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Thondit
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SCHOOL OF CLINICAL MEDICINE

BACHELOR OF SCIENCE IN CLINICAL MEDICINE AND COMMUNITY HEALTH

PROJECT PROPOSAL ON PREVALENCE OF PRE-ECLAMPSIA UNDER AGE OF 25

AT

 THIKA LEVEL 5

BY

MARY CHOLHOK MAYOM AKECH

BSCM/2020/68838

 

 

DECLARATION

I Mary Cholhok Mayon Akech I hereby declare that this work is entirely my own work, in my own words and that all sources used in researching are fully acknowledged and all quotations properly identified and this work has not been previously submitted in whole or in part.

 

Signature…………………………………………………..

 

Date………………………………………………………….

 

This research proposal has been submitted for review with my approval as university supervisor.

 

Signature………………………………………………………..

 

Date……………………………………………………………….

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

DEDICATION

To my father Paul Mayom Akech for his boundless love, understanding, and patience throughout this journey. Your steadfast support has been my anchor, and I am deeply grateful for the sacrifices you’ve made to make this pursuit possible.

To my mentors and advisors, your wisdom and expertise have shaped my approach and fueled my passion for this project. Your commitment to excellence has been a guiding light, and I am fortunate to have had the opportunity to learn from your vast experience.

To my colleagues and collaborators, thank you for your collaboration, insights, and shared enthusiasm for this project. Your collective efforts have enriched the proposal and made it more robust and comprehensive.

To the participants and contributors who generously shared their time and expertise, your involvement has added invaluable perspectives to this proposal, and I am grateful for your willingness to contribute to the advancement of knowledge in this field.

Lastly, to all those who believe in the significance of this project and its potential impact, your belief fuels my determination to see it through. This dedication is a testament to our shared commitment to making a positive difference.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ACKNOWLEDGEMENT:

I am deeply thankful for the guidance and mentorship provided by my supervisor. Your expertise, insightful feedback, and unwavering support have been invaluable throughout the conception and formulation of this proposal.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

LIST OF ABBREVIATIONS AND ACRONYMS

 

 PE: Pre-Eclampsia  
  PIH: Pregnancy-Induced Hypertension  

·        PIH: Pregnancy-Induced Hypertension

BP: Blood Pressure

 

 

·          BP: Blood Pressure

 MAP: Mean Arterial Pressure ·        

·        MAP: Mean Arterial Pressure

  GA: Gestational Age ·        

·        GA: Gestational Age

  NICU: Neonatal Intensive Care Unit ·          NICU: Neonatal Intensive Care Unit
  GDM: Gestational Diabetes Mellitus ·          GDM: Gestational Diabetes Mellitus
  BMI: Body Mass Index ·          BMI: Body Mass Index
  RCT: Randomized Controlled Trial ·          RCT: Randomized Controlled Trial

 

OPERATIONAL DEFINITIONS

Characterization: This is the description of the unpleasant manifestations experienced by the patients under treatment.

Coping strategies: These are mechanisms employed by the patient as a way of adapting or dealing with distressing symptoms.

Distressing symptoms: These are unpleasant manifestations that put a patient in a desperate need and may interfere with the performance of the day-to-day activities.

Patient satisfaction: This refers to a state fulfillment, contentment or gratification with the services offered to in management and assessment of distressing symptoms.

 

ABSTRACT

Pre-eclampsia, a hypertensive disorder specific to pregnancy, poses a significant threat to maternal and fetal health worldwide. This project proposal aims to investigate the prevalence of pre-eclampsia in Thika Level 5 under age of 25, identifying associated risk factors and potential avenues for early detection and intervention. The research will employ a multidisciplinary approach, integrating epidemiological, clinical, and molecular perspectives to achieve a comprehensive understanding of the condition.

The study will encompass a diverse population of pregnant individuals under age of 25 in Thika Level 5, emphasizing inclusivity across demographics, gestational ages, and geographical locations. Through a systematic review of existing literature, we will synthesize current knowledge on pre-eclampsia, shedding light on its global prevalence, regional variations, and the impact on maternal and neonatal outcomes.

Primary data collection will be conducted through a combination of prospective cohort studies and cross-sectional surveys. A wide range of variables, including maternal age, socio-economic status, medical history, and lifestyle factors, will be meticulously analyzed to identify potential risk factors associated with pre-eclampsia development.

Furthermore, the project will explore the molecular underpinnings of pre-eclampsia by investigating genetic, epigenetic, and biochemical markers. This molecular perspective aims to uncover novel biomarkers that could facilitate early diagnosis and improve risk stratification.

The ultimate goal of this project is to contribute to the development of evidence-based preventive strategies and interventions for pre-eclampsia. By combining epidemiological insights with molecular understanding, the research seeks to pave the way for personalized and targeted approaches in maternal healthcare.

Through collaboration with healthcare providers, policy-makers, and community stakeholders, the project aims to translate its findings into actionable recommendations, ultimately improving maternal and neonatal health outcomes on a global scale. The proposed research represents a significant step towards addressing the public health challenge posed by pre-eclampsia and enhancing the quality of antenatal care for pregnant individuals in Thika level 5 and overall, in Kenya.

 

CHAPTER ONE: INTRODUCTION

1.1 Background of the study

Pre-eclampsia is a hypertensive disorder specific to pregnancy, affecting both the mother and the unborn child. It typically manifests after 20 weeks of gestation and is characterized by high blood pressure (hypertension) and signs of damage to organs, commonly the liver and kidneys. This condition contributes significantly to maternal and perinatal morbidity and mortality globally.

Globally, pre-eclampsia affects approximately 5-8% of pregnancies, making it one of the leading causes of maternal and fetal morbidity and mortality.

According to the World Health Organization (WHO), pre-eclampsia and eclampsia are responsible for about 14% of maternal deaths worldwide.

Various risk factors contribute to the development of pre-eclampsia, including a first pregnancy, multiple pregnancies (e.g., twins or triplets), maternal age (young or advanced), obesity, pre-existing conditions (chronic hypertension, diabetes), and a history of pre-eclampsia in previous pregnancies.

The exact cause of pre-eclampsia is not fully understood, but it is thought to involve abnormalities in the placenta, leading to poor blood supply and oxidative stress. These factors contribute to systemic inflammation, endothelial dysfunction, and the characteristic symptoms of pre-eclampsia.

Symptoms of pre-eclampsia include high blood pressure, proteinuria (excessive protein in the urine), edema (swelling), headaches, visual disturbances, and in severe cases, seizures (eclampsia).

The severity of symptoms varies, and pre-eclampsia can progress rapidly, necessitating close monitoring during prenatal care.

The primary treatment for pre-eclampsia involves delivery of the baby, but the timing and method depend on the severity of the condition, gestational age, and overall health of both the mother and the baby.

Medications may be used to control blood pressure and prevent seizures.

Various international organizations, including the WHO and the International Society for the Study of Hypertension in Pregnancy (ISSHP), work towards improving maternal and fetal outcomes by providing guidelines for the management of hypertensive disorders in pregnancy.

In Kenya, as in many other low- and middle-income countries, pre-eclampsia is a significant concern for maternal health. Several factors contribute to the impact of pre-eclampsia in the Kenyan context.

The prevalence of pre-eclampsia in Kenya mirrors global trends, affecting a notable percentage of pregnancies.

Limited access to quality healthcare, especially in rural areas, can result in delayed diagnosis and management of pre-eclampsia, leading to adverse outcomes.

Challenges such as inadequate prenatal care, limited awareness about the condition, and disparities in healthcare resources contribute to the burden of pre-eclampsia in Kenya.

Socioeconomic factors and cultural beliefs may affect healthcare-seeking behaviors, influencing the timely identification and management of pre-eclampsia.

The Kenyan healthcare system has been working towards improving maternal healthcare, including the prevention, early detection, and management of pre-eclampsia.

Efforts are made to enhance prenatal care services, increase awareness among healthcare providers, and provide necessary resources for maternal health.

1.2 Problem Statement

Pre-eclampsia stands as a formidable threat to maternal and fetal health, posing significant challenges worldwide and in specific regional contexts, including Kenya. Despite considerable advancements in maternal healthcare, the persistent prevalence of pre-eclampsia raises concerns about its impact on maternal mortality, perinatal outcomes, and healthcare systems. This problem is exacerbated in low-resource settings, where limited access to quality healthcare further compounds the risks associated with this hypertensive disorder of pregnancy.

In Thika Level 5 hospital, pre-eclampsia remains a leading cause of maternal morbidity and mortality, accounting for a substantial proportion of adverse outcomes during pregnancy. In Kenya, where healthcare disparities, socioeconomic factors, and cultural influences intersect, the burden of pre-eclampsia is particularly poignant. Delayed diagnosis, inadequate prenatal care, and suboptimal management contribute to the high incidence of pre-eclampsia-related complications, placing pregnant individuals at an increased risk of adverse health outcomes.

The problem at hand is not only the prevalence of pre-eclampsia but also the associated disparities in awareness, timely diagnosis, and access to appropriate care. The consequences of uncontrolled pre-eclampsia extend beyond immediate health risks, impacting long-term maternal well-being and the overall health of newborns. Addressing this problem requires a comprehensive understanding of the factors contributing to the prevalence of pre-eclampsia, including genetic predispositions, environmental influences, and systemic healthcare challenges.

In light of these considerations, there is a critical need for focused research and targeted interventions to unravel the complexities of pre-eclampsia, particularly in the context of the Kenyan healthcare landscape. By addressing the prevalence of pre-eclampsia, improving diagnostic strategies, and enhancing access to quality prenatal care, it becomes possible to mitigate the adverse effects of this condition on maternal and neonatal health, ultimately working towards a future where pre-eclampsia ceases to be a significant threat to the well-being of pregnant individuals and their newborns.

1.3 Research Questions

  • What is the overall global prevalence of pre-eclampsia, and how does it vary across different regions and populations?
  • Are there identifiable trends or patterns in the prevalence of pre-eclampsia over time?
  • What demographic and socio-economic factors contribute to an increased risk of pre-eclampsia?

How do lifestyle factors, such as diet, physical activity, and maternal habits, influence t The main objective of the project proposal on the prevalence of pre-eclampsia is to conduct a comprehensive investigation into the occurrence and contributing factors of pre-eclampsia, with the ultimate goal of improving maternal and neonatal health outcomes. The specific objectives include:

 

  • The development of pre-eclampsia?

1.4.1Broad Objective

1.4.2 Specific objective

    • Determine the overall global prevalence of pre-eclampsia and explore variations across different regions and populations.
    • Investigate demographic, socio-economic, lifestyle, and medical factors that contribute to an increased risk of pre-eclampsia.
    • Examine the genetic and molecular underpinnings of pre-eclampsia, seeking to identify specific genetic markers, epigenetic changes, and molecular biomarkers associated with the condition.
    • Analyze variations in the prevalence of pre-eclampsia among different ethnic groups and explore environmental factors specific to certain regions that may influence its occurrence.
    • Evaluate the short-term and long-term health outcomes for mothers who have experienced pre-eclampsia and assess the impact on neonatal outcomes, including birth weight, gestational age at delivery, and neonatal mortality.
    • Examine the role of disparities in healthcare access and quality in contributing to variations in pre-eclampsia prevalence, and assess how socio-economic factors influence early detection and management.
    • Propose evidence-based preventive strategies based on identified risk factors, with the aim of reducing the prevalence and severity of pre-eclampsia.
    • Understand the perspectives and experiences of pregnant individuals regarding pre-eclampsia awareness, prevention, and management.
    • Assess healthcare provider approaches to pre-eclampsia prevention, early detection, and management, and identify opportunities for improvement.

 

1.5 Hypothesis

  • Null Hypothesis (H0): There is no association between genetic factors and the prevalence of pre-eclampsia.
  • Alternative Hypothesis (H1): Specific genetic markers and variations are associated with an increased risk of pre-eclampsia.

 

 

 

1.6 Justification

The justification for conducting a project on the prevalence of pre-eclampsia lies in the significant impact this hypertensive disorder has on maternal and neonatal health globally. Several key reasons support the need for comprehensive research in this area:

The project aims to contribute new knowledge to the scientific community by synthesizing existing literature, conducting original research, and proposing evidence-based recommendations. This can advance the field of maternal-fetal medicine and guide future research endeavors.

1.7 Study Variables

These variables can be measured, analyzed, and compared to identify patterns, associations, and potential risk factors related to the prevalence of pre-eclampsia. The inclusion of a diverse set of variables allows for a comprehensive understanding of the condition from various perspectives, contributing to the depth and breadth of the research.

 

 

 

 

 

 

 

 

 

 

 

 

 

CHAPTER TWO: LITERATURE REVIEW

2.1 Introduction

Pregnancy-induced hypertensive disorders, particularly pre-eclampsia, continue to pose substantial threats to maternal and neonatal health globally. Pre-eclampsia, characterized by new-onset hypertension and evidence of organ dysfunction, remains a leading cause of maternal mortality and morbidity, affecting approximately 5-8% of pregnancies worldwide (Abalos et al., 2013). Despite decades of research, the etiology of pre-eclampsia remains elusive, and its prevalence displays intriguing geographical and ethnic variations. A comprehensive understanding of the prevalence and associated factors is essential for informing evidence-based interventions and improving maternal-fetal health outcomes.

2.2 Background on preclampsia

Pre-eclampsia is a hypertensive disorder that occurs during pregnancy and the postpartum period, characterized by the onset of high blood pressure and signs of damage to organs, most commonly the liver and kidneys. It is a leading cause of maternal and perinatal morbidity and mortality globally, contributing to adverse outcomes for both the mother and the newborn.

Clinical Presentation: Pre-eclampsia typically manifests after 20 weeks of gestation, although it can occur earlier or even postpartum. Common signs and symptoms include hypertension (blood pressure of 140/90 mm Hg or higher), proteinuria (presence of excess protein in the urine), and often edema, particularly in the hands and face. In severe cases, pre-eclampsia can lead to organ dysfunction, seizures (eclampsia), and other serious complications.

Risk Factors: While the exact cause of pre-eclampsia remains unclear, several risk factors have been identified. These include a first pregnancy, multiple pregnancies (e.g., twins or triplets), maternal age (particularly in women younger than 20 or older than 40), obesity, chronic hypertension, diabetes, and a history of pre-eclampsia in a previous pregnancy. Additionally, women with pre-existing conditions such as autoimmune diseases, kidney disease, and certain genetic factors may be at an increased risk.

Pathophysiology: The pathophysiology of pre-eclampsia involves abnormalities in the placenta, the organ that nourishes the fetus during pregnancy. Insufficient blood flow to the placenta can trigger a cascade of events leading to oxidative stress, inflammation, and impaired vascular function. These changes contribute to the characteristic hypertension and organ damage observed in pre-eclampsia.

Complications: Pre-eclampsia can result in a range of complications for both the mother and the baby. Maternal complications may include stroke, organ failure, and the development of HELLP syndrome (Hemolysis, Elevated Liver enzymes, Low Platelet count). Adverse outcomes for the baby may include preterm birth, low birth weight, and in severe cases, stillbirth.

Management and Prevention: The primary treatment for pre-eclampsia involves delivery of the baby. However, the timing and method of delivery depend on factors such as the severity of the condition, gestational age, and the overall health of both the mother and the fetus. Monitoring blood pressure, managing symptoms, and providing supportive care are essential components of pre-eclampsia management.

Public Health Impact: Pre-eclampsia remains a significant global public health challenge, contributing to maternal and neonatal mortality, particularly in low-resource settings. Efforts to improve antenatal care, raise awareness, and identify effective preventive strategies are critical for addressing the impact of pre-eclampsia on maternal and child health.

In conclusion, pre-eclampsia is a complex and multifaceted condition with serious implications for maternal and fetal health. Ongoing research aims to enhance our understanding of its etiology, improve early detection, and develop effective preventive and management strategies to reduce the burden it poses on global maternal and child health.

 

 

2.3 Distressing symptoms in pre-eclampsia patients

Pre-eclampsia is a serious condition that can have distressing symptoms for pregnant individuals. It is crucial to note that not all individuals with pre-eclampsia will experience the same symptoms, and in some cases, the condition may progress without noticeable signs. However, here are some distressing symptoms commonly associated with pre-eclampsia:

  • High Blood Pressure: Pre-eclampsia is characterized by an increase in blood pressure, often defined as a reading of 140/90 mm Hg or higher. Elevated blood pressure can lead to a range of complications and is a key diagnostic criterion for pre-eclampsia.
  • Proteinuria: One of the hallmark signs of pre-eclampsia is the presence of excess protein in the urine (proteinuria). This occurs due to kidney dysfunction, which is common in pre-eclampsia. Proteinuria is usually detected through a urine test.
  • Edema: Swelling, particularly in the hands and face, can be distressing for pregnant individuals with pre-eclampsia. While some swelling is normal in pregnancy, sudden or severe swelling can be indicative of fluid retention associated with pre-eclampsia.
  • Headaches: Persistent and severe headaches are common symptoms of pre-eclampsia. These headaches may not respond well to typical headache remedies and can be accompanied by visual disturbances.
  • Visual Disturbances: Pre-eclampsia can cause visual disturbances, including blurred vision, sensitivity to light (photophobia), and seeing flashing lights or spots. These symptoms may be indicative of increased pressure in the brain.
  • Abdominal Pain: Severe pain in the upper right side of the abdomen, beneath the ribs, may be a sign of liver involvement in pre-eclampsia. This can be a distressing symptom and should be promptly addressed.

 

 

 

 

2.4 Severity of the distressing symptoms among  pre-eclampsia patients

The severity of distressing symptoms among pre-eclampsia patients can vary widely, and it is essential to recognize that not all individuals will experience the same intensity or combination of symptoms. The severity of symptoms is often linked to the stage and progression of pre-eclampsia. Here’s a general overview of how symptoms may manifest at different levels of severity:

The progression from mild to severe pre-eclampsia can be rapid, underscoring the importance of regular prenatal check-ups and monitoring. The severity of symptoms may also prompt healthcare providers to recommend an early delivery if the condition poses a significant risk to the health of the mother or baby.

Any distressing symptoms associated with pre-eclampsia warrant immediate medical attention. Timely diagnosis and management are crucial to prevent complications and ensure the well-being of both the pregnant individual and the baby. Pregnant individuals should communicate openly with their healthcare providers about any concerns or symptoms they may be experiencing.

2.5 Theoretical Model

Creating a theoretical model for pre-eclampsia involves conceptualizing the complex interplay of factors that contribute to the development and progression of the condition. While the exact etiology of pre-eclampsia is not fully understood, various theories and models attempt to integrate genetic, physiological, and environmental factors. Here is a simplified theoretical model for pre-eclampsia:

This theoretical model is a simplified representation and doesn’t capture all complexities associated with pre-eclampsia. It highlights the interconnected nature of genetic, physiological, and environmental factors in the development of pre-eclampsia. Research continues to refine and expand our understanding of pre-eclampsia.

 

CHAPTER THREE: METHODOLOGY

3.1 Introduction

 

This chapter outlines the methodology adopted for investigating the prevalence of pre-eclampsia, a critical aspect of maternal health. The research design, sampling strategy, data collection methods, and data analysis procedures are detailed to ensure a comprehensive and rigorous study.

3.2 Research Design

This study employs a mixed-methods approach, integrating both quantitative and qualitative research methods. The quantitative component involves a cross-sectional survey to assess the prevalence of pre-eclampsia, while the qualitative component includes in-depth interviews and focus group discussions to explore the contextual factors influencing the condition.

3.3 Population and Sampling

3.3.1 Quantitative Sampling

The target population for the quantitative survey comprises pregnant individuals attending prenatal clinics in thika level 5 hospital . A systematic random sampling technique will be employed to select clinics, and pregnant individuals will be selected through systematic sampling.

3.3.2 Qualitative Sampling

The qualitative component will include pregnant individuals diagnosed with pre-eclampsia, healthcare providers specializing in maternal-fetal medicine, and community stakeholders involved in maternal health initiatives. A purposeful sampling method will be used to ensure diversity in experiences and perspectives.

3.4 Data Collection Procedures

3.4.1 Quantitative Data Collection

Quantitative data will be collected through structured surveys administered to pregnant individuals during their routine prenatal visits. The survey will cover demographic information, medical history, lifestyle factors, awareness of pre-eclampsia, and clinical parameters associated with pre-eclampsia.

3.4.2 Qualitative Data Collection

Qualitative data will be collected through in-depth interviews and focus group discussions. Semi-structured interview guides will be developed for pregnant individuals, healthcare providers, and community stakeholders. Interviews will be conducted in private settings, and focus group discussions will be organized in community spaces.

3.5 Data Analysis Procedures

3.5.1 Quantitative Data Analysis

Quantitative data will be entered into statistical software for analysis. Descriptive statistics will be employed to summarize demographic characteristics and prevalence rates. Inferential statistics, such as chi-square tests and logistic regression, will be used to identify associations and risk factors related to pre-eclampsia.

3.5.2 Qualitative Data Analysis

Qualitative data will undergo thematic analysis. Two independent researchers will code the transcripts, and regular meetings will be held to ensure coding consistency. Themes and patterns will be identified, and data will be organized into a coherent framework, providing a nuanced understanding of the contextual factors influencing pre-eclampsia.

3.6 Ethical Considerations

Ethical considerations include obtaining informed consent from all participants, ensuring confidentiality, and prioritizing participant well-being. The research proposal has received ethical approval from Mount Kenya university.

3.7 Limitations of the Study

Acknowledging potential limitations is crucial. The study may face limitations related to self-reporting bias, recall bias, and the availability of healthcare resources in certain geographical location

 

 

 

APPENDIX I: WORKPLAN

Activity MAY 2023 JUNE 2023 JULY 2023 AUG 2023 SEP 2023 OCT 2023 NOV 2023 DEC 2023
Topic selection                
Proposal development                
Proposal writing                
Proposal presentation                
Data collection                
Data analysis                
Project writing                
Project submission                

 

 

 

 

 

 

 

 

 

 

 

 

 

APPENDIX II: BUDGET

S/N ITEMS REQUIRED UNIT PRICE
1 Binding 200
2 Printing 700
3 Internet 2000
4 Typing 800
5 Accommodation 1500
6 Food 1000
7. Miscellaneous Expenses 1000
  TOTAL KSHS. 7200

 

 

 

Appendix III: Questionnaire

Serial Number……………………… Date………………………………….. Instructions

Please follow the instructions below

  1. Do not indicate your name anywhere in the
  2. Please tick in the appropriate response in the space

Section A: Sociodemographic data of the patient

  1. What is your Age? <u> </u>
  2. What’s your marital status? Single

Married <u>   </u>

Divorced <u>   </u>

Widowed <u>   </u>

Separated<u>   </u>

  1. What is your religion? Christian <u> </u> Muslim  Hindu

Others, specify <u>   </u>

  1. Monthly House income
    1. Adequate to meet family needs
    2. Barely adequate to meet family needs
    3. Inadequateto meet family needs
  2. What is your diagnosis?
  1. What is the duration since diagnosis? <u> </u>
  2. Which treatment modality have you had? (Tick all that apply) Chemotherapy

Immunotherapy Radiotherapy Surgery

  1. When did you start treatment? <u> </u>
  2. What is the aim of the current treatment?

 

Curative Palliative

  1. How do you take care of your medical expenses? (Tick all that apply)
    1. Self-sponsored
    2. Hospital waivers
    3. Fundraisers
    4. NHIF
    5. Other insurances

 

SECTION B: Distressing Symptoms

  1. Please indicate if you have experienced any of the following symptoms

 

S/No Symptom Yes No
i. headache    
ii. Tiredness (Lack of Energy)    
iii. Drowsiness    
iv. Nausea    
v. Vomiting    
vi. High blood pressure    
vii. Abdominal pain    
viii. Body swelling    
ix. Depression (Feeling sad)    
x. Shortness of breath    
xi. Visual disturbance    
  1. Do you experience other symptoms apart from those stated above? Yes

No

  1. If YES in the above statement, state the symptoms

 

 

REFERENCES

  1. Abalos E, Cuesta C, Grosso AL, et al. (2013). Global and regional estimates of preeclampsia and eclampsia: a systematic review. European Journal of Obstetrics & Gynecology and Reproductive Biology, 170(1), 1–7.
  2. American College of Obstetricians and Gynecologists (ACOG). (2019). ACOG Practice Bulletin No. 202: Gestational Hypertension and Preeclampsia. Obstetrics and Gynecology, 133(1), e1–e25.
  3. Duckitt K, Harrington D. (2005). Risk factors for pre-eclampsia at antenatal booking: systematic review of controlled studies. BMJ, 330(7491), 565.
  4. Kenny LC, Black MA, Poston L, et al. (2014). Early pregnancy prediction of preeclampsia in nulliparous women, combining clinical risk and biomarkers: the Screening for Pregnancy Endpoints (SCOPE) international cohort study. Hypertension, 64(3), 644–652.
  5. Khan KS, Wojdyla D, Say L, Gülmezoglu AM, Van Look PF. (2006). WHO analysis of causes of maternal death: a systematic review. The Lancet, 367(9516), 1066–1074.
  6. Kuklina EV, Ayala C, Callaghan WM. (2009). Hypertensive disorders and severe obstetric morbidity in the United States. Obstetrics and Gynecology, 113(6), 1299–1306.
  7. Rolnik DL, Wright D, Poon LC, et al. (2017). Aspirin versus Placebo in Pregnancies at High Risk for Preterm Preeclampsia. New England Journal of Medicine, 377(7), 613–622.
  8. Say L, Chou D, Gemmill A, et al. (2014). Global causes of maternal death: a WHO systematic analysis. The Lancet Global Health, 2(6), e323–e333.
  9. World Health Organization (WHO). (2019). WHO recommendations for prevention and treatment of pre-eclampsia and eclampsia. Geneva: World Health Organization.
  10. Zhang J, Meikle S, Trumble A. (2003). Severe maternal morbidity associated with hypertensive disorders in pregnancy in the United States. Hypertension in Pregnancy, 22(2), 203–212.