Nations differ in their immunization requirements for infants aged less than 1 year. In 2009, five of the 34 nations with the best IMRs required 12 vaccine doses, the least amount, while the United States required 26 vaccine doses, the most of any nation. To explore the correlation between vaccine doses that nations routinely give to their infants and their infant mortality rates, a linear regression analysis was performed.

There are many factors that affect the IMR of any given country. For example, premature births in the United States have increased by more than 20% between 1990 and 2006. Preterm babies have a higher risk of complications that could lead to death within the first year of life. 6 However, this does not fully explain why the United States has seen little improvement in its IMR since 2000. 7

Despite the United States spending more per capita on health care than any other country, 4 33 nations have better IMRs. Some countries have IMRs that are less than half the US rate: Singapore, Sweden, and Japan are below 2.80. According to the Centers for Disease Control and Prevention (CDC), “The relative position of the United States in comparison to countries with the lowest infant mortality rates appears to be worsening.” 5

The World Health Organization (WHO) attributes 7 out of 10 childhood deaths in developing countries to five main causes: pneumonia, diarrhea, measles, malaria, and malnutrition—the latter greatly affecting all the others. 1 Malnutrition has been associated with a decrease in immune function. An impaired immune function often leads to an increased susceptibility to infection. 2 It is well established that infections, no matter how mild, have adverse effects on nutritional status. Conversely, almost any nutritional deficiency will diminish resistance to disease. 3

The infant mortality rate (IMR) is one of the most important measures of child health and overall development in countries. Clean water, increased nutritional measures, better sanitation, and easy access to health care contribute the most to improving infant mortality rates in unclean, undernourished, and impoverished regions of the world. 1 – 3 In developing nations, IMRs are high because these basic necessities for infant survival are lacking or unevenly distributed. Infectious and communicable diseases are more common in developing countries as well, though sound sanitary practices and proper nutrition would do much to prevent them. 1

Nations were placed into the following five groups based on the number of vaccine doses they routinely give their infants: 12–14, 15–17, 18–20, 21–23, and 24–26 vaccine doses. The unweighted IMR means of all nations as a function of the number of vaccine doses were analyzed using linear regression. The Pearson correlation coefficient ( r ) and coefficient of determination ( r 2 ) were calculated using GraphPad Prism, version 5.03 (GraphPad Software, San Diego, CA, USA, www.graphpad.com ). Additionally, the F statistic and corresponding p values were computed to test if the best fit slope was statistically significantly non-zero. The Tukey-Kramer test was used to determine whether or not the mean IMR differences between the groups were statistically significant. Following the one-way ANOVA (analysis of variance) results from the Tukey-Kramer test, a post test for the overall linear trend was performed.

The 34 nations were organized into data pairs consisting of total number of vaccine doses specified for their infants and IMRs. Consistent with biostatistical conventions, four nations—Andorra, Liechenstein, Monaco, and San Marino—were excluded from the dataset because they each had fewer than five infant deaths, producing extremely wide confidence intervals and IMR instability. The remaining 30 (88%) of the data pairs were then available for analysis.

A literature review was conducted to determine the immunization schedules for the United States and all 33 nations with better IMRs than the United States. 9 , 10 The total number of vaccine doses specified for infants aged less than 1 year was then determined for each country ( Table 2 ). A vaccine dose is an exact amount of medicine or drug to be administered. The number of doses a child receives should not be confused with the number of ‘vaccines' or ‘injections' given. For example, DTaP is given as a single injection but contains three separate vaccines (for diphtheria, tetanus, and pertussis) totaling three vaccine doses.

The infant mortality rate is expressed as the number of infant deaths per 1000 live births. According to the US Central Intelligence Agency (CIA), which keeps accurate, up-to-date infant mortality statistics throughout the world, in 2009 there were 33 nations with better infant mortality rates than the United States ( Table 1 ). 8 The US infant mortality rate of 6.22 infant deaths per 1000 live births ranked 34th.

The one-way ANOVA using the Tukey-Kramer test yielded F = 650 with p = 0.001, indicating the five mean IMRs corresponding to the five defined dose categories are significantly different ( r 2 = 0.510). Tukey’s multiple comparison test found statistical significance in the differences between the mean IMRs of those nations giving 12–14 vaccine doses and (a) those giving 21–23 doses (1.61, 95% CI, 0.457–2.75) and (b) those giving 24–26 doses (1.83, 95% CI, 0.542–3.11).

The unweighted mean IMR of each category was computed by simply summing the IMRs of each nation comprising a group and dividing by the number of nations in that group. The IMRs were as follows: 3.36 (95% CI, 2.74–3.98) for nations specifying 12–14 doses (mean 13 doses); 3.89 (95% CI, 2.68–5.12) for 15–17 doses (mean 16 doses); 4.28 (95% CI, 3.80–4.76) for 18–20 doses (mean 19 doses); 4.97 (95% CI, 4.44–5.49) for 21–23 doses (mean 22 doses); 5.19 (95% CI, 4.06–6.31) for 24-26 doses (mean 25 doses; Figure 2 ). Linear regression analysis yielded an equation of the best fit line, y = 0.157 x + 1.34 with r = 0.992 ( p = 0.0009) and r 2 = 0.983. Thus, 98.3% of the variation in mean IMRs is explained by the linear model. Again, the F statistic yielded a significantly non-zero slope, with F = 173.9 ( p = 0.0009).

A scatter plot of each of the 30 nation’s IMR versus vaccine doses yielded a linear relationship with a correlation coefficient of 0.70 (95% CI, 0.46–0.85) and p < 0.0001 providing evidence of a positive correlation: IMR and vaccine doses tend to increase together. The F statistic applied to the slope [0.148 (95% CI, 0.090–0.206)] is significantly non-zero, with F = 27.2 ( p < 0.0001; Figure 1 ).

Discussion

Basic necessities for infant survival It is instructive to note that many developing nations require their infants to receive multiple vaccine doses and have national vaccine coverage rates (a percentage of the target population that has been vaccinated) of 90% or better, yet their IMRs are poor. For example, Gambia requires its infants to receive 22 vaccine doses during infancy and has a 91%–97% national vaccine coverage rate, yet its IMR is 68.8. Mongolia requires 22 vaccine doses during infancy, has a 95%–98% coverage rate, and an IMR of 39.9.8,9 These examples appear to confirm that IMRs will remain high in nations that cannot provide clean water, proper nutrition, improved sanitation, and better access to health care. As developing nations improve in all of these areas a critical threshold will eventually be reached where further reductions of the infant mortality rate will be difficult to achieve because most of the susceptible infants that could have been saved from these causes would have been saved. Further reductions of the IMR must then be achieved in areas outside of these domains. As developing nations ascend to higher socio-economic living standards, a closer inspection of all factors contributing to infant deaths must be made.

Crossing the socio-economic threshold It appears that at a certain stage in nations' movement up the socio-economic scale—after the basic necessities for infant survival (proper nutrition, sanitation, clean water, and access to health care) have been met—a counter-intuitive relationship occurs between the number of vaccines given to infants and infant mortality rates: nations with higher (worse) infant mortality rates give their infants, on average, more vaccine doses. This positive correlation, derived from the data and demonstrated in Figures 1 and 2, elicits an important inquiry: are some infant deaths associated with over-vaccination?

A closer inspection of infant deaths Many nations adhere to an agreed upon International Classification of Diseases (ICD) for grouping infant deaths into 130 categories.11–13 Among the 34 nations analyzed, those that require the most vaccines tend to have the worst IMRs. Thus, we must ask important questions: is it possible that some nations are requiring too many vaccines for their infants and the additional vaccines are a toxic burden on their health? Are some deaths that are listed within the 130 infant mortality death categories really deaths that are associated with over-vaccination? Are some vaccine-related deaths hidden within the death tables?

Sudden infant death syndrome (SIDS) Prior to contemporary vaccination programs, ‘Crib death’ was so infrequent that it was not mentioned in infant mortality statistics. In the United States, national immunization campaigns were initiated in the 1960s when several new vaccines were introduced and actively recommended. For the first time in history, most US infants were required to receive several doses of DPT, polio, measles, mumps, and rubella vaccines.14 Shortly thereafter, in 1969, medical certifiers presented a new medical term—sudden infant death syndrome.15,16 In 1973, the National Center for Health Statistics added a new cause-of-death category—for SIDS—to the ICD. SIDS is defined as the sudden and unexpected death of an infant which remains unexplained after a thorough investigation. Although there are no specific symptoms associated with SIDS, an autopsy often reveals congestion and edema of the lungs and inflammatory changes in the respiratory system.17 By 1980, SIDS had become the leading cause of postneonatal mortality (deaths of infants from 28 days to one year old) in the United States.18 In 1992, to address the unacceptable SIDS rate, the American Academy of Pediatrics initiated a ‘Back to Sleep’ campaign, convincing parents to place their infants supine, rather than prone, during sleep. From 1992 to 2001, the postneonatal SIDS rate dropped by an average annual rate of 8.6%. However, other causes of sudden unexpected infant death (SUID) increased. For example, the postneonatal mortality rate from ‘suffocation in bed’ (ICD-9 code E913.0) increased during this same period at an average annual rate of 11.2%. The postneonatal mortality rate from ‘suffocation-other’ (ICD-9 code E913.1-E913.9), ‘unknown and unspecified causes' (ICD-9 code 799.9), and due to ‘intent unknown’ in the External Causes of Injury section (ICD-9 code E980-E989), all increased during this period as well.18 (In Australia, Mitchell et al. observed that when the SIDS rate decreased, deaths attributed to asphyxia increased.19 Overpeck et al. and others, reported similar observations.)20,21 A closer inspection of the more recent period from 1999 to 2001 reveals that the US postneonatal SIDS rate continued to decline, but there was no significant change in the total postneonatal mortality rate. During this period, the number of deaths attributed to ‘suffocation in bed’ and ‘unknown causes,’ increased significantly. According to Malloy and MacDorman, “If death-certifier preference has shifted such that previously classified SIDS deaths are now classified as ‘suffocation,’ the inclusion of these suffocation deaths and unknown or unspecified deaths with SIDS deaths then accounts for about 90 percent of the decline in the SIDS rate observed between 1999 and 2001 and results in a non-significant decline in SIDS”18 (Figure 3). Download Open in new tab Download in PowerPoint

Is there evidence linking SIDS to vaccines? Although some studies were unable to find correlations between SIDS and vaccines,22–24 there is some evidence that a subset of infants may be more susceptible to SIDS shortly after being vaccinated. For example, Torch found that two-thirds of babies who had died from SIDS had been vaccinated against DPT (diphtheria–pertussis–tetanus toxoid) prior to death. Of these, 6.5% died within 12 hours of vaccination; 13% within 24 hours; 26% within 3 days; and 37%, 61%, and 70% within 1, 2, and 3 weeks, respectively. Torch also found that unvaccinated babies who died of SIDS did so most often in the fall or winter while vaccinated babies died most often at 2 and 4 months—the same ages when initial doses of DPT were given to infants. He concluded that DPT “may be a generally unrecognized major cause of sudden infant and early childhood death, and that the risks of immunization may outweigh its potential benefits. A need for re-evaluation and possible modification of current vaccination procedures is indicated by this study.”25 Walker et al. found “the SIDS mortality rate in the period zero to three days following DPT to be 7.3 times that in the period beginning 30 days after immunization.”26 Fine and Chen reported that babies died at a rate nearly eight times greater than normal within 3 days after getting a DPT vaccination.27 Ottaviani et al. documented the case of a 3-month-old infant who died suddenly and unexpectedly shortly after being given six vaccines in a single shot: “Examination of the brainstem on serial sections revealed bilateral hypoplasia of the arcuate nucleus. The cardiac conduction system presented persistent fetal dispersion and resorptive degeneration. This case offers a unique insight into the possible role of hexavalent vaccine in triggering a lethal outcome in a vulnerable baby.” Without a full necropsy study in the case of sudden, unexpected infant death, at least some cases linked to vaccination are likely to go undetected.28

Reclassified infant deaths It appears as though some infant deaths attributed to SIDS may be vaccine related, perhaps associated with biochemical or synergistic toxicity due to over-vaccination. Some infants' deaths categorized as ‘suffocation’ or due to ‘unknown and unspecified causes' may also be cases of SIDS reclassified within the ICD. Some of these infant deaths may be vaccine related as well. This trend toward reclassifying ICD data is a great concern of the CDC “because inaccurate or inconsistent cause-of-death determination and reporting hamper the ability to monitor national trends, ascertain risk factors, and design and evaluate programs to prevent these deaths.”29 If some infant deaths are vaccine related and concealed within the various ICD categories for SUIDs, is it possible that other vaccine-related infant deaths have also been reclassified? 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, sanitation, and health care—several require their infants to receive a relatively high number of vaccine doses and have relatively high infant mortality rates. These nations should take a closer look at their infant death tables to determine if some fatalities are possibly related to vaccines though reclassified as other causes. Of course, all SUID categories should be re-inspected. Other ICD categories may be related to vaccines as well. For example, a new live-virus orally administered vaccine against rotavirus-induced diarrhea—Rotarix®—was licensed by the European Medicine Agency in 2006 and approved by the US Food and Drug Administration (FDA) in 2008. However, in a clinical study that evaluated the safety of the Rotarix vaccine, vaccinated babies died at a higher rate than non-vaccinated babies—mainly due to a statistically significant increase in pneumonia-related fatalities.30 (One biologically plausible explanation is that natural rotavirus infection might have a protective effect against respiratory infection.)31 Although these fatalities appear to be vaccine related and raise a nation’s infant mortality rate, medical certifiers are likely to misclassify these deaths as pneumonia. Several additional ICD categories are possible candidates for incorrect infant death classifications: unspecified viral diseases, diseases of the blood, septicemia, diseases of the nervous system, anoxic brain damage, other diseases of the nervous system, diseases of the respiratory system, influenza, and unspecified diseases of the respiratory system. All of these selected causes may be repositories of vaccine-related infant deaths reclassified as common fatalities. All nations—rich and poor, industrialized and developing—have an obligation to determine whether their immunization schedules are achieving their desired goals. Progress on reducing infant mortality rates should include monitoring vaccine schedules and medical certification practices to ascertain whether vaccine-related infant deaths are being reclassified as ordinary mortality in the ICD.