In this study a significantly smaller fetal BPD was observed by ultrasound when malaria infection occurred in the first half of pregnancy, compared to pregnancies unaffected by malaria. Previous studies have shown that malaria early in pregnancy has an impact on birthweight, but they were limited by small numbers of first trimester exposures 
or by inaccuracy in the dating of gestation 
. In this analysis the women had a documented and treated episode of malaria during a specific period between two ultrasound scans. By studying this selected group the effects of malaria on fetal growth could be quantified in-utero
. Even a single infection of treated P.vivax
was associated with reduced BPD irrespective of whether the woman was symptomatic or not. The mechanisms underlying the adverse effects of malaria in pregnancy are not fully understood 
is thought to sequester in the placenta and interfere with materno-fetal exchanges but other mechanisms may also be involved 
. Systemic or hormonal mechanisms may play a role in P. vivax
related growth restriction, as there is little evidence that P.vivax
sequesters in the placenta, like P.falciparum
. In non-malaria endemic areas, early pregnancy growth restriction has been associated with miscarriage 
, maternal physical characteristics and lifestyle habits related to early fetal growth 
, and low BPD growth rates between the first and second trimester are associated with increased perinatal mortality and IUGR 
. In malaria endemic areas ultrasound studies have related malaria in pregnancy to changes in maternal and fetal blood flow 
and associated malnutrition and malaria in pregnancy with IUGR 
. So the results presented here are not entirely unexpected but show for the first time the direct evidence of the effect of malaria (both falciparum and vivax) on fetal growth. More surprising perhaps is that low BPD growth was observed after a single (even asymptomatic) infection and despite early treatment.
Studies on the impact of malaria in pregnancy have almost always focused on birthweight. However, for infections that occur in early pregnancy, the size of the fetal head may be a more appropriate indicator of growth restriction. It has been shown that the growth velocity of the fetal head (in mm/day) is maximal during the second trimester 
. In contrast the fetal “weight velocity” (in g/week) peaks in the third trimester. This weight gain velocity curve has often been cited wrongly as a fetal “growth velocity” curve 
. The characteristics of the “fetal head size” and “fetal weight” growth velocity curves are similar but the timing is different. One of the strengths of this study is that the timing of the BPD measurement coincided with the maximal growth velocity of the fetal head, making it a better marker of the effect of malaria in early pregnancy than birthweight.
The reduction in BPD size occurred despite prompt treatment with effective antimalarials in this setting, which highlights the importance of prevention in pregnancy. Multiple episodes of P.vivax
are most likely from liver stage relapses instead of newly acquired infections. There is no treatment available in pregnancy for liver stages. Furthermore, in this setting of multidrug resistant parasites there are no safe and effective drugs available to prevent malaria from the start of pregnancy. To protect the developing fetus from growth restriction from both symptomatic and asymptomatic P.vivax
infections, prevention strategies from early pregnancy onwards or even pre-pregnancy interventions should be considered 
There are some limitations to this analysis. Firstly, although dating by CRL is generally considered to be the most accurate method of estimating GA, some factors that may have had an impact on CRL dating, for example maternal age 
or haematocrit 
. Such factors are difficult to control for in this type of population because the date of the last menstrual period is often not available. The second limitation is that the observed difference in BPD is small and within the range of error for most ultrasound machines and sonographers. The scans were obtained by locally trained technicians who were previously reported to have a mean difference of 0.43 (SD 1.21) mm in their BPD measurements in scans between 18 and 24 weeks, corresponding to 0.12 (SD 0.36) weeks 
. The observed reduction in BPD in malaria infected pregnancies at 22 weeks is within the range of this measurement error. However the data of this retrospective analysis were derived from the entire population of women attending ANC for their routine ultrasound scans, which minimizes selection bias. In addition the sonographers were not aware whether women had malaria or not during pregnancy and therefore observer bias is unlikely. If there was no true effect of malaria infection on BPD any observed difference would likely be occulted by the expected measurement error of the examiners. In contrast, within this large population of routine ultrasound scans, malaria in the late first and/or second trimester was the largest risk factor for a smaller BPD. Thirdly, in order to examine the effect of the malaria between the scans on birth outcomes, a highly selected group of women was studied for this analysis. This small group (N
72) had their malaria infections only between the two scans, and was malaria free in the time period where weight gain velocity is highest. Therefore no firm conclusions on the relationship between malaria in early pregnancy, its impact on BPD and birth outcome can be drawn from this analysis. Finally, other biometric parameters, such as fetal head circumference, were not available for most women.
Intermittent preventive treatment, one of the main WHO recommended strategies for malaria prevention and control during pregnancy in areas of stable malaria transmission, aims to provide two or three treatment doses after quickening (around 20 weeks GA) at least one month apart 
. This approach fails to protect women in the gestational weeks of the highest fetal head growth velocity. Fetal growth has been postulated to be a dynamic system where pulsatile characteristics of saltatory growth events are able to change throughout pregnancy 
. Such pulsatile growth events all the way through pregnancy stress the importance of protecting each fetus from the effects of malaria parasites starting as early as possible in pregnancy.