Predictors of response to 17-alpha hydroxyprogesterone caproate for prevention of recurrent spontaneous preterm birth

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Genomics and Proteomics Network for Preterm Birth Research (GPN-PBR)

    Research output: Contribution to journalArticle

    16 Citations (Scopus)

    Abstract

    BACKGROUND: Prematurity is the leading cause of neonatal morbidity and death among nonanomalous neonates in the United States. Intramuscular 17-alpha hydroxyprogesterone caproate injections reduce the risk of recurrent prematurity by approximately one third. Unfortunately, prophylactic 17-alpha hydroxyprogesterone caproate is not always effective, and one-third of high-risk women will have a recurrent preterm birth, despite 17-alpha hydroxyprogesterone caproate therapy. The reasons for this variability in response are unknown. Previous investigators have examined the influence of a variety of factors on 17-alpha hydroxyprogesterone caproate response but have analyzed data that used a fixed outcome of term delivery to define progesterone response.

    OBJECTIVE: We hypothesized that the demographics, history, and pregnancy course among women who deliver at a similar gestational age with 17-alpha hydroxyprogesterone caproate for recurrent spontaneous preterm birth prevention differs when compared with those women who deliver later with 17-alpha hydroxyprogesterone caproate and that these associations could be refined by the use of a contemporary definition of 17-alpha hydroxyprogesterone caproate "responder."

    STUDY DESIGN: This was a planned secondary analysis of a prospective, multicenter, longitudinal study of women with ≥1 previous documented singleton spontaneous preterm birth at <37 weeks gestation. Data were collected at 3 prespecified gestational age epochs during pregnancy. All women who were included in this analysis received 17-alpha hydroxyprogesterone caproate during the studied pregnancy. We classified women as a 17-alpha hydroxyprogesterone caproate responder or nonresponder by calculating the difference in delivery gestational age between the 17-alpha hydroxyprogesterone caproate-treated pregnancy and her earliest spontaneous preterm birth. Responders were defined as those with pregnancy that extended ≥3 weeks later with 17-alpha hydroxyprogesterone caproate, compared with the delivery gestational age of their earliest previous spontaneous preterm birth. Data were analyzed with the use of chi-square test, t-test, and logistic regression.

    RESULTS: One hundred fifty-five women met the inclusion criteria. The 118 responders delivered later on average (37.7 weeks gestation) than the 37 nonresponders (33.5 weeks gestation; P < .001). Among responders, 32% (38/118 women) had a recurrent spontaneous preterm birth. Demographics (age, race/ethnicity, education, and parity) were similar between groups. In the regression model, the gestational age of the previous spontaneous preterm birth (odds ratio, 0.68; 95% confidence interval, 0.56-0.82; P < .001), vaginal bleeding/abruption in the current pregnancy (odds ratio, 0.24; 95% confidence interval, 0.06-0.88; P = .031), and first-degree family history of spontaneous preterm birth (odds ratio, 0.37; 95% confidence interval, 0.15-0.88; P = .024) were associated with response to 17-alpha hydroxyprogesterone caproate. Because women with a penultimate preterm pregnancy were more likely to be 17-alpha hydroxyprogesterone caproate nonresponders, we performed an additional limited analysis examining only the 130 women whose penultimate pregnancy was preterm. In regression models, the results were similar to those in the main cohort.

    CONCLUSION: Several historic and current pregnancy characteristics define women who are at risk for recurrent preterm birth at a similar gestational age, despite 17-alpha hydroxyprogesterone caproate therapy. These data should be studied prospectively in larger cohorts and combined with genetic and environmental data to identify women who are most likely to benefit from this intervention.

    Original languageEnglish (US)
    JournalAmerican Journal of Obstetrics and Gynecology
    Volume214
    Issue number3
    DOIs
    StatePublished - Mar 1 2016

    Fingerprint

    Premature Birth
    Pregnancy
    Gestational Age
    Odds Ratio
    Confidence Intervals
    17-alpha-hydroxy-progesterone caproate
    Demography
    Reproductive History
    Uterine Hemorrhage
    Chi-Square Distribution
    Parity
    Multicenter Studies
    Progesterone
    Longitudinal Studies

    Keywords

    • decidual hemorrhage
    • progesterone
    • recurrent preterm birth
    • spontaneous preterm labor

    ASJC Scopus subject areas

    • Obstetrics and Gynecology

    Cite this

    Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Genomics and Proteomics Network for Preterm Birth Research (GPN-PBR) (2016). Predictors of response to 17-alpha hydroxyprogesterone caproate for prevention of recurrent spontaneous preterm birth. American Journal of Obstetrics and Gynecology, 214(3). https://doi.org/10.1016/j.ajog.2015.12.010

    Predictors of response to 17-alpha hydroxyprogesterone caproate for prevention of recurrent spontaneous preterm birth. / Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Genomics and Proteomics Network for Preterm Birth Research (GPN-PBR).

    In: American Journal of Obstetrics and Gynecology, Vol. 214, No. 3, 01.03.2016.

    Research output: Contribution to journalArticle

    Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Genomics and Proteomics Network for Preterm Birth Research (GPN-PBR) 2016, 'Predictors of response to 17-alpha hydroxyprogesterone caproate for prevention of recurrent spontaneous preterm birth', American Journal of Obstetrics and Gynecology, vol. 214, no. 3. https://doi.org/10.1016/j.ajog.2015.12.010
    Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Genomics and Proteomics Network for Preterm Birth Research (GPN-PBR). Predictors of response to 17-alpha hydroxyprogesterone caproate for prevention of recurrent spontaneous preterm birth. American Journal of Obstetrics and Gynecology. 2016 Mar 1;214(3). https://doi.org/10.1016/j.ajog.2015.12.010
    Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Genomics and Proteomics Network for Preterm Birth Research (GPN-PBR). / Predictors of response to 17-alpha hydroxyprogesterone caproate for prevention of recurrent spontaneous preterm birth. In: American Journal of Obstetrics and Gynecology. 2016 ; Vol. 214, No. 3.
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    abstract = "BACKGROUND: Prematurity is the leading cause of neonatal morbidity and death among nonanomalous neonates in the United States. Intramuscular 17-alpha hydroxyprogesterone caproate injections reduce the risk of recurrent prematurity by approximately one third. Unfortunately, prophylactic 17-alpha hydroxyprogesterone caproate is not always effective, and one-third of high-risk women will have a recurrent preterm birth, despite 17-alpha hydroxyprogesterone caproate therapy. The reasons for this variability in response are unknown. Previous investigators have examined the influence of a variety of factors on 17-alpha hydroxyprogesterone caproate response but have analyzed data that used a fixed outcome of term delivery to define progesterone response.OBJECTIVE: We hypothesized that the demographics, history, and pregnancy course among women who deliver at a similar gestational age with 17-alpha hydroxyprogesterone caproate for recurrent spontaneous preterm birth prevention differs when compared with those women who deliver later with 17-alpha hydroxyprogesterone caproate and that these associations could be refined by the use of a contemporary definition of 17-alpha hydroxyprogesterone caproate {"}responder.{"}STUDY DESIGN: This was a planned secondary analysis of a prospective, multicenter, longitudinal study of women with ≥1 previous documented singleton spontaneous preterm birth at <37 weeks gestation. Data were collected at 3 prespecified gestational age epochs during pregnancy. All women who were included in this analysis received 17-alpha hydroxyprogesterone caproate during the studied pregnancy. We classified women as a 17-alpha hydroxyprogesterone caproate responder or nonresponder by calculating the difference in delivery gestational age between the 17-alpha hydroxyprogesterone caproate-treated pregnancy and her earliest spontaneous preterm birth. Responders were defined as those with pregnancy that extended ≥3 weeks later with 17-alpha hydroxyprogesterone caproate, compared with the delivery gestational age of their earliest previous spontaneous preterm birth. Data were analyzed with the use of chi-square test, t-test, and logistic regression.RESULTS: One hundred fifty-five women met the inclusion criteria. The 118 responders delivered later on average (37.7 weeks gestation) than the 37 nonresponders (33.5 weeks gestation; P < .001). Among responders, 32{\%} (38/118 women) had a recurrent spontaneous preterm birth. Demographics (age, race/ethnicity, education, and parity) were similar between groups. In the regression model, the gestational age of the previous spontaneous preterm birth (odds ratio, 0.68; 95{\%} confidence interval, 0.56-0.82; P < .001), vaginal bleeding/abruption in the current pregnancy (odds ratio, 0.24; 95{\%} confidence interval, 0.06-0.88; P = .031), and first-degree family history of spontaneous preterm birth (odds ratio, 0.37; 95{\%} confidence interval, 0.15-0.88; P = .024) were associated with response to 17-alpha hydroxyprogesterone caproate. Because women with a penultimate preterm pregnancy were more likely to be 17-alpha hydroxyprogesterone caproate nonresponders, we performed an additional limited analysis examining only the 130 women whose penultimate pregnancy was preterm. In regression models, the results were similar to those in the main cohort.CONCLUSION: Several historic and current pregnancy characteristics define women who are at risk for recurrent preterm birth at a similar gestational age, despite 17-alpha hydroxyprogesterone caproate therapy. These data should be studied prospectively in larger cohorts and combined with genetic and environmental data to identify women who are most likely to benefit from this intervention.",
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    T1 - Predictors of response to 17-alpha hydroxyprogesterone caproate for prevention of recurrent spontaneous preterm birth

    AU - Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Genomics and Proteomics Network for Preterm Birth Research (GPN-PBR)

    AU - Manuck, Tracy A.

    AU - Esplin, M. Sean

    AU - Biggio, Joseph

    AU - Bukowski, Radek

    AU - Parry, Samuel

    AU - Zhang, Heping

    AU - Huang, Hao

    AU - Varner, Michael W.

    AU - Andrews, William

    AU - Saade, George

    AU - Sadovsky, Yoel

    AU - Reddy, Uma M.

    AU - Ilekis, John

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    N2 - BACKGROUND: Prematurity is the leading cause of neonatal morbidity and death among nonanomalous neonates in the United States. Intramuscular 17-alpha hydroxyprogesterone caproate injections reduce the risk of recurrent prematurity by approximately one third. Unfortunately, prophylactic 17-alpha hydroxyprogesterone caproate is not always effective, and one-third of high-risk women will have a recurrent preterm birth, despite 17-alpha hydroxyprogesterone caproate therapy. The reasons for this variability in response are unknown. Previous investigators have examined the influence of a variety of factors on 17-alpha hydroxyprogesterone caproate response but have analyzed data that used a fixed outcome of term delivery to define progesterone response.OBJECTIVE: We hypothesized that the demographics, history, and pregnancy course among women who deliver at a similar gestational age with 17-alpha hydroxyprogesterone caproate for recurrent spontaneous preterm birth prevention differs when compared with those women who deliver later with 17-alpha hydroxyprogesterone caproate and that these associations could be refined by the use of a contemporary definition of 17-alpha hydroxyprogesterone caproate "responder."STUDY DESIGN: This was a planned secondary analysis of a prospective, multicenter, longitudinal study of women with ≥1 previous documented singleton spontaneous preterm birth at <37 weeks gestation. Data were collected at 3 prespecified gestational age epochs during pregnancy. All women who were included in this analysis received 17-alpha hydroxyprogesterone caproate during the studied pregnancy. We classified women as a 17-alpha hydroxyprogesterone caproate responder or nonresponder by calculating the difference in delivery gestational age between the 17-alpha hydroxyprogesterone caproate-treated pregnancy and her earliest spontaneous preterm birth. Responders were defined as those with pregnancy that extended ≥3 weeks later with 17-alpha hydroxyprogesterone caproate, compared with the delivery gestational age of their earliest previous spontaneous preterm birth. Data were analyzed with the use of chi-square test, t-test, and logistic regression.RESULTS: One hundred fifty-five women met the inclusion criteria. The 118 responders delivered later on average (37.7 weeks gestation) than the 37 nonresponders (33.5 weeks gestation; P < .001). Among responders, 32% (38/118 women) had a recurrent spontaneous preterm birth. Demographics (age, race/ethnicity, education, and parity) were similar between groups. In the regression model, the gestational age of the previous spontaneous preterm birth (odds ratio, 0.68; 95% confidence interval, 0.56-0.82; P < .001), vaginal bleeding/abruption in the current pregnancy (odds ratio, 0.24; 95% confidence interval, 0.06-0.88; P = .031), and first-degree family history of spontaneous preterm birth (odds ratio, 0.37; 95% confidence interval, 0.15-0.88; P = .024) were associated with response to 17-alpha hydroxyprogesterone caproate. Because women with a penultimate preterm pregnancy were more likely to be 17-alpha hydroxyprogesterone caproate nonresponders, we performed an additional limited analysis examining only the 130 women whose penultimate pregnancy was preterm. In regression models, the results were similar to those in the main cohort.CONCLUSION: Several historic and current pregnancy characteristics define women who are at risk for recurrent preterm birth at a similar gestational age, despite 17-alpha hydroxyprogesterone caproate therapy. These data should be studied prospectively in larger cohorts and combined with genetic and environmental data to identify women who are most likely to benefit from this intervention.

    AB - BACKGROUND: Prematurity is the leading cause of neonatal morbidity and death among nonanomalous neonates in the United States. Intramuscular 17-alpha hydroxyprogesterone caproate injections reduce the risk of recurrent prematurity by approximately one third. Unfortunately, prophylactic 17-alpha hydroxyprogesterone caproate is not always effective, and one-third of high-risk women will have a recurrent preterm birth, despite 17-alpha hydroxyprogesterone caproate therapy. The reasons for this variability in response are unknown. Previous investigators have examined the influence of a variety of factors on 17-alpha hydroxyprogesterone caproate response but have analyzed data that used a fixed outcome of term delivery to define progesterone response.OBJECTIVE: We hypothesized that the demographics, history, and pregnancy course among women who deliver at a similar gestational age with 17-alpha hydroxyprogesterone caproate for recurrent spontaneous preterm birth prevention differs when compared with those women who deliver later with 17-alpha hydroxyprogesterone caproate and that these associations could be refined by the use of a contemporary definition of 17-alpha hydroxyprogesterone caproate "responder."STUDY DESIGN: This was a planned secondary analysis of a prospective, multicenter, longitudinal study of women with ≥1 previous documented singleton spontaneous preterm birth at <37 weeks gestation. Data were collected at 3 prespecified gestational age epochs during pregnancy. All women who were included in this analysis received 17-alpha hydroxyprogesterone caproate during the studied pregnancy. We classified women as a 17-alpha hydroxyprogesterone caproate responder or nonresponder by calculating the difference in delivery gestational age between the 17-alpha hydroxyprogesterone caproate-treated pregnancy and her earliest spontaneous preterm birth. Responders were defined as those with pregnancy that extended ≥3 weeks later with 17-alpha hydroxyprogesterone caproate, compared with the delivery gestational age of their earliest previous spontaneous preterm birth. Data were analyzed with the use of chi-square test, t-test, and logistic regression.RESULTS: One hundred fifty-five women met the inclusion criteria. The 118 responders delivered later on average (37.7 weeks gestation) than the 37 nonresponders (33.5 weeks gestation; P < .001). Among responders, 32% (38/118 women) had a recurrent spontaneous preterm birth. Demographics (age, race/ethnicity, education, and parity) were similar between groups. In the regression model, the gestational age of the previous spontaneous preterm birth (odds ratio, 0.68; 95% confidence interval, 0.56-0.82; P < .001), vaginal bleeding/abruption in the current pregnancy (odds ratio, 0.24; 95% confidence interval, 0.06-0.88; P = .031), and first-degree family history of spontaneous preterm birth (odds ratio, 0.37; 95% confidence interval, 0.15-0.88; P = .024) were associated with response to 17-alpha hydroxyprogesterone caproate. Because women with a penultimate preterm pregnancy were more likely to be 17-alpha hydroxyprogesterone caproate nonresponders, we performed an additional limited analysis examining only the 130 women whose penultimate pregnancy was preterm. In regression models, the results were similar to those in the main cohort.CONCLUSION: Several historic and current pregnancy characteristics define women who are at risk for recurrent preterm birth at a similar gestational age, despite 17-alpha hydroxyprogesterone caproate therapy. These data should be studied prospectively in larger cohorts and combined with genetic and environmental data to identify women who are most likely to benefit from this intervention.

    KW - decidual hemorrhage

    KW - progesterone

    KW - recurrent preterm birth

    KW - spontaneous preterm labor

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