Antenatal Corticosteroids for Fetal Lung Maturity - Too Much of a Good Thing?

Author(s): Lenka Hrabalkova, Tsukasa Takahashi, Matthew W. Kemp, Sarah J. Stock*

Journal Name: Current Pharmaceutical Design

Volume 25 , Issue 5 , 2019

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Background: Between 5-15% of babies are born prematurely worldwide, with preterm birth defined as delivery before 37 completed weeks of pregnancy (term is at 40 weeks of gestation). Women at risk of preterm birth receive antenatal corticosteroids as part of standard care to accelerate fetal lung maturation and thus improve neonatal outcomes in the event of delivery. As a consequence of this treatment, the entire fetal organ system is exposed to the administered corticosteroids. The implications of this exposure, particularly the long-term impacts on offspring health, are poorly understood.

Aims: This review will consider the origins of antenatal corticosteroid treatment and variations in current clinical practices surrounding the treatment. The limitations in the evidence base supporting the use of antenatal corticosteroids and the evidence of potential harm to offspring are also summarised.

Results: Little has been done to optimise the dose and formulation of antenatal corticosteroid treatment since the first clinical trial in 1972. International guidelines for the use of the treatment lack clarity regarding the recommended type of corticosteroid and the gestational window of treatment administration. Furthermore, clinical trials cited in the most recent Cochrane Review have limitations which should be taken into account when considering the use of antenatal corticosteroids in clinical practice. Lastly, there is limited evidence regarding the long-term effects on the different fetal organ systems exposed in utero, particularly when the timing of corticosteroid administration is sub-optimal.

Conclusion: Further investigations are urgently needed to determine the most safe and effective treatment regimen for antenatal corticosteroids, particularly regarding the type of corticosteroid and optimal gestational window of administration. A clear consensus on the use of this common treatment could maximise the benefits and minimise potential harms to offspring.

Keywords: Antenatal, corticosteroids, glucocorticoids, betamethasone, dexamethasone, pregnancy, preterm birth.

Tielsch JM. Global Incidence of Preterm Birth. Nestle Nutr Inst Workshop Ser 2015; 81: 9-15.
Norman JE, Morris C, Chalmers J. The effect of changing patterns of obstetric care in Scotland (1980-2004) on rates of preterm birth and its neonatal consequences: perinatal database study. PLoS Med 2009; 6(9): e1000153.
Costeloe KL, Hennessy EM, Haider S, Stacey F, Marlow N, Draper ES. Short term outcomes after extreme preterm birth in England: comparison of two birth cohorts in 1995 and 2006 (the EPICure studies). BMJ 2012; 345: e7976.
Blencowe H, Cousens S, Oestergaard MZ, et al. National, regional, and worldwide estimates of preterm birth rates in the year 2010 with time trends since 1990 for selected countries: A systematic analysis and implications. Lancet 2012; 379(9832): 2162-72.
Blencowe H, Vos T, Lee AC, et al. Estimates of neonatal morbidities and disabilities at regional and global levels for 2010: introduction, methods overview, and relevant findings from the Global Burden of Disease study. Pediatr Res 2013; 74(Suppl. 1): 4-16.
Khan KA, Petrou S, Dritsaki M, et al. Economic costs associated with moderate and late preterm birth: A prospective population-based study. BJOG 2015; 122(11): 1495-505.
Mangham LJ, Petrou S, Doyle LW, Draper ES, Marlow N. The cost of preterm birth throughout childhood in England and Wales. Pediatrics 2009; 123(2): e312-27.
McCormick MC, Litt JS, Smith VC, Zupancic JA. Prematurity: An overview and public health implications. Annu Rev Public Health 2011; 32: 367-79.
Hillman NH, Kallapur SG, Jobe AH. Physiology of transition from intrauterine to extrauterine life. Clin Perinatol 2012; 39(4): 769-83.
Fowden AL, Li J, Forhead AJ. Glucocorticoids and the preparation for life after birth: Are there long-term consequences of the life insurance? Proc Nutr Soc 1998; 57(1): 113-22.
Chapman K, Holmes M, Seckl J. 11β-hydroxysteroid dehydrogenases: intracellular gate-keepers of tissue glucocorticoid action. Physiol Rev 2013; 93(3): 1139-206.
Reynolds RM. Programming effects of glucocorticoids. Clin Obstet Gynecol 2013; 56(3): 602-9.
Walker N, Filis P, Soffientini U, Bellingham M, O’Shaughnessy PJ, Fowler PA. Placental transporter localization and expression in the Human: the importance of species, sex, and gestational age differences. Biol Reprod 2017; 96(4): 733-42.
Boyle EM, Poulsen G, Field DJ, et al. Effects of gestational age at birth on health outcomes at 3 and 5 years of age: population based cohort study. BMJ 2012; 344: e896.
Liggins GC, Howie RN. A controlled trial of antepartum glucocorticoid treatment for prevention of the respiratory distress syndrome in premature infants. Pediatrics 1972; 50(4): 515-25.
Liggins GC. Premature delivery of foetal lambs infused with glucocorticoids. J Endocrinol 1969; 45(4): 515-23.
Liggins GC, Grieves S. Possible role for prostaglandin F 2 in parturition in sheep. Nature 1971; 232(5313): 629-31.
Liggins GC, Grieves SA, Kendall JZ, Knox BS. The physiological rôles of progesterone, oestradiol-17 and prostaglandin F 2 in the control of ovine parturition. J Reprod Fertil Suppl 1972; 16(Suppl. 16): 85-10.
DeLemos RA, Shermeta DW, Knelson JH, Kotas R, Avery ME. Acceleration of appearance of pulmonary surfactant in the fetal lamb by administration of corticosteroids. Am Rev Respir Dis 1970; 102(3): 459-61.
Crowley P, Chalmers I, Keirse MJ. The effects of corticosteroid administration before preterm delivery: An overview of the evidence from controlled trials. Br J Obstet Gynaecol 1990; 97(1): 11-25.
Effect of corticosteroids for fetal maturation on perinatal outcomes. NIH Consensus Development Panel on the Effect of Corticosteroids for Fetal Maturation on Perinatal Outcomes. JAMA 1995; 273(5): 413-8.
Crowley P. Prophylactic corticosteroids for preterm birth. Cochrane Database Syst Rev 2000; (2): Cd000065.
Roberts D, Brown J, Medley N, Dalziel SR. Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth. Cochrane Database Syst Rev 2017; 3: CD004454.
Roberts D, Dalziel S. Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth. Cochrane Database Syst Rev 2006; (3): CD004454.
Morales WJ, Diebel ND, Lazar AJ, Zadrozny D. The effect of antenatal dexamethasone administration on the prevention of respiratory distress syndrome in preterm gestations with premature rupture of membranes. Am J Obstet Gynecol 1986; 154(3): 591-5.
Kramer BW, Kallapur S, Newnham J, Jobe AH. Prenatal inflammation and lung development. Semin Fetal Neonatal Med 2009; 14(1): 2-7.
Sehdev HM, Abbasi S, Robertson P, et al. The effects of the time interval from antenatal corticosteroid exposure to delivery on neonatal outcome of very low birth weight infants. Am J Obstet Gynecol 2004; 191(4): 1409-13.
Peaceman AM, Bajaj K, Kumar P, Grobman WA. The interval between a single course of antenatal steroids and delivery and its association with neonatal outcomes. Am J Obstet Gynecol 2005; 193(3 Pt 2): 1165-9.
Ring AM, Garland JS, Stafeil BR, Carr MH, Peckman GS, Pircon RA. The effect of a prolonged time interval between antenatal corticosteroid administration and delivery on outcomes in preterm neonates: A cohort study. Am J Obstet Gynecol 2007; 196(5): 457.e1-6.
Kuk JY, An JJ, Cha HH, et al. Optimal time interval between a single course of antenatal corticosteroids and delivery for reduction of respiratory distress syndrome in preterm twins. Am J Obstet Gynecol 2013; 209(3): 256.e1-7.
Guidelines WHO. WHO Guidelines Approved by the Guidelines Review Committee. WHO Recommendations on Interventions to Improve Preterm Birth Outcomes: World Health Organization 2015 Copyright (c) World Health Organization . 2015.
Kemp MW, Newnham JP, Challis JG, Jobe AH, Stock SJ. The clinical use of corticosteroids in pregnancy. Hum Reprod Update 2016; 22(2): 240-59.
Ballard PL, Ballard RA. Scientific basis and therapeutic regimens for use of antenatal glucocorticoids. Am J Obstet Gynecol 1995; 173(1): 254-62.
Petersen MC, Ashley JJ, McBride WG, Nation RL. Disposition of betamethasone in parturient women after intramuscular administration. Br J Clin Pharmacol 1984; 18(3): 383-92.
Ballard PL, Granberg P, Ballard RA. Glucocorticoid levels in maternal and cord serum after prenatal betamethasone therapy to prevent respiratory distress syndrome. J Clin Invest 1975; 56(6): 1548-54.
Kemp MW, Saito M, Usuda H, et al. Maternofetal pharmacokinetics and fetal lung responses in chronically catheterized sheep receiving constant, low-dose infusions of betamethasone phosphate. Am J Obstet Gynecol 2016; 215(6): 775.e1-775.e12.
Kemp MW, Saito M, Usuda H, et al. The efficacy of antenatal steroid therapy is dependent on the duration of low-concentration fetal exposure: evidence from a sheep model of pregnancy. Am J Obstet Gynecol 2018; 219(3): 301.e1-301.e16.
Schmidt AF, Kemp MW, Kannan PS, et al. Antenatal dexamethasone vs. betamethasone dosing for lung maturation in fetal sheep. Pediatr Res 2017; 81(3): 496-503.
Schmidt AF, Kemp MW, Rittenschober-Böhm J, et al. Low-dose betamethasone-acetate for fetal lung maturation in preterm sheep. Am J Obstet Gynecol 2018; 218(1): 132.e1-132.e19.
Subtil D, Tiberghien P, Devos P, et al. Immediate and delayed effects of antenatal corticosteroids on fetal heart rate: A randomized trial that compares betamethasone acetate and phosphate, betamethasone phosphate, and dexamethasone. Am J Obstet Gynecol 2003; 188(2): 524-31.
Khandelwal M, Chang E, Hansen C, Hunter K, Milcarek B. Betamethasone dosing interval: 12 or 24 hours apart? A randomized, noninferiority open trial. Am J Obstet Gynecol 2012; 206(3): 201.e1-201.e11.
Brownfoot FC, Gagliardi DI, Bain E, Middleton P, Crowther CA. Different corticosteroids and regimens for accelerating fetal lung maturation for women at risk of preterm birth. Cochrane Database Syst Rev 2013; (8): CD006764.
Senat MV, Minoui S, Multon O, Fernandez H, Frydman R, Ville Y. Effect of dexamethasone and betamethasone on fetal heart rate variability in preterm labour: A randomised study. Br J Obstet Gynaecol 1998; 105(7): 749-55.
Magee LA, Dawes GS, Moulden M, Redman CW. A randomised controlled comparison of betamethasone with dexamethasone: effects on the antenatal fetal heart rate. Br J Obstet Gynaecol 1997; 104(11): 1233-8.
Baud O, Foix-L’Helias L, Kaminski M, et al. Antenatal glucocorticoid treatment and cystic periventricular leukomalacia in very premature infants. N Engl J Med 1999; 341(16): 1190-6.
Bar-Lev MR, Maayan-Metzger A, Matok I, Heyman Z, Sivan E, Kuint J. Short-term outcomes in low birth weight infants following antenatal exposure to betamethasone versus dexamethasone. Obstet Gynecol 2004; 104(3): 484-8.
Committee Opinion No.713: Antenatal Corticosteroid Therapy for Fetal Maturation. Obstet Gynecol 2017; 130(2): e102-9.
Kfouri J, D’Souza R. Antenatal corticosteroids. CMAJ 2017; 189(8): E319.
Minakami H, Maeda T, Fujii T, et al. Guidelines for obstetrical practice in Japan: Japan Society of Obstetrics and Gynecology (JSOG) and Japan Association of Obstetricians and Gynecologists (JAOG) 2014 edition. J Obstet Gynaecol Res 2014; 40(6): 1469-99.
ACOG Committee on Obstetic Practice.ACOG Committee Opinion No. 475: Antenatal corticosteroid therapy for fetal maturation. Obstet Gynecol 2011; 117(2 Pt 1): 422-4.
Kemp MW, Jobe AH, Usuda H, et al. Efficacy and safety of antenatal steroids. Am J Physiol Regul Integr Comp Physiol 2018; 315(4): R825-39.
American College of Ostetricians and Gynecologists; Society for Maternal-fetal Medicine.Obstetric Care consensus No. 6: Periviable Birth. Obstet Gynecol 2017; 130(4): e187-99.
Implementation of the use of antenatal corticosteroids in the late preterm birth period in women at risk for preterm delivery. Am J Obstet Gynecol 2016; 215(2): B13-5.
Travers CP, Carlo WA, McDonald SA, et al. Mortality and pulmonary outcomes of extremely preterm infants exposed to antenatal corticosteroids. Am J Obstet Gynecol 2018; 218(1): 130.e1-130.e13.
Requejo J, Merialdi M, Althabe F, Keller M, Katz J, Menon R. Born too soon: care during pregnancy and childbirth to reduce preterm deliveries and improve health outcomes of the preterm baby. Reprod Health 2013; 10(Suppl. 1): S4.
Grzeskowiak LE, Grivell RM, Mol BW. Trends in receipt of single and repeat courses of antenatal corticosteroid administration among preterm and term births: A retrospective cohort study. Aust N Z J Obstet Gynaecol 2017; 57(6): 643-50.
Razaz N, Skoll A, Fahey J, Allen VM, Joseph KS. Trends in optimal, suboptimal, and questionably appropriate receipt of antenatal corticosteroid prophylaxis. Obstet Gynecol 2015; 125(2): 288-96.
Makhija NK, Tronnes AA, Dunlap BS, Schulkin J, Lannon SM. Antenatal corticosteroid timing: Accuracy after the introduction of a rescue course protocol. Am J Obstet Gynecol 2016; 214(1): 120.e1-6.
Althabe F, Belizán JM, Mazzoni A, et al. Antenatal corticosteroids trial in preterm births to increase neonatal survival in developing countries: study protocol. Reprod Health 2012; 9: 22.
Althabe F, Belizán JM, McClure EM, et al. A population-based, multifaceted strategy to implement antenatal corticosteroid treatment versus standard care for the reduction of neonatal mortality due to preterm birth in low-income and middle-income countries: the ACT cluster-randomised trial. Lancet 2015; 385(9968): 629-39.
Jobe AH, Goldenberg RL. Antenatal corticosteroids: An assessment of anticipated benefits and potential risks. Am J Obstet Gynecol 2018; 219(1): 62-74.
Kapoor A, Petropoulos S, Matthews SG. Fetal programming of hypothalamic-pituitary-adrenal (HPA) axis function and behavior by synthetic glucocorticoids. Brain Res Brain Res Rev 2008; 57(2): 586-95.
Moisiadis VG, Matthews SG. Glucocorticoids and fetal programming part 1: Outcomes. Nat Rev Endocrinol 2014; 10(7): 391-402.
Moisiadis VG, Matthews SG. Glucocorticoids and fetal programming part 2: Mechanisms. Nat Rev Endocrinol 2014; 10(7): 403-11.
Wintour EM, Moritz KM, Johnson K, Ricardo S, Samuel CS, Dodic M. Reduced nephron number in adult sheep, hypertensive as a result of prenatal glucocorticoid treatment. J Physiol 2003; 549(Pt 3): 929-35.
Ortiz LA, Quan A, Weinberg A, Baum M. Effect of prenatal dexamethasone on rat renal development. Kidney Int 2001; 59(5): 1663-9.
Keller-Wood M, Feng X, Wood CE, et al. Elevated maternal cortisol leads to relative maternal hyperglycemia and increased stillbirth in ovine pregnancy. Am J Physiol Regul Integr Comp Physiol 2014; 307(4): R405-13.
Richards EM, Wood CE, Rabaglino MB, Antolic A, Keller-Wood M. Mechanisms for the adverse effects of late gestational increases in maternal cortisol on the heart revealed by transcriptomic analyses of the fetal septum. Physiol Genomics 2014; 46(15): 547-59.
Antolic A, Wood CE, Keller-Wood M. Chronic maternal hypercortisolemia in late gestation alters fetal cardiac function at birth. Am J Physiol Regul Integr Comp Physiol 2018; 314(3): R342-52.
Agnew EJ, Ivy JR, Stock SJ, Chapman KE. Glucocorticoids, antenatal corticosteroid therapy and fetal heart maturation. J Mol Endocrinol 2018; 61(1): R61-73.
Crowther CA, Doyle LW, Haslam RR, Hiller JE, Harding JE, Robinson JS. Outcomes at 2 years of age after repeat doses of antenatal corticosteroids. N Engl J Med 2007; 357(12): 1179-89.
Dalziel SR, Liang A, Parag V, Rodgers A, Harding JE. Blood pressure at 6 years of age after prenatal exposure to betamethasone: follow-up results of a randomized, controlled trial. Pediatrics 2004; 114(3): e373-7.
Doyle LW, Ford GW, Davis NM, Callanan C. Antenatal corticosteroid therapy and blood pressure at 14 years of age in preterm children Clinical science (London, England : 1979). 2000; 98(2): 137-42.
Dalziel SR, Walker NK, Parag V, et al. Cardiovascular risk factors after antenatal exposure to betamethasone: 30-year follow-up of a randomised controlled trial. Lancet 2005; 365(9474): 1856-62.
Kelly BA, Lewandowski AJ, Worton SA, et al. Antenatal glucocorticoid exposure and long-term alterations in aortic function and glucose metabolism. Pediatrics 2012; 129(5): e1282-90.
Nixon PA, Washburn LK, Michael O'Shea T, Shaltout HA, Russell GB, Snively BM, et al. Antenatal steroid exposure and heart rate variability in adolescents born with very low birth weight Pediatric research . 2017; 81(1-1): 57-62.
South AM, Nixon PA, Chappell MC, Diz DI, Russell GB, Snively BM, et al. Antenatal corticosteroids and the renin-angiotensin-aldosterone system in adolescents born preterm 2017.
De Blasio MJ, Dodic M, Jefferies AJ, Moritz KM, Wintour EM, Owens JA. Maternal exposure to dexamethasone or cortisol in early pregnancy differentially alters insulin secretion and glucose homeostasis in adult male sheep offspring. Am J Physiol Endocrinol Metab 2007; 293(1): E75-82.
De Matteo R, Hodgson DJ, Bianco-Miotto T, et al. Betamethasone-exposed preterm birth does not impair insulin action in adult sheep. J Endocrinol 2017; 232(2): 175-87.
Pettit KE, Tran SH, Lee E, Caughey AB. The association of antenatal corticosteroids with neonatal hypoglycemia and hyperbilirubinemia The journal of maternal-fetal and neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstet . 2014; 27(7): 683-6.
Jolley JA, Rajan PV, Petersen R, Fong A, Wing DA. Effect of antenatal betamethasone on blood glucose levels in women with and without diabetes. Diabetes Res Clin Pract 2016; 118: 98-104.
Christensen HD, Gonzalez CL, Stewart JD, Rayburn WF. Multiple courses of antenatal betamethasone and cognitive development of mice offspring. J Matern Fetal Med 2001; 10(4): 269-76.
Ozdemir H, Guvenal T, Cetin M, Kaya T, Cetin A. A placebo-controlled comparison of effects of repetitive doses of betamethasone and dexamethasone on lung maturation and lung, liver, and body weights of mouse pups. Pediatr Res 2003; 53(1): 98-103.
Nguyen VB, De Matteo R, Harding R, Stefanidis A, Polglase GR, Black MJ. Experimentally Induced Preterm Birth in Sheep Following a Clinical Course of Antenatal Betamethasone: Effects on Growth and Long-Term Survival. Reprod Sci 2017; 24(8): 1203-13.
Braun T, Sloboda DM, Tutschek B, et al. Fetal and neonatal outcomes after term and preterm delivery following betamethasone administration. Int J Gynaecol Obstet 2015; 130(1): 64-9.
Murphy KE, Willan AR, Hannah ME, et al. Effect of antenatal corticosteroids on fetal growth and gestational age at birth. Obstet Gynecol 2012; 119(5): 917-23.
Davis EP, Waffarn F, Uy C, Hobel CJ, Glynn LM, Sandman CA. Effect of prenatal glucocorticoid treatment on size at birth among infants born at term gestation. J Perinatol 2009; 29(11): 731-7.
Murphy KE, Hannah ME, Willan AR, et al. Multiple courses of antenatal corticosteroids for preterm birth (MACS): A randomised controlled trial. Lancet 2008; 372(9656): 2143-51.
Uno H, Lohmiller L, Thieme C, et al. Brain damage induced by prenatal exposure to dexamethasone in fetal rhesus macaques. I. Hippocampus. Brain Res Dev Brain Res 1990; 53(2): 157-67.
Noorlander CW, Tijsseling D, Hessel EV, et al. Antenatal glucocorticoid treatment affects hippocampal development in mice. PLoS One 2014; 9(1): e85671.
Crudo A, Petropoulos S, Suderman M, et al. Effects of antenatal synthetic glucocorticoid on glucocorticoid receptor binding, DNA methylation, and genome-wide mRNA levels in the fetal male hippocampus. Endocrinology 2013; 154(11): 4170-81.
Moisiadis VG, Constantinof A, Kostaki A, Szyf M, Matthews SG. Prenatal Glucocorticoid Exposure Modifies Endocrine Function and Behaviour for 3 Generations Following Maternal and Paternal Transmission. Sci Rep 2017; 7(1): 11814.
Crudo A, Petropoulos S, Moisiadis VG, et al. Prenatal synthetic glucocorticoid treatment changes DNA methylation states in male organ systems: multigenerational effects. Endocrinology 2012; 153(7): 3269-83.
Drake AJ, Walker BR, Seckl JR. Intergenerational consequences of fetal programming by in utero exposure to glucocorticoids in rats. Am J Physiol Regul Integr Comp Physiol 2005; 288(1): R34-8.
Frahm KA, Tobet SA. Development of the blood-brain barrier within the paraventricular nucleus of the hypothalamus: influence of fetal glucocorticoid excess. Brain Struct Funct 2015; 220(4): 2225-34.
Neuhaus W, Schlundt M, Fehrholz M, et al. Multiple Antenatal Dexamethasone Treatment Alters Brain Vessel Differentiation in Newborn Mouse Pups. PLoS One 2015; 10(8): e0136221.
Maturana CJ, Aguirre A, Sáez JC. High glucocorticoid levels during gestation activate the inflammasome in hippocampal oligodendrocytes of the offspring. Dev Neurobiol 2017; 77(5): 625-42.
Tijsseling D, Wijnberger LD, Derks JB, et al. Effects of antenatal glucocorticoid therapy on hippocampal histology of preterm infants. PLoS One 2012; 7(3): e33369.
Crowther CA, McKinlay CJ, Middleton P, Harding JE. Repeat doses of prenatal corticosteroids for women at risk of preterm birth for improving neonatal health outcomes. Cochrane Database Syst Rev 2015; (7): CD003935.
Wapner RJ, Sorokin Y, Mele L, et al. Long-term outcomes after repeat doses of antenatal corticosteroids. N Engl J Med 2007; 357(12): 1190-8.
Paules C, Pueyo V, Marti E, de Vilchez S, Burd I, Calvo P, et al. Long-term outcomes after repeat doses of antenatal corticosteroids. N Engl J Med 2017; 216(2): 157.e1-7.
MacArthur BA, Howie RN, Dezoete JA, Elkins J. Cognitive and psychosocial development of 4-year-old children whose mothers were treated antenatally with betamethasone. Pediatrics 1981; 68(5): 638-43.
MacArthur BA, Howie RN, Dezoete JA, Elkins J. School progress and cognitive development of 6-year-old children whose mothers were treated antenatally with betamethasone. Pediatrics 1982; 70(1): 99-105.
Alexander N, Rosenlöcher F, Stalder T, et al. Impact of antenatal synthetic glucocorticoid exposure on endocrine stress reactivity in term-born children. J Clin Endocrinol Metab 2012; 97(10): 3538-44.
Alexander N, Rosenlöcher F, Dettenborn L, et al. Impact of Antenatal Glucocorticoid Therapy and Risk of Preterm Delivery on Intelligence in Term-Born Children. J Clin Endocrinol Metab 2016; 101(2): 581-9.

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Year: 2019
Published on: 02 June, 2019
Page: [593 - 600]
Pages: 8
DOI: 10.2174/1381612825666190326143814
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