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Placental transfusion results in a significant decrease in the risk of death for extremely preterm infants. With immediate cord clamping (ICC), these infants can leave up to one-half of their normal circulating in utero blood volume in the placenta. Extremely preterm infants are at highest risk of harm from ICC yet are currently the most likely to receive ICC. Receiving a placenta transfusion provides infants with life-saving components and enhanced perfusion. We present some lesser-known but important effects of placental transfusion. New research reveals that enhanced vascular perfusion causes an organ’s endothelial cells to release angiocrine responses to guide essential functions. High progesterone levels and pulmonary artery pressure in the first few hours of life assist with neonatal adaptation. We propose that lack of essential blood volume may be a major factor contributing to inflammation, morbidities, and mortality that preterm infants frequently encounter.