1932

Abstract

While there is not a wide range of pregnancy-specific drugs, there are some very specific high-risk areas of obstetric care for which unique pharmacological approaches have been established. In preterm birth, labor induction and augmentation, and the management of postpartum hemorrhage, these pharmacological approaches have become the bedrock in managing some of the most common and problematic areas of antenatal and intrapartum care. In this review, we summarize the existing established and emerging evidence that supports and broadens these pharmacological approaches to obstetric management and its impact on clinical practice. It is clear that existing therapeutics are limited. They have largely been developed from our knowledge of the physiology of the myometrium and act on hormonal receptors and their signaling pathways or on ion channels influencing excitability. Newer drugs in development are mostly refinements of these two approaches, but novel agents from plants and improved formulations are also discussed.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-pharmtox-051921-122822
2023-01-20
2024-04-25
Loading full text...

Full text loading...

/deliver/fulltext/pharmtox/63/1/annurev-pharmtox-051921-122822.html?itemId=/content/journals/10.1146/annurev-pharmtox-051921-122822&mimeType=html&fmt=ahah

Literature Cited

  1. 1.
    Wray S, Burdyga T, Noble D, Noble K, Borysova L, Arrowsmith S. 2015. Progress in understanding electro-mechanical signalling in the myometrium. Acta Physiol. 213:2417–31
    [Google Scholar]
  2. 2.
    Wray S, Arrowsmith S. 2021. Uterine excitability and ion channels and their changes with gestation and hormonal environment. Annu. Rev. Physiol. 83:331–57
    [Google Scholar]
  3. 3.
    Wray S, Kupittayanant S, Shmygol A, Smith RD, Burdyga T. 2001. The physiological basis of uterine contractility: a short review. Exp. Physiol. 86:2239–46
    [Google Scholar]
  4. 4.
    LeFevre NM, Krumm E, Cobb WJ. 2021. Labor dystocia in nulliparous women. Am. Fam. Physician 103:290–96
    [Google Scholar]
  5. 5.
    Neilson JP, Lavender T, Quenby S, Wray S. 2003. Obstructed labour. Br. Med. Bull. 67:191–204
    [Google Scholar]
  6. 6.
    Maharaj D. 2010. Assessing cephalopelvic disproportion: back to the basics. Obstet. Gynecol. Surv. 65:6387–95
    [Google Scholar]
  7. 7.
    Clapp MA, James KE, Little SE, Robinson JN, Kaimal AJ. 2021. Association between hospital-level cesarean delivery rates and severe maternal morbidity and unexpected newborn complications. Am. J. Obstet. Gynecol. MFM 3:6100474
    [Google Scholar]
  8. 8.
    Bernitz S, Øian P, Rolland R, Sandvik L, Blix E. 2014. Oxytocin and dystocia as risk factors for adverse birth outcomes: a cohort of low-risk nulliparous women. Midwifery 30:3364–70
    [Google Scholar]
  9. 9.
    Karaçam Z, Walsh D, Bugg GJ. 2014. Evolving understanding and treatment of labour dystocia. Eur. J. Obstet. Gynecol. Reprod. Biol. 182:123–27
    [Google Scholar]
  10. 10.
    Brown HC, Paranjothy S, Dowswell T, Thomas J. 2013. Package of care for active management in labour for reducing caesarean section rates in low-risk women. Cochrane Database Syst. Rev. 2013:9CD004907
    [Google Scholar]
  11. 11.
    Prendergast C. 2020. Maternal phenotype: How does age, obesity and diabetes affect myometrial function?. Curr. Opin. Physiol. 13:108–16
    [Google Scholar]
  12. 12.
    Fakhraei R, Denize K, Simon A, Sharif A, Zhu-Pawlowsky J et al. 2022. Predictors of adverse pregnancy outcomes in pregnant women living with obesity: a systematic review. Int. J. Environ. Res. Public Health 19:42063
    [Google Scholar]
  13. 13.
    Carvajal JA, Oporto JI. 2021. The myometrium in pregnant women with obesity. Curr. Vasc. Pharmacol. 19:2193–200
    [Google Scholar]
  14. 14.
    Noble K, Zhang J, Wray S. 2006. Lipid rafts, the sarcoplasmic reticulum and uterine calcium signalling: an integrated approach. J. Physiol. 570:Pt. 129–35
    [Google Scholar]
  15. 15.
    Shmygol A, Noble K, Wray S. 2007. Depletion of membrane cholesterol eliminates the Ca2+-activated component of outward potassium current and decreases membrane capacitance in rat uterine myocytes. J. Physiol. 581:Pt. 2445–56
    [Google Scholar]
  16. 16.
    Smith RD, Babiychuk EB, Noble K, Draeger A, Wray S. 2005. Increased cholesterol decreases uterine activity: functional effects of cholesterol alteration in pregnant rat myometrium. Am. J. Physiol. Cell Physiol. 288:5C982–88
    [Google Scholar]
  17. 17.
    Mauricio R, Khera A. 2022. Statin use in pregnancy: Is it time for a paradigm shift?. Circulation 145:7496–98
    [Google Scholar]
  18. 18.
    Cavazos-Rehg PA, Krauss MJ, Spitznagel EL, Bommarito K, Madden T et al. 2015. Maternal age and risk of labor and delivery complications. Matern. . Child Health J 19:61202–11
    [Google Scholar]
  19. 19.
    Sweeney EM, Dockery P, Crankshaw DJ, O'Brien YM, Walsh JM, Morrison JJ. 2014. Human uterine lower segment myometrial cell and nuclear volume at term: influence of maternal age. J. Anat. 225:6625–33
    [Google Scholar]
  20. 20.
    Arrowsmith S, Robinson H, Noble K, Wray S. 2012. What do we know about what happens to myometrial function as women age?. J. Muscle Res. Cell Motil. 33:3–4209–17
    [Google Scholar]
  21. 21.
    Bugg GJ, Siddiqui F, Thornton JG. 2013. Oxytocin versus no treatment or delayed treatment for slow progress in the first stage of spontaneous labour. Cochrane Database Syst. Rev. 2013:6CD007123
    [Google Scholar]
  22. 22.
    Wray S, Alruwaili M, Prendergast C. 2021. Hypoxia and reproductive health: hypoxia and labour. Reproduction 161:1F67–80
    [Google Scholar]
  23. 23.
    Larcombe-McDouall JB, Harrison N, Wray S 1998. The in vivo relationship between blood flow, contractions, pH and metabolites in the rat uterus. Pflugers Arch 435:6810–17
    [Google Scholar]
  24. 24.
    Peebles DM, Spencer JA, Edwards AD, Wyatt JS, Reynolds EO et al. 1994. Relation between frequency of uterine contractions and human fetal cerebral oxygen saturation studied during labour by near infrared spectroscopy. Br. J. Obstet. Gynaecol. 101:144–48
    [Google Scholar]
  25. 25.
    Prichard N, Lindquist A, Hiscock R, Ruff S, Tong S, Brownfoot FC. 2019. High-dose compared with low-dose oxytocin for induction of labour of nulliparous women at term. J. Matern. Fetal Neonatal Med. 32:3362–68
    [Google Scholar]
  26. 26.
    Kenyon S, Tokumasu H, Dowswell T, Pledge D, Mori R. 2013. High-dose versus low-dose oxytocin for augmentation of delayed labour. Cochrane Database Syst. Rev. 2013:7CD007201
    [Google Scholar]
  27. 27.
    Wiberg-Itzel E. 2021. Amniotic fluid lactate (AFL): a new predictor of labor outcome in dystocic deliveries. J. Matern. Fetal Neonatal Med. https://doi.org/10.1080/14767058.2021.1946790
    [Crossref] [Google Scholar]
  28. 28.
    Quenby S, Pierce SJ, Brigham S, Wray S. 2004. Dysfunctional labor and myometrial lactic acidosis. Obstet. Gynecol. 103:4718–23
    [Google Scholar]
  29. 29.
    Jones NW, Raine-Fenning NJ, Jayaprakasan K, Mousa HA, Taggart MJ, Bugg GJ. 2009. Changes in myometrial ‘perfusion’ during normal labor as visualized by three-dimensional power Doppler angiography. Ultrasound Obstet. Gynecol. 33:3307–12
    [Google Scholar]
  30. 30.
    Harrison N, Larcombe-McDouall JB, Earley L, Wray S. 1994. An in vivo study of the effects of ischaemia on uterine contraction, intracellular pH and metabolites in the rat. J. Physiol. 476:2349–54
    [Google Scholar]
  31. 31.
    Parratt J, Taggart M, Wray S. 1994. Abolition of contractions in the myometrium by acidification in vitro. Lancet 344:8924717–18
    [Google Scholar]
  32. 32.
    Bugg GJ, Riley MJ, Johnston TA, Baker PN, Taggart MJ. 2006. Hypoxic inhibition of human myometrial contractions in vitro: implications for the regulation of parturition. Eur. J. Clin. Investig. 36:2133–40
    [Google Scholar]
  33. 33.
    Shmigol AV, Smith RD, Taggart MJ, Wray S, Eisner DA. 1995. Changes of pH affect calcium currents but not outward potassium currents in rat myometrial cells. Pflugers Arch 431:1135–37
    [Google Scholar]
  34. 34.
    Wiberg-Itzel E, Pembe AB, Järnbert-Pettersson H, Norman M, Wihlbäck AC et al. 2016. Lactate in amniotic fluid: predictor of labor outcome in oxytocin-augmented primiparas’ deliveries. PLOS ONE 11:10e0161546
    [Google Scholar]
  35. 35.
    Hanley JA, Weeks A, Wray S. 2015. Physiological increases in lactate inhibit intracellular calcium transients, acidify myocytes and decrease force in term pregnant rat myometrium. J. Physiol. 593:204603–14
    [Google Scholar]
  36. 36.
    Wiberg-Itzel E, Wray S, Akerud H. 2018. A randomized controlled trial of a new treatment for labor dystocia. J. Matern. Fetal Neonatal Med. 31:172237–44
    [Google Scholar]
  37. 37.
    Ehsanipoor RM, Saccone G, Seligman NS, Pierce-Williams RAM, Ciardulli A, Berghella V. 2017. Intravenous fluid rate for reduction of cesarean delivery rate in nulliparous women: a systematic review and meta-analysis. Acta Obstet. Gynecol. Scand. 96:7804–11
    [Google Scholar]
  38. 38.
    Dawood F, Dowswell T, Quenby S. 2013. Intravenous fluids for reducing the duration of labour in low risk nulliparous women. Cochrane Database Syst. Rev. 2013:6CD007715
    [Google Scholar]
  39. 39.
    Morland C, Lauritzen KH, Puchades M, Holm-Hansen S, Andersson K et al. 2015. The lactate receptor, G-protein-coupled receptor 81/hydroxycarboxylic acid receptor 1: expression and action in brain. J. Neurosci. Res. 93:71045–55
    [Google Scholar]
  40. 40.
    Ma LN, Huang XB, Muyayalo KP, Mor G, Liao AH. 2020. Lactic acid: a novel signaling molecule in early pregnancy?. Front. Immunol. 11:279
    [Google Scholar]
  41. 41.
    Madaan A, Nadeau-Vallée M, Rivera JC, Obari D, Hou X et al. 2017. Lactate produced during labor modulates uterine inflammation via GPR81 (HCA1). Am. J. Obstet. Gynecol. 216:160.e1–17
    [Google Scholar]
  42. 42.
    Muttenthaler M, Andersson Å, Vetter I, Menon R, Busnelli M et al. 2017. Subtle modifications to oxytocin produce ligands that retain potency and improved selectivity across species. Sci. Signal. 10:508eaan3398
    [Google Scholar]
  43. 43.
    Di Giglio MG, Muttenthaler M, Harpsøe K, Liutkeviciute Z, Keov P et al. 2017. Development of a human vasopressin V1a-receptor antagonist from an evolutionary-related insect neuropeptide. Sci. Rep. 7:41002
    [Google Scholar]
  44. 44.
    Bafor EE, Prendergast C, Wray S. 2020. Justicia flava leaf extract potently relaxes pregnant human myometrial contractility: a lead plant for drug discovery of new tocolytic drugs. Exp. Physiol. 105:122033–37
    [Google Scholar]
  45. 45.
    Sukwan C, Wray S, Kupittayanant S. 2014. The effects of Ginseng Java root extract on uterine contractility in nonpregnant rats. Physiol. Rep. 2:12e12230
    [Google Scholar]
  46. 46.
    Dekan Z, Kremsmayr T, Keov P, Godin M, Teakle N et al. 2021. Nature-inspired dimerization as a strategy to modulate neuropeptide pharmacology exemplified with vasopressin and oxytocin. Chem. Sci. 12:114057–62
    [Google Scholar]
  47. 47.
    Bafor EE, Kupittayanant S. 2020. Medicinal plants and their agents that affect uterine contractility. Curr. Opin. Physiol. 13:20–26
    [Google Scholar]
  48. 48.
    Wray S, Carvajal J. 2014. Introduction: myometrial physiology—time to translate?. Exp. Physiol. 99:3487–88
    [Google Scholar]
  49. 49.
    Koehbach J, O'Brien M, Muttenthaler M, Miazzo M, Akcan M et al. 2013. Oxytocic plant cyclotides as templates for peptide G protein-coupled receptor ligand design. PNAS 110:5221183–88
    [Google Scholar]
  50. 50.
    Gallos ID, Papadopoulou A, Man R, Athanasopoulos N, Tobias A et al. 2018. Uterotonic agents for preventing postpartum haemorrhage: a network meta-analysis. Cochrane Database Syst. Rev. 4:4CD011689
    [Google Scholar]
  51. 51.
    Say L, Chou D, Gemmill A, Tunçalp Ö, Moller AB et al. 2014. Global causes of maternal death: a WHO systematic analysis. Lancet Glob. Health 2:6e323–33
    [Google Scholar]
  52. 52.
    Alkema L, Chou D, Hogan D, Zhang S, Moller AB et al. 2016. Global, regional, and national levels and trends in maternal mortality between 1990 and 2015, with scenario-based projections to 2030: a systematic analysis by the UN Maternal Mortality Estimation Inter-Agency Group. Lancet 387:10017462–74
    [Google Scholar]
  53. 53.
    Oyelese Y, Ananth CV. 2010. Postpartum hemorrhage: epidemiology, risk factors, and causes. Clin. Obstet. Gynecol. 53:1147–56
    [Google Scholar]
  54. 54.
    Mavrides E, Allard S, Chandraharan E, Collins P, Green L et al. 2016. Prevention and management of postpartum haemorrhage. BJOG 124:5e106–49
    [Google Scholar]
  55. 55.
    Ferrazzi E, Rigano S, Padoan A, Boito S, Pennati G, Galan HL. 2011. Uterine artery blood flow volume in pregnant women with an abnormal pulsatility index of the uterine arteries delivering normal or intrauterine growth restricted newborns. Placenta 32:7487–92
    [Google Scholar]
  56. 56.
    WHO (World Health Organ.) 2012. WHO recommendations for the prevention and treatment of postpartum haemorrhage. Guid. WHO Geneva, Switz:.
  57. 57.
    Salati JA, Leathersich SJ, Williams MJ, Cuthbert A, Tolosa JE. 2019. Prophylactic oxytocin for the third stage of labour to prevent postpartum haemorrhage. Cochrane Database Syst. Rev. 4:4CD001808
    [Google Scholar]
  58. 58.
    Hunter DJ, Schulz P, Wassenaar W. 1992. Effect of carbetocin, a long-acting oxytocin analog on the postpartum uterus. Clin. Pharmacol. Ther. 52:160–67
    [Google Scholar]
  59. 59.
    Su LL, Chong YS, Samuel M. 2012. Carbetocin for preventing postpartum haemorrhage. Cochrane Database Syst. Rev. 2012:2CD005457
    [Google Scholar]
  60. 60.
    Kalafat E, Gokce A, O'Brien P, Benlioglu C, Koc A et al. 2021. Efficacy of carbetocin in the prevention of postpartum hemorrhage: a systematic review and Bayesian meta-analysis of randomized trials. J. Matern. Fetal Neonatal Med. 34:142303–16
    [Google Scholar]
  61. 61.
    Onwochei DN, Van Ross J, Singh PM, Salter A, Monks DT. 2019. Carbetocin reduces the need for additional uterotonics in elective caesarean delivery: a systematic review, meta-analysis and trial sequential analysis of randomised controlled trials. Int. J. Obstet. Anesth. 40:14–23
    [Google Scholar]
  62. 62.
    Jin XH, Li D, Li X 2019. Carbetocin versus oxytocin for prevention of postpartum hemorrhage after vaginal delivery: a meta-analysis. Medicine 98:47e17911
    [Google Scholar]
  63. 63.
    Widmer M, Piaggio G, Nguyen TMH, Osoti A, Owa OO et al. 2018. Heat-stable carbetocin versus oxytocin to prevent hemorrhage after vaginal birth. N. Engl. J. Med. 379:8743–52
    [Google Scholar]
  64. 64.
    WHO (World Health Organ.) 2018. WHO recommendations: uterotonics for the prevention of postpartum haemorrhage Guid., WHO Geneva, Switz:.
  65. 65.
    Noort WA, van Bulck B, Vereecken A, de Zwart FA, Keirse MJ. 1989. Changes in plasma levels of PGF and PGI2 metabolites at and after delivery at term. Prostaglandins 37:13–12
    [Google Scholar]
  66. 66.
    Tunçalp Ö, Hofmeyr GJ, Gülmezoglu AM. 2012. Prostaglandins for preventing postpartum haemorrhage. Cochrane Database Syst. Rev. 2012:8CD000494
    [Google Scholar]
  67. 67.
    Schmitz T, Tararbit K, Dupont C, Rudigoz RC, Bouvier-Colle MH, Deneux-Tharaux C. 2011. Prostaglandin E2 analogue sulprostone for treatment of atonic postpartum hemorrhage. Obstet. Gynecol. 118:2257–65
    [Google Scholar]
  68. 68.
    Beerendonk CC, Massuger LF, Lucassen AM, Lerou JG, van den Berg PP. 1998. [Circulatory arrest following sulprostone administration in postpartum hemorrhage]. Ned. Tijdschr. Geneeskd. 142:4195–97 (In Dutch)
    [Google Scholar]
  69. 69.
    Parry Smith WR, Papadopoulou A, Thomas E, Tobias A, Price MJ et al. 2020. Uterotonic agents for first-line treatment of postpartum haemorrhage: a network meta-analysis. Cochrane Database Syst. Rev. 11:11CD012754
    [Google Scholar]
  70. 70.
    WOMAN Trial Collab 2017. Effect of early tranexamic acid administration on mortality, hysterectomy, and other morbidities in women with post-partum haemorrhage (WOMAN): an international, randomised, double-blind, placebo-controlled trial. Lancet 389:100842105–16
    [Google Scholar]
  71. 71.
    Chandraharan E, Krishna A. 2017. Diagnosis and management of postpartum haemorrhage. BMJ 358:j3875
    [Google Scholar]
  72. 72.
    Jones L, Othman M, Dowswell T, Alfirevic Z, Gates S et al. 2012. Pain management for women in labour: an overview of systematic reviews. Cochrane Database Syst. Rev. 2012:3CD009234
    [Google Scholar]
  73. 73.
    Klomp T, van Poppel M, Jones L, Lazet J, Di Nisio M, Lagro-Janssen AL. 2012. Inhaled analgesia for pain management in labour. Cochrane Database Syst. Rev. 2012:9CD009351
    [Google Scholar]
  74. 74.
    Maze M, Fujinaga M. 2000. Recent advances in understanding the actions and toxicity of nitrous oxide. Anaesthesia 55:4311–14
    [Google Scholar]
  75. 75.
    Emmanouil DE, Quock RM. 2007. Advances in understanding the actions of nitrous oxide. Anesth. Prog. 54:19–18
    [Google Scholar]
  76. 76.
    Anim-Somuah M, Smyth RM, Cyna AM, Cuthbert A. 2018. Epidural versus non-epidural or no analgesia for pain management in labour. Cochrane Database Syst. Rev. 5:5CD000331
    [Google Scholar]
  77. 77.
    Wilson MJA, MacArthur C, Hewitt CA, Handley K, Gao F et al. 2018. Intravenous remifentanil patient-controlled analgesia versus intramuscular pethidine for pain relief in labour (RESPITE): an open-label, multicentre, randomised controlled trial. Lancet 392:10148662–72
    [Google Scholar]
  78. 78.
    Middleton P, Shepherd E, Morris J, Crowther CA, Gomersall JC. 2020. Induction of labour at or beyond 37 weeks' gestation. Cochrane Database Syst. Rev. 2020:7CD004945
    [Google Scholar]
  79. 79.
    NHS Digital 2018. NHS maternity statistics, England 2017–18 Rep., NHS Digital Leeds, UK:
  80. 80.
    Martin JA, Hamilton BE, Osterman MJK, Driscoll AK, Drake P. 2018. Births: final data for 2017. Natl. Vital Stat. Rep. 67:81–50
    [Google Scholar]
  81. 81.
    Aust. Inst. Health Welf 2020. Australia's mothers and babies 2018—in brief Rep. Aust. Inst. Health Welf. Canberra, Aust:.
  82. 82.
    Grobman WA, Caughey AB. 2019. Elective induction of labor at 39 weeks compared with expectant management: a meta-analysis of cohort studies. Am. J. Obstet. Gynecol. 221:4304–10
    [Google Scholar]
  83. 83.
    Grobman WA, Rice MM, Reddy UM, Tita ATN, Silver RM et al. 2018. Labor induction versus expectant management in low-risk nulliparous women. N. Engl. J. Med. 379:6513–23
    [Google Scholar]
  84. 84.
    Wise J. 2018. Alarming global rise in caesarean births, figures show. BMJ 363:k4319
    [Google Scholar]
  85. 85.
    Boerma T, Ronsmans C, Melesse DY, Barros AJD, Barros FC et al. 2018. Global epidemiology of use of and disparities in caesarean sections. Lancet 392:101551341–48
    [Google Scholar]
  86. 86.
    de Vaan MD, Ten Eikelder ML, Jozwiak M, Palmer KR, Davies-Tuck M et al. 2019. Mechanical methods for induction of labour. Cochrane Database Syst. Rev. 10:10CD001233
    [Google Scholar]
  87. 87.
    Finucane EM, Murphy DJ, Biesty LM, Gyte GM, Cotter AM et al. 2020. Membrane sweeping for induction of labour. Cochrane Database Syst. Rev. 2020:2CD000451
    [Google Scholar]
  88. 88.
    Kavanagh J, Kelly AJ, Thomas J. 2005. Breast stimulation for cervical ripening and induction of labour. Cochrane Database Syst. Rev. 2005:3CD003392
    [Google Scholar]
  89. 89.
    Sharp AN, Stock SJ, Alfirevic Z. 2016. Outpatient induction of labour in the UK: a survey of practice. Eur. J. Obstet. Gynecol. Reprod. Biol. 204:21–23
    [Google Scholar]
  90. 90.
    Sharp A, Faluyi D, Alfirevic Z. 2019. Misoprostol vaginal insert (Mysodelle) versus dinoprostone intravaginal gel (Prostin) for induction of labour. Eur. J. Obstet. Gynecol. Reprod. Biol. 240:41–44
    [Google Scholar]
  91. 91.
    WHO (World Health Organ.) 2011. WHO recommendations for induction of labour 2010 Rep. WHO Geneva, Switz: https://apps.who.int/iris/bitstream/handle/10665/44531/9789241501156_eng.pdf;jsessionid=710DD70AEE08A34F19CF593E069C3109?sequence=1
  92. 92.
    Helmig RB, Hvidman LE. 2020. An audit of oral administration of Angusta® (misoprostol) 25 μg for induction of labor in 976 consecutive women with a singleton pregnancy in a university hospital in Denmark. Acta Obstet. Gynecol. Scand. 99:101396–402
    [Google Scholar]
  93. 93.
    Young DC, Delaney T, Armson BA, Fanning C. 2020. Oral misoprostol, low dose vaginal misoprostol, and vaginal dinoprostone for labor induction: randomized controlled trial. PLOS ONE 15:1e0227245
    [Google Scholar]
  94. 94.
    Hokkila E, Kruit H, Rahkonen L, Timonen S, Mattila M et al. 2019. The efficacy of misoprostol vaginal insert compared with oral misoprostol in the induction of labor of nulliparous women: a randomized national multicenter trial. Acta Obstet. Gynecol. Scand. 98:81032–39
    [Google Scholar]
  95. 95.
    Eriksson A, Jeppesen S, Krebs L. 2020. Induction of labour in nulliparous women—quick or slow: a cohort study comparing slow-release vaginal insert with low-dose misoprostol oral tablets. BMC Pregnancy Childbirth 20:179
    [Google Scholar]
  96. 96.
    NICE (Natl. Inst. Health Care Excell.) 2021. Inducing labour Guid., NICE London, UK: https://www.nice.org.uk/guidance/ng207
  97. 97.
    Coates R, Cupples G, Scamell A, McCourt C. 2019. Women's experiences of induction of labour: qualitative systematic review and thematic synthesis. Midwifery 69:17–28
    [Google Scholar]
  98. 98.
    Howson CP, Kinney MV, McDougall L, Lawn JE Born Too Soon Preterm Birth Action Group. 2013. Born too soon: preterm birth matters. Reprod. Health 10:Suppl. 1S1
    [Google Scholar]
  99. 99.
    Hug L, Sharrow D, You D. 2019. Levels & trends in child mortality: report 2019 Rep. UNICEF New York:
  100. 100.
    Care A, Nevitt SJ, Medley N, Donegan S, Good L et al. 2022. Interventions to prevent spontaneous preterm birth in women with singleton pregnancy who are at high risk: systematic review and network meta-analysis. BMJ 376:e064547
    [Google Scholar]
  101. 101.
    Dodd JM, Crowther CA. 2010. The role of progesterone in prevention of preterm birth. Int. J. Womens Health 1:73–84
    [Google Scholar]
  102. 102.
    Care A, Ingleby L, Alfirevic Z, Sharp A. 2019. The influence of the introduction of national guidelines on preterm birth prevention practice: UK experience. BJOG 126:6763–69
    [Google Scholar]
  103. 103.
    Hassan SS, Romero R, Vidyadhari D, Fusey S, Baxter JK et al. 2011. Vaginal progesterone reduces the rate of preterm birth in women with a sonographic short cervix: a multicenter, randomized, double-blind, placebo-controlled trial. Ultrasound Obstet. Gynecol. 38:118–31
    [Google Scholar]
  104. 104.
    Fonseca EB, Celik E, Parra M, Singh M, Nicolaides KH, Fetal Med. Found. Second Trimester Screen. Group 2007. Progesterone and the risk of preterm birth among women with a short cervix. N. Engl. J. Med. 357:5462–69
    [Google Scholar]
  105. 105.
    Boelig RC, Schoen CN, Frey H, Gimovsky AC, Springel E et al. 2022. Vaginal progesterone versus intramuscular 17-hydroxyprogesterone caproate for prevention of recurrent preterm birth: a randomized controlled trial. Am. J. Obstet. Gynecol. 226:5722.e1–12
    [Google Scholar]
  106. 106.
    Norman JE, Marlow N, Messow CM, Shennan A, Bennett PR et al. 2016. Vaginal progesterone prophylaxis for preterm birth (the OPPTIMUM study): a multicentre, randomised, double-blind trial. Lancet 387:100332106–16
    [Google Scholar]
  107. 107.
    Crowther CA, Ashwood P, McPhee AJ, Flenady V, Tran T et al. 2017. 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. 14:9e1002390
    [Google Scholar]
  108. 108.
    NICE (Natl. Inst. Health Care Excell.) 2015. Preterm labour and birth Guid. NICE London: https://www.nice.org.uk/guidance/ng25/resources/preterm-labour-and-birth-pdf-1837333576645
  109. 109.
    Grobman WA, Thom EA, Spong CY, Iams JD, Saade GR et al. 2012. 17 Alpha-hydroxyprogesterone caproate to prevent prematurity in nulliparas with cervical length less than 30 mm. Am. J. Obstet. Gynecol. 207:5390.e1–8
    [Google Scholar]
  110. 110.
    Blackwell SC, Gyamfi-Bannerman C, Biggio JR Jr., Chauhan SP, Hughes BL et al. 2020. 17-OHPC to Prevent Recurrent Preterm Birth in Singleton Gestations (PROLONG study): a multicenter, international, randomized double-blind trial. Am. J. Perinatol. 37:2127–36
    [Google Scholar]
  111. 111.
    EPPPIC Group 2021. Evaluating Progestogens for Preventing Preterm birth International Collaborative (EPPPIC): meta-analysis of individual participant data from randomised controlled trials. Lancet 397:102801183–94
    [Google Scholar]
  112. 112.
    Neilson JP, West HM, Dowswell T. 2014. Betamimetics for inhibiting preterm labour. Cochrane Database Syst. Rev. 2014:2CD004352
    [Google Scholar]
  113. 113.
    Coler BS, Shynlova O, Boros-Rausch A, Lye S, McCartney S et al. 2021. Landscape of preterm birth therapeutics and a path forward. J. Clin. Med. 10:132912
    [Google Scholar]
  114. 114.
    Flenady V, Reinebrant HE, Liley HG, Tambimuttu EG, Papatsonis DN. 2014. Oxytocin receptor antagonists for inhibiting preterm labour. Cochrane Database Syst. Rev. 2014:6CD004452
    [Google Scholar]
  115. 115.
    Flenady V, Wojcieszek AM, Papatsonis DN, Stock OM, Murray L et al. 2014. Calcium channel blockers for inhibiting preterm labour and birth. Cochrane Database Syst. Rev. 2014:6CD002255
    [Google Scholar]
  116. 116.
    Reinebrant HE, Pileggi-Castro C, Romero CL, Dos Santos RA, Kumar S et al. 2015. Cyclo-oxygenase (COX) inhibitors for treating preterm labour. Cochrane Database Syst. Rev. 2015:6CD001992
    [Google Scholar]
  117. 117.
    Crowther CA, Brown J, McKinlay CJ, Middleton P. 2014. Magnesium sulphate for preventing preterm birth in threatened preterm labour. Cochrane Database Syst. Rev. 2014:8CD001060
    [Google Scholar]
  118. 118.
    Duckitt K, Thornton S, O'Donovan OP, Dowswell T. 2014. Nitric oxide donors for treating preterm labour. Cochrane Database Syst. Rev. 2014:5CD002860
    [Google Scholar]
  119. 119.
    Paul JW, Hua S, Ilicic M, Tolosa JM, Butler T et al. 2017. Drug delivery to the human and mouse uterus using immunoliposomes targeted to the oxytocin receptor. Am. J. Obstet. Gynecol. 216:3283.e1–14
    [Google Scholar]
  120. 120.
    Refuerzo JS, Leonard F, Bulayeva N, Gorenstein D, Chiossi G et al. 2016. Uterus-targeted liposomes for preterm labor management: studies in pregnant mice. Sci. Rep. 6:34710
    [Google Scholar]
  121. 121.
    Doyle LW, Crowther CA, Middleton P, Marret S, Rouse D. 2009. Magnesium sulphate for women at risk of preterm birth for neuroprotection of the fetus. Cochrane Database Syst. Rev. 2009:1CD004661
    [Google Scholar]
  122. 122.
    McGoldrick E, Stewart F, Parker R, Dalziel SR. 2020. Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth. Cochrane Database Syst. Rev. 12:CD004454
    [Google Scholar]
  123. 123.
    Flenady V, Hawley G, Stock OM, Kenyon S, Badawi N 2013. Prophylactic antibiotics for inhibiting preterm labour with intact membranes. Cochrane Database Syst. Rev. 2013:12CD000246
    [Google Scholar]
  124. 124.
    Kenyon SL, Taylor DJ, Tarnow-Mordi W 2001. Broad-spectrum antibiotics for spontaneous preterm labour: the ORACLE II randomised trial. Lancet 357:9261989–94
    [Google Scholar]
  125. 125.
    Kenyon SL, Taylor DJ, Tarnow-Mordi W 2001. Broad-spectrum antibiotics for preterm, prelabour rupture of fetal membranes: the ORACLE I randomised trial. Lancet 357:9261979–88
    [Google Scholar]
  126. 126.
    Jones DP, Pike K, Kenyon S, Pike L, Henderson B et al. 2011. Routine educational outcome measures in health studies: Key Stage 1 in the ORACLE Children Study follow-up of randomised trial cohorts. Arch. Dis. Child. 96:125–29
    [Google Scholar]
  127. 127.
    Marlow N, Bower H, Jones D, Brocklehurst P, Kenyon S et al. 2017. The ORACLE Children Study: educational outcomes at 11years of age following antenatal prescription of erythromycin or co-amoxiclav. Arch. Dis. Child Fetal Neonatal Ed. 102:2F131–35
    [Google Scholar]
  128. 128.
    Arrowsmith S, Kendrick A, Wray S. 2010. Drugs acting on the pregnant uterus. Obstet. Gynaecol. Reprod. Med. 20:8241–47
    [Google Scholar]
/content/journals/10.1146/annurev-pharmtox-051921-122822
Loading
/content/journals/10.1146/annurev-pharmtox-051921-122822
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error