Submitted:
31 March 2026
Posted:
01 April 2026
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Abstract
Background: Produced by indoor Stachybotrys and Trichoderma spp., macrocyclic trichothecenes (MTs), cytotoxic respirable molecules(<0.01–0.03µm) inhibit protein/DNA/RNA production, damage mitochondria, and induce apoptosis. Dust-bound MTs remain toxic despite remediation/disinfection. Upon inhalation, they cross tissue barriers spreading widely, plausibly injurious to placentae and the unborn. Methods: Retrospective epidemiological study of pregnant females and offspring exposed to indoor MTs, Stachybotrys or Trichoderma, correlating professional indoor testing, medical outcomes, exposure variables, mold species, and urine/milk MTs excretion. Results: In eight women from seven MT/mold contaminated homes, with 21 pregnancies, complications occurred in 19 (90%) pregnancies including miscarriages (38%), premature labor (33%). Placental abnormalities in 2 women (25%) from the same home (calcification, chronic villitis, placental infarcts, double placenta, gritty membranitis). Birth defects in infants (38%) included renal hypertrophy, levocardia, patent foramen ovale, ventriculoseptal defect, ptosis, teeth, “goosebump” black/grey skin discoloration. Later abnormalities included developmental delay (46%), oropharyngeal hypotonic dysphagia, refractory eczema, refractory perirectal rash progressing to intussusception. Lactation difficulties included grey-black oronasal drainage, thrush, projectile vomiting, choking, oropharyngeal neurologic damage, apnea, respiratory arrest. Aspergillus +/- Penicillium exposure was documented for all 8 women, Stachybotyrs (75%), Chaetomium (50%) Trichoderma (37%) and indoor MT contamination exposure (75%). Conclusions: In-utero indoor MTs and Stachybotrys exposure correlates strongly with adverse gestational, neonatal complications, including miscarriage, congenital defects, and placental abnormalities. Exposure timing and severity correlate with adverse outcomes. Breastfeeding with indoor exposure appears hazardous. Environmental/human MTs testing appears useful identifying contamination +/or exposure.
Keywords:
macrocyclic trichothecenes
; Stachybotrys
; mycotoxin
; indoor fungal contamination
; indoor hazardous exposure
; miscarriage
; birth defects
; biomarkers
; lactation risk
1. Introduction
Most pregnancies result in healthy babies and most neonates thrive. Miscarriages occur more often in the first trimester, at a rate of ~15%, with other serious complications of pregnancy in <10% of all pregnancies delivering live babies. The causes of most miscarriages are uncertain, as are the reasons for most cases of pre-eclampsia, intrauterine growth retardation and premature labor. Exogenous exposures may be one contributing factor to these adverse events.
Macrocyclic trichothecenes (MTs), potent cytotoxic respirable molecules (<0.01–0.03 µm), inhibit intracellular protein/DNA/RNA production, damage mitochondria, and induce apoptosis [1,2,3,4,5,6,7,8,9]. Being both hydrophilic and lipophilic, MTs easily cross tissue barriers and penetrate cell membranes. Direct MT injury to placentae, and the unborn is plausible [8,9]. Little data linking human illness to the MTs found in water-damaged homes exists since direct exposure studies are unethical. This study investigates correlations between environmental MTs and Stachybotyrs and/or Trichoderma indoor exposure, indoor activities, and disease severity of obstetrical and neonatal outcomes.
Our objectives were to 1) define adverse obstetrical and neonatal outcomes linked to indoor MTs, Stachybotrys, or Trichoderma exposure, and 2) correlate exposure variables with adverse outcomes to identify hazardous exposure risks and markers.
2. Methods
This study is a focused epidemiological retrospective assessment of 8 pregnant females with 21 conceptuses exposed in 7 homes contaminated with indoor dust MTs, with or without Stachybotrys or Trichoderma contamination. Homes were assessed by professional environmental inspection, including fungal air spore trap analysis/bulk sample fungal microscopic analysis, mold specific quantitative PCR analysis, and dust MT measurement by ELISA (Realtime Laboratories, Lewisville, TX [10].
Mothers were clinically assessed after pregnancy by one of the authors (IHG), usually on multiple occasions. Data on maternal and neonatal clinical outcomes were collected using a systematic and thorough data collection tool, to include the following: indoor contamination data, including , mold species and mycotoxins detected in the home, exposure timing, estimated individual exposure severity, maternal pregnancy/postpartum and pediatric symptoms, signs, physical examinations and diagnoses. After miscarriage or childbirth, data on the loss of pregnancy or birth itself and the appearance of the placenta was collected from available hospital obstetric documentation. Medical data on each mother and child born to exposed mothers was assembled from medical and pediatric clinical notes where available. Mothers were tested for the development of specific fungal quantitative IgG antibody responses in serum (Quest Diagnostics Stachybotrys chartarum/atra (RGm24) IgG by immunoassay and Hypersensitivity Pneumonitis Evaluation for Trichoderma viride by Double Diffusion and ImmunoCAP® methodologies) and MT excretion in urine and breast milk measured by ELISA (Realtime Laboratories) [10].
Electronic extraction and analysis of longitudinal clinical, environmental, and laboratory data were conducted. Biostatistical methods were used to correlate indoor exposure intensity, indoor human activities, building conditions, and clinical outcomes. As all patients were referred for clinical review and provided all samples and data voluntarily to IHG, no additional ethical (IRB) review was warranted. All data is anonymized.
3. Results
Eight pregnant females and 21 in-utero conceptuses with documented exposure in 7 MT- contaminated homes were retrospectively analyzed.
3.1. Environmental Contamination Hazards and Maternal Exposures (Table 1A)
Water damage and other exposure variables in the homes are shown in Tables 1A and 1B. All 8 mothers (100%) had chronic exposure: 7 (88%) were exposed to uncontrolled water intrusion or odors, 6 (75%) to visible mold, demolition, intense personal unprotected exposure, or dust dispersion without containment, and 5 (63%) to a contaminated HVAC system/air conditioner or basement exposures. All 8 moved out and 5 (63%) became homeless looking for new place, 4 (50%) lost most of their belongings. Four (50%) remained ill despite discontinuing exposure.
Table 1A.
Maternal ndoor exposure variables.
| Chronic Exposure | Uncontrolled Water leaks Intrusion | Odor or Musty Smell | Visible Mold | Demolition | Intense Personal Exposure | Disturbed without Containment | HVAC or AC Contaminated | Basement Exposure | ||
|---|---|---|---|---|---|---|---|---|---|---|
| # Mothers | 8 | 7 | 7 | 6 | 3 | 6 | 6 | 6 | 5 | 5 |
| TOTAL % | 100% | 86% | 86% | 71% | 29% | 71% | 71% | 57% | 57% | 57% |
As one example of the building issues, home #7 was incorrectly constructed promoting high humidity, water intrusion and microbial contamination, including both Stachybotrys and Trichoderma. A professional inspection revealed widespread construction defects, including improper foundation drainage, missing window flashings, inappropriate vapor barrier placement, and noncompliant backfill. Water intrusion, condensation, and interstitial moisture led to visible fungal growth, rusted fasteners, and damaged materials throughout the structure. Mold and environmental testing confirmed significant microbial contamination on all three floors, indicating grossly defective building practices and poor indoor air quality.
3.1.1. Environmental Analysis (Tables 1B and 2)
All 7 homes had fungal contamination documented or inferred. Each home’s hazardous risk was ranked based on severity of pediatric outcomes (see Table 1B.). One home (3) had extensive prolonged water damage with widespread mold visible but was not formally tested. Two homes had high Stachybotrys airborne spore counts (>10/m3 air sampled), and three homes had visible mold and Stachybotyrs proliferation detected by microscopy. Macrocyclic trichothecenes (MTs) were detected in all 5 homes tested (Table 2). The two homes not tested for MTs were identified as highly probable for MT contamination based on either airborne Stachybotrys spores detected (home #1) or Trichoderma identified in dust and MTs in the mother’s breast milk (home #3). Stachybotyrs chartarum was found in 5/7 (71%) homes and Trichoderma in 3/7 (37%) by dust PCR in 2/7 (29%) and by spores or dust microscopy in 1/7 (14%) (Table 2). Both Stachybotyrs and Trichoderma spp. were present together in 2/7 homes (29%). Aspergillus spp. was found in 100% of homes, Penicillium spp. in 5/7 (71%) and Chaetomium spp. in 4/7 (57%) (Table 2.). Other fungi were present in these homes but were not fully characterized and are not known to produce MTs, the focus of this report.
Table 1B.
Exposure variables in homes ranked by worst pediatric outcome.
| Chronic Exposure | Uncontrolled Water leaks Intrusion | Odor or Musty Smell | Visible Mold | Invisible Mold (Only Inside Walls & Vents) | Demolition | Intense Personal Exposure | Disturbed without Containment | HVAC or AC Contaminated | Basement Exposure | |
|---|---|---|---|---|---|---|---|---|---|---|
| Home #1 | 1 | 1 | 1 | 1 | 1 | 1 | ||||
| Home #2 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | |||
| Home #3 | 1 | 1 | 1 | 1 | 1 | 1 | ||||
| Home #4 | 1 | 1 | 1 | 1 | 1 | 1 | ||||
| Home #5 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | |
| Home #6 | 1 | 1 | 1 | 1 | 1 | 1 | ||||
| Home #7 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 |
| TOTAL # | 7 | 6 | 6 | 5 | 2 | 5 | 5 | 5 | 4 | 4 |
| TOTAL % | 100% | 86% | 86% | 71% | 29% | 71% | 71% | 57% | 57% | 57% |
Table 2.
Exposures to macrocyclic trichothecenes, stachybotyrs and trichoderma.
| Exposure documented | Homes (n = 7) | Mothers (n = 8) | Conceptuses (n = 21) | |||
|---|---|---|---|---|---|---|
| # | % | # | % | # | % | |
| Macrocyclic trichothecenes * | 5 | 100% | 6 | 75% | 19 Gestational Complications | 90% |
| (8 miscarriages/11 births) | ||||||
| Stachybotrys** | 5 | 71% | 6 | 75% | 13 | 21% |
| Trichoderma** | 2 | 29% | 3 | 38% | 6 | 29% |
| Chaetomium | 4 | 57% | 5 | 63% | 9 | 43% |
| Aspergillus/Penicillium | 7 | 100% | 8 | 100% | 21 | 100% |
* Only 5 homes tested; ** produces macrocyclic trichothecenes.
3.1.2. Maternal Clinical Observations:
Six (75%) gravidas experienced unexplained severe fatigue, skin symptoms [4 rashes, 3 redness, 4 bruising], nasal symptoms [6 nasal congestion, 5 postnasal drainage, 4 nostril drainage, 4 sinus congestion, 4 sinus pain and 3 sinusitis], throat symptoms [6 chronic hoarseness, loss of voice, 4 chronic throat pain] and, respiratory symptoms [6 chronic cough, 3 shortness of breath], headaches, eye irritation, ear symptoms [5 tinnitus, 3 ear pain], nasal congestion, sinus pain, and GI symptoms [ 5 nausea, 3 fluctuating irritable bowel symptoms].
Neurological symptoms were common: 6 (75%) mothers had impaired concentration, memory, focus, and/or attention; 4 (50%) had twitches, uncontrolled jerks, agitation, anxiety and/or depression; 3 (38%) had signs of encephalopathy, delirium, agitation, aphasia, disorganization, and/or vertigo.
Five (63%) experienced periorbital edema, cervical-submandibular lymphadenopathy [4 neck]. All 5 mothers who developed sinusitis while pregnant were MTs-exposed. Four (50%) experienced unexplained body burning sensations, including burning skin and urine with normal urinalysis, severe unexplained refractory pain, multiple chemical intolerance “sensitivity”, facial pain, unexplained bruising, postnasal drainage, sinus pain chronic pharyngitis, and muscle pain.
On physical exam, throat inflammation with injected capillaries and lymphoid hyperplasia was found in all 8 mothers (100%), nasal findings [red raw nostril mucosa in 7/8 (88%), red turbinates 5/8 (63%), loss of nasal mucosa and hairs in 4/8 (50%), palpable cervical submandibular lymph nodes in 5/8 (63%), tonsillar enlargement in 6/8 (75%) and oral pathology 6/9 (67%) including abnormally swollen soft palette, swollen deformed uvula.
Of five mothers tested, Stachybotrys IgG was detected, but was not elevated. Of the 3 mothers not tested for Stachybotyrs IgG testing, all were exposed to severe indoor Stachybotrys contamination. Of 3 mothers tested for Trichoderma IgG, low levels were detected in two. MTs were found in urine of all 4 mothers tested (100%) and in breast milk in one without urine testing [her baby’s urine was positive]. Of the 4 mothers not tested for MTs, all were exposed to indoor MT’s and heavy indoor Stachybotrys growth, and 2 untested mothers’ babies had detectable urine MTs.
3.1.3. Matching Maternal Findings with Home Contamination (Table 3)
The woman in home #1 exposed to airborne Stachybotrys had recurrent nosebleeds, detectable serum Stachybotrys chartarum IgG and detectable MTs in her urine.
The other untested home #3 was classified as extremely contaminated with extensive prolonged water damaged and widespread visible mold growth, including Trichoderma contamination, but not Stachybotrys. However, the mycological testing was not thorough. The mother became severely ill, developing pneumonia in the 2nd trimester. She had detectable, but not elevated Stachybotrys IgG. MTs were found in her breast milk and her baby’s urine, tested simultaneously when her infant developed oropharyngeal paresis and grey black oronasal discharge.
Home #6 had chronic recurrent unabated water intrusion over a year from torrential rain flooding into the basement which eventually dislodged the foundation of the house. While MTs were found in this home, neither Stachybotrys nor Trichoderma were detected. The mother experienced four miscarriages before having twins born prematurely. In the next year, faulty construction resulted in continuous water intrusion, and visible mold appeared in the basement. The mother developed vaginal pain. After the family moved out, the mother had chronic persistent pain in her neck, shoulders, legs, vagina and bladder. Re-entry into the home triggered red eyes, nasal congestion, throat swelling, bladder pain, rectal fissures, rectal bleeding, burning sensations [scalp, eyes, bladder and urine], hoarseness, loss of voice, cough, cognitive impairment [impaired memory, forgetfulness, getting lost], twitches and jerks. On examination, she had scleritis, diffuse mucosal inflammation with ulcerative nasal mucositis, oral thrush, soft palate inflammation, pharyngeal cobblestone lymphatic hyperplasia, and tender lymphadenopathy in the neck and groin, and a left lower lobe lung nodule on imaging. Both Stachybotrys IgG and Trichoderma IgG were detected. Urinalysis showed leukocytes without bacteria on culture. Urine MTs were elevated in the mother and all of her children. On follow up on year later, after moving out, symptoms resolved and MTs were no longer detected.
Table 3.
Ranking environmental contamination with clinical variables by maternal pediatric outcome severity.
Table 3.
Ranking environmental contamination with clinical variables by maternal pediatric outcome severity.
| RANKING METHODOLOGY : | 1 Moderate, 2 Severe, 3 Extreme, 4 Death |
| STACHYBOTRYS CONTAMINATION: | 5/7 homes Stachybotrys contaminated with 3/5 high levels and 1/5 airborne |
| MOLD SCORE: | 5/7 homes Moderate, 2 Severe Mold Contamination |
| WATER SCORE: | 4/7 homes Moderate, 2 Severe, 1 Extreme Water Damage |
| HOMES , MOTHERS & CONCEPTIONS |
ENVIRONMENTAL CONTAMINATION |
MATERNAL BIOMARKERS & OUTCOME | PEDIATRIC OUTCOMES | |||||||||||||
| Homes* | Mothers | Conceptuses | Water | Molds | Stachybotrys | Trichoderma | Dust MTs | Maternal MTs | Maternal Stachybotrys IgG | Maternal Trichoderma IgG | Maternal Outcome Score | Conceptus Outcome Score | Miscarriage |
Birth defect |
Details | Lactation Problem |
| Home #1 | 1 | 1 | Moderate | Severe | 1 [airborne] | 0 | not done | Urine Trace | 0 | 2 | 1 | Rough pregnancy |
1 | |||
| Home #2 | 1 | 1 | Moderate | Moderate | 1 High | 0 | 1 | not done | 1 | 1 | 3 | 1 | 9-month infant hospitalized |
1 | ||
| Home #3 | 1 | 1 | Moderate | Moderate | 0 | 1 | not done | Milk | 1 | 3 | 3 | 1 | Newborn hospitalized, damaged | 1 | ||
| Home #4 | 1 | 2 | Moderate | Moderate | 1 | 1 | Urine | 1 | 2 | 4 | 2 | No birth | 2 miscarriages |
No birth | ||
| Home #5 | 1 | 3 | Severe | Severe MT HVAC & Refrigerator coils | 1 High | Not done | 1 | not done | Not afford | 3 | 4 | 1 | 1 | 1 miscarriage, 2 Premi Twins | 0 | |
| Home #6 | 1 | 7 | Severe | Moderate | 0 | 0 | 1 | Urine | 1 | 1 | 3 | 4 | 4 | 4 miscarriages; Premi twins, sickly | 1 | |
| Home #7 | 1 | 5 | Extreme | Severe | 1 High | 1 | 1 | Urine | 1 | 3 | 4 | 1 | 1 | Miscarriage, hospitalized, multiple sick neonates | 1 | |
| [Mother #8] | 1 | 1 | “ | “ | “ | “ | “ | Not done | Not done | 3 | 3 | 1 | Skin | 1 | ||
| TOTAL | 8 | 21 | 5 | 2 | 5 | 5 | 4 | 2 | 8 | 5 | 6 | |||||
| * Homes ranked by worst pediatric outcome | ||||||||||||||||
3.1.4. Pregnancy Complications (Table 3 and Table 4)
Six mothers (75%) lacked underlying health problems before this exposure. Mother #3 [with the MT+ breast milk] had Factor V Leiden mutation, polycystic ovary syndrome with diabetes, chronic fatigue syndrome.
Mother #4 had chronic fatigue syndrome, environmental chemical sensitivity and recurrent sinusitis.
Gestational complications occurred in 19/21 (90%) conceptuses (Tables 2. and 3.). There were 8 (38%) first trimester miscarriages, all in mothers exposed to MTs, and 4/8 (50%) exposed to Stachybotrys. Of the four women who miscarried, all were exposed to indoor MTs. Three were exposed to high levels of Stachybotrys (2 also with Chaetomium) and one to Trichoderma.
Seven other pregnancy complications occurred in MT-exposed mothers: 7 premature labor, 2 intrauterine growth retardation, 1 severe preeclampsia and two fetal renal hypertrophies.
Three abnormal placentas were documented from 2 gravidas living together at the same time in Home #7: placental calcification, chronic villitis, and double placenta with gritty membranitis.
Mother #7 had 2 pregnancies while in Home #7 where the placentae were analyzed. The first placenta showed calcifications. Her 2nd placenta analyzed was also abnormal: a gritty, double placenta with membranitis (inflammation of the membrane on the outer surface of the placenta on the infant’s side). The maternal surface was diffusely covered with firm salt-like granules and loosely adherent dark brown blood clot materials which on examination was sponge-like tissue with granular material. No other diagnostic studies were done. At birth, the baby’s skin was strikingly red and was later diagnosed as severe eczema refractory to steroids. This baby was breastfed for 5 months and also developed a cough while in the house.
Mother #8, the simultaneously pregnant sister of mother #7, moved into in Home #7 during her 2nd trimester, and developed preterm labor and preeclampsia. This third placenta had small chronic infarcts, also with dark grey discoloration and yellow lesions diagnosed as “chronic villitis (inflammation) of unknown ethology “on pathology. Her baby's skin was also unusual with sandpaper texture and permanent dark grey mottled discoloration unlike his parents’ skin. After delivery upon returning to Home #7, mother #8 developed hypertension, severe headaches, and chronic sinusitis and her breastfed infant was evaluated in the ER for choking.
Table 4.
Clinical maternal/child outcomes and mt/mold exposure.
| CLINICAL OUTCOMES |
Number | Environmental MT-Exposed | Stachybotrys-Exposed | Trichoderma Exposed | Comments |
|---|---|---|---|---|---|
| Mothers | 8 | 6 | 6 | 3 | 4/8 (50%) mothers received MT testing [4 Urine, 1 breast milk] |
| Total Pregnancies |
21 | 19 | 19 | 7 | 15 1st Trimester exposures |
| 4 2nd Trimester | |||||
| 2 3rd Trimester | |||||
| Gestational Complications | 19/21 (90%) | 8 Miscarriages 11 Births |
8 Miscarriages 11 Births | [6/7 also exposed to Stachybotrys] |
8 Miscarriages 5 Preterm Labor 1 Pre-eclampsia |
| Miscarriages |
8 (38%) | 8(100%) | 4 (50%) | 0 | |
| Births | 13 | 11 | 9 | 3 | 6/13 (46%) babies had urine MT testing |
| 7 Male, 6 Female | |||||
| Placental Abnormalities |
3 (100%) | 3 (100%) | 3 (100%) | 3 (100%) | Calcification, chronic villitis with placental infarcts, double placenta, gritty membranitis |
| Birth Defects |
5 | 4 | 4 | 3 | 2 Cardiac (murmur, VSD), 2 renal hypertrophy, 1 ptosis |
| Neonatal Dermatologic Complications |
6 | 4 | 4 | 3 | 1 Severe refractory eczema, 1 bleeding refractory perirectal “diaper rash” progressed to intussusception, 1 diffuse permanent “goosebump” textured black-grey skin mottling |
| Neonatal Neurologic Complications |
6 | 4 | 4 | 3 | 6 Developmental delay, 1 ptosis, 1 oropharyngeal hypotonic dysphagia |
3.1.5. Birth Defects (Table 4)
Birth defects occurred in eight neonates (40%) of whom five (63%) were MT-exposed. Enlarged kidneys were seen in two, as documented by ultrasound prior to birth. Two babies had cardiac defects (levocardia with patent foramen ovale, and 1 ventriculoseptal defect). One baby had 2 fully developed teeth. Six neonates had unusual skin changes: two with diffuse redness. Another Hispanic baby of mother #8 was born with unusual widespread mottled blotchy permanent sandpapery “goosebump” melanotic grey skin discoloration, unlike his parents’ skin.
3.1.6. Breastfeeding Complications (Table 5)
Adverse lactation consequences occurred in the majority breastfed (70%): 3 grey black oronasal drainage, 3 projectile vomiting, 3 choking, 2 oronasal bleeding, 2 grey-black tongue coat, 1 oropharyngeal neurologic damage, 1 apnea/respiratory arrest, 1 intussusception, 1 refractory perirectal rash. The baby of home #1 was exposed in the second or third trimester, was unable to tolerate breastfeeding and experienced developmental delay.
No significant complications occurred in the 2 babies that were never breastfed.
The baby from home #3, exposed in the first trimester, was born with a ventricular septal defect (VSD). In the first 2 weeks, he failed to gain weight despite frequent feeding. By the 3d week, breast feeding triggered excessive spitting, coughing, crying, projectile vomiting, choking, and black, brown nasal drainage. Macrocyclic trichothecenes were detected in the mother’s breast milk and urine. At 4 weeks when breastfeeding was discontinued, the nasal drainage stopped. At age 6 weeks, developmental delay, oropharyngeal dysphagia and neuromuscular paresis with inability to suck or swallow, due to neurotoxicity from MT ingestion were diagnosed by a pediatric neurologist.
MT-exposed mother in Home #2 could not afford urine testing for herself, However, after acute unprotected exposure to uncontained mold disturbing indoor repairs, and continued breastfeeding, her 8-month-old baby acutely developed black-gray thrush, intolerance to breastfeeding, bleeding rectal rash, intussusception and had elevated urine MTs.
Table 5.
Breastfeeding complications.
| LACTATION COMPLICATIONS | Number of Children born n=13 | Comments |
|---|---|---|
| Lactation Exposure | 10/13 (76%) | |
| Milk Intolerance | 7/10 (70%) | |
| Projectile Vomiting | 3/10 (30%) | 2 Choking |
| Choking | 3/10 (30%) | 2 Hospitalized |
| 1 Oropharyngeal Paresis from MT+ | ||
| Breast Milk | ||
| Grey/Black Tongue ** | 2 | 1 Environmental MTs |
| 1 MT+ Breast Milk | ||
| Oronasal Bleeding | 2 | |
| Refractory Bleeding Perirectal “Diaper Rash” ** | 1 | Grey/Black Tongue |
| Intussusception** | 1 | Grey/Black Tongue |
| Apnea/Pulmonary Hemorrhage/ICU | 1 | Choking |
| Oropharyngeal Motor Paresis after MT+ Breast Milk ingestion | 1 | Grey/Black Tongue |
| **Same infant |
3.1.7. Determining Exposure Hazards
- ▪
- Analysis of indoor contamination variables by severity of pediatric outcomes: (Table 3.)
Ranking indoor environmental contamination variables by severity of pediatric outcomes showed that the worst outcomes, miscarriages, paralleled severity of water intrusion (Table 3). Severe outcomes also paralleled indoor MT, Stachybotrys and Trichoderma contamination. All miscarriages occurred in MT contaminated homes. Stachybotrys was found in 5/7 homes (71%). However, while neither Stachybotrys nor Trichoderma were found in Home #6 on environmental testing, mother #6, who had 4 miscarriages, had IgG titters to both molds and MTs in her urine. Urine MTs were also found in all 3 children, all conceived in Home #6.
- ▪
- Risk Analysis of Exposure Variables: Hazardous dust production and unprotected exposure to uncontained repairs
One gravida developed gestational DM while 7 months pregnant after moving into Home #2 with both Stachybotrys and MTs contamination of the central HVAC and AC. The baby was born with 2 fully developed teeth. Sleeping and breast feeding under the leaking visibly contaminated blackened air vent, the infant promptly developed chronic cough, diarrhea and a refractory anal “diaper” rash. Six months later, the whole family became ill after turning on the AC and heavy rain caused persistent roof leaking. Another 2 months later, when uncontained roof and vent repairs were done without containment (i.e. air separation from the inside of the home), the baby became acutely ill within 3-4 weeks with a grey-black tongue coat, grey nasal discharge, “snuffles”, stridor, cough and vomiting followed by hospitalization for rectal prolapse and intussusception. Microscopy of both sheet rock and HVAC dust showed prolific Stachybotrys growth and MTs.
Home #7 had chronic extreme water intrusion and severe contamination with extensive Stachybotrys growth, MT contamination, multiple microfungi including Chaetomium and Trichoderma. Mother #7 sustained a miscarriage and 4 pregnancies with multiple complications in this home. At birth, one neonate exposed in utero to uncontained construction developed projectile vomiting with breastfeeding. At 2 weeks he began choking requiring Emergency Room evaluation. The next day he stopped breathing after breastfeeding and required ICU care for 4 weeks for respiratory arrest, pulmonary hemorrhage, patent foramen ovale. He also developed speech delay.
4. Discussion
4.1. Principal Findings
This study supports a causal link between exposure of pregnant or nursing mothers and their newborns to indoor MTs, Stachybotrys or Trichoderma and serious, even life-threatening medical outcomes, especially for the unborn and neonate. At present, there is no epidemiological evidence directly linking macrocyclic trichothecenes or Stachybotrys exposure with obstetrical or neonatal complications. A major limitation in this topic area is the lack of quality human data for this underrecognized exposure. Since controlled clinical trials to investigate such exposures in any humans, especially pregnant women and neonates, would be unethical, detailed observational and environmental studies are essential for advancing knowledge.
In this study, severe pregnancy outcomes correlated with exposure to dust-dispersing, air-contaminating activities as well as unprotected personal exposure. The worst outcomes were from exposures to uncontained construction, demolition, remodeling, and contaminated ventilation systems. Indoor sewage contamination appears particularly hazardous. Heavy water intrusion, the main risk for Stachybotyrs proliferation, was also the most frequent environmental variable associated with significant illness. Accurately documented exposure severity and duration is inherently challenging in a study of this type but occurred over many months in all cases.
Given the documentation of Stachybotrys chartarum and other mycotoxin-producing fungi in large quantities, the presumption is that the mycotoxins produced by these fungi were inhaled in the mother’s homes leading to illness. This contention is supported by detection of MTs in the environment and in both mothers’ and babies’ clinical samples. Two important caveats remain however: 1) other inhaled mycotoxins could be fully or partly responsible for the disease observed and 2) the diagnostic accuracy of the MT assay(s) is not documented and its validation weak.
4.2. Results in the Context of What Is Known
The maternal symptoms and physical findings described here correspond with military medicine reports of MT injury to skin and respiratory or gastrointestinal mucosa [1,9]. Inhalation of MTs appears to be the most toxic in prior reports. Maternal burning and bleeding were frequent symptoms, with oronasal pharyngeal mucosal barrier defense injuries the most common sites involved, consistent with both animal model and military data[1,11]. Neurological symptomatology, including maternal cognitive and pediatric neurodevelopmental impairment also matched animal research showing inhaled trichothecenes injure mucosa on contact and rapidly spread directly into the brain from the nasal mucosa via olfactory cranial nerve axonal penetration [11].
Being amphiphilic molecules [both polar hydrophilic and lipophilic], MTs easily enter the body in direct contact of any tissue. Inhalation is the most efficient and harmful route of exposure [1,9,12,13,14,15]. As respirable molecules (<0.01-0.03 microns), they reach deeply into the lung periphery, inducing alveolar macrophage apoptosis, and penetrate directly into the systemic circulatory system [4,9,13,14,16]. MTs form covalent protein adducts, causing multiple toxic pathophysiological effects dependent on dose and site reached, through tight covalent binding to serum and tissue macromolecules [7].
In water-damaged indoor environments, macrocyclic trichothecenes accumulate in large quantities in Stachybotrys biofilm fragments and debris, as well as dust [17]. Potentially a serious persistent indoor health hazard, they remain toxic for prolonged duration, if not indefinitely, despite remediation and disinfection by standard methods, including heat, since they are heat-stable [1,9,16,18,19]. While MTs are not volatile themselves, they attach to miniscule, highly respirable particulates (0.03-0.3 microns), and accumulate in indoor dust, especially from cellulose-containing building materials, such as straw, fiberboard, gypsum, wall board, ceiling tile, wallpaper, lint and belongings [2,20,21,22,23,24]. Activities disturbing dust in Stachybotrys-contaminated homes increase airborne MTs [18,25].
Mechanisms of MT toxicity are multiple including cytotoxicity and apoptosis via oxidative stress, protein synthesis inhibition, inflammatory gene expression via ribotoxic stress response involving activation of P38 mitogen-activated protein kinases (MA PKs) /JNK, RNA/DNA synthesis inhibition, opening phosphorescent pt (II)-coproporphyrin and mitochondrial damage through loss of transmembrane potential and mitochondrial translation inhibition [1,2,3,5,6,7,8,9]. MTs block protein synthesis processes by inactivating ribosomal peptidyl transferase [1,3,4,7,8,9]. They also induce cellular apoptosis [3,7,26], and can trigger inflammatory cytokine cascades [6,27]. They impair mucosal barriers in the airways and gut sometimes leading to ulceration with epistaxis the most frequent [1,9,17,18,20,28,29]. The potency of different MTs varies with Type D MTs 10 to 100 times more potent than type A or type D in activating MAPKs, impairing leukocyte proliferation and inducing apoptosis [7,26].
Diagnosing MT exposure requires epidemiologically linking exposure to environmental Stachybotrys and/or MT contamination with consistent clinical symptomatology, and biomarkers, such as urine or tissue MTs [16,17,22]. MTs have been detected in multiple human specimens from people exposed to water-damaged Stachybotrys-contaminated environments [10,12,18].
Neonatal outcomes reported here correspond in part to the route of exposure: (1) cutaneous (rashes); (2) inhalation (both neurological developmental delays and respiratory symptoms); and (3) ingestion (oropharyngeal paresis, rectal bleeding, prolapse and intussusception). Other correlations may have been missed due to difficulty evaluating mucosal injury in children.
Neonatal breast milk intolerance occurred in 7/10 (70%). In one baby, ingestion of MT-contaminated milk caused fluoroscopy-confirmed oropharyngeal motor nerve paresis. Another baby progressed to respiratory arrest and pulmonary hemorrhage requiring ICU care. Thrasher et al. also described a 16-month-old infant who died with upper airway bleeding, pulmonary hemorrhage after exposure to a water-damaged home contaminated with Stachybotrys and MTs. At autopsy, trichothecenes were found in his lung liver and brain [29].
Most research on pregnancy exposure has focused on the simple trichothecenes of Fusarium contaminating food and grains, such as Type A T-2 toxin, and Type B Deoxynivalenol (DON) and nivalenol. DON crosses the placenta in sows [30] and causes reproductive toxicity and fetal abnormalities in experimental animals [31]. Intravenous T2 toxin-induced abortion and swine but placentas were not evaluated [32]. In a dual perfusion ex-vivo model with five term human placentae, DON transferred across the placenta, with approximately 20% of the maternal concentration detected on the fetal side [29]. In in-vitro placenta and in human biomonitoring studies, DON was found in serum and blood of pregnant women [33] and has been linked with autism in children [34]. DON and nivalenol were also found in 1st trimester human amniotic fluid sampling in a study screening pregnancies for genetic risks [35].
4.3. Clinical Implications
Our data is concerning and applying the cautionary principle, pregnant and lactating women as well as neonates should avoid all contact with indoor environments contaminated with MTs. Ideally, they need to be relocated before construction, demolition or remodeling activities are begun.
In water-damaged buildings, with mold apparent, personal protection is critical. Macrocyclic trichothecenes toxicity is probably cumulative and, in some instances, results in permanent health effects. Unlike the simple trichothecenes, there is no known antidote for MT exposure. Protective gear is needed--including respiratory, eye and skin protection, as well as disposable gowning covering hair, shoes and clothing [8]. This is impractical for families, so relocation is usually the best solution. Should MT contamination be found, all items that cannot be decontaminated need to be quarantined or safely discarded.
4.4. Research Implications
This study opens the question of whether moldy indoor conditions are hazardous to the pregnant or lactating mother, the unborn and neonate. The hazardous indoor environment is an emerging area for future research Involving toxicology, microbiology, medicine and epidemiology. Reliable assays and biomarkers are needed for biomonitoring. Placentae and breast milk analysis may prove useful.
Indoor macrocyclic trichothecenes, Stachybotrys and Trichoderma may prove to be reliable indicators for exceptionally hazardous indoor conditions. Human biomonitoring studies are needed wherever significant contamination with Stachybotyrs or Trichoderma is found Airborne Stachybotrys spores, unusual in the indoor built environment, may prove to be a useful marker for an unusually hazardous space and the need for further fungal and MT testing. Practical, affordable and reliable screening methods need to be developed.
4.5. Strengths and Limitations
The main strength of this study is in its real-world chronological, detailed medical observational assessments linked with professional indoor inspection. The clinical evaluation of mothers and babies was thorough, with multiple medical records from each department available.
There are several key weaknesses in this study. One uncertainty relates to the ELISA methodology used to detect MTs. This assay is of uncertain diagnostic performance and is only able to identify and quantitate MTs as a group. Better and validated assays are required, but there were no alternatives available in the USA at the time the testing was done. Another weakness lies in that the data collection in each home was done by different inspectors and their observations and measurements were not precisely coincident with exposure. Also, the frequency of mucosal damage in infants is probably underestimated since oronasal examination in small children was difficult, limiting any observations of ulceration or other reasons for symptomatology and poor feeding.
5. Conclusions
In summary, consistent with in in vitro and animal model research, combined with military medicine experience, these epidemiological correlations of real-world clinical chronological exposure data and environmental data support a direct causal relationship between indoor MT or Stachybotrys exposure and adverse pregnancy and neonatal outcomes. We hope this report stimulates the development of improved MT assays and additional epidemiological work related to water-damaged buildings and pregnancy. Further investigation with human biomonitoring recommended for conditions where Stachybotyrs or Trichoderma are found with environmental and clinical testing, including MCTs, done as synchronously as possible. Indoor macrocyclic trichothecenes, Stachybotrys and Trichoderma may prove to be reliable indicators for exceptionally hazardous indoor conditions. Further research into exposure and reproductive risks, particularly during gestation and lactation, is warranted.
Author Contributions
Conceptualization, IHG; methodology, IHG.; validation, IHG and HA.; formal analysis, IHG and HA; data curation, IHG.; writing—original draft preparation, IHG.; writing—review and editing, IHG, HA. All authors have read and agreed to the published version of the manuscript.
Funding
This research received no external funding.
Institutional Review Board Statement
As all patients were referred for clinical review and provided all samples and data voluntarily to IHG, no additional ethical (IRB) review was warranted. All data is anonymized.
Data Availability Statement
Data is unavailable due to health information privacy and security regulations.
Acknowledgements
Dedicated to Donald Armstrong, MD, FIDSA, Infectious Disease Specialist, Past President of the Infectious Disease Society of America, and Jack Thrasher PhD, MD, FIDSA, Environmental Immunotoxicologist, who both guided this research before their deaths.
Disclosure of Information
Irene Grant and Harriet Ammann have served as expert witnesses in mold exposure litigation.
Assistance
All writing and data analysis was done by both authors. Generative AI was never used.
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