Point-of-care Ultrasound Abnormalities in Eclampsia - Prevalence and Association Between Pulmonary Interstitial Syndrome and Cardiac Dysfunction, Brain Natriuretic Peptide, and Serum Albumin
Phase: NA
Conditions: Eclampsia
Sponsor: University of Cape Town

 
 
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2022 Study Protocol 
 
Point-of-care ultrasound abnormalities in eclampsia - prevalence and association 
between pulmonary interstitial syndrome and cardiac dysfunction, brain natriuretic 
peptide, and serum albumin 
 
Principal Investigator:  
Robert A Dyer, PhD 
Emeritus Professor 
Department of Anaesthesia and Perioperative Medicine 
University of Cape Town  
Cape Town, South Africa 
 
Co-investigators:  
Dominique van Dyk 
Specialist 
Department of Anaesthesia and Perioperative Medicine 
University of Cape Town  
Cape Town, South Africa 
 
Margot Flint, PhD 
Department of Anaesthesia and Perioperative Medicine 
University of Cape Town  
Cape Town, South Africa 
 
Francois Uys 
Registrar  
Department of Anaesthesia and Perioperative Medicine 
University of Cape Town  
Cape Town, South Africa 
 

 
 
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Justiaan LC Swanevelder 
Professor and Head 
Department of Anaesthesia and Perioperative Medicine 
University of Cape Town  
Cape Town, South Africa 
 
Clemens M Ortner, MD, MSc, DESA 
Clinical Associate Professor 
Department of Anesthesiology, Perioperative and Pain Medicine  
Stanford School of Medicine 
Stanford, CA-94305, USA 
Email: cortner@stanford.edu 
 
Carl J Lombard 
Chief Specialist Statistician 
Biostatistics Unit 
South African Medical Research Council 
Cape Town, South Africa 
 
Nicole L Fernandes 
Specialist   
Department of Anaesthesia and Perioperative Medicine 
University of Cape Town, 
Cape Town, SA 
 
David G Bishop 
Associate Professor 
Department of Anaesthesiology and Critical Care 
University of KwaZulu-Natal, 
Durban, South Africa 
 

 
 
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Mushi Matjila 
Professor and Head 
Department of Obstetrics and Gynaecology 
University of Cape Town 
Cape Town, SA 
 
Ayesha Osman 
Head Clinical Unit 
Department of Obstetrics and Gynaecology 
University of Cape Town 
Cape Town, SA 
 
Raffaella Fantin 
Specialist 
Department of Anaesthesiology and Critical Care 
University Hospital of Innsbruck  
Austria 
 
Thomas Shütz 
Resident 
Department of Cardiology and Internal Medicine 
University Hospital of Innsbruck  
Austria 
 
 
 

 
 
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Introduction / Primary Aim 
 
I. 
Methods / Procedures 
A) Patient screening, enrolment, inclusion, non-inclusion and consent 
B) Inclusion / Non-inclusion criteria 
C) Exclusion criteria 
D) Time point of ultrasound examination and blood sampling 
E) Ultrasound procedures: 
Ea) Cardiac Ultrasound 
 Eaa) 2D echocardiography 
 Eab) Speckle tracking echocardiography 
Eb) Lung Ultrasound 
Ec) Ultrasound of optic nerve sheath (ONS) 
F) Statistical analysis 
 Sample size calculation 
 
II. 
Ethics considerations 
III. 
References 
IV. 
Appendix 
A. Maternal data collection and indication for preterm hospitalization 
B. Neonatal data collection  
 

 
 
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I. 
Introduction 
Preeclampsia is a life-threatening hypertensive disorder involving the heart and vasculature 
affecting 5-8% of pregnancies1. Untreated, 2-10% of women develop eclampsia2, defined 
as new onset of seizures in the setting of preeclampsia3. Eclamptic seizures are estimated 
to occur in 2-8 per 10.000 deliveries in high-income countries (HIC) and with a higher 
prevalence of up to 16-69 per 10.000 deliveries in low-income countries (LIC)4,5. 
Eclampsia is associated with significant maternal and neonatal morbidity, with a case 
fatality rate as high as 25-50 % in LIC2,6, and associated with a 16-26 fold odds of death in 
HIC4,5. Associated maternal complications include intracranial hemorrhage (ICH), cerebral 
edema, acute kidney injury, acute respiratory syndrome (ARDS), cardiac failure, 
coagulopathy and postpartum hemorrhage4. Obstetric and medical management include 
seizure prophylaxis and control, aggressive blood pressure management and the urgent 
delivery of the baby3. Anesthesia management can be challenging and has to be tailored to 
the clinical condition of the eclamptic woman. Unless the usual contraindications to 
regional anesthesia (RA) apply, spinal anesthesia (SPA) has been described as the method 
of choice in parturients in whom the Glasgow Coma Scale (GCS) is ≥ 14, and cardiac 
failure is absent. For patients with persistent decreased level of consciousness, general 
anesthesia (GA) is recommended.7 However, in eclamptic women both anesthesia 
techniques may be associated with significant complications. Raised intracranial pressure 
(ICP) present in eclamptic women raises the possibility of cerebellar tonsillar herniation in 
association with SPA. Cardiac diastolic dysfunction, with or without preserved ejection 
fraction, has been described in preeclamptic women. With preserved ejection fraction, 
induction of RA or GA is generally hemodynamically well tolerated. However, in women 
with decreased systolic function, induction of anesthesia can lead to life-threatening 
cardiovascular collapse, which may only be prevented by cautious titration of anesthesia 
agents. This might be in conflict with the need to administer high dosages of induction 
agents to blunt the hypertensive response to tracheal intubation that, if untreated, may lead 
to life-threatening ICH and pulmonary edema. Consequently, early detection of increased 
ICP and knowledge of cardiopulmonary function in the individual case are essential to the 
obstetric anesthetist to guide appropriate management.  

 
 
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Cardiopulmonary and optic nerve sheath point-of-care ultrasound (POCUS) protocols 
might be particularly suitable for this purpose.8,9 These involve a defined bedside 
ultrasound examination to identify critical cardiopulmonary pathophysiology, which may 
remain undetected by clinical examination alone8,10,11. The identification of increased optic 
nerve sheath diameter (ONSD) on ultrasound may suggest raised ICP12.  
It is further well documented that the serum brain natriuretic peptide (BNP) level, a marker 
of cardiac dysfunction, is increased in preeclampsia13,14. However, no data is available to 
confirm that elevated BNP levels identify those eclamptic women at risk for 
cardiopulmonary abnormalities15. 
 
Therefore, this study is planned to describe the prevalence and severity of cardiac, lung 
and ONS US abnormalities in women with eclampsia. In a recent study on POCUS 
findings in late onset preeclampsia, the absence of pulmonary interstitial syndrome (PIS) 
may exclude raised LVEDP16. The primary aim of the current study is to examine the 
association between PIS, as identified by lung ultrasound, and cardiac dysfunction on 
echocardiography, in eclamptic women. The secondary aims are the performance of a 
comprehensive cardiac ultrasound assessment including a strain analysis, and to explore 
the association between PIS and ONSD, serum BNP and albumin.  
 
 

 
 
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II. 
Methods 
In this prospective cohort study, preeclamptic women presenting with new onset tonic-
clonic, focal, or multifocal seizures in the absence of other causative conditions such as 
epilepsy, cerebral arterial ischemia and infarction or intracranial hemorrhage arising from 
non-obstetric pathology, or drug use, will be enrolled. Preeclampsia will be defined 
according to the recommendations of the American College of Obstetricians and 
Gynecologists (Table 1)17. Early onset disease will be defined as diagnosis before 34 weeks 
of gestation, and late onset disease as after 34 weeks. Given the high prevalence of the 
disease and the presence of established detailed management protocols, data collection will 
be performed in the Maternity Centre at Groote Schuur Hospital at the University of Cape 
Town, Cape Town, South Africa.  
 
 
A) Patient screening, enrolment, inclusion, non-inclusion and consent 
On a daily basis, the obstetrics consultant and/or senior registrar in charge will inform the 
anaesthesia member of the research team should a patient be eligible for the study and her 
clinical condition allow recruitment and conduction of the ultrasound protocol.  
The patient will be approached after completion of normal obstetric treatment protocols, 
and asked for permission to study their medical file for research purposes. After screening 

 
 
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for inclusion and non-inclusion criteria, the patient will be enrolled and written consent 
obtained. For details of the consent process, please see III. Ethics Considerations, pages 
16-17. 
 
B) Inclusion / Non-inclusion criteria 
Inclusion criteria are diagnosis of preeclampsia following ACOG definition (Table 1) with 
new onset of tonic-clonic seizures. Non-inclusion criteria are chronic pulmonary disease, 
collagen disorders, HIV infection, chronic renal or hepatic disease, urinary tract infection, 
sepsis, and body mass index (BMI) > 50 kg/m2, history of seizure disorder, intracranial 
hemorrhage, or history of benign or malignant intracranial neoplasia.   
 
C) Exclusion criteria 
Following consent and inclusion in the study, women either withdrawing consent, or not 
giving retrospective consent, will be excluded. 
 
D) Time point of ultrasound examination  
Maternal ultrasound examinations will be performed after normal obstetric treatment 
protocols have been completed, i.e., the conduction of the study will contribute no delay in 
routine or emergency patient management. Ultrasound examination will be repeated after 
72-96 hours, subject to the same conditions.  
 
E) Ultrasound procedures 
An ultrasound examination (approximately 35-40 minutes in duration) will be performed, 
at which time a venous blood sample will be taken. In addition to venepuncture for 
measurement of BNP, an additional 2 x 5 ml samples (in vacutainer serum separation 
collection tubes) will be taken for storage (-80oC) and subsequent batch serum 
measurement of sFlt-1, PlGF and Kisspeptin as surrogate biomarkers for placental 
dysfunction. The ultrasound examination will consist of evaluation of lung- and cardiac 
ultrasound, as well as optic nerve sheath diameter.  
 
Ea) Cardiac Ultrasound: 

 
 
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Eaa) 2D echocardiography 
The cardiac ultrasound examination will be performed using a GE Vivid Q® ultrasound 
machine equipped with a 3.5-MHz transducer. Images will be acquired at rest in the left 
lateral decubitus position from standard parasternal and apical views. Digital loops of 3 
cardiac cycles with associated electrocardiogram information will be stored on the hard 
disk of the ultrasound machine and transferred to a GE EchoPac® work-station for offline 
analysis. Analysis will be performed according to existing guidelines.18-20 Ventricular wall 
and chamber dimensions will be measured in the parasternal long axis view. Left atrial 
volume (LAV) and left ventricular volume in diastole (LVEDV) will be calculated from 
apical views. Right atrial area, right ventricular basal and mid cavity diameter and right 
ventricular longitudinal diameter will be measured from apical views. Proximal and distal 
right ventricular outflow tract (prox. and dist. RVOT) will be measured in parasternal short 
axis views. Tricuspid annular plane systolic excursion (TAPSE) will be measured from 
apical M-Mode images. Right ventricular fractional area change will be calculated from 
apical views. Doppler images will be used to measure early and late mitral and tricuspid 
valve inflow velocities (E and A, RV E and RV A), mitral and tricuspid inflow deceleration 
time (DT, RV DT), isovolumetric relaxation time (IVRT), systolic and diastolic flow in the 
pulmonary veins, duration of the late mitral valve inflow (A dur), duration of the flow in 
the pulmonary vein during atrial contraction (AR dur) and acceleration time of the flow 
through the pulmonary valve (PV acc. time). Tissue Doppler images will be used to 
measure systolic (S'), early diastolic (E') and late diastolic (A') tissue velocities at the septal 
and lateral mitral valve and at the right ventricular free wall. Left ventricular mass will be 
calculated using the Devereux formula 0.8(1.04[([LVEDD + IVSd + PWd]3 − LVEDD3)]) 
+ 0.6, where LVEDD is left ventricular end diastolic diameter, IVSd is thickness of the 
interventricular septum in diastole and PWd is posterior wall thickness in diastole. Relative 
wall thickness will be calculated using the formula (2*PWd)/LVEDD. Total vascular 
resistance (TVR) will be calculated using the formula 80*MAP/(CO/1000), where MAP is 
mean arterial pressure and CO cardiac output. Diastolic dysfunction will be classified 
according to the guidelines of the American Society of Echocardiography and European 
Society of Cardiovascular Imaging, applying the age and gender adapted values from the 
2016 Guidelines.21 

 
 
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Eab) Speckle tracking echocardiography 
The myocardium will be traced manually and EchoPac® software used to identify the area 
of interest, by delimiting the endocardium and epicardium. The operator will readjust this 
area before the software will calculate deformation. LV and RV global longitudinal strain 
and strain rate will be calculated from apical views, with negative values indicating fiber 
shortening. LV rotation and de-rotation will be calculated from apical and basal parasternal 
short axis views, with negative values indicating rotation in the clockwise direction. LV 
twist is the difference between the apical and the basal rotation, LV torsion is LV twist 
divided by left ventricular length in diastole. If >1 segment is rejected, subjects will be 
excluded from statistical analysis. 
 
Eb) Lung Ultrasound 
Lung ultrasound will be performed with the patient in the supine position. A phased-array 
transducer will be used for lung ultrasound, and will be used for the assessment of B-lines, 
which arise from the pleural line and extend to the bottom of the screen, and move with the 
sliding lung (Figure 122). We will quantify the B-line burden in lung regions using the 
validated eight-region method23, as previously described: Two anterior and two lateral 
regions in each hemithorax will be evaluated. If 3 or more B-lines (any size and spaced 
apart by any distance) are present in a particular region, that region is considered positive. 
Two or more positive regions per side define a “B-line pattern.”  
 
Ec) Ultrasound of optic nerve sheath (ONS) 
Measurement of optic nerve sheath diameter will be performed applying the coronal 
technique24 with a linear transducer placed in a vertical (cephalad-caudal) orientation at the 
lateral canthus and aimed nasally and posteriorly until a circular optic nerve is seen at its 
largest diameter. Measurements will be taken in a superior-inferior direction to minimize 
artifact if the image is taken at a slightly oblique angle (Figure 224).The patient will be 
positioned supine (with or without left uterine displacement, depending on clinical 
circumstances), with a 30 degree head elevation. After the point of entry of the optic nerve 
into the globe has been identified, the image will be frozen. Optic nerve sheath diameter 

 
 
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will be measured 3 mm behind the globe in a perpendicular axis to the nerve (Figure 325). 
Two measurements will be taken per eye, and the mean of the 4 values will represent the 
optic nerve sheath diameter. 
 
F) Statistical analysis 
Data will be presented as mean and standard deviation for continuous variables, and 
frequency and percentage for categorical variables. For the a priori defined ultrasound 
outcomes of PIS, diastolic dysfunction, and increased ONSD, the prevalence and 95% 
confidence intervals will be calculated. In addition, the prevalence and 95% confidence 
intervals of systolic dysfunction and of raised LVEDP will be calculated.  
Patients with and without ultrasound abnormalities will be compared with respect to 
admission systolic and diastolic blood pressures, clinical features of disease severity, and 
mean BNP levels using 2-sample t-test and the Chi-square test, for continuous and 
categorical variables respectively. The associations between PIS, increased ONSD or 
diastolic dysfunction with clinical severity features (=high arterial blood pressures, 
presence of pulmonary edema, headaches or visual disturbances, raised liver or renal 
laboratory parameters tests, and low platelet count), serum albumin level, BNP level, and 
between cardiac and pulmonary ultrasound abnormalities, will be explored using the 2-
sample t-test and the Chi-square test, for categorical and continuous variables respectively.  
To adjust for multiple comparisons, including primary and secondary outcomes, a 
Benjamini-Hochberg correction will be applied using a 10% false discovery rate. 
Assuming that the p-value will result from 32 direct comparisons made in the study, the 
significance level will be adjusted to p < 0.025.  
In order to determine pre- and post-test probabilities of PIS to predict elevated LVEDP, 
and of BNP at a level above 200 pg/ml to predict systolic dysfunction, diastolic 
dysfunction, elevated LVEDP, and the presence of PIS, sensitivity, specificity, positive 
and negative predictive value will be calculated.  
Intra- and inter-observer agreement will evaluated using the Bland and Altman method, 
after reviewing 10% of lung- (using total B-line score), cardiac- (using left ventricular 
internal diameter in diastole (LVEDD), and optic nerve (using the left optic nerve sheath 

 
 
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diameter) parameters; results will be expressed both graphically and quantitatively as mean 
difference (bias) and 95% limits of agreement. 
Sample size calculation 
The sample size calculation is based upon the primary aim, which is to examine the 
association between PIS on lung ultrasound and raised LVEDP on cardiac ultrasound. 
Available data on women with late onset preeclampsia and severe features suggest that the 
incidences of PIS and raised LVEDP are 23/95 (24%; 95% CI: 16-34%), and 20/80 (25%; 
95% CI: 16-36%) respectively.16 In that population, the proportion of women with raised 
LVEDP was 12% in patients without PIS, and 55% in those who had PIS. A sample size 
of 60 (45 LVEDP negative and 15 LVEDP positive) will be required to detect a significant 
difference in incidence of PIS between the 2 groups (52% [expected PIS positive rate in 
women with raised LVEDP] versus 15% [expected PIS positive rate in women with normal 
LVEDP]) with a power of 80% and significance level of 0.05. To allow for the possibility 
of poor image acquisition during positive pressure ventilation, 70 patients will be recruited.       
 
 
 

 
 
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Figure 1: Comparison of normal lung in Panel A versus B-line pattern in Panel B22.  
 

 
 
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Figure 2 (Image from Ref.24): Measurement of the optic nerve sheath diameter in the 
coronal axis. The view is obtained in a sharply demarcated circle, measured in its widest 
diameter (A). If edema is seen, the measurement is taken at the outer edge (B, outer 
calipers).24 
 
 
 
 
A 
B 
 

 
 
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III. 
Ethics considerations  
 
A. Risks and benefits  
There is very little risk to subjects participating in this study. If possible, venous blood 
samples will be taken as part of routine sampling performed in patients diagnosed with 
eclampsia. If not possible, a maximum of one venipuncture (1-2 ml) will be required in 
addition to routine blood sampling. In all cases, the blood samples will be taken and 
examinations performed as soon possible after admission, always allowing for prior 
initiation of normal obstetrics treatment protocols. Expected duration of blood sampling 
and ultrasound examinations is 30-45 minutes. In the event of demonstration of decreased 
systolic function (ejection fraction < 40%) and/or valvular heart disease, the obstetrics and 
anesthesia management team would be informed, since such findings could influence 
further management. 
 
B. Informed Consent 
Details of the consent process and data inclusion in the study are as follows: 
1 Patients with eclampsia who are scheduled for induction of labour will have adequate 
cognition and the capacity for informed consent before the onset of labour. Patients will be 
given the consent form and given sufficient time to read it and ask questions. The 
discussion will be presented in an open, non-intimidating and educational format, in the 
patient’s preferred language. All attempts will be made to minimise any anxiety that our 
study procedure may provoke; we will continually communicate with the patient regarding 
what to expect and explain that the investigations are noninvasive. 
2 Patients who are scheduled for urgent caesarean section for maternal and/or fetal 
indications, will not have the capacity for informed consent at this time. In these cases, we 
will only be able to explain the study to the patient after clinical improvement from the 
post-anaesthesia state, and/or clinical improvement of their condition. Should the patient 
receive spinal anaesthesia, or be extubated immediately post-general anaesthesia, consent 
will proceed as in 1, above, as soon as there is full recovery from anaesthesia, and the 
patient has capacity.   

 
 
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3 In patients who require postoperative ventilation and who  are haemodynamically stable,  
in order to avoid the risk of futility (since the important  pathophysiological changes could 
be missed by delaying the noninvasive ultrasound protocol), the research group asks for an 
initial waiver of consent. We respectfully request that the family will not be contacted at 
this point, in the interest of allaying their anxiety in a stressful situation. The researchers 
therefore request “delayed consent”, which can be given by the patient (following 
stabilisation or recovery), or next of kin, or a legal representative or proxy. If the patient 
refuses consent, the data will not be used. 
4 In view of recent work showing that in South Africa teenage mothers are at highest risk 
of eclampsia (Nathan et al, Journal of Global Health 2018:8: 020401), we request that 
minors (patients under the age of 18 years) may also be recruited for these noninvasive 
ultrasound scans. In these circumstances, parental approval will be requested, together with 
assent by the patient. The same initial waiver is respectfully requested for a patient 
requiring mechanical ventilation, as in 3, above. “Delayed consent” would then involve 
requesting parental approval and the assent of the patient after recovery. Should it be 
impossible to make contact with the parents, the research group will contact the HREC for 
a decision in the individual case. 
4 In the unusual event of a diagnosis of intracerebral haemorrhage or stroke, the patient 
will be excluded from the study. In the rare event of the demise of a patient for any reason 
other than intracerebral haemorrhage or stroke, the researchers request that the data be 
included and analysed, after discussion with the HREC, for the reasons below.  
The justifications for the above consent process and data inclusion are the following: 
Exclusion of patients without the capacity for consent, including minors, would lead to a 
biased sample, and data which is not generalisable to the majority of women with 
eclampsia. The generation of biased and poorly generalisable data would not address the 
research question and would thus dishonour the contributions of the other included patients, 
and would be wasteful research in a resource-limited environment. 
 
C. Steps during the recruitment process to minimize potential coercion and anxiety  
Patients will be assured that confidentiality will be guaranteed concerning any stored data, 
and that participation or non-participation in the study will not influence their quality of 

 
 
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care. Any patient anxiety will be allayed by sensitive discussion during the consent process; 
patients will be assured that the risks of ultrasound examination are minimal, and that the 
procedure is completely noninvasive. Patients will also be assured that they can withdraw 
from the study at any point. 
 
D. Data Management 
The study data will be coded, and we will maintain identifiers separate from the coded 
study data. The link between subject medical record number (MRN) and study code 
number will be kept in a locked office in a locked file, separate from data collected during 
the course of the study. 
Only members of the research team will have access to the data until final collection and 
analysis is complete. Once the data is input into a database the data will be identified by 
study code number. The link to patient identity will similarly be kept in a password 
protected file in a locked office until the links are finally deleted. Information from the 
research study will NOT be placed in the patients’ medical record. Ultrasound recordings 
will be saved on ultrasound machine de-identified under the study code number. Identifiers 
will be kept until 7 years of completion of enrollment to ensure accuracy of data collection 
during analysis.  
 
 
 
 

 
 
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References 
1. 
Leffert LR. What's new in obstetric anesthesia? Focus on preeclampsia. Int J 
Obstet Anesth 2015;24:264-71. 
2. 
Goldenberg RL, Jones B, Griffin JB, et al. Reducing maternal mortality from 
preeclampsia and eclampsia in low-resource countries--what should work? Acta 
Obstet Gynecol Scand 2015;94:148-55. 
3. 
Sutton ALM, Harper LM, Tita ATN. Hypertensive Disorders in Pregnancy. 
Obstet Gynecol Clin North Am 2018;45:333-47. 
4. 
Liu S, Joseph KS, Liston RM, et al. Incidence, risk factors, and associated 
complications of eclampsia. Obstet Gynecol 2011;118:987-94. 
5. 
Fong A, Chau CT, Pan D, Ogunyemi DA. Clinical morbidities, trends, and 
demographics of eclampsia: a population-based study. Am J Obstet Gynecol 
2013;209:229 e1-7. 
6. 
O'Connor HD, Hehir MP, Kent EM, et al. Eclampsia: trends in incidence and 
outcomes over 30 years. Am J Perinatol 2013;30:661-4. 
7. 
Hofmeyr R, Matjila M, Dyer R. Preeclampsia in 2017: Obstetric and 
Anaesthesia Management. Best Pract Res Clin Anaesthesiol 2017;31:125-38. 
8. 
Barber RL, Fletcher SN. A review of echocardiography in anaesthetic and 
peri-operative practice. Part 1: impact and utility. Anaesthesia 2014;69:764-76. 
9. 
Holm JH, Frederiksen CA, Juhl-Olsen P, Sloth E. Perioperative use of focus 
assessed transthoracic echocardiography (FATE). Anesth Analg 2012;115:1029-32. 
10. 
Fagley RE, Haney MF, Beraud AS, et al. Critical Care Basic Ultrasound 
Learning Goals for American Anesthesiology Critical Care Trainees: 
Recommendations from an Expert Group. Anesth Analg 2015;120:1041-53. 
11. 
Lichtenstein D. Lung ultrasound in the critically ill. Curr Opin Crit Care 
2014;20:315-22. 
12. 
Amini A, Kariman H, Arhami Dolatabadi A, et al. Use of the sonographic 
diameter of optic nerve sheath to estimate intracranial pressure. Am J Emerg Med 
2013;31:236-9. 
13. 
Rafik Hamad R, Larsson A, Pernow J, Bremme K, Eriksson MJ. Assessment of 
left ventricular structure and function in preeclampsia by echocardiography and 
cardiovascular biomarkers. J Hypertens 2009;27:2257-64. 
14. 
Fayers S, Moodley J, Naidoo DP. Cardiovascular haemodynamics in pre-
eclampsia using brain naturetic peptide and tissue Doppler studies. Cardiovasc J Afr 
2013;24:130-6. 
15. 
Afshani N, Moustaqim-Barrette A, Biccard BM, Rodseth RN, Dyer RA. Utility of 
B-type natriuretic peptides in preeclampsia: a systematic review. Int J Obstet Anesth 
2013;22:96-103. 
16. 
Ortner CM, Krishnamoorthy V, Neethling E, et al. Point-of-Care Ultrasound 
Abnormalities in Late-Onset Severe Preeclampsia: Prevalence and Association With 
Serum Albumin and Brain Natriuretic Peptide. Anesth Analg 2019; 28: 1208-16. 
17. 
ACOG Practice Bulletin No. 202: Gestational Hypertension and Preeclampsia. 
Obstet Gynecol 2019;133:e1-e25. 
18. 
Lang RM, Badano LP, Mor-Avi V, et al. Recommendations for cardiac chamber 
quantification by echocardiography in adults: an update from the American Society 

 
 
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of Echocardiography and the European Association of Cardiovascular Imaging. J Am 
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19. 
Mitchell C, Rahko PS, Blauwet LA, et al. Guidelines for Performing a 
Comprehensive Transthoracic Echocardiographic Examination in Adults: 
Recommendations from the American Society of Echocardiography. J Am Soc 
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Nagueh SF, Smiseth OA, Appleton CP, et al. Recommendations for the 
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Nagueh SF, Smiseth OA, Appleton CP, et al. Recommendations for the 
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Enghard P, Rademacher S, Nee J, et al. Simplified lung ultrasound protocol 
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Volpicelli G, Elbarbary M, Blaivas M, et al. International evidence-based 
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Agrawal A, Cheng R, Tang J, Madhok DY. Comparison of Two Techniques to 
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IV. 
Appendix: 
Maternal and Neonatal data collection and definition of adverse perinatal outcome: 
A) Neonatal variables preterm: 
- 
Cardiotocogram (CTG): reactive, non-reactive, abnormal 
- 
normogram estimated fetal weight (intrauterine growth restriction) 
- 
placental abruption,  
- 
fetal distress requiring cesarean section 
 
B) Neonatal post-delivery variables: 
- 
Neonatal birth weight,  
- 
APGAR scores at 1 and 5 minutes   
- 
perinatal death  
- 
admission to neonatal ICU 
 
C) Ultrasound data: 
 
-optic nerve sheath diameter 
 
-B-line score 
 
-diastolic Doppler parameters 
 
D) Maternal demographic data: 
- 
patient age,  
- 
BMI, parity,  
- 
gestational age at diagnosis of severe disease 
- 
past medical history 
- 
smoking status 
 
E) Maternal clinical data: 
 
- blood pressure 
 
- proteinuria 
 
- urine output 
 
- presence of headache or visual disturbances 
 
- oxygen saturation 

 
 
21 
 
- presence of abdominal pain 
 
- liver function 
 
- coagulation status 
 
- need for C-section 
 
- indication for C-section