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Placental Function Tests PDF 12: The Latest Advances in Measuring Placental Products and Predicting



Moreover, abnormal results of placental biomarkers increase the risk of placenta accreta spectrum. For example, unexplained elevation in maternal serum alpha fetoprotein is associated with an increased risk of placenta accreta spectrum 14 15 16. However, maternal serum alpha fetoprotein is a poor predictor of placenta accreta spectrum and is not accurate enough to be clinically useful. Other placental analytes linked to placenta accreta spectrum include pregnancy-associated plasma protein A, pro B-type natriuretic peptide, troponin, free β-hCG (mRNA), and human placental lactogen (cell-free mRNA) 16 17 18 19 20. In addition, other proposed markers of aberrant trophoblast invasion, such as total placental cell-free mRNA, may be associated with placenta accreta spectrum 21. As with alpha fetoprotein, they are too nonspecific for clinical use.




placental function tests pdf 12



The use of color flow Doppler imaging may facilitate the diagnosis. Turbulent lacunar blood flow is the most common finding of placenta accreta spectrum on color flow Doppler imaging. Other Doppler findings of placenta accreta spectrum include increased subplacental vascularity, gaps in myometrial blood flow, and vessels bridging the placenta to the uterine margin 9 28 29.


Although rare, cesarean scar pregnancy may be diagnosed in the first trimester and is strongly associated with subsequent placenta accreta spectrum if untreated 35 36. This occurs when the gestational sac is embedded in the uterine window at the site of a cesarean scar. The risk of placenta accreta spectrum approaches 100% if the pregnancy is allowed to continue 35 36. Other first trimester features of placenta accreta spectrum visible on ultrasonograpy include a gestational sac that is located in the lower uterine segment and the presence of multiple irregular vascular spaces within the placental bed 28 29.


Preoperative counseling should include review of planned and possible alternate surgical strategies and complications. The most generally accepted approach to placenta accreta spectrum is cesarean hysterectomy with the placenta left in situ after delivery of the fetus (attempts at placental removal are associated with significant risk of hemorrhage). Many standard routine operative procedures, including use of standard perioperative antibiotic prophylaxis, remain applicable 68. Many clinicians will rapidly close the uterine incision and then proceed with hysterectomy after verification that the placenta will not spontaneously deliver. Attempts at forced placental removal often result in profuse hemorrhage and are strongly discouraged 24 26. If an antenatal diagnosis of placenta accreta spectrum is uncertain or the preoperative diagnosis is unclear, a period of intraoperative observation for spontaneous uterine placental separation is appropriate as long as preparations for uterine removal are in place. Alternative conservative approaches aimed at fertility preservation have been used and are discussed in subsequent sections.


Patients are frequently best served by being placed in dorsal lithotomy positioning to allow for impromptu access to the vagina and bladder as well as optimal surgical visualization of the pelvis. Because of a lack of comparative data, choice of skin incision is left to operator judgment, although many employ vertical incisions for better access and visualization. Reasonable alternatives are wide transverse incisions such as a Maylard or Cherney incision. Inspection of the uterus after peritoneal entry is obtained is highly recommended to discern the level of placental invasion and specific placental location, which allows for optimizing the approach to the uterine incision for delivery and likely hysterectomy. Whenever possible, the incision in the uterus should avoid the placenta, which sometimes makes a nontraditional incision necessary. Likewise, cystoscopy is sometimes necessary to discern anatomy if bladder involvement is suspected on direct visualization.


Hypofibrinogenemia is the biomarker most predictive of severe postpartum hemorrhage 79. In addition to standard assessment of fibrinogen levels, hypofibrinogenemia can be assessed in functional assays using viscoelastic coagulation testing such as thromboelastography or rotational thromboelastometry. Results of these tests can be obtained quickly, and detection of hypofibrinogenemia by rotational thromboelastometry predicts the severity of postpartum hemorrhage 81. A systematic review also noted that use of these tests reduced bleeding and transfusion, but not morbidity or mortality, in nonobstetric hemorrhage 82. The usefulness of rotational thromboelastometry specifically in placenta accreta spectrum is uncertain but has recently been shown to reduce mortality in trauma surgery and other surgical specialties.


Several other factors should be considered in the setting of hemorrhage and placenta accreta spectrum. Patients should be kept warm because many clotting factors function poorly if the body temperature is less than 36C. Acidosis also should be avoided. If blood loss is excessive, often defined as estimated blood loss of 1,500 mL or greater, prophylactic antibiotics should be re-dosed 68. Laboratory testing is critical to the management of obstetric hemorrhage. Baseline assessment at the initiation of bleeding should include platelet count, prothrombin time, partial thromboplastin time, and fibrinogen levels, which are normally elevated in pregnant women. Rapid and accurate results can facilitate transfusion management, although the massive transfusion protocol is not based on laboratory studies. Thus, developing a protocol that allows for rapid results from a centralized laboratory or having point of care testing on the labor and delivery unit or in the general operating room is desired.


Many of the same principles apply when placenta accreta spectrum is inadvertently discovered with the uterus already open immediately after delivery. Once the diagnosis of placenta accreta spectrum is established and it is clear that placental removal will not occur with usual maneuvers, then rapid uterine closure and proceeding to hysterectomy as judiciously as possible should be considered. Mobilization of appropriate resources should occur concurrently with ongoing hysterectomy in conjunction with the operating room nursing staff and anesthetic team. If the patient is stable after delivery of the fetus and the center is unable to perform the hysterectomy under optimal conditions, transfer should be considered. Temporizing maneuvers, packing the abdomen, tranexamic acid infusion, and transfusion with locally available products should be considered.


Uterine preservation , referred to here as conservative management, is usually defined as removal of placenta or uteroplacental tissue without removal of the uterus. Expectant management is defined as leaving the placenta either partially or totally in situ. Because placenta accreta spectrum is potentially life threatening, hysterectomy is the typical treatment. Consideration of conservative or expectant approaches should be rare and considered individually. Major complications of treatment of placenta accreta spectrum are loss of future fertility, hemorrhage, and injury to other pelvic organs. To reduce these complications, some have advocated conservative or expectant management in patients with placenta accreta spectrum 83 84.


As defined previously, conservative management is removal of the placenta or uteroplacental tissue without removing the uterus. For patients with focal placental adherence, removal of the placenta by either manual extraction or surgical excision followed by repair of the resulting defect has been associated with uterine preservation in some cases 83. Although randomized trials that compared hysterectomy to this approach are not available, it is apparent that blood loss is significantly less in a patient with a small defect using this approach. In patients with too large a defect to subsequently repair, there are data that suggest that en bloc removal of the entire uteroplacental defect followed by uterine closure results in reduced blood loss and maintains potential fertility 85. Alternatively, in a recent report, placental removal alone followed by insertion of a Bakri balloon was successful in preventing hysterectomy in 84% (16/19) of patients with placenta accreta spectrum 86. It is noteworthy that these conservative approaches have been reported only in small numbers of cases and it is unclear that all the patients included actually had placenta accreta spectrum. Accordingly, efficacy remains uncertain.


In patients with more extensive placenta accreta spectrum, expectant management is considered an investigational approach. With expectant management, the cord is ligated near the placenta and the entire placenta is left in situ, or only the placenta that spontaneously separates is removed before uterine closure. Data are limited to case series when evaluating expectant management. In the largest series, 22% (36/167) of patients required hysterectomy after an attempt at expectant management, whereas 78% (131/167) did not require hysterectomy 87. These data are consistent with other smaller case series where hysterectomy was required in 42% (14/33) and 94% (17/18) of patients 88 89. In the larger series, those with successful expectant management had a median time to placental involution of 13.5 weeks. Of the 36 patients who required hysterectomy, 18 were primary failures, occurring within 24 hours of primary cesarean, and 18 were delayed failures, occurring more than 24 hours after delivery 87. All early failures and the majority of secondary failures were secondary to increased bleeding. In addition to bleeding, infection or febrile morbidity was common and occurred in 28% (47/167) of patients but was an indication for hysterectomy in only 14% (5/36) of patients that failed expectant management. Severe morbidity , defined as sepsis, septic shock, peritonitis, uterine necrosis, fistula, injury to adjacent organs, acute pulmonary edema, acute renal failure, deep vein thrombophlebitis or pulmonary embolism, or death occurred in 6% (10/167) of patients, with 70% (7/10) of these severe outcomes occurring in the delayed hysterectomy group. Maternal sepsis occurred in 70% (7/10) of patients with severe morbidity 87. 2ff7e9595c


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