Experimental drugs for the inhibition of preterm labor

References

• March of Dimes P, Save the Children, WHO. Born Too Soon: the Global Action Report on Preterm Birth. Geneva: WHO; 2012.
   Google Scholar
• Harrison MS, Goldenberg RL. Global burden of prematurity. Semin Fetal Neonatal Med. 2016;21(2):74–79.
   PubMed Web of Science ®Google Scholar
• Romero R, Dey S, Fisher SJ. Preterm labor: one syndrome, many causes. Science. 2014;345(6198):760–765.
   PubMed Web of Science ®Google Scholar
• Keelan JA. Pharmacological inhibition of inflammatory pathways for the prevention of preterm birth. J Reprod Immunol. 2011;88(2):176–184.
   PubMed Web of Science ®Google Scholar
• Ng P, Ireland D, Keelan J. Drugs to block cytokine signaling for the prevention and treatment of inflammation induced preterm birth. Front Immunol. 2015;6(166). DOI:10.3389/fimmu.2015.00166
   PubMedGoogle Scholar
• Rinaldi SF, Hutchinson JL, Rossi AG, et al. Anti-inflammatory mediators as physiological and pharmacological regulators of parturition. Expert Rev Clin Immunol. 2011;7(5):675–696.
   PubMed Web of Science ®Google Scholar
• Lappas M, Permezel M, Rice GE. Mitogen-Activated Protein Kinase Proteins Regulate LPS-Stimulated Release of Pro-inflammatory Cytokines and Prostaglandins from Human Gestational Tissues. Placenta. 2007;28(8–9):936–945.
   PubMed Web of Science ®Google Scholar
• Menon R, Fortunato SJ. The Role of Matrix Degrading Enzymes and Apoptosis in Rupture of Membranes. Thousand Oaks, CA: Sage Publications; 2004. p. 427–437.
   Google Scholar
• Grace YC, Gabriel N. Sterile inflammation: sensing and reacting to damage. Nat Rev Immunol. 2010;10(12):826.
   PubMed Web of Science ®Google Scholar
• Gomez‐Lopez N, Romero R, Plazyo O, et al. Intra‐Amniotic Administration of HMGB1 Induces Spontaneous Preterm Labor and Birth. Am J Reprod Immunol. 2016;75(1):3–7.
   PubMed Web of Science ®Google Scholar
• Boyle AK, Rinaldi SF, Norman JE, et al. Preterm birth: inflammation, fetal injury and treatment strategies. J Reprod Immunol. 2017;119:62–66.
   PubMed Web of Science ®Google Scholar
• Flenady V, Wojcieszek AM, Papatsonis DNM, et al. Calcium channel blockers for inhibiting preterm labour and birth. Cochrane Database Syst Rev. 2014;6:CD002255.
   Google Scholar
• Neilson JP, West HM, Dowswell T. Betamimetics for inhibiting preterm labour. Cochrane Database of Systematic Reviews. 2014;2:CD004352
   Google Scholar
• Reinebrant HE, Pileggi‐Castro C, Romero CLT, et al. Cyclo‐oxygenase (COX) inhibitors for treating preterm labour. Cochrane Database Syst Rev. 2015;6:CD001992.
   Google Scholar
• Hendricks SK, Smith JR, Moore DE, et al. Oligohydramnios associated with prostaglandin synthetase inhibitors in preterm labour. Br J Obstet Gynaecol. 1990;97(4):312–316.
   PubMedGoogle Scholar
• Norton ME, Merrill J, Cooper BA, et al. Neonatal complications after the administration of indomethacin for preterm labor. N Engl J Med. 1993;329(22):1602–1607.
   PubMed Web of Science ®Google Scholar
• Hammers AL, Sanchez-Ramos L, Kaunitz AM. Antenatal exposure to indomethacin increases the risk of severe intraventricular hemorrhage, necrotizing enterocolitis, and periventricular leukomalacia: a systematic review with metaanalysis. Am J Obstet Gynecol. 2015;212(4):505.e1-13.
   PubMed Web of Science ®Google Scholar
• Luo G, Abrahams VM, Tadesse S, et al. Progesterone inhibits basal and TNF-alpha-induced apoptosis in fetal membranes: a novel mechanism to explain progesterone-mediated prevention of preterm birth. Reprod Sci. 2010;17(6):532–539.
   PubMed Web of Science ®Google Scholar
• Kumar D, Springel E, Moore RM, et al. Progesterone inhibits in vitro fetal membrane weakening. Am J Obstet Gynecol. 2015;213(4):520.e1-9.
   Web of Science ®Google Scholar
• Meis PJ, Klebanoff M, Thom E, et al. Prevention of Recurrent Preterm Delivery by 17 Alpha-Hydroxyprogesterone Caproate. N Engl J Med. 2003;348(24):2379–2385.
   PubMed Web of Science ®Google Scholar
• Spong CY, Meis PJ, Thom EA, et al. Progesterone for prevention of recurrent preterm birth: impact of gestational age at previous delivery. Am J Obstet Gynecol. 2005;193(3, Supplement):1127–1131.
   PubMed Web of Science ®Google Scholar
• Da Fonseca EB, Bittar RE, Carvalho MHB, et al. Prophylactic administration of progesterone by vaginal suppository to reduce the incidence of spontaneous preterm birth in women at increased risk: A randomized placebo-controlled double-blind study. Am J Obstet Gynecol. 2003;188(2):419–424.
   PubMed Web of Science ®Google Scholar
• Dodd JM, Jones L, Flenady V, et al. Prenatal administration of progesterone for preventing preterm birth in women considered to be at risk of preterm birth. Cochrane Database Syst Rev. 2013;7:Cd004947.
   PubMed Web of Science ®Google Scholar
• Norman JE, Marlow N, Messow CM, et al. Vaginal progesterone prophylaxis for preterm birth (the OPPTIMUM study): a multicentre, randomised, double-blind trial. Lancet. 2016;387(10033):2106–2116.
   PubMed Web of Science ®Google Scholar
• Crowther CA, Ashwood P, McPhee AJ, et al. Vaginal progesterone pessaries for pregnant women with a previous preterm birth to prevent neonatal respiratory distress syndrome (the PROGRESS Study): A multicentre, randomised, placebo-controlled trial. PLoS Med. 2017;14(9):e1002390.
   PubMed Web of Science ®Google Scholar
• Romero R, Conde-Agudelo A, Da Fonseca E, et al. Vaginal progesterone for preventing preterm birth and adverse perinatal outcomes in singleton gestations with a short cervix: a meta-analysis of individual patient data. Am J Obstet Gynecol. 2018;218(2):161–180.
   PubMed Web of Science ®Google Scholar
• Gonzalez JM, Xu H, Ofori E, et al. Toll-like receptors in the uterus, cervix, and placenta: is pregnancy an immunosuppressed state? Am J Obstet Gynecol. 2007;197(3):296.e1-.e6.
   PubMed Web of Science ®Google Scholar
• Sheldon IM, Roberts MH, Receptor T-L. 4 Mediates the Response of Epithelial and Stromal Cells to Lipopolysaccharide in the Endometrium (TLR4 in the Endometrium). PLoS ONE. 2010;5(9):e12906.
   PubMed Web of Science ®Google Scholar
• Moço NP, Martin LF, Pereira AC, et al. Gene expression and protein localization of TLR-1, −2, −4 and −6 in amniochorion membranes of pregnancies complicated by histologic chorioamnionitis. Eur J Obstet Gynecol Reprod Biol. 2013;171(1):12–17.
   PubMed Web of Science ®Google Scholar
• Wahid HH, Dorian CL, Chin PY, et al. Toll-Like Receptor 4 Is an Essential Upstream Regulator of On-Time Parturition and Perinatal Viability in Mice. Endocrinology. 2015;156(10):3828–3841.
   PubMed Web of Science ®Google Scholar
• Li L, Kang J, Lei W. Role of Toll-like receptor 4 in inflammation-induced preterm delivery. Mol Hum Reprod. 2010;16(4):267–272.
   PubMed Web of Science ®Google Scholar
• Liu H, Redline R, Han Y. Fusobacterium nucleatum Induces Fetal Death in Mice via Stimulation of TLR4-Mediated Placental Inflammatory Response. J Immunol. 2007;179(4):2501–2508.
   PubMed Web of Science ®Google Scholar
• Adams Waldorf KM, Persing D, Novy MJ, et al. Pretreatment With Toll-like Receptor 4 Antagonist Inhibits Lipopolysaccharide-Induced Preterm Uterine Contractility, Cytokines, and Prostaglandins in Rhesus Monkeys. Reprod Sci. 2008;15(2):121–127.
   PubMed Web of Science ®Google Scholar
• Hutchinson MR, Zhang Y, Brown K, et al. Non‐stereoselective reversal of neuropathic pain by naloxone and naltrexone: involvement of toll‐like receptor 4 (TLR4. Eur J Neurosci. 2008;28(1):20–29.
   PubMed Web of Science ®Google Scholar
• Chin P, Dorian C, Hutchinson M, et al. Novel Toll-like receptor-4 antagonist (+)-naloxone protects mice from inflammation-induced preterm birth. Sci Rep. 2016;6(6):36112.
   PubMedGoogle Scholar
• Ireland DJ, Kemp MW, Miura Y, et al. Intra-amniotic pharmacological blockade of inflammatory signalling pathways in an ovine chorioamnionitis model. Mol Hum Reprod. 2015;21(5):479–489.
   PubMed Web of Science ®Google Scholar
• Ireland DJ, Nathan EA, Li S, et al. Preclinical evaluation of drugs to block inflammation-driven preterm birth. Innate Immun. 2017;23(1):20–33.
   PubMed Web of Science ®Google Scholar
• Sullivan MHF, Alvi SA, Brown NL, et al. The effects of a cytokine suppressive anti-inflammatory drug on the output of prostaglandin E 2 and interleukin-1 from human fetal membranes. Mol Hum Reprod. 2002;8(3):281–285.
   PubMed Web of Science ®Google Scholar
• Shoji T, Yoshida S, Mitsunari M, et al. Involvement of p38 MAP kinase in lipopolysaccharide-induced production of pro- and anti-inflammatory cytokines and prostaglandin E 2 in human choriodecidua. J Reprod Immunol. 2007;75(2):82–90.
   PubMed Web of Science ®Google Scholar
• Stinson LF, Ireland DJ, Kemp MW, et al. Effects of cytokine-suppressive anti-inflammatory drugs on inflammatory activation in ex vivo human and ovine fetal membranes. Reproduction. 2014;147(3):313–320.
   PubMed Web of Science ®Google Scholar
• Vaillancourt C, Lanoix D, Le Bellego F, et al. Involvement of MAPK Signalling in Human Villous Trophoblast Differentiation. Mini Rev Med Chem. 2009;9(8):962–973.
   PubMed Web of Science ®Google Scholar
• Chengxing Z, Jiong Y, Qiaoling P, et al. Hypoxia-inducible factor-2 alpha promotes the proliferation of human placenta-derived mesenchymal stem cells through the MAPK/ERK signaling pathway. Sci Rep. 2016;6(1):1–13.
   Google Scholar
• LaMarca HL, Dash PR, Vishnuthevan K, et al. Epidermal growth factor-stimulated extravillous cytotrophoblast motility is mediated by the activation of PI3-K, Akt and both p38 and p42/44 mitogen-activated protein kinases. Hum Reprod. 2008;23(8):1733–1741.
   PubMed Web of Science ®Google Scholar
• De Silva D, Mitchell M, Keelan J. Inhibition of choriodecidual cytokine production and inflammatory gene expression by selective I‐κB kinase (IKK) inhibitors. Br J Pharmacol. 2010;160(7):1808–1822.
   PubMed Web of Science ®Google Scholar
• Toda A, Sawada K, Fujikawa T, et al. Targeting Inhibitor of κB Kinase β Prevents Inflammation-Induced Preterm Delivery by Inhibiting IL-6 Production from Amniotic Cells. Am J Pathol. 2016;186(3):616–629.
   PubMed Web of Science ®Google Scholar
• Keelan J, Khan S, Yosaatmadja F, et al. Prevention of Inflammatory Activation of Human Gestational Membranes in an Ex Vivo Model Using a Pharmacological NF-kappa B Inhibitor. J Immunol. 2009;183(8):5270–5278.
   PubMed Web of Science ®Google Scholar
• Lappas EM, Permezel EM, Rice EG. N-Acetyl-Cysteine Inhibits Phospholipid Metabolism, Proinflammatory Cytokine Release, Protease Activity, and Nuclear Factor-κB Deoxyribonucleic Acid-Binding Activity in Human Fetal Membranes in Vitro. J Clin Endocrinol Metab. 2003;88(4):1723–1729.
   PubMed Web of Science ®Google Scholar
• Beloosesky R, Gayle DA, Ross MG. Maternal N-acetylcysteine suppresses fetal inflammatory cytokine responses to maternal lipopolysaccharide. Am J Obstet Gynecol. 2006;195(4):1053–1057.
   PubMed Web of Science ®Google Scholar
• Beloosesky R, Weiner Z, Khativ N, et al. Prophylactic maternal n-acetylcysteine before lipopolysaccharide suppresses fetal inflammatory cytokine responses. Am J Obstet Gynecol. 2009;200(6):665.e1-.e5.
   PubMed Web of Science ®Google Scholar
• Awad N, Khatib N, Ginsberg Y, et al. N-acetyl-cysteine (NAC) attenuates LPS-induced maternal and amniotic fluid oxidative stress and inflammatory responses in the preterm gestation. Am J Obstet Gynecol. 2011;204(5):450.e15-450.e20.
   PubMed Web of Science ®Google Scholar
• Buhimschi IA, Buhimschi CS, Weiner CP. Protective effect of N-acetylcysteine against fetal death and preterm labor induced by maternal inflammation. Am J Obstet Gynecol. 2003;188(1):203–208.
   PubMed Web of Science ®Google Scholar
• Chang EY, Zhang J, Sullivan S, et al. N-acetylcysteine prevents preterm birth by attenuating the LPS-induced expression of contractile associated proteins in an animal model. J Matern Fetal Neonatal Med. 2012;25(11):2395–2400.
   PubMed Web of Science ®Google Scholar
• Chang EY, Zhang J, Sullivan S, et al. N-acetylcysteine attenuates the maternal and fetal proinflammatory response to intrauterine LPS injection in an animal model for preterm birth and brain injury. J Matern Fetal Neonatal Med. 2011;24(5):732–740.
   PubMed Web of Science ®Google Scholar
• Sharabi H, Khatib N, Ginsberg Y, et al. Therapeutic N-Acetyl-Cysteine (Nac) Following Initiation of Maternal Inflammation Attenuates Long-Term Offspring Cerebral Injury, as Evident in Magnetic Resonance Imaging (MRI). Neuroscience. 2019;403:118–124.
   PubMed Web of Science ®Google Scholar
• Shahin AY, Hassanin IMA, Ismail AM, et al. Effect of oral N‐acetyl cysteine on recurrent preterm labor following treatment for bacterial vaginosis. Int J Gynecol Obstet. 2009;104(1):44–48.
   PubMed Web of Science ®Google Scholar
• Jenkins DD, Wiest DB, Mulvihill DM, et al. Fetal and Neonatal Effects of N-Acetylcysteine When Used for Neuroprotection in Maternal Chorioamnionitis. J Pediatr. 2016;168(67–76.e6). DOI:10.1016/j.jpeds.2015.09.076.
   PubMedGoogle Scholar
• McElhatton PR, Sullivan FM, Volans GN, et al. Paracetamol Poisoning in Pregnancy: an Analysis of the Outcomes of Cases Referred to the Teratology Information Service of the National Poisons Information Service. Hum Exp Toxicol. 1990;9(3):147–153.
   PubMed Web of Science ®Google Scholar
• Østensen M, Förger F. How safe are anti-rheumatic drugs during pregnancy? Curr Opin Pharmacol. 2013;13(3):470–475.
   PubMed Web of Science ®Google Scholar
• Rahimi R, Nikfar S, Rezaie A, et al. Pregnancy outcome in women with inflammatory bowel disease following exposure to 5-aminosalicylic acid drugs: A meta-analysis. Reprod Toxicol. 2008;25(2):271–275.
   PubMed Web of Science ®Google Scholar
• Nath CA, Ananth CV, Smulian JC, et al. ORIGINAL ARTICLE: can Sulfasalazine Prevent Infection-Mediated Pre-Term Birth in a Murine Model? Am J Reprod Immunol. 2010;63(2):144–149.
   PubMed Web of Science ®Google Scholar
• Lappas M, Permezel M, Georgiou HM, et al. Nuclear factor kappa B regulation of proinflammatory cytokines in human gestational tissues in vitro. Biol Reprod. 2002;67(2):668–673.
   PubMed Web of Science ®Google Scholar
• Peltier MR, Tee SC, Kinzler WL, et al. ORIGINAL ARTICLE: effect of Sulfasalazine on Basal and Bacteria‐Stimulated Interleukin‐8 Production by Endocervical Epithelial Cells. Am J Reprod Immunol. 2009;61(3):190–195.
   PubMed Web of Science ®Google Scholar
• Romero R, Espinoza J, Goncalves LF, et al. The role of inflammation and infection in preterm birth. Semin Reprod Med. 2007;25(1):21–39.
   PubMed Web of Science ®Google Scholar
• Sadowsky DW, Adams KM, Gravett MG, et al. Preterm labor is induced by intraamniotic infusions of interleukin-1β and tumor necrosis factor-α but not by interleukin-6 or interleukin-8 in a nonhuman primate model. Am J Obstet Gynecol. 2006;195(6):1578–1589.
   PubMed Web of Science ®Google Scholar
• Burdet J, Sacerdoti F, Cella M, et al. Role of TNF-α in the mechanisms responsible for preterm delivery induced by Stx2 in rats. Br J Pharmacol. 2013;168(4):946–953.
   PubMed Web of Science ®Google Scholar
• Holmgren C, Esplin MS, Hamblin S, et al. Evaluation of the use of anti-TNF-α in an LPS-induced murine model. J Reprod Immunol. 2008;78(2):134–139.
   PubMed Web of Science ®Google Scholar
• Fidel PL, Romero R, Cutright J, et al. Treatment With the Interleukin-1 Receptor Antagonist and Soluble Tumor Necrosis Factor Receptor Fc Fusion Protein Does Not Prevent Endotoxin-Induced Preterm Parturition in Mice. J Soc Gynecologic Invest. 1997;4(1):22–26.
   Google Scholar
• Mourabet M, El-Hachem S, Harrison J, et al. Anti-TNF Antibody Therapy for Inflammatory Bowel Disease During Pregnancy: A Clinical Review. Curr Drug Targets. 2010;11(2):234–241.
   PubMed Web of Science ®Google Scholar
• Djokanovic N, Klieger-Grossmann C, Pupco A, et al. Safety of infliximab use during pregnancy. Reprod Toxicol. 2011;32(1):93–97.
   PubMed Web of Science ®Google Scholar
• Nadeau-Vallée M, Quiniou C, Palacios J, et al. Novel Noncompetitive IL-1 Receptor-Biased Ligand Prevents Infection- and Inflammation-Induced Preterm Birth. J Immunol. 2015;195(7):3402–3415.
   PubMed Web of Science ®Google Scholar
• Quiniou C, Sapieha P, Lahaie I, et al. Development of a novel noncompetitive antagonist of IL-1 receptor. J Immunol. 2008;180(10):6977.
   PubMed Web of Science ®Google Scholar
• Nadeau-Vallée M, Chin P-Y, Belarbi L, et al. Antenatal Suppression of IL-1 Protects against Inflammation-Induced Fetal Injury and Improves Neonatal and Developmental Outcomes in Mice. J Immunol. 2017;198(5):2047.
   PubMed Web of Science ®Google Scholar
• Girardi G. Can statins prevent pregnancy complications? J Reprod Immunol. 2014;101-102(1):161–167.
   PubMedGoogle Scholar
• Zarek J, Koren G. The Fetal Safety of Statins: A Systematic Review and Meta-Analysis. J Obstet Gynaecology Canada. 2014;36(6):506–509.
   PubMedGoogle Scholar
• Karalis DG, Hill AN, Clifton S, et al. The risks of statin use in pregnancy: A systematic review. J Clin Lipidol. 2016;10(5):1081–1090.
   PubMed Web of Science ®Google Scholar
• Basraon SK, Menon R, Makhlouf M, et al. Can statins reduce the inflammatory response associated with preterm birth in an animal model? Am J Obstet Gynecol. 2012;207(3):224.e1-.e7.
   PubMed Web of Science ®Google Scholar
• Basraon SK, Costantine MM, Saade G, et al. The Effect of Simvastatin on Infection‐Induced Inflammatory Response of Human Fetal Membranes. Am J Reprod Immunol. 2015;74(1):54–61.
   PubMed Web of Science ®Google Scholar
• Gonzalez JM, Pedroni SMA, Girardi G. Statins prevent cervical remodeling, myometrial contractions and preterm labor through a mechanism that involves hemoxygenase-1 and complement inhibition. Mol Hum Reprod. 2014;20(6):579–589.
   PubMed Web of Science ®Google Scholar
• Boyle AK, Rinaldi SF, Rossi AG, et al. Repurposing simvastatin as a therapy for preterm labor: evidence from preclinical models. Faseb J. 2019;33(2):2743–2758.
   PubMed Web of Science ®Google Scholar
• Leghi GE, Muhlhausler BS. The effect of n-3 LCPUFA supplementation on oxidative stress and inflammation in the placenta and maternal plasma during pregnancy. Prostaglandins, Leukotrienes and Essential Fatty Acids (PLEFA). 2016;113:33–39.
   PubMed Web of Science ®Google Scholar
• Taguchi A, Yamashita A, Kawana K, et al. Recent Progress in Therapeutics for Inflammation-Associated Preterm Birth: A Review. Reprod Sci. 2017;24(1):7–18.
   PubMed Web of Science ®Google Scholar
• Schebb NH, Ostermann AI, Yang J, et al. Comparison of the effects of long-chain omega-3 fatty acid supplementation on plasma levels of free and esterified oxylipins. Prostaglandins Other Lipid Mediators. 2014;113-115:21–29.
   Google Scholar
• Brazle A, Johnson B, Webel S, et al. Omega-3 fatty acids in the gravid pig uterus as affected by maternal supplementation with omega-3 fatty acids1. J Anim Sci. 2009;87(3):994–1002.
   PubMed Web of Science ®Google Scholar
• Zhou SJ, Best K, Gibson R, et al. Study protocol for a randomised controlled trial evaluating the effect of prenatal omega-3 LCPUFA supplementation to reduce the incidence of preterm birth: the ORIP trial. BMJ Open. 2017;7(9):e018360.
   PubMedGoogle Scholar
• Middleton P, Gomersall JC, Gould JF, et al. Omega‐3 fatty acid addition during pregnancy. Cochrane Database Syst Rev. 2018;11:CD003402.
   Google Scholar
• Makrides M, Best K, Yelland L, et al. A Randomized Trial of Prenatal n−3 Fatty Acid Supplementation and Preterm Delivery. N Engl J Med. 2019;381(11):1035–1045.
   PubMed Web of Science ®Google Scholar
• Serhan CN, Chiang N. Resolution phase lipid mediators of inflammation: agonists of resolution. Curr Opin Pharmacol. 2013;13:632–640.
   PubMed Web of Science ®Google Scholar
• Elliott E, Hanson CK, Anderson-Berry AL, et al. The role of specialized pro-resolving mediators in maternal-fetal health. Prostaglandins, Leukotrienes Essent Fatty Acids. 2017;126:98–104.
   PubMed Web of Science ®Google Scholar
• Keelan JA, Mas E, D’Vaz N, et al. Effects of maternal n-3 fatty acid supplementation on placental cytokines, pro-resolving lipid mediators and their precursors. Reproduction. 2015;149(2):171–178.
   PubMed Web of Science ®Google Scholar
• Aki Y, Kei K, Kensuke T, et al. Increased tissue levels of omega-3 polyunsaturated fatty acids prevents pathological preterm birth. Sci Rep. 2013;3(1):1–7.
   Google Scholar
• Chandrasekharan JA, Sharma-Walia N. Lipoxins: nature’s way to resolve inflammation. J Inflamm Res. 2015;8:181–192.
   PubMed Web of Science ®Google Scholar
• Rinaldi SF, Catalano RD, Wade J, et al. 15-epi-lipoxin A 4 reduces the mortality of prematurely born pups in a mouse model of infection-induced preterm birth. Mol Hum Reprod. 2015;21(4):359–368.
   PubMed Web of Science ®Google Scholar
• Maldonado-Pérez D, Golightly E, Denison FC, et al. A role for lipoxin A4 as anti-inflammatory and proresolution mediator in human parturition. Faseb J. 2011;25(2):569.
   PubMed Web of Science ®Google Scholar
• Borra M, Smith B, Denu J. Mechanism of human SIRT1 activation by resveratrol. J Biol Chem. 2005;280(17):17187–17195.
   PubMed Web of Science ®Google Scholar
• Lappas M, Mitton A, Lim R, et al. SIRT1 Is a Novel Regulator of Key Pathways of Human Labor 1. Biol Reprod. 2010;84(1):167–178.
   PubMed Web of Science ®Google Scholar
• Manna SK, A M, Aggarwal BB. Resveratrol suppresses TNF-induced activation of nuclear transcription factors NF-kappa B, activator protein-1, and apoptosis: potential role of reactive oxygen intermediates and lipid peroxidation. J Immunol. 2000;164(12):6509.
   PubMed Web of Science ®Google Scholar
• Furuya H, Taguchi A, Kawana K, et al. Resveratrol Protects Against Pathological Preterm Birth by Suppression of Macrophage-Mediated Inflammation. Reprod Sci. 2015;22(12):1561–1568.
   PubMed Web of Science ®Google Scholar
• Bariani MV, Correa F, Leishman E, et al. Resveratrol protects from lipopolysaccharide-induced inflammation in the uterus and prevents experimental preterm birth. Mol Hum Reprod. 2017;23(8):571–581.
   PubMed Web of Science ®Google Scholar
• Novaković R, Radunović N, Marković-Lipkovski J, et al. Effects of the polyphenol resveratrol on contractility of human term pregnant myometrium. Mol Hum Reprod. 2015;21(6):545–551.
   PubMed Web of Science ®Google Scholar
• Roberts VHJ, Pound LD, Thorn SR, et al. Beneficial and cautionary outcomes of resveratrol supplementation in pregnant nonhuman primates. Faseb J. 2014;28(6):2466–2477.
   PubMed Web of Science ®Google Scholar
• Agarwal R, Agarwal C, Ichikawa H, et al. Anticancer potential of silymarin: from bench to bed side. Anticancer Res. 2006;26(6B):4457–4498.
   PubMed Web of Science ®Google Scholar
• Abenavoli L, Capasso R, Milic N, et al. Milk thistle in liver diseases: past, present, future. Chichester, UK: John Wiley & Sons, Ltd.; 2010. p. 1423–1432.
   Google Scholar
• Bremner P, Heinrich M. Natural products as targeted modulators of the nuclear factor-KB pathway. J Pharm Pharmacol. 2002;54(4):453–472.
   PubMed Web of Science ®Google Scholar
• Cristofalo R, Bannwart-Castro CF, Magalhães CG, et al. Silibinin attenuates oxidative metabolism and cytokine production by monocytes from preeclamptic women. Free Radic Res. 2013;47(4):268–275.
   PubMed Web of Science ®Google Scholar
• Giorgi VSI, Peracoli MTS, Peracoli JC, et al. Silibinin modulates the NF-κb pathway and pro-inflammatory cytokine production by mononuclear cells from preeclamptic women. J Reprod Immunol. 2012;95(1):67–72.
   PubMed Web of Science ®Google Scholar
• Ratana L, Carrington JM, Gillian B, et al. Effect of silibinin in reducing inflammatory pathways in in vitro and in vivo models of infection-induced preterm birth. PLoS ONE. 2014;9(3):e92505.
   PubMed Web of Science ®Google Scholar
• Sarah AR, Hanan HW, Peck Yin C, et al. Toll-like Receptor-4: A New Target for Preterm Labour Pharmacotherapies? Curr Pharm Des. 2018;24(9):960–973.
   PubMed Web of Science ®Google Scholar
• Professor Jeff Keelan Preventing Preterm Birth and Improving Infant Outcomes. Scientia. 21 September 2017; 92–95.
   Google Scholar
• Preclinical evaluation of a novel allosteric IL-1R inhibitor (rytvela) for the prevention of perinatal inflammation-induced fetal injury [2018-2021] [cited 2020 Jan 1]. http://purl.org/au-research/grants/nhmrc/1145295
   Google Scholar
• Loiselle S-E, Zanre N, Hou X. MN-VCQSRDOSC. P02: optimal dose and time of administration of Rytvela for prevention of inflammation‐induced preterm birth and fetal tissue injury. Am J Reprod Immunol. 2019;81(S1):39–40.
   Google Scholar
• Whyte S A feasibility study investigating pravastatin for the prevention of preterm birth in women. 2018 [cited 2020 Jan 1]. https://doi.org/10.1186/ISRCTN82984919
   Google Scholar