Immune stimulation through exposure to commensal microbes may protect against allergy development. Oral microbes may be transferred from parents to infants via pacifiers. We investigated whether pacifier cleaning practices affected the risk of allergy development.
A birth-cohort of 184 infants was examined for clinical allergy and sensitization to airborne and food allergens at 18 and 36 months of age and, in addition, promptly on occurrence of symptoms. Pacifier use and pacifier cleaning practices were recorded during interviews with the parents when the children were 6 months old. The oral microbiota of the infants was characterized by analysis of saliva samples collected at 4 months of age.
Children whose parents “cleaned” their pacifier by sucking it (n = 65) were less likely to have asthma (odds ratio [OR] 0.12; 95% confidence interval [CI] 0.01–0.99), eczema (OR 0.37; 95% CI 0.15–0.91), and sensitization (OR 0.37; 95% CI 0.10–1.27) at 18 months of age than children whose parents did not use this cleaning technique (n = 58). Protection against eczema remained at age 36 months (hazard ratio 0.51; P = .04). Vaginal delivery and parental pacifier sucking yielded independent and additive protective effects against eczema development. The salivary microbiota differed between children whose parents cleaned their pacifier by sucking it and children whose parents did not use this practice.
Parental sucking of their infant’s pacifier may reduce the risk of allergy development, possibly via immune stimulation by microbes transferred to the infant via the parent’s saliva.
Comments
"I feed my baby the traditional way; I chew the food for him".
In light of the recent publication by Hesselmar et al (1), I wish to communicate a personal observation. In April of 2012, I travelled as a tourist to rural areas of Arunachal Pradesh in Northeastern India. Here, I met with a young woman who told me about the local infant feeding practices.
One night I stayed at the hotel Pemaling, located on a hillside above the small Himalayan town of Dirang. In the evening, guests and staff alike were scattered around the sitting area in the lobby. On a thick carpet was the center of attention: a boy 8 months old, in good health as judged by appearance, and his young mother who we can call Mrs. L. The hotel was mainly staffed by young local people and Mrs. L had been one of them. She had worked at the hotel a year earlier, but left when she got married and she was now visiting to let her friends see her first child. She was ethnically Monpa, originally Tibetan people. She had learned to speak English in order to work in the tourist industry.
I introduced myself with help of our local guide, as a pediatrician with an interest in child nutrition, and Mrs. L readily agreed to tell me about the local infant feeding practices. We soon came to the subject of introduction of solids, and she started out by saying "I feed my baby the traditional way; I chew the food for him". I followed up with some specific questions, and here is a transcript from my notebook:
Chewing baby food has always been the traditional way, and I have seen my mother doing this. My baby was breast fed but I have been chewing small portions of red rice with butter for him as a supplement already since he was two days old. I take the food from my mouth with my fingers and give to him, but I have heard in some places the babies are fed directly mouth to mouth. Apart from red rice, I just chew whatever I eat and give to him, fish, chicken, and meat. This goes on until he can eat on his own. It depends on the child but also on when he gets his teeth. A few months ago we were in Delhi and I was feeding him like that. People were looking at us and making faces.
Maternal chewing of infant food is likely to be an ancient phenomenon, and is likely to vanish as soon as young parents are exposed to alternative ways, which by most will be perceived as more modern and thus, somehow better. I propose that such feeding practice could influence the maturation of the child's immune system, and that it should be specifically asked for in epidemiological surveys of, for example, food allergies. I would, however, not recommend this practice in any situation where there could be risk for transmission of disease. Not all children in rural societies are necessarily healthy.
1. Bill Hesselmar, Fei Sj?berg, Robert Saalman, Nils ?berg, Ingegerd Adlerberth, and Agnes E. Wold Pediatrics 2013 131:e1829-e1837; doi:10.1542/peds.2012-3345 Pacifier Cleaning Practices and Risk of Allergy Development
Conflict of Interest:
No competing interests. The findings and opinions reflected in this report are those of the author and do not necessarily represent the official position of AstraZeneca.
Methodological limitations in "Pacifier Cleaning Practices and Risk of Allergy"
Recently Hesselmar et al.1 reported that, "Parental sucking of their infant's pacifier may reduce the risk of allergy development." Though the findings are provocative, they may not be valid because of substantial methodological limitations. Furthermore, their proposal of parental pacifier sucking as a "simple and safe method to reduce allergy development" may create some important health risks.
The study's assessment of exposure is based on a single question about pacifier use: "Is it cleaned by boiling, rinsing in tap water, or by the parents sucking on it?" The exposure was assessed only once, at 6 months. The parents were not asked about frequency or duration of the practice, nor did they report what pacifier sucking, if any, happened in the subsequent 12-30 months before the allergy outcomes were assessed. Unfortunately, children who never used pacifiers were not included in the analyses, so this important unexposed group was unavailable for comparison. Given the multitude of factors that are likely to contribute to allergy development, and the extended possible exposure period (18 or 36 months), it seems biologically implausible that such a limited measure of a single exposure risk could predict the development of such a complex disease process.
The allergies in question are associated with, as the authors describe, poverty, crowding, large family size, early contact with animals, exposure to foodborne microbes, Cesarean delivery, and genetic factors, among other things, all of which could conceivably have also been associated with parental pacifier sucking. Several of these factors were not assessed as potential confounders in Table 4 and therefore were not controlled for; of those that were examined, most were crude rather than detailed measures and were excluded from multivariate analyses based on p- values for the association with the exposure variable, a sub-optimal confounder-selection strategy.2 In addition, any confounding factors that may have occurred after 6 months were not measured and therefore were not considered in analyses.
The limitations in exposure assessment and control of confounding are especially problematic because of the relatively small number of children studied and even smaller number of disease outcomes (N=46 for eczema, N=10 for asthma, and N=25 for sensitization). This led to very wide confidence intervals (e.g., 0.15-0.91 for eczema, 0.01-0.99 for asthma) that would have overlapped with the null values if just a handful of children had different exposures or disease outcomes, or if even a small amount of uncontrolled confounding was present.
Given these important methodological limitations, the authors' primary conclusions are not warranted. Even if the association turns out to be real, their proposal of parental pacifier sucking to reduce allergy development inadequately weighs the potential harms with the supposed benefits. Such behavior may put children at risk for increased dental caries3 and may put both parents and children at risk for infections not assessed in the study, including cytomegalovirus, which a pregnant woman could acquire from sucking a pacifier and then transmit to her fetus with potentially devastating results.4
References
1. Hesselmar B, Sjoberg F, Saalman R, Aberg N, Adlerberth I, Wold AE. Pacifier cleaning practices and risk of allergy development. Pediatrics. 2013;131(6):e1829-e1837.
2. Vansteelandt S, Bekaert M, Claeskens G. On model selection and model misspecification in causal inference. Stat Methods Med Res. 2012;21(1):7-30.
3. Berkowitz RJ. Mutans streptococci: Acquisition and transmission. Pediatr Dentistry. 2006;28(2):106-109.
4. Sharon B, Schleiss MR. Congenital cytomegalovirus infection: an unrecognized epidemic. Infect Med. 2007;24:402-415.
Conflict of Interest:
No competing interests. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.
Parental Pacifier Cleaning: Is Sharing Really Caring?
Re: "Pacifier Cleaning Practices and Risk of Allergy Development," which appeared in the May 2013 issue of Pediatrics.
This article left a bad taste in my mouth. The study examined the relationship between pacifier cleaning technique and allergy development in 184 infants to determine if parents who rinsed pacifiers in their own saliva versus boiled water altered their infant's oral flora in a way that offers "primary prevention" against eczema and allergies. The study admirably controlled for the mode-of-delivery when reporting their findings, acknowledging the importance of both parental and vaginally acquired microbacteria in immunologic protection. Infants who were delivered vaginally and had a "shared" pacifier had the lowest prevalence of eczema (20%), while those born via C-section and who used a pacifier cleaned in boiling water had the highest prevalence of eczema (54%).
The study was based on the "hygiene hypothesis," which postulates that a lack of early childhood exposure to commensurable bacteria suppresses the body's natural immune system development, thus increasing the risk of allergic diseases. Within this view, poverty, small and crowded households, large families, early contact with animals, and food- borne microbes reduce the risk of allergy development. As a medical student, I rarely hear about "the perks" of low socioeconomic status (SES). In reporting what happened to the babies with "natural" versus sterilely cleaned pacifiers, the authors detract from an important notion: who shares the pacifier. These babies were not randomized to a pacifier group; moms retrospectively self-reported their own habits. Yes, we know that to be included, all subjects had one parent with a significant allergy, but what about mom's dental hygiene, cavities, and oral infections? Are certain moms more likely to favor shared pacifiers over sterile ones? And are these moms the ones we want to be practicing what Dr. Hesselmar and colleagues' preach? Those with a university degree had a non-significant but noteworthy tendency to favor the "sterile" pacifier practice. Numerous studies have demonstrated higher prevalence of caries among children from minority and/or lower-SES background, relating children's caries to high levels of maternal sugar consumption and salivary concentrations of Strep Mutans. While the prospect of pacifier immunity is soothing to moms and babies alike, the medical community must remember that moms should also focus on passing along good habits such as beneficial dietary behaviors, healthy feeding practices, and proper oral hygiene and dental health. These aspects of infant care also play a role in preventive medicine, and they may be passed from mother to child just as easily as antibodies.
Sincerely,
Christine I. Kansky MSIII
Conflict of Interest:
None declared
Balancing the risks and benefits of inoculating children with oral bacteria
We read with some concern the article titled "Pacifier cleaning practices and risk of allergy development" by Hesselmar et al.1 Our concern lies not with the quality of the study or the potential reduction in risk for allergy development, but with the potential increased risk for dental caries and the negative consequences of such a common childhood disease.
Dental caries is the most common chronic disease of childhood. In the United States, dental caries is five times more common than asthma and 7 times more common than allergic rhinitis.2 Dental caries is an infectious disease caused by cariogenic bacteria that, if at high enough levels in the oral microbiome, can cause significant acid mediated destruction of the tooth structure.
High maternal levels of cariogenic bacteria is associated with higher levels of cariogenic bacteria in their child, a precursor to dental disease.3 The caregiver with this oral microbiome profile who chooses to clean a pacifier by sucking could repeatedly inoculate her infant with the same disease causing bacteria.3,4 Though the authors reference a review that concluded there is not a strong or consistent association between pacifier use and early childhood caries, the behavior in question is not merely the use of a pacifier but the cleaning of the pacifier by sucking. It is the addition of saliva and the transmission of the oral microbiome that makes the difference both in dental caries and, in the author's study, allergy development.
So what are caregivers to do? First, we agree with the authors that it is important to reevaluate the findings from this study in larger studies, and in older children with a better-defined asthma and established atopic profile. Second, we encourage all caregivers to maintain good oral hygiene and an ongoing relationship with a dental provider. Caregivers with untreated dental caries have children that are nearly twice as likely to have children with dental caries and of greater severity.5 Third, we encourage all caregivers to maintain good oral hygiene in their children and connect them with a dental home by age one. Finally, we discourage cleaning pacifiers by sucking. It is too early to tell if the benefits hinted at in this study outweigh the risks of dental disease.
1. Hesselmar B, Sj?berg F, Saalman R, ?berg N, Adlerberth I, Wold AE. Pacifier cleaning practices and risk of allergy. Pediatrics. 2013;131:1-9.
2. U.S. Department of Health and Human Services. Oral Health in America: A Report of the Surgeon General.Rockville, MD: U.S. Department of Health and Human Services, National Institute of Dental and Craniofacial Research, National Institutes of Health, 2000. 3. Berkowitz RJ. Mutans streptococci: Acquisition and transmission. Pediatr Dent. 2006;28(2):M106-109.
4. Weintraub JA, Prakash P, Shain SG, Laccabue M, Gansky SA. Mothers' caries increases odds of children's caries. J Dent Res. 2010;89(9):954- 958.
5. Douglass JM, Li Y, Tinanoff N. Association of Mutans streptococci between caregivers and their children. Pediatr Dent. 2008;29(5):375-387.
Conflict of Interest:
None declared
Re:Potential Risk and Confounders Associating Parental Pacifier Cleaning with Allergy
I think that there is more to just the cleaning practices of the pacifiers by the family. I'm sure that those parents who cleaned the pacifiers with their mouths were the ones that also exposed their babies more to their environment, and this just adds more true to the "hygiene" hypothesis. It would have been very interestimg if the authors looked also to such practices in their investigation.
Conflict of Interest:
None declared
Potential Risk and Confounders Associating Parental Pacifier Cleaning with Allergy
Hesselmar et al. found that infants exposed repeatedly to parental oral microbiota through pacifier use, and/or maternal vaginal microbiota at birth were less likely to develop allergic disease. They concluded that the transferred microbes may be responsible for reducing this risk.
The authors demonstrate a statistical association between shared microorganisms and reduced allergy risk. However, pacifier sharing can transmit immune modulating chronic viral infections, such as herpesviruses. Janson found the risk of allergic disease was reduced by prior infection with 3 or more organisms including Helicobacter pylori and Chlamydia pneumoniae, as well as Herpes simplex virus-1, Epstein-Barr virus (EBV), and cytomegalovirus (CMV). (1) Of these viral infections, Epstein-Barr virus prior to 2 years of age was associated with the greatest protective effect against allergic disease, and this effect was enhanced by co-infection with CMV. (2) Numerous other studies suggest saliva, urine, and breast milk are likely routes of transmission of CMV and possibly EBV to children from parents or amongst young children. (3) Pacifier sharing may merely enhance transmission of these viruses between infected and uninfected individuals. Since both microbiota and chronic viral infections have been statistically associated with reduced allergy risk, this study cannot distinguish between these two potential causal factors. If future studies could more precisely document these additional associations, the protective mechanism may become more apparent.
Before one suggests that parental pacifier sharing or cleaning by mouth may be beneficial overall, one should consider the possible disadvantages, which may outweigh the reduced risk of allergic disease. Chronic infection with EBV and CMV are postulated to be examples of "antagonistic pleiotropy" in which these viral infections produce a beneficial effect early in life, but earlier mortality and greater morbidity in older individuals. (3, 4) EBV infection is well known to predispose to a variety of lymphoproliferative disorders, especially in immunocompromised individuals such as post transplant or in association with HIV. Evidence also suggests that EBV is associated with other cancers and autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis in adulthood. Evidence is growing that CMV gene products may promote tumors as an oncogenic virus, with strong support for a role in glioblastoma and other CNS tumors, as well as breast, prostate, colon, and salivary gland tumors. (5) Further evidence supports the role of CMV infection in impaired immune responses in adults, or "immunosenescence," which includes depletion of naive T-cells. (3) A specific example of immunosenescence is an impaired T-cell immune response to live influenza virus after vaccination. (4)
One must consider long term consequences of practices which enhance transmission of chronic viral infections. Factors that improve health in adult life, such as avoiding chronic viral infections, may become increasingly important from a public health perspective by reducing the disability associated with ageing.
References: 1. Janson C, Asbjornsdottir H, Birgisdottir A, Sigurjonsdottir RB, Gunnbjoernsdottir M, Gislason D, Olafsson I, Cook E, Joegi R, Gislason T, Thjodleifsson B. The effect of infections burden on the prevalence of atopy and respiratory allergies in Iceland, Estonia, and Sweden. J Allergy Clin Immunol. 2007; 120: 673-9.
2. Nilsson C, Sigfrinius AKL, Montgomery SM, Sverremark-Ekstroem E, Linde A, Lilja G, Blomberg MT. Epstein-Barr virus and cytomegalovirus are differentially associated with numbers of cytokine producing cells and early atopy. Clinical Experimental Allergy. 2009; 39: 509-17.
3. Griffiths PD. Burden of disease associated with human cytomegalovirus and prospects for elimination by universal immunisation. Lancet Infect Dis 2012; 12: 790-8
4. Pawelec G, McElhaney JE, Aiello AE, Derhovanessian E. The impact of CMV infection on survival in older humans. Current Opinion in Immunology. 2012; 24:507-11.
5. Johnsen JI, Baryawno N, S?derberg-Naucler C. Is human cytomegalovirus a target in cancer therapy? Oncotarget, 2011; 2: 1329-38
Conflict of Interest:
None declared
Balancing the risks and benefits of inoculating children with oral bacteria
We read with some concern the article titled "Pacifier cleaning practices and risk of allergy development" by Hesselmar et al.1 Our concern lies not with the quality of the study or the potential reduction in risk for allergy development, but with the potential increased risk for dental caries and the negative consequences of such a common childhood disease.
Dental caries is the most common chronic disease of childhood. In the United States, dental caries is five times more common than asthma and 7 times more common than allergic rhinitis.2 Dental caries is an infectious disease caused by cariogenic bacteria that, if at high enough levels in the oral microbiome, can cause significant acid mediated destruction of the tooth structure.
High maternal levels of cariogenic bacteria is associated with higher levels of cariogenic bacteria in their child, a precursor to dental disease.3 The caregiver with this oral microbiome profile who chooses to clean a pacifier by sucking could repeatedly inoculate her infant with the same disease causing bacteria.3,4 Though the authors reference a review that concluded there is not a strong or consistent association between pacifier use and early childhood caries, the behavior in question is not merely the use of a pacifier but the cleaning of the pacifier by sucking. It is the addition of saliva and the transmission of the oral microbiome that makes the difference both in dental caries and, in the author's study, allergy development.
So what are caregivers to do? First, we agree with the authors that it is important to reevaluate the findings from this study in larger studies, and in older children with a better-defined asthma and established atopic profile. Second, we encourage all caregivers to maintain good oral hygiene and an ongoing relationship with a dental provider. Caregivers with untreated dental caries have children that are nearly twice as likely to have children with dental caries and of greater severity.5 Third, we encourage all caregivers to maintain good oral hygiene in their children and connect them with a dental home by age one. Finally, we discourage cleaning pacifiers by sucking. It is too early to tell if the benefits hinted at in this study outweigh the risks of dental disease.
1. Hesselmar B, Sjoberg F, Saalman R, Aberg N, Adlerberth I, Wold AE. Pacifier cleaning practices and risk of allergy. Pediatrics. 2013;131:1-9.
2. U.S. Department of Health and Human Services. Oral Health in America: A Report of the Surgeon General.Rockville, MD: U.S. Department of Health and Human Services, National Institute of Dental and Craniofacial Research, National Institutes of Health, 2000.
3. Berkowitz RJ. Mutans streptococci: Acquisition and transmission. Pediatr Dent. 2006;28(2):M106-109.
4. Weintraub JA, Prakash P, Shain SG, Laccabue M, Gansky SA. Mothers' caries increases odds of children's caries. J Dent Res. 2010;89(9):954- 958.
5. Douglass JM, Li Y, Tinanoff N. Association of Mutans streptococci between caregivers and their children. Pediatr Dent. 2008;29(5):375-387.
Conflict of Interest:
None declared