Postpartum trend in blood pressure and renal function in women with severe preeclampsia and eclampsia: A prospective cohort-study at Mulago hospital, Kampala, Uganda

Background Preeclampsia/Eclampsia is a multisystem disorder of pregnancy with kidney involvement. Our objective was to assess the postpartum trend in blood pressure, renal function and proteinuria and, to investigate their predictors in Ugandan women with severe preeclampsia and eclampsia. Methods This was a prospective cohort study that involved 97 women with severe preeclampsia and Eclampsia, conducted at Mulago National referral hospital from August 2017 to April 2018. The clinical and laboratory variables were collected from the women on day1, 7, 21 and day 42 after delivery. Kaplan-Meier Survival analysis, Cox-proportional Regression and Log-Rank tests were used to compare the baseline and the follow-up variables with changes in blood pressure, renal function and urine protein. Results Most women (93.8%) recovered from hypertension within 6 weeks of childbirth with the mean time to resolution of 2.49 weeks (95% CI: 2.13-2.82). About 81% of the women recovered their renal function and the mean time to recovery was 24.54 days (95% CI: 20.14-28.95). Proteinuria resolved in approximately 84% of the women and the mean time resolution of urine protein of 32.85 days (95% CI: 30.31-35.39). Having multiple pregnancy versus a singleton pregnancy was associated with persistence of hypertension six weeks after child birth (P-value = 0.013). Conclusion In this study, the blood pressure and renal function of most women with severe preeclampsia and eclampsia normalized within six weeks after childbirth. A special interdisciplinary follow up for patients with preeclampsia/eclampsia by an obstetrician and physician is needed in the postpartum period to reduce the maternal morbidity and mortality associated with this condition in our community.


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Conclusion 21 In this study, the blood pressure and renal function of most women with severe preeclampsia and 22 eclampsia normalized within six weeks after childbirth. A special interdisciplinary follow up for 23 patients with preeclampsia/eclampsia by an obstetrician and physician is needed in the 24 postpartum period to reduce the maternal morbidity and mortality associated with this condition 25 in our community. Preeclampsia is a multisystem human specific pregnancy disorder characterized by new onset 48 hypertension and proteinuria after 20 weeks of pregnancy(1). It affects 2-8% of all pregnancies 49 worldwide and contributes significantly to maternal, fetal and neonatal morbidity and mortality 50 (2). Preeclampsia with other hypertensive disorders in pregnancy contributed to 14% of maternal 51 deaths worldwide (3). It is estimated to cause 8% of the severe maternal morbidity in Uganda is 52 the leading cause of maternal deaths (4). Women with preeclampsia have an increased risk of 53 renal, cerebrovascular and cardiovascular complications after delivery(5). In low resource 54 settings, preeclampsia is an important cause acute kidney injury and contributes to one third of 55 the cases seen in late pregnancy (6). Half of the women with acute kidney injury require dialysis 56 and when dialysis is not available as is commonly the case in many low resource settings, acute 57 kidney injury frequently leads to death of the women. Studies show that women recover their 58 renal function after preeclampsia (7), however, other workers have revealed that women with 59 preeclampsia are at a 5 to 12-fold increased risk of end-stage renal disease (8) and therefore 60 require prolonged nephrological follow up. The development of renal disease after preeclampsia 61 is not clearly understood. The renal injury may be due to extensive endothelial or podocyte 62 injury (9) seen in women with preeclampsia. This leads to nephron loss and later development of 63 renal disease.

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Women with preeclampsia on the other hand are at increased risk of cardiovascular disease 65 compared to normotensive women. They therefore require long time follow up regarding 66 hypertension after delivery(10). The mechanisms of developing chronic hypertension is not 67 clear. However, it may be due organ damage or preeclampsia may be a risk factor for later 5 68 development chronic hypertension. (1). Studies in Uganda have shown that up to one third of the 69 women with preeclampsia had persistent hypertension after the puerperium (11, 12). The 70 predictors for persistent hypertension were participants age (11,12), gestational age at delivery 71 and parity of the mother (12).

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It is therefore important that women with preeclampsia are followed after the puerperium if the 73 blood pressure and renal dysfunction do not resolve. The purpose of this study therefore was to 74 evaluate the postpartum trend in blood pressure, renal dysfunction and, proteinuria and to 75 determine the factors associated with their resolution in women with severe preeclampsia and 76 Eclampsia in Mulago hospital.

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This was a prospective cohort study conducted from August 2017 to April 2018 in Uganda. This  The study population consisted of women with severe preeclampsia and eclampsia who delivered 91 at Mulago hospital during the study period. Women with a known history of hypertension, 92 diabetes mellitus and kidney disease were excluded from the study. least 4 hours or more apart. Proteinuria was defined as urine protein of ≥300mg/24h urine 98 collection or protein/creatinine ratio of ≥ 0.3 or a dipstick reading of ≥2+. Preeclampsia was 99 taken as hypertension with proteinuria after 20 weeks gestation.

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A woman with preeclampsia was taken to have severe preeclampsia if she had BP of ≥160 101 mmHg systolic or ≥110 mmHg diastolic, severe headache or visual disturbances, 102 thrombocytopenia of ≤100,000/µL, aspartate transaminase or alanine transaminase > 2times the 103 upper limit with severe epigastric or upper quadrant pain, pulmonary edema or serum creatinine 104 ≥1.1mg/dL. A woman with preeclampsia was taken to have eclampsia if she developed a 105 convulsion that could not be attributed to any other cause (14).

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Sample size 107 We assumed that the persistence of hypertension would be 42.6% as was found in a study by 108 Kaze et.al (15) and parity as a biggest risk factor for preeclampsia with an odds ratio of 3.71 as 109 was found in a study in Mulago hospital (16). With these estimates a sample size of 97 110 participants would be sufficient with power of 80% at confidence level of 95% taking in account 111 of the anticipated loss to follow up of 5%.

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The research assistants who were qualified midwives identified women with severe preeclampsia 114 and eclampsia from the labour ward and the high dependence unit of the hospital. They 115 approached the attendants of the women and gave them information about the study. The 116 attendants were conducted through an informed consent procedure and gave a written informed 117 consent. The women later gave informed consent when they improved. Information was obtained 8 118 from the attendants and from the abstraction of the charts and later verified from the women 119 when they improved. The eligible participants were recruited consecutively until the required 120 sample size was achieved. The information from the women was collected using an interviewer-121 administered questionnaire, participants' examination, and biochemical investigations. Urine was 122 collected from the women for urine protein estimation and blood was drawn for serum creatinine 123 measurement.

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Follow up 125 The women were followed for 6 weeks after delivery. The women were reviewed on day 1,7,21

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In this study 97 women with severe preeclampsia/Eclampsia were followed up for 6 weeks after 154 childbirth. The time to resolution of hypertension, renal function and proteinuria, and the 155 associated factors were determined.

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All the 97 participants had hypertension, 20 were censored: 2 women died, 12 were lost to 157 follow-up by the third visit, and 6 had persistent hypertension by the end of this study.

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Forty seven participants had abnormal renal functions, 10 were censored: 9 women had 159 persistent renal dysfunction by the end of the study and 1 woman was lost follow up. 160 Finally, 92 had proteinuria: 29 were censored because 15 women had persistent proteinuria by 161 the end of the study and 14 women were lost to follow up (Fig 1).

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The mean age of the participants was 26.6±5.4 years, mean gestation age was 35.9±4.0 weeks 163 and a modal parity was 2 with a range of 1-6. The mean time to resolution of hypertension was 2.49 weeks (CI: 2.13-2.84). The blood 179 pressure decreased over the 6 weeks period of follow-up. Only 6 women (6.2%) had persistent 180 hypertension 6 weeks after delivery (Fig 2). The decrease of blood pressure was not affected by

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After controlling for other variables, having multiple pregnancy versus singleton pregnancy was 184 significantly associated with persistence of hypertension 6 weeks after delivery (p value =0.013) 185 (Fig 3). Other factors like time of development of preeclampsia, parity and mode of delivery 186 were not associated with persistence of hypertension 6 weeks after childbirth.

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The mean time for the recovery of the renal function was 24.5 days (95% CI: 20.14-28.95). The 188 renal function improved during the six weeks of follow up and only 9 (19.1%) women had 189 persistent renal dysfunction at 6 weeks follow-up (Fig 4). There recovery of the renal function This was a prospective cohort study in which 97 women with severe preeclampsia and eclampsia 235 were followed after childbirth. In this study, 93.8% (91/97) of the women recovered from 236 hypertension within 42 days after childbirth. This is in agreement with a study by Wei et al (18) 237 in which 90% of their patients recovered from hypertension within 60 days after childbirth and 238 Mikami et al (19) in which 90% of the women required 77 days to recover from hypertension. 239 We considered the blood pressure to be normal if it was less than 140/90mmHg without using 240 antihypertensive treatment for at least one week. In our study most women had an earlier 241 recovery than the women in these other studies by Wei et al (18) and Mikami et al (19). This was 242 probably because most mothers in our study had late onset preeclampsia at a gestational age of 243 35.9±4.0 weeks. Many studies have shown an association of a late onset of preeclampsia with 244 early recovery of hypertension (11,19). In our study 6 (6/97, 6.2%) women had persistent  In this study, there was a statistically significant difference in the time to resolution of 253 hypertension between singleton pregnancy versus multiple pregnancy: the time to resolution of 255 to multiple pregnancy (43.5±31.4 days). This finding disagrees with what Mikami et. al. (19) 256 found in their study. The normalization of blood pressure was significantly longer in singleton 257 pregnancy than multiple pregnancy.

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Renal dysfunction is due glomerular endotheliosis which occurs in women with 265 preeclampsia/eclampsia. Other studies have reported that resolution of the renal lesions may take 266 up to two years (21). In our study, 18.6% of the women had persistent renal dysfunction six 267 weeks after delivery. This is a reflection of the persistent effect of endothelial damage seen in 268 preeclampsia(22). Most of these women are expected to recover within two years after delivery 269 as this does not indicate chronic disease (23). However, this calls for prolonged follow up with a 270 nephrologist. 271 We observed persistence of proteinuria of 16.3% at six weeks after delivery. This was lower than 272 what was found in other studies (15,19). Proteinuria is due endothelial dysfunction which plays In this study, 16.3% participants had persistent proteinuria, 6% had persistent hypertension and 294 19.6% had persistent renal function six weeks after delivery. Special interdisciplinary follow up 295 of the patients with preeclampsia/eclampsia by an obstetrician and a physician after delivery is 296 required to reduce maternal morbidity and mortality associated with preeclampsia/eclampsia in 297 our community.