Background: Antenatal betamethasone (BM) treatment for mothers at risk for premature delivery is effective in reducing neonatal morbidity. Immunodepression, defined as monocyte human leukocyte antigen (HLA)-DR expression <60%, is common in patients in intensive care. In very low birth weight (VLBW) infants, immunodepression correlates with gestational age and may predispose to infections. Objectives: To evaluate whether timing of antenatal BM associates with immunodepression in VLBW infants. Methods: We determined monocyte HLA-DR expression by flow cytometry and measured 13 cytokines, cortisol, and BM in plasma from 56 VLBW infants. We calculated total glucocorticoid index as the sum of BM and cortisol at the ratio 33.3:1. Results: HLA-DR expression both in cord (R2 = 0.175, p = 0.033, n = 26) and on day 1 (R2 = 0.125, p = 0.011, n = 51) showed an association with timing of BM. A short interval from BM to birth induced more pronounced and prolonged immunodepression, with lower HLA-DR% on postnatal day 7. On day 3, 25 infants (45%) met the criteria of immunodepression. HLA-DR expression correlated negatively with total glucocorticoid index (cord: R2 = -0.573, p = 0.003, n = 13; day 1: R2 = -0.213, p = 0.008, n = 32). Elapsed time from maternal BM correlated positively with concentrations of cytokines IL-6 and IL-10 on day 1. Conclusions: In VLBW infants, antenatal BM associated with transient immunodepression in a time-dependent manner. Suppression of both anti- and proinflammatory cytokines occurred. These effects may lead to an increased risk for later infections.

Liggins GC, Howie RN: A controlled trial of antepartum glucocorticoid treatment for prevention of the respiratory distress syndrome in premature infants. Pediatrics 1972;50:515-525.
Roberts D, Dalziel S: Antenatal corticosteroids for accelerating foetal lung maturation for women at risk of preterm birth. Cochrane Database Syst Rev 2006;3:CD004454.
Miracle X, Di Renzo G, Stark A, Fanaroff A, Carbonell- Estrany X, Saling E, Coordinators of WAPM Prematurity Working Group: Guideline for the use of antenatal corticosteroids for foetal maturation. J Perinat Med 2008;36:191-196.
Ballard PL, Ballard RA: Cytoplasmic receptor for glucocorticoids in lung of the human fetus and neonate. J Clin Invest 1974;53:477-486.
DeLemos RA, Shermeta JW, Knelson JH, Kotas R, Avery ME: Acceleration of appearance of pulmonary surfactant in the foetal lamb by administration of corticosteroids. Am Rev Respir Dis 1970;102:459-461.
Motoyama EK, Orzalesi Y, Kikkawa M, Kaibara B, Wu C, Zigas J, Cook CD: Effect of cortisol on the maturation of foetal rabbit lungs. Pediatrics 1971;48:547-555.
Schacke H, Döcke WD, Asadullah K: Mechanisms involved in the side effects of glukocorticoids. Pharmacol Ther 2002;96:23-43.
Turunen R, Nupponen I, Siitonen S, Repo H, Andersson S: Onset of mechanical ventilation is associated with rapid activation of circulating phagocytes in preterm infants. Pediatrics 2006;117;448-454.
Turunen R, Andersson S, Laivuori H, Kajantie E, Siitonen S, Repo H, Nupponen I: Increased postnatal inflammation in mechanically ventilated preterm infants born to mothers with early-onset preeclampsia. Neonatology 2011;100:241-247.
Bohrer B, Silveira RC, Neto EC, Procianoy RS: Mechanical ventilation of newborns infant changes in plasma pro- and anti-inflammatory cytokines. J Pediatr 2010;156:16-19.
Kanakoudi-Tsakalidou F, Debonera V, Drossou-Agakidou V, Sarafidis K, Tzimouli V, Taparkou A, Kremenopoulos G: Flow-cytomeric measurement of HLA-DR expression on circulating monocytes in healthy and sick neonates using negative selection. Clin Exp Immunol 2001;123:402-407.
Volk T, Schmutzler M, Engelhardt L, Döcke W, Volk H, Konertz W, Kox WJ: Influence of aminosteroid and glucocorticoid treatment on inflammation and immune function during cardiopulmonary bypass. Crit Care Med 2001;29:2137-2142.
Le Tulzo Y, Pangault C, Amiot L, Guilloux V, Tribut O, Arvieux C, Camus C, Fauchet R, Thomas R, Drénou B: Monocyte human leukocyte antigen-DR transcriptional downregulation by cortisol during septic shock. Am J Respir Crit Care Med 2004;169:1144-1151.
Palojärvi A, Petäjä J, Siitonen S, Janér C, Andersson S: Low monocyte HLA-DR expression as an indicator of immunodepression in very low birth weight infants. Pediatr Res 2013;73:469-475.
Azizia M, Lloyd J, Allen M, Klein N, Peebles D: Immune status in very preterm neonates. Pediatrics 2012;129:967-974.
Kramer BW, Ikegami M, Moss TJ, Nitsos I, Newnham JP, Jobe AH: Antenatal betamethasone changes cord blood monocyte responses to endotoxin in preterm lambs. Pediatr Res 2004;55:764-768.
Ballard P, Gluckman P, Liggins G, Kaplan S, Grumbach M: Steroid and growth hormone levels in premature infants after prenatal betamethasone therapy to prevent respiratory distress syndrome. Pediatr Res 1980;14:122-127.
Nykänen P, Raivio T, Heinonen K, Jänne O, Voutilainen R: Circulating glucocorticoid bioactivity and serum cortisol concentrations in premature infants: the influence of exogenous glucocorticoids and clinical factors. Eur J Endocrinol 2007;156:577-583.
Ng C, Li K, Wong R, Chui K, Wong E, Li G, Fok T: Proinflammatory and anti-inflammatory cytokine responses in preterm infants with systemic infections. Arch Dis Child Fetal Neonatal Ed 2003;88:F209-F213.
Gogos CA, Drosou E, Bassaris HP, Skoutelis A: Pro- versus anti-inflammatory cytokine profile in patients with severe sepsis: a marker for prognosis and future therapeutic options. J Infect Dis 2000;181:176-180.
Fumeaux T, Pugin J: Role of interleukin-10 in the intracellular sequestration of human leukocyte antigen-DR in monocytes during septic shock. Am J Respir Crit Care Med 2002;166:1475-1482.
Pachot A, Lepape A, Vey S, Bienvenu J, Mougin B, Monneret G: Systemic transcriptional analysis in survivor and non-survivor septic shock patients: a preliminary study. Immunol Lett 2006;106:63-71.
Livingston DH, Appel SH, Wellhausen SR, Sonnenfield G, Polk HC Jr: Depressed interferon gamma production and monocyte HLA-DR expression after severe injury. Arch Surg 1988;123:1309-1312.
Monneret G, Lepape A, Voirin N, Bohé J, Venet F, Debard AL, Thizy H, Bienvenu J, Gueyffler F, Vanhems P: Persisting low monocyte human leukocyte antigen-DR expression predicts mortality in septic shock. Intens Care Med 2006;32:1175-1183.
Allen ML, Peters MJ, Goldman A, Elliott M, James I, Callard R, Klein NJ: Early postoperative monocyte deactivation predicts systemic inflammation and prolonged stay in pediatric cardiac intensive care. Crit Care Med 2002;30:1140-1145.
Peltoniemi O, Kari A, Tammela O, Lehtonen L, Marttila R, Halmesmäki E, Jouppila P, Hallman M: Randomized trial of a single repeat dose of prenatal betamethasone treatment in imminent preterm birth. Pediatrics 2007;119:290-298.
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