The role of adiponectin, leptin, TNF-α and resistin in HIV associated pre-eclampsia.

Abstract

Introduction and aims Hypertensive disorders of pregnancy, in particular, pre-eclampsia, remains an enigmatic problem with global disease burden shared amongst industrialised and non-industrialised countries. It has been estimated that hypertensive disorders complicate 5 – 10% of pregnancies. The leading cause of maternal deaths in sub-saharan Africa is AIDS (43.7%). The Saving Mothers Guidelines for the tri-ennium 2005 – 2007 in South Africa found that hypertensive disorders were directly linked to maternal deaths in 15.7% of cases, of which 83% represents pre-eclampsia. Additionally South Africa now faces the challenge of obesity. These three conditions (HIV, pre-eclampsia and obesity) impact on each other causing adipokine dysregulation. The aim of the study was to examine the levels of adiponectin/leptin/TNF-α and resistin amongst non-pregnant, normotensive and pre-eclamptic pregnant cohorts in respect of their BMI and HIV status. Methods Following institutional ethical approval and informed consent, serum was obtained from a total of 328 women attending the RK Khan Hospital, a regional and district hospital in eThekwini, KwaZulu-Natal. Women were recruited into two groups ie., non-pregnant (n = 120; 36.58%) and pregnant group (n = 208; 63.41%). Pregnant women were further, categorised into the normotensive pregnant (n = 118; 35.97%) and the pre-eclamptic (n = 90; 27.43%) groups. The pregnant cohort was also sub-stratified in accordance with their HIV status. Clinical demographics, height, weight, body mass index (BMI), mid upper arm circumference (MUAC), triceps skin fold thickness were recorded. Indications and mode of delivery as well as associated complications, fetal ultrasound abnormalities, neonatal outcomes (APGARS), weight, placental shape weight and appearance were noted. Serum was assessed by a double antibody sandwich ELISA technique using the DuoSet ELISA Development System for human adiponectin and TNF-α. Additionally, serum leptin and resistin was detected by the Bioplex immunoassay (Biorad). Absorbance was read spectrophotometrically at 450 nm (Systems). SPSS version 21 was used to analyse the demographic and experimental data. A p value < 0.05 was considered as statistically significant. Results Irrespective of the HIV status, body mass index and maternal weight (p = 0.325 vs 0.138) were not statistically significantly different between the normotensive and pre-eclamptic groups respectively. Likewise, the distribution of BMI was the same across the study groups with respect to HIV status (p = 0.124). Mean adiponectin levels varied between 897.93±126.18, 17.19±11.56, 23.16±21.39 and 24.61±12.869 in the non-pregnant, normotensive pregnant, EOPE and LOPE groups respectively. Leptin levels varied from 4887.25±705.29, 2732.27±580.18, 955.75±527.64 and 310.23±177.43 in the non-pregnant, normotensive pregnant, EOPE and LOPE groups respectively. TNF-α was undetected in the non-pregnant group as compared to 608.52±84.89, 661.03±202.60 and 616.43±117.53 in the normotensive pregnant, EOPE and LOPE groups respectively. Resistin varied from 7497.13±1921.95 in the non-pregnant group compared to 3536.50±730.04, 1017.63±69.58 and 286.92±160.30 in normotensive pregnant, EOPE and LOPE groups accordingly. The levels of TNF-α, leptin and resistin were significantly different within the normotensive pregnant versus pre-eclamptic groups. Except for adiponectin (p < 0.292); TNF-α (p < 0.044), leptin (p < 0.004) and resistin (p < 0.006) were statistically significantly different within the pregnant cohorts. The study demonstrated statistically significant differences in adiponectin/ leptin/ TNF-α and resistin between non-pregnant, normotensive and pre-eclamptic cohorts with respect to HIV status and BMI. There were significant differences in the levels of adiponectin/leptin/resistin and TNF-α with respect to HIV status (p=0.00). Additionally, a statistically significant difference in the level of adiponectin in the non-pregnant as compared to the normotensive cohorts (p<0.00) was noted. Furthermore,, there were statistically significant differences in the levels of TNF-α, leptin and resistin in the normotensive as compared to pre-eclamptic cohorts (p<0.000). This study was able to depict baseline adiponectin / leptin / resistin and TNF-α levels according to BMI in the local population. Conclusion This study was expedient in the fact that patients were all standardized according to ethnicity, sub-analysed according to BMI and all samples taken from the third trimester of pregnancy – one of the first such studies to be performed within South Africa as well as globally. This study reports significant differences in the BMI of the non-pregnant and pregnant groups, but no significant differences within the pregnant cohorts. In conclusion this study establishes an adipokine baseline for future reference with regards to South African Black pregnant and non-pregnant women. Albeit at term, the study shows a statistically significant difference in the levels of adiponectin/leptin/resistin and TNF-α in HIV positive patients within the non-pregnant versus pregnant population. Within the pre-eclamptic cohort there was no statistically significant difference in EOPE versus LOPE.