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Risk factors for placenta previa in an Asian population
International Journal of Gynecology and Obstetrics (2007) 97, 26–30
a v a i l a b l e a t w w w. s c i e n c e d i r e c t . c o m
w w w. e l s e v i e r. c o m / l o c a t e / i j g o
CLINICAL ARTICLE
Risk factors for placenta previa in an Asian population Tai-Ho Hung, Ching-Chang Hsieh, Jenn-Jeih Hsu, Tsung-Hong Chiu, Liang-Ming Lo, T'sang-T'ang Hsieh ⁎ Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Taipei, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan Received 16 September 2006; received in revised form 12 December 2006; accepted 13 December 2006
KEYWORDS Placenta; Placenta previa; Risk factors; Technology-assisted conception
Abstract Objective: To identify the risk factors for placenta previa in an Asian population. Methods: This retrospective cohort study involved Taiwanese women delivered between July 1990 and December 2003 at Chang Gung Memorial Hospital, Taipei, Taiwan. Pregnancies complicated by multiple gestation and fetal anomalies were excluded. Results: There were 457 cases of placenta previa (1.2%) among the 37,702 pregnancies analyzed. Risk factors for placenta previa included a prior preterm birth (OR, 6.6; 95% confidence interval [CI], 4.1–10.6); technology-assisted conception (OR, 4.8; 95% CI, 2.9–7.8); smoking (OR, 3.3; 95% CI, 1.2–9.1) or working (OR, 3.8; 95% CI, 2.8–5.3) during pregnancy; maternal age of, or greater than 35 years (OR, 2.0 to 2.2; 95% CI, 1.3–3.7); and previous induced abortions (OR, 1.3–3.0; 95% CI, 1.1–7.1). Conclusion: The risk factors for placenta previa were found to be the same for Asian women as those previously recorded for American and European women, but additional factors were detected. © 2007 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.
1. Introduction Placenta previa is a major cause of third-trimester hemorrhage [1], complicating between 0.3% and 0.5% of pregnancies [2–4] and accounting for significant maternal and perinatal morbidity and mortality [4–6]. Although the etiology of placenta previa remains speculative, several risk factors associated with this condition have been established. These include advanced maternal age, multi⁎ Corresponding author. Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, 199 Dun-hua North Road, Taipei 105, Taiwan. Tel.: +886 2 27135211x3576; fax: +886 2 27197368. E-mail address: [email protected] (T.'-T.' Hsieh).
parity, multiple gestation, smoking during pregnancy, a male fetus, previous abortion, previous cesarean delivery, and placenta previa in a previous pregnancy [1,2,4,7,9–11]. Most of these studies, however, were based on birth certificates that were often incomplete and thus open to informational errors and misclassification. Moreover, some of these studies did not control for important confounders, including maternal demographic characteristics, reproductive history, and current pregnancy complications, as such information is not available from birth certificates. Other relevant factors would include whether the conception was technology assisted, whether the woman worked during the index pregnancy, and a possible history of induced abortions, preterm deliveries, and placenta previa.
0020-7292/$ - see front matter © 2007 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijgo.2006.12.006
Risk factors for placenta previa in an Asian population More importantly, most of these studies did not take into account the possibility that women may have been delivered more than once during their study periods, an omission that may have caused inappropriate weighting of certain characteristics. Furthermore, most of these studies mainly investigated European [10,11] and American populations [1,2,4,7–9], even though racial variations have been suggested regarding the frequency of, and risk factors for, placenta previa [12,13]. The present study was conducted to examine whether the risk factor profile for placenta previa outlined in previous studies also applied to a large, homogeneous Taiwanese population.
Table 1
Maternal age, y < 20 20–34 (referent) 35–40 >40 Parity 1 (referent) 2 3 ≥4 Previous induced abortions 0 (referent) 1–2 3–4 ≥5 Previous cesarean delivery 0 (referent) 1 ≥2 Prepregnancy BMI c < 19:8 19.8–24.2 (referent) >24.2 Education, y <9 9–12 (referent) >12 Prior fetal death Prior preterm birth Prior placenta previa Unmarried Amniocentesis Technology-assisted conception Uterine fibroids Uterine malformation Working during pregnancy Smoking during pregnancy Gestational hypertensive diseases Gestational diabetes Overt diabetes Male fetus b c
2. Materials and methods Data concerning demographic characteristics, medical and obstetric history, pregnancy course, and perinatal outcomes were obtained for all the women delivered at Chang Gung Memorial Hospital between July 1990 and December 2003. The data were abstracted by trained personnel from the hospital's computerized obstetrics database of medical and delivery records, and, if necessary, complemented with a postpartum interview. Audits of these data were routinely performed at weekly departmental meetings. Details of the database's organization have been previously reported [14–16]. The study
Characteristics of women with placenta previa and controls a
Variable
a
27
Placenta previa (n = 457)
Controls (n = 37,245)
P value b
1 (0.2) 326 (71.3) 110 (24.1) 20 (4.4)
256 31,706 4616 667
(0.7) (85.1) (12.4) (1.8)
0.38 1.00 < 0:01 < 0:01
193 (42.2) 175 (38.3) 71 (15.5) 18 (3.9)
18,938 13,959 3762 585
(50.8) (37.5) (10.1) (1.6)
1.00 < 0:05 < 0:01 < 0:01
215 (47.0) 197 (43.1) 39 (8.5) 6 (1.3)
21,724 13,795 1578 148
(58.3) (37.0) (4.2) (0.4)
1.00 < 0:01 < 0:01 0.01
405 (88.6) 38 (8.3) 14 (3.1)
34,704 (93.2) 1973 (5.3) 568 (1.5)
1.00 < 0:01 0.02
128 (28.0) 283 (61.9) 46 (10.1)
12,591 (33.8) 21,543 (57.8) 3111 (8.4)
0.01 1.00 0.2
18 (3.9) 408 (89.3) 31 (6.8) 11 (2.4) 25 (5.5) 1 (0.2) 1 (0.2) 86 (18.8) 19 (4.2) 2 (0.4) 1 (0.2) 418 (91.5) 4 (0.9) 16 (3.5) 36 (7.9) 1 (0.2) 265 (58.0)
2244 32,287 2714 273 249 34 108 4877 311 273 55 27,528 105 640 2403 80 19,748
Values are given as number (percentage) unless otherwise indicated. P values based on χ2 tests or binary logistic regression. Body mass index, calculated as weight in kilograms divided by the square of height in meters.
(6.0) (86.7) (7.3) (0.7) (0.7) (0.1) (0.3) (13.1) (0.8) (0.7) (0.1) (73.9) (0.3) (1.7) (6.5) (0.2) (53.0)
0.08 1.00 0.78 < 0:01 < 0:01 0.35 0.99 < 0:01 < 0:01 0.78 0.50 < 0:01 0.04 0.01 0.21 0.63 0.04
28
T.-H. Hung et al.
Table 2 Results of multiple logistic regression analysis on risk factors for placenta previa a Variable
Adjusted OR 95% CI
Prior preterm birth Technology-assisted conception Working during pregnancy Smoking during pregnancy Maternal age, y 20–34 35–40 > 40 No. of previous induced abortion 0 1–2 3–4 ≥5
6.6 4.8 3.8 3.3
4.1–10.6 2.9–7.8 2.8–5.3 1.2–9.1
1.0 2.0 2.2
Referent 1.5–2.6 1.3–3.7
1.0 1.3 2.0 3.0
Referent 1.1–1.6 1.4–2.9 1.3–7.1
Abbreviations: OR, odds ratio; CI, confidence interval. a Adjusted for all the variables listed in Table 1.
was approved by the institutional review board of Chang Gung Memorial Hospital (Approval No. 95-0352B). Of the 51,266 deliveries performed between July 1990 and December 2003, those complicated by multiple gestation (n = 1738) or known chromosomal or structural fetal anomalies (n = 683) were excluded. During the study period 8903 women had 2 pregnancies, 971 had 3 pregnancies, 38 had 4 pregnancies, and 1 had 5 pregnancies. The study population consisted of
Table 3
37,702 women for whom only 1 pregnancy was randomly selected for analysis, as previously described [15,16]. Placenta previa was defined as complete or partial covering of the internal cervical os by placental tissues, a condition that was diagnosed ultrasonographically and confirmed during cesarean delivery. Gestational age was estimated based on the first day of the mother's last normal menstrual period or ultrasonographically if the date was unknown or uncertain. At Chang Gung Memorial Hospital, women routinely undergo an ultrasonographic scan between the 8th and 12th week of pregnancy when dating needs to be ascertained, and a scan between the 18th and 22nd week for examination of fetal anatomy, growth, and placental location. The women found to have placenta previa on the second-trimester sonographic scan undergo a transvaginal scan between the 32nd and 34th week to determine whether the placenta previa has persisted. The following variables were evaluated as potential confounding factors: maternal age at delivery, parity, prepregnancy body mass index (BMI, calculated as weight in kilograms divided by the square of height in meters), years of education, marital status, work during pregnancy, conception method (natural or assisted by reproductive technology), fetal sex, having undergone amniocentesis, cigarette smoking, previous fetal death, previous preterm birth, previous cesarean deliveries, previous induced abortions, previous placenta previa, diabetes mellitus (overt or gestational), gestational hypertensive diseases (including chronic hypertension, gestational hypertension, pre-eclampsia, and eclampsia), as well as uterine fibroids and malformations (including didelphys, bicornuate, and septate uterus).
Maternal complications and adverse perinatal outcomes associated with placenta previa a
Variable
Placenta previa (n = 457)
Controls (n = 37245)
Adjusted OR b
95% CI
Gestational hypertensive diseases Placental abruption Placenta accreta PPROM Chorioamnionitis Polyhydramnios Oligohydramnios Meconium-stained amniotic fluid 1-min Apgar score < 7 5-min Apgar score < 7 Delivery before 37 weeks Delivery before 34 weeks Birth weight < 1500 g Birth weight < 2500 g Birth weight > 4000 g Small-for-gestational age Large-for-gestational age Postpartum hemorrhage NICU transfer Fetal death Neonatal death
16 47 31 25 10 8 19 23 82 36 198 67 38 119 8 37 57 16 89 20 10
640 (1.7) 332 (0.9) 122 (0.3) 771 (2.1) 416 (1.1) 193 (0.5) 434 (1.2) 3577 (9.6) 1014 (2.7) 466 (1.3) 2399 (6.4) 655 (1.8) 399 (1.1) 1895 (5.1) 1289 (3.5) 2400 (6.4) 4231 (11.4) 2390 (6.4) 1576 (4.2) 208 (0.6) 228 (0.6)
1.5 11.0 17.3 1.8 1.7 3.4 2.8 0.5 6.0 4.8 9.1 6.6 5.3 5.3 0.5 1.3 1.0 0.5 4.4 2.4 2.7
0.9–2.5 7.9–15.5 11.2–26.7 1.2–2.7 0.9–3.2 1.6–7.0 1.7–4.6 0.3–0.8 4.6–7.8 3.3–7.1 7.4–11.1 4.9–9.0 3.6–7.9 4.2–6.7 0.2–1.0 0.9–1.8 0.7–1.3 0.3–0.8 3.4–5.6 1.2–4.8 1.2–6.4
(3.5) (10.3) (6.8) (5.5) (2.2) (1.8) (4.2) (5.0) (17.9) (7.9) (43.3) (14.7) (8.3) (26.0) (1.8) (8.1) (12.5) (3.5) (19.5) (6.0) (2.2)
Abbreviations: CI, confidence interval; NICU, neonatal intensive care unit; PPROM, preterm premature rupture of membranes; OR, odds ratio. a Values are given as number (percentage) unless otherwise indicated. b Adjusted for maternal age, parity, previous induced abortion, previous cesarean deliveries, prepregnancy body mass index, years of education, previous fetal death, previous preterm birth, previous placenta previa, marital status, amniocentesis, conception methods, presence of uterine fibroids, uterine malformation, employment during pregnancy, smoking during pregnancy, and fetal sex.
Risk factors for placenta previa in an Asian population The statistical package SPSS for Windows, release 11.0 (SPSS Inc., Chicago, IL, USA) was used for statistical analysis. χ2 tests and binary logistic regression were used to characterize the placenta previa and control cohorts. Multiple logistic regression analysis with backward elimination and stepwise regression procedures was used to evaluate the association between placenta previa and the various risk factors while controlling for potential confounders. Adjusted odds ratios (ORs) with their associated confidence intervals (CIs) were used to describe the relative risk of each potential risk factor.
3. Results Placenta previa affected 457 (1.2%) of the 37,702 singleton pregnancies analyzed in the study. The characteristics of the study population are shown in Table 1. The placenta previa cohort was characterized by a significantly higher prevalence of women who were older than 35 years or were multiparous, or had a history of induced abortion, cesarean delivery, working during pregnancy, technology-assisted conception, gestational hypertensive diseases, smoking during pregnancy, amniocentesis, fetal death, preterm birth, or who carried a male fetus in the index pregnancy. Multiple logistic regression results are presented in Table 2. Significant independent risk factors for placenta previa included a history of preterm delivery, technology-assisted conception, working or smoking during pregnancy, and maternal age of, or greater than 35 years. The risk for placenta previa also increased with the number of induced abortions. Although a higher proportion of women with previous cesarean delivery, multiparity, and a male fetus were noted in the placenta previa cohort, these factors did not reach statistical significance in the multivariable logistic regression analysis. Table 3 summaries the incidence of various maternal complications and adverse perinatal outcomes in women with and without placenta previa. In general, women with placenta previa were more likely to experience complications and adverse perinatal outcomes than controls. These complications included placental abruption, placenta accreta, preterm premature rupture of membranes, polyhydramnios, oligohydramnios, 1-minute and 5-minute Apgar score less than 7, delivery before 34 or 37 weeks of pregnancy, birth weight less than 1500 or 2500 g, neonatal intensive care unit admission, fetal death, and neonatal death.
4. Discussion Estimates generated by logistic regression analysis of data in any retrospective cohort study should be interpreted with caution, especially when numbers for risk factors are small and confidence intervals wide. Nevertheless, the strength of this study lies in its ability to adjust for as many confounding factors as possible, and in the use of patient interview and medical record data rather than vital statistics or birth certificate data. Thus the association between each potential risk factor and the presence of placenta previa was objectively investigated. Moreover, only 1 pregnancy was randomly selected for the women who were delivered more than once during the study period. The incidence of placenta previa (1.2%) in this homogenous Taiwanese population was higher than the estimates
29 reported for previous population-based studies [2–4]. This higher rate may be caused by case concentration, as Chang Gung Memorial Hospital is a referral medical center for Northern Taiwan. The rate of placenta previa may also have been underreported in previous population-based studies because of the inaccuracy of birth certificates and hospital discharge data. Indeed, using the medical record as the gold standard, a population-based validation study involving 19 nonfederal short-stay hospitals showed that the true positive fraction for placenta previa was 33% for birth certificates and 70% for hospital discharge data, respectively [17]. Another possible explanation is a racial disparity in the frequency of placenta previa. A recent study revealed an incidence of 1.0% among Asian and Pacific Islanders compared with 0.5% in a white population [12]. The findings of the present study confirm those of most prior studies [1,2,4,8,9], that the risk of placenta previa increases with advancing maternal age and the number of induced abortions. The impact of maternal age on the risk of placenta previa most likely relates to aging of the uterus and the effects of repeated pregnancies [1], and vacuum aspiration or dilation and curettage may cause scarring and adhesions in the uterus that impede proper placentation in subsequent pregnancies. Although abortion procedures were not reported in the patient records, this study's findings are of clinical significance. Women may be delaying childbearing [18], but more than one-third of the women who opt for pregnancy termination intend to have children later in life [8]. Several reports have shown that male fetuses were significantly associated with placenta previa [4,7], but the mechanism underlying this association has not been determined. In this study there was a higher rate of women with a male fetus in the placenta previa cohort than in the control cohort, but the difference did not reach statistical significance in the multiple logistic regression analysis (OR, 1.2; 95% CI, 0.99–1.4). It is possible that controlling for important confounding factors such as conception method, and adjusting for repeated pregnancies within the study period, reduced the magnitude of the association between fetal sex and placenta previa. The use of reproductive technology has been reported to be associated with adverse pregnancy outcomes, including abnormalities in the location and function of the placenta [19]. An inherent difference in the nature of the placenta when the formation of the chorion is initiated in vitro was thought to be responsible for the abnormal placentation [20]. Two recent studies showed the risk of placenta previa to be increased 3.6- to 6.0-fold following the use of in vitro fertilization compared with pregnancies unaided by assisted reproductive technology [20,21], and the present study adds further support to this observation. Although the present study found that prior preterm delivery and working during pregnancy were significantly associated with placenta previa, the biologic mechanisms for these associations remain unclear. It is possible that women with physical or psychological stress are predisposed to placental implantation in the lower uterine segment, or to a lesser likelihood of placenta previa resolution as the gestation advances. More studies are needed to verify these findings. There are several limitations to this study. First, it has the attendant limitation of a hospital-based study, i.e., the risk
30 of bias due to both overdiagnosis and underdiagnosis. Yet, the risk factor profile for placenta previa found in this very homogenous Taiwanese population was a similar to those reported for other ethnic groups in most population-based studies. The second limitation is the small sample size for some important variables such as “prior placenta previa” and “more than 3 cesarean deliveries”, and the small samples may be the reason why no significant associations were detected between these factors and placenta previa. Finally, because there were no non-Asian women in the control group, the comparison of the study's findings with findings for other ethnicities is limited. Most Taiwanese are the descendants of early settlers from the southeast coast of China and are genetically related to other south Asian populations [22]. This study's results suggest that the risk factors for placenta previa are the same for Asian women as those previously recorded for American and European women, but there may be additional factors.
Acknowledgments This work was supported by the National Science Council of Taiwan (NSC grant 94-2314-B-182A-142) and Chang Gung Memorial Hospital (CMRPG grant 32096). T-H Hung is supported by Chang Gung Memorial Hospital as a physician scientist.
References [1] Ananth CV, Wilcox AJ, Savitz DA, Bowes Jr WA, Luther ER. Effect of maternal age and parity on the risk of uteroplacental bleeding disorders in pregnancy. Obstet Gynecol 1996;88: 511—6. [2] Faiz AS, Ananth CV. Etiology and risk factors for placenta previa: an overview and meta-analysis of observational studies. J Matern Fetal Neonatal Med 2003;13:175—90. [3] Ananth CV, Demissie K, Smulian JC, Vintzileos AM. Relationship among placenta previa, fetal growth restriction, and preterm delivery: a population-based study. Obstet Gynecol 2001;98: 299—306. [4] Ananth CV, Demissie K, Smulian JC, Vintzileos AM. Placenta previa in singleton and twin births in the United States, 1989 through 1998: a comparison of risk factor profiles and associated conditions. Am J Obstet Gynecol 2003;188:275—81. [5] Ananth CV, Smulian JC, Vintzileos AM. The effect of placenta previa on neonatal mortality: a population-based study in the United States, 1989 through 1997. Am J Obstet Gynecol 2003;188: 1299—304.
T.-H. Hung et al. [6] McShane PM, Heyl PS, Epstein MF. Maternal and perinatal morbidity resulting from placenta previa. Obstet Gynecol 1985;65: 176—82. [7] Demissie K, Breckenridge MB, Joseph L, Rhoads GG. Placenta previa: preponderance of male sex at birth. Am J Epidemiol 1999;149:824—30. [8] Johnson LG, Mueller BA, Daling JR. The relationship of placenta previa and history of induced abortion. Int J Gynecol Obstet 2003;81:191—8. [9] Ananth CV, Smulian JC, Vintzileos AM. The association of placenta previa with history of cesarean delivery and abortion: a metaanalysis. Am J Obstet Gynecol 1997;177:1071—8. [10] Rasmussen S, Albrechtsen S, Dalaker K. Obstetric history and the risk of placenta previa. Acta Obstet Gynecol Scand 2000;79:502—7. [11] Monica G, Lilja C. Placenta previa, maternal smoking and recurrence risk. Acta Obstet Gynecol Scand 1995;74:341—5. [12] Healy AJ, Malone FD, Sullivan LM, Porter TF, Luthy DA, Comstock CH, et al. Early access to prenatal care: implications for racial disparity in perinatal mortality. Obstet Gynecol 2006;107:625—31. [13] Rathore SS, McMahon MJ. Racial variation in the frequency of intrapartum hemorrhage. Obstet Gynecol 2001;97:178—83. [14] Hsieh TT, Chen SF, Shau WY, Hsieh CC, Hsu JJ, Hung TH. The impact of interpregnancy interval and previous preterm birth on the subsequent risk of preterm birth. J Soc Gynecol Investig 2005;12:202—7. [15] Hung TH, Shau WY, Hsieh CC, Chiu TH, Hsu JJ, Hsieh TT. Risk factors for placenta accreta. Obstet Gynecol 1999;93:545—50. [16] Lee CJ, Hsieh TT, Chiu TH, Chen KC, Lo LM, Hung TH. Risk factors for pre-eclampsia in an Asian population. Int J Gynecol Obstet 2000;70:327—33. [17] Lydon-Rochelle MT, Holt VL, Cardenas V, Nelson JC, Easterling TR, Gardella C, et al. The reporting of pre-existing maternal medical conditions and complications of pregnancy on birth certificates and in hospital discharge data. Am J Obstet Gynecol 2005;193:125—34. [18] Mathews TJ, Hamilton BE. Mean age of mother, 1970–2000. Natl Vital Stat Rep 2002;51:1–13. [19] Jackson RA, Gibson KA, Wu YW, Croughan MS. Perinatal outcomes in singletons following in vitro fertilization: a metaanalysis. Obstet Gynecol 2004;103:551—63. [20] Shevell T, Malone FD, Vidaver J, Porter TF, Luthy DA, Comstock CH, et al. Assisted reproductive technology and pregnancy outcome. Obstet Gynecol 2005;106:1039—45. [21] Kallen B, Finnstrom O, Nygren KG, Otterblad OP, Wennerholm UB. In vitro fertilisation in Sweden: obstetric characteristics, maternal morbidity and mortality. BJOG 2005;112:1529—35. [22] Lin M, Chu CC, Chang SL, Lee HL, Loo JH, Akaza T, et al. The origin of Minnan and Hakka, the so-called “Taiwanese”, inferred by HLA study. Tissue Antigens 2001;57:192—9.
a v a i l a b l e a t w w w. s c i e n c e d i r e c t . c o m
w w w. e l s e v i e r. c o m / l o c a t e / i j g o
CLINICAL ARTICLE
Risk factors for placenta previa in an Asian population Tai-Ho Hung, Ching-Chang Hsieh, Jenn-Jeih Hsu, Tsung-Hong Chiu, Liang-Ming Lo, T'sang-T'ang Hsieh ⁎ Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Taipei, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan Received 16 September 2006; received in revised form 12 December 2006; accepted 13 December 2006
KEYWORDS Placenta; Placenta previa; Risk factors; Technology-assisted conception
Abstract Objective: To identify the risk factors for placenta previa in an Asian population. Methods: This retrospective cohort study involved Taiwanese women delivered between July 1990 and December 2003 at Chang Gung Memorial Hospital, Taipei, Taiwan. Pregnancies complicated by multiple gestation and fetal anomalies were excluded. Results: There were 457 cases of placenta previa (1.2%) among the 37,702 pregnancies analyzed. Risk factors for placenta previa included a prior preterm birth (OR, 6.6; 95% confidence interval [CI], 4.1–10.6); technology-assisted conception (OR, 4.8; 95% CI, 2.9–7.8); smoking (OR, 3.3; 95% CI, 1.2–9.1) or working (OR, 3.8; 95% CI, 2.8–5.3) during pregnancy; maternal age of, or greater than 35 years (OR, 2.0 to 2.2; 95% CI, 1.3–3.7); and previous induced abortions (OR, 1.3–3.0; 95% CI, 1.1–7.1). Conclusion: The risk factors for placenta previa were found to be the same for Asian women as those previously recorded for American and European women, but additional factors were detected. © 2007 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.
1. Introduction Placenta previa is a major cause of third-trimester hemorrhage [1], complicating between 0.3% and 0.5% of pregnancies [2–4] and accounting for significant maternal and perinatal morbidity and mortality [4–6]. Although the etiology of placenta previa remains speculative, several risk factors associated with this condition have been established. These include advanced maternal age, multi⁎ Corresponding author. Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, 199 Dun-hua North Road, Taipei 105, Taiwan. Tel.: +886 2 27135211x3576; fax: +886 2 27197368. E-mail address: [email protected] (T.'-T.' Hsieh).
parity, multiple gestation, smoking during pregnancy, a male fetus, previous abortion, previous cesarean delivery, and placenta previa in a previous pregnancy [1,2,4,7,9–11]. Most of these studies, however, were based on birth certificates that were often incomplete and thus open to informational errors and misclassification. Moreover, some of these studies did not control for important confounders, including maternal demographic characteristics, reproductive history, and current pregnancy complications, as such information is not available from birth certificates. Other relevant factors would include whether the conception was technology assisted, whether the woman worked during the index pregnancy, and a possible history of induced abortions, preterm deliveries, and placenta previa.
0020-7292/$ - see front matter © 2007 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijgo.2006.12.006
Risk factors for placenta previa in an Asian population More importantly, most of these studies did not take into account the possibility that women may have been delivered more than once during their study periods, an omission that may have caused inappropriate weighting of certain characteristics. Furthermore, most of these studies mainly investigated European [10,11] and American populations [1,2,4,7–9], even though racial variations have been suggested regarding the frequency of, and risk factors for, placenta previa [12,13]. The present study was conducted to examine whether the risk factor profile for placenta previa outlined in previous studies also applied to a large, homogeneous Taiwanese population.
Table 1
Maternal age, y < 20 20–34 (referent) 35–40 >40 Parity 1 (referent) 2 3 ≥4 Previous induced abortions 0 (referent) 1–2 3–4 ≥5 Previous cesarean delivery 0 (referent) 1 ≥2 Prepregnancy BMI c < 19:8 19.8–24.2 (referent) >24.2 Education, y <9 9–12 (referent) >12 Prior fetal death Prior preterm birth Prior placenta previa Unmarried Amniocentesis Technology-assisted conception Uterine fibroids Uterine malformation Working during pregnancy Smoking during pregnancy Gestational hypertensive diseases Gestational diabetes Overt diabetes Male fetus b c
2. Materials and methods Data concerning demographic characteristics, medical and obstetric history, pregnancy course, and perinatal outcomes were obtained for all the women delivered at Chang Gung Memorial Hospital between July 1990 and December 2003. The data were abstracted by trained personnel from the hospital's computerized obstetrics database of medical and delivery records, and, if necessary, complemented with a postpartum interview. Audits of these data were routinely performed at weekly departmental meetings. Details of the database's organization have been previously reported [14–16]. The study
Characteristics of women with placenta previa and controls a
Variable
a
27
Placenta previa (n = 457)
Controls (n = 37,245)
P value b
1 (0.2) 326 (71.3) 110 (24.1) 20 (4.4)
256 31,706 4616 667
(0.7) (85.1) (12.4) (1.8)
0.38 1.00 < 0:01 < 0:01
193 (42.2) 175 (38.3) 71 (15.5) 18 (3.9)
18,938 13,959 3762 585
(50.8) (37.5) (10.1) (1.6)
1.00 < 0:05 < 0:01 < 0:01
215 (47.0) 197 (43.1) 39 (8.5) 6 (1.3)
21,724 13,795 1578 148
(58.3) (37.0) (4.2) (0.4)
1.00 < 0:01 < 0:01 0.01
405 (88.6) 38 (8.3) 14 (3.1)
34,704 (93.2) 1973 (5.3) 568 (1.5)
1.00 < 0:01 0.02
128 (28.0) 283 (61.9) 46 (10.1)
12,591 (33.8) 21,543 (57.8) 3111 (8.4)
0.01 1.00 0.2
18 (3.9) 408 (89.3) 31 (6.8) 11 (2.4) 25 (5.5) 1 (0.2) 1 (0.2) 86 (18.8) 19 (4.2) 2 (0.4) 1 (0.2) 418 (91.5) 4 (0.9) 16 (3.5) 36 (7.9) 1 (0.2) 265 (58.0)
2244 32,287 2714 273 249 34 108 4877 311 273 55 27,528 105 640 2403 80 19,748
Values are given as number (percentage) unless otherwise indicated. P values based on χ2 tests or binary logistic regression. Body mass index, calculated as weight in kilograms divided by the square of height in meters.
(6.0) (86.7) (7.3) (0.7) (0.7) (0.1) (0.3) (13.1) (0.8) (0.7) (0.1) (73.9) (0.3) (1.7) (6.5) (0.2) (53.0)
0.08 1.00 0.78 < 0:01 < 0:01 0.35 0.99 < 0:01 < 0:01 0.78 0.50 < 0:01 0.04 0.01 0.21 0.63 0.04
28
T.-H. Hung et al.
Table 2 Results of multiple logistic regression analysis on risk factors for placenta previa a Variable
Adjusted OR 95% CI
Prior preterm birth Technology-assisted conception Working during pregnancy Smoking during pregnancy Maternal age, y 20–34 35–40 > 40 No. of previous induced abortion 0 1–2 3–4 ≥5
6.6 4.8 3.8 3.3
4.1–10.6 2.9–7.8 2.8–5.3 1.2–9.1
1.0 2.0 2.2
Referent 1.5–2.6 1.3–3.7
1.0 1.3 2.0 3.0
Referent 1.1–1.6 1.4–2.9 1.3–7.1
Abbreviations: OR, odds ratio; CI, confidence interval. a Adjusted for all the variables listed in Table 1.
was approved by the institutional review board of Chang Gung Memorial Hospital (Approval No. 95-0352B). Of the 51,266 deliveries performed between July 1990 and December 2003, those complicated by multiple gestation (n = 1738) or known chromosomal or structural fetal anomalies (n = 683) were excluded. During the study period 8903 women had 2 pregnancies, 971 had 3 pregnancies, 38 had 4 pregnancies, and 1 had 5 pregnancies. The study population consisted of
Table 3
37,702 women for whom only 1 pregnancy was randomly selected for analysis, as previously described [15,16]. Placenta previa was defined as complete or partial covering of the internal cervical os by placental tissues, a condition that was diagnosed ultrasonographically and confirmed during cesarean delivery. Gestational age was estimated based on the first day of the mother's last normal menstrual period or ultrasonographically if the date was unknown or uncertain. At Chang Gung Memorial Hospital, women routinely undergo an ultrasonographic scan between the 8th and 12th week of pregnancy when dating needs to be ascertained, and a scan between the 18th and 22nd week for examination of fetal anatomy, growth, and placental location. The women found to have placenta previa on the second-trimester sonographic scan undergo a transvaginal scan between the 32nd and 34th week to determine whether the placenta previa has persisted. The following variables were evaluated as potential confounding factors: maternal age at delivery, parity, prepregnancy body mass index (BMI, calculated as weight in kilograms divided by the square of height in meters), years of education, marital status, work during pregnancy, conception method (natural or assisted by reproductive technology), fetal sex, having undergone amniocentesis, cigarette smoking, previous fetal death, previous preterm birth, previous cesarean deliveries, previous induced abortions, previous placenta previa, diabetes mellitus (overt or gestational), gestational hypertensive diseases (including chronic hypertension, gestational hypertension, pre-eclampsia, and eclampsia), as well as uterine fibroids and malformations (including didelphys, bicornuate, and septate uterus).
Maternal complications and adverse perinatal outcomes associated with placenta previa a
Variable
Placenta previa (n = 457)
Controls (n = 37245)
Adjusted OR b
95% CI
Gestational hypertensive diseases Placental abruption Placenta accreta PPROM Chorioamnionitis Polyhydramnios Oligohydramnios Meconium-stained amniotic fluid 1-min Apgar score < 7 5-min Apgar score < 7 Delivery before 37 weeks Delivery before 34 weeks Birth weight < 1500 g Birth weight < 2500 g Birth weight > 4000 g Small-for-gestational age Large-for-gestational age Postpartum hemorrhage NICU transfer Fetal death Neonatal death
16 47 31 25 10 8 19 23 82 36 198 67 38 119 8 37 57 16 89 20 10
640 (1.7) 332 (0.9) 122 (0.3) 771 (2.1) 416 (1.1) 193 (0.5) 434 (1.2) 3577 (9.6) 1014 (2.7) 466 (1.3) 2399 (6.4) 655 (1.8) 399 (1.1) 1895 (5.1) 1289 (3.5) 2400 (6.4) 4231 (11.4) 2390 (6.4) 1576 (4.2) 208 (0.6) 228 (0.6)
1.5 11.0 17.3 1.8 1.7 3.4 2.8 0.5 6.0 4.8 9.1 6.6 5.3 5.3 0.5 1.3 1.0 0.5 4.4 2.4 2.7
0.9–2.5 7.9–15.5 11.2–26.7 1.2–2.7 0.9–3.2 1.6–7.0 1.7–4.6 0.3–0.8 4.6–7.8 3.3–7.1 7.4–11.1 4.9–9.0 3.6–7.9 4.2–6.7 0.2–1.0 0.9–1.8 0.7–1.3 0.3–0.8 3.4–5.6 1.2–4.8 1.2–6.4
(3.5) (10.3) (6.8) (5.5) (2.2) (1.8) (4.2) (5.0) (17.9) (7.9) (43.3) (14.7) (8.3) (26.0) (1.8) (8.1) (12.5) (3.5) (19.5) (6.0) (2.2)
Abbreviations: CI, confidence interval; NICU, neonatal intensive care unit; PPROM, preterm premature rupture of membranes; OR, odds ratio. a Values are given as number (percentage) unless otherwise indicated. b Adjusted for maternal age, parity, previous induced abortion, previous cesarean deliveries, prepregnancy body mass index, years of education, previous fetal death, previous preterm birth, previous placenta previa, marital status, amniocentesis, conception methods, presence of uterine fibroids, uterine malformation, employment during pregnancy, smoking during pregnancy, and fetal sex.
Risk factors for placenta previa in an Asian population The statistical package SPSS for Windows, release 11.0 (SPSS Inc., Chicago, IL, USA) was used for statistical analysis. χ2 tests and binary logistic regression were used to characterize the placenta previa and control cohorts. Multiple logistic regression analysis with backward elimination and stepwise regression procedures was used to evaluate the association between placenta previa and the various risk factors while controlling for potential confounders. Adjusted odds ratios (ORs) with their associated confidence intervals (CIs) were used to describe the relative risk of each potential risk factor.
3. Results Placenta previa affected 457 (1.2%) of the 37,702 singleton pregnancies analyzed in the study. The characteristics of the study population are shown in Table 1. The placenta previa cohort was characterized by a significantly higher prevalence of women who were older than 35 years or were multiparous, or had a history of induced abortion, cesarean delivery, working during pregnancy, technology-assisted conception, gestational hypertensive diseases, smoking during pregnancy, amniocentesis, fetal death, preterm birth, or who carried a male fetus in the index pregnancy. Multiple logistic regression results are presented in Table 2. Significant independent risk factors for placenta previa included a history of preterm delivery, technology-assisted conception, working or smoking during pregnancy, and maternal age of, or greater than 35 years. The risk for placenta previa also increased with the number of induced abortions. Although a higher proportion of women with previous cesarean delivery, multiparity, and a male fetus were noted in the placenta previa cohort, these factors did not reach statistical significance in the multivariable logistic regression analysis. Table 3 summaries the incidence of various maternal complications and adverse perinatal outcomes in women with and without placenta previa. In general, women with placenta previa were more likely to experience complications and adverse perinatal outcomes than controls. These complications included placental abruption, placenta accreta, preterm premature rupture of membranes, polyhydramnios, oligohydramnios, 1-minute and 5-minute Apgar score less than 7, delivery before 34 or 37 weeks of pregnancy, birth weight less than 1500 or 2500 g, neonatal intensive care unit admission, fetal death, and neonatal death.
4. Discussion Estimates generated by logistic regression analysis of data in any retrospective cohort study should be interpreted with caution, especially when numbers for risk factors are small and confidence intervals wide. Nevertheless, the strength of this study lies in its ability to adjust for as many confounding factors as possible, and in the use of patient interview and medical record data rather than vital statistics or birth certificate data. Thus the association between each potential risk factor and the presence of placenta previa was objectively investigated. Moreover, only 1 pregnancy was randomly selected for the women who were delivered more than once during the study period. The incidence of placenta previa (1.2%) in this homogenous Taiwanese population was higher than the estimates
29 reported for previous population-based studies [2–4]. This higher rate may be caused by case concentration, as Chang Gung Memorial Hospital is a referral medical center for Northern Taiwan. The rate of placenta previa may also have been underreported in previous population-based studies because of the inaccuracy of birth certificates and hospital discharge data. Indeed, using the medical record as the gold standard, a population-based validation study involving 19 nonfederal short-stay hospitals showed that the true positive fraction for placenta previa was 33% for birth certificates and 70% for hospital discharge data, respectively [17]. Another possible explanation is a racial disparity in the frequency of placenta previa. A recent study revealed an incidence of 1.0% among Asian and Pacific Islanders compared with 0.5% in a white population [12]. The findings of the present study confirm those of most prior studies [1,2,4,8,9], that the risk of placenta previa increases with advancing maternal age and the number of induced abortions. The impact of maternal age on the risk of placenta previa most likely relates to aging of the uterus and the effects of repeated pregnancies [1], and vacuum aspiration or dilation and curettage may cause scarring and adhesions in the uterus that impede proper placentation in subsequent pregnancies. Although abortion procedures were not reported in the patient records, this study's findings are of clinical significance. Women may be delaying childbearing [18], but more than one-third of the women who opt for pregnancy termination intend to have children later in life [8]. Several reports have shown that male fetuses were significantly associated with placenta previa [4,7], but the mechanism underlying this association has not been determined. In this study there was a higher rate of women with a male fetus in the placenta previa cohort than in the control cohort, but the difference did not reach statistical significance in the multiple logistic regression analysis (OR, 1.2; 95% CI, 0.99–1.4). It is possible that controlling for important confounding factors such as conception method, and adjusting for repeated pregnancies within the study period, reduced the magnitude of the association between fetal sex and placenta previa. The use of reproductive technology has been reported to be associated with adverse pregnancy outcomes, including abnormalities in the location and function of the placenta [19]. An inherent difference in the nature of the placenta when the formation of the chorion is initiated in vitro was thought to be responsible for the abnormal placentation [20]. Two recent studies showed the risk of placenta previa to be increased 3.6- to 6.0-fold following the use of in vitro fertilization compared with pregnancies unaided by assisted reproductive technology [20,21], and the present study adds further support to this observation. Although the present study found that prior preterm delivery and working during pregnancy were significantly associated with placenta previa, the biologic mechanisms for these associations remain unclear. It is possible that women with physical or psychological stress are predisposed to placental implantation in the lower uterine segment, or to a lesser likelihood of placenta previa resolution as the gestation advances. More studies are needed to verify these findings. There are several limitations to this study. First, it has the attendant limitation of a hospital-based study, i.e., the risk
30 of bias due to both overdiagnosis and underdiagnosis. Yet, the risk factor profile for placenta previa found in this very homogenous Taiwanese population was a similar to those reported for other ethnic groups in most population-based studies. The second limitation is the small sample size for some important variables such as “prior placenta previa” and “more than 3 cesarean deliveries”, and the small samples may be the reason why no significant associations were detected between these factors and placenta previa. Finally, because there were no non-Asian women in the control group, the comparison of the study's findings with findings for other ethnicities is limited. Most Taiwanese are the descendants of early settlers from the southeast coast of China and are genetically related to other south Asian populations [22]. This study's results suggest that the risk factors for placenta previa are the same for Asian women as those previously recorded for American and European women, but there may be additional factors.
Acknowledgments This work was supported by the National Science Council of Taiwan (NSC grant 94-2314-B-182A-142) and Chang Gung Memorial Hospital (CMRPG grant 32096). T-H Hung is supported by Chang Gung Memorial Hospital as a physician scientist.
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