Risk factors for pre-eclampsia in low and middle-income countries, a case study of Tanzania

Abstract

This PhD research focuses on understanding a maternal pregnancy condition known as pre-eclampsia. This condition contributes to around 14 % of the global burden of maternal mortality and fivefold of perinatal mortality in developing countries. Genetic, environmental, nutritional and socioeconomic factors are thought to disproportionately affect the burden of pre-eclampsia in low and middle-income countries (LMIC). The first chapter gives an overview; it introduces pre-eclampsia and outlines its contribution to the burden of maternal and infant mortality and morbidity. It summarises all chapters in this thesis. The second chapter gives the background of the literature review. This chapter describes pre-eclampsia in the context of hypertensive disorders of pregnancy. It then explains some of the risk factors of pre-eclampsia, the natural history of the disease and the health system response: current modalities in screening, the evolution of the definition pre-eclampsia, diagnosis, prevention and management. The third chapter describes the scoping study, which aims at summarising explored risk factors in Africa, to identify potential gaps and the feasibility of conducting a systematic review. Its results showed that there were twenty studies done in Africa that had explored relatively few risk factors. These studies had methodological limitations of size and rigour, hence produced conflicting and inconclusive associations between pre-eclampsia outcome and most explored risk factors, including malaria infection. They also showed a gap in the literature regarding models built by risk factors that attempted to classify pre-eclampsia outcome in African populations. The fourth chapter describes the systematic review that explores the relationship between malaria infection and gestational hypertension (GH) with proteinuria (pre-eclampsia) or without. It considers two pathways that malaria possibly exert its effect on causing gestational hypertension. One pathway being through a dysfunctional placenta and the other pathway is by endothelial inflammation of blood vessels from malaria toxins. The result of the meta-analysis was a pooled odds ratio (OR) of 2.6, 95 % confidence interval (CI) 1.5 to 4.5. The odds of pre-eclampsia among pregnant women with malaria infection were 2.6 times than pregnant women without malaria infection. The fifth chapter describes the analysis of secondary data from Tanzania. This data analysis has four objectives. The sixth chapter describes the results of the four objectives, while chapter Seven presents the discussions of the four objectives. This data analysis used data from two sources: a hospital maternity register from northern Tanzania and a clinical trial in Dar es Salaam, Tanzania. The data analysis had four objectives; objective one determined the incidence pre-eclampsia to be 1.9 %, 95 % CI 1.3 % to 2.2 % in Dar es Salaam city, Tanzania. Objective two describes the sociodemographic characteristics of women with pre-eclampsia compared with those without pre-eclampsia in northern Tanzania population. Preeclampsia was more frequent among women with age above 35 years, single and tertiary level education. Objective three aimed to identify biomedical risk factors for pre-eclampsia among women in northern Tanzania. Then, I used these identified risk factors to build prediction models for pre-eclampsia. I later assessed the ability of these models to classify women with and without pre-eclampsia. Maternal age, weight before pregnancy, contraceptive intrauterine device (IUD) use, a diagnosis of malaria, diagnosis of infections, history of hypertension and HIV treatment were statistically significant predictors in some of my models. My final models in predicting pre-eclampsia in all deliveries, term and preterm delivery subgroups produced an area under the curve of 69.4 %, 71.2 % and 66.9 % respectively. The points of maximum sensitivity and specificity produced sensitivity values of 65 %, 65 % and 59 % respectively, while also producing specificity values of 63 %, 65 % and 66 % respectively. The risk factors and the prediction models were developed on a hospital-based register where the incidence of pre-eclampsia was 3.5%. Since hospital estimates tend to overestimate the incidence compared to population survey, the results of my prediction models will differ in women populations with a high risk of pre-eclampsia. The fourth objective describes the pregnancy outcome of women with preeclampsia compared to women without pre-eclampsia. The results showed there were more stillbirths among women with pre-eclampsia. The odds of stillbirth were 4.8 (95 % CI 3.7 – 6.3) times among women with preeclampsia than women without pre-eclampsia in all deliveries. Upon stratifying by term and preterm deliveries the odds were 2.6 (95 % CI 1.6 – 4.3) and 2.9 (95 % CI 2.0 – 4.1) respectively. The surviving offspring have worse developmental indicators compared to their counterparts in terms of low a Apgar score at 1-minute, low birth weight, small head circumference and short birth length. The odds of a low Apgar score (0 – 3) baby was 4.3 times (95 % CI 3.4 - 5.4) among pre-eclampsia women in all deliveries compared to normal Apgar score (4 – 10) babies. The association was maintained in the subgroups of term and preterm delivery (OR = 2.3, 95 % CI 1.5 – 3.5 and 2.8, 95 % CI 2.0 - 3.9 respectively). Chapter Eight covers the conclusion and recommendations of this thesis, which are: (i) Few studies that explored risk factors in Africa, more studies are needed to resolve conflicting and inconclusive findings from these studies. (ii) Malaria infection is associated with pre-eclampsia and gestational hypertension in malaria endemic regions. Malaria control should be intensified among pregnant women and further studies should explore the causal mechanisms. (iii) The incidence of pre-eclampsia should be tracked to observe changes in its trends in the evolving urban populations of LMIC. (iv) Affordable and feasible prediction models for pre-eclampsia should be developed and assessed for performance to enable identification and provision of prevention services on women with a high risk of developing preeclampsia. (v) Women with pre-eclampsia should receive appropriate treatment to mitigate the negative impact on their pregnancy outcome.