Interprofessional Consensus Regarding Design Requirements for Liquid-Based Perinatal Life Support (PLS) Technology

Not many large studies have reported the true impact of lower-grade intraventricular hemorrhages in preterm infants. We studied the neurodevelopmental outcomes of extremely preterm infants in relation to the severity of intraventricular hemorrhage. A regional cohort study of infants born at 23 to 28 weeks' gestation and admitted to a NICU between 1998 and 2004. Primary outcome measure was moderate to severe neurosensory impairment at 2 to 3 years' corrected age defined as developmental delay (developmental quotient >2 SD below the mean), cerebral palsy, bilateral deafness, or bilateral blindness. Of the 1472 survivors assessed, infants with grade III-IV intraventricular hemorrhage (IVH; n = 93) had higher rates of developmental delay (17.5%), cerebral palsy (30%), deafness (8.6%), and blindness (2.2%). Grade I-II IVH infants (n = 336) also had increased rates of neurosensory impairment (22% vs 12.1%), developmental delay (7.8% vs 3.4%), cerebral palsy (10.4% vs 6.5%), and deafness (6.0% vs 2.3%) compared with the no IVH group (n = 1043). After exclusion of 40 infants with late ultrasound findings (periventricular leukomalacia, porencephaly, ventricular enlargement), isolated grade I-II IVH (n = 296) had increased rates of moderate-severe neurosensory impairment (18.6% vs 12.1%). Isolated grade I-II IVH was also independently associated with a higher risk of neurosensory impairment (adjusted odds ratio 1.73, 95% confidence interval 1.22-2.46). Grade I-II IVH, even with no documented white matter injury or other late ultrasound abnormalities, is associated with adverse neurodevelopmental outcomes in extremely preterm infants. Show more

In the developed world, extreme prematurity is the leading cause of neonatal mortality and morbidity due to a combination of organ immaturity and iatrogenic injury. Until now, efforts to extend gestation using extracorporeal systems have achieved limited success. Here we report the development of a system that incorporates a pumpless oxygenator circuit connected to the fetus of a lamb via an umbilical cord interface that is maintained within a closed ‘amniotic fluid' circuit that closely reproduces the environment of the womb. We show that fetal lambs that are developmentally equivalent to the extreme premature human infant can be physiologically supported in this extra-uterine device for up to 4 weeks. Lambs on support maintain stable haemodynamics, have normal blood gas and oxygenation parameters and maintain patency of the fetal circulation. With appropriate nutritional support, lambs on the system demonstrate normal somatic growth, lung maturation and brain growth and myelination. Show more

The physiology of the fetus is fundamentally different from the neonate, with both structural and functional distinctions. The fetus is well-adapted to the relatively hypoxemic intrauterine environment. The transition from intrauterine to extrauterine life requires rapid, complex, and well-orchestrated steps to ensure neonatal survival. This article explains the intrauterine physiology that allows the fetus to survive and then reviews the physiologic changes that occur during the transition to extrauterine life. Asphyxia fundamentally alters the physiology of transition and necessitates a thoughtful approach in the management of affected neonates. Show more