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Breast Milk: Influence of the Micro-transcriptome Profile on Atopy in Children Over Time

Study Purpose

This is an observational cohort study of 221 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.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.

An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.

Searching Both is inclusive of interventional and observational studies.

Observational [Patient Registry]
Eligible Ages 0 Days - 7 Days
Gender All
More Inclusion & Exclusion Criteria

Inclusion Criteria:

  • - Mothers between the ages of 18 years adn 35 years.
  • - Mothers plan to breast feed for minimum of 16 weeks (cessation of breastfeeding prior to this timepoint will not result in exclusion) - Infants delivered at term (37 - 42 weeks)

    Exclusion Criteria:

    - Maternal morbidities that could affect ability to breastfeed or influence the breast milk micro-transcriptome (eg.
cancer, drug addiction, HIV).
  • - Plan for infant adoption, or family move >150 km from the medical center within 12 months of delivery.
- Presence of congenital anomaly or neonatal condition that significantly affects a newborn's ability to feed (e.g. cleft lip/palate, metabolic disease, or prolonged neonatal intensive care unit (NICU) admission >7 days) - Plan to seek primary pediatric care outside the academic medical center

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.


Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

Milton S. Hershey Medical Center
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Steven Hicks, MD/PhD
Principal Investigator Affiliation Milton S. Hershey Medical Center
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Overall Status Active, not recruiting
Countries United States

The disease, disorder, syndrome, illness, or injury that is being studied.

Atopy, Atopic Dermatitis Eczema, Wheezing, Food Allergy in Infants
Additional Details

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 221 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, the investigators hypothesize that: 1) MBM concentrations of miR-146b, miR-21, miR-148b, 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, the investigators 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, the investigators 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.

Arms & Interventions


: Mother-infant dyads

221 mother-infant dyads enrolled at delivery and followed longitudinally at regularly scheduled well child checks (4, 16, 24, and 48- weeks) at a primary care outpatient pediatric clinic affiliated with an academic medical center. Eligible mothers will be those who plan to breast feed for 16 weeks and infants born at term (37-42 weeks). The cohort will be divided post-hoc into atopic and non-atopic groups based on the primary outcome measure (described below). No intervention will be administered.


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Milton S. Hershey Medical Center, Hershey, Pennsylvania



Milton S. Hershey Medical Center

Hershey, Pennsylvania, 17033

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