Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a protein with anti-atherogenic and vasoprotective effects that has never been studied in newborns exposed to preeclampsia. Our aim was to examine TRAIL serum concentrations in such neonates after birth and during the transitional period.
Serum TRAIL levels were measured on the first and fifth day of life (DOL1 and DOL5, respectively) in 38 newborns exposed to early-onset preeclampsia and 38 controls born of normotensive mothers.
TRAIL values on DOL1 and DOL5 did not differ between cases and controls. However, from DOL1 to DOL5 TRAIL levels increased in controls (from 20.54 ± 7.35 to 23.93 ± 11.02 pg/ml, p = 0.044) but decreased in those exposed to preeclampsia (from 25.58 ± 15.74 to 20.53 ± 10.72 pg/ml, p = 0.035). Overall, the relative change of TRAIL values from DOL1 to DOL5 was positively related to birth weight (beta coefficient 0.234, p = 0.042) and inversely related to preeclampsia (beta coefficient –0.241, p = 0.036).
Newborns exposed to early-onset preeclampsia present a decrease in serum TRAIL levels during the transitional period. This pattern is exactly the opposite from what is observed in neonates born to normotensive mothers, and most likely points towards a defective mechanism of extrauterine adaptation related to preeclampsia exposure in utero.
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) levels during the transitional period do not differ between infants exposed to early-onset preeclampsia and controls
The pattern of change of TRAIL levels after birth is different; TRAIL decreases in newborns exposed to preeclampsia but increases in controls
The decrease of TRAIL levels during the transitional period points towards a defective mechanism of extrauterine adaptation and an altered cardiometabolic profile in newborns exposed to early-onset preeclampsia.
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The data that support the findings of this study are available from the corresponding author (Dr. Karatza) but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available. Data are however available from the authors upon reasonable request and with permission of the corresponding author (Dr. Karatza).
Mol, B. W. J. et al. Pre-eclampsia. Lancet 387, 999–1011 (2016).
Raymond, D. & Peterson, E. A critical review of early-onset and late-onset preeclampsia. Obstet. Gynecol. Surv. 66, 497–506 (2011).
Bokslag, A., van Weissenbruch, M., Mol, B. W. & de Groot, C. J. Preeclampsia; short and long-term consequences for mother and neonate. Early Hum. Dev. 102, 47–50 (2016).
Story, L. & Chappell, L. C. Preterm pre-eclampsia: What every neonatologist should know. Early Hum. Dev. 114, 26–30 (2017).
Backes, C. H. et al. Maternal preeclampsia and neonatal outcomes. J. Pregnancy. 2011, 214365. (2011).
Amaral, L. M., Cunningham, M. W. Jr, Cornelius, D. C. & LaMarca, B. Preeclampsia: long-term consequences for vascular health. Vasc. Health Risk. Manag. 11, 403–415 (2015).
Karatza, A. A. & Dimitriou, G. Preeclampsia emerging as a novel risk factor for cardiovascular disease in the offspring. Curr. Pediatr. Rev. 16, 194–199 (2020).
Davis, E. F. et al. Pre-eclampsia and offspring cardiovascular health: mechanistic insights from experimental studies. Clin. Sci. (Lond.) 123, 53–72 (2012).
Hofbauer, L. C. & Schoppet, M. Clinical implications of the osteoprotegerin/RANKL/RANK system for bone and vascular diseases. JAMA 292, 490–495 (2004).
Venuraju, S. M., Yerramasu, A., Corder, R. & Lahiri, A. Osteoprotegerin as a predictor of coronary artery disease and cardiovascular mortality and morbidity. JACC 55, 2049–2061 (2010).
Montagnana, M., Lippi, G., Danese, E. & Guidi, G. C. The role of osteoprotegerin in cardiovascular disease. Ann. Med. 45, 254–264 (2013).
Perez de Ciriza, C., Lawrie, A. & Varo, N. Osteoprotegerin in cardiometabolic disorders. Int. J. Endocrinol., 2015, Article ID 564934 (2015).
Bernardi, S., Bossi, F., Toffoli, B. & Fabris, B. Roles and Clinical Applications of OPG and TRAIL as Biomarkers in Cardiovascular Disease. Biomed. Res. Int. 2016, 1752854 (2016).
Secchiero, P. et al. Potential prognostic significance of decreased serum levels of TRAIL after acute myocardial infarction. PLoS. One. 4, e4442 (2009).
Almasan, A. & Ashkenazi, A. Apo2L/TRAIL: apoptosis signaling, biology, and potential for cancer therapy. Cytokine. Growth Factor. Rev. 14, 337–348 (2003).
Blanco, O., Leno-Durán, E., Morales, J. C., Olivares, E. G. & Ruiz-Ruiz, C. Human decidual stromal cells protect lymphocytes from apoptosis. Placenta 30, 677–685 (2009).
Morano, D. et al. Lower maternal serum tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) levels in early preeclampsia. A retrospective study. Pregnancy Hypertens. 12, 1–5 (2018).
Zauli, G. et al. The circulating levels of TRAIL are extremely low after delivery but rapidly recover in both mothers and newborns. Cytokine 64, 51–53 (2013).
Report of the American College of Obstetricians and Gynecologists’ Task Force on Hypertension in Pregnancy. Hypertension in pregnancy: executive summary. Obstet. Gynecol. 122, 1122–1131 (2013).
Chou, J. H., Roumiantsev, S. & Singh, R. PediTools electronic growth chart calculators: applications in clinical care, research, and quality improvement. J. Med. Internet Res. 22, e16204 (2020).
Marsters, S. A., Pitti, R. A., Sheridan, J. P. & Ashkenazi, A. Control of apoptosis signaling by Apo2 ligand. Recent. Prog. Horm. Res. 54, 225–234 (1999).
Lorz, C., Benito, A., Ucero, A. C., Santamaría, B. & Ortiz, A. Trail and kidney disease Front. Biosci. (Landmark Ed.) 14, 3740–3749 (2009).
Phillips, T. A. et al. TRAIL (Apo-2L) and TRAIL receptors in human placentas: implications for immune privilege. J. Immunol. 162, 6053–6059 (1999).
Chen, L. et al. Localization and variation of TRAIL and its receptors in human placenta during gestation. Life. Sci. 74, 1479–1486 (2004).
Spradley, F. T. Metabolic abnormalities and obesity’s impact on the risk for developing preeclampsia. Am. J. Physiol. Regul. Integr. Comp. Physiol. 312, R5–R12 (2017).
Harith, H. H., Morris, M. J. & Kavurma, M. M. On the TRAIL of obesity and diabetes. Trends Endocrinol. Metab. 24, 578–587 (2013).
Oikonomou, N. et al. Osteoprotegerin and RANKL serum concentrations in neonates of mothers with early-onset pre-eclampsia: comparison with neonates of normotensive mothers. Early Hum. Dev. 135, 1–5 (2019).
Oikonomou, N. et al. Aortic intima-media thickness in neonates exposed to early-onset preeclampsia. Early Hum. Dev. 151, 105166 (2020).
Chourdakis, E. et al. Effect of early-onset preeclampsia on offspring’s blood pressure during the first month of life. J. Pediatr. 220, 21–26.e1 (2020).
This research is co-financed by Greece and the European Union (European Social Fund- ESF) through the Operational Programme «Human Resources Development, Education and Lifelong Learning» in the context of the project “Strengthening Human Resources Research Potential via Doctorate Research” (MIS-5000432), implemented by the State Scholarships Foundation (ΙΚΥ). The publication of the article has been financed by the research committee of the university of Patras.
The authors declare no competing interests.
The study was approved by the local Ethics Committee of the University hospital of Patras, Greece and a written informed consent was obtained from the parents.
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Oikonomou, N., Fouzas, S., Kritikou, D. et al. Preterm newborns exposed to early-onset preeclampsia have altered postnatal Tumor Necrosis Factor-related apoptosis-inducing ligand trends versus controls. Pediatr Res (2022). https://doi.org/10.1038/s41390-022-02301-7