This is the first time, to our knowledge, that contemporary species-specific estimates of the annual number of pregnancies at risk of malaria globally have been made. Our findings suggest that in 2007 approximately 125 million pregnancies occurred in areas with P. falciparum and/or P. vivax transmission, resulting in 83 million live births; representing approximately 60% of all pregnancies globally. Approximately 85 million pregnancies occurred in areas with P. falciparum transmission and 93 million in areas with transmission of P. vivax transmission, of which about 53 million occurred in areas where both species co-exist. The pregnancies at risk estimates for P. falciparum and P. vivax in Africa (32 million [30 million in the WHO-AFRO region]) are consistent with the previous estimates by WHO (25–30 million). By contrast, the numbers at risk outside Africa are much higher (95 million) than previously estimated (25 million). Comparisons between the estimates produced in this study and the previous WHO estimates are made difficult because details of the methodology used by the WHO is not provided and it is not clear if they included all transmission areas or only areas with stable malaria transmission. Inclusion of only those areas with stable P. falciparum transmission in our study resulted in global risk estimates of just less than 55 million pregnancies, 31 million in Africa and 23 million in the other regions, i.e., very similar to the previous WHO estimates. However, the numbers of pregnancies at risk outside Africa increase almost 4-fold if areas with unstable P. falciparum transmission are included (clinical incidence <1 per 10,000 population/year) (30 million) and areas situated in the temperate regions outside the limits of P. falciparum transmission that have P. vivax transmission only (40 million) are also included. It is also not clear if the previous WHO estimates included pregnancies resulting in live births only or included adjustments for induced abortions or spontaneous pregnancy loss. Since only approximately two-thirds of all pregnancies result in live births, estimates that include all pregnancies are about one-third higher than estimates based on live births only.
Although risk estimates are widely quoted figures, it is important to place them in perspective. The estimates provided here merely define the global distribution of pregnancies that occur within the global spatial limits of malaria transmission. These estimates therefore represent “any risk” of exposure to malaria during pregnancy, and do not represent the distribution of actual incidence or health burden on mothers and unborn babies, which is beyond the scope of this paper. More than half (71 million) of the 125 million pregnancies occur in areas with unstable P. falciparum transmission (31 million) or with transmission of P. vivax only (40 million), and the risk of acquiring malaria in these areas is extremely low. Thus, although these 71 million pregnancies represent more than 50% of the global number of pregnancies at risk, they may only contribute a small proportion to the number of infections in pregnancy. For example, if the actual incidence of malaria infection in these very low transmission areas is 1 in 10,000 per person-year (52 wk), and if the average pregnancy resulting in a live birth takes 38 wk from fertilisation to term, then 71 million pregnancies at risk may result in only 5,188 actual malaria infections, whereas in areas with infection rates of 1.36 or higher per person-year, all term pregnancies have been potentially exposed to malaria. Furthermore, the definition of stable transmission for P. falciparum used included all areas with more than one clinical case per 10,000 population per year. This included almost all pregnancies at risk in the AFRO Region (99% of the 30 million pregnancies at risk) and 25 million of the 95 million (26%) pregnancies in the other WHO regions. However, these stable transmission strata cover a very wide range of transmission intensities and the actual risk of infection to the 55 million individuals and the impact on maternal and infant health varies enormously within this range.
At the higher end of the transmission spectrum, the majority of malaria infections in pregnancy remain asymptomatic or pauci-symptomatic, yet are a major cause of severe maternal anaemia and preventable low birth weight, especially in the first and second pregnancies. In areas with stable, but low transmission, and certainly in areas with unstable and exceptionally low transmission, infections can become severe in all gravidae groups because most women of childbearing age in these regions have low levels of pre-pregnancy and pregnancy-specific protective immunity to malaria 
. The most recent version of the World Malaria Map 
from the Malaria Atlas Project shows that 89% of the populations in stable P. falciparum
areas outside Africa live in areas characterised by low malaria endemicity (defined as P. falciparum
parasite rate in children 2–10 y of age of ≤5%). This total includes all of the stable P. falciparum
transmission areas in the Americas, and 88% of the populations at risk in the Central and South-East Asia-Pacific region 
. Our estimates do not take seasonality into account and include all pregnancies occurring throughout the year, whereas those pregnancies that occur outside of the transmission season may be at no risk, or very low risk of exposure.
Our risk estimates for P. vivax
are likely to be less accurate than those for P. falciparum
because of greater uncertainties about the basic biology of transmission and clinical epidemiology. For example, the climatic constraints on P. vivax
transmission are less well defined, the accuracy of clinical reporting of P. vivax
in areas with coincidental P. falciparum
is poor, and the untreated hypnozoite stage of P. vivax
, which can remain dormant in infected liver cells for months or years, provides an additional challenge to the interpretation of prevalence and incidence data 
. We used a refined P. vivax
risk map that resulted in a 19% increase over previous population at risk estimates (adjusted for population growth) 
, principally resulting from the removal of the population density masks and thereby the inclusion of many large cities. In most of these cities, pregnancies will be at low or very low risk of autochthonous infections. Imported malaria associated with travel to rural areas may be a greater risk factor in these cities. We did not consider infections with P. ovale
or P. malariae
, as their distribution is not well described and the adverse effects on maternal health and the newborn infant are unknown.
In the current analysis we used the map of the global spatial limits of P. falciparum
malaria, which stratifies the malaria endemic world by stable and unstable transmission published in 2008 
.This map uses a simple divide between very low risk and higher transmission intensities and a crude proxy to account for the corresponding levels of acquired immunity in women of childbearing age. As a next step, we will examine the burden of malaria in pregnancy in terms of health impact on the pregnant women (e.g., febrile episodes, impact on maternal anaemia and maternal mortality), the newborn baby (e.g., impact on the frequency of preterm births and low birth-weight) and the infant (e.g., susceptibility to malaria). For this project, we will use the more refined P. falciparum
transmission intensity model of risk within the defined stable limits which was developed recently by the Malaria Atlas Project 
, allowing disease impact calculations across multiple transmission strata to be made. It is also important to take the different pregnancy outcomes into account in these further burden estimates. Of the 125 million pregnancies, one in five are estimated to be terminated voluntarily during the period of risk for miscarriage, and only about two-thirds (82.6 millions) are expected to result in live births. Although malaria in pregnancy is associated with miscarriages and stillbirths 
, the majority of the health and economic burden is likely through the impact on pregnancies that result in live births by increasing the risk of preterm births and low birth-weight 
and by modifying the susceptibility to malaria in the infant 
Most of the existing research and policy guidance for malaria control in pregnancy has focussed on P. falciparum in the stable transmission regions of sub-Saharan Africa. The results of this study are consistent with the previous WHO-RBM risk estimates for areas with stable P. falciparum malaria in Africa, but our work offers advancement on the existing risk estimates for malaria endemic countries outside Africa. In these regions, the burden of malaria in pregnancy is less well defined, both in terms of the number of pregnancies and its actual impact on health. Policy guidelines for malaria control in pregnancy are also less well developed for these regions.
These estimates of the number of pregnancies at risk of malaria provide a first step towards a spatial map of the burden of malaria in pregnancy and a more informed platform with which to estimate the associated disease and economic impact and its geographical distribution. Such global estimates provide guidance in terms of priority setting for resource allocation for both research and policy for the control of malaria in pregnancy. This project provides a dynamic framework that allows risk estimates to be updated when new risk maps of P. falciparum and P. vivax become available as the world attempts to move towards malaria elimination and eradication.