DOI: 10.6084/m9.figshare.29637401.v1
title: Data collected from pregnant women for the analysis of placental anemia, placental malaria, Cytokines and birth anthropometric indices

description: Placental malaria (PM) has long been recognized as a complication of malaria in pregnancy in areas of stable transmission and is particularly frequent and more severe in primigravidae [1]. In clinical practice, maternal peripheral parasitemia is used to detect malaria during pregnancy. However, it has been shown that while peripheral parasitemia may remain below the levels of microscopic detection, these parasites are detectable in the placenta [2]. Although the mechanism for placental parasitization is not yet known with certainty, certain parasite strains have been on the increase in pregnant women. During pregnancy, the burden of adverse obstetrical and neonatal outcomes occurs as a result of PM, when the parasite-infected red blood cells sequester in the intervillous spaces of the placenta. In endemic regions, PM may be present in up to 63% of pregnant women, irrespective of malaria infection symptomatology now [3]. They both pose a great health risk to mother and her fetus and result in complications, such as abortion, still birth, intra uterine growth retardation (IUGR), and low birth weight (LBW), preterm birth, and small-for-gestational-age neonates, among others. Placental inflammatory responses (PIS) may be the primary drivers of these complications. Associated factors contributing to adverse outcomes may include maternal gravidity, timing of perinatal infection, and parasite burden. The heavy infiltration of Plasmodium falciparum-infected red blood cells (RBCs) in the intervillous spaces of placenta seems to be responsible for all the complications observed. Infected RBCs in the placenta cause an inflammatory environment with increase in inflammatory cells and cytokines which is deleterious to the placenta. Increased inflammatory responses in the infected placenta result into oxidative stress that in turn causes oxidative stress-induced placental cell death. Pathologies associated with PM seems to be the effect of a change in immune status from antibody-mediated immune response to cell-mediated immune response resulting into excess inflammation, oxidative stress, apoptosis, and decreased heat shock protein expression [4]. Recently, it was found that PM stimulates placental expression of inflammasomes which are linked to placental secretion and maturation of IL-1β, a pro-inflammatory cytokine [5]. A recent study in Southeast Nigeria reported an increase in cytokine parameters in malaria-infected compared with malaria-uninfected placental blood placental blood in the former over the later [6]. Successful pregnancy requires carefully coordinated communications between the mother and fetus. Immune cells and cytokine signaling pathways participate as mediators of these communications to promote healthy pregnancy. However, inflammatory conditions, consequent on certain infections such as malaria in pregnant mothers may cause severe disease and result in detrimental impacts on the developing fetus.<b>Rational and Objectives for the study: </b>Malaria infections during pregnancy is responsible for 75,000 to 200,000 infant deaths annually in sub-Saharan Africa [7] due to the subsequent adverse health outcomes including intrauterine growth retardation, low birth weight, prematurity, intrauterine death and still birth [8-9]. Women leaving in malaria endemic areas are at high risks for malaria infections and they might acquire significant clinical immunity before pregnancy, and placental malaria, though often asymptomatic, could have harmful effects on the fetus [10]. In PM, P. falciparum-infected erythrocytes adhere to placental receptors, triggering placental inflammation and subsequent damage, causing harm to both mother and her baby. A significant role for increased cytokines (TNF, IFN-γ and IL-10) and apoptosis in trophoblast damage, low birth weight and preterm delivery during PM, has been observed no [11]. <i>Plasmodium falciparum</i> expresses on the surface of infected RBCs variant surface antigens, mainly the VAR2CSA molecule [12]. The variant surface antigens mediate a range of interactions and adhere to receptors such as CD36 and ICAM1 on the host endothelial cells, platelets, uninfected erythrocytes, and dendritic cells. The adherence to CD36 and ICAM1 results in acquiring antibody response. The principal VAR2CSA molecule is P. falciparum erythrocyte membrane protein 1 (PfEMP-1) [13]. The altered physiology and immunity during pregnancy and ability of P. falciparum-infected erythrocytes to sequester to various organs are all together responsible for severe malaria in pregnant women especially in first pregnancy and associated intra-uterine growth retardation (IUGR) and low birth weight (LBW) in infants [14]. The burden of malaria in pregnancy is highest in the tropical regions, including Nigeria, and in first and second pregnancy respectively. Despite this, there is a paucity of data on the pattern, risk factors for and outcome of pregnancy in placental malaria in Nigeria. More especially, the role of placenta inflammatory agents in primigravida and secundigravida has not been satisfactorily documented and data on neonatal responses to these agents in sub-Saharan African pregnant women are rare and inconclusive. This study is therefore designed to explore relationship between placental cytokines such as interleukins, interferon-gamma (IF-γ), and tumor necrosis factor alpha (TNF-α) and aftermath of pregnancy among first and second-time pregnant women with and without PM. Its aim is to determine the adverse effects of placental malaria cytokines on neonatal outcomes in these groups of pregnant women. Results from this study will not only add to knowledge but also recognize the role of submicroscopic <i>P. falciparum</i> infection of the placenta on inflammatory responses and neonatal morbidity and mortality. Hence, a better understanding of the mechanisms behind placental alterations and damage during placental malaria is needed for the design of effective interventions. <b><i>Innovation: </i></b>The study will employ ICP-OES Agilent latest technology for metal analysis and ultra-sensitive Plasmodium falciparum molecular detection method that targets a multicopy-copy parasite gene to elucidate impact of cytokines on pregnancy outcomes in Nigeria.<b><i>Hypothesis:</i></b> (i) Cytokines from placental malaria correlation with birthweight (normal, low, and very low), APGAR score (1 minute, 5 minutes) and with neonatal asphyxia (ii) Cytokines from placental malaria do not correlate with birthweight (normal, low, and very low), APGAR score (1 minute, 5 minutes) and with neonatal asphyxia<i>Study objectives</i><b><i>General objective: </i></b>To determine the concentration of various cytokines in parturient with and without <i>P. falciparum</i> parasitized placenta relative to birthweight, neonatal asphyxia, and APGAR score at 1 minute and 5 mutes.<b><i>Specific objectives:</i></b>I. To determine the placental microscopic and sub-microscopic P. falciparum parasite density among primigravidae and secundigravidae.2. To determine and correlate the placental concentration of inflammatory markers (IL-10. IFN Alpha and TNF) with the P. Falciparum density 3. To compare the concentration of inflammatory markers in Placenta malaria positive mother with placenta malaria negative mothers 4. To determine the associate between the maternal placenta malaria density, inflammatory markers with the pregnancy outcome (placenta malaria infected versus placenta malaria non-infected; alive versus dead). 5. To determine the associate between the maternal placenta malaria density, inflammatory markers with live babies’ parameters (neonatal birthweight, birth length, head circumference, MUAC, skinfold thickness, and APGAR scores).<b><i>Study question:</i></b> Do inflammatory responses to placental malaria correlate with birth outcomes?