Abstract
Objective
This study reviews the surgical pathology reports of post-partum hemorrhages to support clinicians in malpractice litigation and, potentially, to enhance pregnancy-related diagnoses.
Study design
This work is a retrospective study of surgical pathology reports of term pregnancies between January 2000 and January 2012 selected from the Surgical Pathology database of the I.R.C.C.S Azienda Ospedaliera Universitaria San Martino-IST (Istituto Nazionale per la Ricerca sul Cancro, Genoa).
Results
Ninety-five revision reports were identified (0.22% “placenta accrete,” 0.46% “non-accreta placental tissue retention,” and 0.31% “no placental fragments retention”). Secondary post-partum hemorrhages occurred in 0.3%, and primary PPH occurred in 0.05%, regardless of the group examined. Both types of PPH were most often associated with vaginal deliveries (58%). The most frequent endometrial finding was post-partum endometritis (43%). The entire placenta was submitted to the pathologist in 22/95 cases (23%). Hypermaturity and/or villous immaturity were the main histological patterns.
Conclusions
This review supports the hypothesis that the pathological placenta abnormalities observed, rather than underlying myometrium abnormalities, may underlie the contractile failure and the incomplete removal of the placenta. For these reasons, the authors emphasized the importance of investigating the placenta in cases of complicated deliveries not associated with PPH to support clinicians in malpractice claims.
One major clinical and medico-legal issue regarding post-partum hemorrhage (PPH) is misdiagnosis or delayed diagnosis. Several investigators have proposed that these issues are due to the lack of a standardized and simple definition of PPH, which can result in inadequate pharmacological and surgical treatment. 1 The most common definition used in the majority of obstetric textbooks is the definition proposed by the World Health Organization in 1990, that PPH is “any blood loss from the genital tract during delivery above 500 ml.” 2 Several investigators reported that clinical measurements demonstrate that the average blood loss during vaginal and cesarean delivery frequently exceeds 500 and 1000 ml, respectively. 3 Despite measurement methodologies that are optimized to assess the amount of blood loss, the definition of PPH based on the quantification of blood loss has been recently noted as variable even among clinical guidelines. Coker and Oliver 4 proposed a classification based not only on the amount of the blood loss but also on the combined clinical signs and symptoms.
Another criterion used to classify PPH is based upon the timing of the onset of bleeding relative to the delivery. PPH is generally classified as an early or primary event (within the first 24 hours of delivery) or as a late or secondary event (more than 24 hours but less than 12 weeks after delivery). Secondary PPH is less common than primary PPH. The absolute blood loss is often underestimated because of difficulties with visual quantitation.5–7
The causes of PPH can represent a basis for PPH classification. Primary PPH is traditionally considered to be a disorder of one or more of the following processes: uterine atony, retained clots or placental debris, genital lesions or trauma, and coagulation disorders. Secondary PPH (SPPH) is mainly attributed to uterine infection, retained placental fragments, and abnormal involution of the placental site. English language articles and the relevant chapters of related textbooks consistently attribute the main cause of primary PPH to uterine atony. It is possible that the absence of a prospective standardized definition of PPH and the lack of consistent consideration of several clinically relevant variables (e.g. the length of labor, labor augmentation, parity) might influence the actual incidence of the different causes of PPH. This finding is particularly true for SPPH, for which inadequate pathophysiological knowledge of the postpartum period is considered by Babarinsa et al. 8 to be the major obstacle for the reliable clinical classification and proper pharmacological or surgical management.
We retrospectively investigated the placental modifications and endometrial findings observed during post-partum curettage that can constitute a more optimal pathophysiological definition of PPH and thus support clinicians more effectively in malpractice litigation situations and to enhance pregnancy-related diagnoses.
Materials and methods
The study data were derived from the Surgical Pathology Archive database of the I.R.C.C.S Azienda Ospedaliera Universitaria San Martino - IST (Istituto Nazionale per la Ricerca sul Cancro, Genoa), from which all of the surgical pathological reports of uterine revisions performed by clinicians for PPH cases between January 2000 and January 2012 were selected. The surgical pathological reports of uterine revisions were not restricted in terms of the time of delivery, although the lengths of the pregnancies were included. The surgical reports were previously anonymized by removing the patient names and the hospital medical numbers. The surgical pathological reports showed the type of delivery, the time of gestation, the patient’s age, and the timing of the onset of bleeding relative to the time of delivery. No clinical or laboratory information were recorded for the majority of the reports. These surgical pathological reports were grouped according to Armed Force Institute of Pathology 9 as follows: group A “placenta accreta” included the reports that indicated trophoblastic tissue invasion deep into the uterine wall; group B “non-accreta placental tissue retention” included the reports where fragments of placental tissue were evident without invasion into the uterine tissue; group C “no placental fragments retention” included the reports where no placental fragments were retained within the uterine wall.
The retrospective review was performed according to the “Data Protection Code – Legislative Decree n.196/2003” and the “General Authorization to Process Personal Data for Scientific Research Purposes” guidelines delineated by the Italian Data Protection Authority.
Results
Study population features.
PPH: post-partum hemorrhage; SPPH: secondary post-partum hemorrhage.
Table 1 shows that 0.22% of the samples belonged to group A, 0.46% belonged to group B, and 0.31% belonged to group C. The types of specimens were predominantly from retroplacental curettage.
Table 1 shows endometritis in 43% of the cases (24% of group A, 50% of group B, and 47% of group C). Group A comprised four vaginal deliveries (three that were associated with SPPH and one for which the onset of bleeding was not reported). In one case, the type of delivery and the onset of bleeding were not reported. Group B comprised 14 vaginal deliveries and five cesarean deliveries (all of which were associated with SPPH except one); there were three cases for which the type of delivery and the onset of bleeding were not reported. Group C comprised six cases of vaginal deliveries and four cesarean deliveries (all of which were associated with SPPH); the type of delivery was not reported for four cases (two of which were associated with SPPH and two in which the onset of bleeding was not reported).
The endometrial patterns of endometritis in 17% of the cases were combined with extra villous trophoblastic proliferation (in four Group C cases) or vascular pathologies (in three Group B cases). All of the cases were associated with SPPH and vaginal deliveries, except one Group C case, for which the onset of bleeding and the type of delivery were undetermined. The extra villous trophoblastic proliferation was scant, focal, and there were no observations of a nodular pattern observed. Mitotic activity appeared negligible.
In 15% of the cases, the placental curettage showed that the endometrial pattern of endometritis was associated with ischemic villous necrosis secondary to severe reduction of the maternal arterial flow (in two group A and four group B cases).
In 44% of the cases, the curettage did not show endometrial pathology (62% of group A cases, 43% of group B cases, and 33% of group C cases). Group A comprised seven vaginal deliveries (six that were associated with SPPH and one with PPH), four cesarean deliveries (all associated with SPPH) and two for which the type of delivery was not reported (one was associated with SPPH and 1 for which the onset of bleeding was unknown). The placental curettage material of group A showed ischemic villous necrosis secondary to severe reduction of the maternal arterial flow in 11 cases (nine cases associated with SPPH and two with PPH). Group B comprised 16 vaginal deliveries (10 that were associated with SPPH, four with PPH, and two for which the onset of bleeding was not reported) and two cesarean deliveries (both associated with SPPH) and one for which the type of delivery and the onset of bleeding were not reported. The placental curettage material of group B showed ischemic villous necrosis secondary to severe reduction of the maternal arterial flow in 10 cases (eight associated with SPPH and two with PPH). Group C comprised four cesarean deliveries (three associated with SPPH and 1 with PPH), three vaginal deliveries with combined SPPH, and three for which the type of delivery was not reported (one that was associated with SPPH and two for which the onset of bleeding was unknown). The placental curettage results were not reported for group C.
The endometrial findings for 13% of the cases showed the presence of extra villous trophoblastic proliferation (three group A, one group B and three group C cases) or vascular pathology (two group B and three group C cases) alone. The extra villous trophoblastic proliferation was scant and focal, and no nodular pattern was observed. Mitotic activity appeared negligible. Group A comprised three cases (in one of which the onset of bleeding and the type of delivery were undetermined; one case that was spontaneous was associated with PPH; and one case that was a cesarean delivery in which the onset of bleeding was undetermined). Regarding the three group B cases, two were vaginal deliveries with spontaneous afterbirth and one was an operative delivery (all combined SPPH). Regarding the six group C cases, three were vaginal deliveries and three were cesarean deliveries (all associated with SPPH). The remaining case was a vaginal delivery with primary PPH.
The entire placenta was submitted to the surgical pathologist in 23% of the cases (14% of group A, 25% of Group B, and 27% of Group C). The placental histological patterns of the group A and group B cases were identically (except one group B case that showed hydrops) characterized by “hypermaturity” and/or villous dysmaturity. This morphological placental alteration was defined according to Altshuler and Herman 10 as large villi with numerous stromal cells, a lack of syncytiotrophoblast and syncytiotrophoblastic knots.
The gross examination of the group C placentas found infarcts (25%), lacerations (12%), and no pathological alteration (62%). The placental histological patterns of these cases reflected villi dysmaturity, except for one that did not show any alteration.
Comment
Etiology determination by inspection of the lower genital tract and exploration of the uterus must be considered an imperative first step in primary PPH assessment. Surgical interventions including cesarean hysterectomy are limited to those women who continue to bleed (“second-line therapy”). 11 Despite the lack of randomized controlled trials to determine the management of woman with SPPH, the examination under anesthesia and the surgical evacuation of the uterus is generally indicated when retained placental tissue is suspected clinically or after ultrasound examination11,12; uterine revision is more frequently performed as a diagnostic than as a therapeutic procedure.13–15
Our study showed that between January 2000 and January 2012 uterine revision for PPH was required by the clinicians of the IRCCS Azienda Ospedaliera Universitaria San Martino in 0.37% of the at-term deliveries; 0.27% of the cases exhibited SPPH and 0.035% of the cases involved primary PPH, regardless of the group examined (the time of onset of bleeding was not indicated in 0.06% of the cases). The frequency of SPPH is difficult to estimate because of classification or bias problems as indicated in the following finding: “hospital-based figures may only reflect severe SPPH, or a self-selected group of patients who bypass their primary care givers” and by inadequate knowledge of the pathophysiology of the postpartum period among clinicians. 8 Boyd et al. 13 reported that 0.2% of women who delivered in two US hospitals were re-admitted for SPPH, although an online review estimated the percentage to be 1–2%. 8
From the surgical pathology reports, the purpose of the curettage was diagnostic. Both types of PPH were mainly associated with vaginal deliveries (58%), although most of the group C cases (those for which the onset of bleeding was known) were related to cesarean deliveries. According to other studies, 16 the most common cause of SPPH is endometritis (43%).
Table 1 shows that in group B, placental investigation was performed in six cases with endometritis (all combined with SPPH), and all the cases except one exhibited identical placental alterations. The equivalent microscopic placental alterations (“hypermaturity” and/or villous dysmaturity) were observed in an additional five cases that did not show post-partum endometritis at curettage. Eleven group B cases reported dysfunctional deliveries. The term villous dysmaturity is controversial, but these placental alterations are related to preplacental and uteroplacental hypoxia or dismetabolic changes such as those that occur in cases of gestational diabetes. It has been previously demonstrated in vitro that hypoxia alters cytotrophoblast differentiation and invasion. 17 Despite a lack of clear pathophysiology knowledge, the failure of the uterine contraction phase is known to be not limited to the post-partum period. The placenta, rather than an underlying myometrium abnormality, underlies uterine contractile failure. 18 The relationship of an occurrence of “non-accrete placenta” and dysfunctional labor has been previously elucidated by Weeks. 18 These observations suggest that the morphological placental alterations observed in our retrospective study might influence the uterine contraction phase with consequent incomplete removal of the placenta.
This possibility might have medico-legal implications. In general, in cases in which a small part of the placenta has been retained within the uterus, particularly following a vaginal delivery, the care provided by the midwife or obstetrician was unacceptable and the patient will likely file a claim for the morbidity associated with re-admission to the hospital and for the additional pain and suffering that sometimes causes depression. It is important to ensure that all of the products of conception are delivered. The absolute integrity of the maternal surface of the placenta cannot be reassured post-partum. It is not uncommon that the retained products are often classified as acts of negligence based upon the endometrial curettage results. In contrast, the evidence of villous changes in all eleven of the placentas of the group B cases corroborate the notion that the retention of placental tissue should be considered an inevitable complication without medico-legal implications. Placental retention must be attributed to the negligence of the attending hospital staff and the failure to diagnose and treat the symptoms. The placental and the endometrial findings are relevant from a clinical standpoint. It is unclear in the 11 cases examined whether the obstetricians submitted the placentas to the surgical pathologist according to the guidelines developed by the College of American Pathologists, 19 and if that were the case, the precise indications were also unclear. The placenta and endometrial findings reported herein suggest that in cases of manual removal of the placenta or of operative vaginal delivery, as well as in cases of therapeutic cesarean delivery, the histological evaluation of the placenta is important.
Further consideration comes from the review of the surgical pathological reports grouped as A and C.
The entire placenta was available in 14% of the group A cases, all of which were associated with retroplacental laceration and with the identical histological pattern characterized by villous dysmaturity. This data and the fact that SPPH was the most represented pathology raised the possibility that our initial classification of the surgical pathology reports was inaccurate, although all of the group A histological endometrial curettages showed trophoblastic tissue invasion deep into the uterine wall, even if only locally, and the villous ischemic necrosis observed in the majority of the curettage materials can be caused by abnormal placental detachment. This finding emphasizes the importance of accurate placental examination at the time of birth by obstetricians.
The placental examinations of 27% of the group C cases revealed a normal gross pattern in five cases, infarcts in two cases and focal retroplacental laceration in one of the cases. Among the five cases without gross abnormalities, one case did not exhibit any placental and endometrial alteration that would suggest an incorrect diagnosis of PPH by the obstetrician and consequently result in an unnecessary curettage. Despite the lack of extensive clinical information, it is probable that the loss of blood would be from a second “wave” of lochia, which can exhibit a longer duration and occur between 14 and 28 days postpartum, as described by Sherman et al. 20 Two of the four cases reporting normal gross placental appearances were associated with manual removal or operative vaginal deliveries and show the identical histological patterns of the placenta observed in the 11 cases in group B. This finding emphasizes the importance of a prospective or a retrospective case–control study to evaluate more effectively the entire placenta in cases of manual removal, operative vaginal deliveries, and therapeutic cesarean deliveries. In two additional cases, gross placental examination revealed the presence of infarcts, whereas the histology showed villous dysmaturity; both of the cases were associated with SPPH and vaginal deliveries. The curettage showed trophoblastic extravillar proliferation or a vascular pathology alone or associated with endometritis, supporting the hypothesis that the subinvolution of the placental site is an anatomic cause of post-partum uterine bleeding.21,22 In this case, endometrial curettage has not been considered curative, and bleeding might occasionally require a hysterectomy, regardless of the fluid maintenance and coagulation.
Our retrospective analysis has several limitations. Absent from this study were extensive clinical and laboratory data and the details on the medical indications of the cesarean deliveries, as well as the conditions under which each manual removal of the placenta was performed. According to Tandberg et al., 23 the lack of such data could influence the definition of “non-accrete placental tissue retained,” the grouping of all cases investigated and their incidence. We found a 0.2% (0.17%) incidence of retained placenta in this study, which surveyed nearly 25,470 deliveries. This finding indicated a significantly low incidence rate relative to that found in previously published studies that reported incidences ranging from 1% to 5.5%. 24 This disparity cannot be explained only by the different focus of our study on PPH (i.e. in this study, the retained placentas were counted only when complicated by bleeding that required curettage). Another limitation is that the entire placenta was investigated in only 23% (22/95) of the cases, which constitutes an important bias.
These results have a number of practical implications for obstetricians. In this paper, a significant number of uterine revisions was required by clinicians for SPPH, and in the cases in which a placental examination was performed by the surgical pathologist, there were potential benefits for the mother and the newborn for the following reasons: the detection of an even latent hyperglycemia or placental alterations from preplacental and uteroplacental hypoxia might predict the risk for long-term neonatal neurodevelopmental problems; distinguishing a PPH from lochial blood loss might result in the avoidance of useless curettage; placental examination might provide evidence that post-partum uterine bleeding was due to subinvolution of the placental site for which endometrial curettage has not been considered curative. The placenta and endometrial findings reported herein suggest that the histological evaluation of the placenta should likely provide notable insight about a pathogenic relationship between placenta retention and dysfunctional labor, even if without complication by PPH. Scientific evidence requires extensive study, and cost-effectiveness is an important issue in health care. Nevertheless, the findings of the study and feto-maternal health considerations support emphasizing the indication developed by the College of American Pathologists to refrigerate the entire placenta for at least 3 days, even when the gross examination is normal. As recently underlined by Sills et al., 25 the charges for placenta examinations are minuscule compared with the price of a single malpractice settlement.
Footnotes
Funding
This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
Declaration of conflicting interests
The authors declare that they do not have any conflict of interest.