Ultrasound Evidence of Early Fetal Growth Restriction after Maternal Malaria Infection

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

Effect of malaria on placental volume measured using three-dimensional ultrasound: a pilot study

Background: The presence of malaria parasites and histopathological changes in the placenta are associated with a reduction in birth weight, principally due to intrauterine growth restriction. The aim of this study was to examine the feasibility of studying early pregnancy placental volumes using three-dimensional (3D) ultrasound in a malaria endemic area, as a small volume in the second trimester may be an indicator of intra-uterine growth restriction and placental insufficiency. Methods: Placenta volumes were acquired using a portable ultrasound machine and a 3D ultrasound transducer and estimated using the Virtual Organ Computer-aided AnaLysis (VOCAL) image analysis software package. Intraobserver reliability and limits of agreement of the placenta volume measurements were calculated. Polynomial regression models for the mean and standard deviation as a function of gestational age for the placental volumes of uninfected women were created and tested. Based on these equations each measurement was converted into a z -score. The z-scores of the placental volumes of malaria infected and uninfected women were then compared. Results: Eighty-four women (uninfected = 65; infected = 19) with a posterior placenta delivered congenitally normal, live born, single babies. The mean placental volumes in the uninfected women were modeled to fit 5th, 10th, 50th, 90th and 95th centiles for 14-24 weeks’ gestation. Most placenta volumes in the infected women were below the 50th centile for gestational age; most of those with Plasmodium falciparum were below the 10th centile. The 95% intra-observer limits of agreement for first and second measurements were ± 37.0 mL and ± 25.4 mL at 30 degrees and 15 degrees rotation respectively. Conclusion: The new technique of 3D ultrasound volumetry of the placenta may be useful to improve our understanding of the pathophysiological constraints on foetal growth caused by malaria infection in early pregnancy

Effect of malaria in pregnancy on foetal cortical brain development: a longitudinal observational study

<p>Abstract</p> <p>Background</p> <p>Malaria in pregnancy has a negative impact on foetal growth, but it is not known whether this also affects the foetal nervous system. The aim of this study was to examine the effects of malaria on foetal cortex development by three-dimensional ultrasound.</p> <p>Methods</p> <p>Brain images were acquired using a portable ultrasound machine and a 3D ultrasound transducer. All recordings were analysed, blinded to clinical data, using the 4D view software package. The foetal supra-tentorial brain volume was determined and cortical development was qualitatively followed by scoring the appearance and development of six sulci. Multilevel analysis was used to study brain volume and cortical development in individual foetuses.</p> <p>Results</p> <p>Cortical grading was possible in 161 out of 223 (72%) serial foetal brain images in pregnant women living in a malaria endemic area. There was no difference between foetal cortical development or brain volumes at any time in pregnancy between women with immediately treated malaria infections and non-infected pregnancies.</p> <p>Conclusion</p> <p>The percentage of images that could be graded was similar to other neuro-sonographic studies. Maternal malaria does not have a gross effect on foetal brain development, at least in this population, which had access to early detection and effective treatment of malaria.</p

Selection of pregnant women.

<p>Selection of pregnant women.</p

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

<p>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 (<b>+</b>, n = 3,443) between 16 and 24 GA weeks were superimposed on the 2.5^th, 50^th and 97.5^th centiles of a reference equation for this population <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0031411#pone.0031411-Rijken4" target="_blank">[29]</a>. Note that the majority of fetal BPD measurements in malaria infected women lie below the 50^th 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).</p

Demographics of the refugee and migrant women from Thai Burmese border, 2001–2010.

<p>Median [IQR], or as indicated.</p><p>BMI body mass index, Hct Haematocrit at first consultation, MUAC middle upper arm circumference, NOC number of consultations.</p>+<p>between the 1^st and 2^nd scans.</p><p>*Weight gain from the first to the second scan; available from 301 in malaria and 2,677 in no malaria group.</p>#<p>Available from 292 in malaria and 2,626 in no malaria group.</p>$<p>Available from 314 in malaria and 3,044 in no malaria group.</p

Species, episodes and severity of malaria and mean BPD z-score of women infected between the first and second scan.

<p>Median [min-max], or mean (SD). BPD biparietal diameter; hyper = hyperparasitaemia (≥4% red blood cells infected), n.a. not applicable, P plasmodium.</p>#<p>Missing data n = 2.</p