Current Medical Science x 7 DOT hups/doiorg/10.1007/s11596-018-1919.9 _S8(4!597-601,2018 507 Risk Factors and Pregnancy Outcomes: Complete versus Incomplete Placenta Previa in Mid-pregnancy* Yun FENG', Xue-yin LP, Juan XIAO!, Wei LI, Jing LI Qing-ling KANG?, Su-hua CHEN "Department of Obstetrics and Gynecology. Tongji Hospital, Tongji Medical College, Huazhong, University of Science and Technology, Wuhan 43000, China “Department of Urology, Zhengzhou First People’s Hospital, Zhengzhou 450000, China , Xue ZENG!, Xi CHEN', Kai-yue CHEN', Lei FAN', (© Huazhong University of Science and Technology 2018 Summary: This prospective study was conducted to compare risk factors and pregnaney ‘outcomes between women with complete placenta previa and those with ineomplete placenta, previa diagnosed in mid-pregnancy. The study was carried out from April 2014 to December 2015, during which 70 patients with complete previa and 113 with incomplete previa between 20° weeks and 25° weeks of gestation were included. Matemal demographics and pregnancy outcomes were compared between the two groups. Comparisons between categorical variables were tested by chi-squared test and those between continuous variables by Student test. Resolution of previa occurred in 87.43% of the studied women. The mean, gestational age at resolution was 32.124.4 weeks. Incidence of matemal age >35 years and incidence of prior uterine operation >3 were high in women with complete previa (28.6% vs, 8.8%, P=0.003; 28.6% vs, 8.89%, P~0.003). Resolution of previa occurred less often in complete previa group (74.3% us. 95.6%, P=0.001). Women with complete previa admitted earlier (37.342.0 weeks vs. 38.141.4 weeks, P-0.011) and delivered earlier (37.741.2 weeks vs, 38.3414 weeks, P=0.025). Maternal age 235 years and prior uterine operation 3 increase the risk of complete previa in mid-pregnancy. Placenta previa is more likely to persist in women with complete previa than those with incomplete previa diagnosed in mid- pregnancy. What is more, women with complete previa in mid-pregnancy delivers earlier Key words: complete placenta previa; risk factor; uterine operation; pregnancy outcome; resolution ‘Traditionally, placenta previa has been classified as complete, partial, marginal or low-lying. The incidence of complete placenta previa detected at second-trimester ultrasound examination is reported to be between 0.49% and 5.6%!" “| Complete placenta previa is a major cause of severe postpartum hemorrinage (PPH). Development of complete placenta ‘Yun FENG, E-mail; 981559962@qq.com ‘Corresponding author, E-mail: ij esh@163.com “This project was supported by grants from National Natural Science Foundation of China (Nos. 81701476 and 81200354), Hubei Provincial Population and Family Planning Commission of China (No. JS-20130017), and Applied Basie Research Plan of Wuhan (No. 2015060101010037). previa increases both maternal-perinatal morbidity and mortality” Several prior studies suggested that complete previa might be clinically different entity from incomplete previa, associated with worsening ‘maternal and perinatal outcome’, More than 90% of placenta previa diagnosed in the second trimester will resolve by delivery, but complete previa is more likely to persist®!. However, there is limited information available on the difference in risk factors and pregnancy outcomes between patients with complete previa and those with incomplete previa discovered in mid-pregnancy. With the development of ultrasound and routine use of transvaginal sonography, the relationship between the placental implantation site and the intemal cervical os can be described more598 accurately. Thus, the differentiation of the types of previa is now more reliable. This study was carried out to compare risk factors and pregnancy outcomes between women with complete placenta previa and those with incomplete placenta previa discovered in mid-pregnaney. 1 MATERIALS AND METHODS ‘This prospective study conforms to the provisions of the Declaration of Helsinki; it has obtained approval from Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Institutional Review Board before it was carried out. This study was conducted on singleton pregnant women who took ultrasound examination in the ‘Current Medical Science 38(4):2018 second trimester at Tongji Hospital. Sonographers with appropriate expertise in ultrasound scanning performed all examinations with Voluson ES Expert (GE Healthcare Ultrasound, USA) and Accuvix XG (Samsung Medison Healthcare, South Korea) ultrasound systems using 4-S-MHz. transabdominal probes. The placenta was located transabdominally with a normally filled bladder; this was followed by 4 transvaginal scan in cases where the transabdominal scan was suggestive of placenta previa, Patients diagnosed with placenta previa at the 20° and 25°* weeks scan underwent further ultrasound examinations around 32 and 37 weeks” gestation as part of routine clinical practice. Those who did not deliver at Tongji Hospital or delivered at less than 28 completed weeks of gestation were excluded. From April 2014 to Enrollment Assessed for clit (n=1358) acd 1149) ‘© Not meeting inhson rite n1045) 4 Desined parce 8) ‘Other estos 35) Complete pers | [upcaoa | [Isom revi 78) iss (rts) iscaet fe ido dtr Teng Hospital (n " Follow-up on Jo Delve a2 wes of Hop geaadon =D) Fellow aa Follow. dua avalible t=78) avail 13) Amys Revel 5) Resolved 108) Fig. 1 Flow-char illustrating patient selection and recruitment Singleton pregnant women diagnosed wit placenta previa between 20° weeks and 25° weeks of gestation and were included in the study. Those who did aot deliver at Tongji Hospital or delivered at less than 28 comple ‘weeks? gestation were excluded, During April 2014 to December 2015, 183 cases were reeruited othe stad. December 2015, 183 cases were recruited to our study and verbal informed consent for the examination was obtained from each patient (fig. 1). Patient anonymity has been well preserved. In this study, complete placenta previa referred to a placenta totally overlapping the cervical os, while incomplete placenta previa was designated when the placental edge ended less than 2 em from the intemal cervical os (including partially overlapping the cervical os). Obstetric history including previous caesarean section (CS), dilatation and curettage, uterine surgery and assisted reproductive technology and other demographic data (including age, gravity, parity, history of fibroid and endometriosis) were documented. Data pertaining to obstetric outcomes and neonatal outcomes were derived from the hospital's inpatient electronic medical record. Obstetric outcomes: included the following: mode of delivery (vaginal, CS), gestational age (GA) at admission and delivery, placenta previa, estimated blood loss, postpartum haemorthage (©500 mL for a vaginal delivery and >1000 mL for a cesarean delivery), blood transfusion, intensive care unit admission, hospitalization days. Additional uterotonic included misoprostol, metiylergonovine,Current Medical Science 38(4):2018 599, and carboprost which were used in the event of excess blood toss in labor. Neonatal outcomes included birthweight, low birth weight (<2500 g), preterm birth (37 weeks), neonatal intensive care unit admission and fetal growth restriction ‘The statistical analysis was performed using the Statistical Packages of Social Sciences for Windows version 16.0 (SPSS, USA). Continuous variables were presented as meandstandard deviation or median, Qualitative variables were presented as absolute frequency and percentage. Comparisons between categorical variables were tested by the use of contingency tables and calculation of the chi-squared test. Comparisons between continuous variables were performed using analysis of the Student r test. All tests were 2 tailed, and P<0,05 was considered significant. 2. RESULTS Seventy cases of complete previa and 113 cases of incomplete previa were enrolled in this study. The mean maternal age was 31.144.1 years (es) (range, 23-42 years). The mean GA at initial diagnosis was 23.041.7 weeks (zs) (range, 20-26 weeks). Resolution of previa occurred in 87.43% of the studied women. ‘The mean GA at resolution was 32.1144 weeks (74s). Table 1 showed the socio-demographic and pregnancy characteristies ofthese pregnancies stratified according to previa type. Incidence of maternal age 235 years was higher in women with complete previa than those with incomplete previa (28.6% vs. 8.8%, P=0.003). Incidence of prior uterine operation (including prior cesarean section, prior dilatation and curettage, prior assisted reproductive technology and prior uterine surgery) >3 was obviously higher in women with complete previa (28.6% vs. 8.8%, P-0,003). No significant difference was observed in frequency of multigravity and multiparity, history of fibroid and endometriosis between the two groups ‘Table 1 Socio-demographie datas stratified according to the type of previa Chaactristie COMPlte previa Incomplele previa (70) (e113) Maternal age=35 20 (08.6%) 1008 0.005 Maternal age 31.7641.639 304933.496 0.072 Multigravity 47 (67.1%) $9(52.2%) 0.072 Multiparity —21(30.0%) —2118.6%) 0.126 Prior uterine operation ° IS@14%) —4186.2%) 0.084 13 35,50.0%) —62,(549%) 0.549 >3 20(28.6%) —_10(8.8%) 0.003 History of fibroid (7.1%) 302.7%) 0.420 History of oar) 3m) 0.470 ‘endometriosis Data are presented as meani8D or number (percentage). Prior uterine operation includes prior cesarean section, prior dilatation and curetage, rir assisted reproductive technology and prior uterine surgery. Table 2 reported the obstetric outcomes stratified according to previa type. GA at initial detection of the two groups were 22.921.7 weeks (zis) and 23.041.8 weeks (#5) individually, with no significant difference. ‘Women with complete previa admitted earlier (37.3+2.0 weeks us. 38.1414 weeks, P-0.011) and delivered earlier (37.7#1.2 weeks vs. 3831.4 weeks, P=0.025), No difference was found in other obstetric outcomes and neonatal outcomes (table 3) between the two groups. Persistence of placenta previa to delivery occurred in 5 of the 113 initially diagnosed incomplete previa Eighteen of the initially diagnosed complete previa persisted to delivery, including 12 cases of complete previa, | case of partial previa, 3 cases of marginal previa, and 2 cases of low-lying placenta, leading to a significantly lower incidence of resolution than incomplete previa (74.3% vs, 95.6%, P=0.000) Characteristics of 12 cases of persisting complete previa were shown in table 4, 3 DISCUSSION In this study we showed that matemal age >35 years and prior uterine operation >3 increased the risk ‘of complete previa in mid-pregnancy and that complete previa in mid-pregnancy was a high-risk subgroup, which is destined for poorer outcome. Placental development is a complex process and the mechanism of placental localization is not well understood. A favorable endometrial environment is essential to ensure the development of an adequate fetal-matemnal interface. We have shown that history of increased uterine operations was associated with complete previa detected in mid-pregnaney, suggesting its influence on placentation, However, the significance of this observation is not clear. One of the possible ‘mechanisms which may play a role is that increased uterine operations might disrupt the junctional zone of the uterus. Growing body of evidence suggests that compromised placental development and its subsequent effects on pregnancy outcome are caused by impaired decidualization("”. Should the history of increased uterine operations disturbed the normal process of decidualization, this may have implications for potential fertility, likelihood of miscarriage and placental development, As recent study is increasingly focusing on the uterine inflammatory response and its association with successful implantation, this concept seems plausible. Our results also found the relationship between matemal age >35 years and complete previa, indicating that matemal age might have an effect on placental location. The incidence of placenta previa decreases as pregnancy proceeds because of “placental600 ‘Current Medical Science 38(4):2018 migration”, However, the mechanism behind this phenomenon has not been fully clucidated. One proposed theory is a process of so-called placental trophotropism or dynamic placentation!. It is related to atrophy of thin placental margins due to a poor vascular supply, compared with other placental regions that continue to grow and therefore migrate toward more vascular sites. There have been several studies reporting the association between previa type and placental migration™*:"“"" In our study, it was found that placental migration was a commonly observed phenomenon in patients with preliminary diagnosis of incomplete previa while in the case of complete previa it ocourred significantly less often, This is consistent with the work of Dashe et af, They carried out a retrospective study on 714 pregnancies and found that at each studied pregnancy interval, complete previa ‘was more likely to persist than incomplete previa fable 2 Obstetric outcomes stratified according to the type of pre Complete previa Incomplete previa Charactritis mt mie P Gestational age a initial detection 29217 TORS 03 Gestational age at admission (weeks) 37.3420 SRL oon Gestational age at delivery (weeks) 37712 383814 0.025 ICU admission oom 801%) 6.066 Hospitalization days before delivery 2219 22126 0.910 Hospitalization days after delivery sas Ssu14 0274 Cesarean section 65 029%) 100 (885%) 0.367 Hospitalization days 14.22 72129 04 Emergency cesarean section ows 10 88% 0.994 Estimated blood loss 421.61321.4 465.156283 0.618 Postpartum hemorrhage 9.129%) 2006» 0.602 Blood transfusion 710.0%) 87.1%) 0363 Additional uerotonie use 37 (52.9%) 52 (46.0%) 0435 Pelvic vessel ligation saa 12(10.6%) 0.887 Bakr Balloon Tamponade 10.4%) 302.7%) 0.994 Pressurized suture 1.4%) 514%) 0.602 BeLynchy suture 10.4%) 5 (44%) 0.602 Hysterorhexis 1.4%) 0K 2099) Hysterectomy 109%) 0.994 Hemorrhagic shock 1.4%) 30%) 0990 Pre-op hemoglobin (gm) 12254134 Iost19 0.822 Post-op hemoglobin (gimL) 199.5215.0 los0ei43 0.125 Placenta increta 10043%) 16(142%) 0.972 Manual removal of placenta a7. 28(248%) 0.380 Premature rupture of membrane 9029 1815.9 0.604 ICU, intensive care unit, Data are presented as meanSD or number (percentage), ‘Table 3 Neonatal outcomes satified according to the type of previa ‘Complete previa Incomplete previa Characteristic P Bink weight (@) 30 Oe Low birth weight $(7.1%) 87.1%) 0.99 Pretermbirth 104.3%) 16(142%) 0.972 Nicu 500.1%) 15(13.3%) 0.248 PGR 14%) 240.7%) 0.972 NICU, neonatal intensive care unit; FGR, fetal growih, restriction, Data are presented as mean=SD or number (percent, Currently, all types of previa (complete and incomplete) at third trimester are managed similarly, as they all are potentially associated with threatening hemorthage during labor. We agree with Green that the degree of previa cannot alone predict the clinical course accurately, nor can it serve as the sole guide for ‘management decisions! However, knowledge gained from the current study about pregnancy outcomes may allow us to identify complete previa in mid-pregnancy as a high- risk subgroup, which is destined for poorer outcome. We identified patients with complete previa in mid- pregnancy as more likely to deliver earlier in gestation, and their previa are more likely to persist to delivery. Information on these potential risk factors for adverse pregnancy outcomes may allow proper patient counseling and appropriate preparations regarding staffing, The main strength of our study is the prospective design. One of the limitations is relatively small number of cases recruited, being a single center study. ‘A larger and multicenter study is necessary to confirm the findings in our study.Current Medical Science 38(4):2018 601 Table 4 Analysis of 12 patients whose complete previa persisted to delivery ABO) ga Ay Same oT PFO Pace loeioa CRM BmergeneyS PPK Hystetomy Stock Bas ¢ Poor 353 Nee Ne Ne mas 4 Poster mo No Ye No NG ae 5 Postir 372 No Ne NO aos 7 Poster 256 No No No No aos 1 Aerio 96 No No NO NG Mos 3 ‘ir 6 Yes No Noes mest) 2 ‘attr 265 No No No No 2 ms 4 ‘esr 318 No No No NG & 1 Postion 380 No Yes NaN 2s 5 Ante 290 No No No NO 2a i Aerie Ms No Ns NX aa 5 eit 266 No_No No Na GA, gestational age; CS, eesarcan section; PPHT, postpartum hemorrhage; y, yeas;weeks Acknowledgements ‘The authors would like to thank the staff of the Ultrasound Department of Obstetties and Gynaecology and Medical Records Department. Conflict of Interest Statement ‘The authors declare that they have no conflict of interest RENCI 1 Wexler P, Gottesfeld KR. Early diagnosis of placenta previa. Obstet Gynecol, 1979,54(2):231-234 2. Becker RH, Vonk R, Mende BC, etal. The relevance of placental location at 20-23 gestational weeks for prediction of placenta previa at delivery: evaluation of 8650 cases, Ultrasound Obstet Gynecol, 2001.17(6):496-501 3 Twaovie L. Complete versus incomplete placenta previa and obstetric outcome, Int J Gynaecol Obstet, 2006,93(2):110-117 4 Dola C, Garite TJ, Dowling DD, ef al. Placenta previa: does its type alTect pregnancy outcome? Am J Perinatol, 2003,20(7):353-360 S Gorodeski 1G, Bahari CM, The effect of placenta previa localization upon maternal and {etal-neonatal outcome. J Perinat Med, 1987,15(2):169-177 6 Morgan J. Placenta praevia: report on a series of $38 ceases (1938-1962). ] Obstet Gynaecol Br Commonw, 1965,72(5):700-705 7 Crenshaw C Jr, Jones DE, Parker RT, et al, Placenta previa: a survey of twenty years experience with improved perinatal survival by expectant therapy and cesarean delivery. Obstet Gynecol Surv, 1973,28(7):461-470 8 Cotton DB, Read JA, Paul RH, etal. The conservative aggressive management of placenta previa. Am J ‘Obstet Gynecol, 1980,137(6):687-695 9 Dashe JS, McIntire DD, Ramus RM, etal. Persistence of placenta previa according to gestational age at ultrasound detection. Obstet Gynecol, 2002,9%(5 Pr 1):692-697 10 Salker M, Teklenburg G, Molokhia M, et al Natural selection of human embryos: impaired decidualization of endometrium disables embryo- ‘matemal interactions and causes recurrent pregnancy loss, Plos One, 2010,5(4):010287 11 Cho JY, Lee YH, Moon MH, et al. Difference in migration of placenta according to the location and. type of placenta previa. J Clin Ultras, 2008,36(2):79- 84 12 King DL. Placental migration demonstrated by ultrasonography. A hypothesis of dynamic placentation. Radiology, 1973,109(1):167-170 13 Varma TR. The implication of a low implantation of the placenta detected by ultrasonography in carly pregnancy. Acta Obstet Gynecol Scand, 1981,60(3):265-268 14. Debski R, Makuch K. Ultrasonographic assessment ‘of changes in the location of the lower border (termed, migration) of the placenta. Wiadomosci lekarskie, 1990,43(11):506-510 15. LiWZ, Yong TZ. Continuous ultrasonic observation ‘on the change of location of placenta in placenta, previa, Zhonghua Fu Chan Ke Za Zhi (Chinese), 1990, 25(6):335-336 16 Green JR. Placenta previa and abruptio placenta. In: Creasy RK, Resnik R, (eds) Maternal-Fetal Medicine: Principles and Practice. 3rd ed. Philadelphia: WB Saunders, 1994,602-607, (Received Sep. 15, 2017; revised June 20, 2018)