Pre-term birth and the altered HPA axis

 It is known that stress leads to an increase in cortisol levels, and this can have different outcomes depending on short term vs. long term stress. As we know cortisol is released, by the adrenal cortex, in response to stress turning the sympathetic nervous system on. This results in an increase in blood glucose for brain and muscle use, decrease in digestion, reproduction, and growth, and an increased heart rate, respiratory rate and blood pressure. However, while in the short-term this is a beneficial response, in the long term this disrupts the body’s normal need to rest and repair.

Currently there is a lot of research that has found a correlation between preterm birth and a decreased functioning of the hypothalamic-pituitary axis. One such study found that the young adults between the ages of 19-27 born preterm have lower cortisol and insulin levels in response to psychosocial stress than do young adults of the same age group born at term (Kaseva 2014). Reduced cortisol levels tell us that the preterm young adults have a reduced stress responses than young adults born at term. Babies born preterm are at risk for being born with underdeveloped organs and vital physiological functions. A peptide, adrenomedullin, highly concentrated in preterm babies has an inhibitory effect on the production of cortisol which may be influencing the low cortisol levels of preterm babies (Travers 2021). Therefore, preterm babies have a reduced HPA axis to begin with, which carries on to their reduced hormone production later in life.

This is a relatively new area of study because new medical knowledge and equipment has increased the survival rate of babies born preterm. Children born preterm would have not survived 50 or more years ago, but with modern technology these children are able to live long and full lives. Thus, the long-term effect of preterm birth is only now coming to light. Some effects may include cardiovascular issues, high blood glucose, high blood pressure, and neurodevelopmental disorders (Luu, Rehman, Nuyt 2017). As stated above, insulin levels in preterm babies reduces that amount of glucose taken up by tissue cells, leaving high amounts of glucose in the blood. The increased blood glucose alters the osmotic balance increasing blood pressure. Blood pressure among other preterm underdevelopments affect the cardiovascular circulation, thus altering the structure of the heart. Overall, the reduced functioning of the HPA axis found in individuals born preterm alters the steroid production and normal responses to environmental stimuli.

Another study that introduces the social factor of race into the correlation between cortisol levels and preterm birth found that black adolescents had the same cortisol levels as term adolescents, and preterm non-black adolescents had the expected reduced cortisol levels. Further studies of these results should look into the social factors that disproportionately affect these groups. Preterm black individuals may be experiencing higher levels of stress due to social factors that appears as a normal cortisol level for a term adolescent. The preterm black adolescents may still have a blunted HPA axis, but the response is higher because of an increased stimulus. Many environmental factors influence the daily lives of humans which may not have detrimental effects in the short term, but in the long term can alter an individual’s normal physiology. Overall social issues must also be viewed with a scientific lens and vice versa.

Brown, C. L., Myers, K., South, A. M., Shaltout, H. A., Jensen, E. T., Nixon, P. A., & Washburn, L. K. (2020). Influence of race on the effect of premature birth on salivary cortisol response to stress in adolescents. Pediatric research, 87(6), 1100–1105. https://doi.org/10.1038/s41390-019-0682-3

Kaseva, N., Wehkalampi, K., Pyhälä, R., Moltchanova, E., Feldt, K., Pesonen, A. K., Heinonen, K., Hovi, P., Järvenpää, A. L., Andersson, S., Eriksson, J. G., Räikkönen, K., & Kajantie, E. (2014). Blunted hypothalamic-pituitary-adrenal axis and insulin response to psychosocial stress in young adults born preterm at very low birth weight. Clinical endocrinology, 80(1), 101–106. https://doi.org/10.1111/cen.12251

Luu, T. M., Rehman Mian, M. O., & Nuyt, A. M. (2017). Long-Term Impact of Preterm Birth: Neurodevelopmental and Physical Health Outcomes. Clinics in perinatology, 44(2), 305–314. https://doi.org/10.1016/j.clp.2017.01.003

Travers, S., Martinerie, L., Xue, Q. Y., Perrot, J., Viengchareun, S., Caron, K. M., Blakeney, E. S., Boileau, P., Lombès, M., & Pussard, E. (2021). Adrenomedullin: new inhibitory regulator for cortisol synthesis and secretion. The Journal of endocrinology, 251(1), 97–109. https://doi.org/10.1530/JOE-20-0564