Uneke: Effects of placental malaria on perinatal outcome 97 analysis of 17 cross-sectional studies from sub-Saharan Africa [23]. However, in some studies in individual countries [21,24], this association was not always found to be sta- tistically significant. Interestingly, placental malaria infection has been identified as pos- sibly protective against perinatal mortality among low birth weight (LBW†) infants [25]. The explanations for this, however, re- main a mystery and therefore require further exploration. Low birth weight In sub-Saharan Africa, the rate of LBW (i.e., < 2.5kg) newborns ranges from 3.9 per- cent to 24 percent [22,26-29], and malaria is thought to be an important contributor to the 3.5 million LBW babies born annually in sub-Saharan Africa [30]. Malaria is thought to reduce birth weight through a combina- tion of systemic and local effects [26]. Al- though malaria may affect birth weight through malaria-induced anemia, it also may reduce birth weight via the effects of placen- tal infection [22,31,32]. In this case, para- sites either directly cause a mechanical compromise of placental circulation via widespread trophoblast basement thickening and increased fibrinoid necrosis and cytro- phoblast prominence or indirectly interfere with placental functions and/or induce pathological lesions [33,34]. Despite the prevalence of placental infections for women of all gravidities, ranging from 5 percent to 52 percent, infection-associated LBW risk is elevated two to four times in various studies [28,29,35]. A contradictory study in The Gambia showed increased birth weight in infected placentas, but widespread trophoblast basement membrane thickening was associated with decreased birth weight. A non-significant correlation was found be- tween LBW and increased fibrinoid necrosis and cytotrophoblast prominence [36]. Simi- larly, in Ubangi district, Zaire, malarious placentas had no consistent relationship to birth weight, and although infants born to in- fected mothers with malarious placentas av- eraged 100 g less, there was, however, no significant difference in the trend [24]. There is still no agreement as to the main mechanisms mediating reductions in birth weight in placental malaria [26]. When birth weight is stratified and related to the types of placental infections (chronic or active) in different studies, there were conflicting find- ings [22]. Since LBW is the single greatest risk factor for neonatal and infant mortality, its prevention through effective control of pla- cental malaria cannot be overstated [37]. In some studies in sub-Saharan Africa, infant mortality is three times higher for LBW ba- bies than for those of normal weight; effects on neonatal mortality are even more marked, with a LBW baby being nine times more likely to die in the first month of life [38-39]. Preterm delivery and intrauterine growth retardation The relationship between placental malaria and preterm delivery (PTD)/in- trauterine growth retardation (IUGR) has been evaluated in various studies. Two ear- lier studies among semi-immune women failed to show a difference in the proportion of PTD among infected and non-infected mothers, but other reports across sub-Saha- ran Africa have shown that placental malaria was significantly associated with PTD and IUGR [40-43]. This is in contrast with re- ports from Yaoundé, Cameroon, Malawi, and The Gambia, where, after adjusting for po- tentially confounding variables, the associa- tion of placental malaria with PTD was not found to be significant [21,44,45]. Although the precise effect of malaria- parasitized placentas on PTD is uncertain, malaria-infected placentas frequently carry antibodies, cytokines, and macrophages, which are indicative of an active immune re- sponse, and this immune response may stim- ulate early labor [35,46]. The biological processes that mediate IUGR as a result of placental malaria remain uncertain, given that they can be studied only after the pla- centa has been delivered. However, the IUGR effect appears to relate to nutrient transport to the fetus [35]. A high density of parasites and chronic parasite infection in the placental blood and the associated cellular immune response may result in consumption