Pathophysiological indicators of pregnancy-induced hypertension in Ghanaian women

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Pregnancy-Induced Hypertension (PIH) is the abnormal increase in blood pressure (BP) of pregnant women who do not have pre-gestational chronic hypertension or renal diseases or proteinuria before the final half of gestation, but present with high BP and proteinuria in the final half of pregnancy which normalizes postnatally. PIH ranges from high BP without proteinuria, through high BP with proteinuria and multiorgan dysfunction to high BP with proteinuria, multiorgan dysfunction with seizures. PIH is usually diagnosed when BP rises above 140/90 mmHg.Ten percent (10%) of complications of pregnancy are as a result of hypertension and this accounts for the increased risk of adverse foetal, neonatal and maternal outcomes. This necessitates early diagnosis to avert these fatal outcomes. This study sought to find the biomarkers that would assist in the early diagnosis of pregnancy-induced hypertension in Ghanaian women. To achieve this, the following specific objectives were set: The determination of the concentrations of biomarkers of systemic inflammation, endothelial injury and systemic oxidative stress in PIH and controls;the evaluation of the relationship of hepcidin levels with iron regulation and systemic inflammation in PIH and controls; the determination of the concentrations of Soluble urokinase plasminogen activator receptor, Interlukin-6 and C-reactive protein in PIH and healthy pregnancy were studied in order to evaluate the best marker for the characterization of the inflammatory status during pregnancy and the determination of serum lipids levels and its correlation with C-reactive protein, Interlukin-6, 8-iso-prostagladin F2α and fibronectin in PIH.This research took place at the antenatal clinics of Ridge Regional Hospital, Accra, La General Hospital, Accra and Lister Hospital and Fertility Centre, Accra, Ghana from June, 2014 to July, 2015. This study involved forty-eight (48) women with gestational hypertension, fifty-seven (57) with preeclampsia, eighteen (18) with eclampsia and forty-five (45) normotensive pregnant women (controls) in at least their second trimester of gestation. All participants were within 18yrs to 40 yrs of age and with singleton pregnancy based on ultra-sound results. After ethical approval and informed consent had been obtained, blood (ie. EDTA whole blood, heparinized-plasma and serum) and urine samples of participants were obtained for biochemical, haematological and urine analysis. There were significantly higher levels of markers of systemic inflammation : IL-6 (19.60±10.32pg/ml vs 13.85±2.80pg/ml, p=0.04), CRP (3.31±2.81ng/L vs 0.98±0.05ng/L, p<0.0001), suPAR (2.04±0.66pg/ml vs 1.57±0.56pg/ml, p=0.03), endothelial injury: FN (21.87±11.95ng/ml vs 13.85±2.80ng/ml, p=0.01) and systemic oxidative stress: 8-iso-PGF2α (43.03±27.29pg/ml vs 5.55±5.33pg/ml, p=0.03) in PIH women compared to controls respectively.The results of the level of hepcidin in relation to iron homeostasis and systemic inflammation among the participants indicates significant increase in the levels of hepcidin (7.72±1.07 vs 6.46±0.82, p<0.0001), ferritin (183.0±156.2 vs 37.1±30.5, p<0.0001), IL-6 (19.60±10.32 vs 13.85±2.80, p=0.04) and CRP (3.31±2.81 vs 0.98±0.05, p<0.0001) in the PIH women compared to the normotensive ones respectively. Whereas there was significantly lower iron (85±39.09 vs 138±30.33, p<0.0001) and TIBC (308.9±95.29 vs 360±68.0, p=0.0013) levels in the PIH compared to normotensive women respectively.
A thesis submitted in fulfillment of the requirements for the degree of Doctor of Philosophy in the Department of Molecular Medicine School of Medical Sciences,Kwame Nkrumah University of Science & Technology, Kumasi,