Infant mortality rates regressed against number of vaccine doses routinely given: Is there a biochemical or synergistic toxicity?

2011·0.24 MB·English

by  Miller, Neil Z

Original Article
HumanandExperimentalToxicology
30(9)1420–1428
Infant mortality rates regressed
ªTheAuthor(s)2011
Reprintsandpermission:
against number of vaccine doses sagepub.co.uk/journalsPermissions.nav
DOI:10.1177/0960327111407644
routinely given: Is there a het.sagepub.com
biochemical or synergistic toxicity?
Neil Z Miller and Gary S Goldman
Abstract
Theinfant mortality rate(IMR)is oneofthemostimportant indicatorsof thesocio-economicwell-being and
publichealthconditionsofacountry.TheUSchildhoodimmunizationschedulespecifies26vaccinedosesfor
infantsagedlessthan1year—themostintheworld—yet33nationshavelowerIMRs.Usinglinearregression,
the immunization schedules of these 34 nations were examined and a correlation coefficient of r ¼ 0.70
(p<0.0001)wasfoundbetweenIMRsandthenumberofvaccinedosesroutinelygiventoinfants.Nationswere
alsogroupedintofivedifferentvaccinedoseranges:12–14,15–17,18–20,21–23,and24–26.ThemeanIMRsof
all nations within each group were then calculated. Linear regression analysis of unweighted mean IMRs
showed a high statistically significant correlation between increasing number of vaccine doses and increasing
infantmortalityrates,withr¼0.992(p¼0.0009).UsingtheTukey-Kramertest,statisticallysignificantdiffer-
encesinmeanIMRswerefoundbetweennationsgiving12–14vaccinedosesandthosegiving21–23,and24–26
doses.Acloserinspectionofcorrelationsbetweenvaccinedoses,biochemicalorsynergistictoxicity,andIMRs
is essential.
Keywords
infantmortalityrates,suddeninfantdeath,SIDS,immunizationschedules,childhoodvaccines,drugtoxicology,
synergistic effects, linear regression model
Introduction adecreaseinimmunefunction.Animpairedimmune
function often leads to an increased susceptibility to
The infant mortality rate (IMR) is one of the most
infection.2 It is well established that infections, no
important measures of child health and overall
matter how mild, have adverse effects on nutritional
development in countries. Clean water, increased
status. Conversely, almost any nutritional deficiency
nutritional measures, better sanitation, and easy
will diminish resistance to disease.3
accesstohealthcarecontributethemosttoimproving
DespitetheUnitedStatesspendingmorepercapita
infantmortalityratesinunclean,undernourished,and
on health care than any other country,4 33 nations
impoverished regions of the world.1–3 In developing
havebetterIMRs.SomecountrieshaveIMRsthatare
nations,IMRsarehighbecausethesebasicnecessities
less than half the US rate: Singapore, Sweden, and
forinfantsurvivalarelackingorunevenlydistributed.
Japan are below 2.80. According to the Centers for
Infectious and communicable diseases are more
DiseaseControlandPrevention(CDC),‘‘Therelative
common 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 appears
do much to prevent them.1
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,
Correspondingauthor:
malaria,andmalnutrition—thelattergreatlyaffecting
NeilZMiller,POBox9638,SantaFe,NM87504,USA
all the others.1 Malnutrition has been associated with Email:[email protected]
Miller N Z and Goldman G S 1421
Table 1.2009Infantmortality rates,top34 nations8 nations routinely give to their infants and their
infantmortalityrates,alinearregressionanalysiswas
Rank Country IMR
performed.
1 Singapore 2.31
2 Sweden 2.75
3 Japan 2.79 Methods and design
4 Iceland 3.23
Infant mortality
5 France 3.33
6 Finland 3.47
The infant mortality rate is expressed as the
7 Norway 3.58
number of infant deaths per 1000 live births.
8 Malta 3.75
According to the US Central Intelligence Agency
9 Andorra 3.76
(CIA), which keeps accurate, up-to-date infant
10 CzechRepublic 3.79
11 Germany 3.99 mortality statistics throughout the world, in 2009
12 Switzerland 4.18 there were 33 nations with better infant mortality
13 Spain 4.21 rates than the United States (Table 1).8 The US
14 Israel 4.22 infant mortality rate of 6.22 infant deaths per
15 Liechtenstein 4.25
1000 live births ranked 34th.
16 Slovenia 4.25
17 SouthKorea 4.26
Immunization schedules and vaccine doses
18 Denmark 4.34
19 Austria 4.42 A literature review was conducted to determine the
20 Belgium 4.44
immunization schedules for the United States and all
21 Luxembourg 4.56
33nationswithbetterIMRsthantheUnitedStates.9,10
22 Netherlands 4.73
The total number of vaccine doses specified for
23 Australia 4.75
24 Portugal 4.78 infantsagedless than 1year was then determinedfor
25 United Kingdom 4.85 each country (Table 2). A vaccine dose is an exact
26 NewZealand 4.92 amount of medicine or drug to be administered. The
27 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 5.16
tion but contains three separate vaccines (for
31 Italy 5.51
diphtheria, tetanus, and pertussis) totaling three vac-
32 SanMarino 5.53
33 Cuba 5.82 cine doses.
34 United States 6.22
Nations organized into data pairs
CIA.Countrycomparison:infantmortalityrate(2009).TheWorld
Factbook.www.cia.gov(Datalastupdated13April2010).8 The34nationswereorganizedintodatapairsconsist-
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 the
United States have increased by more than 20%
dataset because they each had fewer than five infant
between1990and2006.Pretermbabieshaveahigher
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.
explainwhytheUnitedStateshasseenlittleimprove-
ment in its IMR since 2000.7
Nations organized into groups
Nations differ in their immunization requirements
for infants aged less than 1 year. In 2009, five of the Nations were placed into the following five groups
34 nations with the best IMRs required 12 vaccine based on the number of vaccine doses they routinely
doses, the least amount, while the United States give their infants: 12–14, 15–17, 18–20, 21–23, and
required 26 vaccine doses, the most of any nation. 24–26 vaccine doses. The unweighted IMR means
Toexplorethecorrelationbetweenvaccinedosesthat of all nations as a function of the number of vaccine
1422 Human and Experimental Toxicology 30(9)
Table2.SummaryofInternationalImmunizationSchedules:vaccinesrecommended/requiredpriortooneyearofagein
34nations
Totalb Group
Nation Vaccines prior toone yearof age doses (range ofdoses)
Sweden DTaP (2),Polio (2),Hib(2), Pneumo (2) 12 1(12–14)
Japan DTaP (3),Polio (2),BCG 12
Iceland DTaP (2),Polio (2),Hib(2), MenC(2) 12
Norway DTaP (2),Polio (2),Hib(2), Pneumo (2) 12
Denmark DTaP (2),Polio (2),Hib(2), Pneumo (2) 12
Finland DTaP (2),Polio (2),Hib(2), Rota(3) 13
Malta DTaP (3),Polio (3),Hib(3) 15 2(15–17)
Slovenia DTaP (3),Polio (3),Hib(3) 15
South Korea DTaP (3),Polio (3),HepB (3) 15
Singapore DTaP (3),Polio (3),HepB (3), BCG,Flu 17
New Zealand DTaP (3),Polio (3),Hib(2), HepB (3) 17
Germany DTaP (3),Polio (3),Hib(3), Pneumo (3) 18 3(18–20)
Switzerland DTaP (3),Polio (3),Hib(3), Pneumo (3) 18
Israel DTaP (3),Polio (3),Hib(3), HepB (3) 18
Liechtensteina DTaP (3),Polio (3),Hib(3), Pneumo (3) 18
Italy DTaP (3),Polio (3),Hib(3), HepB (3) 18
SanMarinoa DTaP (3),Polio (3),Hib(3), HepB (3) 18
France DTaP (3),Polio (3),Hib(3), Pneumo (2),HepB (2) 19
CzechRepublic DTaP (3),Polio (3),Hib(3), HepB (3),BCG 19
Belgium DTaP (3),Polio (3),Hib(3), HepB (3),Pneumo (2) 19
United Kingdom DTaP (3),Polio (3),Hib(3), Pneumo (2),MenC (2) 19
Spain DTaP (3),Polio (3),Hib(3), HepB (3),MenC (2) 20
Portugal 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) 22
Cuba DTaP (3),Polio (3),Hib(3), HepB (4),MenBC (2),BCG 22
Andorraa DTaP (3),Polio (3),Hib(3), HepB (3),Pneumo (3), MenC(2) 23
Austria DTaP (3),Polio (3),Hib(3), HepB (3),Pneumo (3), Rota(2) 23
Ireland DTaP (3),Polio (3),Hib(3), HepB (3),Pneumo (2), MenC(2), BCG 23
Greece DTaP (3),Polio (3),Hib(3), HepB (3),Pneumo (3), MenC(2) 23
Monacoa DTaP (3),Polio (3),Hib(3), HepB (3),Pneumo (3), HepA,BCG 23
Netherlands 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 24
Australia DTaP (3),Polio (3),Hib(3), HepB (4),Pneumo (3), Rota(2) 24
United States DTaP (3),Polio (3),Hib(3), HepB (3),Pneumo (3), Rota(3), Flu(2) 26
aThesefournationswereexcludedfromtheanalysisbecausetheyhadfewerthanfiveinfantdeaths.
bDTaPisadministeredasasingleshotbutcontainsthreeseparatevaccines(fordiphtheria,tetanus,andpertussis).Thus,DTaPgiven
threetimesininfancyisequivalenttoninevaccinedoses.
Immunizationschedulesarefor2008–2009.9,10
doses were analyzed using linear regression. The resultsfromtheTukey-Kramertest,aposttestforthe
Pearson correlation coefficient (r) and coefficient of overall linear trend was performed.
determination (r2) were calculated using GraphPad
Prism, version 5.03 (GraphPad Software, San Diego,
Results
CA, USA, www.graphpad.com). Additionally, the
Nations organized into data pairs
Fstatisticandcorrespondingpvalueswerecomputed
to test if the best fit slope was statistically signifi- A scatter plot of each of the 30 nation’s IMR versus
cantly non-zero. The Tukey-Kramer test was used to vaccinedosesyieldedalinearrelationshipwithacor-
determine whether or not the mean IMR differences relation coefficient of 0.70 (95% CI, 0.46–0.85) and
betweenthegroupswerestatisticallysignificant.Fol- p < 0.0001 providing evidence of a positive correla-
lowing the one-way ANOVA (analysis of variance) tion:IMRandvaccinedosestendtoincreasetogether.
Miller N Z and Goldman G S 1423
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 e 6
ate y rat
Infant mortality r(deaths/1000) 45 best fit line an infant mortalit(deaths/1,000) 45 18−20 21−23 24−26
3 95% CI Me 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 Doses
Figure 1. 2009 Infant mortality rates and number of Figure 2. 2009 Mean infant mortality rates and mean
vaccine dosesfor30 nations. numberof vaccine doses(five categories).
Discussion
The F statistic applied to the slope [0.148 (95% CI,
Basic necessities for infant survival
0.090–0.206)]issignificantlynon-zero,withF¼27.2
(p<0.0001;Figure1). It is instructive to note that many developing nations
requiretheirinfantstoreceivemultiplevaccinedoses
and have national vaccine coverage rates (a percent-
ageofthetargetpopulationthathasbeenvaccinated)
Nations organized into groups
of 90% or better, yet their IMRs are poor. For exam-
The unweighted mean IMR of each category was ple, Gambiarequires its infants toreceive 22vaccine
computed by simply summing the IMRs of each doses during infancy and has a 91%–97% national
nationcomprisingagroupanddividingbythenumber vaccine coverage rate, yet its IMR is 68.8. Mongolia
of nations in that group. The IMRs were as follows: requires 22 vaccine doses during infancy, has a
3.36 (95% CI, 2.74–3.98) for nations specifying 95%–98% coverage rate, and an IMR of 39.9.8,9
12–14 doses (mean 13 doses); 3.89 (95% CI, These examples appear to confirm that IMRs will
2.68–5.12) for 15–17 doses (mean 16 doses); remain high in nations that cannot provide clean
4.28 (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 22doses);5.19(95% CI,4.06–6.31)for24-26 improve in all of these areas a critical threshold will
doses (mean 25 doses; Figure 2). Linear regression eventuallybereachedwherefurtherreductionsofthe
analysis yielded an equation of the best fit line, infant mortality rate will be difficult to achieve
y ¼ 0.157x þ 1.34 with r ¼ 0.992 (p ¼ 0.0009) and because most of the susceptible infants that could
r2¼0.983.Thus,98.3%ofthevariationinmeanIMRs have been saved from these causes would have been
isexplainedbythelinearmodel.Again,theFstatistic saved. Further reductions of the IMR must then be
yieldedasignificantlynon-zeroslope,withF¼ 173.9 achievedinareasoutsideofthesedomains.Asdevel-
(p¼0.0009). opingnationsascendtohighersocio-economicliving
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 defined
dose categories are significantly different (r2 ¼
Crossing the socio-economic threshold
0.510).Tukey’smultiplecomparisontestfoundstatis-
ticalsignificanceinthedifferencesbetweenthemean Itappearsthatatacertainstageinnations’movement
IMRs of those nations giving 12–14 vaccine doses upthesocio-economicscale—afterthebasicnecessi-
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 been
95% CI, 0.542–3.11). met—a counter-intuitive relationship occurs between
1424 Human and Experimental Toxicology 30(9)
the number of vaccines given to infants and infant anaverageannualrateof8.6%.However,othercauses
mortality rates: nations with higher (worse) infant of sudden unexpected infant death (SUID) increased.
mortality rates give their infants, on average, more Forexample,thepostneonatalmortalityratefrom‘suf-
vaccinedoses.Thispositivecorrelation,derivedfrom focationinbed’(ICD-9codeE913.0)increasedduring
the data and demonstrated in Figures 1 and 2, elicits this same period at an average annual rate of 11.2%.
an 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 to
A closer inspection of infant deaths ‘intentunknown’intheExternalCausesofInjurysec-
tion(ICD-9codeE980-E989),allincreasedduringthis
Many nations adhere to an agreed upon International
periodaswell.18(InAustralia,Mitchelletal.observed
Classification of Diseases (ICD) for grouping infant
thatwhentheSIDSratedecreased,deathsattributedto
deathsinto130 categories.11–13 Among the34nations
asphyxia increased.19 Overpeck et al. and others,
analyzed, those that require the most vaccines tend to
reported similar observations.)20,21
have the worst IMRs. Thus, we must ask important
Acloserinspectionofthemorerecentperiodfrom
questions:isitpossiblethatsomenationsarerequiring
1999 to 2001 reveals that the US postneonatal SIDS
too many vaccines for their infants and the additional
ratecontinuedtodecline,buttherewasnosignificant
vaccines 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 to
death categories really deaths that are associated with
‘suffocationinbed’and‘unknowncauses,’increased
over-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 classified
Sudden infant death syndrome (SIDS)
as ‘suffocation,’ the inclusion of these suffocation
Prior to contemporary vaccination programs, ‘Crib deathsandunknownorunspecifieddeathswithSIDS
death’ was so infrequent that it was not mentioned deaths then accounts for about 90 percent of the
in infant mortality statistics. In the United States, decline in the SIDS rate observed between 1999 and
national immunization campaigns were initiated in 2001 and results in a non-significant decline in
the1960swhenseveralnewvaccineswereintroduced SIDS’’18 (Figure 3).
and actively recommended. For the first time in his-
tory,mostUSinfantswererequiredtoreceiveseveral
Is there evidence linking SIDS to vaccines?
doses of DPT, polio, measles, mumps, and rubella
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 some
deathsyndrome.15,16In1973,theNationalCenterfor evidencethatasubsetofinfantsmaybemoresuscep-
Health Statistics added a new cause-of-death cate- tible to SIDS shortly after being vaccinated. For
gory—for SIDS—to the ICD. SIDS is defined as the example, Torch found that two-thirds of babies who
sudden and unexpected death of an infant which haddiedfromSIDShadbeenvaccinatedagainstDPT
remains 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%,and70%within1,2,and3weeks,respectively.
respiratory system.17 By 1980, SIDS had become the Torch also found that unvaccinated babies who died
leading cause of postneonatal mortality (deaths of of SIDS did so most often in the fall or winter while
infants from 28 days to one year old) in the United vaccinated babies died most often at 2 and 4
States.18 months—the same ages when initial doses of DPT
In1992,toaddresstheunacceptableSIDSrate,the were given to infants. He concluded that DPT ‘‘may
American Academy of Pediatrics initiated a ‘Back to be a generally unrecognized major cause of sudden
Sleep’ campaign, convincing parents to place their infant and early childhood death, and that the risks
infants supine, rather than prone, during sleep. From of immunization may outweigh its potential benefits.
1992 to 2001, the postneonatal SIDS rate dropped by Aneedforre-evaluationandpossiblemodificationof
Miller N Z and Goldman G S 1425
may also be cases of SIDS reclassified within the
Reclassification of SIDS Deaths to
Suffocation in Bed and Unknown Causes ICD. Some of these infant deaths may be vaccine
90 related as well. This trend toward reclassifying ICD
data is a great concern of the CDC ‘‘because inaccu-
00 80 77.4 77.1 75.4 rate or inconsistent cause-of-death determination and
0
00, 70 reporting hamper the ability to monitor national
1
r 61.6
h pe 60 57.1 trends,ascertain riskfactors,anddesignandevaluate
at 50.9 programs to prevent these deaths.’’29 If some infant
e
D 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
Of the 34 nations that have crossed the socio-
SIDS + Suffocation + Unknown Causes
economic threshold and are able to provide the basic
necessitiesforinfantsurvival—cleanwater,nutrition,
Figure3.Reclassificationofsuddeninfantdeathsyndrome
sanitation, and health care—several require their
(SIDS) deaths to suffocation in bed and unknown causes.
infantstoreceivearelativelyhighnumberofvaccine
ThepostneonatalSIDSrateappearstohavedeclinedfrom
61.6 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 Thesenationsshouldtakeacloserlookattheirinfant
increase 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 other
unexpectedinfantdeaths(SUIDs)arecombinedwithSIDS
causes. Of course, all SUID categories should be re-
deaths,thetotalSIDSrateremainsrelativelystable,result-
inspected. Other ICD categories may be related to
ingina non-significant decline.
vaccinesaswell.Forexample,anewlive-virusorally
administered vaccine against rotavirus-induced
current vaccination procedures is indicated by this
1
study.’’25Walkeretal.found‘‘theSIDSmortalityrate diarrhea—Rotarix —was licensed by the European
Medicine Agency in 2006 and approved by the US
intheperiodzerotothreedaysfollowingDPTtobe7.3
Food and Drug Administration (FDA) in 2008.
times that in the period beginning 30 days after
immunization.’’26FineandChenreportedthatbabies However, in a clinical study that evaluated the safety
of the Rotarix vaccine, vaccinated babies died at a
died at a rate nearly eight times greater than normal
within3daysaftergettingaDPTvaccination.27 higher rate than non-vaccinated babies—mainly due
to a statistically significant increase in pneumonia-
Ottavianietal.documentedthecaseofa3-month-old
related fatalities.30(One biologicallyplausible expla-
infantwhodiedsuddenlyandunexpectedlyshortlyafter
nation is that natural rotavirusinfection might havea
beinggivensixvaccinesinasingleshot:‘‘Examination
protective effect against respiratory infection.)31
of the brainstem on serial sections revealed bilateral
Although these fatalities appear to be vaccine related
hypoplasiaofthearcuatenucleus.Thecardiacconduc-
and raise a nation’s infant mortality rate, medical
tion system presented persistent fetal dispersion and
certifiers are likely to misclassify these deaths as
resorptive degeneration. This case offers a unique
pneumonia.
insight into the possible role of hexavalent vaccine in
SeveraladditionalICDcategoriesarepossiblecan-
triggeringalethaloutcomeinavulnerablebaby.’’With-
didates for incorrect infant death classifications:
out a full necropsy study in the case of sudden, unex-
unspecified viral diseases, diseases of the blood,
pected infant death, at least some cases linked to
vaccinationarelikelytogoundetected.28 septicemia, diseases of the nervous system, anoxic
brain damage, other diseases of the nervous system,
diseases of the respiratory system, influenza, and
Reclassified infant deaths
unspecified diseases of the respiratory system. All
It appears as though some infant deaths attributed to of these selected causes may be repositories of
SIDSmaybevaccinerelated,perhapsassociatedwith vaccine-related infant deaths reclassified as common
biochemical or synergistic toxicity due to over- fatalities. All nations—rich and poor, industrialized
vaccination.Someinfants’deathscategorizedas‘suf- and developing—have an obligation to determine
focation’ordueto‘unknownandunspecifiedcauses’ whether their immunization schedules are achieving
1426 Human and Experimental Toxicology 30(9)
their desired goals. Progress on reducing infant of the nations in this study had coverage rates in the
mortality rates should include monitoring vaccine 90%–99% range for the most commonly recom-
schedulesandmedicalcertificationpracticestoascer- mended vaccines—DTaP, polio, hepatitis B, and Hib
tain whether vaccine-related infant deaths are being (when these vaccines were included in the schedule).
reclassified as ordinary mortality in the ICD. Therefore,thisfactorisunlikelytohaveimpactedthe
analyses.9
Howmanyinfantscanbesavedwithanimproved
IMR? Minority races
Slight improvements in IMRs can make a substantial IthasbeenarguedthattheUSIMRispoorincompar-
difference.In2009,therewereapproximately4.5mil- isontomanyothernationsbecauseAfrican–American
lionlivebirthsand28,000infantdeathsintheUnited infants are at greater risk of dying relative to White
States, resulting in an infant mortality rate of 6.22/ infants, perhaps due to genetic factors or disparities
1000.Ifhealthauthoritiescanfindawaytoreducethe inlivingstandards.However,in2006theUSIMRfor
rate by 1/1000 (16%), the United States would rise infants of all races was 6.69 and the IMR for White
in international rank from 34th to 31st and about infantswas5.56.13In2009,thisimprovedratewould
4500 infants would be saved. havemovedtheUnitedStatesupbyjustonerankinter-
nationally,from34thplaceto33rdplace.8Inaddition,
theIMRsforHispanicsofMexicandescentandAsian–
Limitations of study and potential AmericansintheUnitedStatesaresignificantlylower
confounding factors thantheIMRforWhites.6Thus,diverseIMRsamong
differentracesintheUnitesStatesexertonlyamodest
This analysis did not adjust for vaccine composition,
influence over the United States’ international infant
national vaccine coverage rates, variations in the
mortalityrank.
infant mortality rates among minority races, preterm
births, differences in how some nations report live
births,orthepotentialforecologicalbias.Afewcom- Preterm births
mentsabouteachofthesefactorsareincludedbelow.
Preterm birth rates in the United States have steadily
increased since the early 1980s. (This rise has been
Vaccine composition tied to a greater reliance on caesarian deliveries,
This analysis calculated the total number of vaccine inducedlabor,andmorebirthstooldermothers.)Pre-
doses received by children but did not differentiate term babies are more likely than full-term babies to
between the substances, or quantities of those sub- die within the first year of life. About 12.4% of US
stances, in each dose. Common vaccine substances births are preterm. In Europe, the prevalence rate of
includeantigens(attenuatedviruses,bacteria,toxoids), premature birth ranges from 5.5% in Ireland to
preservatives (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 is
salts), additives (ammonium sulfate, glycerin, sodium important to note that some nations such as Ireland
borate, polysorbate 80, hydrochloric acid, sodium and Greece, which have very low preterm birth rates
hydroxide, potassium chloride), stabilizers (fetal (5.5% and 6%, respectively) compared to the United
bovine serum, monosodium glutamate, human serum States,requiretheirinfantstoreceivearelativelyhigh
albumin,porcinegelatin),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.6,32
purposes of this study, all vaccine doses were equally
weighted. Differences in reporting live births
Infant mortality rates in most countries are reported
Vaccine 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 the
age rates—a percentage of the target population that infant,butdodefinea‘livebirth’asababybornwith
received the recommended vaccines. However, most any signs of life for any length of time.12 However,
Miller N Z and Goldman G S 1427
four nations in the dataset—France, the Czech giventoinfants.Whennationsweregroupedintofive
Republic,theNetherlands,andIreland—donotreport 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 in
These countries add an additional requirement that IMR was explained by the unweighted linear
livebabiesmustalsobeatleast22weeksofgestation regression model. These findings demonstrate a
orweighatleast500grams.Ifbabiesdonotmeetthis counter-intuitive relationship: nations that require
requirement and die shortly after birth, they are morevaccinedosestendtohavehigherinfantmortal-
reportedasstillbirths.Thisinconsistencyinreporting ity rates.
live births artificially lowers the IMRs of these Efforts to reduce the relatively high US IMR have
nations.32,33AccordingtotheCDC,‘‘Therearesome been elusive. Finding ways to lower preterm birth
differences among countries in the reporting of very rates should be a high priority. However, preventing
smallinfantswhomaydiesoonafterbirth.However, premature births is just a partial solution to reduce
itappearsunlikelythatdifferencesinreportingarethe infant deaths. A closer inspection of correlations
primary explanation for the United States’ relatively between vaccine doses, biochemical or synergistic
low international ranking.’’32 Nevertheless, when the toxicity,andIMRs,isessential.Allnations—richand
IMRsofFrance,theCzechRepublic,theNetherlands, poor, advanced and developing—have an obligation
and Ireland were adjusted for known underreporting to determine whether their immunization schedules
of live births and the 30 data pairs retested for are achieving their desired goals.
significance, the correlation coefficient improved
from 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
reviewingthe manuscript andsharing their expertise.
Ecological bias occurs when relationships among
individuals are inferred from similar relationships
Funding
observed among groups (or nations). Although most
This research received no specific grantfrom any funding
of the nations in this study had 90%–99% of their
agencyinthepublic,commercial,ornot-for-profitsectors.
infants fully vaccinated, without additional data we
do not know whether it is the vaccinated or unvacci-
References
natedinfantswhoaredyingininfancyathigherrates.
1. Wegman ME. Infant mortality in the 20th century,
However, respiratory disturbances have been docu-
dramatic but uneven progress. J Nutr 2001; 131:
mentedin closeproximity toinfant vaccinations, and
401S–408S.
lethal changes in the brainstem of a recently vacci-
2. BeckMA.Theroleofnutritioninviraldisease.JNutri
nated baby have been observed. Since some infants
Biochem1996; 7:683–690.
may be more susceptible to SIDS shortly after being
3. ScrimshawNSandSanGiovanniJP.Synergismofnutri-
vaccinated, and babies vaccinated against diarrhea
tion, infection, and immunity: an overview. Am J Clin
diedfrompneumoniaatastatisticallyhigherratethan
Nutr1997; 66:464S–477S.
non-vaccinatedbabies,thereisplausiblebiologicand
4. AndersonGF,HussayPS,FrognerBK,andWatersHR.
causalevidencethattheobservedcorrelationbetween
HealthspendingintheUnitedStatesandtherestofthe
IMRs and the number of vaccine doses routinely
industrializedworld.HealthAffairs2005;24:903–914.
giventoinfantsshouldnotbedismissedasecological
5. MacDorman MF and Mathews TJ. Recent trends in
bias.
infant mortality inthe United States. NCHS DataBrief
(CDC),no9.Hyattsville,MD,USA:NationalCenterfor
Conclusion
Health Statistics,2008.
The US childhood immunization schedule requires 6. KentMM.Prematurebirthshelptoexplainhigherinfant
26vaccinedosesforinfantsagedlessthan1year,the mortality rate. Population Reference Bureau.
most in the world, yet 33 nations have better IMRs. www.prb.org/articles/2009/prematurebirth.aspx
Using linear regression, the immunization schedules (accessed December2009).
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 Rep
IMRs and the number of vaccine doses routinely 2009;58:6.
1428 Human and Experimental Toxicology 30(9)
8. CIA.Countrycomparison:infantmortalityrate(2009). infant death syndrome: no increased risk after
TheWorldFactbook.www.cia.gov(accessed13April immunisation. Vaccine 2007; 25:336–340.
2010). 23. Stratton K, Almario DA, Wizemann TM, and
9. WHO/UNICEF.ImmunizationSummary:AStatistical McCormick MC. Immunization safety review: vacci-
Reference Containing Data Through 2008 (The 2010 nations and sudden unexpected death in infancy.
Edition).www.childinfo.org. Washington DC, USA: National Academies Press,
10. Up-to-date European vaccination schedules may be 2003.
foundhere: www.euvac.net (accessed 13April2010). 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:WorldHealthOrgani- fatalitiesreportedtothevaccineadverseeventreport-
zation,1979. ing system 1990-1997. Pharmacoepidemiol Drug Saf
12. WHO. International Statistical Classification of Dis- 2001; 10:279–285.
eases and Related Health Problems, 10th Revision. 25. TorchWC.Diphtheria-pertussis-tetanus(DPT)immu-
Geneva,Switzerland:WorldHealthOrganization,1992. nization: a potential cause of the sudden infant death
13. CDC. Table 31. Number of infant deaths and infant syndrome (SIDS). American Academy of Neurology,
mortalityratesfor130selectedcauses,byrace:United 34thAnnualMeeting,Apr25-May1,1982.Neurology
States,2006.Natl Vital StatRep2009; 57:110–112. 32(4): pt.2.
14. IannelliV.Immunizationtimeline.KeepKidsHealthy. 26. Walker AM, Jick H, Perera DR, Thompson RS, and
keepkidshealthy.com (accessed 21 April2010). 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 of
16. MacDormanMFandRosenbergHM.Trendsininfant 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:NationalCenterforHealthSta- infantdeathsyndrome(SIDS)shortlyafterhexavalent
tistics,U.S. Government Printing,1993. vaccination: another pathology in suspected SIDS?
17. NationalCenterforHealthStatistics.VitalStatisticsof 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: PublicHealth Service, 1991. investigation (SUIDI) reporting form. Department
18. MalloyMH andMacDorman M.Changes inthe clas- of Health and Human Services (accessed 20 May
sification of sudden unexpected infant deaths: United 2010).
1
States,1992-2001.Pediatrics 2005; 115:1247–1253. 30. GlaxoSmithKline.Rotarix (RotavirusVaccine,Live,
19. Mitchell E, Krous HF, Donald T, and Byard RW. Oral) Oral Suspension. Product insert fromthe manu-
Changing trends in the diagnosis of sudden infant facturer (April 2008):6.
death.AmJForensicMedPathol2000;21:311–314. 31. FDA. Center for biologics evaluation and research,
20. OverpeckMD,BrennerRA,CosgroveC,TrumbleAC, vaccinesandrelatedbiologicalproductsadvisorycom-
Kochanek K, and MacDorman M. National under mittee meeting (20February 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, no
21. ByardRWandBealSM.Haschangingdiagnosticpre- 23.Hyattsville,MD,USA:NationalCenterforHealth
ferencebeenresponsiblefortherecentfallinincidence Statistics, 2009.
of sudden infant death syndrome in South Australia? 33. Euro-Peristat Project, with SCPE, Eurocat, Euroneo-
JPediatr ChildHealth1995; 31:197–199. stat. European Perinatal Health Report: Data for
22. Vennemann MM, Butterfass-Bahloul T, Jorch G, 2004 (The 2008 Edition): Table 3.1:40. www.
BrinkmannB,FindeisenM,SauerlandC,etal.Sudden europeristat.com.