Safety review of hydroxyprogesterone caproate in women with a history of spontaneous preterm birth

Sibai, Baha M.; Saade, George R.; Das, Anita; Gudeman, Jennifer

doi:10.1038/s41372-020-00849-y

Cited by 7 publications

(4 citation statements)

References 14 publications

(18 reference statements)

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“…To establish whether IAV infection-induced P4 suppression was the cause of adverse maternal and fetal outcomes, a subset of IAV-infected and mock-inoculated dams were treated with a single dose of either 17-α-hydroxyprogesterone caproate (17-OHPC), a synthetic progestin that is safe to use during pregnancy ( 74 ) or vehicle. The administration of 17-OHPC to mock-inoculated dams had no adverse impact on pregnancy outcomes.…”

Section: Resultsmentioning

confidence: 99%

Suppression of progesterone by influenza A virus mediates adverse maternal and fetal outcomes in mice

Creisher,

Parish,

Lei

et al. 2024

mBio

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Influenza A virus infection during pregnancy can cause adverse maternal and fetal outcomes but the mechanism responsible remains elusive. Infection of outbred mice with 2009 H1N1 at embryonic day (E) 10 resulted in significant maternal morbidity, placental tissue damage and inflammation, fetal growth restriction, and developmental delays that lasted through weaning. Restriction of pulmonary virus replication was not inhibited during pregnancy, but infected dams had suppressed circulating and placental progesterone (P4) concentrations that were caused by H1N1-induced upregulation of pulmonary cyclooxygenase (COX)-1-, but not COX-2-, dependent synthesis and secretion of prostaglandin (PG) F2α. Treatment with 17-α-hydroxyprogesterone caproate (17-OHPC), a synthetic progestin that is safe to use in pregnancy, ameliorated the adverse maternal and fetal outcomes from H1N1 infection and prevented placental cell death and inflammation. These findings highlight the therapeutic potential of progestin treatments for influenza during pregnancy. IMPORTANCE Pregnant individuals are at risk of severe outcomes from both seasonal and pandemic influenza A viruses. Influenza infection during pregnancy is associated with adverse fetal outcomes at birth and adverse consequences for offspring into adulthood. When outbred dams, with semi-allogenic fetuses, were infected with 2009 H1N1, in addition to pulmonary virus replication, lung damage, and inflammation, the placenta showed evidence of transient cell death and inflammation that was mediated by increased activity along the arachidonic acid pathway leading to suppression of circulating progesterone. Placental damage and suppressed progesterone were associated with detrimental effects on perinatal growth and developmental delays in offspring. Treatment of H1N1-infected pregnant mice with 17-OHPC, a synthetic progestin treatment that is safe to use in pregnancy, prevented placental damage and inflammation and adverse fetal outcomes. This novel therapeutic option for the treatment of influenza during pregnancy should be explored clinically.

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Section: Resultsmentioning

confidence: 99%

Suppression of progesterone by influenza A virus mediates adverse maternal and fetal outcomes in mice

Creisher,

Parish,

Lei

et al. 2024

mBio

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“…According to the U.S. Food and Drug Administration [ 29 ] and a narrative review [ 30 ] of two large RCTs [ 12 , 16 ], 17OHPC is well tolerated and has a favorable safety profile. The most frequently reported adverse events of 17OHPC are mild injection-related side effects, such as tenderness, swelling, bruising, itching, and urticaria.…”

Section: Discussionmentioning

confidence: 99%

17-alpha hydroxyprogesterone caproate for the prevention of recurrent preterm birth among singleton pregnant women with a prior history of preterm birth: a systematic review and meta-analysis of six randomized controlled trials

et al. 2021

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To perform a systematic review and meta-analysis of all randomized controlled trials (RCTs) that investigated the clinical benefits of 17-alpha hydroxyprogesterone caproate (17OHPC) in the prevention of recurrent preterm birth (PTB) among singleton pregnant women with a previous history of PTB. We searched four major databases up till April 2021 and assessed the risk of bias in the included studies. We meta-analyzed various maternal-neonatal endpoints (n=18) and pooled them as mean difference or risk ratio (RR) with 95% confidence interval (CI) using the random-effects model. Six RCTs met the inclusion criteria, comprising 2,573 patients (17OHPC=1,617, control=956). RCTs revealed an overall low risk of bias. The rates of PTB <35 weeks (n=5 RCTs; RR, 0.77; 95% CI, 0.63-0.93; P=0.008), PTB <32 weeks (n=3 RCTs; RR, 0.68; 95% CI, 0.51-0.91; P=0.009), neonates with low birth weight (<2.5 kg) at delivery (n=3 RCTs; RR, 0.63; 95% CI, 0.5-0.79; P<0.001), and neonatal death (n=4 RCTs; RR, 0.41; 95% CI, 0.20-0.84; P=0.02) were significantly reduced in the 17OHPC group compared with the control group. Moreover, 17OHPC treatment correlated with a significantly decreased rate of retinopathy (n=2 RCTs; RR, 0.42; 95% CI, 0.18-0.97; P=0.004). However, there were no significant differences in the rates of neonatal intensive care unit admission, cesarean delivery, and other pretermrelated complications between both the groups. Among singleton pregnant women with a prior history of PTB, 17OHPC may favorably decrease the risks of recurrent PTB and reduce the rate of neonatal death.

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“…To establish whether IAV-infection induced P4 suppression was the cause of adverse maternal and fetal outcomes, a subset of IAV-infected and mock inoculated dams were treated with a single dose of either 17-α-hydroxyprogesterone caproate (17-OHPC), a synthetic progestin that is safe to use during pregnancy (Sibai et al, 2021) or vehicle. The administration of 17-OHPC to mock-inoculated dams had no adverse impact on pregnancy outcomes.…”

Section: Synthetic Progestin Treatment Improves Iav-induced Maternal ...mentioning

confidence: 99%

Suppression of progesterone by influenza A virus mediates adverse maternal and fetal outcomes in mice

Creisher,

Parish,

Lei

et al. 2023

Preprint

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Influenza A virus infection during pregnancy can cause adverse maternal and fetal outcomes, but the mechanism responsible remains elusive. Infection of outbred mice with 2009 H1N1 at embryonic day (E) 10 resulted in significant maternal morbidity, placental tissue damage and inflammation, fetal growth restriction, and developmental delays that lasted through weaning. Restriction of pulmonary virus replication was not inhibited during pregnancy, but infected dams had suppressed circulating and placental progesterone (P4) concentrations that were caused by H1N1-induced upregulation of pulmonary cyclooxygenase (COX)-1, but not COX-2-, dependent synthesis and secretion of prostaglandin (PG) F2α. Treatment with 17-α-hydroxyprogesterone caproate (17-OHPC), a synthetic progestin that is safe to use in pregnancy, ameliorated the adverse maternal and fetal outcomes from H1N1 infection and prevented placental cell death and inflammation. These findings highlight the therapeutic potential of progestin treatments for influenza during pregnancy.

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Safety review of hydroxyprogesterone caproate in women with a history of spontaneous preterm birth

Cited by 7 publications

References 14 publications

Suppression of progesterone by influenza A virus mediates adverse maternal and fetal outcomes in mice

Suppression of progesterone by influenza A virus mediates adverse maternal and fetal outcomes in mice

17-alpha hydroxyprogesterone caproate for the prevention of recurrent preterm birth among singleton pregnant women with a prior history of preterm birth: a systematic review and meta-analysis of six randomized controlled trials

Suppression of progesterone by influenza A virus mediates adverse maternal and fetal outcomes in mice

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