Your SlideShare is downloading. ×
15 vaccinations mortality rates miller
Upcoming SlideShare
Loading in...5

Thanks for flagging this SlideShare!

Oops! An error has occurred.

Saving this for later? Get the SlideShare app to save on your phone or tablet. Read anywhere, anytime – even offline.
Text the download link to your phone
Standard text messaging rates apply

15 vaccinations mortality rates miller


Published on

You can just read the conclusion on page 8 if you don't want to read the whole study. Really interesting... …

You can just read the conclusion on page 8 if you don't want to read the whole study. Really interesting...

Patty James

  • Be the first to comment

  • Be the first to like this

No Downloads
Total Views
On Slideshare
From Embeds
Number of Embeds
Embeds 0
No embeds

Report content
Flagged as inappropriate Flag as inappropriate
Flag as inappropriate

Select your reason for flagging this presentation as inappropriate.

No notes for slide


  • 1. Human & Experimental Toxicology Infant mortality rates regressed against number of vaccine doses routinely given: Is there a biochemical or synergistic toxicity? Neil Z Miller and Gary S Goldman Hum Exp Toxicol published online 4 May 2011 DOI: 10.1177/0960327111407644 The online version of this article can be found at: Published by: Additional services and information for Human & Experimental Toxicology can be found at: This is an open-access article distributed under the terms of the Creative Commons Attribution Open License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Access Email Alerts: Subscriptions: Reprints: Permissions: Downloaded from by guest on May 4, 2011
  • 2. Human and Experimental Toxicology 000(00) 1–9Infant mortality rates regressed ª The Author(s) 2011 Reprints and permission: number of vaccine doses DOI: 10.1177/0960327111407644 het.sagepub.comroutinely given: Is there abiochemical or synergistic toxicity?Neil Z Miller and Gary S GoldmanAbstractThe infant mortality rate (IMR) is one of the most important indicators of the socio-economic well-being andpublic health conditions of a country. The US childhood immunization schedule specifies 26 vaccine doses forinfants aged less than 1 year—the most in the world—yet 33 nations have lower IMRs. Using linear regression,the immunization schedules of these 34 nations were examined and a correlation coefficient of r ¼ 0.70(p < 0.0001) was found between IMRs and the number of vaccine doses routinely given to infants. Nations werealso grouped into five different vaccine dose ranges: 12–14, 15–17, 18–20, 21–23, and 24–26. The mean IMRs ofall nations within each group were then calculated. Linear regression analysis of unweighted mean IMRsshowed a high statistically significant correlation between increasing number of vaccine doses and increasinginfant mortality rates, with r ¼ 0.992 (p ¼ 0.0009). Using the Tukey-Kramer test, statistically significant differ-ences in mean IMRs were found between nations giving 12–14 vaccine doses and those giving 21–23, and 24–26doses. A closer inspection of correlations between vaccine doses, biochemical or synergistic toxicity, and IMRsis essential.Keywordsinfant mortality rates, sudden infant death, SIDS, immunization schedules, childhood vaccines, drug toxicology,synergistic effects, linear regression modelIntroduction a decrease in immune function. An impaired immune function often leads to an increased susceptibility toThe infant mortality rate (IMR) is one of the most infection.2 It is well established that infections, noimportant measures of child health and overall matter how mild, have adverse effects on nutritionaldevelopment in countries. Clean water, increased status. Conversely, almost any nutritional deficiencynutritional measures, better sanitation, and easy will diminish resistance to disease.3access to health care contribute the most to improving Despite the United States spending more per capitainfant mortality rates in unclean, undernourished, and on health care than any other country,4 33 nationsimpoverished regions of the world.1–3 In developing have better IMRs. Some countries have IMRs that arenations, IMRs are high because these basic necessities less than half the US rate: Singapore, Sweden, andfor infant survival are lacking or unevenly distributed. Japan are below 2.80. According to the Centers forInfectious and communicable diseases are more Disease Control and Prevention (CDC), ‘‘The relativecommon in developing countries as well, though position of the United States in comparison to coun-sound sanitary practices and proper nutrition would tries with the lowest infant mortality rates appearsdo much to prevent them.1 to be worsening.’’5 The World Health Organization (WHO) attributes7 out of 10 childhood deaths in developing countriesto five main causes: pneumonia, diarrhea, measles, Corresponding author:malaria, and malnutrition—the latter greatly affecting Neil Z Miller, PO Box 9638, Santa Fe, NM 87504, USAall the others.1 Malnutrition has been associated with Email: Downloaded from by guest on May 4, 2011
  • 3. 2 Human and Experimental Toxicology 000(00)Table 1. 2009 Infant mortality rates, top 34 nations8 nations routinely give to their infants and their infant mortality rates, a linear regression analysis wasRank Country IMR performed.1 Singapore 2.312 Sweden 2.753 Japan 2.79 Methods and design4 Iceland 3.235 France 3.33 Infant mortality6 Finland 3.47 The infant mortality rate is expressed as the7 Norway 3.58 number of infant deaths per 1000 live births.8 Malta 3.759 Andorra 3.76 According to the US Central Intelligence Agency10 Czech Republic 3.79 (CIA), which keeps accurate, up-to-date infant11 Germany 3.99 mortality statistics throughout the world, in 200912 Switzerland 4.18 there were 33 nations with better infant mortality13 Spain 4.21 rates than the United States (Table 1).8 The US14 Israel 4.22 infant mortality rate of 6.22 infant deaths per15 Liechtenstein 4.25 1000 live births ranked 34th.16 Slovenia 4.2517 South Korea 4.2618 Denmark 4.34 Immunization schedules and vaccine doses19 Austria 4.42 A literature review was conducted to determine the20 Belgium 4.44 immunization schedules for the United States and all21 Luxembourg 4.5622 Netherlands 4.73 33 nations with better IMRs than the United States.9,1023 Australia 4.75 The total number of vaccine doses specified for24 Portugal 4.78 infants aged less than 1 year was then determined for25 United Kingdom 4.85 each country (Table 2). A vaccine dose is an exact26 New Zealand 4.92 amount of medicine or drug to be administered. The27 Monaco 5.00 number of doses a child receives should not be con-28 Canada 5.04 fused with the number of ‘vaccines’ or ‘injections’29 Ireland 5.05 given. For example, DTaP is given as a single injec-30 Greece 5.1631 Italy 5.51 tion but contains three separate vaccines (for32 San Marino 5.53 diphtheria, tetanus, and pertussis) totaling three vac-33 Cuba 5.82 cine doses.34 United States 6.22CIA. Country comparison: infant mortality rate (2009). The World Nations organized into data pairsFactbook. (Data last updated 13 April 2010).8 The 34 nations were organized into data pairs consist- ing of total number of vaccine doses specified for their infants and IMRs. Consistent with biostatistical There are many factors that affect the IMR of any conventions, four nations—Andorra, Liechenstein,given country. For example, premature births in the Monaco, and San Marino—were excluded from theUnited States have increased by more than 20% dataset because they each had fewer than five infantbetween 1990 and 2006. Preterm babies have a higher deaths, producing extremely wide confidence inter-risk of complications that could lead to death within vals and IMR instability. The remaining 30 (88%)the first year of life.6 However, this does not fully of the data pairs were then available for analysis.explain why the United States has seen little improve-ment in its IMR since 2000.7 Nations differ in their immunization requirements Nations organized into groupsfor infants aged less than 1 year. In 2009, five of the Nations were placed into the following five groups34 nations with the best IMRs required 12 vaccine based on the number of vaccine doses they routinelydoses, the least amount, while the United States give their infants: 12–14, 15–17, 18–20, 21–23, andrequired 26 vaccine doses, the most of any nation. 24–26 vaccine doses. The unweighted IMR meansTo explore the correlation between vaccine doses that of all nations as a function of the number of vaccine Downloaded from by guest on May 4, 2011
  • 4. Miller N Z and Goldman G S 3Table 2. Summary of International Immunization Schedules: vaccines recommended/required prior to one year of age in34 nations Totalb GroupNation Vaccines prior to one year of age doses (range of doses)Sweden DTaP (2), Polio (2), Hib (2), Pneumo (2) 12 1 (12–14)Japan DTaP (3), Polio (2), BCG 12Iceland DTaP (2), Polio (2), Hib (2), MenC (2) 12Norway DTaP (2), Polio (2), Hib (2), Pneumo (2) 12Denmark DTaP (2), Polio (2), Hib (2), Pneumo (2) 12Finland DTaP (2), Polio (2), Hib (2), Rota (3) 13Malta DTaP (3), Polio (3), Hib (3) 15 2 (15–17)Slovenia DTaP (3), Polio (3), Hib (3) 15South Korea DTaP (3), Polio (3), HepB (3) 15Singapore DTaP (3), Polio (3), HepB (3), BCG, Flu 17New Zealand DTaP (3), Polio (3), Hib (2), HepB (3) 17Germany DTaP (3), Polio (3), Hib (3), Pneumo (3) 18 3 (18–20)Switzerland DTaP (3), Polio (3), Hib (3), Pneumo (3) 18Israel DTaP (3), Polio (3), Hib (3), HepB (3) 18Liechtensteina DTaP (3), Polio (3), Hib (3), Pneumo (3) 18Italy DTaP (3), Polio (3), Hib (3), HepB (3) 18San Marinoa DTaP (3), Polio (3), Hib (3), HepB (3) 18France DTaP (3), Polio (3), Hib (3), Pneumo (2), HepB (2) 19Czech Republic DTaP (3), Polio (3), Hib (3), HepB (3), BCG 19Belgium DTaP (3), Polio (3), Hib (3), HepB (3), Pneumo (2) 19United Kingdom DTaP (3), Polio (3), Hib (3), Pneumo (2), MenC (2) 19Spain DTaP (3), Polio (3), Hib (3), HepB (3), MenC (2) 20Portugal DTaP (3), Polio (3), Hib (3), HepB (3), MenC (2), BCG 21 4 (21–23)Luxembourg DTaP (3), Polio (3), Hib (3), HepB (2), Pneumo (3), Rota (3) 22Cuba DTaP (3), Polio (3), Hib (3), HepB (4), MenBC (2), BCG 22Andorraa DTaP (3), Polio (3), Hib (3), HepB (3), Pneumo (3), MenC (2) 23Austria DTaP (3), Polio (3), Hib (3), HepB (3), Pneumo (3), Rota (2) 23Ireland DTaP (3), Polio (3), Hib (3), HepB (3), Pneumo (2), MenC (2), BCG 23Greece DTaP (3), Polio (3), Hib (3), HepB (3), Pneumo (3), MenC (2) 23Monacoa DTaP (3), Polio (3), Hib (3), HepB (3), Pneumo (3), HepA, BCG 23Netherlands DTaP (4), Polio (4), Hib (4), Pneumo (4) 24 5 (24–26)Canada DTaP (3), Polio (3), Hib (3), HepB (3), Pneumo (3), MenC (2), Flu 24Australia DTaP (3), Polio (3), Hib (3), HepB (4), Pneumo (3), Rota (2) 24United States DTaP (3), Polio (3), Hib (3), HepB (3), Pneumo (3), Rota (3), Flu (2) 26a These four nations were excluded from the analysis because they had fewer than five infant deaths.b DTaP is administered as a single shot but contains three separate vaccines (for diphtheria, tetanus, and pertussis). Thus, DTaP giventhree times in infancy is equivalent to nine vaccine doses.Immunization schedules are for 2008–2009.9,10doses were analyzed using linear regression. The results from the Tukey-Kramer test, a post test for thePearson correlation coefficient (r) and coefficient of overall linear trend was performed.determination (r2) were calculated using GraphPadPrism, version 5.03 (GraphPad Software, San Diego, ResultsCA, USA, Additionally, theF statistic and corresponding p values were computed Nations organized into data pairsto test if the best fit slope was statistically signifi- A scatter plot of each of the 30 nation’s IMR versuscantly non-zero. The Tukey-Kramer test was used to vaccine doses yielded a linear relationship with a cor-determine whether or not the mean IMR differences relation coefficient of 0.70 (95% CI, 0.46–0.85) andbetween the groups were statistically significant. Fol- p < 0.0001 providing evidence of a positive correla-lowing the one-way ANOVA (analysis of variance) tion: IMR and vaccine doses tend to increase together. Downloaded from by guest on May 4, 2011
  • 5. 4 Human and Experimental Toxicology 000(00) 7 best fit line: y = 0.148x + 1.566, r = 0.7 (p < 0.0001) 7 best fit line: y = 0.157x +1.34, r = 0.992 (p = 0.0009) slope F−statistic: F = 27.2, p < 0.0001 slope F−statistic: F = 173.9, p = 0.0009 6 6 Mean infant mortality rate Infant mortality rate (deaths/1000) (deaths/1,000) 5 5 4 21−23 4 24−26 18−20 best fit line 3 95% CI 3 best fit line 12−14 15−17 2 2 9 12 15 18 21 24 27 13 16 19 22 25 Number of vaccine doses Vaccine DosesFigure 1. 2009 Infant mortality rates and number of Figure 2. 2009 Mean infant mortality rates and meanvaccine doses for 30 nations. number of vaccine doses (five categories). DiscussionThe F statistic applied to the slope [0.148 (95% CI,0.090–0.206)] is significantly non-zero, with F ¼ 27.2 Basic necessities for infant survival(p < 0.0001; Figure 1). It is instructive to note that many developing nations require their infants to receive multiple vaccine doses and have national vaccine coverage rates (a percent- age of the target population that has been vaccinated)Nations organized into groups of 90% or better, yet their IMRs are poor. For exam-The unweighted mean IMR of each category was ple, Gambia requires its infants to receive 22 vaccinecomputed by simply summing the IMRs of each doses during infancy and has a 91%–97% nationalnation comprising a group and dividing by the number vaccine coverage rate, yet its IMR is 68.8. Mongoliaof nations in that group. The IMRs were as follows: requires 22 vaccine doses during infancy, has a3.36 (95% CI, 2.74–3.98) for nations specifying 95%–98% coverage rate, and an IMR of 39.9.8,912–14 doses (mean 13 doses); 3.89 (95% CI, These examples appear to confirm that IMRs will2.68–5.12) for 15–17 doses (mean 16 doses); remain high in nations that cannot provide clean4.28 (95% CI, 3.80–4.76) for 18–20 doses (mean water, proper nutrition, improved sanitation, and bet-19 doses); 4.97 (95% CI, 4.44–5.49) for 21–23 doses ter access to health care. As developing nations(mean 22 doses); 5.19 (95% CI, 4.06–6.31) for 24-26 improve in all of these areas a critical threshold willdoses (mean 25 doses; Figure 2). Linear regression eventually be reached where further reductions of theanalysis yielded an equation of the best fit line, infant mortality rate will be difficult to achievey ¼ 0.157x þ 1.34 with r ¼ 0.992 (p ¼ 0.0009) and because most of the susceptible infants that couldr2 ¼ 0.983. Thus, 98.3% of the variation in mean IMRs have been saved from these causes would have beenis explained by the linear model. Again, the F statistic saved. Further reductions of the IMR must then beyielded a significantly non-zero slope, with F ¼ 173.9 achieved in areas outside of these domains. As devel-(p ¼ 0.0009). oping nations ascend to higher socio-economic living The one-way ANOVA using the Tukey-Kramer standards, a closer inspection of all factors contribut-test yielded F ¼ 650 with p ¼ 0.001, indicating the ing to infant deaths must be made.five mean IMRs corresponding to the five defineddose categories are significantly different (r2 ¼0.510). Tukey’s multiple comparison test found statis- Crossing the socio-economic thresholdtical significance in the differences between the mean It appears that at a certain stage in nations’ movementIMRs of those nations giving 12–14 vaccine doses up the socio-economic scale—after the basic necessi-and (a) those giving 21–23 doses (1.61, 95% CI, ties for infant survival (proper nutrition, sanitation,0.457–2.75) and (b) those giving 24–26 doses (1.83, clean water, and access to health care) have been95% CI, 0.542–3.11). met—a counter-intuitive relationship occurs between Downloaded from by guest on May 4, 2011
  • 6. Miller N Z and Goldman G S 5the number of vaccines given to infants and infant an average annual rate of 8.6%. However, other causesmortality rates: nations with higher (worse) infant of sudden unexpected infant death (SUID) increased.mortality rates give their infants, on average, more For example, the postneonatal mortality rate from ‘suf-vaccine doses. This positive correlation, derived from focation in bed’ (ICD-9 code E913.0) increased duringthe data and demonstrated in Figures 1 and 2, elicits this same period at an average annual rate of important inquiry: are some infant deaths associ- The postneonatal mortality rate from ‘suffocation-ated with over-vaccination? other’ (ICD-9 code E913.1-E913.9), ‘unknown and unspecified causes’ (ICD-9 code 799.9), and due toA closer inspection of infant deaths ‘intent unknown’ in the External Causes of Injury sec- tion (ICD-9 code E980-E989), all increased during thisMany nations adhere to an agreed upon International period as well.18 (In Australia, Mitchell et al. observedClassification of Diseases (ICD) for grouping infant that when the SIDS rate decreased, deaths attributed todeaths into 130 categories.11–13 Among the 34 nations asphyxia increased.19 Overpeck et al. and others,analyzed, those that require the most vaccines tend to reported similar observations.)20,21have the worst IMRs. Thus, we must ask important A closer inspection of the more recent period fromquestions: is it possible that some nations are requiring 1999 to 2001 reveals that the US postneonatal SIDStoo many vaccines for their infants and the additional rate continued to decline, but there was no significantvaccines are a toxic burden on their health? Are some change in the total postneonatal mortality rate. Dur-deaths that are listed within the 130 infant mortality ing this period, the number of deaths attributed todeath categories really deaths that are associated with ‘suffocation in bed’ and ‘unknown causes,’ increasedover-vaccination? Are some vaccine-related deaths significantly. According to Malloy and MacDorman,hidden within the death tables? ‘‘If death-certifier preference has shifted such that previously classified SIDS deaths are now classifiedSudden infant death syndrome (SIDS) as ‘suffocation,’ the inclusion of these suffocationPrior to contemporary vaccination programs, ‘Crib deaths and unknown or unspecified deaths with SIDSdeath’ was so infrequent that it was not mentioned deaths then accounts for about 90 percent of thein infant mortality statistics. In the United States, decline in the SIDS rate observed between 1999 andnational immunization campaigns were initiated in 2001 and results in a non-significant decline inthe 1960s when several new vaccines were introduced SIDS’’18 (Figure 3).and actively recommended. For the first time in his-tory, most US infants were required to receive severaldoses of DPT, polio, measles, mumps, and rubella Is there evidence linking SIDS to vaccines?vaccines.14 Shortly thereafter, in 1969, medical certi- Although some studies were unable to find correla-fiers presented a new medical term—sudden infant tions between SIDS and vaccines,22–24 there is somedeath syndrome.15,16 In 1973, the National Center for evidence that a subset of infants may be more suscep-Health Statistics added a new cause-of-death cate- tible to SIDS shortly after being vaccinated. Forgory—for SIDS—to the ICD. SIDS is defined as the example, Torch found that two-thirds of babies whosudden and unexpected death of an infant which had died from SIDS had been vaccinated against DPTremains unexplained after a thorough investigation. (diphtheria–pertussis–tetanus toxoid) prior to death.Although there are no specific symptoms associated Of these, 6.5% died within 12 hours of vaccination;with SIDS, an autopsy often reveals congestion and 13% within 24 hours; 26% within 3 days; and 37%,edema of the lungs and inflammatory changes in the 61%, and 70% within 1, 2, and 3 weeks, respectively.respiratory system.17 By 1980, SIDS had become the Torch also found that unvaccinated babies who diedleading cause of postneonatal mortality (deaths of of SIDS did so most often in the fall or winter whileinfants from 28 days to one year old) in the United vaccinated babies died most often at 2 and 4States.18 months—the same ages when initial doses of DPT In 1992, to address the unacceptable SIDS rate, the were given to infants. He concluded that DPT ‘‘mayAmerican Academy of Pediatrics initiated a ‘Back to be a generally unrecognized major cause of suddenSleep’ campaign, convincing parents to place their infant and early childhood death, and that the risksinfants supine, rather than prone, during sleep. From of immunization may outweigh its potential benefits.1992 to 2001, the postneonatal SIDS rate dropped by A need for re-evaluation and possible modification of Downloaded from by guest on May 4, 2011
  • 7. 6 Human and Experimental Toxicology 000(00) Reclassification of SIDS Deaths to may also be cases of SIDS reclassified within the Suffocation in Bed and Unknown Causes ICD. Some of these infant deaths may be vaccine 90 related as well. This trend toward reclassifying ICD 80 77.4 77.1 data is a great concern of the CDC ‘‘because inaccu- Death per 100,000 75.4 rate or inconsistent cause-of-death determination and 70 reporting hamper the ability to monitor national 61.6 60 57.1 trends, ascertain risk factors, and design and evaluate 50.9 programs to prevent these deaths.’’29 If some infant 50 deaths are vaccine related and concealed within the 40 various ICD categories for SUIDs, is it possible that 1999 2000 2001 other vaccine-related infant deaths have also been reclassified? SIDS SIDS + Suffocation + Unknown Causes Of the 34 nations that have crossed the socio- economic threshold and are able to provide the basic necessities for infant survival—clean water, nutrition,Figure 3. Reclassification of sudden infant death syndrome(SIDS) deaths to suffocation in bed and unknown causes. sanitation, and health care—several require theirThe postneonatal SIDS rate appears to have declined from infants to receive a relatively high number of vaccine61.6 deaths (per 100,000 live births) in 1999 to 50.9 in doses and have relatively high infant mortality rates.2001. However, during this period there was a significant These nations should take a closer look at their infantincrease in postneonatal deaths attributed to suffocation death tables to determine if some fatalities are possi-in bed and due to unknown causes. When these sudden bly related to vaccines though reclassified as otherunexpected infant deaths (SUIDs) are combined with SIDS causes. Of course, all SUID categories should be re-deaths, the total SIDS rate remains relatively stable, result- inspected. Other ICD categories may be related toing in a non-significant decline. vaccines as well. For example, a new live-virus orallycurrent vaccination procedures is indicated by this administered vaccine against rotavirus-inducedstudy.’’25 Walker et al. found ‘‘the SIDS mortality rate diarrhea—Rotarix1—was licensed by the Europeanin the period zero to three days following DPT to be 7.3 Medicine Agency in 2006 and approved by the UStimes that in the period beginning 30 days after Food and Drug Administration (FDA) in 2008.immunization.’’26 Fine and Chen reported that babies However, in a clinical study that evaluated the safetydied at a rate nearly eight times greater than normal of the Rotarix vaccine, vaccinated babies died at awithin 3 days after getting a DPT vaccination.27 higher rate than non-vaccinated babies—mainly due Ottaviani et al. documented the case of a 3-month-old to a statistically significant increase in pneumonia-infant who died suddenly and unexpectedly shortly after related fatalities.30 (One biologically plausible expla-being given six vaccines in a single shot: ‘‘Examination nation is that natural rotavirus infection might have aof the brainstem on serial sections revealed bilateral protective effect against respiratory infection.)31hypoplasia of the arcuate nucleus. The cardiac conduc- Although these fatalities appear to be vaccine relatedtion system presented persistent fetal dispersion and and raise a nation’s infant mortality rate, medicalresorptive degeneration. This case offers a unique certifiers are likely to misclassify these deaths asinsight into the possible role of hexavalent vaccine in pneumonia.triggering a lethal outcome in a vulnerable baby.’’ With- Several additional ICD categories are possible can-out a full necropsy study in the case of sudden, unex- didates for incorrect infant death classifications:pected infant death, at least some cases linked to unspecified viral diseases, diseases of the blood,vaccination are likely to go undetected.28 septicemia, diseases of the nervous system, anoxic brain damage, other diseases of the nervous system, diseases of the respiratory system, influenza, andReclassified infant deaths unspecified diseases of the respiratory system. AllIt appears as though some infant deaths attributed to of these selected causes may be repositories ofSIDS may be vaccine related, perhaps associated with vaccine-related infant deaths reclassified as commonbiochemical or synergistic toxicity due to over- fatalities. All nations—rich and poor, industrializedvaccination. Some infants’ deaths categorized as ‘suf- and developing—have an obligation to determinefocation’ or due to ‘unknown and unspecified causes’ whether their immunization schedules are achieving Downloaded from by guest on May 4, 2011
  • 8. Miller N Z and Goldman G S 7their desired goals. Progress on reducing infant of the nations in this study had coverage rates in themortality rates should include monitoring vaccine 90%–99% range for the most commonly recom-schedules and medical certification practices to ascer- mended vaccines—DTaP, polio, hepatitis B, and Hibtain whether vaccine-related infant deaths are being (when these vaccines were included in the schedule).reclassified as ordinary mortality in the ICD. Therefore, this factor is unlikely to have impacted the analyses.9How many infants can be saved with an improvedIMR? Minority racesSlight improvements in IMRs can make a substantial It has been argued that the US IMR is poor in compar-difference. In 2009, there were approximately 4.5 mil- ison to many other nations because African–Americanlion live births and 28,000 infant deaths in the United infants are at greater risk of dying relative to WhiteStates, resulting in an infant mortality rate of 6.22/ infants, perhaps due to genetic factors or disparities1000. If health authorities can find a way to reduce the in living standards. However, in 2006 the US IMR forrate by 1/1000 (16%), the United States would rise infants of all races was 6.69 and the IMR for Whitein international rank from 34th to 31st and about infants was 5.56.13 In 2009, this improved rate would4500 infants would be saved. have moved the United States up by just one rank inter- nationally, from 34th place to 33rd place.8 In addition, the IMRs for Hispanics of Mexican descent and Asian–Limitations of study and potential Americans in the United States are significantly lowerconfounding factors than the IMR for Whites.6 Thus, diverse IMRs among different races in the Unites States exert only a modestThis analysis did not adjust for vaccine composition, influence over the United States’ international infantnational vaccine coverage rates, variations in the mortality rank.infant mortality rates among minority races, pretermbirths, differences in how some nations report livebirths, or the potential for ecological bias. A few com- Preterm birthsments about each of these factors are included below. Preterm birth rates in the United States have steadily increased since the early 1980s. (This rise has beenVaccine composition tied to a greater reliance on caesarian deliveries,This analysis calculated the total number of vaccine induced labor, and more births to older mothers.) Pre-doses received by children but did not differentiate term babies are more likely than full-term babies tobetween the substances, or quantities of those sub- die within the first year of life. About 12.4% of USstances, in each dose. Common vaccine substances births are preterm. In Europe, the prevalence rate ofinclude antigens (attenuated viruses, bacteria, toxoids), premature birth ranges from 5.5% in Ireland topreservatives (thimerosal, benzethonium chloride, 11.4% in Austria. Preventing preterm births is essen-2-phenoxyethanol, phenol), adjuvants (aluminum tial to lower infant mortality rates. However, it issalts), additives (ammonium sulfate, glycerin, sodium important to note that some nations such as Irelandborate, polysorbate 80, hydrochloric acid, sodium and Greece, which have very low preterm birth rateshydroxide, potassium chloride), stabilizers (fetal (5.5% and 6%, respectively) compared to the Unitedbovine serum, monosodium glutamate, human serum States, require their infants to receive a relatively highalbumin, porcine gelatin), antibiotics (neomycin, strep- number of vaccine doses (23) and have correspond-tomycin, polymyxin B), and inactivating chemicals ingly high IMRs. Therefore, reducing preterm birth(formalin, glutaraldehyde, polyoxyethylene). For the rates is only part of the solution to reduce IMRs.6,32purposes of this study, all vaccine doses were equallyweighted. Differences in reporting live births Infant mortality rates in most countries are reportedVaccine coverage rates using WHO standards, which do not include any ref-No adjustment was made for national vaccine cover- erence to the duration of pregnancy or weight of theage rates—a percentage of the target population that infant, but do define a ‘live birth’ as a baby born withreceived the recommended vaccines. However, most any signs of life for any length of time.12 However, Downloaded from by guest on May 4, 2011
  • 9. 8 Human and Experimental Toxicology 000(00)four nations in the dataset—France, the Czech given to infants. When nations were grouped into fiveRepublic, the Netherlands, and Ireland—do not report different vaccine dose ranges (12–14, 15–17, 18–20,live births entirely consistent with WHO standards. 21–23, and 24–26), 98.3% of the total variance inThese countries add an additional requirement that IMR was explained by the unweighted linearlive babies must also be at least 22 weeks of gestation regression model. These findings demonstrate aor weigh at least 500 grams. If babies do not meet this counter-intuitive relationship: nations that requirerequirement and die shortly after birth, they are more vaccine doses tend to have higher infant mortal-reported as stillbirths. This inconsistency in reporting ity births artificially lowers the IMRs of these Efforts to reduce the relatively high US IMR havenations.32,33 According to the CDC, ‘‘There are some been elusive. Finding ways to lower preterm birthdifferences among countries in the reporting of very rates should be a high priority. However, preventingsmall infants who may die soon after birth. However, premature births is just a partial solution to reduceit appears unlikely that differences in reporting are the infant deaths. A closer inspection of correlationsprimary explanation for the United States’ relatively between vaccine doses, biochemical or synergisticlow international ranking.’’32 Nevertheless, when the toxicity, and IMRs, is essential. All nations—rich andIMRs of France, the Czech Republic, the Netherlands, poor, advanced and developing—have an obligationand Ireland were adjusted for known underreporting to determine whether their immunization schedulesof live births and the 30 data pairs retested for are achieving their desired goals.significance, the correlation coefficient improvedfrom 0.70 to 0.74 (95% CI, 0.52–0.87). Acknowledgments The authors wish to thank Gerard Jungman, PhD, Paul G.Ecological bias King, PhD, and Peter Calhoun for their assistance in reviewing the manuscript and sharing their expertise.Ecological bias occurs when relationships amongindividuals are inferred from similar relationships Fundingobserved among groups (or nations). Although most This research received no specific grant from any fundingof the nations in this study had 90%–99% of their agency in the public, commercial, or not-for-profit sectors.infants fully vaccinated, without additional data wedo not know whether it is the vaccinated or unvacci- Referencesnated infants who are dying in infancy at higher rates. 1. Wegman ME. Infant mortality in the 20th century,However, respiratory disturbances have been docu- dramatic but uneven progress. J Nutr 2001; 131:mented in close proximity to infant vaccinations, and 401S–408S.lethal changes in the brainstem of a recently vacci- 2. Beck MA. The role of nutrition in viral disease. J Nutrinated baby have been observed. Since some infants Biochem 1996; 7: 683–690.may be more susceptible to SIDS shortly after being 3. Scrimshaw NS and SanGiovanni JP. Synergism of nutri-vaccinated, and babies vaccinated against diarrhea tion, infection, and immunity: an overview. Am J Clindied from pneumonia at a statistically higher rate than Nutr 1997; 66: 464S–477S.non-vaccinated babies, there is plausible biologic and 4. Anderson GF, Hussay PS, Frogner BK, and Waters HR.causal evidence that the observed correlation between Health spending in the United States and the rest of theIMRs and the number of vaccine doses routinely industrialized world. Health Affairs 2005; 24: 903–914.given to infants should not be dismissed as ecological 5. MacDorman MF and Mathews TJ. Recent trends inbias. infant mortality in the United States. NCHS Data Brief (CDC), no 9. Hyattsville, MD, USA: National Center forConclusion Health Statistics, 2008.The US childhood immunization schedule requires 6. Kent MM. Premature births help to explain higher infant26 vaccine doses for infants aged less than 1 year, the mortality rate. Population Reference Bureau.most in the world, yet 33 nations have better IMRs. linear regression, the immunization schedules (accessed December 2009).of these 34 nations were examined and a correlation 7. Xu Jiaquan, Kochaneck KD, and Tejada-Vera B.coefficient of 0.70 (p < 0.0001) was found between Deaths: preliminary data for 2007. Natl Vital Stat RepIMRs and the number of vaccine doses routinely 2009; 58: 6. Downloaded from by guest on May 4, 2011
  • 10. Miller N Z and Goldman G S 9 8. CIA. Country comparison: infant mortality rate (2009). infant death syndrome: no increased risk after The World Factbook. (accessed 13 April immunisation. Vaccine 2007; 25: 336–340. 2010). 23. Stratton K, Almario DA, Wizemann TM, and 9. WHO/UNICEF. Immunization Summary: A Statistical McCormick MC. Immunization safety review: vacci- Reference Containing Data Through 2008 (The 2010 nations and sudden unexpected death in infancy. Edition). Washington DC, USA: National Academies Press,10. Up-to-date European vaccination schedules may be 2003. found here: (accessed 13 April 2010). 24. Silvers LE, Ellenberg SS, Wise RP, Varricchio FE,11. WHO. International Classification of Diseases, 9th Mootrey GT, and Salive ME. The epidemiology of Revision. Geneva, Switzerland: World Health Organi- fatalities reported to the vaccine adverse event report- zation, 1979. ing system 1990-1997. Pharmacoepidemiol Drug Saf12. WHO. International Statistical Classification of Dis- 2001; 10: 279–285. eases and Related Health Problems, 10th Revision. 25. Torch WC. Diphtheria-pertussis-tetanus (DPT) immu- Geneva, Switzerland: World Health Organization, 1992. nization: a potential cause of the sudden infant death13. CDC. Table 31. Number of infant deaths and infant syndrome (SIDS). American Academy of Neurology, mortality rates for 130 selected causes, by race: United 34th Annual Meeting, Apr 25-May 1, 1982. Neurology States, 2006. Natl Vital Stat Rep 2009; 57: 110–112. 32(4): pt. 2.14. Iannelli V. Immunization timeline. Keep Kids Healthy. 26. Walker AM, Jick H, Perera DR, Thompson RS, and (accessed 21 April 2010). Knauss TA. Diphtheria-tetanus-pertussis immuniza-15. Bergman AB. The ‘‘Discovery’’ of Sudden Infant tion and sudden infant death syndrome. Am J Public Death Syndrome. New York, NY, USA: Praeger Pub- Health 1987; 77: 945–951. lishers, 1986. 27. Fine PE and Chen RT. Confounding in studies of16. MacDorman MF and Rosenberg HM. Trends in infant adverse reactions to vaccines. Am J Epidemiol 1992; mortality by cause of death and other characteristics, 136: 121–135. 1960-88 (vital and health statistics), Volume 20. 28. Ottaviani G, Lavezze AM, and Matturri L. Sudden Hyattsville, MD, USA: National Center for Health Sta- infant death syndrome (SIDS) shortly after hexavalent tistics, U.S. Government Printing, 1993. vaccination: another pathology in suspected SIDS?17. National Center for Health Statistics. Vital Statistics of Virchows Archiv 2006; 448: 100–104. the United States 1988, Volume II, Mortality, Part A. 29. CDC. About the sudden unexpected infant death Washington, DC, USA: Public Health Service, 1991. investigation (SUIDI) reporting form. Department18. Malloy MH and MacDorman M. Changes in the clas- of Health and Human Services (accessed 20 May sification of sudden unexpected infant deaths: United 2010). States, 1992-2001. Pediatrics 2005; 115: 1247–1253. 30. GlaxoSmithKline. Rotarix1 (Rotavirus Vaccine, Live,19. Mitchell E, Krous HF, Donald T, and Byard RW. Oral) Oral Suspension. Product insert from the manu- Changing trends in the diagnosis of sudden infant facturer (April 2008): 6. death. Am J Forensic Med Pathol 2000; 21: 311–314. 31. FDA. Center for biologics evaluation and research,20. Overpeck MD, Brenner RA, Cosgrove C, Trumble AC, vaccines and related biological products advisory com- Kochanek K, and MacDorman M. National under mittee meeting (20 February 2008): 127–128. ascertainment of sudden unexpected infant deaths 32. MacDorman MF and Mathews TJ. Behind interna- associated with deaths of unknown cause. Pediatrics tional rankings of infant mortality: how the United 2002; 109: 274–283. States compares with Europe. NCHS data brief, no21. Byard RW and Beal SM. Has changing diagnostic pre- 23. Hyattsville, MD, USA: National Center for Health ference been responsible for the recent fall in incidence Statistics, 2009. of sudden infant death syndrome in South Australia? 33. Euro-Peristat Project, with SCPE, Eurocat, Euroneo- J Pediatr Child Health 1995; 31: 197–199. stat. European Perinatal Health Report: Data for22. Vennemann MM, Butterfass-Bahloul T, Jorch G, 2004 (The 2008 Edition): Table 3.1:40. www. Brinkmann B, Findeisen M, Sauerland C, et al. Sudden Downloaded from by guest on May 4, 2011