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Ophthalmic Pathology of Preeclampsia
Introduction
Preeclampsia, formerly called toxemia of pregnancy, is a disorder that affects pregnant women, most commonly in their third trimester. Characterized by hypertension and proteinuria, it can involve nearly every organ system and often results in significant end-organ dysfunction. Preeclampsia is relatively common in pregnancy, affecting up to 3% to 8% of pregnancies worldwide.[1][2] Eclampsia is defined by the occurrence of convulsions in a previously preeclamptic woman in the absence of a pre-existing neurologic condition that could account for the seizures. With an incidence of 0.3% of pregnancies, it is less common than preeclampsia but nearly always includes visual symptoms.[3][4] Hemolysis, elevated liver enzymes, and low platelets (HELLP) is a specific syndrome that can occur during the last trimester of pregnancy or shortly after birth; also a complication of pregnancy, it may represent a severe form of preeclampsia where hypertension and renal and central nervous system abnormalities are present, but not the predominant pathology.[1][5]
Visual symptoms occur in 25% to 40% of patients with preeclampsia and can involve nearly every part of the visual pathway. Symptoms can include decreased vision, diplopia, scotoma, or photopsia.[3][6][7] While there are reports on visual dysfunction in preeclampsia in the medical literature dating back to at least the 1930s, the exact mechanisms have remained elusive until the 21st century.[8][9] Although the numerous changes that occur in a woman's body during pregnancy usually revert to their pre-pregnant state during the puerperium, many ocular and cortical alterations caused by preeclampsia can persist after parturition. Identification of the specific etiologies of visual dysfunction in preeclampsia may meaningfully alter their management and prognosis.
Etiology
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Etiology
The etiologies of visual changes in preeclampsia are numerous, as are their resulting manifestations. Preeclampsia is defined as the first instance after 20 weeks of gestation of systolic blood pressure above 140 mm Hg or diastolic blood pressure above 90 mm Hg and proteinuria of greater than 300 mg/day.[1][3][4][3] Visual pathology from preeclampsia can arise de novo or result from exacerbation of pre-existing ocular or intracranial disease by hypertension, which is a hallmark of preeclampsia, and blood-glucose dysregulation that can also be associated.[10] Furthermore, the side effects of pharmacologic agents used in the treatment of toxemia during pregnancy (ie, magnesium sulfate, benzodiazepines, and phenytoin) may result in visual disturbances.[11][12][13]
Epidemiology
Visual changes are physiologic in pregnancy and can be caused by ocular surface, corneal stromal, and lenticular thickness changes, which respond to the expected hormonal variations during the gestational period. These can lead to refractive changes in the structure of the eye but usually result in a myopic shift of less than 1 diopter magnitude.[3] Blurry vision from these structural shifts can be challenging to differentiate from the pathology found in preeclampsia without a comprehensive eye examination, including funduscopy. Optic nerve and retinal changes are not expected in normal pregnancy. Retinal arterial and structural abnormalities are identified in 30 to 100% of patients with preeclampsia and eclampsia. Retinal vascular anomalies have been found in 70% of fundus examinations of patients with preeclampsia; they include arteriole narrowing, tortuosity, and segmental retinal artery vasospasm.[14] Serous retinal detachment (SRD) is found in 1% to 2% of patients with severe preeclampsia and 10% of patients with eclampsia, but the incidence of SRD in HELLP syndrome has not yet been identified. However, numerous case reports have described SRD as the sole presenting symptom of HELLP.[15][16][17][18][19][20]
Blindness, both reversible and irreversible, has been shown to have a rate of 0.1% to 3%.[3][14][3][21][22] One study of 84,628 deliveries performed at a tertiary referral center had a relatively high incidence of preeclampsia (11.7%) and exhibited an incidence of blindness of 0.17%, with a predominance of cortical blindness as the cause.[21] Cortical blindness has been identified as a cause of visual pathology in 1% to 15% of pregnancies complicated by preeclampsia.[14][23] Nearly one-third of those with preeclampsia and eclampsia have posterior reversible encephalopathy syndrome (PRES)—the most common etiology of cortical visual pathology. The strongest independent risk factors identified for cortical blindness are the presence of seizures and a history of multiple pregnancies.[24] Few studies have been performed to analyze the incidence and prevalence of intraocular and visual pathway pathology in specific populations with preeclampsia. To the author’s knowledge, there are no studies that identify specific risk factors for acute ischemic stroke causing visual symptoms nor ocular/visual pathway toxicity of commonly administered medications in patients with preeclampsia.
Pathophysiology
The pathophysiology of preeclampsia is complex and discussed elsewhere. In brief, abnormal placentation leads to placental ischemia. The ischemia results in the release of hypoxia-induced factors into circulation that are both angiogenic and anti-angiogenic and decreases circulating nitric oxide and hydrogen sulfide. This leads to subsequent endothelial dysfunction, hypertension, vasodilation, proteinuria, and platelet/red blood cell hemolysis.[2] Classic definitions of preeclampsia include only hypertension after 20 weeks of gestation with associated proteinuria. Still, more recently, the American College of Obstetricians and Gynecologists has sought to broaden the definition to include hypertension and end-organ dysfunction after 20 weeks of gestation.[2][25]
Very little is known about cortical visual pathology in pregnancy and preeclampsia. Gilbert, Prassad, and Mallory have published an excellent review of the effect of pregnancy on neuro-ophthalmologic diagnoses, which include pathophysiologic changes in the brain, the eye, and the visual pathway. Still, there are scarce data regarding many of these conditions for preeclampsia.[26] Visual evoked potentials (VEP) have been used to determine the effect of preeclampsia on cortical vision even without visual symptoms. One study by Brusse et al (2018) evaluated VEP by comparing pregnant patients with chronic hypertension, preeclampsia, or normal blood pressure, most of which did not have visual symptoms. They found that VEP latency and amplitude decreased in normotensive mothers and did not change throughout pregnancy. At the same time, patients with preeclampsia, especially severe preeclampsia, had higher VEP latency and were affected by blood pressure alterations. This change was not appreciated in chronically hypertensive mothers. This small study may indicate cerebral changes that are prominent in patients with preeclampsia even without visual symptoms.[27]
One of the most common causes of cortical visual pathology in preeclampsia is progressive reversible encephalopathy syndrome (PRES). PRES is a radiographic and clinical diagnosis of a constellation of central nervous system findings, including visual disturbances. Vasogenic edema in the posterior cerebral lobes can lead to numerous neurologic syndromes involving visual pathways. Although the posterior circulation and associated cerebral lobes (occipital and parietal) are involved, the involvement of the frontal lobes, temporal lobes, basal ganglia, brain stem, and cerebellum has also been demonstrated. The predominant theory that explains why hypertensive changes preferentially affect the posterior cerebral pathways is that the anterior cerebral circulation contains significantly more sympathetic innervation than the posterior cerebral circulation. Thus, when there are sudden changes to intraarterial fluid pressure, the posterior circulation is slower in its physiologic response. Preeclampsia can lead to sudden changes in blood pressure. This likely is why up to a third of patients with preeclampsia who have neurological symptoms are shown to have PRES.[24][28]
Additionally, cortical visual loss can be caused by ischemic cortical disease. Patients with uncomplicated pregnancies experience a hypercoagulable state related to dehydration, hemoconcentration, and markedly upregulated clotting factor levels and experience stroke at three times the rate of age-matched non-pregnant women. Although the incidence of stroke is much lower in reproductive-age women, 7.7% of pregnancy-related deaths in the United States are caused by strokes, and worldwide this number ranges from 2.7% to 20% of pregnancies. Preeclampsia and eclampsia subsequently increase the risk of both hemorrhagic and ischemic stroke, increasing the risk between 2- and 5-fold.[29][30][31][32][33] Strokes associated with preeclampsia and eclampsia have been shown to occur most frequently after delivery.[34] Numerous case studies have shown visual disability in these patients stemming from parietal, occipital, and temporal lobe strokes.[35][36][37]
Diplopia is an uncommon neuro-ophthalmologic presentation in pregnancy, but one of its principal causes is abducens nerve palsy. The sixth cranial nerve, the abducens nerve, runs a long intracranial course and is the most exposed cranial nerve that runs through the cavernous sinus.[38] This long intracranial course makes it vulnerable to various intracranial pathologies, including increased intracranial pressure, inflammation, and ischemia, all of which can be induced by preeclampsia.[39][40] Multiple case reports have documented diplopia peripartum from abducens nerve palsies and have all resolved relatively quickly after parturition.[41][42][43] Recent studies have shown intraocular pathology in preeclampsia with and without visual symptoms in addition to specific presenting diseases. Significant data identify chorioretinal changes that can be recognized on imaging and ophthalmoscopy. The retina has a dual circulation and is supplied anteriorly by the intraretinal vasculature, while the posterior retina is fed by choroidal circulation.
Studies of the retina are mostly comparative, and the pathophysiology of disease in patients with preeclampsia is limited to correlation with other diseases and observational studies utilizing clinical imaging equipment. Because of this, there are no studies of histopathological specimens from the retinas of patients with preeclampsia. Fundus photography and optical coherence tomography (OCT) imaging of patients with hypertensive retinopathy and those of patients with preeclampsia have shown that both sets of patients develop serious retinal detachments (SRD), subretinal drusenoid deposits (SDDs), and choroidal vascular abnormalities at similar rates and that are clinically indistinguishable.[44][45][46]
Histopathologic specimens of patients with malignant hypertension show significant choroidal arteriole fibrinoid necrosis and subsequent bullous SRD.[44][47] The choroid has different regulatory mechanisms to compensate for changes in blood pressure and is more affected by sudden hypertensive episodes than the retinal vasculature. Choroidal thickening develops in these episodes of sudden hypertension and has been shown in both patients with malignant hypertension and patients with preeclampsia to lead to choroidal ischemia.[45][47][48][47] Further, choroidal ischemia in hypertensive choroidopathy leads to SDDs, such as those seen in preeclampsia.[49] Choroidal ischemia is one of the proposed mechanisms for geographic chorioretinal atrophy, leading to significant permanent central visual acuity loss.[50] Choroidal ischemia has been demonstrated in 30 to 100% of patients with preeclampsia. The choroid supplies the highest blood flow per area in the body. Choroidal blood flow abnormalities lead to retinal pigment epithelium (RPE) pathology and subsequent retinal pathology due to loss of RPE function. Choroidal thickness- and implied subsequent dysfunction- is increased as measured by OCT in patients within one week after delivery. This thickness resolves postpartum. These changes are specific to preeclampsia and are not seen in an uncomplicated pregnancy.[51][52][53][54]
This change has been postulated to be related to the increased vascular endothelial growth factor (VEGF) production in preeclampsia, and that choroidal vasculature is VEGF-responsive.[55][56] Further, OCT-angiography has shown changes in the choriocapillaris, the smallest capillary channels of the choroid located closest to the posterior retina. Choriocapillaris blood flow is reduced in preeclampsia and may be the cause of these structural changes.[57] More data are required in this field to determine pathophysiologic changes to the retina and choroid in preeclampsia. In contrast to choroidal measurements, retinal structural and functional pathology have been less well-documented. Peripapillary retinal nerve fiber layer (RNFL) measurements are no different during pregnancy when compared with and without preeclampsia. Still, two months post-delivery, RNFL measurements are significantly lower in patients with preeclampsia. RNFL measurements during pregnancy are likely thickened secondary to fluid retention in pregnancy. The difference in RNFL thickness may only be appreciated after resolving the fluid shifts expected during pregnancy.[58][59][60]
Specific pathophysiologic mechanisms are dependent on the cause of pathology. Retinal vasculature changes are not routine in uncomplicated pregnancies, but between 40-100% of pregnancies complicated by preeclampsia show retinal vascular abnormalities, including arterial tortuosity, vessel narrowing, vasospasms, or occlusion. Measurements of retinal artery caliber show that for every 10 mm Hg increase in systolic blood pressure, the luminal volume of retinal arteries decreases by 1.9 µm.[61][62] Despite earlier evidence of exudates, retinal hemorrhages, vitreous hemorrhages, and cotton wool spots, recent prospective OCT analysis of patients with preeclampsia shows that these retinal findings are not associated with blood pressure measurements in these patients. Data in these studies find that fundus changes are related to changes in vascular structure as opposed to those induced by hypertension.[9]
Therapy for preeclampsia may also cause visual disturbances. Magnesium sulfate can cause visual changes due to impaired accommodation, impaired convergence, and ptosis.[12] Benzodiazepines, although less commonly used, decrease contrast sensitivity, impair visual perception, and cause cortical visual cognitive difficulties, especially regarding higher-level visual integration pathways.[13][63] Phenytoin, used as a second-line agent for seizure treatment and prophylaxis in preeclampsia and eclampsia, can cause cone and rod dysfunction and color vision deficits.[64] Although blood pressure needs to be managed in preeclampsia, rapid decreases in blood pressure may prolong visual symptoms.[21][65]
History and Physical
A thorough history can narrow the broad differential diagnosis for vision changes in preeclampsia. Prior pregnancy history, ocular history, medical history, therapeutic interventions, specific descriptions of the visual deficit, and the time-course of visual symptoms are all crucial in determining the etiology of the visual disturbance. Patients' complaints of blurry vision may be specified to include diplopia, visual field defects, metamorphopsia, or other distortions. Physical examination of patients with intracerebral causes of visual impairment can reveal concomitant neurological deficits associated with the location of pathology. Dilated fundus examination findings are common in patients with preeclampsia and most commonly include arterial narrowing, indicative of the hypertensive state. Additional findings may include peripapillary thickening, choroidal thickening, cotton wool spots, retinal hemorrhages, retinal edema, serous retinal detachments, optic nerve edema, or vitreous hemorrhage.[21]
Evaluation
Blood pressure measurements, both systolic and diastolic, and serum creatinine levels are staples of monitoring patients with preeclampsia and may be predictive of changes in dilated fundus examinations.[3] Ophthalmic evaluation, like most interventions in pregnancy, balances the unknown fetal risks of diagnostic maneuvers with the risks of maternal visual and systemic disease. Retinal angiography most commonly involves the intravenous administration of fluorescein dye and is indispensable in diagnosing retinal vascular disease. Although fluorescein can cross the placenta and can be found in breast milk after administration, the authors have found no studies identifying a known risk for its use during pregnancy, and it is currently categorized as a US Food and Drug Administration pregnancy category C drug (risk unknown but cannot be ruled out).[7][66]
However, other valuable diagnostic tools in ophthalmology offer no risk to fetal development, including fundus autofluorescence, B-scan ultrasonography, and optical coherence tomography. These non-invasive tools are essential in the evaluation of retinal, optic nerve, and choroidal pathology.[46][67] Visual field testing, another non-invasive diagnostic modality, can identify scotomata and help localize pathology. Defects can include blind spot enlargement or specific patterns of deficits such as hemi- and quadrantanopsias.[68][69][70] Magnetic resonance imaging of the brain also poses no known risk to the mother or fetus and can demonstrate posterior cerebral edema as seen in PRES; it can also reveal the presence of ischemic or hemorrhagic strokes.[24][29][30][31][32][33]
Treatment / Management
Identifying the etiology of visual impairment affects overall visual prognosis but is most important in systemic disease management and identifying risks to maternal and fetal life. In addition to prompt delivery of the baby, treatment of patients with HELLP syndrome often requires acute blood transfusions and possible liver transplantation; patients with this serious pregnancy complication can be identified by dilated fundus examination. Management of visual impairment in preeclampsia is achieved by controlling the pathophysiologic mechanisms responsible for the condition – specifically, pharmacologic stabilization of abnormal vital signs and metabolic imbalances, magnesium sulfate administration for seizure prophylaxis, and labor induction or delivery as soon as feasible.[1][71][72] Treatment of blood pressure abnormalities in patients with cortical vision loss due to PRES from preeclampsia has been shown to result in the resolution of visual impairment and radiologic findings.[73](B3)
Differential Diagnosis
Vogt Koyanagi Harada Syndrome
- Patients with this syndrome may present with serous retinal detachments but differ in that their presentation includes bilateral uveitis, vitiligo, poliosis, orbital pain, and auditory symptoms.
Postural and Volume-dependent Vision Changes
- Patients can develop transient episodes of vision loss related to decreased intraarterial volume in states of dehydration.
Posterior Ischemic Optic Neuropathy
- Patients with severe volume losses, such as in cases of significant postpartum hemorrhage, can have vision loss due to decreased perfusion of the optic nerve posterior to the lamina cribrosa.
Amniotic Fluid Embolus
- In case reports, amniotic fluid emboli have been shown to lead to intraocular fundus changes consistent with Purtscher-like retinopathy after delivery.
Increased Intracranial Pressure
- Increased intracranial pressure often presents with papilledema, headaches, and visual changes. This can be primary (idiopathic intracranial hypertension, [IIH]) or secondary (mass lesion, cerebral venous sinus thrombosis, eclampsia, meningitis). In patients who are pregnant, it can be challenging to discern if pregnancy and its associated weight gain and related hormonal changes cause IIH or are exacerbating a patient’s pre-existing disease. Furthermore, cerebral venous sinus thrombosis, which occurs more commonly in pregnant than nonpregnant women, is an important diagnosis not to miss as it is thought to cause approximately 2% of pregnancy-related strokes.
Pertinent Studies and Ongoing Trials
Current studies are evaluating normal and abnormal fundus findings in patients with preeclampsia.[74] Results from a recent study showed a significant relationship between proteinuria and retinal thickness changes similar to hypertensive retinopathy.[9]
Prognosis
Visual impairment and blindness are reversible, with the majority of ocular pathology seen in preeclampsia. In postpartum studies, the majority of patients who experienced visual symptoms of preeclampsia recovered completely. However, longitudinal studies of patients with preeclampsia have shown permanent changes to retinal microvasculature and cerebral white matter. Long-term studies have also demonstrated an increased risk for retinal structural and vascular disease. Patients with preeclampsia have 5.3 times the risk of tractional retinal detachments, an 8.5-fold increase in non-diabetic and diabetic retinopathy, and 3.7 times the risk of retinal breaks later in life.[75] Changes in retinal vasculature have been shown to persist for at least 6 years postpartum.[74]
Patients with preeclampsia have exhibited an increased incidence of white matter lesions and cerebral pathology postpartum. The distribution of lesions in one small study showed statistically significant differences in the location of white matter lesions when comparing patients with and without preeclampsia and eclampsia. Patients with preeclampsia who had white matter lesions had a 100% incidence of frontal lesions and the highest rate of temporal white matter lesions. Patients with eclampsia most represented the presence of parietal white matter lesions.[76][77][78] Patients with a history of eclampsia have reported significant visual morbidity due to these white matter lesions. Visual field testing in patients after preeclampsia and eclampsia has shown intact visual fields.[79][80]
Complications
Retinal vascular changes and their progression are an indicator of fetal and maternal mortality.[81] Further, improperly managed preeclampsia and eclampsia can lead to permanent visual impairment. Up to 8.5% of patients with preeclampsia can develop subsequent geographic atrophy that significantly affects central vision.[50] Cortical changes have been noted to persist long after delivery and recovery. A long-term study of patients with a history of preeclampsia found increased temporal lobe white matter lesions independent of cardiovascular status and increased in frequency with time after delivery.[82] The visual corroboration with these radiographic findings has yet to be studied.
Preeclampsia is an independent risk factor for future stroke in patients later in life. Estimates of the increased risk include a roughly 80% increased risk for stroke, with the relative risk/odds ratio between 1.87 and 2.02. Childbearing alone can be a risk for atherosclerosis and carotid disease, which can further cause visual symptoms.[83] Stroke and cardiovascular disease during or after pregnancy can lead to numerous causes of visual impairment and is an important sex-specific differential in causes of cerebrovascular accidents.[84][85][86][33] Systemic health concerns exist in patients with preeclampsia, including a 2- to 7-fold increased risk for cardiovascular disease and an increased risk for renal disease.[87][88]
Deterrence and Patient Education
Vision changes in pregnancies complicated by preeclampsia are most commonly due to ocular and/or brain pathology but can occasionally be caused by medical therapy. Patients should be evaluated by obstetric and ophthalmologic professionals to determine the cause. The development of preeclampsia during pregnancy can increase the risk for other eye and brain diseases post-partum.
Pearls and Other Issues
Vision changes in pregnancies complicated by preeclampsia can be caused by intraocular pathology, cortical changes, and medical therapy. Although vision often returns to baseline, retinal abnormalities and white matter lesions can develop during preeclampsia and persist, sometimes even many years after giving birth.
Enhancing Healthcare Team Outcomes
The evaluation and management of preeclampsia in a pregnant patient require collaboration and coordinated care between multiple medical specialties. Technological advancements in intraocular imaging have allowed for a greater appreciation of retinal vascular changes in this condition. Although our understanding of these processes has improved considerably, there is a need for continued study of these patients to improve visual outcomes both during and after pregnancy. Health care providers should be alert to complaints of acute visual changes in pregnant patients as they can be a presenting sign of significant impending morbidity.
References
Mol BWJ, Roberts CT, Thangaratinam S, Magee LA, de Groot CJM, Hofmeyr GJ. Pre-eclampsia. Lancet (London, England). 2016 Mar 5:387(10022):999-1011. doi: 10.1016/S0140-6736(15)00070-7. Epub 2015 Sep 2 [PubMed PMID: 26342729]
Chappell LC, Cluver CA, Kingdom J, Tong S. Pre-eclampsia. Lancet (London, England). 2021 Jul 24:398(10297):341-354. doi: 10.1016/S0140-6736(20)32335-7. Epub 2021 May 27 [PubMed PMID: 34051884]
Chandran JR, Narayanan IB, Rajan J. Ocular Manifestations: Are They Significant in Hypertensive Disorders of Pregnancy? Journal of obstetrics and gynaecology of India. 2021 Apr:71(2):118-123. doi: 10.1007/s13224-020-01385-7. Epub 2020 Nov 17 [PubMed PMID: 34149212]
Vousden N,Lawley E,Seed PT,Gidiri MF,Goudar S,Sandall J,Chappell LC,Shennan AH,CRADLE Trial Collaborative Group., Incidence of eclampsia and related complications across 10 low- and middle-resource geographical regions: Secondary analysis of a cluster randomised controlled trial. PLoS medicine. 2019 Mar; [PubMed PMID: 30925157]
Level 1 (high-level) evidenceDe Barros JFS, Amorim MM, De Lemos Costa DG, Katz L. Factors associated with severe maternal outcomes in patients with eclampsia in an obstetric intensive care unit: A cohort study. Medicine. 2021 Sep 24:100(38):e27313. doi: 10.1097/MD.0000000000027313. Epub [PubMed PMID: 34559147]
Royburt M, Seidman DS, Serr DM, Mashiach S. Neurologic involvement in hypertensive disease of pregnancy. Obstetrical & gynecological survey. 1991 Oct:46(10):656-64 [PubMed PMID: 1945196]
Digre KB. Neuro-ophthalmology and pregnancy: what does a neuro-ophthalmologist need to know? Journal of neuro-ophthalmology : the official journal of the North American Neuro-Ophthalmology Society. 2011 Dec:31(4):381-7. doi: 10.1097/WNO.0b013e31823920cb. Epub [PubMed PMID: 22089502]
Soma-Pillay P,Pillay R,Wong TY,Makin JD,Pattinson RC, The effect of pre-eclampsia on retinal microvascular caliber at delivery and post-partum. Obstetric medicine. 2018 Sep; [PubMed PMID: 30214476]
Shim KY, Bae JG, Lee JK, Kim YC. Relationship between proteinuria and optical coherence tomographic features of the chorioretina in patients with pre-eclampsia. PloS one. 2021:16(5):e0251933. doi: 10.1371/journal.pone.0251933. Epub 2021 May 20 [PubMed PMID: 34015042]
Qin Q, Chen C, Cugati S. Ophthalmic associations in pregnancy. Australian journal of general practice. 2020 Oct:49(10):673-680. doi: 10.31128/AJGP-10-19-5113. Epub [PubMed PMID: 33015686]
Level 2 (mid-level) evidenceBelfort MA. The effect of magnesium sulphate on blood flow velocity in the maternal retina in mild pre-eclampsia: a preliminary colour flow Doppler study. British journal of obstetrics and gynaecology. 1992 Aug:99(8):641-5 [PubMed PMID: 1390468]
Digre KB,Varner MW,Schiffman JS, Neuroophthalmologic effects of intravenous magnesium sulfate. American journal of obstetrics and gynecology. 1990 Dec; [PubMed PMID: 2256494]
Pompéia S, Pradella-Hallinan M, Manzano GM, Bueno OF. Effects of lorazepam on visual perceptual abilities. Human psychopharmacology. 2008 Apr:23(3):183-92. doi: 10.1002/hup.927. Epub [PubMed PMID: 18318455]
Cunningham FG, Fernandez CO, Hernandez C. Blindness associated with preeclampsia and eclampsia. American journal of obstetrics and gynecology. 1995 Apr:172(4 Pt 1):1291-8 [PubMed PMID: 7726272]
Schultz KL, Birnbaum AD, Goldstein DA. Ocular disease in pregnancy. Current opinion in ophthalmology. 2005 Oct:16(5):308-14 [PubMed PMID: 16175045]
Level 3 (low-level) evidenceWolfensberger TJ, Tufail A. Systemic disorders associated with detachment of the neurosensory retina and retinal pigment epithelium. Current opinion in ophthalmology. 2000 Dec:11(6):455-61 [PubMed PMID: 11141641]
Level 3 (low-level) evidenceSánchez Zamora P, Alina Mejía Arnaud R, Saz Castro R, Gómez Del Pulgar Vázquez B, José Correa Barrera J. Bilateral serous retinal detachment in a patient with atypical presentation of preeclampsia due to HELLP syndrome. Revista espanola de anestesiologia y reanimacion. 2021 Jun 17:():. pii: S0034-9356(21)00015-3. doi: 10.1016/j.redar.2020.11.015. Epub 2021 Jun 17 [PubMed PMID: 34148693]
Haque OI, Waris A, Rizvi SA. Bilateral serous retinal detachment: an unusual complication of HELLP syndrome. BMJ case reports. 2021 Mar 2:14(3):. doi: 10.1136/bcr-2019-233282. Epub 2021 Mar 2 [PubMed PMID: 33653827]
Level 3 (low-level) evidenceScheer H, Pielen A, Bajor A, Framme C, Hufendiek K. [Bilateral posterior serous retinal detachment associated with HELLP syndrome]. Der Ophthalmologe : Zeitschrift der Deutschen Ophthalmologischen Gesellschaft. 2021 Nov:118(11):1140-1142. doi: 10.1007/s00347-020-01257-5. Epub 2020 Nov 4 [PubMed PMID: 33146775]
Kini AT, Tabba S, Mitchell T, Al Othman B, Lee AG. Simultaneous Bilateral Serous Retinal Detachments and Cortical Visual Loss in the PRES HELLP Syndrome. Journal of neuro-ophthalmology : the official journal of the North American Neuro-Ophthalmology Society. 2021 Mar 1:41(1):e60-e63. doi: 10.1097/WNO.0000000000000942. Epub [PubMed PMID: 32235215]
Radha Bai Prabhu T. Serious Visual (Ocular) Complications in Pre-eclampsia and Eclampsia. Journal of obstetrics and gynaecology of India. 2017 Oct:67(5):343-348. doi: 10.1007/s13224-017-0975-6. Epub 2017 Mar 10 [PubMed PMID: 28867885]
Jaffe G, Schatz H. Ocular manifestations of preeclampsia. American journal of ophthalmology. 1987 Mar 15:103(3 Pt 1):309-15 [PubMed PMID: 3826237]
Do DV, Rismondo V, Nguyen QD. Reversible cortical blindness in preeclampsia. American journal of ophthalmology. 2002 Dec:134(6):916-8 [PubMed PMID: 12470768]
Level 3 (low-level) evidenceDong XY, Bai CB, Nao JF. Clinical and radiological features of posterior reversible encephalopathy syndrome in patients with pre-eclampsia and eclampsia. Clinical radiology. 2017 Oct:72(10):887-895. doi: 10.1016/j.crad.2017.06.009. Epub 2017 Aug 7 [PubMed PMID: 28797767]
Barton JR, Sibai BM. Controversies Regarding Diagnosis and Treatment of Severe Hypertension in Pregnancy. Clinical obstetrics and gynecology. 2017 Mar:60(1):198-205. doi: 10.1097/GRF.0000000000000254. Epub [PubMed PMID: 28005594]
Gilbert AL, Prasad S, Mallery RM. Neuro-Ophthalmic Disorders in Pregnancy. Neurologic clinics. 2019 Feb:37(1):85-102. doi: 10.1016/j.ncl.2018.09.001. Epub [PubMed PMID: 30470277]
Brussé IA, van den Berg CB, Duvekot JJ, Cipolla MJ, Steegers EAP, Visser GH. Visual evoked potentials in women with and without preeclampsia during pregnancy and postpartum. Journal of hypertension. 2018 Feb:36(2):319-325. doi: 10.1097/HJH.0000000000001521. Epub [PubMed PMID: 28837424]
Motolese F, Ferrante M, Rossi M, Magliozzi A, Sbarra M, Ursini F, Marano M, Capone F, Travaglino F, Antonelli Incalzi R, Di Lazzaro V, Pilato F. Posterior Reversible Encephalopathy Syndrome and brain haemorrhage as COVID-19 complication: a review of the available literature. Journal of neurology. 2021 Dec:268(12):4407-4414. doi: 10.1007/s00415-021-10709-0. Epub 2021 Jul 21 [PubMed PMID: 34291313]
Swartz RH, Cayley ML, Foley N, Ladhani NNN, Leffert L, Bushnell C, McClure JA, Lindsay MP. The incidence of pregnancy-related stroke: A systematic review and meta-analysis. International journal of stroke : official journal of the International Stroke Society. 2017 Oct:12(7):687-697. doi: 10.1177/1747493017723271. Epub [PubMed PMID: 28884652]
Level 1 (high-level) evidenceElgendy IY, Bukhari S, Barakat AF, Pepine CJ, Lindley KJ, Miller EC, American College of Cardiology Cardiovascular Disease in Women Committee. Maternal Stroke: A Call for Action. Circulation. 2021 Feb 16:143(7):727-738. doi: 10.1161/CIRCULATIONAHA.120.051460. Epub 2021 Feb 15 [PubMed PMID: 33587666]
Reddy M, Fenn S, Rolnik DL, Mol BW, da Silva Costa F, Wallace EM, Palmer KR. The impact of the definition of preeclampsia on disease diagnosis and outcomes: a retrospective cohort study. American journal of obstetrics and gynecology. 2021 Feb:224(2):217.e1-217.e11. doi: 10.1016/j.ajog.2020.08.019. Epub 2020 Aug 12 [PubMed PMID: 32795430]
Level 2 (mid-level) evidenceLeffert LR, Clancy CR, Bateman BT, Bryant AS, Kuklina EV. Hypertensive disorders and pregnancy-related stroke: frequency, trends, risk factors, and outcomes. Obstetrics and gynecology. 2015 Jan:125(1):124-131. doi: 10.1097/AOG.0000000000000590. Epub [PubMed PMID: 25560114]
Level 2 (mid-level) evidenceWu P, Haththotuwa R, Kwok CS, Babu A, Kotronias RA, Rushton C, Zaman A, Fryer AA, Kadam U, Chew-Graham CA, Mamas MA. Preeclampsia and Future Cardiovascular Health: A Systematic Review and Meta-Analysis. Circulation. Cardiovascular quality and outcomes. 2017 Feb:10(2):. pii: e003497. doi: 10.1161/CIRCOUTCOMES.116.003497. Epub 2017 Feb 22 [PubMed PMID: 28228456]
Level 2 (mid-level) evidenceMiller EC, Gatollari HJ, Too G, Boehme AK, Leffert L, Marshall RS, Elkind MSV, Willey JZ. Risk Factors for Pregnancy-Associated Stroke in Women With Preeclampsia. Stroke. 2017 Jul:48(7):1752-1759. doi: 10.1161/STROKEAHA.117.017374. Epub 2017 May 25 [PubMed PMID: 28546324]
Tolefac PN, Awungafac NS, Minkande JZ. Spontaneous haemorrhagic stroke complicating severe pre-eclampsia in pregnancy: a case report in a resource-limited setting in Cameroon. BMC pregnancy and childbirth. 2018 Dec 27:18(1):506. doi: 10.1186/s12884-018-2157-7. Epub 2018 Dec 27 [PubMed PMID: 30587133]
Level 3 (low-level) evidenceFerraldeschi M, Tari Capone F, Di Lisi F, Patella R, Ceschim V, Cao M, Cannoni S, Rasura M. When a pregnancy required a neurological consultation: a case report. La Clinica terapeutica. 2012 Nov:163(6):487-90 [PubMed PMID: 23306742]
Level 3 (low-level) evidenceOzkan SO, Korbeyli B, Bese T, Erel CT. Acute cortical blindness complicating pre-eclampsia. Archives of gynecology and obstetrics. 2001 Nov:265(4):231-2 [PubMed PMID: 11789756]
Level 3 (low-level) evidenceAzarmina M, Azarmina H. The six syndromes of the sixth cranial nerve. Journal of ophthalmic & vision research. 2013 Apr:8(2):160-71 [PubMed PMID: 23943691]
Craft I, Ah-Moye M, Al-Shawaf T, Fiamanya W, Lewis P, Robertson D, Serhal P, Shrivastav P, Simons E, Brinsden P. Analysis of 1071 gift procedures--the case for a flexible approach to treatment. Lancet (London, England). 1988 May 14:1(8594):1094-8 [PubMed PMID: 2896921]
Level 3 (low-level) evidenceFung TY, Chung TK. Abducens nerve palsy complicating pregnancy: a case report. European journal of obstetrics, gynecology, and reproductive biology. 1999 Apr:83(2):223-4 [PubMed PMID: 10391537]
Level 3 (low-level) evidenceBarry-Kinsella C, Milner M, McCarthy N, Walshe J. Sixth nerve palsy: an unusual manifestation of preeclampsia. Obstetrics and gynecology. 1994 May:83(5 Pt 2):849-51 [PubMed PMID: 8159373]
Level 3 (low-level) evidenceVallejo-Vaz AJ, Stiefel P, Alfaro V, Miranda ML. Isolated abducens nerve palsy in preeclampsia and hypertension in pregnancy. Hypertension research : official journal of the Japanese Society of Hypertension. 2013 Sep:36(9):834-5. doi: 10.1038/hr.2013.50. Epub 2013 May 30 [PubMed PMID: 23719126]
Level 3 (low-level) evidencePark CM, Kim SY. Abducens nerve palsy in pre-eclampsia after delivery: An unusual case report. The journal of obstetrics and gynaecology research. 2007 Aug:33(4):543-5 [PubMed PMID: 17688626]
Level 3 (low-level) evidenceOtero-Marquez O, Chung H, Lee CS, Choi EY, Ledesma-Gil G, Alauddin S, Lee M, Bhuiyan A, Smith RT. Subretinal Deposits in Pre-eclampsia and Malignant Hypertension: Implications for Age-Related Macular Degeneration. Ophthalmology. Retina. 2021 Aug:5(8):750-760. doi: 10.1016/j.oret.2020.10.018. Epub 2020 Oct 28 [PubMed PMID: 33130003]
Lee CS, Choi EY, Lee M, Kim H, Chung H. Serous retinal detachment in preeclampsia and malignant hypertension. Eye (London, England). 2019 Nov:33(11):1707-1714. doi: 10.1038/s41433-019-0461-8. Epub 2019 May 14 [PubMed PMID: 31089238]
Jayaraj S, Samanta R, Puthalath AS, Subramanian K. Pre-eclampsia associated bilateral serous retinal detachment. BMJ case reports. 2020 Sep 15:13(9):. doi: 10.1136/bcr-2020-238358. Epub 2020 Sep 15 [PubMed PMID: 32933916]
Level 3 (low-level) evidenceBourke K, Patel MR, Prisant LM, Marcus DM. Hypertensive choroidopathy. Journal of clinical hypertension (Greenwich, Conn.). 2004 Aug:6(8):471-2 [PubMed PMID: 15308890]
Garg A, Wapner RJ, Ananth CV, Dale E, Tsang SH, Lee W, Allikmets R, Bearelly S. Choroidal and retinal thickening in severe preeclampsia. Investigative ophthalmology & visual science. 2014 Jul 29:55(9):5723-9. doi: 10.1167/iovs.14-14143. Epub 2014 Jul 29 [PubMed PMID: 25074772]
Level 2 (mid-level) evidenceJanuszewicz A, Guzik T, Prejbisz A, Mikołajczyk T, Osmenda G, Januszewicz W. Malignant hypertension: new aspects of an old clinical entity. Polskie Archiwum Medycyny Wewnetrznej. 2016:126(1-2):86-93 [PubMed PMID: 26658350]
Saito Y, Tano Y. Retinal pigment epithelial lesions associated with choroidal ischemia in preeclampsia. Retina (Philadelphia, Pa.). 1998:18(2):103-8 [PubMed PMID: 9564689]
Level 3 (low-level) evidenceNeudorfer M, Spierer O, Goder M, Newman H, Barak S, Barak A, Asher-Landsberg I. The prevalence of retinal and optical coherence tomography findings in preeclamptic women. Retina (Philadelphia, Pa.). 2014 Jul:34(7):1376-83. doi: 10.1097/IAE.0000000000000085. Epub [PubMed PMID: 24393833]
Sharudin SN, Saaid R, Samsudin A, Mohamad NF. Subfoveal Choroidal Thickness in Pre-eclampsia. Optometry and vision science : official publication of the American Academy of Optometry. 2020 Feb:97(2):81-85. doi: 10.1097/OPX.0000000000001480. Epub [PubMed PMID: 32011579]
Benfica CZ, Zanella T, Farias LB, Oppermann MLR, Canani LHS, Lavinsky D. Choroidal thickness in preeclampsia measured by spectral-domain optical coherence tomography. International ophthalmology. 2019 Sep:39(9):2069-2076. doi: 10.1007/s10792-018-1043-7. Epub 2018 Nov 26 [PubMed PMID: 30478754]
Ziai N, Ory SJ, Khan AR, Brubaker RF. Beta-human chorionic gonadotropin, progesterone, and aqueous dynamics during pregnancy. Archives of ophthalmology (Chicago, Ill. : 1960). 1994 Jun:112(6):801-6 [PubMed PMID: 8002840]
Blaauwgeers HG, Holtkamp GM, Rutten H, Witmer AN, Koolwijk P, Partanen TA, Alitalo K, Kroon ME, Kijlstra A, van Hinsbergh VW, Schlingemann RO. Polarized vascular endothelial growth factor secretion by human retinal pigment epithelium and localization of vascular endothelial growth factor receptors on the inner choriocapillaris. Evidence for a trophic paracrine relation. The American journal of pathology. 1999 Aug:155(2):421-8 [PubMed PMID: 10433935]
Level 3 (low-level) evidenceCelik H, Avci B, Işik Y. Vascular endothelial growth factor and endothelin-1 levels in normal pregnant women and pregnant women with pre-eclampsia. Journal of obstetrics and gynaecology : the journal of the Institute of Obstetrics and Gynaecology. 2013 May:33(4):355-8. doi: 10.3109/01443615.2013.769944. Epub [PubMed PMID: 23654314]
Level 2 (mid-level) evidenceUrfalıoglu S, Bakacak M, Özdemir G, Güler M, Beyoglu A, Arslan G. Posterior ocular blood flow in preeclamptic patients evaluated with optical coherence tomography angiography. Pregnancy hypertension. 2019 Jul:17():203-208. doi: 10.1016/j.preghy.2019.07.001. Epub 2019 Jul 4 [PubMed PMID: 31487642]
Arab M, Entezari M, Ghamary H, Ramezani A, Ashori A, Mowlazadeh A, Yaseri M. Peripapillary retinal nerve fiber layer thickness in preeclampsia and eclampsia. International ophthalmology. 2018 Dec:38(6):2289-2294. doi: 10.1007/s10792-017-0718-9. Epub 2017 Sep 23 [PubMed PMID: 28942577]
Acmaz G, Atas M, Gulhan A, Acmaz B, Atas F, Aksoy H, Zararsiz G, Gokce G. Assessment of Macular Peripapillary Nerve Fiber Layer and Choroidal Thickness Changes in Pregnant Women with Gestational Diabetes Mellitus, Healthy Pregnant Women, and Healthy Non-Pregnant Women. Medical science monitor : international medical journal of experimental and clinical research. 2015 Jun 18:21():1759-64. doi: 10.12659/MSM.893221. Epub 2015 Jun 18 [PubMed PMID: 26084958]
Ciloglu E, Okcu NT, Dogan NÇ. Optical coherence tomography angiography findings in preeclampsia. Eye (London, England). 2019 Dec:33(12):1946-1951. doi: 10.1038/s41433-019-0531-y. Epub 2019 Jul 17 [PubMed PMID: 31316159]
Lupton SJ, Chiu CL, Hodgson LA, Tooher J, Ogle R, Wong TY, Hennessy A, Lind JM. Changes in retinal microvascular caliber precede the clinical onset of preeclampsia. Hypertension (Dallas, Tex. : 1979). 2013 Nov:62(5):899-904. doi: 10.1161/HYPERTENSIONAHA.113.01890. Epub 2013 Sep 9 [PubMed PMID: 24019405]
Lupton SJ, Chiu CL, Hodgson LA, Tooher J, Lujic S, Ogle R, Wong TY, Hennessy A, Lind JM. Temporal changes in retinal microvascular caliber and blood pressure during pregnancy. Hypertension (Dallas, Tex. : 1979). 2013 Apr:61(4):880-5. doi: 10.1161/HYPERTENSIONAHA.111.00698. Epub 2013 Feb 11 [PubMed PMID: 23399715]
Level 2 (mid-level) evidenceBoucart M, de Visme P, Wagemans J. Effect of benzodiazepine on temporal integration in object perception. Psychopharmacology. 2000 Oct:152(3):249-55 [PubMed PMID: 11105934]
Level 1 (high-level) evidenceThakral A, Shenoy R, Deleu D. Acute visual dysfunction following phenytoin-induced toxicity. Acta neurologica Belgica. 2003 Dec:103(4):218-20 [PubMed PMID: 15008507]
Level 3 (low-level) evidenceMitas L, Rogulski L. Acute cortical blindness in preeclampsia--a case of reversible posterior encephalopathy syndrome. Ginekologia polska. 2012 Jun:83(6):469-72 [PubMed PMID: 22880469]
Level 3 (low-level) evidenceHalperin LS,Olk RJ,Soubrane G,Coscas G, Safety of fluorescein angiography during pregnancy. American journal of ophthalmology. 1990 May 15 [PubMed PMID: 1970705]
Kızıltunç PB, Varlı B, Büyüktepe TÇ, Atilla H. Ocular vascular changes during pregnancy: an optical coherence tomography angiography study. Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie. 2020 Feb:258(2):395-401. doi: 10.1007/s00417-019-04541-6. Epub 2019 Nov 21 [PubMed PMID: 31754828]
Waghamare S, Juneja A, Samanta R, Gaurav A. Posterior reversible encephalopathy syndrome-associated bilateral cortical blindness as presenting feature of severe pre-eclampsia. BMJ case reports. 2021 Jul 15:14(7):. doi: 10.1136/bcr-2021-244797. Epub 2021 Jul 15 [PubMed PMID: 34266831]
Level 3 (low-level) evidenceCitirik M, Simsek T, Zilelioglu O. Bilateral permanent concentric visual field defect secondary to severe pre-eclampsia. Clinical ophthalmology (Auckland, N.Z.). 2008 Jun:2(2):465-8 [PubMed PMID: 19668739]
Level 3 (low-level) evidenceMiller EC,Vollbracht S, Neurology of Preeclampsia and Related Disorders: an Update in Neuro-obstetrics. Current pain and headache reports. 2021 Apr 7; [PubMed PMID: 33825997]
Edomwonyi NP, Idehen H. Cortical blindness in obstetric patients: case report of two different presentations. The Nigerian postgraduate medical journal. 2013 Jun:20(2):158-61 [PubMed PMID: 23959359]
Level 3 (low-level) evidencePhipps EA, Thadhani R, Benzing T, Karumanchi SA. Pre-eclampsia: pathogenesis, novel diagnostics and therapies. Nature reviews. Nephrology. 2019 May:15(5):275-289. doi: 10.1038/s41581-019-0119-6. Epub [PubMed PMID: 30792480]
Park AJ, Haque T, Danesh-Meyer HV. Visual loss in pregnancy. Survey of ophthalmology. 2000 Nov-Dec:45(3):223-30 [PubMed PMID: 11094246]
Level 3 (low-level) evidenceBenschop L, Schalekamp-Timmermans S, Roeters van Lennep JE, Jaddoe VWV, Wong TY, Cheung CY, Steegers EAP, Ikram MK. Gestational hypertensive disorders and retinal microvasculature: the Generation R Study. BMC medicine. 2017 Aug 14:15(1):153. doi: 10.1186/s12916-017-0917-2. Epub 2017 Aug 14 [PubMed PMID: 28803548]
Coleman AL, Olsen TW, Lum F, Parke DW 2nd. Preeclampsia and Long-term Risk of Maternal Retinal Disorders. Obstetrics and gynecology. 2017 May:129(5):946-947. doi: 10.1097/AOG.0000000000002026. Epub [PubMed PMID: 28426606]
Wiegman MJ, Zeeman GG, Aukes AM, Bolte AC, Faas MM, Aarnoudse JG, de Groot JC. Regional distribution of cerebral white matter lesions years after preeclampsia and eclampsia. Obstetrics and gynecology. 2014 Apr:123(4):790-5. doi: 10.1097/AOG.0000000000000162. Epub [PubMed PMID: 24785606]
Level 2 (mid-level) evidenceAukes AM, De Groot JC, Wiegman MJ, Aarnoudse JG, Sanwikarja GS, Zeeman GG. Long-term cerebral imaging after pre-eclampsia. BJOG : an international journal of obstetrics and gynaecology. 2012 Aug:119(9):1117-22. doi: 10.1111/j.1471-0528.2012.03406.x. Epub 2012 Jun 18 [PubMed PMID: 22703533]
Level 2 (mid-level) evidenceAukes AM, de Groot JC, Aarnoudse JG, Zeeman GG. Brain lesions several years after eclampsia. American journal of obstetrics and gynecology. 2009 May:200(5):504.e1-5. doi: 10.1016/j.ajog.2008.12.033. Epub 2009 Mar 9 [PubMed PMID: 19268882]
Wiegman MJ, de Groot JC, Jansonius NM, Aarnoudse JG, Groen H, Faas MM, Zeeman GG. Long-term visual functioning after eclampsia. Obstetrics and gynecology. 2012 May:119(5):959-66. doi: 10.1097/AOG.0b013e31824da5a8. Epub [PubMed PMID: 22525906]
Level 2 (mid-level) evidenceAukes AM, Wessel I, Dubois AM, Aarnoudse JG, Zeeman GG. Self-reported cognitive functioning in formerly eclamptic women. American journal of obstetrics and gynecology. 2007 Oct:197(4):365.e1-6 [PubMed PMID: 17904961]
van Esch JJA, van Heijst AF, de Haan AFJ, van der Heijden OWH. Early-onset preeclampsia is associated with perinatal mortality and severe neonatal morbidity. The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians. 2017 Dec:30(23):2789-2794. doi: 10.1080/14767058.2016.1263295. Epub 2017 Feb 23 [PubMed PMID: 28282780]
Siepmann T, Boardman H, Bilderbeck A, Griffanti L, Kenworthy Y, Zwager C, McKean D, Francis J, Neubauer S, Yu GZ, Lewandowski AJ, Sverrisdottir YB, Leeson P. Long-term cerebral white and gray matter changes after preeclampsia. Neurology. 2017 Mar 28:88(13):1256-1264. doi: 10.1212/WNL.0000000000003765. Epub 2017 Feb 24 [PubMed PMID: 28235810]
Skilton MR, Sérusclat A, Begg LM, Moulin P, Bonnet F. Parity and carotid atherosclerosis in men and women: insights into the roles of childbearing and child-rearing. Stroke. 2009 Apr:40(4):1152-7. doi: 10.1161/STROKEAHA.108.535807. Epub 2009 Feb 10 [PubMed PMID: 19211493]
Level 2 (mid-level) evidenceMcDermott M, Miller EC, Rundek T, Hurn PD, Bushnell CD. Preeclampsia: Association With Posterior Reversible Encephalopathy Syndrome and Stroke. Stroke. 2018 Mar:49(3):524-530. doi: 10.1161/STROKEAHA.117.018416. Epub 2018 Feb 8 [PubMed PMID: 29438078]
Okoth K, Chandan JS, Marshall T, Thangaratinam S, Thomas GN, Nirantharakumar K, Adderley NJ. Association between the reproductive health of young women and cardiovascular disease in later life: umbrella review. BMJ (Clinical research ed.). 2020 Oct 7:371():m3502. doi: 10.1136/bmj.m3502. Epub 2020 Oct 7 [PubMed PMID: 33028606]
Level 1 (high-level) evidencede Havenon A, Delic A, Stulberg E, Sheibani N, Stoddard G, Hanson H, Theilen L. Association of Preeclampsia With Incident Stroke in Later Life Among Women in the Framingham Heart Study. JAMA network open. 2021 Apr 1:4(4):e215077. doi: 10.1001/jamanetworkopen.2021.5077. Epub 2021 Apr 1 [PubMed PMID: 33900402]
Bellamy L, Casas JP, Hingorani AD, Williams DJ. Pre-eclampsia and risk of cardiovascular disease and cancer in later life: systematic review and meta-analysis. BMJ (Clinical research ed.). 2007 Nov 10:335(7627):974 [PubMed PMID: 17975258]
Level 1 (high-level) evidenceChen CW, Jaffe IZ, Karumanchi SA. Pre-eclampsia and cardiovascular disease. Cardiovascular research. 2014 Mar 15:101(4):579-86. doi: 10.1093/cvr/cvu018. Epub 2014 Feb 13 [PubMed PMID: 24532051]
Level 3 (low-level) evidence