Clinical Significance of Placenta Previa Detected at Early Routine Transvaginal Scan

Clinical Significance of Placenta Previa Detected at Early Routine Transvaginal Scan Paolo Rosati, MD, Lorenzo Guariglia, MD Transvaginal ultrasonography in early pregnancy was used to determine the prevalence of placenta previa and the rate of persistence until delivery. The location of the placenta was registered systematically in 2342 pregnant women who underwent transvaginal ultrasonography at 10 to 16 weeks gestation as a primary examination. The outcome of pregnancy as well as the presence or absence of placenta previa at delivery was noted in a total of 2158 cases. A receiver operating characteristic curve was generated for the different measurements from the edge of the placenta to the internal cervical os versus placenta previa at delivery. In 105 of the 2158 women screened in the early stages of pregnancy (4.9%) the placenta extended to or over the internal P lacenta previa leads to increased maternal and fetal morbidity, caused primarily by hemorrhage, particularly in undiagnosed ABBREVIATIONS TVS, Transvaginal sonography; ICO, Internal cervical os; ROC, Receiver operating characteristic; CI, Confidence interval; SD, Standard deviation; PPV, Positive predictive value; NPV, Negative predictive value Received January 13, 2000, from the Department of Obstetrics and Gynecology, Catholic University of the Sacred Heart, Rome, Italy. Revised manuscript accepted for publication May 4, 2000. This study was supported by grants No. 98.03047.CT04 from the Italian Council of Research (CNR) and No. 8101651-98 from the Ministry of University and Scientific and Technological Research (MURST). Address correspondence and reprint requests to Paolo Rosati, MD, Department of Obstetrics and Gynecology, Catholic University of the Sacred Heart, Largo A. Gemelli, 8 00168 Rome, Italy. cervical os, and in 34 of 2158 patients (1.6%) the distance to the placental edge beyond the internal cervical os was equal to or greater than 14 mm. Of the eight cases of placenta previa at delivery, six (75%) were identified in our study, and two cases were missed. When a cutoff value of greater than 14 mm is used for the receiver operating characteristic curve the likelihood is 17.6% (95% confidence interval = 6.8 to 34.5) for placenta previa at delivery. Although a high percentage of false-positive results occur owing to the low prevalence at delivery, this screening procedure can identify high-risk patients who should be rescanned later in pregnancy. KEY WORDS: Placenta previa; Pregnancy, early; Ultrasonography, transvaginal. cases. 1,2 Thus, an accurate and early diagnosis of placenta previa would be important and useful in clinical obstetrical practice. Recently, with the introduction of high-frequency TVS, earlier and safer visualization of the lower placental edge and the ICO is possible by the transabdominal route, 3,4 and therefore a more timely and accurate diagnosis of placenta previa is feasible. The aims of the present study were to evaluate retrospectively (1) the ability to predict in early pregnancy, using TVS, the risk of placenta previa at delivery and (2) the usefulness of an early assessment of placental location in relation to the ICO and its implications for the normal evolution of pregnancy. In addition, we examined whether the distance the placenta extended over the ICO had clinical significance. 2000 by the American Institute of Ultrasound in Medicine J Ultrasound Med 19:581 585, 2000 0278-4297/00/$3.50

582 PLACENTA PREVIA AT EARLY SCANNING J Ultrasound Med 19:581 585, 2000 SUBJECTS AND METHODS During the period April 1995 through February 1999, a cross-sectional study of TVS examinations in 2342 pregnant patients with a live singleton fetus between 10 and 16 weeks gestation was performed. The reasons for referral of patients were advanced maternal age (73.7%), family history of chromosomal or morphologic abnormalities (14.7%), abnormal results of second trimester maternal serum screening for fetal aneuploidy (5.1%), and other indications (6.5%). In addition to fetal measurements and morphologic evaluation, the location of the placenta was registered systematically, and in cases of placental extension to or over the ICO, the distance from the edge of the placenta to the ICO was measured. When the placenta did not reach the ICO, the distance of the nearest placental edge to the ICO was also measured, and a negative measurement was assigned. These cases are not considered for the study. Placental position (anterior or posterior) also was recorded. Excluded from the study were 184 patients: 151 cases were lost to follow-up, 9 elected termination of pregnancy elsewhere on maternal request, and 24 resulted in spontaneous abortion. The pregnancy outcome and the presence or absence of placenta previa at delivery were determined in 2158 cases. The mean age of the patients was 32.1 years (range, 16 to 44 years); 53% of the mothers were nulliparous, whereas 34% had one and 13% had two or more previous births. In order to evaluate the reproducibility of the measurements, 40 patients were studied by two independent observers (P.R., L.G.), and the differences in measurements were calculated for each case. All of the patients had three different consecutive measurements of the distance from the edge of the placenta to the ICO taken by each sonographer, who was unaware of the results obtained by the other. The interobserver and intraobserver coefficient of variation were calculated. Sonographic examinations were performed using a high-resolution apparatus (model SSA-270 A and SSA-340 A; Toshiba Medical Corporation, Tokyo, Japan) equipped with 5.0 to 7.0 MHz transvaginal probes with a maximal angle of vision of 86 degrees and 121 degrees, respectively. All the scans were performed by the authors (60% by P.R., 40% by L.G.). The patients were examined in a supine lithotomy position with an empty bladder. The lower edge of the placenta and the ICO were identified with the probe placed in the anterior fornix of the vagina. The measurements were obtained with electronic calipers, and in each case two measurements were performed, of which the shorter was used. Placenta previa was defined as the presence of a placenta extending to or over the ICO; the condition was considered marginal if the distance to the placental edge beyond the ICO was 10 mm or less at ultrasonographic examination, and as total if the distance was greater than 10 mm. An ROC curve was generated for the different measurements from the edge of the placenta to the ICO versus placenta previa at delivery and is provided to allow assessment of cutoff values that meet sensitivity and specificity requirements. A cutoff value was chosen that maximized the sensitivity while minimizing the false positive rate (1- specificity). 5 Statistical analysis to compare the placental location (anterior versus posterior) was obtained using the chi-square test, with statistical significance of differences assigned at P < 0.01. Binomial exact 95% CI values were calculated using Stata 6.0 software (Stata, College Station, TX). RESULTS The presence of placental extension to or over the ICO was diagnosed in a total of 105 women (4.9%) among the 2158 patients who underwent early transvaginal scanning. The prevalence was 6.4% at 10 weeks gestation and diminished to 4.3% at 16 weeks gestation but was fairly constant between 12 and 15 weeks gestation with a value of about 5%. In 58 cases (55.2%) the placenta was anterior and in 47 (44.8%) it was posterior. This difference was not statistically significant. In 69 cases (65.7%) the placenta previa was defined as marginal, and in 36 cases (34.3%) it was categorized as total. Of the 69 cases with a TVS diagnosis of marginal placenta previa, only one was associated with a bleeding episode prior to term; this case would have been diagnosed regardless and was confirmed at the cesarean delivery. The mean values of interobserver and intraobserver measurements (± SD) for the location of the placenta over the ICO were 0.8 ± 0.4 and 0.7 ± 0.4, respectively, and the coefficient of variation was 0.5% and 0.6%, respectively. Eight of the 2158 women (0.37%) had placenta previa at delivery, and two cases were undiagnosed by early transvaginal scan (Table 1). The diagnosis of placenta previa was confirmed in all eight cases by ultrasonographic examination performed in the third trimester of pregnancy. The ROC curve generated from the various measurements of the placental edge extending over the

J Ultrasound Med 19:581 585, 2000 ROSATI AND GUARIGLIA 583 Table 1: Placental Characteristics and Pregnancy Outcome Screening Outcome GA at TVS Extension of Placenta Initial Bleeding GA at Delivery Mode of Type of (weeks) Over ICO (mm) Episode (GA) (weeks) Delivery Placenta Previa 12.3 15 30.3 33.0 CD Total 11.4 29 27.1 29.4 CD Total 13.2 16 26.4 31.2 CD Total 12.6 21 33.1 35.4 CD Marginal 14.1 18 34.0 36.2 CD Marginal 13.0 26 29.6 34.4 CD Total 12.1 7 35.3 38.2 CD Marginal 15.3 * 38.2 39.1 CD Marginal GA, Gestational age; CD, cesarean delivery. *Posterior placenta not extending over the ICO. ICO shows 14 mm as the most efficient cutoff point optimizing both sensitivity and specificity (Fig. 1). With a cutoff value of 14 mm, 34 of the 105 patients (32.4%) in whom the placenta extended to or over the ICO at TVS were screen-positive, and 6 had a placenta previa found at delivery (17.6%; 95% CI = 6.8 to 34.5). With a cutoff value of 12 mm, 42 patients (40%) were screen-positive, and 14.3% (6/42; 95% CI = 5.4 to 28.5) of cases persisted to delivery. With a cutoff value of 16 mm, 27 patients (25.7%) were screen-positive, and 4 had placenta previa at delivery (14.8%; 95% CI = 4.2 to 33.7) (Table 2). DISCUSSION In our study, performed between 10 and 16 weeks gestation, 4.9% of the women screened revealed a placenta that extended to or over the ICO. These data are slightly less than those reported by Hill and coworkers 6 and by Taipale and colleagues 7 for the same gestation period of 9 to 13 weeks, and they are higher than those reported by Lauria and coauthors 8 and by Taipale and associates 9 for midpregnancy by either transvaginal or transabdominal ultrasonography. These results reporting a higher prevalence at 9 to 13 weeks gestation may possibly be attributed to the rate of the placental migration, since from the fourth month until delivery the placenta grows more slowly than the uterus, 10,11 and the development of the lower uterine segment is more rapid than that of the uterine fundus. Because of this phenomenon, Townsend and coworkers 12 preferred the terminology differential lower uterine segment/placental growth rate to describe changes in the position of the placenta. Subsequently, the development of the lower uterine segment permitted a vaginal delivery in over 90% of cases diagnosed as associated with placenta previa by a second trimester sonographic examination, 11 further supporting a high false-positive rate for placenta previa when early placental location is used. Moreover, placental migration also occurs in the first half of pregnancy. Taipale and colleagues 7 reported a prevalence of placenta previa by transvaginal scanning of 5.5% at 12 to 13 weeks of gestation, which decreased to 2.4% at 15 to 16 weeks gestation. Placental migration from the region of Figure 1 ROC curve generated for placenta previa at delivery in 105 patients with the placenta edge extending to or over the ICO with different cutoff points (in millimeters) at screening. A cutoff value was chosen that maximized the sensitivity while minimizing the false-positive rate (1-specificity).

584 PLACENTA PREVIA AT EARLY SCANNING J Ultrasound Med 19:581 585, 2000 Table 2: Placenta Previa Observed at 10 to 16 Weeks Transvaginal Screening (105 Cases) in Predicting Placenta Previa at Delivery Placental Edge over the ICO at TVS 12 mm 14 mm 16 mm Variable n/n % (95% CI) n/n % (95% CI) n/n % (95% CI) Sensitivity 6/7 85.7 (41.1, 99.6) 6/7 85.7 (42.1, 99.6) 4/7 57.1 (18.4, 90.1) Specificity 62/98 63.3 (52.9, 72.8) 70/98 71.4 (61.4, 80.1) 75/98 76.5 (66.9, 94.5) PPV 6/42 14.3 (5.4, 28.5) 6/34 17.6 (6.8, 34.5) 4/27 14.8 (4.2, 33.7) NPV 62/63 98.4 (91.5, 99.9) 70/71 98.6 (92.4, 99.9) 75/78 96.2 (89.2, 99.2) the ICO occurred at a variable rate that was not always related to the degree to which the placenta covered the ICO. In some cases a marked change in placental location was noted between the first and second trimesters, whereas in other cases the ICO region was not free of the placenta until the third trimester. 6 In our study, the percentage of the placenta that covered the ICO remained quite similar between 11 and 15 weeks gestation. The different prevalence rates for low-lying placenta observed with transabdominal versus transvaginal scanning not only are related to the gestational age at which the sonographic examination was performed but also reflect attention to scanning technique. In fact, higher false-positive rates of placenta previa are found with the transabdominal than with the transvaginal technique and may possibly be due to an overdistended bladder, uterine contractions, or poor visualization. 8,13 In our study, if at 10 to 16 weeks gestation the edge of the placenta extended for at least 14 mm over the ICO, the PPV of placenta previa at delivery was 17.6% (95% CI = 6.8 to 34.5). This cutoff point was quite similar to that previously reported by Hill and coworkers 6 at 9 to 13 weeks gestation and by Taipale and colleagues 7 at 12 to 16 weeks gestation. In addition, the risk of placenta previa at delivery in our study was similar to the 20% reported by Hill and coauthors 6 but higher than the 5.1% and 4.6% reported by Taipale and coworkers 7 and Zelop and associates, 14 respectively. A higher risk of 18.5% in predicting placenta previa at delivery was also described by Taipale and associates9 when transvaginal sonography was performed at 18 to 23 weeks gestation. The prevalence of placenta previa at delivery ranged from 1.5 to 6.0 per 1000 births. 2,3,8,9,11,13,15,16 In our study, placenta previa occurred at delivery in 1 of 270 cases (0.37%), data similar to those reported in a large epidemiological study 13 but greater when compared to other recent studies of a low-risk population. 8,9 Furthermore, racial, genetic, age, and parity differences 2,13,17 may exist in the prevalence of placenta previa. The findings of our study indicate that, by transvaginal scanning at 10 to 16 weeks gestation and using a 14 mm overlap as the cutoff point, 75% of the cases of placenta previa at delivery were identified. In two cases placenta previa was present at delivery, but the placental edge covering the ICO was less than 14 mm at screening. Finally, of the total number of the cases in which the distance to the placental edge beyond the ICO was equal or greater than 14 mm, the likelihood was that only 17.6% (95% CI = 6.8 to 34.5) will result in a clinical placenta previa at delivery. Notwithstanding, despite the high percentage of false-positive results related to the low prevalence of this pathologic condition at delivery, the precise location of the placenta as diagnosed by early transvaginal scan could be considered to be the first, accurate prediction of patients at risk for placenta previa. Placenta previa is frequently revealed with bleeding episodes prior to term, which facilitates a diagnosis, but it may be asymptomatic 14 and appear as a sudden catastrophic hemorrhage or bleeding as the pregnancy approaches term, putting both the mother and fetus at increased risk for a poor outcome. 18 Since, in our experience, the measure of placental extension diagnosed by TVS remained fairly constant from 12 to 15 weeks gestation, an early TVS at this particular period of pregnancy could provide a useful criterion for diagnosing cases of possible placenta previa that would need an ultrasonographic reexamination in the third trimester of pregnancy.

J Ultrasound Med 19:581 585, 2000 ROSATI AND GUARIGLIA 585 REFERENCES 1. Meshame PM, Heye PS, Epstein MF: Maternal and perinatal morbidity resulting from placenta previa. Obstet Gynecol 65:176, 1985 2. Gorodeski IG, Bahari CM: The effect of placenta previa localization upon maternal and fetal-neonatal outcome. J Perinat Med 15:167,1987 3. Chapman MG, Furness ET, Jones WR, et al: Significance of the ultrasound location of placenta site in early pregnancy. Br J Obstet Gynaecol 86:846, 1979 4. Timor-Tritsch IE, Yunis RA: Confirming the safety of transvaginal sonography in patients suspected of placenta previa. Obstet Gynecol 81,742, 1993 5. Richardson DK, Schwartz JS, Weinbaum PJ, et al: Diagnostic test in obstetrics: A method for improved evaluation. Am J Obstet Gynecol 152:613, 1985 6. Hill LM, Di Nofrio DM, Chenevey P: Transvaginal sonographic evaluation of first-trimester placenta previa. Ultrasound Obstet Gynecol 5:30, 1995 7. Taipale P, Hilesmaa V, Ylostalo P: Diagnosis of placenta previa by transvaginal sonographic screening at 12-16 weeks in a non selected population. Obstet Gynecol 89:364, 1997 8. Lauria MR, Smith RS, Treadwell MC, et al: The use of second-trimester transvaginal sonography to predict placenta previa. Ultrasound Obstet Gynecol 8:337, 1996 9. Taipale P, Hiilesmaa V, Ylostalo P: Transvaginal ultrasonography at 18 23 weeks in predicting placenta previa at delivery. Ultrasound Obstet Gynecol 12:422, 1998 10. King DL: Placental migration demonstrated by ultrasonography. Radiology 109:167, 1973 11. Rizos N, Doran TA, Miskin M, et al: Natural history op placenta previa ascertain by diagnostic ultrasound. Am J Obstet Gynecol 133:287, 1979 12. Townsend RR, Laing FC, Nyberg DA, et al: Technical factors responsible for placental migration : Sonographic assessment. Radiology 160:105, 1986 13. Iyasu S, Saftlas AK, Rowley DL, et al: The epidemiology of placenta previa in the United States, 1979 through 1987. Am J Obstet Gynecol 168:1424, 1993 14. Zelop CC, Bromley B, Frigoletto FD, et al: Second trimester sonographically diagnosed placenta previa: Prediction of persistent previa at birth. Int J Gynecol Obstet 44:207, 1994 15. Mills JL, Graubard BI, Klebanoff MA: Association of placenta previa and sex ratio at birth. Br Med J 294:544, 1987 16. Saari-Kemppainen A, Karjalainen O, Ylostalo P, et al: Ultrasound screening and perinatal mortality: Controlled trial of systematic one-stage screening in pregnancy. Lancet 336:38, 1990 17. Rose GL: Aetiological factors in placenta preavia: A case controlled study. Br J Obstet Gynaecol 93:586, 1986 18. Iyasu S, Saftlas AK, Rowley DL, et al: The epidemiology of placenta previa in the United States, 1979 through 1987. Am J Obstet Gynecol 168:1424, 1993