Breast Milk: Influence of the Micro-transcriptome Profile on Atopy in Children and Toddlers

2019-07-16 10:38:31 | BioPortfolio


This is an observational cohort study of 200 breast-feeding mother-infant dyads delivered at term. The goal of the study is to investigate whether levels of immune-related microRNAs (miRNAs) in maternal breast milk (MBM) influence child atopy risk in the first 12 months, defined as atopic dermatitis, wheezing, or food allergy. Infant exposure to individual miRNA components will be quantified at 0, 4, and 16-weeks after delivery using high throughput RNA sequencing of MBM samples and detailed dietary logs employing the Infant Feeding Practices (IFP) survey. The relationship of individual miRNA exposures (parts per million) and presence/absence of atopy in the 48 weeks after delivery will be assessed, while controlling for environmental exposures (National Survey of Lead hazards and Allergens in Housing), maternal diet, and genetic predisposition. Potential transfer of MBM miRNAs to the infant oropharynx and subsequent impact on immune reactivity will also be explored through RNA sequencing of infant saliva and quantification of cytokine profiles.


Atopy is a common condition that often emerges in infancy with atopic dermatitis (AD), wheezing, or food allergies. Atopy results from a heightened immune response to environmental allergens that appears to be imprinted from infancy. The developmental origins that trigger atopic conditions are not completely understood. Exclusive breastfeeding beyond three months has been shown to reduce infant atopy risk, but it is unclear how maternal breast milk (MBM) confers this benefit. One explanation may be microRNAs (miRNAs), non-coding molecules that regulate protein production and are highly concentrated in MBM. In humans with atopic conditions miRNA expression is "altered". Thus, MBM miRNAs packaged within protective vesicles, may be transferred to the infant gut may and functionally incorporated to prime development of the infant immune system.

This study will follow 200 breastfeeding mother-infant dyads for 12 months after birth and examine the relationship between infant MBM miRNA exposure and infant atopy risk.

The goal of this study is to investigate whether levels of immune-related miRNAs in MBM influence infant atopy risk, defined as AD, wheezing, or food allergy in the first 12 months.

The objectives are to: 1) characterize longitudinal changes in immune-related breast milk miRNAs during the first 4 months after birth (when protective benefits are conferred); 2) compare breast milk miRNA profiles between atopic and non-atopic infant-mother dyads; 3) determine whether concentrations of infant saliva miRNAs correlate with MBM levels; 4) explore medical, demographic, and environmental factors that may influence MBM miRNA levels; and 5) examine relationships between saliva miRNAs and cytokines implicated in atopy.

Based on our preliminary studies which identified immune-related miRNAs that are concentrated in MBM and "altered" in the saliva of atopic children, we hypothesize that: 1) MBM concentrations of miR-146b, miR-21, and miR-375 will be disrupted in mothers of atopic infants; and 2) disruptions in these milk miRNAs will correlate with saliva miRNA levels in the infant. Furthermore, we posit that levels of these three miRNAs will be influenced by modifiable maternal/infant factors and correlate with infant cytokine profiles.

Aim 1: will employ a prospective observational cohort design. MBM miRNA will be quantified with RNA sequencing (RNAseq) at 0, 4, and 16 weeks post-delivery and compared with infant atopy status from 4-48 weeks. Sub-analyses will assess MBM miRNA differences across atopy subgroups (AD, wheezing, and food allergy) and examine the relationship between maternal factors (diet, allergen exposure, medical/demographic variables) and MBM miRNA concentrations.

Aim 2: Infant saliva miRNA will be quantified with RNAseq at 24 weeks and compared with: 1) infant atopy status; 2) total MBM miRNA exposure in the first 4-months after birth (ppm/day); 3) infant Th1/Th2 cytokines; and 4) infant immunoglobulin E (IgE) profiles. Sub-analyses will assess the relationship of infant saliva miRNA concentrations to medical/demographic factors, allergen exposures, and infant diet.

Primary outcome measure:

The primary outcome will be infant atopy, defined by standardized measures of AD (Scoring Atopic Dermatitis; SCORAD), wheezing (International Study of Wheezing in Infants Survey; EISL-WQ), and food allergy (Infant Feeding Practices II Survey; IFP) at 4, 16, 24, or 48 weeks. These three atopic conditions were selected because they typify onset of the atopic march (while allergic rhinitis and asthma are typically diagnosed later).

Secondary outcome measures:

1. Cytokines (e.g. Th1 (IFN-γ, IL-2) and Th2 (IL-6, IL-10, IL-13)) in infant saliva and maternal breastmilk at 0, 4, 16, 24, and 48 weeks respectively.

2. Maternal-infant environmental allergen exposures: National Survey of Lead Hazards and Allergens in Housing (NSLAH) at 4 weeks.

3. Infant diet: IFP survey at 4, 16, 24, and 48 weeks.

4. MBM miRNA concentrations: RNAseq at 0, 4, and 16 weeks; normalized reads counts expressed as parts per million (ppm). MBM miRNA concentrations may be determined at 24 and 48 weeks for mothers who continue breastfeeding.

5. Maternal diet: Diet History Questionnaire-II at 0, 4, and 16 weeks.

6. Infant MBM miRNA exposure: determined from MBM miRNA concentrations and IFP survey of breastfeeding patterns. Total infant exposure to MBM miRNAs of interest will be quantified as ppm/day between 0 and 48 weeks.

7. Infant saliva miRNA concentrations: RNAseq at 24 weeks.

8. Infant allergen-specific IgE at 48 weeks (atopic infants only).

9. Infant weight trajectory (retrospective review of growth charts) through 5 years of age

10. Infant developmental trajectory (Survey of Wellbeing in Young Children) at 9 months, 18-months, and 30 months.

11. Presence or absence of infant atopic conditions through 5 years of age

12. Infant Colic (Modified Infant Colic Scale) at 4 weeks

13. Infant Sleep (Brief Infant Sleep Questionnaire) at 4, 16, 24, and 48 weeks.

Though several studies have described the miRNA composition of MBM, this will be among the first to examine how breast milk miRNA levels relate to infant health outcomes. This study will improve our understanding of how nutritional miRNA impacts developmental origins. Using the paradigm of infant atopy, we will identify individual MBM miRNAs associated with AD, wheezing, and food allergy. This knowledge may be used to provide anticipatory guidance for breastfeeding mothers regarding the factors that impact their child's atopy risk, or to improve infant formula composition to curb atopy risk.

Study Design




Milton S. Hershey Medical Center
United States




Milton S. Hershey Medical Center

Results (where available)

View Results


Published on BioPortfolio: 2019-07-16T10:38:31-0400

Clinical Trials [25 Associated Clinical Trials listed on BioPortfolio]

Use Cord Blood Single Nucleotide Polymorphism to Predict the Later Development of Atopy and Allergy

The aim of our study was firstly to detect in cord bloods the polymorphism of genes related to atopy and allergic diseases and to examine their mutual interaction and their associations wi...

Markers of Atopy in Children With Presumed Early Exposure to Allergens, Unhygienic Conditions, and Infections

There are many studies regarding possible causes of increasing trend in frequency of allergic diseases in the last three decades. Main causes of this trend are: decrease of infectious dise...

Atopy Patch Test in Normal Population : Pilot Study

Atopy patch test in normal population

MAPS & ITEC Cohorts: 6-8 Years Follow-up

This study represents the follow-up, age 6-8 years, of children recruited at birth into two cohorts. The first cohort, the Mite Allergen Prevention Study (MAPS) was a double-blind, randomi...

The Effects of PG102, a Water Soluble Extract From Actinidia Arguta, on Serum Total IgE Levels

The aim of this study was to evaluate the efficacy of PG102 at lowering levels of total IgE in asymptomatic subjects with atopy.

PubMed Articles [36 Associated PubMed Articles listed on BioPortfolio]

DNA methylation in nasal epithelium, atopy, and atopic asthma in children: a genome-wide study.

Epigenetic mechanisms could alter the airway epithelial barrier and ultimately lead to atopic diseases such as asthma. We aimed to identify DNA methylation profiles that are associated with-and could ...

Atopy and Sensitization to Allergens Known to Cause Systemic Contact Dermatitis.

Atopic dermatitis (AD) associated with respiratory atopy may represent a form of systemic contact dermatitis (SCD), whereby AD flares after ingestion or inhalation of allergens.

Associations between fungal and bacterial microbiota of airways and asthma endotypes.

The relationship between asthma, atopy and underlying type-2 (T2) airway inflammation is complex. While the bacterial airway microbiota is known to differ in asthmatic patients, the fungal and bacteri...

Age at cytomegalovirus, Epstein Barr virus and varicella zoster virus infection and risk of atopy: the Born in Bradford cohort, UK.

The prevalence of allergic diseases has increased in recent decades but the causes remain unclear. Changes in the epidemiology of childhood infections could have contributed but the current evidence i...

DNA methylation signatures of atopy and asthma.

Medical and Biotech [MESH] Definitions

None available.

More From BioPortfolio on "Breast Milk: Influence of the Micro-transcriptome Profile on Atopy in Children and Toddlers"

Quick Search


Relevant Topics

Breast Cancer
Track and monitor developments in breast cancer research and commercial development.  Follow the tabs above to read the latest global news, research, clinical trials on breast cancer and follow companies active in the development of breast cancer tr...

Pediatrics is the general medicine of childhood. Because of the developmental processes (psychological and physical) of childhood, the involvement of parents, and the social management of conditions at home and at school, pediatrics is a specialty. With ...

Eczema is a common itchy skin disease characterized by reddening and vesicle formation, which may lead to weeping and crusting. It is endogenous, or constitutional. There are five main types; atopic, seborrhoeic, discoid, gravitational or varicose. ...

Searches Linking to this Trial