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Our earlier studies of preeclampsia (PE) at delivery have demonstrated the alteration of one carbon cycle, reduced placental omega 3 fatty acids, altered circulating levels of angiogenic factors and differential placental gene-specific methylation patterns of angiogenic factors. This study was undertaken to examine changes in the levels of angiogenic factors and angiotensin II type 1 receptor autoantibodies (AT1-AAs) throughout gestation, from early pregnancy until delivery, in women with PE and to examine their association with cord angiogenic factors, blood pressure and infant weight. A total of 81 pregnant women (46 normotensive and 35 with PE) were followed at three different time points during pregnancy: 16-20 weeks (T1), 26-30 weeks (T2) and at the time of delivery (T3). The plasma levels of angiogenic factors and AT1-AAs were determined in the maternal and cord plasma by commercial enzyme-linked immunosorbent assay kits. Maternal plasma levels of vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) were lower (P<0.05 for both), whereas soluble fms-like tyrosine kinase-1 (sFlt-1; P<0.05) and the sFlt-1/PlGF ratio (P<0.01) were higher in early pregnancy in the PE group. Maternal plasma AT1-AA levels were higher (P<0.05) at T2 in women with PE. Cord plasma VEGF and soluble kinase insert domain receptor (sKDR) levels were lower (P<0.01 and P<0.05, respectively), whereas AT1-AA levels were higher (P<0.05) in the PE group. Maternal plasma VEGF levels in early pregnancy were positively associated with systolic blood pressure, whereas the sFlt-1/PlGF ratio at T2 was negatively associated with infant weight in the PE group. Low levels of proangiogenic factors (VEGF and PlGF) and high levels of AT1-AAs and antiangiogenic factors (sFlt-1 and sFlt-1/PlGF ratio) are present in the maternal circulation during early gestation in women with PE.

Our results indicate that higher homocysteine levels exist in women with PE from early pregnancy and continue till delivery.

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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.

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.

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