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ORIGINAL RESEARCH |
From the Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Taipei, Taiwan, and Institution of Epidemiology, College of Public Health, National Taiwan University, Taipei, Taiwan.
Address reprint requests to: T’sang-T’ang Hsieh, MD, Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, 199 Tun Hwa North Road, Taipei 105, Taiwan, E-mail: tth3388{at}tpts1.seed.net.tw
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Abstract |
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Methods: Data for this study came from the Taiwan Down Syndrome Screening Group, an ongoing project on feasibility of serum screening in an Asian population. Women who had serum screening for Down syndrome at 14–22 weeks’ gestation using alpha-fetoprotein (AFP) and free ß-hCG between January 1994 and June 1997, and delivered in the same institution, were included (n = 10,672). Those who had multiple gestations (n = 200), overt diabetes (n = 11), or fetal malformations (n = 101) were excluded. If a woman was involved more than once, one randomly selected pregnancy was included in the analysis (n = 9349). Twenty-eight pregnancies were complicated by placenta accreta, diagnosed by clinical presentation (n = 26) or histologic confirmation (n = 2). Multiple logistic regression with adjustment for potentially confounding variables was used to identify independent risk factors for placenta accreta.
Results: Women who had placenta previa (odds ratio [OR] 54.2; 95% confidence interval [CI] 17.8, 165.5) and second-trimester serum levels of AFP and free ß-hCG greater than 2.5 multiples of the median (OR 8.3; 95% CI 1.8, 39.3 and OR 3.9; 95% CI 1.5, 9.9, respectively), and were 35 years and older (OR 3.2; 95% CI 1.1, 9.4) were at increased risk of having placenta accreta.
Conclusion: Risk factors for placenta accreta include placenta previa, abnormally elevated second-trimester AFP and free ß-hCG levels, and advanced maternal age.
Several risk factors were associated with placenta accreta, including placenta previa,1–5 previous cesarean delivery1–4,6 or uterine surgery,5,6 previous uterine curettage,2,5,6 advanced maternal age,1,3–6 multiparity,1,4,6 and high gravidity.2,5,6 Increased female births also were associated with the event,7 but the etiology of placenta accreta remains vague and speculative. Previous observations did not account for important confounding variables, such as age, parity, and obstetric history. Some observations only evaluated retrospectively birth certificates that were often incomplete and subject to misclassification and information errors.
Two reports of maternal serum alpha-fetoprotein (AFP) screening suggested that there was increased frequency of placenta accreta among women with abnormally elevated serum marker levels.8,9 Because those studies had limited sample sizes, the prevalence of that risk is not clear. The Taiwan Down Syndrome Screening Group is a prospective study of feasibility of serum screening in an Asian population using AFP and free ß-hCG.10 The data gathered from the current study provided an opportunity to examine the risk factors of placenta accreta, with adjustment for potential confounding factors, including maternal serum levels of AFP and free ß-hCG, in a large cohort.
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Materials and Methods |
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Details of organization of the data base and measurements of maternal serum AFP and free ß-hCG were from earlier reports.10,11 Values of the two analytes were adjusted for maternal weight and expressed as multiples of the median (MoM). A serum AFP level greater than 2.5 MoM was used to define positive screens for open neural tube defect. For women with abnormally elevated serum AFP levels, a detailed ultrasound examination was done to rule out fetal neural tube defect or other congenital malformations. Serum free ß-hCG values greater than 2.5 MoM were considered elevated, which corresponded approximately to the mean MoM plus one standard deviation (SD) for our population.
Every woman received a detailed inquiry about her pregnancy, medical history, and exposure to potential risk factors during her first antenatal visit. Pregnancy outcome information was taken from labor and delivery records and reviewed weekly, with a postpartum interview, if necessary, to collect supplemental information.
In our institution, placenta accreta was diagnosed mostly by clinical presentation and histologic confirmation. We believe it is a clinical entity, because the problems obstetricians have with unduly adherent placentas are unaffected by whether later histologic examinations confirm true placenta accreta.5 We defined placenta accreta as the presence of one of the following criteria: 1) difficult manual, piecemeal removal of placenta, done if there was no evidence of placental separation 20 minutes after parturition, despite active management in third-stage labor, according to written hospital protocols, including intravenous infusion of synthetic oxytocin (Piton-S, N. V. Organon, Oss, Holland) of 5 IU after delivery, palpation of the uterine fundus, and transabdominal uterine massage if the uterus was not firm, and controlled, gentle cord traction; 2) sonographic evidence of retained placental fragments requiring curettage after a vaginal delivery; 3) heavy bleeding from implantation site after placental removal during cesarean, managed conservatively with excision of part of the uterine wall and the attached placenta, or oversewing the bleeding defects; and 4) histologic confirmation of a hysterectomy specimen.
Independent variables treated categorically in the analysis included 1) maternal factors such as age in years at delivery, gravidity, parity, obstetric history (fetal deaths and preterm deliveries), conception methods (natural or assisted by reproductive techniques), and diseases during pregnancy (pregnancy-induced hypertension, gestational diabetes); 2) previous uterine curettage, cesarean, uterine surgery, uterine malformations, and fibroids; and 3) other factors that include placenta previa, gestational age at delivery, and fetal gender.
Statistical analysis used SPSS for Windows, Release 7.0 (Statistical Package for Social Sciences; SPSS, Inc., Chicago, IL). Chi-square and Fisher exact tests were used to analyze categoric variables. Student t test was used for continuous variables. Multiple logistic regression was used to evaluate the association between placenta accreta and the various risk factors, while controlling for potentially confounding variables. Adjusted odds ratios (ORs) were calculated to approximate the relative risk from the regression coefficients, and the associated standard errors were used to determine 95% confidence intervals (CIs).
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Results |
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Table 1
compares the 28 women with placenta accreta with the 9321 controls. The mean (± standard deviation [SD]) gravidity and maternal serum levels of AFP and free ß-hCG were statistically significantly higher in women with placenta accreta than in controls. The percentage of women with 13 years or more of education also was higher among those with placenta accreta than among controls. There were no statistical differences in mean maternal age, parity, prepregnancy weight, gestational age at delivery, or birth weight. Incidence of other demographic variables, such as marital status, pregnancy-induced hypertension, gestational diabetes, history of fetal deaths, preterm delivery, or prepregnancy body mass index, were not significantly different between groups.
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summarizes the incidence of different potential determinants in the two groups. Incidences of placenta previa, second-trimester serum levels of AFP greater than 2.5 MoM, free ß-hCG greater than 2.5 MoM, gravida 5 or greater, three or more prior uterine curettages, and age 35 years or older were significantly higher in placenta accreta women than controls. No women with placenta accreta had second-trimester maternal serum AFP or free ß-hCG levels of less than 0.5 MoM, were para 4 or more, delivered at 42 weeks’ gestation or later, had uterine malformations, or had conception assisted by reproductive techniques; therefore, those variants were not included in the logistic regression model.
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. Placenta previa had the strongest association with placenta accreta as we defined it, with 54 times the risk. In women with abnormally elevated second-trimester serum levels of AFP and free ß-hCG, the likelihood of placenta accreta was increased eight and four times, respectively. Women who were 35 years of age or older also were at an increased risk of placenta accreta. We found an increasing trend in the risk of placenta accreta developing in women with previous uterine curettages and cesareans, based on a 
2 test for trend for those ordinal variables. Such association was not statistically significant when adjusted for other potential confounding factors in the multiple logistic regression. Other determinants that did not reach a statistically significant level of difference included gravidity, parity, gestational ages at delivery, previous uterine surgeries, fibroids, and fetal genders.
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Discussion |
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Previous observations suggested that cesarean deliveries, uterine surgeries and curettages, multiparity, high gravidity, and female fetal gender were significant risk factors of placenta accreta. The current study, after adjustments on mutually confounding effects among potential variants, was unable to confirm such associations. The discordance might be a result of the different methodologies in study designs, different diagnostic criteria of placenta accreta, or inability to include more cases with two or more prior cesarean deliveries in the short period of the study.
Ananth and colleagues,12 in a meta-analysis, found a strong association between previous cesarean deliveries, spontaneous or induced abortions, and placenta previa, the risk increasing with number of prior cesarean deliveries. Placenta previa might be further predisposed to placenta accreta because of inadequate decidual response of the lower uterine segment.13 Trophoblast adherence or invasion would be enhanced if previous myometrial disruption by cesarean or curettage further impaired the scant decidualization of the lower uterine segment.4,5 We observed that the association of previous cesareans or uterine curettages with placenta accreta was mediated largely by their effects on placenta previa. Histories of cesarean deliveries or uterine curettages without subsequent placenta previa seems to have little influence on developing placenta accreta.
Our data confirmed studies1–6 that found maternal ages of 35 years and older increasing risks of placenta accreta, even after adjustments for controlling confounding effects of potential determinants. Previous reports did not speculate on the biologic mechanism behind this association, perhaps because it was related to the progressive vascular endothelial damage that occurs with aging.14 Inadequate development of decidua or uteroplacental perfusion leads to implantation of the placenta toward the lower uterine segment, increasing the risk of placenta previa and accreta. Several studies found increasing trends in risks of placenta previa with increasing age.15,16 More information, especially histopathologic evidence, is needed to verify this hypothesis.
After excluding structural defects with ultrasound and amniocentesis, other causes for unexplained, elevated maternal serum AFP and free ß-hCG must be considered. Alpha-fetoprotein is synthesized early in gestation by the yolk sac, and later by the fetal gastrointestinal tract and liver. It is then excreted into fetal urine and transported to maternal serum through the placenta or by diffusion across fetal membranes.17,18 The placental interface with maternal circulation, the amnion, and fetal renal glomerular absorption are major barriers to diffusion.19 Theoretic mechanisms for elevated maternal serum levels of AFP with a structurally normal fetus were postulated as resulting from breakdown of the fetal-maternal-placental barrier,20 placental vascular damage from early abruption, feto-maternal bleeding,21,22 or fetoplacental ischemia.23ß-Human chorionic gonadotropin is produced by the placental cytotrophoblast and excreted directly into maternal circulation. Several factors were found that influence production of hCG by the trophoblast, including the number of trophoblastic cells24; decrease in oxygen to the cytotrophoblast, resulting in increased hCG production by hyperplasia of the cells25; and inflammatory cytokines.26 Because the characteristic histopathologic feature of placenta accreta is total or partial absence of the decidua basalis, the placental villi are usually normal. They do not usually show evidence of trophoblastic abnormalities or hyperplasia.5 The amniotic fluid AFP levels are usually normal in women with unexplained, elevated maternal serum AFP.9 As a result of our observation that elevated maternal serum levels of AFP or free ß-hCG with structurally normal fetuses are significantly associated with placenta accreta, increases of these biochemical markers in this clinical condition might be caused by disruption of the maternal-fetal interface, which can lead to greater than normal transfer of AFP and free ß-hCG. The increase might be caused by increased surface area, across which AFP and free ß-hCG can diffuse from the fetoplacental to maternal circulation.21 Our results further indicated that abnormally elevated maternal serum levels of those biochemical markers might operate through the same mechanism. With unexplained second-trimester AFP or free ß-hCG elevation, an ultrasonographic examination to exclude placental accreta, confirm gestational age, and rule out fetal abnormality appears necessary.
Because we used clinical recognition of abnormal uteroplacental adherence as the basis for diagnosis of placenta accreta, there might be discordance between suspected and histologically confirmed cases. Miller and colleagues3 stated that clinical suspicion of placenta accreta was unreliable, with only 48% of cases identified correctly by means of microscopy of hysterectomy specimens. Jacques and coworkers6 found that careful histopathologic examination of the placenta might show mild or focal forms of placenta accreta in cases not requiring hysterectomy, even without clinical suspicion. Thus, the exclusion of histologically unconfirmed cases might not find true incidence of placenta accreta. Failure to find myometrial tissue adherent to the maternal surface of the placenta cannot be used to exclude diagnoses of placenta accreta, because the entire surface is not sampled, and even in areas of intact cotyledons, there might be no myometrial tissue adherent to the placenta, depending on the plane of abnormal separation.6
Another limitation might be the possibility of selection bias, because the study was hospital-based and might not represent the general population. We believe that this is a strength of the present study rather than a limitation, because by using a homogeneous group of women who had prenatal care at the same hospital, we minimized the risk of unaccounted confounding variables. The inclusion of pregnant women having second-trimester serum screening, complete pregnancy outcome information, and exclusion of births occurring after high-risk antenatal referral, provided some protection against that bias.
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Footnotes |
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Received July 2, 1998. Received in revised form September 15, 1998. Accepted October 1, 1998.
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2. Breen JL, Neubecker R, Gregori CA, Franklin JE. Placenta accreta, increta, and percreta. Obstet Gynecol 1977;49:43–7.
3. Miller DA, Chollet JA, Goodwin TM. Clinical risk factors for placenta previa–placenta accreta. Am J Obstet Gynecol 1997;177:210–4.[Medline]
4. Clark SL, Koonings PP, Phelan JP. Placenta previa/accreta and prior cesarean section. Obstet Gynecol 1985;66:89–92.
5. Fox H. Placenta accreta, 1945–1969. Obstet Gynecol Surv 1972;27: 475–90.
6. Jacques SM, Qureshi F, Trent VS, Ramirez NC. Placenta accreta: Mild cases diagnosed by placental examination. Int J Gynecol Pathol 1996;15:28–33.[Medline]
7. Khong TY, Healy DL, McCloud PI. Pregnancies complicated by abnormally adherent placenta and sex ratio at birth. BMJ 1991;302: 625–6.
8. Zelop C, Nadel A, Frigoletto FD Jr, Pauker S, MacMillan M, Benacerraf BR. Placenta accreta/percreta/increta: A cause of elevated maternal serum alpha-fetoprotein. Obstet Gynecol 1992;80: 693–4.
9. Kupferminc MJ, Tamura RK, Wigton TR, Glassenberg R, Socol ML. Placenta accreta is associated with elevated maternal serum alpha-fetoprotein. Obstet Gynecol 1993;82:266–9.
10. Hsu JJ, Hsieh TT, Hsieh FJ. Down syndrome screening in an Asian population using alphafetoprotein and free ß-hCG: A report of the Taiwan Down Syndrome Screening Group. Obstet Gynecol 1996; 87:943–7.[Abstract]
11. Hsieh TT, Hung TH, Hsu JJ, Shau WY, Su CW, Hsieh FJ. Prediction of adverse perinatal outcome by maternal serum screening for Down syndrome in an Asian population. Obstet Gynecol 1997;89:937–40.[Abstract]
12. 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.[Medline]
13. Kistner RW, Hertig AT, Reid DE. Simultaneously occurring placenta previa and placenta accreta. Surg Gynecol Obstet 1952;94:141–4.
14. Naeye RL. Maternal age, obstetric complications, and the outcome of pregnancy. Obstet Gynecol 1983;61:210–6.
15. Zhang J, Savitz DA. Maternal age and placenta previa: A population-based case-control study. Am J Obstet Gynecol 1993;166: 641–5.
16. Ananth CV, Wilcox AJ, Savitz DA, Bowes WA Jr, Luther ER. Effect of maternal age and parity on the risk of uteroplacental bleeding disorders in pregnancy. Obstet Gynecol 1996;88:511–6.[Abstract]
17. Los FJ, De Bruijn HW, van Beek Calkoen-Carpay T, Huisjes HJ. AFP transport across the fetal membranes in the human. Prenat Diagn 1985;5:277–81.[Medline]
18. Brumfield CG, Cloud GA, Davis RO, Finley SC, Hauth JL, Boots L. The relationship between maternal serum and amniotic fluid 
-fetoprotein in women undergoing early amniocentesis. Am J Obstet Gynecol 1990;163:903–5.[Medline]
19. Elias S, Simpson JL, eds. Maternal serum screening for fetal genetic disorders. New York, NY: Churchill Livingstone, 1992.
20. Berkeley AS, Killackey MA, Cederqvist LL. Elevated maternal serum alpha-fetoprotein levels with breakdown in fetal-maternal-placental barrier. Am J Obstet Gynecol 1983;146:859–61.[Medline]
21. Perkes EA, Baim RS, Goodman KJ, Marci JN. Second trimester placental changes associated with elevated maternal -fetoprotein. Am J Obstet Gynecol 1982;144:935–8.[Medline]
22. Salafia CM, Silberman L, Herrera NE, Mahoney MJ. Placental pathology at term associated with elevated midtrimester maternal serum -fetoprotein concentration. Am J Obstet Gynecol 1988;158: 1064–6.[Medline]
23. Spong CY, Ghidini A, Walker CN, Ossandon M, Pezzullo JC. Elevated maternal serum midtrimester alpha-fetoprotein levels are associated with fetoplacental ischemia. Am J Obstet Gynecol 1997;177:1085–7.[Medline]
24. Easterman A, Finlay TH, Dancis J. The effect of hypoxia on term trophoblast: Hormone synthesis and release. Placenta 1996;17:217–22.[Medline]
25. Fox H. Effect of hypoxia on trophoblast in organ culture: A morphologic and autoradiographic study. Am J Obstet Gynecol 1970;107:1058–64.[Medline]
26. Li Y, Matsuzaki N, Masuhiro K, Kameda T, Taniguchi T, Saji F, et al. Trophoblast-derived tumor necrosis factor induces release of human chorionic gonadotropin using interleukin-6 (IL-6) and IL-6 receptor-dependent system in the normal human trophoblast. J Clin Endocrinol Metab 1992;74:184–91.[Abstract]
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