Erken Doğumda Progesteron Kullanımı - TJOD …tjodizmir.org.tr/uploads/slaytlar/635370549284381250.pdfAkut Preterm Eylemde Tokolitik Tedavi Tocolytic therapy for preterm delivery:

Erken Doğumda Progesteron Kullanımı

Dr. Erkan Çağlıyan

Dokuz Eylül Üniversitesi Tıp Fakültesi

Kadın Hastalıkları ve Doğum Anabilim Dalı

Preterm Doğum Hızı

% 11.8

Preterm Doğum

Erken Doğum Sınıflama

Akut Preterm Eylemde Tokolitik Tedavi

Tocolytic therapy for preterm delivery: systematic review and network meta-analysis .BMJ 2012

Erken Doğum –Öngörüsü ‘Prediction is the basis of Prevention’

Goldenberg et al. American Journal of Public Health,1998

Goldenberg et al. American Journal of Public Health,1998

Erken Doğum -Öngörüsü

Comparison 9. Comparison 01 FFN knowledgeversusno knowledge, Outcome09 Tocolysis

Outcomeor subgroup titleNo. of

studies

No. of

participants Statistical method Effect size

1 Outcome09 Tocolysis 4 350 Risk Ratio (M-H, Fixed, 95% CI) 1.01 [0.78, 1.30]

Comparison 10. Comparison 01 FFN knowledge versus no knowledge, Outcome 10 Steroids for fetal lung

maturity


studies

No. of


1 Outcome10 Steroidsfor Fetal

Lung Maturity

3 270 Risk Ratio (M-H, Fixed, 95% CI) 1.23 [0.85, 1.79]

Comparison 11. Comparison 01 FFN knowledgeversusno knowledge, Outcome11 Timeto evaluate (hours)


studies

No. of


1 Outcome11 Timeto evaluate 3 234 Mean Difference(IV, Fixed, 95% CI) 0.04 [-0.39, 0.47]

Analysis 1.1. Comparison 1 Comparison 01 FFN knowledge versus no knowledge, Outcome 01 Preterm

birth < 37 week, Outcome 1 Outcome 01 Preterm birth < 37 weeks.

Review: Fetal fibronectin testing for reducing the risk of preterm birth

Comparison: 1 Comparison 01 FFN knowledge versusno knowledge, Outcome 01 Preterm birth < 37 week

Outcome: 1 Outcome 01 Preterm birth < 37 weeks

Study or subgroup Treatment Control Risk Ratio Weight Risk Ratio

n/N n/N M-H,Fixed,95%CI M-H,Fixed,95%CI

Grobman 2004 10/50 13/50 33.1 % 0.77 [ 0.37, 1.59 ]

Ness2007 6/42 15/43 37.7 % 0.41 [ 0.18, 0.95 ]

Plaut 2003 5/43 12/47 29.2 % 0.46 [ 0.17, 1.19 ]

Total (95% CI) 135 140 100.0 % 0.54 [ 0.34, 0.87 ]

Total events: 21 (Treatment), 40 (Control)

Heterogeneity: Chi2 = 1.44, df = 2 (P= 0.49); I2 =0.0%

Test for overall effect: Z = 2.53 (P= 0.011)

Test for subgroup differences: Not applicable

0.05 0.2 1 5 20

Favours treatment Favours control

15Fetal fibronectin testing for reducing the risk of preterm birth (Review)

Copyright © 2008 The Cochrane Collaboration. Published by John W iley & Sons, Ltd.

Erken Doğum -Öngörüsü Fetal Fibronectin

Berghella V. et al, Cochrane Review,2008


birth < 34 week, Outcome 1 Outcome 02 Preterm birth < 34 week.

Review: Fetal fibronectin testingfor reducing the risk of preterm birth


Outcome: 1 Outcome 02 Preterm birth < 34 week



Grobman 2004 5/50 3/50 33.5 % 1.67 [ 0.42, 6.60 ]

Ness2007 2/46 4/45 45.2 % 0.49 [ 0.09, 2.54 ]

Plaut 2003 2/43 2/47 21.3 % 1.09 [ 0.16, 7.42 ]

Total (95% CI) 139 142 100.0 % 1.01 [ 0.41, 2.47 ]





0.01 0.1 1 10 100




Erken Doğum Öngörüsü Fetal Fibronectin



birth < 32 week, Outcome 1 Outcome 03 Preterm birth < 32 week.

Review: Fetal fibronectin testingfor reducing the risk of preterm birth


Outcome: 1 Outcome 03 Preterm birth < 32 week



Grobman 2004 3/50 2/50 30.6 % 1.50 [ 0.26, 8.60 ]

Ness 2007 0/47 3/45 54.7 % 0.14 [ 0.01, 2.58 ]

Plaut 2003 2/43 1/47 14.6 % 2.19 [ 0.21, 23.26 ]

Total (95% CI) 140 142 100.0 % 0.85 [ 0.28, 2.58 ]


Heterogeneity: Chi2 = 2.50, df = 2 (P= 0.29); I2 =20%



0.01 0.1 1 10 100






• Asemptomatik hastalarda erken doğum için tarama testi olarak

duyarlılığı düşük

• Etkin tedavi seçenekleri sınırlı

• Asemptomatik hastalarda test (+) olması halinde bile < 1 hft

doğum ihtimali az

• Erken Doğum Taraması amacıyla kullanılması önerilmemekte

• Semptomatik hastalada triaj için yararlı


ACOG Practice Bulletin, Number 130, 2012

Prediction of Preterm Birth: Cervical Sonography

Maria Teresa Mella, MD, and Vincenzo Berghella, MD

The cervix has to open to allow vaginal birth. Ultrasound has now shown that this lower part

of the uterus begins to show changes weeks before eventual birth. Only transvaginal

ultrasound should be used to evaluate the cervix for prediction of preterm birth (PTB). The

shortest best cervical length (CL) is the most effective measurement for clinical use. Proper

technique is paramount for accurate results. The risk of PTB increases with ever shorter CL

(< 25 mm). Other factors that must be carefully considered when using CL for prediction of

PTB are number of fetuses, risk factors for PTB, and gestational age at screening.

Semin Perinatol 33:317-324 © 2009 Elsevier Inc. All rights reserved.

KEYWORDScervical length, prediction, preterm birth

Prediction Is the

Basis of Prevention

The aim of any healthcare worker assisting a patient is to

prevent disease. Often, thefirst step in preventing disease is

early prediction. In thecaseof preterm birth (PTB), oneof the

best, if not the best, predictive test has been shown to be

cervical sonography. Thecervix has to open to allow vaginal

birth. Aswehaveknown for decades, theprocess of parturi-

tion takes months of preparation, and early changes can be

detected in human beings.

With regard to thecervix, ultrasound hasnow shown that

this lower part of the uterus begins to show changes weeks

before eventual birth. Even for PTB, which often we had

characterized in the past as something happening suddenly

and unexpectantly, thechangesaregradual and usually very

slow. In fact, in many high-risk women delivering preterm,

thecervix startstoshorten afew monthsbeforepreterm labor

(PTL) or preterm premature rupture of membranes occurs.

Early detection of change is paramount in allowing inter-

ventions thechance to work before thepathology isso far in

itspathways asto thwart prevention. In thischapter, wewill

review the evidence for cervical sonography as a screening

test for theprediction of PTB. Therearenow morethan 1000

manuscripts published on this topic, and ample evidence to

support theefficacy of cervical sonography in theprevention

of PTB.

Evaluation of CervicalLength–Technical Aspects

Evaluation of cervical length (CL) may be done either sono-

graphically or through direct physical examination of the

cervix. Sonographic detection of CL may be approached

through transabdominal, translabial, or transvaginal routes,

with each method having itsown benefitsand limitations.

Physical ExaminationIn the past, serial digital and speculum examinations have

been used to follow-up women with suspected cervical insuf-

ficiency. The physical changes notable on examination, re-

vealing the likelihood of cervical insufficiency, includebulg-

ing membranes, a pink or tan discharge, or appreciable

softening of the cervix and lower uterine segment. Of these

findings, softening and development of the lower uterine

segment is most strongly correlated with early effacement.

However, these reported physical changes are often not evi-

dent until the cervix is significantly effaced, as this process

begins at the internal os. Therefore, the absence of these

physical findings cannot exclude cervical insufficiency. In

addition, a digital examination has been found to besignifi-

cantly less consistent than ultrasound in assessing CL. On

average, manual estimationsof CL areshorter by 11 mm than

sonographic measurements of CL.1 Cervical funneling at the

internal os may also occur while the external os is fully

closed. Many multiparous women who deliver at term have

cervices that are already dilated 1-2 cm in the late second

trimester.1

Division of Maternal-Fetal Medicine, Department of Obstetrics and Gyne-

cology, Jefferson Medical College, Thomas Jefferson University, Phila-

delphia, PA.

Address reprint requests to Vincenzo Berghella, MD, Division of Maternal-

Fetal Medicine, Department of Obstetrics and Gynecology, Thomas Jef-

ferson University, 834 Chestnut St, Suite 400, Philadelphia, PA 19107.

E-mail: [email protected]

3170146-0005/09/$-see front matter © 2009 Elsevier Inc. All rights reserved.

doi:10.1053/j.semperi.2009.06.007

Erken Doğum -Öngörüsü Transvaginal Servikal Uzunluk

Prediction of Preterm Birth: Cervical Sonography

Maria Teresa Mella, MD, and Vincenzo Berghella, MD

The cervix has to open to allow vaginal birth. Ultrasound has now shown that this lower part

of the uterus begins to show changes weeks before eventual birth. Only transvaginal

ultrasound should be used to evaluate the cervix for prediction of preterm birth (PTB). The

shortest best cervical length (CL) is the most effective measurement for clinical use. Proper

technique is paramount for accurate results. The risk of PTB increases with ever shorter CL

(< 25 mm). Other factors that must be carefully considered when using CL for prediction of

PTB are number of fetuses, risk factors for PTB, and gestational age at screening.

Semin Perinatol 33:317-324 © 2009 Elsevier Inc. All rights reserved.

KEYWORDScervical length, prediction, preterm birth

Prediction Is the

Basis of Prevention

The aim of any healthcare worker assisting a patient is to

prevent disease. Often, thefirst step in preventing disease is

early prediction. In thecaseof preterm birth (PTB), oneof the

best, if not the best, predictive test has been shown to be

cervical sonography. Thecervix has to open to allow vaginal

birth. Aswehaveknown for decades, theprocess of parturi-

tion takes months of preparation, and early changes can be

detected in human beings.

With regard to thecervix, ultrasound hasnow shown that

this lower part of the uterus begins to show changes weeks

before eventual birth. Even for PTB, which often we had

characterized in the past as something happening suddenly

and unexpectantly, thechangesaregradual and usually very

slow. In fact, in many high-risk women delivering preterm,

thecervix startstoshorten afew monthsbeforepreterm labor

(PTL) or preterm premature rupture of membranes occurs.

Early detection of change is paramount in allowing inter-

ventions thechance to work before thepathology isso far in

itspathways asto thwart prevention. In thischapter, wewill

review the evidence for cervical sonography as a screening

test for theprediction of PTB. Therearenow morethan 1000

manuscripts published on this topic, and ample evidence to

support theefficacy of cervical sonography in theprevention

of PTB.

Evaluation of CervicalLength–Technical Aspects

Evaluation of cervical length (CL) may be done either sono-

graphically or through direct physical examination of the

cervix. Sonographic detection of CL may be approached

through transabdominal, translabial, or transvaginal routes,

with each method having itsown benefitsand limitations.

Physical ExaminationIn the past, serial digital and speculum examinations have

been used to follow-up women with suspected cervical insuf-

ficiency. The physical changes notable on examination, re-

vealing the likelihood of cervical insufficiency, includebulg-

ing membranes, a pink or tan discharge, or appreciable

softening of the cervix and lower uterine segment. Of these

findings, softening and development of the lower uterine

segment is most strongly correlated with early effacement.

However, these reported physical changes are often not evi-

dent until the cervix is significantly effaced, as this process

begins at the internal os. Therefore, the absence of these

physical findings cannot exclude cervical insufficiency. In

addition, a digital examination has been found to besignifi-

cantly less consistent than ultrasound in assessing CL. On

average, manual estimationsof CL areshorter by 11 mm than

sonographic measurements of CL.1 Cervical funneling at the

internal os may also occur while the external os is fully

closed. Many multiparous women who deliver at term have

cervices that are already dilated 1-2 cm in the late second

trimester.1

Division of Maternal-Fetal Medicine, Department of Obstetrics and Gyne-

cology, Jefferson Medical College, Thomas Jefferson University, Phila-

delphia, PA.

Address reprint requests to Vincenzo Berghella, MD, Division of Maternal-

Fetal Medicine, Department of Obstetrics and Gynecology, Thomas Jef-

ferson University, 834 Chestnut St, Suite 400, Philadelphia, PA 19107.

E-mail: [email protected]

3170146-0005/09/$-see front matter © 2009 Elsevier Inc. All rights reserved.

doi:10.1053/j.semperi.2009.06.007

Erken Doğum -Öngörüsü Transvaginal Servikal Uzunluk

Servikal uzunluk cut-off 25 mm < 34 hft doğum için sensivite %36 spesifite %94

Transvaginal Ultrason Servikal Uzunluk Ölçüm Tekniği

Cervical Length Education and Review CLEAR

https://clear.perinatalquality.org

Erken Doğum -Öngörüsü TV Cl –Ne Zaman ?

Çoğul Gebelikler

Tarama önerilmemekte

Tekil Gebelikler

Obstetrik Öykü TVU CL Ölçümü CL Ölçüm Sıklığı

Erken Doğum Öyküsü Yok 18-24 hft (?)

14-27 hft erken doğum 14 -24 hft 2 hft aralarla 25-30 mm haftada

28-36 hft erken doğum 16-24 hft 2 hft aralarla 25-30 mm haftada

Progesteron: CAP gen ekspresyonunda

azalma (iyon kanalları,oksitosin ve prostaglandin res., gap junction)

Hangi hastalar?

Progesteron tipi ,dozu,uygulama yolu?

Erken Doğum –Önlenmesi Progesteron

Hasta Seçimi Prenatal administration of progesterone for preventing

preterm birth in women considered to be at risk of preterm

birth (Review)

Dodd JM, JonesL, Flenady V, CincottaR, Crowther CA

Thisisareprint of aCochranereview, prepared and maintained byTheCochraneCollaboration and published in TheCochraneLibrary

2013, Issue7

http://www.thecochranelibrary.com

Prenatal administration of progesterone for preventing preterm birth in women considered to be at risk of preterm birth (Review)


Spontan preterm doğum öyküsü olan hastalar?

TVU CL kısa saptanan hastalar?

Çoğul Gebelikler ?

Prenatal administration of progesterone for preventing


birth (Review)



2013, Issue7




IM progesteron kullanımı perinatal mortalitede azalma RR : 0.41 (0.23-0.73)

3.1 Supplementation

commenced prior to 20 weeks’

gestation

1 168 Risk Ratio (M-H, Random, 95% CI) 0.83 [0.30, 2.27]

3.2 Supplementation

commenced after 20 weeks’

gestation

1 99 Risk Ratio (M-H, Random, 95% CI) 0.25 [0.05, 1.10]

Analysis 1.1. Comparison 1 Progesterone versus placebo/no treatment: previous history spontaneous

preterm birth (singletons), Outcome 1 Perinatal mortality.

Review: Prenatal administration of progesterone for preventing preterm birth in women considered to be at risk of preterm birth

Comparison: 1 Progesterone versusplacebo/no treatment: previous history spontaneouspreterm birth (singletons)

Outcome: 1 Perinatal mortality

Study or subgroup Progesterone Placebo Risk Ratio Weight Risk Ratio


1 Intramuscular

Ibrahim 2010 4/25 13/25 21.0 % 0.31 [ 0.12, 0.81 ]

Johnson 1975 0/18 7/26 10.0 % 0.09 [ 0.01, 1.56 ]

Meis 2003 14/306 11/153 23.7 % 0.64 [ 0.30, 1.37 ]

Subtotal (95% CI) 349 204 54.8 % 0.41 [ 0.23, 0.73 ]

Total events: 18 (Progesterone), 31 (Placebo)

Heterogeneity: Chi2 = 2.65, df = 2 (P = 0.27); I2 =24%

Test for overall effect: Z = 3.01 (P = 0.0026)

2 Vaginal

Akbari 2009 3/69 10/72 15.8 % 0.31 [ 0.09, 1.09 ]

O’Brien 2007 11/309 11/302 18.0 % 0.98 [ 0.43, 2.22 ]

Subtotal (95% CI) 378 374 33.9 % 0.67 [ 0.34, 1.29 ]




3 Oral

Rai 2009 3/74 7/74 11.3 % 0.43 [ 0.12, 1.59 ]

Subtotal (95% CI) 74 74 11.3 % 0.43 [ 0.12, 1.59 ]


Heterogeneity: not applicable


Total (95% CI) 801 652 100.0 % 0.50 [ 0.33, 0.75 ]




Test for subgroup differences: Chi2 = 1.21, df = 2 (P= 0.55), I2 =0.0%

0.1 0.2 0.5 1 2 5 10

Favours progesterone Favours placebo

105Prenatal administration of progesterone for preventing preterm birth in women considered to be at risk of preterm birth (Review)


Spontan preterm doğum öyküsü Perinatal Mortalite?



birth (Review)



2013, Issue7





preterm birth (singletons), Outcome 3 Preterm birth less than 37 weeks.



Outcome: 3 Preterm birth less than 37 weeks


n/N n/N

M-H,Random,95%

CI

M-H,Random,95%

CI

1 Intramuscular

Ibrahim 2010 8/25 13/25 9.0 % 0.62 [ 0.31, 1.22 ]

Johnson 1975 2/18 12/25 3.5 % 0.23 [ 0.06, 0.91 ]

Meis 2003 111/306 84/153 17.0 % 0.66 [ 0.54, 0.81 ]

Saghafi 2011a 16/50 30/50 12.5 % 0.53 [ 0.34, 0.85 ]

Subtotal (95% CI) 399 253 42.1 % 0.62 [ 0.52, 0.75 ]


Heterogeneity: Tau2 = 0.0; Chi2 = 2.84, df = 3 (P= 0.42); I2 =0.0%

Test for overall effect: Z = 5.11 (P < 0.00001)

2 Vaginal

Akbari 2009 8/69 23/72 8.4 % 0.36 [ 0.17, 0.76 ]

Cetingoz 2011 9/37 17/34 9.3 % 0.49 [ 0.25, 0.94 ]

da Fonseca2003 10/72 20/70 9.0 % 0.49 [ 0.25, 0.96 ]

Majhi 2009 6/50 19/50 7.2 % 0.32 [ 0.14, 0.72 ]

O’Brien 2007 129/309 123/302 17.3 % 1.03 [ 0.85, 1.24 ]

Subtotal (95% CI) 537 528 51.2 % 0.52 [ 0.29, 0.92 ]


Heterogeneity: Tau2 = 0.32; Chi2 = 20.39, df = 4 (P = 0.00042); I2 =80%


3 Oral

Glover 2011 5/19 8/14 6.7 % 0.46 [ 0.19, 1.11 ]

Subtotal (95% CI) 19 14 6.7 % 0.46 [ 0.19, 1.11 ]




0.1 0.2 0.5 1 2 5 10


(Continued . . . )



IM-Vaginal progesteron kullanımı 37 hft önce doğum oranında azalma RR 0.55 (0.42,0.74)

Spontan preterm doğum öyküsü 37 hft önce doğum ?



birth (Review)



2013, Issue7





preterm birth (singletons), Outcome 2 Preterm birth less than 34 weeks.

Review: Prenatal administration of progesterone for preventingpreterm birth in women considered to be at risk of preterm birth




n/N n/N

M-H,Random,95%

CI

M-H,Random,95%

CI

1 Intramuscular

Subtotal (95% CI) 0 0 0.0 % 0.0 [ 0.0, 0.0 ]



Test for overall effect: not applicable

2 Vaginal

Akbari 2009 2/69 16/72 17.4 % 0.13 [ 0.03, 0.55 ]

Cetingoz 2011 2/37 9/34 17.0 % 0.20 [ 0.05, 0.88 ]

da Fonseca2003 2/72 13/70 17.1 % 0.15 [ 0.04, 0.64 ]

Majhi 2009 2/50 3/50 13.8 % 0.67 [ 0.12, 3.82 ]

Subtotal (95% CI) 228 226 65.3 % 0.21 [ 0.10, 0.44 ]




3 Oral

Rai 2009 22/74 37/74 34.7 % 0.59 [ 0.39, 0.90 ]

Subtotal (95% CI) 74 74 34.7 % 0.59 [ 0.39, 0.90 ]




Total (95% CI) 302 300 100.0 % 0.31 [ 0.14, 0.69 ]


Heterogeneity: Tau2 = 0.45; Chi2 = 9.15, df = 4 (P= 0.06); I2 =56%


Test for subgroup differences: Chi2 = 5.77, df = 1 (P= 0.02), I2 =83%

0.05 0.2 1 5 20



Copyright © 2013 The Cochrane Collaboration. Published by John W iley & Sons, Ltd. Vaginal/Oral progesteron kullanımı 34 hft önce doğum oranında azalma 0.31 (0.14,0.69)

Spontan preterm doğum öyküsü 34 hft önce doğum ?



birth (Review)



2013, Issue7





preterm birth (singletons), Outcome 9 Infant birthweight less than 2500 g.


Comparison: 1 Progesterone versusplacebo/no treatment: previoushistory spontaneouspreterm birth (singletons)

Outcome: 9 Infant birthweight less than 2500 g


n/N n/N

M-H,Random,95%

CI

M-H,Random,95%

CI

1 Intramuscular

Ibrahim 2010 5/25 10/25 10.7 % 0.50 [ 0.20, 1.25 ]

Johnson 1975 4/18 11/26 9.6 % 0.53 [ 0.20, 1.39 ]

Meis2003 82/306 62/151 73.2 % 0.65 [ 0.50, 0.85 ]

Subtotal (95% CI) 349 202 93.5 % 0.63 [ 0.49, 0.81 ]




2 Vaginal

Akbari 2009 3/69 14/72 6.5 % 0.22 [ 0.07, 0.74 ]

Subtotal (95% CI) 69 72 6.5 % 0.22 [ 0.07, 0.74 ]




Total (95% CI) 418 274 100.0 % 0.58 [ 0.42, 0.79 ]





0.1 0.2 0.5 1 2 5 10




IM/Oral progesteron kullanımı <2500 gr.doğum oranında azalma 0.58 (0.42,0.79)

Spontan preterm doğum öyküsü <2500 gr. doğum ?



birth (Review)



2013, Issue7





preterm birth (singletons), Outcome 20 Neonatal death.


Comparison: 1 Progesterone versus placebo/no treatment: previoushistory spontaneouspreterm birth (singletons)

Outcome: 20 Neonatal death



1 Intramuscular

Ibrahim 2010 1/25 4/25 9.5 % 0.25 [ 0.03, 2.08 ]

Johnson 1975 0/18 2/26 4.9 % 0.28 [ 0.01, 5.59 ]

Meis2003 8/306 9/153 28.6 % 0.44 [ 0.17, 1.13 ]

Subtotal (95% CI) 349 204 43.1 % 0.38 [ 0.17, 0.87 ]


Heterogeneity: Chi2 = 0.29, df = 2 (P = 0.86); I2 =0.0%


2 Vaginal

Akbari 2009 3/69 10/72 23.3 % 0.31 [ 0.09, 1.09 ]

O’Brien 2007 6/309 7/302 16.9 % 0.84 [ 0.28, 2.46 ]

Subtotal (95% CI) 378 374 40.2 % 0.53 [ 0.24, 1.18 ]




3 Oral

Rai 2009 3/74 7/74 16.7 % 0.43 [ 0.12, 1.59 ]

Subtotal (95% CI) 74 74 16.7 % 0.43 [ 0.12, 1.59 ]




Total (95% CI) 801 652 100.0 % 0.45 [ 0.27, 0.76 ]





0.02 0.1 1 10 50




IM progesteron kullanımı neonatal ölüm oranında azalma RR 0.45 (0.27,0.76)

Spontan preterm doğum öyküsü Neonatal ölüm ?



birth (Review)



2013, Issue7





preterm birth by cumulative weekly dose (< 500 mg v >= 500 mg, singletons), Outcome 2 Preterm birth less

than 37 weeks.


Comparison: 3 Progesteroneversusplacebo/no treatment:previoushistoryspontaneouspreterm birth by cumulative weekly dose (< 500 mgv >= 500 mg, singletons)



n/N n/N

M-H,Random,95%

CI

M-H,Random,95%

CI

1 Dose < 500 mg per week

Johnson 1975 2/18 12/25 4.0 % 0.23 [ 0.06, 0.91 ]

Meis2003 111/306 84/153 18.2 % 0.66 [ 0.54, 0.81 ]

Saghafi 2011a 16/50 30/50 13.7 % 0.53 [ 0.34, 0.85 ]

Subtotal (95% CI) 374 228 36.0 % 0.59 [ 0.44, 0.80 ]




2 Dose >= 500 mg per week

Akbari 2009 8/69 23/72 9.3 % 0.36 [ 0.17, 0.76 ]

Cetingoz 2011 9/37 17/34 10.4 % 0.49 [ 0.25, 0.94 ]

da Fonseca2003 10/72 20/70 10.0 % 0.49 [ 0.25, 0.96 ]

Glover 2011 5/19 8/14 7.6 % 0.46 [ 0.19, 1.11 ]

Majhi 2009 6/50 19/50 8.1 % 0.32 [ 0.14, 0.72 ]

O’Brien 2007 129/309 123/302 18.5 % 1.03 [ 0.85, 1.24 ]

Subtotal (95% CI) 556 542 64.0 % 0.51 [ 0.31, 0.85 ]




Total (95% CI) 930 770 100.0 % 0.54 [ 0.40, 0.74 ]





0.05 0.2 1 5 20




500mg/hft < veya > plaseboya göre Etkin

Spontan preterm doğum öyküsü Doz ?



birth (Review)



2013, Issue7




Analysis 4.12. Comparison 4 Progesterone versus placebo: ultrasound identified short cervix, singletons,

Outcome 12 Preterm birth less than 37 weeks.


Comparison: 4 Progesterone versusplacebo: ultrasound identified short cervix, singletons




1 Vaginal

Hassan 2011 71/235 76/223 40.3 % 0.89 [ 0.68, 1.16 ]

Subtotal (95% CI) 235 223 40.3 % 0.89 [ 0.68, 1.16 ]




2 Intramuscular

Grobman 2012 82/327 80/330 41.1 % 1.03 [ 0.79, 1.35 ]

Rozenberg 2012 37/94 36/94 18.6 % 1.03 [ 0.72, 1.47 ]

Subtotal (95% CI) 421 424 59.7 % 1.03 [ 0.83, 1.28 ]




Total (95% CI) 656 647 100.0 % 0.97 [ 0.82, 1.15 ]





0.2 0.5 1 2 5




Progesteron profilaksinin etkisi yok

Düşük Risk Grubunda TV Cl kısa saptanan hastalarda <37 hft doğum oranı?



birth (Review)



2013, Issue7











1 Vaginal

Fonesca2007 26/125 45/125 70.3 % 0.58 [ 0.38, 0.87 ]

Subtotal (95% CI) 125 125 70.3 % 0.58 [ 0.38, 0.87 ]




2 Intramuscular

Rozenberg 2012 15/94 19/94 29.7 % 0.79 [ 0.43, 1.46 ]

Subtotal (95% CI) 94 94 29.7 % 0.79 [ 0.43, 1.46 ]




Total (95% CI) 219 219 100.0 % 0.64 [ 0.45, 0.90 ]





0.1 0.2 0.5 1 2 5 10




Vaginal Progesteron <34 hft doğum oranında azalma RR 0.58 (0.38,0.87)




birth (Review)



2013, Issue7




Vaginal Progesteron <28. hft doğum oranında azalma RR 0.50 ( 0.25,0.97)





Outcome: 13 Preterm birth lessthan 28 weeks



1 Vaginal

Hassan 2011 12/235 23/223 51.9 % 0.50 [ 0.25, 0.97 ]

Subtotal (95% CI) 235 223 51.9 % 0.50 [ 0.25, 0.97 ]




2 Intramuscular

Grobman 2012 15/327 22/330 48.1 % 0.69 [ 0.36, 1.30 ]

Subtotal (95% CI) 327 330 48.1 % 0.69 [ 0.36, 1.30 ]




Total (95% CI) 562 553 100.0 % 0.59 [ 0.37, 0.93 ]





0.2 0.5 1 2 5







birth (Review)



2013, Issue7




Analysis 6.1. Comparison 6 Progesterone versus placebo: multiple pregnancy, Outcome 1 Perinatal death.


Comparison: 6 Progesterone versusplacebo: multiple pregnancy

Outcome: 1 Perinatal death


n/N n/N

M-H,Random,95%

CI

M-H,Random,95%

CI

1 Intramuscular

Combs 2010 19/168 2/75 14.3 % 4.24 [ 1.01, 17.75 ]

Combs 2011 0/320 3/156 5.1 % 0.07 [ 0.00, 1.34 ]

Hartikainen 1980 4/78 2/76 11.9 % 1.95 [ 0.37, 10.33 ]

Lim 2011 23/681 34/674 27.0 % 0.67 [ 0.40, 1.12 ]

Subtotal (95% CI) 1247 981 58.3 % 1.06 [ 0.30, 3.71 ]




2 Vaginal

Aboulghar 2012 4/98 5/84 16.0 % 0.69 [ 0.19, 2.47 ]

Rode 2011 10/664 7/678 20.3 % 1.46 [ 0.56, 3.81 ]

Serra 2013 0/194 5/190 5.3 % 0.09 [ 0.00, 1.60 ]

Subtotal (95% CI) 956 952 41.7 % 0.75 [ 0.24, 2.41 ]




Total (95% CI) 2203 1933 100.0 % 0.93 [ 0.45, 1.94 ]





0.1 0.2 0.5 1 2 5 10




progesteron profilaksinin perinatal ölümler üzerinde etkisi yok

Çoğul gebeliklerde progesteron profilaksisi Perinatal ölümler ?



birth (Review)



2013, Issue7




Analysis 6.11. Comparison 6 Progesterone versus placebo: multiple pregnancy, Outcome 11 Preterm birth

less than 37 weeks.





n/N n/N

M-H,Random,95%

CI

M-H,Random,95%

CI

1 Intramuscular

Combs 2011 113/160 46/78 12.3 % 1.20 [ 0.97, 1.48 ]

Hartikainen 1980 15/39 9/38 1.5 % 1.62 [ 0.81, 3.25 ]

Lim 2011 186/336 165/332 19.6 % 1.11 [ 0.96, 1.29 ]

Rouse 2007 226/325 232/330 27.2 % 0.99 [ 0.89, 1.09 ]

Subtotal (95% CI) 860 778 60.6 % 1.09 [ 0.96, 1.22 ]




2 Vaginal

Aboulghar 2012 31/49 28/42 7.0 % 0.95 [ 0.70, 1.28 ]

Cetingoz 2011 29/39 22/38 6.1 % 1.28 [ 0.93, 1.78 ]

Rode 2011 158/334 179/341 18.6 % 0.90 [ 0.77, 1.05 ]

Serra 2013 48/97 47/96 7.6 % 1.01 [ 0.76, 1.35 ]

Subtotal (95% CI) 519 517 39.4 % 0.98 [ 0.85, 1.13 ]




Total (95% CI) 1379 1295 100.0 % 1.04 [ 0.95, 1.14 ]





0.1 0.2 0.5 1 2 5 10




Progesteron profilaksinin <37 hft doğumlar ETKİSİ YOK

Çoğul gebeliklerde progesteron profilaksisi <37 hft doğum?



birth (Review)



2013, Issue7





less than 34 weeks.


Comparison: 6 Progesterone versus placebo: multiple pregnancy



n/N n/N

M-H,Random,95%

CI

M-H,Random,95%

CI

1 Vaginal

Aboulghar 2012 8/49 10/42 8.7 % 0.69 [ 0.30, 1.58 ]

Cetingoz 2011 4/39 7/28 5.1 % 0.41 [ 0.13, 1.27 ]

Norman 2009 55/247 44/247 29.7 % 1.25 [ 0.88, 1.78 ]

Rode 2011 51/334 63/341 31.4 % 0.83 [ 0.59, 1.16 ]

Serra 2013 13/97 13/96 11.3 % 0.99 [ 0.48, 2.02 ]

Subtotal (95% CI) 766 754 86.2 % 0.92 [ 0.69, 1.23 ]




2 Intramuscular

Combs2011 31/160 11/78 13.8 % 1.37 [ 0.73, 2.59 ]

Subtotal (95% CI) 160 78 13.8 % 1.37 [ 0.73, 2.59 ]




Total (95% CI) 926 832 100.0 % 0.97 [ 0.74, 1.27 ]





0.05 0.2 1 5 20





Çoğul gebeliklerde progesteron profilaksisi <34 hft doğumlar ?



birth (Review)



2013, Issue7





less than 28 weeks.






1 Intramuscular

Combs2010 9/56 2/25 9.2 % 2.01 [ 0.47, 8.63 ]

Combs2011 3/160 1/78 4.5 % 1.46 [ 0.15, 13.83 ]

Lim 2011 19/336 18/332 60.1 % 1.04 [ 0.56, 1.95 ]

Subtotal (95% CI) 552 435 73.7 % 1.19 [ 0.68, 2.07 ]




2 Vaginal

Rode 2011 9/334 7/341 23.0 % 1.31 [ 0.49, 3.48 ]

Serra 2013 1/97 1/96 3.3 % 0.99 [ 0.06, 15.60 ]

Subtotal (95% CI) 431 437 26.3 % 1.27 [ 0.51, 3.19 ]




Total (95% CI) 983 872 100.0 % 1.21 [ 0.75, 1.95 ]





0.01 0.1 1 10 100





Çoğul gebeliklerde progesteron profilaksisi 28 hft doğumlar ?



birth (Review)



2013, Issue7




(. . . Continued)Study or subgroup Progesterone Placebo Risk Ratio Weight Risk Ratio

n/N n/N

M-H,Random,95%

CI

M-H,Random,95%

CI

Total (95% CI) 955 795 100.0 % 0.55 [ 0.42, 0.74 ]





0.1 0.2 0.5 1 2 5 10



preterm birth (singletons), Outcome 4 Threatened preterm labour.


Comparison: 1 Progesterone versus placebo/no treatment: previoushistory spontaneouspreterm birth (singletons)

Outcome: 4 Threatened preterm labour


n/N n/N

M-H,Random,95%

CI

M-H,Random,95%

CI

1 Intramuscular

Meis2003 49/306 21/153 53.8 % 1.17 [ 0.73, 1.87 ]

Subtotal (95% CI) 306 153 53.8 % 1.17 [ 0.73, 1.87 ]




2 Vaginal

da Fonseca2003 14/72 22/70 46.2 % 0.62 [ 0.35, 1.11 ]

Subtotal (95% CI) 72 70 46.2 % 0.62 [ 0.35, 1.11 ]




Total (95% CI) 378 223 100.0 % 0.87 [ 0.47, 1.62 ]





0.1 0.2 0.5 1 2 5 10




Erken Doğum Tehdidi sonrası progesteron profilaksisinin ETKİSİ YOK

Erken Doğum Tehdidi sonrası profilaksi ?

Progesteron Tipi,Dozu, ve Uygulama yolu

Progesteron supp. 90- 200 mg. tanıdan 36. gebelik haftasına kadar

100 mg mikronize progesteron vaginal tablet

90 mg ( %8 ) mik.progesteron vaginal gel

18-24 gebelik haftaları arasında TVU Servikal Uzunluk

< 20 mm

Tekil gebelik, spontan preterm doğum öyküsü yok


Progesteron Tipi,Dozu, ve Uygulama yolu

Serklaj

Servikal uzunluk< 25mm , gebelik haftası< 24 hft ise

Servikal Uzunluk Ölçümü 14/16. hft itibaren 24. hft kadar 2 hft aralarla

25-30mm haftada

Hidroksiprogesteron caproat 250 mg. IM/hft 16-20. hft itibaren 36 hft kadar

Tekil gebelik, spontan preterm doğum öyküsü var

Normal Servikal Uzunluk


‘Prediction is the basis of prevention’

Teşekkürler

Documents

Erken Doğumda Progesteron Kullanımı - TJOD …tjodizmir.org.tr/uploads/slaytlar/635370549284381250.pdfAkut Preterm Eylemde Tokolitik Tedavi Tocolytic therapy for preterm delivery: