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NICU-based stress response and preterm infant neurobehavior: exploring the critical windows for exposure

Abstract

Background

Exposure to maternal stress in utero negatively impacts cognitive and behavioral outcomes of children born at term. The neonatal intensive care unit (NICU) can be stressful for preterm infants during a developmental period corresponding to the third trimester of gestation. It is unknown whether stress in the NICU contributes to adverse neurodevelopment among NICU graduates. The aim was to examine the association between salivary cortisol and early neurodevelopment in preterm infants.

Methods

We examined the association between cortisol levels during the NICU hospitalization and subsequent performance on the NICU Network Neurobehavioral Scales (NNNS), estimating time-specific associations and considering sex differences.

Results

Eight hundred and forty salivary cortisol levels were measured from 139 infants. Average cortisol levels were inversely associated with NNNS Regulation scores for both male and female infants (β = −0.19; 95% CI: −0.44, −0.02). Critical developmental windows based on postmenstrual age were identified, with cortisol measured <30 weeks PMA positively associated with Habituation and Lethargy scores (β = 0.63–1.04). Critical developmental windows based on chronological age were identified, with cortisol measured in the first week of life inversely associated with Attention score (β = −1.01 for females; −0.93 for males).

Conclusions

Stress in the NICU at specific developmental time points may impact early preterm infant neurodevelopment.

Impact

  • Stress in the neonatal intensive care unit can impact the neurodevelopmental trajectory of premature infants.

  • The impact of stress is different at different points in development.

  • The impact of stress is sexually dimorphic.

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Fig. 1: Salivary cortisol concentration (nmol/l) by the timing of specimen collection.
Fig. 2: The results of rDLM examining associations between salivary cortisol and NNNS Habituation and Lethargy scores.
Fig. 3: The results of rDLM examining associations between salivary cortisol and the NNNS Attention and Regulation scores.
Fig. 4: The results of rDLM examining the association between salivary cortisol level and Handling subscale score by PMA and CA, respectively.

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Acknowledgements

We thank John Smith, Shaliz Pourkaviani, and Mount Sinai NICU nurses for their assistance with data collection.

Funding

Funding for NICU-HEALTH came through pilot grants from the Passport Foundation, the Mount Sinai Children’s Environmental Health Center, a National Institute of Environmental Health Sciences (NIEHS) mentored award K23ES022268 to A.S., an NIEHS Center Core Grant P30ES023515, and the National Institutes of Health ECHO program UG3OD02332 and UH3OD023337.

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Contributions

Substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data: X.Z., H.-H.L.H., C.G., A.S. Drafting the article or revising it critically for important intellectual content: X.Z., A.S. Final approval of the version to be published: E.S., H.-H.L.H., C.G.

Corresponding author

Correspondence to Xueying Zhang.

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The authors declare no competing interests.

Ethics approval and consent to participate

All participants provided written informed consent prior to enrollment in the NICU Hospital Exposures and Long-Term Health (NICU-HEALTH) study. The study was approved by the Program for the Protection of Research Subjects at the Icahn School of Medicine at Mount Sinai (IRB-16-01139; GCO#12-0332).

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Zhang, X., Spear, E., Hsu, HH.L. et al. NICU-based stress response and preterm infant neurobehavior: exploring the critical windows for exposure. Pediatr Res (2022). https://doi.org/10.1038/s41390-022-01983-3

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  • DOI: https://doi.org/10.1038/s41390-022-01983-3

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