Keywords
cesarean section - nulliparity - placenta previa - postpartum hemorrhage - uterine
bleeding
Introduction
Placenta previa refers to an abnormally placed placenta, which covers the internal
ostium of the cervix. The underlying etiologic reason has not been fully understood
yet. Impaired endometrial receptivity in the upper part of the uterus (previous placenta
previa and caesarean section scar) and big placental volume (multiple pregnancies)
are found to be the main risk factors.[1] On the other hand, some risk factors for placenta previa have also been described
in the literature, such as advanced maternal age, multiparity, spontaneous or induced
miscarriage, cigarette smoking, and assisted reproductive technology (ART) pregnancies.[2]
[3]
The prevalence of placenta previa is ∼ 3 to 5 per 1,000 deliveries.[4] This obstetric issue is related with serious maternal complications and adverse
fetal/neonatal outcomes. Maternal morbidity and mortality is increased in women with
placenta previa, most frequently due to massive bleeding and surgical complications.[5]
[6] Uterotonic medications, intrauterine balloon tamponade, serious surgical interventions
(uterine compression sutures, uterine/hypogastric artery ligation, etc.) and hysterectomy
may be required to control the massive hemorrhage.[7]
The abnormal implantation of the placenta in a nulliparous woman is interesting, and
the etiology remains unclear. Moreover, these women are also at increased risk for
massive bleeding during surgery. Therefore, we aimed to investigate the risk factors
to predict massive bleeding in nulliparous women with placenta previa.
Methods
We have retrospectively evaluated the data of pregnant women who delivered between
September 2010 and September 2016 at the Etlik Zubeyde Hanim Women's Health Care,
Training and Research Hospital, University of Health Sciences, Ankara, Turkey. The
study group consisted of 69 nulliparous women with prenatally diagnosed placenta previa.
The exclusion criteria were: previous delivery history (> 500 gr or > 20th gestational week), previous uterine surgery, multiple pregnancy, and fetuses with
any chromosomal abnormality or structural malformation.
Prenatal complete placenta previa diagnosis was based on the transvaginal ultrasonographic
findings of the classical image of the placental tissue covering the internal cervical
os totally. For cases with a placental distance to the cervical os < 20 mm, the diagnosis
was as low-lying placenta previa.
Data of the maternal characteristics (age, body mass index, previous miscarriage history,
and coexisting diseases), obstetric outcome (preterm delivery, intrauterine growth
restriction [IUGR], fetal demise, and premature rupture of membranes [PPROM]), and
neonatal outcome (birthweight, APGAR scores at 1th and 5th minute, and gestational week at birth) were analyzed. All cases were delivered by
caesarean section. Operative interventions such as uterine compression sutures, intrauterine
balloon tamponade, and uterine/hypogastric artery ligation were recorded from the
files of the patients. Need for red blood cell transfusion was also assessed.
The cases were classified into two groups in terms of bleeding complications. Postpartum
massive hemorrhage diagnosis was based on the criteria defined by American College
of Obstetricians and Gynecologists.[8] Estimated blood loss was calculated with the following formula: calculated pregnancy
volume (0.75 [maternal height X 50]+ [maternal weight X 25]) x blood volume loss percentage
(predelivery hematocrit – postdelivery hematocrit/ predelivery hematocrit).Women with
a calculated blood loss ≥ 1,000 mL were included in the massive bleeding group. Women
without any signs or symptoms related with hypovolemia or calculated bleeding volume < 1,000 mL
were categorized into the non-massive bleeding group. Estimated blood loss was calculated
by using the formulas previously described in the literature. Maternal height together
with weight and hematocrit levels (both predelivery and postdelivery) were used for
this purpose.[9] The transfusion of each unit of packed red blood cells was accepted to raise postoperative
hemoglobin and hematocrit levels by 1% (g/dL) and 3%, respectively. Estimated blood
loss was calculated carefully for women who were transfused with red blood cell packages.
The groups were compared in terms of the maternal and fetal characteristics described
above.
The study protocol was approved by the Local Committee of Ethics of our hospital with
the number of 219 (21.12.2016). The authors have complied with the World Medical Association
Declaration of Helsinki regarding the ethical conduct of research. Statistical analyses
were performed by using the IBM SPSS Statistics for Windows, Version 23.0. (IBM Corp.,
Armonk, NY, USA). The mean and standard deviation values along with the median, minimum,
and maximum values were calculated, and the percentages were calculated where necessary.
Normality of the data distribution was assessed with the Kolmogorov-Smirnov test.
Parametric data were examined with independent two-sample or t-test, and non-parametric data were compared using Mann Whitney-U test. Percentages
were compared with chi-squared test. A p-value < 0.05 indicates statistically significant differences.
Results
The total number of deliveries were 93,045 during the study period. Placenta previa
was diagnosed in 395 women, with a rate of 0.42%. Among all placenta previa cases,
there were 69 nulliparous women (17.4%), who were included in the study group. There
was no definitive diagnosis of placenta accreta spectrum disorders in these cases.
Among all cases, 73.9% (n = 51) were primigravida, while the remaining patients had at least one miscarriage
history. The number of previous miscarriages was once in 12 cases (17.4%), twice in
3 cases (4.3%), 3 times in 2 cases (2.9%), and 4 times in 1 case (1.4%).
The mean maternal age was 28.55 ± 5.88, and the mean body mass index (BMI) was found
to be 27.38 ± 3.96. Spontaneous pregnancy was noted in 59 cases (85.5%), while the
number of intrauterine insemination and in vitro fertilization pregnancies were 2
(2.9%) and 8 (%11.6), respectively. The cigarette smoking rate was 5.8% among all
cases.
Total placenta previa was observed in 40 cases, with a rate of 58%, and the remaining
29 pregnancies were complicated by low-lying placenta. Placenta was located anteriorly
in 36 cases (52.2%), while 33 cases (47.8%) had posterior placenta. Cesarean delivery
was performed at 37 weeks of gestation for planned cases. Uterine compression sutures,
intrauterine balloon tamponade, and uterine artery ligation were performed in 7.2%
(n = 5), 13% (n = 9), and 1.4% (n = 1) of the cases, respectively.
Gestational week at birth ranged between 20 and 40 (35.9 ± 2.48) weeks, and the mean
birthweight was found to be 2,719 ± 567 g. The preterm delivery rate was 43.5%, and
9 out of 30 cases were before the 34th week of gestation. Also, PPROM was noted in 3 cases, with a rate of 4.3%. There was
1 intrauterine fetal demise (1.4%) and 11 cases of IUGR (15.9%).
There were 28 patients (40.6%) in the massive bleeding group, whereas the remaining
41 cases (59.4%) had a calculated blood loss < 1,000 mL. Red blood cell transfusion
was required in 14 cases (20.3%). The majority of the cases (n = 10) had been stabilized after the transfusion of 2 units. In the remaining 4 cases,
more transfusion of red blood cell packages was necessary (3, 4, and 5 units of red
blood cell packages in 2, 1 and 1 cases, respectively). There was no statistically
significant difference in terms of maternal, fetal, and delivery characteristics between
the two groups, as shown in [Table 1]. Calculated blood loss and number of cases with requirement of red blood cell transfusion
were statistically different between the groups (< 0.005 and 0.002, respectively).
Table 1
Comparison of the groups
|
Non-massive bleeding (n = 41)
|
Massive bleeding (n = 28)
|
p-value
|
|
Calculated blood loss (mL)
|
411.52 (102–976)
|
1,393 (1,000–3,431)
|
< 0.005
|
|
Transfusion requirement
|
3 (7.3%)
|
11 (39.3%)
|
0.002
|
|
Age
|
28.02 ± 5.794
|
29.32 ± 6.019
|
0.637
|
|
BMI
|
27.34 ± 3.779
|
27.43 ± 4.290
|
0.438
|
|
Miscarriage history
|
10 (24.4%)
|
8 (28.5%)
|
0.783
|
|
Assisted reproductive technology
|
5 (12.2%)
|
5 (17.9%)
|
0.221
|
|
IUI
|
2 (4.9%)
|
0
|
|
IVF
|
3 (7.3%)
|
5 (17.9%)
|
|
Smoking
|
3 (7.3%)
|
1 (3.6%)
|
0.513
|
|
Placenta location
|
|
|
0.625
|
|
Anterior
|
20 (48.8%)
|
16 (57.1%)
|
|
Posterior
|
21 (51.2%)
|
12 (42.9%)
|
|
Type of previa
|
|
|
0.806
|
|
Placenta previa
|
18 (43.9%)
|
11 (39.3%)
|
|
Low-lying placenta
|
23(56.1%)
|
17 (60.7%)
|
|
Preterm delivery
|
17 (41.5%)
|
13 (46.4%)
|
0.806
|
|
IUGR
|
5 (12.2%)
|
6 (21.4%)
|
0.304
|
|
PPROM
|
3 (7.3%)
|
0
|
0.143
|
|
Gestational week at birth
|
37 (27–40)
|
37 (27–39)
|
0.904
|
|
Birthweight (grams)
|
2,890 (1,040–3,400)
|
2,765 (1,110–3,775)
|
0.673
|
|
Postpartum hospital stay (day)
|
2 (2–5)
|
3 (2–11)
|
0.369
|
|
Preoperative Hb (g/dL)
|
11.2 ± 1.326
|
11.3 ± 1.516
|
0.847
|
|
Preoperative Htc (%)
|
33.7 ± 3.851
|
34.4 ± 4.295
|
0.566
|
Abbreviations: BMI, body mass index; IUI, intrauterine insemination; IVF, in vitro fertilization;
IUGR, intrauterine growth restriction; PPROM, premature rupture of membranes.
Discussion
Placenta previa may be responsible for peripartum massive bleeding, and the risk increases
with adherent placenta. Additionally, hysterectomy, blood transfusion, septicemia
and thrombophlebitis are also responsible for increased maternal morbidity and mortality
in these women.[10] Thus, placenta previa should be managed in an experienced center with a team consisting
of an obstetrician, a pediatrician, and an anesthesiologist.
A recent systematic review reported the incidence of massive hemorrhage in women with
placenta previa. They have shown that the frequency of postpartum bleeding was 22.3%
in placenta previa cases.[11] On the other hand, controversial results were also given by different authors, and
rates differed from the lowest (3%) to the highest (56%) in these heterogeneous studies.[12]
[13] Nur Azurah et al.[14] reported that postpartum hemorrhage rate was 23.4% in primigravida women without
a significant difference from multigravidas. Our study found higher incidence of massive
bleeding in nulliparous women with placenta previa. Among 61 women, 40.6% of the deliveries
were complicated with postpartum hemorrhage. This can be explained by two scenarios.
First, our hospital is a referral hospital located in the capital city of Turkey.
Referred patients may be admitted to our center at a later stage, when delivery has
already started. Second, the operators are not the same in all surgeries, and experience
levels differ among the surgeons. Most of the elective surgeries are performed in
the morning shifts after preparing blood products. A team composed of residents of
perinatology and gynecology and obstetrics perform the surgery under the supervision
of a maternal fetal medicine specialist. In the night shifts, there is also a team
consisting of residents on duty every day.
Identifying risk factors, even in the antenatal period, to predict excessive bleeding
may be useful. Several studies were conducted for this purpose.[14]
[15] The most important factor related with bleeding is reported to be placental adherence,
with an adjusted odds ratio [OR] of 123.1 (95% Cl, 4.5–3,395.2).[15] Placenta previa in a patient with a prior caesarean section is the prominent factor
for placenta accreta spectrum. Repeated cesarean sections are also known to increase
the risk of placenta accreta ∼ 2.6 times.[16] Because of the worldwide increased rates of caesarean delivery, adherent placenta
and related complications started to be a major health problem. However, placenta
accreta spectrum is very rare in nulliparous pregnancies, and no placental attachment
disorder was diagnosed in our series.
Some studies have shown that complete placenta previa is more likely related with
peripartum bleeding because of the increased placental area on the cervix.[17]
[18] Additionally, anterior placenta is reported to be associated with increased hemorrhage
compared with posterior placenta. The risk was especially important in the occurrence
of a previous uterine scar.[18]
[19] However, a recent article has shown that the rate of postpartum massive bleeding
in pregnancies with an incomplete and posterior placenta previa is 11%.[20] In the current study, we did not find a significant difference between the localization
of the placenta and bleeding volume. These findings together with the previous results
show that placenta previa may be complicated by excessive hemorrhage beside the type
of placenta previa. Thus, all women with placenta previa should be managed carefully
in the pre- and perinatal periods because of the potential excessive bleeding risk.
Maternal characteristic and ultrasonographic findings are used to create a scoring
model to identify women at high risk for massive bleeding. Caesarean delivery, advanced
maternal age and sponge-like appearance of the cervix were reported to be risk factors
for postpartum hemorrhage in placenta previa cases.[15] Caucasian ethnicity and multiple pregnancy has also been found to be related with
bleeding complications.[4] However, most of the previous studies were designed to diagnose placenta accreta
spectrum disorders. On the other hand, advanced maternal age, antepartum bleeding
history, anterior placenta, multiple lacunae in placenta, and increased vascularity
have been shown to be related with massive bleeding in placenta previa cases, even
without an adherent placenta.[21] Because of the retrospective design of our study, ultrasonographic findings could
not be evaluated in the present study. It seems reasonable to use sonography carefully
and use an internationally accepted standard protocol in all placenta previa cases.
Fetal and neonatal complications are another important point of placenta previa management.
Previous studies revealed that the rate of preterm delivery, fetal growth restriction,
and perinatal mortality has been higher in pregnancies complicated with placenta previa.[22] The histopathological evaluation of the placenta previa by Weiner et al.[23] has shown that placental vascular problems (both hemorrhage and thrombosis) are
more common in placenta previa. Thus, abnormal placentation is related with impaired
maternal fetal perfusion, which is most probably responsible from improper fetal growth.[23] Preterm delivery and its consequences are another issue related with placenta previa.
A recent systematic meta-analysis has found that prematurity, perinatal mortality,
and neonatal intensive care unit admission are increased in placenta previa cases.
The preterm delivery rate is especially higher in the presence of adherent placenta
and vasa previa.[24] According to our findings, preterm delivery rate is 43.5% and IUGR is 15.9% in nulliparous
women with placenta previa, in accordance with the findings in the literature.
Conclusion
Maternal excessive bleeding may complicate placenta previa pregnancies in nulliparous
women. We did not find any predictive features for massive hemorrhage based on clinical
features, delivery features, or placental location in primigravida patients. Thus,
all women with a placenta previa diagnosis carry a risk for bleeding, regardless of
their placenta location or type and maternal characteristics. Moreover, these women
should be monitored in terms of preterm delivery and IUGR during antenatal care. An
experienced team and blood bank are the key points to minimize the maternal and fetal
adverse outcomes.
