasma renin activity increased
significantly 5 minutes after venipuncture in full-term neonates and returned to
basal levels 60 minutes thereafter; no changes occurred in the plasma levels of
cortisol, epinephrine, or norepinephrine after venipuncture.121 In preterm
neonates receiving ventilation therapy, chest physiotherapy and endotracheal
suctioning produced significant increases in plasma epinephrine and
norepinephrine; this response was decreased in sedated infants.122 In neonates
undergoing circumcision without anesthesia, plasma cortisol levels increased
markedly during and after the procedure.123,124 Similar changes in cortisol
levels were not inhibited in a small number of neonates given a local
anesthetic,125 but the efficacy of the nerve block was questionable in these
cases.
Further detailed hormonal studies126 in preterm and full-term neonates
who underwent surgery under minimal anesthesia documented a marked release of
catecho- lamines,127 growth hormone,128 glucagon,127 cortisol, aldosterone, and
other corticosteroids,129,130 as well as suppression of insulin secretion.131
These responses resulted in the breakdown of carbohydrate and fat
stores,127,132,133 leading to severe and prolonged hyperglycemia and marked
increases in blood lactate, pyruvate, total ketone bodies, and nonesterified
fatty acids. Increased protein breakdown was documented during and after surgery
by changes in plasma amino acids, elevated nitrogen excretion, and increased
3-methyl- histidine:creatinine ratios in the urine (Anand KJS, Aynsley-Green A:
unpublished data). Marked differences also occurred between the stress responses
of premature and full-term neonates (Anand KJS, Aynsley-Green A: unpublished
data) and between the responses of neonates undergoing different degrees of
surgical stress.134 Possibly because of the lack of deep anesthesia, neonatal
stress responses were found to be three to five times greater than those in
adults, although the duration was shorter.126 These stress responses could be
inhibited by potent anesthetics, as demonstrated by randomized, controlled
trials of halothane and fentanyl. These trials showed that endocrine and
metabolic stress responses were decreased by halothane anesthesia in full-term
neonates 35 and abolished by low-dose fentanyl anesthesia in preterm
neonates.136 The stress responses of neonates undergoing cardiac surgery were
also decreased in randomized trials of high-dose fentanyl and sufentanil
anesthesia.126,137,138 These results indicated that the nociceptive stimuli
during surgery performed with minimal anesthesia were responsible for the
massive stress responses of neonates. Neonates who were given potent anesthetics
in these randomized trials were more clinically stable during surgery and had
fewer postoperative complications as compared with neonates under minimal
anesthesia.126,129 There is preliminary evidence that the pathologic stress
responses of neonates under light anesthesia during major cardiac surgery may be
associated with an increased postoperative morbidity and mortality (Anand KJS,
Hickey PR: unpublished data). Changes in plasma stress hormones (e.g., cortisol)
can also be correlated with the behavioral states of newborn infants,124,139,140
which are important in the postulation of overt subjective distress in neonates
responding to pain.
BEHAVIORAL CHANGES ASSOCIATED WITH PAIN Penis EnlargementRCEPTION
Simple Motor Responses
Early studies of the motor responses of newborn infants to pinpricks
reported that the babies responded with a "diffuse body movement" rather than a
purposeful withdrawal of the limb,2 whereas other studies found reflex
withdrawal to be the most common response.141-143 More recently, the motor
responses of 24 healthy full-term neonates to a pinprick in the leg were
reported to be flexion and adduction of the upper and lower limbs associated
with grimacing, crying, or both, and these responses were subsequently
quantified.144,145 Similar responses have also been documented in very premature
neonates, and in a recent study, Fitzgerald et al. found that premature neonates
(<30 weeks) not only had lower thresholds for a flexor response but also had
increased sensitization after repeated stimulation.146
Facial Expressions
Distinct facial expressions are associated with pleasure, pain, sadness,
and surprise in infants.147 These expressions, especially those associated with
pain, have been objectively classified and validated in a study of infants being
immunized.102,148 With use of another method of objectively classifying facial
expressions of neonates, different responses were observed with different
techniques of heel lancing and with different behavioral states149 (and Grunau
RVE, Craig KD: unpublished data). These findings suggest that the neonatal
response to pain is complex and may be altered by the behavioral state and other
factors at the time of the stimulus.150
Crying
Crying is the primary method of communication in newborn infants and is
also elicited by stimuli other than pain.151 Several studies have classified
infant crying according to the type of distress indicated and its spectrographic
properties.152-154 These studies have shown that cries due to pain, hunger, or
fear can be distinguished reliably by the subjective evaluation of trained
observers and by spectrographic analysis.155-160 This has allowed the cry
response to be used as a measure of pain in numerous recent studies.
22,99,100,102,106,152
The pain cry has specific behavioral characteristics and spectrographic
properties in healthy full-term neonates.161-164 Pain cries of preterm neonates
and neonates with neurologic impairment, hyperbilirubinemia, or meningitis are
considerably different, thereby indicating altered cortical function in these
babies.165-168 Changes in the patterns of neonatal cries have been correlated
with the intensity of pain experienced during circumcision and were accurately
differentiated by adult listeners.169 In other studies of the painful
procedures, neonates were found to he more sensitive to pain than older infants
(those 3 to 12 months old) but had similar latency periods between exposure to a
painful stimulus and crying or another motor response.99-101,103,152,170 This
supports the contention that slower conduction speed in the nerves of neonates
is offset by the smaller inter-neuron distances traveled by the impulse.
Complex Behavioral Responses
Alterations in complex behavior and sleep-wake cycles have been studied
mainly in newborn infants undergoing circumcision without anesthesia. Emde and
coworkers observed that painful procedures were followed by prolonged periods of
non-rapid-eye-movement sleep in newborns and confirmed these observations in a
controlled study of neonates undergoing circumcision without anesthesia.171
Similar observations have been made in adults with prolonged stress. Other
subsequent studies have found increased wakefulness and irritability for an hour
after circumcision, an altered arousal level in circumcised male infants as
compared with female and uncircumcised male infants, and an altered sleep-wake
state in neonates undergoing heel-stick procedures.103,172,173 In a
double-blind, randomized controlled study using the Brazelton Neonatal
Behavioral Assessment
Scale, 90 percent of neonates had changed behavioral
states for more than 22 hours after circumcision, whereas only 16 percent of the
uncircumcised infants did.174 It was therefore proposed that such painful
procedures may have prolonged effects on the neurologic and psychosocial
development of neonates.175 A similar randomized study showed the absence of
these behavioral changes in neonates given local anesthetics for
circumcision.176 For two days after circumcision, neonates who had received
anesthetics were more attentive to various stimuli and had greater orientation,
better motor responses, decreased irritability, and a greater ability to quiet
themselves when disturbed. A recent controlled study showed that intervention
designed to decrease the amount of sensory input and the intensity of stressful
stimuli during intensive care of preterm neonates was associated with improved
clinical and developmental outcomes.177 Because of their social validity and
communicational specificity, the behavioral responses observed suggest that the
neonatal response to pain is not just a reflex response.178-180
MEMORY OF PAIN IN NEONATES
The persistence of specific behavioral changes after circumcision in
neonates implies the presence of memory. In the short term, these behavioral
changes may disrupt the adaptation of newborn infants to their postnatal
environment,174-176 the development of parent-infant bonding, and feeding
schedules.182,183 In the long term, painful experiences in neonates could
possibly lead to psychological sequelae,22 since several workers have shown that
newborns may have a much greater capacity for memory than was previously
thought.183-186
Pain itself cannot be remembered, even by adults187; only the experiences
associated with pain can be recalled. However, the question of memory is
important, since it has been argued that memory traces are necessary for the
"maturation" of pain perception,3 and a painful experience may not be deemed
important if it is not remembered. Long-term memory requires the functional
integrity of the limbic system and diencephalon (specifically, the hippocampus,
amygdala, anterior and mediodorsal thalamic nuclei, and mamillary nuclei)188;
these structures are well developed and functioning during the newborn period.42
Furthermore, the cellular, synaptic, and molecular changes required for memory
and learning depend on brain plasticity, which is known to be highest during the
late prenatal and neonatal periods.189,190 Apart from excellent studies in
animals demonstrating the long-term effects of sensory experiences in the
neonatal period,191 evidence for memories of pain in human infants must, by
necessity, be anecdotal.178,192,193 Early painful experiences may be stored in
the phylogenically old "procedural memory," which is not accessible to conscious
recall.182,183,194 Although Janov195 and Holden196 have collected clinical data
that they claim indicate that adult neuroses or psychosomatic illnesses may have
their origins in painful memories acquired during infancy or even neonatal life,
their findings have not been substantiated or widely accepted by other workers.
CONCLUSIONS
Numerous lines of evidence suggest that even in the human fetus, pain
pathways as well as cortical and subcortical centers necessary for pain
perception are well developed late in gestation, and the neurochemical systems
now known to be associated with pain transmission and modulation are intact and
functional. Physiologic responses to painful stimuli have been well documented
in neonates of various gestational ages and are reflected in hormonal,
metabolic, and cardiorespiratory changes similar to but greater than those
observed in adult subjects. Other responses in newborn infants are suggestive of
integrated emotional and behavioral responses to pain and are retained in memory
long enough to modify subsequent behavior patterns.
None of the data cited herein tell us whether neonatal nociceptive
activity and associated responses are experienced subjectively by the neonate as
pain similar to that experienced by older children and adults. However, the
evidence does show that marked nociceptive activity clearly constitutes a
physiologic and perhaps even a psychological form of stress in premature or
full-term neonates. Attenuation of the deleterious effects of pathologic
neonatal stress responses by the use of various anesthetic techniques has now
been demonstrated. Recent editorials addressing these issues have promulgated a
wide range of opinions, without reviewing all the available evidence.197-201 The
evidence summarized in this paper provides a physiologic rationale for
evaluating the risks of sedation, analgesia, local anesthesia, or general
anesthesia during invasive procedures in neonates and young infants. Like
persons caring for patients of other ages, those caring for neonates must
evaluate the risks and benefits of using analgesic and anesthetic techniques in
individual patients. However, in decisions about the use of these techniques,
current knowledge suggests that humane 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.
REFERENCES
Menskey H, Albe-Fessard DG, Bonica JJ, et al. Pain terms: a list with
definitions and notes on usage: recommended by the IASP Subcommittee on
Taxonomy. Pain 1979; 6:249-52.
McGraw MD. The neuromuscular maturation of the human infant. New York:
Columbia University Press, 1943.
Merskey H. On the development of pain. Headache 1970; 10:116-23.
Levy DM. The infant's earliest memory of inoculation: a contribution to public
health procedures. J Gen Psychol 1960; 96:3-46.
Harris FC, Lahey BB. A method for combining occurrence and nonoccurrence
interobserver agreement scores. J Appl Behav Anal 1978; 11: 523-7.
Bondy AS. Infancy. In: Gabel S, Erickson MT, eds. Child development and
developmental disabilities. Boston: Little, Brown, 1980:3-19.
Eland JM, Anderson JE. The experience of pain in children. In: Jacox AK, ed.
Pain: a source book for nurses and other health professionals . Boston:
Little, Brown, 1977:453-73.
Wallerstein E. Circumcision: the uniquely American medical enigma. Urol Clin N
Am 1985; 12:123- 32.
Anand KJS, Aynsley-Green A. Metabolic and endocrine effects of surgical
ligation 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.
Lippmann N, Nelson RJ, Emmanouilides GC, Diskin J, Thibeault DW. Ligation of
patent ductus arteriosus in premature infants. Br J Anaesth 1976; 48:365-9.
Shaw EA. Neonatal anaesthesia. Hosp Update 1982;8:423-34.
Katz J. The question of circumcision. Int Surg 1977; 62:490-2.
Swafford LI, Allan D. Pain relief in the pediatric patient. Med Clin North Am
1968; 52:131-6.
Rees GJ. Anesthesia in the newborn. Br Med J 1950; 2:1419-22.
Betts EK, Downes JJ. Anesthetic considerations in newborn surgery. Semin
Anesth 1984; 3:59-74.
Inkster JS. Paediatric anaesthesia and intensive care. Int Anesthesiol Clin
1978; 16:58-91.
Norman EA. Pulse oximetry during repair of congenital diaphragmatic hernia. Br
J Anaesth 1986; 58:934-5.
Hatch DJ. Analgesia in the neonate. Br Med J 1987; 294:920.
Shearer MH. Surgery on the paralysed, unanesthetized newborn. Birth 1986;
13:79.
Robinson S, Gregory GA. Fentanyl-air-oxygen anesthesia for ligation of patent
ductus arteriosus in preterm infants. Anesth Analg 1981; 60:331-4.
Weiss C. Does circumcision of the newborn require an anesthetic? Clin Pediatr
(Phila) 1968; 7:128-9.
Owens ME. Pain in infancy: conceptual and methodological issues.Pain 1984;
20:213-30.
Richards T. Can a fetus feel pain? Br Med J 1985; 291:1220-1.
Gleiss J, Stuttgen G. Morphologic and functional development of the skin. In:
Stave U, ed. Physiology of the perinatal period . Vol. 2. New York:
Appleton-Century Crofts, 1970:889-906.
Humphrey T. Some correlations between the appearance of human fetal reflexes
and the development of the nervous system. Prog Brain Res 1964; 4:93-135.
Valnaan HB, Pearson JF. What the fetus feels. Br Med J 1980; 280:233-4.
Okado N. Onset of synapse formation in the human spinal cord. J Comp Neurol
1981; 201:211-9.
Wozniak W, O'Rahilly R, Olszewska B. The fine structure of the spinal cord in
human embryos and early fetuses. J Hirnforsch 1980; 21:101-24.
Rievi T, Wadhwa S, Bijlani V. Development of spinal substrate for nociception.
Pain Suppl 1987; 4:195.
Tilney F, Rosett J. The value of brain lipoids as an index of brain
development. Bull Neurol Inst NY 1931; 1:28-71.
Schulte FJ. Neurophysiological aspects of brain development. Mead Johnson Symp
Perinat Dev Med 1975; 6:38-47.
Idem. Gestation, wachsturn und hirnentwicklung. In: Linneweh F, ed.
Fortscritte der Paedologie. Vol. 2. Berlin: Springer-Verlag, 1968:46-64.
Gilles FJ, Shankle W, Dooling EC. Myelinated tracts: growth patterns. In:
Gilles FH, Leviton A, Dooling EC, eds. The developing human brain: growth and
epidemiologic neuropathology. Boston: John Wright, 1983: 117-83.
Marin-Padilla M. Structural organization of the human cerebral cortex prior to
the appearance of the cortical plate. Anat Embryol (Berl) 1983; 168:21-40.
Molliver ME, Kostovic I, Van der Loos H. The development of synapses in
cerebral cortex of the human fetus. Brain Res 1973; 50:403-7.
Rakic P, Goldman-Rakic PS. Development and modifiability of the cerebral
cortex: early developmental effects: cell lineages, acquisition of neuronal
positions, and areal and larninar development. Neurosci Res Prog Bull 1982;
20:433-51.
Kostovic I, Rakic P. Development of prestriate visual projections in the
monkey and human fetal cerebrum revealed by transient cholinesterase staining.
J Neurosci 1984; 4:25-42.
Kostovic I, Goldman-Rakic PS. Transient cholinesterase staining in the
mediodorsal nucleus of the thalamus and its connections in the developing
human and monkey brain. J Comp Neurol 1983; 219:431-47.
Spehlmann R. In: EEG primer. New York: Elsevier/North-Holland, 1981:159-65.
Torres F, Anderson C. The normal EEG of the human Newborn. J Clin Neurophysiol
1985; 2:89-103.
Henderson-Smart DJ, Pettigrew AG, Campbell DJ. Clinical apnea and brain-stem
neural function in preterm infants. N Engl J Med 1983; 308:353-7.
Prechtl HFR, ed. Continuity of neural functions from prenatal to postnatal
life. Oxford: Blackwell, 1984.
Chugani HT, Phelps ME. Maturational changes in cerebral function in infants
determined by 18FDG positron emission tomography. Science 1986; 231:840-3.
Arduini D, Rizzo G, Giorlandino C, Valensise H, Dell'acqua S, Romanini C. The
development of fetal behavioural states: A longitudinal study. Prenat Diagn
1986; 6:117-24.
Sammons WAH. Premature behavior and the neonatal intensive care unit
environment. In: Cloherty JP, Stark AR, eds. Manual of neonatal care. Boston:
Little, Brown, 1980:359-63.
Flower MJ. Neuromaturation of the human fetus. J Med Philos 1985; 10:237-51.
Ralston HJ. Synaptic organization of spinothalamic projections to the
thalamus, with special reference to pain. Adv Pain Res Ther 1984; 6:183-95.
Nawa H, Hirose T, Takashima H, Inayama S, Nakanishi S. Nucleotide sequences of
cloned cDNAs for two types of bovine brain substance P precursor. Nature 1983;
306:32-6.
Watson SP, Sandberg BEB, Hanley MR, Iversen LL. Tissue selectivity of
substance P alkyl esters: suggesting multiple receptors. Eur J Pharmacol 1983;
87:77-84.
Mantyh PW, Maggio JE, Hunt SP. The autoradiographic distribution of kassinin
and substance K binding sites is different from the distribution of substance
P binding sites in rat brain. Eur J Pharmacol 1984;102:361-4.
Valentino KL, Tatemoto K, Hunter J, Barchas JD. Distribution of neuropeptide
K-immunoreactivity in the rat central nervous system. Peptides 1986:
7:1043-59.
Pernow B. Substance P. Pharmacol Rev 1983; 35:85-141.
Otsuka M, Konishi S. Substance P - the first peptide neurotransmitter? Trends
Neurosci 1983; :317-20.
Henry JL. Relation of substance P to pain transmission: neurophysiological
evidence. In: Porter R, O'Connor M, eds. Substance P in the nervous system,
Ciba Foundation Symposium 91. London: Pitman, 1982:206-24.
Pearson J, Brandeis L, Cuello AC. Depletion of substance P-containing axons in
substantia gelatinosa of patients with diminished pain sensitivity. Nature
1982; 295:61-3.
Jessel T, Iversen LL. Opiate analgesics inhibit substance P release from rat
trigeminal nucleus. Nature1977; 268:549-51.
Chamay Y, Paulin C, Chayvialle J-A, Dubois PM. Distribution of substance
P-like immunoreactivity in the spinal cord and dorsal root ganglia of the
human foetus and infant. Neuroscience 1983; 10:41-55.
Paulin C, Chamay Y, Dubois PM, Chayvialle J-A. Localisation de substance P
dans le systeme nerveux du foetus humain: resultats preliminaires. C R Acad
Sci Paris Series D 1980; 291:257-60.
Pickel VM, Sumal KK, Reis DJ, Miller RI, Hervonen A. Immunocytochemical
localization ofenkephalin and substance Pin the dorsal tegmental nuclei in the
human fetal brain. J Comp Neurol 1980; 193:805-14.
Roizen MF, Newfield P, Eger El II, Hosobuchi Y, Adams JE, Lamb S. Reduced
anesthetic requirement after electrical stimulation of periaqueductal gray
matter. Anesthesiology 1985; 62:120-3.
Del Fiacco M, Dessi ML, Leranti MC. Topographical localization of sub-stance P
in the human post-mortem brainstem: an immunohistochemical study in the
newborn and adult tissue. Neuroscience 1984; 12:591-611.
Nomura H, Shiosaka S, Inagaki S, et al. Distribution of substance P-like
immunoreactivity in the lower brainstem of the human fetus: an
immunohistochemical study. Brain Res 1982; 252:315-25.
Helke CA, Charlton CG, Keeler JR. Bulbospinal substance P and sympathetic
regulation of the cardiovascular system: a review. Peptides 1985; 6:Suppl
2:69-74.
Inagaki S, Sakanaka M, Shiosaka S, et al. Ontogeny of substance P-containing
neuron system of the rat: immunohistochemical analysis. Neuroscience 1982;
7:251-77, 1097-126.
Quirion R, Dam T-V. Ontogeny of substance Preceptor binding sites in rat
brain. J Neurosci 1986; 6:2187-99.
Jonsson G, Hallman H. Substance P counteracts neurotoxin damage on
norepinephrine neurons in rat brain during ontogeny. Science 1982; 215:75-7.
Idem. Effect of substance P on neonatally axotomized noradrenaline neurons in
rat brain. Med Biol 1983; 61:179-85.
Narumi S, Fujita T. Stimulatory effects of substance P and nerve growth factor
(NGF) on neurite outgrowth in embryonic chick dorsal root ganglia.
Neuro-pharmacology 1978; 17:73-6.
Pert CB, Snyder SH. Opiate receptor: demonstration in nervous tissue. Science
1973; 179:1011-4.
Terenius L. Stereospecific interaction between narcotic analgesics and a
synaptic plasma membrane fraction of rat cerebral cortex. Aeta Pharmacol
Toxicol (Copenh) 1973; 32:317-20.
Hughes J. Isolation of an endogenous compound from the brain with
pharmacological properties similar to morphine. Brain Res 1975; 88:295-308.
Jacob JJC, Ramabadran K. Role of opiate receptors and endogenous ligands in
nociception. In: Williams NE, Wilson H, eds. Pain and its management. Oxford:
Pergamon Press, 1983:13-32.
Hosobuehi Y, Li CH. The analgesic activity of human beta-endorphin in
man.Commun Psychopharmacol 1978; 2:33-7.
Paterson DJ, Robson LE, Kosterlitz MW. Classification of opioid receptors. Br
Med Bull 1983; 39:31-6.
Bigeot M, Dubois MP, Dubois PM. Immunologic localization of a- and
B-endorphins and B-lipotropin in corticotropic cells of the normal and
an-encephalic fetal pituitaries. Cell Tissue Res 1978; 193:413-22.
Li JY, Dubois MP, Dubois PM. Ultrastructural localization of immunoreactive
corticotropin, B-lipotropin, a- and B-endorphin in cells of the human fetal
anterior pituitary. Cell Tissue Res1979; 204:37-51.
Gibbs DM, Stewart RD, Liu JH, Vale W, Rivier J, Yen SSC. Effects of synthetic
corticotropin-releasing factor and dopamine on the release of immunoreactive
B-endorphin/B-lipotropin and a-melanocyte-stimulating hormone from human fetal
pituitaries in vitro. J Clin Endocrinol Metab 1982; 55:1149-52.
Csontos K, Rust M, Hollt V, Mahr W, Kromer W, Teschemacher HJ. Elevated plasma
B-endorphin levels in pregnant women and their neonates. Life Sci 1979;
25:835-44.
Vuolteenaho 0, Leppaluoto J, Hoyhtya M, Hirvonen J. B-endorphin-like peptides
in autopsy pituitaries from adults, neonates and foetuses. Acta Endocrinol
(Copenh) 1983; 102:27-34.
Gautray JP, Jolivet A, Vielh JP, Guillemin R. Presence of immunoassayable
B-endorphin in human amniotic fluid: elevation in cases of fetal distress. Am
J Obstet Gynecol 1977; 129:211-2.
Wardlaw SL, Stark RI, Baxi L, Frantz AG. Plasma B-endorphin and B-lipotropin
in the human fetus at delivery: correlation with arterial pM and pO2. J Clin
Endocrinol Metab 1979; 49:888-91.
Puolakisa J, Kauppila A, Leppaluoto J, Vuolteenaho 0. Elevated betaendorphin
immunoreactivity in umbilical cord blood after complicated delivery. Acta
Obstet Gynecol Scand 1982; 61:513-4.
Shaaban MM, Hung TT, Hoffman Dl, Lobo RA, Goebelsmann U. B-endorphin and
B-lipotropin concentrations in umbilical cord blood. Am J Obstet Gynecol 1982;
144:560-9.
Browning AJF, Butt WR, Lynch
SS, Shakespear RA, Crawford JS. Maternal and cord
plasma concentrations of B-lipotropin, B-endorphin and y-lipotropin at
delivery: effect of analgesia. Br J Obstet Gynecol 1983; 90:1152-6.
Pohjavuori M, Rovamo L. Laatikainen T. Plasma immunoreactive B-endorphin and
cortisol in the newborn infant after elective caesarean section and after
spontaneous labour. Eur J Obstet Gynecol Reprod Biol 1985; 19:67-74.
Pohjavuori M, Rovamo L, Laatikainen T, Kariniemi V, Pettersson J. Stress of
delivery and plasma endorphins and catecholamines in the newborn infant. Biol
Res Pregnancy Perinatol 1986; 7:1-5.
Paneral AE, Martini A, Di Giulio AM, et al. Plasma B-endorphin, B-slipotropin,
and met-enkephalin concentrations during pregnancy in normal and drug-addicted
women and their newborn. J Clin Endocrinol Metab 1983; 57:537-43.
MacDonald MG, Moss IR, Kefale GG, Ginzburg [words=https://officialhydromaxpump.com/?uid=6&oid=2&affid=98 ]
Hydromax[/words], Fink RI, Chin L. Effect of
naltrexone on apnea of prematurity and on plasma beta-endorphin-like
immunoreactivity. Dev Pharmacol Ther 1986; 9:301-9.
Orlowski JP. Cerebrospinal fluid endorphins and the infant apnea syndrome.
Pediatrics 1986; 78:233-7.
Sankaran K, Hindmarsh KW, Watson VG. Plasma beta-endorphin Concentration in
infants with apneic spells. Am J Perinatol 1984; 1:331-4.
Hindmarsh KW, Sankaran K, Watson VG. Plasma beta-endorphin Concentrations in
neonates associated with acute stress. Dev Pharinacol Ther 1984; 7:198-204.
Sankaran K, Hindmarsh KW, Watson VG. Hypoxic-ischemic encephalopathy and
plasma B-endorphin. Dev Pharmacol Ther 1984; 7:377-83,
Hindmarsh KW, Sankaran K. Endorphins and the neonate. Can Med Assoc J 1985;
132:331-4.
Lerman J, Robinson S, Willis MM, Gregory GA. Anesthetic requirements for
halothane in young children 0-1 month and 1-6 months of age. Anesthesiology
1983; 59:421-4.
Foley KM, Kourides IA1 Inturrisi CE, et al. B-endorphin: analgesic and
hormonal effects in humans. Proc Natl Acad Sci USA 1979; 76:5377-81.
Facchinetti F, Bagnoli F, Bracci R, Genazzani AR. Plasma opioids in the first
hours of life. Pediatr Res 1982; 16:95-8.
Moss IR, Conner H, Yee WFH, Iorio P, Scarpelli EM. Human B-endorphin-like
immunoreactivity in the perinatal/neonatal period. J Pediatr 1982; 101:443-6.
Burnard ED, Todd DA, John E, Hindmarsh KW. Beta-endorphin levels in newborn
Cerebrospinal fluid. Aust Paediatr J 1982; 18:258-63.
Williamson PS, Williamson ML. Physiologic stress reduction by a local
anesthetic during newborn circumcision. Pediatrics 1983; 71:36-40.
Holve RL, Bromberger BJ, Groverman HD, Klauber MR, Dixon SD, Snyder JM.
Regional anesthesia during newborn circumcision: effect on infant pain
response. Clin Pediatr (Phila) 1983; 22:813-8.
Owens ME, Todt EH. Pain in infancy: neonatal reaction to a heel lance. Pain
1984; 20:77-86.
Johnson CC, Strada ME. Acute pain response in infants: a multidimensional
description. Pain 1986; 24:373-82.
Field T, Goldson E. Pacifying effects of nonnutritive sucking on term and
preterm neonates during heelstick procedures. Pediatrics 1984; 74:1012-5.
Clifton RK, Graham FK, Hatton [words=https://officialhydromaxpump.com/?uid=6&oid=2&affid=98 ]
Hydromax[/words]. Newborn heart-rate response and response
habituation as a function of stimulus duration. J Exp Child Psychol 1968;
6:265-78.
Kagan J. Heart rate and heart rate variability as signs of a temperamental
dimension in infants. In: Izard CE, ed. Measuring emotions in infants and
children. Cambridge: Cambridge University Press, 1982:38-66.
Maxwell LG, Yaster M, Wetzel RC. Penile nerve block reduces the physiologic
stress of newborn circumcision, Anesthesiology 1986; 65:A432. abstract.
Berg KM Berg WK, Graham FK. Infant heart rate response as a function of
stimulus and state. Psychophysiology 1971; 8:30-44.
Campos JJ. Heart rate: a sensitive tool for the study of emotional
develop-ment in the infant. In: Lipsitt LD, ed. Developmental psychobiology.
Hillsdale, N.J.: Lawrence Erlbaum Associates, 1976:1-31.
Weile P, Hayden W, Miller T. Continuous measurement of transcutaneous oxygen
tension of neonates under general anesthesia. J Pediatr Surg 1980); 15:257-60.
Venus B, Patel KC, Pratap KS, Konchigeri H, Vidyasagar D. Transcutaneous PO2
monitoring during pediatric surgery. Crit Care Med 1981; 9:714-6.
Messner JT, Loux PC, Grossman LB. Intraoperative transcutaneous pO2 monitoring
in infants. Anesthesiology 1979; 51:S319. abstract.
Rawlings DJ, Miller [words=http://www.mattersofsize.com/join-now.html]
PA[/words], Engel RR. The effect of circumcision on transcutaneous
PO2 in term infants. Am J Dis Child 1980; 134:676-8.
Kelly MA, Finer NN. Nasotracheal intubation in the neonate: physiologic
responses and effects of atropine and pancuronium. J Pediatr 1984; 105:303-9.
Marshall TA, Deeder R, Pai S, Berkowitz GP, Austin TL. Physiologic changes
associated with endotracheal intubation in preterm infants. Crit Care Med
1984; 12:501-3.
Gibbons [words=http://www.mattersofsize.com/join-now.html]
PA[/words], Swedlow DB. Changes in oxygen saturation during elective tracheal
intubation in infants. Anesth Analg 1986; 65:S58. abstract.
Raju TNK, Vidyasagar D, Torres C, Grundy D, Bennett EJ. Intracranial pressure
during intubation and anesthesia in infants. J Pediatr 1980; 96:860-2.
Friesen RH, Honda AT, Thieme RE. Changes in anterior fontanel pressure in
preterm neonates during tracheal intubation. Anesth Analg 1987; 66:874-8.
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.
Harpin VA, Rutter N. Development of emotional sweating in the newborn infant.
Arch Dis Child 1982; 57:691-5.
Idem. Making heel pricks less painful. Arch Dis Child 1983; 58:226-8.
Fiselier T, Monnens L, Moerman E, Van Munster P, Jansen M, Peer P. Influence
of the stress of venepuncture on basal levels of plasma renin activity in
infants and children. Int J Pediatr Nephrol 1983; 4:181-5.
Oreisen G, Frederiksen PS, Hertel J, Christensen NJ. Catecholamine response to
chest physiotherapy and endotracheal suctioning in preterm infants. Acta
Paediatr Scad 1985; 74:525-9.
Talbert [words=http://www.mattersofsize.com/forum/showthread.php?83577-Length-master-official-order-thread-now-shipping-06-16-2014!!!]
LM[/words], Kraybill EN, Potter HD. Adrenal cortical response to circumcision
in the neonate. Obstet Gynecol 1976; 48:208-10.
Gunnar MR, Fisch RO, Korsvik S, Donhowe JM. The effects of circumcision on
serum cortisol and behavior. Psychoneuroendocrinology 1981; 6:269-75.
Williamson PS, Evans ND. Neonatal cortisol response to circumcision with
anesthesia. Clin Pediatr (Phila) 1986; 25:412-5.
Anand KJS. Hormonal and metabolic functions of neonates and infants undergoing
surgery. Curr Opin Cardiol 1986; 1:681-9.
Anand KJS, Brown MJ, Bloom SR, Aynsley-Green A. Studies on the hormonal
regulation of fuel metabolism in the human newborn infant undergoing
anaesthesia and surgery. Horm Res 1985; 22:115-28.
Milne EMG, Elliott MJ, Pearson DT, Holden MP, Orskov H, Alberti KGMM. The
effect on intermediary metabolism of open-heart surgery with deep hypothermia
and circulatory arrest in infants of less than 10 kilograms body
weight.
Perfusion 1986; 1:29-40.
Obara H, Sugiyama D, Maekawa N, et al. Plasma cortisol levels in paediatric
anaesthesia. Can Anaesth Soc J 1984; 31:24-7.
Srinivasan 0, Jain R, Pildes RS, Kannan CR. Glucose homeostasis during
anesthesia and surgery in infants. J Pediatr Surg 1986; 21:718-21.
Anand KJS, Brown MJ, 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.
Pintir A. The metabolic effects of anaesthesia and surgery in the newborn
infant: changes in the blood levels of glucose, plasma free fatty acid
amino-nitrogen, plasma amino-acid ratio and lactate in the neonat. Z
Kinderchir 1973; 12:149-62.
Elphick MC, Wilkinson AW. The effects of starvation and surgical injury on the
plasma levels of glucose, free fatty acids, and neutral lipids in newborn
babies suffering from various congenital anomalies. Pediatr Res 1981;
15.313-8.
Anand KJS, Aynsley-Green A. Measuring the severity of surgical stress in
newborn infants. J Pediatr Surg (in press).
Idem. Does the newborn infant require anesthesia during surgery? Answers from
a randomised trial of halothane anesthesia. Pain Res Clin Manage(in press).
Anand KJS, Sippell WG, Aynsley-Green A. Randomised trial of fentanyl
anaesthesia in preterm neonates undergoing surgery: effects on the stress
response. Lancet 1987; 1:243-8.
Anand KJS, Carr DB, Hickey PR. Randomized trial of high-dose sufentanil
anesthesia in neonates undergoing cardiac surgery: hormonal and hemodynamic
stress responses. Anesthesiology 1987; 67:A50 abstract.
Anand KJS, Hickey PR. Randomized trial of high-dose sufentanil anesthesia in
neonates undergoing cardiac surgery: effects on the metabolic stress response.
Anesthesiology 1987; 67: A502. abstract.
Anders TF, Sachar EJ, Kream J, Roffwarg [words=https://officialhydromaxpump.com/?uid=6&oid=2&affid=98 ]HP[/words], Hellman L. Behavioral state and
plasma cortisol response in the human newborn. Pediatrics 1970; 46:532-7.
Tennes K, Carter D. Plasma cortisol levels and behavioral states in early
infancy. Psychosom Med 1973; 35:121-8.
Lipsitt LP, Levy N. Electrotactual threshold in the neonate. Child Dev 1959;
30:547-54.
Dockeray FC, Rice C. Responses of newborn infants to pain stimulation. Ohio
State Univ Stud Contrib Psychol 1934; 12:82-93.
Sherman M, Sherman IC. Sensori-motor responses in infants. J Comp Psychol
1925; 5:53-68.
Rich EC, Marshall RE, Volpe JJ. The normal neonatal response to pinprick. Dev
Med Child Neurol 1974; 16:432-4.
Franck LS. A new method to quantitatively describe pain behavior in infants.
Nurs Res 1986; 35:28-31.
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 Neurol (in press).
Ekman P, Oster H. Facial expressions of emotion. Annu Rev Psychol 1979;
30:527-54.
Izard CE, Huebner RR, Risser D, McGinnes GC, Dougherty [words=http://www.mattersofsize.com/forum/showthread.php?83577-Length-master-official-order-thread-now-shipping-06-16-2014!!!]
LM[/words]. The young infant's
ability to produce discrete emotional expressions. Dev Psychol 1980;
16:132-40.
Grunau RVE, Craig KD. Pain expression in neonates: facial action amd cry. Pain
1987; 28:395-410.
Melzack R, Wall PD. Pain mechanisms: a new theory. Science 1965 150:971-9.
Lester [words=https://officialhydromaxpump.com/?uid=6&oid=2&affid=98 ]
Bathmate[/words]. A biosocial model of infant crying. In: Lipsill L, ed. Advances in
infancy research. New York: Ablex, 1984:167-212.
Levine JD, Gordon NC. Pain in prelingual children and its evaluation
pain-induced vocalisation. Pain 1982; 14:85-93.
Wasz-Hockert 0, Lind J, Vuorenkoski V. The infant cry: a spectrographic and
auditory analysis. Clin Dev Med 1968; 2:9-42.
Michelsson K, Raes J, Thoden C-J, Wasz-Hockert 0. Sound spectrographic cry
analysis in neonatal diagnostics: an evaluative study. J Phonetics 1982;
10:79-88.
Zeskind PL, Sale J, Majo ML, Huntington L, Weisemari JR. Adult perceptions of
pain and hunger cries: a synchrony of arousal. Child Dev 1985: 56:549-54.
Boukydis CFZ. Perception of infant crying as an interpersonal event. In:
Lester, [words=https://officialhydromaxpump.com/?uid=6&oid=2&affid=98 ]
Bathmate[/words], Boukydis CFZ, eds. Infant crying: theoretical and research
perspectives. New York: Plenum Press, 1985:187-215.
Muny T, Amundson P, Hollien H. Acoustical characteristics of infant cries
fundamental frequency. J Child Lang 1977; 3:321-8.
Wasz-Hockert 0, Partanen T, Vourenkoski V, Valanne E, Michelsson K. Effect of
training on ability to identify preverbal vocalizations. Dev Med Child Neurol
1964; 6:393-6.
Gladding ST. Effects of training Versus non-training in identification of
cry-signals: a longitudinal study. Percept Mot Skills 1979; 48:752-4.
Johnston CC, O'Shaugnessy D. Acoustical attributes of infant pain cries:
discriminating features. Pain 1987; Suppl 4:233.
Wolff PH. The natural history of crying and other vocalizations in early
infancy. In: Foss [words=https://officialhydromaxpump.com/?uid=6&oid=2&affid=98 ]
Bathmate[/words], ed. Determinants of infant behaviour. Vol. 4. London:
Methuen, 1969:88-295.
Wasz-Hockert 0, Michelsson K, Lind J. Twenty-five years of Scandinavian cry
research. In: Lester [words=https://officialhydromaxpump.com/?uid=6&oid=2&affid=98 ]
Bathmate[/words], Boukydis CFZ, eds. Infant crying: theoretical and
research perspectives. New York: Plenum Press, 1985:83-104.
Michelsson K, Jarvenpaa A-L, Rinne A. Sound spectrographic analysis of pain
cry in preterm infants. Early Hum Dev 1983; 8:141-9.
Friedman SL, Zahn-Waxler C, Radke-Yarrow M. Perceptions of cries of full-term
and preterm infants. Infant Behav Dev 1982; 5:161-73.
Michelsson K, Sirvio P, Wasz-Hockert 0. Pain cry in full-term asphyxiated
newborn infants correlated with late findings. Acta Paediatr Scand 1977;
66:611-6.
Fisichelli VR, Coxe M, Rosenfeld L, Haber A, Davis J, Karelitz S. The phonetic
content of the cries; of normal infants and those with brain damage. J Psychol
1966; 64:119-26.
Wasz-Hockert 0, Koivisto M, Vuorenkoski V, Partanen Ti, Lind J. Spectrographic
analysis of pain cry in hyperbilirubinemia. Biol Neonate 1971; 17:260-71.
Michelsson K, Sirvio P, Wasz-Hockert 0. Sound spectrographic cry analyses of
infants with bacterial meningitis. Dev Med Child Neurol 1977; 19:309-15.
Porter [words=http://fleshlight.sjv.io/c/348327/302851/4702]FL[/words] Miller RH, Marshall RE. Neonatal pain cries: effect of circumcision
on acoustic features and perceived urgency. Child Dev 1986; 57:790-802.
Fisichelli VR, Karelitz S, Fisichelli RM, Cooper J. The course of induced
crying activity in the first year of life. Pediatr Res 1974; 8:921-8.
Emde RN, Harmon RJ, Metcalf D, Koenig KL, Wagonfeld S. Stress and neonatal
sleep. Psychosom Med 1971; 33:491-7.
Anders TF, Chalemian RJ. The effects of circumcision on sleep-wake states in
human neonates. Psychosom Med 1974; 36:174-9.
Brackbill Y. Continuous stimulation and arousal level in infancy: effects of
stimulus intensity and stress. Child Dev 1975; 46:364-9.
Marshall RE, Stratton WC, Moore JA, Boxerman SB. Circumcision I: Effects upon
newborn behaviour. Infant Behav Dev 1980; 3;1-14.
Richards MPM, Bernal JF, Brackbill Y. Early behavioral differences: gender or
circumcision? Dev Psychobiol 1976; 9:89-95.
Dixon S, Snyder J, Holve R, Bromberger P. Behavioural effects of circumcision
with and without anesthesia. J Dev Behav Pediatr 1984; 5:246-50.
Als H, Lawhon G, Brown E, et al. Individualized behavioral and environmental
care for the very low birth
weight preterm infant at high risk for
bronchopulmonary dysplasia: neonatal intensive care unit and developmental
outcome. Pediatrics 1986; 78: 1123-32.
Darwin C. The expression of the emotions in man and animals. London: John
Murray, 1872:65-7.
Kazdin AE. Assessing the clinical or applied importance of behavior change
through social validation. Behav Modif 1977; 1:427-52.
D'Apolito K. The neonate's response to pain. Am J Matern Child Nurs 1984;
9:256-8.
Marshall RE, Porter [words=http://fleshlight.sjv.io/c/348327/302851/4702]FL[/words], Rogers AU, Moore JA, Anderson B, Boxerman SB.
Circumcision. II. Effects upon mother-infant interaction. Early Hum Dev 1982;
7:367-74.
Osofsky JD. Neonatal characteristics and mother-infant interaction in two
observational situations. Child Dev 1976; 47:1138-47.
Lipsitt LP. The study of sensory and learning processes of the newborn. Clin
Perinatol 1977; 4:163-86.
Stone LJ, Smith H, Murphy LB, eds. The competent infant: research and
commentary. New York: Basic Books, 1973.
Moscovitch M. Infant memory; its relation to normal and pathological memory in
humans and other animals. New York: Plenum Press, 1984.
Kolata G. Early signs of school age IQ. Science 1987; 236:774-5.
Jones E. Pain. Int J Psychoanal 1957; 38:255.
Squire LR. Mechanisms of memory. Science 1986; 232:1612-9.
Will B, ScHydromaxitt P, Dalrymple-Alford J. Brain plasticity, learning and memory:
historical background and conceptiial perspectives. Adv.Behav Biol 1985;
28:1-11.
Bischof H-J. Influence of developmental factors on imprinting. Behav Biol
1985; 28:51-9.
Fillion TJ, Blass EM. Infantile experience with suckling odors determines
adult sexual behavior in male rats. Science 1986; 231:729-31.
Wachter-Shikora NL. Pain theories and their relevance to the pediatric
population. Issues Compr Pediatr Nurs 1981; 5:321-6.
Dale JC. A multidimensional study of infants' responses to painful stimuli.
Pediatr Nurs 1986; 12:27-31.
Reynolds 0E, Hutchins HC. Reduction of central hyper-irritability following
block anesthesia of peripheral nerve. Am J Physiol 1948; 152:658-62.
Janov A. The anatomy of mental illness. New York: Putnam's Sons, 1971.
Holden EM. Primal pathophysiology. J Psychosom Res 1977; 21:341-50. abstract.
Hatch DJ. Analgesia in the neonate. Br Med J 1987; 294:920.
Berry FA, Gregory GA. Do premature infants require anesthesia for surgery?
Anesthesiology 1987; 67:291-3.
Booker PD. Postoperative analgesia for neonates? Anaesthesia 1987; 42:343-4.
Pain, anaesthesia and babies. Lancet 1987; 2:543-5.
Yaster M. Analgesia and anesthesia in neonates. J Pediatr 1987; 111:394-6.
Citation:
Anand KJS, Hickey PR. Pain and its effects in the human neonate and fetus. New
Engl J Med 1987;317(21):1321-1329.