Familial Occurrence of Sudden Infant Death Syndrome and Apnea of Infancy

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Familial

Occurrence

of Sudden

Infant

Death

Syndrome

and Apnea

of Infancy

Joseph

Oren,

MD, Dorothy

H. Kelly,

MD, and Daniel

C. Shannon,

MD

From the Pediatric Pulmonary Unit, Massachusetts General Hospital, Boston

ABSTRACT. We sought to determine the outcome of

infants born to families with multiple victims of sudden infant death syndrome (SIDS) and/or apnea of infancy. Seventy-three infants, born to families who had two or more previous siblings who had either died of SIDS or who were monitored at home for apnea of infancy or for

abnormal results on polysomnogram and/or pneumogram recording, were prospectively monitored. The infants

underwent polysomnogram and pneumogram recording and were subsequently monitored at home with a cardi-orespiratory monitor. All episodes of apnea were imme-diately reviewed. Thirteen infants (18%) had subsequent severe episodes of apnea and five other infants (7%) died during a subsequent episode. All deaths occurred in fam-ilies who had two or more SIDS victims. The outcome for the 17 infants who were half siblings was similar to the outcome for full siblings. Clinical data of the infants

and results of evaluation were not predictive of outcome.

Pediatrics 1987;80:355-358; sudden infant death

syn-drome, apnea, sibling.

Sudden infant death syndrome (SIDS) is not considered to be genetically determined. However, repeated SIDS events have been reported in a fam-ily,’ and recent data indicate that the risk of SIDS

is increased 3.6- to tenfold in subsequent siblings of SIDS victims.2’3 The pathophysiology leading to repeated deaths in some families is unknown, and the role played by genetic or environmental factors is still being debated. Further insight into this issue can be gained by studying subsequent infants born to families who lost two or more infants to SIDS.

Some infants with apnea of infancy have died of SIDS”4’5 and families have been reported with more than one infant with SIDS and/or apnea of

iii-fancy.”2’4’6 Although the pathophysiology of SIDS,

apnea of infancy, and abnormal sleep study findings

Received for publication June 5, 1986; accepted Oct 31, 1986. Reprint requests to (D.H.K.) Pediatric Pulmonary Unit, Mas-sachusetts General Hospital, Boston, MA 02114.

may be different, the effects of the occurrence of one or more of these conditions on subsequently

born infants in these families needs further

inves-tigation. Therefore, in this study, we sought to determine the outcome of infants who were born to families who had two or more previous infants who had either died of SIDS or who had been monitored at home for apnea of infancy or because they had a sleep polysomnogram or pneumogram recording with abnormal results.

PATIENT SELECTION AND METHODS

The infants in this study were selected from a population of 1,341 infants who had been monitored at home under the supervision of the staff of the

Pediatric Pulmonary Laboratory of the

Massachu-setts General Hospital after Jan 1, 1973, and who

had completed monitoring by Jan 1, 1986. We

iden-tified 73 infants who had two or more previous siblings who either had died of SIDS or were mon-itored at home because they had apnea of infancy

or abnormal results on polysomnogram and/or overnight pneumogram recording. The recordings were analyzed by a program physician according to

previously described criteria.4 Apnea of infancy was

defined as an apparent life-threatening episode,

usually occurring during sleep, characterized by

apnea and a change in tone and color that required

vigorous stimulation or resuscitation to terminate.7

Of 65 subsequent siblings who were monitored from birth, eight were monitored following an episode of apnea of infancy. The infants underwent initial evaluation that included physical examination, a

12-hour overnight pneumogram recording, and polysomnogram recording. All caretakers were in-structed in infant cardiopulmonary resuscitation, the use of monitoring equipment, and methods of observation and intervention.4

Subsequent episodes of severe apnea of infancy

and/or bradycardia that terminated only with

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356 SUDDEN

INFANT

DEATH

AND

APNEA

immediately by the program physician to determine whether the intervention used was appropriate. These symptomatic infants underwent a second complete evaluation as outlined by Guilleminault and Korobkin7 in search of a treatable cause that might explain the apneic episode. If no cause could be identified, caretakers were instructed to continue cardiorespiratory monitoring and their training was reviewed. All infants were monitored until they met the following criteria: (1) no apnea requiring any stimulation for 2 consecutive months, (2) no apnea requiring resuscitation or vigorous stimulation for 3 consecutive months, and (3) resolution of abnor-malities on pneumogram or polygraphic recordings.

The infants were placed in five groups based on

family history (Table 1). Group 1 infants were born

to families who had two or more siblings who died of SIDS based on history and a review of the written autopsy results. Group 2 infants were born to

fam-ilies in which one infant died of SIDS and a second

infant had apnea of infancy. Group 3 infants were born to families in which one infant died of SIDS and a second infant had an abnormal pneumogram

or polygraph findings but no apnea. Group 4 infants

TABLE 1. Family History of Siblings5

Group First Sibling Second Sibling

1 SIDS SIDS

2 SIDS AOl

3 SIDS AP

4 AOl AOl

5 AOl AP

5 Abbreviations: SIDS, sudden infant death syndrome;

AOl, apnea of infancy; AP, abnormal pneumogram and/

or polysomnogram.

TABLE 2. Clinical Data fo r 73 Infants

Characteristic Value Range

Sex (M/F) 35/38

No. of preterm infants 10 (37 wk)

Gestational age (wk) 39.2 ± 2.1* 32-42 Birth wt (kg) 3.3 ± #{216}#{149}751.8-5.0

Duration of monitoring 36.6 ± 21.8* 4-112 for surviving infants

(wk)

S Values are means ± SEM.

were born to families in which two or more previous infants had apnea of infancy. Group 5 infants were born to families in which one infant had apnea of infancy and a second infant had abnormal pneu-mogram or polygraph findings but no apnea. The differences in clinical data were tested with the Student’s t test. The Fisher exact test was used for categorical variables. We accepted P < .05 as

ex-cluding the null hypothesis.

RESULTS

We studied 73 infants whose clinical

character-istics are shown in Table 2. The groups were similar

with respect to the selected clinical characteristics. Of the 73 infants, 37 had abnormal results on pneumogram and/or polysomnogram recordings during the initial or subsequent evaluation (Table 3). Of the 18 infants who had an adverse outcome, 13 infants had subsequent severe episodes of apnea

and/or bradycardia and five other infants died dur-ing a subsequent episode (Table 3). The diagnosis of SIDS was confirmed by autopsy in three of these

five infants and was suggested by review of circum-stances of death in the other two.

The clinical data (sex, gestational age, birth weight) and the presence of abnormal results of pneumogram and/or polysomnographic testing were not predictive of adverse outcome as deter-mined by the occurrence of subsequent episodes of apnea of infancy or death. All deaths occurred in group 1. The clinical data of the infants in this

group and the incidence of abnormal results on

pneumogram recording and/or polysomnogram

were not different from those of the other groups.

However, the incidence of death (5/28 v 0/45, P <

.007) and of subsequent severe episodes of apnea (8/28 V 5/45, P < .06) was higher in group 1 infants than in infants in other groups.

There were 51 infants who had at least two symptomatic siblings with either apnea of infancy or SIDS (groups 1, 2, and 4). The results of clinical testing on those infants were not different from results in the other study infants (groups 3 and 5) who had only bne symptomatic sibling. However, infants with at least two symptomatic siblings had

TABLE 3. Results of Stu dies and Outcome for 73 Infants5

Group No. of

Infants Abnormal Poly-somnogram Abnormal Pneumogram Subsequent Severe Apnea Death

1 28(7) 3(0) 13(4) 8(2) 5(1)

2 17(6) 2(1) 4(1) 3(0) 0

3 19 (3) 1 (0) 7 (1) 0 0

4 6(0) 0 4(0) 2(0) 0

5 3(1) 1(0) 2(0) 0 0

Total 73 (17) 7 (1) 30 (6) 13 (2) 5 (1)

SResults in parentheses are numbers of half-siblings.

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a significantly higher incidence of subsequent epi-sodes of apnea of infancy than infants having no symptomatic siblings (13/51 v 0/22, P < .006). The incidence of death was not different.

Of the

73

infants, 17 were half siblings. The clinical data, the incidence of abnormal results on testing, and the outcome were not different for the half siblings compared with the full siblings. Seven infants in group 1 were half siblings and, although the number affected was small, they had a higher risk for adverse outcome than half siblings in the other groups (3/7 v 0/10, P = .05).

DISCUSSION

We have prospectively followed 73 infants who had two or more previous siblings who either died

of SIDS, had symptoms of apnea of infancy, or had abnormalities on polygraph or pneumogram record-ings. There was a distinct difference in mortality rate between infants who were siblings of two or more previous SIDS victims and the remaining 45 infants. The death rate for siblings of two or more SIDS victims in this study (17.9%) is higher than that reported by Peterson et al2 (1.9%) and Irgens et al3 (0.56%) for siblings of one SIDS victim.

It is apparent from this and other reports that there is a tendency for familial aggregation of SIDS victims. Whether this is due to genetic or environ-mental factors, or is prenatal or postnatal in origin, is unknown. Current evidence does not support a genetic etiology for SIDS. It is conceivable that most SIDS events are sporadic and that the major-ity of siblings have the same risk as the general population, but that a relatively small number of families with a high incidence of SIDS alters the overall average risk.

Families with SIDS repetition have been evalu-ated with respect to various social and environmen-tal factors and, although no significant associations

were found, mothers of multiple SIDS victims

tended to be younger and had fewer full brothers and sisters than mothers with only a single SIDS victim.1 Seven infants in group 1 were half siblings

(25%), which may be an indication of a disruptive social situation in families with clustering of SIDS cases. A recent report by Rosen et al,8 based on a family with three previous SIDS victims, suggests that some cases of SIDS were parentally induced

and represent a form of child abuse. Included in the

present study are two families who had four SIDS victims and two families who had three SIDS

vic-tims; however, we are unable to identify any evi-dence of child abuse in these families.

Previous studies have shown that subsequent siblings of SIDS victims have an increased

mci-dence of periodic breathing and apnea of short

duration during sleep.9 Ofthe patients in this study, 33% had abnormal results on initial or subsequent

pneumogram recordings, and 8% had

hypoventila-tion during sleep. Abnormal results on these tests

had no correlation with the outcome. However, because some of the recordings were obtained

dur-ing treatment with methylxanthines, it is possible that this treatment may have altered the incidence of abnormalities and affected the outcome.

The risk of adverse outcome is significantly

greater for an infant born into a family with two or more previous infants with SIDS and/or apnea of

infancy, than for infants in families with only one symptomatic infant and a second infant with

ab-normal tests. The only deaths in this study occurred

in those families with two or more previous infants

who died of SIDS. The increased risk of death among infants in this latter group might be the

result of a defect in physiology or in the parental response to the event. However, if the parents had been successful in resuscitating all five infants, the

incidence of adverse outcome in this group would be significantly greater than that of adverse out-come in all other groups combined (13/28 v 5/45, P

< .001). Although the numbers are small, these data suggest that a third sibling who is born to families

who had two previous infants who were monitored because of apnea or abnormal screening tests is not

at high risk of death if monitored properly. Further studies on similar populations need to be done to

better identify a determinant of adverse outcome. Until this is done, home monitoring should be considered for infants born to families in which two or more full or half siblings of the new infant have died of SIDS or had apnea of infancy.

ACKNOWLEDGMENTS

We thank Denise Strieder, MD, for reviewing the

manuscript, Janet Grimes for technical help, and Barbara

Perry for manuscript preparation.

REFERENCES

1. Steinschneider A: Prolonged apnea and the sudden infant

death syndrome: Clinical and laboratory observations. Pe-diatrics 1972;50:646-654

2. Peterson DR, Chinn NM, Fisher LD: The sudden infant

death syndrome: Repetitions in families. J Pediatr

1980;97:265-267

3. Irgens LM, Skjaerven R, Peterson DR: Prospective

assess-ment of recurrent risk in sudden infant death syndrome

siblings. J Pediatr 1984;104:349

4. Oren J, Kelly D, Shannon DC: Identification of a high-risk group for sudden infant death syndrome among infants who

were resuscitated for sleep apnea. Pediatrics 1986;77:495-499

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358 SUDDEN INFANT DEATH AND APNEA

6. Shannon DC, Kelly DH: SIDS and near-SIDS. N Engl J Med 1982;306:959-965

7. Guilleminault C, Korobkin R: Sudden infant death: Near miss events and sleep research: Some recommendations to

improve comparability of results among investigators. Sleep

1979;1:423-433

8. Rosen CL, Frost JD Jr, Bricker T, et al: Two siblings with recurrent cardiorespiratory arrest: Munchausen syndrome by proxy or child abuse? Pediatrics 1983;71:715-720

9. Kelly DH, Walker AM, Cahen L, et al: Periodic breathing

in siblings of sudden infant death syndrome victims. Pedi-atrics1980;66:515-520

IT’S ALL THERE

BUT

THE

THRILL

Not long ago the British journal Nature published a report titled, “A new

class of Echinodermata from New Zealand.” In it the authors describe an animal previously unknown to science, nine of which were discovered on waterlogged wood dredged up from the ocean off the New Zealand coast.

The report in Nature follows the standard format for announcing such a

discovery. Missing, as from all such reports, are the thoughts and emotions of

the discoverers. Of them, we know only their names and their place of employ-ment.

By a self-imposed prohibition, scientific reporting allows little room for human emotion. We must rely on the imagination to supply the feelings that were present at that magical moment when the two New Zealanders and the Australian recognized that they had found something significantly new-ela-tion, laughter, amazement, relief, joy in the successful hunt, surprise, gratitude, the electrifying tingle in the spine.

From Raymo C: Science musings. Globe, Sept 15, 1986.

Submitted by Mary Ellen Avery

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1987;80;355

Pediatrics

Joseph Oren, Dorothy H. Kelly and Daniel C. Shannon