Regenerative Prophylaxis In Utero

Abstract

Technology advances have raised the outlook for regenerative solutions aimed at restoring organ health. Fetal surgery, implemented to reinstate early organ growth and restitute function in select congenital conditions, is increasingly considered with the prospect of improved postnatal outcomes. Here, we highlight clinical prenatal interventions for rescue of fetal lung development in congenital diaphragmatic hernia, and fetal neurological regeneration for spina bifida. Regenerative therapeutic care in utero is poised to transform management algorithms.

Health Care Evolves From Reactive to Proactive

“…Accordingly, in utero surgical repair approaches have been developed, and children who underwent this procedure had improved brain and motor function and reduced risk of postnatal hydrocephalus, resulting in higher psychomotor development scores. 18 These observations highlight the transformative potential of regenerative therapeutic care in utero to preventive postnatal disease and disability. 19 These considerations underscore the importance of maintaining a focus on preventive approaches that complement therapeutic interventions, as our mechanistic armamentarium evolves from discoveries of the biological bases of health and disease.…”

“…Advances in ultrasound technology allow diagnosis of this condition as early as the first trimester. Accordingly, in utero surgical repair approaches have been developed, and children who underwent this procedure had improved brain and motor function and reduced risk of postnatal hydrocephalus, resulting in higher psychomotor development scores . These observations highlight the transformative potential of regenerative therapeutic care in utero to preventive postnatal disease and disability …”

“…Congenital diaphragmatic hernia affects 1 in 3,836 births and is associated with a high morbidity and mortality due to severe pulmonary hypoplasia and pulmonary arterial hypertension. In that regard, fetal endoscopic tracheal occlusion has been performed for isolated severe congenital diaphragmatic hernia to promote fetal lung regrowth and restitution of organ development . Furthermore, spina bifida is a congenital defect of the neural tube defined by the exposure of meninges and spinal cord due to incomplete closure of the spinal canal.…”

“…16 At the other extreme of the developmental continuum, novel approaches in regenerative medicine are being applied in utero to address severe congenital conditions at the prenatal stage, offering a unique opportunity for the earliest forms of disease prevention and prophylaxis. 18 In that context, prenatal regenerative prophylaxis harnesses the plasticity of developing fetal organs to deliver postnatal pediatric health. Herein, fetal surgery, implemented to reconstitute early normal organ growth and restore function in select congenital conditions, is increasingly considered to improve postnatal outcomes.…”

“…In that regard, fetal endoscopic tracheal occlusion has been performed for isolated severe congenital diaphragmatic hernia to promote fetal lung regrowth and restitution of organ development. 18 Furthermore, spina bifida is a congenital defect of the neural tube defined by the exposure of meninges and spinal cord due to incomplete closure of the spinal canal. Exposure of the neural tube to amniotic fluid and trauma in utero increases the risk of paralysis, abnormal mental development, and bladder and/or bowel dysfunction.…”