Ultrasound evidence of early fetal growth restriction after maternal malaria infection

Abstract

Background: Intermittent preventive treatment (IPT), the main strategy to prevent malaria and reduce anaemia and low birthweight, focuses on the second half of pregnancy. However, intrauterine growth restriction may occur earlier in pregnancy. The aim of this study was to measure the effects of malaria in the first half of pregnancy by comparing the fetal biparietal diameter (BPD) of infected and uninfected women whose pregnancies had been accurately dated by crown rump length (CRL) before 14 weeks of gestation.

Methodology/principal findings: In 3,779 women living on the Thai-Myanmar border who delivered a normal singleton live born baby between 2001-10 and who had gestational age estimated by CRL measurement <14 weeks, the observed and expected BPD z-scores (<24 weeks) in pregnancies that were (n = 336) and were not (n = 3,443) complicated by malaria between the two scans were compared. The mean (standard deviation) fetal BPD z-scores in women with Plasmodium (P) falciparum and/or P.vivax malaria infections were significantly lower than in non-infected pregnancies; -0.57 (1.13) versus -0.10 (1.17), p<0.001. Even a single or an asymptomatic malaria episode resulted in a significantly lower z-score. Fetal female sex (p<0.001) and low body mass index (p = 0.01) were also independently associated with a smaller BPD in multivariate analysis.

Conclusions/significance: Despite early treatment in all positive women, one or more (a)symptomatic P.falciparum or P.vivax malaria infections in the first half of pregnancy result in a smaller than expected mid-trimester fetal head diameter. Strategies to prevent malaria in pregnancy should include early pregnancy.

Conflict of interest statement

Competing Interests: The authors have read the journal's policy and have the following conflicts: Professor Francois Nosten is an academic editor of PLoS ONE. This does not alter the authors' adherence to all the PLoS ONE policies on sharing data and materials.

Figures

Figure 1. Selection of pregnant women.

Figure 2. Fetal biparietal diameter measurements in Burmese and Karen pregnant women with and without malaria.

The x-axis shows the gestational age (GA) in weeks, based on first trimester dated pregnancies on the Thai-Burmese border from 2001 to 2010. The y-axis depicts the fetal biparietal diameter measurement (BPD) in centimeters. The fetal BPD in pregnant women with malaria (red diamonds, n = 336) and in women without malaria (+, n = 3,443) between 16 and 24 GA weeks were superimposed on the 2.5th, 50th and 97.5th centiles of a reference equation for this population . Note that the majority of fetal BPD measurements in malaria infected women lie below the 50th centile in both the main figure (16 to 24 GA weeks) and in the inset (17 to 20 GA weeks, where 90% (302/336) of the measurements in malaria infected women were obtained).

Figure 3. Z-scores of fetal biparietal diameter in Burmese and Karen pregnant women with and without malaria.

The x-axis shows the z-score and the y-axis depicts the distribution in percentages. The distribution of z-scores of fetal biparietal diameter in pregnant women with malaria (n = 336, red bars) is significantly lower than in women without malaria (n = 3,443, grey bars) on the Thai-Burmese border from 2001 to 2010.