Sudden Infant Death A
Syndrome
Prospective Study
Richard L.
Naeye, MD;
Bertha
Ladis; Joseph S. Drage, MD
\s=b\ One hundred twenty-five sudden infant death syndrome (SIDS) victims followed up since birth from a large prospective study were compared with matched controls. Some of the future SIDS victims showed evidences of neonatal brain dysfunction including abnormalities in respiration, feeding, temperature regulation, and specific neurologic tests. These abnormalities could not be related to events in labor or delivery. A greater proportion of the future victims were mildly underweight for gestational age. The gestations that produced the SIDS victims were characterized by a greater frequency of mothers who smoked cigarettes and had anemia. The demographic profile of SIDS families proved to be indentical to the profile for families with excessive perinatal mortality. Many of the SIDS victims showed a retardation in postnatal growth prior to death. (Am J Dis Child 130:1207-1210, 1976)
number of pathogenic mecha¬ nisms have been proposed to explain the sudden infant death
A
syndrome (SIDS). Early hypotheses postulated a precipitous event in an apparently normal infant. Recent
From the Department of Pathology, Milton S. Hershey Medical Center, Pennsylvania State University College of Medicine, Hershey (Dr Naeye and Ms Ladis), and the National Institute of Neurologic and Communicative Disorders and Stroke, Bethesda, Md (Dr Drage). Reprint requests to Department of Pathology, Milton S. Hershey Medical Center, Hershey, PA 17033 (Dr Naeye).
studies have found that a substantial proportion of SIDS victims exhibit features of antecedent chronic pul¬ monary hypoventilation and hypoxemia.1 These observations support the view that SIDS may sometimes be due to abnormal maturation or injury to the brain stem centers that regu¬ late respiration.14 Whether due to dysmaturity or to injury, it would be surprising if functional abnormalities were confined to respiration, because brain stem areas that control respira¬ tion are not completely segregated from other vital centers. The current study examined brain functions unre¬ lated to respiratory control in future SIDS victims. A search was also made for events that might have damaged fetal or infant brains and thereby predisposed to SIDS. -''
PATIENTS AND METHODS The Collaborative Perinatal Project of the National Institute of Neurological and Communicative Disorders and Stroke pro¬ vides a unique opportunity to study SIDS prospectively. It followed up the course of 59,379 pregnancies and recorded events of gestation, labor, delivery, and the neonatal period as well as children's mental, motor, and physical development to 8 years of age.7'" All of the children were born between 1959 and 1966 in collaborating hospitals in the following cities: Boston Buffalo, NY; New Orleans; New York
Baltimore; Richmond, Va; Philadelphia Minneapolis; Portland, Ore; Providence, RI and Memphis, Tenn. A single investigator (R.N.) personally reviewed all the clinical and postmortem material from the 3,987 unsuccessful pregnancies and infant
deaths in the study. One hundred twentyfive of these deaths were categorized as SIDS because they were sudden, complete¬ ly unexpected, and unexplained by any acute disease process found at postmortem examination. This made the overall SIDS incidence rate 2.3/1,000 births. Ages of SIDS victims at death ranged from 2 weeks to 18 months. The demographic character¬ istics of the SIDS victims were determined by comparing them with all 53,721 infants of the collaborative study who were born alive, survived the neonatal period, and had the relevant demographic data recorded. They were subsequently designated "un¬ matched controls." Comparisons were then made with 375 infants matched with the victims for place of birth, date of delivery, gestational age, sex, race, and socioeconomic status. These are subsequently designated "matched controls." All of these matched controls are still alive. No infants who had major congenital anomalies were included in the SIDS or matched controls categories. The 2 and Student ( tests were used to determine the significance of differences between SIDS victims and controls. Definitions and details of clinical tests, laboratory investigations, and other observations have been published previous¬ ly.7'" Data were complete or nearly complete for all categories analyzed in both SIDS victims and matched controls.
RESULTS Factors
Demographic
Sudden infant death syndrome
significantly
was
in
blacks, males, and infants with blood type (Table 1). It was also more common more common
when mothers were young, of low socioeconomic status, low educational level, unmarried, and lived in crowded
Downloaded From: http://archpedi.jamanetwork.com/ by a DALHOUSIE UNIVERSITY-DAL-11762 User on 06/19/2015
There were no differences in prepregnancy body
housing (Table 1).
Table 1 .—Demographic Information on Sudden Infant Death Syndrome (SIDS) Victims and Controls
weight, height, or gestational weight gain between mothers of future SIDS victims and controls, but a dispropor¬ tionate number of future victims were in low weight categories at birth for
gestational age, indicating a mild degree of fetal growth retardation (Table 2). Obstetrical History and Current Pregnancy
Mothers of future SIDS victims had more prior fetal losses (Table 1). They had no excess of previous abortions or deaths of older children. They also had no excess of multiple births, preterm deliveries, consanguinity, or a wide variety of congenital and acquired disorders including those that involve the neuromuscular systems. Maternal cigarette smoking was greater in both rate and amount in gestations that produced SIDS victims (Table 3). Maternal anemia, proteinuria, vaginitis, and puerperal infections were more common in the gestations that produced victims. Mothers of the victims made fewer prenatal clinic visits. They had no excess of toxemia, hydramnios, abdominal x-irradiation, or
vaginal bleeding.
Two hundred sixty-nine different drugs and immunizing agents were used by one or more SIDS and matched control mothers during preg¬ nancy. Utilization rates for these agents were less in SIDS cases than in the controls, with several exceptions.
exceptions were as follows, expressed as rates for SIDS and control mothers, respectively: poly¬ valent influenza vaccine, 3.2% and 2.7%; smallpox vaccine, 1.6% and 0%; phénobarbital, 7.2% and 0%; iron dextran, 9.6% and 3.2%; hydrochloroThe
thiazide, 15.2% and
Siblings
There was no excess of any congen¬ ital or acquired disorder in fathers or siblings of SIDS victims by compar¬ ison with controls.
Delivery
during labor that distinguished future SIDS victims from controls, including There
or
were no
delivery
events
Unmatched Controls
Matched Controls
(N
(N=375)
=
53,721)
Cases
(N Neonates White Black Male Blood group Mothers
=
125)
46
No. (%)
No.
(37) 76(61) 84 (67) 35 (28)
24,711 (46) 25,249(47) 27,398(51) 8,461 (16)
Syndrome
Prospective Study
Richard L.
Naeye, MD;
Bertha
Ladis; Joseph S. Drage, MD
\s=b\ One hundred twenty-five sudden infant death syndrome (SIDS) victims followed up since birth from a large prospective study were compared with matched controls. Some of the future SIDS victims showed evidences of neonatal brain dysfunction including abnormalities in respiration, feeding, temperature regulation, and specific neurologic tests. These abnormalities could not be related to events in labor or delivery. A greater proportion of the future victims were mildly underweight for gestational age. The gestations that produced the SIDS victims were characterized by a greater frequency of mothers who smoked cigarettes and had anemia. The demographic profile of SIDS families proved to be indentical to the profile for families with excessive perinatal mortality. Many of the SIDS victims showed a retardation in postnatal growth prior to death. (Am J Dis Child 130:1207-1210, 1976)
number of pathogenic mecha¬ nisms have been proposed to explain the sudden infant death
A
syndrome (SIDS). Early hypotheses postulated a precipitous event in an apparently normal infant. Recent
From the Department of Pathology, Milton S. Hershey Medical Center, Pennsylvania State University College of Medicine, Hershey (Dr Naeye and Ms Ladis), and the National Institute of Neurologic and Communicative Disorders and Stroke, Bethesda, Md (Dr Drage). Reprint requests to Department of Pathology, Milton S. Hershey Medical Center, Hershey, PA 17033 (Dr Naeye).
studies have found that a substantial proportion of SIDS victims exhibit features of antecedent chronic pul¬ monary hypoventilation and hypoxemia.1 These observations support the view that SIDS may sometimes be due to abnormal maturation or injury to the brain stem centers that regu¬ late respiration.14 Whether due to dysmaturity or to injury, it would be surprising if functional abnormalities were confined to respiration, because brain stem areas that control respira¬ tion are not completely segregated from other vital centers. The current study examined brain functions unre¬ lated to respiratory control in future SIDS victims. A search was also made for events that might have damaged fetal or infant brains and thereby predisposed to SIDS. -''
PATIENTS AND METHODS The Collaborative Perinatal Project of the National Institute of Neurological and Communicative Disorders and Stroke pro¬ vides a unique opportunity to study SIDS prospectively. It followed up the course of 59,379 pregnancies and recorded events of gestation, labor, delivery, and the neonatal period as well as children's mental, motor, and physical development to 8 years of age.7'" All of the children were born between 1959 and 1966 in collaborating hospitals in the following cities: Boston Buffalo, NY; New Orleans; New York
Baltimore; Richmond, Va; Philadelphia Minneapolis; Portland, Ore; Providence, RI and Memphis, Tenn. A single investigator (R.N.) personally reviewed all the clinical and postmortem material from the 3,987 unsuccessful pregnancies and infant
deaths in the study. One hundred twentyfive of these deaths were categorized as SIDS because they were sudden, complete¬ ly unexpected, and unexplained by any acute disease process found at postmortem examination. This made the overall SIDS incidence rate 2.3/1,000 births. Ages of SIDS victims at death ranged from 2 weeks to 18 months. The demographic character¬ istics of the SIDS victims were determined by comparing them with all 53,721 infants of the collaborative study who were born alive, survived the neonatal period, and had the relevant demographic data recorded. They were subsequently designated "un¬ matched controls." Comparisons were then made with 375 infants matched with the victims for place of birth, date of delivery, gestational age, sex, race, and socioeconomic status. These are subsequently designated "matched controls." All of these matched controls are still alive. No infants who had major congenital anomalies were included in the SIDS or matched controls categories. The 2 and Student ( tests were used to determine the significance of differences between SIDS victims and controls. Definitions and details of clinical tests, laboratory investigations, and other observations have been published previous¬ ly.7'" Data were complete or nearly complete for all categories analyzed in both SIDS victims and matched controls.
RESULTS Factors
Demographic
Sudden infant death syndrome
significantly
was
in
blacks, males, and infants with blood type (Table 1). It was also more common more common
when mothers were young, of low socioeconomic status, low educational level, unmarried, and lived in crowded
Downloaded From: http://archpedi.jamanetwork.com/ by a DALHOUSIE UNIVERSITY-DAL-11762 User on 06/19/2015
There were no differences in prepregnancy body
housing (Table 1).
Table 1 .—Demographic Information on Sudden Infant Death Syndrome (SIDS) Victims and Controls
weight, height, or gestational weight gain between mothers of future SIDS victims and controls, but a dispropor¬ tionate number of future victims were in low weight categories at birth for
gestational age, indicating a mild degree of fetal growth retardation (Table 2). Obstetrical History and Current Pregnancy
Mothers of future SIDS victims had more prior fetal losses (Table 1). They had no excess of previous abortions or deaths of older children. They also had no excess of multiple births, preterm deliveries, consanguinity, or a wide variety of congenital and acquired disorders including those that involve the neuromuscular systems. Maternal cigarette smoking was greater in both rate and amount in gestations that produced SIDS victims (Table 3). Maternal anemia, proteinuria, vaginitis, and puerperal infections were more common in the gestations that produced victims. Mothers of the victims made fewer prenatal clinic visits. They had no excess of toxemia, hydramnios, abdominal x-irradiation, or
vaginal bleeding.
Two hundred sixty-nine different drugs and immunizing agents were used by one or more SIDS and matched control mothers during preg¬ nancy. Utilization rates for these agents were less in SIDS cases than in the controls, with several exceptions.
exceptions were as follows, expressed as rates for SIDS and control mothers, respectively: poly¬ valent influenza vaccine, 3.2% and 2.7%; smallpox vaccine, 1.6% and 0%; phénobarbital, 7.2% and 0%; iron dextran, 9.6% and 3.2%; hydrochloroThe
thiazide, 15.2% and
Siblings
There was no excess of any congen¬ ital or acquired disorder in fathers or siblings of SIDS victims by compar¬ ison with controls.
Delivery
during labor that distinguished future SIDS victims from controls, including There
or
were no
delivery
events
Unmatched Controls
Matched Controls
(N
(N=375)
=
53,721)
Cases
(N Neonates White Black Male Blood group Mothers
=
125)
46
No. (%)
No.
(37) 76(61) 84 (67) 35 (28)
24,711 (46) 25,249(47) 27,398(51) 8,461 (16)
