Abstract
Improved intensive care therapies have increased the survival of children born preterm. Yet, many preterm children experience long-term neurodevelopmental sequelae. Indeed, preterm birth remains a leading cause of lifelong neurodevelopmental disability globally, posing significant challenges to the child, family, and society. Neurodevelopmental disability in children born preterm is traditionally linked to acquired brain injuries such as white matter injury and to impaired brain maturation resulting from neonatal illness such as chronic lung disease. Socioeconomic status (SES) has long been recognized to contribute to variation in outcome in children born preterm. Recent brain imaging data in normative term-born cohorts suggest that lower SES itself predicts alterations in brain development, including the growth of the cerebral cortex and subcortical structures. Recent evidence in children born preterm suggests that the response to early-life brain injuries is modified by the socioeconomic circumstances of children and families. Exciting new data points to the potential of more favorable SES circumstances to mitigate the impact of neonatal brain injury. This review addresses emerging evidence suggesting that SES modifies the relationship between early-life exposures, brain injury, and neurodevelopmental outcomes in children born preterm. Better understanding these relationships opens new avenues for research with the ultimate goal of promoting optimal outcomes for those children born preterm at highest risk of neurodevelopmental consequence.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
References
Statistics Canada. Births. Statistics Canada Catalogue. 2007: 84-F02-10X.
Stoll, B. J. et al., Human Development Neonatal Research Network. Trends in care practices, morbidity, and mortality of extremely preterm neonates, 1993–2012. JAMA 314, 1039–1051 (2015).
Miller, S. P. et al. Early brain injury in premature newborns detected with magnetic resonance imaging is associated with adverse early neurodevelopmental outcome. J. Pediatr. 147, 609–616 (2005).
Chau, V. et al. Effect of chorioamnionitis on brain development and injury in premature newborns. Ann. Neurol. 66, 155–164 (2009).
Grunau, R. E., Whitfield, M. F. & Fay, T. B. Psychosocial and academic characteristics of extremely low birth weight (< or =800 g) adolescents who are free of major impairment compared with term-born control subjects. Pediatrics 114, e725–e732 (2004).
Back, S. A. & Miller, S. P. Brain injury in premature neonates: a primary cerebral dysmaturation disorder? Ann. Neurol. 75, 469–486 (2014).
Synnes, A. R. et al. School entry age outcomes for infants with birth weight ≤800 grams. J. Pediatr. 157, 989–994.e981 (2010).
Morgan, R. L., Whaley, P., Thayer, K. A. & Schunemann, H. J. Identifying the PECO: a framework for formulating good questions to explore the association of environmental and other exposures with health outcomes. Environ. Int. 121, 1027–1031 (2018).
Krieger, N. A glossary for social epidemiology. J. Epidemiol. Community Health 55, 693–700 (2001).
Braveman, P. A. et al. Socioeconomic status in health research: one size does not fit all. JAMA 294, 2879–2888 (2005).
Leijser, L. M., Siddiqi, A. & Miller, S. P. Imaging evidence of the effect of socio-economic status on brain structure and development. Semin. Pediatr. Neurol. 27, 26–34 (2018).
Bhutta, A. T., Cleves, M. A., Casey, P. H., Cradock, M. M. & Anand, K. J. Cognitive and behavioral outcomes of school-aged children who were born preterm: a meta-analysis. JAMA 288, 728–737 (2002).
Cirino, P. T. et al. Measuring socioeconomic status: reliability and preliminary validity for different approaches. Assessment 9, 145–155 (2002).
Farah, M. J. The neuroscience of socioeconomic status: correlates, causes, and consequences. Neuron 96, 56–71 (2017).
von Stumm, S. & Plomin, R. Socioeconomic status and the growth of intelligence from infancy through adolescence. Intelligence 48, 30–36 (2015).
Linsell, L., Malouf, R., Morris, J., Kurinczuk, J. J. & Marlow, N. Prognostic factors for poor cognitive development in children born very preterm or with very low birth weight: a systematic review. JAMA Pediatr. 169, 1162–1172 (2015).
Ko, G., Shah, P., Lee, S. K. & Asztalos, E. Impact of maternal education on cognitive and language scores at 18 to 24 months among extremely preterm neonates. Am. J. Perinatol. 30, 723–730 (2013).
Vohr, B. R. et al. Neurodevelopmental and functional outcomes of extremely low birth weight infants in the National Institute of Child Health and Human Development Neonatal Research Network, 1993–1994. Pediatrics 105, 1216–1226 (2000).
Joseph, R. M., O’Shea, T. M., Allred, E. N., Heeren, T. & Kuban, K. K. Maternal educational status at birth, maternal educational advancement, and neurocognitive outcomes at age 10 years among children born extremely preterm. Pediatr. Res 83, 767–777 (2018).
Noble, K. G. et al. Family income, parental education and brain structure in children and adolescents. Nat. Neurosci. 18, 773–778 (2015).
Campbell, F. et al. Early childhood investments substantially boost adult health. Science 343, 1478–1485 (2014).
Heckman, J., Pinto, R. & Savelyev, P. Understanding the mechanisms through which an influential early childhood program boosted adult outcomes. Am. Econ. Rev. 103, 2052–2086 (2013).
Campbell, F. A. & Ramey, C. T. Effects of early intervention on intellectual and academic achievement: a follow-up study of children from low-income families. Child Dev. 65, 684–698 (1994).
McCormick, M. C. et al. Early intervention in low birth weight premature infants: results at 18 years of age for the Infant Health and Development Program. Pediatrics 117, 771–780 (2006).
Kerr-Wilson, C. O., Mackay, D. F., Smith, G. C. & Pell, J. P. Meta-analysis of the association between preterm delivery and intelligence. J. Public Health (Oxf.) 34, 209–216 (2012).
Bruckert, L. et al. White matter plasticity in reading-related pathways differs in children born preterm and at term: a longitudinal analysis. Front. Hum. Neurosci. 13, 139 (2019).
Gui, L. et al. Longitudinal study of neonatal brain tissue volumes in preterm infants and their ability to predict neurodevelopmental outcome. Neuroimage 185, 728–741 (2019).
Kilbride, H. W., Thorstad, K. & Daily, D. K. Preschool outcome of less than 801-gram preterm infants compared with full-term siblings. Pediatrics 113, 742–747 (2004).
Schmidt, B. et al. Prediction of late death or disability at age 5 years using a count of 3 neonatal morbidities in very low birth weight infants. J. Pediatr. 167, 982–986.e982 (2015).
Synnes, A. et al. Determinants of developmental outcomes in a very preterm Canadian cohort. Arch. Dis. Child Fetal Neonatal Ed. 102, F235–F234 (2017).
Guo, T. et al. Quantitative assessment of white matter injury in preterm neonates: association with outcomes. Neurology 88, 614–622 (2017).
Back, S. A. & Rivkees, S. A. Emerging concepts in periventricular white matter injury. Semin. Perinatol. 28, 405–414 (2004).
Back, S. A. Perinatal white matter injury: the changing spectrum of pathology and emerging insights into pathogenetic mechanisms. Ment. Retard Dev. Disabil. Res. Rev. 12, 129–140 (2006).
Back, S. A. & Rosenberg, P. A. Pathophysiology of glia in perinatal white matter injury. Glia 62, 1790–1815 (2014).
Buser, J. R. et al. Arrested preoligodendrocyte maturation contributes to myelination failure in premature infants. Ann. Neurol. 71, 93–109 (2012).
McClendon, E. et al. Prenatal cerebral ischemia triggers dysmaturation of caudate projection neurons. Ann. Neurol. 75, 508–524 (2014).
Duerden, E. G. et al. Midazolam dose correlates with abnormal hippocampal growth and neurodevelopmental outcome in preterm infants. Ann. Neurol. 79, 548–559 (2016).
Duerden, E. G. et al. Early procedural pain is associated with regionally-specific alterations in thalamic development in preterm neonates. J. Neurosci. 38, 878–886 (2018).
Ball, G. et al. Development of cortical microstructure in the preterm human brain. Proc. Natl. Acad. Sci. USA 110, 9541–9546 (2013).
Chau, V. et al. Abnormal brain maturation in preterm neonates associated with adverse developmental outcomes. Neurology 81, 2082–2089 (2013).
Schneider, J. et al. Evolution of T1 relaxation, ADC, and fractional anisotropy during early brain maturation: a serial imaging study on preterm infants. Am. J. Neuroradiol. 37, 155–162 (2016).
Vinall, J. et al. Slower postnatal growth is associated with delayed cerebral cortical maturation in preterm newborns. Sci. Transl. Med 5, 168ra168 (2013).
Tam, E. W. et al. Preterm cerebellar growth impairment after postnatal exposure to glucocorticoids. Sci. Transl. Med. 3, 105ra105 (2011).
Tam, E. W. et al. Cerebellar development in the preterm neonate: effect of supratentorial brain injury. Pediatr. Res. 66, 102–106 (2009).
Tam, E. W. et al. Differential effects of intraventricular hemorrhage and white matter injury on preterm cerebellar growth. J. Pediatr. 158, 366–371 (2011).
Adams, E. et al. Tractography-based quantitation of corticospinal tract development in premature newborns. J. Pediatr. 156, 882–888, 888.e881 (2010).
Brummelte, S. et al. Procedural pain and brain development in premature newborns. Ann. Neurol. 71, 385–396 (2012).
Chau, V. et al. Postnatal infection is associated with widespread abnormalities of brain development in premature newborns. Pediatr. Res. 71, 274–279 (2012).
Bonifacio, S. L. et al. Extreme premature birth is not associated with impaired development of brain microstructure. J. Pediatr. 157, 726–732.e721 (2010).
Card, D. et al. Brain metabolite concentrations are associated with illness severity scores and white matter abnormalities in very preterm infants. Pediatr. Res. 74, 75–81 (2013).
Schneider, J. et al. Nutrient intake in the first two weeks of life and brain growth in preterm neonates. Pediatrics 141, e20172169 (2018).
Horbar, J. D. et al. Racial segregation and inequality in the neonatal intensive care unit for very low-birth-weight and very preterm infants. JAMA Pediatr. 173, 455–461 (2019).
Benavente-Fernández, I. et al. Association of socioeconomic status and brain injury with neurodevelopmental outcomes of very preterm children. JAMA Netw. Open 2, e192914–e192914 (2019).
McDermott, C. L. et al. Longitudinally mapping childhood socioeconomic status associations with cortical and subcortical morphology. J. Neurosci. 39, 1365–1373 (2019).
Vinall, J., Miller, S. P., Synnes, A. R. & Grunau, R. E. Parent behaviors moderate the relationship between neonatal pain and internalizing behaviors at 18 months corrected age in children born very prematurely. Pain 154, 1831–1839 (2013).
O’Brien, K. et al. Effectiveness of family integrated care in neonatal intensive care units on infant and parent outcomes: a multicentre, multinational, cluster-randomised controlled trial. Lancet Child Adolesc. Health 2, 245–254 (2018).
Betancourt, L. M. et al. Effect of socioeconomic status (SES) disparity on neural development in female African-American infants at age 1 month. Dev. Sci. 19, 947–956 (2016).
Hanson, J. L., Chandra, A., Wolfe, B. L. & Pollak, S. D. Association between income and the hippocampus. PLoS ONE 6, e18712 (2011).
Raizada, R. D., Richards, T. L., Meltzoff, A. & Kuhl, P. K. Socioeconomic status predicts hemispheric specialisation of the left inferior frontal gyrus in young children. Neuroimage 40, 1392–1401 (2008).
Noble, K. G., Houston, S. M., Kan, E. & Sowell, E. R. Neural correlates of socioeconomic status in the developing human brain. Dev. Sci. 15, 516–527 (2012).
Noble, K. G., Korgaonkar, M. S., Grieve, S. M. & Brickman, A. M. Higher education is an age-independent predictor of white matter integrity and cognitive control in late adolescence. Dev. Sci. 16, 653–664 (2013).
Jednoróg, K. et al. The influence of socioeconomic status on children’s brain structure. PLoS ONE 7, e42486 (2012).
Luby, J. et al. The effects of poverty on childhood brain development: the mediating effect of caregiving and stressful life events. JAMA Pediatr. 167, 1135–1142 (2013).
Hair, N. L., Hanson, J. L., Wolfe, B. L. & Pollak, S. D. Association of child poverty, brain development, and academic achievement. JAMA Pediatr. 169, 822–829 (2015).
Fox, S. E., Levitt, P. & Nelson, C. A. 3rd How the timing and quality of early experiences influence the development of brain architecture. Child Dev. 81, 28–40 (2010).
Cioni, G., Inguaggiato, E. & Sgandurra, G. Early intervention in neurodevelopmental disorders: underlying neural mechanisms. Dev. Med. Child Neurol. 58(Suppl. 4), 61–66 (2016).
Diamond, M. C., Krech, D. & Rosenzweig, M. R. The effects of an enriched environment on the histology of the rat cerebral cortex. J. Comp. Neurol. 123, 111–120. (1964).
Kempermann, G., Kuhn, H. G. & Gage, F. H. More hippocampal neurons in adult mice living in an enriched environment. Nature 386, 493–495 (1997).
Bennett, E. L., Rosenzweig, M. R. & Diamond, M. C. Rat brain: effects of environmental enrichment on wet and dry weights. Science 163, 825–826 (1969).
Leger, M. et al. Environmental enrichment duration differentially affects behavior and neuroplasticity in adult mice. Cereb. Cortex 25, 4048–4061 (2015).
Brenes, J. C. et al. Differential effects of social and physical environmental enrichment on brain plasticity, cognition, and ultrasonic communication in rats. J. Comp. Neurol. 524, 1586–1607 (2016).
Faverjon, S. et al. Beneficial effects of enriched environment following status epilepticus in immature rats. Neurology 59, 1356–1364 (2002).
Sale, A., Berardi, N. & Maffei, L. Environment and brain plasticity: towards an endogenous pharmacotherapy. Physiol. Rev. 94, 189–234 (2014).
Nithianantharajah, J. & Hannan, A. J. Enriched environments, experience-dependent plasticity and disorders of the nervous system. Nat. Rev. Neurosci. 7, 697–709 (2006).
van Praag, H., Kempermann, G. & Gage, F. H. Neural consequences of environmental enrichment. Nat. Rev. Neurosci. 1, 191–198 (2000).
Nelson, C. A. 3rd et al. Cognitive recovery in socially deprived young children: the Bucharest Early Intervention Project. Science 318, 1937–1940 (2007).
Kidokoro, H. et al. Brain injury and altered brain growth in preterm infants: predictors and prognosis. Pediatrics 134, e444–e453 (2014).
Woodward, L. J., Clark, C. A., Bora, S. & Inder, T. E. Neonatal white matter abnormalities an important predictor of neurocognitive outcome for very preterm children. PLoS ONE 7, e51879 (2012).
Woodward, L. J., Anderson, P. J., Austin, N. C., Howard, K. & Inder, T. E. Neonatal MRI to predict neurodevelopmental outcomes in preterm infants. N. Engl. J. Med. 355, 685–694 (2006).
Joseph, R. M. et al. Neurocognitive and academic outcomes at age 10 years of extremely preterm newborns. Pediatrics 137 (2016).
Nguyen, T. N. et al. Developmental trajectory of language from 2 to 13 years in children born very preterm. Pediatrics 141 (2018).
Scherjon, S., Briet, J., Oosting, H. & Kok, J. The discrepancy between maturation of visual-evoked potentials and cognitive outcome at five years in very preterm infants with and without hemodynamic signs of fetal brain-sparing. Pediatrics 105, 385–391 (2000).
Voss, W., Jungmann, T., Wachtendorf, M. & Neubauer, A. P. Long-term cognitive outcomes of extremely low-birth-weight infants: the influence of the maternal educational background. Acta Paediatr. 101, 569–573 (2012).
Doyle, L. W. et al. Biological and social influences on outcomes of extreme-preterm/low-birth weight adolescents. Pediatrics 136, e1513–e1520 (2015).
Tich, S. N. et al. Neurodevelopmental and perinatal correlates of simple brain metrics in very preterm infants. Arch. Pediatr. Adolesc. Med. 165, 216–222. (2011).
Groenendaal, F., Termote, J. U., van der Heide-Jalving, M., van Haastert, I. C. & de Vries, L. S. Complications affecting preterm neonates from 1991 to 2006: what have we gained? Acta Paediatr. 99, 354–358 (2010).
Twilhaar, E. S. et al. Cognitive outcomes of children born extremely or very preterm since the 1990s and associated risk factors: a meta-analysis and meta-regression. JAMA Pediatr. 172, 361–367 (2018).
Wolke, D. & Meyer, R. Cognitive status, language attainment, and prereading skills of 6-year-old very preterm children and their peers: the Bavarian Longitudinal Study. Dev. Med. Child Neurol. 41, 94–109 (1999).
Burnett, A. C., Cheong, J. L. Y. & Doyle, L. W. Biological and social influences on the neurodevelopmental outcomes of preterm infants. Clin. Perinatol. 45, 485–500 (2018).
Basten, M., Jaekel, J., Johnson, S., Gilmore, C. & Wolke, D. Preterm birth and adult wealth: mathematics skills count. Psychol. Sci. 26, 1608–1619 (2015).
McGowan, E. C. & Vohr, B. R. Neurodevelopmental follow-up of preterm infants: What is new? Pediatr. Clin. N. Am. 66, 509–523 (2019).
Wong, H. S. & Edwards, P. Nature or nurture: a systematic review of the effect of socio-economic status on the developmental and cognitive outcomes of children born preterm. Matern. Child Health J. 17, 1689–1700 (2013).
Asztalos, E. V. et al., Canadian Neonatal Follow-up Network I. Association between primary caregiver education and cognitive and language development of preterm neonates. Am. J. Perinatol. 34, 364–371 (2017).
Beaino, G. et al. Predictors of cerebral palsy in very preterm infants: the EPIPAGE prospective population-based cohort study. Dev. Med. Child Neurol. 52, e119–e125 (2010).
Potharst, E. S. et al. High incidence of multi-domain disabilities in very preterm children at five years of age. J. Pediatr. 159, 79–85 (2011).
Mangin, K. S., Horwood, L. J. & Woodward, L. J. Cognitive development trajectories of very preterm and typically developing children. Child Dev. 88, 282–298 (2017).
Wolke, D., Jaekel, J., Hall, J. & Baumann, N. Effects of sensitive parenting on the academic resilience of very preterm and very low birth weight adolescents. J. Adolesc. Health 53, 642–647 (2013).
Vandell, D. L., Belsky, J., Burchinal, M., Steinberg, L. & Vandergrift, N., Network NECCR. Do effects of early child care extend to age 15 years? Results from the NICHD study of early child care and youth development. Child Dev. 81, 737–756 (2010).
Spittle, A., Orton, J., Anderson, P. J., Boyd, R. & Doyle, L. W. Early developmental intervention programmes provided post hospital discharge to prevent motor and cognitive impairment in preterm infants. Cochrane Database Syst. Rev. CD005495 (2015).
Provenzi, L., Guida, E. & Montirosso, R. Preterm behavioral epigenetics: A systematic review. Neurosci. Biobehav. Rev. 84, 262–271 (2018).
Santos, H. P. Jr. et al. Epigenome-wide DNA methylation in placentas from preterm infants: association with maternal socioeconomic status. Epigenetics 14, 751–765 (2019).
Acknowledgements
We received financial support from the Bloorview Children’s Hospital Chair in Pediatric Neuroscience, Canadian Institutes of Health Research, Kids Brain Health Network, Ontario Brain Institute and Cerebral Palsy Alliance (S.P.M.), Canada Research Chair in Population Health Equity (A.S.), and the European Regional Development Fund-Junta de Andalucía Health Board 2014-2020/PI-0052-2017 (I.B.-F.).
Author information
Authors and Affiliations
Contributions
I.B.-F., A.S. and S.P.M. made substantial contributions to conception and design of this review, drafting the manuscript and revising it critically for important intellectual content; all three authors agree with the final version of this review.
Corresponding author
Ethics declarations
Competing interests
The authors declare no competing interests.
Additional information
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Benavente-Fernández, I., Siddiqi, A. & Miller, S.P. Socioeconomic status and brain injury in children born preterm: modifying neurodevelopmental outcome. Pediatr Res 87, 391–398 (2020). https://doi.org/10.1038/s41390-019-0646-7
Received:
Revised:
Accepted:
Published:
Issue date:
DOI: https://doi.org/10.1038/s41390-019-0646-7
This article is cited by
-
Unconditional cash transfers to low-income preterm infants and their families: a pilot randomized controlled trial
Journal of Perinatology (2025)
-
Stay cool and keep moving forwards
Pediatric Research (2025)
-
FGF21 Alleviates Hypoxic-Ischemic White Matter Injury in Neonatal Mice by Mediating Inflammation and Oxidative Stress Through PPAR-γ Signaling Pathway
Molecular Neurobiology (2025)
-
Home-ics: how experiences of the home impact biology and child neurodevelopmental outcomes
Pediatric Research (2024)
-
Advancing brain MRI as a prognostic indicator in hypoxic-ischemic encephalopathy
Pediatric Research (2024)
