Vaginal Microbiome Exposure and Immune Responses in C-section Infants

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.

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*).

Exclusion Criteria:

For C-Section Mothers:

- In labor with evidence of cervical change prior to the scheduled C-section;

- Rupture of the amniotic sac; or

- Vaginal pH > 4.5 on the day of delivery.

For Vaginal Delivery Mothers:

- Use of induction agents for cervical ripening (cervical prostaglandin or Foley catheter).

For All Mothers and Their Infants:

- Inability or unwillingness of a participant to give written informed consent or comply
with study protocol;

- History of active atopic dermatitis within the past 5 years in the mother;

- Express no intention to breastfeed;

- History of diabetes mellitus or gestational diabetes mellitus;

- History of inflammatory bowel disease (IBD) (e.g., Crohn's Disease or ulcerative
colitis);

- Evidence of an active sexually transmitted infection (STI) (e.g., primary herpes or
genital warts, or trichomonas), yeast infection, or vaginosis on the day of delivery;

- Evidence of prior or current hepatitis B or C infection as demonstrated by the
presence of the hepatitis B surface antigen, antibody positivity against the hepatitis
B core antigen, or antibody positivity against the hepatitis C virus;

--Assessment for active hepatitis B and hepatitis C infection will be repeated for
this study even if prior testing during the current pregnancy was negative;

- Evidence of Human Immunodeficiency Virus (HIV) infection (e.g., positive HIV serology
or detectable viral load);

- Positive Group B Streptococcus (GBS) test results by rectovaginal swab performed
within 5 weeks of delivery, a prior infant with invasive GBS disease, or GBS
bacteriuria at any point during pregnancy;

- Evidence of N. gonorrhoeae or C. trachomatis infection by testing performed within 5
weeks of delivery;

- History of antibiotic administration during the third trimester of the current
pregnancy;

- Mothers with serious chronic conditions during pregnancy;

- Mothers with complicated pregnancies including pre-eclampsia, chorioamnionitis,
placenta previa, vasa previa, placental abruption, or active vaginal bleeding;

- Maternal fever on the day of delivery (visit 0);

- Infants with complications during delivery, such that the infant requires more than
the standard neonatal resuscitation after delivery;

- Infants delivered prior to 37 weeks of gestation;

- Thick particulate meconium noted upon delivery of the infant;

- Presence of a congenital abnormality in the infant for which study participation is
not recommended;

- Current, diagnosed mental illness or current, diagnosed or self-reported drug or
alcohol abuse in the mother that, in the opinion of the investigator, would interfere
with the participant's ability to comply with study requirements;

- Use of investigational drugs during the third trimester of pregnancy; or

- Past or current medical problems or findings from physical examination or laboratory
testing that are not listed above, which, in the opinion of the investigator may:

- Pose additional risks from participation in the study,

- Interfere with the participant's ability to comply with study requirements, or

- May impact the quality or interpretation of the data obtained from the study.