Allergic Diseases, Asthma
Conditions
Keywords
Vaginal seeding, Immune responses, Allergen sensitization
Brief summary
The purpose of this research study is to assess at how differences in the microbiome (naturally occurring bacteria) of a baby may protect, or put a baby at risk, for allergic problems. The microbiome refers to the thousands of bacteria and molds that live in and on our bodies. The microbiome plays an important role in our health. Differences in the microbiome can affect our immune system in ways that might make some people more likely to get allergies and asthma. Early life events and exposures are very important for establishing the human microbiome. The newborn baby's microbiome changes very quickly during the first weeks and months of life. There is information that suggests C-section birth is associated with higher risk of certain diseases, including allergies and asthma. Some researchers think one reason for this is that passing through the mother's vaginal canal during birth exposes the baby to bacteria that promote healthy immune system development, something that C-section babies don't get. Transferring these potentially beneficial vaginal bacteria to C-section babies may help prevent some diseases later.
Detailed description
This is a pilot study of 120 pregnant women and their infants conducted at hospitals in the Mount Sinai Health System in New York, NY. Eighty women will deliver via elective, unlabored C-section, and 40 will undergo spontaneous vaginal delivery. The 80 women undergoing C-section will be randomized in a masked (blinded) 1:1 fashion to have their neonates undergo vaginal seeding or placebo seeding immediately after birth (within 10 minutes) followed by standard care.The infants of the 40 women undergoing spontaneous vaginal delivery will receive usual standard care. All 120 pregnant women will have biospecimens collected to assess their vaginal, skin, gut, placental, breast milk, and oral microbiome. All infants will have biospecimens collected to assess their gut, skin, nasal, and oral microbiome, as well as blood to assess allergen sensitization and immune markers. Infants will be followed with at-home stool collections and questionnaires weekly for the first 4 weeks and at weeks 8, 26, and 39. An in-person study visit will occur at 13 weeks and 52 weeks, and the primary endpoint will be assessed at 52 weeks. Study enrollment is projected to occur over 24 months.
Interventions
DRUGVaginal seeding
Mother-infant pair randomized to vaginal microbiota intervention. As soon as the infant is delivered, the infant will be brought to the neonate lamp, and unless the obstetrician or pediatric staff believes it is not in the best interest of the infant, s/he will be swabbed with the vaginal microbiota soaked gauze. Swabbing will take place ideally within 1 minute after delivery (but no longer than 5 minutes). The swabbing should take approximately 15 seconds. Infants will only undergo the seeding procedure once.
DRUGPlacebo Seeding
Mother-infant pair randomized to placebo microbiota intervention. As soon as the infant is delivered, the infant will be brought to the neonate lamp, and unless the obstetrician or pediatric staff believes it is not in the best interest of the infant, s/he will be swabbed with the placebo gauze. Swabbing will take place ideally within 1 minute after delivery (but no longer than 5 minutes). The swabbing should take approximately 15 seconds. Infants will only undergo the seeding procedure once.
OTHERStandard care
Mother-infant pair, with both receiving standard of care which includes standard physical exams, vital signs monitoring and medication administration given as standard care for the delivery
OTHERPost-seeding Care
Following the seeding procedure, infants will then receive the standard detailed examination for newborns and standard of care, except that the first infant bath will occur at least 12 hours after delivery.
Sponsors
Immune Tolerance Network (ITN)
PPD Development, LP
Rho Federal Systems Division, Inc.
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
With the exception of the study nurse performing the vaginal seeding procedure, all study participants and study personnel will be masked (blinded) to the infant's randomization status.
Intervention model description
This study will enroll pregnant women during the third trimester of pregnancy whose infants have a first-degree relative ( the mother, biological father, or full sibling) with atopic disease or food allergy.The study excludes women with a history of active atopic dermatitis within the past 5 years to avoid the potential transfer of vaginal microbiota to the infant that may predispose to atopic disease.Women undergoing elective, unlabored C-section will be randomized to have their infants undergo vaginal seeding or placebo seeding plus standard of care. Women and infants who undergo placebo seeding will serve as a control population.In addition, women and infants undergoing vaginal delivery will also be included as a second control group, in part to determine if vaginal seeding will decrease allergen sensitization rates to a level similar to vaginally delivered infants, and also to serve as a comparator group for gut microbiome development during the infant's first year of life.
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 45 Years
Healthy volunteers
No
Inclusion criteria
* Pregnant woman must be able to understand and provide informed consent; * Pregnant women with singleton pregnancies with a non-anomalous, appropriately-grown fetus; and * Atopic disease (asthma, allergic rhinoconjunctivitis, or atopic dermatitis) or food allergy in a first-degree relative of the infant to-be-delivered (for exception, see
Exclusion criteria
\*).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Presence of Sensitization to at Least One Food Allergen at 12 months of age - by Treatment Group | Infants at 12 months of age (=Month 12 visit) | Evaluation for the presence of food allergens (egg, milk, and peanut) in infants at 12 months of age. Sensitization is defined by a serum IgE ≥ 0.1 kUA/mL for each allergen. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Presence of Sensitization to at Least One Aeroallergen at 12 months of age - by Treatment Group | Infants at 12 months of age (=Month 12 visit) | Evaluation for the presence of aeroallergens (house dust mite (Dermatophagoides pteronyssinus), cat (Felis domesticus), and/or cockroach (Blattella germanica)), in infants at 12 months of age as determined by serum IgE assessment. Sensitization is defined by a serum IgE ≥ 0.1 kUA/mL for each allergen. |
| Level of Allergen-Specific Atopy at 12 months of age - by Treatment Group | Infants at 12 months of age (=Month 12 visit) | Defined by serum IgE levels. Sensitization is defined by a serum IgE ≥ 0.1 kUA/mL for each allergen. The following allergen-specific IgE levels will be included: egg, milk, peanut, house dust mite (Dermatophagoides pteronyssinus), cat (Felis domesticus) and cockroach (Blattella germanica). |
| Occurrence of Adverse Events (AEs) -by Treatment Group | From birth to 12 months of age (=Month 12 visit) | Adverse events reported as possibly related, probably related, or definitely related to study participation. |
| Number of Food Allergens and Aeroallergens Each Infant is Sensitized to at 12 Months of Age-by Treatment Group | Infants at 12 months of age (=Month 12 visit) | Defined by serum IgE levels. Sensitization is defined by a serum IgE ≥ 0.1 kUA/mL. |
| Severity of Atopic Dermatitis - by Treatment Group | Infants at 3 months and 12 months of age (=Month 3 and -12 visits) | Severity will be measured using the Eczema Area and Severity Index (EASI), a standardized investigator-assessed instrument. |
| Level of Combined Allergen-Specific Atopy at 12 Months of Age - by Treatment Group | Infants at 12 months of age (=Month 12 visit) | Defined as the sum of the serum IgE levels to: egg, milk, peanut, house dust mite (Dermatophagoides pteronyssinus), cat (Felis domesticus), and cockroach (Blattella germanica). Necessary for inclusion in this outcome measure: Available results for all six allergen-specific IgE levels. |
Other
| Measure | Time frame | Description |
|---|---|---|
| EXPLORATORY: Evaluation of the Maternal Vaginal Microbiome Transfer | Infants at 12 months of age (=Month 12 visit) | Skin and oral samples from mothers and infants will be profiled to determine the extent of transfer from the mother to the infant gut microbiota. |
| EXPLORATORY: Comparison by Treatment Group in Bacterial Composition of the Infant Microbiome | Infants at 12 months of age (=Month 12 visit) | Microbiome composition will be examined initially by 16S rRNA sequencing in order to determine the bacterial communities present in samples, their relative abundance, and overall diversity. Samples: gastrointestinal, oral, skin and nasal samples. |
| EXPLORATORY: Comparison by Treatment Group in Transepidermal Water Loss (TEWL) | Month 3 and month 12 Follow-up Visits | TEWL skin barrier assessment is a noninvasive in vivo measurement of water loss across the stratum corneum that is used to characterize skin water barrier function. |
| EXPLORATORY: Comparison by Treatment Group in Fungal Composition of the Infant Microbiome | Infants at 12 months of age (=Month 12 visit) | Microbiome composition will be examined initially by 16S rRNA sequencing in order to determine the fungal communities present in samples, their relative abundance, and overall diversity. Samples: gastrointestinal, oral, skin and nasal samples. |
| EXPLORATORY: Comparison by Treatment Group in T Cell Profiles | Infants at 12 months of age (=Month 12 visit) | Evaluation of differences by treatment group in Th2 cell and Treg populations. |
| EXPLORATORY: Comparison by Treatment Group in Innate Immune System Profiles | Infants at 12 months of age (=Month 12 visit) | Evaluation of differences by treatment group in pro-inflammatory cytokine production. |
| EXPLORATORY: Comparison by Treatment Group in the Composition of Metabolites of the Fecal Metabolome | Infants at day of delivery and months 3, -6, -9 and -12 | Qualitative assessment: Fecal samples will be assessed to evaluate differences in profile of pro-inflammatory metabolites. |
| EXPLORATORY: Comparison by Treatment Group in the Concentration of Metabolites of the Fecal Metabolome | Infants at day of delivery and months 3, -6, -9 and -12 | Quantitative assessment: Fecal samples will be assessed to evaluate differences in the amount of profiled pro-inflammatory metabolites. |
| EXPLORATORY: Comparison by Treatment Group in Immunomodulatory Influences of the Fecal Metabolome | Infants at day of delivery through month 12 | An exploration of how vaginal seeding influences subsequent development of the infant microbiome for the first 12 months of life. |
Countries
United States
Outcome results
None listed