To determine whether children who received recommended vaccines on time during the first year of life had different neuropsychological outcomes at 7 to 10 years of age as compared with children with delayed receipt or nonreceipt of these vaccines.
Publicly available data, including age at vaccination, from a previous VaccineSafety Datalink study of thimerosal exposure and 42 neuropsychological outcomes were analyzed. Vaccine receipt was defined as timely when each vaccine was received within 30 days of the recommended age. Associations between timeliness and each outcome were tested in univariate analyses. Multivariable regression models were constructed for further assessment of the impact of timeliness on neuropsychological outcomes after adjustment for potential confounders. Secondary analyses were performed on a subset of children with the highest and lowest vaccine exposures during the first 7 months of life.
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. In secondary analyses, children with the greatest vaccine exposure during the first 7 months of life performed better than children with the least vaccine exposure on 15 outcomes in univariate testing; these differences did not persist in multivariable analyses. No statistically significant differences favored the less vaccinated children.
Timely vaccination during infancy has no adverse effect on neuropsychological outcomes 7 to 10 years later. These data may reassure parents who are concerned that children receive too many vaccines too soon.
Comments
Re: Conflicts of Interest and Numbers Do Not Add Up
Dear Dr. Rosen,
Thank you for your interest in our study. As you note, there are indeed two typographic errors in the first sentence of the results section. The correct breakdown of patients is as follows: 491 (47%) received all recommended vaccines on time, 245 (23%) received all recommended vaccines during the first year of life, but not on time, and 311 (30%) did not receive all recommended vaccines during the first year of life. All 1047 children are accounted for in Tables 1 and 2.
Additionally, your references to “considerable potential biases given where [our] funding comes from” and “payroll” suggest that our potential (but not necessarily real) conflicts of interest were not adequately explained. This study was conducted without funding from any company (e.g., vaccine manufacturer) or agency (e.g., the CDC). We conducted this study on our own after requesting and receiving the publicly available data that were used for the analyses. Our unrelated interactions with vaccine manufacturers have been appropriately disclosed for full transparency in accordance with our own ethical standards as well as formal guidelines from the Academy of Pediatrics and the University of Louisville.
We hope that you and others will find the results of this study comforting within the limits of this type of secondary data analysis.
Sincerely,
Michael J. Smith and Charles R. Woods
Conflict of Interest:
As outlined above
Concerns on Study Methodology
The study on vaccine timeliness and neuropsychological outcomes by Smith and Woods (1) would have benefitted from inclusion of all the vaccines given in order to maximize the exposure differences and more accurately assign children to exposure groups. Vaccines received beyond 3 DTP, 3 Hib, 2 hepatitis B and 2 polio vaccines were omitted from the analysis. The ACIP recommended schedule for this time period allowed for a third dose of hepatitis B and polio vaccines as early as 6 months (2), and Table 1 shows that many of the study children did receive these third doses in the first year of life: the average number of polio vaccines was 2.62, and hepatitis B averaged 2.71. Some children in the study received other vaccines in the first year of life, including those for influenza, hepatitis A, MMR, pneumococcal, tuberculosis, tetanus toxoid, varicella, and meningococcal.(3) Whether a child did or did not receive these additional doses was not factored into the analysis.
Smith and Woods controlled for cumulative ethylmercury exposure, without providing justification for doing so. Cumulative ethylmercury is positively associated with receipt of 3 of the 4 vaccines in the analysis (hepatitis B, DPT and Hib) and thus with overall vaccine receipt. Including this variable would have the effect of reducing variance (P value) observed for the exposure variable of interest, vaccine receipt. A number of additional variables in the model such as familial and SES factors were associated with vaccine receipt as well as the outcome measures. The authors do not state whether diagnostic tests were conducted for multicollinearity and whether their model was impacted by collinearity, for these and other variables.
(1) Smith MJ, Charles R. Woods CR. On-time Vaccine Receipt in the First Year Does Not Adversely Affect Neuropsychological Outcomes. Pediatrics. Published online May 24, 2010. (2) CDC. Notice to Readers: Recommended Childhood Immunization Schedule -- United States, January-June 1996. MMWR. January 05, 1996 / 44(51&52);940- 3. (3) Thompson WW et al. Early Thimerosal Exposure and Neuropsychological Outcomes at 7 to 10 Years. NEJM. Sept 27, 2007. Table B of the Supplementary Appendix.
Conflict of Interest:
Author has a child with autism and is president of SafeMinds which focuses on the environmental causes of autism including mercury and vaccines.
Exclusionary Medical Conditions
I note with interest that children with low birth weight and those that were preterm were excluded from the dataset, so presumably any conclusion drawn from this evaluation is inapplicable to them.
I further note that the list of exclusionary medical conditions included some common comorbidities of autism (Fragile X, Prader-Willi, Tuberous Sclerosis, other chromosomal anomalies), and that some children with autism or autistic spectrum disorders may have been excluded from this analysis for this reason.
Conflict of Interest:
None declared
Are 20th Century Stats Still Germane?
I noticed that on the initial analysis, a statistically significant percent of the mothers of the fully-vaccinated babies were college- educated.
During the first half of my career, this seemed to be the case. Low vaccine rate was associated with teen parents, parental substance abuse, mental illness, and family dysfunction. (In fact, the local CPS still uses vaccination rate as a benchmark of good parenting.) Perhaps this would explain the association of timely vaccination back then with better performance.
In the last ten years, the situation has flipped – at least for my practice. Low vaccine rates are now associated with parents having high education (college professors, lawyers, ICU nurses, nuclear physicists, etc). A teen parent doesn't really care whether or not there is porcine circovirus in the rotavirus vaccine. The professors do.
Conflict of Interest:
None declared
Conflicts of Interest and Numbers Do Not Add Up
Dear Sirs,
I read with great interest Smith and Woods article, "On-time Vaccine Receipt in the First Year Does Not Adversely Affect Neuropsychological Outcomes." This issue is of paramount importance in clinical primary care practice today. However, I was dismayed by two factors within minutes of reading the piece. One, of perhaps lesser importance, in the Results Section, the numbers, simply put, do not add up. If all of the subjects are added as listed, a total of 1037 (not 1047) is obtained. Furthermore, the percentages are incorrect as listed. The final group (311) is in fact 30% of the incorrect total, not 20% as listed. It always concerns me and forces me to question the validity of the other findings when a mistake like this is notable. In any case, the finding that approximately 50% (depending on the true numbers) received an alternative vaccine schedule, even as long ago as 1993-1997 is of interest.
Of greater concern to me, personally, is the Financial Disclosure listings. It is very difficult in this day and age to review the authors' conclusions without considering their considerable potential biases given where their funding comes from. I believe every known vaccine manufacturer is listed on the payroll. Until we have well-done, conflict- free published research on this topic, both the public and skeptical physicians must continue to look for honest answers.
Conflict of Interest:
None declared