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Invited Commentary
Pediatrics
July 12, 2019

Social Relationships, Preterm Birth or Low Birth Weight, and the Brain

Author Affiliations
  • 1Centre for the Developing Brain, Department of Perinatal Imaging and Health, Division of Imaging Sciences and Biomedical Engineering, King’s College London, London, United Kingdom
  • 2Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, United Kingdom
JAMA Netw Open. 2019;2(7):e196960. doi:10.1001/jamanetworkopen.2019.6960

Survival of individuals who are born preterm or with low birth weight has increased owing to significant breakthroughs in neonatal intensive care practices that occurred in the 1970s and 1980s, antenatal corticosteroids, surfactant therapy, and high-frequency ventilation. As a result, a generation of infants born preterm or with low birth weight has now reached adulthood. The study by Mendonça et al1 contributes to increasing the current understanding of the long-term sequelae of preterm birth or low birth weight by presenting a meta-analysis of the literature that investigates the association of preterm birth or low birth weight with social outcomes in adulthood, including the establishment and quality of romantic relationships, sexual activity, parenthood, and peer social support.1 Among the more than 4 million participants included in the studies analyzed by Mendonça et al,1 adults who were born preterm or with low birth weight were less likely than the control groups to be involved in romantic partnerships, showed decreased engagement in sexual activity, and were less likely to become parents. All these factors could contribute to overall poorer well-being and mental health. Results of the meta-analysis by Mendonça et al1 highlight a gradient risk of severity associated with gestational age, with individuals who were born extremely preterm (<28 weeks) or with extremely low birth weight (<1000 grams) representing the most likely subgroup to have worse social outcomes. However, encouragingly, the data suggest that the reported quality of relationships with partners and friends did not differ between adults who were born preterm or with low birth weight and their peers who were born at term.

These findings provide further support to the hypothesis that perinatal events exert lifelong influence on socioemotional functioning,2 emphasizing the need to identify early predictors of risk to inform the development and implementation of targeted strategies aimed at improving psychosocial and possibly mental health outcomes in vulnerable populations. This highlights the importance of studying socioemotional outcomes as contributing factors exacerbating the risk of adverse long-term physical and mental health outcomes as well as possible consequences of such sequelae among survivors of preterm birth or low birth weight. The identification of difficulties in establishing social transitions into adulthood, namely romantic relationships, sexual activity, and parenthood, further emphasizes that it is crucial to continue monitoring the well-being of individuals who were born preterm or with low birth weight throughout life and offer adequate support. However, to make accurate predictions of risk and to guide and implement support strategies, further studies are needed to increase our understanding of the mechanisms underlying the specific socioemotional concerns of individuals who were born preterm or with low birth weight.

The social outcomes in the study by Mendonça et al1 can be regarded as interpersonal relationships with emotion regulation as a common feature. Emotion regulation can be defined as a set of processes involved in dealing with contextual demands that influence the type of emotions triggered by specific stimuli, the timing of the onset of such emotions, their affective evaluation, and their expression to promote flexible, goal-oriented behaviors. In daily life, emotion regulation is used to adapt emotions in response to people and situations, with a range of cognitive, physiological, and behavioral processes and responses. Therefore, the capacity to regulate one’s emotions has important implications for mental health, personal well-being, and the ability to successfully navigate the social world. Further insight into the potential mechanisms associated with socioemotional impairments in individuals who were born preterm or with low birth weight could be gained by combining developmental imaging with social neuroscience research, a discipline that studies how the brain mediates social processes and behavior. Within this framework, alterations in structural and functional network architecture involved in emotion regulation could be studied as an underlying biological mechanism of the association of preterm birth or low birth weight with socioemotional vulnerability.

The immature nervous system is susceptible to injury and abnormal development, and infants who are born preterm or with low birth weight show widespread alterations in brain connectivity and network architecture.3 These neurodevelopmental alterations have been shown to predict later neurocognitive function3 and to persist in adult life.4 While several studies documented structural and functional alterations in brain areas that are involved in understanding others, ie, the social brain,2 in individuals who were born preterm or with low birth weight, current theoretical frameworks have shifted the focus of attention from single regions to intrinsically organized, large-scale, domain-general brain networks. Functional specialization is then studied as emerging from interactions between these domain-general intrinsic networks. Of specific relevance to social functioning and emotion regulation are the salience network and the default mode network,5 which have demonstrated reduced functional connectivity in adults who were born preterm compared with controls,4 especially in individuals who experienced self-regulatory problems in infancy.6

What are the implications of increased awareness of the long-term socioemotional problems associated with preterm or low birth weight for prevention and intervention? The developmental imaging literature suggests that the neural circuitry implicated in social processes is not apparent in neonates and matures throughout childhood,7 which suggests that it may be malleable to environmental input. Therefore, early experiences have the potential to affect the architecture of children’s social brains as well as their behavior in adult life.5 For infants who are born preterm or with low birth weight, it means that the stress associated with neonatal intensive care, which often involves lifesaving but invasive medical procedures, may have an effect on emerging self-regulatory processes and brain development.8 However, the malleability of neonates to environmental input also offers the potential for interventions aimed at improving outcomes to be delivered during the period of maximal plasticity. Although this area of research is still in its infancy, encouraging results are provided by studies promoting multisensory experiences in the neonatal intensive care unit. For instance, results of a 2019 music intervention trial by Lejeune et al9 not only showed that music-exposed preterm infants displayed increased functional connectivity among large-scale brain networks compared with non–music-exposed peers at term-equivalent age, they also reported fewer socioemotional problems during the first 2 years of life.9 The early characterization of brain mechanisms underlying socioemotional difficulties associated with preterm birth or low birth weight may provide a mechanistic starting point to promote brain plasticity through targeted neurobehavioral interventions.

A key challenge for the field is to identify the most significant features of environmental experience that can promote socioemotional development in individuals born preterm or with low birth weight at different stages of their lives, as well as to better delineate the timing of maturation of their underlying neurobiological mechanisms. Such knowledge could be used to improve the life course outcomes of individuals who were born preterm or with low birth weight by leveraging the serve and return interaction between the brain and the environment.

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Article Information

Published: July 12, 2019. doi:10.1001/jamanetworkopen.2019.6960

Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2019 Nosarti C. JAMA Network Open.

Corresponding Author: Chiara Nosarti, PhD, Centre for the Developing Brain, Department of Perinatal Imaging and Health, Division of Imaging Sciences and Biomedical Engineering, King’s College London, St Thomas’ Hospital, First Floor South Wing, London SE1 7EH, United Kingdom (chiara.nosarti@kcl.ac.uk).

Conflict of Interest Disclosures: None reported.

References
1.
Mendonça  M, Bilgin  A, Wolke  D.  Association of preterm birth and low birth weight with romantic partnership, sexual intercourse, and parenthood in adulthood: a systematic review and meta-analysis.  JAMA Netw Open. 2019;2(7):e196961. doi:10.1001/jamanetworkopen.2019.6961Google Scholar
2.
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Ball  G, Pazderova  L, Chew  A,  et al.  Thalamocortical connectivity predicts cognition in children born preterm.  Cereb Cortex. 2015;25(11):4310-4318. doi:10.1093/cercor/bhu331PubMedGoogle ScholarCrossref
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White  TP, Symington  I, Castellanos  NP,  et al.  Dysconnectivity of neurocognitive networks at rest in very-preterm born adults.  Neuroimage Clin. 2014;4:352-365. doi:10.1016/j.nicl.2014.01.005PubMedGoogle ScholarCrossref
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Atzil  S, Gao  W, Fradkin  I, Barrett  LF.  Growing a social brain.  Nat Hum Behav. 2018;2(9):624-636. doi:10.1038/s41562-018-0384-6Google ScholarCrossref
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Bäuml  JG, Baumann  N, Avram  M,  et al.  The default mode network mediates the impact of infant regulatory problems on adult avoidant personality traits.  Biol Psychiatry Cogn Neurosci Neuroimaging. 2019;4(4):333-342. doi:10.1016/j.bpsc.2018.11.005PubMedGoogle ScholarCrossref
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Gao  W, Lin  W, Grewen  K, Gilmore  JH.  Functional connectivity of the infant human brain: plastic and modifiable.  Neuroscientist. 2017;23(2):169-184. doi:10.1177/1073858416635986PubMedGoogle ScholarCrossref
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Brummelte  S, Grunau  RE, Chau  V,  et al.  Procedural pain and brain development in premature newborns.  Ann Neurol. 2012;71(3):385-396. doi:10.1002/ana.22267PubMedGoogle ScholarCrossref
9.
Lejeune  F, Lordier  L, Pittet  MP,  et al.  Effects of an early postnatal music intervention on cognitive and emotional development in preterm children at 12 and 24 months: preliminary findings.  Front Psychol. 2019;10:494. doi:10.3389/fpsyg.2019.00494PubMedGoogle ScholarCrossref
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