eTable 2. Articles excluded from the analyses of case-control studies to establish
clinical validity, with reasons for exclusion
Aksoy M, Tek I, Karabulut H, Berker B, Soylemez F: The role of thrombofilia related to Factor
V Leiden and Factor II G20210A mutations in recurrent abortions. J Pak Med Assoc,
55:104-108, 2005. Reason: The high rate of consanguinity (29%) in cases and controls
(6%) in this Turkish population could bias the observed carrier rates.
Ayadurai T, Muniandy S, Omar SZ. Thrombophilia investigation in Malaysian women with
recurrent pregnancy loss. J Obstet Gynaecol Res 2009;35:1061-1068. Reason: The only
women tested for F5 were APC resistance positive; cannot compute ORs as zero variants
observed in the control groups.
Balasch J, Reverter JC, Fabregues F, et al. First-trimester repeated abortion is not
associated with activated protein C resistance. Hum Reprod 1997;12:1094-1097.
Reason: The only women tested for F5 were APC resistance positive.
Behjati R, Modarressi MH, Jeddi-Tehrani M, et al. Thrombophilic mutations in Iranian patients
with infertility and recurrent spontaneous abortion. Ann Hematol 2006;85:268-271.
Reason: Cannot compute ORs; zero variants observed in the F5 control group.
Biswas A, Choudhry P, Mittal A, et al. Recurrent abortions in Asian Indians: no role of factor V
Leiden Hong Kong/Cambridge mutation and MTHFR polymorphism. Clin Appl Thromb
Hemost 2008;14:102-104. Reason: Cannot compute an OR; zero variants observed in
the F5 control group.
Brenner B, Mandel H, Lanir N, et al. Activated protein C resistance can be associated with
recurrent pregnancy loss. Br J Haematol 1997;97:551-554. Reason: The only women
tested for F5 were APC resistance positive.
Coulam CB, Jeyendran RS, Fishel LA, Roussev R. Multiple thrombophilic gene mutations
rather than specific gene mutations are risk factors for recurrent miscarriage. Am J
Reprod Immunol 2006;55:360-368. Reason: Cannot compute an OR for F5 or F2; zero
variants observed in the RPL and control groups.
Dizon-Townson DS, Kinney S, Branch DW, Ward K. The factor V Leiden mutation is not a
common cause of recurrent miscarriage. J Reprod Immunol 1997;34:217-223. Reasons:
Cannot compute an OR for F5 as zero variants observed in the RPL and control groups.
Gonen R, Lavi N, Attias D, Schliamser L, Borochowitz Z, Toubi E, Ohel G: Absence of
association of inherited thrombophilia with unexplained third-trimester intrauterine fetal
death. Am J Obstet Gynecol, 192:742-746, 2005. Reason: Cannot compute an OR for
F2 as zero variants were observed in the RPL group; the high rate of consanguinity in the
Arab population (about 50% of cases) could bias the observed carrier rates.
Goodman CS, Coulam CB, Jeyendran RS, Acosta VA, Roussev R: Which thrombophilic gene
mutations are risk factors for recurrent pregnancy loss? Am J Reprod Immunol, 56:230236, 2006. Reason: No control population (compared to published data); suspected data
overlap with another article.
Hashimoto K, Shizusawa Y, Shimoya K, et al. The Factor V Leiden mutation in Japanese
couples with recurrent spontaneous abortion. Hum Reprod 1999;13:1872-1874. Reason:
Asian populations are known to have an absent or low F5 allele frequency; as expected,
no variants were identified in cases or controls.
Jivraj S, Rai R, Underwood J, Regan L: Genetic thrombophilic mutations among couples with
recurrent miscarriage. Hum Reprod, 21:1161-1165, 2006. Reason: Frequency of
heterozygotes not provided for the case-control subset with RPL of unexplained etiology.
Kobashi G, Kato EH, Morikawa M, Shimada S, Ohta K, Fujimoto S, Minakami H, Yamada H.
MTHFR C677T Polymorphism and Factor V Leiden Mutation Are Not Associated with
Recurrent Spontaneous Abortion of Unexplained Etiology in Japanese Women. Sem
Thromb Hemost 2005;31;266-271. Reason: Asian populations are known to have a low
F5 allele frequency; as expected, no F5 variants were identified in cases or controls.
Mitic G, Kovac M, Povazan L, Magic Z, Djordjevic V, Salatic I, Mitic I, Novakov-Mikic A.
Inherited Thrombophilia is Associated with Pregnancy Losses That Occur After 12th
Gestational Week in Serbian Population. Clin App Thromb/Hem 2010;16:435-439.
Reason: The only women tested for F5 were APC resistance positive. F2 data used.
Mtiraoui N, Borgi L, Hizem S, Nsiri B, Finan RR, Gris JC, Almawi WY, Mahjoub T: Prevalence
of antiphospholipid antibodies, factor V G1691A (Leiden) and prothrombin G20210A
mutations in early and late recurrent pregnancy loss. Eur J Obstet Gynecol Reprod Biol
2005;119:164-170. Reason: Appears to represent a subset of data from Mahjoub et al.,
2005.
Mukhopadhyay R, Saraswathy KN, Ghost PK. MTHFR C677T and Factor V Leiden in
Recurrent Pregnancy Loss: A Study Among an Endogamous Group in North India. Gen
Testing Molec Biomarkers 2009;13:861-865. Reason: Cannot compute an OR for F5;
zero variants observed in the control group of Rajputs from northern India.
Rothbart H, Ohel G, Younis J, Lanir N, Brenner B. High Prevalence of Activated Protein C
Resistance Due to Factor V Leiden Mutation in Cases of Intrauterine Fetal Death. J Mat
Fet Med 1999;8:228-230. Reason: The only women tested for F5 were APC resistance
positive.
Sarig G, Younis JS, Hoffman R, Lanir N, Blumenfeld Z, Brenner B. Thrombophilia is common
in women with idiopathic pregnancy loss and is associated with late pregnancy wastage.
Fertil Steril 2002;77:342-347. Reason: The only women tested for F5 were APC
resistance positive.
Tal J, Schliamser LM, Leibovitz Z, Ohel G, Attias D. A possible role for activated protein C
resistance in patients with first and second trimester pregnancy failure. Hum Reprod
1999;14:1624-1627. Reason: The only women tested for F5 were APC resistance
positive.
Vora S, Shetty S, Ghosh K. Thrombophilic dimension of recurrent fetal loss in Indian patients.
Blood Coagul Fibrinolysis 2008;19:581-584. Reason: Cannot compute an OR for F2;
zero variants observed in the RPL and control groups.
Weiner Z, Beck-Fruchter R, Weiss A, Hujirat Y, Shalev E, Shalev SA: Thrombophilia and
stillbirth: possible connection by intrauterine growth restriction. Bjog, 111:780-783, 2004.
Reason: Cannot compute an OR for F2 as zero variants observed in the RPL group in this
Israeli study. F5 data not consistent with Hardy-Weinberg proportions (P = .04).
Wolf CE, Haubelt H, Pauer HU, et al. Recurrent pregnancy loss and its relation to FV Leiden,
FII G20210A and polymorphisms of plasminogen activator and plasminogen activator
inhibitor. Pathophysiol Haemost Thromb 2003;33:134-137. Reason: Overlap with Pauer
et al., 2003; cannot compute a F2 OR as zero variants observed in the RPL group.
Yenicesu GI, Cetin M, Ozdemir O, Cetin A, Ozen F, Yenicesu C, Yildiz C, Kocak N. A
prospective case-control study analyzes 12 thrombophilic gene mutations in Turkish
couples with recurrent pregnancy loss. Am J Reprod Immunol 2010;63:126-136. Reason:
Could not derive raw data for F5, and no F2 variants observed in the control group.
Younis JS, Ohel G, Brenner B, et al. The effect of thrombophylaxis on pregnancy outcome in
patients with recurrent pregnancy loss associated with factor V Leiden mutation. Bjog
2000;107:415-419. Reason: The only women tested for F5 were APC resistance positive.
Yusoff NM, Abdullah WZ, Ghazali S, Othman MS, Baba AA, Abdullah N, Isa MN, Chong CL.
The absence of factor V Leiden mutation in Malays with recurrent spontaneous abortions.
Aust N Z J Obstet Gynaecol 2002;42:164-166. Reason: Cannot compute a F5 OR; no
variants observed in case or control groups.
eTable 3. Articles excluded from the analyses of cohort studies to establish clinical
validity, with reasons for exclusion
Bare SN, Poka R, Balogh I, Ajzner E: Factor V Leiden as a risk factor for miscarriage and
reduced fertility. Aust N Z J Obstet Gynaecol, 40:186-190, 2000. Reasons: Cohort of
women infertile for 1 year who completed a questionnaire and were tested for F5;
insufficient description of pregnancy history; high allele frequency (0.111) suggests bias;
miscarriage and infertility outcomes could not be separated.
Biron-Andreani C, Bauters A, Le Cam-Duchez V, Delahousse B, Lequerric A, Dutrillaux F, et
al. Factor V Leiden Homozygous Genotype and Pregnancy Outcomes. Obstet. Gynecol
2009;114:1249-1253). Reason: Genotype frequencies not consistent with HardyWeinberg; likely biased ascertainment in a referral center and specifically focused on late
fetal loss.
Carp H, Dolitzky M, Tur-Kaspa I, Inbal A. Hereditary hemophilias are not associated with a
decreased live birth rate in women with recurrent miscarriage. Fertil Steril 2002;78:58-62.
Reasons: Small study in a tertiary referral unit (i.e., potential bias toward high risk); not all
patients tested for F5 / F2 with no reason provided.
Meinardi JR, Middeldorp S, de Kam PJ, Koopman MM, van Pampus EC, Hamulyak K, Prins
MH, Buller HR, van der Meer J: Increased risk for fetal loss in carriers of the factor V
Leiden mutation. Ann Intern Med, 130:736-739, 1999. Reason: Cohort study apparently
based on the same European study group as the Coppens 2009 paper (EPCOT), which
has a larger N and provides information through 3 pregnancies.
Preston FE, Rosendaal FR, Walker ID, Briet E, Berntorp E, Conard J, Fontcuberta J, Makris
M, Mariani G, Noteboom W, Pabinger I, Legnani C, Scharrer I, Schulman S, van der Meer
FJ: Increased fetal loss in women with heritable thrombophilia. Lancet, 348:913-916,
1996. Reason: Like Meinardi, a cohort study apparently based on the same European
study group as the Coppens 2009 paper (EPCOT), which has a larger N and provides
information through 3 pregnancies; subset of data also published as Vossen et al., 2004.
Rodger MA, Betancourt MT, Clark P, Lindqvist PG, Dizon-Townson D, Said J, Seligsohn U,
Carrier M, Salomon O, Greer IA. The Association of Factor V Leiden and Prothrombin
Gene Mutation and Placenta-Mediated Pregnancy Complications: A Systematic Review
and Meta-analysis of Prospective Cohort Studies. PLoS Med 2010; 7;1-11. Reason: The
Rodger 2007 cohort data sets presented in Table 1 and Figures 2 and 3 in this article are
referenced to an abstract; no other source of published data could be identified.
Sarig G, Younis JS, Hoffman R, Lanir N, Blumenfeld Z, Brenner B: Thrombophilia is common
in women with idiopathic pregnancy loss and is associated with late pregnancy wastage.
Fertil Steril, 77:342-347, 2002. Reason: Prospective observational study includes 4 cases
with previous VTE; has mixed ethnicity (about half Jewish and half Arab, matched);
number of pregnancies/losses unclear.
Sedano-Balbas S, Lyons M, Cleary B, Murray M, Gaffney G, Maher M. APCR, factor V gene
known and novel SNPs and adverse pregnancy outcomes in an Irish cohort of pregnant
women. BMC Preg Childbirth 2010;10:11-18. Reason: APCR pre-testing.
Simchen MJ, Ofir K, Moran O, Kedem A, Sivan E, Schiff E. Thrombophilic risk factors for
placental stillbirth. Eur J Obstet Gynecol Reprod Biol 2010;153:160-164. Reason: Small
prospective cohort focused on differentiating placental and non-placental stillbirth
outcomes.
Tormene D, Simioni P, Prandoni P, Luni S, Innella B, Sabbion P, Girolami A: The risk of fetal
loss in family members of probands with factor V Leiden mutation. Thromb Haemost,
82:1237-1239, 1999. Reason: Retrospective cohort (may also be EPCOT) study in
women who had been pregnant at least once (pregnancy history not provided) and had a
family member(s) with F5/VTE. Insufficient information provided for occurrence or
recurrence analysis in single pregnancies.
Vossen CY, Preston FE, Conard J, Fontcuberta J, Makris M, van der Meer FJ, Pabinger I,
Palareti G, Scharrer I, Souto JC, Svensson P, Walker ID, Rosendaal FR: Hereditary
thrombophilia and fetal loss: a prospective follow-up study. J Thromb Haemost, 2:592596, 2004. Reason: European cohort study of 191 women enrolled in EPCOT (131 with
thrombophilia; 21 F5) who had a pregnancy outcome during prospective follow-up.
Insufficient information.
eFigure 1. Forest plots of the association of F5 genotype and pregnancy loss, stratified
by study design. The 33 case-control studies are in alphabetical order, and have a summary
OR of 2.02. The 12 cohort studies that follow are in order of publication, most recent first. Four
studies in women with a history of ≥ 2 previous losses report a higher recurrence of fetal loss in
those with F5 genotypes than in non-carriers (OR 1.93). Eight studies in unselected cohorts of
women report a higher occurrence of fetal loss in those with F5 genotypes (OR = 2.03). The
overall OR is 2.01 for all studies.
F5 Forest Plots by Study Design
Group by
Study design
Study name
Statistics for each study
Odds ratio and 95% CI
Odds Lower Upper
ratio limit
limit p-Value
Case-Control
Case-Control
Case-Control
Case-Control
Case-Control
Case-Control
Case-Control
Case-Control
Case-Control
Case-Control
Case-Control
Case-Control
Case-Control
Case-Control
Case-Control
Case-Control
Case-Control
Case-Control
Case-Control
Case-Control
Case-Control
Case-Control
Case-Control
Case-Control
Case-Control
Case-Control
Case-Control
Case-Control
Case-Control
Case-Control
Case-Control
Case-Control
Case-Control
Case-Control
RPL Cohort
RPL Cohort
RPL Cohort
RPL Cohort
RPL Cohort
Unselected Cohort
Unselected Cohort
Unselected Cohort
Unselected Cohort
Unselected Cohort
Unselected Cohort
Unselected Cohort
Unselected Cohort
Unselected Cohort
Overall
Agorastos
Altinitas
Brenner
Carp
Fatini
Foka
Glueck
Grandone
Hefler
Hohlagschwandtner
Hopmeier
Ivanov
Jaslow
Krause
Kutteh
Many
Metz
Mougiou
Murphy
Onderoglu
Pasquier
Pauer
Pihusch
Rai
Raziel
Reznikoff-Etievant
Ridker
Sotiriadis
Sottilotta
Souza
Subrt
Toth
Wramsby
3.429
1.134
3.986
0.592
3.849
5.538
3.233
4.394
1.124
2.798
2.146
1.998
0.988
3.963
1.091
2.081
1.745
0.975
2.079
5.391
1.164
1.693
0.915
0.821
3.800
2.412
2.277
1.755
3.000
2.333
6.479
1.138
7.225
2.019
Lund RPL Cohort
1.951
Jivraj RPL Cohort
1.436
Coppens RPL Cohort 0.500
Rai RPL Cohort
3.759
1.932
Said Cohort
8.846
Clark Cohort
0.373
Karakantza Cohort
2.147
Coppens Cohort
1.649
Lindqvish Cohort
1.481
Dizon-Townson Cohort 1.079
Lissalde-Lavigne Cohort 3.212
Murphy Cohort
5.269
2.027
2.006
0.336
0.469
1.810
0.154
0.747
1.759
1.467
1.314
0.435
0.900
0.601
0.812
0.542
1.644
0.094
0.401
0.423
0.346
0.453
2.236
0.604
0.683
0.354
0.435
0.715
1.169
0.979
0.408
0.914
0.271
1.878
0.502
1.534
1.597
0.967
0.635
0.026
1.291
1.207
1.599
0.051
0.672
1.100
0.809
0.522
2.392
1.407
1.295
1.659
34.950
2.745
8.780
2.279
19.845
17.439
7.128
14.698
2.906
8.695
7.669
4.917
1.801
9.556
12.679
10.810
7.198
2.742
9.542
12.997
2.241
4.196
2.367
1.549
20.194
4.978
5.298
7.550
9.845
20.086
22.349
2.581
34.044
2.553
3.936
3.250
9.457
10.946
3.093
48.933
2.702
6.861
2.472
2.709
2.229
4.314
19.730
3.174
2.426
0.298
0.780
0.001
0.446
0.107
0.003
0.004
0.016
0.809
0.075
0.240
0.132
0.968
0.002
0.945
0.383
0.441
0.961
0.347
0.000
0.651
0.256
0.855
0.542
0.117
0.017
0.056
0.450
0.070
0.440
0.003
0.756
0.012
0.000
0.062
0.385
0.644
0.015
0.006
0.012
0.329
0.197
0.016
0.203
0.837
0.000
0.014
0.002
0.000
0.01
Meta Analysis
0.1
1
10
100
eFigure 2. Forest plot of the association of F5 genotype and recurrent pregnancy loss.
The 33 case-control studies are in order of publication, from 1997 to 2010.
F5 Forest Plot by Year of Publication
Study name
Subgroup within study
Statistics for each study
Odds ratio and 95% CI
Odds Lower Upper
ratio
limit
limit Z-Value p-Value
Grandone
Metz
Ridker
Brenner
Kutteh
Souza
Fatini
Foka
Murphy
Wramsby
Pihusch
Rai
Raziel
Reznikoff-Etievant
Agorastos
Carp
Many
Hohlagschwandtner
Pauer
Hefler
Krause
Onderoglu
Sottilotta
Altinitas
Sotiriadis
Glueck
Hopmeier
Mougiou
Pasquier
Subrt
Toth
Ivanov
Jaslow
1997.000
1997.000
1998.000
1999.000
1999.000
1999.000
2000.000
2000.000
2000.000
2000.000
2001.000
2001.000
2001.000
2001.000
2002.000
2002.000
2002.000
2003.000
2003.000
2004.000
2005.000
2006.000
2006.000
2007.000
2007.000
2008.000
2008.000
2008.000
2008.000
2008.000
2008.000
2009.000
2010.000
4.394
1.745
2.277
3.986
1.091
2.333
3.849
5.538
2.079
7.225
0.915
0.821
3.800
2.412
3.429
0.592
2.081
2.798
1.693
1.124
3.963
5.391
3.000
1.134
1.755
3.233
2.146
0.975
1.164
6.479
1.138
1.998
0.988
2.019
1.314
0.423
0.979
1.810
0.094
0.271
0.747
1.759
0.453
1.534
0.354
0.435
0.715
1.169
0.336
0.154
0.401
0.900
0.683
0.435
1.644
2.236
0.914
0.469
0.408
1.467
0.601
0.346
0.604
1.878
0.502
0.812
0.542
1.597
14.698
7.198
5.298
8.780
12.679
20.086
19.845
17.439
9.542
34.044
2.367
1.549
20.194
4.978
34.950
2.279
10.810
8.695
4.196
2.906
9.556
12.997
9.845
2.745
7.550
7.128
7.669
2.742
2.241
22.349
2.581
4.917
1.801
2.553
2.403
0.770
1.910
3.432
0.070
0.771
1.611
2.925
0.941
2.501
-0.183
-0.610
1.566
2.383
1.040
-0.762
0.872
1.779
1.137
0.242
3.067
3.753
1.812
0.279
0.756
2.910
1.176
-0.048
0.453
2.958
0.310
1.506
-0.040
5.868
RPL
Controls
0.016 7 / 43 5 / 118
0.441 6 / 100 3 / 85
0.056 9 / 113 16 / 437
0.001 24 / 76 11 / 106
0.945 1 / 23
2 / 50
0.440 1 / 28 6 / 384
0.107 6 / 59
2 / 70
0.003 15 / 80 4 / 100
0.347 2 / 41 13 / 540
0.012 11 / 62 2 / 69
0.855 8 / 101 11 / 128
0.542 74 / 1111 12 / 150
0.117 6 / 36
2 / 40
0.017 27 / 260 11 / 240
0.298 1 / 8
4 / 100
0.446 4 / 108 5 / 82
0.383 3 / 40
3 / 80
0.075 15 / 145 4 / 101
0.256 12 / 101 9 / 122
0.809 10 / 94 9 / 94
0.002 24 / 133 7 / 133
0.000 29 / 102 7 / 102
0.070 5 / 55 7 / 217
0.780 9 / 114 13 / 185
0.450 5 / 99 3 / 102
0.004 9 / 44 47 / 638
0.240 8 / 49
4 / 48
0.961 8 / 212 7 / 181
0.651 15 / 311 25 / 599
0.003 18 / 206 3 / 206
0.756 13 / 151 12 / 157
0.132 20 / 153 7 / 100
0.968 21 / 311 25 / 366
0.000 426 / 4569301 / 6130
0.01
0.1
1
10
100
eFigure 3. Forest plots of the association of F2 genotype and pregnancy loss, stratified
by study design. The 29 case-control studies are in alphabetical order, and have a summary
OR of 2.07. The 5 cohort studies that follow are in order of publication, most recent first. Only
one study was found in women with a history of ≥ 2 previous losses. Four studies in unselected
cohorts of women report a higher occurrence of fetal loss in those with F2 genotypes (OR =
1.77). The overall OR is 2.05 for all studies.
F2 Forest Plots by Study Design
Group by
Study design
Study name
Statistics for each study
Odds ratio and 95%CI
Odds Lower Upper
ratio limit
limit Z-Value p-Value
Case-Control
Case-Control
Case-Control
Case-Control
Case-Control
Case-Control
Case-Control
Case-Control
Case-Control
Case-Control
Case-Control
Case-Control
Case-Control
Case-Control
Case-Control
Case-Control
Case-Control
Case-Control
Case-Control
Case-Control
Case-Control
Case-Control
Case-Control
Case-Control
Case-Control
Case-Control
Case-Control
Case-Control
Case-Control
Case-Control
RPL Cohort
RPL Cohort
Unselected Cohort
Unselected Cohort
Unselected Cohort
Unselected Cohort
Unselected Cohort
Overall
Agorastos
7.000
Altinitas
1.083
Brenner
2.186
Carp
0.748
Fatini
1.190
Foka
4.699
Hefler
1.810
Hohlagschwandtner 2.891
Ivanov
6.619
Jaslow
2.132
Krause
2.047
Kupferminc
3.356
Kutteh
2.227
Many
5.571
Mitic
4.042
Mougiou
0.975
Onderoglu
2.020
Pasquier
1.293
Pauer
0.741
Pickering
0.929
Pihusch
6.546
Raziel
2.294
Reznikoff-Etievant 2.774
Soririadis
2.633
Sottilotta
3.517
Souza
3.519
Subrt
0.901
Toth
1.595
Wramsby
1.119
2.068
Lund
3.289
3.289
Said
8.305
Silver
0.964
Karakantza
1.119
Lissalde-Lavigne 2.410
1.772
2.049
0.563
0.178
0.595
0.209
0.073
0.948
0.512
0.601
1.947
0.640
0.501
0.606
0.133
1.030
1.125
0.346
0.180
0.574
0.121
0.164
0.753
0.199
1.151
0.499
1.032
0.380
0.092
0.554
0.217
1.585
0.594
0.594
0.948
0.486
0.243
1.757
0.870
1.602
86.996
6.584
8.030
2.673
19.441
23.282
6.403
13.906
22.510
7.099
8.363
18.573
37.258
30.122
14.522
2.742
22.633
2.914
4.525
5.258
56.949
26.429
6.683
13.902
11.986
32.585
8.824
4.595
5.757
2.698
18.199
18.199
72.724
1.913
5.151
3.307
3.608
2.622
1.513
0.087
1.178
-0.447
0.122
1.895
0.921
1.324
3.027
1.233
0.998
1.387
0.557
1.995
2.141
-0.048
0.570
0.621
-0.325
-0.083
1.702
0.666
2.274
1.140
2.010
1.108
-0.089
0.865
0.134
5.353
1.364
1.364
1.912
-0.105
0.144
5.454
1.576
5.705
0.130
0.931
0.239
0.655
0.903
0.058
0.357
0.185
0.002
0.218
0.318
0.166
0.577
0.046
0.032
0.961
0.568
0.535
0.745
0.934
0.089
0.505
0.023
0.254
0.044
0.268
0.929
0.387
0.893
0.000
0.173
0.173
0.056
0.916
0.885
0.000
0.115
0.000
0.01
0.1
1
10
100
eFigure 4. Forest plot of the association of F2 genotype and recurrent pregnancy loss.
The 29 case-control studies are in order of publication, from 1999 to 2010.
F2 Forest Plot by Year of Publication
Study name
Statistics for each study
Odds
ratio
Brenner
Kutteh
Souza
Fatini
Foka
Kupferminc
Wramsby
Pickering
Pihusch
Raziel
Reznikoff-Etievant
Agorastos
Carp
Many
Hohlagschwandtner
Pauer
Hefler
Krause
Onderoglu
Sottilotta
Altinitas
Soririadis
Mougiou
Pasquier
Subrt
Toth
Ivanov
Jaslow
Mitic
2.186
2.227
3.519
1.190
4.699
3.356
1.119
0.929
6.546
2.294
2.774
7.000
0.748
5.571
2.891
0.741
1.810
2.047
2.020
3.517
1.083
2.633
0.975
1.293
0.901
1.595
6.619
2.132
4.042
2.068
Lower
limit
Upper
limit
0.595
0.133
0.380
0.073
0.948
0.606
0.217
0.164
0.753
0.199
1.151
0.563
0.209
1.030
0.601
0.121
0.512
0.501
0.180
1.032
0.178
0.499
0.346
0.574
0.092
0.554
1.947
0.640
1.125
1.585
8.030
37.258
32.585
19.441
23.282
18.573
5.757
5.258
56.949
26.429
6.683
86.996
2.673
30.122
13.906
4.525
6.403
8.363
22.633
11.986
6.584
13.902
2.742
2.914
8.824
4.595
22.510
7.099
14.522
2.698
F2 / Total
Z-Value p-Value
1.178
0.557
1.108
0.122
1.895
1.387
0.134
-0.083
1.702
0.666
2.274
1.513
-0.447
1.995
1.324
-0.325
0.921
0.998
0.570
2.010
0.087
1.140
-0.048
0.621
-0.089
0.865
3.027
1.233
2.141
5.353
RPL
Odds ratio and 95% CI
Controls
0.239
6 / 76
4 / 106
0.577
1 / 23
1 / 50
0.268
1 / 28
4 / 384
0.903
1 / 59
1 / 70
0.058
7 / 80
2 / 100
0.166
2 / 20
5 / 156
0.893
3 / 62
3 / 69
0.934 4 / 103
2 / 48
0.089 5 / 102
1 / 128
0.505
2 / 36
1 / 40
0.023 20 / 260
7 / 240
0.130
1/8
2 / 100
0.655 5 / 108
5 / 82
0.046
5 / 40
2 / 80
0.185 8 / 145
2 / 101
0.745 2 / 101
3 / 113
0.357
7 / 94
4 / 94
0.318 6 / 133
3 / 133
0.568 2 / 102
1 / 102
0.044
5 / 55
6 / 217
0.931 2 / 114
3 / 185
0.254
5 / 99
2 / 101
0.961 8 / 212
7 / 181
0.535 10 / 311
15 / 599
0.929 3 / 206
1 / 62
0.387 9 / 151
6 / 157
0.002 26 / 153
3 / 100
0.218 5 / 143
6 / 359
0.032 13 / 147
3 / 128
0.000 174 / 3171 105 / 4285
0.01
0.1
1
10
100