Adverse Outcomes Associated with Postpartum Rubella or MMR Vaccine ---F. Edward Yazbak, MD, FAAP and Kathy L. Lang-Radosh, MS

Adverse Outcomes Associated with Postpartum Rubella or MMR Vaccine
F. Edward Yazbak, MD, FAAP and Kathy L. Lang-Radosh, MS

ABSTRACT

We identified 60 rubella-susceptible mothers who were revaccinated in the postpartum period with either the measles-mumps-rubella (MMR) or the monovalent rubella vaccine and whose children later received MMR vaccine. Forty-five of these women have children diagnosed with autistic spectrum disorder (ASD); another ten women have children with autistic symptoms, ADD/ADHD or other developmental delays; and four women have children with other health problems, mostly immunologic. These outcomes raise concerns about the practice of postpartum vaccination and suggest that an immune mechanism may increase children's susceptibility to ASD.

Background

Although parents continue to report that their previously typical children begin to display symptoms of autism and lose previously acquired skills after receiving routine childhood immunizations (particularly the MMR vaccine), the medical community has tended to discount the possibility of a link between autism and vaccination. Most medical researchers, in fact, completely dismiss such "anecdotal evidence" as scientifically invalid. While it is true that parents have only the observations of their own children to rely on, there can be no closer monitoring of a child than that done by its own parent. To ignore the information provided by parents of autistic children as desperate conclusions drawn by grieving individuals is pretentious and overlooks potentially valuable data.

Women are routinely tested for rubella immunity before marriage, and those susceptible are promptly vaccinated if they are not pregnant. The Center for Disease Control and Prevention (CDC) recommends that women be tested again at the time of their first obstetrical visit, and that those found to lack rubella immunity be vaccinated in the postpartum period. The vaccine manufacturer states that it has been found "convenient" to vaccinate women in the postpartum period, but adds that "caution should be exercised." The monovalent rubella vaccine was used exclusively in the past. Lately, the MMR vaccine, on the recommendation of the CDC, has largely replaced it.

The intent of this study was to examine what effect the mothers' revaccination during the postpartum period may have had on their children.

Methods

The questionnaire reproduced in Appendix A was distributed by e-mail and newsletter to parent groups in the United Kingdom, Australia, and the United States and posted on several web sites. The study was also mentioned in a popular book on autism(1) and in publications by the Autism Research Institute and the Autism Autoimmunity Project. A total of 440 questionnaires had been received by the time of this analysis. Each entry was assigned a number, and an immediate effort was made to contact the mother to notify her of her study number and to complete any missing information. Questionnaires were excluded if they were incomplete and contact information was not supplied: about 70 questionnaires had to be discarded for this reason. Of the remaining 370 respondents, sixty had received MMR or rubella vaccine in the postpartum period and were included in this study. All questionnaires are available for review, and the data from the 60 subjects of this report are available in digital format.

Selected Case Presentations

1. Although this patient, a psychologist, born in 1958, had measles and rubella as a child, she was found to be rubella-susceptible when she was pregnant in 1984, 1986, 1992, and 1998. She received no vaccines following the first three pregnancies. Her two older children (a boy, age 16, and a girl, age 13) are healthy. A third infant died at age 2 days from prematurity-related complications. After her fourth pregnancy, the mother received MMR vaccine in the immediate postpartum period. The baby was breast-fed beyond 18 months of age. In the first year of life, he was severely constipated and had three "viral illnesses with generalized exanthems." He was immunized on the recommended schedule and received his first MMR at the age of 12 months. Prior to this time, the boy had appropriate speech and above-average cognitive abilities, but he stopped progressing after his first birthday and then went on to lose previously acquired skills. A developmental evaluation done at a chronological age of 20 months revealed an approximate developmental age of 11-13 months (language, motor and cognitive). Autistic symptoms are now apparent and a diagnosis of autism is forthcoming. The mother developed severe arthritis of her knees, ankles, and hips following her own vaccination.

2. Though she was vaccinated as a child, this patient, who was born in 1957 and is afflicted with scleroderma, failed to develop protective rubella titers. In 1997, she delivered her first child, a son, and was given an MMR booster postpartum. She became febrile and developed a rash but had no joint symptoms. The boy, who was born at full term and was breast-fed, appeared bright, verbal, and sociable during the first year of life. At the age of 15 months, he received his first MMR. He reacted promptly with fever, irritability, and loose stools. Shortly thereafter, he lost previously acquired speech and withdrew from social contact. He currently has persistent diarrhea, sleep difficulties, and extensive eczema. He has been diagnosed with ASD.

3. This mother, who had received all recommended immunizations, delivered her first child, a girl, in 1984 and received rubella vaccine postpartum because she had remained rubella-susceptible. The baby was not breast-fed and is normal. After 3 miscarriages, the patient delivered a boy in September 1987, and received another postpartum rubella vaccine because she still had no detectable rubella immunity. The boy was breast-fed for 4 months and developed normally at first. At the age of 29 months, he received his first MMR vaccine. He lost all language by the age of 36 months and has now been diagnosed with autism. While breastfeeding her third child, a girl, the mother received her third rubella booster in four years, as she was still rubella-susceptible. The child has severe dyslexia, serious learning disabilities, and ADHD.

4. This mother's first pregnancy resulted in a daughter who is now 22 years old, in good health and attending college. Her second child, a boy, died at the age of three months; the cause of death was listed as Sudden Infant Death Syndrome (SIDS). After the birth of the third child, a boy, in 1979, she was told that she had no immunity to rubella and was given MMR vaccine. The child was breast-fed for six months and at first developed normally. He received his MMR vaccine at age 15 months. By age 18 months, he developed chronic diarrhea, stopped talking, and became withdrawn. He has been diagnosed with autism, after an extensive work-up that was otherwise negative, including normal chromosomal studies. Of the mother's subsequent children, one girl and four boys were afflicted with learning disabilities, mental retardation, or pervasive developmental disorder (PDD); one also had Tourette syndrome. The last child, who was premature, had hypoplastic left heart syndrome and a single kidney. She only lived two days. Family history was negative for autism, and the mother had normal chromosomal studies.

5. Despite being vaccinated routinely, this mother, born in 1964, still developed all three diseases: measles, rubella, and mumps. Because of a diagnosis of "some immune problem," she received injections of gamma globulin for a while. In 1983, she received an MMR vaccine because of an outbreak of measles at college. In 1991, 1992, and 1997, she was found to be immune to measles. She was also immune to rubella in 1991, when she was pregnant with her first boy, who is in good health. During her second pregnancy, in 1992, she was found to be rubella-susceptible. After she delivered, she was given yet another MMR "that same day against my will." This boy, who was breast-fed, apparently assumed a fetal position on the 4th day of life and screamed for 24 hours. He was severely constipated through the first year of life but has had diarrhea since then. He has been diagnosed with autism. A third child, a girl, is normal. The mother received the hepatitis B vaccine series in 1998-1999. She reports having several markers for lupus at this time.

6. A mother with a family history of immune disease, who was born in 1959, was routinely vaccinated but "needed" and received a rubella booster shortly after she delivered her first child, a girl, in 1987. This child is developmentally normal and has received all recommended vaccines. After a miscarriage, the patient delivered a boy in 1989. This child has significant speech difficulties; he has received all recommended vaccines except hepatitis B. After a second miscarriage, a boy was born in 1992 and was nursed for 18 months. He was severely constipated but seemed to be developing normally. He was routinely vaccinated, including the hepatitis B series in infancy, an MMR vaccine at age 12 months, and a monovalent measles vaccine at 61 months of age. Between 12 and 15 months of age, he lost eye contact and the few words he had acquired. He has been diagnosed with autism.

All six of these mothers above, and many others like them, remained rubella-susceptible following vaccination. Their postpartum revaccination did not always result in immunity, and was followed by problems with their own health and that of their children.

Results

A total of 60 respondents received MMR (32) or monovalent rubella vaccine (28) postpartum. In 45 cases (75%), children born to these women have been diagnosed with autistic spectrum disorder (ASD). In another 10 cases (17%), there is a child with autistic behaviors, developmental delays, or ADD. Some of these children have been diagnosed on the spectrum since the mothers initial response. Four other women (7%) had children with other medical problems: endocrine, allergic or immunologic with associated frequent infections. One mother in this group had a normal child, an only daughter who was not breast-fed.

In 21 cases, the child born just prior to the revaccination has been diagnosed on the autism spectrum. In 22 cases, a subsequent child born to these women has been diagnosed. One mother has children on the spectrum from both the pregnancy followed by the vaccine and the next pregnancy. There were 3 cases in which a third pregnancy (the second subsequent to revaccination) produced a child who became autistic. There are also many cases in which siblings of the autistic children have been diagnosed with ADD/ADHD, other developmental delays, or other medical problems.

The data are inconclusive on the relationship between breastfeeding and the subsequent diagnosis of ASD. Among the children resulting from the pregnancy followed by vaccination, at least 27 were breast-fed for varying lengths of time. Of these, 17 (63%) became autistic. However, at least two children born just before maternal revaccination developed autism although they were never breast-fed. In one case a male child who was not breast-fed is severely affected on the autism spectrum, has very elevated rubella and measles titers, and has tested positive for Myelin Basic Protein antibodies. There were also cases in which children with autism resulting from subsequent pregnancies were not breast-fed.

No correlation was apparent between the type of vaccine given to the mother (MMR or rubella) and the outcome for the child. Among the children born just prior to revaccination, 13 (41%) of the children born to the women who received the MMR became autistic, and eight (29%) of the children born to women given the rubella vaccine were later diagnosed.

Twelve mothers in this study reported that their autistic children began to display symptoms after receiving their MMR vaccination. Two mothers reported that their children had symptoms of ASD prior to MMR vaccination, but that their symptoms worsened after receiving the vaccine. Only one mother reported that her third child (the second after her revaccination) was displaying significant autistic symptoms prior to his own vaccination. Curiously, three separate mothers reported that one of their children had reacted to DPT vaccination, but none of these children have been diagnosed with ASD. (One boy with "cerebral palsy" has classical behaviors associated with autism but has never been diagnosed.)

Among the children born just prior to their mother's revaccination, the diagnosis of ASD was highly correlated to gender (Table 1), with 49% of the males, 13% females, and one of the two surviving gender-unknown children resulting from the first pregnancy becoming autistic. These numbers include one set of twins in which the male has been diagnosed on the spectrum and the female required significant speech therapy.

The gender selection was also obvious among second children born to these mothers: 69% of the males, 31% of the females (and one gender unknown child) resulting from these pregnancies became autistic (Table 2). These numbers include two sets of twin boys. In one set, both twins have typical autism, while the other set includes one child with ASD and the other with other delays. Tables 1 and 2 together include all the children of the 60 mothers, except those born prior to the pregnancy followed immediately by vaccination.

Although the mothers' reactions were not a focus of this study, several mothers reported reactions to MMR or rubella vaccine. Two women reported short-term reactions such as fever and rash; four women reported joint pain/arthritis; and three women reported other long-term health problems. Only two of the women who noted their own reactions indicated that they had any health problems prior to their revaccination. Six of the mothers in this study, who had no prior obstetrical difficulties, reported having miscarriages after receiving the postpartum vaccination. There were also two cases of difficult pregnancies, and one case in which a woman carrying twins lost one of the children.

Discussion

Prospective studies to investigate problems with vaccines are not feasible in the United States at the present time because of mandates. Retrospective studies should include very large samples to be meaningful. This is extremely difficult because of the need to identify and contact participants with no assurance of response. The individual researcher is therefore left with the case presentation approach to illustrate unusual and unexpected outcomes. These cases are self-selected women who read materials that focus on suspected adverse effects of vaccines.

The study design does not permit a calculation of the incidence of the severe effects reported nor any comparison with their incidence in mothers who were not revaccinated. However, even the rare occurrence of such severe effects following postpartum vaccination warrants careful examination and a search for a possible mechanism.

As is frequently stated, any risk from vaccines should be viewed in perspective with the danger from vaccine-preventable disease. The prevention of Congenital Rubella Syndrome (CRS) in future pregnancies is the main indication for postpartum revaccination. Maternal rubella infection during the first trimester of pregnancy may affect the fetus and result in the development of CRS, a terrible complication which is manifested by somatic, developmental, neurological, cardiac, and sensory defects and disorders.

Autism is not any less devastating a disease than CRS. It is also a lifetime sentence of pain and suffering to the involved child and parents and an unending burden on the community. If, in any way, maternal revaccination contributes to the children's autism, then it is imperative that a complete and true disclosure of the risks and benefits be made to the mother before she is revaccinated. A review and definition of the present dangers and risks of CRS is therefore in order.

Rubella and the CRS became nationally reportable diseases in 1966, and the CRS is currently tracked through the National CRS Registry of the National Immunization Program. In 1969, there was a large rubella outbreak with approximately 57,686 cases. The rubella vaccine was licensed that year and has been used ever since, singly or in the MMR. Since 1983, there have been fewer than 1,000 cases of rubella per year nationwide except for two small outbreaks in 1990 and 1991 in California and in Pennsylvania's Amish Country. Since 1992, only around 200 cases of rubella are reported nationally every year. Except during early pregnancy, rubella is a relatively mild disease.

There is no exact count of CRS cases prior to 1969, when the vaccine was introduced in the United States. In 1970, there were 67 cases reported to the registry, the largest number ever, in a single year. Since 1980, however, only five to six cases of CRS on average have been reported each year, except during the 1990 and 1991 outbreaks, when there were 25 and 33 cases. Only 9 cases of CRS were reported in 1997. The mothers of all 9 infants were born in Latin America or the Caribbean.(2) The recommendation to revaccinate rubella-susceptible women was issued in 1977. There were only 22 cases of CRS nationwide the year before.

The administration of rubella (and MMR) vaccine in the postpartum period is convenient for the medical practitioners, and little consideration is given to the viral transmission between the mother and her infant child.

Although vaccine virus may be isolated from the pharynx, vaccinees do not transmit rubella to others, except occasionally in the case of the vaccinated breast-feeding woman. In this situation, the infant may be infected, presumably through breast milk, and may develop a mild rash illness, but serious effects have not been reported.(3)

Though the Physicians' Desk Reference states that "caution should be exercised" when Meruvax II (or MMR II) is administered to a nursing mother,(4) not a single woman in the study recalled being informed that such viral excretion occurred, nor asked if she was planning future pregnancies.

While there have been no reports of possible viral transmission between mother and child except via breast milk, the cases of two children in this study, who were not breast-fed and developed autism, suggest that direct transmission may occur.

It is not known whether measles and mumps viruses are excreted in breast milk, but a report in the veterinary literature seems to suggest that the canine distemper virus, a morbillivirus closely related to the measles virus, may have caused distemper in nursing pups.(5)

Is there a mechanism that could account for the induction of autism in children of these sixty mothers? Comi and coworkers6 have reported a higher incidence of autism in families with immune disorders. They also found that the more immune defects in a family, the higher the incidence of autism, and that a mother who has an immune disease has a nine-fold increased chance to have a child with autism.

The failure of certain women to develop or maintain protective antibodies after immunization may be an expression of an immune defect, which may predispose their children to autism. This risk may increase if the mothers are given added vaccines or if the children are exposed to early, combined, or severe antigenic insults, namely their own immunizations. Preser-vatives in some vaccines may also contribute to further toxic and immune injury and lead to more damage.(7)

Others have adduced evidence of the immunological aspects of autism. Notably, Dr. Vijendra Singh has made a compelling argument for autism being considered an autoimmune disorder.(8) The mechanism by which a developing brain might be affected would likely be an immune response resulting in antibodies against the brain or neurological tissue. It has been theorized that certain viruses may induce this autoimmune response. Evidence of antibodies to Myelin Basic Protein (MBP),(9) neuron-axon filament proteins,(10) and serotonin receptors(11) have been found in autistic children. More specifically, Dr. Singh and his colleagues have also found that measles virus and human herpesvirus-6 viral antibody levels were higher in the blood of autistic children, and that they often co-occurred with brain autoantibodies. They found a 90% correlation between the presence of measles-IgG-positive sera and MBP autoantibodies, which confirms reports from parents, including at least one family in this study. This relationship between measles antibodies and MBP is particularly troubling in light of parental reports that their children became autistic following their MMR vaccination. Recent research has also shown live vaccine strain measles virus in the intestines of autistic children.(12-14) It has also been found that the measles virus (or vaccine) can cause immunosuppression.(15)

There have been no studies on the possibility of cumulative effects of a mother's revaccination or the second generational effects on their children when they are themselves vaccinated. The cases reported here suggest cause for concern.

The mothers in this study were also adversely affected by their revaccination in some cases. The reports of joint problems and arthritis are not surprising as rubella vaccination has been linked to arthritis in several studies.(16-18) However, the reports of miscarriages and difficult pregnancies, reported here for the first time, were unexpected and alarming. As we have no theory to explain this finding, further study is clearly needed in this area.

Recommendations

In the light of the information obtained through this study and the supportive findings of other researchers, we make the following recommendations:

1. The routine administration of a live virus vaccine booster, during the postpartum period, to previously vaccinated women who have remained rubella-susceptible, should be reconsidered. The present minute risk of CRS does not justify revaccination of women at such a critical time. Indeed, the same caution should be exercised in the case of all women who have failed to produce or maintain adequate protective titers after vaccination.

2. When obtaining "informed consent," medical practitioners should clearly explain to mothers that it is known that the rubella virus from vaccine may be excreted in their nose, throat, and breast milk.

3. Further research into the possibility of viral transmission through close contact between a mother and infant child should be done.

4. The excretion of the measles virus from vaccine in breast milk should be investigated.

5. Whether "routine" hepatitis B vaccination in the newborn period is an antigenic insult which increases the risk of developing autism should be examined.

6. Early and combined frequent vaccinations of children should be reviewed.

References

1. Seroussi K. Unraveling the mystery of autism and pervasive developmental disorder: a mother's story of research and recovery.
Simon & Schuster, 2000.
2. Atkinson W, Humiston S, Wolf C, Nelson R, eds. Epidemiology and Prevention of Vaccine-Preventable Diseases, ed 5. National Immunization Program, Centers for Disease Control and Prevention (CDC), January, 1999, pp. 178-179.
3. Atkinson W, et al. op. Cit., p. 185.
4. Physicians' Desk Reference 1999; pp. 1820, 1834.
5. McCandlish IAP, Cornwall HJC, Thompson H, Nash AS, Lowe CM. Distemper encephalitis in pups after vaccination of the dam. The Veterinary Record 1992;130(2): 27-30.
6. Comi AM, Zimmerman AW, Frye VH, Law PA, Peeden JN 1999. Familial clustering of autoimmune disorders and evaluation of medical risk factors in autism. J Child Neurol. 1999;14(6):388-94.
7. Redwood, L. Mercury and Autism: Coincidence or cause and effect? Autism/Asperger's Digest 2000; July /August.
8. Singh VK. Autism, Autoimmunity and immunotherapy: a commentary. The Autism Autoimmunity Project Newsletter, 1999;1(December).
9. Weizman A, Weizman R, Szekely GA, Wijsenbeek H, Livni E. Abnormal immune response to brain tissue antigen in the syndrome of autism. Am J Psychiatry 1982;139(11):1462-5.
10. Singh VK, Lin SX, Yang VC. Serological association of measles virus and human herpesvirus-6 with brain autoantibodies in autism. Clin Immunol Immunopathol. 1998;89(1):105-8.
11. Todd RD, Ciaranello RD. Demonstration of inter- and intraspecies differences in serotonin binding sites by antibodies from an autistic child. Proc Natl Acad Sci USA. 1985;82(2):612-6.
12. Wakefield AJ, Murch SH, Anthony A, et al: Ileal-lymphoid hyperplasia, non-specific colitis, and pervasive developmental disorder in children. Lancet 1998;351:637-41.
13. O'Leary JJ, Uhlmann V, Wakefield AJ. Measles virus and autism. Lancet 2000; 356(9231):772.
14. Kawashima H, Mori T, Kashiwagi Y, Takekuma K, Hoshika A, Wakefield A. Detection and sequencing of measles virus from peripheral mononuclear cells from patients with inflammatory bowel disease and autism. Dig Dis Sci. 2000;45(4):723-9.
15. Halsey NA. Increased mortality after high titer measles vaccines: too much of a good thing. Pediatr Infect Dis J. 1993;12(6):462-5.
16. Howson CP, Katz M, Johnston RB Jr, Fineberg HV. Chronic arthritis after rubella vaccination. Clin Infect Dis.1992;15(2):307-12.
17. Tingle AJ, Mitchell LA, Grace M, Middleton P, Mathias R, MacWilliam L, Chalmers A. Randomised double-blind placebo-controlled study on adverse effects of rubella immunization in seronegative women. Lancet 1997;349(9061):1277-81.
18. Weibel RE, Benor DE. 1996. Chronic arthropathy and musculoskeletal symptoms associated with rubella vaccines. A review of 124 claims submitted to the National Vaccine Injury Compensation Program. Arthritis Rheum. 1996;39(9):1529-34.

F. Edward Yazbak, MD, FAAP, and Kathy L. Lang-Radosh, MS, TL Autism Research, West Falmouth, MA, E-mail: TLAutStudy@aol.com.

This article was originally published in the Medical Sentinel 2001;6(3):95-99, 108. Copyright © 2001, Association of American Physicians and Surgeons (AAPS).

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