Breast Milk: Influence of the Micro-transcriptome Profile on Atopy in Children and Toddlers
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 入组人数
- 221
- 试验地点
- 1
- 主要终点
- Atopy
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 0 Days 至 7 Days（Child）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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)
排除标准
- •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
研究组 & 干预措施
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.
结局指标
主要结局
Atopy
时间窗: 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.
Atopic Dermatitis
时间窗: 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
时间窗: 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
Reactive Airway
时间窗: 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.
Food Allergy
时间窗: 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.
次要结局
- Infant saliva micro-transcriptome(0, 4, 16, 24, and 48-weeks after delivery)
- Infant Development(9, 18, and 30-months after delivery)
- Long-term Child Atopy(2, 3, 4, and 5 years after birth)
- Infant IgE(48-weeks after delivery)
- Infant stool micro-transcriptome(0-weeks and 48-weeks after delivery)
- Infant cytokines(24-weeks after delivery)
- Infant genetics(48-weeks after delivery)
- Infant Growth(0, 4, 16, 24, 48-weeks; 2, 3, 4, and 5 years after delivery)
- Maternal breast milk cytokines(4-weeks, 16-weeks, 24-weeks)
- Maternal genetics(0-weeks after delivery)
- 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)
研究者
Steven Hicks
Assistant Professor of Pediatrics
Milton S. Hershey Medical Center