ELSEVIER Early Human Development 38 (1994) 165-179 Infant care practices and the investigation of physiological mechanisms Paul Johnson Nuffield Department of Obsretrics, John Radcliffe Hospital. Oxford, UK Accepted I June 1994 Abstract It is strange that some aspects of infant care have been strongly promoted by modern medi- cine while others have been neglected. Thus prone sleeping which has been strongly promoted is now related to an increase in SIDS, whereas the promotion of breast feeding in developed countries has been less successful. Unfortunately there has not been sufficient physiological investigation of many infant care practices and some of the proposed mechanisms for SIDS and prone sleeping have not been substantiated. Thus further work is needed on hypercapnia, hypothermia and periodic breathing and respiratory control. Studying infants alone may leave out important physiological mechanisms such as the effect on body warmth when the infant is close to the mother. More investigation is needed of antenatal factors related to SIDS and it is critically important that physiological investigation should not look for single mechanisms but be concerned with the interaction of many physiological factors. Kcyvords; Sudden infant death syndrome (SIDS); physiology; mechanisms; infant care 1. Introduction The dramatic decline in SIDS associated with a return to supine sleeping position in many Western countries has overshadowed the fact that this was a practice, amongst several others, which most other cultures had not adopted in their care of infants. Western medicine seems equally slow to appreciate, or reluctant to admit, that they had introduced the prone sleeping position for term infants in the early seventies. It had been shown that there was some advantage to this position in preterm infants with respiratory distress. While extrapolation to the term infant was * Corresponding author. 0378-3782/94/$07.00 0 1994 Elsevier Science Ireland Ltd. All rights reserved SSDI 0378-3782(94)01558-7
Transcript
ELSEVIER Early Human Development 38 (1994) 165-179
Infant care practices and the investigation of physiological mechanisms
Paul Johnson
Nuffield Department of Obsretrics, John Radcliffe Hospital. Oxford, UK
Accepted I June 1994
Abstract
It is strange that some aspects of infant care have been strongly promoted by modern medi- cine while others have been neglected. Thus prone sleeping which has been strongly promoted is now related to an increase in SIDS, whereas the promotion of breast feeding in developed countries has been less successful. Unfortunately there has not been sufficient physiological investigation of many infant care practices and some of the proposed mechanisms for SIDS and prone sleeping have not been substantiated. Thus further work is needed on hypercapnia, hypothermia and periodic breathing and respiratory control. Studying infants alone may leave out important physiological mechanisms such as the effect on body warmth when the infant is close to the mother. More investigation is needed of antenatal factors related to SIDS and it is critically important that physiological investigation should not look for single mechanisms but be concerned with the interaction of many physiological factors.
Kcyvords; Sudden infant death syndrome (SIDS); physiology; mechanisms; infant care
1. Introduction
The dramatic decline in SIDS associated with a return to supine sleeping position in many Western countries has overshadowed the fact that this was a practice, amongst several others, which most other cultures had not adopted in their care of infants. Western medicine seems equally slow to appreciate, or reluctant to admit, that they had introduced the prone sleeping position for term infants in the early seventies. It had been shown that there was some advantage to this position in preterm infants with respiratory distress. While extrapolation to the term infant was
* Corresponding author.
0378-3782/94/$07.00 0 1994 Elsevier Science Ireland Ltd. All rights reserved SSDI 0378-3782(94)01558-7
166 P. Johnson/Early Hum. Dev. 38 (1994) 165-179
mostly permissive, it was apparently applied rigorously in New Zealand in the early seventies - along with swaddling, and regimented 4 hourly feeding. On the otherhand attempts to promote breast feeding and restrain maternal smoking met with little success as elsewhere in industrialised societies. Is this why a very high inci- dence of SIDS developed in the South Island particularly? Apparently satisfied with the view that overheating or carbon dioxide rebreathing caused death during prone sleeping - both unlikely causes on such a scale - a further taboo was cast on par- ental infant bed-sharing [ 11. The latter conclusion, which flies in the face of the eth- nic evidence now available, was negated in their study, when it was found that it was coincidence with maternal smoking which caused infants sharing the parental bed to have an increased incidence of SIDS [2]. The incidence of SIDS in New Zealand and many other countries including those parts of the UK that have radically chang- ed sleeping position remains substantially higher than many ethnic communities [3], including those in UK and Belgium.
In addition to discounting increasing evidence that other factors, such as crowded households and bedrooms, including infant co-sleeping, in congested urban en- vironments in most other cultures was related to a low incidence of SIDS, notions that carbon dioxide rebreathing [4] and/or over-heating in the prone position [5] caused death have become the focus for debate. These ideas stemmed from ‘single mechanism’ experiments which has confounded SIDS research for over thirty years. Physiologists, clinicians, with pathologists in their wake attempting to lit mechan- isms to their findings, have investigated mechanisms in isolation such as chemo- receptors, vagal reflexes, arousal responses, sleep, temperature control. They appeared to lose sight of the fact that most vital mechanisms are multifactorial with multiple redundancy ensuring against failure.
Thus epidemiology, fed with an incomplete hand of cards, has, not surprisingly, failed to detect the role of sleeping position in SIDS. In many studies this factor, probably inaccurate when retrospectively ascertained, appears to have been ‘con- founded’ by related factors e.g. smoking, social class. The relationship between sleeping position and SIDS is still not accepted in the USA, where the confounding factors may be more complex since many urban non-white communities there are representative of transitional societies. None-the-less the American Academy of Pediatrics has proclaimed a more rational set of guidelines for infant sleeping posi- tion [6] than many western countries which simply ‘turned over’. Strong epidemi- ological evidence in favour of the protective benefits of ethnic infant care practices from Hong Kong [3] had been ignored before the New Zealand ‘discovery’ of sleep- ing position and SIDS. Thus the chance to actively consider and identify the critical ingredients of cultural infant care practices in large multi-national surveys passed.
2. Unsubstantiated mechanisms for SIDS related to prone sleeping
2.1. Hypercapnia
Re-breathing CO1 is an unlikely cause of SIDS on a scale to explain the decline in SIDS. The studies conducted to support this idea are in the main unphysiological,
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some for ethical reasons. Most of the studies have been poor and unrealistic. Placing ‘models’ of the human infant head over that on an anaesthetised animal is ludicrous- ly simplistic, Clinical studies realistically conducted show that inspired CO2 did not rise above 2-3% and only increased expired CO, from 36 Torr to 40 Torr in the worst situation (i.e. while sleeping prone, well covered, and on an impervious mattress) [7,8]. Oxygen levels were unchanged. The infants breathing, effort not frequency, responded to these modest levels of CO,; a possible stimulus in the co- bedsharing studies. One infant of 11 tested in the latter study who did not hyperven- tilate or arouse, subsequently died of progressive neurological disease. All the evi- dence on neonatal respiratory and arousal responses to inhaled CO, is that these are brisk, potent and sustained after birth [9], in contrast to hypoxia [lo]. Clearly hypercapnia following hypoxemia is different.
2.2. Hyperthermia
There are important inconsistencies in the recent papers relating to environment and sleeping position. Some claim that prone position and environmental heating are independent risk factors [4,5], while others consider heating to be an effect modifier of the prone sleeping position [ 111. Two reports come from the same group and the other refers to infants older than 3 months. One claims that restriction by swaddling and not over wrapping is also an effect modifier whereas the other claims overwrapping to be critical. Hyperthermia of the environment seems to be con- sidered synonomously with hyperthermia of the infant.
Overheating is equally unlikely to be a major cause of SIDS in the prone sleeping position. While a theoretical possibility, all the evidence is that the newborn favours a warm environment and has highly efficient heat conserving and losing mechanisms [12]. Just as the pursuit of ventilatory responses as a guide to adequacy of respiratory control with no reference to metabolic rate or environmental temperature has prov- ed of limited value, so has measurement of body temperature alone as a guide to ade- quacy of temperature control [13]. As to mechanisms, rises in brain temperature causing apnea have been suggested [14]; heat stress in preterm infants [15] and in term infants [16] was cited. However, the first [ 151 were observations in preterm in- fants and oscillatory increases in incubator temperature (not stress) and apnea. The second [16] was a report of one very over-wrapped 6-month-old infant-(environmen- tal temperature unknown) who became very hyperthermic (40°C) and who, subse- quent to active cooling, became comatose, hypercapnic, hypoxic and acidotic before later recovering.
The fact that periodic breathing was found to be related to environmental warm- ing [ 12,14,17] led some to speculate that ‘respiratory instability’ or ‘involvement of respiratory control’ was a likely cause of SIDS [ 141. This is an unjustified conclusion.
Periodic breathing, properly defined, is common in the newborn and relates to temperature control and not risk for respiratory failure [ 121. Similarly, the idea that the delayed postnatal emergence of temperature rhythms, expressed as a delay in the fall of body temperature during the night, equates with risk factors for SIDS in white infants, is cast in doubt when seen to occur normally in Asian infants [ 181. The im-
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portance of diurnal rhythms notwithstanding, temperature, heart rate, and breathing frequency parallel metabolic rate during sleep. Increasing thermolysis and ther- mogenesis both led to arousal. Co-bedsharing infants have more arousals and activ- ity than solitory sleeping infants.
2.3. Periodic breathing and apnea
The ‘apnea hypothesis’ for SIDS, as a primary or rapid secondary cause, has been popular but unsubstantiated. One of the reasons for this is that apnea and periodic breathing have been confused. It is now clear that periodic breathing (PB) is com- mon in the newborn, and of a different central origin to that seen in adult life (which is mainly due to chemoreceptor control). We showed this to be primarily linked to thermoregulation (it exists after carotid body denervation in lambs) i.e. when infants are in a warm environment and metabolic rate is minimal [19]. It was found to occur in older infants, girls more than boys, in low weight infants but seldom in infants of mothers who smoked. The latter have limitation of respiratory function obvious at birth [20] which, paradoxically in a way, provides a ‘tonic’ vagal stimulus to breathing. The PB cycle is similar to the well described thermal-vasomotor oscilla- tion and is fixed in length 12-14 s. Thus the associated apneic pause range from 1- 11 s depending on the amplitude of this oscillation. While $02 also oscillates, depending as much on the response time of the oximeter used, as on the low oxygen stores of the infant, neither progressive hypoxemia, hypercapnia, or prolonged apnea normally occurs.
We investigated the links between metabolic rate, environmental temperature, sleep and cardiorespiratory responses in growing infants [21]. It is surprising therefore to find periodic breathing (and apnea) from such studies continuing to be cited as implicating ‘respiratory instability’ or ‘abnormal control’ in SIDS [22,23]. This culminated in the Chief Medical Officer’s expert committees’ unsubstantiated conclusion that ‘apnea seems the most likely possibility’ from over-heating [24]. Over heating of the environment or the infant? Clinicians and physiologists, as well as epidemiologists, cannot resist finding a new phenomenon, especially if age- related, to give it prominence as a cause.
3. Respiratory control - tonic drives to breathing
This is the balance between the inhibitory and stimulatory factors acting on a cen- tral network in which there are many oscillators of which a brain stem respiratory centres is but one. We demonstrated that developmental changes in metabolic rate (MR) exert an important influence on breathing responses. In fetal life MR is minimal (thermogenesis is inhibited probably by similar mechanisms to breathing which is normally episodic - PGE2, adenosine [ 121). Acute hypoxia inhibits breath- ing whereas CO2 is a stimulus. Yet, fetal breathing is vigorous high energy breath- ing, with inspiratory obstruction which ensures lung growth [25]. Sleep state is an important modulator of breathing though much less so in the human fetus than other species studied.
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The inhibitory balance for breathing in utero is high; after birth hormonal inhibi- tion is removed and sensory and thermal stimulation is high and MR increases. These are powerful tonic stimuli to the cardiorespiratory system. Hypoxia at ther- moneutrality did not stimulate breathing in term infants [9], whereas CO* did [16]. The terhmogenic ‘tonic’ drive to breathing declines later in infancy when spontane- ous and thermally induced PB becomes more common. Thyroid function was critical to survival in the post neonatal period: lambs with low T3 levels at BMR and im- paired BAT thermogenesis, died unexpectedly [26]. Behavioural adjustments (arousal state and posture) form key responses to thermoregulatory challenge. Newborn lambs reduce REM sleep on modest environmental cooling whereas human infants increase REM - whereas both species increase REM on warming until arousal. Breathing control is not inherently fragile although its dependence on ‘tonic’ drives, which are complex, are crucial during development [ 121. Our evidence points toward the pre-optic area of the hypothalamus as being a critical focus for the regulation of arousal behaviour, metabolism and cardiorespiratory control.
4. Maternal-infant care practices and postnatal physiological development
Two papers finally and clearly identified the potent advantages of some culturally established infant care practices of ethnic groups living in western communities; Asians in Birmingham, and North Africans in Belgium. Both had a lower incidence of SIDS inspite of higher infant mortality rates. These findings upheld the earlier reports from Hong Kong showing that SIDS in the Chinese community was much lower than in whites [3]. Perhaps because the Hong Kong studies found that urban domestic overcrowding was not a risk factor for SIDS (or because they were not con- ducted in western countries?) they did not have the appropriate impact on research and infant care practices.
In fact it was in New Zealand where the practice of prone sleeping position was most rigorously instituted in the early seventies that a rise in SIDS was observed, as is now also documented for Norway [27]. But it was reported to have risen slowly to its extraordinary level (WI000 in Dunedin) in the eighties. Perhaps it was the relax- ation of the draconian 4 hourly feeding regime, whilst still maintaining the prone swaddled sleeping position, and thus leaving the infant alone for longer periods in a sensorily deprived hostile micro-environment, that related to the high level of SIDS. This peak rightly caused anxiety, investigation and ultimately action. How- ever, a pro-active campaign against prone infant sleeping, smoking, and in favour of breast feeding (although the last two remain remarkably resistant to change) without consideration of the other physiological implications of maternal infant care practices seems both naive and a further risk [28].
5. Maternal infant bedsharing
The extraordinary studies conducted on sleep patterns of infants and mothers sleeping together have shown that infant-parent co-sleeping not only mitigates a variety of suspected SIDS risk factors such as, the timing, form and frequency of
170 P. Johnson /Early Hum. Dev. 38 (1994) 165- I79
arousal, form and duration of nursing, infant sleep position, ambient gas pressures surrounding the infant’s head, the intervals between maternal inspections, but calls into question some of the developmental data conducted on isolated sleeping infants currently considered as defining normal development. A striking feature of these studies is that apparently purposeful ‘reflex’ interaction goes on between mother (parent) and infant which prevents longer epochs of quiet deep sleep in younger infants (to some the pattern would appear to be fragmented sleep - yet is reported as very satisfying by the mother). In this context the earlier observation that infants slept better prone than supine [29], needs recondiseration. When then is the normal or ‘control’ postnatal environment?
6. Physiological investigation
Studies of respiratory control, a favoured cause for SIDS, are fundamentally af- fected by these newer observations on infant behaviour and sleep. Environmental factors have been shown to play a major part in cardiorespiratory control in early postnatal life. Thermometabolism provides a major basal, or ‘tonic’, stimulus to breathing. As a result of the newly appreciated importance of maternal infant inter- action on behaviour, we decided to review recent clinical and basic physiological data.
The lamb, extensively used for studies on physiological development, has in the main been studied without the presence of the ewe and in many cases reared as an orphan to permit serial studies without the interference of the ewe on recording techniques. The step from acute studies, where the effects of anaesthesia and seda- tion grossly distorted results, to chronic continuous physiological measurement revealed developmental changes previously unsuspected [ 121. However, an earlier study in which lambs telemetered while being reared with their ewes has shown striking differences in behaviour and respiratory patterns over the first few weeks of postnatal life. Some of these are well illustrated in Fig. 1 where a typical l-h section of an overnight recording of a 14-q-old lamb with its ewe. This lamb, simul- taneously videod, was observed to sleep against the flank (rumen) of the ewe, which can be some 3°C above maternal body temperature - a veritable radiator. It can be seen that the lamb alternates between high voltage slow wave (quiet) sleep (QS), REM (rapid eye movement) sleep and wakefulness. The constant expiratory activity of the thyroarytenoid muscle (the principle laryngeal constrictor) which generates endogenous expiratory pressure, stimulates breathing and thus protects lung volume [12], can be seen in QS except where the breathing frequency increased in excess of 100 breaths/min some minutes before arousal and change of position occurred. Tachypnoea is achieved principly by shortening of expiratory time and thus lung volume is protected. The lamb ‘repeated’ elective sleeping against the ewes flank three times during this period of recording. This is probably a respiratory themolytic response since there is no increase in heart rate which normally occurs with hyper- thermia. Older lambs, over three weeks of age, slept separately although close to their ewe.
It was assumed that the ewe represented a heat source - however we do not know
P. Johnson /Early Hum. Dev. 38 (1994) 165-l 79 171
ECoG
EOG
Diaphragm
PCA <in@
TA kxp)
10 minutes
Fig. I. A ‘IO-min section from an 8-h overnight recording on a 14 day old lamb telemetered while sleeping with its ewe. From above down are shown the electrocorticogram (ECOG), electrooculogram (EOG), diaphragm electromyogram, Posterior crycoarytenoid electromyogram (PCA): inspiratory abductor mus- cle, thyroarytenoid electromyogram (TA): expiratory abductor muscle, respiratory rate, and heart rate. Cycling between quiet and REM sleep can be seen after initial wakefulness. Three episodes of tachypnoes (frequency limited at 100 breaths/min by amplifier ‘cut-off): occur during quiet sleep followed by arousal. The simultaneous video showed the lamb sleeping against the flank of the ewe.
Table I The sleep wake time of the lambs reared with ewes (ER): and without (AR):
The data from the AR lambs is shown for thennoneutrality and cool (where metabolic rate is higher than at thermoneutrality). Clearly, wakefullness and REM are increased and quiet sleep less in the ER lamb than in the orphan lamb even when the latter is sleeping at thermoneutrality. It seems likely that the presence of the ewe contributes to the differences in arousal state. *P < 0.05. **p < 0.01. ***P < 0.001 (sem).
172 P. Johnson/ Early Hum. Dev. 38 (1994) 165-179
the cues for their lying together. When the data from ewe-reared lambs was com- pared with that from ‘orphan’ lambs it was found that their respiratory rates during sleep were higher during the first 14 days of life and they had less QS, and more REM sleep and wakefullness (Table 1; Fig. 2). Young lambs were stimulated (nudg- ed, occasionally kicked to feed) whereas older lambs often had to stimulate (nudge, jump on) the ewe to stand up and let them feed. Their interfeed cycle was also shorter than orphan lambs (89 vs. 114 min), both being shorter than the fetal swallowing cycle (200 min).
Plainly the presence of the ewe had substantial behavioural and thermoregulatory effects on the lamb, which elected a warm stimulated environment. The contribution of thermolytic and sensory stimulation to the lambs respiratory and behavioural responses are not distinguished by these studies. However, rabbit pups also elect a high environmental temperature in preference to other cues (nest, food) which decreases with postnatal age matching minimal metabolic rate as the energy demands of thermoregulation decrease [30]. Of considerable clinical importance is
90
80
h A
70 El 3 60
4 8 50
:“, \ , , , ~oqcutral
o 10 20 30 40 SO 60 Age days
Fig. 2. Show breathing frequency with age during quiet sleep compared between the ewe-reared lambs and the upper and lower critical limits of ‘orphan’ lambs tested in cool to warm ambient environments. The high breathing frequencies in the ewe-reared lambs occur during the first 2 weeks when the lambs were observed to sleep against their ewes, after which they chose to sleep separately.
P. Johnson/Early Hum. Dev. 38 (1994) 165-179 173
the fact that fetal malnutrition, including the smaller pups in this study, leads to a lower postnatal BMR and choice of environmental temperature to the neonate [3 11. This is contrary to clinical practice which is to ensure against hypothermia and hypoglycemia in intra uterine growth retarded (IUGR) infants by providing ad- ditional warmth.
Clearly a ‘cosy’ thermal environment and continuous maternal infant contact naturally occurs in early postnatal life in most species both more and less precocial than man. In clinical studies in which infants were studied sequentially overnight once a month to 6 months of age at home, it was noted that most infants slept through the night without being fed by 4-5 months of age. Mean heart rates and breathing rates rose from the first week of life to plateau between 1 and 2 months before declining. This coincides with increased metabolic rate and body temperature [12]. Differences related to QS and REM sleep were maintained, values for all these variables being higher in REM than QS in human infants. However, a steep fall in these values occurred between 3 and 4 months of age coincident with elimination of night time feeding. In Fig. 3 over-night recordings from the same infant at 2 and 5 months of age is shown. In (a) two feeding periods occurred during the night whereas in (b) none occurred. It can be seen that sleep time and pattern differs with frequent feeding and the heart rate and breathing frequency are higher after each feed and subside over l-2 h to basal levels. Clearly a comparison between infants at these ages with and without nocturnal feeding would be required before age-related changes can be determined. Much of the normative data on sleep and car- diorespiratory patterns have not taken nocturnal feeding into account. It can, unfor- tunately, be safely assumed that the ‘sensory’ presence of the mother was excluded from such studies.
The patterns observed with frequent feeding are closer to those observed during maternal infant co-sleeping. If it is an advantage, or natural, to have shorter periods of quiet sleep and a stimulated cardiorespiratory system, then social drive to elimi- nate the nocturnal feed seemingly one of the goals of western maternal infant care could have a number of disadvantages. The importance of continuous family-infant interaction on physiological development seems hard to ignore when the benefits of skin-to-skin contact of the preterm infant are also considered. Higher oxygen and heart rate levels, less panea, faster growth, less sleep and more alertness as well as earlier discharge home [32]. Continuous sensory stimulation which leads to more arousals is a stimulus to infants with apnea of prematurity. How sensory stimulation provides a ‘tonic’ stimulus to breathing which is linked to arousal state requires in- vestigation.
Meanwhile persistence with physiological studies which measure heart rate, breathing, temperature and metabolic rate in isolation are only providing physi- ological surrogates, just like prone sleeping position is likely a surrogate for lack of maternal infant interaction. Nocturnal temperature patterns, just like heart rate and breathing frequency patterns relate to arousal, activity and metabolic rate. ‘Delayed’ (re-)appearance of adult nocturnal temperature rhythms initially considered to be associated with risk for SIDS in white infants [13] have been observed in Asian infants who are at lower risk for SIDS by the same investigators [ 181. Asian infants
P. Johnson/Early Hum. Dev. 38 (1994) 165-179
b w i!_
Fig,3. Show two overnight (10 h) recordings from the same infant at home at (a) 2 months of age and (b) 4 months of age. Oxygen saturation, heart rate, breathing frequency, and computed sleep state are shown from above downward. In (a) it can be seen that two feedings occurred during the night when the recordings are disturbed. Heart rate and breathing frequencies increased and slowly declined after each feed. Quiet sleep substitutes for wakefulness with age as feeding is ‘dropped’ at night. Thus mean heart rate and breathing frequencies were higher in younger infants.
are likely to have nocturnal family interaction and feeding. Clearly both temperature and heart rate relate to metabolism, modulated by sleep state and activity. Function- al abnormalities such as chronic lung disease will, depending on severity, exert influ- ence on homeostatic control.
It seems remarkable that the recent focus on the effects of prone supine sleeping position fail to consider let alone identify other elements of maternal infant
P. Johnson /Early Hum. Dev. 38 (1994) 165-179 175
Fig. 4. A similar overnight recording in a IO-month-old infant initially sleeping on his own after which he woke and remained distressed. The mother then took him into the bed beside her for the remainder of the night. Additional channels show chest excursion as a proportion of the ‘sum’ of the chest and abdominal excursions -the high levels occurred during quiet sleep. Below that are the body movements from a thin mattress under the infant. Annotation by the mother on the record can be seen. The cycles between quiet and active sleep can be readily seen before and after the period of wakefulness. Variability and body movements occurred during active sleep (channel 6 from the top). The expansions below show two episodes of active sleep before and after the infant is bed with his mother. In these displays the indi- vidual breaths can be seen from the chest and abdominal bands and below that from the pad from which breathing and movement are identified. The microphone is placed near the babies head..lt is effective with the mother sleeping close by. Thus non-contact measurement recorded continuously is highly informative of sleep pattern and breathing patterns and whether the latter is noisy.
healthcare practices during perinatal development [24]. Hyperthermia is blindly pur- sued as a causative factor with apnea being implicated as the fatal result. The clinical and experimental studies cited above are wholly inappropriate, as is the pursuit of thermal environmental factors just because breathing pattern is influenced by tem- perature control [23] in the form of periodic breathing in particular. The latter is normal and common [ 121.
Monocular clinical and physiological views on development must change radically if appropriate studies of antenatal and postnatal factors are to be conducted. A
176 P. Johnson/Early Hum. Dev. 38 (1994) 165-179
recent paper elegantly and convincingly lays out the ethnic argument [33]. Two important quibbles though: (1) Breathing control is not as fragile as stated. It is a robust system with many redundancies ensuring survival. However, there are powerful inhibitory and excitatory mechanisms well established in utero. The transition from an inhibitory state in utero to an excitatory tonic stimulus after birth involves the change in environment. A number of factors have been considered above, especially those that are less easily quantified and testable such as thermometabolism. Yet their demands on respiration are large. Even so we clearly have completely undervalued the impor- tance of the maternal sensory environment in this hierarchy. (2) The importance of these ethnic factors extend beyond SIDS; their impact on western perinatal care is probably of greater importance. The increased survival of the high risk fetus, both identified and unidentified, produces more high risk neo- nates, at the same time as industrialised societies have decreased their birth rate and thus proportion of low risk infants. Thus a household size averaging 2.49 occupants (compared to > 5 in immigrant communities in the UK) places a high premium on the mother to provide a continual natural stimulus to the developing infant.
7. Antenatal factors
Other factors arising in fetal life relate to risk. Pathological evidence has increas- ingly implicated abnormal fetal development, usually interpreted as hypoxic in origin. Identified abnormalities extend to the arrest of maturation of kidneys and lungs, together with delay in myelination and abnormalities of the substantia nigra (previously ascribed to hypoxia). However, experimental fetal undernutrition pro- duces similar abnormalities, as do chronic infusions of catecholamines and B nimetics into the fetus [34]. Determining the contributions of malnutrition and hypoxia to outcome is crucial.
7. I. Smoking
Smoking has a ‘dual’ effect on development, since nicotine has a direct effect on placental function affecting nutrient and oxygen supply, and on the nervous control of breathing. Fetal breathing is crucial for lung and airways development. Hypoxia and hypoglycemia decrease fetal breathing and as little as 10 days of reduced or altered fetal breathing in late fetal life can have a major effect on lung growth (50% reduction in growth) [25]. The evidence for selective effects on organ growth and function, especially later in gestation, coincides with the recent post-mortem findings on renal and lung abnormalities in SIDS [35]. Prenatal maternal smoking has significant effects on neonatal airway development and/or lung elastic properties, even when corrected for their lower birthweight [20].
7.2. Hypoxic or nutritional injury
Many of the CNS changes found in Stillbirths, SIDS and cerebral palsy have
P. Johnson /Early Hum. Dev. 38 (1994) 165-I 79 171
previously been ascribed to hypoxic/ischemic injury both clinically [36] and ex- perimentally [37]; with very little attention paid to nutrition and metabolism at the time. It is no longer believed that hyperglycemia contributes to hypoxic CNS injury (by lactacidosis) [37,38], and may actually be protective during asphyxia.
7.3. Growth Indices
The fact that major abnormalities of growth and development can occur with only a modest disturbance of mean body weight is now clear in experimental and clinical studies. The disproportionately grown fetus often passes within the normal centiles for population and does not attract the medical and epidemiological attention of the classical ‘small-for-dates’ infant. The normal ‘average weight’ growth retarded infant has increasingly been found to have a legacy of long-term deficits (premature cardio- vascular disease and respiratory disease [39]) which would coincide with some of the deficits in organ function now described in such fetuses.
Recently, a practical proposal for differentiating abnormalities of fetal growth from growth potential was made by comparing predicted birthweight with actual birth weight from current ante natal measurements. By taking into account maternal and fetal physiological factors, an individualised birthweight ratio for each individu- al baby, redefined as normally grown, 41% of babies previously below the 10th cen- tile, and 46% of those above the 90th centile: 4% of normal weight babies were also redefined as growth retarded [40]. Such a redistribution would have massive effects on national figures based on centile charts - yet this is just a start. Infants of smok- ing mothers and SIDS have lower weights - but within normal centile ranges. Ad- ding appropriate anthropometric measurements at birth to individualised fetal sizing, and placental weight, into the ratio, is the only logical way to assess fetal growth [41,42]. Outcome measures of a pregnancy in terms of birth weight should be estimated as the differences between potential, anticipated, and actual.
A solution seems obvious: a return to basics. However, can industrialised societies re-adopt culturally proven maternal-infant practices when successfully promoting increasing survival of high risk fetuses (including IVF) while reducing the number of low risk progeny by birth control. Difficult; when the social structure, especially the household has perhaps irreversibly changed.
Meanwhile it is imperative that physiological investigation abandons its single mechanism approach and focuses on the impact of the sensory environment on postnatal development. Techniques to non-invasively measure the infant in the non- solitary environment at home now exist [43,44] (Fig. 4). However, a matching im- provement in fetal assessment of growth and development is needed in order to base objective postnatal physiological investigation.
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[I21 Johnson, P. and Andrews, D.C. (1992): Thermometabolism and cardio respiratory control during the perinatal period. In: Respiratory control disorders in infants and children, pp. 76-88. Editors: Beckennan, Boruillett and Hunt. Williams and Wilkins, Baltimore, MD.
[I31 Lodemore, M.R., Petersen, S.A. and Wailoo, M.P. (1992): Factors affecting the development of night time temperature rhythms. Arch. Dis. Child., 67, 1259-1261.
[I41 Fleming, P.J. et al. (1993): Interactions between thermoregulation and the control of respiration in infants: possible relationship to sudden infant death. Acta. Paediatr. Suppl., 389, 7-9.
[15] Perlstein, P.H. et al. (1970): Apnoea in premature infants and incubator air temperature changes. N. Engl. J. Med., 282, 461.
[I61 Gozal, D., Cohn, A.A., Daskalovic, Y.I. and Jaffe, M. (1988): Environmental overheating as a cause of transient respiratory chemoreceptor dysfunction in an infant. Pediatrics, 82, 738-740.
[17] Johnson, P., Head, J., Hughes, M. and Sands, P. (1990): Periodic breathing in healthy infants monitored at home. Am. Rev. Respir. Dis., 141 (4), 1108.
[ 181 Wailoo, M.P. and Petersen, S.A. (1994): Development of night time temperatures in Asian infants. Early Hum. Dev., 38, 181-186.
[I91 Andrews, D.C., Symonds, M.E. and Johnson, P. (199l)a: Thermoregulations and the control of breathing during N-REM sleep in the lamb. J. Dev. Physiol., 16, 27-36.
[20] Hanrahan, J.P., Tager, M.E., Segal, T.D., Tosteson, T.D., Castile, R.G., van Vunakis, H., Weiss, ST. and Speizer, F.E. (1992): The effect of maternal smoking during pregnancy on early infant lung function. Am. Rev. Respir. Dis., 145, 1129-l 135.
[2l] Azaz, Y., Fleming, P.J., Levine, M., McCabe, R., Stewart, A. and Johnson, P. (1992): The relation- ship between environmental temperature, metabolic ra e, sleep state and evaporative water loss in
.a infants from birth to three months. Pediatr. Res., 32, 17-423. [22] Fleming, P.J., Howell, T., Clements, M. and Lucas, J. (1994): Thermal balance and metabolic rate
during upper respiratory tract infection in infants. Arch. Dis. Child., 70, 187-191. [23] Fleming, P.J. (1993): Interactions between thermoregulation and the control of respiration in in-
fants: possible relationship to sudden infant death. Acta. Paediatr. Suppl.. 389, 7-9. [24] Chief Medical Ollicer’s Expert Group, Sleeping position of infants and cot death. London: HMSO,
1993; 72. (251 Fewell, J.E. and Johnson, P. (1983): Upper airway dynamics during breathing and during apnoea
in fetal sheep. J. Physiol., 339, 495-504. [26] Symonds, M.E., Andrews, D.C. and Johnson, P. (1989): The control of thermoregulation in the
developing lamb during slow wave sleep. J. Dev. Physiol., 11. 289-298. [27] Mitchell, E.A., Brunt, J.M. and Everad. C. (1986-1992): Reduction in mortality from sudden infant
death syndrome in New Zealand.
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Markestad, T., Irgens, L.M., Baste, V., Oyen, N. and Schreuder, P. (1993): Infants sleeping position and SIDS in Norway, 1970-1991. In: Proceedings of 3rd ESPID Contress, Oxford. J. Dev. Physiol., (in press). Brackbill, Y., Douthitt, T.C. and West, H. (1973): Psychophysiological effects in the neonate of prone vs. supine placement. J. Pediatr., 82, 82-84. Hull, J. and Hull, D. (1982): Behavioural thermoregulation in newborn rabbits. J. Comp. Physiol. Psychol., 96, 143-147. Conradi, N.G., Muntsing, K., Sourander, P. and Hamberger, A. (1984): Effect of ambient tempera- ture on rectal temperature in normal and malnourished rats during early postnatal development. Acta. Physiol. Stand., 121, 147-153. Anderson, G.C. (1991): Current knowledge about skin-to-skin (kangaroo): care for preterm infants. J. Perinatol., 216-226. Davies, D.P. and Gantley, M. (1994): Ethnicity and the aetiology of SIDS. Arch. Dis. Child., 70, 349-353. Bassett, J.M. (1993): Glucose and fetal growth derangement. In: Fetus and Neonate Volume III: Growth. Editors: M.A. Hanson, J.A.D. Spencer and C.H. Rodeck. Cambridge University Press, Cambridge. Hinchcliffe, S.A., Howard, C.V., Lynch, M.R.J.. Sargent, P.H., Judd, B.A. and van Velzen, R. (1993): Renal developmental arrest in sudden infant death syndrome. Pediatr. Pathol., 13, 333-344. Gaffney, G., Squier, M. et al. (1994): Clinical associations of prenatal ischemic white matter injury. Arch. Dis. Child., 70F, 101-106. Johnson, P. (1993): Birth asphyxia: should it be redefined or abandoned? In: lntrapartum perinatal surveillance. Editors: J.A.D. Spencer and R.H.T. Wart. RCOG Press, 157-180. Vannucci, R.C. and Mujsce, D.J. (1992): Effect of glucose on perinatal hypoxic-ischemic brain damage. Biol. Neonate, 62, 215-224. Barker, D.J.P., Bull, A.R., Osmond and Simmonds, S.J. (1990): Fetal placental size and risk of hy- pertension in adult life. Br. Med. J., 310, 259-262. Wilcox, M.A., Johnson, I.R., Maynard, P.V., Smith, S.J. and Chilvers, C.E.D. (1993): The in- dividualised birthweight ratio: a more logical outcome measure of pregnancy than birthweight alone. Br. J. Obstet. Gynaecol., 100, 342-347. Patterson, R.M. and Pouliot, R.N. (1987): Neonatal morphometrics and perinatal outcome: Who is growth retarded? Am. J. Obstet. Gynecol., 157, 691-693. Beattie, R.B. and Johnson, P. (1994): Practical assessment of nutritional status - beyond birth weight criteria. Submitted Br. J. Obstet and Gynae. Johnson, P. and Andrews, D.C. (1994): Non-invasive cardiorespiratory monitoring in infants and children at home and in hospital. In: Fetus and Neonate: Physiological and clinical appications. 2: Respiration. Editors: M.A. Hanson, J.A.D. Spencer and C.H. Rodeck. Cambridge University Press. Thoman, E.B. and Feudigman, K.A. (1991): Nonintrusive monitoring of sleep in newborns: deliv- ery mode, sex differences, and prediction of later development. Sleep Res., 8, 217.
