Abstract
Background
Extremely preterm (EPT) birth has been related to dysregulation of stress responses and behavioral/learning problems at school age. Early adverse experiences can blunt HPA axis reactivity. We hypothesized that an attenuated cortisol awakening response would be associated with developmental and behavioral problems at school age in EPT children.
Methods
This secondary analysis of a sub-cohort of the SUPPORT study included children born between 24 and 27 weeks, evaluated at 6–7 years with a neurodevelopmental battery and cortisol measures. Differences were tested between EPT and a term-born group. Relationships of cortisol awakening response to test scores were analyzed.
Results
Cortisol was measured in 110 EPT and 29 term-born 6–7 year olds. Unadjusted WISC-IV and NEPSY-II scores were significantly worse among EPT children only. Conners Parent Rating Scale behavior scores were significantly worse among EPT children. After adjusting for covariates, blunted cortisol awakening responses were found to be associated with poorer scores on memory tests and greater problems with inattention for the EPT group (p < 0.05) only.
Conclusions
Among children born EPT, we identified an association of blunted cortisol awakening response with memory and inattention problems. This may have implications related to stress reactivity and its relationship to learning problems in children born EPT.
ClinicalTrials.gov ID
Extended Follow-up at School Age for the SUPPORT Neuroimaging and Neurodevelopmental Outcomes (NEURO) Cohort: NCT00233324.
Impact
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In children born EPT, stress reactivity may have a relationship to learning problems.
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Cortisol awakening response should be a component for follow-up in EPT born children.
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Components of executive function, such as memory and attention, are related to stress reactivity.
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Data availability
Data reported in this paper may be requested through a data use agreement. Further details are available at https://neonatal.rti.org/index.cfm?fuseaction=DataRequest.Home.
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Acknowledgements
Participating NRN sites collected data and transmitted it to RTI International, the data coordinating center (DCC) for the network, which stored, managed, and analyzed the data for this study. On behalf of the NRN, RTI International had full access to all of the data in the study, and with the NRN Center Principal Investigators, takes responsibility for the integrity of the data and accuracy of the data analysis. We are indebted to our medical and nursing colleagues and the infants and their parents who agreed to take part in this study.
Funding
The National Institutes of Health, the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), and the National Heart, Lung, and Blood Institute (NHLBI) provided grant support for the Neonatal Research Network’s Extended Follow-up at School Age for the SUPPORT Neuroimaging and Neurodevelopmental Outcomes (NEURO) Cohort through cooperative agreements. While NICHD staff had input into the study design, conduct, analysis, and manuscript drafting, the comments and views of the authors do not necessarily represent the views of NICHD, the National Institutes of Health, the Department of Health and Human Services, or the U.S. Government.
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J.L. and K.L.W.: conception and design, acquisition, analysis and interpretation of data, drafting the article, and final approval of the version to be published. J.F.F.: acquisition of data, critical revision of the article for important intellectual content, and final approval of the version to be published. A.D.: conception and design, drafting the article and final approval of the version to be published. B.D. and A.G.D.: analysis and interpretation of the data, revising it critically for important intellectual content, and final approval of the version to be published. C.M.B.: analysis and interpretation of the data, revising it critically for important intellectual content, final approval of the version to be published. K.E.G.: substantial contributions to conception, design, acquisition of data, drafting the article revising it critically for important intellectual content, and final approval of the version to be published. B.R.V.: acquisition and interpretation of data, critical revision of the article for important intellectual content, and final approval of the version to be published. S.R.H.: conception and acquisition of the data, revising it critically for important intellectual content, and final approval of the version to be published.
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A.G.D. is founder and chief scientific and strategy advisor at Salimetrics LLC and Salivabio LLC. The nature of those relationships is managed by the policies of the committees on conflict of interest at the Johns Hopkins University School of Medicine and the University of California at Irvine.
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Lowe, J., Fuller, J.F., Dempsey, A.G. et al. Cortisol awakening response and developmental outcomes at 6–7 years in children born extremely preterm. Pediatr Res 93, 689–695 (2023). https://doi.org/10.1038/s41390-022-02113-9
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DOI: https://doi.org/10.1038/s41390-022-02113-9
