“Childhood Vaccine Schedule Safe, IOM Says” [1]
“Report Confirms Safety of Childhood Immunization Schedule” [2]
“Schedule Of Childhood Vaccines Declared Safe” [3]
You may be inclined to interpret that our current National Vaccine Schedule is safe if you’ve read the new public reports on the recent evaluation completed by the Institute of Medicine
Before reading the report, I was very curious - I had yet to read any quality, scientific studies to support the safety of the current CDC (ACIP) recommended schedule for children under 6 years of age.
What new research had been done? What literature is this safety based on?
This held a prime opportunity to take initiative, read the report and review the literature testifying the safety of the current schedule in place…
Almost immediately I was met with some bizarre wording like:
Pg 117
The committee found no significant evidence to imply that the recommend immunization schedule is not safe. Furthermore, existing surveillance and response systems have identified adverse events known to be associated with vaccination.
So let me get this right –
No evidence was found that the childhood immunization schedule is not safe = the current US
Whoa - say that again?
The schedule is safe… I mean, it would be safe if it could be proven not-unsafe.
Let’s just get down to it. Did the committee determine that the current number of doses and timing that a child receives is or is not associated with an increase in significant health problems?
You may be surprised that the committee pointed not to a body of evidence that had been overlooked but rather to the fact that existing research has not been designed to test the entire immunization schedule… (pg 83)
The 37 Studies Reviewed
Here is my offering to you my friends…the studies included in the committee’s review. But wait – let me preface with a few excerpts:
pg 69
The committee did not have the time or the resources to conduct formal reviews meeting all criteria for systematic reviews for each question of interest, nor did it find substantial evidence to conduct a quantitative synthesis. Therefore, the committee searched for, assembled and summarized information already available in the peer-reviewed literature....
No substantial evidence was found – so the committee summarized information already published and available to determine their findings….
Oh goodie, gret ready for a pseudo-synthesis of unsubstantial literature… basically a glorified bibliography to determine how not unsafe the current schedule is. [4]
pg 70
The searches initially yielded 748 references. This number was further reduced to 143...
…in the end 37 articles were chosen.
More appalling news…less then 40 studies published within the last decade exist that the committee determined to address the current 0-6 yr old vaccine schedule.
At least it made it easy to review all of them and include them here in this post. (pages 71-87 in the report give a brief review of the literature/research that was selected)
I give a brief summary below with the following points extracted from the committee report or via the published work itself. I provide a link to the abstract (and in some cases a full PDF) for each article used in the study – just click on the title to review.
Origin: included to determine how relevant the study is to US
Size/Popluation: included determine statistical significance
Time period: included to determine how relevant the study is to current schedule
Vaccine(s): included to determine how relevant the study is to current schedule
Outcome: these were listed by the committee or authors of published work
Limitations/bias: these were listed by the committee
Allergy and Asthma
Although Ovid MEDLINE literature search initially identified 40 references to articles on the relationship between immunization or vaccines and asthma or hypersensitivity – the number was reduced to 14 papers after exclusion criteria was applied.
1
Origin: Australia
Size/Popluation: 620
Time period: 1989-1995
Vaccine(s):DTP/DT, OPV, MMR (my note: DTP and OPV are not on the US
Outcome: No relationship found, however, administration of DT in the first year of life was associated with increased in asthma at 6 years of age (My note: children following the US schedule receive 3 injections of DT(aP) prior to the first year of life)
Limitations/bias: self-report and small sample size
2
Origin: Australia
Size/Popluation: 5,729
Time period: 1968, follow-up of 44yr olds
Vaccine(s):DTAP, polio, smallpox
Outcome: No association found
Limitations/bias: self-report
3
Origin: France
Size/Popluation: 718 (694=vaccinated, 24=unvaccinated)
Time period: 2005
Vaccine(s):DTAP, polio, smallpox
Outcome: Vaccinated adolescents were significantly less like to have asthma, allergic rhinitis and eczema-the relationship DID NOT depend on the vaccination schedule or number of inoculations. Stated directly in the abstract: A higher protection was observed in the case of the two live vaccines (oral polio and bacilli Camille-Guerin) ..both of which are NOT on the US
Limitations/bias: self-report
4
Origin: Australia
Size/Popluation: 4,500
Time period: 1992, with follow up in 2004
Vaccine(s): MMR, DTAP,OPV, Heb B
Outcome: no significant association found
Limitations/bias: recall bias due to the collection of data via mailed questionnaire
5
Origin: United Kingdom
Size/Popluation: 29,238 (children 0-11 yrs)
Time period: 1988-1999
Vaccine(s): compared the results of DPPT (diphtheria,polio,pertussis,tetanus)and MMR
Outcome: association between MMR and DPPT vaccination and an increase in asthma and eczema was found but the authors of the original study dismissed this as ascertainment bias.
Limitations/bias: very small number of unvaccinated population, ascertainment bias
6
Origin: Germany
Size/Popluation: 7,609 (this number is reported in the IOM's report - however, when referencing the abstract for the study the number of total children is 943)
Time period: 1990-1995 (5 years)
Vaccine(s): only references 'doses', does not determine/specify which vaccine
Outcome: Higher vaccination coverage seems to be associated with dermatitis, asthma and allergic sensitization rates. (The committee makes note that this study may serve as an example by which the US
Limitations/bias: very small number of unvaccinated population, ascertainment bias
7
Origin: United Kingdom
Size/Popluation: 6,811
Time period: 1993-1997 (monitored till 2003)
Vaccine(s):DTP (not on the US recommended schedule)
Outcome: No association found between vaccination against DTP and asthma (please note the frequency of vaccination was not addressed, nor at what age the vaccine was administered-two key factors in determining a national immunization schedule)
Limitations/bias: very few children were in the unvaccinated group (96.9 percent were fully vaccinated)
8
Origin: Canada
Size/Popluation: Report states approximately 14,000 (after review of literature, number confirmed is 13,980. The number who completed the 4 dose schedule is 11,531)
Time period: 1993-1997 (monitored till 2003)
Vaccine(s):DTP (not on the US recommended schedule)
Outcome: Association was found between timing of DTP (the first dose and the second dose)received and an increase in asthma by age 7. For each month delayed in time, the risk decreased.
Limitations/bias: ascertainment bias, nonrandom reasons for delay, variations in socioeconomic status (SES). Committee states a prospective study using DT(aP) would be needed to confirm results.
9
Origin: Canada
Size/Popluation: report states 13,971, after reviewing the literature evaluation of 13,810 children was completed (340 in the un-vaccinated group)
Time period: 1993-1997 (monitored till 2003)
Vaccine(s):DTP (not on the US recommended schedule)
Outcome: Committee states no association was found. In the literature, unadjusted analyses showed significant association in asthma but this was dismissed because of small numbers in some groups and because the results did not support the hypothesis (?!)
Limitations/bias: none reported
10
Origin: Sweden
Size/Popluation:538 children age 7
Time period: this study was a follow up to a prior randomized control trial
Vaccine(s): 4 vaccines were compared: 2-component pertussis, 5-component pertussis, whole cell DTP and DT (to the best of my knowledge, none of these are used in the US
Outcome: an increase in asthma was associated with the 2-component pertussis vaccine after booster vaccination. The other vaccines were not seen as a risk factor for the development of allergy in the first 7 years of life.
Limitations/bias: none reported
11
Origin: United States
Size/Popluation:538 children age 7
Time period: 1960-2004
Vaccine(s): the entire immunization schedule at that time (no one particular vaccine was examined)
Outcome: increase in asthma reported in NHIS preceded the increase in the recommend number of vaccines which supports that there is no association with increased immunizations and asthma. (my notes: according to the chart, a sharp increase occurred mid-1980 – Hib was added to the schedule in 1988 > please review this study finding a positive association with asthma and Hib)
Limitations/bias: none reported
12
Origin: United States
Size/Popluation: 7,098
Time period: 1987-2001
Vaccine(s): DTP, MMR and BCG (DTP and BCG is not currently on the US
Outcome: Completing MMR after 2 years was associated with reduced hay fever.
Limitations/bias: Data on immunizations and other variable were collected retrospectively. Limited variation in vaccine exposure.
13
Origin: United States
Size/Popluation: ecological study n=1,074
Time period: 1987-2001
Vaccine(s): the entire immunization schedule at that time
Outcome: Atopy cases received fewer antigen doses/occurrences when there was less exposure to Hib B, HiB, mumps and rubella vaccines during the first 2 years of life-with limited statistical power, the study concluded that no association was found between atopy and vaccine exposure
Limitations/bias: Data on immunizations and other variable were collected retrospectively. Limited variation in vaccine exposure.
14
Origin: United Kingdom
Size/Popluation: 7,098
Time period: reviewed data from two databases GPRD and Doctors Independent Network
Vaccine(s): DTP, MMR and BCG (DTP and BCG is not currently on the US
Outcome: Completing MMR after 2 years was associated with reduced hay fever as well as a slightly reduction when delaying DTP. Those children who received BCG had an increased risk of hay fever.
Limitations/bias: Limited by source and limited value because DTP and BCG is not on US schedule
Autoimmune Disease
Although Ovid MEDLINE literature search initially identified 50 references to articles on the relationship between immunization or vaccines and autoimmune disease – the number was reduced to 4 papers after exclusion criteria was applied
15
Origin: UnitedStates
Size/Popluation: 1.8 million children
Time period: 2000-2009
Vaccine(s): all vaccines except MMR (because the risk of developing ITP is already established with MMR)
Outcome: There was no elevated risk of ITP after any vaccine in early childhood other than MMR in the 12-19 month age group. There was a significantly elevated risk of ITP after hepatitis A vaccine at 7 to 17 years of age, and for varicella vaccine and tetanus-diphtheria-acellular pertussis vaccine at 11 to 17 years of age. For hepatitis A, varicella, and tetanus-diphtheria-acellular pertussis vaccines, elevated risks were based on one to two vaccine-exposed cases.
Limitations/bias: ITP is a rare adverse event and it is difficult to examine the risk in association with immunization with other vaccines independently when these vaccines are routinely given at the same time
(Quickly, I would like to mention here that 2 months, early Dec 2012, had a co-worker whose daughter of 16 months of age received confirmation with ITP diagnosis within 3 weeks of vaccination of the MMR vaccine. I presented him information; however this was never reported to VAERS or VSD. They were informed by their doctors that no one knows how or why ITP occurs in pediatric populations unless a pre-existing conditions, such as leukemia, exists. In my experience, this occurs much more frequently then reported…as I assume other adverse events do as well. It’s truly unfortunate.)
16
Epidemiology of paediatric immune thrombocytopenia in the General Practice Research Database.
Origin: United Kingdom
Size/Popluation: 1,145
Time period: 1990-2005
Vaccine(s): all vaccines except MMR (because the risk of developing ITP is already established with MMR)
Outcome: 40.9% of the 257 pediatric patients that were diagnosed with ITP had received the MMR within 6 weeks. Significantly higher incidence in boys to girls age 2-5 yrs was seen. Among teenagers (13-17 years) the overall incidence was lower and a similar incidence witness in boys and girls.
Limitations/bias: Cases were identified via computerized records instead of questionnaires which may have failed to capture a number of mild infections that did not lead to prompt contact with a physician
17
Childhood vaccination and type 1 diabetes.
Origin: Denmark
Size/Popluation: 739,694
Time period: 1990-2000
Vaccine(s): all vaccines on the Demark schedule during that time
Outcome: The results did not support a causal relation between childhood vaccination and type 1 diabetes.
Limitations/bias: The study used the Danish National Hospital Register rather then the National Diabetes Registry which goes back only to 1996 (this was done to make sure they had large enough numbers of children for analysis). One strength noted by the committee was that this was a nationwide cohort with longitudinal, individual-level information on vaccination and diabetes incidence.
18
Analysis of adverse events of potential autoimmune aetiology in a large integrated safety database of AS04 adjuvant vaccines. (Full PDF here)
Origin: International analysis of all safety trials
Size/Popluation: 68,000
Time period: N/A
Vaccine(s): This evaluation focused on AS04 adjuvant which are used in the HPV vaccines and Hep B
Outcome: No statistically significant difference in adverse event rates between the AS04 adjuvant and the control groups (aluminum adjuvant or aluminum hydroxide).
Limitations/bias: none listed
Autism
Although literature search initially identified 32 references to articles on the relationship between immunization or vaccines and autoimmune disease – the number was reduced to 4 papers after exclusion criteria was applied
19
Origin:Canada
Size/Popluation: 27,749
Time period: 1987-1998
Vaccine(s): MMR (single does and second dose)
Outcome: A continuous increase was seen in the incidence of PDD (pervasive developmental disorder), despite the elimination of thimerosal in the MMR vaccine and a decrease in MMR vaccine coverage.
Limitations/bias: Reliance on administrative codes for diagnosis of PDD. The study also used one school district which some PDD cases may have moved into that board which would have inflated the numbers.
20
Thimerosal exposure in infants and developmental disorders: a retrospective cohort study in the United kingdom does not support a causal association.
Origin: United Kingdom
Size/Popluation: 109,863
Time period: 1988-1997
Vaccine(s): DTP or DT exposures
Outcome: With the exception of tics, there was no evidence that thimerosal exposure via DTP/DT vaccines causes neuro-developmental disorders.
Limitations/bias: The inability to adjust for socio-economic status and other medical conditions.
21
Association between thimerosal-containing vaccine and autism.
Origin:Denmark
Size/Popluation: 467,450
Time period: 1990-1996
Vaccine(s): DTP Thimerosal-containg versus DTP thimerosal-free formulation
Outcome: The risk of autism and other autistic-spectrum disorders did not differ significantly between children vaccinated with thimerosal-containing vaccine and children vaccinated with thimerosal-free vaccine (RR, 0.85 [95% confidence interval [CI], 0.60-1.20] for autism; RR, 1.12 [95% CI, 0.88-1.43] for other autistic-spectrum disorders). Furthermore, we found no evidence of a dose-response association
Limitations/bias: The only aspect of the (Denmark
22
Thimerosal and the occurrence of autism: negative ecological evidence from Danish population-based data.
Origin:Denmark
Size/Popluation: 956
Time period: 1971-2000
Vaccine(s): all vaccines administered on the Danish schedule within that time frame (in children 2-10 yrs of age)
Outcome: There was no trend toward an increase in the incidence of autism during that period when thimerosal was used in Denmark
Limitations/bias: This was an ecological study and so it cannot confirm an association. The paper provided no real information about the immunization schedule.
Other Neurodevelopment Disorders
Although literature search initially identified 41 references to articles on the relationship between immunization or vaccines and autoimmune disease – the number was reduced to 6 papers after exclusion criteria was applied
23
Origin:Italy
Size/Popluation: 1403
Time period: 1992/1993 initial enrollment. Participants were contacted 10 years later in 2003 for follow up
Vaccine(s): Pertussis vaccines containing thimerosal
Outcome: 2 neuropsychological outcomes were significantly associated with thimerosal exposure. Girls with higher thimerosal intake had lower mean scores in the finger-tapping test with the dominant hand and in the Boston Naming Test.
Limitations/bias: Given the large number of comparisons, these significant differences could be attributed to chance. Also, in this study, the cumulative dose of thimerosal was low compared with the doses that had been used in the United States
24
Origin: United States
Size/Popluation: 1047 enrolled; aged 7 and 10 years old
Time period: analysis performed in 2007 –immunization status was retrospectively assessed for the first 7 months of life
Vaccine(s): Pertussis vaccines containing thimerosal
Outcome: Among the 42 neuropsychological outcomes, we detected only a few significant associations with exposure to mercury from thimerosal. The detected associations were small and almost equally divided between positive and negative effects.
Limitations/bias: The study was limited by only a 30 percent participation rate which may have resulted in a selection bias.
25
(Citing incorrectly in the paper)
On-time vaccine receipt in the first year does not adversely affect neuropsychological outcomes. (Full PDF here)
Also - This paper utilized data gathered from this study)
Origin: United States
Size/Popluation: 1047
Time period: children born between 1993-1997
Vaccine(s): Fully up-to date vaccinated population (N=491) = 2 hep B, 3 DTP, 3 Hib B, 2 polio. Children who did not meet this definition were classified as having untimely vaccine receipt (N=235). The ‘least’ vaccinated group received 6 or less vaccine doses during the first 7 months of life (N=311)
Outcome: Timely vaccination during infancy has no adverse effect on neuropsychological outcomes 7 to 10 years later. Timely vaccination was associated with better performance on 12 outcomes in univariate testing and remained associated with better performance for 2 outcomes in multivariable analyses. No statistically significant differences favored delayed receipt.
Limitations/bias: Because the children in this study were born between 1993 and 1997, these results may not be generalizable to the current infant immunization schedule which now includes 3 doses of heptavalent pneumococcal conjugate vaccine, 3 doses of oral rotavirus, and 1 or 2 doses of influenza in the first year of life.
26
Origin: Brazil
Size/Popluation: 84 infants
Time period: performed in 2007 – data assessed at 6 months of age
Vaccine(s): thimerosal containing Hep B and DTP
Outcome: Compared to the group immunized 2-4 days after hospital discharge, the group immunized within 24 h showed no significant difference in ND delays. We speculate that breastfeeding remains a significant strategy to improve central nervous system protection of infants facing early exposure challenges.
Limitations/bias: Small sample size. Research focused on a minimal alteration in the immunization schedule that may have been so minor that an effect on ND would not be expected.
27
Origin: United Kingdom
Size/Popluation: >14,000 (specific geographic area-Avon, UK
Time period: children born in 1991/1992
Vaccine(s): thimerosal containing vaccines administered at 3, 4 and 6 months of age
Outcome: Contrary to expectation, it was common for the unadjusted results to suggest a beneficial effect of thimerosal exposure. The study found 1 result of 69 to be in the direction hypothesized-poor prosocial behavior at 47 months.
Limitations/bias: None reported
28
Origin: United States
Size/Popluation: not specified
Time period: children born between 1992-1999
Vaccine(s): thimerosal containing vaccines administered at 3, 4 and 6 months of age
Outcome: In phase I at HMO A, cumulative exposure at 3 months resulted in a significant positive association with. At HMO B, increased risks of language delay were found for cumulative exposure at 3 and 7 months. In phase II at HMO C, no significant associations were found. However – study states no consistent significant associations were found between TCVs and neurodevelopmental outcomes.
Limitations/bias: For resolving the conflicting findings, studies with uniform neurodevelopmental assessments of children with a range of cumulative thimerosal exposures are needed.
Seizure, Febrile Seizures, and Epilepsy
Although literature search initially identified 58 references to articles on the relationship between immunization or vaccines and autoimmune disease – the number was reduced to 4 papers after exclusion criteria was applied
29
Origin: Denmark
Size/Popluation: 378,834 children
Time period: children born between 2003-2008 (followed up through 2009)
Vaccine(s): DTaP-IPV-Hib combination given at 3, 5 and 12 months
Outcome: DTaP-IPV-Hib vaccination was associated with an increased risk of febrile seizures on the day of the first 2 vaccinations given at 3 and 5 months, although the absolute risk was small.
Limitations/bias: The investigators did not address whether children with a high risk of developing febrile seizures or epilepsy were less likely to have been vaccinated
30
Origin: United States
Size/Popluation: 83,107 children aged 12-23 months
Time period: 2000-2008
Vaccine(s): MMR+V compared to MMR
Outcome: The investigators determined that both MMRV and MMR are associated with increases outpatient visits for fever and seizures 7-10 days following vaccination, with MMR+V increase the risk of fever and seizure twice as much as MMR plus varicella separately.
Providers who recommend MMRV should communicate to parents that it increases the risk of fever and seizure over that already associated with measles-containing vaccines.
Limitations/bias: This study determined febrile seizure by the outline of the International Classification of Diseases Ninth Revision – which may have somewhat overestimated the risk of this adverse event.
31
Origin: United States
Size/Popluation: 206,174 (ages 6-59 months)
Time period: Nov-Dec 2010
Vaccine(s): TIV (inactivated influenza vaccine) and PCV13 (pneumococcal conjugate vaccine)
Outcome: Increased risk of febrile seizure was detected occurring between 0 and 1 days following the frist dose of TIV. The risk was higher is both TIV and PCV13 was administered simultaneously (versus TIV or PCV13 alone).
The risk was highest for children at 16 months of age (authors note that this was not surprising as studies of the natural history of febrile seizure indicate that this age has the greatest risk).
The results of this study led the manufacture to include information of increased risk of febrile seizure who concomitantly receive both TIV and PCV13.
Limitations/bias: Study did not evaluate the possible effects of other vaccines (such as DTaP). Also, researchers were not able to exclude cases who had intercurrent infection as the cause of febrile seizure.
32
Origin: The Netherlands
Size/Popluation: 28,796
Time period: 2003-2007
Vaccine(s): DTP, DT(aP), DT(aP)+pneumococcal vaccine (Prevnar)
Outcome: Whole cell pertussis vaccine showed a significantly higher reactogenicity regarding the adverse events analyzed, while addition of conjugated pneumococcal vaccine administered simultaneously with acellular pertussis showed no statistically different adverse event profile.
Possible febrile seizure was noted after the fourth dose of aP with only two cases occurring in the group receiving whole-cell pertussis- however this was considered statistically insignificant.
Limitations/bias: Limited by the 54 percent questionnaire return rate with a probable bias of an increase rate of return from parents of children who had reactions. Also, some at-risk children received HebB vaccine at the same time as pertussis vaccine, but this clinical feature was not factored into the analysis.
Immunization of Premature Infants
The literature search identified 6 papers on the immunization of preterm infants since 2002. The papers were not specifically listed in the review and only a brief one paragraph summary was included.
33-37
An increased risk of cardio-respiratory events after vaccination may exist. The authors of several papers suggest that infants be monitored in the hospital after the first and perhaps the second round of immunizations. Risk factors include: lower birth weight, ongoing complications and underlying medical conditions.
Conclusion and Recommendations
After reading the brief synopsis of the studies reviewed, you may very well come to the exact same conclusion as the committee themselves!
Pg 75
No evidence is available from studies that have directly examined the current immunization schedule (most studies enrolled children in the 1990s, and most were not conducted in the United States
Pg 84
The available evidence is reassuring, but it is also fragmentary and inconclusive on many issues.
It’s unfortunate that this isn’t in any of the headlines...considering many will read as far as that and stop.
The committee made 5 recommendations in their review of the literature and data from VSD – several of which I strongly agree with (surprised?):
4-1
Assess evidence about the public confidence in the federally recommended child vaccine schedule to improve communication between doctors and the public (my note: hopefully making this dialogue stronger between both parties involved)
5-1
Target potential vaccine adverse events and populations biologically at an increased risk for suffering vaccine reactions and injury (my note; PRIOR to any reaction(s) happening in the first place)
6-1
To make the safety of the child vaccine schedule a scientific research priority
The first three recommendations have the potential to be very constructive, however - the last two recommendations are not as promising: of which suggests that future safety research be conducted using previously existing data in closed databases systems, particularly VSD.
Pg 116
The committee finds that secondary analyses of existing systems are more promising approaches to examination of the (…) childhood immunization schedule.
The VSD (Vaccine Safety Database) is currently the best available system for studying the safety of the immunization schedule in the United States
Hmm… the committee seriously deems clinical and/or cohort safety trials as ineffective in understanding the current vaccine schedule?? Boooo.
And what was that about comparing an unvaccinated population again?
Pg 115
Some stakeholders have suggested that further work is warranted, such as a comparison of vaccinated children with unvaccinated children or children receiving immunizations on alternative immunization schedules.
The committee supports the NVACSWG statement that “the strongest study design, a prospective, randomized clinical trial that includes a study arm receiving no vaccine or vaccine not given according to the current recommended schedule (…) would be unethical and therefore cannot be done.
Pg 116
Recommendation 6-2: The Department of Health and Human Services should refrain from initiating randomized controlled trials of the childhood immunization schedule that compare safety outcomes in fully vaccinated children with those in unvaccinated children or those vaccinated by use of an alternative schedule.
Ok, but what about at least testing an alternative schedule?
Pg 116
The committee found that a trial of a modified version of the ACIP schedule… would be ethical; however, it would add substantial costs to both parents and providers and, moreover, may be unacceptable to insurers if its effectiveness –measured as a decrease rate of adverse safety outcomes-was negligible.
Would you consider paying more money to determine if the vaccine schedule you are currently using is the safest for your child(ren)?
Hmm…me too.
Deep gratitude for all the time you've put into research and then compiling your insight in a respectful and intelligent manner. This is a great service.
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