Differential Diagnosis of Preeclampsia: A Comprehensive Guide

Hypertensive disorders in pregnancy remain a significant global health concern, contributing substantially to maternal and perinatal mortality. Preeclampsia, characterized by new-onset hypertension and often proteinuria after 20 weeks of gestation, is a condition that exists on a spectrum, ranging from gestational hypertension to severe preeclampsia, eclampsia, and HELLP syndrome. Affecting 2% to 8% of pregnancies, preeclampsia is linked to over 50,000 maternal and 500,000 fetal deaths worldwide. Timely diagnosis and appropriate management are critical for preventing complications through symptom control and strategic delivery planning.

This article delves into the Differential Diagnosis Of Preeclampsia, aiming to distinguish it from other conditions that may present with similar symptoms during pregnancy. Understanding the nuances of differential diagnosis is crucial for accurate management and improved patient outcomes.

Introduction

Preeclampsia, a pregnancy-specific hypertensive disorder, is defined by the onset of new hypertension, typically accompanied by proteinuria, after the 20th week of gestation, frequently occurring near term. It is part of a spectrum of hypertensive conditions in pregnancy, starting with gestational hypertension and potentially progressing to severe preeclampsia and its critical manifestations like eclampsia and HELLP syndrome.[1] This condition complicates 2% to 8% of pregnancies and is a major contributor to global maternal and perinatal mortality.[2] Early and accurate diagnosis, especially the differential diagnosis, is paramount for effective management and to mitigate maternal and neonatal risks through symptomatic treatment and delivery planning.

The diagnostic criteria for hypertension in pregnancy, defining the “mild range,” include a systolic blood pressure (SBP) of ≥140 mm Hg or diastolic blood pressure (DBP) of ≥90 mm Hg on two separate occasions at least four hours apart. In cases of “severe range” hypertension, defined as SBP ≥160 mm Hg or DBP ≥110 mm Hg, the interval can be shorter. These measurements must be taken after 20 weeks of gestation. Hypertension identified before 20 weeks is classified as pre-existing or chronic hypertension.[3]

Preeclampsia often manifests initially in late pregnancies. Pregnancy-induced hypertension (PIH) is understood to begin with gestational hypertension, progressing to more severe forms characterized by specific laboratory and clinical findings.[4, 5, 6] The understanding of PIH pathophysiology has evolved, shifting diagnostic focus from the classical triad of hypertension, edema, and proteinuria to hypertension and organ dysfunction (renal, hepatic, neurologic, hematological, or uteroplacental). Current definitions by bodies like the American College of Obstetrics and Gynecology (ACOG) are largely based on expert consensus rather than solely on primary research.[7, 5] Therefore, when considering a diagnosis of preeclampsia, it is vital to consider other conditions that might mimic its presentation—the differential diagnosis is key to accurate patient care.

Etiology

While the clinical presentation, diagnostic criteria, and management protocols for preeclampsia are well-established, the precise underlying cause remains elusive. Uteroplacental ischemia is considered the primary mechanism in the etiology of preeclampsia and eclampsia. This theory is supported by observations of placental infarctions in eclamptic patients and animal studies where placental extracts induced eclampsia-like symptoms.[4, 8, 9] The pathophysiology of preeclampsia is thought to involve the release of toxins leading to widespread vasculopathy, potentially progressing to severe complications like eclamptic seizures.[8]

The link between placental ischemia and preeclampsia is supported by substantial research, including:

Despite this consensus on uteroplacental ischemia, ongoing research continues to explore the fundamental mechanisms involved in PIH and preeclampsia. In the context of differential diagnosis, understanding the multifactorial nature of preeclampsia’s etiology helps to consider and exclude other conditions with similar pathophysiological pathways.

Epidemiology

Preeclampsia and eclampsia contribute to over 50,000 maternal deaths annually worldwide. The incidence of preeclampsia, similar to other hypertensive disorders, varies with ethnicity and race, with higher prevalence among Black and Hispanic populations, who account for approximately 26% of maternal deaths in the US due to this condition.[4, 18, 2, 19] Globally, preeclampsia affects 2% to 8% of pregnancies, with incidence variations across racial and ethnic groups and geographical locations.[20] Studies suggest higher morbidity in developing countries, particularly in Africa and Latin America, while Asian populations may have a lower risk.[21, 22] Consistent with these findings, lower preeclampsia rates have been reported in China, New Zealand, and among Asian Americans compared to Native Americans, Black Americans, and Europeans.[23, 24, 4]

Several risk factors and predisposing conditions are associated with preeclampsia, including pre-existing chronic hypertension, diabetes mellitus, renal disease, obesity, short stature, nutritional deficiencies, prior gestational hypertension, family history, autoimmune disorders (systemic lupus erythematosus, antiphospholipid antibody syndrome), hydatidiform mole, multiple pregnancies, fetal macrosomia, nulliparity, advanced maternal age, high BMI, and assisted reproductive technology.[4, 5, 25, 26] These risk factors are also relevant when considering the differential diagnosis, as some overlap with conditions that can mimic preeclampsia.

Pathophysiology

Preeclampsia is broadly classified into early-onset (placental) and late-onset (maternal) subtypes, each with distinct etiologies and clinical presentations.[27] Early-onset preeclampsia is primarily attributed to placental factors. Placentas from preeclamptic pregnancies often show placental infarcts and arterial sclerosis, leading to placental hypoperfusion due to impaired trophoblast invasion and subsequent ischemia.[28]

Late-onset preeclampsia is thought to arise from an interaction between a healthy placenta and maternal factors, potentially causing maternal endothelial dysfunction. This form typically occurs later in gestation and may be managed expectantly until 37 weeks. In late-onset preeclampsia, arterial conversion is less affected, and placental perfusion is relatively maintained.[29] Understanding these pathophysiological differences is crucial in differential diagnosis, as early- and late-onset preeclampsia might necessitate different considerations when ruling out other conditions.

Histopathology

The histopathology of preeclampsia involves a complex interplay of maternal and placental factors. Placental tissue examination often reveals maternal vascular malperfusion (MVM) lesions, characterized by abnormalities in the maternal blood supply to the placenta. These lesions may include fibrinoid necrosis, atherosis, and an increased number of syncytial knots. Trophoblast abnormalities, such as increased syncytial knot formation and reduced invasion into maternal spiral arteries, are also common. Inflammatory responses, marked by immune cell infiltration and changes in placental vasculature, are evident.

Studies have shown a higher prevalence of MVM lesions and altered placental weight in preeclampsia cases.[30] Diffuse vasculopathy, if prolonged, can lead to severe complications like eclamptic seizures. Delivery remains the definitive treatment to halt this progression by removing the inciting factors from the placenta. Histopathological findings are not only important for confirming preeclampsia but also in differentiating it from other placental pathologies that may present with similar clinical signs.

History and Physical Examination in Differential Diagnosis

Preeclampsia typically presents with characteristic historical and physical findings, but atypical presentations can complicate diagnosis. A thorough history and physical exam are crucial in the differential diagnosis process.

Common historical findings in preeclampsia include new-onset, persistent headaches unresponsive to usual treatments, not explained by other diagnoses like migraines. These headaches may be accompanied by visual disturbances. Patients might also report right upper quadrant or epigastric pain, often with nausea or vomiting. New or worsening shortness of breath and increased swelling beyond normal pregnancy-related edema may also be reported.

Key historical indicators that should raise suspicion for preeclampsia include:

• New-onset, persistent headache: Unlike typical headaches, these are often severe and do not respond to common analgesics. It’s important to differentiate these from migraines or tension headaches, which might be pre-existing conditions or have different triggers.
• Visual disturbances: These can range from blurred vision and seeing spots (scotomata) to photophobia. These symptoms are less common in other hypertensive disorders of pregnancy but can overlap with neurological conditions.
• Right upper quadrant or epigastric pain: This pain, sometimes with nausea and vomiting, can mimic gastrointestinal issues, but in pregnancy, it’s a red flag for liver capsule distention due to preeclampsia or HELLP syndrome. Differential diagnosis must consider conditions like gastritis, cholecystitis, or appendicitis.
• Sudden worsening edema: While mild edema is common in pregnancy, a sudden increase, particularly in the face and hands (non-dependent edema), is more concerning for preeclampsia. It should be differentiated from physiological edema of pregnancy and conditions like deep vein thrombosis or cellulitis which present with unilateral swelling and other distinct signs.
• Shortness of breath: New-onset dyspnea could indicate pulmonary edema secondary to preeclampsia or other respiratory or cardiac conditions exacerbated by pregnancy.

A comprehensive physical examination is essential. Vital signs, particularly blood pressure, are critical. An SBP ≥140 mmHg or DBP ≥90 mmHg should prompt suspicion for preeclampsia, especially after 20 weeks of gestation. Two readings at least 4 hours apart are recommended for diagnosis in non-severe cases. For severe hypertension (SBP ≥160 mmHg or DBP ≥110 mmHg), timely intervention is necessary, and repeat readings within minutes are sufficient for diagnosis.

According to ACOG guidelines, severe range blood pressures in patients with gestational hypertension warrant a diagnosis of preeclampsia with severe features, regardless of other diagnostic criteria. In patients presenting with shortness of breath, lung auscultation and percussion are necessary to rule out pulmonary edema or other respiratory issues. Palpation of the right upper quadrant and epigastric area can reveal tenderness indicative of liver involvement. Edema evaluation should assess both dependent (lower extremities) and independent edema (face, hands). [4]

Evaluation and Differential Diagnosis

Following history and physical examination, diagnostic testing is crucial for patients with suspected preeclampsia. Initial tests include pregnancy-induced hypertension labs, such as urinalysis for proteinuria (dipstick ≥2+, 24-hour urine collection ≥300 mg, or urine protein to creatinine ratio ≥0.3), and a complete blood count to check for thrombocytopenia (platelet count <100,000/µL). Liver function tests to assess for elevated transaminases (ALT, AST) and serum creatinine to evaluate renal function are also critical.

While hypertension and proteinuria are classic diagnostic criteria, preeclampsia can occur without proteinuria. In such cases, new-onset symptoms like thrombocytopenia, renal insufficiency, pulmonary edema, impaired liver function, or new-onset headache with visual disturbances can establish the diagnosis. This is often termed preeclampsia without severe features, even if severe range blood pressures (SBP ≥160 mmHg, DBP ≥110 mmHg on two readings at least 4 hours apart) are present without other severe features. [4, 31]

The differential diagnosis of preeclampsia is broad and includes conditions that can mimic its signs and symptoms. It’s essential to systematically rule out other potential diagnoses to ensure accurate management. Key conditions in the differential diagnosis include:

1. Gestational Hypertension:

   • Distinguishing Features: Gestational hypertension is defined by new-onset hypertension after 20 weeks of gestation without proteinuria or end-organ dysfunction. It may progress to preeclampsia.
   • Differential Points: Absence of proteinuria and other systemic signs of preeclampsia. Regular monitoring is crucial as gestational hypertension can evolve into preeclampsia.

2. Chronic Hypertension:

   • Distinguishing Features: Hypertension diagnosed before pregnancy or before 20 weeks of gestation.
   • Differential Points: Early onset of hypertension. However, women with chronic hypertension can develop superimposed preeclampsia, indicated by new-onset proteinuria or worsening hypertension and end-organ dysfunction after 20 weeks.

3. Antiphospholipid Antibody Syndrome (APS):

   • Distinguishing Features: Autoimmune disorder characterized by hypercoagulability, recurrent pregnancy loss, and arterial or venous thrombosis. APS can present with hypertension and proteinuria in pregnancy, mimicking preeclampsia.
   • Differential Points: History of recurrent miscarriages, thrombosis, or known autoimmune conditions. Positive antiphospholipid antibodies (lupus anticoagulant, anticardiolipin, anti-β2 glycoprotein-I antibodies) confirm APS. Preeclampsia typically resolves postpartum, while APS-related complications may persist.

4. Thrombotic Microangiopathies (TMAs):

   • Distinguishing Features: Conditions like Hemolytic Uremic Syndrome (HUS) and Thrombotic Thrombocytopenic Purpura (TTP) involve microangiopathic hemolytic anemia, thrombocytopenia, and organ damage. HELLP syndrome, a severe form of preeclampsia, is also a TMA and part of this differential.
   • Differential Points: Severe thrombocytopenia, microangiopathic hemolytic anemia (schistocytes on peripheral smear, elevated LDH, decreased haptoglobin), and renal failure are prominent in TMAs. While HELLP syndrome shares features with TMAs, differentiating requires careful evaluation of the clinical context and laboratory findings. TTP often presents with neurological symptoms and fever, which are less typical in preeclampsia unless it is very severe.

5. Lupus Nephritis:

   • Distinguishing Features: Renal involvement in systemic lupus erythematosus (SLE). Can present with hypertension, proteinuria, and renal dysfunction during pregnancy, similar to preeclampsia.
   • Differential Points: History of SLE or other autoimmune diseases. Serological markers for lupus (ANA, anti-dsDNA, low complement levels) and renal biopsy can differentiate lupus nephritis. Lupus flares can occur during pregnancy, complicating the differential diagnosis.

6. Epilepsy or Seizure Disorder:

   • Distinguishing Features: Pre-existing seizure disorder can be confused with eclampsia, the seizure manifestation of preeclampsia.
   • Differential Points: History of epilepsy, typical seizure patterns for the patient, and lack of hypertension and proteinuria initially may suggest epilepsy. However, preeclamptic women can develop seizures (eclampsia). New-onset seizures in pregnancy should always prompt evaluation for both eclampsia and underlying seizure disorders.

7. Chronic Renal Disease:

   • Distinguishing Features: Pre-existing renal disease can cause hypertension and proteinuria, potentially mimicking preeclampsia.
   • Differential Points: History of renal disease, abnormal renal function tests before pregnancy or early in pregnancy. Worsening renal function in the latter half of pregnancy in a woman with known renal disease might represent superimposed preeclampsia. Baseline renal function tests are critical for differentiation.

8. Chronic Liver Disease:

   • Distinguishing Features: Liver diseases can cause abnormal liver function tests, which can be seen in HELLP syndrome.
   • Differential Points: History of liver disease, jaundice, ascites, and other signs of chronic liver disease. While HELLP syndrome involves liver dysfunction, chronic liver disease has a different clinical course and history.

9. Pheochromocytoma and other Endocrinopathies:

   • Distinguishing Features: Rare conditions like pheochromocytoma (adrenal tumor causing episodic hypertension) or hyperthyroidism can cause hypertension in pregnancy.
   • Differential Points: Episodic hypertension, palpitations, sweating, and headaches in pheochromocytoma. Hyperthyroidism may present with tachycardia, heat intolerance, and goiter. These conditions are less common but should be considered in atypical presentations of hypertension in pregnancy. Specific endocrine tests (metanephrines for pheochromocytoma, thyroid function tests for hyperthyroidism) are diagnostic.

Treatment and Management in Light of Differential Diagnosis

Management of preeclampsia centers on blood pressure control and seizure prevention, initiated upon early diagnosis. However, the differential diagnosis influences management strategies. For instance, if chronic hypertension with superimposed preeclampsia is diagnosed, pre-existing antihypertensive medications may need adjustment, and closer monitoring for preeclampsia progression is essential. In cases where APS is suspected, anticoagulation might be indicated alongside preeclampsia management. If TMAs are considered, especially TTP or HUS, specific treatments like plasma exchange may be necessary, which are distinct from preeclampsia management. Ruling out other conditions ensures that treatment is appropriately targeted and avoids mismanagement based on a presumptive diagnosis of preeclampsia alone.

Antihypertensive Management:
Effective antihypertensive drugs safe for fetal use include beta-blockers (labetalol), calcium-channel blockers (nifedipine), alpha-2 agonists (clonidine), and vasodilators (hydralazine). For severe hypertension, IV labetalol, IV hydralazine, or oral immediate-release nifedipine are commonly used. Medication choice often depends on IV access availability. Maintenance antihypertensives include oral labetalol, extended-release nifedipine, and extended-release clonidine.

Antiseizure Management:
IV magnesium sulfate is the first-line agent for seizure prophylaxis in preeclampsia with severe features. Leviteracetam is an alternative if magnesium sulfate is contraindicated. Eclampsia management involves initial seizure control with IV benzodiazepines. For recurrent seizures despite magnesium sulfate, lorazepam, diazepam, phenytoin, or levetiracetam can be used.

Antepartum Management and Delivery Timing:
Fetal evaluation includes ultrasound for amniotic fluid index and estimated fetal weight, and antenatal testing (non-stress tests, biophysical profiles). Delivery is the definitive treatment for preeclampsia. For gestational hypertension or preeclampsia without severe features at 37 0/7 weeks, delivery is recommended. For preeclampsia with severe features at or beyond 34 0/7 weeks, delivery is advised after maternal stabilization. Expectant management before 34 0/7 weeks for severe preeclampsia is controversial and based on individualized assessment. Delivery before 34 0/7 weeks should include antenatal steroids for fetal lung maturation, without delaying delivery.

Prognosis

Early diagnosis, timely intervention, and careful maternal and fetal monitoring significantly improve outcomes in preeclampsia. Prompt care and routine monitoring are essential to reduce morbidity and mortality, especially in high-risk ethnic groups. However, the prognosis also depends on the accuracy of the diagnosis. Misdiagnosis or delayed differential diagnosis can lead to poorer outcomes if underlying conditions are missed or treatment is delayed.

Complications

Delayed delivery in late preterm preeclampsia increases the risk of severe complications: eclampsia, HELLP syndrome, pulmonary edema, myocardial infarction, ARDS, stroke, renal and retinal injury, fetal growth restriction, placental abruption, and fetal or maternal death. Medical management side effects, such as tachycardia, hypotension, and fetal heart abnormalities, can occur with labetalol, hydralazine, or nifedipine. Magnesium sulfate for seizure prophylaxis carries risks of respiratory depression and cardiac arrest, necessitating close monitoring of serum magnesium levels and frequent physical exams. Accurate differential diagnosis can help prevent some complications by ensuring appropriate and timely management.

Deterrence and Patient Education

Early diagnosis and management of preeclampsia are vital for reducing morbidity and mortality. Patient education is crucial, including awareness of preeclampsia, “red-flag” symptoms, and individual risk factors. Clinicians must understand community-specific barriers to care and tailor patient education accordingly, especially for high-risk and lower socioeconomic populations, to improve understanding and adherence to management plans. Education should also include awareness of conditions that can mimic preeclampsia, prompting patients to seek timely medical attention for any concerning symptoms.

Enhancing Healthcare Team Outcomes through Accurate Differential Diagnosis

Managing preeclampsia is complex, requiring a multidisciplinary team. Accurate differential diagnosis enhances team communication and targeted management. Effective interprofessional collaboration among physicians, advanced practitioners, nurses, pharmacists, and other healthcare professionals is essential for optimal care, patient safety, and improved maternal and fetal outcomes. This includes clear communication regarding patient symptoms, vital signs, lab results, treatment plans, and delivery strategies, all informed by a robust differential diagnosis process.

Conclusion

The differential diagnosis of preeclampsia is a critical aspect of managing hypertensive disorders in pregnancy. By systematically considering and excluding other conditions that mimic preeclampsia, healthcare professionals can ensure accurate diagnoses and tailor management strategies to improve maternal and fetal outcomes. A thorough understanding of the clinical presentations, risk factors, and specific diagnostic criteria for preeclampsia, as well as its mimics, is essential for providing optimal care and reducing the global burden of this significant pregnancy complication.

References

1.Erez O, Romero R, Jung E, Chaemsaithong P, Bosco M, Suksai M, Gallo DM, Gotsch F. Preeclampsia and eclampsia: the conceptual evolution of a syndrome. Am J Obstet Gynecol. 2022 Feb;226(2S):S786-S803.

2.Macedo TCC, Montagna E, Trevisan CM, Zaia V, de Oliveira R, Barbosa CP, Laganà AS, Bianco B. Prevalence of preeclampsia and eclampsia in adolescent pregnancy: A systematic review and meta-analysis of 291,247 adolescents worldwide since 1969. Eur J Obstet Gynecol Reprod Biol. 2020 May;248:177-186.

3.Battarbee AN, Sinkey RG, Harper LM, Oparil S, Tita ATN. Chronic hypertension in pregnancy. Am J Obstet Gynecol. 2020 Jun;222(6):532-541.

4.Gestational Hypertension and Preeclampsia: ACOG Practice Bulletin, Number 222. Obstet Gynecol. 2020 Jun;135(6):e237-e260.

5.Homer CS, Brown MA, Mangos G, Davis GK. Non-proteinuric pre-eclampsia: a novel risk indicator in women with gestational hypertension. J Hypertens. 2008 Feb;26(2):295-302.

6.Tanner MS, Davey MA, Mol BW, Rolnik DL. The evolution of the diagnostic criteria of preeclampsia-eclampsia. Am J Obstet Gynecol. 2022 Feb;226(2S):S835-S843.

7.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. Am J Obstet Gynecol. 2021 Feb;224(2):217.e1-217.e11.

8.Phipps EA, Thadhani R, Benzing T, Karumanchi SA. Pre-eclampsia: pathogenesis, novel diagnostics and therapies. Nat Rev Nephrol. 2019 May;15(5):275-289.

9.Jung E, Romero R, Yeo L, Gomez-Lopez N, Chaemsaithong P, Jaovisidha A, Gotsch F, Erez O. The etiology of preeclampsia. Am J Obstet Gynecol. 2022 Feb;226(2S):S844-S866.

10.BERGER M, CAVANAGH D. TOXEMIA OF PREGNANCY. THE HYPERTENSIVE EFFECT OF ACUTE EXPERIMENTAL PLACENTAL ISCHEMIA. Am J Obstet Gynecol. 1963 Oct 01;87:293-305.

11.Labarrere CA, DiCarlo HL, Bammerlin E, Hardin JW, Kim YM, Chaemsaithong P, Haas DM, Kassab GS, Romero R. Failure of physiologic transformation of spiral arteries, endothelial and trophoblast cell activation, and acute atherosis in the basal plate of the placenta. Am J Obstet Gynecol. 2017 Mar;216(3):287.e1-287.e16.

12.Staff AC, Johnsen GM, Dechend R, Redman CWG. Preeclampsia and uteroplacental acute atherosis: immune and inflammatory factors. J Reprod Immunol. 2014 Mar;101-102:120-126.

13.McMaster-Fay RA. Failure of physiologic transformation of the spiral arteries of the uteroplacental circulation in patients with preterm labor and intact membranes. Am J Obstet Gynecol. 2004 Nov;191(5):1837-8; author reply 1838-9.

14.Mlambo ZP, Khaliq OP, Moodley J, Naicker T. Circulatory and Placental Expression of Soluble Fms-like Tyrosine Kinase- 1 and Placental Growth Factor in HIV-infected Preeclampsia. Curr Hypertens Rev. 2023;19(1):27-33.

15.Young J. The Etiology of Eclampsia and Albuminuria and Their Relation to Accidental Hæmorrhage. Trans Edinb Obstet Soc. 1914;39:153-202.

16.De Wolf F, Robertson WB, Brosens I. The ultrastructure of acute atherosis in hypertensive pregnancy. Am J Obstet Gynecol. 1975 Sep 15;123(2):164-74.

17.Gallo DM, Poon LC, Akolekar R, Syngelaki A, Nicolaides KH. Prediction of preeclampsia by uterine artery Doppler at 20-24 weeks’ gestation. Fetal Diagn Ther. 2013;34(4):241-7.

18.Miller EC, Wilczek A, Bello NA, Tom S, Wapner R, Suh Y. Pregnancy, preeclampsia and maternal aging: From epidemiology to functional genomics. Ageing Res Rev. 2022 Jan;73:101535.

19.Wheeler SM, Myers SO, Swamy GK, Myers ER. Estimated Prevalence of Risk Factors for Preeclampsia Among Individuals Giving Birth in the US in 2019. JAMA Netw Open. 2022 Jan 04;5(1):e2142343.

20.Shi P, Zhao L, Yu S, Zhou J, Li J, Zhang N, Xing B, Cui X, Yang S. Differences in epidemiology of patients with preeclampsia between China and the US (Review). Exp Ther Med. 2021 Sep;22(3):1012.

21.Osungbade KO, Ige OK. Public health perspectives of preeclampsia in developing countries: implication for health system strengthening. J Pregnancy. 2011;2011:481095.

22.Fasanya HO, Hsiao CJ, Armstrong-Sylvester KR, Beal SG. A Critical Review on the Use of Race in Understanding Racial Disparities in Preeclampsia. J Appl Lab Med. 2021 Jan 12;6(1):247-256.

23.Chu H, Ramola R, Jain S, Haas DM, Natarajan S, Radivojac P. Using Association Rules to Understand the Risk of Adverse Pregnancy Outcomes in a Diverse Population. Pac Symp Biocomput. 2023;28:209-220.

24.Yang Y, Le Ray I, Zhu J, Zhang J, Hua J, Reilly M. Preeclampsia Prevalence, Risk Factors, and Pregnancy Outcomes in Sweden and China. JAMA Netw Open. 2021 May 03;4(5):e218401.

25.Sibai BM, el-Nazer A, Gonzalez-Ruiz A. Severe preeclampsia-eclampsia in young primigravid women: subsequent pregnancy outcome and remote prognosis. Am J Obstet Gynecol. 1986 Nov;155(5):1011-6.

26.Thoma ME, Boulet S, Martin JA, Kissin D. Births resulting from assisted reproductive technology: comparing birth certificate and National ART Surveillance System Data, 2011. Natl Vital Stat Rep. 2014 Dec 10;63(8):1-11.

27.Nirupama R, Divyashree S, Janhavi P, Muthukumar SP, Ravindra PV. Preeclampsia: Pathophysiology and management. J Gynecol Obstet Hum Reprod. 2021 Feb;50(2):101975.

28.Goswami D, Tannetta DS, Magee LA, Fuchisawa A, Redman CW, Sargent IL, von Dadelszen P. Excess syncytiotrophoblast microparticle shedding is a feature of early-onset pre-eclampsia, but not normotensive intrauterine growth restriction. Placenta. 2006 Jan;27(1):56-61.

29.Dionisio LM, Favero GM. Platelet indices and angiogenesis markers in hypertensive disorders of pregnancy. Int J Lab Hematol. 2024 Apr;46(2):259-265.

30.Dankó I, Kelemen E, Tankó A, Cserni G. Correlations of Placental Histopathology, Neonatal Outcome, and Cardiotocogram Baseline Variability and Acceleration Patterns in the Growth Restricted Preterm Population. Pediatr Dev Pathol. 2023 Sep-Oct;26(5):447-457.

31.Kattah AG, Garovic VD. The management of hypertension in pregnancy. Adv Chronic Kidney Dis. 2013 May;20(3):229-39.

32.Vigil-De Gracia P, Lasso M, Ruiz E, Vega-Malek JC, de Mena FT, López JC., or the HYLA treatment study. Severe hypertension in pregnancy: hydralazine or labetalol. A randomized clinical trial. Eur J Obstet Gynecol Reprod Biol. 2006 Sep-Oct;128(1-2):157-62.

33.Xu B, Charlton F, Makris A, Hennessy A. Antihypertensive drugs methyldopa, labetalol, hydralazine, and clonidine improve trophoblast interaction with endothelial cellular networks in vitro. J Hypertens. 2014 May;32(5):1075-83; discussion 1083.

34.Magley M, Hinson MR. StatPearls [Internet]. StatPearls Publishing; Treasure Island (FL): Oct 6, 2024. Eclampsia.

35.Fu J, Li C, Gou W, Lee A, Li X, Chen Q. Expectant or outpatient management of preeclampsia before 34 weeks: safe for mother but associated with increased stillbirth risk. J Hum Hypertens. 2019 Sep;33(9):664-670.

36.Duvekot JJ, Duijnhoven RG, van Horen E, Bax CJ, Bloemenkamp KW, Brussé IA, Dijk PH, Franssen MT, Franx A, Oudijk MA, Porath MM, Scheepers HC, van Wassenaer-Leemhuis AG, van Drongelen J, Mol BW, Ganzevoort W., TOTEM study collaboration group. Temporizing management vs immediate delivery in early-onset severe preeclampsia between 28 and 34 weeks of gestation (TOTEM study): An open-label randomized controlled trial. Acta Obstet Gynecol Scand. 2021 Jan;100(1):109-118.

37.Amaral LM, Wallace K, Owens M, LaMarca B. Pathophysiology and Current Clinical Management of Preeclampsia. Curr Hypertens Rep. 2017 Aug;19(8):61.