Considering risk contexts in explaining the paradoxical HIV increase among female sex workers in Mumbai and Thane, India.

BACKGROUND: The period 2006-2009 saw intensive scale-up of HIV prevention efforts and an increase in reported safer sex among brothel and street-based sex workers in Mumbai and Thane (Maharashtra, India). Yet during the same period, the prevalence of HIV increased in these groups. A better understanding of sex workers' risk environment is needed to explain this paradox. METHODS: In this qualitative study we conducted 36 individual interviews, 9 joint interviews, and 10 focus group discussions with people associated with HIV interventions between March and May 2012. RESULTS: Dramatic changes in Mumbai's urban landscape dominated participants' accounts, with dwindling sex worker numbers in traditional brothel areas attributed to urban restructuring. Gentrification and anti-trafficking efforts explained an escalation in police raids. This contributed to dispersal of sex work with the sex-trade management adapting by becoming more hidden and mobile, leading to increased vulnerability. Affordable mobile phone technology enabled independent sex workers to trade in more hidden ways and there was an increased dependence on lovers for support. The risk context has become ever more challenging, with animosity against sex work amplified since the scale up of targeted interventions. Focus on condom use with sex workers inadvertently contributed to the diversification of the sex trade as clients seek out women who are less visible. Sex workers and other marginalised women who sell sex all strictly prioritise anonymity. Power structures in the sex trade continue to pose insurmountable barriers to reaching young and new sex workers. Economic vulnerability shaped women's decisions to compromise on condom use. Surveys monitoring HIV prevalence among 'visible' street and brothel-bases sex workers are increasingly un-representative of all women selling sex and self-reported condom use is no longer a valid measure of risk reduction. CONCLUSIONS: Targeted harm reduction programmes with sex workers fail when implemented in complex urban environments that favour abolition. Increased stigmatisation and dispersal of risk can no longer be considered as unexpected. Reaching the increasing proportion of sex workers who intentionally avoid HIV prevention programmes has become the main challenge. Future evaluations need to incorporate building 'dark logic' models to predict potential harms.

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.

A prospective study of maternal fatty acids, micronutrients and homocysteine and their association with birth outcome.

Our earlier studies both in animals and in humans have indicated that micronutrients (folic acid, vitamin B12) and long-chain polyunsaturated fatty acids, especially docosahexaenoic acid (DHA), are interlinked in the one-carbon cycle, which plays an important role in fetal 'programming' of adult diseases. The present study examines the levels of maternal and cord plasma fatty acids, maternal folate, vitamin B12 and homocysteine in healthy mothers at various time points during pregnancy and also examine an association between them. A longitudinal study of 106 normal pregnant women was carried out, and maternal blood was collected at three time points, viz., T1 = 16-20th week, T2 = 26-30th week and T3 = at delivery. Cord blood was collected at delivery. Fatty acids were estimated using a gas chromatograph. Levels of folate, vitamin B12 and homocysteine were estimated by the chemiluminescent microparticle immunoassay (CMIA) technology. Maternal plasma folate (P < 0.05), vitamin B12 (P < 0.01) and DHA (P < 0.05) levels were lowest, while maternal homocysteine levels were highest (P < 0.01) at T3. There was a negative association between maternal DHA and homocysteine at T2 (P < 0.05) and T3 (P < 0.01). There was a positive association between plasma DHA in maternal blood at T3 and cord blood. Furthermore, there was a positive association between maternal folate and vitamin B12 at T3 and baby weight, whereas maternal homocysteine at T1 were inversely associated with baby weight at delivery. Our study provides evidence for the associations of folic acid, vitamin B12, homocysteine with DHA and baby weight, suggesting that a balanced dietary supplementation of folate-vitamin B12-DHA during pregnancy may be beneficial.

Matrix metalloproteinases-2, -3 and tissue inhibitors of metalloproteinases-1, -2 in placentas from preterm pregnancies and their association with one-carbon metabolites.

Maternal nutrition is an important determinant of one-carbon metabolism and defects in the one-carbon metabolism may lead to poor obstetric outcomes. This study was designed to test the hypothesis that altered intake/metabolism of micronutrients (folic acid and vitamin B12) and docosahexaenoic acid (DHA) contributes to increased homocysteine and oxidative stress leading to altered levels of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in women delivering preterm. We have earlier reported increased vitamin B12, homocysteine, and oxidative stress along with reduced placental DHA in women delivering preterm. In this study, we further examine the placental levels of MMP2, MMP3, TIMP1, and TIMP2 in 75 women delivering at term and 73 women delivering preterm. Placental levels of MMPs and TIMPs were determined by ELISA. Placental MMP2 and MMP3 levels were higher (P<0.01) in women delivering preterm as compared with term. There was no difference in the placental TIMP1 and TIMP2 levels in women delivering preterm and at term. Further placental MMP2 and MMP3 levels were higher (P<0.01) in women with preterm labor as compared with those in labor at term, suggesting that MMPs may favor degradation of extracellular matrix in the placenta during preterm labor. Our study for the first time suggests a crucial role of micronutrients and MMPs in preterm birth. Future studies need to examine if epigenetic modifications through the one-carbon cycle contribute to increased levels of MMPs leading to preterm deliveries.

Longitudinal Assessment of Calcium and Magnesium Levels in Women with Preeclampsia.

The present study reports the levels of maternal serum calcium and magnesium from early pregnancy until delivery, along with cord levels, in women who developed preeclampsia (PE) and compares them with those without PE. A total of 324 pregnant women (216 non-PE and 108 PE women) were included in this retrospective case-control study of prospectively collected data nested in an observational cohort study. Maternal blood was collected at 4 time points during pregnancy (V1 = 11-14 weeks, V2 = 18-22 weeks, V3 = 26-28 weeks, and V4 = at delivery) and umbilical cord blood at delivery. Independent t tests were used to compare calcium, magnesium, and their ratio between two groups, and their associations with PE were studied using regression models. Calcium levels were similar between groups at all time points. Magnesium levels were lower (p = 0.021) at V2 in PE group as compared with non-PE group. Maternal calcium and magnesium levels were negatively associated, with blood pressure in early pregnancy. In fully adjusted logistic regression analysis, lower magnesium levels were associated with an increased risk of PE at V2 (OR 0.25 [95% CI 0.07, 0.94] p = 0.04). Lower magnesium in mid-pregnancy was associated with higher risk of PE. These changes were observed before the diagnosis of PE, thereby suggesting that they may have a role in the etiology of PE.

Association of maternal vitamin D status with the risk of preeclampsia.

The aim of this study was to examine serum vitamin D concentrations from early pregnancy until delivery in women who did and did not develop preeclampsia. This longitudinal study was carried out in Pune, India. A total of 1154 women with singleton pregnancies were recruited in early pregnancy from two hospitals. Blood samples were collected and stored at four time points across gestation: V1 = 11-14 weeks, V2 = 18-22 weeks, V3 = 26-28 weeks and V4 = at delivery. 108 women who developed preeclampsia (PE) and 216 who did not develop PE (Non-PE) were randomly selected from the remainder. Serum 25-hydroxy vitamin D concentrations (25(OH)D) were estimated in their samples using commercially available ELISA kits. Independent t-tests were used to compare 25(OH)D between PE and non-PE groups. Logistic and linear regressions were used to examine associations of 25(OH)D with the risk of preeclampsia and birth outcomes, respectively, after adjusting for confounders. The mean (SD) 25(OH)D at V1 was 21.95 (19.64) in the Non-PE group and 17.76 (13.21) in the PE group. A decrease in the concentrations of vitamin D (ng ml-1) in mid-pregnancy (V2) and at delivery was associated with an increased risk of preeclampsia (0.31 [95% CI 0.11, 0.86], p = 0.024 and 0.24 [95% CI 0.08, 0.77], p = 0.016), respectively. Our finding of lower vitamin D concentrations in mid-pregnancy, before women developed clinical preeclampsia, suggests that vitamin D may have a role in its pathophysiology.

Reduced folate, increased vitamin B(12) and homocysteine concentrations in women delivering preterm.

BACKGROUND AND AIM: Maternal nutrition is an important determinant of the duration of pregnancy and fetal growth, and thereby influences pregnancy outcome. Folic acid and vitamin B(12) are involved in one-carbon metabolism and are reported to underlie intrauterine programming of adult diseases. METHODS: In the present study, the levels of folate, vitamin B(12) and homocysteine were measured in mothers delivering preterm (PT; gestation <37 weeks; n = 67), those delivering preterm due to preeclampsia (PT-PE; n = 49) and women delivering at term (control group; n = 76). RESULTS: Increased vitamin B(12) and homocysteine levels (p < 0.05 for both) were seen in the PT-PE and PT groups as compared to the controls. In addition, reduced folate levels (p < 0.05) were observed in the PT group. A negative association of maternal plasma homocysteine with birth weight was seen in the idiopathic preterm group. CONCLUSIONS: Altered maternal micronutrients and resultant increased homocysteine concentrations exist in women delivering preterm. These alterations may also be partly associated with other factors such as undiagnosed inflammatory conditions or inadequate placentation in some women. Since these micronutrients play an important role in epigenetic regulation of vital genes involved in the fetal programming of adult diseases, further studies need to be undertaken to understand their role in preterm deliveries.

Gestational weight gain in the REVAMP pregnancy cohort in Western India: Comparison with international and national references.

Objective: To determine the trimester specific gestational weight gain (GWG) in a population of pregnant women from Western India and compare it with the Intergrowth-21st international and an Indian reference (GARBH-Ini cohort-Group for Advanced Research on BirtH outcomes). Study design: A prospective longitudinal observational study was undertaken in Pune, West India and data for gestational weight gain was collected [the REVAMP study (Research Exploring Various Aspects and Mechanisms in Preeclampsia)]. Generalized Additive Models for Location, Scale and Shape method (GAMLSS model) were used to create GWG centile curves according to gestational age, stratified by BMI at recruitment (n = 640) and compared with Intergrowth-21st reference and GARBH-Ini cohort. Multivariable regression analysis was used to evaluate the relationship between GWG and antenatal risk factors. Results: The median GWG was 1.68, 5.80, 7.06, and 11.56 kg at gestational ages 18, 26, 30, and 40 weeks, respectively. In our study, pregnant women gained less weight throughout pregnancy compared to Intergrowth-21st study, but more weight compared to the GARBH-Ini cohort centile curves in all the BMI categories. GWG in overweight/obese women (BMI ≥ 25) was significantly lower (<0.001) as compared to underweight (BMI < 18.5), or normal weight women (BMI ≥ 18.5 and <25). The median GWG at 40 weeks in underweight, normal and overweight/obese women was 13.18, 11.74, and 10.48 kg, respectively. Higher maternal BMI, older maternal age, higher parity and higher hemoglobin concentrations were associated with lower GWG, while taller maternal height was associated with greater GWG. Conclusion: GWG of Indian women is lower than the prescriptive standards of the Intergrowth charts.

Cognitive function and behavioral problems in children born to mothers with preeclampsia: an Indian study.

Studies from high-income countries report associations of preeclampsia (PE) with reduced cognitive function and adverse behavioural outcomes in children. We examined these associations in Indian children aged 5-7 years. Children of mothers with PE (n=74) and without PE (non-PE; n=234) were recruited at delivery at Bharati Hospital, Pune, India. The cognitive performance was assessed using 3 core tests from the Kaufman Assessment Battery and additional tests including Verbal fluency, Kohs block design, and Coding A (from Wechsler Intelligence Scale for Children). The parent-reported Strengths and Difficulties Questionnaire (SDQ) was used to assess children's behavioral characteristics. Scores were compared between children from PE and non-PE groups, and associations analyzed further using regression models, adjusted for potential confounders. After adjusting for age, sex, socio-economic status and maternal education, children of PE mothers had lower Kohs block design scores (adjusted odds ratio per score category 0.57, [95% CI 0.34-0.96] p=0.034; 0.62 [95%CI (0.36, 1.07), p=0.09 on further adjustment for birth weight and gestation) compared to children of mothers without PE. In the SDQ, there was a lower prevalence of abnormal 'conduct problem' scores in PE group than non-PE group (OR=0.33, 95% CI 0.13-0.83, p=0.018, in the fully adjusted model); there were no differences for other behavioral domains. This preliminary study in Indian children suggests that fetal exposure to maternal PE may have an adverse impact on visuo-spatial performance but does not adversely affect behavior. Further studies with larger sample sizes are essential to understand effects of maternal PE on cognitive/behavioral outcomes in children.

Associations of long-chain polyunsaturated fatty acid concentrations with birth outcome in term Indian mothers and their neonates.

The purpose of this study was to examine the maternal and cord long-chain polyunsaturated fatty acid (LCPUFA) concentrations and their associations with birth outcome in term deliveries. Pregnant women (n = 253) delivering at term were divided into two groups based on their babies' birth weights (1) normal birth weight (NBW), that is, ≥2.5 kg (n = 190) and (2) low-birth weight (LBW), that is, <2.5 kg (n = 63). Each group is further divided into two groups according to the baby's sex, that is, male NBW (M-NBW), female NBW (F-NBW), male LBW (M-LBW), and female LBW (F-LBW) groups. Maternal plasma docosahexaenoic acid and erythrocyte arachidonic acid (AA) levels were lower (P < 0.05 for both), while cord plasma docosahexaenoic acid and erythrocyte AA levels were higher (P < 0.05 for both) in LBW group when compared to the NBW group. Maternal erythrocyte AA levels were positively associated with birth weight (P = 0.001), while cord plasma docosahexaenoic acid levels were negatively (P = 0.05) associated with birth weight. Reduced maternal and increased cord LCPUFA levels exist in mothers delivering LBW babies, especially in mothers delivering female babies, indicative of sex-specific effects.

Association of preeclampsia with anthropometric measures and blood pressure in Indian children.

BACKGROUND AND OBJECTIVE: Birth weight and post-natal growth are important predictors of adult health. Preeclampsia (PE) is associated with low birth weight and may have long term effects on the health of the children. The current study aims to compare anthropometry and blood pressure between children of mothers with and without PE in an Indian cohort. METHODS: We studied children born to women with (PE; n = 211) and without preeclampsia (non-PE; n = 470) at Bharati Hospital, Pune, India. Anthropometry and blood pressure were measured in children at 3-7 years of age. Weight and height Z-scores were calculated using the WHO 2006 growth reference. Independent t-tests were used to compare means between the two groups, and associations between preeclampsia and child outcomes were analyzed using multiple linear regression, adjusting for potential confounders. RESULTS: Weight and height Z-scores (p = 0.04 and 0.008), and subscapular skinfold thickness (p = 0.03) were higher among children of PE compared with children of non-PE mothers. Systolic blood pressure was also higher in children of PE mothers (1.70 mmHg [95% CI 0.05, 2.90] p = 0.006). BMI and diastolic blood pressure did not differ between groups. In regression models adjusted for newborn weight and gestational age, current age and sex, and maternal height, BMI and socio-economic status, children of PE mothers had higher weight Z-score (0.27 SD [95%CI 0.06, 0.48] p = 0.01), height Z-score (0.28 SD [95%CI 0.09, 0.47] p = 0.005), and subscapular skinfold thickness (0.38 mm [95%CI 0.00, 0.76] p = 0.049). A trend for higher systolic blood pressure (1.59 mmHg [95%CI -0.02, 3.20] p = 0.053) in the children was also observed in the adjusted model. The difference in systolic blood pressure was attenuated after adjusting further for the child's weight and height (1.09 mmHg [95%CI -0.48, 2.67] p = 0.17). There was no evidence of differences in effects between boys and girls. CONCLUSION: Children of PE mothers were taller and heavier, and had higher systolic blood pressure, partly explained by their increased body size, than children of non-PE mothers. In utero exposure to preeclampsia may increase the risk of future cardiovascular disease.

Higher maternal plasma folate, vitamin B12 and homocysteine levels in women with preeclampsia.

Micronutrients like vitamin B12 and folate play an important role in nucleic acid metabolism, cell growth, and are important determinants of fetal growth. The present study examined the levels of maternal and cord plasma folate, vitamin B12, homocysteine, and their association with birth outcome in women with preeclampsia (PE). This study includes 450 normotensive control (NC) and 350 women with PE. PE women were further classified into women delivering at term (n = 224) and preterm (n = 126). Maternal and cord blood was collected at delivery. The levels of maternal vitamin B12 (p < 0.05), folate (p < 0.01), and homocysteine (p < 0.01) were higher in the PE group as compared to the NC group. Maternal folate levels were higher in both term and preterm groups, while vitamin B12 levels were higher only in the preterm group as compared to NC group. In contrast, homocysteine was higher only in the term PE group. Similar changes were also observed in the cord plasma. There was a positive association of maternal plasma homocysteine with systolic (r = 0.151, p = 0.000, n = 578) and diastolic blood pressure (r = 0.213, p = 0.000, n = 578) in the whole cohort. A negative association of maternal folate with systolic blood pressure (r = -0.105, p = 0.048, n = 352) while a positive association with baby weight in the NC group (r = 0.116, p = 0.029, n = 352). The present study suggests that maternal and cord micronutrient levels are altered in women with PE.

Repeated pregnancy among women with known HIV status in Pune, India.

HIV-positive women of reproductive age face challenges in decision making related to pregnancy. Understanding factors influencing repeat pregnancies in women with known HIV status are necessary to guide interventions and counseling strategies to better inform and support them. We compared three groups of women attending a large antenatal clinic in Pune, India. They include: Group A--63 HIV-positive women coming for care for a repeat pregnancy after being diagnosed in a previous pregnancy; Group B--64 HIV-negative (repeat) pregnant women attending this antenatal clinic; and Group C--63 HIV-positive non-pregnant women currently enrolled in an ongoing clinical trial. Comparisons of Group A and B indicate that the likelihood of unplanned repeat pregnancies was significantly higher in HIV-positive (70%) than HIV-negative (36%) women (OR=4.1, CI: 2.0-8.7). Inability to terminate the pregnancy (31%) and familial obligations (40%) appear to be important for continuing the unplanned repeat pregnancy. Despite high reported contraceptive use by HIV-positive women, pregnancies still occurred. Death of their youngest child is an important factor as 21% of HIV-positive pregnant women lost their youngest child compared with 3% of HIV-negative women and 3% of HIV-positive non-pregnant women (p<0.001). Repeat pregnancies were more likely to occur for women who did not disclose their HIV status to their spouse. Thus the majority of the repeat pregnancies for HIV-positive women were both unplanned and unwanted.

Nurses' health education program in India increases HIV knowledge and reduces fear.

Few health care facilities are adequately prepared to manage and care for HIV/AIDS patients in India. Nurses play a critical role in patient care but are often ill-equipped to deal with their own fears of occupational risk and handle the clinical aspects of HIV/AIDS care, leading to stigma and discrimination toward HIV-positive patients. The authors examine the impact of a 4-day HIV/AIDS health education program on knowledge and attitudes of nurses in a government hospital. This education program was developed using a training of trainers model and qualitative research. A total of 21 master trainers underwent 6 days of training and began training of 552 hospital nurses (in 2004-2005). Using a pretest-posttest design, the authors assessed changes in knowledge and attitudes of 371 trained nurses. Significant improvements were seen in nurses' HIV/AIDS knowledge in all areas including care, treatment, and issues of confidentiality and consent. Fear of interaction with people living with HIV/AIDS was reduced significantly. The short course was successful in increasing nurses' knowledge in all aspects. There is great potential to expand this stigma-reduction intervention to other public and private hospitals.

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.

Altered maternal proportions of long chain polyunsaturated fatty acids and their transport leads to disturbed fetal stores in preeclampsia.

Our previous cross-sectional studies have shown altered proportions of long chain polyunsaturated fatty acids (LCPUFA) in preeclampsia (PE) at the end of pregnancy when the pathology has already progressed. The present longitudinal study for the first time reports fatty acid proportions from 16th week of gestation till delivery and placental transport in PE. This is a hospital based study where women were recruited in early pregnancy. Maternal blood was collected at 3 time points i.e. T1=16-20th week, T2=26-30th week and T3=at delivery. Cord blood and placenta were collected at delivery. This study reports data on 140 normotensive control (NC) and 54 PE women. In PE we report lower proportions of DHA in maternal plasma at T1, cord plasma and placenta (p<0.05 for all). The mRNA levels of placental ∆5 desaturase, fatty acid transport proteins -1, -4, were lower (p<0.05 for all) in PE. There was also a positive association between cord and maternal plasma DHA and total omega-3 fatty acids at T1. This study demonstrates that women with PE have lower fatty acids stores at 16-20th week of gestation and lower placental synthesis and transport. It is likely that supplementation of omega-3 fatty acids during the 16-20th week of gestation may help in improving fatty acid status in infants born to mothers with 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.

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.

Gestation dependant changes in angiogenic factors and their associations with fetal growth measures in normotensive pregnancy.

BACKGROUND: Earlier studies indicate that altered angiogenesis at birth is associated with poor birth outcome in women with preeclampsia. Now, we hypothesize that the progressive gestation dependant changes in markers of angiogenesis will be more useful to predict birth weight early even in a normotensive pregnancy. This study for the first time examines the association of gestation dependant changes in the levels of maternal angiogenic factors in addition to their levels in cord with birth weight. METHOD: Ninety two pregnant women were followed at three different time points: 16-20 weeks, 26-30 weeks and at delivery during pregnancy. Plasma levels of angiogenic and anti angiogenic factors were determined by commercial enzyme-linked immunosorbent assay (ELISA) kits. RESULTS: Maternal plasma VEGF levels increased (p<0.01) till the second time point and decreased (p<0.05) up to delivery while plasma sFlt-1 levels increased (p<0.01) at delivery. PlGF levels peaked (p<0.01) at second time point and decreased (p<0.01) at delivery. Cord plasma VEGF levels were higher (p<0.01) and sFlt-1 levels were lower (p<0.01) as compared to maternal values at all time points. Maternal plasma VEGF levels at first time point and PlGF levels at delivery were positively (p<0.05 and p<0.01 respectively), while sFlt-1/PlGF ratio at delivery was negatively associated (p<0.05) with birth weight. CONCLUSION: Levels of pro- and anti-angiogenic factors may be differentially regulated across gestation. Maternal VEGF levels at early gestation (16-20 weeks) may be predictive of birth weight in healthy term pregnancies.