Gielchinsky, Yuval MD; Mankuta, David MD; Rojansky, Nathan MD; Laufer, Neri MD; Gielchinsky, Ilan BMedSc; Ezra, Yossef MD
Placenta accreta is defined as an abnormal adherence of the placenta to the uterine wall. Histopathologically, there is a direct attachment of the chorionic villi to the myometrium, which is due to the absence of both the decidua basalis and Nitabuch's layer.
The reported incidence of placenta accreta varies between 1:540 to 1:93,000 deliveries depending on differences in definitions (clinical versus histopathological), the studied populations, and the different periods that these studies represent.1,2
Factors suggested as being associated with a higher incidence of placenta accreta include scarred uterus, multiparity, previous uterine surgery, advanced maternal age, previous uterine curettage, placenta previa,3,4 and a female fetus.5,6 Furthermore, the possibility of a genetic etiology for placenta accreta was postulated by several recent studies.7–9
Maternal complications in cases of placenta accreta usually occur in the third stage of labor and, rarely, in cases of placenta percreta during the pregnancy period. Patients may present with a severe life-threatening hemorrhage requiring extensive surgical interventions, such as major pelvic vessel ligation and/or hysterectomy. A more conservative approach, using angiographic embolization, was recently applied for this indication with promising preliminary results.10,11 As a consequence of placental invasion to adjacent organs, reconstruction of the urinary bladder or bowel may be necessary. Massive blood and blood product transfusions are the rule in these dramatic cases. Maternal morbidity and mortality have been reported.12
In contrast to maternal complications, we could not find in a MEDLINE search (using the key words “placenta accreta,” “perinatal outcome,” “small for gestational age,” “preterm birth,” and “perinatal mortality,” PubMed; January 1966 to August 2003) any controlled study regarding the perinatal outcome of pregnancies complicated by placenta accreta. Because placenta accreta, by definition, is characterized by an abnormal placental implantation, we may assume that fetal development would be affected. This study was therefore undertaken to investigate the perinatal outcome of pregnancies complicated by placenta accreta.
MATERIALS AND METHODS
A case-control study was performed. All cases of placenta accreta during the years 1990–2000 at Hadassah Ein-Kerem Medical Center, Jerusalem, Israel, were collected by reviewing delivery room records and patients’ files. Three of the authors who were not blinded to case or control status reviewed the relevant perinatal data. This study was exempted from review by the Institutional Review Board.
The definition of pregnancy complicated by placenta accreta was according to clinical or histological criteria8,13–15 based on the presence of one or more of the following: 1) difficult manual, piecemeal removal of the placenta, which was performed if no evidence of placental separation was noticed at least 20 minutes after parturition, despite active management of the third stage of labor (ie, administration of intravenous oxytocin, transabdominal manual massage of the uterus, drainage of blood from the placenta, and firm, controlled traction of the umbilical cord); 2) sonographic evidence of retained placental fragments requiring curettage after vaginal delivery; 3) heavy bleeding from the implantation site after removing the placenta during conservatively managed cesarean delivery, with excision of part of the uterine wall and the attached placenta or oversewing of the bleeding defects; and 4) histological confirmation after hysterectomy.
Women with malformed or myomatous uterus were excluded from the study because these conditions may be associated with difficulties in removal of the placenta, although separation would be normal.
Variables included in the analysis were gestational age at delivery, birth weight, Apgar scores at 1 and 5 minutes, and perinatal mortality. Newborns under the fifth and tenth percentiles according to gestational age birth weight distribution were defined as small for gestational age (SGA).16
The gestational age was based on the date of last menstrual period (LMP), unless a difference of more than 5 days was found between the LMP and first trimester ultrasonography. In these cases, the date of the ultrasound estimation was chosen.
Each case of singleton pregnancy complicated with placenta accreta was matched with the next patient who shared all of the following factors: mode of delivery, maternal age group, and parity. Mode of delivery included cesarean or vaginal delivery. Each woman under the age of 45 years was matched to a control subject who was no more than 1 year older or younger. However, in women over the age of 45, there were differences of up to 3 years in age between control and study parturients. Parity was controlled by dividing the patients into 4 groups: primiparous, multiparous (2–5 deliveries), grand multiparous (6–10 deliveries), and grand grand multiparous (> 10 deliveries) and controlling accordingly. For twin pregnancies, controls were matched with twin pregnancies with similar factors.
We performed an analysis of the data using both the unpaired and paired approach.
1. The unpaired approach: To test the difference between the 2 studied groups for continuous variables, we applied the 2-sample t test. The relationship between studied groups and categorical variables was analyzed by χ2 and Fisher exact tests. The analysis of covariance model was applied to evaluate which variables predict birth weight, controlling for possible confounders.
2. The paired approach: The paired t test was applied to assess whether the difference between pairs of cases and controls was significant for continuous variables. For categorical variables, the McNemar χ2 test was applied.
Statistical significance was designated as P < .05.
During the years 1990–2000, there were 34,450 deliveries at the Hadassah Ein-Kerem Medical Center, from which 310 cases of placenta accreta were diagnosed (0.9% of all deliveries) and matched with 310 control parturients. The mean maternal ages in the study and the control groups were 30.7 years (range 20–47) and 30.6 years (range 20–44), respectively. There were 10 (3.2%) twin pregnancies and 15 (4.8%) cesarean deliveries in each group. In each group, 25% (79/310) were primiparous, 60% (185/310) multiparous, 14% (42/310) grand multiparous, and 1% (4/310) grand grand multiparous. In 7 cases (2.2%) of placenta accreta, the placenta was also previa.
The main perinatal outcomes are summarized in Table 1. Parturients with placenta accreta delivered earlier and had a higher incidence of preterm deliveries than the controls. Neonates from pregnancies complicated by placenta accreta weighed, on average, 300 g less then neonates born to women with normal placental implantation. Moreover, these neonates had a significantly increased incidence of SGA below the fifth and tenth percentiles compared with the controls. No difference was found between the male/female ratio in the 2 groups. Three cases (1%) of perinatal death occurred in pregnancies complicated by placenta accreta, with none in the controls. This difference did not reach statistical significance. There was no statistical difference in the 1-minute and 5-minute Apgar scores between the 2 groups.
Analysis of covariance was applied to assess the effect of placenta accreta and week of delivery on fetal birth weight, controlling for the possible confounders, placenta previa and suspicion of accreta in antenatal ultrasonography. Both confounders were found to be nonsignificant (P = .065 and 0.19, respectively), whereas the other parameters, placenta accreta and week of delivery, were found to be highly significant (P < .001).
When a one-to-one matching was performed using paired t test and McNemar χ2 test, we found that, in 15.5% of the paired case-control couples, the cases had smaller babies (< fifth percentile) than the controls. Whereas in only 4% of the paired case-control couples, the control subjects had smaller babies than the cases (P < .001).
When the same analysis was performed after excluding the twin pregnancies, the significance of the results remained the same.
In the present study, we found that pregnancies complicated by placenta accreta have an increased incidence of preterm deliveries. The neonates have a lower birth weight and an increased risk for SGA (both under the fifth and tenth percentiles). Perinatal mortality was higher in the accreta group, 3 versus none (not statistically significant).
Because most cases of placenta accreta were diagnosed during labor, the higher rate of prematurity could not be attributed to planned earlier delivery or cesarean delivery and is probably due to the pathogenesis of this condition.
We found a 1% preterm delivery rate in the control group, which is lower than the published one. However, the annual rate of preterm delivery in our center ranges between 4% and 7%, and this includes triplet pregnancies, malformed fetuses, and known uterine malformations, which were not included in this study.
One of the major difficulties with studies on placenta accreta is the definition of the condition. Some studies are based on clinical criteria, whereas others are based on histopathology.4,17 Because placenta accreta is a clinical obstetrical emergency and its management is based on early clinical diagnosis, we believe that clinical criteria for definition may be more appropriate. Postpartum histological examination of the placenta may be confusing because only a few placental surfaces are sampled, and small areas that might contain myometrial tissue may be missed. Moreover, incidental finding of placenta accreta in histological examination is not uncommon.13 Jacques et al,3 in their histopathologic study on placentas, concluded that, in cases of clinically suspected placenta accreta, failure to demonstrate adherence of myometrial tissue to the maternal surface of the placenta could not be used to exclude the diagnosis of placenta accreta. They also noted that many of the mild cases of placenta accreta that were diagnosed histologically might be clinically unnoticed. In this study, therefore, we defined placenta accreta according to clinical or histological criteria.13–15,18 However, it is important not to confuse placenta accreta with simple retention of the placenta after birth, which is quite a common condition that may be easily managed by conventional means. In our population the incidence of placenta accreta is similar to studies that used the same clinical criteria for the diagnosis of placenta accreta.15 However, studies that used only histopathological criteria had a lower rate of this diagnosis (0.001%).17
Similarly to our findings, it was found that increased neonatal risk was also associated with pregnancies complicated with placenta previa, another condition of abnormal placental implantation. Increased fetal and neonatal death, prematurity, and fetal growth restriction were reported.19–21 Recently, a large study22 revealed a neonatal mortality rate of 1.07% in cases of placenta previa. Mean birth weight was 210 g less than in babies born to women without placenta previa, and 44.3% of the cases had preterm deliveries. It appears likely that the high mortality rate in cases of placenta previa is mainly due to prematurity.23
Studies with placenta accreta and previa demonstrate similar perinatal complications. These findings may be explained by abnormal placental implantation that causes placental insufficiency. It is important to point out that the etiology of these cases is different. In the case of placenta previa, it is speculated that the abnormal placental location, repeated bleeding, fibrosis, and infarctions might cause placental insufficiency and fetal growth restriction.24,25 On the other hand, placenta accreta is associated with the lack of the decidual layer. This is secondary to local trauma, progressive vascular endothelial damage that occurs with aging, inappropriate decidual reaction, or genetic predisposition.
In the present study, only 2.2% of all cases of placenta accreta were also complicated by placenta previa. This confounder was found to have no statistical significance to the perinatal outcome.
In conclusion, pregnancies complicated by placenta accreta are at a higher risk for adverse perinatal outcome. These findings may result from pathological implantation of the placenta that interferes with normal placental function and leads to abnormal fetal growth.
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