AtopyIMPACTNCT04017520
Breast Milk: Influence of the Micro-transcriptome Profile on Atopy in Children Over Time
An observational study of Atopy and Atopic Dermatitis Eczema, run by Milton S. Hershey Medical Center at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 0 to 7 daysHealthy volunteers can take part
- Conditions the study is for
- Atopy, Atopic Dermatitis Eczema, Wheezing
- How many people
- 221 participants
- Where
- 1 siteUnited States
- Study dates
- 18 Jan 2018to 30 Dec 2028
- How long will I take part?
- 5 Years
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 0 to 7 days
- All sexes
- Healthy volunteers accepted
- Child
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).
Who may be able to join
- 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)
Who cannot join
- 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 locations and contacts
1 site in 1 country.
United States1 site
Milton S. Hershey Medical Center
Hershey, Pennsylvania, 17033
About this study
Official title: Breast Milk: Influence of the Micro-transcriptome Profile on Atopy in Children and Toddlers
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.
Read the detailed description
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:
- 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.
- Maternal-infant environmental allergen exposures: National Survey of Lead Hazards and Allergens in Housing (NSLAH) at 4 weeks.
- Infant diet: IFP survey at 4, 16, 24, and 48 weeks.
- 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.
- Maternal diet: Diet History Questionnaire-II at 0, 4, and 16 weeks.
- 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.
- Infant saliva miRNA concentrations: RNAseq at 24 weeks.
- Infant allergen-specific IgE at 48 weeks (atopic infants only).
- Infant weight trajectory (retrospective review of growth charts) through 5 years of age
- Infant developmental trajectory (Survey of Wellbeing in Young Children) at 9 months, 18-months, and 30 months.
- Presence or absence of infant atopic conditions through 5 years of age
- Infant Colic (Modified Infant Colic Scale) at 4 weeks
- 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.
- Conditions
- Atopy, Atopic Dermatitis Eczema, Wheezing, Food Allergy in Infants
- Keywords
- Atopy, Wheezing, Eczema, Allergy, Food allergies
- Medical subject headings
- Respiratory Sounds, Eczema, Hypersensitivity, Food Hypersensitivity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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).
Measured: 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
Measured: 0-23 weeks after delivery
Secondary outcomes (14)
Allergen Exposures
Documented for mother-infant dyads at 4-weeks post delivery using the National Survey of Lead hazards and Allergens in Housing (NSLAH) Survey, developed by the Department of Housing and Urban Development in coordination with the National Institute of Environmental Health. The survey asks about the age of housing, number of occupants, heating source, and the presence/absence of air conditioning, air filtration system, mold/mildew, dehumidifier, pets, cockroaches, mice/rats, and cigarette smokers in the home.
Measured: 4-weeks after delivery
Maternal Diet
Documented at 0, 4, and 16 weeks using a modified version of the Diet History Questionnaire (DHQ), developed by the National Cancer Institute. Briefly, the survey measures servings of: hot/cold cereals, milk, soda, fruit juice, coffee/tea, sweetened fruit/sports drinks, fruit, green leafy vegetables, fried potatoes, other potatoes, beans, rice, salsa, pizza, tomatoes, cheese, red meat, processed meat, bread, chocolate, doughnuts/muffins, baked goods, ice cream, and pop-corn. Responses are recorded as: never, once per month, 2-3 times per month, once per week, 2 times per week, 3-4 times per week, once per day, 2-3 times per day, and 3-4 times or more per day.
Measured: 0, 4, and 16-weeks after delivery
Infant Sleep
The Brief Infant Sleep Questionnaire (BISQ) will be administered at 4, 16, 24, and 48-weeks. Nine qualitative questions about infant sleep practices are recorded, including: sleeping arrangement, sleep position, time spent during sleep (in hours), time spent in daytime sleep (in hours), average number of night time awakenings, amount of night-time wakefulness, sleep onset latency, mode of sleep initiation, time of sleep initiation. Affirmative parental response to, "Do you consider your child's sleep to be a problem?" will be used to dichotomize those with atypical sleep habits.
Measured: 4, 16, 24, and 48-weeks after delivery
Infant Fussiness
A modified version of the Infant Colic Scale (ICS) will be administered at 4-weeks. This modified scale assesses 12 items on a six point Likert scale (strongly disagree, disagree, slightly disagree, slightly agree, agree, strongly agree). A higher score portends greater likelihood of colic, with average score across the 12 items of >2.9 being consistent with colic. Questions generally assess gastrointestinal symptoms, infant temperament, and parent-infant interaction.
Measured: 4-weeks after delivery
Infant Growth
Weight for length z-score will be recorded from the electronic medical record at 0, 4, 16, 24, and 48 weeks, as well as 2, 3, 4, and 5 years after delivery. The change in weight for length z-score from 0-48 weeks will be the primary outcome, where a positive z-score change will indicate relative weight increase, and a negative z-score change will indicate relative weight decrease.
Measured: 0, 4, 16, 24, 48-weeks; 2, 3, 4, and 5 years after delivery
Infant Development
Survey of Wellbeing in Young Children (SWYC) scores will be abstracted from the electronic medical record at 9, 18, and 30-months. Children with a total score <12 (at 9-months of age), <9 (at 18-months of age), or <11 (at 30-months of age) will be defined as those with potential developmental delays.
Measured: 9, 18, and 30-months after delivery
Long-term Child Atopy
Child development of one or more of the following atopic conditions at any point during the first 5 years after birth:
- Atopic dermatitis
- Wheezing
- Food allergy
- Allergic rhinitis
- Allergic conjunctivitis
- Asthma
All defined by clinical documentation in the child's medical problem within the electronic medical record.
Measured: 2, 3, 4, and 5 years after birth
Infant stool micro-transcriptome
Small non-coding RNAs (including bacterial RNAs) will be quantified in stool from each infant at 0-weeks and 48-weeks using high throughput RNA sequencing.
Measured: 0-weeks and 48-weeks after delivery
Infant saliva micro-transcriptome
Small non-coding RNAs (including bacterial RNAs) will be quantified in saliva from each infant at 0, 4, 16, 24, and 48-weeks using high throughput RNA sequencing.
Measured: 0, 4, 16, 24, and 48-weeks after delivery
Infant cytokines
TH1 and TH2 cytokines, including CCL5, IFN-gamma, IL-1, IL-4, IL-5, IL-6, IL-8, IL-10, IL-13, eotaxin, TNF-alpha, TGF-beta-1, and TGF-beta-2 will be measured in infant saliva using a luminex assay.
Measured: 24-weeks after delivery
Maternal breast milk cytokines
T-helper (TH-)1 and TH-2 cytokines, including C-C Motif Chemokine Ligand (CCL)-5, interferon (IFN)-gamma, interleukin (IL)-1, IL-4, IL-5, IL-6, IL-8, IL-10, IL-13, eotaxin, tumor necrosis factor (TNF)-alpha, transforming growth factor (TGF)-beta-1, and TGF-beta-2 will be measured in maternal breast milk using a luminex assay. Serotonin and melatonin will also be interrogated.
Measured: 4-weeks, 16-weeks, 24-weeks
Infant genetics
Deoxy-ribonucleic acid will be extracted from infant saliva for interrogation of single nucleotide polymorphisms and copy number variants related to atopy risk.
Measured: 48-weeks after delivery
Maternal genetics
Deoxy-ribonucleic acid will be extracted from maternal saliva for interrogation of single nucleotide polymorphisms and copy number variants related to atopy risk.
Measured: 0-weeks after delivery
Infant IgE
Specific IgEs will be measured in the serum of all infants who meet atopy criteria at 48-weeks, including 1) aeroallergens (bermuda grass, timothy grass, cockroach, penicillium notatum, cladosporium herbarum, aspergillus fumigatus, mucor racemosus, alternaria tenuis, box elder maple, common silver birch, oak, elm, walnut tree, maple leaf sycamore, cottonwood poplar, white ash, mulberry, red cedar, ragweed, mugwort, pigweed, sheep sorrel, cat dander, dog dander, mouse); 2) food allergens (cow's milk, wheat, almond, shrimp, egg yolk, egg white, codfish, sesame seed, soybean, hazelnut, tuna, salmon, scallop, pecan, cashew, walnut, and peanut); and 3) total IgE.
Measured: 48-weeks after delivery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jul 2019
- Study start18 Jan 2018
- Primary completion30 Oct 2021
- Study completion30 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for AtopyStudies of the same condition, open and under way.
- More trials run by Milton S. Hershey Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 221 participants (actual)
- Target duration
- 5 Years
Sponsor and investigators
- Lead sponsor
- Milton S. Hershey Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- The Gerber Foundation
- Responsible party
- Principal investigator, Steven Hicks, Milton S. Hershey Medical Center
- Investigators
- Steven Hicks, MD/PhD, Principal investigator, Milton S. Hershey Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04017520
- Sponsor's protocol ID
- STUDY00008657
- Other IDs
- 5295
- Acronym
- IMPACT
- Status last verified
- Jan 2026
- First submitted
- 9 Jul 2019
- Last updated
- 28 Jan 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: There is a plan to share high throughput RNA sequencing data as de-identified fastq files linked with basic medical and demographic data through the Short Read Archive.
Publications
Van Syoc E, Stegman M, Sullivan R, Confair A, Warren K, Hicks SD. Associations of Maternal Breastmilk microRNAs and Infant Obesity Status at 1 Year. Genes (Basel). 2024 Jun 20;15(6):813. doi: 10.3390/genes15060813.
PubMed 38927748Massare BA, Irvin CN, Hicks SD. Increased Sleep Latency and Decreased Sleep Duration are Associated With Elevated Risk of Bed Sharing Among Mother-Infant Dyads. Clin Pediatr (Phila). 2024 Jun;63(5):708-713. doi: 10.1177/00099228231188211. Epub 2023 Jul 24.
PubMed 37488931
Study at a glance
From the registry record, last updated by the sponsor on 28 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Breast Milk: Influence of the Micro-transcriptome Profile on Atopy in Children and Toddlers
- ClinicalTrials.gov ID
- NCT04017520
- Acronym / sponsor ID
- IMPACT / STUDY00008657
- Conditions
- Atopy, Atopic Dermatitis Eczema, Wheezing, Food Allergy in Infants
- Keywords
- Atopy, Wheezing, Eczema, Allergy, Food allergies
- Study type
- Observational
- Recruitment status
- Active, not recruiting
- Enrolment
- 221 participants (actual)
- Lead sponsor
- Milton S. Hershey Medical CenterUniversity, hospital or other
- Collaborators
- The Gerber Foundation
- Study start
- 18 Jan 2018 (actual)
- Primary completion
- 30 Oct 2021 (actual)
- Study completion
- 30 Dec 2028 (estimated)
- First posted
- 12 Jul 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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:
- 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.
- Maternal-infant environmental allergen exposures: National Survey of Lead Hazards and Allergens in Housing (NSLAH) at 4 weeks.
- Infant diet: IFP survey at 4, 16, 24, and 48 weeks.
- 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.
- Maternal diet: Diet History Questionnaire-II at 0, 4, and 16 weeks.
- 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.
- Infant saliva miRNA concentrations: RNAseq at 24 weeks.
- Infant allergen-specific IgE at 48 weeks (atopic infants only).
- Infant weight trajectory (retrospective review of growth charts) through 5 years of age
- Infant developmental trajectory (Survey of Wellbeing in Young Children) at 9 months, 18-months, and 30 months.
- Presence or absence of infant atopic conditions through 5 years of age
- Infant Colic (Modified Infant Colic Scale) at 4 weeks
- 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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 5 Years
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 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. |
Who may qualify
- Ages
- 0 to 7 days
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
- 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).
Key inclusion criteria (3 listed)
- 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)
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Atopy
Time frame: 0-48 weeks after delivery
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.
Food Allergy
Time frame: 0-48 weeks after delivery
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.
Reactive Airway
Time frame: 0-48 weeks after delivery
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.
Atopic Dermatitis
Time frame: 0-48 weeks after delivery
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).
Cumulative infant exposure to breast milk micro-transcriptome components
Time frame: 0-23 weeks after delivery
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
14 secondary outcomes
Allergen Exposures
Time frame: 4-weeks after delivery
Maternal Diet
Time frame: 0, 4, and 16-weeks after delivery
Infant Sleep
Time frame: 4, 16, 24, and 48-weeks after delivery
Infant Fussiness
Time frame: 4-weeks after delivery
Infant Growth
Time frame: 0, 4, 16, 24, 48-weeks; 2, 3, 4, and 5 years after delivery
Infant Development
Time frame: 9, 18, and 30-months after delivery
Long-term Child Atopy
Time frame: 2, 3, 4, and 5 years after birth
Infant stool micro-transcriptome
Time frame: 0-weeks and 48-weeks after delivery
Infant saliva micro-transcriptome
Time frame: 0, 4, 16, 24, and 48-weeks after delivery
Infant cytokines
Time frame: 24-weeks after delivery
Maternal breast milk cytokines
Time frame: 4-weeks, 16-weeks, 24-weeks
Infant genetics
Time frame: 48-weeks after delivery
Maternal genetics
Time frame: 0-weeks after delivery
Infant IgE
Time frame: 48-weeks after delivery
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jan 2026.
- Derived from this study: PubMed 38927748Van Syoc E, Stegman M, Sullivan R, Confair A, Warren K, Hicks SD. Associations of Maternal Breastmilk microRNAs and Infant Obesity Status at 1 Year. Genes (Basel). 2024 Jun 20;15(6):813. doi: 10.3390/genes15060813.
- Derived from this study: PubMed 37488931Massare BA, Irvin CN, Hicks SD. Increased Sleep Latency and Decreased Sleep Duration are Associated With Elevated Risk of Bed Sharing Among Mother-Infant Dyads. Clin Pediatr (Phila). 2024 Jun;63(5):708-713. doi: 10.1177/00099228231188211. Epub 2023 Jul 24.
- Individual participant dataSharing planned: No. There is a plan to share high throughput RNA sequencing data as de-identified fastq files linked with basic medical and demographic data through the Short Read Archive.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Steven Hicks, MD/PhD principal investigator
Milton S. Hershey Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Atopy and Atopic Dermatitis Eczema, run by Milton S. Hershey Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 28 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Atopy (time frame: 0-48 weeks after delivery). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04017520, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jan 2026.