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Background: Pre-eclampsia/eclampsia usually resolves after delivery but sometimes hypertension persists and cardiovascular disease develops later. Our objective was to determine the incidence and maternal socio-demographic and obstetric risk factors for persistence of hypertension in women with pre-eclampsia/eclampsia. Methods: This was a prospective cohort study conducted from July 2009 to June 2011 at Mulago Hospital labour ward and postnatal clinics. We followed up 188 women admitted with pre-eclampsia/eclampsia until 3 months after delivery. Data was collected using interviewer-administered questionnaires, examination of participants and review of medical records. Stata (version12) software was used for data analysis. Univariable analysis was used to compute the relative risk of persistent hypertension at the 95% confidence level. This was followed by multivariable logistic regression analysis to determine factors independently associated with persistence of hypertension. Results: 64 (34%) out of the 188 women analysed had persistent hypertension three months after delivery. Maternal age, gestational age at delivery and parity were predictors of persistent hypertension. Conclusion: The proportion of women with pre-eclampsia/eclampsia at risk of persistent hypertension at three months after delivery was high, with nearly one of three mothers remaining hypertensive. Follow up of mothers who develop pre-eclampsia is important so that early diagnosis and management of chronic hypertension can be made to avoid long term morbidity and mortality. © 2013 Nakimuli et al.
The study was conducted at Mulago, Uganda’s national referral hospital, located in Kampala with a catchment area of Kampala District and the surrounding districts of Wakiso, Mukono and Mpigi. These surrounding districts are within a radius of 10 to 20 km from Mulago Hospital. Few obstetricians are available in the public hospitals in the districts and therefore women with complications such as pre-eclampsia are referred to Mulago Hospital where the obstetricians are and the health care services are free. Mulago Hospital occasionally receives referrals from other parts of the country. In addition to the referred women, local women routinely deliver in Mulago Hospital and there are 80-90 deliveries daily and more than 30,000 deliveries per year. This was a prospective cohort study conducted in the labour ward and postnatal clinic between July 2009 and June 2011 and was linked to a larger case-control study primarily designed to study the genetics of pre-eclampsia (Nakimuli, manuscript in preparation). The genes studied were Killer Immunoglobulin-like receptor (KIR) and Human Leukocyte Antigen C (HLA-C) and their role in development of pre-eclampsia in an African population was investigated. Participants in the case-control study were women with pre-eclampsia or eclampsia consecutively recruited after admission to Mulago Hospital. Pre-eclampsia was defined as presence of hypertension and proteinuria occurring after 20 weeks of gestation. Hypertension was defined as a blood pressure (BP) measurement of 140/90 mmHg or more, measured at rest on more than one occasion at least 4 hours apart. Proteinuria was defined as urine protein measurement of +2 or more by dipstick on more than one occasion at least 4 hours apart. Severe pre-eclampsia was defined as presence of hypertension of 160/110 mmHg or more and proteinuria of 3+ or more at any time during management. Mild pre-eclampsia was defined as presence of hypertension of less than 160/110 mmHg and proteinuria of 2+ at any time during management. Eclampsia was diagnosed when a patient with pre-eclampsia had generalized tonic-clonic convulsions. All cases were at 20 weeks of gestation or more at the time the diagnosis of pre-eclampsia was made, assessed by weeks of amenorrhoea or ultrasound scan. The majority of the women recruited to the larger genetic case-control study were included in the prospective follow up study apart from those who had no reliable residential address or phone contact and those living beyond a radius of 20 Km from Mulago Hospital due to difficulties in follow up. Women who missed reviews were traced by phone or midwives were sent to trace them personally to minimize loss to follow up. Women with prior chronic hypertension, renal disease before or during that pregnancy were also excluded because they already had the outcome of interest (persistent hypertension). These were self reported diagnoses and not backed my medical records. Some women reported using antihypertensive medication. Women with BP measurements of 140/90 mmHg or more before 20 weeks of gestation were also excluded as these are considered to have chronic hypertension. Participants were followed up for 3 months after delivery and persistent hypertension was diagnosed if by 3 months after delivery a woman had a blood pressure of 140/90 mmHg or more, or if antihypertensive medication was required to keep the BP below 140/90 mmHg. Approval to conduct the study was given by the Higher Degrees Research and Ethics Committee of Makerere University College of Health Sciences and the Uganda National Council for Science and Technology (UNCST). The participants gave written informed consent to participate in the study. Permission was sought to study minors (below 18 years of age) from the ethics committees. Minors signed assent forms while their next of kin or caretakers signed the consent forms. Withdrawal from the study never jeopardized health care and this was provided free to all women. The women were interviewed and BP measurement taken by the same medical attendant (AN). Additional information was obtained from participants’ medical charts. The data collected included socio-demographic characteristics, ethnic group, obstetric, medical and present pregnancy history (gestational age at onset of pre-eclampsia and severity of pre-eclampsia). The Ethnic group was determined by asking women what their fathers’ languages were and this information was not used as a basis for recruitment in to the study. No biochemical data was collected as part of this study. Blood pressure measurements were done using manual mercury sphygmomanometers in a sitting position. Urine protein was measured using dipsticks. 5 mls of blood was taken from women and maternal genomic DNA was isolated using the QIAmp DNA Maxi Blood Kit (QIAGEN). KIR genotyping was based on the primers and methods described previously [28,35]. The sample size was estimated according to Kesley at al using OpenEpi version 2.3.1 software [36]. The incidence of persistent hypertension among all pre-eclamptics was 28% in an earlier study in the same study setting as ours [24]. The assumptions were that 25% of the women without the exposure (without KIR AA genotype) had persistent hypertension and that the risk was twice among the exposed (with KIR AA genotype). A sample size of 127 gave the study 80% power to detect the effect of KIR genotype on persistence of hypertension, including 8% loss to follow up. The clinical management of all the participants was according to Mulago Hospital’s standard protocols. All women with diastolic blood pressures of 110 mmHg or more were diagnosed as severe pre-eclampsia and were given magnesium sulphate therapy as follows: a loading dose of magnesium sulphate of 14 g was given (4 g intravenously and 10 g intramuscularly), followed by 5 g intramuscularly four hourly for 24 hours. Intravenous hydralazine 5 mg was also given every 30 minutes until the diastolic pressure was 100 mmHg or less. Thereafter, the blood pressure control was achieved using oral nifedipine 10 mg with or without aldomet 250 mg. Those diagnosed as mild pre-eclampsia (diastolic blood pressure of less than 110 mmHg) were given oral nifedipine 10mg with or without aldomet 250 mg or atenolol 50 mg. The decision to deliver the women and mode of delivery plus subsequent care was also according the hospital’s standard protocols. For the first week all the pre-eclamptic women were left on antihypertensive drugs. In subsequent reviews the doses of the antihypertensive drugs were changed or the treatment was stopped altogether, depending on the blood pressure measurements. Treatment was stopped in those women whose blood pressure measurements fell below 120/70 mmHg and they were followed up weekly for three weeks. Those whose blood pressure measurements remained at or below 120/70 mmHg during this period were told to return or call in case of complaints like headache, but if all remained well they were told to return at 3 months post delivery for the final evaluation.On the other hand, the women whose blood pressure measurements fluctuated between 120/70 and 140/90 mmHg continued with fortnightly reviews and if the blood pressure measurements went above 140/90 mmHg they were put back on antihypertensive treatment. Fortnightly follow up reviews continued until the measurements fell below 120/70 mmHg or until 3 months post delivery, whichever came first. Data was entered into Access databases and the datasets were later imported into and analyzed using STATA version 12. First, we investigated the normality of the data for the continuous variables graphically using histograms and in addition we used the Shapiro-Wilk tests for normality. Then baseline characteristics were compared between those who had persistent hypertension and those who resolved within three months after delivery. Categorical data was compared using the chi-square test while for numerical data the Student’s t-test. To assess risk factors for persistence of hypertension, univariable analysis was performed to compute risk ratios at the 95% significance level. To assess independent contribution of these risk factors to persistent hypertension, multivariate analysis was performed, where all independent variables with a p-value of less than 0.2 at univariate analysis were considered for multivariable logistic regression. Associations with p values less than 0.05 were considered statistically significant.
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