To assess for the influence of possible confounding variables, a logistic regression model was generated. After controlling for race, maternal age, marital status, insurance status, number of fetuses, maternal disease, and prenatal care, all of the significant associations between maternal morbidities and increasing number of cesarean deliveries remained similar and statistically significant. For example, the unadjusted odds ratio (OR) for placenta accreta with increasing number of cesarean deliveries as a continuous variable is 1.949 (95% confidence interval [CI] 1.724–2.204). The adjusted OR is 1.750 (95% CI 1.533–1.997). For hysterectomy, the unadjusted OR is 1.752 (95% CI 1.569–1.956), and the adjusted OR is 1.594 (95% CI 1.418–1.793).
There were too many medical centers (n = 19) included in the study to include them all in a model to address the potential effect of center-to-center variation. However, the three centers contributing the most patients were included in a multivariable model. Again, all of the associations between maternal morbidities and increasing number of cesarean deliveries remained similar and statistically significant. Thus, it is unlikely that center-to-center variation influenced our results.
Serious maternal morbidity increases with increasing number of cesarean deliveries. The majority of this risk is attributable to that associated with placenta accreta and/or the need for hysterectomy. Placenta accreta was present in more than 2% of patients having their fourth and in 6.7% of those undergoing their sixth or greater cesarean delivery. Almost 1 in 40 (2.4%) women undergoing their fourth cesarean delivery required hysterectomy (compared with 0.65% of primary cesareans); the risk increased to 1 in 11 (9%) having their sixth or greater procedure. In the absence of placenta accreta or the need for hysterectomy, there still was an association between maternal morbidity and increasing cesarean delivery number for all morbidities other than deep venous thrombosis. Thus, even in the absence of placenta previa or placenta accreta, women undergoing multiple repeat cesarean deliveries cannot be entirely reassured. Other surgical morbidity, including blood transfusion of 4 units or more, cystotomy, bowel injury, ureteral injury, previa, ileus, the need for (maternal) postoperative ventilation, intensive care unit admission, operative time, and days of hospitalization, also was increased with increasing number of cesarean deliveries.
Previous studies examining the risk of surgical morbidity with repeat cesarean delivery have reported mixed results. Some have reported no association.10,11 We speculate that this discrepancy may be due to the relatively small number of subjects included in those cohorts. We performed a PubMed search of papers written in English from January 1980 to August 2005, using the keywords “cesarean delivery,” “multiple,” and “complications.” In the largest previously reported cohort of repeat cesarean deliveries, including 3,191 cases from Saudi Arabia (1,585 with 3 or more cesarean deliveries), Makoha and colleagues also noted increased maternal morbidity, including placenta previa, placenta accreta, hysterectomy, adhesions, bladder injury, postoperative hemoglobin deficit, and need for blood transfusion with increasing number of cesarean deliveries.12 As with our cohort, most morbidity was associated with placenta accreta and hysterectomy.
Although repeat cesarean delivery was associated with increased maternal morbidity, outcomes were good in most women undergoing these procedures. Maternal death was rare, and in only 2 cases (in women having their second cesarean delivery) could it potentially be attributable to cesarean delivery morbidity. Thus, there does not appear to be an absolute threshold number of cesarean deliveries beyond which patients should be unequivocally counseled to forgo future pregnancies. Others also have not definitively delineated a threshold for number of cesarean deliveries.11,12 On the other hand, our study did not have enough power to adequately evaluate whether rare but serious events such as death were increased with increasing number of cesarean deliveries. Indeed, the rates for rare complications are estimates, especially in women with 4 or more cesarean deliveries. Nonetheless, there was a substantial increase in the risk for several morbidities, including placenta accreta, cystotomy, and need for hysterectomy or intensive care unit admission with the fourth or greater cesarean delivery. Women should be counseled regarding the progressive increase in the risk for meaningful morbidity with repeat cesarean deliveries.
The rate of placenta previa (after the first cesarean delivery) increased with increasing number of cesarean deliveries in our cohort. This is similar to others who reported an association between repeat cesarean deliveries and placenta previa.12,16 However, Hershkowitz and colleagues17 found no association between many cesarean deliveries and placenta previa. Different results may be attributable to differences in patient population because the Hershkowitz study included relatively few women having their fourth or greater cesarean delivery.17 We cannot comment on the relative effects of parity, a known risk factor for placenta previa,18 because our cohort included only cesarean deliveries, as opposed to all deliveries.
Our results confirmed the strong association between placenta accreta and increasing number of cesarean deliveries in women with placenta previa.12,19 In cases of placenta previa, the risk of placenta accreta was 40% for those having their third cesarean delivery and over 60% for the fourth or greater cesarean delivery. These results are similar to previous studies.12,19 However, placenta accreta occurred in only 11% of our patients having their second cesarean delivery with a placenta previa. This is substantially less than the risk of 24% that has been generally accepted.19 The subjective nature of the diagnosis in some cases may account for differences among studies. Also, the current study includes substantially more women with placenta previa and prior cesarean delivery than previous investigations. Finally, because the data are more recent, they may more accurately reflect current management of placenta previa in the setting of prior cesarean delivery. Another recent cohort found no placenta accretas in 23 women with placenta previa and one prior cesarean delivery.12
The large percentage of cases performed by resident physicians may introduce bias toward unfavorable outcomes and is a potential limitation of the study. It is not possible to evaluate this issue since participation of resident physicians in each case was not assessed. The relatively large proportion of “high risk” cases seen in these referral centers is an additional potential source of bias toward worse outcomes. Conversely, the inclusion of cases from mostly tertiary care, large, urban hospitals may introduce bias toward more favorable outcomes because of the availability of blood banks and consultant subspecialty surgeons. Accordingly, results may not be generalizable to smaller rural hospitals, and our data likely underestimate the actual risk in smaller hospitals without special services. Another possible limitation was our use of a clinical definition for placenta accreta. However, histologic diagnosis of placenta accreta was not always possible because not all women given the diagnosis of placenta accreta underwent hysterectomy. Finally, obesity was a potential confounder. As expected with increasing parity and age, obesity was more common in women with increasing number of cesarean deliveries. Although obesity is a known risk factor for cesarean morbidity,20 it was unlikely to account for the most serious morbidities in the study, such as placenta accreta. Data regarding obesity were incomplete, with 30% of patients having missing values. Thus, it was not possible to adequately assess the effects of obesity in a multivariable model.
A major strength of the study was its size. This cohort is substantially larger than previous investigations, including over 6,000 women with third cesarean deliveries, almost 1,500 with fourth cesarean deliveries, and 347 with fifth or greater cesarean deliveries. The cohort also included 723 women with placenta previa. Other strengths include an inclusive prospective cohort, multicenter participation, recent data reflecting current management of placenta accreta, and the use of trained obstetric research nurses for data collection.
We believe that our data have important implications for counseling patients regarding elective cesarean delivery and trial of labor after previous cesarean delivery. The cesarean delivery rate in the United States is currently over 29% and continues to rise.1 We estimate that over 80,000 women in the United States had their fourth or more cesarean delivery last year, a number that will certainly increase. Although the general safety of cesarean delivery is well established,3–5 morbidity from multiple procedures may not be taken into account. It is important to consider not only the morbidity from the initial cesarean delivery, but that from subsequent pregnancies as well. Thus, women planning large families should consider the risks of repeat cesarean deliveries when contemplating elective cesarean delivery or attempted vaginal birth after cesarean delivery. Our data also will facilitate counseling of women with placenta previa and prior cesarean deliveries regarding their risks of placenta accreta.
1. Menacker F. Trends in cesarean rates for first births and repeat cesarean rates for low-risk women: United States, 1990–2003. Natl Vital Stat Rep 2005;54:1–8.
2. Lockwood C. Why the CD rate is on the rise (Part 1). Contemporary OB/Gyn 2004;Oct 1:8–11.
3. Paterson-Brown S, Fisk NM. Caesarean section: every woman’s right to choose? Curr Opin Obstet Gynecol 1997;9:351–5.
4. Frigoletto FD Jr., Ryan KJ, Phillippe M. Maternal mortality rate associated with cesarean section: an appraisal. Am J Obstet Gynecol 1980;136:969–70.
5. Sachs BP, Kobelin C, Castro MA, Frigoletto F. The risks of lowering the cesarean-delivery rate. N Engl J Med 1999;340:54–7.
6. Greene MF. Vaginal birth after cesarean revisited. N Engl J Med 2004;351:2647–9.
7. Seidman DS, Paz I, Nadu A, Dollberg S, Stevenson DK, Gale R, et al. Are multiple cesarean sections safe? Eur J Obstet Gynecol Reprod Biol 1994;57:7–12.
8. Kirkinen P. Multiple caesarean sections: outcomes and complications. Br J Obstet Gynaecol 1988;95:778–82.
9. Tamale-Sali EG, Iskander MN. Is there a risk of lower segment scar rupture in pregnancy after multiple caesarean section? J Obstet Gynecol 1992;12:19–21.
10. Soltan MH, Al Nuaim L, Khashoggi T, Chowdhury N, Kangave D, Adelusi B. Sequelae of repeat cesarean sections. Int J Gynaecol Obstet 1996;52:127–32.
11. Lynch CM, Kearney R, Turner MJ. Maternal morbidity after elective repeat caesarean section after two or more previous procedures. Eur J Obstet Gynecol Reprod Biol 2003;106:10–3.
12. Makoha FW, Felimban HM, Fathuddien MA, Roomi F, Ghabra T. Multiple cesarean section morbidity. Int J Gynaecol Obstet 2004;87:227–32.
13. Landon MB, Hauth JC, Leveno KJ, Spong CY, Leindecker S, Varner MW, et al. Maternal and perinatal outcomes associated with a trial of labor after prior cesarean delivery. N Engl J Med 2004;351:2581–9.
14. Margolin B. Test for trend in proportions. In: Klotz S, Johnson NL, editors. Encyclopedia of statistical sciences. Vol. 9. New York (NY): John Wiley & Sons; 1988. p. 334–6.
15. Pirie W. Jonckheere tests for ordered alternatives. In: Klotz S, Johnson NL, editors. Encyclopedia of statistical sciences. Vol. 4. New York (NY): John Wiley & Sons; 1983. p. 315–8.
16. Gilliam M, Rosenberg D, Davis F. The likelihood of placenta previa with greater number of cesarean deliveries and higher parity. Obstet Gynecol 2002;99:976–80.
17. Hershkowitz R, Fraser D, Mazor M, Leiberman JR. One or multiple previous cesarean sections are associated with similar increased frequency of placenta previa. Eur J Obstet Gynecol Reprod Biol 1995;62:185–8.
18. Babinszki A, Kerenyi T, Torok O, Grazi V, Lapinski RH, Berkowitz RL. Perinatal outcome in grand and great-grand multiparity: effects of parity on obstetric risk factors. Am J Obstet Gynecol 1999;181:669–74.
19. Clark SL, Koonings PP, Phelan JP. Placenta previa/accreta and prior cesarean section. Obstet Gynecol 1985;66:89–92.
20. Hall LF, Neubert AG. Obesity and pregnancy. Obstet Gynecol Surv 2005;60:253–60.
In addition to the authors, other members of the National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network are as follows:
Ohio State University: J. Iams, F. Johnson, S. Meadows, H Walker
University of Alabama at Birmingham: D. Rouse, A. Northen, S. Tate
University of Texas Southwestern Medical Center: S. Bloom, J. McCampbell, D. Bradford
University of Utah: M. Varner, M. Belfort, F. Porter, B. Oshiro, K. Anderson, A. Guzman
University of Chicago: J. Hibbard, P. Jones, M. Ramos-Brinson, M. Moran, D. Scott
University of Pittsburgh: K. Lain, M. Cotroneo, D. Fischer, M. Luce
Wake Forest University: M. Harper, M. Swain, C. Moorefield, K. Lanier, L. Steele
Thomas Jefferson University: A. Sciscione, M. DiVito, M. Talucci, M. Pollock
Wayne State University: M. Dombrowski, G. Norman, A. Millinder, C. Sudz, B. Steffy
University of Cincinnati: T. Siddiqi, H. How, N. Elder
Columbia University: F. Malone, M. D’Alton, V. Pemberton, V. Carmona, H. Husami
Brown University: H. Silver, J. Tillinghast, D. Catlow, D. Allard
Northwestern University: M. Socol, D. Gradishar, G. Mallett
University of Miami, Miami, FL: G. Burkett, J. Gilles, J. Potter, F. Doyle, S. Chandler
University of Tennessee: W. Mabie, R. Ramsey
University of Texas at San Antonio: O. Langer, S. Barker, M. Rodriguez
University of North Carolina: K. Moise, K. Dorman, S. Brody, J. Mitchell
University of Texas at Houston: L. Gilstrap, M. Day, M. Kerr, E. Gildersleeve
Case Western Reserve University: P. Catalano, C. Milluzzi, B. Slivers, C. Santori
The George Washington University Biostatistics Center: C. MacPherson, S. Gilbert, H. Juliussen-Stevenson, M. Fischer
National Institute of Child Health and Human Development: D. McNellis, K. Howell, S. Pagliaro
Vanderbilt University: S. Gabbe