Immunization uptake in younger siblings of children with autism spectrum disorder

Abstract

Background:

Parental concerns persist that immunization increases the risk of autism spectrum disorder, resulting in the potential for reduced uptake by parents of younger siblings of children with autism spectrum disorder (“younger sibs”).

Objective:

To compare immunization uptake by parents for their younger child relative to their older child with autism spectrum disorder (“proband”) and controls.

Design:

Immunization status was obtained for 98 “younger sibs,” 98 “probands,” and 65 controls.

Results:

A significant group difference emerged for overall immunization status (Fisher’s exact test = 62.70, p < .001). One or more immunizations in 59/98 younger sibs were delayed (47/98; 48%) or declined (12/98; 12.2%); immunizations were delayed in 16/98 probands (16.3%) and declined in only one. All controls were fully immunized, with only 6 (9.2%) delayed. Within the “younger sibs” group, 25/98 received an autism spectrum disorder diagnosis; 7 of whom (28%) were fully immunized. The rates of autism spectrum disorder diagnosis did not differ between immunized and nonimmunized younger sib groups, although small sample size limits interpretability of this result.

Conclusion:

Parents who already have one child with autism spectrum disorder may delay or decline immunization for their younger children, potentially placing them at increased risk of preventable infectious diseases.

Keywords

autism autism spectrum disorder diphtheria-pertussis-tetanus-polio immunization measles-mumps-rubella vaccine younger siblings

Introduction

Over the last three decades, the prevalence of the autism spectrum disorders (ASD) has risen, in large part, due to broadened case definition, improved awareness, and earlier recognition (Fombonne, 2007). Recent Centers for Disease Control and Prevention (CDC, 2012) reports have documented a prevalence rate of 1 in 88 children in the United States. Over the past decade, the combined measles, mumps, and rubella (MMR) vaccine, together with thimerosal, an ethylmercury-containing preservative in MMR, have been under scrutiny as potential causative factors in the development of ASD (Wakefield et al., 1998), despite compelling evidence to the contrary (Farrington et al., 2001; Madsen et al., 2002; Offit, 2007; Taylor et al., 1999). The uptake of the MMR vaccine has fallen dramatically in some countries (Asaria & MacMahon, 2006; McWha et al., 2004) thereby increasing the risk of vaccine-preventable diseases to vulnerable members of the population. The outbreaks of measles and mumps have occurred and continue to occur mainly in unvaccinated communities, in Europe, the United States, and Canada, with the most recent in Quebec, Canada, where over 200 cases of measles were identified in May 2011 (CDC, 2011; Roggendorf et al., 2010; Toronto Public Health, 2011).

Despite the lack of scientific evidence linking MMR vaccination or thimerosal to the risk of ASD (e.g. see Madsen et al., 2002), parental concerns about MMR vaccination clearly persist. Even the removal of thimerosal in 1999 does not seem to have allayed the fear of a possible causal link (Offit, 2007). A general population survey in 2001 (Dempsey et al., 2011) revealed that 7.9% of the total sample (i.e. over half of the 13% who used a revised immunization schedule) reported having used a revised schedule because it “seemed safer.” The rates of parental concern are considerably higher in families with a child with ASD. Indeed, in a 2006 survey, just over half of the parents of children with ASD believed that immunizations were the cause of their child’s autism (Harrington et al., 2006). More recently, a large-scale survey from the Interactive Autism Network (IAN) registry, a voluntary, Internet-based research registry, revealed that close to 20% of almost 500 respondents had delayed or declined MMR immunization for younger siblings of children with ASD who were born after the older sibling exhibited developmental differences (Rosenberg et al., 2012). In this survey, the likelihood of delaying/declining immunization was highly associated with the parental belief that their older child’s immunization “definitely played a role in [their] child’s ASD.” These findings point to the ongoing parental concern about the vaccine-autism link and suggest that these beliefs are influencing parents’ decisions about immunizing their children. One outstanding question from the Rosenberg et al.’s survey is whether this same set of parents had delayed/declined immunization for their older child with ASD. Without this information, it may be difficult to draw conclusions about the motivation for delaying/declining immunization for the younger child.

The primary objective of this article is to examine the immunization uptake of parents from a longitudinal study of the younger siblings of children with ASD, expanding upon our preliminary report from this sample (Kuwaik et al., 2008). This was accomplished by comparing the immunization rates for the younger siblings relative to their older siblings with ASD and controls. Siblings of children with ASD are known to be at increased risk of ASD compared to the general population (Ozonoff et al., 2011), and this group of parents may be particularly sensitized to mixed messages about vaccine safety in the media and within the advocacy community (Nagaraj, 2006). We therefore hypothesized that relative to controls, parents of a child with ASD would be more likely to delay or abstain from immunizing subsequent children. Our secondary objective was to examine, on an exploratory basis, the rates of ASD in the immunized versus nonimmunization groups/delayed immunization groups in the younger siblings of children with ASD. Despite considerable evidence of a lack of association in population-based studies, it remained possible that the siblings of children with ASD may represent a unique group given their increased genetic risk of ASD. Thus, we examined the rates of ASD in the younger siblings in relation to their immunization status.

Methods

Participants

Parents were recruited as part of a prospective study of early development in ASD, which takes place in three academic urban health science centers in Canada providing tertiary-level care to a mixed sample of rural and urban dwellers (0–18 years): McMaster Children’s Hospital in Hamilton, Ontario; The Hospital for Sick Children in Toronto, Ontario; and the IWK Health Centre in Halifax, Nova Scotia (Zwaigenbaum et al., 2005). Parents in the larger study were referred by community physicians, other clinicians working with families of children with ASD or were self-referred. Parents joined the study prior to their younger child’s first birthday. The study was approved by the Research Ethics Boards at the three participating centers, and parents who were invited to participate gave a written informed consent for their children to enroll in this study. The sample consisted of parents of 261 children (176 boys and 85 girls); of whom 98 were the younger siblings of children with ASD (hereafter, “younger sibs”), 98 were their older siblings with ASD (probands), and 65 were “low-risk” controls (with no family history of ASD). Control babies were roughly group matched to the younger sib group based on age and sex, and only the younger of any sibling pairs in the control group were included in the current analyses. Most participants were recruited when their younger children were 6 months (91/98 younger sibs and 59/65 controls), the remainder enrolled when their children were 12 months; all have been followed up to at least the age of 3 years. The recruitment of controls was from various sources in the community.

The diagnosis of ASD in the proband had been made by a developmental specialist and/or multidisciplinary team at our respective centers or in the community using Diagnostic and Statistical Manual of Mental Disorders (4th ed., text rev.; DSM-IV-TR) criteria and in most cases confirmed by research staff using the Autism Diagnostic Interview–Revised (ADI-R) (Lord et al., 1994) and Autism Diagnostic Observation Schedule (ADOS; Lord et al., 2000; confirmation using ADOS and ADI-R is still pending in some probands given resource constraints). Control children had no known first-, second-, or third-degree relatives with an ASD diagnosis. All participants were born at 37–42 weeks’ gestation, had a birth weight greater than 2500 g, and had no identified genetic or neurological conditions. Data were collected regarding immunization up to the age of 36 months for all the children. This strategy allowed for more easily interpretable comparisons between probands and controls since the focus was on vaccines routinely given by the age of 18 months, generally prior to the ASD diagnosis. Socioeconomic status (SES) was measured (available in only 77% of the sample; data are missing in the remaining 23%) using the system developed by Hollingshead (1975) in which information about parents’ marital status, current occupation, and education level generates an estimated income level and social stratum. In families with more than one child born after the proband, we included only the first sibling to be followed up through our study, to ensure the independence of the data.

Study design and procedures

The present study was a longitudinal, mixed (between- and within-groups) design. Parents were asked for the immunization records of their children; none refused. Data were collected regarding diphtheria, pertussis, tetanus, and polio (DPTP) and MMR immunizations between 2005 and 2009, and corresponded to immunization records for the enrolled babies from 1999 to 2009 and for the probands from 1993 to 2006.

We chose to focus on the DPTP and MMR immunization data for two reasons. First, these represented the most commonly administered vaccines until Canada’s 2005 expansion of the publicly funded immunization program (Infectious Diseases and Immunization Committee, Canadian Pediatric Society, 2005). Second, there is a particular controversy surrounding MMR immunization as a potential risk factor for ASD, although there is also concern surrounding the DPTP vaccine due to the perception that it contains thimerosal, even though it has not since 1992 in Canada (Doja & Roberts, 2006). The DPTP is typically administered at 2, 4, and 6 months, with two booster doses at 18 months and 4–6 years of age, whereas the MMR is administered at 12 and 18 months (Public Health Agency of Canada, 2006a). However, the 18-month MMR was not included in our data collection, as this second dose was introduced in Canada in 1997 and thus does not apply to children born earlier (i.e. some of the probands). In addition, the recommended timing of the MMR, which can be administered either at 18 months or at 4–6 years, differs depending on the year of birth and the province/territory of residence (Infectious Diseases and Immunization Committee, Canadian Pediatric Society, 2005; Public Health Agency of Canada, 2007).

Immunization status was divided into three predefined categories: (a) Fully immunized: Children with four doses of DPTP (2, 4, 6, and 18 months) and the initial MMR dose at 12 months, (b) Partial/delayed immunizations: Children with any missing dose of DPTP or MMR at any age or a delay of 3 months or more for at least one of the doses of DPTP or MMR, and (c) Not immunized/declined: Children for whom all immunizations had been withheld as of 3 years of age.

Analysis

Group differences in SES were explored using a one-way analysis of variance (ANOVA). The primary analyses of interest were conducted using chi-square (χ²) to examine group differences among the younger sibs, probands, and low-risk controls in overall immunization status and then for MMR and DPTP separately. In order to compare groups more directly, planned chi-square analyses were conducted to compare the immunization status between the younger siblings and the proband within the same family, as well as both groups versus controls. Where chi-square analyses yielded expected cell counts < 5, Fisher’s exact tests were used. In an exploratory analysis, the Fisher’s exact test was used to analyze the relation between immunization status and the diagnoses of ASD within the younger sibling group.

Results

Demographic information

SES and ethnicity

A one-way ANOVA was used to examine group differences in SES (as described earlier). Mean SES did not differ across groups (F_1,131 = .77, p = .38; mean = 52.10 vs 53.77 for families with ASD vs controls, both of which are in the social stratum described as “medium business, minor professional, technical”; Hollingshead, 1975). The majority of parents were Caucasian (76%) with 24% of the sample describing themselves as First Nations, Hispanic, Black, Asian, or mixed ethnicities.

Parent age

The ANOVA was used to examine group differences in parental age at child’s birth (for the younger sibs and controls only), revealing significant group differences for both paternal age (mean = 37.38 vs 34.29 years, respectively; F_{1, 139} = 9.23, p = .003) and maternal age (mean = 34.93 vs 32.81 years, respectively; F_{1, 138} = 9.06, p = .003). Of note, however, parental age did not differ across groups based on immunization status for MMR, DPTP, or “both” (ps range = .30–.64 for paternal age; .23–.75 for maternal age).

Birth order of controls

Among the controls, 65.5% were firstborn (vs 100% of the younger sibs being later-born children by definition). To explore the possibility that birth order may have influenced immunization decisions in the controls, we conducted three Fisher’s exact tests for MMR, DPTP, and both, in which all yielded nonsignificant results (ps = .14, .66, and .66, respectively).

Information source

Parents of 22.2% (58/261) of the children provided a copy of their child’s immunization record or had it sent by their doctor; for the remaining 77.8%, status report was based on parent recall (note that this information was typically gathered at each visit, at 3- to 6-month intervals, to avoid recall bias). Due to the potential for recall bias (e.g. see Dorell et al., 2011, for bias in recall for the older children), we examined the influence of information source (card copy vs parent recall) on immunization status. No significant relationship was found for MMR (Fisher’s exact test = .38, p = .84), DPTP (Fisher’s exact test = 1.71, p = .44), or “both” (Fisher’s exact test = 1.58, p = .48).

Immunization uptake

Overall immunization uptake (MMR or DPTP)

Overall immunization status (fully immunized, delayed, or declined) was calculated based on either MMR or DPTP status, with a significant group difference emerging (Fisher’s exact test = 62.70, p < .001). At least one of the recommended immunizations (MMR or DPTP) in 59 of the 98 (60.2%) younger sibs had been delayed (47/98; 48%) or declined (i.e. not received; 12/98; 12.2%). In contrast, one or more immunizations was delayed in only 16 of 98 probands (16.3%) and declined in only one proband (1%). All 65 controls were fully immunized, of whom only 6 (9.2%) had received delayed immunization. Moreover, the younger sibs were less likely to be fully immunized and without delay than probands with ASD in the same families (χ² = 39.26, p < .001). Among the younger sibs with delayed immunization, 76% of their older siblings diagnosed with ASD had been fully immunized on time. See Figure 1 for rates of on-time immunization uptake for MMR, DPTP, and total immunization for each group.

Figure 1.

On-time uptake rate (%) for MMR, DPTP, and total immunizations in the younger sibs, probands, and controls.

MMR immunization uptake

The analysis revealed a significant group difference in MMR immunization status (Fisher’s exact test = 80.82, p < .001). Bearing in mind that the Public Health Agency of Canada recommends that children receive their initial MMR vaccine at 12 months (in contrast to the United States, where it is recommended at 12–15 months; Public Health Agency of Canada, 2006a; CDC, 2011), only 42 of the 98 (43%) younger sibs received the 12-month MMR vaccine on time (i.e. by at least 15 months of age; see Figure 2); an additional 38 (39%) received the vaccine after 15 months of age, and 18 (18%) had not been immunized against MMR by the age of 3 years. In contrast, 88 of 98 (90%) probands received the MMR by 15 months, 9 (9.2%) were delayed, and only 1 had not been immunized by the age of 3 years. Similarly, 63 of 65 (97%) controls had completed their MMR immunization on time (i.e. only two were delayed, and none had parents who had fully declined).

Figure 2.

Uptake of MMR immunization for the younger sibs versus probands versus controls.

DPTP immunization uptake

A significant group difference was also found for DPTP immunization status (Fisher’s exact test = 38.95, p < .001), with just over half (55.1%) of the younger sibs having been immunized on time (31.6% were delayed, and 13.3% were not immunized by the age of 3 years; see Figure 3). The rates of DPTP uptake were higher for probands (86.7% immunized on time, 12.2% delayed, and 1% not immunized) and controls (90.8% immunized on time, 9.2% delayed, and none declined).

Figure 3.

Uptake of DPTP immunization for the younger sibs versus probands versus controls.

Within-family analyses and direct comparisons with controls

A planned chi-square analysis was conducted to compare immunization status between the younger sibs and the probands (i.e. their own siblings with ASD), for each type of immunization. Group differences remained significant for both MMR (χ² (2) = 49.38) and DPTP (χ² (2) = 25.60), both ps < .001. Post hoc analyses compared each group to the controls as follows: (1) younger sibs versus controls: group effects remained significant for both MMR (χ² (2) = 49.97) and DPTP (χ² (2) = 24.43), both ps < .001; and (2) probands versus controls: no group differences were identified for MMR (Fisher’s exact test = 2.85, p = .20) or DPTP uptake (Fisher’s exact test = .94, p = .77).

Relationship between immunization uptake and diagnosis

Of the 39 younger sibs who had completed their immunizations on time, 6 (15.7%) were diagnosed with ASD and 2 with speech-language delay (SLD). Of the 47 younger sibs for whom immunization was delayed, 15 (31.2%) received an ASD diagnosis and 2 had SLD. Of the 12 younger sibs who had not received any immunizations, 4 (33.3%) were diagnosed with ASD and 1 with SLD. Note that of those children who did not receive a diagnosis, 43.8% were fully immunized. The Fisher’s exact tests revealed no significant difference in the rates of diagnoses between immunized and nonimmunized groups for MMR (Fisher’s exact test = 5.46, p = .22), DPTP (Fisher’s exact test = 3.65, p = .44), or both (Fisher’s exact test = 4.13, p = .37), although small sample size renders these comparisons exploratory only.

Interpretation

In our study, parents of the younger siblings of children with ASD have withheld or delayed having their younger child immunized, resulting in significantly lower immunization rates in these later-born children than in either their older sibling with ASD (probands) or comparison children from the same age cohort. Compared to our preliminary findings from a smaller sample from the same study (previously published in a “letter to the editor”; Kuwaik et al., 2008), the data presented in this report are drawn from a larger sample and involved 1:1 matching of probands to their younger siblings to allow us to explore within-family immunization uptake. To our knowledge, this is the first Canadian report of reduced immunization uptake by parents of children with ASD, for their younger child, and is the first report to compare directly parents’ uptake with their younger child to that for their older child with ASD. Our findings have important implications for reduced herd immunity and increased vulnerability to vaccine-preventable illness in this high-risk group.

Several factors may contribute to reduced immunization uptake in these children, relative to the comparison groups. First, parental concerns about vaccines clearly still exist in the general population (Dempsey et al., 2011; Glanz et al., 2009; Gust et al., 2008), and these may be even more prevalent among families who already have a child with ASD (Harrington et al., 2006; Rosenberg et al., 2012). These families may be more likely to perceive that the risks of immunization outweigh the benefits. This may be particularly true in the current cohort of parents who have not witnessed the serious impacts of vaccine-preventable diseases such as measles. Parents may also feel that since most of the population is immunized, the likelihood of exposure to these infections is slim. Nevertheless, declining immunization coverage in the general population will diminish the herd immunity effect (Asaria & MacMahon, 2006; Glanz et al., 2009), further increasing the vulnerability of nonimmunized children to a serious infection. The first reported measles death in the United Kingdom since 1992, when the controversy entered press headlines, occurred as a natural consequence of the dropping immunization rate and has alerted the public to the magnitude and the potential consequences of mass refusal and reduced immunization uptake (Asaria and MacMahon, 2006). Unfortunately, if an epidemic does occur, those at greatest risk would include children who are not immunized.

In the face of spurious claims of a vaccine-autism link, many parents of children with ASD report believing that they may have contributed to their older child’s disorder by deciding to immunize them (Harrington et al., 2006; Hilton et al., 2007). The decision to immunize the second child may then be particularly difficult, and parents may have delayed the immunization of their subsequent children in the hope of protecting their infants during a critical period and perhaps decreasing the risk of developing ASD. This is consistent with the strong relationship between delaying/declining MMR and parental belief that immunization caused their older child’s ASD reported recently (Rosenberg et al., 2012). The lack of difference between the immunization status of probands and controls in our study argues against the possibility of a general bias on the part of parents of children with ASD (i.e. prior to their first child’s diagnosis) toward nonimmunization. Moreover, the immunization rate in the younger siblings who did not receive an ASD diagnosis argues against the protective effort of declining or delaying these immunizations. However, this preliminary finding is limited by a small sample size, and this conclusion would be best supported by the population studies (e.g. Madsen et al., 2002). Although parents in the present study were not explicitly asked the reasons for delayed/declined immunizations, some shared anecdotally that their primary care physicians had supported delayed immunization, possibly reinforcing their own underlying concerns. While it would be unfair to assume that this happened in the majority of cases, it does highlight the potential role for primary care providers in helping parents make decisions about immunization. In a general population survey of almost 4000 parents (Gust et al., 2008), 28.3% reported some level of doubt about the safety of immunizations. In cases in which parents changed their minds and immunized their child despite concerns, close to half reported that they had done so because their health-care provider had assured them about safety.

Possibly supporting their own fears, parents may also be unduly swayed by the strong antivaccine messages portrayed by the popular media and highly visible celebrity campaigns and may consequently mistrust health professionals and/or public health officials when they attempt to refute these claims. Around the time when many of the younger sibs and controls were due for their immunizations, media attention was focused on the Poling et al.’s (2006) case, a 19-month-old girl who was reported to have developed typically until she received the set of five immunizations recommended in the United States. Subsequently, she regressed developmentally and later was diagnosed with ASD. Further investigation revealed a presumably preexisting mitochondrial dysfunction, associated with predisposition to developmental regression, and the family was compensated through the National Vaccine Injury Compensation Program in 2008. Although such a presentation is rare (Oliveira et al., 2005), parents of a child with ASD, upon hearing about this case, may question whether their younger child also has a predisposition for a mitochondrial disorder and may be unwilling to expose their child to the perceived risk of vaccinations. Trusted primary care providers may be able to help alleviate some of these fears and have been shown to affect parents’ decision to immunize (e.g. see Gust et al., 2008; also see Taylor et al., 1997; 2002).

Limitations

The participants were recruited from a longitudinal study of the younger siblings of children with ASD. The recruitment was from three major ASD centers across Canada with mixed urban and rural coverage and diverse ethnic and socioeconomic representation. No effort was made to include specific groups as ethnicity was voluntarily documented. Our sample was primarily Caucasian, thus limiting the generalizability of our findings to other ethno-cultural groups. Our sample was also of relatively high SES, although SES did not differ across the parent groups, reducing the likelihood that it accounts for observed differences in immunization uptake. We also acknowledge that relying on parent recall for some families (vs viewing the immunization record) may have presented a bias. However, this was explored by comparing uptake rates based on the information source, which yielded no significant association, thus mitigating the possibility that recall bias influenced parent reports. It also remains possible that our sample was not representative of all parents. Parents of children with ASD who participated in our study may perhaps have been more anxious about their younger child’s development or more sensitized to the increased risk of ASD than other families of children with ASD. These parents may also be particularly likely to delay or avoid immunizing their younger children. Given our small sample size, we recognize that power was insufficient to detect modest differences in diagnostic outcome rates based on immunization status. Moreover, parents in our sample may not represent the Canadian population, given our higher immunization rates for controls and probands than the 73%–93% cited in the Public Health Agency of Canada (2006b). However, given that both parent groups (i.e. of children with ASD and younger sibs vs controls) had higher immunization uptake than the general population, our comparisons, perhaps most importantly, within the ASD families, remain valid. Finally, parental age at the birth of the (younger) child also differed across groups, presenting a possible bias. However, examination of children’s immunization status by parental age failed to yield a significant association (for either mothers or fathers), reducing the likelihood that age differences contributed to the differences in immunization uptake across groups.

Conclusions and future directions

Parents of children with ASD in our sample have delayed and/or reduced the overall immunization rates in their younger children, compared to the general population and to their older children with ASD. This potentially places the younger siblings at increased risk of serious and preventable infectious diseases (e.g. see Glanz et al., 2009). Parents, educators, and medical professionals need to be aware of this vulnerability in order to protect these children and others in case of the outbreaks. Parents who refuse or delay immunization contribute to the lowering of the herd immunity threshold and may unwittingly be placing both their own and other children at risk (Glanz et al., 2009). There is a lack of systematic national surveillance data on childhood immunizations in the general population in Canada (Kondro, 2007), and the few available estimates may suggest a coverage that is lower than the Health Canada target of at least 97%, with reports of 73%–89% uptake for DPTP and 93.2% for MMR by 2 years of age (Public Health Agency of Canada, 2006b). Thus, educating families and childcare providers about early signs and symptoms of infectious diseases may help to reduce the spread of these illnesses in the community (Kondro, 2007). Despite ongoing efforts aimed at unraveling genetic links in ASD, the etiology remains unknown for most cases. Until there are clear answers regarding causes, some parents may need additional counseling regarding the lack of association between ASD and immunization.

Careful and timely counseling from community physicians and other primary care providers may be needed to encourage informed discussions about vaccination, particularly for these vulnerable parents who are already concerned about ASD recurrence (Gust et al., 2008). Despite the recent retraction of the original article by Wakefield (Editors of the Lancet 2010), which first claimed an MMR-ASD link, repercussions of this and other claims continue to affect the attitudes and behaviors of the lay public with respect to immunization uptake. It will be interesting to monitor the changes in parental perspectives and immunization decisions especially after the withdrawal and subsequent discrediting (Deer, 2011) of the Wakefield’s article. Increased emphasis on communication and counseling skills in medical training and continuing education clearly need to be prioritized. Family physicians and pediatricians may refer to professional bodies for up-to-date, family friendly information on vaccination safety (e.g. the National Advisory Committee on Immunization in Canada and the CDC in the United States; Canadian Paediatric Society, 2008). We would argue that it is also important that physicians continue to support and educate parents regardless of their initial decisions about whether or when to immunize their children (Gust et al., 2008; Halperin et al., 2007). Discontinuing medical care for these children who are already at risk not only eliminates the possibility of subsequent counseling but also may further fuel parents’ mistrust of the health-care system. Ultimately, there is a need for further development and evaluation of educational strategies aimed at helping parents make informed decisions regarding immunization of their children.

Footnotes

Declaration of conflicting interests

The authors declare that there is no conflict of interest.

Funding

This research was funded by the Canadian Institutes of Health Research and Autism Speaks.

References

Asaria

MacMahon

(2006) Measles in the United Kingdom: can we eradicate it by 2010? British Medical Journal 333: 890–895.

Canadian Paediatric Society (2008) MMR vaccine: myths and facts. Available at: http://www.caringforkids.cps.ca/resources/Copyright.htm (accessed 24 May 2012).

Centers for Disease Control and Prevention (CDC) (2011) Measles, United States, January–May 20, 2011. Morbidity and Mortality Weekly Report 60(20): 666–668. Available at: www.cdc.gov/mmwr/preview/mmwrhtml/mm6020a7.htm

Centers for Disease Control and Prevention (2012, March 30) Prevalence of Austism Spectrum disorders - Autism and Developmental Disabilities monitoring network, 14 Sites, United States, 2008. Morbidity and Mortality Weekly Report 61(3): 1-19. Available at: www.cdc.gov/mmwr/preview/mmwrhtml/ss6103al.htm.

Deer

(2011, Jan 8) Secrets of the MMR scare: the Lancet’s two days to bury bad news. British Medical Journal 342: 77–84.

Dempsey

Schaffer

Sinder

. (2011) Alternative vaccination schedule preferences among parents of young children. Pediatrics 128(5): 848–856.

Doja

Roberts

(2006) Immunizations and autism: a review of the literature. Canadian Journal of Neurological Sciences 33: 341–346.

Dorell

Jain

Yankey

(2011) Validity of parent-reported vaccination status for adolescents aged 13-17 years: National Immunization Survey-Teen, 2008. Communicable Disease and Public Health 5(4): 305–310.

Editors of the Lancet (2010, Feb) Retraction: ileal lymphiod nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in Children. Lancet 373:445.

10.

Farrington

Miller

Taylor

(2001) MMR and autism: further evidence against a causal association. Vaccine 19(27): 3632–3635.

11.

Fombonne

(2007) Epidemiological surveys of pervasive developmental disorders. In: Volkmar

(ed.) Autism and Pervasive Developmental Disorders. 2nd ed. New York: Cambridge University Press, pp. 33–68.

12.

Glanz

McClure

Magid

. (2009) Parental refusal of pertussis vaccination is associated with an increases risk of pertussis infection in children. Pediatrics 123(6): 1446–1451.

13.

Gust

Darling

Kennedy

. (2008) Parents with doubts about vaccines: which vaccines and reasons why. Pediatrics 122(4): 718–725.

14.

Halperin

Melnychuk

Downie

. (2007) When is it permissible to dismiss a family who refuses vaccines? Paediatrics & Child Health 12(3): 843–845.

15.

Harrington

Rosen

Garnecho

. (2006) Parental perceptions and use of complementary and alternative medicine practices for children with autism spectrum disorders in private practice. Journal of Developmental and Behavioral Pediatrics 27(2): 156–161.

16.

Hilton

Hunt

Petticrew

(2007) MMR marginalized, misrepresented and rejected? Autism: a focus group study. Archives of Disease in Childhood 92: 322–332.

17.

Hollingshead

(1975) A four-factor index of social status. Unpublished working paper, Department of Sociology, Yale University, New Haven, CT.

18.

Infectious Diseases and Immunization Committee Canadian Paediatric Society (2005) Immunization update 2005. Paediatrics & Child Health 10(6): 315–316.

19.

Kondro

(2007) Progress report on the National Immunization Strategy. Canadian Medical Association Journal 176: 1811–1813.

20.

Kuwaik

Roberts

Brian

. (2008) Immunization uptake in siblings of children with Autism. Pediatrics 122: 684–685.

21.

Lord

Risi

Lambrecht

. (2000) The autism diagnostic observation schedule-generic: a standard measure of social and communicative deficits associated with the spectrum of autism. Journal of Autism and Developmental Disorders 30: 205–223.

22.

Lord

Rutter

Le Couteur

(1994) Autism diagnostic interview–revised: a revised version of a diagnostic interview for caregivers of individuals with possible pervasive developmental disorders. Journal of Autism and Developmental Disorders 24: 659–685.

23.

McWha

MacArthur

Badiani

. (2004) Measuring up: results from the National Immunization Coverage Survey 2002. Canada Communicable Disease Report 30: 37–50.

24.

Madsen

Hviid

Vestergaard

. (2002) A population-based study of measles, mumps, and rubella vaccination and autism. New England Journal of Medicine 347(19): 1477–1482.

25.

Nagaraj

(2006) Does qualitative synthesis of anecdotal evidence with that from scientific research help in understanding public health issues: a review of low MMR uptake. European Journal of Public Health 16: 85–88.

26.

Offit

(2007) Thimerosal and vaccines—a cautionary tale. New England Journal of Medicine 357(13): 1278–1279.

27.

Oliveira

Diogo

Grazina

. (2005) Mitochondrial dysfunction in autism spectrum disorders: a population-based study. Developmental Medicine and Child Neurology 47(3): 185–189.

28.

Ozonoff

Young

Carter

. (2011) Recurrence risk for autism spectrum disorders: a baby siblings research consortium study. Pediatrics 10(1542): 2010–2825.

29.

Poling

Frye

Shoffne

. (2006) Developmental regression and mitochondrial dysfunction in a child with autism. Journal of Child Neurology 21(2): 170–172.

30.

Public Health Agency of Canada (2006a) Canadian Immunization Guide. 7th ed. Federal Publications Inc.

31.

Public Health Agency of Canada (2006b, Nov) Canadian Communicable Disease Report - Supplement: National Report on Immunization, 2006 32S3.

32.

Public Health Agency of Canada (2007) Mumps in Canada. Available at: http://www.phac-aspc.gc.ca/mumps-oreillons/prof-eng.php (accessed 24 May 2012).

33.

Roggendorf

Mankertz

Kundt

(2010) Spotlight on measles 2010: measles outbreak in a mainly unvaccinated community in Essen, Germany. Euro Surveillance 15(26): 19605.

34.

Rosenberg

Law

Anderson

. (2012) Survey of vaccination beliefs and practices among families affected by autism spectrum disorders. Clinical Pediatrics (published online 2 March 2012). Available at: http://cpj.sagepub.com/content/early/2012/02/22/0009922812438435.citation

35.

Taylor

Miller

Farrington

. (1999) Autism and measles, mumps, and rubella vaccine: no epidemiological evidence for a causal association. Lancet 353(9169): 2026–2069.

36.

Taylor

Darden

Brooks

. (2002) Practitioner policies and beliefs and practice immunization rates: a study from pediatric research office settings and the national medical association. Pediatrics 109(2): 293–300.

37.

Taylor

Darden

Slora

. (1997) The influence of provider behavior, parental characteristics, and a public policy initiative on the immunization status of children followed by private pediatricians: a study from pediatric research in office settings. Pediatrics 99(2): 209–215.

38.

Toronto Public Health. Communicable Disease Surveillance Update 2011. Available at: http://www.toronto.ca/health/cdc/communicable_disease_surveillance/monitoring/index.htm (accessed 8 June 2011); http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6020a7.htm (accessed 8 June 2011).

39.

Wakefield

Murch

Anthony

. (1998) Ileal-lymphoid-nodular hyperplasia, nonspecific colitis, and pervasive developmental disorder in children. Lancet 351: 637–641.

40.

Zwaigenbaum

Bryson

Rogers

. (2005) Behavioral manifestations of autism in the first year of life. International Journal of Developmental Neuroscience 23(2): 143–152.