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

NCT04017520 | Active Not Recruiting

• 2 other identifiers: STUDY000086575295
• Study Type: observational
• Target: 221
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Atopy; Wheezing; Food Allergy in Infants; Atopic Dermatitis Eczema

Keywords

Atopy; Wheezing; Eczema; Allergy; Food allergies

Outcome Measures

Primary Outcomes (5)

• Atopy

  Infant development of one or more of the following atopic conditions at any point during the first 12 months (48 weeks) after birth: atopic dermatitis, reactive airway (wheezing), or food allergy. When possible specific allergy will be confirmed with IgE serum testing at 48 weeks.

  0-48 weeks after delivery

• Food Allergy

  Food allergy: defined by affirmative parent response to "Has your baby ever had problems caused by food, such as an allergic reaction, sensitivity, or intolerance?" on the Infant Feeding Practices (IFP) Survey, administered at 4, 16, 24, and 48 weeks. Confirmed by serum RAST testing at 48 weeks.

  0-48 weeks after delivery

• Reactive Airway

  Defined by an affirmative parent response to "Has your baby had wheezing in the chest or bronchitis or whistling during his/her first 12 months of life?" on the International Study of Wheezing in Infants (EISL-WQ) Survey, administered at 48 weeks. Confirmed by serum RAST testing with the Northeast Allergen Panel at 48 weeks. Applied to Pediatric Asthma Risk Score criteria.

  0-48 weeks after delivery

• Atopic Dermatitis

  Defined by ICD-10 diagnosis and quantified by SCORing Atopic Dermatitis (SCORAD) Survey at 4, 16, 24, or 48 weeks (\<25: mild, 25-50: moderate, \>50: severe).

  0-48 weeks after delivery

• Cumulative infant exposure to breast milk micro-transcriptome components

  For each infant, exposure to individual small non-coding RNAs that are robustly expressed (counts \> 10 in \>90% of samples with RNA sequencing depth of 5 million reads) in maternal breast milk (MBM) will be calculated as follows (example for hsa-miR-26a): * Exposure in weeks 0-3: Volume of MBM/day x \[miR-26a\] (ppm) x 28 days (or until breastfeeding ceased) x Proportion of feeds consisting of MBM plus... * Exposure in weeks 4-15: Volume of MBM/day x \[miR-26a\] (ppm) x 84 days (or until breastfeeding ceased) x Proportion of feeds consisting of MBM plus... * Exposure in weeks 16-23: Volume of MBM/day x \[miR-26a\] (ppm) x 56 days (or until breastfeeding ceased) x Proportion of feeds consisting of MBM = Total miR-26a exposure (ppm) in the first 6 months

  0-23 weeks after delivery

Secondary Outcomes (14)

• Allergen Exposures

  4-weeks after delivery

• Maternal Diet

  0, 4, and 16-weeks after delivery

• Infant Sleep

  4, 16, 24, and 48-weeks after delivery

• Infant Fussiness

  4-weeks after delivery

• Infant Growth

  0, 4, 16, 24, 48-weeks; 2, 3, 4, and 5 years after delivery

Study Arms (1)

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.

Eligibility Criteria

• Age: 0 Days - 7 Days
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)
• Sampling Method: Non-Probability Sample

Study Population

The study population will be divided post-hoc into two groups based on the presence or absence of infant atopy in the first 12 months after birth (as defined by development of AD, wheezing, or food allergy, by American Academy of Allergy, Asthma, and Immunology guidelines). Given published rates of infant atopy \~30% of infants will experience atopy in the first 12 months. Thus, the projected enrollment of 221 mother-infant dyads should yield 66 atopic infants and 134 non-atopic infants. Drop outs will be replaced. The investigators expect to enroll at least 20% of mother-infant dyads that self-report as racial/ethnic minorities. Equal enrollment of male and female infants is anticipated across atopic and non-atopic groups. To encourage breastfeeding beyond 16 weeks all participants will have access to on-site lactation support at each study visit. A balanced sub-analysis of 66 atopic and 66 non-atopic dyads may be utilized to match for breastfeeding duration and frequency).

You may qualify if:

• Mothers between the ages of 18 years adn 35 years
• Infants delivered at term (37 - 42 weeks)

You may not qualify if:

• 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

Sponsors & Collaborators

• The Gerber Foundation: collaborator
• Milton S. Hershey Medical Center: lead

Study Sites (1)

Milton S. Hershey Medical Center

Hershey, Pennsylvania, 17033, United States

Location

Biospecimen

Retention: SAMPLES WITH DNA

Maternal breast milk (0, 4, 16, 24, and 48 weeks after birth - when available) Infant saliva (0, 4, 16, 24, and 48 weeks after birth) Infant stool (0 and 48-weeks after birth) Maternal saliva (0 weeks after birth)

MeSH Terms

Conditions

Respiratory Sounds; Eczema; Hypersensitivity; Food Hypersensitivity

Condition Hierarchy (Ancestors)

Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Dermatitis; Skin Diseases; Skin and Connective Tissue Diseases; Skin Diseases, Eczematous; Immune System Diseases; Hypersensitivity, Immediate

Study Officials

• Steven Hicks, MD/PhD

  Milton S. Hershey Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 5 Years
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Pediatrics

Study Record Dates

• First Submitted: July 9, 2019
• First Posted: July 12, 2019
• Study Start: January 18, 2018
• Primary Completion: October 30, 2021
• Study Completion (Estimated): December 30, 2028
• Last Updated: January 28, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)