Trypanosoma cruzi Infection in Pregnancies without Congenital Transmission Is Associated with Reduced Fetal Growth: A Cross-Sectional Study in Argentina, Honduras, and Mexico.

We aimed to measure the association between Trypanosoma cruzi infection in pregnancy and reduced fetal growth in the absence of T. cruzi congenital transmission. We conducted a cross-sectional study of secondary data of all singleton live births between 2011 and 2013 in five hospitals from Argentina, Honduras, and Mexico. We excluded newborns with T. cruzi infection. Noninfected pregnant people were those without any positive rapid tests. The main study outcomes were birth weight, head circumference, and length for gestational age and sex. Logistic regression models were adjusted for country, age, education level, and obstetric history. Of the 26,544 deliveries, 459 (1.7%) pregnant people were found by rapid tests to be positive for T. cruzi. Of these, 320 were positive by enzyme-linked immunosorbent assay and 231 had a positive polymerase chain reaction (PCR) test. Uninfected newborns from T. cruzi-infected pregnant people were more likely to have birth weights below the 5th and 10th percentiles and head circumferences below the 3rd and 10th percentiles. Among T. cruzi-infected pregnant people diagnosed by PCR, the odds ratios were 1.58 for birth weight below the 10th percentile (95% CI, 1.12-2.23) and 1.57 for birth weight below the 5th percentile (95% CI, 1.02-2.42). Higher T. cruzi parasitic loads in pregnancy had a stronger association with reduced fetal growth (both in birth weight and head circumference), with an odds ratio of 2.31 (95% CI, 1.36-3.91) for a birth weight below the 5th percentile. The association shows, irrespective of causality, that newborns of pregnancies with T. cruzi have an increased risk of reduced fetal growth. We recommend further studies to assess other potential confounders and the causality of these associations.

Maternal and fetal outcome of pregnancy in Swiss mice infected with Plasmodium berghei ANKAGFP.

Malaria in pregnant women is associated with risk of maternal and perinatal morbidity and mortality, and there are few antimalarial drugs considered safe to treat them, so it is necessary to develop safer antimalarial medicines. The goal of this study was to develop an animal model for human malaria during pregnancy by characterizing the maternal and fetal outcomes in malaria infected Swiss mice. For that, in the present study, we evaluated the outcome of pregnancy in Swiss mice infected with Plasmodium berghei ANKAGFP. We observed a reduction of fetal body weight and signs of skeletal ossification retardation in the offspring of mice infected on GD 12. The group of mice infected with malaria presented premature deliveries and histopathology changes consistent with placental malaria. Our study suggests that Swiss Webster mice infected with P. berghei ANKAGFP on GD 12 might be a valuable model to investigate the safety and the efficacy of new antimalarial drugs indicated to pregnant women.

Diagnóstico y manejo de la restricción del crecimiento intrauterino en fetos de gestantes provenientes de zonas endémicas para la malaria / Diagnosis and management of intrauterine growth restriction in fetuses of pregnant women from endemic areas for malaria

RESUMEN Introducción: La malaria es una enfermedad infecciosa tropical de gran impacto epidemiológico a nivel mundial; las poblaciones con mayor susceptibilidad de padecerla son los niños menores de 5 años y las gestantes, en quienes, se pude no solo comprometer la salud de la madre sino también la del producto y su desarrollo, pudiendo ocurrir diferentes desenlaces adversos entre ellos la restricción del crecimiento intrauterino (RCIU), incrementando sustancialmente las tasas de mortalidad materna y perinatal. Es importante establecer un diagnóstico preciso y oportuno de la RCIU en fetos de gestantes que padecen de malaria, con el fin de llevar a cabo un enfoque de seguimiento y de manejo que puedan disminuir las complicaciones asociadas a la enfermedad. Métodos: Se realizó una búsqueda bibliográfica en la base de datos de Cochrane y PubMed, libros de la especialidad y consensos de sociedades científicas, relativos a los términos de: malaria during pregnancy, intrauterine growth restriction y malaria and fetal growth restriction. Se seleccionaron finalmente 42 artículos para análisis completo y crítico, que justificara la elaboración de esta revisión. Conclusión: esta revisión aporta elementos para establecer un alto grado de sospecha diagnóstica de malaria durante el embarazo en zonas endémicas para la malaria; además revela la necesidad de implementar protocolos de manejo especifico ante la RCIU según sea la etiología; ya que estas medidas impactaran positivamente en los resultados adversos de la enfermedad, sin olvidar que lo primordial es proteger plenamente a las mujeres contra la malaria desde el comienzo del embarazo hasta el parto.

Effects of Plasmodium falciparum infection on umbilical artery resistance and intrafetal blood flow distribution: a Doppler ultrasound study from Papua New Guinea.

BACKGROUND: Doppler velocimetry studies of umbilical artery (UA) and middle cerebral artery (MCA) flow help to determine the presence and severity of fetal growth restriction. Increased UA resistance and reduced MCA pulsatility may indicate increased placental resistance and intrafetal blood flow redistribution. Malaria causes low birth weight and fetal growth restriction, but few studies have assessed its effects on uteroplacental and fetoplacental blood flow. METHODS: Colour-pulsed Doppler ultrasound was used to assess UA and MCA flow in 396 Papua New Guinean singleton fetuses. Abnormal flow was defined as an UA resistance index above the 90th centile, and/or a MCA pulsatility index and cerebroplacental ratio (ratio of MCA and UA pulsatility index) below the 10th centile of population-specific models fitted to the data. Associations between malaria (peripheral infection prior to and at ultrasound examination, and any gestational infection, i.e., 'exposure') and abnormal flow, and between abnormal flow and birth outcomes, were estimated. RESULTS: Of 78 malaria infection episodes detected before or at the ultrasound visit, 62 (79.5%) were Plasmodium falciparum (34 sub-microscopic infections), and 16 were Plasmodium vivax. Plasmodium falciparum infection before or at Doppler measurement was associated with increased UA resistance (adjusted odds ratio (aOR) 2.3 95% CI 1.0-5.2, P = 0.047). When assessed by 'exposure', P. falciparum infection was significantly associated with increased UA resistance (all infections: 2.4, 1.1-4.9, P = 0.024; sub-microscopic infections 2.6, 1.0-6.6, P = 0.051) and a reduced MCA pulsatility index (all infections: 2.6, 1.2-5.3, P = 0.012; sub-microscopic infections: 2.8, 1.1-7.5, P = 0.035). Sub-microscopic P. falciparum infections were additionally associated with a reduced cerebroplacental ratio (3.64, 1.22-10.88, P = 0.021). There were too few P. vivax infections to draw robust conclusions. An increased UA resistance index was associated with histological evidence of placental malaria (5.1, 2.3-10.9, P < 0.001; sensitivity 0.26, specificity 0.93). A low cerebroplacental Doppler ratio was associated with concurrently measuring small-for-gestational-age, and with low birth weight. DISCUSSION/CONCLUSION: Both microscopic and sub-microscopic P. falciparum infections impair fetoplacental and intrafetal flow, at least temporarily. Increased UA resistance has high specificity but low sensitivity for the detection of placental infection. These findings suggest that interventions to protect the fetus should clear and prevent both microscopic and sub-microscopic malarial infections. Trial Registration ClinicalTrials.gov NCT01136850. Registered 06 April 2010.

Fish Parasites: A Growing Concern During Pregnancy.

Intestinal parasitic worms affect more than 2 billion people worldwide according to the World Health Organization. Fish-borne parasitic infections are becoming more common with the increasing popularity of sushi, sashimi, Carpaccio, tartare, gefilte, and ceviche. The ingestion of these parasites can cause serve anemia, malabsorption, severe abdominal pain, nausea, vomiting, strong allergic reactions, and gastric ulcers. Knowledge about fish parasites and pregnancy is limited. A literature search on PubMed and Web of Science used the search terms "fish parasites" OR "diphyllobothrium" OR "anisakiasis" OR "pseudoterranova" OR ("food borne parasites" AND "fish") AND "pregnancy" OR "maternal" OR "fetus" OR "fetal" OR "newborn" OR "neonatal" OR "childbirth." No limit was put on the number of years searched. There were 281 publications identified. The abstracts of all of these publications were read. After exclusion of the articles that were not relevant to pregnancy, pregnancy outcome, and fish parasites, there were 24 articles that became the basis of this review. The pathophysiology, altered maternal immunity related to the infection, limited information about fish-borne parasitic infections and pregnancy, and treatments are discussed. The main impact of a fish-borne parasitic infection on pregnant women is anemia and altered immunity, which may increase the risk of a maternal infection. The primary fetal effects include intrauterine growth restriction and preterm delivery.

Syncytiotrophoblast Functions and Fetal Growth Restriction during Placental Malaria: Updates and Implication for Future Interventions.

Syncytiotrophoblast lines the intervillous space of the placenta and plays important roles in fetus growth throughout gestation. However, perturbations at the maternal-fetal interface during placental malaria may possibly alter the physiological functions of syncytiotrophoblast and therefore growth and development of the embryo in utero. An understanding of the influence of placental malaria on syncytiotrophoblast function is paramount in developing novel interventions for the control of placental pathology associated with placental malaria. In this review, we discuss how malaria changes syncytiotrophoblast function as evidenced from human, animal, and in vitro studies and, further, how dysregulation of syncytiotrophoblast function may impact fetal growth in utero. We also formulate a hypothesis, stemming from epidemiological observations, that nutrition may override pathogenesis of placental malaria-associated-fetal growth restriction. We therefore recommend studies on nutrition-based-interventional approaches for high placental malaria-risk women in endemic areas. More investigations on the role of nutrition on placental malaria pathogenesis are needed.

A novel lineage transcription factor based analysis reveals differences in T helper cell subpopulation development in infected and intrauterine growth restricted (IUGR) piglets.

Research in mouse and human clearly identified subsets of T helper (Th) cells based on nuclear expression of specific lineage transcription factors. In swine, however, transcription factor based detection of functional subpopulations of porcine Th cells by flow cytometry is so far limited to regulatory T cells via Foxp3. T-bet and GATA-3 are the transcription factors that regulate commitment to Th1 or Th2 cells, respectively. In this study we prove GATA-3 and T-bet expression in porcine CD4(+) cells polarized in vitro. Importantly, GATA-3 and T-bet expressing cells were detectable in pigs infected with pathogens associated with Th2 and Th1 immune responses. Increased frequencies of GATA-3 positive CD4(+) cells are found in vivo in pigs experimentally infected with the nematode Trichuris suis, whereas porcine reproductive and respiratory syndrome virus (PRRSV) infection elicited T-bet positive CD4(+) T cells. Analysing the immune status of pre-weaning piglets with intrauterine growth restriction (IUGR) we found an increased expression of Foxp3, T-bet and GATA-3 in CD4(+) and CD4(+)CD8(+) double-positive T cells in systemic and intestinal compartments of IUGR piglets. Hence, we established the detection of porcine Th1 and Th2 cells via T-bet and GATA-3 and show that the porcine lineage transcription factors are differentially regulated very early in life depending on the developmental status.

Effects of vivax malaria acquired before 20 weeks of pregnancy on subsequent changes in fetal growth.

The resistance index (RI), pulsatility index (PI), fetal biometry, fetal heart rate (FHR), placental thickness, and hemoglobin levels were compared in 30 Plasmodium vivax-infected women between 14 and 20 weeks of pregnancy and a control group. Evaluations were performed at the moment of the malaria diagnosis and 26 weeks of pregnancy. The malaria group had lower levels of hemoglobin and greater placental thickness in both assessments, higher FHR in the first evaluation, and lower values on fetal biometry in the second assessment. There were no differences when comparing RI and PI on umbilical arteries between the two groups. Birth weight and height were lower in newborns in the malaria group than the control group. The results suggest that P. vivax infections at an earlier gestational age do not affect umbilical arteries blood flow but do affect fetal biometry in the second trimester of pregnancy and at birth.

Complement activation and the resulting placental vascular insufficiency drives fetal growth restriction associated with placental malaria.

Placental malaria (PM) is a major cause of fetal growth restriction, yet the underlying mechanism is unclear. Complement C5a and C5a receptor levels are increased with PM. C5a is implicated in fetal growth restriction in non-infection-based animal models. In a case-control study of 492 pregnant Malawian women, we find that elevated C5a levels are associated with an increased risk of delivering a small-for-gestational-age infant. C5a was significantly increased in PM and was negatively correlated with the angiogenic factor angiopoietin-1 and positively correlated with angiopoietin-2, soluble endoglin, and vascular endothelial growth factor. Genetic or pharmacological blockade of C5a or its receptor in a mouse model of PM resulted in greater fetoplacental vessel development, reduced placental vascular resistance, and improved fetal growth and survival. These data suggest that C5a drives fetal growth restriction in PM through dysregulation of angiogenic factors essential for placental vascular remodeling resulting in placental vascular insufficiency.

Malaria and fetal growth alterations in the 3(rd) trimester of pregnancy: a longitudinal ultrasound study.

BACKGROUND: Pregnancy associated malaria is associated with decreased birth weight, but in-utero evaluation of fetal growth alterations is rarely performed. The objective of this study was to investigate malaria induced changes in fetal growth during the 3(rd) trimester using trans-abdominal ultrasound. METHODS: An observational study of 876 pregnant women (398 primi- and secundigravidae and 478 multigravidae) was conducted in Tanzania. Fetal growth was monitored with ultrasound and screening for malaria was performed regularly. Birth weight and fetal weight were converted to z-scores, and fetal growth evaluated as fetal weight gain from the 26th week of pregnancy. RESULTS: Malaria infection only affected birth weight and fetal growth among primi- and secundigravid women. Forty-eight of the 398 primi- and secundigravid women had malaria during pregnancy causing a reduction in the newborns z-score of -0.50 (95% CI: -0.86, -0.13, P = 0.008, multiple linear regression). Fifty-eight percent (28/48) of the primi- and secundigravidae had malaria in the first half of pregnancy, but an effect on fetal growth was observed in the 3(rd) trimester with an OR of 4.89 for the fetal growth rate belonging to the lowest 25% in the population (95%CI: 2.03-11.79, P<0.001, multiple logistic regression). At an individual level, among the primi- and secundigravidae, 27% experienced alterations of fetal growth immediately after exposure but only for a short interval, 27% only late in pregnancy, 16.2% persistently from exposure until the end of pregnancy, and 29.7% had no alterations of fetal growth. CONCLUSIONS: The effect of malaria infections was observed during the 3(rd) trimester, despite infections occurring much earlier in pregnancy, and different mechanisms might operate leading to different patterns of growth alterations. This study highlights the need for protection against malaria throughout pregnancy and the recognition that observed changes in fetal growth might be a consequence of an infection much earlier in pregnancy.

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.

[Intrauterine growth retardation, low birth weight and prematurity in neonates of pregnant women with malaria in Colombia]. / Retardo no crescimento intrauterino, baixo peso ao nascer e prematuridade em recém-nascidos de grávidas com malária, na Colômbia.

INTRODUCTION: Association between malaria and pregnancy complications, such as prematurity, intrauterine growth restriction, low birthweight and infant mortality has been reported. These effects have been studied widely in areas hyperendemic for malaria, but studies in low-endemic areas are scarce. The study investigated the relation between gestational malaria and low birthweight and intrauterine growth retardation in neonates of a malarial endemic region in Colombia, between 1993 and 2007. METHODS: The pattern of development in 1,716 neonates of women with and without malaria infection during pregnancy was evaluated in a cohort study. A total of 394 infected (27% by P. falciparum and 73% by P. vivax) and 1,322 noninfected pregnant women were followed. RESULTS: Exposure to gestational malaria was associated with increased risk of low birth weight (RR = 1.37; 1.03-1.83), short height (RR = 1.52; 1.25-1.85), intrauterine growth retardation (RR = 1.29; 1.0-1.66) and prematurity (RR = 1.68; 1.3-2.17). Prematurity was 77% higher in infants of mothers with malaria by P. falciparum than infants of mothers with malaria by P. vivax (RR = 1.77; 1.2-2.6). CONCLUSIONS: Low birth weight and intrauterine growth retardation were associated with malaria during pregnancy. Infection with P. vivax was related with adverse effects on the newborn, similar to that reported for P. falciparum.

Retardo no crescimento intrauterino, baixo peso ao nascer e prematuridade em recém-nascidos de grávidas com malária, na Colômbia / Intrauterine growth retardation, low birth weight and prematurity in neonates of pregnant women with malaria in Colombia

INTRODUÇÃO: É frequente a associação da malária com complicações como prematuridade, retardo no crescimento intrauterino, baixo peso ao nascer e mortalidade infantil, efeitos pouco estudados em áreas hipoendêmicas para malaria. O objetivo deste estudo foi analisar a relação da malária gestacional com estes efeitos em recém-nascidosnuma região endêmica para malária na Colômbia, entre 1993 e 2007. MÉTODOS: Foram estudadas as características em 1.716 recém-nascidos num estudo de coorte. Fez-se seguimento em 394 gestantes com malária (27 por cento por Plasmodium falciparum e 73 por cento por P. vivax) e 1.322 sem malária. RESULTADOS: Foi encontrada uma relação entre a exposição à malária na gestação e o risco maior de baixo peso ao nascer (RR = 1,37; 1,03-1,83), assim como estatura baixa (RR = 1,52; 1,25-1,85), retardo no crescimento intrauterino (RR = 1,29; 1,0-1,66) e prematuridade (RR = 1,68; 1,3-2,17). A frequência de nascimentos prematuros foi maior nas mães com malária por P. falciparum (77 por cento) que aquelas com P. vivax (RR = 1,77; IC 95 por cento: 1,2-2,6). CONCLUSÕES: O baixo peso ao nascer e o retardo no crescimento foi associado com malária na gestação na Colômbia. A infecção por P. vivax foi relacionada com efeitos adversos sobre o recém-nascido, de modo semelhante em relação ao P. falciparum.

INTRODUCTION: Association between malaria and pregnancy complications, such as prematurity, intrauterine growth restriction, low birthweight and infant mortality has been reported. These effects have been studied widely in areas hyperendemic for malaria, but studies in low-endemic areas are scarce. The study investigated the relation between gestational malaria and low birthweight and intrauterine growth retardation in neonates of a malarial endemic region in Colombia, between 1993 and 2007. METHODS: The pattern of development in 1,716 neonates of women with and without malaria infection during pregnancy was evaluated in a cohort study. A total of 394 infected (27 percent by P. falciparum and 73 percent by P. vivax) and 1,322 noninfected pregnant women were followed. RESULTS: Exposure to gestational malaria was associated with increased risk of low birth weight (RR = 1.37; 1.03-1.83), short height (RR = 1.52; 1.25-1.85), intrauterine growth retardation (RR = 1.29; 1.0-1.66) and prematurity (RR = 1.68; 1.3-2.17). Prematurity was 77 percent higher in infants of mothers with malaria by P. falciparum than infants of mothers with malaria by P. vivax (RR = 1.77; 1.2-2.6). CONCLUSIONS: Low birth weight and intrauterine growth retardation were associated with malaria during pregnancy. Infection with P. vivax was related with adverse effects on the newborn, similar to that reported for P. falciparum.

Malaria in pregnancy: small babies, big problem.

Placental malaria is hypothesized to lead to placental insufficiency, which causes fetal growth restriction (FGR). In this review, recent discoveries regarding the mechanisms of pathogenesis by which malaria causes FGR are discussed in the wider context of placental function and fetal growth. Placental malaria and associated host responses can induce changes in placental structure and function, affecting pregnancy-associated growth-regulating hormones and predisposing the offspring to hypertension and vascular dysfunction. Risk factors associated with FGR are highlighted, and potential interventions and studies to uncover remaining mechanisms of pathogenesis are proposed. Together, these strategies aim to decrease the burden of FGR associated with malaria in pregnancy.

Placental hypoxia during placental malaria.

BACKGROUND: Placental malaria causes fetal growth retardation (FGR), which has been linked epidemiologically to placental monocyte infiltrates. We investigated whether parasite or monocyte infiltrates were associated with placental hypoxia, as a potential mechanism underlying malarial FGR. METHODS: We studied the hypoxia markers hypoxia inducible factor (HIF)-1alpha, vascular endothelial growth factor (VEGF), placental growth factor, VEGF receptor 1 and its soluble form, and VEGF receptor 2. We used real-time polymerase chain reaction (in 59 women) to examine gene transcription, immunohistochemistry (in 30 women) to describe protein expression, and laser-capture microdissection (in 23 women) to examine syncytiotrophoblast-specific changes in gene expression. We compared gene and protein expression in relation to malaria infection, monocyte infiltrates, and birth weight. RESULTS: We could not associate any hallmark of placental malaria with a transcription, expression, or tissue-distribution profile characteristic of a response to hypoxia, but we found higher HIF-1alpha levels (P= .0005) and lower VEGF levels (P= .0026) in the syncytiotrophoblasts of cases of malaria than in those of asymptomatic control placentas. CONCLUSIONS: Our data are inconsistent with a role for placental hypoxia in the pathogenesis of malaria-associated FGR. The laser-capture microdissection study was small, but its results suggest (1) that malaria affects syncytiotrophoblast-gene transcription and (2) novel potential mechanisms for placental malaria-associated FGR.

Efecto de la infección aguda por diferentes cepas de Trypanosoma cruzi sobre el crecimiento intrauterino de fetos de ratón / Effect of the acute infection by different strains of Trypanosoma cruzi intrauterine growth of the mouse fetuses

El objetivo de este trabajo fue evaluar los efectos de la infección aguda materna con diferentes cepas de T. cruzi sobre el crecimiento intrauterino del ratón. Animales grávidos, de 60 días, fueron inoculados i.p. con 2 x 105 tripomastigotes sanguíneos de T. cruzi (cepa colombiana, Y, Bolivia o RC). Los resultados muestran que la infección afecta el crecimiento intrauterino, con reducción de peso y de longitud del cuerpo, longitud del cordón umbilical, relación peso corporal/peso placentario y relación peso corporal/longitud del cordón umbilical. Las cepas usadas muestran comportamiento diferente. En general, la menos perjudicial para el crecimiento fue la cepa RC, mientras que las más deletéreas fueron las cepas Bolivia e Y. Las curvas parasitemicas de estas cepas tienen el crecimiento más rápido, alcanzando el máximo al 5o y 7o día, respectivamente. Como la inoculación fue hecha de modo a coincidir los niveles máximos de parasitemia con el fin de la gravidez, estas cepas causan un proceso infeccioso más rápido, con altos índices de parasitemia, sin permitir la adaptación materna.

The sick placenta-the role of malaria.

The human placenta is an ideal site for the accumulation of Plasmodium falciparum malaria parasites, and as a consequence serious health problems arise for the mother and her baby. The pathogenesis of placental malaria is only partially understood, but it is clear that it leads to a distinct epidemiological pattern of malaria during pregnancy. The objectives of this review are: (1) To review recent data on the epidemiology of malaria in pregnancy, with emphasis on placental malaria; (2) to describe the pathological changes and immunological factors related to placental malaria; and (3) to discuss briefly the functional consequences of this infection for the mother and her baby. The review attempts to bring together local events at the maternal-fetal interface which encompass immunological and pathological processes which relate to the epidemiological pattern of malaria in pregnancy in areas of both high and low malaria transmission. An integrated understanding of the epidemiological, immunological and pathological processes must be achieved in order to understand how to control malaria in pregnancy. The yearly exposure of at least 50 million pregnancies to malaria infection makes it the commonest and most recurrent parasitic infection directly affecting the placenta. These statistics and our limited understanding of its pathogenesis suggest the research priorities on this subject.

Importance and prevention of malaria in pregnancy.

Malaria in pregnancy is one of the most important preventable causes of low birthweight deliveries worldwide. It is also a major cause of severe maternal anaemia contributing to maternal mortality. It is estimated that 40% of the world's pregnant women are exposed to malaria infection during pregnancy. The clinical features of Plasmodium falciparum malaria in pregnancy depend to a large extent on the immune status of the woman, which in turn is determined by her previous exposure to malaria. In pregnant women with little or no pre-existing immunity, such as women from non-endemic areas or travellers to malarious areas, infection is associated with high risks of severe disease with maternal and perinatal mortality. Women are at particular risk of cerebral malaria, hypoglycaemia, pulmonary oedema and severe haemolytic anaemia. Fetal and perinatal loss has been documented to be as high as 60-70% in non-immune women with malaria. Adults who are long-term residents of areas of moderate or high malaria transmission, including large parts of sub-Saharan Africa, usually have a high level of immunity to malaria. Infection is frequently asymptomatic and severe disease is uncommon. During pregnancy this immunity to malaria is altered. Infection is still frequently asymptomatic, so may go unsuspected and undetected, but is associated with placental parasitization. Malaria in pregnancy is a common cause of severe maternal anaemia and low birthweight babies, these complications being more common in primigravidae than multigravidae. Preventative strategies include regular chemoprophylaxis, intermittent preventative treatment with antimalarials and insecticide-treated bednets.

The effect of dual infection with HIV and malaria on pregnancy outcome in western Kenya.

OBJECTIVE: To determine the effect of dual infection with HIV and malaria on birth outcomes and maternal anaemia among women delivering at a large public hospital in Kisumu, western Kenya. SUBJECTS AND METHODS: Data on obstetric and neonatal characteristics, maternal and placental parasitaemia, and postpartum haemoglobin levels were collected from women enrolled in a cohort study of the interaction between malaria and HIV during pregnancy. RESULTS: Between 1996 and 1999, data were available from 2466 singleton deliveries. The maternal HIV seroprevalence was 24.3%, and at delivery 22.0% of the women had evidence of malaria. Low birthweight, preterm delivery (PTD), intrauterine growth retardation (IUGR) and maternal anaemia (haemoglobin < 8 g/dl) occurred in 4.6, 6.7, 9.8 and 13.8% of deliveries, respectively. Maternal HIV, in the absence of malaria, was associated with a 99 g (95% CI 52-145) reduction in mean birthweight among all gravidae. Malaria was associated with both IUGR and PTD, resulting in a reduction in mean birthweight of 145 g (95% CI 82-209) among HIV-seronegative and 206 g (95% CI 115-298) among HIV-seropositive primigravidae, but not among multigravidae. Both HIV and malaria were significant risk factors for postpartum maternal anaemia, and HIV-seropositive women with malaria were twice as likely to have anaemia than HIV-seronegative women with or without malaria. CONCLUSION: Women with dual infection are at particular risk of adverse birth outcomes. In areas with a moderate or high prevalence of HIV and malaria, all pregnant women should be the focus of malaria and anaemia control efforts to improve birth outcomes.

Effects of malaria during pregnancy on infant mortality in an area of low malaria transmission.

Malaria during pregnancy reduces birth weight, and low birth weight is a major determinant of infant mortality. The authors estimated the impact of malaria during pregnancy on infant mortality in a Karen population living in Thailand. Between 1993 and 1996, a cohort of 1,495 mothers and their infants was followed weekly from admission of the mother to antenatal clinics until the first birthday of the infant. Both falciparum malaria and vivax malaria during pregnancy were associated with low birth weight but did not shorten gestation. Febrile illness in the week before delivery was associated with premature birth. Preterm and full-term low birth weight and fever in the week before delivery were associated with neonatal mortality. Maternal fevers close to term were also associated with the deaths of infants aged between 1 and 3 months, whereas no risk factors could be identified for deaths that occurred later in infancy. Thus, malaria during pregnancy increased neonatal mortality by lowering birth weight, whereas fever in the week before birth had a further independent effect in addition to inducing premature birth. The prevention of malaria in pregnancy and, thus, of malaria-attributable low birth weight should increase the survival of young babies.