Furthermore, the Mann Whitney U test showed a significant difference between the non-pregnant and normotensive groups (p<0.01). A significant difference was noted between HIV-positive non-pregnant and HIV-negative non-pregnant (p<0.05).
Maternal Deaths 2
In 2013, more than half of all maternal deaths occurred in sub-Saharan Africa and about a quarter in South Asia. In South Africa, the top 5 causes of maternal deaths are non-pregnant related, obstetric haemorrhage, medical disorders, hypertension in pregnancy and sepsis.
Pre-eclampsia 4
- Pathogenesis
- Management
Currently, the clinical signs used for the diagnosis of pre-eclampsia are hypertension, proteinuria, glomerular endotheliosis, HELLP (Young et al., 2010). Abnormal cytotrophoblast migration and invasion of the decidual myometrial junction is limited in pre-eclampsia (Naicker et al., 2003).
Human Immunodeficiency Virus
- Definition and clinical characteristics
HIV and Pregnancy
- Adipokines & Pregnancy
- Adipokines, HIV and pre-eclampsia
- C-peptide
- Ghrelin
- Gastric inhibitory polypeptide (GIP)
- Glucagon-like peptide 1(GLP-1)
- Insulin
- Glucagon
- Plasminogen activator inhibitor (PAI)-1
- Visfatin
According to Kunt et al., (1999) insulin is first produced as a single polypeptide called pre-proinsulin, which contains a 24-residue signal peptide responsible for directing the nascent polypeptide chain to the rough endoplasmic reticulum (RER) . Furthermore, Gudinchet et al., (1988) reported that PAI-1 is associated with multiple sclerosis in the nervous system.
Aims, objectives and null hypothesis
- Aims
- Objectives
- Null Hypothesis
- STUDY DESIGN
- Recruitment of participants
- STUDY POPULATION
- Inclusion criteria
- Exclusion criteria
- SAMPLE COLLECTION AND PREPARATION
- METHOD
- Principles of multiplex analysis
- Multiplex method
- DATA ANALYSIS
The principles of the Bioplex diabetes tests are otherwise the same as those of the ELISA test and can be used for direct, indirect, competitive and sandwich immunoassays. For sample preparation, 20 µl of sample and 80 µl of assay diluent were mixed together to obtain a total. The diluted beads were vortexed for 10-20 seconds before 50 µl beads were added to each well of the assay plate.
The diluted standards, samples and controls were vortexed before adding 50 µl to each well (the pipette tip was replaced after each volume transfer) of the assay plate. This was followed by covering the plate with a sealing tape and then incubating on a shaker at 850 +/- 50 rpm at room temperature for 1 hour. While the samples were incubating, the 20x detection antibody was vortexed and spun rapidly for 30 seconds before pipetting, to collect the entire required volume at the bottom of the vial.
Detection antibodies (25 μl) were then gently added to each well and the plate was incubated for 30 min on a shaker at 850+/- 50 rmp at room temperature. While the detection antibody was incubating with 10 minutes remaining in the incubation time, a rapid spin centrifugation of streptavidin-PE (100x) was performed before pipetting in order to collect the entire volume at the bottom of the vial. This was followed by the addition of 50 μl streptavidin-PE (1x) to each well, the plate was then covered with foil and incubated for 10 min.
DEMOGRAPHIC AND CLINICAL DATA OF PATIENTS
- Maternal age
- Maternal weight
- Gestational age (GA)
- Maternal Blood Pressure
- Body mass index
- Further analysis of clinical demographics
- Baby weight
- Placental weight
In contrast, the early-onset HIV-positive pre-eclamptic group was younger than their corresponding HIV-negative group. Similarly, gestational age was higher in the non-pregnant group compared to the early-onset pre-eclampsia group. A Kruskal-Wallis H test showed that there was a significant difference in systolic blood pressure between study groups (χ p<0.001).
Moreover, systolic blood pressure was significantly higher in late-onset pre-eclampsia compared to the normotensive group which had a mean rank of 60.59; (U=70.50; p<0.001). Furthermore, there was a significant difference in the early-onset pre-eclamptic groups versus the normotensive groups (U=20.00; p<0.001). Furthermore, systolic blood pressure was significantly higher in late-onset pre-eclampsia compared to normotensive groups (U=70.50; . p<0.001).
In addition, systolic blood pressure was elevated in patients with early preeclampsia compared to normotensive groups (U=20.00; p<0.001). Pearson's chi-square test showed a statistically significant difference between the normotensive and preeclamptic groups (p<0.001). There was also a significant difference between HIV-negative with early-onset preeclampsia and HIV-positive with late-onset preeclampsia (p<0.001), HIV-negative with early-onset preeclampsia and HIV-negative with late-onset preeclampsia (p<0.001) and HIV-positive with late-onset preeclampsia. onset compared to HIV-negative groups with late-onset preeclampsia (p<0.05).
ANALYSIS OF ADIPOKINES
- C-peptide
- Ghrelin
- Gastric inhibitory polypeptide
- Glucagon-like peptide 1
- Glucagon
- Insulin
- Plasminogen activator inhibitor-1
- Visfatin
The Mann-Whitney U test showed a significant difference between non-pregnant and normotensives (p = 0.01) and between the normotensive group and the late-onset group (p = 0.01). In addition, a pairwise comparison test found a significant difference between nonpregnant and normotensives (p<0.01); normotensive compared to early onset (p<0.05; . Figure 3.11) and normotensive compared to late onset group (p<0.01). When performing the Mann Whitney U test, we found a significant difference between the non-pregnant and normotensive groups (p<0.05).
However, a Mann-Whitney U test showed a significant difference between HIV-positive non-pregnant and HIV-negative non-pregnant (p<0.05). The non-pregnant and early pregnancy groups have the same levels of glucagon regardless of HIV status. However, a Mann Whitney U test revealed a significant difference between the non-pregnant and normotensive groups (p<0.05).
In addition, a Mann-Whitney U test found a significant difference between the non-pregnant versus normotensive group (p<0.05) and the late onset versus the non-pregnant group (p<0.01). A Mann-Whitney U test revealed that there is a significant difference between the HIV positive versus negative non-pregnant groups (p<0.05). Visfatin was increased in the pre-eclamptic groups when compared to the non-pregnant and the normotensive group.
MATERNAL DEMOGRAPHICS
- Maternal age
- Maternal weight
- Body Mass Index
- Blood pressure
- Gestational Age
- Birthweight
- Placental weight
- Mode of delivery
- HELLP
- HIV infection
Maternal age appears to be an independent obstetric risk factor for early-onset preeclampsia and impaired fetal growth (Lamminpää et al., 2012). Insulin resistance is associated with endothelial dysfunction and increased secretion of endothelin 1, a potent vasoconstrictor (Marasciulo et al., 2006). The relationship between BMI and hypertension was investigated in subpopulations of the Ethiopian, Vietnamese, and Indonesian populations (Tesfaye et al., 2006).
A strong association between preeclampsia and high BMI has also been reported (Duckitt, K & Harrington, 2005; Machado Elizabeth Stankiewicz et al., 2014). This trend is in line with the development of insulin resistance, obesity and hypertension in HIV infection (Gazzaruso et al., 2003). Although earlier studies by Minkoff et al., (1990) found no association between HIV infection and risk of low birth weight, these studies were small.
In contrast, studies by Stratton et al., (1999) support the correlation between low birth weight and HIV infection (Stratton et al., 1999). Poor fetal/neonatal outcomes, particularly lower birthweight and birthweight, have been previously reported in the EOPE group ( Lisonkova et al., 2013 ). The shallow placentation with consequent reduced blood flow and consequent lower placental weight in the early-onset preeclampsia group explains the placental inefficiency (Naicker et al., 2003).
ADIPOKINES
- C-peptide
- Ghrelin
- Gastric inhibitory polypeptide (GIP)
- Glucagon-like peptide 1 (GLP-1)
- Glucagon
- Insulin
- Plasminogen activator inhibitor (PAI)-1
- Visfatin
Moreover, insulin has been reported to be one of the most important adipokines that play a role in the pathophysiology of preeclampsia by causing insulin resistance (Shangguan et al., 2009). Recent studies have reported that ghrelin plays a role in increasing hypertriglyceridemia, thereby promoting hepatic triglyceride (TG) deposition in HIV-positive people (Falasca et al., 2006). Studies conducted by Chen and associates have reported increased levels of GIP during pregnancy compared to non-pregnant women (Chen et al., 1995).
Rondanelli and colleagues have recently reported β-cell dysfunction in HIV-infected individuals, particularly in individuals on anti-retroviral treatment (Rondanelli et al., 2004). The markedly elevated levels of PAI-1 and fibronectin that occur early in pregnancies that subsequently develop pre-eclampsia suggest that these variables may have predictive value (Halligan et al., 1994). During pregnancy, profound changes occur in the hemostatic system, PAI-1 levels increase (Kruithof et al., 1987).
The decreased levels of fibrinolytic activity observed during pregnancy are said to be due to increased levels of PAI-1 derived from the placenta (Kruithof et al., 1987). Maternal plasma visfatin peaks between 19–26 weeks of gestation in normal weight pregnant women (Mazaki-Tovi et al., 2009). There are few reports on circulating visfatin concentrations in pregnant women (Chan et al., 2006; Fasshauer et al., 2008).
OBESITY AND PRE-ECLAMPSIA
HIV AND OBESITY
HIV AND PRE-ECLAMPSIA
In addition, high levels of adhesion markers have been reported in HIV-positive cohorts, implying that inflammation is also high. In addition, Wimmalasundera et al. (2002) found a high incidence of preeclampsia among HIV-positive women, suggesting that HIV does not confer immunity against preeclampsia. A brief survey conducted by a European collaborative study in 2003 further reported identifying preeclampsia as one of the most common conditions among HIV-positive women, but only in those receiving HARRT.
This was further supported by the study done by Suy and colleagues in 2003, who reported that they found a high incidence in the number of cases of pre-eclampsia in HIV-positive individuals on HAART. In addition, they also found that the incidence of fetal deaths is high in individuals with pre-eclampsia and HIV positive. Preeclampsia and fetal deaths were found to coexist more frequently in HIV-positive individuals.
Moreover, a systematic review on maternal infection and pre-eclampsia found no association between pre-eclampsia and HIV (Conde-Agudelo et al., 2008). Furthermore, another more recent study argues that women have a high risk of developing pre-eclampsia only if they were on HAART for a long time before pre-pregnancy, additionally, there is a strong link between pre-eclampsia and showed high BMI (Machado et al. al., 2014). A study by Frank and colleagues to determine whether HIV-positive women have lower rates of pre-eclampsia than HIV-negative women found no reduction (Frank et al., 2004).
CONCLUSION
LIMITATIONS OF THE STUDY
FURTHER DIRECTION
The AmRo study: pregnancy outcome in HIV-1-infected women under effective highly active antiretroviral therapy and a policy of vaginal delivery Br. Low birth weight in infants born to African HIV-infected women: relationship to maternal body weight during pregnancy: Pregnancy and HIV Study Group (EGE). Maternal imbalance between pro-angiogenic and anti-angiogenic factors in HIV-infected women with pre-eclampsia.
Metabolic regulation of growth hormone by free fatty acids, somatostatin and ghrelin in HIV lipodystrophy. Hypertension, preeclampsia and eclampsia among HIV-infected pregnant women from Latin American and Caribbean countries. Incidence of metabolic syndrome in HIV-infected patients receiving highly active antiretroviral therapy using International Diabetes Foundation and Adult Treatment Panel III criteria: associations with insulin resistance, impaired body fat distribution, elevated C-reactive protein, and [corrected].
Von Wilebrand factor antigen, tissue plasminogen activator antigen, and risk of death in human immunodeficiency virus-1-associated clinical disease: independent prognostic significance of tissue plasminogen activator. Obstetric and neonatal outcomes in a cohort of HIV-infected pregnant women: report of the transmission study in women and infants. Increased risk of preeclampsia and fetal death in HIV-infected pregnant women receiving highly active antiretroviral therapy.
