The impact of placental proteins on prematurity - each year, ~15 million infants worldwide - approximately 10% of all births - are born preterm (before 37 weeks of gestation)

The National Institute of Child Health and Human Development awarded The Regents Of The University Of Colorado, doing business as University Of Colorado-Denver, $114,268 in project grant funding on August 25, 2026, under the Child Health and Human Development Extramural Research program (CFDA 93.865).

The award funds research investigating how placental proteins influence prematurity outcomes. The project tests the hypothesis that proteins secreted by the preterm placenta—with documented involvement in brain, lung, and liver development—improve outcomes in prematurely born animals, using induced preterm delivery models. The researcher identified 142 proteins secreted by the human placenta before 32 weeks of gestation; the work examines whether proteins associated with neurogenesis, lung development, and angiogenesis are essential for normal fetal organ development and whether their loss in premature infants contributes to neonatal complications including intraventricular hemorrhage, respiratory distress syndrome, necrotizing enterocolitis, and long-term sequelae such as chronic lung disease and neurodevelopmental dysfunction.

Performance extends from the award date through July 31, 2028. Work is performed in Aurora, Colorado. University Of Colorado-Denver is a child entity under The Regents Of The University Of Colorado system.

Despite the high incidence of preterm birth, the underlying mechanisms remain poorly understood and with the exception of progesterone in a limited number of cases, there are currently no effective interventions to prevent preterm labor. While advancements in the management of preterm infants over the past 30 years have improved survival rates, prematurity continues to be the second leading cause of death among children under five years of age. Moreover, infants born prematurely face a significant risk of neonatal complications such as intraventricular hemorrhage, respiratory distress syndrome, and necrotizing enterocolitis, as well as long-term sequelae including chronic lung disease, retinopathy, poor neurodevelopmental outcomes and metabolic dysfunction-associate steatotic liver disease. Emerging evidence from animal studies highlights the critical role of placental factors in fetal organ development. One of the fundamental differences between fetal and postnatal life is the immediate cessation of umbilical circulation at birth, depriving the premature infant of key placental factors, including proteins, essential for normal fetal organ development. We identified 142 proteins secreted by the human placenta prior to 32 weeks of gestation. Notably, a substantial number of these proteins have been associated with developmental processes such as neurogenesis, lung development, and angiogenesis, suggesting that these proteins may be crucial for normal fetal organ development that are often compromised in preterm infants. I will test the central hypothesis that proteins secreted by the human preterm placenta into the fetal circulation, with known involvement in development of the brain, lung, and liver, improve outcomes in prematurely born guinea pigs. Our approach will be to induce preterm delivery in guinea pigs, providing them with 24/7 support in a guinea PIG neonatal intensive care unit. Pups will either receive a cocktail of five placental proteins or vehicle by a subcutaneous mini-osmotic pump for 7 days after preterm delivery. We propose three aims: aim 1 (K99): determine the effect of human placental proteins on mortality and short-term respiratory and hepatic outcomes in premature guinea pigs. Aim 2 (K99): establish the effects of human placental proteins on long-term neurodevelopmental and hepatic outcomes in premature guinea pigs. Aim 3 (R00): determine the effects of administration of human placental proteins on outcomes in extremely premature non-human primates. My proposal is conceptually highly novel because IT has the potential to lead to the development of fundamentally novel intervention strategies that may alleviate perinatal mortality and morbidity, as well as long-term sequelae in extremely premature babies. The proposal also provides critical training and career development to support my long-term career goal of becoming an independent investigator with expertise in prematurity research.