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This document is also available as a PDF. January 17, 1997 / 46(02);33-35 Update: Pulmonary Hemorrhage/Hemosiderosis
Among Infants -- Cleveland, Ohio, 1993-1996
In November 1994, private physicians and public health officials in Cleveland, Ohio, and CDC reported a
cluster of eight cases of acute pulmonary hemorrhage/ hemosiderosis that had occurred during January
1993-November 1994 among infants in one area of the city (1). Two additional cases were identified in
December 1994. All 10 infants lived within seven contiguous postal tracts in eastern metropolitan
Cleveland. Pulmonary hemorrhages recurred in five of the infants after they returned to their homes
shortly after hospital discharge; one infant died as a result of pulmonary hemorrhage. This report
summarizes the findings of the follow-up investigation, including a case-control study and an assessment
by the county coroner of cases of infant death. These findings documented an association between acute
pulmonary hemorrhage/hemosiderosis in this cluster of cases and mold growth in their water-damaged
homes. Case-Control Study of Risk Factors for Pulmonary Hemorrhage To determine risk factors for acute pulmonary hemorrhage among the infants in the cluster, the Rainbow
Babies and Childrens Hospital (RBCH), the Cuyahoga County Board of Health, the Cleveland
Department of Public Health, and CDC conducted a case-control study. A case was defined as an episode
of acute, diffuse pulmonary hemorrhage of unknown etiology during the first year of life in a previously
healthy infant that required hospitalization at RBCH during January 1993-December 1994. The study
compared 10 case-infants with 30 age-matched control infants from the same area in Cleveland (2). Of the 10 case-infants, nine were male; in comparison, of the 30 controls, 15 (50%) were male (p less
than 0.05). Breastfeeding was reported for none of the case-infants but for 11 (37%) of the controls
(odds ratio {OR}=0.2; 95% confidence interval {CI}=0-1.2}. In addition, nine of 10 case-infants and 16
(53%) of 30 controls resided in households with smokers (OR=7.9; 95% CI=0.9-70.6). All 10
case-infants and seven (23%) of the 30 controls resided in homes where major water damage (as a result
of chronic plumbing leaks or flooding) had occurred during the previous 6 months (OR=16.3; 95%
CI=2.6-infinity). The latter finding prompted a visual inspection and quantitative air sampling for and
microscopic identification of fungi in the study homes. The quantity of fungi, including the toxigenic
fungus Stachybotrys atra (whose toxins have been implicated in hemorrhagic disorders in animals), was
higher in the homes of case-infants than in those of controls (OR=1.6; 95% CI=1.0-30.8). Active surveillance by the RBCH identified an additional 11 cases of acute pulmonary
hemorrhage/hemosiderosis among infants in the Cleveland area during January 1995-December 1996. Of
these 11 infants, two had died as a result of acute pulmonary hemorrhage. The demographic
characteristics and clinical presentation of these 11 cases was consistent with the initial cluster of cases. Based on the findings of the case-control study, health authorities in Cleveland recommended prompt
clean-up and disposal of all moldy materials in the water-damaged homes and have designed a prevention
program focusing on water-damaged homes. Coroner's Investigation of Infant Deaths 1 of 3 11/4/99 1:01 PM Pulmonary Hemorrhage/Hemosiderosis Among Infants -- Cleveland, OH http://www.cdc.gov/epo/mmwr/preview/mmwrhtml/00045680.htm The three infant deaths resulting from pulmonary hemorrhage prompted the county coroner to re-examine
all infant deaths in Cuyahoga County during January 1993-December 1995 to determine whether cases of
pulmonary hemorrhage had been misclassified. Postmortem examinations were reviewed for all 172
infants who died in the county during that period, including 117 deaths attributed to SIDS; premature
infants who died in a hospital were excluded. Pathologic lung specimens were sectioned, stained with
Prussian blue, and screened for the presence of hemo-siderin. Extensive hemosiderin-laden macrophages were present in lung tissue of nine (5%) infants -- a finding
indicating major pulmonary hemorrhage preceding death. Of these nine deaths, two resulted from
homicide, and one had a recent history of child abuse. No apparent etiologies for pulmonary
hemorrhage/hemosiderosis were identified for the other six infants presumed to have died from SIDS, all
of whom had lived in the same postal tracts as the initial cluster; three were male, and two were siblings.
A review of the clinical circumstances for five infants indicated that some symptoms of pulmonary
hemorrhage had been present before death: two infants had had episodes of epistaxis or mild hemoptysis
within 7 days before death, and four had had additional symptoms (e.g., cough, pulmonary congestion, or
black stools). Reported by: DG Dearborn, MD Infeld, PG Smith, LJ Brooks, C Carroll-Pankhurst, R Kosick, BB
Dahms, Rainbow Babies and Childrens Hospital; EK Balraj, R Challener, Cuyahoga County Coroner's
Office; TM Allan, TE Horgan, Cuyahoga County Board of Health; R Staib, C Wallace, Cleveland Dept
of Public Health; TJ Halpin, MD, State Epidemiologist, Ohio Dept of Health. BB Jarvis, Univ of
Maryland, College Park. JD Miller, Agri-Canada, Ottawa, Ontario. Air Pollution and Respiratory Health
Br, Div of Environmental Hazards and Health Effects, National Center for Environmental Health, CDC. Editorial Note Editorial Note: The findings of the investigation described in this report suggest that, in Cleveland, the
infants with pulmonary hemorrhage were more likely than controls to reside in homes that had been
affected by major water damage during the previous 6 months. The water damage may have promoted
the growth of fungi, including S. atra. Because S. atra requires water-saturated cellulose-based materials
for growth in buildings, it is considered uncommon in homes. Although S. atra has been associated with
gastrointestinal hemorrhaging in animals that had consumed moldy grain (3), the fungus previously has
not been associated with disease in infants. SIDS is diagnosed only after exclusion of other known causes of death. The review by the Cuyahoga
County coroner indicated that some infant deaths initially attributed to SIDS actually resulted from
pulmonary hemorrhage. Agonal alveolar hemorrhage may occur in approximately two thirds of infant
autopsies (4); however, the presence of extensive hemosiderosin-laden macrophages within the alveoli
indicates major predeath pathologic processes, which precludes the diagnosis of SIDS. Macrophages
require approximately 48 hours to convert the iron of the ingested erythrocytes into hemosiderin;
therefore, the presence of hemosiderin-laden macrophages in alveoli indicates alveolar bleeding for at
least 2 days preceding death (5). Causes of such bleeding and pulmonary hemosiderosis may include
cardiac lesions associated with increased left atrial pressure, trauma, pneumonia, and perhaps suffocation. The findings of this investigation -- including the association of environmental factors with pulmonary
hemorrhage/hemosiderosis and the presence of extensive hemosiderin-laden macrophages in some infants
with SIDS -- underscore the need for further investigation of these relations. In particular, further efforts
are needed to clarify the association between pulmonary hemorrhage in infants and exposure to
water-damaged building materials and to evaluate pathologic methods to identify and quantify pulmonary 2 of 3 11/4/99 1:01 PM Pulmonary Hemorrhage/Hemosiderosis Among Infants -- Cleveland, OH http://www.cdc.gov/epo/mmwr/preview/mmwrhtml/00045680.htm hemorrhage and hemosiderosis. References 1. CDC. Acute pulmonary hemorrhage/hemosiderosis among infants -- Cleveland, January
1993-November 1994. MMWR 1994;43:881-3. 2. Montaċa E, Etzel RA, Allan T, Horgan TE, Dearborn DG. Environmental risk factors associated
with pediatric idiopathic pulmonary hemorrhage and hemosiderosis in a Cleveland community.
Pediatrics 1997;99:e5. World-Wide Web site http://www.pediatrics.org/cgi/content/full/99/1/e5 3. Hintikka E-L. Stachybotryotoxicosis as a veterinary problem. In: Rodricks JV, Hesseltine CW,
Mehlman MA, eds. Mycotoxins in human and animal health. Park Forest South, Illinois: Pathotox
Publishers, 1977:277-84. 4. Valdes-Depena M. The postmortem examination. Pediatr Ann 1995;24:365-72. 5. Stewart S, Fawcett J, Jacobson W. Interstitial haemosiderin in the lungs of sudden infant death
syndrome: a histological hallmark of 'near-miss' episodes? J Pathol 1995;145:53-8. Disclaimer All MMWR HTML versions of articles are electronic conversions from ASCII text into HTML. This
conversion may have resulted in character translation or format errors in the HTML version. Users should not rely on this HTML
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tables. An original paper copy of this issue can be obtained from the Superintendent of Documents, U.S. Government Printing
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