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Progestogens in singleton gestations with preterm prelabor rupture of membranes: a systematic review and metaanalysis of randomized controlled trials.
Am J Obstet Gynecol. 2018 10; 219(4):346-355.e2.AJ

Abstract

OBJECTIVE DATA

Preterm prelabor rupture of membranes occurs in 3% of all pregnancies. Neonatal benefit is seen in uninfected women who do not deliver immediately after preterm prelabor rupture of membranes. The purpose of this study was to evaluate whether the administration of progestogens in singleton pregnancies prolongs pregnancy after preterm prelabor rupture of membranes.

STUDY

Searches were performed in MEDLINE, OVID, Scopus, EMBASE, ClinicalTrials.gov, and the Cochrane Central Register of Controlled Trials with the use of a combination of keywords and text words related to "progesterone," "progestogen," "prematurity," and "preterm premature rupture of membranes" from the inception of the databases until January 2018. We included all randomized controlled trials of singleton gestations after preterm prelabor rupture of membranes that were randomized to either progestogens or control (either placebo or no treatment). Exclusion criteria were trials that included women who had contraindications to expectant management after preterm prelabor rupture of membranes (ie, chorioamnionitis, severe preeclampsia, and nonreassuring fetal status) and trials on multiple gestations. We planned to include all progestogens, including but not limited to 17-α hydroxyprogesterone caproate, and natural progesterone.

STUDY APPRAISAL AND SYNTHESIS METHODS

The primary outcome was latency from randomization to delivery. Metaanalysis was performed with the use of the random effects model of DerSimonian and Laird to produce relative risk with 95% confidence interval. Analysis was performed for each mode of progestogen administration separately.

RESULTS

Six randomized controlled trials (n=545 participants) were included. Four of the included trials assessed the efficacy of 17-α hydroxyprogesterone caproate; 1 trial assessed rectal progestogen, and 1 trial had 3 arms that compared 17-α hydroxyprogesterone caproate, rectal progestogen, and placebo. The mean gestational age at time randomization was 26.9 weeks in the 17-α hydroxyprogesterone caproate group and 27.3 weeks in the control group. 17-α Hydroxyprogesterone caproate administration was not found to prolong the latency period between randomization and delivery (mean difference, 0.11 days; 95% confidence interval, -3.30 to 3.53). There were no differences in mean gestational age at delivery, mode of delivery, or maternal or neonatal outcomes between the 2 groups. Similarly, there was no difference in latency for those women who received rectal progesterone (mean difference, 4.00 days; 95% confidence interval, -0.72 to 8.72).

CONCLUSION

Progestogen administration does not prolong pregnancy in singleton gestations with preterm prelabor rupture of membranes.

Authors+Show Affiliations

Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Thomas Jefferson University Hospital, Philadelphia, PA.Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Thomas Jefferson University Hospital, Philadelphia, PA.Department of Obstetrics, Gynecology and Reproductive Sciences at Magee-Women's Hospital of University of Pittsburgh Medical Center, Pittsburgh, PA.Department of Neuroscience, Reproductive Sciences and Dentistry, School of Medicine, University of Naples Federico II, Naples, Italy.Department of Neuroscience, Reproductive Sciences and Dentistry, School of Medicine, University of Naples Federico II, Naples, Italy.Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Thomas Jefferson University Hospital, Philadelphia, PA. Electronic address: vincenzo.berghella@jefferson.edu.

Pub Type(s)

Journal Article
Meta-Analysis
Systematic Review

Language

eng

PubMed ID

29614278

Citation

Quist-Nelson, Johanna, et al. "Progestogens in Singleton Gestations With Preterm Prelabor Rupture of Membranes: a Systematic Review and Metaanalysis of Randomized Controlled Trials." American Journal of Obstetrics and Gynecology, vol. 219, no. 4, 2018, pp. 346-355.e2.
Quist-Nelson J, Parker P, Mokhtari N, et al. Progestogens in singleton gestations with preterm prelabor rupture of membranes: a systematic review and metaanalysis of randomized controlled trials. Am J Obstet Gynecol. 2018;219(4):346-355.e2.
Quist-Nelson, J., Parker, P., Mokhtari, N., Di Sarno, R., Saccone, G., & Berghella, V. (2018). Progestogens in singleton gestations with preterm prelabor rupture of membranes: a systematic review and metaanalysis of randomized controlled trials. American Journal of Obstetrics and Gynecology, 219(4), 346-e2. https://doi.org/10.1016/j.ajog.2018.03.027
Quist-Nelson J, et al. Progestogens in Singleton Gestations With Preterm Prelabor Rupture of Membranes: a Systematic Review and Metaanalysis of Randomized Controlled Trials. Am J Obstet Gynecol. 2018;219(4):346-355.e2. PubMed PMID: 29614278.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Progestogens in singleton gestations with preterm prelabor rupture of membranes: a systematic review and metaanalysis of randomized controlled trials. AU - Quist-Nelson,Johanna, AU - Parker,Pamela, AU - Mokhtari,Neggin, AU - Di Sarno,Rossana, AU - Saccone,Gabriele, AU - Berghella,Vincenzo, Y1 - 2018/03/31/ PY - 2018/02/08/received PY - 2018/03/20/revised PY - 2018/03/24/accepted PY - 2018/4/4/pubmed PY - 2019/8/14/medline PY - 2018/4/4/entrez KW - 17-α hydroxyprogesterone caproate KW - PROM KW - latency KW - preterm prelabor rupture of membranes KW - progesterone KW - progestogens SP - 346 EP - 355.e2 JF - American journal of obstetrics and gynecology JO - Am J Obstet Gynecol VL - 219 IS - 4 N2 - OBJECTIVE DATA: Preterm prelabor rupture of membranes occurs in 3% of all pregnancies. Neonatal benefit is seen in uninfected women who do not deliver immediately after preterm prelabor rupture of membranes. The purpose of this study was to evaluate whether the administration of progestogens in singleton pregnancies prolongs pregnancy after preterm prelabor rupture of membranes. STUDY: Searches were performed in MEDLINE, OVID, Scopus, EMBASE, ClinicalTrials.gov, and the Cochrane Central Register of Controlled Trials with the use of a combination of keywords and text words related to "progesterone," "progestogen," "prematurity," and "preterm premature rupture of membranes" from the inception of the databases until January 2018. We included all randomized controlled trials of singleton gestations after preterm prelabor rupture of membranes that were randomized to either progestogens or control (either placebo or no treatment). Exclusion criteria were trials that included women who had contraindications to expectant management after preterm prelabor rupture of membranes (ie, chorioamnionitis, severe preeclampsia, and nonreassuring fetal status) and trials on multiple gestations. We planned to include all progestogens, including but not limited to 17-α hydroxyprogesterone caproate, and natural progesterone. STUDY APPRAISAL AND SYNTHESIS METHODS: The primary outcome was latency from randomization to delivery. Metaanalysis was performed with the use of the random effects model of DerSimonian and Laird to produce relative risk with 95% confidence interval. Analysis was performed for each mode of progestogen administration separately. RESULTS: Six randomized controlled trials (n=545 participants) were included. Four of the included trials assessed the efficacy of 17-α hydroxyprogesterone caproate; 1 trial assessed rectal progestogen, and 1 trial had 3 arms that compared 17-α hydroxyprogesterone caproate, rectal progestogen, and placebo. The mean gestational age at time randomization was 26.9 weeks in the 17-α hydroxyprogesterone caproate group and 27.3 weeks in the control group. 17-α Hydroxyprogesterone caproate administration was not found to prolong the latency period between randomization and delivery (mean difference, 0.11 days; 95% confidence interval, -3.30 to 3.53). There were no differences in mean gestational age at delivery, mode of delivery, or maternal or neonatal outcomes between the 2 groups. Similarly, there was no difference in latency for those women who received rectal progesterone (mean difference, 4.00 days; 95% confidence interval, -0.72 to 8.72). CONCLUSION: Progestogen administration does not prolong pregnancy in singleton gestations with preterm prelabor rupture of membranes. SN - 1097-6868 UR - https://www.unboundmedicine.com/medline/citation/29614278/Progestogens_in_singleton_gestations_with_preterm_prelabor_rupture_of_membranes:_a_systematic_review_and_metaanalysis_of_randomized_controlled_trials_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0002-9378(18)30242-4 DB - PRIME DP - Unbound Medicine ER -