Population
We included women with pre-eclampsia and normotensive pregnancies who were recruited to the PROVE biobank and database at Tygerberg Hospital, Cape Town, South Africa. Tygerberg Hospital is a referral hospital that manages only high-risk pregnancies and delivers over 7000 women a year. The PROVE biobank is an ongoing collaborative project that recruits women with pre-eclampsia and control pregnancies to facilitate research in the field of pre-eclampsia and in particular pre-eclampsia with severe features, focusing on eclampsia and pulmonary oedema. The study is registered with ISCRTN, registration number ISRCTN10623443. PROVE collects the recommended predictors and core-outcome sets recommended by CoLab to facilitate data sharing in preeclampsia research.11
For this study, we included women with singleton pregnancies who were able to speak and understand English, Xhosa or Afrikaans. Exclusion criteria included known neurological or cardiac disease. For normotensive women, additional exclusion criteria were chronic hypertension and diabetes mellitus. We included women with eclampsia, pulmonary oedema (as an example of pre-eclampsia with severe features), pre-eclampsia without complications and normotensive pregnancies.
Pre-eclampsia was defined according to the NICE guidelines.12 Eclampsia was confirmed when pre-eclampsia was complicated by generalized tonic-clonic seizures in the absence of another etiology. Pulmonary oedema was diagnosed when there was worsening dyspnea, fine bibasal inspiratory crackles on auscultation and features of pulmonary oedema on chest x-ray. Women were considered to have pre-eclampsia without severe features if they did not meet the NICE guidelines classification of severe pre-eclampsia.12 Pregnancies were considered to be normotensive if the women consistently had a systolic blood pressure below 140 mmHg and a diastolic blood pressure below 90 mmHg during pregnancy. Hemolysis, Elevated Liver Enzymes and Low Platelets syndrome (HELLP) was defined according to NICE guidelines12 and renal impairment was defined as a serum creatinine above 120 umol/L.
Baseline data were obtained by interview and extraction from medical records. All data were entered and stored using REDCap (Research Electronic Data Capture) tools hosted at Stellenbosch University.13, 14 Data were double checked for accuracy and controlled with original data collection forms.