Infections are implicated in SIDS

Most SIDS cases occur at ages one to four months. This probably reflects a specific, temporary physiological vulnerability during this time. At birth, infants have an immune system that is biased toward a Th2 response, which would make them more susceptible to certain infections and manifestations of those infections. At the ages of greatest risk of sudden infant death, maternal antibody levels have decreased while the infant's own immune system is still immature. Only 2 or 3 percent of SIDS deaths occur after the age of one year.

The socioeconomic associations with SIDS are nearly identical with those of chorioamnionitis, which is the cause of perinatal illnesses blamed on smoking. Smoking, black race, lower socioeconomic status, etc., are all associated with both, and these are just markers for markers for earlier and more frequent exposure to a larger number of pathogens postnatally as well as prenatally.

Sleeping position is the most important risk found to date

In The Netherlands, the prone sleeping position was rarely used for infants before 1972. After 1971, publicity from the Dutch medical and popular media promoting this position increased its use from about 10% to 55-65% of infants. From 1969 to 1983-4, the death rates from SIDS rose from 0.44 per 1000 in 1969 to between 1.08 and 1.31 per 1000 in 1977-87. Also during this period, the percentage of women smokers aged 20-34 years declined from 58% to around 35%. SIDS death rates in The Netherlands dropped sharply, to 0.44 per 1000 in 1991, after publicity advocating placing infants on their backs to sleep instead (AC Engelberts, GA de Jonge, PJ Kostense. An analysis of trends in the incidence of sudden infant death in The Netherlands 1969-89. Paediatr Child Health 1991 Dec;27(6):329-333; Sleeping position for infants and cot death in The Netherlands 1985-91. GA de Jonge, RJ Burgmeijer, AC Engelberts, J Hoogenboezem, PJ Kostense, AJ Sprij. Arch Dis Child 1993 Dec;69(6):660-663).

The contribution of changes in the prevalence of prone sleeping position to the decline in Sudden Infant Death Syndrome in Tasmania. T Dwyer, AL Ponsonby, L Blizzard, NM Newman, JA Cochrane. JAMA 1995 Mar 8;273(10):783-789. "The Tasmanian SIDS rate decreased (P < .01) from 3.8 (95% confidence interval [CI], 3.5 to 4.2) deaths per 1000 live births from 1975 through 1990 to a rate of 1.5 (95% CI, 0.9 to 2.2) deaths per 1000 live births in 1991 through 1992."

News. Cot deaths. BMJ 1995 Jan 7;310(6971):7-10; Trends in rates and seasonal distribution of sudden infant deaths in England and Wales, 1988-92. EA Gilman, KK Cheng, HR Winter, R Scragg. BMJ 1995 Mar 11;310(6980):631-632. "[S]udden infant death rates rose more or less continuously from 1971 to a peak of 2.30 deaths per 1000 live births in 1988. Rates then fell steadily to 1.44 in 1991 and abruptly to 0.70 in 1992."

The epidemic of SIDS in Norway 1967-93: changing effects of risk factors. AK Daltveit, N Øyen, R Skjærven, LM Irgensa. Arch Dis Child 1997 Jul;77:23-27. "The SIDS rate was 1.25 in 1967, reached a peak of 2.69 in 1988 and declined to 0.59 in 1993."

Case-control study of current validity of previously described risk factors for SIDS in The Netherlands. MP l'Hoir, AC Engelberts, GT van Well, P Westers, GJ Mellenbergh, WH Wolters, J Huber. Arch Dis Child 1998 Nov;79(5):386-393. In 1995, the death rates had declined to 0.26 per 1000 livebirths.

Changes in the epidemiology of sudden infant death syndrome in Sweden 1973-1996. B Alma, S G Norveniusa, G Wennergrena, R Skjærvenb, N Øyenb, J Mileradc, M Wennborgc, J Kjaerbecka, K Helweg-Larsend, L M Irgensb, on behalf of the Nordic Epidemiological SIDS Study. Arch Dis Child 2001;84:24-30. In Sweden, between 1973 and 1992, there was a dramatic rise in the rates of sudden, unexplained infant deaths, from about 0.3 to 1.1 per thousand. In 1992, after publicity advocating face-up instead of face-down sleeping for infants, there was an even more dramatic fall in the incidence, with the rates returning to 1973 levels over a period of six years (Fig. 1). These dramatic changes in the incidence of SIDS do not correlate at all with the small, steady declines in smoking during the same 26-year period. Furthermore, as in the United States, the rates of both low birth weight and preterm births were higher in the 1990s than in the 1970s.

Needless to say, rather than abandon their false hypothesis blaming smoking, the anti-smoking ideologues deliberately deceive the public by claiming that odds ratios for SIDS increased for smoking and prematurity. In fact, the phony smoking risk is based upon using defective studies that do not include pathological examinations for chorioamnionitis, which is the real cause of both preterm births and most other poor perinatal outcomes. In the absence of pathological exams, 90% of these cases are missed. (See "Chorioamnionitis Causes Perinatal Illnesses Blamed on Smoking.")

Changes in the Classification of Sudden Unexpected Infant Deaths: United States, 1992–2001. MH Malloy, M MacDorman. Pediatrics 2005 May;115:1247-1253. MacDorman is with the US National Center for Health Statistics, Hyattsville, Maryland. "The all-cause postneonatal mortality rate declined 27% and the postneonatal SIDS rate declined 55% between 1992 and 2001. However, for the period from 1999 to 2001 there was no significant change in the overall postneonatal mortality rate, whereas the postneonatal SIDS rate declined by 17.4%. Concurrent increases in postneonatal mortality rates for unknown and unspecified causes and suffocation account for 90% of the decrease in the SIDS rate between 1999 and 2001." Their work is designed more to obfuscate than to clarify, because that brief 2-year span receives the most attention! Overall, however, the death rates from the 2 ICD chapters "Symptoms, Signs, and Ill-Defined Conditions" and "External Causes of Injury" which contain all of the sudden unexpected infant deaths rose after 1970 and remained high until approximately 1990, when they declined; while residual deaths fell.

The reason that sleeping position is important is not known. But, after the change in infants' sleeping position from prone to supine, most SIDS cases apparently result from other underlying causes, most likely of an infectious nature.

Seasonal Changes in SIDS Deaths Mirror Respiratory Disease Deaths

Infant respiratory death rates mirror sudden infant deaths (Letter re Gilman). DL Crombie, KW Cross, DM Fleming. BMJ 1995 Jun 17;310(6994):1603.

An infectious aetiology of sudden infant death syndrome. AR Highet. J Appl Microbiol 2008 Sep;105(3):625-635. Review.

Viruses in SIDS

PCR-based diagnosis of enterovirus and parvovirus B19 in paraffin-embedded heart tissue of children with suspected sudden infant death syndrome. A Baasner, R Dettmeyer, M Graebe, J Rissland, B Madea. Lab Invest 2003 Oct;83(10):1451-1455. 60 SIDS cases and 36 controls with well-known causes of sudden death. Enteroviruses were found in 14 SIDS cases versus 0 controls; parvovirus B19 was found in 7 SIDS cases vs 3 controls.

Virological analysis in the diagnosis of sudden children death: a medico-legal approach. A Fernández-Rodríguez, S Ballesteros, F de Ory, JE Echevarría, R Alvarez-Lafuente, G Vallejo, J Gómez. Forensic Sci Int 2006 Aug 10;161(1):8-14. 64 cases. "According to pathological findings, death could only be attributed to an adenovirus infection in one amygdalitis with upper airways stenosis and asphyxia. Human herpes virus 6 (HHV-6) was detected by PCR in one case with pathological findings characteristic of SIDS. Recent infection by respiratory syncytial virus (RSV), Epstein-Barr virus (EBV) and cytomegalovirus (CMV) were also detected. Meanwhile, 85.9% of the cases yielded negative viral results. Twenty-eight infants were finally categorised as SIDS. Pathological findings of infection were detected in 12 patients despite the negativity of viral analyses."

The role of post-mortem investigations in determining the cause of sudden unexpected death in infancy. MA Weber, MT Ashworth, RA Risdon, JC Hartley, M Malone, NJ Sebire. Arch Dis Child 2008 Dec;93(12):1048-1053. "Retrospective analysis of >1500 consecutive post-mortem examinations carried out by specialist paediatric pathologists at a single centre during a 10-year period according to a common autopsy protocol that included the use of detailed ancillary investigations.... Of 1516 paediatric post-mortem examinations, 546 presented as SUDI. In 202 infants (37%), death was explained by the autopsy findings. The other 344 cases (63%) remained unexplained. Of the explained deaths, over half (58%) were infective, most commonly due to pneumonia (22%). The component of the post-mortem examination that primarily determined the final cause of death was histological examination in 92 infants (46%), macroscopic examination in 61 (30%), microbiological investigations in 38 (19%) and clinical history in 10 (5%)."

Staphylococcus aureus is implicated in SIDS

Detection and toxin production of Staphylococcus aureus in sudden infant death cases in Hungary. Z Csukás, K Töró, I Jankovics, F Rozgonyi, P Sótonyi. Acta Microbiol Immunol Hung 2001;48(2):129-141. 13 SIDS cases, 9 non-SIDS, 100 healthy infants. "S. aureus was isolated from 54% of SIDS cases and 37% from healthy infants /OR = 1.986 (95% Confidence interval = 0.55-7.33), p = 0243/. The enterotoxin and TSST-1 toxin producing activity of S. aureus showed the characteristic difference. The toxigenic S. aureus was detected in 46% of SIDS cases and 16% of healthy infants /OR = 4.5 (95% CI = 1.15-17.72), p = 0.010/. The distribution of toxigenic and nontoxigenic isolates was 86% in SIDS cases and 43% in healthy infants /OR = 7.875 (CI = 0.78-191.89), p = 0.041/."

Infection and sudden unexpected death in infancy: a systematic retrospective case review. MA Weber, NJ Klein, JC Hartley, PE Lock, M Malone, NJ Sebire. Lancet 2008 May 31;371(9627):1848-1853. "Significantly more isolates from infants whose deaths were explained by bacterial infection (78/322, 24%) and from those whose death was unexplained (440/2306, 19%) contained group 2 pathogens than did those from infants whose death was explained by a non-infective cause (27/243, 11%; difference 13.1%, 95% CI 6.9-19.2, p<0.0001 vs bacterial infection; and 8.0%, 3.2-11.8, p=0.001 vs unexplained). Significantly more cultures from infants whose deaths were unexplained contained Staphylococcus aureus (262/1628, 16%) or Escherichia coli (93/1628; 6%) than did those from infants whose deaths were of non-infective cause (S aureus: 19/211, 9%; difference 7.1%, 95% CI 2.2-10.8, p=0.005; E coli: 3/211, 1%, difference 4.3%, 1.5-5.9, p=0.003)."

Dynamics and determinants of Staphylococcus aureus carriage in infancy: the Generation R Study. A Lebon, JA Labout, HA Verbrugh, VW Jaddoe, A Hofman, W van Wamel, HA Moll, A van Belkum. J Clin Microbiol 2008 Oct;46(10):3517-3521. 443 infants sampled at 1.5, 6, and 14 months. "The main difference between our findings and the studies on determinants of carriage by Bogaert et al. and Peacock et al. is our failure to identify family size, passive smoking, or breast-feeding as significant determinants of carriage (2, 16). However, our data on breast-feeding seems to be more precise than those of the earlier studies, with very little missing data; furthermore, our data cover a larger cohort of children in the same age group (first year of life) than do the two previously mentioned studies."

Sterile site infection at autopsy in sudden unexpected deaths in infancy. PN Goldwater. Arch Dis Child 2009 Apr;94(4):303-307. Autopsy report review of 130 sudden infant death syndrome (SIDS) cases (2004 definition), 32 cases of sudden unexpected death in infancy (SUDI) due to infection and 33 cases of non-infectious sudden deaths. "10.76% of SIDS had S aureus present in a sterile site, compared with 18.75% of cases of infection-related deaths. S aureus was not found in sudden accidental deaths. The incidence of coliform bacteria in NSS in SIDS was not significantly different from that seen in deaths from other cause."

E. coli is implicated in SIDS

SIDS, infection could be linked. Researchers study E. coli byproduct. By Emma Ross, The Associated Press 2002 Apr 26. "'Mainstream researchers have concentrated on respiratory obstruction as a possible mechanism, without any evidence that would support such a mode of death,' said Dr. Paul Goldwater, who presented his study at the European Congress of Clinical Microbiology and Infectious Diseases in Milan. 'Those researchers ignored autopsy findings that consistently show wet, heavy lungs in SIDS babies. This is never seen' in cases of suffocation, said Goldwater, a researcher at the Women's and Children's Hospital in North Adelaide, Australia. Such a lung condition is often seen in cases of infection. Autopsies also consistently show small hemorrhages on the heart and lungs -- which is rare in suffocation -- and the blood of SIDS babies is unclotted, which is something never seen in suffocation cases, he added. Furthermore, he said, SIDS deaths captured on medical monitors have shown that these babies died of a shock-like process, Goldwater said. 'The serum from babies who have died of SIDS is toxic to chick embryos and mice -- indicating the presence of a toxin,' he said." The bacteria was found in all SIDS babies and 80% of normal babies, but all SIDS babies versus no healthy babies had the E coli curlin protein in their bloodstreams.

Sudden infant death syndrome: a critical review of approaches to research. PN Goldwater. Arch Dis Child 2003 Dec;88(12):1095-1100. Review.

Supporting evidence is that "Enteric infections alter bowel permeability which allows absorption of otherwise excluded food components [and presumably also bacteria and bacterial products -cast]. Several studies of both human and porcine models indicate that significant quantities of unwanted proteins can be absorbed by damaged gut tissue and that maximum expression of diarrhea corresponds with peak protein uptake." (JA Lindsay. Chronic sequelae of foodborne illnes. Emerging Infectious Diseases 1997 Oct-Dec;3(4):.) E coli (along with other pathogens) could be responsible for damaging the gut.

Expression of and cytokine activation by Escherichia coli curli fibers in human sepsis. Z Bian, A Brauner, Y Li, S Normark. J Infect Dis 2000 Feb;181(2):602-612. "These data, therefore, provide direct evidence that curli are expressed in vivo in human sepsis and suggest a possible role for curli and CsgA" in human E coli sepsis.

Activation of inducible nitric oxide synthase/nitric oxide by curli fibers leads to a fall in blood pressure during systemic Escherichia coli infection in mice. Z Bian, ZQ Yan, GK Hansson, P Thoren, S Normark. J Infect Dis 2001 Feb 15;183(4):612-619.

Role of Escherichia coli curli operons in directing amyloid fiber formation. MR Chapman, LS Robinson, JS Pinkner, R Roth, J Heuser, M Hammar, S Normark, SJ Hultgren. Science 2002 Feb 1;295(5556):851-855. "Amyloid is associated with debilitating human ailments including Alzheimer's and prion diseases. Biochemical, biophysical, and imaging analysis revealed that fibers produced by Escherichia coli called curli were amyloid."

The frequency of molecular detection of virulence genes encoding cytolysin A, high-pathogenicity island and cytolethal distending toxin of Escherichia coli in cases of sudden infant death syndrome does not differ from that in other infant deaths and healthy infants. AR Highet, AM Berry, KA Bettelheim, PN Goldwater. J Med Microbiol 2009 Mar;58(Pt 3):285-289. In 145 SIDS and 101 dead control and healthy infants, there was no correlation of SIDS with clyA (cytolysin A), irp2 [high-pathogenicity island (HPI)-specific gene] and cdt (cytolethal distending toxin).

Pneumocystis carinii (Pneumocystis jirovecii)

The protozoan Pneumocystis carinii has been known chiefly as an opportunistic infection that causes pneumonia in AIDS patients and others with immune deficiencies. It is generally considered harmless in normal infants and adults. Howwever, studies by Vargas et al in three different countries have shown that infants classified as SIDS deaths are more likely to have clusters of P carinii in their lungs than those who died of other causes. P carinii was found in a relatively high proportion of cases, from 15 top 35 percent. Reduced levels of lung surfactant have been hypthesized to trigger sudden death in a number of SIDS cases, and decreased surfactant has been found in the lungs of animals in the early stages of P carinii infection.

Association of primary Pneumocystis carinii infection and sudden infant death syndrome. SL Vargas, CA Ponce, WT Hughes, AE Wakefield, JC Weitz, S Donoso, AV Alloa, P Madrid, S Gould, JJ Latorre, R Avila, S Benveniste, M Gallo, J Belletti, R Lopez. Clin Infect Dis 1999 Dec;29(6):1489-1493; Pneumocystis carinii infection linked to sudden infant death syndrome. Medscape - Reuters Health 2000 Jan 11.

The impact of CMV on the respiratory burst of macrophages in response to Pneumocystis carinii. AL Laursen, SC Mogensen, HM Andersen, PL Andersen, S Ellermann-Eriksen. Clin Exp Immunol 2001 Feb;123(2):239-246. "Infection of human monocyte-derived macrophages with CMV decreased the respiratory burst when cells were stimulated with opsonized zymosan or Pneumocystis carinii (P. carinii).... The effect was most pronounced in cells obtained from CMV antibody-negative donors."

Identification of Pneumocystis carinii in the lungs of infants dying of sudden infant death syndrome. DJ Morgan, SL Vargas, M Reyes-Mugica, JN Walterspiel, W Carver, F Gigliotti. Pediatr Infect Dis J 2001 Mar;20(3):306-309. P carinii found in 14% of 79 SIDS deaths in Rochester, NY.

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cast 05-29-09