Premature babies are at risk for bleeding in their brain, referred to as intraventricular hemorrhage (IVH), which often results in developmental delays or other neurological problems such as cerebral palsy. Delaying the time at which the umbilical cord is clamped after birth by 30-60 seconds has been shown to reduce IVH and has become the standard of care in the delivery of preterm infants. However, delayed cord clamping (DCC) does not reduce severe IVH, which may be due to inadequate placental transfusion in infants at risk for severe IVH. A recent study (Bhatt et al.) compared DCC to immediate cord clamping (ICC) in ventilated lambs and found DCC prevented a rapid increase in carotid artery pressure while increasing pulmonary blood flow (PBF) to the lungs. The majority of infants at risk for severe IVH (compromised and extremely premature infants) are born by cesarean section (C/S) and therefore do not receive the benefit of passage through the birth canal, which facilitates fluid clearance from the newborn lungs and increases PBF. Previous studies have demonstrated suboptimal placental transfusion (via hematocrit levels) from DCC for infants born by C/S. Opening the premature infant's lungs with ventilation during DCC could increase placental transfusion, thereby improving PBF and facilitating physiological transition. Ventilation during the period of DCC in the delivery room is not currently practiced. A sterile T-piece will be used to achieve lung recruitment simultaneously with placental transfusion from DCC. We will test the hypothesis that a simple sterile ventilation circuit (with which we have extensive experience) can be employed with no impediment to obstetrical care and provide benefit to the premature infant during DCC.
Specific Aims : 1) Compare the volume of placental transfusion with ventilation during delayed cord clamping (V-DCC) to delayed cord clamping alone (DCC) between infants born by C/S or vaginal delivery (VD). 2) Compare the physiological changes in the first 6 hours of life (HOL) between infants born by C/S or VD randomized to V-DCC or to DCC alone. 3) Compare the clinical outcomes between infants born by either C/S or VD, randomized to V-DCC or to DCC alone. 4) Compare the effects of mode of delivery on volume of placental transfusion, physiological changes, and clinical outcomes between all 4 groups. Design: This is a blinded randomized controlled clinical trial. Both groups will receive the same resuscitation interventions once the umbilical cord is clamped. Brain oxygenation and cardiac output will be continuously measured beginning in the delivery room until 6 HOL. An early heart ultrasound will be performed (<6 HOL) to measure systemic blood flow and detect fetal shunts. Adequacy of placental transfusion will be assessed by 12 HOL hematocrit. Clinicians will be blinded to whether the infant did or did not receive ventilation during DCC. This will be the first blinded randomized study to evaluate the effect of ventilation on DCC in very preterm infants delivered by C/S with a comparison group of VD preterm infants randomized to the same interventions.

Public Health Relevance

Delayed cord clamping (DCC), a method of delaying the traditional timing of clamping the umbilical cord before it is cut, improves transfusion of placentl blood into the newborn and has been shown to reduce bleeding in the brain, or intraventricular hemorrhage (IVH). However, DCC has not reduced severe IVH, which may be due to the lack of benefit for extremely premature newborns who are (a) unable to breathe on their own, (b) have increased risk for severe IVH and (c) are most often born by cesarean section. This study will determine whether helping newborns to expand their lungs (i.e. improving ventilation) during DCC helps them receive more blood from the placenta and reduce the incidence and severity of IVH.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Exploratory/Developmental Grants (R21)
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Special Emphasis Panel (ZRG1)
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Raju, Tonse N
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Sharp Memorial Hospital
San Diego
United States
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Katheria, Anup C (2018) Umbilical Cord Milking: A Review. Front Pediatr 6:335
Katheria, A C; Lakshminrusimha, S; Rabe, H et al. (2017) Placental transfusion: a review. J Perinatol 37:105-111
Katheria, Anup; Poeltler, Debra; Durham, Jayson et al. (2016) Neonatal Resuscitation with an Intact Cord: A Randomized Clinical Trial. J Pediatr 178:75-80.e3