Increased oxidative stress from early pregnancy in women who develop preeclampsia.

Preeclampsia (PE) is a pregnancy-specific disorder, defined as new onset of maternal hypertension and proteinuria after 20 weeks of gestation. Our earlier study has shown increased maternal oxidative stress at delivery to be associated with poor birth outcome in PE. However, these results were observed when the pathology had progressed and may have been secondary to the effects of the disorder. To understand the role of antioxidant defense mechanisms in PE right from early pregnancy, in this prospective study, we measured malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione (GSH) concentrations in maternal blood at 3 time-points of gestation [16-20 weeks (T1), 26-30 weeks (T2), at delivery (T3)] and in cord blood. Gene expression of SOD and GPx and protein levels of endothelial nitric oxide synthase (eNOS) enzyme were also analyzed in the placenta. MDA levels were higher at T1 (p < 0.01) and T2 (p < 0.01) in women with PE as compared with control. GPx levels were higher at T3 (p < 0.05) while SOD levels were lower at T2 (p < 0.05), T3 (p < 0.01) and in cord (p < 0.01) in PE. GSH levels at T1 (p < 0.05) and expression of GPx in the placenta were lower in PE as compared with control. In conclusion, this study demonstrates that women who develop PE exhibit increased oxidative stress right from 16 to 20 weeks of gestation. This may alter placental development and lead to fetal programming of adult non-communicable disease in the offspring.

Maternal nerve growth factor levels during pregnancy in women with preeclampsia: A longitudinal study.

Preeclampsia (PE) is characterized by hypertension and proteinuria. Improper development of the placenta due to altered angiogenesis is the main culprit in PE. Nerve growth factor (NGF) is an angiogenic factor which is expressed and localized in the placenta. Our earlier cross sectional study has shown altered NGF levels at delivery in women with PE. However, there are no studies on NGF levels in PE early in pregnancy before manifestation of the disease. Thus, there is a need to examine the role of NGF in vascular development during different stages of gestation in PE. A longitudinal study was carried out where pregnant women were enrolled from two major hospitals from Pune, Bharati hospital and Gupte hospital. They were followed at three different time points [16-20 weeks (T1), 26-30 weeks (T2) and at delivery (T3)] during pregnancy and maternal blood at every time point and cord blood at delivery was collected and processed. This study included normotensive women (n=88) and women with PE (n=48). NGF levels were measured from maternal and cord plasma using the Emax Immuno Assay System (Promega). The data was analyzed using the SPSS/PC+ package (Version 20.0, Chicago, IL, USA). Maternal NGF levels did not change at all time points while cord NGF levels were higher (p<0.05) in women with PE. Further, maternal NGF levels were negatively associated with blood pressure while cord NGF levels were positively associated with baby head circumference. Our data suggests that there may possibly be a compensatory role for NGF in the foeto-placental circulation in PE.

Levels of brain derived neurotrophic factors across gestation in women with preeclampsia.

Preeclampsia (PE) is a major pregnancy complication of placental origin which leads to adverse pregnancy outcome. Brain derived neurotrophic factor (BDNF) is suggested to promote trophoblast growth and regulate placental and fetal development. This study for the first time examines the levels of maternal plasma BDNF at various time points during gestation, cord plasma and placental BDNF levels and their association with birth outcome in women with PE. Normotensive control (NC) women (n=89) and women with PE (n=61) were followed at three different time points [16-20 weeks (T1), 26-30 weeks (T2) and at delivery (T3)]. Maternal blood at all time points and cord blood was collected. Results indicate that maternal BDNF levels at T1 (p=0.050) and T3 (p=0.025) were lower in women with PE than in NC women. Cord BDNF levels at delivery in women with PE were lower (p=0.032) than those in NC women. Placental BDNF gene expression was also lower (p=0.0082) in women with PE than in NC women. Our data suggests that BDNF plays an important role in the development of the materno-fetal-placental unit during pregnancy. Alteration in the levels of BDNF during pregnancy may be associated with an abnormal development of the placenta resulting in PE.

Differential regulation of brain-derived neurotrophic factor in term and preterm preeclampsia.

Our earlier studies in preeclampsia (PE) suggest a causal relationship between altered angiogenic factors and birth outcomes. Recent studies suggest that brain-derived neurotrophic factor (BDNF) can stimulate angiogenesis. The present study examines the levels of maternal and cord BDNF in women with PE (n = 106; full term [n = 60] and preterm [n = 46]) and normotensive women (n = 95; control) delivering at term. Maternal BDNF levels were lower (P < .05) in women with PE when compared to normotensive women. Cord BDNF levels were higher (P < .01) in women with PE delivering at term, while it was lower (P < .01) in women delivering preterm. Maternal BDNF levels were negatively associated with systolic and diastolic blood pressure (P < .01 for both). Our data for the first time suggest a possible role for BDNF in the pathophysiology of PE. Differential regulation of cord BDNF levels in preterm PE suggests a need to follow-up children to assess the neurodevelopmental effects in later life.