Compassion in World Farming Conference – March 2005
CIWF Paper fin3.doc
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
Onset of sentience: the potential for suffering
in fetal and newborn farm animals
David J Mellor and Tamara J Diesch
Animal Welfare Science and Bioethics Centre,
Massey University, Palmerston North, New Zealand
Abstract
Sentience and consciousness are prerequisites of suffering. Thus, animals must
have sufficiently sophisticated neural mechanisms to receive sensory information
and to transduce this information into sensations, and they must also be
conscious to be able to perceive those sensations. Moreover, those sensations must
be sufficiently noxious or aversive to cause suffering. The neural apparatus of
embryos and fetuses of farm animals is inadequate to support sentience for at
least the first half of pregnancy, but the required structures and mechanisms do
develop by the time of birth. Thus, although one of the preconditions for
suffering is satisfied shortly before birth, the embryo and fetus are apparently
never conscious for the following reasons. The embryo-fetus initially does not
have brain structures that are functionally capable of supporting consciousness,
and subsequently, when the fetal brain might have that capability, it displays
electrical activity indicating a continuous state of sleep and therefore
unconsciousness. Furthermore, the fetus is apparently actively maintained in
sleep-like states by several endogenous neuroinhibitory mechanisms which
involve adenosine (a potent neuroinhibitory and sleep inducing agent),
allopregnanolone and pregnanolone (two neurosteroidal anaesthetics),
prostaglandin D2 (a potent sleep-inducing hormone), a placental neural inhibitor,
warmth, buoyancy and cushioned tactile stimulation. Consciousness evidently
appears for the first time only after birth. This results from a substantial
withdrawal of the neuroinhibitors, especially adenosine, and the involvement of
neuroactivators including 17β-oestradiol (a potent neuroactive steroid with
widespread excitatory effects in the brain), noradrenaline (released from
excitatory locus coeruleus nerves that extend throughout the brain), and a
barrage of novel sensory information associated with the newborn’s first exposure
to air, gravity, hard surfaces, unlimited space and, usually, to cold ambient
conditions. We conclude that the embryo and fetus cannot suffer before or during
birth. Furthermore, we conclude that suffering can only occur in the newborn
when the onset of breathing oxygenates its tissues sufficiently to substantially
reduce the dominant adenosine inhibition of brain electrical activity. The
implications of these observations for managing fetuses and newborns in ways
that minimise suffering are considered briefly.
Corresponding author:
Professor David J Mellor
Phone
+64 6 350 4807
Fax
+64 6 350 5657
1
Compassion in World Farming Conference – March 2005
CIWF Paper fin3.doc
48
Email
D.J.Mellor@massey.ac.nz
2
Compassion in World Farming Conference – March 2005
CIWF Paper fin3.doc
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
66
67
68
69
70
71
72
73
74
75
76
77
78
79
80
81
82
83
84
85
86
87
88
89
90
91
92
93
94
95
Introduction
An animal must be both sentient and conscious for suffering to occur. The first
prerequisite, therefore, is that the required neural apparatus for sentience must be
in place and operational. Internal and environmental stimuli must be able to elicit
impulse transmission along nerves from sensory receptors to the animal’s brain,
and its brain stuctures must be operationally sophisticated enough to tranduce
those nerve impulses into perceived sensations. The second requirement is that the
brain must be in a functional state that allows the animal to perceive sensations; it
must be in a state that supports consciousness, as unconsciousness nullifies
perception. Third, for a conscious animal to suffer, and for its welfare thereby to be
compromised (Mellor and Stafford, 2001; Mellor and Reid, 1994), the character,
intensity and/or duration of the sensations it perceives must result in significantly
noxious or aversive experiences.
Although it is not clear whether there is a distinct place delineating those animals
in the phylogenetic hierarchy that are and are not sentient or whether sentience
exhibits different levels (Mellor, 1998; Kirkwood, 2005), it is generally accepted
that mammals are sentient. However, this generalisation requires some
qualification because it does not allow for different phases of development. Adult
and autonomous young mammals are evidently sentient, as are neurologically
mature young very soon after birth (Mellor and Gregory, 2003; Mellor and
Stafford, 2004), but the situation in neurologically immature newborns and in
mammalian young before birth is less obvious.
The present paper explores the potential of fetuses and newborns to suffer by
outlining the development of the neural apparatus required to support sentience
and the functional state of that apparatus with respect to consciousness before
and after birth. State changes at birth and the impact of other factors on the
potential for suffering after birth are also considered. Although most reported
observations relate to fetal and newborn sheep, the principles are considered to
be generally applicable to farmed ungulates (e.g. sheep, goats, cattle, deer, horses
and pigs).
Prenatal development
sentience
of the neural apparatus
required
for
Neural tissue begins to differentiate after fertilisation, progressing via sparsely
connected rudimentary precursors of nerve tracts and brain structures in the
embryo to the well-defined, complex, sophisticated and operationally effective, yet
still maturing, structures that are present in the fetus just before birth (Mellor and
Gregory, 2003). As part of this development, sensory and numerous other
neurological structures need to mature sufficiently in utero to enable the newborn
to use sight, hearing, smell, taste, touch, proprioception and thermal sensitivity to
secure its survival during the critical first few minutes and hours after birth (Mellor
and Gregory, 2003; Mellor and Stafford, 2004). The operation of such sensory
3
Compassion in World Farming Conference – March 2005
CIWF Paper fin3.doc
96
97
98
99
100
101
102
103
104
105
106
107
108
109
110
111
112
113
114
115
116
117
118
119
120
121
122
123
124
125
126
127
128
129
130
131
132
133
134
135
136
137
138
139
140
141
142
143
perception very soon after birth shows that the required structures are in place
immediately before birth, and possibly earlier. Fetal sense organs therefore have
the potential to operate in utero. The question is, do they? In fact, the sensory
environment in utero is significant and varied, and the fetus in late pregnancy is
responsive to stimulation in most of the modalities evident after birth (Bradley and
Mistretta, 1975; Abrams et al., 1996; Bauer et al., 1997). Thus, fetal sense organs do
operate, but this does not mean that the fetus perceives the associated sensory
input. For that to occur, a fetal neural state that supports consciousness would need
to be present.
Functional state of the neural apparatus
in the fetus
The nervous system is evidently too immature to support any activity resembling
consciousness during the embryonic stage of development and this immaturity
apparently continues at least into the early fetal stage (Joseph, 2000). Indeed, the
establishment of the necessary neural pathways and their connections to lower
brain centres and then to the cerebral cortex, together with the evolution of
mature fetal brain electrical activity (described briefly below) and cortical
responses to somatic tactile stimulation (Bradley & Mistretta, 1975; Fitzgerald,
1999; Joseph, 2000; Mellor & Gregory, 2003), suggest that, even if the
physiological environment of the brain permitted it, neural development could
not support fetal consciousness until later in pregnancy.
The electrical activity of the fetal cerebral cortex (EEG activity) provides
apparently definitive evidence of the absence of consciousness in utero. Thus,
from mid-pregnancy fetal EEG activity evolves from rudimentary and
discontinuous patterns into two coherent, discrete states resembling rapid-eyemovement sleep and non-rapid-eye-movement sleep in postnatal animals
(Harding et al 1981; Clewlow et al 1983; Szeto and Hinman, 1985; Berger et al
1986; Dawes 1988). By late pregnancy these two sleep-like states occupy 95% of
fetal EEG activity during each day, the other 5% representing transitions between
the two sleep-like states (Mellor et al., 2005). Accordingly, the embryo-fetus
initially does not have brain structures which are functionally capable of
supporting consciousness, and subsequently, when the brain might have that
capability, the fetus displays EEG activity indicating that it is continuously asleep
and therefore unconscious.
Maintenance
of fetal sleep-like
states
The above conclusion is further strengthened by an increasing body of evidence
which shows that there are several suppressors in utero which act to inhibit
neural activity in the fetus. Thus, the uterus plays a key role in providing the
chemical and physical factors that together help to keep the fetus continuously
asleep. We propose that this is achieved, among other things, through the
combined neuroinhibitory actions of a powerful EEG suppressor and sleep
inducing agent (adenosine), two neurosteroidal anaesthetics (allopregnanolone,
4
Compassion in World Farming Conference – March 2005
CIWF Paper fin3.doc
144
145
146
147
148
149
150
151
152
153
154
155
156
157
158
159
160
161
162
163
164
165
166
167
168
169
170
171
172
173
174
175
176
177
178
179
180
181
182
183
184
185
186
187
188
189
190
191
pregnanolone) and a potent sleep-inducing hormone (prostaglandin D2), acting
together with a possible peptide inhibitor produced by the placenta, further
supported by the warmth, buoyancy and cushioned tactile stimulation of the
uterine environment (Mellor & Gregory, 2003; Mellor et al., 2005).
Adenosine is a potent neural inhibitor which promotes sleep and/or
unconsciousness and is produced by placental and fetal tissues in quantities that
maintain its circulating concentrations two- to four-fold higher in the fetus than
in the mother (Ball et al., 1995, 1996; Dunwiddie & Masino, 2001). Superimposed
on these high background concentrations are variations due to changes in fetal
oxygen status, such that hypoxaemia (oxygen shortage) elevates and
hyperoxaemia (experimentally induced oxygen abundance) reduces adenosine
concentrations, which in turn lead, respectively, to suppressive and activating
effects on fetal EEG, breathing and behavioural activities (Szeto and Hinman,
1985; Szeto and Umans, 1985; Koos and Matsuda 1990; Sawa et al., 1991; Avital et
al., 1993; Kubonoya and Power, 1997; Koos et al., 2001).
Allopregnanolone and pregnanolone are neuroactive steroids with wellestablished anaesthetic, sedative/hypnotic and analgesic effects (Majewska, 1992;
Paul and Purdy, 1992; Miller, 1998). They are produced from cholesterol or
progesterone by the placenta and the fetal brain, exhibit high circulating
concentrations in the fetus and have suppressive effects on fetal EEG, eye
movements, breathing movements and postural changes (Crossley et al., 1997:
Nicol et al., 1997, 1998, 1999, 2001; Hirst et al., 2000).
Prostaglandin D2, a potent sleep-inducing agent in adult mammals (Hayaishi and
Urade, 2002), is evidently active as a suppressor of eye, breathing and postural
muscle movements, and associated EEG activity, in the late gestation fetus (Lee et
al., 2002).
Likewise, a possible placental peptide inhibitor, warmth, cushioned tactile
stimulation and buoyancy are also considered to contribute to the maintenance of
sleep-like EEG activity in the fetus until birth (Mellor and Gregory, 2003).
It appears, therefore, that the above factors, and others (Mellor et al 2005),
contribute to actively maintaining the continuous sleep-like state of the fetus
(indicated by its EEG) throughout the last one-third to one-half of pregnancy.
Changes in the functional
state of the brain at birth
Suppressors of brain function and their removal
As labour approaches there is a progression towards fetal EEG activity indicating a
predominance of deeper sleep-like states (Berger et al 1986; Shinozuka and
Nathanielsz 1998), and during labour fetal motor systems, including the
respiratory system, are largely quiescent (Berger et al 1986; Fraser and Broom
1990; Hasan and Rigaux 1991). Moreover, hypoxaemia-induced elevations in
5
Compassion in World Farming Conference – March 2005
CIWF Paper fin3.doc
192
193
194
195
196
197
198
199
200
201
202
203
204
205
206
207
208
209
210
211
212
213
214
215
216
217
218
219
220
221
222
223
224
225
226
227
228
229
230
231
232
233
234
235
236
237
238
239
adenosine concentrations transiently inhibit fetal EEG activity during strong
labour contractions and, if the hypoxaemia is severe and protracted enough, EEG
activity may be almost completely suppressed (indicated by an isoelectric trace),
an effect which is usually rapidly reversed if fetal normoxaemia is restored
between contractions (Mallard et al., 1992; Hunter et al., 2003). Likewise, with loss
of placental oxygen supply due to severance of the umbilical cord immediately
after birth, the EEG of the newborn would progress towards an isoelectric state,
reached after 60 to 90 seconds (Mallard et al., 1992; Hunter et al., 2003), and this
would usually be reversed only when successful breathing begins.
Although an isoelectric EEG trace indicates very marked suppression of activity in
the cerebral cortex, the normal functions of which are required for consciousness
to occur, brain stem function supporting the reflexes involved in the initiation of
breathing (among other functions) is safeguarded, even during protracted periods
of hypoxaemia (Jensen et al., 1987). Thus, severance of the umbilical cord and the
associated fall in oxygen and rise in carbon dioxide tensions in the newborn’s
blood stimulate gasping, and if the respiratory system is mature enough, this
leads to successful inflation of the lungs, the onset of breathing and a rapid
elevation in oxygen tensions which eventually rise to well above maximum fetal
levels (Mellor and Gregory, 2003). This oxygenation of the newborn, together
with the loss of the placental source of adenosine, would result in a very rapid
decrease in circulating and cerebral adenosine concentrations and a decrease in
adenosine suppression of the cerebral cortex. We consider this to be critical for
the onset of consciousness after birth.
Loss at birth of the placental source of allopregnanolone and pregnanolone
(and/or of their precursors) and loss of the placental peptide inhibitor would also
contribute to the onset of consciousness in the newborn, but cerebral
pregnanolone (and presumably allopregnanolone) concentrations do not
apparently change much during labour (Nguyen et al., 2003). Accordingly, these
particular neuroactive steriods presumably continue to exert some suppressive
effects on the EEG even after birth. However, a number of EEG activators begin to
operate just before and during labour, especially during the final delivery stage,
and immediately after birth (Mellor and Gregory, 2003). In view of the
apprearance of consciousness in newborn farm animals shortly after birth (Mellor
and Gregory, 2003; Mellor and Stafford, 2004), the combined stimulatiory effects
of these activators are evidently sufficient to overcome any marked residual
effects of the suppressors noted above.
Activators of brain function
The principal activators briefly considered here are 17β-oestradiol, noradrenaline
and a barrage of sensory input associated with birth and entry into the postnatal
environment.
17β-oestradiol is a neuroactive steroid, which, in contrast to allopregnanolone and
pregnanolone, has rapid-onset excitatory effects widely within the brain (Wong et
al. 1996; Woolley, 1999; McEwen, 2002). When injected into the fetus or
6
Compassion in World Farming Conference – March 2005
CIWF Paper fin3.doc
240
241
242
243
244
245
246
247
248
249
250
251
252
253
254
255
256
257
258
259
260
261
262
263
264
265
266
267
268
269
270
271
272
273
274
275
276
277
278
279
280
281
282
283
284
285
286
premature newborn it stimulates arousal behaviour and breathing activity (Mellor
and Gregory, 2003). As its fetal plasma concentrations rise progressively during
labour (Challis & Patrick, 1981), 17β-oestradiol presumably contributes to
preparing the brain to support the increase in behavioural activity and the onset
of breathing, which usually occur immediately after birth (Mellor and Gregory,
2003), and the subsequent appearance of consciousness.
The locus coeruleus extends noradrenaline-releasing nerves widely within the
brain from the cerebral cortex to the brain stem and has major roles in
stimulating arousal and alert vigilance, as reflected in specific EEG states
(Svensson, 1987; Berridge & Waterhouse, 2003). The locus coeruleusnoradrenaline system is particularly responsive to painful stimuli and to
hypoxaemia and hypercapnia (elevated blood carbon dioxide tensions), and is
present and operational, although not particularly active, in the fetus before
labour (Joseph & Walker, 1990). However, strong tactile stimulation (including
pain receptor input) associated with head and body compression during labour,
and especially during the final stage before delivery (Mellor & Gregory, 2003),
and the transient episodes of hypoxaemia/hypercapnia associated with labour
contractions and, after birth, with severance of the umbilical cord before
breathing starts (see above), are potent stimuli to the locus coeruleus brain
activating effects. These presumably also prime the brain for the onset of arousal
and consciousness very soon after birth.
Immediately after birth the newborn is exposed to air, gravity, hard surfaces,
unlimited space and, usually, to cold challenge for the first time (Mellor and
Gregory, 2003), and this will be associated with a barrage of novel sensory
information which is likely to be arousing. Cold stimulation of skin
thermoreceptors in particular is a potent stimulus to both fetal and newborn
arousal and breathing, and tactile stimulation of the head and ears either by
maternal licking or manually by farm staff apparently also has activating effects
(Mellor and Gregory, 2003).
Integrated summary of suppression and
consciousness in the fetus and newborn
activation
of
The above analysis suggests that fetuses subjected to normal in utero sensory
input remain in sleep-like (unconscious) states and that awareness appears for the
first time only after birth.
Suppression of fetal consciousness-related EEG activity is evidently achieved by
the combined effects of a high brain adenosine, allopregnanolone/pregnanolone
and PGD2 status acting together with a placental inhibitor (a peptide), warmth,
buoyancy and cushioned tactile stimulation. This suppression continues during
labour despite marked rises in the circulating concentrations of 17β-oestradiol
and locus coeruleus-induced noradrenaline release, both of which are putative
activators of behavioural arousal and consciousness. The 17β-oestradiol surge
7
Compassion in World Farming Conference – March 2005
CIWF Paper fin3.doc
287
288
289
290
291
292
293
294
295
296
297
298
299
300
301
302
303
304
305
306
307
308
309
310
311
312
313
314
315
316
317
318
319
320
321
322
323
324
325
326
327
328
329
330
331
332
333
results from the progressive switch in placental steroidogenesis away from
progesterone and begins some days before birth. The rise in locus coeruleusinduced noradrenaline release, which is apparently particularly marked in the
final stage of labour, is due to stimulation of the locus coeruleus by head and
body compression (and sometimes injury) during passage of the fetus through the
cervix and vagina. It is also due to locus coeruleus responses to acute, usually
transient, periods of fetal hypoxaemia/hypercapnia during uterine contractions.
However, as the hypoxaemia would also lead to an increase in brain production of
adenosine and its suppression of EEG activity, the two effects may nullify each
other.
After birth, during the period between severance of the umbilical cord and the
onset
of
breathing,
the
newborn becomes progressively more
hypoxaemic/hypercapnic and the adenosine concentrations of the brain would
rise markedly, thereby further suppressing its electrical activity. Studies of
umbilical cord occlusion in near-term fetal sheep show that if the onset of
effective breathing after birth is delayed for about 60 to 90 seconds the EEG
would become isoelectric (Mallard et al. 1992; Hunter et al. 2003), an effect which
would be rapidly reversed with the onset of breathing. In fact, gasping as a
prelude to regular breathing usually occurs in vigorous newborns within the first
minute after birth. This, and the subsequent onset of regular breathing lead to a
rapid rise in circulating, and therefore tissue, oxygen tensions to well above usual
fetal levels (Mellor & Gregory, 2003). This, together with loss of placental
adenosine input, would cause a speedy reduction in brain concentrations of
adenosine and its suppressive effects on EEG activity. This rapid postnatal
removal of what is evidently an overriding suppression by adenosine presumably
then allows the brain activators to operate. High circulating 17β-oestradiol
concentrations and strong stimulation of the locus coeruleus-noradrenaline
system are present during labour and after birth. With the onset of breathing
after birth, they presumably act together with cold stimulation of cutaneous
thermoreceptors and with tactile stimulation through contact with hard surfaces
and maternal licking to promote the first appearance of consciousness. Marked
changes in auditory and visual inputs, which undoubtedly occur at birth (Mellor
& Gregory, 2003), may also contribute.
Although adenosine suppression evidently declines very rapidly after birth, some
effects of pregnanolone (and presumably allopregnanolone) are likely to continue
at least during the first day, despite loss of the placenta as a major source of it,
because its circulating concentrations are still significant three days after birth
(Nguyen et al. 2003). Likewise, the decline in the plasma concentrations of the
placental peptide inhibitor, due to loss of the placenta after birth, would probably
not be as rapid as withdrawal of adenosine suppression. It is likely, therefore, that
the above noted activators are required to overcome residual suppression by
allopregnanolone, pregnanonlone, the placental inhibitor and other agents as
their suppressive effects wane after birth.
8
Compassion in World Farming Conference – March 2005
CIWF Paper fin3.doc
334
335
336
337
338
339
340
341
342
343
344
345
346
347
348
349
350
351
352
353
354
355
356
357
358
359
360
361
362
363
364
365
366
367
368
369
370
371
372
373
374
375
376
377
378
379
380
381
Implications
for suffering
in the fetus and newborn
Prior to and during birth
For any animal to suffer it must be both sentient and conscious (see above). The
analysis provided here shows that neurological development is insufficient for
sentience until at least half way through pregnancy, and that the capacity for
sentience evident in neurologically mature farm animals after birth develops
during the last half of pregnancy. Nevertheless, even when the capacity for
sentience has developed the fetus remains unconscious, as indicated by its sleeplike EEG states and the demonstrated operation in utero of a range of
neuroinhibitory mechanisms that actively maintain the fetus asleep. It follows
that although one precondition for suffering, i.e. the capacity for sentience, is met
during late pregnancy, the absence of the other precondition, i.e. consciousness,
before birth means that the fetus, and the embryo before it, cannot perceive by
the senses and therefore cannot suffer.
However, there remains the possibility that the fetus might be arousable to a state
of consciousness by noxious stimulation. Three examples will clarify this. First,
surgical interventions in the naturally unconscious (i.e. sleeping) fetus in an
anaesthetised dam usually impede placental gas exchange and thereby cause
various degrees of fetal hypoxaemia during and for some time after the surgery
(Mellor and Gregory, 2003), and the associated rise in fetal cerebral adenosine
concentrations would lead to even deeper states of unconsciousness, not arousal.
Second, during slaughter of the dam, the rapid cessation of fetal oxygen supply
and the linked rapid increase in fetal adenosine concentrations acting on the
already unconscious fetus would lead to an isoelectric EEG within 60 to 90
seconds (Mallard et al. 1992; Hunter et al. 2003), not arousal to consciousness.
This observation contributed to the development of principles for the humane
slaughter of the fetuses of pregnant ruminants (Mellor, 2003). Third,
vibroacoustic stimulation of the fetus of sufficient intensity to induce movement
does not cause the EEG to change from a sleep-like to an aroused or conscious
state (Leader et al., 1988; Abrams et al., 1996: Bauer et al., 1997; Schwab et al.,
2000). These observations suggest that the fetus in utero is not arousable to a
state of consciousness.
Fetal unconsciousness persists throughout labour and may indeed become deeper,
partly through changes that are not related to hypoxaemia (Berger et al 1986;
Shinozuka and Nathanielsz 1998) and partly through repeated transient
hypoxaemia-adenosine induced suppression of brain function during intense
and/or protracted labour contractions (see above). Thus, although mechanical and
pain receptor nerve pathways will be activated by the marked compression and,
when it occurs, injury, which are associated with labour and delivery, the fetus is
protected from suffering because of its unconscious state. This is reassuring for the
conduct of fetotomy on those occasions when living fetuses need to be
dismembered in utero in order to resolve intractable dystocia (Mellor and Gregory,
2003).
9
Compassion in World Farming Conference – March 2005
CIWF Paper fin3.doc
382
383
384
385
386
387
388
389
390
391
392
393
394
395
396
397
398
399
400
401
402
403
404
405
406
407
408
409
410
411
412
413
414
415
416
417
418
419
420
421
422
423
424
425
426
427
428
429
After birth
The first appearance of consciousness after birth occurs only when breathing
oxygenates the newborn sufficiently to remove the dominant adenosine inhibition
of brain function. The newborn that never breathes will have an isoelectric EEG
and will die without suffering. The newborn that does breathe, but not sufficiently
to effect an oxygen-induced reduction in adenosine to levels compatible with
consciousness, will remain unconscious and will die without suffering. On the
other hand, most newborn farm animals become conscious within minutes of
birth through the operation of the mechanisms outlined above. Once conscious,
they have the potential to perceive noxious and other sensations and to suffer if
the character, intensity and/or duration of those sensations are sufficiently
noxious or aversive (Mellor and Stafford, 2004).
In their evaluation of the welfare implications of mortality and morbidity in
newborn farm animals Mellor and Stafford (2004) considered that the major
noxious subjective experiences of animal welfare concern are breathlessness,
hypothermia, hunger, sickness and pain. Reference to documented responses of
farm animals and, where appropriate, to human experience, suggested that
breathlessness and hypothermia usually represent less severe neonatal welfare
insults than do hunger, sickness and pain. However, two or more of these
experiences can overlap, sometimes with greater negative welfare consequences
(e.g. sickness plus pain), and sometimes where one mitigates the effects of another
(e.g. where hypothermia dulls consciousness in hungry or sick newborns).
Fortunately, major science-based improvements in the management of pregnancy
and birth have markedly reduced the overall amount of welfare compromise
experienced by newborn farm animals (Mellor and Stafford, 2004) and further
improvements may be expected as knowledge is refined and extended in the
future.
Acknowledgements
We are particularly grateful to Associate Professors Laura Bennet and Alistair
Gunn (Department of Physiology, University of Auckland), Dr David Walker,
Department of Physiology, Monash University) and Dr David Bayvel (Animal
Welfare Group, Ministry of Agriculture and Forestry - MAF) for helpful discussion
on the topics covered here, and to the Agricultural and Marketing Research and
Development Trust and MAF Science Policy for financial support for related
research projects.
References
Abrams R.M., Schwab M., Gerhardt K.J., Bauer, R., Peters A.J.M., 1996.
Vibroacoustic stimulation with a complex signal: effect on behavioral state in fetal
sheep. Biol. Neonate 70, 155-164.
10
Compassion in World Farming Conference – March 2005
CIWF Paper fin3.doc
430
431
432
433
434
435
436
437
438
439
440
441
442
443
444
445
446
447
448
449
450
451
452
453
454
455
456
457
458
459
460
461
462
463
464
465
466
467
468
469
470
471
472
473
474
475
476
Avital A., Jansen A.H., Sitar D.S., Chernick V., 1993. Influence of prolonged
adenosine receptor blockade on fetal sleep and breathing patterns. Resp. Physiol.
91, 227-236.
Ball K.T., Gunn T.R., Gluckman P.D., Power G.G., 1996. Suppressive action of
endogenous adenosine on ovine fetal nonshivering thermogenesis. J. Appl.
Physiol. 81, 2393-2398.
Ball K.T., Gunn T.R., Power G.G., Asakura H., Gluckman P.D., 1995. A potential role
for adenosine in the inhibition of non-shivering thermogenesis in the fetal sheep.
Pediar. Res. 37, 303-309.
Bauer R., Schwab M., Abrams R.M., Stein J., Gerhardt K.J., 1997. Electrocortical
and heart rate response during vibroacoustic stimulation in fetal sheep. Am. J.
Obstet. Gynecol. 177, 66-71.
Berger P.J., Walker A.M., Horne R., Brodecky V., Wilkinson M.H., Wilson F.,
Maloney J.E., 1986. Phasic respiratory activity in the fetal lamb during late
gestation and labour. Resp. Physiol. 65, 55-68.
Berridge C.W., Waterhouse B.D., 2003. The locus coeruleus-noradrenergic system:
modulation of behavioural state and state-dependent cognitive processes. Brain
Res. Rev. 42, 33-84.
Bradley R.M., Mistretta C.M., 1975. Fetal sensory receptors. Physiol. Rev. 55, 352382
Challis J.R.G., Patrick J.E., 1981. Fetal and maternal oestrogen concentrations
throughout pregnancy in sheep. Can. J. Physiol. Pharm. 59, 970-978.
Clewlow F., Dawes G.S., Johnston B.M., Walker D.W., 1983. Changes in breathing,
electrocortical and muscle activity in the unanaesthetized fetal lamb with age. J.
Physiol. Lond. 341, 463-476.
Crossley K.J., Nicol M.B., Hurst J.J., Walker D.W., Thorburn G.D., 1997.
Suppression of arousal by progesterone in fetal sheep. Reprod. Fert. Develop. 9,
767-773.
Dawes G.S., 1988. The 1987 James A.F. Stevenson Memorial Lecture. The
development of fetal behavioural patterns. Can. J. Physiol. Pharm. 66, 541-548.
Dunwiddie T.V., Masino S.A., 2001. The role and regulation of adenosine in the
central nervous system. Annu Rev Neurosci 24, 31-55.
Fitzgerald M. 1999. Developmental neurobiology of pain. In: Wall, P.D., Melzack,
R. (Eds), Textbook of Pain, 4th edition. Churchill Livingston, London, pp 235-251.
11
Compassion in World Farming Conference – March 2005
CIWF Paper fin3.doc
477
478
479
480
481
482
483
484
485
486
487
488
489
490
491
492
493
494
495
496
497
498
499
500
501
502
503
504
505
506
507
508
509
510
511
512
513
514
515
516
517
518
519
520
521
522
523
524
Fraser A.F., Broom D.M., 1990. Farm animal behaviour and welfare. Beilliere
Tindall, London, pp 198-207.
Harding R., Poore E.R., Cohen G.L., 1981. The effect of brief episodes of
diminished uterine blood flow on breathing movements, sleep states and heart
rate in fetal sheep. J. Dev. Physiol. 3, 231-243.
Hasan S.U., Rigaux A., 1991. The effects of lung distension, oxygenation, and
gestational age on fetal behavior and breathing movements in sheep. Pediatr. Res.
30, 193-201.
Hayaishi O., Urade Y., 2002. Prostaglandin D2 in sleep-wake regulation: recent
progress and perspectives. Neuroscientist 8, 12-15.
Hirst J.J., Egodagamage K., Walker D.W., 2000. Effect of a neuroactive steroid
infused into the cerebral ventricles of fetal sheep in utero using small infusion
volumes. J. Neurosci. Meth. 97, 37-44.
Hudson, R., Distel, H., 1986. Olfactory guidance of nipple-search behaviour in
newborn rabbits. In: Breipohl, W. (Ed.). Ontogeny of Olfaction. Springer-Verlag,
Berlin, pp. 243-254.
Hunter C.J., Bennett L., Power G.G., Roelfsems V., Blood A.B., Quaedackers J.S.,
George S., Guan J., Gunn A.J., 2003. Key Neuroprotective role for endogenous
adenosine A1 receptor activation during asphyxia in the fetal sheep. Stroke 34,
2240-2245.
Jensen A., Hohmann M., Kunzel W., 1987. Dynamic changes in organ blood flow
and oxygen consumption during acute asphyxia in fetal sheep. J. Dev. Physiol. 9,
543-559.
Joseph R., 2000. Fetal brain behavior and cognitive development. Dev Rev 20, 8198.
Joseph S.A., Walker D.W., 1990. Catecholamine neurons in fetal brain: effects on
breathing movements and electrocorticogram. J. Appl. Physiol. 69, 1903-1911.
Kirkwood, J., 2005. The distribution of the capacity for sentience in the animal
kingdom. In: From Darwin to Dawkins: the science and implications of animal
sentience. Present proceedings: Appl. Anim. Behav. Sci. Supplement X, pp ??????
Koos B.J., Maeda T., Jan C., 2001. Adenosine A1 and A2A receptors modulate sleep
state and breathing in fetal sheep. J. Appl. Physiol. 91, 343-350.
Koos B.J., Matsuda K, 1990. Fetal breathing, sleep state and cardiovascular
responses to adenosine in sheep. J Appl Physiol 68, 489-495.
12
Compassion in World Farming Conference – March 2005
CIWF Paper fin3.doc
525
526
527
528
529
530
531
532
533
534
535
536
537
538
539
540
541
542
543
544
545
546
547
548
549
550
551
552
553
554
555
556
557
558
559
560
561
562
563
564
565
566
567
568
569
570
571
572
Kubonoya K., Power G.G., 1997. Plasma adenosine responses during repeated
episodes of umbilical cord occlusion. Am. J. Obstet. Gynecol. 177, 395-401.
Larson, M.A., Stein, B.E., 1984. The use of tactile and olfactory cues in neonatal
orientation and localisation of the nipple. Dev. Psychol. 17, 423-436.
Leader L.R., Stevens A.D., Lumbers E.R., 1988. Measurement of fetal responses to
vibroacoustic stimuli. Habituation in fetal sheep. Biol. Neonate 53, 73-85.
Lee B., Hirst J.J., Walker D.W., 2002. Prostaglandin D synthase in the prenatal
ovine brain and effects of its inhibition with selenium chloride on fetal
sleep/wake activity in utero. J. Neurosci. 22, 5679-5686.
Majewska M.D., 1992. Neurosteroids: Endogenous bimodal modulators of the
GABAA receptor. Mechanism of action and physiological significance. Prog.
Neurobiol. 38, 379-395.
Mallard E.C., Gunn A.J., Williams C.E., Johnston B.M., Gluckman P.D., 1992.
Transient umbilical cord occlusion causes hippocampal damage in the fetal sheep.
Am. J. Obstet. Gynecol. 167, 1423-1430.
McEwen B., 2002. Estrogen actions throughout the brain. Rec. Prog. Horm. Res. 57,
357-384.
Mellor, D.J., 1998. How can animal-based scientists demonstrate ethical integrity?
In: Mellor, D.J., Fisher, M., Sutherland, G. (Eds), Ethical Approaches to AnimalBased Science. Australian and New Zealand Council for the Care of Animals in
Research and Teaching, The Royal Society of New Zealand, Wellington, New
Zealand pp 19-31.
Mellor D.J., 2003. Guidelines for the humane slaughter of the fetuses of pregnant
ruminants. Surveillance 30, 26-28.
Mellor, D.J., Gregory, N.G., 2003. Responsiveness, behavioural arousal and
awareness in fetal and newborn lambs: experimental, practical and therapeutic
implications. New Zeal. Vet. J. 51, 2-13.
Mellor, D.J., Reid, C.S.W., 1994. Concepts of animal well-being and predicting the
impact of procedures on experimental animals. In: Baker, R.M., Jenkin, G, Mellor,
D.J. (Eds), Improving the Well-being of Animals in the Research Environment.
Australian and New Zealand Council for the Care of Animals in Research and
Teaching, Glen Osmond, South Australia, pp 3-18.
Mellor, D.J., Stafford, K.J., 2001. Integrating practical, regulatory and ethical
strategies for enhancing farm animal welfare. Aust. Vet. J. 79, 762-768.
Mellor, D.J., Stafford, K.J., 2004. Animal welfare implications of neonatal mortality
and morbidity in farm animals. Vet. J. 168, 118-133.
13
Compassion in World Farming Conference – March 2005
CIWF Paper fin3.doc
573
574
575
576
577
578
579
580
581
582
583
584
585
586
587
588
589
590
591
592
593
594
595
596
597
598
599
600
601
602
603
604
605
606
607
608
609
610
611
612
613
614
615
616
617
618
619
620
Mellor, D.J., Diesch, T.J., Gunn, A.J., Bennet, L. (2005). The importance of
‘awareness’ for understanding fetal pain. Brain Res. Rev. (in press).
Miller W.L., 1998. Steroid hormone biosynthesis and actions in the materno-fetoplacental unit. Clin. Perinatol. 25, 799-817.
Morrow-Tesch, J., McClone, J.J., 1990. Sensory systems and nipple attachment
behaviour in neonatal pigs. Physiol. Behav. 47, 1-4.
Nguyen P.N., Billiards S.S., Walker D.W., Hirst J.J., 2003. Changes in 5alphapregnane steroids and neurosteroidogenic enzyme expression in the perinatal
sheep. Pediatr. Res. 53, 956-964.
Nicol M.B., Hirst J.J., Walker D.W., 1999. Effects of pregnanolone on behavioural
parameters and the responses to GABA(a) receptor antagonists in the late
gestation fetal sheep. Neuropharmacology 38, 49-63.
Nicol M.B., Hirst J.J., Walker D.W., 2001. Effect of finasteride on behavioural
arousal and somatosensory evoked potentials in fetal sheep. Neurosci. Lett. 306,
13-16.
Nicol M.B., Hirst J.J., Walker D.W., 1998. Effect of pregnane steroids on
electrocortical activity and somatosensory evoked potentials. Neurosci. Lett. 253,
111-114.
Nicol M.B., Hirst J.J., Walker D., Thorburn G.D., 1997. Effect of alteration of
maternal plasma progesterone concentrations on fetal behavioural state during
late gestation. J. Endocrinol. 152, 379-386.
Paul S.M., Purdy R.H., 1992. Neuroactive steroids. FASEP 6, 2311-2322.
Sawa R., Asakura H., Power G.G., 1991. Changes in plasma adenosine during
stimulated birth of fetal sheep. J. Appl. Physiol. 70, 1524-1528.
Schwab M., Schmidt K., Witte, H., Abrams M., 2000. Investigation of nonlinear
ECoG changes during spontaneous sleep state changes and cortical arousal in fetal
sheep. Cereb. Cortex 10, 142-148
Shinozuka, N., Nathanielsz, P.W., 1998. Electrocortical activity in fetal sheep in the
last seven days of gestation. J. Physiol. Lond. 513, 273-281.
Svensson T.H., 1987. Peripheral, autonomic regulation of locus coeruleus
noradrenergic neurons in brain: putative implications for psychiatry and
psychopharmacology. Psychopharmacology 92,1-7.
Szeto H., Hinman D.J., 1985. Prenatal development of sleep-wake patterns in
sheep. Sleep 8, 347-355.
14
Compassion in World Farming Conference – March 2005
CIWF Paper fin3.doc
621
622
623
624
625
626
627
628
629
630
631
632
633
Szeto H.H., Umans J.G., 1985. The effects of a stable adenosine analogue on fetal
behavioural, respiratory and cardiovascular functions. In: The Physiological
Development of the Fetus and Newborn. Eds, Jones C.T. and Nathanielsz P.W., pp
649-652, Academic Press, London.
Wong M., Thompson T.L., Moss R.L., 1996. Nongenomic actions of estrogen in the
brain: physiological significance and cellular mechanisms. Crit. Rev. Neurobiol.
10, 189-203.
Woolley C.S., 1999. Electrophysiological and cellular effects of estrogen on
neuronal function. Crit. Rev. Neurobiol. 13, 1-20.
15