FOR IMMEDIATE RELEASE
Orthomolecular Medicine News Service, May 29, 2025

Born Defenseless: Why Infant Liver Maturity May Be the Missing Piece in Understanding Vaccine Safety, SIDS, and NDDs

by Richard Z. Cheng, M.D., Ph.D., Gary S. Goldman, Ph.D.

📌 New Research Highlights a Missing Link in Pediatric Risk

A 2025 study [1] by Dr. Gary S. Goldman and myself, both board members of the Orthomolecular Medicine News Service (OMNS), sheds new light on the immature liver detoxification system in infants-an overlooked but critical factor in understanding vaccine safety, sudden infant death syndrome (SIDS), and the rising burden of chronic childhood diseases.

🏗️ Underdeveloped Liver Detox Pathways in Infants

The liver detoxifies foreign chemicals through three major phases:

Phase	Function	Immaturity in Infants
Phase I	CYP450 enzymes modify toxins	↓ Activity (10-50% of adult levels)
Phase II	Conjugation (e.g., glutathione, methylation)	↓ UGT, GST, SULT enzymes
Phase III	Transport and excretion (bile, urine)	↓ Transporter protein function

🔍 Key Insight: These immature pathways reduce the infant's capacity to metabolize pharmaceutical agents, vaccine components (e.g., aluminum, polysorbate 80), and environmental toxins.

🌍 Global Vaccine Coverage and Infant Vulnerability

• Over 75% of all vaccines are administered during infancy and early childhood, a critical window for neurodevelopment and immune programming.
• In 2023, 84% of infants globally received three doses of DTP3. Coverage for Hepatitis B, MMR, Polio, and Varicella is similarly high [2].
• In the U.S., >90% of children are vaccinated by age 2 years [3].

⚠️ Vaccines = Pharmacological Agents Requiring Liver Detoxification

Vaccines are not benign. They contain:

• Adjuvants (aluminum salts)
• Preservatives (formaldehyde, phenol)
• Surfactants (polysorbate 80)
• mRNA or antigen payloads

Without a mature liver detox system, these ingredients may accumulate, especially in metabolically or genetically vulnerable infants.

🧬 Genetic Polymorphisms and Metabolic Risk

The CYP450 enzyme family is not only underdeveloped in infants but also highly polymorphic. Differences in gene variants mean some infants are poor metabolizers, while others are ultrarapid metabolizers [4,5].

👉Pharmacogenomic testing could identify infants most at risk for adverse vaccine reactions-something current public health policies do not yet include [6,7].

🚨 Potential Vaccine-Associated Toxicities in Infants

Category	Conditions Linked[1,8-14]
🧠 Neurological	Autism spectrum disorder (ASD), developmental delay, seizures
💨 Respiratory & Immune	Asthma, allergies, autoimmune diseases
❤️ Cardiovascular & Metabolic	SIDS, mitochondrial dysfunction, metabolic imbalance
🧬 Detoxification Overload	Aluminum retention, impaired CYP450 clearance, oxidative stress

🧬 Immature Detox + Immune Activation = Perfect Storm

Newborns and infants not only start life with underdeveloped liver detox pathways-but immune activation during illness or vaccination can further suppress their already limited detox capacity.

📉 Cytokine-Mediated Suppression of Detox Enzymes [15-17]:

• Inflammatory cytokines like TNF-α and IL-6 can downregulate CYP450 enzymes, impairing Phase I detox.
• This immune-driven suppression occurs during infection, inflammation, or vaccination.
• In infants-whose metabolic systems are still immature-this double hit further compromises their ability to clear toxins.

🎯 Result:

Even less ability to process toxins when it's needed the most.

This compounding effect may explain vaccine-associated regression, seizures, or SIDS-like events in genetically or nutritionally vulnerable infants. Yet, current public health policies rarely factor in these biochemical realities.

🔍 Factoring New Risk Dimensions into Vaccine Policy

A comprehensive risk-benefit analysis of early-life vaccination should not ignore:

• The prevalence of Autism Spectrum Disorder (ASD), now 1 in 31 children in the U.S. [18].
• The plausible link between SIDS and immature CYP450 enzyme systems and 5-HT brainstem networks involved in autonomic control [19,20].
• Statistically significant findings from Mawson et al. and the Florida Medicaid retrospective study, which show higher NDD rates in vaccinated vs. unvaccinated children-especially in preterm infants [21].

🧠 Investigating the Timing of Immunization: A Metabolic Perspective

Given that CYP450 enzyme systems mature only after 2-3 years of age, these research questions must be asked:

1. Should universal early-life immunization schedules be re-evaluated?

Yes. Not all infants face the same risk. CYP450 immaturity, compounded by genetic polymorphisms, can increase susceptibility to vaccine-related adverse effects, particularly in preterm infants and those with specific genotypes.

2. What is the risk comparison: Infectious mortality vs. NDDs?

• Vaccine-preventable diseases (e.g., pertussis) can be fatal but are rare in modern healthcare systems.
• NDDs (ASD, ADHD, epilepsy) are rising and may have lifelong consequences.
  • Florida Medicaid Study (N > 47,000) showed significantly higher odds of NDDs among fully vaccinated children.
  • Mawson et al. observed higher ASD and chronic disease rates in vaccinated homeschooled children.

✅ Point of balance: Infectious disease risk is highest in early infancy; NDDs last a lifetime. Personalized scheduling may benefit at-risk subgroups.

3. Does breastfeeding reduce infection risk and shift vaccine timing?

Yes. Breastfeeding confers:

• Passive immunity (antibodies)
• Antioxidants (e.g., vitamin C, glutathione precursors)
• Anti-inflammatory factors

This may justify delaying non-urgent vaccinations in breastfed or low-risk infants.

📚 OM Perspective: Orthomolecular Nutrition as Public Health Strategy

Supporting detox pathways with optimal nutrition can mitigate risk. Nutrition-based strategies-especially when initiated prenatally-help mature liver function, reduce oxidative stress, and support immune tolerance.

🍊 Orthomolecular Nutrients That Enhance Infant Detox Capacity [22-27]

Nutrient	Function
Vitamin D3	Gene regulation, immune modulation
Vitamin C	Glutathione recycling, antioxidant
B Vitamins (B2, B6, B12, Folate)	Phase II methylation, neurotransmitter balance
Magnesium, Selenium	Enzyme cofactors for detox pathways
Zinc	Antioxidant, immune regulation, heavy metal binding
N-Acetylcysteine (NAC)	Glutathione precursor (best via maternal intake)

👩‍🍼 Maternal and Infant Supplementation Matters

• Maternal nutrient optimization during pregnancy and lactation enhances infant resilience.
• Breast milk provides vital glutathione precursors and immune factors.
• Infants may benefit from supplemental vitamin D, C, and probiotics under medical supervision.

🧩 Call to Action: Integrate Orthomolecular, Pediatric, and Public Health Fields

• Recognize detox immaturity in pediatric vaccination policy.
• Delay or adjust vaccine schedules for genetically or metabolically vulnerable infants.
• Promote individualized risk-benefit communication with parents.
• Implement prenatal and early-life orthomolecular nutrition policies.

✅ Conclusion

"Infants are biochemically distinct from adults. They cannot detoxify at the same level. Public health must reflect this physiological truth." - Richard Z. Cheng, M.D., Ph.D.

Vaccine safety must include detoxification readiness. This readiness is shaped by developmental maturity, genetic variability, and nutritional status.

Through orthomolecular support, informed risk stratification, and precision vaccine scheduling, we can protect infants from both infectious diseases and neurodevelopmental harms.

🧾 About the Author

Richard Z. Cheng, M.D., Ph.D. - Editor-in-Chief, Orthomolecular Medicine News Service (OMNS). Dr. Cheng is a practicing physician based in the USA and China, specializing in integrative and orthomolecular approaches to health. His clinical interests include nutrition-based therapy, functional medicine, low-carb medicine, and anti-aging medicine. He also works internationally as a health consultant and educator.

Gary S. Goldman, Ph.D. - Independent computer scientist and consultant specializing in epidemiological studies and vaccine safety. He served as the Research Analyst in a project funded by the Centers for Disease Control and Prevention (CDC), where he utilized capture-recapture statistical methods in connection with reports of varicella and herpes zoster cases to derive ascertainment-corrected incidence rates. Goldman is on the editorial board of OMNS and serves as an unpaid consultant to Physicians for Informed Consent. His work continues to influence discussions on vaccine policy and public health.

References:

1. Goldman, G. S. & Cheng, R. Z. The Immature Infant Liver: Cytochrome P450 Enzymes and their Relevance to Vaccine Safety and SIDS Research. Int J Med Sci 22, 2434-2445 (2025).

2. WHO. Immunization coverage. https://www.who.int/news-room/fact-sheets/detail/immunization-coverage.

3. Hill, H. A. Vaccination Coverage by Age 24 Months Among Children Born in 2019 and 2020 - National Immunization Survey-Child, United States, 2020-2022. MMWR Morb Mortal Wkly Rep 72, (2023).

4. Zhou, S.-F., Liu, J.-P. & Chowbay, B. Polymorphism of human cytochrome P450 enzymes and its clinical impact. Drug Metab Rev 41, 89-295 (2009).

5. Manworren, R. C. B. et al. Pharmacogenetic Testing for Analgesic Adverse Effects: Pediatric Case Series. Clin J Pain 32, 109-115 (2016).

6. Thomas, C. & Moridani, M. Interindividual variations in the efficacy and toxicity of vaccines. Toxicology 278, 204-210 (2010).

7. Kearns, G. L. Pharmacogenetics and development: are infants and children at increased risk for adverse outcomes? Curr Opin Pediatr 7, 220-233 (1995).

8. Tomljenovic, L. & Shaw, C. Mechanisms of aluminum adjuvant toxicity and autoimmunity in pediatric populations. Lupus 21, 223-230 (2012).

9. Boretti, A. Reviewing the association between aluminum adjuvants in the vaccines and autism spectrum disorder. J Trace Elem Med Biol 66, 126764 (2021).

10. Shaw, I. C. Chemical residues, food additives and natural toxicants in food - the cocktail effect - Shaw - 2014 - International Journal of Food Science & Technology - Wiley Online Library. International Journal of Food Sciences + Technology 49, 2149-2157 (2014).

11. Angrand, L., Masson, J.-D., Rubio-Casillas, A., Nosten-Bertrand, M. & Crépeaux, G. Inflammation and Autophagy: A Convergent Point between Autism Spectrum Disorder (ASD)-Related Genetic and Environmental Factors: Focus on Aluminum Adjuvants. Toxics 10, 518 (2022).

12. Tomljenovic, L. & Shaw, C. A. Aluminum vaccine adjuvants: are they safe? Curr Med Chem 18, 2630-2637 (2011).

13. Mawson, A. R. & Croft, A. M. Multiple Vaccinations and the Enigma of Vaccine Injury. Vaccines (Basel) 8, 676 (2020).

14. Miller, N. Z. Vaccines and sudden infant death: An analysis of the VAERS database 1990-2019 and review of the medical literature. Toxicol Rep 8, 1324-1335 (2021).

15. Williams, J. F. Cytochrome P450 isoforms. Regulation during infection, inflammation and by cytokines. J Fla Med Assoc 78, 517-519 (1991).

16. Dickmann, L. J., Patel, S. K., Rock, D. A., Wienkers, L. C. & Slatter, J. G. Effects of interleukin-6 (IL-6) and an anti-IL-6 monoclonal antibody on drug-metabolizing enzymes in human hepatocyte culture. Drug Metab Dispos 39, 1415-1422 (2011).

17. Yanev, S. Immune system - drug metabolism interactions: Toxicological insight. Adipobiology 6, 30-36 (2014).

18. Shaw, K. A. Prevalence and Early Identification of Autism Spectrum Disorder Among Children Aged 4 and 8 Years - Autism and Developmental Disabilities Monitoring Network, 16 Sites, United States, 2022. MMWR Surveill Summ 74, (2025).

19. Duncan, J. R. et al. Brainstem serotonergic deficiency in sudden infant death syndrome. JAMA 303, 430-437 (2010).

20. Paterson, D. S. et al. Multiple serotonergic brainstem abnormalities in sudden infant death syndrome. JAMA 296, 2124-2132 (2006).

21. Mawson, A. R. & Jacob, B. Vaccination and Neurodevelopmental Disorders: A Study of Nine-Year-Old Children Enrolled in Medicaid - Science, Public Health Policy and the Law. Science, Public Health Policy and the Law (2025).

22. Teixeira, V., Mohamed, I. & Lavoie, J.-C. Neonatal Vitamin C and Cysteine Deficiencies Program Adult Hepatic Glutathione and Specific Activities of Glucokinase, Phosphofructokinase, and Acetyl-CoA Carboxylase in Guinea Pigs' Livers. Antioxidants (Basel) 10, 953 (2021).

23. Böhles, H. Antioxidative vitamins in prematurely and maturely born infants. Int J Vitam Nutr Res 67, 321-328 (1997).

24. Grant, W. B., Wimalawansa, S. J., Pludowski, P. & Cheng, R. Z. Vitamin D: Evidence-Based Health Benefits and Recommendations for Population Guidelines. Nutrients 17, 277 (2025).

25. Biswas, S. A., Rukunuzzaman, M., Biswas, R. K., Rahman, S. M. H. & Alam, M. S. Serum Vitamin D Status in Infants with Cholestatic Jaundice. Mymensingh Med J 34, 192-199 (2025).

26. Pratt, C. A., Garcia, M. G. & Kerner, J. A., Jr. Nutritional Management of Neonatal and Infant Liver Disease. NeoReviews 2, e215-e222 (2001).

27. Mager, D. R., Marcon, M., Wales, P. & Pencharz, P. B. Use of N-acetyl cysteine for the treatment of parenteral nutrition-induced liver disease in children receiving home parenteral nutrition. J Pediatr Gastroenterol Nutr 46, 220-223 (2008).

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