Effectiveness of progestogens to improve perinatal outcome in twin pregnancies: an individual participant data meta-analysis

Global Obstetrics Network (GONet) collaboration; E Schuit; S Stock; L Rode; Dj Rouse; Ac Lim; J. E. Norman; Ah Nassar; V Serra; Ca Combs; C Vayssiere; Mm Aboulghar; S Wood; E Çetingöz; Cm Briery; Eb Fonseca; K Worda; A Tabor; Ea Thom; Sn Caritis; J Awwad; Im Usta; A Perales; J Meseguer; K Maurel; T Garite; Ma Aboulghar; Ym Amin; S Ross; C Cam; A Karateke; Jc Morrison; Ef Magann; Kh Nicolaides; Npa Zuithoff; Rhh Groenwold; Kgm Moons; A Kwee; Bwj Mol

doi:10.1111/1471-0528.13032

Effectiveness of progestogens to improve perinatal outcome in twin pregnancies: an individual participant data meta-analysis

Global Obstetrics Network (GONet) collaboration, E Schuit, S Stock, L Rode, Dj Rouse, Ac Lim, J. E. Norman, Ah Nassar, V Serra, Ca Combs, C Vayssiere, Mm Aboulghar, S Wood, E Çetingöz, Cm Briery, Eb Fonseca, K Worda, A Tabor, Ea Thom, Sn CaritisJ Awwad, Im Usta, A Perales, J Meseguer, K Maurel, T Garite, Ma Aboulghar, Ym Amin, S Ross, C Cam, A Karateke, Jc Morrison, Ef Magann, Kh Nicolaides, Npa Zuithoff, Rhh Groenwold, Kgm Moons, A Kwee, Bwj Mol

Research output: Contribution to journal › Article › peer-review

Abstract

BACKGROUND: In twin pregnancies, the rates of adverse perinatal outcome and subsequent long-term morbidity are substantial, and mainly result from preterm birth (PTB).

OBJECTIVES: To assess the effectiveness of progestogen treatment in the prevention of neonatal morbidity or PTB in twin pregnancies using individual participant data meta-analysis (IPDMA).

SEARCH STRATEGY: We searched international scientific databases, trial registration websites, and references of identified articles.

SELECTION CRITERIA: Randomised clinical trials (RCTs) of 17-hydroxyprogesterone caproate (17Pc) or vaginally administered natural progesterone, compared with placebo or no treatment.

DATA COLLECTION AND ANALYSIS: Investigators of identified RCTs were asked to share their IPD. The primary outcome was a composite of perinatal mortality and severe neonatal morbidity. Prespecified subgroup analyses were performed for chorionicity, cervical length, and prior spontaneous PTB.

MAIN RESULTS: Thirteen trials included 3768 women and their 7536 babies. Neither 17Pc nor vaginal progesterone reduced the incidence of adverse perinatal outcome (17Pc relative risk, RR 1.1; 95% confidence interval, 95% CI 0.97-1.4, vaginal progesterone RR 0.97; 95% CI 0.77-1.2). In a subgroup of women with a cervical length of ≤25 mm, vaginal progesterone reduced adverse perinatal outcome when cervical length was measured at randomisation (15/56 versus 22/60; RR 0.57; 95% CI 0.47-0.70) or before 24 weeks of gestation (14/52 versus 21/56; RR 0.56; 95% CI 0.42-0.75).

AUTHOR'S CONCLUSIONS: In unselected women with an uncomplicated twin gestation, treatment with progestogens (intramuscular 17Pc or vaginal natural progesterone) does not improve perinatal outcome. Vaginal progesterone may be effective in the reduction of adverse perinatal outcome in women with a cervical length of ≤25 mm; however, further research is warranted to confirm this finding.

Original language	English
Pages (from-to)	27-37
Number of pages	11
Journal	BJOG: An International Journal of Obstetrics and Gynaecology
Volume	122
Issue number	1
Early online date	22 Aug 2014
DOIs	https://doi.org/10.1111/1471-0528.13032
Publication status	Published - Jan 2015

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10.1111/1471-0528.13032

Sarah Stock
- Deanery of Molecular, Genetic and Population Health Sciences - Reader
- Usher Institute - Wellcome Trust Clinical Career Development Fellow
- Centre for Medical Informatics
Person: Academic: Research Active

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Global Obstetrics Network (GONet) collaboration, Schuit, E., Stock, S., Rode, L., Rouse, D., Lim, A., Norman, J. E., Nassar, A., Serra, V., Combs, C., Vayssiere, C., Aboulghar, M., Wood, S., Çetingöz, E., Briery, C., Fonseca, E., Worda, K., Tabor, A., Thom, E., ... Mol, B. (2015). Effectiveness of progestogens to improve perinatal outcome in twin pregnancies: an individual participant data meta-analysis. BJOG: An International Journal of Obstetrics and Gynaecology, 122(1), 27-37. https://doi.org/10.1111/1471-0528.13032

Global Obstetrics Network (GONet) collaboration ; Schuit, E ; Stock, S ; Rode, L ; Rouse, Dj ; Lim, Ac ; Norman, J. E. ; Nassar, Ah ; Serra, V ; Combs, Ca ; Vayssiere, C ; Aboulghar, Mm ; Wood, S ; Çetingöz, E ; Briery, Cm ; Fonseca, Eb ; Worda, K ; Tabor, A ; Thom, Ea ; Caritis, Sn ; Awwad, J ; Usta, Im ; Perales, A ; Meseguer, J ; Maurel, K ; Garite, T ; Aboulghar, Ma ; Amin, Ym ; Ross, S ; Cam, C ; Karateke, A ; Morrison, Jc ; Magann, Ef ; Nicolaides, Kh ; Zuithoff, Npa ; Groenwold, Rhh ; Moons, Kgm ; Kwee, A ; Mol, Bwj. / Effectiveness of progestogens to improve perinatal outcome in twin pregnancies : an individual participant data meta-analysis. In: BJOG: An International Journal of Obstetrics and Gynaecology. 2015 ; Vol. 122, No. 1. pp. 27-37.

@article{ba1f3d5e87b74787928c9f3db9d94553,

title = "Effectiveness of progestogens to improve perinatal outcome in twin pregnancies: an individual participant data meta-analysis",

abstract = "BACKGROUND: In twin pregnancies, the rates of adverse perinatal outcome and subsequent long-term morbidity are substantial, and mainly result from preterm birth (PTB).OBJECTIVES: To assess the effectiveness of progestogen treatment in the prevention of neonatal morbidity or PTB in twin pregnancies using individual participant data meta-analysis (IPDMA).SEARCH STRATEGY: We searched international scientific databases, trial registration websites, and references of identified articles.SELECTION CRITERIA: Randomised clinical trials (RCTs) of 17-hydroxyprogesterone caproate (17Pc) or vaginally administered natural progesterone, compared with placebo or no treatment.DATA COLLECTION AND ANALYSIS: Investigators of identified RCTs were asked to share their IPD. The primary outcome was a composite of perinatal mortality and severe neonatal morbidity. Prespecified subgroup analyses were performed for chorionicity, cervical length, and prior spontaneous PTB.MAIN RESULTS: Thirteen trials included 3768 women and their 7536 babies. Neither 17Pc nor vaginal progesterone reduced the incidence of adverse perinatal outcome (17Pc relative risk, RR 1.1; 95% confidence interval, 95% CI 0.97-1.4, vaginal progesterone RR 0.97; 95% CI 0.77-1.2). In a subgroup of women with a cervical length of ≤25 mm, vaginal progesterone reduced adverse perinatal outcome when cervical length was measured at randomisation (15/56 versus 22/60; RR 0.57; 95% CI 0.47-0.70) or before 24 weeks of gestation (14/52 versus 21/56; RR 0.56; 95% CI 0.42-0.75).AUTHOR'S CONCLUSIONS: In unselected women with an uncomplicated twin gestation, treatment with progestogens (intramuscular 17Pc or vaginal natural progesterone) does not improve perinatal outcome. Vaginal progesterone may be effective in the reduction of adverse perinatal outcome in women with a cervical length of ≤25 mm; however, further research is warranted to confirm this finding.",

author = "{Global Obstetrics Network (GONet) collaboration} and E Schuit and S Stock and L Rode and Dj Rouse and Ac Lim and Norman, {J. E.} and Ah Nassar and V Serra and Ca Combs and C Vayssiere and Mm Aboulghar and S Wood and E {\c C}eting{\"o}z and Cm Briery and Eb Fonseca and K Worda and A Tabor and Ea Thom and Sn Caritis and J Awwad and Im Usta and A Perales and J Meseguer and K Maurel and T Garite and Ma Aboulghar and Ym Amin and S Ross and C Cam and A Karateke and Jc Morrison and Ef Magann and Kh Nicolaides and Npa Zuithoff and Rhh Groenwold and Kgm Moons and A Kwee and Bwj Mol",

note = "{\textcopyright} 2014 Royal College of Obstetricians and Gynaecologists.",

year = "2015",

month = jan,

doi = "10.1111/1471-0528.13032",

language = "English",

volume = "122",

pages = "27--37",

journal = "BJOG: An International Journal of Obstetrics and Gynaecology",

issn = "1470-0328",

publisher = "Wiley",

number = "1",

}

Global Obstetrics Network (GONet) collaboration, Schuit, E, Stock, S, Rode, L, Rouse, D, Lim, A, Norman, JE, Nassar, A, Serra, V, Combs, C, Vayssiere, C, Aboulghar, M, Wood, S, Çetingöz, E, Briery, C, Fonseca, E, Worda, K, Tabor, A, Thom, E, Caritis, S, Awwad, J, Usta, I, Perales, A, Meseguer, J, Maurel, K, Garite, T, Aboulghar, M, Amin, Y, Ross, S, Cam, C, Karateke, A, Morrison, J, Magann, E, Nicolaides, K, Zuithoff, N, Groenwold, R, Moons, K, Kwee, A & Mol, B 2015, 'Effectiveness of progestogens to improve perinatal outcome in twin pregnancies: an individual participant data meta-analysis', BJOG: An International Journal of Obstetrics and Gynaecology, vol. 122, no. 1, pp. 27-37. https://doi.org/10.1111/1471-0528.13032

Effectiveness of progestogens to improve perinatal outcome in twin pregnancies : an individual participant data meta-analysis. / Global Obstetrics Network (GONet) collaboration; Schuit, E; Stock, S; Rode, L; Rouse, Dj; Lim, Ac; Norman, J. E.; Nassar, Ah; Serra, V; Combs, Ca; Vayssiere, C; Aboulghar, Mm; Wood, S; Çetingöz, E; Briery, Cm; Fonseca, Eb; Worda, K; Tabor, A; Thom, Ea; Caritis, Sn; Awwad, J; Usta, Im; Perales, A; Meseguer, J; Maurel, K; Garite, T; Aboulghar, Ma; Amin, Ym; Ross, S; Cam, C; Karateke, A; Morrison, Jc; Magann, Ef; Nicolaides, Kh; Zuithoff, Npa; Groenwold, Rhh; Moons, Kgm; Kwee, A; Mol, Bwj.

In: BJOG: An International Journal of Obstetrics and Gynaecology, Vol. 122, No. 1, 01.2015, p. 27-37.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Effectiveness of progestogens to improve perinatal outcome in twin pregnancies

T2 - an individual participant data meta-analysis

AU - Global Obstetrics Network (GONet) collaboration

AU - Schuit, E

AU - Stock, S

AU - Rode, L

AU - Rouse, Dj

AU - Lim, Ac

AU - Norman, J. E.

AU - Nassar, Ah

AU - Serra, V

AU - Combs, Ca

AU - Vayssiere, C

AU - Aboulghar, Mm

AU - Wood, S

AU - Çetingöz, E

AU - Briery, Cm

AU - Fonseca, Eb

AU - Worda, K

AU - Tabor, A

AU - Thom, Ea

AU - Caritis, Sn

AU - Awwad, J

AU - Usta, Im

AU - Perales, A

AU - Meseguer, J

AU - Maurel, K

AU - Garite, T

AU - Aboulghar, Ma

AU - Amin, Ym

AU - Ross, S

AU - Cam, C

AU - Karateke, A

AU - Morrison, Jc

AU - Magann, Ef

AU - Nicolaides, Kh

AU - Zuithoff, Npa

AU - Groenwold, Rhh

AU - Moons, Kgm

AU - Kwee, A

AU - Mol, Bwj

PY - 2015/1

Y1 - 2015/1

N2 - BACKGROUND: In twin pregnancies, the rates of adverse perinatal outcome and subsequent long-term morbidity are substantial, and mainly result from preterm birth (PTB).OBJECTIVES: To assess the effectiveness of progestogen treatment in the prevention of neonatal morbidity or PTB in twin pregnancies using individual participant data meta-analysis (IPDMA).SEARCH STRATEGY: We searched international scientific databases, trial registration websites, and references of identified articles.SELECTION CRITERIA: Randomised clinical trials (RCTs) of 17-hydroxyprogesterone caproate (17Pc) or vaginally administered natural progesterone, compared with placebo or no treatment.DATA COLLECTION AND ANALYSIS: Investigators of identified RCTs were asked to share their IPD. The primary outcome was a composite of perinatal mortality and severe neonatal morbidity. Prespecified subgroup analyses were performed for chorionicity, cervical length, and prior spontaneous PTB.MAIN RESULTS: Thirteen trials included 3768 women and their 7536 babies. Neither 17Pc nor vaginal progesterone reduced the incidence of adverse perinatal outcome (17Pc relative risk, RR 1.1; 95% confidence interval, 95% CI 0.97-1.4, vaginal progesterone RR 0.97; 95% CI 0.77-1.2). In a subgroup of women with a cervical length of ≤25 mm, vaginal progesterone reduced adverse perinatal outcome when cervical length was measured at randomisation (15/56 versus 22/60; RR 0.57; 95% CI 0.47-0.70) or before 24 weeks of gestation (14/52 versus 21/56; RR 0.56; 95% CI 0.42-0.75).AUTHOR'S CONCLUSIONS: In unselected women with an uncomplicated twin gestation, treatment with progestogens (intramuscular 17Pc or vaginal natural progesterone) does not improve perinatal outcome. Vaginal progesterone may be effective in the reduction of adverse perinatal outcome in women with a cervical length of ≤25 mm; however, further research is warranted to confirm this finding.

AB - BACKGROUND: In twin pregnancies, the rates of adverse perinatal outcome and subsequent long-term morbidity are substantial, and mainly result from preterm birth (PTB).OBJECTIVES: To assess the effectiveness of progestogen treatment in the prevention of neonatal morbidity or PTB in twin pregnancies using individual participant data meta-analysis (IPDMA).SEARCH STRATEGY: We searched international scientific databases, trial registration websites, and references of identified articles.SELECTION CRITERIA: Randomised clinical trials (RCTs) of 17-hydroxyprogesterone caproate (17Pc) or vaginally administered natural progesterone, compared with placebo or no treatment.DATA COLLECTION AND ANALYSIS: Investigators of identified RCTs were asked to share their IPD. The primary outcome was a composite of perinatal mortality and severe neonatal morbidity. Prespecified subgroup analyses were performed for chorionicity, cervical length, and prior spontaneous PTB.MAIN RESULTS: Thirteen trials included 3768 women and their 7536 babies. Neither 17Pc nor vaginal progesterone reduced the incidence of adverse perinatal outcome (17Pc relative risk, RR 1.1; 95% confidence interval, 95% CI 0.97-1.4, vaginal progesterone RR 0.97; 95% CI 0.77-1.2). In a subgroup of women with a cervical length of ≤25 mm, vaginal progesterone reduced adverse perinatal outcome when cervical length was measured at randomisation (15/56 versus 22/60; RR 0.57; 95% CI 0.47-0.70) or before 24 weeks of gestation (14/52 versus 21/56; RR 0.56; 95% CI 0.42-0.75).AUTHOR'S CONCLUSIONS: In unselected women with an uncomplicated twin gestation, treatment with progestogens (intramuscular 17Pc or vaginal natural progesterone) does not improve perinatal outcome. Vaginal progesterone may be effective in the reduction of adverse perinatal outcome in women with a cervical length of ≤25 mm; however, further research is warranted to confirm this finding.

U2 - 10.1111/1471-0528.13032

DO - 10.1111/1471-0528.13032

M3 - Article

C2 - 25145491

VL - 122

SP - 27

EP - 37

JO - BJOG: An International Journal of Obstetrics and Gynaecology

JF - BJOG: An International Journal of Obstetrics and Gynaecology

SN - 1470-0328

IS - 1

ER -

Effectiveness of progestogens to improve perinatal outcome in twin pregnancies: an individual participant data meta-analysis

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