In this observational study, women delivering at a district hospital in rural southern Ghana after the implementation of IPTp-SP had significantly less placental malaria and anaemia and babies of higher birth weight than six years before when pyrimethamine chemoprophylaxis was the common mode of malaria prevention. This is a substantial improvement which, however, cannot exclusively be attributed to the implementation of IPTp since further factors known to be or potentially involved, e.g. antenatal care attendance, residence, and educational status, also changed over time. A further limitation of the present study is that malaria incidence or transmission intensity in Agogo and surroundings could have declined between 2000 and 2006. The implementation of e.g. artemisinin-based combination treatment in Ghana and other interventions might have led to a reduced malaria transmission and burden of disease. However, no dependable data are available to substantiate this. Though, in women in 2006 who did not take IPTp, the prevalence of placental infection (but not of LBW or anaemia) was lower than in 2000. However, this reduction did not have the magnitude seen in the 2006 group overall or among women having used IPTp. Moreover, comparing women delivering in 2006 with and without previous IPTp points into the same direction suggesting that IPTp in fact has markedly reduced the burden of malaria in pregnancy and related consequences. Still, 32% of women delivering after the implementation of IPTp were found to be P. falciparum infected, and maternal anaemia and LBW occurred in 24% and 12%, respectively, with higher figures among primiparae. This likely results from both, incomplete IPTp coverage and a remnant burden of disease which cannot further lowered even by complete coverage with this one measure of malaria control.
Data on IPTp-SP in West Africa are rare. In Mali and as compared to chloroquine chemoprophylaxis, 2-dose IPTp-SP significantly reduced the risks of placental parasitaemia, maternal anaemia, and LBW . In a smaller trial from Nigeria, IPTp-SP was superior to pyrimethamine chemoprophyaxis in the prevention of parasitaemia and anaemia which was confirmed and complemented by a beneficial effect on birth weight in a recent observational study [29, 30]. In Burkina Faso, the implementation of IPTp-SP in one district reduced placental parasitaemia and LBW, the latter, however, only when three doses had been taken . Lastly, in The Gambia, IPTp-SP benefited multigravidae only when not protected by a bednet . Altogether, these data show that IPTp-SP in West Africa is superior to available chemoprophylactic approaches but the effects achieved vary geographically and with the characteristics of the target population.
In the present study, only a quarter of delivering women had received all three recommended doses of IPTp-SP, and only half had taken two or more doses. Antenatal care attendance and both, use of IPTp-SP and number of doses were associated illustrating that efforts to promote antenatal care will likely be paralleled by increasing IPTp coverage, and, consequently, lead to even more pronounced effects than observed here. At Agogo hospital, the first dose of IPTp-SP was taken at a median gestational age of 24 weeks, i.e. roughly at halftime of pregnancy. While observed treatment during antental care visits is a major asset of IPTp, its comparatively late utilisation during pregnancy in general is a major drawback. Malaria early in pregnancy not only contributes to abortion but also to intrauterine growth retardation and LBW . So far, it is unknown whether the pathophysiological changes and foetal damage induced by infections in early pregnancy are reversible and, thus, the extent of morbidity due to the relatively late initiation of IPTp cannot be estimated. Education and information campaigns flanking IPTp as well as community-based delivery systems may promote early initiation of IPTp and also improve access, attendance and adherence to the programme [33, 34]. Further measures of malarial control, however, are needed to cover the vulnerable period of early pregnancy. Insecticide treated nets (ITNs) are a suitable and effective option , but the bed net coverage rate (8%) seen in this study is far too low.
Primiparae in 2006 showed an only slightly lower rate of IPTp usage than multiparae arguing for a similar level of information and acceptance among women of different parities. Elsewhere, however, primiparity, young age, and, thereby, a presumed low level of malaria-related knowledge, might be an obstacle in taking up interventions such as IPTp. IPTp should be most effective in primiparae in whom antimalarial immunity is lowest and infection rates are highest [1, 4, 6, 7, 23]. In fact, data from East Africa and from multigravidae in The Gambia point into this direction [8, 32]. Adjusting for the recruitment period, the reductions in placental malaria observed between 2000 and 2006 were similar in primi- and multiparae but the the reduction in maternal anaemia was significant only in the latter. The proportion of LBW, in contrast, declined significantly only in primiparae. Further adjustment for potential confounders did not fundamentally change these findings. These parity-dependent differences could reflect a differential effect of reducing the prevalence of malaria: in multiparae, increasing Hb concentrations might be the most visible sign of improved malaria prevention whereas the contribution of malaria to LBW is comparatively small . In fact, the rate of LBW among multiparae in this study closely resembles the figure among African Americans . In contrast, in primiparae the proportion of malaria-attributable LBW is larger than in multiparae , and IPTp-SP thus can achieve a greater extent of LBW reduction. So far, it is unclear why primiparae did not benefit from IPTp in haematological terms. Beyond a comparatively small sample size, this could stem from the still high prevalence of placental malaria in this group, or alternatively, reflect the importance of other, non-malaria causes of anemia. Such could involve e.g. iron deficiency which has previously been observed in only 5–18% of pregnant women in Agogo  and HIV infection, which occurs among 3% of pregnant women in Ghana .
No straightforward trend for less malaria, anaemia or LBW with increasing number of IPTp doses was observed in this study. Stratification into relatively small subgroups might be one reason. The sample size also impeded a meaningful analysis of the effects by parity and of the time when the last IPTp dose was given. The latter has been shown to unevenly influence the risk reduction of placental malaria in Kenya . Selection of drug-resistant parasites during the course of IPTp-SP could also be involved but, so far, it is not understood whether and to which extent this occurs. In children, a substantial increase in the proportion of resistant parasites has been observed within weeks after preventive SP treatment .
Drug resistance might also be responsible for the prevalence of 26% of placental P. falciparum infection observed in women who had taken all three doses of IPTp-SP. Already in 2000, 52% of placental P. falciparum isolates from Agogo hospital exhibited the triple dihydrofolate reductase mutation (Ile51+Arg59+Asn108)  which in Ghanaian children increases the risk of SP treatment failure ten-fold . Preliminary data from a subset of the study participants indicate that this figure has increased to more than 75% in 2006. While these findings support the utilisation of preventive approaches in addition to IPTp-SP they also question the useful lifespan of IPTp-SP in the study area and support the urgent evaluation of alternative drugs.