Pre-eclampsia, one of the most common medical complications of pregnancy, it affects approximately 10% of all human births [¹]. It is a leading cause of maternal mortality worldwide, as well as an important cause of perinatal mortality [²]. It has been estimated that 90% of the global malaria burden occurs in sub-Saharan Africa, where during pregnancy 40% women are exposed to malaria infections [³]. Malaria during pregnancy poses a substantial risk to the mother, her fetus and the neonate [⁴]. Although pre-eclampsia and maternal malaria would be expected frequently to occur concurrently in malarious areas, their interaction on the health of the mother and her baby has been little studied [⁵]. Seasonal changes in the incidence of pre-eclampsia have been described in tropics, which are consistent with malaria transmission periods [⁶]. Placental malaria is likely to impair placental development and cause maternal hypertension and placental vascular dysfunction [⁷].

Few data exist concerning placental malaria and its association with pre-eclampsia. While some of these studies have reported the association between malaria and pre-eclampsia and malaria and hypertension during pregnancy [⁸,⁹], other studies failed to find a significant association between malaria and pre-eclampsia [¹⁰,¹¹]. Furthermore some of these studies did not differentiate between pre-eclampsia and other types of hypertension.

Malaria during pregnancy is a major health problem in Sudan, where pregnant Sudanese women are more susceptible to malaria, and it is associated with maternal anaemia and poor maternal and perinatal outcomes [^12-14]. Both malaria and pre-eclampsia were among the common causes of high maternal mortality in Sudan [¹⁵,¹⁶]. The current study was conducted in Wad Medani maternity hospital in central Sudan to investigate the association between placental malaria and pre-eclampsia, so as to add on the standing and the recent research on both placental malaria and pre-eclampsia in Sudan [¹⁷,¹⁸]. The area is characterized by unstable malaria transmission and Plasmodium falciparum is the sole malaria species in the area [¹⁹].

During the study period, there were 4,620 deliveries. Of these, 160 had pre-eclampsia. One hundred and forty-three pre-eclamptic women had complete data including placental histology and were included in the final analyses. These data were compared with equal number of controls with complete data, Table 1. In comparison to the controls, significantly higher numbers of cases were primigravidae, had history of malaria infections in the index pregnancy and had family history of hypertension, Table 1. There was no significant difference in the mean (SD) age [28.9 (6.2) vs. 28.4(6.0) years], and body mass index [24.4 (2.2) vs.25.0 (3.5) kg/m²] in preeclamptic vs. controls women. The coverage of bed nets was low in the two groups, Table 1.

Maternal and placental blood films for malaria were positive in one of the cases and one of the controls had positive placental blood film. Twenty-eight (19.6%) vs. 16 (11.2%); P = 0.04 of the cases vs. controls, had placental malaria infections. Five (2%), 1 (2%) and 22 (28.0%) vs. 1, 2 and 13 of the placentae showed acute, chronic and past infection on histopathology examination in the two groups respectively, while 115 (80.4%) vs.127 (88.8%) of them showed no infection, P = 0.04.

The main findings of the current study were; there was no significant association between age, educational level, body mass index and blood group and pre-eclampsia. While women with family history of hypertension and those who had placental malaria infections were at higher risk of pre-eclampsia in multivariate analyses, primigravidae, lack of antenatal care and history of malaria in the index pregnancy were associated with pre-eclampsia in univariate analysis only. Recently, age, parity, body mass index were the risk factors for pre-eclampsia observed among Latin American and Caribbean women [²⁰].

In the current study women who had placental malaria infections were twice at higher risk for pre-eclampsia (OR = 2.3, 95% CI = 1.0-5.2; P = 0.04) compared with women without pre-eclampsia. This is consistent with the previous observation in Senegal with a 3.3-fold increase in the risk of placental malaria infections within women with diastolic blood pressure greater than or equal to 90 mm Hg compared with controls, where it was less than 90 mm Hg [⁸]. The difference between the current study and the later one is the classification of hypertensive women according to the presence or absence of significant proteinuria in the current study. Pre-eclampsia has also been shown to be more common in Senegal during the rainy season [²²]. Likewise, in Tanzania, young first-time mothers with placental malaria had significantly increased risk of hypertension [²³]. Interestingly, recently Ndao et al [⁹] observed association between placental malaria infections (using placental histology as diagnostic tool) and non-proteinuric hypertension in women living in a malaria-hypoendemic area in Senegal. Yet they did not find an association between placental malaria and pre-eclampsia [⁹]. However in neighbouring Kenya studies failed to find a relationship between malaria during pregnancy and pre-eclampsia [¹⁰,¹¹].

The majority of the placental infections in the current study were past infections.

There is a critical phase in early/mid pregnancy when transformation of the spiral arteries should take place, which is critical in pathogenesis of future pre-eclampsia.

Massive sequestration of parasites in the placenta leads to placental ischemia and loss of placental integrity, increases production of pro-inflammatory cytokines, and increases endothelial dysfunction [²⁴,²⁵]. Moreover, it has recently been observed that the production/imbalance of cytokines as pathophysiologic mechanisms of pre-eclampsia and placental malaria infections in two different studies [¹⁷,¹⁸]. In 2006 in Tanzania, Muehlenbachs et al [²³] have suggested that maternal-foetal conflict involving the inflammatory mediator, vascular endothelial growth factor pathway occurs during placental malaria and that its inhibitor, soluble vascular endothelial growth factor receptor 1 may be involved in a possible relation between chronic placental malaria infections and hypertension in primigravidae. However, it might still not be clear which the cause of effect is.

Family history of hypertension and placental malaria were associated with pre-eclampsia. Larger longitudinal studies are needed.

The authors declare that they have no competing interests.

IA and MIE coordinated, carried out the study and participated in the statistical analysis and procedures, EME participated in the clinical work and statistical analysis. AM and MS participated in the lab work. All the authors read and approved the final version.

We wish to thank all the patients for their excellent cooperation and we are very grateful to the local health authority in Geizera State and to the entire staff of Medani Maternity Hospital. This work has been funded by National Fund for promotion of Medical Service, Khartoum, Sudan.