Human infectious diseases and risk of preeclampsia: an updated review of the literature.

BACKGROUND: Preeclampsia (PE) is one of the major causes of maternal and perinatal morbidity and mortality, especially in low- and middle-income countries. In recent years, a growing body of literatures suggests that infections by bacteria, viruses, and parasites and their related inflammations play an important role in the pathogenesis of PE. METHODS: We searched PubMed, Google scholar, and Cochrane databases using the following search words: "infection and preeclampsia," "bacterial infection and preeclampsia," "viral infection and preeclampsia" and "parasitic infection and preeclampsia." RESULTS: The literature review revealed that many bacteria including Helicobacter pylori, Chlamydia pneumonia, and those are involved in periodontal disease or urinary tract infections (UTIs) and some viral agents such as Cytomegalovirus, herpes simplex virus type-2, human immunodeficiency virus, and some parasites especially Plasmodium spp. and Toxoplasma gondii can be effective in development of PE. Inflammation responses against infections has major role in the inducement of PE. The shift of immunological cytokine profile of Th2 toward Th1 and high levels of pro-inflammatory cytokines (TNF-ɑ, IL-12, IFN-γ, etc.), increase of oxidative stress, increase of anti-angiogenic proteins, increase of vascular endothelial growth factor receptor 1 (sVEGFR1), and complement C5a are the main potential mechanisms related to infections and enhanced development of PE. CONCLUSION: Thus, early diagnosis and treatment of bacterial, viral, and parasitic infections could be an effective strategy to reduce the incidence of PE.

Hydatoxi lualba: the worm that wasn't!

Pre-eclampsia is a disorder that occurs only during pregnancy and the postpartum period and affects both the mother and the unborn child. Affecting at least 5-8% of all pregnancies, it can be a rapidly progressive condition characterised by hypertension and proteinuria. Oedema, sudden weight gain, headaches and changes in vision are important symptoms. However, some women with rapidly advancing disease report few symptoms.

Study on changes of IGF-I and leptin levels in serum and placental tissue of prceclampsia patients and their associativity.

AIM: To explore the changes of IGF-I and leptin levels in serum and placental tissue of prceclampsia patients, and to study the associativity of IGF-I and leptin at the onset and in the development of prceclampsia further. METHODS: The levels of IGF-I and leptin in serum and placental tissue of 80 patients with prceclampsia and 50 normal pregnancy were detected with ELISA and immunohistochemistry. RESULTS: The serum IGF-I level of mild and severe prceclampsia was significantly lower than that of normal pregnancy group (P<0.05), and the serum leptin level of mild and severe prceclampsia was significantly lower than that of normal pregnancy group (P<0.05). The serum IGF-I level in severe prceclampsia group was lower than that in mild prceclampasia and the serum leptin level in severe prceclampsia was higher than that in mild prceclampsia ( P<0.05). There were significantly difference in the expression of IGF-I and leptin among normal pregnancy group, mild and severe prceclampsia group (P<0.05). CONCLUSION: The level of IGF-I and leptin may be involved in the pathogenesis and development of prceclampsia and can be a index to test the prognosis of prceclampsia patient.

Peroxisome proliferator-activated receptors are altered in pathologies of the human placenta: gestational diabetes mellitus, intrauterine growth restriction and preeclampsia.

BACKGROUND: Common complications of pregnancy arise in part from dysfunctional placental development, and include gestational diabetes mellitus (GDM), intrauterine growth restriction (IUGR) and preeclampsia (PE). Peroxisome proliferator-activated receptors (PPARs), and their partner retinoid X receptor a (RXRalpha), mediate trophoblast differentiation and thus may offer insight into the pathophysiology of these diseases. METHODS: Human placentae were obtained from women at term with GDM and were compared to uncomplicated term placentae. Placentae from women who delivered preterm with IUGR, PE or co-existing PE and IUGR were compared to matched controls. Quantitative RT-PCR and Western blotting were used to examine mRNA and protein expression of PPARalpha, PPARdelta, PPARgamma and RXRalpha. DNA binding activity of PPAR isoforms were measured in nuclear protein extracts. RESULTS: GDM was associated with significantly lower placental PPARgamma mRNA and protein, PPARalpha protein and RXRalpha protein expression, while PPAR DNA binding activity remained unchanged. Placentae from women with PE did not demonstrate any changes in mRNA or protein expression or PPAR DNA binding activity, while IUGR/PE placenta showed significant increases in PPARalpha protein, PPARgamma mRNA and protein and RXRalpha mRNA and protein expression. Significantly elevated protein expression of PPARalpha and RXRalpha were associated with IUGR placentae. IUGR and IUGR/PE placentae had significantly higher PPARgamma DNA binding activity compared to controls. CONCLUSIONS: The data presented herein suggest that PPARs may be involved in the pathophysiology of GDM, PE and IUGR.

Placental malarial infection as a risk factor for hypertensive disorders during pregnancy in Africa: a case-control study in an urban area of Senegal, West Africa.

In tropical countries, malaria and hypertension are common diseases of pregnancy. They have physiopathologic similarities such as placental ischemia, endothelial dysfunction, and production of proinflammatory cytokines. Recent findings suggested their possible link. The authors conducted a case-control study to explore the relation between malaria and hypertension at Guediawaye, a hypoendemic malarial setting in Senegal. Cases were pregnant women admitted to the delivery unit for hypertension. Controls were pregnant women admitted for normal delivery, without any history of hypertension or proteinuria during the present pregnancy. Malarial infection was determined by placental tissue examination. From January to December 2002, 77 cases of gestational hypertension, 113 cases of preeclampsia, 59 cases of eclampsia, and 241 controls were enrolled. Placental malarial infection (PMI) was present in 14 cases (6.3%) and in 15 controls (6.2%). The prevalence of PMI was 4.6% for eclampsia, 4.0% for preeclampsia, and 11.6% for gestational hypertension. In multivariate analysis, PMI appeared to be an independent risk factor for gestational hypertension (adjusted odds ratio = 2.7, 95% confidence interval: 1.0, 7.6). The authors found an association between PMI and nonproteinuric hypertension in women living in a malaria-hypoendemic area. The exact significance of such relation should be clarified in further studies in different settings of malarial endemicity.

Plasmodium in the placenta: parasites, parity, protection, prevention and possibly preeclampsia.

The epidemiology of pregnancy malaria infection and disease is complex but reflects underlying interactions between the Plasmodium falciparum parasite, the mother, and the foetus. Parasites sequester in the human placenta by binding to chondroitin sulfate A (CSA), a novel receptor that does not commonly support binding of other parasites. Women become resistant to P. falciparum malaria over successive pregnancies as they acquire antibodies against the CSA-binding placental parasite forms. Due to acquired immunity, placental malaria is briefer and less inflammatory in multigravid women than primigravid women, and these parity differences may account for the different outcomes these women and their offspring experience. Commonly recognized sequelae of malaria-like maternal anaemia and low birth weight primarily occur in first and second pregnancies. Hypertension may result from maternal-foetal conflict over the inflammatory response to placental malaria, and occurs in young, first-time mothers. Placental malaria can either increase or decrease parasitaemia risk in the offspring, depending on the mother's parity. The burden of disease due to pregnancy malaria, and the benefits of an effective vaccine, may be much greater than is currently appreciated.

Evidence that a toxemia-related organism (Hydatoxi lualba) is an artifact.

Preeclampsia-eclampsia and trophoblastic disease have been associated with a wormlike organism, Hydatoxi lualba, recently discovered in smears from circulating blood, trophoblastic tumor tissue, and placental tissue of toxemic patients. To investigate these findings peripheral blood smears from patients with preeclampsia-eclampsia, patients with hydatidiform mole, normal pregnant patients, and nonpregnant subjects were studied. The smears were stained with toluidine blue-O and Giemsa. The average size of wormlike forms found was 2.5 by 0.23 mm. None stained with Giemsa. The frequency of positivity for toxemic patients was 56.5% and 81.8% for normal pregnant patients. Samples from molar pregnancies were negative. Observations performed directly in fresh blood were also negative. The forms were observed not only in peripheral blood but also in serum obtained after centrifugation or passage through Millipore filters. No evidence of reproductive elements was found, and electron microscopy revealed no particular structure. The results suggest that the organism is an artifact.

'Hydatoxi lualba', an artefact.

Blood samples from controls, pre-eclamptic patients and cord blood from their infants were examined for the so-called Hydatoxi lualba parasite. Using a further modified TBO staining technique on blood-smears made on slides cleaned manually, the 'eggs, larva and worms' could be demonstrated to be successive stages of artefacts originating from threads deposited by the cotton swabs used in manual cleaning. These successive stages of 'worms' could only rarely be found in smears made on industrially cleaned slides.

The question of a helminthic cause of preeclampsia.

Two recent reports have suggested that wormlike structures characteristic of helminths are associated with preeclampsia. We identified these vermiform structures in toluidine blue O-stained venous blood smears from four women with preeclampsia, cord blood taken at delivery of three of their neonates, and venous blood from five control subjects without preeclampsia and from five healthy beagle dogs. The structures, which had diameters between 30 and 670 microns, could not be concentrated by passing the blood through a 12-microns filter, yet they could be demonstrated in stained smears prepared from blood that had been filtered. We conclude that these structures are not helminths; they are most likely artifacts of staining.

Experimental induction of a toxemia-like syndrome in the pregnant beagle.

A toxemia-like syndrome was induced in pregnant beagles by intraperitoneal inoculation of concentrates prepared from placentas of patients with preeclampsia-eclampsia and hydatidiform mole, which contained an agent, Hydatoxi lualba, that stained in a unique fashion with toluidine blue-O-. The pregnant dogs inoculated with either of these concentrates progressively developed hypertension, eyeground changes consistent with hypertensive retinopathy, proteinuria, disseminated intravascular coagulation, and hepatic dysfunction in addition to intrauterine growth retardation and intrauterine fetal death. Hepatic periportal hemorrhage and glomeruloendotheliosis, lesions usually seen in preeclampsia-eclampsia, were also noted to occur in pregnant beagles inoculated with these concentrates. A significant increased sensitivity to angiotensin II infusion was also noted. The toxemia-like syndrome did not develop in pregnant beagles when inoculated in a similar fashion with concentrates prepared from placentas from normal term pregnancies which were free of Hydatoxi lualba or in nonpregnant beagles inoculated with concentrates containing Hydatoxi lualba. Although the agent was not injected in pure form, the inoculation of concentrates containing Hydatoxi lualba appears to be required for the manifestation of the toxemia-like syndrome.

Observation of an organism found in patients with gestational trophoblastic disease and in patients with toxemia of pregnancy.

This is an initial descriptive report of observations of multiple forms of an organism found in patients with gestational trophoblastic disease and in patients with preeclampsia-eclampsia. The worm-like forms most frequently observed have an average length of 1.0 to 1.5 mm. Larva-like forms have an average length of 150 mu; primordial eggs and egg-like forms in developmental stages range from 7 to 43 mu in diameter; and sperm-like forms are 3.5 mu or slightly smaller in size. These forms have been observed in contact smears prepared from 3 ml samples of peripheral circulating blood from both groups of patients, from trophoblastic tumor tissue, from contact smears prepared from placentas of patients with preeclampsia-eclampsia, and from umbilical cord blood of infants delivered of patients with preeclampsia-eclampsia. The various forms of this organism share morphologic characteristics of several orders of helminths, i.e., hookworms, roundworms and tapeworms. The taxonomy of these forms has not yet been determined. Until the time of taxonomic classification, the various forms will be referred to as Hydatoxi lualba. We have experimental evidence that this organism has biologic activity in BALB/c mice and in beagle dogs.