Study design and setting
We conducted a cross-sectional study of women with pre-eclampsia admitted to the antenatal ward of Mbarara Regional Referral Hospital (MRRH) in southwestern Uganda from November 2019 to May 2020. MRRH is a government-funded public tertiary hospital. The records show that the hospital conducted approximately 9,000 deliveries for the calendar year 2019. The hospital’s maternal mortality ratio stands high at 261 per 100,000 live births  with pre-eclampsia among top three causes.
We studied all pregnant women, including emancipated minors under the age of 18 years diagnosed with pre-eclampsia. We defined preeclampsia as de novo and sustained hypertension (≥140/90mmHg) at ≥ 20 weeks of gestation with proteinuria or at least one feature of end-organ dysfunction for those without proteinuria.
We included gravid women at or past 20 weeks of gestation with hypertension and proteinuria or at least one severity feature of pre-eclampsia for those without proteinuria. We excluded women with chronic hypertension and gestational hypertension.
Sample size estimation and sampling procedure
All pregnant women diagnosed with preeclampsia between November 2019 and May 2020 at MRRH were consecutively screened and enrolled in the survey without a priori-determined sample size.
Research staff consecutively approached all pregnant women who presented to the antenatal unit of the maternity ward of MRRH, explained the study approach and invited them to participate. Of women who accepted to be screened, those that passed the study eligibility criteria were enrolled in the study. To identify those with hypertension, all pregnant women presenting at or above 20 weeks of gestation, had a screening blood pressure measured by research staff on admission. Our blood pressure measurement standard operating procedure was as follows: We used a Visomat® Electronic digital dial blood pressure machine (manufactured byOBL: Visomat, Zum Ottersberg Wertheim am Main, GERMANY) to measure the blood pressure. A woman was allowed time to rest seated without talking for at least 5minutes. Blood pressure cuff was placed 1-2cm above the elbow on either arm supported at heart level—on a table or a chair armrest while she was seated leaning back against a chair, without tight clothing around the upper arm and both feet on the floor. Women were instructed not to move, strain or talk while the measurement was being taken. The machine was turned on and the cuff allowed to automatically inflate, deflate and the display result was taken as the correct woman’s blood pressure—the process was repeated upon displaying an ‘error’ reading. We defined hypertension as sustained elevated blood pressure that is, systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg four-hours apart or single reading of severe hypertension is defined as systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥110 mmHg or documented antihypertensive medication use to control the blood pressure via woman’s medical records review.
Each woman who screened positive for hypertension parallelly underwent further clinical evaluation and laboratory screening—full hemogram, renal function test and liver enzymes test and bedside proteinuria measurement to diagnose pre-eclampsia. The clinical evaluation included history taking, physical examination and medical records (antenatal card) review.
To measure spot proteinuria, the research assistant gave each woman a uniquely labelled sterile urine container and instructed her to collect about 10mls of clean-catch urine or collected it at urine drainage port after removing urine bag for those who had urethral catheter in-situ. Research assistant immersed a Cypress Diagnostics ® colour-coded 10 parameter urine dipsticks (manufactured by Cypress Diagnostics, Hulshout, Belgium) in the sample for 60 seconds and then compared to container visual colour codes following the manufactures instructions on the package insert. The read off result was further classified as non-proteinuric if ≤+1 and proteinuria if ≥+2.
For hematologic tests, ten millilitres of blood sample were drawn from an easily accessible vein on the arm and halved into EDTA and plain vacutainers. These samples with complete laboratory request forms were taken to MRRH laboratory for full hemogram, liver enzymes and renal function testing. The Humastar-200 ® clinical chemistry analyser (manufactured by HUMAN Biochemica und Diagnostica GmbH, Wiesbaden, Germany) was used to measure the serum creatinine in mg/dL, liver transaminases in IU/L on the 5mls blood in plain vacutainer. The other 5mls in EDTA vacutainer bottle was run in the Sysmex XN-1000i ® 5-part haematology analyser (manufactured by Sysmex America, Inc. Lincolnshire, Illinois, USA) to measure haemoglobin concentration in g/dL and platelet count per microliter.
We diagnosed pre-eclampsia if a gravid woman at or past 20 weeks of gestation had hypertension and proteinuria—proteinuric pre-eclampsia or hypertension and at least one severity feature of pre-eclampsia if without proteinuria—non-proteinuric pre-eclampsia. We defined end-organ dysfunction as presence of at least any one of the following in a woman who screened positive for pre-eclampsia: 1) unexplained severe headache or blurred vision or coma or convulsion–cerebral dysfunction; liver transaminases level at least twice of the normal upper limit—hepatic dysfunction; 3) thrombocytopenia < 100,000/μL—hematologic dysfunction; 4) serum creatinine > 1.1 mg/dL—renal dysfunction; and, 5) multi-organ dysfunction if ≥1 organ dysfunction was diagnosed concomitantly in one woman.
We interviewed women with pre-eclampsia (abstracted some of the data from the woman’s clinical record) and captured the data using a pretested-structured questionnaire. The variables recorded included: 1) socio-demographic data —age, level of education, marital status, employment status, age, occupation, alcohol use or smoking; 2) clinical data— chronic hypertension, renal disease, liver disease; unexplained severe headache, visual disturbances, convulsions, epigastric pain, dyspnoea, plus weight and height measurements; 3) obstetric data—parity, gestational age, multifetal gestation, history of pre-eclampsia during previous pregnancies, antenatal attendance and booking blood pressure; and 4) blood test results data—full hemogram, renal function and liver transaminases.
Data were then entered into a secure online backed up RECaP® database version 8.2 hosted at Department of Obstetrics and Gynecology at Mbarara University of science and Technology (MUST). Statistical analyses were performed using Stata Statistical Software: Release 14 (StataCorp LP, College Station, Texas USA).
We computed descriptive statistics and tabulated the baseline participant characteristics as frequency proportions and percentages for categorical variables, or mean with standard deviation for continuous variables—compared across the non-proteinuric and proteinuric groups. The prevalence of non-proteinuric pre-eclampsia was determined as a proportion of participants with non-proteinuria and expressed as a percentage. We used binary logistic regression to determine sociodemographic, obstetric, clinical and laboratory variables associated with dependent variables. Independent variables with at p<0.2 were entered into a multivariable logistic-regression model to analyse factors independently associated with non-proteinuric preeclampsia using adjusted OR at 95% confidence interval, p<0.05. To compare the frequency of end-organ dysfunction, Pearson's chi-squared test statistic (χ2) was calculated for women with non-proteinuric and proteinuric pre-eclampsia, at one degree of freedom and p<0.05.
Ethical approval to conduct this study was obtained from the Mbarara University Research Ethics Committee (Protocol reference number 14/01-19). Written informed consent was obtained from all study participants using prior-approved consent forms in English and local language translated versions. Informed consent was obtained from all adults aged 18 years and over independently while parent or legal guardian gave informed consent for study participants below 18 years of age.