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Wednesday, March 03, 2010

SAPE NAK TOLONG, AKU KENE BACA SUME JOURNAL NIH DALAM MASA SEMINGGU T_T

1. BMJ. 2010 Feb 2;340:c655. doi: 10.1136/bmj.c655.

MMR vaccine and autism.

Bedford HE, Elliman DA.

PMID: 20124364 [PubMed - indexed for MEDLINE]


2. Pediatrics. 2008 Sep;122(3):684-5; author reply 685-6.

Immunization uptake in siblings of children with autism.

Kuwaik G, Roberts W, Brian J, Bryson S, Smith IM, Szatmari P, Zwaigenbaum L.

Comment on:
    Pediatrics. 2008 Apr;121(4):e836-43.

PMID: 18762548 [PubMed - indexed for MEDLINE]


3. Pediatrics. 2008 Apr;121(4):e836-43.

Media coverage of the measles-mumps-rubella vaccine and autism controversy and
its relationship to MMR immunization rates in the United States.

Smith MJ, Ellenberg SS, Bell LM, Rubin DM.

Division of Infectious Diseases, Children's Hospital of Philadelphia,
Philadelphia, Pennsylvania, USA. mjsmit22@louisville.edu

Comment in:
    Pediatrics. 2008 Sep;122(3):684-5; author reply 685-6.

OBJECTIVE: The purpose of this work was to assess the association between media
coverage of the MMR-autism controversy and MMR immunization in the United States.
METHODS: The public-use files of the National Immunization Survey were used to
estimate annual MMR coverage from 1995 to 2004. The primary outcome was selective
measles-mumps-rubella nonreceipt, that is, those children who received all
childhood immunizations except MMR. Media coverage was measured by using
LexisNexis, a comprehensive database of national and local news media. Factors
associated with MMR nonreceipt were identified by using a logistic regression
model. RESULTS: Selective MMR nonreceipt, occurring in as few as 0.77% of
children in the 1995 cohort, rose to 2.1% in the 2000 National Immunization
Survey. Children included in the 2000 National Immunization Survey were born when
the putative link between MMR and autism surfaced in the medical literature but
before any significant media attention occurred. Selective nonreceipt was more
prevalent in private practices and unrelated to family characteristics. MMR
nonreceipt returned to baseline before sustained media coverage of the MMR-autism
story began. CONCLUSIONS: There was a significant increase in selective MMR
nonreceipt that was temporally associated with the publication of the original
scientific literature, suggesting a link between MMR and autism, which preceded
media coverage of the MMR-autism controversy. This finding suggests a limited
influence of mainstream media on MMR immunization in the United States.

PMID: 18381512 [PubMed - indexed for MEDLINE]


4. Arch Dis Child. 2008 Oct;93(10):832-7. Epub 2008 Feb 5.

Measles vaccination and antibody response in autism spectrum disorders.

Baird G, Pickles A, Simonoff E, Charman T, Sullivan P, Chandler S, Loucas T,
Meldrum D, Afzal M, Thomas B, Jin L, Brown D.

Newcomen Centre for Child Development, Guy's & St Thomas' NHS Foundation Trust,
London, UK. gillian.baird@gstt.nhs.uk

Erratum in:
    Arch Dis Child. 2008 Dec;93(12):1079.

Comment in:
    Arch Dis Child. 2008 Oct;93(10):905; author reply 906-7.
    Arch Dis Child. 2008 Oct;93(10):905-6; author reply 906-7.
    Arch Dis Child. 2008 Oct;93(10):905; author reply 906-7.

OBJECTIVE: To test the hypothesis that measles vaccination was involved in the
pathogenesis of autism spectrum disorders (ASD) as evidenced by signs of a
persistent measles infection or abnormally persistent immune response shown by
circulating measles virus or raised antibody titres in children with ASD who had
been vaccinated against measles, mumps and rubella (MMR) compared with controls.
DESIGN: Case-control study, community based. METHODS: A community sample of
vaccinated children aged 10-12 years in the UK with ASD (n = 98) and two control
groups of similar age, one with special educational needs but no ASD (n = 52) and
one typically developing group (n = 90), were tested for measles virus and
antibody response to measles in the serum. RESULTS: No difference was found
between cases and controls for measles antibody response. There was no
dose-response relationship between autism symptoms and antibody concentrations.
Measles virus nucleic acid was amplified by reverse transcriptase-PCR in
peripheral blood mononuclear cells from one patient with autism and two typically
developing children. There was no evidence of a differential response to measles
virus or the measles component of the MMR in children with ASD, with or without
regression, and controls who had either one or two doses of MMR. Only one child
from the control group had clinical symptoms of possible enterocolitis.
CONCLUSION: No association between measles vaccination and ASD was shown.

PMID: 18252754 [PubMed - indexed for MEDLINE]


5. Arch Dis Child. 2007 Apr;92(4):322-7.

MMR: marginalised, misrepresented and rejected? Autism: a focus group study.

Hilton S, Hunt K, Petticrew M.

MRC Social and Public Health Sciences Unit, 4, Lilybank Gardens, Glasgow, UK.
shona@msoc.mrc.gla.ac.uk

OBJECTIVE: To explore how the measles, mumps, and rubella (MMR) vaccine
controversy impacted on the lives of parents caring for children with autism.
DESIGN: Qualitative focus group study. SETTING: United Kingdom. PATIENTS: A
purposively selected sample of 38 parents took part in 10 focus group discussions
between March 2003 and May 2005. RESULTS: Many parents felt that the MMR vaccine
could be too potent for children who are susceptible to developing autism. Of the
parents whose children received the MMR vaccine, many felt guilty that they may
have caused or contributed to their child's autism. Some parents felt frustrated
by health professionals' lack of understanding of the negative impact the MMR
controversy has had on them. Some parents were anxious about subsequent MMR
decision-making for their children. CONCLUSIONS: The controversy has had a
negative impact on some parents of children with autism. This has implications
for health professionals, who need to be particularly aware of the issues these
parents face in future MMR decision-making for their affected child and younger
siblings. It is anticipated that these findings will raise awareness among health
professionals of the difficulties faced by such parents. More generally, there is
a need to promote a greater awareness of the important role health visitors can
play in parental decision-making and for research examining whether health
professionals feel they receive sufficient training in communication skills. It
is also essential that the latest scientific research findings are disseminated
quickly to these parents and to those health professionals advising parents on
matters of vaccine safety.

PMID: 17376937 [PubMed - indexed for MEDLINE]


6. Pediatrics. 2006 Oct;118(4):1664-75.

No evidence of persisting measles virus in peripheral blood mononuclear cells
from children with autism spectrum disorder.

D'Souza Y, Fombonne E, Ward BJ.

Division of Infectious Diseases, McGill University Health Center, Montreal,
Quebec, Canada.

Erratum in:
    Pediatrics. 2006 Dec;118(6):2608.

Comment in:
    Pediatrics. 2006 Oct;118(4):1744-5.

OBJECTIVES: Despite epidemiologic evidence to the contrary, claims of an
association between measles-mumps-rubella vaccination and the development of
autism have persisted. Such claims are based primarily on the identification of
measles virus nucleic acids in tissues and body fluids by polymerase chain
reaction. We sought to determine whether measles virus nucleic acids persist in
children with autism spectrum disorder compared with control children. PATIENTS
AND METHODS: Peripheral blood mononuclear cells were isolated from 54 children
with autism spectrum disorder and 34 developmentally normal children, and up to 4
real-time polymerase chain reaction assays and 2 nested polymerase chain reaction
assays were performed. These assays targeted the nucleoprotein, fusion, and
hemagglutinin genes of measles virus using previously published primer pairs with
detection by SYBR green I. Our own real-time assay targeted the fusion gene using
novel primers and an internal fluorescent probe. Positive reactions were
evaluated rigorously, and amplicons were sequenced. Finally, anti-measles
antibody titers were measured by enzyme immunoassay. RESULTS: The real-time
assays based on previously published primers gave rise to a large number of
positive reactions in both autism spectrum disorder and control samples. Almost
all of the positive reactions in these assays were eliminated by evaluation of
melting curves and amplicon band size. The amplicons for the remaining positive
reactions were cloned and sequenced. No sample from either autism spectrum
disorder or control groups was found to contain nucleic acids from any measles
virus gene. In the nested polymerase chain reaction and in-house assays, none of
the samples yielded positive results. Furthermore, there was no difference in
anti-measles antibody titers between the autism and control groups.
INTERPRETATION: There is no evidence of measles virus persistence in the
peripheral blood mononuclear cells of children with autism spectrum disorder.

PMID: 17015560 [PubMed - indexed for MEDLINE]


7. BMJ. 2005 Jul 9;331(7508):111.

Horizon: Does the MMR jab cause autism? Has the fat lady sung then?

Challoner A.

PMCID: PMC558629
PMID: 16002902 [PubMed - indexed for MEDLINE]


8. Lancet. 2004 Sep 11-17;364(9438):963-9.

MMR vaccination and pervasive developmental disorders: a case-control study.

Smeeth L, Cook C, Fombonne E, Heavey L, Rodrigues LC, Smith PG, Hall AJ.

Department of Epidemiology and Population Health, London School of Hygiene and
Tropical Medicine, London, UK. autism@lshtm.ac.uk

BACKGROUND: Concern that measles-mumps-rubella (MMR) vaccination might cause
autism has led to a fall in vaccine coverage. We investigated whether MMR
vaccination is associated with an increased risk of autism or other pervasive
developmental disorders. METHODS: We did a matched case-control study using the
UK General Practice Research Database. Cases were people born in 1973 or later
who had first recorded diagnosis of pervasive developmental disorder while
registered with a contributing general practice between 1987 and 2001. Controls
were matched on age, sex, and general practice. FINDINGS: 1294 cases and 4469
controls were included. 1010 cases (78.1%) had MMR vaccination recorded before
diagnosis, compared with 3671 controls (82.1%) before the age at which their
matched case was diagnosed. After adjustment for age at joining the database, the
odds ratio for association between MMR and pervasive developmental disorder was
0.86 (95% CI 0.68-1.09). Findings were similar when restricted to children with a
diagnosis of autism, to those vaccinated with MMR before the third birthday, or
to the period before media coverage of the hypothesis linking MMR with autism.
INTERPRETATION: Our findings suggest that MMR vaccination is not associated with
an increased risk of pervasive developmental disorders.

PMID: 15364187 [PubMed - indexed for MEDLINE]


9. Lancet. 2004 Feb 14;363(9408):567-8; author reply 568-9.

MMR and autism: the debate continues.

Thrower D.

Comment on:
    Lancet. 2003 Nov 1;362(9394):1498-9.

PMID: 14975622 [PubMed - indexed for MEDLINE]


10. Pediatrics. 2004 Feb;113(2):259-66.

Age at first measles-mumps-rubella vaccination in children with autism and
school-matched control subjects: a population-based study in metropolitan
atlanta.

DeStefano F, Bhasin TK, Thompson WW, Yeargin-Allsopp M, Boyle C.

National Immunization Program, Centers for Disease Control and Prevention,
Atlanta, Georgia 30333, USA. fxd1@cdc.gov

OBJECTIVE: To compare ages at first measles-mumps-rubella (MMR) vaccination
between children with autism and children who did not have autism in the total
population and in selected subgroups, including children with regression in
development. METHODS: A case-control study was conducted in metropolitan Atlanta.
Case children (N = 624) were identified from multiple sources and matched to
control children (N = 1824) on age, gender, and school. Vaccination data were
abstracted from immunization forms required for school entry. Records of children
who were born in Georgia were linked to Georgia birth certificates for
information on maternal and birth factors. Conditional logistic regression was
used to estimate odds ratios (ORs). RESULTS: The overall distribution of ages at
MMR vaccination among children with autism was similar to that of matched control
children; most case (70.5%) and control children (67.5%) were vaccinated between
12 and 17 months of age. Similar proportions of case and control children had
been vaccinated before 18 or before 24 months. No significant associations for
either of these age cutoffs were found for specific case subgroups, including
those with evidence of developmental regression. More case (93.4%) than control
children (90.6%) were vaccinated before 36 months (OR: 1.49; 95% confidence
interval: 1.04-2.14 in the total sample; OR: 1.23; 95% confidence interval:
0.64-2.36 in the birth certificate sample). This association was strongest in the
3- to 5-year age group. CONCLUSIONS: Similar proportions of case and control
children were vaccinated by the recommended age or shortly after (ie, before 18
months) and before the age by which atypical development is usually recognized in
children with autism (ie, 24 months). Vaccination before 36 months was more
common among case children than control children, especially among children 3 to
5 years of age, likely reflecting immunization requirements for enrollment in
early intervention programs.

PMID: 14754936 [PubMed - indexed for MEDLINE]


11. Arch Pediatr Adolesc Med. 2003 Jul;157(7):628-34.

Association of autistic spectrum disorder and the measles, mumps, and rubella
vaccine: a systematic review of current epidemiological evidence.

Wilson K, Mills E, Ross C, McGowan J, Jadad A.

Department of Medicine and Health Policy, University of Toronto, Ontario, Canada.

Comment in:
    Evid Based Nurs. 2004 Jan;7(1):25.
    Arch Pediatr Adolesc Med. 2003 Jul;157(7):619-21.

OBJECTIVE: To systematically review the evidence for and against the existence of
an association between autistic spectrum disorder (ASD) and the measles, mumps,
and rubella (MMR) vaccine. Study DESIGN: We conducted a systematic review of the
medical literature to identify all controlled epidemiological articles examining
for an association between ASD and the MMR vaccine. We extracted data from the
articles on the characteristics and objectives of the study as well as evidence
of an association. RESULTS: Twelve articles met the inclusion criteria. One study
found no difference in the rates of ASD and the MMR vaccine in children who were
vaccinated and those who were not. Six studies examined for evidence of an
increase in ASD associated with an increase in the MMR vaccine coverage, none of
which showed evidence of an association. Four studies examined if a variant form
of ASD was associated with the MMR vaccine, none of which showed evidence of an
association. Eight studies attempted to determine if there was a temporal
association between developing ASD and receiving the MMR vaccine. Of these, 1
study identified an increase in parental concern in the 6-month period following
vaccination with MMR in one of its analyses. The results of all other studies
showed no association between ASD and the MMR vaccine. CONCLUSIONS: The current
literature does not suggest an association between ASD and the MMR vaccine;
however, limited epidemiological evidence exists to rule out a link between a
rare variant form of ASD and the MMR vaccine. Given the real risks of not
vaccinating and that the risks and existence of variant ASD remain theoretical,
current policies should continue to advocate the use of the MMR vaccine.

PMID: 12860782 [PubMed - indexed for MEDLINE]


12. Pediatrics. 2003 Jul;112(1 Pt 1):206.

Measles-mumps-rubella vaccine and autism.

Mullins ME.

Comment on:
    Pediatrics. 2002 Nov;110(5):957-63.

PMID: 12837894 [PubMed - indexed for MEDLINE]


13. N Engl J Med. 2003 Mar 6;348(10):951-4; author reply 951-4.

Measles, mumps, and rubella vaccination and autism.

Mullins ME.

Comment on:
    N Engl J Med. 2002 Nov 7;347(19):1477-82.

PMID: 12622122 [PubMed - indexed for MEDLINE]


14. Arch Dis Child. 2002 Dec;87(6):493-4.

Recall bias, MMR, and autism.

Andrews N, Miller E, Taylor B, Lingam R, Simmons A, Stowe J, Waight P.

Statistics Unit, Public Health Laboratory Service, 61 Colindale Avenue, London
NW9 5EQ, UK.

Parents of autistic children with regressive symptoms who were diagnosed after
the publicity alleging a link with measles, mumps, and rubella (MMR) vaccine
tended to recall the onset as shortly after MMR more often than parents of
similar children who were diagnosed prior to the publicity. This is consistent
with the recall bias expected under such circumstances.

PMCID: PMC1755823
PMID: 12456546 [PubMed - indexed for MEDLINE]


15. Pediatrics. 2002 Nov;110(5):957-63.

Neurologic disorders after measles-mumps-rubella vaccination.

Mäkelä A, Nuorti JP, Peltola H.

Hospital for Children and Adolescents, Helsinki University Central Hospital,
Helsinki, Finland. annamari.makela@hus.fi

Comment in:
    Pediatrics. 2003 Jul;112(1 Pt 1):206.

OBJECTIVE: The possibility of adverse neurologic events has fueled much concern
about the safety of measles-mumps-rubella (MMR) vaccinations. The available
evidence concerning several of the postulated complications is controversial. The
aim of this study was to assess whether an association prevails between MMR
vaccination and encephalitis, aseptic meningitis, and autism. METHODS: A
retrospective study based on linkage of individual MMR vaccination data with a
hospital discharge register was conducted among 535 544 1- to 7-year-old children
who were vaccinated between November 1982 and June 1986 in Finland. For
encephalitis and aseptic meningitis, the numbers of events observed within a
3-month risk interval after vaccination were compared with the expected numbers
estimated on the basis of occurrence of encephalitis and aseptic meningitis
during the subsequent 3-month intervals. Changes in the overall number of
hospitalizations for autism after vaccination throughout the study period were
searched for. In addition, hospitalizations because of inflammatory bowel
diseases were checked for the children with autism. RESULTS: Of the 535 544
children who were vaccinated, 199 were hospitalized for encephalitis, 161 for
aseptic meningitis, and 352 for autistic disorders. In 9 children with
encephalitis and 10 with meningitis, the disease developed within 3 months of
vaccination, revealing no increased occurrence within this designated risk
period. We detected no clustering of hospitalizations for autism after
vaccination. None of the autistic children made hospital visits for inflammatory
bowel diseases. CONCLUSIONS: We did not identify any association between MMR
vaccination and encephalitis, aseptic meningitis, or autism.

PMID: 12415036 [PubMed - indexed for MEDLINE]


16. Lancet. 2002 Jun 15;359(9323):2113.

Autism, bowel inflammation, and measles.

Thrower D.

Comment on:
    Lancet. 2002 Feb 23;359(9307):705-6.

PMID: 12086786 [PubMed - indexed for MEDLINE]


17. Lancet. 2002 Jun 15;359(9323):2113.

Autism, bowel inflammation, and measles.

Eden OB.

Comment on:
    Lancet. 2002 Feb 23;359(9307):637.

PMID: 12086785 [PubMed - indexed for MEDLINE]


18. Lancet. 2002 Jun 15;359(9323):2112-3.

Autism, bowel inflammation, and measles.

Smeeth L, Hall A, Rodrigues L, Cook C, Fombonne E.

Comment on:
    Lancet. 2002 Feb 23;359(9307):705-6.

PMID: 12086784 [PubMed - indexed for MEDLINE]


19. Lancet. 2002 Jun 15;359(9323):2112.

Autism, bowel inflammation, and measles.

Barr R.

Comment on:
    Lancet. 2002 Feb 23;359(9307):705-6.

PMID: 12086783 [PubMed - indexed for MEDLINE]


20. Lancet. 2002 Jun 15;359(9323):2112.

Autism, bowel inflammation, and measles.

Elphinstone P.

Comment on:
    Lancet. 2002 Feb 23;359(9307):705-6.

PMID: 12086782 [PubMed - indexed for MEDLINE]


21. Lancet. 2002 Feb 23;359(9307):705-6.

Autism, bowel inflammation, and measles.

Walker-Smith J.

Comment in:
    Lancet. 2002 Jun 15;359(9323):2112.
    Lancet. 2002 Jun 15;359(9323):2113.
    Lancet. 2002 Jun 15;359(9323):2112-3.
    Lancet. 2002 Jun 15;359(9323):2112.
    Lancet. 2002 Feb 23;359(9307):637.

PMID: 11879886 [PubMed - indexed for MEDLINE]


22. Lancet. 2002 Feb 23;359(9307):637.

Time to look beyond MMR in autism research.

[No authors listed]

Comment in:
    Lancet. 2002 Aug 24;360(9333):645.
    Lancet. 2002 Jun 15;359(9323):2113.

Comment on:
    Lancet. 2002 Feb 23;359(9307):705-6.

PMID: 11879853 [PubMed - indexed for MEDLINE]


23. BMJ. 2002 Feb 16;324(7334):393-6.

Measles, mumps, and rubella vaccination and bowel problems or developmental
regression in children with autism: population study.

Taylor B, Miller E, Lingam R, Andrews N, Simmons A, Stowe J.

Centre for Community Child Health, Royal Free and University College Medical
School, University College London Royal Free Campus, London.
b.taylor@rfc.ucl.ac.uk

Comment in:
    Mol Psychiatry. 2003 Feb;8(2):133-4.

Objectives: To investigate whether measles, mumps, and rubella (MMR) vaccination
is associated with bowel problems and developmental regression in children with
autism, looking for evidence of a "new variant" form of autism. Design:
Population study with case note review linked to independently recorded vaccine
data. Setting: Five health districts in north east London. Participants: 278
children with core autism and 195 with atypical autism, mainly identified from
computerised disability registers and born between 1979 and 1998. Main outcome
measures: Recorded bowel problems lasting at least three months, age of reported
regression of the child's development where it was a feature, and relation of
these to MMR vaccination. Results: The proportion of children with developmental
regression (25% overall) or bowel symptoms (17%) did not change significantly (P
value for trend 0.50 and 0.47, respectively) during the 20 years from 1979, a
period which included the introduction of MMR vaccination in October 1988. No
significant difference was found in rates of bowel problems or regression in
children who received the MMR vaccine before their parents became concerned about
their development (where MMR might have caused or triggered the autism with
regression or bowel problem), compared with those who received it only after such
concern and those who had not received the MMR vaccine. A possible association
between non-specific bowel problems and regression in children with autism was
seen but this was unrelated to MMR vaccination. Conclusions: These findings
provide no support for an MMR associated "new variant" form of autism with
developmental regression and bowel problems, and further evidence against
involvement of MMR vaccine in the initiation of autism.

PMCID: PMC65532
PMID: 11850369 [PubMed - indexed for MEDLINE]


24. BMJ. 2002 Feb 9;324(7333):315.

New research on autism and measles "proves nothing".

Eaton L.

PMCID: PMC1122257
PMID: 11834548 [PubMed - indexed for MEDLINE]


25. Pediatrics. 2001 Oct;108(4):E58.

No evidence for a new variant of measles-mumps-rubella-induced autism.

Fombonne E, Chakrabarti S.

Institute of Psychiatry, Department of Child and Adolescent Psychiatry, King's
College London, London, United Kingdom.

OBJECTIVE: A link has been postulated between measles-mumps-rubella (MMR) vaccine
and a form of autism that is a combination of developmental regression and
gastrointestinal symptoms that occur shortly after immunization. This hypothesis
has involved 3 separate claims: 1) that there is new phenotype of autism
involving regression and gastrointestinal symptoms, 2) that this new variant is
responsible for the alleged rise of autism rates, and 3) that this phenotype is
associated with biological findings suggestive of the persistence of measles
infection. We tested the first of these claims. If this new "autistic
enterocolitis" syndrome had some validity, then 1 or several of the following 6
predictions should be supported by empirical data: 1) childhood disintegrative
disorder has become more frequent, 2) the mean age of first parental concern for
autistic children who are exposed to MMR is closer to the mean immunization age
than in children who are not exposed to MMR, 3) regression in the development of
children with autism has become more common in MMR-vaccinated children, 4) the
age of onset for autistic children with regression clusters around the MMR
immunization date and is different from that of autistic children without
regression, 5) children with regressive autism have distinct symptom and severity
profiles, and 6) regressive autism is associated with gastrointestinal symptoms
and/or inflammatory bowel disorder. METHODS: Three samples were used.
Epidemiologic data on 96 children (95 immunized with MMR at a median age of 13.5
months) who were born between 1992 and 1995 and had a pervasive developmental
disorder diagnosis as reported in a recent UK survey (post-MMR sample) were
compared with data from 2 previous clinical samples (1 pre-MMR [n = 98] and 1
post-MMR [n = 68]) of autistic patients. All patients were assessed with the
standardized Autism Diagnostic Interview (ADI), allowing rigorous comparison of
age at first parental concerns and rates of regression across samples.
Reliability was excellent on ADI scores, age of parental concern, and
developmental regression. Furthermore, data on bowel symptoms and disorders were
available in the epidemiologic survey from both pediatric and parental sources,
and immunization dates were obtained from computerized records. RESULTS: The
prevalence of childhood disintegrative disorder was 0.6/10 000 (95% confidence
interval: 0.02-3.6/10 000); this very low rate is consistent with previous
estimates and is not suggestive of an increased frequency of this form of
pervasive developmental disorder in samples of children who are immunized with
MMR. There was no difference in the mean age at first parental concern between
the 2 samples exposed to MMR (19.3 and 19.2 months) and the pre-MMR sample (19.5
months). Thus, MMR immunization was not associated with a shift toward an earlier
age for first parental concerns. Similarly, the rate of developmental regression
reported in the post-MMR sample (15.6%) was not different from that in the
pre-MMR sample (18.4%); therefore, there was no suggestion that regression in the
developmental course of autism had increased in frequency since MMR was
introduced. In the epidemiologic sample, the subset of autistic children with
regression had no other developmental or clinical characteristics, which would
have argued for a specific, etiologically distinct phenotype. Parents of autistic
children with developmental regression detected the first symptoms at a very
similar age (19.8 months) to those of autistic children without regression (19.3
months). Moreover, the mean intervals from MMR immunization to parental
recognition of autistic symptoms were comparable in autistic children with or
without regression (248 vs 272 days; not significant). In the epidemiologic
sample, gastrointestinal symptoms were reported in 18.8% of children.
Constipation was the most common symptom (9.4%), and no inflammatory bowel
disorder was reported. Furthermore, there was no association between
developmental regression and gastrointestinal symptoms (odds ratio: 0.63; 95%
confidence interval: 0.06-3.2; not significant), and only 2.1% of the sample
experienced both problems, a rate that did not exceed chance expectations.
CONCLUSIONS: No evidence was found to support a distinct syndrome of MMR-induced
autism or of "autistic enterocolitis." These results add to the recent
accumulation of large-scale epidemiologic studies that all failed to support an
association between MMR and autism at population level. When combined, the
current findings do not argue for changes in current immunization programs and
recommendations.

PMID: 11581466 [PubMed - indexed for MEDLINE]


26. BMJ. 2001 Jul 21;323(7305):163-4.

Measles, mumps, and rubella (MMR) vaccine and autism. MMR cannot be exonerated
without explaining increased incidence of autism.

Yazbak FE.

Comment on:
    BMJ. 2001 Feb 24;322(7284):460-3.

PMID: 11484720 [PubMed - indexed for MEDLINE]


27. JAMA. 2001 May 23-30;285(20):2567-9.

Congressional autism hearings continue: no evidence MMR vaccine causes disorder.

Vastag B.

PMID: 11368715 [PubMed - indexed for MEDLINE]


28. Pediatrics. 2001 May;107(5):E84.

Measles-mumps-rubella vaccine and autistic spectrum disorder: report from the New
Challenges in Childhood Immunizations Conference convened in Oak Brook, Illinois,
June 12-13, 2000.

Halsey NA, Hyman SL; Conference Writing Panel.

BACKGROUND: Parents and physicians are understandably concerned about the causes
and treatment of autism, a devastating disease that affects the entire family.
Although much has been learned about autism, there are many gaps in our knowledge
about what causes the disorder and how it can be prevented. Autistic symptoms
occur along a spectrum, often referred to as autistic spectrum disorder (ASD).
Concern has been raised about a possible association between
measles-mumps-rubella (MMR) vaccine and inflammatory bowel disease (IBD) and ASD,
especially autism with regression. Also, increased requests for educational
services related to ASD have raised concerns about possible increases in the
incidence of ASD. METHODS: On June 12-13, 2000, the American Academy of
Pediatrics (AAP) convened a conference titled "New Challenges in Childhood
Immunizations" in Oak Brook, Illinois. At this conference, parents,
practitioners, and scientists presented information and research on MMR vaccine
and ASD. Attendees included representatives from select AAP committees and
sections as well as federal and other organizations that address related issues.
The multidisciplinary panel of experts reviewed data on what is known about the
pathogenesis, epidemiology, and genetics of ASD and the available data on
hypothesized associations with IBD, measles, and MMR vaccine. Supplemental
information was requested from authors who have proposed the hypotheses and other
experts in relevant areas. RESULTS: Autism is a complex disorder of uncertain and
probably multiple etiologies. Genetic predisposition to ASD may involve as many
as 10 genes. Many experts believe that the abnormal brain development in autism
occurs before 30 weeks' gestation in most instances. In utero rubella is a known
cause of autism. Animal model data support the biologic plausibility that
exposure to yet unrecognized infectious or other environmental agents could cause
ASD. Several factors may contribute to apparent increases in incidence of ASD in
recent years. Most data indicate increased recognition and reporting as primary
factors, but the epidemiologic data are insufficient to determine if there has
been a true increase in the incidence of ASD. Increased reporting of ASD in
recent years has occurred long after the introduction of MMR vaccine in the
United States in 1971 and widespread use of this vaccine in the 1970s for routine
immunization of children at 12 to 15 months of age. Appropriate detailed studies
are needed to define the true incidence and prevalence of ASD. Epidemiologic
studies in Europe indicate no association between MMR vaccine and ASD. Some
children with ASD have gastrointestinal symptoms, but an increased rate of any
specific gastrointestinal disorder in children with ASD has not been established.
Studies to detect evidence of measles virus in intestinal tissue specimens from
patients with IBD or autism with gastrointestinal symptoms have not used uniform
techniques. Several laboratories have found no evidence of measles viruses in
tissue specimens from patients with IBD, but 2 groups have found evidence of
measles virus using different techniques. A group that found evidence of measles
virus in affected tissue specimens from patients with IBD has also reported
detecting portions of measles virus in peripheral blood lymphocytes and
intestinal tissue specimens from patients with autism and gastrointestinal
disorders. Finding a portion of a virus using molecular techniques does not
constitute evidence for a causal relationship, because some viruses persist in
unaffected hosts. Additional controlled studies in several laboratories are
needed to determine if portions of measles virus persist in intestinal and other
tissues of people with and without gastrointestinal disease and/or ASD.
CONCLUSIONS: Although the possible association with MMR vaccine has received much
public and political attention and there are many who have derived their own
conclusions based on personal experiences, the available evidence does not
support the hypothesis that MMR vaccine causes autism or associated disorders or
IBD. Separate administration of measles, mumps, and rubella vaccines to children
provides no benefit over administration of the combination MMR vaccine and would
result in delayed or missed immunizations. Pediatricians need to work with
families to ensure that children are protected early in the second year of life
from these preventable diseases. Continued scientific efforts need to be directed
to the identification of the causes of ASD.

PMID: 11331734 [PubMed - indexed for MEDLINE]


29. Lancet. 2001 Apr 28;357(9265):1341.

US expert group rejects link between MMR and autism.

Ashraf H.

PMID: 11343745 [PubMed - indexed for MEDLINE]


30. JAMA. 2001 Mar 7;285(9):1183-5.

Time trends in autism and in MMR immunization coverage in California.

Dales L, Hammer SJ, Smith NJ.

Immunization Branch, California Department of Health Services, 2151 Berkeley Way,
Room 712, Berkeley, CA 94704, USA. ldales@dhs.ca.gov

Comment in:
    JAMA. 2001 Jun 13;285(22):2852-3.

CONTEXT: Considerable concern has been generated in the lay and medical
communities by a theory that increased measles-mumps-rubella (MMR) immunization
among young children may be the cause of an apparent marked increase in autism
occurrence. OBJECTIVE: To determine if a correlation exists in secular trends of
MMR immunization coverage among young children and autism occurrence. DESIGN,
SETTING, AND PARTICIPANTS: Retrospective analyses of MMR immunization coverage
rates among children born in 1980-1994 who were enrolled in California
kindergartens (survey samples of 600-1900 children each year) and whose school
immunization records were reviewed to retrospectively determine the age at which
they first received MMR immunization; and of autism caseloads among children born
in these years who were diagnosed with autism and were enrolled in the California
Department of Developmental Services regional service center system. MAIN OUTCOME
MEASURES: Measles-mumps-rubella immunization coverage rates as of ages 17 months
and 24 months and numbers of Department of Developmental Services system
enrollees diagnosed with autism, grouped by year of birth. RESULTS: Essentially
no correlation was observed between the secular trend of early childhood MMR
immunization rates in California and the secular trend in numbers of children
with autism enrolled in California's regional service center system. For the
1980-1994 birth cohorts, a marked, sustained increase in autism case numbers was
noted, from 44 cases per 100 000 live births in the 1980 cohort to 208 cases per
100 000 live births in the 1994 cohort (a 373% relative increase), but changes in
early childhood MMR immunization coverage over the same time period were much
smaller and of shorter duration. Immunization coverage by the age of 24 months
increased from 72% to 82%, a relative increase of only 14%, over the same time
period. CONCLUSIONS: These data do not suggest an association between MMR
immunization among young children and an increase in autism occurrence.

PMID: 11231748 [PubMed - indexed for MEDLINE]


31. BMJ. 2001 Feb 24;322(7284):460-3.

Mumps, measles, and rubella vaccine and the incidence of autism recorded by
general practitioners: a time trend analysis.

Kaye JA, del Mar Melero-Montes M, Jick H.

Boston Collaborative Drug Surveillance Program, Boston University School of
Medicine, 11 Muzzey Street, Lexington, MA 02421, USA. jkaye@narsil.com

Comment in:
    Epidemiology. 2003 Sep;14(5):630-2.
    BMJ. 2001 Jul 21;323(7305):163; author reply 164.
    BMJ. 2001 Jul 21;323(7305):163; author reply 164.
    BMJ. 2001 Jul 21;323(7305):163-4.

OBJECTIVE: To estimate changes in the risk of autism and assess the relation of
autism to the mumps, measles, and rubella (MMR) vaccine. DESIGN: Time trend
analysis of data from the UK general practice research database (GPRD). SETTING:
General practices in the United Kingdom. SUBJECTS: Children aged 12 years or
younger diagnosed with autism 1988-99, with further analysis of boys aged 2 to 5
years born 1988-93. Main outcome measures: Annual and age specific incidence for
first recorded diagnoses of autism (that is, when the diagnosis of autism was
first recorded) in the children aged 12 years or younger; annual, birth cohort
specific risk of autism diagnosed in the 2 to 5 year old boys; coverage
(prevalence) of MMR vaccination in the same birth cohorts. RESULTS: The incidence
of newly diagnosed autism increased sevenfold, from 0.3 per 10 000 person years
in 1988 to 2.1 per 10 000 person years in 1999. The peak incidence was among 3
and 4 year olds, and 83% (254/305) of cases were boys. In an annual birth cohort
analysis of 114 boys born in 1988-93, the risk of autism in 2 to 5 year old boys
increased nearly fourfold over time, from 8 (95% confidence interval 4 to 14) per
10 000 for boys born in 1988 to 29 (20 to 43) per 10 000 for boys born in 1993.
For the same annual birth cohorts the prevalence of MMR vaccination was over 95%.
CONCLUSIONS: Because the incidence of autism among 2 to 5 year olds increased
markedly among boys born in each year separately from 1988 to 1993 while MMR
vaccine coverage was over 95% for successive annual birth cohorts, the data
provide evidence that no correlation exists between the prevalence of MMR
vaccination and the rapid increase in the risk of autism over time. The
explanation for the marked increase in risk of the diagnosis of autism in the
past decade remains uncertain.

PMCID: PMC26561
PMID: 11222420 [PubMed - indexed for MEDLINE]


32. J Pediatr. 2000 Jan;136(1):125-6.

Autism and measles, mumps, and rubella vaccine: No epidemiological evidence for a
causal association.

DeStefano F, Chen RT.

Vaccine Safety and Development Branch, National Immunization Program, Centers for
Disease Control and Prevention, Atlanta, GA 30333, USA.

PMID: 10681219 [PubMed - indexed for MEDLINE]


33. Lancet. 1999 Sep 11;354(9182):951.

MMR vaccination and autism.

Roberts GT.

Comment on:
    Lancet. 1999 Jun 12;353(9169):2026-9.

PMID: 10489979 [PubMed - indexed for MEDLINE]


34. Lancet. 1999 Sep 11;354(9182):949-50.

MMR vaccination and autism.

Wakefield AJ.

Comment on:
    Lancet. 1999 Jun 12;353(9169):2026-9.

PMID: 10489978 [PubMed - indexed for MEDLINE]


35. Lancet. 1999 Jun 12;353(9169):2026-9.

Autism and measles, mumps, and rubella vaccine: no epidemiological evidence for a
causal association.

Taylor B, Miller E, Farrington CP, Petropoulos MC, Favot-Mayaud I, Li J, Waight
PA.

Department of Community Child Health, Royal Free and University College Medical
School, University College London, UK.

Comment in:
    Lancet. 1999 Sep 11;354(9182):951.
    Lancet. 1999 Sep 11;354(9182):949-50.
    Lancet. 1999 Jun 12;353(9169):1987-8.
    Lancet. 2000 Jul 8;356(9224):160-1.
    Lancet. 2000 Jul 8;356(9224):161-2.
    Lancet. 2000 Jan 29;355(9201):409-10.

BACKGROUND: We undertook an epidemiological study to investigate whether measles,
mumps, and rubella (MMR) vaccine may be causally associated with autism. METHODS:
Children with autism born since 1979 were identified from special
needs/disability registers and special schools in eight North Thames health
districts, UK. Information from clinical records was linked to immunisation data
held on the child health computing system. We looked for evidence of a change in
trend in incidence or age at diagnosis associated with the introduction of MMR
vaccination to the UK in 1988. Clustering of onsets within defined
postvaccination periods was investigated by the case-series method. FINDINGS: We
identified 498 cases of autism (261 of core autism, 166 of atypical autism, and
71 of Asperger's syndrome). In 293 cases the diagnosis could be confirmed by the
criteria of the International Classification of Diseases, tenth revision (ICD10:
214 [82%] core autism, 52 [31%] atypical autism, 27 [38%] Asperger's syndrome).
There was a steady increase in cases by year of birth with no sudden "step-up" or
change in the trend line after the introduction of MMR vaccination. There was no
difference in age at diagnosis between the cases vaccinated before or after 18
months of age and those never vaccinated. There was no temporal association
between onset of autism within 1 or 2 years after vaccination with MMR (relative
incidence compared with control period 0.94 [95% CI 0.60-1.47] and 1.09
[0.79-1.52]). Developmental regression was not clustered in the months after
vaccination (relative incidence within 2 months and 4 months after MMR
vaccination 0.92 [0.38-2.21] and 1.00 [0.52-1.95]). No significant temporal
clustering for age at onset of parental concern was seen for cases of core autism
or atypical autism with the exception of a single interval within 6 months of MMR
vaccination. This appeared to be an artifact related to the difficulty of
defining precisely the onset of symptoms in this disorder. INTERPRETATION: Our
analyses do not support a causal association between MMR vaccine and autism. If
such an association occurs, it is so rare that it could not be identified in this
large regional sample.

PMID: 10376617 [PubMed - indexed for MEDLINE]


36. Lancet. 1999 Jun 12;353(9169):1987-8.

Negative association between MMR and autism.

DeStefano F, Chen RT.

Vaccine Safety and Development Branch, National Immunization Program, Centers for
Disease Control and Prevention, Atlanta, GA 30333, USA.

Comment on:
    Lancet. 1999 Jun 12;353(9169):2026-9.

PMID: 10376608 [PubMed - indexed for MEDLINE]


37. Lancet. 1998 May 2;351(9112):1358.

Autism, inflammatory bowel disease, and MMR vaccine.

Kiln MR.

Comment on:
    Lancet. 1998 Feb 28;351(9103):637-41.
    Lancet. 1998 Mar 21;351(9106):907; author reply 908-9.

PMID: 9643823 [PubMed - indexed for MEDLINE]


38. Lancet. 1998 May 2;351(9112):1357.

Autism, inflammatory bowel disease, and MMR vaccine.

Tettenborn MA.

Comment on:
    Lancet. 1998 Feb 28;351(9103):637-41.

PMID: 9643821 [PubMed - indexed for MEDLINE]


39. Lancet. 1998 May 2;351(9112):1357.

Autism, inflammatory bowel disease, and MMR vaccine.

Bhatt R.

Comment on:
    Lancet. 1998 Feb 28;351(9103):637-41.

PMID: 9643820 [PubMed - indexed for MEDLINE]


40. Lancet. 1998 May 2;351(9112):1356-7.

Autism, inflammatory bowel disease, and MMR vaccine.

Walker-Smith JA.

Comment on:
    Lancet. 1998 Mar 21;351(9106):905; author reply 908-9.
    Lancet. 1998 Mar 21;351(9106):906; author reply 908-9.
    Lancet. 1998 Mar 28;351(9107):955.
    Lancet. 1998 Mar 21;351(9106):906-7; author reply 908-9.
    Lancet. 1998 Mar 21;351(9106):905-6; author reply 908-9.
    Lancet. 1998 Mar 21;351(9106):907; author reply 908-9.
    Lancet. 1998 Mar 21;351(9106):907-8; author reply 908-9.
    Lancet. 1998 Mar 21;351(9106):907; author reply 908-9.

PMID: 9643819 [PubMed - indexed for MEDLINE]


41. Lancet. 1998 May 2;351(9112):1356.

Autism, inflammatory bowel disease, and MMR vaccine.

Rouse A.

Comment in:
    Lancet. 2004 Apr 17;363(9417):1327-8; discussion 1328.

Comment on:
    Lancet. 1998 Feb 28;351(9103):637-41.

PMID: 9643818 [PubMed - indexed for MEDLINE]


42. Lancet. 1998 May 2;351(9112):1355-6; author reply 1356.

Autism, inflammatory bowel disease, and MMR vaccine.

Richmond P, Goldblatt D.

Comment on:
    Lancet. 1998 Feb 28;351(9103):637-41.

PMID: 9643817 [PubMed - indexed for MEDLINE]


43. Lancet. 1998 May 2;351(9112):1355; author reply 1356.

Autism, inflammatory bowel disease, and MMR vaccine.

Sinclair L.

Comment on:
    Lancet. 1998 Feb 28;351(9103):637-41.

PMID: 9643816 [PubMed - indexed for MEDLINE]


44. Lancet. 1998 May 2;351(9112):1355; author reply 1356.

Autism, inflammatory bowel disease, and MMR vaccine.

Walker DR.

Comment on:
    Lancet. 1998 Feb 28;351(9103):637-41.
    Lancet. 1998 Mar 21;351(9106):905; author reply 908-9.

PMID: 9643815 [PubMed - indexed for MEDLINE]


45. BMJ. 1998 Jun 13;316(7147):1824.

MMR vaccination and autism 1998. There is no causal link between MMR vaccine and
autism.

Roberts R.

Comment on:
    BMJ. 1998 Mar 7;316(7133):715-6.

PMCID: PMC1113325
PMID: 9624080 [PubMed - indexed for MEDLINE]

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