Anthony R Mawson1*, Brian D Ray2, Azad R Bhuiyan3 and Binu Jacob4
Reprinted from Journal of Translational Science – OAT – Open Access Text -ISSN: 2059-268X
Vaccinations have prevented millions of infectious illnesses, hospitalizations and deaths among U.S. children, yet the long-term health outcomes of the vaccination schedule remain uncertain. Studies have been recommended by the U.S. Institute of Medicine to address this question. This study aimed 1) to compare vaccinated and unvaccinated children on a broad range of health outcomes, and 2) to determine whether an association found between vaccination and neurodevelopmental disorders (NDD), if any, remained significant after adjustment for other measured factors. A cross-sectional study of mothers of children educated at home was carried out in collaboration with homeschool organizations in four U.S. states: Florida, Louisiana, Mississippi and Oregon. Mothers were asked to complete an anonymous online questionnaire on their 6- to 12-year-old biological children with respect to pregnancy-related factors, birth history, vaccinations, physician-diagnosed illnesses, medications used, and health services. NDD, a derived diagnostic measure, was defined as having one or more of the following three closely-related diagnoses: a learning disability, Attention Deficient Hyperactivity Disorder, and Autism Spectrum Disorder. A convenience sample of 666 children was obtained, of which 261 (39%) were unvaccinated. The vaccinated were less likely than the unvaccinated to have been diagnosed with chickenpox and pertussis, but more likely to have been diagnosed with pneumonia, otitis media, allergies and NDD. After adjustment, vaccination, male gender, and preterm birth remained significantly associated with
NDD. However, in a final adjusted model with interaction, vaccination but not preterm birth remained associated with NDD, while the interaction of preterm birth and vaccination was associated with a 6.6-fold increased odds of NDD (95% CI: 2.8, 15.5). In conclusion, vaccinated homeschool children were found to have a higher rate of allergies and NDD than unvaccinated homeschool children. While vaccination remained significantly associated with NDD after controlling for other factors, preterm birth coupled with vaccination was associated with an apparent synergistic increase in the odds of NDD. Further research involving larger, independent samples and stronger research designs is needed to verify and understand these unexpected findings in order to optimize the impact of vaccines on children’s health.
Abbreviations: ADHD: Attention Deficit Hyperactivity Disorder; ASD: Autism Spectrum Disorder; AOM: Acute Otitis Media; CDC: Centers for Disease Control and Prevention; CI: Confidence Interval; NDD: Neurodevelopmental Disorders; NHERI: National Home Education Research Institute; OR: Odds Ratio; PCV-7: Pneumococcal Conjugate Vaccine-7; VAERS: Vaccine Adverse Events Reporting System.
Vaccines are among the greatest achievements of biomedical science and one of the most effective public health interventions of the 20th century . Among U.S. children born between 1995 and 2013, vaccination is estimated to have prevented 322 million illnesses, 21 million hospitalizations and 732,000 premature deaths, with overall cost savings of $1.38 trillion . About 95% of U.S. children of kindergarten age receive all of the recommended vaccines as a requirement for school and daycare attendance [3,4], aimed at preventing the occurrence and spread of targeted infectious diseases . Advances in biotechnology are contributing to the development of new vaccines for widespread use .
Under the currently recommended pediatric vaccination schedule , U.S. children receive up to 48 doses of vaccines for 14 diseases from birth to age six years, a figure that has steadily increased since the 1950s, most notably since the Vaccines for Children program was created in 1994. The Vaccines for Children program began with vaccines targeting nine diseases: diphtheria, tetanus, pertussis, polio,
Haemophilus influenzae type b disease, hepatitis B, measles, mumps, and rubella. Between 1995 and 2013, new vaccines against five other diseases were added for children age 6 and under: varicella, hepatitis A, pneumococcal disease, influenza, and rotavirus vaccine.
Although short-term immunologic and safety testing is performed on vaccines prior to their approval by the U.S. Food and Drug Administration, the long-term effects of individual vaccines and of the vaccination program itself remain unknown . Vaccines are acknowledged to carry risks of severe acute and chronic adverse effects, such as neurological complications and even death , but such risks are considered so rare that the vaccination program is believed to be safe and effective for virtually all children .
There are very few randomized trials on any existing vaccine recommended for children in terms of morbidity and mortality, in
part because of ethical concerns involving withholding vaccines from children assigned to a control group. One exception, the high-titer measles vaccine, was withdrawn after several randomized trials in west Africa showed that it interacted with the diphtheria-tetanus-pertussis vaccine, resulting in a significant 33% increase in child mortality . Evidence of safety from observational studies includes a limited number of vaccines, e.g., the measles, mumps and rubella vaccine, and hepatitis B vaccine, but none on the childhood vaccination program itself. Knowledge is limited even for vaccines with a long record of safety and protection against contagious diseases . The safe levels and long-term effects of vaccine ingredients such as adjuvants and preservatives are also unknown . Other concerns include the safety and cost-effectiveness of newer vaccines against diseases that are potentially lethal for individuals but have a lesser impact on population health, such as the group B meningococcus vaccine .
Knowledge of adverse events following vaccinations is largely based on voluntary reports to the Vaccine Adverse Events Reporting System (VAERS) by physicians and parents. However, the rate of reporting of serious vaccine injuries is estimated to be <1% . These considerations led the former Institute of Medicine (now the National Academy of Medicine) in 2005 to recommend the development of a five-year plan for vaccine safety research by the Centers for Disease Control and Prevention (CDC) [16,17]. In its 2011 and 2013 reviews of the adverse effects of vaccines, the Institute of Medicine concluded that few health problems are caused by or associated with vaccines, and found no evidence that the vaccination schedule was unsafe [18,19]. Another systematic review, commissioned by the US Agency for Healthcare Research and Quality to identify gaps in evidence on the safety of the childhood vaccination program, concluded that severe adverse events following vaccinations are extremely rare . The Institute of Medicine, however, noted that studies were needed: to compare the health outcomes of vaccinated and unvaccinated children; to examine the long-term cumulative effects of vaccines; the timing of vaccination in relation to the age and condition of the child; the total load or number of vaccines given at one time; the effect of other vaccine ingredients in relation to health outcomes; and the mechanisms of vaccine-associated injury .
A complicating factor in evaluating the vaccination program is that vaccines against infectious diseases have complex nonspecific effects on morbidity and mortality that extend beyond prevention of the targeted disease. The existence of such effects poses a challenge to the assumption that individual vaccines affect the immune system independently of each other and have no physiological effect other than protection against the targeted pathogen . The nonspecific effects of some vaccines appear to be beneficial, while in others they appear to increase morbidity and mortality [22,23]. For instance, both the measles and Bacillus Calmette–Guérin vaccine reportedly reduce overall morbidity and mortality , whereas the diphtheria-tetanus-pertussis  and hepatitis B vaccines  have the opposite effect. The mechanisms responsible for these nonspecific effects are unknown but may involve inter alia: interactions between vaccines and their ingredients, e.g., whether the vaccines are live or inactivated; the most recently administered vaccine; micronutrient supplements such as vitamin A; the sequence in which vaccines are given; and their possible combined and cumulative effects .
A major current controversy is the question of whether vaccination plays a role in neurodevelopmental disorders (NDDs), which broadly include learning disabilities, Attention Deficit Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD). The controversy has been fueled by the fact that the U.S. is experiencing what has been described as a “silent pandemic” of mostly subclinical developmental neurotoxicity, in which about 15% of children suffer from a learning disability, sensory deficits, and developmental delays [27,28]. In 1996 the estimated prevalence of ASD was 0.42%. By 2010 it had risen to 1.47% (1 in 68), with 1 in 42 boys and 1 in 189 girls affected . More recently, based on a CDC survey of parents in 2011–2014, 2.24% of children (1 in 45) were estimated to have ASD. Rates of other developmental disabilities, however, such as intellectual disability, cerebral palsy, hearing loss, and vision impairments, have declined or remained unchanged . Prevalence rates of Attention Deficit Hyperactivity Disorder (ADHD) have also risen markedly in recent decades . Earlier increases in the prevalence of learning disability have been followed by declining rates in most states, possibly due to changes in diagnostic criteria .
It is believed that much of the increase in NDD diagnoses in recent decades has been due to growing awareness of autism and more sensitive screening tools, and hence to greater numbers of children with milder symptoms of autism. But these factors do not account for all of the increase . The geographically widespread increase in ASD and ADHD suggests a role for an environmental factor to which virtually all children are exposed. Agricultural chemicals are a current focus of research [34-37].