Antibiotic exposure in early infancy and risk for childhood atopy

doi:10.1016/j.jaci.2005.04.020

Journal of Allergy and Clinical Immunology

Volume 115, Issue 6, June 2005, Pages 1218-1224

https://doi.org/10.1016/j.jaci.2005.04.020 Get rights and content

Background

The increase in pediatric allergy and asthma parallels the increase in use of antibiotics. Antibiotics disturb the flora of the gastrointestinal tract, possibly perturbing the developing immune system.

Objective

We evaluated whether antibiotic use during early infancy increased the risk for atopy.

Methods

Antibiotic prescriptions documented in medical records were collected from a birth cohort born from 1987 through 1989 (n = 725). At 6 to 7 years of age, 448 were followed by means of examination, including skin prick tests and serum IgE measurements to common allergens.

Results

Adjusted odds ratios (aORs) and 95% CIs were calculated comparing children with any versus those with no antibiotic use in the first 6 months and the outcomes of atopy (any positive skin test response), seroatopy (any positive specific IgE test result), either atopy or seroatopy, and both atopy and seroatopy. Atopy increased with antibiotic use approaching statistical significance (aOR, 1.48; 95% CI, 0.94-2.34; P = .09); however, the risk was concentrated among children with less than 2 pets in the home (aOR, 1.73; 95% CI, 1.07-2.80; P = .024) and children breast-fed for 4 or more months (aOR, 3.02; 95% CI, 1.27-7.17; P = .013). The aORs were generally in the same direction for seroatopy and the combined categories.

Conclusion

Antibiotic use in early life appears to contribute to increased risk for atopy in certain subgroups of children.

Section snippets

Study population and follow-up

The recruitment of the Childhood Allergy Study population has been described elsewhere.²¹ All pregnant women enrolled in the medical group component of the largest Michigan health maintenance organization and living in a defined middle-class suburban area north of Detroit were potentially eligible. Women had to be 18 years of age or older, with a due date between April 15, 1987, and August 31, 1989, and were interviewed by study nurses during appointments in their obstetricians' offices after

Results

A total of 1194 pregnant woman were eligible, and 953 consented to their child's participation. The 835 children with valid cord blood IgE measurements were enrolled. Medical records were not retrievable for 51 children, and 59 children did not have at least 12 months of follow-up in the medical record (because of change of insurance, clinician, or residence), leaving 725 eligible children. Of these, 448 (61.8%) children underwent the clinical examination at age 6 to 7 years, 176 children were

Discussion

The results from the Detroit prospective birth cohort suggest that antibiotic use is a risk factor for atopic indicators, specifically for children with other risk factors for atopy, as observed in 2 previous reports.6, 11 A US birth cohort study of high-risk children in the Boston area did not implicate antibiotic use in the first year of life as a risk factor for the outcomes of asthma and atopy at age 5 years, as reported by parents.¹⁴ However, odds ratios from this study were close to unity

References (27)

R. Beasley et al.
Prevalence and etiology of asthma
J Allergy Clin Immunol
(2000)
J. Levy
The effects of antibiotic use on gastrointestinal function
Am J Gastroenterol
(2000)
J.S. Alm et al.
Atopy in children of families with an anthroposophic lifestyle
Lancet
(1999)
T.M. McKeever et al.
Early exposure to infections and antibiotics and the incidence of allergic disease: a birth cohort study with the West Midlands General Practice Research Database
J Allergy Clin Immunol
(2002)
A. Wright et al.
Breast-feeding, maternal IgE, and total serum IgE in childhood
J Allergy Clin Immunol
(1999)
S.T. Remes et al.
Dog exposure in infancy decreases the subsequent risk of frequent wheeze but not atopy
J Allergy Clin Immunol
(2001)
D.R. Ownby et al.
Maternal smoking does not influence cord serum IgE or IgD concentrations
J Allergy Clin Immunol
(1991)
L.K. Williams et al.
The relationship between early fever and allergic sensitization at age 6 to 7 years
J Allergy Clin Immunol
(2004)
N. Oyama et al.
Antibiotic use during infancy promotes a shift in Th1/Th2 balance toward Th2-dominant immunity in mice
J Allergy Clin Immunol
(2001)
D. Strachan
Family size, infection and atopy: the first decade of the “hygiene hypothesis”
Thorax
(2000)

P.G. Holt et al.

Atopic versus infectious diseases in childhood: a question of balance?

Pediatr Allergy Immunol

(1997)

J.A. Finkelstein et al.

Decreasing antibiotic use among US children: the impact of changing diagnosis patterns

Pediatrics

(2003)

I.S. Farooqi et al.

Early childhood infection and atopic disorder

Thorax

(1998)

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Antibiotic exposure and adverse long-term health outcomes in children: A systematic review and meta-analysis
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Citation Excerpt :
The overall odds ratio (OR) for developing atopic dermatitis after antibiotic exposure was 1.40, 95% confidence interval (CI) 1.30 to 1.52, p < 0.01 (Fig. 2). Twenty-three studies in 34,806 children (8952 cases) investigated the association between antibiotic exposure and the risk of developing allergic sensitisation diagnosed by skin prick test or serum immunoglobulin (Ig) E levels (Table 1).24,40,43,49,60,70,79,80,82,87,93,105,116,126,135,153,175–178,181,183,184 Of the studies, 21 (91%) investigated the effect of antibiotic exposure in the first five years of life (18 (78%) in the first two years of life).24,40,43,49,60,70,79,80,82,93,105,116,126,135,153,175–178,181,183
Antibiotics are amongst the most commonly used drugs in children. In addition to inducing antibiotic resistance, antibiotic exposure has been associated with adverse long-term health outcomes.
A systematic search using PRISMA guidelines to identify original studies reporting associations between antibiotic exposure and adverse long-term health outcomes in children. Overall pooled estimates of the odds ratios (ORs) were obtained using random-effects models.
We identified 160 observational studies investigating 21 outcomes in 22,103,129 children. Antibiotic exposure was associated with an increased risk of atopic dermatitis (OR 1.40, 95% confidence interval (CI) 1.30–1.52, p < 0.01), allergic symptoms (OR 1.93, 95%CI 1.66–2.26, p < 0.01), food allergies (OR 1.35, 95%CI 1.20–1.52, p < 0.01), allergic rhinoconjunctivitis (OR 1.66, 95%CI 1.51–1.83, p < 0.01), wheezing (OR 1.81, 95%CI 1.65–1.97, p < 0.01), asthma (OR 1.96, 95%CI 1.76–2.17, p < 0.01), increased weight gain or overweight (OR 1.18, 95%CI 1.11–1.26, p < 0.01), obesity (OR 1.21, 95%CI 1.05–1.40, p < 0.01), juvenile idiopathic arthritis (OR 1.74, 95%CI 1.21–2.52, p < 0.01), psoriasis (OR 1.75, 95%CI 1.44–2.11, p < 0.01), autism spectrum disorders (OR 1.19, 95%CI 1.04–1.36, p = 0.01) and neurodevelopment disorders (OR 1.29, 95%CI 1.09–1.53, p < 0.01). Dose-response effects and stronger effects with broad-spectrum antibiotic were often reported. Antibiotic exposure was not associated with an altered risk of allergic sensitisation, infantile colic, abdominal pain, inflammatory bowel disease, celiac disease, type 1 diabetes, fluorosis, and attention deficit hyperactivity disorder.
Although a causal association cannot be determined from these studies, the results support the meticulous application of sound antibiotic stewardship to avoid potential adverse long-term health outcomes.
Pediatric asthma incidence rates in the United States from 1980 to 2017
2021, Journal of Allergy and Clinical Immunology
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It remains for investigators to consider and evaluate possible reasons for such a change. A strong candidate as 1 such factor is the changing use of antibiotics during early infancy in response to antimicrobial stewardship promotion, an exposure that has been examined in the past with respect to risk of allergies and asthma with conflicting results.62-64 In a 2020 comprehensive article, Patrick et al reported that according to health care administrative data, antibiotic prescribing to children in the province of British Columbia, Canada, who were younger than 1 year had declined by 77% from 1996 to 2016, and from 2000 to 2014, this decline was associated with a significant decrease in asthma diagnoses in children from the age 1 to 4 years.65
Few studies have examined longitudinal asthma incidence rates (IRs) from a public health surveillance perspective.
Our aim was to calculate descriptive asthma IRs in children over time with consideration for demographics and parental asthma history.
Data from 9 US birth cohorts were pooled into 1 population covering the period from 1980 to 2017. The outcome was earliest parental report of a doctor diagnosis of asthma. IRs per 1,000 person-years were calculated.
The racial/ethnic backgrounds of the 6,283 children studied were as follows: 55% European American (EA), 25.5% African American (AA), 9.5% Mexican-Hispanic American (MA) and 8.5% Caribbean-Hispanic American (CA). The average follow-up was 10.4 years (SD = 8.5 years; median = 8.4 years), totaling 65,291 person-years, with 1789 asthma diagnoses yielding a crude IR of 27.5 per 1,000 person-years (95% CI = 26.3-28.8). Age-specific rates were highest among children aged 0 to 4 years, notably from 1995 to 1999, with a decline in EA and MA children in 2000 to 2004 followed by a decline in AA and CA children in 2010 to 2014. Parental asthma history was associated with statistically significantly increased rates. IRs were similar and higher in AA and CA children versus lower but similar in EA and MA children. The differential rates by sex from birth through adolescence principally resulted from a decline in rates among males but relatively stable rates among females.
US childhood asthma IRs varied dramatically by age, sex, parental asthma history, race/ethnicity, and calendar year. Higher rates in the 0- to 4-year-olds group, particularly among AA/CA males with a parental history of asthma, as well as changes in rates over time and by demographic factors, suggest that asthma is driven by complex interactions between genetic susceptibility and variation in time-dependent environmental and social factors.
Dysfunctional microbiota with reduced capacity to produce butyrate as a basis for allergic diseases
2019, Journal of Allergy and Clinical Immunology
Effects of antibiotic residues in milk on growth, ruminal fermentation, and microbial community of preweaning dairy calves
2019, Journal of Dairy Science
The aim of this study was to evaluate the effects of antibiotic residues in milk on growth, ruminal fermentation, and microbial community of dairy calves in their first 35 d of age. Twenty newborn Holstein bull calves were assigned to 1 of 2 treatments equally: milk replacer without antibiotics (control) and milk replacer plus 4 antibiotics: 0.024 mg/L of penicillin, 0.025 mg/L of streptomycin, 0.1 mg/L of tetracycline, and 0.33 mg/L of ceftiofur (ANT). Starter intake and fecal consistency scores of each calf were recorded on a daily basis. Body weight, withers height, body length, and heart girth were measured on d 1, 7, 14, 21, 28, and 35 before feeding in the morning. Rumen fluid was collected on d 15, 25, and 35 to determine ruminal pH, volatile fatty acids (VFA), and NH₃-N concentrations. A total of 10 (5 per treatment) samples of rumen fluid taken on d 35 were analyzed for microbial community. Rumen tissues from the cranial ventral sac and cranial dorsal sac were collected from 8 calves of each group for morphology analysis on d 35 after being harvested. The results showed that calves in 2 treatments had similar starter intake, body weight, withers height, body length, heart girth, and average daily gain. The ANT group showed a lower diarrhea frequency in wk 4, and no differences were found for other weeks. Calves in the ANT group exhibited a greater concentration of acetic acid in the rumen and no differences for other VFA, total VFA, rumen pH, or NH₃-N. As for rumen morphology, the length of papillae from cranial ventral sac of the ANT group was longer than that of the control group. The results of ruminal microbial community showed that antibiotic residues had minor effects on bacteria phyla and bacteria diversity. At the genus level, calves in the ANT group showed lower richness of Prevotella and higher richness of Acetitomaculum. In conclusion, antibiotic residues stimulated the development of ruminal papillae and increased the production of acetic acid in rumen, which might be caused by the influence of antibiotics on the ruminal microbial community.
Intestinal Microbiota in Early Life and Its Implications on Childhood Health
2019, Genomics, Proteomics and Bioinformatics
Trillions of microbes reside in the human body and participate in multiple physiological and pathophysiological processes that affect host health throughout the life cycle. The microbiome is hallmarked by distinctive compositional and functional features across different life periods. Accumulating evidence has shown that microbes residing in the human body may play fundamental roles in infant development and the maturation of the immune system. Gut microbes are thought to be essential for the facilitation of infantile and childhood development and immunity by assisting in breaking down food substances to liberate nutrients, protecting against pathogens, stimulating or modulating the immune system, and exerting control over the hypothalamic–pituitary–adrenal axis. This review aims to summarize the current understanding of the colonization and development of the gut microbiota in early life, highlighting the recent findings regarding the role of intestinal microbes in pediatric diseases. Furthermore, we also discuss the microbiota-mediated therapeutics that can reconfigure bacterial communities to treat dysbiosis.
Antibiotic Use in Early Life, Rural Residence, and Allergic Diseases in Argentinean Children
2017, Journal of Allergy and Clinical Immunology: In Practice
Little is known about differential effects of antibiotic use on allergic diseases in rural versus urban environments.
To examine whether area of residence in the first year of life modifies the relation between antibiotic use in early life and allergic diseases during childhood.
Cross-sectional study of allergic diseases in 1517 children (ages 6-7 years) attending 101 schools in urban and rural areas of San Francisco (Córdoba, Argentina). Current asthma, wheeze, and allergic rhinoconjunctivitis were defined on the basis of responses to a validated questionnaire from the International Study of Asthma and Allergies in Childhood. Multivariate logistic regression was used for the analysis of antibiotic use and allergic diseases.
After adjustment for paracetamol use, bronchiolitis, and other covariates, antibiotic use in the first year of life was associated with increased odds of current wheeze (odds ratio [OR], 1.8; 95% CI, 1.3-2.6) and allergic rhinoconjunctivitis (OR, 1.9; 95% CI, 1.3-2.7). After stratification by area of residence, antibiotic use was associated with current wheeze (OR, 2.4; 95% CI, 1.5-4.0) and allergic rhinoconjunctivitis (OR, 2.1; 95% CI, 1.3-3.4) among children who lived in an urban area in their first year of life, but not among those who lived in a rural area in their first year of life.
Early-life antibiotic use is associated with current wheeze and allergic rhinoconjunctivitis in Argentinean children who lived in urban areas during their first year of life. Exposure to a rural environment early in life may protect against the adverse effects of antibiotics on atopic diseases in children.

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: Supported by US National Institutes of Health (AI24156, AI50681, HL67427, PO3ES06639), the Blue Cross Blue Shield Foundation of Michigan, and the Fund for Henry Ford Hospital.

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Environmental and occupational respiratory disordersAntibiotic exposure in early infancy and risk for childhood atopy

Background

Objective

Methods

Results

Conclusion

Section snippets

Study population and follow-up

Results

Discussion

J Allergy Clin Immunol

Am J Gastroenterol

Lancet

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

Family size, infection and atopy: the first decade of the “hygiene hypothesis”

Thorax

Atopic versus infectious diseases in childhood: a question of balance?

Pediatr Allergy Immunol

Decreasing antibiotic use among US children: the impact of changing diagnosis patterns

Pediatrics

Early childhood infection and atopic disorder

Thorax

Environmental and occupational respiratory disorders
Antibiotic exposure in early infancy and risk for childhood atopy