Cardiorespiratory function in 16 full-term infants with sudden infant death syndrome

Twenty-four-hour tape recordings of ECG and breathing movements from 16 term infants (greater than or equal to 37 weeks' gestation) who subsequently died of sudden infant death syndrome (SIDS) were compared with recordings from surviving infants from the same populations. Apneic pauses of varying durations, periodic and regular breathing patterns, heart and respiratory rates during regular breathing were measured. Only one of 16 full-term infants with SIDS had findings outside the range of age-matched control infants (an excess of periodic breathing patterns and an absence of regular breathing). When the first recordings of each of infants who died of SIDS, except one who had cyanotic episodes prior to death, were compared to recordings of survivors (six for each case) closely matched for age, gestation, and weight at birth, no differences in breathing patterns or heart or respiratory rates during regular breathing could be demonstrated. These particular measurements of cardiorespiratory function were, therefore, unable to identify the majority of full-term infants at risk for SIDS.     

Size for gestational age at birth: impact on risk for sudden infant death and other causes of death, USA 2002

Background

Small for gestational age (SGA) infants have been reported to be at higher risk for sudden infant death syndrome (SIDS).

Objective

To compare the risk of SIDS among SGA and large for gestational age (LGA) infants with that of death from other causes of sudden unexpected deaths in infancy (SUDI) and the residual “other” causes of infant death.

Methods

The 2002 US period infant birth and death certificate linked file was used to identify infant deaths classified as SIDS (ICD‐10 code R95), SUDI (ICD‐10 codes R00‐Y84 excluding R95) or all other residual codes. The 2002 race and sex‐specific birth cohorts were used to generate the 10th and 90th percentiles of birth weight for each gestational age week from 24 to 42 weeks'' gestation. Demographic variables previously identified as associated with SIDS were used in multiple logistic regression equations to determine the risk for death among SGA and LGA infants (birth weight <10th percentile and >90th percentile, respectively) independent of other potentially confounding variables.

Results

Complete data on 1956 SIDS deaths, 2012 SUDI, and 11 592 other deaths were available. The adjusted OR for SIDS, SUDI and “other” causes for SGA infants was 1.65 (95% CI 1.47 to 1.85), 1.78 (1.59 to 2.00) and 4.68 (4.49 to 4.88), respectively. The adjusted OR for LGA infants was reduced for SIDS (0.73 (0.60 to 0.89)), SUDI (0.81 (0.68 to 0.98)) and “other” (0.42 (0.38 to 0.46)).

Conclusion

Although SGA infants seem to be at slightly increased risk for SIDS or SUDI their risk for “other” residual causes is about 2.5 times higher. LGA infants seem to be at reduced risk of mortality for all causes. The mechanisms by which restricted intrauterine growth increases risk of mortality and excessive intrauterine growth offers protective effects are uncertain.Small for gestational age (SGA) infants have been reported to be at 1.4 to 2.0 times greater risk for sudden infant death syndrome (SIDS).1,2,3,4,5 Other causes of death have also been reported to be associated with being SGA by some authors,6,7 in particular, preterm SGA infants are reported to have an increased risk of death ranging from 2.4 to 3.6 times that of appropriate for gestational age (AGA) preterm infants.8,9 Other authors, however, have observed no increase in risk for other causes of death among term SGA infants after adjusting for racial disparities in birth weight.10 The mechanisms associated with the increased risk for SIDS among SGA infants remain unclear, but some investigators have suggested that the risk may be secondary to the hypoxia these infants are suspected of being exposed to in utero.11,12 Why in utero hypoxia may make an infant more vulnerable to SIDS has been hypothesised to be related to a reduction of serotonergic receptors in multiple brainstem nuclei.13,14Despite the biological plausibility of the hypoxic‐related vulnerability of SGA infants for SIDS, comparative studies of just how much greater risk such an infant has for SIDS compared with other causes of death are not replete in the literature. Thus, the purpose of this analysis was to determine whether SGA infants were at greater risk for SIDS compared with other causes of death. The risk of large for gestational age (LGA) infants for SIDS has not been closely examined and an examination of this relationship was thus included in the analysis. Because of a trend towards the reclassification of SIDS deaths to other causes of sudden unexpected causes of death (SUDI),15 the risk of SUDI excluding SIDS for SGA infants as well as the risk of the remaining residual “other” causes of death among these infants was examined for the USA for the year 2002.     

Polysomnographic studies and home monitoring of siblings of SIDS victims and of infants with no family history of sudden infant death

We report preliminary results of a prospective study conducted to prevent sudden death in asymptomatic infants. From 1977–1984, 3658 infants were studied polygraphically. There were 923 siblings of SIDS victims and 2735 infants with no personal of family history of SIDS. The infants were studied at 8 weeks of age. Polygraphic risk factors were defined by central apnoeas longer than 15s; periodic breathing above 5% sleep time; or obstructive apnoeas above 3s. In 937 infants risk factors were seen and a second study was requested 4 weeks later. Out of 891 infants re-studied at 12 weeks, 153 still presented some risk factors and were selected for a home monitoring programme; 150 families agreed to monitor their infants at home with a cardiorespiratory monitor with the alarms set at 20s apnoea, and 50 beats per min bradycardia. Repeated alarms were reported for 97/150 (65%) infants; 48/150 (32%) infants were stimulated and 8/150 (5.3%) were resuscitated on at least one occasion. No death occurred during monitoring, which could be interrupted before the end of the first year of life in all infants. In the group of 3459 infants with normal results and not monitored, three siblings (0.35%) and one infant without history (0.04%) died of SIDS. Of the infants with abnormal polygraphic results, one sibling not returned for the second recording, and two out of three infants for whom the parents refused monitoring, died of SIDS. It is concluded that the programme, may prevent the death of some infants, but that the outcome of a child with normal results cannot be foreseen.Abbreviation SIDS sudden infant death syndrome     

Risk factors for SIDS in Japan: A record-linkage study based on vital statistics

This study examines the effect of items as reported on birth certificates on sudden infant death. We linked infant death certificates with birth certificates for the infants born in 1989 to residents of the Tohoku, Tokai and Kyushu regions in Japan (n = 409 679), that is, about one-third of the infants born in Japan that year. The mortality rate from sudden infant death, including 88 deaths from sudden infant death syndrome (SIDS) and 17 deaths from instantaneous death, was 25.6 per 100 000 live births. Elevated risk of sudden infant death was associated with low birthweight, late birth order, illegitimacy, male gender and young maternal age. These results correspond to previous studies from Western countries, suggesting a similar pattern for SIDS in Japan.     

Prevention of sudden infant death syndrome (SIDS) due to an active health monitoring system 20 years prior to the public "Back to Sleep" campaigns

Background

Before reunification, the post‐neonatal mortality rate was lower in East Germany than in West Germany. Moreover, the incidence of SIDS (sudden infant death syndrome) was much lower in the East.

Methods

Mortality data on sudden infant death syndrome (SIDS) from West and East Germany since 1980 as well as post‐neonatal mortality data for both states since 1970 were examined. 95% Confidence intervals were calculated for the rates. Witnesses from the former East Germany who were involved at the time were also interviewed and archives were searched.

Results

We found that as early as 1972 active monitoring of infant and child mortality rates in East Germany had shown that the prone sleeping position was dangerous for infants: the post‐neonatal mortality rate was approximately 1 per 1000 live births lower in East than in West Germany during the 20 years before reunification. In contrast, in the West, prone sleeping was only discovered to be a risk factor for SIDS in the early 1990s.

Conclusions

Active monitoring is an effective tool in the early detection of risk factors and serves to prevent unnecessary deaths.     

Sudden infant death syndrome in pediatric surgical cases and consequences for postoperative care

We encountered 5 cases of sudden infant death syndrome (SIDS) at the Pediatric Surgical Clinic of the University Children's Hospital of Munich from 1976 to 1985. This corresponded to 0.2 of the cases treated as inpatients during this 10-year period. Consequently, all infants requiring anesthesia and surgery during their first 6 months of life and who were premature, have had apneic spells or other respiratory problems, or have congenital heart disease are monitored for at least 4 days following surgery, even if they undergo operations that would otherwise be performed in the frame of 1-day surgery. No further case of SIDS was encountered since the introduction of this measure in 1985. Moreover, a former premature who was operated on for umbilical hernia and developed bradycardia postoperatively was saved by intensive care. Without monitoring, this child could well have been our 6th case of SIDS (near-miss event). Offprint requests to: T. A. Angerpointner     

Sudden infant death syndrome in infants born to HIV-infected and opiate-using mothers

Objective

This study was undertaken to determine the role of opiate use during pregnancy as a predisposing factor for sudden infant death syndrome (SIDS) in infants born to HIV‐infected mothers.

Methods

In order to identify all infant deaths and their cause and association with maternal opiate use, the data of a nationwide prospective cohort study of HIV‐infected mothers and their children were extracted and analysed for a 13‐year period.

Results

24 (5.1%) infant deaths were observed out of 466 infants followed up until death or at least 12 months of life. 3 (0.6%) of them were due to non‐accidental trauma and were not associated with maternal opiate use. 7 (1.5%) died due to SIDS, which was confirmed by autopsy. All SIDS cases occurred in infants born to mothers reporting use of opiates during pregnancy (n = 124). The relative risk of SIDS compared to the general population was 18 (95% CI 9 to 38) for all infants of HIV‐infected mothers, and 69 (95% CI 33 to 141) for those with intrauterine opiate exposure (p<0.001).

Conclusions

Compared to the Swiss general population, the risk for SIDS in this cohort of infants born to HIV‐infected mothers was greatly increased, but only for mothers reporting opiate use during pregnancy. This effect appeared not to be mediated by prematurity, low birth weight, perinatal HIV infection or antiretroviral drug exposure.The evidence for a link between opiate use and sudden infant death syndrome (SIDS) in the general infant population is inconsistent.^1,2,3,4 In infants of HIV‐infected mothers, an increased rate of verified SIDS possibly related to maternal opiate use was noted in several cohorts, namely 5/1000 live births in the European Collaborative Study,⁵ 6/1000 in France⁶ and 14/1000 in Switzerland.⁷ Thus, a detailed analysis of this link in the Swiss cohort was thought to be worthwhile.This study was undertaken to determine the frequency and causes of non‐HIV‐related infant deaths in the Swiss Mother & Child HIV Cohort (MoCHiV), with special attention given to SIDS and the role of maternal heroin and/or methadone consumption during pregnancy. In addition, the role of non‐accidental trauma and of potential risk factors such as prematurity, low birth weight, maternal HIV infection and antiretroviral medication, were explored.     

A clinical comparison of SIDS and explained sudden infant deaths: how healthy and how normal?

OBJECTIVES—To compare the clinical characteristics associated with sudden infant death syndrome (SIDS) and explained sudden unexpected deaths in infancy (SUDI).
DESIGN—Three year population based, case control study with parental interviews for each death and four age matched controls.
SETTING—Five regions in England (population, > 17 million; live births, > 470 000).
SUBJECTS—SIDS: 325 infants; explained SUDI: 72 infants; controls: 1588infants.
RESULTS—In the univariate analysis, all the clinical features and health markers at birth, after discharge from hospital, during life, and shortly before death, significant among the infants with SIDS were in the same direction among the infants who died of explained SUDI. In the multivariate analysis, at least one apparent life threatening event had been experienced by more of the infants who died than in controls (SIDS: 12% v 3% controls; odds ratio (OR) = 2.55; 95% confidence interval (CI), 1.02 to 6.41; explained SUDI: 15% v 4% controls; OR = 16.81; 95% CI, 2.52 to 112.30). Using a retrospective illness scoring system based on "Baby Check", both index groups showed significant markers of illness in the last 24 hours (SIDS: 22% v 8% controls; OR = 4.17; 95% CI, 1.88to 9.24; explained SUDI: 49% v 8% controls; OR = 31.20; 95% CI, 6.93 to 140.5).
CONCLUSIONS—The clinical characteristics of SIDS and explained SUDI are similar. Baby Check might help identify seriously ill babies at risk of sudden death, particularly in high risk infants.
     

Serum 25-hydroxyvitamin D concentrations in sudden infant death syndrome

Among the many theories put forth to explain sudden infant death syndrome (SIDS) is a theory of vitamin D deficiency. 25-Hydroxyvitamin D (25-OHD) serum concentrations were measured in 31 SIDS and 24 postmortem control infants. 25-OHD was 19.0 +/- 7.9 mg/ml in SIDS, 16.9 +/- 5.2 ng/ml in acute death control infants, and 11.9 +/- 4.4 ng/ml in in-hospital deaths. For four "near miss" infants the mean serum 25-OHD concentration was 21.1 +/- 4.1 ng/ml. The mean serum 25-OHD concentration of 39 living premature or small-for-gestational-age infants at 3 months of age was 26 +/- 9.9. Serum calcium and serum copper concentrations were also the same in SIDS and control infants. Parathyroid hormone was measured in ten and was detectable in five SIDS infants. These data eliminate a simple vitamin D deficiency or a 25-OHD deficiency as a significant contribution to the pathophysiology of SIDS.     

Sudden infant death syndrome and sleeping position in pre-term and low birth weight infants: an opportunity for targeted intervention

Aims

To determine the combined effects of sudden infant death syndrome (SIDS) risk factors in the sleeping environment for infants who were “small at birth” (pre‐term (<37 weeks), low birth weight (<2500 g), or both).

Methods

A three year population based, case‐control study in five former health regions in England (population 17.7 million) with 325 cases and 1300 controls. Parental interviews were carried out after each death and reference sleep of age matched controls.

Results

Of the SIDS infants, 26% were “small at birth” compared to 8% of the controls. The most common sleeping position was supine, for both controls (69%) and those SIDS infants (48%) born at term or ⩾2500 g, but for “small at birth” SIDS infants the commonest sleeping position was side (48%). The combined effect of the risk associated with being “small at birth” and factors in the infant sleeping environment remained multiplicative despite controlling for possible confounding in the multivariate model. This effect was more than multiplicative for those infants placed to sleep on their side or who shared the bed with parents who habitually smoked, while for those “small at birth” SIDS who slept in a room separate from the parents, the large combined effect showed evidence of a significant interaction. No excess risk was identified from bed sharing with non‐smoking parents for infants born at term or birth weight ⩾2500 g.

Conclusion

The combined effects of SIDS risk factors in the sleeping environment and being pre‐term or low birth weight generate high risks for these infants. Their longer postnatal stay allows an opportunity to target parents and staff with risk reduction messages.     

The velo-cardio-facial (Shprintzen) syndrome

Twenty-eight children whose parents reported sleep apnoea were investigated. In 15 infants apnoeic periods during sleep could be confirmed during clinical observation. Ventilatory responses to CO₂ were measured in all infants, in 23 during sleep in 5 only when awake. A very wide range of CO₂ sensitivities was found. In four children there was no ventilatory response or even a paradox one: a decrease in ventilation as PACO₂ was increased. Two of these non-responding children died later, one still sleeps in a respirator aged three, and one developed a normal CO₂ sensitivity a few months later. It is concluded that the parent's account of an apnoeic incident during sleep is not always reliable. A ventilatory response to CO₂ is a useful tool with which to identify infants at risk of death, possibly related to a defective control of ventilation. The actual value of the CO₂ sensitivity hardly gives any useful information, due to the wide range of normal reactions. No or negative ventilatory responses to CO₂ seem to be indicators of high risk children, and may possibly play a role in SIDS incidents.Abbreviations REM rapid eye movements - SIDS sudden infant death syndrome - EOG electro oculo gram     

Sudden infant death syndrome and sleeping position in pre-term and low birth weight infants: an opportunity for targeted intervention.

AIMS: To determine the combined effects of sudden infant death syndrome (SIDS) risk factors in the sleeping environment for infants who were "small at birth" (pre-term (<37 weeks), low birth weight (<2500 g), or both). METHODS: A three year population based, case-control study in five former health regions in England (population 17.7 million) with 325 cases and 1300 controls. Parental interviews were carried out after each death and reference sleep of age matched controls. RESULTS: Of the SIDS infants, 26% were "small at birth" compared to 8% of the controls. The most common sleeping position was supine, for both controls (69%) and those SIDS infants (48%) born at term or > or =2500 g, but for "small at birth" SIDS infants the commonest sleeping position was side (48%). The combined effect of the risk associated with being "small at birth" and factors in the infant sleeping environment remained multiplicative despite controlling for possible confounding in the multivariate model. This effect was more than multiplicative for those infants placed to sleep on their side or who shared the bed with parents who habitually smoked, while for those "small at birth" SIDS who slept in a room separate from the parents, the large combined effect showed evidence of a significant interaction. No excess risk was identified from bed sharing with non-smoking parents for infants born at term or birth weight > or =2500 g. CONCLUSION: The combined effects of SIDS risk factors in the sleeping environment and being pre-term or low birth weight generate high risks for these infants. Their longer postnatal stay allows an opportunity to target parents and staff with risk reduction messages.     

Epidemiology of sudden infant death syndrome in Japan

An epidemiological survey was carried out to examine the present situation with respect to sudden infant death syndrome (SIDS) in Kanagawa Prefecture. Questionnaires on sudden unexpected death of infants aged < 1 year in 1990-91 were sent to the hospitals and clinics in Kanagawa Prefecture which may take care of such infants. By analysing information from 10 485 replies, 48 out of 73 reported sudden infant deaths were confirmed to be SIDS, although autopsy was not performed in 13 cases (27%). The incidence of SIDS per 1000 live births in Kanagawa Prefecture was 0.29 in 1990 and 0.31 in 1991; and if limited to autopsy cases 0.19 and 0.25, respectively. Sudden infant death syndrome cases in Japan were found to occur more frequently when infants were < 6 months old, at home and sleeping alone, but less in the winter and between midnight and early morning. There was little difference between the numbers in prone and supine sleeping positions at discovery. It was not clear whether SIDS occurred more often to babies sleeping prone than supine, because there were no controls matched with the SIDS cases. In future, continuous epidemiological surveys of SIDS in Japan should be carried out.     

Effects of naloxone on apnoea duration during sleep in infants at risk for SIDS

The effects of intravenous injections of the opiate antagonist naloxone (0.005–0.4 mg/kg body weight) on respiratory pattern, apnoea duration and frequency were investigated in six infants with severe sleep apnoea syndrome. Since several authors found elevated plasma- and CSF-levels of endogenous opioids (endorphines) in infants with sleep apnoea syndrome, we wanted to determine whether the impairment of the control mechanisms of respiration during sleep is due to an effect of endogenous opioids.Independent of the dose, naloxone did not exert any effect on respiratory pattern and occurrence of periodic apnoea. We were unable to prove that endorphines play a major role in pathogenesis of sleep apnoea syndrome in infancy and possibly in sudden infant death syndrome (SIDS).We speculate that elevated levels of endorphines reported by some investigators rather seem to be a consequence of hypoxic stress than a cause for sleep apnoeas.Abbreviations SIDS sudden infant death syndrome - CSF cerebral spinal fluid Supported by the Austrian Research Fund     

Concentrations of antimony in infants dying from SIDS and infants dying from other causes.

OBJECTIVES: Raised concentrations of antimony have been found in infants dying of sudden infant death syndrome (SIDS). The presumed source of this antimony is toxic gases generated from fire retardants that are present in cot mattresses. The aim of this study was to determine the role of antimony in SIDS. DESIGN: Samples of liver, brain, serum, and urine were collected from all patients dying from SIDS and a group of aged matched control infants who had died of other causes. SETTING: Nationwide study in Ireland. SUBJECTS: 52 infants dying from SIDS and 19 control infants aged > 7 days and < 1 year. RESULTS: The median concentration of antimony in the liver and brain of infants dying of SIDS was < 1 ng/g, with no difference detected between the infants dying from SIDS and the control infants. The range of antimony in the serum of infants dying of SIDS was 0.09-0.71 microg/litre (median, 0.26). Although no difference was found between infants dying from SIDS and control infants, SIDS infants were found to have higher concentrations when compared with healthy infants in the 1st year of life, probably as a result of release of antimony into serum after death. Urine antimony concentrations in infants dying from SIDS were < 3.91 ng/mg (corrected for creatinine) and similar to values found both in control infants and healthy infants. CONCLUSION: There is no evidence to support a causal role for antimony in SIDS.     

Neurocardiogenic syncope: a model for SIDS

A 5 1/2 month old male infant who had suffered three acute life threatening episodes was admitted for overnight sleep studies but was found dead after their completion while still in hospital. A necropsy classified the cause of death as sudden infant death syndrome (SIDS). The sleep studies had shown no periods of apnoea (> 20 seconds) or bradycardia (< 90 beats/min), and a rapid response to nasal occlusion (5 seconds). However, autonomic function during sleep was poor, with reduced heart rate variability (6 beats/min v control 24 beats/min, SD 6.2) and postural hypotension (a 12-14% fall in resting systolic blood pressure) associated with a fall in heart rate when tilted to a vertical position. Postural hypotension with bradycardia occurs in adults with unexplained syncopal episodes and is called a neurocardiac reflex. It involves poor vasomotor tone with peripheral pooling of blood, a consequent reduction in central venous return and cardiac distension, and in some individuals a neurally mediated bradycardia, as seen in this infant, rather than the expected tachycardia. A progressive bradycardia is the predominant mechanism of death seen in SIDS infants dying on cardiorespiratory monitors at home. This case suggests that a neurocardiac reflex occurs in infants, may have been involved in this infant's death, and deserves further study in the context of SIDS.     

Pre- and perinatal clinical characteristics of infants who suffer sudden infant death syndrome

In a population-based study, clinical and physiological data were collected in the neonatal period on 7,496 full-term (greater than or equal to 37 weeks) infants of birthweights greater than 2.50 kg born in 3 hospitals. The sample excluded a small number of infants who were born with severe illnesses from which there was no period of recovery before death in the neonatal period. Twenty-seven of the infants had died by the time all of the population had passed their third birthday. Twenty-one of these cases died suddenly and unexpectedly, and in 13 there was no adequate explanation for death (sudden infant death syndrome-SIDS). Pre- and early postnatal clinical data on the infants who had died were compared to a randomly selected sample of 478 survivors. This analysis showed that the infants who suffered SIDS showed similar clinical characteristics to those previously reported. Unlike the SIDS group, however, the prenatal histories of the non-SIDS deaths were similar to controls, showing no evidence of a sub-optimal intra-uterine environment.     

S cases have increased levels of interleukin-6 in cerebrospinal fluid

Cerebrospinal fluid (CSF) from 20 infants who died of sudden infant death syndrome (SIDS), 7 cases of infectious death and 5 cases of violent death were examined with respect to concentrations of interleukin-6 (IL-6). The measurements were performed by ELISA. IL-6 levels in SIDS were significantly lower than in infectious death (p < 0.02), but significantly higher than in violent death (p < 0.02). Since IL-6 plays an important role in immune responses and may induce fever, the findings may suggest that immune activation plays a role in SIDS. The presence of cytokines in the central nervous system (CNS) may cause respiratory depression, especially in vulnerable infants.     

Altered placental development in pregnancies resulting in sudden infant death syndrome (SIDS)

Background

Sudden infant death syndrome (SIDS) is postulated to be a developmental disorder originating during fetal life in utero. Knowledge regarding the intrauterine environment in which SIDS infants develop is, however, inadequate and how the placenta develops prior to a SIDS event has not been studied.

Aim

To investigate the morphological development of the placenta obtained from full-term infants who subsequently succumbed to SIDS.

Study design

To estimate the percentage and total volumes of the chorionic villi and villous trophoblast membrane using stereological techniques.

Subjects

Placentas were obtained retrospectively from normal birthweight (SIDS-NBW n = 18) and small-for-gestational age (SIDS-SGA, n = 14) infants who had succumbed to SIDS, and compared to either control (n = 8) or SGA placentas (n = 7), respectively.

Results

SIDS-NBW placentas displayed evidence of augmented villous growth shown by significantly greater volumes of placental chorionic villi (gas-exchanging (GE) villi) in comparison to controls; this was not observed for SIDS-SGA placentas. However, both SIDS-NBW and SIDS-SGA placentas displayed significantly greater volumes of the cytotrophoblast (CT) (SIDS-NBW only), syncytiotrophoblast (SIDS-SGA only) and syncytial knots (SCT-K) and those displaying apoptotic syncytial nuclei (AP SCT-K). In contrast, SGA placentas displayed significantly reduced volumes of chorionic villi, GE villi and the villous trophoblast indicating a SIDS-specific effect associated with augmented placental growth.

Conclusions

Our findings provide initial evidence that placental abnormality, although not necessarily causative, may precede a subset of SIDS cases supporting the hypothesis that the origins of SIDS begin during fetal life in utero.     

IL-6 cerebrospinal fluid levels are related to laryngeal IgA and epithelial HLA-DR response in sudden infant death syndrome.

The objective was to investigate whether there is any correlation between signs of central and peripheral immune stimulation in victims of sudden infant death syndrome (SIDS), the former expressed by IL-6 in cerebrospinal fluid (CSF), the latter by IgA, IgG, and IgM immunocytes, T lymphocytes, and HLA-DR expression in laryngeal mucosa. Seventeen SIDS cases with low CSF IL-6 levels (< or =5 pg/mL) and 20 cases with high CSF IL-6 levels (> or =30 pg/mL) were subjected to immunohistochemical quantitation of IgA, IgG, and IgM immunocytes; semiquantitative scoring of T lymphocytes in the mucosa of epiglottis and larynx, and semiquantitative evaluation of HLA-DR expression. SIDS cases with IL-6 levels > or =30 pg/mL had a significantly higher number of IgA immunocytes in laryngeal mucosa (p = 0.007) and in epiglottis (p = 0.03) than cases with IL-6 levels < or =5 pg/mL. Furthermore, laryngeal HLA-DR expression was significantly more extensive in SIDS cases with IL-6 levels > or =30 pg/mL than in those with levels < or =5 pg/mL (p = 0.05). No differences were found for IgG and IgM immunocytes or for T cells. In addition, babies found prone more often had symptoms of slight infection before death and had a higher number of IgA immunocytes in the larynx (p = 0.02) than babies sleeping on their side or back. Because IL-6 levels > or =30 pg/mL correspond to the levels found in infants who die from infectious diseases such as meningitis/septicemia and pneumonia, the findings favor the hypothesis that many SIDS cases may be caused by an "overreaction" of the immune system to an otherwise harmless infection.