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

Global Obstetrics Network (GONet) Collaboration

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

Research output: Contribution to journal › Review article (Academic Journal) › peer-review

127 Citations (Scopus)

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
DOIs	https://doi.org/10.1111/1471-0528.13032
Publication status	Published - Jan 2015

Bibliographical note

Keywords

17 alpha-Hydroxyprogesterone Caproate
Administration, Intravaginal
Adult
Bronchopulmonary Dysplasia/prevention & control
Cerebral Hemorrhage/prevention & control
Cervical Length Measurement
Cervix Uteri/diagnostic imaging
Enterocolitis, Necrotizing/prevention & control
Female
Humans
Hydroxyprogesterones/therapeutic use
Infant, Newborn
Infant, Newborn, Diseases/prevention & control
Perinatal Death/prevention & control
Pregnancy
Pregnancy, Twin
Premature Birth/prevention & control
Progesterone/therapeutic use
Progestins/therapeutic use
Respiratory Distress Syndrome, Newborn/prevention & control
Treatment Outcome

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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.",

keywords = "17 alpha-Hydroxyprogesterone Caproate, Administration, Intravaginal, Adult, Bronchopulmonary Dysplasia/prevention & control, Cerebral Hemorrhage/prevention & control, Cervical Length Measurement, Cervix Uteri/diagnostic imaging, Enterocolitis, Necrotizing/prevention & control, Female, Humans, Hydroxyprogesterones/therapeutic use, Infant, Newborn, Infant, Newborn, Diseases/prevention & control, Perinatal Death/prevention & control, Pregnancy, Pregnancy, Twin, Premature Birth/prevention & control, Progesterone/therapeutic use, Progestins/therapeutic use, Respiratory Distress Syndrome, Newborn/prevention & control, Treatment Outcome",

author = "{Global Obstetrics Network (GONet) Collaboration} and E Schuit and S Stock and L Rode and Rouse, {D J} and Lim, {A C} and Norman, {J E} and Nassar, {A H} and V Serra and Combs, {C A} and C Vayssiere and Aboulghar, {M M} and S Wood and E {\c C}eting{\"o}z and Briery, {C M} and Fonseca, {E B} and K Worda and A Tabor and Thom, {E A} and Caritis, {S N} and J Awwad and Usta, {I M} and A Perales and J Meseguer and K Maurel and T Garite and Aboulghar, {M A} and Amin, {Y M} and S Ross and C Cam and A Karateke and Morrison, {J C} and Magann, {E F} and Nicolaides, {K H} and Zuithoff, {N P A} and Groenwold, {R H H} and Moons, {K G M} and A Kwee and Mol, {B W J}",

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",

}

Effectiveness of progestogens to improve perinatal outcome in twin pregnancies: an individual participant data meta-analysis. / Global Obstetrics Network (GONet) Collaboration.
In: BJOG: An International Journal of Obstetrics and Gynaecology, Vol. 122, No. 1, 01.2015, p. 27-37.

Research output: Contribution to journal › Review article (Academic Journal) › 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, D J

AU - Lim, A C

AU - Norman, J E

AU - Nassar, A H

AU - Serra, V

AU - Combs, C A

AU - Vayssiere, C

AU - Aboulghar, M M

AU - Wood, S

AU - Çetingöz, E

AU - Briery, C M

AU - Fonseca, E B

AU - Worda, K

AU - Tabor, A

AU - Thom, E A

AU - Caritis, S N

AU - Awwad, J

AU - Usta, I M

AU - Perales, A

AU - Meseguer, J

AU - Maurel, K

AU - Garite, T

AU - Aboulghar, M A

AU - Amin, Y M

AU - Ross, S

AU - Cam, C

AU - Karateke, A

AU - Morrison, J C

AU - Magann, E F

AU - Nicolaides, K H

AU - Zuithoff, N P A

AU - Groenwold, R H H

AU - Moons, K G M

AU - Kwee, A

AU - Mol, B W J

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.

KW - 17 alpha-Hydroxyprogesterone Caproate

KW - Administration, Intravaginal

KW - Adult

KW - Bronchopulmonary Dysplasia/prevention & control

KW - Cerebral Hemorrhage/prevention & control

KW - Cervical Length Measurement

KW - Cervix Uteri/diagnostic imaging

KW - Enterocolitis, Necrotizing/prevention & control

KW - Female

KW - Humans

KW - Hydroxyprogesterones/therapeutic use

KW - Infant, Newborn

KW - Infant, Newborn, Diseases/prevention & control

KW - Perinatal Death/prevention & control

KW - Pregnancy

KW - Pregnancy, Twin

KW - Premature Birth/prevention & control

KW - Progesterone/therapeutic use

KW - Progestins/therapeutic use

KW - Respiratory Distress Syndrome, Newborn/prevention & control

KW - Treatment Outcome

U2 - 10.1111/1471-0528.13032

DO - 10.1111/1471-0528.13032

M3 - Review article (Academic Journal)

C2 - 25145491

SN - 1470-0328

VL - 122

SP - 27

EP - 37

JO - BJOG: An International Journal of Obstetrics and Gynaecology

JF - BJOG: An International Journal of Obstetrics and Gynaecology

IS - 1

ER -

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

Abstract

Bibliographical note

Keywords

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