There is controversy regarding the role of prior abortion on placenta previa in subsequent pregnancies. We conducted an updated, comprehensive meta-analysis of placenta previa after prior abortion. The search was conducted from PubMed, Web of Science and Scopus databases from the database inception to January 31, 2017. The heterogeneity across studies was evaluated by Q-test and I2 statistical test. Publication bias was assessed by Begg's test and Egger's test. Results of odds ratio (OR) estimates with their corresponding 95% confidence intervals (CI) were pooled using random-effects modeling. The literature search included 872 articles up until January 2017 with 2,134,529 participants. Based on OR estimates obtained from case-control and cohort studies, we found a significant association between prior spontaneous abortions and placenta previa (1.77; 95% CI: 1.60, 1.94) and between prior induced abortions and placenta previa (1.36; 95% CI: 1.02, 1.69). The meta-analysis study herein showed that prior abortion is a risk factor for placenta previa.
Placenta previa is defined as the implantation of the placenta in the lower segment of the uterus. It occurs in 3 out of every 1000 pregnancies Findeklee and Costa, 2015 . The risk factors for placenta previa are smoking, previous cesarean sections, advanced maternal age, multiparity and conception by in vitro fertilization (IVF) Shobeiri et al., 2017 . Abortions have been proposed to be associated with fetal pathology, congenital abnormality, low birth weight and preterm labor in subsequent pregnancies Kashanian et al., 2006 .
There is controversy regarding the role of prior abortion on placenta previa in subsequent pregnancies. Some studies have reported an increased risk of placenta previa following abortions Chelmow et al., 1996 Eniola et al., 2002 Handler et al., 1994 Newton et al., 1984 ROSE and CHAPMAN, 1986 Thom et al., 1992 , while others saw no correlation Bakshi et al., 2015 Kashanian et al., 2006 Latif et al., 2015 Usta et al., 2005 .
Two previous meta-analyses have shown a positive association between previous abortion(s) and placenta previa in subsequent pregnancies Ananth et al., 1997a Faiz and Ananth, 2003 . However, such studies have encountered limitations, such as the limited number of primary databases. Thus, in this study, we performed meta-analysis, based on a larger number of subjects and databases to screen, to address the association of previous abortions and placenta previa. Thus, we conducted an updated and comprehensive meta-analysis of the placenta previa after previous abortion(s).
The present meta-analysis study was conducted based on the PRISMA guidelines.
Criteria for including studies
Observational studies (cross-sectional, retrospective and prospective studies) were included in participants declared development of placenta previa following a spontaneous or induced abortion. The following were factors which were excluded in the analysis based on the following criteria: placenta previa following abortion (spontaneous or induced), case report studies, review articles, editorials, and letters or miscellaneous in which full data was not accessible following request from the primary or corresponding authors. The factor of interest was abortion (spontaneous and induced) and the outcome of interest was placenta previa.
Two independent authors searched PubMed, Medline and Scopus databases from their time of inception to January 31, 2017. The search terms were conducted based on the following: (placenta previa) and (miscarriage OR induced abortion OR spontaneous abortion OR elective abortion).
After initial evaluation, the studies were independently and carefully evaluated by two authors, and data extraction was performed according to the selection criteria. We extracted the following variables: first author, year of publication, survey years, study country, total sample size, and odds ratio (OR) and their associated 95% confidence intervals (CI). Where discrepancies existed, discussions took place between the two authors until a consensus could be reached.
We assessed the methodological quality of each study independently by two authors via the Newcastle Ottawa Statement Manual (NOS) scale Wells et al., 2012 . The scale was from 0 to a maximum of nine stars, and included the following evaluation criteria: selection, comparability, exposure and outcome. Articles scored with seven stars or more were considered high-quality; articles scored with lower stars were considered low-quality Poorolajal and Jenabi, 2016 .
Heterogeneity and publication bias
Statistical heterogeneity was determined by the Q statistic test, which was quantified by the I-square values for assessing inconsistency across the studies Higgins et al., 2003 . Funnel plot and the Begg's and Egger's tests Begg and Mazumdar, 1994 were used to evaluate the probability of publication bias. Data were analyzed and the outcomes were reported using the random effect model DerSimonian and Laird, 1986 . The Stata software, version 13 (StataCorp, College Station, TX) was used for statistical analysis; a statistical significance was set at p< 0.05.
Description of studies
Our search yielded 872 publications of which 20 studies included met inclusion criteria until Jan 2017 ( Figure 1 ). We found 3 cohort studies Bakshi et al., 2015 Kashanian et al., 2006 Rosenberg et al., 2011 and 17 case-control studies Chelmow et al., 1996 Eniola et al., 2002 Handler et al., 1994 Hung et al., 2007 Johnson et al., 2003 Kramer et al., 1991 Latif et al., 2015 Macones et al., 1997 Newton et al., 1984 ROSE and CHAPMAN, 1986 Sheiner et al., 2001 Shobeiri et al., 2017 Sumigama et al., 2014 Taylor et al., 1994 Thom et al., 1992 Usta et al., 2005 Williams et al., 1991 with 2,134,529 participants. All studies were published in English ( Table 1 ).
Flow of information through the different phases of the systematic review
Summary of the study results
Effects of exposure
In the present meta-analysis, the association between prior abortion and risk of placenta previa was based on observational studies ( Figure 2 ). Based on OR estimates obtained from case-control and cohort studies, there was a significant association between prior spontaneous abortion and the risk of placenta previa (1.77; 95% CI: 1.60, 1.94) and between prior induced abortion and the risk of placenta previa (1.36; 95% CI: 1.02, 1.69). The results indicated that the measure of the effect was homogenous.
Forest plot of the association between prior abortion and placenta previa
The graphical funnel plots appeared to be symmetrical ( Figure 3 ). The Beggâ€™s (z = 0.90, P = 0.366) and Eggerâ€™s test (t = 0.81, P = 0.428) indicated there was no evidence for publication bias.
Funnel plot of the association between prior abortion and placenta previa
Quality of the studies
In this meta-analysis, seven studies were of high quality and thirteen studies were of low quality, based on the NOS scale ( Table 1 ).
The meta-analysis described herein and based on observational studies show that there is an association between prior abortion and placenta previa. Our results suggest that prior abortion is a risk factor for placenta previa. It has been previously reported that placenta previa is correlated with maternal and fetal complication, such as antenatal and post-partum hemorrhage, preterm delivery, intrauterine growth restriction, malpresentation and poor neonatal outcomes Rombauts et al., 2014 .
In a meta-analysis report published by Ananth et al. in 1997 Ananth et al., 1997b , the authors showed that based on OR estimates from all the studies they evaluated, there was a significant increase in the risk of placenta previa after prior spontaneous abortions (1.7; 95% CI: 1.5, 2.0) and after prior induced abortions (1.5; 95% CI: 1.3, 1.7). However, this meta-analysis was limited to eight studies and they searched only the Medline database.
In another meta-analysis, conducted in 2003 by Faiz et al. and which evaluated all articles up to year 2000, the authors showed that prior abortion increased the risk of placenta previa. Based on their results, there was significant association in the increased risk of placenta previa after prior spontaneous abortions (2.0; 95% CI: 1.7, 2.3) and after prior induced abortions (1.5; 95% CI: 1.3, 1.9) Faiz and Ananth, 2003 . For their analysis, the authors searched only the Medline database and the meta-analysis included 9 observational studies.
The mechanisms involved in the association of prior abortions and placenta previa is unknown. The damage and scarring to myometrium and endometrium of the uterus during spontaneous and induced abortions may influence the low implantation of placenta in the uterus in subsequent pregnancies Faiz and Ananth, 2003 .
The meta-analysis described herein had two limitations. While some studies report only the unadjusted form of OR, we tried to use the adjusted form to control for risk factors which may have impacted the studies included in this meta-analysis. However, doing so might introduce information bias in our results. Also, in the present study, we attempted to identify all published studies. However, in spite of our efforts, we could not find two studies that might have reported data on placenta previa. Despite these limitations, the present meta-analysis study was drawn from a large sample size; the 20 studies should efficiently estimate the association between prior abortion and risk of placenta previa. Our results indicate, based on odds ratio reports in epidemiological studies, that prior abortion (spontaneous and induced) can increase the risk of placenta previa.
We showed based on our present meta-analysis of observational studies that prior spontaneous and induced abortions can increase the risk of placenta previa. Therefore, prior abortion is a risk factor for placenta previa.
EJ and MK designed the study and processed the data. MK and EJ performed the statistical analysis. EJ and MK interpreted the results and wrote the first draft. Two authors read and approved the final manuscript.
- C.V. Ananth, W.A. Bowes, D.A. Savitz, E.R. Luther. Relationship between pregnancy-induced hypertension and placenta previa: a population-based study. American journal of obstetrics and gynecology. 1997a;177:997-1002. Google Scholar
- C.V. Ananth, J.C. Smulian, A.M. Vintzileos. The association of placenta previa with history of cesarean delivery and abortion: a metaanalysis. American journal of obstetrics and gynecology. 1997b;177:1071-1078. Google Scholar
- K. Bakshi, T.U. Rani, P.P. Kumar, G. Prabhakar. Risk of adverse pregnancy outcomes after prior spontaneous abortion. Current Medicine Research and Practice. 2015;5:258-261. Google Scholar
- C.B. Begg, M. Mazumdar. Operating characteristics of a rank correlation test for publication bias. Biometrics. 1994;:1088-1101. Google Scholar
- D. Chelmow, D.E. Andrew, E.R. Baker. Maternal cigarette smoking and placenta previa. Obstetrics & Gynecology. 1996;87:703-706. Google Scholar
- R. DerSimonian, N. Laird. Meta-analysis in clinical trials Control Clin Trials 7: 177-188. Find this article online. 1986;:. Google Scholar
- A. Eniola, A. Bako, D. Selo-Ojeme. Risk factors for placenta praevia in southern Nigeria. East African medical journal. 2002;79:536-538. Google Scholar
- A. Faiz, C. Ananth. Etiology and risk factors for placenta previa: an overview and meta-analysis of observational studies. The Journal of Maternal-Fetal & Neonatal Medicine. 2003;13:175-190. Google Scholar
- S. Findeklee, S. Costa. Placenta Accreta and Total Placenta Previa in the 19th Week of Pregnancy. Geburtshilfe und Frauenheilkunde. 2015;75:839-843. Google Scholar
- A.S. Handler, E.D. Mason, D.L. Rosenberg, F.G. Davis. The relationship between exposure during pregnancy to cigarette smoking and cocaine use and placenta previa. American journal of obstetrics and gynecology. 1994;170:884-889. Google Scholar
- J. Higgins, S. Thompson, J. Deeks, D. Altman. Measuring inconsistency in meta-analyses BMJ 327: 557-560. Find this article online. 2003;:. Google Scholar
- T.H. Hung, C.C. Hsieh, J.J. Hsu, T.H. Chiu, L.M. Lo. Risk factors for placenta previa in an Asian population. International Journal of Gynecology & Obstetrics. 2007;97:26-30. Google Scholar
- L. Johnson, B. Mueller, J. Daling. The relationship of placenta previa and history of induced abortion. International Journal of Gynecology & Obstetrics. 2003;81:191-198. Google Scholar
- M. Kashanian, A. Akbarian, H. Baradaran, S. Shabandoust. Pregnancy outcome following a previous spontaneous abortion (miscarriage). Gynecologic and obstetric investigation. 2006;61:167-170. Google Scholar
- M.D. Kramer, V. Taylor, D.E. Hickok, J.R. Daling, T.L. Vaughan, K.A. Hollenbach. Maternal smoking and placenta previa. Epidemiology. 1991;:221-223. Google Scholar
- L. Latif, U.J. Iqbal, M.U. Aftab. Associated risk factors of placenta previa a matched case control study. Pakistan Journal of Medical and Health Sciences. 2015;9:1344-1346. Google Scholar
- G.A. Macones, H.M. Sehdev, S. Parry, M.A. Morgan, J.A. Berlin. The association between maternal cocaine use and placenta previa. American journal of obstetrics and gynecology. 1997;177:1097-1100. Google Scholar
- E.R. Newton, V. Barss, C.L. Cetrulo. The epidemiology and clinical history of asymptomatic midtrimester placenta previa. American journal of obstetrics and gynecology. 1984;148:743-748. Google Scholar
- J. Poorolajal, E. Jenabi. The association between body mass index and preeclampsia: a meta-analysis. The Journal of Maternal-Fetal & Neonatal Medicine. 2016;29:3670-3676. Google Scholar
- L. Rombauts, C. Motteram, E. Berkowitz, S. Fernando. Risk of placenta praevia is linked to endometrial thickness in a retrospective cohort study of 4537 singleton assisted reproduction technology births. Human Reproduction. 2014;29:2787-2793. Google Scholar
- G.L. ROSE, M.G. CHAPMAN. Aetiological factors in placenta praevia a case controlled study. BJOG: An International Journal of Obstetrics & Gynaecology. 1986;93:586-588. Google Scholar
- T. Rosenberg, G. Pariente, R. Sergienko, A. Wiznitzer, E. Sheiner. Critical analysis of risk factors and outcome of placenta previa. Archives of gynecology and obstetrics. 2011;284:47-51. Google Scholar
- E. Sheiner, I. Shoham-Vardi, M. Hallak, R. Hershkowitz, M. Katz, M. Mazor. Placenta previa: obstetric risk factors and pregnancy outcome. Journal of Maternal-Fetal Medicine. 2001;10:414-419. Google Scholar
- F. Shobeiri, E. Jenabi, M. Karami, S. Karimi. Determinants of placenta previa: a case-control study. Biomedical Research and Therapy. 2017;4:1411-1419. Google Scholar
- S. Sumigama, C. Sugiyama, T. Kotani, H. Hayakawa, A. Inoue, Y. Mano, H. Tsuda, M. Furuhashi, O. Yamamuro, Y. Kinoshita. Uterine sutures at prior caesarean section and placenta accreta in subsequent pregnancy: a case-control study. BJOG: An International Journal of Obstetrics & Gynaecology. 2014;121:866-875. Google Scholar
- V.M. Taylor, M.D. Kramer, T.L. Vaughan, S. Peacock. Placenta Previa and Prior Cesarean Delivery: How Strong is the Association?. Obstetrics & Gynecology. 1994;84:55-57. Google Scholar
- D.H. Thom, L.M. Nelson, T.L. Vaughan. Spontaneous abortion and subsequent adverse birth outcomes. American journal of obstetrics and gynecology. 1992;166:111-116. Google Scholar
- I.M. Usta, E.M. Hobeika, A.A.A. Musa, G.E. Gabriel, A.H. Nassar. Placenta previa-accreta: risk factors and complications. American journal of obstetrics and gynecology. 2005;193:1045-1049. Google Scholar
- G. Wells, B. Shea, D. Oâ€™Connell, J. Peterson, V. Welch, M. Losos. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. Ottawa, Ontario, Canada: Ottawa Hospital Research Institute. 2012;2013:. Google Scholar
- M.A. Williams, R. Mittendorf, E. Lieberman, R.R. Monson, S.C. Schoenbaum, D.R. Genest. Cigarette smoking during pregnancy in relation to placenta previa. American journal of obstetrics and gynecology. 1991;165:28-32. Google Scholar