Umbilical Cord Milking in Non-Vigorous Infants - NIRS Sub-study (MINVI_NIRS)

Rationale: Caregivers and researchers raised theoretical concerns that the UCM technique may
deliver blood rapidly toward a non-vigorous newborn predisposing them to higher rates of
brain injury or dislodging cellular debris into the brain. However, of the 13 studies on term
infants comparing UCM to ECC, none have reported adverse outcomes. Even in more fragile
preterm infants, no harm has been reported. All demonstrated improvements similar to DCC with
increased red cell mass (measured by hematocrit or hemoglobin) improved blood pressure,
increased pulmonary blood flow and improved ferritin at 6 weeks to 6 months of age with UCM.
Nevertheless, careful assessment of safety is essential. Immediate physiological measurements
on a subset (n=200) of infants of the two sub-study sites where the use of NIRS is standard
of care, University of Alberta and SMBHWN, to establish the safety and efficacy of UCM. This
aim will further test our hypotheses that infants in the UCM group will have improved early
cardiac and cerebral hemodynamics within the first 10 minutes.

The Near-infrared spectroscopy (NIRS) is a technology that allows non-invasive continuous
real-time measurement of the regional tissue oxygen saturation (StO2) of organs such as the
brain. There are well-established reference cerebral StO2 values for uncomplicated term and
preterm deliveries; however, there are no completed RCTs using NIRS in the delivery room. Our
group is currently leading the first multicenter trial (1R01HD088646-01A1) comparing DCC and
UCM measuring NIRS at birth in premature infants. If cerebral oxygenation is improved, it
will provide one plausible explanation for the long-term benefits expected with UCM. While
published data exists on cerebral oxygenation directly comparing UCM with DCC, some studies
demonstrated increases in cerebral oxygenation at 4 hours of age with DCC, and a decrease in
cerebral oxygenation at birth with DCC compared to immediate cord clamping. To our knowledge,
no studies using cerebral oxygenation in non-vigorous term/near-term infants have ever been
performed. This sub-study (n=200) will yield the largest available sample of specific
measurements of cerebral oximetry in non-vigorous term newborns.

Substudy Sites: Two sites experienced with NIRS (University of Alberta and SMBHWN) will
obtain and report the physiological changes with UCM and ECC at 10 minutes of life. Data from
the non-invasive monitoring devices are recorded using a continuous real-time data
acquisition system that provides a second-by-second record of the resuscitation that is also
time-linked to the video recordings. Both sites have 24/7 research team coverage that attend
all high-risk deliveries. The research team will ensure accurate sensor placement and data
collection. These two exceptional settings will allow us to collect significant data
regarding resuscitation outcomes linked to cerebral oxygenation.

Protocol for NIRS Sub-Study: At the two sub-study sites, the use of NIRS is standard of care.

As part of the NIRS sub-study, sites will collect physiological and resuscitation data from
birth (mean airway pressure, fractional oxygen) in addition to cerebral oxygenation. Once the
newborn is delivered, receives the intervention (UCM or ECC), and is stabilized during
resuscitation, a NIRS sensor (Fore-Sight, CAS Medical, Branford, CT) will be placed on the
right forehead within 10 minutes of the newborn being placed on the warmer. While arterial
saturation and heart rate data will be available to the clinical team, data from NIRS will be
blinded. Data on all study infants will be recorded for the first 10 minutes in the delivery
room at the two sites. Heart rate, oxygen saturations, and cerebral oxygenation will be
downloaded as per both site's practice for neonatal resuscitation.

Inclusion Criteria:

- Non-vigorous newborns born between 35-42 weeks gestation

- Born at NIRS Sub-study site

Exclusion Criteria:

- Known major congenital or chromosomal anomalies of newborn

- Known cardiac defects other than small ASD, VSD and PDA

- Complete placental abruption/cutting through the placenta at time of delivery

- Monochorionic multiples

- Cord Avulsion

- Presence of non-reducible nuchal cord

- Perinatal providers unaware of the protocol