Elizabeth T. Abrams

Placental Tumor Necrosis Factor Alpha but Not Gamma Interferon Is Associated with Placental Malaria and Low Birth Weight in Malawian Women

ABSTRACT Malaria in pregnancy predisposes to maternal anemia and low birth weight (LBW). We examined the possible roles of the cytokines tumor necrosis factor alpha (TNF-α) and gamma interferon (IFN-γ) in these adverse outcomes. We measured cytokine concentrations in placental, peripheral, and cord blood plasma in relation to malaria parasitemia and placental monocyte accumulation in 276 Malawian women. Maternal hemoglobin concentration, human immunodeficiency virus status, and infant birth weight were determined. Concentrations of TNF-α in placental blood were correlated with densities of Plasmodium falciparum-infected erythrocytes (P < 0.0001) and of intervillous monocyte infiltrates (P < 0.0001) on placental histology. Peripheral blood TNF-α concentrations were relatively low and were weakly associated with malaria. TNF-α concentrations were higher in placental blood, where they were strongly associated with malaria. Placental plasma TNF-α levels were higher in women who had LBW babies (P = 0.0027), women with febrile symptoms (P < 0.0001), and teenage mothers (P = 0.04) than in other women. The presence of TNF-α in cord blood was not associated with malaria infection. IFN-γ levels were infrequently elevated, and elevated IFN-γ levels were not associated with poor pregnancy outcomes. Placental production of TNF-α, but not of IFN-γ, may be implicated in impaired fetal growth in Malawian women.

The effect of Plasmodium falciparum malaria on peripheral and placental HIV-1 RNA concentrations in pregnant Malawian women.

Objective: To investigate the effect of placental Plasmodium falciparum malaria infection on peripheral and/or placental HIV-1 viral load. Design: A cross-sectional study of HIV-infected pregnant women, with and without placental malaria, delivering at Queen Elizabeth Central Hospital in Malawi. Methods: Peripheral blood samples were collected from consenting women and tested for HIV. HIV-infected women received nevirapine at the onset of labor. At delivery, placental blood and tissue specimens were collected. HIV-1 RNA concentrations were measured in peripheral and placental plasma samples, and malaria infection was determined by placental histopathology. Results: Of the 480 HIV-infected women enrolled, 304 had placental histopathology performed, of whom 74 (24.3%) had placental malaria. Compared with women without placental malaria, those with placental malaria had a 2.5-fold higher geometric mean peripheral HIV-1 RNA concentration (62 359 versus 24 814 copies/ml; P = 0.0007) and a 2.4-fold higher geometric mean placental HIV-1 RNA concentration (11 733 versus 4919 copies/ml; P = 0.008). In multivariate analyses, after adjusting for CD4 cell count and other covariates, placental malaria was associated with a 1.7-fold increase in geometric mean peripheral HIV-1 RNA concentration (47 747 versus 27 317 copies/ml; P = 0.02) and a 2.0-fold increase in geometric mean placental HIV-1 RNA concentration (9670 versus 4874 copies/ml; P = 0.03). Conclusion: Placental malaria infection is associated with an increase in peripheral and placental HIV-1 viral load, which might increase the risk of mother-to-child transmission of HIV.

Host response to malaria during pregnancy: Placental monocyte recruitment is associated with elevated beta chemokine expression

Malaria during pregnancy is associated with poor birth outcomes, particularly low birth weight. Recently, monocyte infiltration into the placental intervillous space has been identified as a key risk factor for low birth weight. However, the malaria-induced chemokines involved in recruiting and activating placental monocytes have not been identified. In this study, we determined which chemokines are elevated during placental malaria infection and the association between chemokine expression and placental monocyte infiltration. Placental malaria infection was associated with elevations in mRNA expression of three β chemokines, macrophage-inflammatory protein 1 (MIP-1) α (CCL3), monocyte chemoattractant protein 1 (MCP-1; CCL2), and I-309 (CCL1), and one α chemokine, IL-8 (CXCL8); all correlated with monocyte density in the placental intervillous space. Placental plasma concentrations of MIP-1α and IL-8 were increased in women with placental malaria and were associated with placental monocyte infiltration. By immunohistochemistry, we localized placental chemokine production in malaria-infected placentas: some but not all hemozoin-laden maternal macrophages produced MIP-1β and MCP-1, and fetal stromal cells produced MCP-1. In sum, local placental production of chemokines is increased in malaria, and may be an important trigger for monocyte accumulation in the placenta.

Malaria during pregnancy and foetal haematological status in Blantyre, Malawi

BackgroundAlthough maternal anaemia often stems from malaria infection during pregnancy, its effects on foetal haemoglobin levels are not straightforward. Lower-than-expected cord haemoglobin values in malarious versus non-malarious regions were noted by one review, which hypothesized they resulted from foetal immune activation to maternal malaria. This study addressed this idea by examining cord haemoglobin levels in relation to maternal malaria, anaemia, and markers of foetal immune activation.MethodsCord haemoglobin levels were examined in 32 malaria-infected and 58 uninfected women in Blantyre, Malawi, in relation to maternal haemoglobin levels, malaria status, and markers of foetal haematological status, hypoxia, and inflammation, including TNF-α, TGF-β, and ferritin. All women were HIV-negative.ResultsAlthough malaria was associated with a reduction in maternal haemoglobin (10.8 g/dL vs. 12.1 g/dL, p < 0.001), no reduction in cord haemoglobin and no significant relationship between maternal and cord haemoglobin levels were found. Cord blood markers of haematological and hypoxic statuses did not differ between malaria-infected and uninfected women. Maternal malaria was associated with decreased TGF-β and increased cord ferritin, the latter of which was positively correlated with parasitaemia (r = 0.474, p = 0.009). Increased cord ferritin was associated with significantly decreased birth weight and gestational length, although maternal and cord haemoglobin levels and malaria status had no effect on birth outcome.ConclusionIn this population, cord haemoglobin levels were protected from the effect of maternal malaria. However, decreased TGF-β and elevated ferritin levels in cord blood suggest foetal immune activation to maternal malaria, which may help explain poor birth outcomes.

The roles of the immune system in Women's reproduction: Evolutionary constraints and life history trade-offs

Life history theory posits that, as long as survival is assured, finite resources are available for reproduction, maintenance, and growth/storage. To maximize lifetime reproductive success, resources are subject to trade-offs both within individuals and between current and future investment. For women, reproducing is costly and time-consuming; the bulk of available resources must be allocated to reproduction at the expense of more flexible systems like immune function. When reproducing women contract infectious diseases, the resources required for immune activation can fundamentally shift the patterns of resource allocation. Adding to the complexity of the reproductive-immune trade-offs in women are the pleiotropic effects of many immune factors, which were modified to serve key roles in mammalian reproduction. In this review, we explore the complex intersections between immune function and female reproduction to situate proximate immunological processes within a life history framework. After a brief overview of the immune system, we discuss some important physiological roles of immune factors in womens reproduction and the conflicts that may arise when these factors must play dual roles. We then discuss the influence of reproductive-immune trade-offs on the patterning of lifetime reproductive success: (1) the effect of immune activation/infectious disease on the timing of life history events; (2) the role of the immune system, immune activation, and infectious disease on resource allocation within individual reproductive events, particularly pregnancy; and (3) the role of the immune system in shaping the offsprings patterns of future life history trade-offs. We close with a discussion of future directions in reproductive immunology for anthropologists.

Risk Factors and Mechanisms of Preterm Delivery in Malawi

Problem:  We examined risk factors and mechanisms of preterm delivery (PTD) in malaria‐exposed pregnant women in Blantyre, Malawi.

Framing Postpartum Hemorrhage as a Consequence of Human Placental Biology: An Evolutionary and Comparative Perspective

Postpartum hemorrhage (PPH), the leading cause of maternal mortality worldwide, is responsible for 35 percent of maternal deaths. Proximately, PPH results from the failure of the placenta to separate from the uterine wall properly, most often because of impairment of uterine muscle contraction. Despite its prevalence and its well-described clinical manifestations, the ultimate causes of PPH are not known and have not been investigated through an evolutionary lens. We argue that vulnerability to PPH stems from the intensely invasive nature of human placentation. The human placenta causes uterine vessels to undergo transformation to provide the developing fetus with a high plane of maternal resources; the degree of this transformation in humans is extensive. We argue that the particularly invasive nature of the human placenta increases the possibility of increased blood loss at parturition. We review evidence suggesting PPH and other placental disorders represent an evolutionarily novel condition in hominins.

Appetite Sensations and Nausea and Vomiting in Pregnancy: An Overview of the Explanations

We review information about the potential mechanisms underlying nausea and vomiting in pregnancy (NVP), food cravings, and/or aversions in pregnancy. In addition to providing overviews about genetic predispositions and hormonal associations with appetite sensations and NVP, we review two functional explanations: the “maternal and embryo protection” and the “placental growth and development” hypotheses. We conclude with a discussion about the kinds of data that would enable us to better evaluate the relative advantages and disadvantages of NVP across disparate resource and ecological conditions.

CenteringPregnancy-Africa: a pilot of group antenatal care to address Millennium Development Goals.

BACKGROUND severe health worker shortages and resource limitations negatively affect quality of antenatal care (ANC) throughout sub-Saharan Africa. Group ANC, specifically CenteringPregnancy (CP), may offer an innovative approach to enable midwives to offer higher quality ANC. OBJECTIVE our overarching goal was to prepare to conduct a clinical trial of CenteringPregnancy-Africa (CP-Africa) in Malawi and Tanzania. In Phase 1, our goal was to determine the acceptability of CP as a model for ANC in both countries. In Phase 2, our objective was to develop CP-Africa session content consistent with the Essential Elements of CP model and with national standards in both Malawi and Tanzania. In Phase 3, our objective was to pilot CP-Africa in Malawi to determine whether sessions could be conducted with fidelity to the Centering process. SETTING Phases 1 and 2 took place in Malawi and Tanzania. Phase 3, the piloting of two sessions of CP-Africa, occurred at two sites in Malawi: a district hospital and a small clinic. DESIGN we used an Action Research approach to promote partnerships among university researchers, the Centering Healthcare Institute, health care administrators, health professionals and women attending ANC to develop CP-Africa session content and pilot this model of group ANC. PARTICIPANTS for Phases 1 and 2, members of the Ministries of Health, health professionals and pregnant women in Malawi and Tanzania were introduced to and interviewed about CP. In Phase 2, we finalised CP-Africa content and trained 13 health professionals in the Centering Healthcare model. In Phase 3, we conducted a small pilot with 24 pregnant women (12 at each site). MEASUREMENTS AND FINDINGS participants enthusiastically embraced CP-Africa as an acceptable model of ANC health care delivery. The CP-Africa content met both CP and national standards. The pilot established that the CP model could be implemented with process fidelity to the 13 Essential Elements. Several implementation challenges and strategies to address these challenges were identified. KEY CONCLUSIONS preliminary data suggest that CP-Africa is feasible in resource-constrained, low-literacy, high-HIV settings in sub-Saharan Africa. By improving the quality of ANC delivery, midwives have an opportunity to make a contribution towards Millennium Development Goals (MDG) targeting improvements in child, maternal and HIV-related health outcomes (MDGs 4, 5 and 6). A clinical trial is needed to establish efficacy. IMPLICATIONS FOR PRACTICE CP-Africa also has the potential to reduce job-related stress and enhance job satisfaction for midwives in low income countries. If CP can be transferred with fidelity to process in sub-Saharan Africa and retain similar results to those reported in clinical trials, it has the potential to benefit pregnant women and their infants and could make a positive contribution to MGDs 4, 5 and 6.

Malaria during pregnancy in endemic areas: A lens for examining maternal–fetal conflict

Most of our knowledge about maternal–fetal conflict derives from the battle over scarce nutritional resources. How do other stressors like infectious diseases alter the maternal–fetal relationship? In this article, we use the example of malaria infection during pregnancy to explore the altered maternal–fetal relationship in the presence of an infectious disease. While adults living in regions endemic to Plasmodium falciparum malaria are generally immune, pregnant women experience significantly more frequent and severe infections. These infections generally resolve within a few days of birth and rarely cross the placenta, but the infants often experience poor birth outcomes, particularly low birth weight. This article summarizes what is known about the proximate, or physiological, mechanisms by which malaria causes more severe or frequent infections for pregnant versus nonpregnant women in endemic regions and then utilizes an evolutionary approach to focus on the altered maternal–fetal relationship during malaria‐infected pregnancy. Am. J. Hum. Biol. 2009.