Vaginal Microbiome Seeding and Health Outcomes in Cesarean-delivered Neonates.

Cesarean section (CS) delivery is a common surgical procedure intended to increase the
chances of successful delivery and to protect the health of the mother and baby. Yet this
intervention is overused and has been associated with higher risk of immune and metabolic
disorders in the offspring. It is hypothesized that these associations are due to
CS-delivered newborns not receiving the full inoculum of maternal microbes at birth.

While restoring labor is not possible, restoring the microbes that colonize infants during
birth through exposure to vaginal flora, is feasible, and has been shown in a small pilot
study, to normalize the microbiota of the intestine, skin and mouth during the first month of
life.

The investigators hypothesize that the restoration of the vaginal microbiota to the infant at
birth will restore the infant microbiome and decrease the risk of obesity and other
immune-mediated diseases linked with CS. The investigators aim to test this hypothesis in a
randomized controlled trial by first examining the effect of vaginal seeding, in CS-delivered
newborns, on the gut microbiota composition, structure and function (Phase I of study; first
50 infants) and then on the BMI z score and other immune-mediated outcomes (Phase II of
study; 600 infants).

Methods: CS-delivered neonates will be randomized to either an experimental arm with exposure
to the maternal vaginal microbiota at birth, or a control arm with no exposure. Feces, skin
and vaginal swabs will be collected for microbiome analysis. The investigators will obtain
clinical information from in-person visits, surveys and the electronic health record.

Implications: this randomized controlled clinical study will provide evidence of whether the
"vaginal seeding" procedure can safely transfer microbes from mom-to-baby, and whether these
microbes are beneficial for the metabolic and immune health of the child.

Inclusion Criteria for Mother:

- Scheduled for cesarean delivery at >/= 37 weeks

- Pregnant with single fetus, in good general health, age 18 years or older

- Negative maternal testing for infections transmitted through vaginal and/or other body
fluids performed as standard of care tests in early pregnancy

- Negative testing for GBS at 35-37 weeks gestation

- Vaginal pH < 4.5 indicative of Lactobacillus-dominated vaginal microbiota

- No maternal or fetal complications that may inhibit the ability to perform microbiome
restoration per protocol

- English or Spanish speaking

Inclusion Criteria for Infant:

-Infant condition after delivery requires no more than standard neonatal resuscitation* or
is otherwise medically unable to receive the full VMT procedure

*Standard neonatal resuscitation may include: tactile stimulation, bulb suction, oxygen
without positive pressure and drying

Exclusion Criteria for Mother:

- Delivery at a hospital other than Inova Health System

- Systemic medication for immunosuppression including biological agent within three
months of cesarean delivery (exclusive of medications used for non-immunosuppressive
purposes - e.g. betamethasone for fetal lung maturation)

- CD scheduled for active infection that would have interfered with vaginal delivery
such as genital herpetic lesions

- Onset of labor or rupture of membranes prior to scheduled CD

- Bacterial vaginosis

- Symptomatic urinary tract infection

- Antibiotic therapy within 30 days of cesarean delivery (exclusive of medication use
for prophylaxis at the time of surgery)

- Symptoms on admission suggesting Chorioamnionitis, e.g. maternal fever, fundal
tenderness

- Symptoms on delivery admission of possible vaginal infection such as genital herpetic
lesions

- History positive testing for GBS infection

- History of a child with a diagnosis of GBS sepsis

- Pregnancy a result of donor egg or surrogacy

- Preexisting history of Type I or Type II Diabetes