Extreme prematurity: Risk and resiliency

Abstract

Individuals born extremely preterm (before 28 weeks of gestation) comprise only about 0.7% of births in the United States and an even lower proportion in other high resource countries. However, these individuals account for a disproportionate number of children with cerebral palsy, intellectual deficit, autism spectrum disorder, attention deficit hyperactivity disorder, and epilepsy. This review describes two large multiple center cohorts comprised of individuals born extremely preterm: the EPICURE cohort, recruited 1995 in the United Kingdom and the Republic of Ireland, and the Extremely Low Gestational Age Newborn (ELGAN), recruited 2002-2004 in five states in the United States. The primary focus of these studies has been neurodevelopmental disorders, but also of interest are growth, respiratory illness, and parent- and self-reported global health and well-being. Both of these studies indicate that among individuals born extremely preterm the risks of most neurodevelopmental disorders are increased. Early life factors that contribute to this risk include perinatal brain damage, some of which can be identified using neonatal head ultrasound, bronchopulmonary dysplasia, and neonatal systemic inflammation. Prenatal factors, particularly the family's socioeconomic position, also appear to contribute to risk. For most adverse outcomes, the risk is higher in males. Young adults born extremely preterm who have neurodevelopmental impairment, as compared to those without such impairment, rate their quality of life lower. However, young adults born extremely preterm who do not have neurodevelopmental impairments rate their quality of life as being similar to that of young adults born at term. Finally, we summarize the current state of interventions designed to improve the life course of extremely premature infants, with particular focus on efforts to prevent premature birth and on postnatal efforts to prevent adverse neurodevelopmental outcomes.

Figure 1.

Frequencies for neurodevelopmental outcomes: comparison of the ELGAN cohort with reference data from the United States Joseph RM et al. Pediatrics. 2016; Kuban KC et al. J Pediatr. 2008;153(4):466–72; Douglass LM et al. Pediatr Neurol. 2017;73:13–9; Joseph RM et al. Autism Res. 2017;10(2):224–32; Dvir Y et al. J Dev Behav Pediatr. 2019;40(9):725–34; Zablotsky B et al. Pediatrics. 2019;144(4).

Figure 2.

Conceptual model for relationships among prenatal initiators of preterm birth, neonatal complications of extreme prematurity, neonatal systemic inflammation, and quality of life for individuals born preterm. Examples of environmental exposures that contribute to preterm birth include air pollution and racism. Examples of specific maternal conditions that contribute to preterm birth include severe preeclampsia and placenta abrutption.