Authors: Nicholas A. Orlando, Kelsey Mumford, Marika Toscano, Jeremy Johnson, Erin N. Gomez
Categories: Case Report, Magnetic resonance imaging, Placental imaging, Preeclampsia, HELLP syndrome, Placental infarction
Source: Radiology Case Reports
Authors: Nicholas A. Orlando, Kelsey Mumford, Marika Toscano, Jeremy Johnson, Erin N. Gomez
Preeclampsia (PEC) spectrum disorders, including HELLP syndrome, are significant causes of maternal morbidity and mortality, affecting 2%-8% of pregnancies. While clinical signs and symptoms are pathognomonic, imaging can play a crucial role in diagnosis. We present a case of a 25-year-old primigravida at 27 weeks 4 days gestation who presented with severe upper abdominal pain and mild hypertension without other initial signs of PEC. Initial evaluation revealed early-onset fetal growth restriction with elevated umbilical artery Doppler ratios. Due to uncontrolled pain despite multimodal management, MRI was performed, revealing multiple T2 hypointense, T1 hyperintense lesions with diffusion restriction, suggesting multifocal intraplacental hematomas or villous infarcts. These findings prompted increased fetal surveillance and closer monitoring for PEC progression. Subsequently, the patient developed laboratory abnormalities consistent with PEC with severe features, including thrombocytopenia and elevated liver enzymes. Following antenatal corticosteroids and magnesium prophylaxis, she underwent urgent cesarean delivery at 28 weeks due to concerning fetal status. Histopathologic analysis confirmed features of maternal vascular malperfusion with multiple infarcts. The patient's laboratory values normalized postpartum, and she was normotensive at 6-week follow-up. This case highlights the potential role of MRI in identifying placental pathology that may precede clinical manifestations of PEC spectrum disorders, potentially allowing for earlier intervention and improved outcomes.
Preeclampsia (PEC) is a complex, heterogeneous pregnancy-related disorder composed of multiple overlapping clinical phenotypes. Thought to be mediated by the placenta, PEC is characterized by new-onset hypertension after 20 weeks of gestation in combination with either new onset (1) proteinuria and/or (2) thrombocytopenia, renal insufficiency, impaired liver function, pulmonary edema, or persistent neurological symptoms. PEC affects 2%-8% of pregnancies, and can progress to life-threatening complications, leading to death in 7.8% of all U.S. cases of maternal mortality [1]. HELLP syndrome (hemolysis, elevated liver enzymes, low platelets) is a more severe variant of PEC associated with increased maternal morbidity and mortality. HELLP affects approximately 0.5%-0.9% of all pregnancies and develops in 10%-20% of patients with severe preeclampsia [2,3]. HELLP syndrome typically presents in the third trimester with symptoms of colicky right upper quadrant or epigastric pain, general malaise, nausea, and vomiting, though the clinical spectrum may vary significantly, creating diagnostic challenges for clinicians [4,5]. Clinical signs include platelet value < 100,000/dL, liver aminotransferases 2-fold the upper limits of normal, and elevated lactate dehydrogenase 2-fold the upper reference limit [6].
While these clinical signs and symptoms are pathognomonic for PEC, research suggests that imaging of the placenta can also play an adjunctive and pivotal role in the diagnosis PEC spectrum disorders. Magnetic resonance imaging (MRI) has emerged as a valuable diagnostic tool in evaluating pregnancy-related complications, particularly in cases where ultrasound findings are equivocal or insufficient for diagnosis [7]. The improved soft tissue resolution, large field of view imaging, and multiplanar capabilities of MRI allow for detailed evaluation of fetal, uterine, and placental architecture [8]. Placental MRI can aid in the characterization of a spectrum of findings occurring in pre-eclampsia spectrum disorders, including intraplacental hemorrhage, infarction, and abnormal patterns of placental perfusion [[9], [10], [11]]. These imaging features may precede clinical deterioration and can provide crucial information that may guide treatment and delivery planning.
The relationship between placental imaging findings and clinical outcomes remains an area of active investigation. In this article, we describe a case of a pregnant patient presenting with isolated abdominal pain of undetermined etiology at 27 weeks gestation without accompanying signs or symptoms suggestive of a specific cause. She underwent abdominopelvic MRI demonstrating multiple hemorrhagic placental infarcts, which were otherwise occult to clinical examination, sonography, and fetal monitoring. The patient was ultimately diagnosed with PEC with severe features requiring an urgent delivery.
A 25-year-old primigravida patient at 27 weeks 4 days gestation presented to labor and delivery triage with diffuse upper abdominal pain radiating to her back, unresponsive to over-the-counter analgesics. The pain, described as 10/10 in severity, was associated with mild nausea and worsening shortness of breath but no vomiting, fever, chills, chest pain, contractions, vaginal bleeding, or rupture of membranes. Fetal movement remained intact and monitoring showed Category 1 external fetal heart rate monitoring with acontractile tocodynamometer. Initial evaluation included benign physical exam (including abdominal exam), closed cervix on speculum exam, normal bedside fetal ultrasound, and unremarkable urinalysis (Fig. 1). As there was no clear explanation for her symptoms, she was admitted for pain control, observation, and further evaluation.Fig. 12D transabdominal ultrasound survey of the placenta (red outline) showing sagittal planes [(A) fundal – uterine body; (B) lower uterine body] and transverse planes [(C) right uterus; (D) left uterus].Fig 1
On admission, the patient was diagnosed with gestational hypertension with multiple mildly elevated blood pressures over 4 hours apart. Her blood pressures were predominantly in the 140s/90s range, with a few isolated blood pressures in the low 150s/100s. Her blood pressures improved to being mostly normotensive once better pain control was achieved, and the patient was hemodynamically stable throughout her triage stay and on admission. Initial PEC labs were within normal limits (hemoglobin 14 g/dL, platelets 236,000/dL, creatinine 0.6 mg/dL, aspartate aminotransferase (AST) 25 U/L, alanine aminotransferase (ALT) 23 U/L, urine protein/creatinine ratio 0.15). Diagnostic fetal ultrasound demonstrated early-onset fetal growth restriction, with estimated fetal weight 892 g in the 4.2 percentile and abdominal circumference in the 4.1 percentile in combination with elevated systolic/diastolic ratio of umbilical artery Dopplers (5.97 cm/s, >97.5 percentile), a placental cyst measuring 1.9 cm × 1.7 cm × 1.3 cm without increased vascularity, and normal amniotic fluid index (12.39 cm) (Fig. 2). Given her continued uncontrolled upper abdominal pain despite multimodal pain management, including gabapentin, acetaminophen, cyclobenzaprine and opioids, and the potential for hepatic or placental pathology as the etiology, an abdominopelvic MRI was performed. Multiplanar T2-weighted images, T1 noncontrast images and DWI with corresponding ADC map were acquired on a 1.5T scanner.Fig. 2Hypoechoic, avascular, well circumscribed placental lesion (white arrows) in the lower uterine segment measuring 1.91 × 1.69 × 1.25 cm. (right sagittal; left transverse).Fig 2
MRI of the abdomen and pelvis without contrast was independently interpreted by a board-certified radiologist with subject matter expertise in the interpretation of MRI in obstetric patients. The MRI revealed heterogeneity of the placental parenchyma with multiple T2 hypointense lesions demonstrating intrinsic T1 hyperintensity and with associated diffusion restriction (Fig. 3, Fig. 4). A diagnosis of multifocal intraplacental hematomas or villous infarcts was suggested. Notably, no retroplacental hematoma or subchorionic hemorrhage was identified. There was no evidence of placenta accreta spectrum or other placentation anomaly. Additionally, MR evaluation of the liver was unremarkable, without subcapsular hemorrhage, and no other hepatic or intra-abdominal abnormality was identified to account for the patient’s pain (Fig. 5). While no placental abruption was visualized, the radiologic findings raised concern for abnormal placental perfusion.Fig. 3(A) Coronal T2 weighted image of the abdomen demonstrating multiple T2 hypointense foci (arrowheads) within the placenta (dashed white line). Additional site of placental signal abnormality. (B) Axial T2 weighted image of the pelvis demonstrating multiple rounded T2 hypointense foci (arrowheads), one of which demonstrates central T2 hyperintensity. (C) Corresponding axial noncontrast T1 weighted image demonstrating intrinsic hyperintensity within the lesions (arrowheads).Fig 3Fig. 4Additional site of placental signal abnormality with ovoid lesion demonstrating T2 hypointensity (A), intrinsic T1 hyperintensity (B) and hyperintensity on diffusion-weighted imaging (C) with corresponding dark signal on ADC map (D).Fig 4Fig. 5Axial (A) and coronal (B) T2-weighted images of the abdomen demonstrating normal MR appearance of the liver and upper abdomen.Fig 5
Given the MRI findings, the clinical care of the patient was modified. Fetal monitoring was adjusted from once daily nonstress test to twice daily nonstress tests due to concerns about potential progression of these placental lesions and risks of fetal hypoxia/acidemia, with heightened concern as the fetus was already known to be growth restricted with evidence of placental dysfunction. Diagnostic imaging suggested the etiology of the patient’s pain may have been related to evolving placental infarcts. As infarcts are known to be associated with resultant release of inflammatory markers and mediators contributing to systemic inflammation, she was observed very closely for worsening PEC, with serial labs, blood pressure monitoring, and frequent symptom evaluation.
On hospital day 1, Nifedipine XL 30 mg once daily was added for blood pressure optimization, though this was subsequently changed to labetalol 200 mg 3 times daily due to maternal intolerance. The labetalol was then downtitrated to 100 mg 3 times daily after overtreatment to blood pressures in the 90s/50s was observed. The gastroenterology service was consulted for management of her continued epigastric pain. Two days after admission, serial laboratory evaluation demonstrated new-onset thrombocytopenia with a decrease in platelet count from 236 to 135 K, and elevated liver transaminases above twice the upper limit of normal (AST 89 U/L, ALT 73 U/L, with the upper limit of normal being 31 U/L for both), leading to a differential diagnosis of evolving PEC with severe features and/or HELLP syndrome. The patient was started on intravenous magnesium for seizure prophylaxis with continuous electronic fetal heart rate monitoring and had a single nonsustained severe range blood pressure not requiring acute antihypertensives during this observation period. She also received antenatal corticosteroids for fetal lung maturity and consultation with neonatology, in anticipation of likely preterm delivery. On this second day of admission, her upper abdominal pain became well-controlled with the aforementioned multimodal pain management regimen.
Three days after admission, the fetal heart rate demonstrated minimal variability without accelerations or decelerations, and a biophysical profile [BPP] score was 2/10, prompting recommendation for delivery. The patient underwent an urgent mid-segment Cesarean section at 28 weeks 0 days gestation. A viable neonate weighing 840g was delivered with Apgar scores of 5 and 8 at 1 and 5 minutes, respectively, and an umbilical cord arterial pH of 7.24 with base excess −3.2. Intraoperatively, the placenta appeared calcified with areas suggestive of ischemia and hemorrhage. The placenta separated normally. A 3-vessel umbilical cord and a loose nuchal cord were noted. Upon inspection the uterus, fallopian tubes, and ovaries were otherwise normal. The estimated blood loss during the delivery was 422 mL and the procedure was otherwise uncomplicated. The infant was transferred to the pediatrics team and taken to the NICU.
Postoperatively, the patient received intravenous magnesium sulfate for 24 hours for seizure prophylaxis for a diagnosis of PEC with severe features based on elevated liver transaminases. Her pain was well controlled on oral medications. Her creatinine remained within normal limits (0.42-0.6 mg/dL) and her platelet counts and transaminases stabilized over the following 4 days (platelets 135K to 246K, AST 89 U/L to 45 U/L, ALT 73 U/L to 70 U/L). Her blood pressures remained in the normal to low mild range (140s/90s) on labetalol 100 mg 3 times daily, which was continued on discharge. She was discharged 4 days after delivery. One week after discharge, all lab values returned to within normal limits (Platelets 448K, AST 17 U/L, ALT 28 U/L, creatinine 0.69 mg/dL). Her blood pressures at that time were mostly in the 90s-100s/50s-60s, and the decision was made to discontinue labetalol. She was normotensive at her 6-week follow-up postpartum visit. The infant survived and was discharged from the hospital 1 month after birth for feeding rehabilitation. Table 1 Outlines the clinical course.Table 1Timeline of clinical events.Table 1EventTimelinePresentation to labor and delivery with diffuse upper abdominal pain-Maternal RUQ Ultrasound9 hours after admissionMRI of abdomen and pelvis without contrast18 hours after admissionContinued epigastric pain with rising liver transaminases and falling platelet countHospital Day 2Fetal heart tracing with minimal variability and a 2/10 Biophysical Profile ScoreHospital Day 3Cesarean Delivery, APGARs 5 and 8 at 1 and 5 minutesHospital Day 3Return of blood pressure, platelets and transaminases to within normal limits11 days after admission (1-week postpartum visit)
Histopathologic analysis of the placenta revealed features of maternal vascular malperfusion, with multiple centrally and peripherally located infarcts (ranging 0.4-1.7 cm in size), patchy villous agglutination, accelerated villous maturation, and a peripherally located intervillous thrombus (2.5 cm in size) (Figs. 6A and B). The maternal placental surface showed diffuse calcifications involving 60% of the surface. There was a hypercoiled 3-vessel umbilical cord. Fetal membranes showed no significant histologic abnormality.Fig. 6Hematoxylin and Eosin (H&E) stains of the placental disc with features of maternal vascular malperfusion. (A) multiple placental infarcts. (B) Accelerated villous maturation.Fig 6
Preeclampsia is a multisystem disorder with complex and heterogeneous phenotypes and pathophysiology involving placental dysfunction, angiogenic imbalance, and maternal systemic inflammation [3]. The hypothesized primary pathogenic mechanism involves inadequate remodeling of maternal spiral arteries, leading to placental ischemia and the release of anti-angiogenic factors that cause widespread endothelial dysfunction [12]. These factors oppose the normal angiogenic state of pregnancy and contribute to the maternal syndrome of hypertension and end-organ damage [13]. In approximately 10-20% of cases, preeclampsia can progress to HELLP syndrome, representing a severe variant of the disease characterized by microangiopathic hemolysis and liver dysfunction [14].
This case highlights the utility of placental imaging as an adjunct in the risk assessment and management of maternal vascular disorders of pregnancy. On ultrasound, preeclamptic placentas may show cystic areas, heterogeneous echogenicity, and variations in thickness, with peripherally echogenic irregular cystic spaces which are occasionally referred to as ‘‘destructive lesions’’ [15]. Ultrasound may also reveal hypoechoic filling defects without vascular flow, which can represent rounded intraplacental hematomas that subsequently evolve into hemorrhagic villous infarctions over time [11]. Recent studies in advanced MRI techniques have demonstrated reduced placental oxygenation in preeclampsia through T2* mapping, which displays increased heterogeneity, indicating higher levels of deoxygenated hemoglobin [16,17].
In HELLP syndrome, the same placental findings may be found but are also accompanied by hepatic manifestations, primarily assessed by ultrasound or CT when complications are suspected. Hepatic imaging findings may include enlargement of the right hepatic lobe, subcapsular hematoma, hepatic rupture, or infarction [18,19]. While MRI can also characterize hepatic complications, CT is often preferred in the acute settings due to its widespread availability and short exam time. The decision to perform CT requires careful consideration of fetal radiation exposure versus the clinical necessity. The typical fetal dose from a CT of the abdomen and pelvis is 10-50 mGy and the subsequent risk of childhood cancer is 1000-1:200; while the risk of normal childhood cancer is 500 [20]. Imaging should not be delayed if maternal or fetal health is at risk. The presence of both placental and hepatic imaging abnormalities can help differentiate HELLP syndrome from other pregnancy-related complications or maternal medical conditions and guide management decisions, including the timing of delivery.
While ultrasound remains first-line for placental evaluation, the superior tissue characterization afforded by MRI permits a more detailed characterization of placental architecture and identification of hemorrhage, particularly given the ability to image the placenta in its entirety and in the context of the surrounding uterus in a single image [7]. In this case, MRI demonstrated multiple T2 hypointense, T1 hyperintense foci within the placenta, which were hypothesized to represent intraplacental hematomas or villous infarcts. A potential mimic of these findings could be placental venous lakes, which can similarly appear T2 hypointense due to large flow voids, and this was a differential diagnosis in this case [21]. However, pathology of the placenta confirmed the findings of multiple placental infarcts. Although the patient did not have evidence of a placental abruption either clinically or on imaging, given the association with multiple placental hematomas and her abdominal pain, impending abruption could not be excluded [11]. Importantly, these imaging features served as early indicators of placental dysfunction prior to subsequent maternal-fetal clinical deterioration. Her imaging findings, along with her worsening laboratory parameters, persistent severe abdominal pain and nonreassuring fetal status guided the decision for urgent delivery. While timing delivery in PEC with severe features or HELLP syndrome remains challenging at preterm gestational ages, concerning placental findings on MRI can provide additional evidence to support clinical decisions. In this case, the relatively quick normalization of laboratory parameters postdelivery (within 1 week), confirms delivery as definitive management of PEC and HELLP and highlights the reversible nature of these syndromes when appropriately managed [3].
The relationship between PEC, HELLP syndrome and placental hemorrhage requires further characterization and prompts multiple questions about their inter-relatedness. Intraplacental hematomas may represent either a cause or consequence of maternal vascular dysfunction. The altered and abnormal microvascular environment present in HELLP syndrome may predispose to placental hemorrhage, while conversely, placental dysfunction could contribute to the development of HELLP syndrome. Understanding these relationships impacts both diagnostic approaches and management strategies. Importantly, the favorable maternal and fetal outcomes in this case underscore the significance of prompt recognition and management of both imaging findings and maternal symptoms.
Preeclampsia and HELLP syndrome are severe complications of pregnancy. Intraplacental hemorrhagic infarcts identified by pelvic MRI multiple days prior to clinical diagnosis of pre-eclampsia with severe features and HELLP syndrome helped modify this patient’s clinical management. It remains unknown if these were the cause or effect of dysfunctional placental microenvironment. MRI of the pelvis can be an adjunctive modality to guide risk assessment and clinical decision-making in cases of PEC or HELLP syndrome.
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