Walani SR. Global burden of preterm birth. Int J Gynaecol Obstet. 2020;150:31–3.

Article  PubMed  Google Scholar 

March of Dimes Peristats™ Report. www.marchofdimes.org/peristats/reports/united-states/prematurity-profile (accessed April 12, 2024).

Meis PJ, Klebanoff M, Thom E, Dombrowski MP, Sibai B, Moawad AH, et al. National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Prevention of recurrent preterm delivery by 17 alpha-hydroxyprogesterone caproate. N Engl J Med. 2003;348:2379–85.

Article  PubMed  CAS  Google Scholar 

Approves Makena FDA, Feb DRUGSCOM. 4, 2011). www.drugs.com/newdrugs/fda-approvesmakena-reduce-risk-preterm-birth-risk-pregnant-women-2518.html (accessed April 13, 2024).

American College of Obstetricians and Gynecologists Committee on Practice Bulletins–Obstetrics. Prediction and prevention of preterm birth: ACOG Practice Bulletin 130. Obstet Gynecol. 2012;120:964–73.

Article  Google Scholar 

American College of Obstetricians and Gynecologists Committee on Practice Bulletins–Obstetrics. Prediction and prevention of preterm birth: ACOG Practice Bulletin 234. Obstet Gynecol 2021; 138.e65-138.e90.

Society for Maternal-Fetal Medicine Publications Committee. Progesterone and preterm birth prevention: translating clinical trials data into clinical practice. Am J Obstet Gynecol. 2012;206:376–86.

Article  Google Scholar 

Society for Maternal-Fetal Medicine Statement: Response to EPPPIC and considerations of the use of progestogens for the prevention of preterm birth. (March 30, 2021). https://www.smfm.org/publications/383-smfm-statementresponse-to-epppic-and-considerations-ofthe-use-of-progestogens-for-the-preventionof-preterm-birth. https://s3.amazonaws.com/cdn.smfm.org/publications/383/download-d37b137ec0d26f8c268933be6800dd27.pdf (accessed April 14, 2024).

Likis FE, Andrews JC, Woodworth AL, Velez Edwards DR, Jerome RN, Fonnesbeck CJ, McKoy JN, Hartmann KE. Progestogens for prevention of preterm birth [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2012 Sep. Report No.: 12-EHC105-EF. PMID: 23101048.

U.S. Food and Drug Administration. Final Decision on the Proposal to Withdraw Approval of Makena Docket No. FDA-2020-N-2029, FDA (April 5, 2023). www.govinfo.gov/content/pkg/FR-2023-05-15/pdf/2023-10264.pdf (accessed April 13, 2024).

https://downloads.regulations.gov/FDA-2020-N-2029-0385/attachment_1.pdf (accessed April 14, 2024).

Morrow T. Resurrection of preterm labor drug evokes questions of fairness. Biotechnol Healthc. 2011;8:27–9.

PubMed  PubMed Central  Google Scholar 

Kim S. The Orphan Drug Act: how the FDA unlawfully usurped market exclusivity. Northwest J Technol Intellect Property 2013; 11(6). https://scholarlycommons.law.northwestern.edu/cgi/viewcontent.cgi?article=1200&context=njtip (accessed April 13, 2024).

Word RA, Li X-H, Hnat M, Carrick K. Dynamics of cervical remodeling during pregnancy and parturition: mechanisms and current concepts. Semin Reprod Med. 2007;25:69–79.

Article  PubMed  CAS  Google Scholar 

Norman JE, Yuan M, Anderson L, et al. Effect of prolonged in vivo administration of progesterone in pregnancy on myometrial gene expression, peripheral blood leukocyte activation, and circulating steroid hormone levels. Reprod Sci. 2011;18:435–46.

Article  PubMed  CAS  Google Scholar 

Dante G, Vaccaro V, Facchinetti F. Use of progestagens during early pregnancy. Facts Views Vis Obgyn. 2013;5:66–71.

PubMed  PubMed Central  CAS  Google Scholar 

Romero R, Stanczyk FZ. Progesterone is not the same as 17α-hydroxyprogesterone caproate: implications for obstetrical practice. Am J Obstet Gynecol. 2013;208:421–6.

Article  PubMed  CAS  Google Scholar 

Attardi BJ, Zeleznik A, Simhan H, Chiao JP, Mattison DR, Caritis SN. Comparison of progesterone and glucocorticoid receptor binding and stimulation of gene expression by progesterone, 17-alpha hydroxyprogesterone caproate, and related progestins. Am J Obstet Gynecol 2007; 197:599.e1-599.e7.

Caritis SN, Zhao Y, Bettinger J, Venkataramanan R. Qualitative and quantitative measures of various compounded formulations of 17-alpha hydroxyprogesterone caproate. Am J Obstet Gynecol. 2013;208:e4701–5.

U.S. Federal Register 75-FR-36419. Determination that Delalutin (hydroxy-progesterone caproate) injection, 125 mg/mL and 250 mg/mL, was not withdrawn from sale for reasons of safety or effectiveness. FDA (June 25, 2010). www.federalregister.gov/documents/2010/06/25/2010-15416/determination-that-delalutin-hydroxyprogesterone-caproate-injection-125-milligramsmilliliter-and-250 (accessed April 13, 2024).

Federal Register No US. October 10,. FR-1973-10-10. FDA proposes reevaluation of certain progestin drugs, FDA (1973). www.govinfo.gov/app/details/FR-1973-10-10 (accessed April 13, 2024).

Johnson JW, Austin KL, Jones GS, Davis GH, King TM. Efficacy of 17alpha-hydroxy-progesterone caproate in the prevention of premature labor. N Engl J Med. 1975;293:675–80.

Article  PubMed  CAS  Google Scholar 

Yemeni M, Borenstein R, Dreazen E, et al. Prevention of premature labor by 17 alpha-hydroxyprogesterone caproate. Am J Obstet Gynecol. 1985;151:574–7.

Article  Google Scholar 

Hartikainen-Sorri AL, Kauppila A, Tuimala R. Inefficacy of 17 alpha-hydroxyprogesterone caproate in the prevention of prematurity in twin pregnancy. Obstet Gynecol. 1980;56:692–5.

PubMed  CAS  Google Scholar 

Hauth JC, Gilstrap LC 3rd, Brekken AL, Hauth JM. The effect of 17 alpha-hydroxyprogesterone caproate on pregnancy outcome in an active duty military population. Am J Obstet Gynecol. 1983;146:187–90.

Article  PubMed  CAS  Google Scholar 

Keirse MJ. Progestogen administration in pregnancy may prevent preterm delivery. Br J Obstet Gynaecol. 1990;97:149–54.

Article  PubMed  CAS  Google Scholar 

Schardein JL. Congenital abnormalities and hormones during pregnancy: a clinical review. Teratology. 1980;22:251–70.

Article  PubMed  CAS  Google Scholar 

Resseguie LJ, Hick JF, Bruen JA, et al. Congenital malformations among offspring exposed in utero to progestins, Olmsted County, Minnesota, 1936–1974. Fertil Steril. 1985;43:514–9.

Article  PubMed  CAS  Google Scholar 

Raman-Wilms L, Tseng AL, Wighardt S, et al. Fetal genital effects of first-trimester sex hormone exposure: a meta-analysis. Obstet Gynecol. 1995;85:141–9.

Article  PubMed  CAS  Google Scholar 

da Fonseca EB, Bittar RE, Carvalho MH, Zugaib M. 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;188:419–24.

Article  PubMed  Google Scholar 

O’Brien JM, Adair CD, Lewis DF, et al. Progesterone vaginal gel for the reduction of recurrent preterm birth: primary results from a randomized, double-blind, placebo-controlled trial. Ultrasound Obstet Gynecol. 2007;30:687–96.

Article  PubMed  Google Scholar 

Center for Evidence-based Policy. (March 2019, updated November 2019). Effectiveness and harms of 17-α hydroxyprogesterone caproate (Makena) to prevent preterm birth. https://centerforevidencebasedpolicy.org/wp-content/uploads/2019/12/17P-evidence_Final_12-11-19.pdf (assessed April 14, 2024).

Briery CM, Veillon EW, Klauser CK, et al. Women with preterm premature rupture of the membranes do not benefit from weekly progesterone. Am J Obstet Gynecol. 2011;204:e541–5.

Rouse DJ, Caritis SN, Peaceman AM, et al. National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. A trial of 17 alpha-hydroxyprogesterone caproate to prevent prematurity in twins. N Engl J Med. 2007;357:454–61.

Article  PubMed  CAS  Google Scholar 

Norman JE, Mackenzie F, Owen P, et al. Progesterone for the prevention of preterm birth in twin pregnancy (STOPPIT): a randomised, double-blind, placebo-controlled study and metaanalysis. Lancet. 2009;373:2034–40.

Article  PubMed  CAS  Google Scholar 

Combs CA, Garite T, Maurel K, et al. Obstetrix Collaborative Research Network. 17-hydroxyprogesterone caproate for twin pregnancy: a double-blind, randomized clinical trial. Am J Obstet Gynecol. 2011;204:e2211–221.e8.

Article  Google Scholar 

Caritis SN, Rouse DJ, Peaceman AM, et al. National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Prevention of preterm birth in triplets using 17alpha-hydroxyprogesterone caproate: a randomized controlled trial. Obstet Gynecol. 2009;113:285–92.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Berghella V, Figueroa D, Szychowski JM, et al. 17-alpha-hydroxyprogesterone caproate for the prevention of preterm birth in women with prior preterm birth and a short cervical length. Am J Obstet Gynecol. 2010;202:e3511–6.

Food US, Administration D, Center for Drug Evaluation and Research. accessed May 30,. Summary minutes of the Advisory Committee for Reproductive Health Drugs, FDA CDER (August 29, 2006). http://www.fda.gov/ohrms/dockets/ac/06/minutes/2006-4227M1.pdf (2024).

Caritis SN, Sharma S, Venkataramanan R, et al. Pharmacology and placental transport of 17-hydroxyprogesterone caproate in singleton gestation. Am J Obstet Gynecol. 2012;207:e3981–398.e8.

Article  Google Scholar 

Sharma S, Caritis S, Hankins G, Miodovnik M, Herbert MF, Mattison D, Venkataramanan R. Population pharmacokinetics of 17α-hydroxyprogesterone caproate in singleton gestation. Br J Clin Pharmacol. 2016;82:1084–93.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Sharma S, Ellis EC, Dorko K, et al. Metabolism of 17alpha-hydroxyprogesterone caproate, an agent for preventing preterm birth, by fetal hepatocytes. Drug Metab Dispos. 2010;38:723–7.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Check JH, Rankin A, Teichman M. The risk of fetal anomalies as a result of progesterone therapy during pregnancy. Fertil Steril. 1986;45:575–7.

Article  PubMed  CAS  Google Scholar 

Michaelis J, Michaelis H, Glück E, Koller S. Prospective study of suspected associations between certain drugs administered during early pregnancy and congenital malformations. Teratology. 1983;27:57–64.

Article