Richard W . O l m s t e d , E d i t o r
Sudden infant death syndrome temperament before death A retrospective study was made of the behavioral patterns of 46 infants whose deaths were attributed to the sudden infant death syndrome. Controls were the victims" siblings. Data concerning the infants' behavioral pattern were collected retrospectively from the parents, utilizing a modification of the Carey temperament questionnaire. The parents" recollection of the victims indicated that they: (1) had less intense reactions to environmental stimuli, (2) were less active physically, (3) were more breathless and exhausted during feeding, and (4) had more abnormal cries. These behavioral characteristics had a positive correlation with various postmortem evidences o f antecedent chronic" hypoventilation and hypoxemia. It wouM be a serious error for any parent to be told that their infant was at risk based on the behavioral pattern reported retrospectively by parents of victims of SIDS, because the pattern is also a common one in other infants.
The cautionary note expressed here by the author as well as in the last paragraph of the text cannot be overstressed. (See also the commentary by Dr. Carey.) Ed.
Richard L. Naeye, M.D., J o h n M e s s m e r III, T h o m a s Specht, H e r s h e y , Pa., and T. Allen M e r r i t t , M . D . , S a n D i e g o , Calif.
RECENT STUDIES have found multiple evidences of neonatal brain dysfunction in some infants whose subsequent deaths were attributed to the sudden infant death syndrome. The observations included abnormalities in respiration, feeding, temperature regulation, specific neurologic tests, and Apgar scores? Many of the victims also had postmortem evidences of antecedent chronic alveolar hypoventilation and hypoxemia. 2-5 Many of these abnormalities could be due to abnormal "maturation or injury to brainstem structures. To explore possible dysfunction at higher brain levels, a retrospective analysis was undertaken of behavioral characteristics of SIDS victims using a modification of the Carey questionnaire. ~ PATIENTS Deaths were categorized as SIDS when they were sudden, completely unexpected, and unexplained by clinSupported by United States Public Health Service grant H L 14297-03 and contract NO1-HD-4-2817. Reprint address: Department of Pathology, M.S. Hershey Medical Center, Hershey, Pa. 17033.
ical or commonly recognized postmortem findings. A SIDS parents' organization, the International Guild For Infant Survival, recruited 45 member families with one to six surviving children for the Study in the Baltimore and Philadelphia areas. All but two of the victims died within the three years prior to the study. The families were mainly middle class and 93% of them were white. Thirty Abbreviation used SIDS: sudden infant death syndrome of the SIDS victims were male and 16 were female. By comparison, 50 of the sibling controls were male and 40 were female. The gestational ages of the SIDS victims at birth ranged from 33 to 42 weeks with a mean of 39.3 + 0.3 ( _ 1 SE) weeks; the mean value for the controls was 39.5 _+ 013. The SIDS victims as a group had a mean birth weight percentile of 50.6 + 4.1; the controls, 55.4 -+- 3.0. Data on postnatal growth were obtained from baby books kept by the parents and from physicians' records. Two thirds of the SIDS victims had a decrease in body weight percentile after birth, whereas only 35% of The Journal of P E D I A T R I C S Vol. 88, No. 3, pp. 511-515
Naeye et al.
the controls had such a decrease (P < 0.05, chi square). The mean decrease in the SIDS victims was 7.6 +_ 4.4 percentile points, whereas the sibling controls had a mean increase of 2.8 _+ 5.3 points. Ages at death for the SIDS victims ranged from 389 weeks to 4~/i months with a mean of 2.9 _+ 0.2 months. Autopsy material of 21 of the victims was available for analysis in the current study. None of the sibling controls has died. Nineteen (41%) of the SIDS victims had signs and symptoms of a mild respiratory tract infection at the time of death. Two other victims had fever, four had mild diarrhea, one an episode of vomiting, and one a rash for which medical attention was secured just prior to death. Four other infants who were thought to be well had unexpected periods of protracted crying during the night in which they died. Only 15 of the victims appeared to be completely free of illnesses or unexplained crying within a short time of death.
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had died. s, 9 Therefore attempts were made to determine the reliability and validity of the behavioral data by comparing it with abnormalities in the SIDS victims that could be verified. Abnormalities that could be verified included: (1) increased muscle i-n the small pulmonary arteries, (2) extramedullary erythropoiesis in the liver, and (3) retarded postnatal growth. These three abnormalities are common in SIDS and have been presumed to be consequences of chronic alveolar hypoventilation and hypoxemia. 1-s The point counting method was used to quantitate the amount of muscle in pulmonary arteriesY The ratio of area of arterial media to area of arterial intimal nuclei was used as the measure of arterial muscle mass? Extramedullary erythropoiesis was recorded when nests of hematopoietic cells, including normoblasts, were identified between the cords of hepatic parenchymal cells, a RESULTS
METHODS The study began with open-ended interviews of parents of SIDS victims. They were asked to describe the behavior, growth, and development of the SIDS victim and that of siblings at a comparable age. The first three interviews produced spontaneous descriptions of almost identical differences between victims and their siblings. The Carey 70-item questionnaire was then introduced to make the data collection more systematic and comprehensiveY An open-ended interview preceded each self-administered use of the questionnaire. The Carey questionnaire is based on the research interview of Thomas and associates, 7 which is designed to determine the behavioral style of infants in the early months of life. Each of the 70 statements has three choices for completion, describing specific behavior of the infant. The infant's actual response is queried from the parents and not their reactions and interpretations. There are no good, bad, right, or wrong answers. We added 18 items to the Carey questionnaire relating to the following: (1) upper airway obstruction, (2) regurgitation of food, (3) breathlessness or exhaustion during feeding, (4) apneie periods and changes in color during sleep and various waking activities, (5) physical activity during sleep and ease of arousal from sleep by various stimuli, (6) pitch or shrillness of cry, and (7) distinctions between cries to express different needs and moods. Deviation of the patterns of the SIDS victims from those of the control subjects were recorded for each item in the questionnaire. Retrospective analyses of behavior are subject to inaccuracies because memories fade with time and are subject to fantasy, particularly when they relate to an infant who
The mean value for. muscle mass in small pulmonary arteries in the current SIDS victims was 7.3 _+ 0.6, a value very close to the 6.8 _+ 0.6 figure for a group of 62 SID$ victims previously studied in our laboratory. ~ The mean value for presumably nonhypoxic controls in the previous study was 4.5 _+ 0.2 (P < 0.05)? No such control values are available for the current study because all of the sibling controls are still alive. Three of the 21 current SIDS victims for whom autopsy material was available had extramedullary erythropoiesis in their livers. We have never found erythropoiesis in the liver of a nonhypoxemic control?. 5 The SIDS victims differed significantly from their sibling controls on all seven activity items in the questionnaire and on five of the 12 intensity items. The victims were less active and had a less intense response to a variety of environmental stimuli (Table I). The victims also had a lower response to the remaining seven intensity items on the questionnaire, but the differences were not statistically significant. SIDS victims had a significantly lower response than controls to two persistence items in the questionnaire (Table I). SIDS victims also differed significantly from controls on three of the items which were added to the Carey questionnaire, i.e., SIDS victims were more easily exhausted during feeding and had differently pitched cries with less distinctions between various types of cries than their siblings (Table I). Items in Table I were divided into two groups. The first 14 items were judged most subject to distortion by fading memory or fantasy and were placed in group 1. The last three items, exhaustion during feeding, abnormal'pitch of cry, and absence of distinctions between various types of cries, were placed in group 2 because they were judged
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Sudden infant death syndrome
Table I. Distribution o f level of b e h a v i o r a l r e s p o n s e o f SIDS victims a n d sibling controls
Level of activity, intensity, persistence (%) l IntermeHigh diate
Level of significance
Group 1 behavioral characteristic Activity items 1. Moving about, explorhag during play 2. Level of activity, vocalization during play 3. Movement about crib during sleep 4. Squirming, kicking when diapered & dressed 5. Moving about during bath 6. Vigor of suck 7. Physical activity during feeding
37 (75) 33 (18)
20 (50) 52 (46)
39 (64) 29 (32)
19 (63) 39 (26) 42 (11)
21 (57) 61 (43)
50 (86) 29 (14) 21 (0) 7 (32) 54 (54) 39 (14)
< 0.02 < 0.02
25 (54) 36 (29) 39 (17)
15 (28) 32 (11)
37 (62) 25 (19) 38 (19)
39 (68) 43 (29)
50 (64) 46 (25)
Intensity items 8. Intensity of response to bath 9. Intensity of reaction to loud sounds, bright lights 10. Intensity of reaction to differences in people 11. Intensity of crying when hungry 12. Intensity of reaction to changes to food
.Persistence items 13. Amuses self for one half hour or more 14. Crying when not get type of food desired
54 (26) 36 (48) 10 (26)
4 (32) 28 (40) 68 (28)
Group 2 behavioral characteristics 1. Breathless spells, ex3 (1) 31 (9) 66 (90) haustion during feeding 2. Different cries to ex43 (62) 38 (32) 19 (6) press different needs, moods 3. Pitch, shrillness of cry 39 (69) 25 (24) 36 (7) similar to siblings
Values for the controls are in parentheses. The wording of statements is much abbreviated from that actually used in the study. Group 1 contains behavioral items judged subject to distortion by fading memories and fantasies. Group 2 contains items judged less subject to such distortions. Chi square analysis was used. not as likely to be distorted by fading m e m o r y or fantasy. A n a t t e m p t was t h e n m a d e to d e t e r m i n e the significance of the group 1 items b y c o m p a r i n g t h e m with g r o u p 2 items a n d with other data that could b e verified. To m a k e
Table II. Relationship of b e h a v i o r a l scores in SIDS victims to various features o f SIDS that can b e verified or are j u d g e d not likely to be distorted by f a d i n g m e m o r y or fantasy
SIDS victims 1. Gestational age under 38 weeks Gestational age 38 weeks and over 2. Birthweight below fiftieth percentile Birthweight fiftieth percentile and above 3. Body weight percentile decreased after birth Body weight percentile unchanged or increased 4. Pulmonary arterial muscle mass < 7.1t Pulmonary arterial muscle mass > 7.1t 5. Hepatic erythropoiesis absent Hepatic erythropoiesis present 6. Breathless spells or exhaustion during feeding No such spells or exhaustion during feeding 7. Pitch or shrillness of cry like siblings Pitch or shrillness of cry unlike siblings 8. Distinctive cries to express needs and moods No distinction between cries 9. Respiratory illness at time of death No respiratory illness at death
Behavioral score 1.8 4.7 4.8 3.9
_+ 1.0" _+ 1.0 _+ 0.4 _+ 3.3
5.6 2.2 1.3 4.6 2.0 6.3 6.9 3.5 2.6 8.6 2.3 8.5 2.4 5.5
_+ 1.3" _+ 1.3 _ 1.0" _+ 1.7 _+ 1.2" _ 2.4 • 1.35 _ 1.1 + 0.7~ _+ 1.8 __+0.5:~ _ 1.6 _+ 1.1" ___ 1.1
All values are + 1 SE of the mean for the designated subgroup of SIDS victims; t-test was used to determine the level of significance of differences between paired values. *P < 0.05. tSee text or reference 2 for method used to measure pulmonary arterial muscle mass. :~P < 0.01 by comparison with other item in a pair. this comparison, a behavioral score was calculated for the 14 items in group 1. Each item was scored + 1 for a SIDS victim, i f the victim deviated f r o m the m e a n score for his sibling controls in the same direction t h a t all SIDS victims deviated from all the controls in T a b l e I. A score of 0 was assigned if there was no d e v i a t i o n a n d a score o f - 1 if the deviation was opposite to the d e v i a t i o n for all SIDS cases. Thus, in Table I, if a SIDS victim h a d the lowest level o f m o v i n g a b o u t a n d exploring d u r i n g play a n d the m e a n activity value for his siblings was at a h i g h e r level, this item would be scored + 1 for the victim b e c a u s e the SIDS victims as a whole h a d less m o v i n g a b o u t a n d exploring during play t h a n did their sibling controls. U s i n g this system, the total score for a n i n d i v i d u a l SIDS victim could range from - 1 4 to + 14. These scores were t h a n c o m p a r e d with abnormalities in the SIDS victims t h a t could be verified including increased muscle in the small p u l m o n a r y arteries, hepatic erythropoiesis, growth retardation, a n d respiratory illness at the time o f d e a t h (Table II). As previously m e n t i o n e d , c o m p a r i s o n s were also m a d e with g r o u p 2 items in T a b l e I. The term SIDS victims h a d a m o r e positive b e h a v i o r a l
Naeye et al.
score than the victims who were born before term (Table II). Thus, the term SIDS victims had a behavioral pattern more unlike their siblings than did the preterm victims. Postnatal, but not prenatal, growth retardation was positively correlated with a strongly positive behavioral score (Table II). The various anatomic markers of chronic alveolar hypoventilation and chronic hypoxemia were positively correlated with positive behavioral scores as were abnormal cries, exhaustion during feeding, and absence of respiratory illness at the time of death (Table II). Parents did not remember any increase in signs or symptoms of upper airway obstruction or of regurgitation of food in the victims. One victim was reported to be periodically blue when either awake or sleeping. Another victim had a prolonged apneic spell in the newborn nursery which required resuscitation. DISCUSSION In the present study SIDS victims were reported by their parents to have had less intense reactions to numerous environmental stimuli than their siblings. The victims were also reported to have been less physically active and were more often breathless and exhausted during feeding than were their siblings. The pitch or shrillness of the victims' cries were reported to be different from that of siblings, and it was often said to be difficult to differentiate between a victim's needs and moods by means of differences in cries. Each of these abnormalities suggests the possibility of central nervous system dysfunction above the brainstem level. A recent prospective study from our laboratory found other multiple evidences of such dysfunction in infants who subsequently became SIDS victims? These included: neonatal abnormalities in respiration, labile temperature regulation, neurologic variants, and low Apgar scores. Some of the infants who became victims in this prospective study had a weak suck in the neonatal period, a possible antecedent of the exhaustion during feeding reported in the current study? Postmortem evidences of antecedent chronic alveolar hypoventilation and hypoxemia have been identified in SIDS victims in both the current and previous studies. ~-5 These could be consequences of abnormal brainstem control of respiration.1-3 Their positive correlation with certain of the victims' behavioral characteristics increases the possibility that the behavioral descriptions are valid. Such independent corroboration is important because retrospective analyses of behavior are subject to serious inaccuracies, owing to fading memories and to fantasy3. 9 The correlation of positive behavioral scores in SIDS
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victims with absence of terminal respiratory illness may have significance. Infections of the respiratory tract sometimes prolong and increase the frequency of apneic periods during sleep in early infancy?.... Such apneic episodes appear to have preceded death in some SIDS victims.lO, ~. 13 Frequent and prolonged periods of apnea during sleep are a common manifestation of chronic alveolar hypoventilation, and SIDS victims have postmortem evidences of antecedent hypoventilation, such evidences being less in the victims who die with mild respiratory infectionsY, 3 The more abnormal behavioral scores in the victims who had no respiratory illness may be a reflection of the underlying brain dysfunction that made these infants prone to death from apnea or other abnormalities in the central control mechanisms. More normal infants may require a respiratory tract infection or other disturbance to uncover abnormalities in these central mechanisms of control. Only a third of the current SIDS victims were completely free from illness or unexplained crying just before death. Both the illnesses and the crying may be associated with interruptions of normal sleep patterns, another possible trigger to disruption of respiratory or other central control mechanisms. The behavioral pattern associated with SIDS is found in a substantial proportion of normal infants so it would be quite unwise to convey to parents the idea that this pattern places their infants at increased risk of sudden death, In the current study many siblings of SIDS victims had the same behavioral pattern as the victims. None of these siblings have died. A repeat of SIDS in a family is very uncommon. The behavioral findings in the current study should serve only as an indication that exploration of higher brain functions may eventually be useful in determining the causes of SIDS. The authors thank Dr. Russell Fisher, Chief Medical Examiner, State of Maryland, for access to postmortem material used in the study. Dr. William Carey, Media, Pa., made valuable suggestions about the questionnaire and the manuscript. Dr. James Bosma of the National Institutes of Health suggested some of the questions that were used. REFERENCES
1. Nae,ye RL, and Drage JS: Sudden infant death syndrome, a prospective study, Pediatr Res 9:298, 1975. 2. Naeye RL: Pulmonary arterial abnormalities in the sudden infant death syndrome, N Engl J Med 289:1167, 1973. 3. Naeye RL: Hypoxemia and the sudden infant death syndrome, Science 186:837, 1974. 4. Mason JM, Mason LH, Jackson M, Bell JS, Fransisco JT, and Jennings BR: Pulmonary vessels in SIDS, N Engl J Med 292:479, 1975. 5. Valdes-Dapena M: Crib death: Some promising leads but no solutions yet, Science 189:367, 1975.
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Carey WB: A simplified method for measuring infant temperament, J PEDIATR 77:188, 1970. Thomas A, Chess S, and Birch HG: Temperament and behavior disorders in children, New York, 1968, New York University Press. Mednick SA, and Shaffer JB: Mothers' retrospective reports in child rearing research, Am J Orthopsychiatry 33:457, 1963. Wenar C: The reliability of developmental histories, Psychosom Med 25:505, 1963. Stevens LH: Sudden unexplained death in infancy, Am J Dis Child 110:243, 1.965.
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11. Steinschneider A: The concept of sleep apnea as related to SIDS, SIDS 1974, Proceedings Francis E Camps International Symposium on Sudden and Unexpected Deaths in Infancy, Toronto, 1974, Canadian Foundation for the Study of Infant Death. 12. Steinsehneider A: Prolonged apnea and the sudden infant death syndrome: Clinical and laboratory observations, Pediatrics 50:646, 1972. 13. Geertinger P: Sudden death in infancy, Springfield, I11, 1968, Charles C Thomas, Publisher.