Comparison of fetal growth patterns from Western India with Intergrowth-21st.

OBJECTIVE: To generate longitudinal fetal growth data in an Indian population and compare it with Intergrowth-21st. MATERIAL AND METHODS: Fetal biometry data was collected in a prospective longitudinal observational study (REVAMP: Research Exploring Various Aspects and Mechanisms in Preeclampsia) from 2017 to 2022. Fetal crown-rump length (CRL) was measured at 11-14 weeks gestation, and biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC), and femur length (FL) at 18-22 and 32-35 weeks, and converted into Z-scores using the Intergrowth standard. Generalized Additive Models for Location, Scale and Shape (GAMLSS) models were used to construct fetal growth centile curves compared against Intergrowth centiles. RESULTS: Out of 1096 singleton pregnancies in REVAMP, this analysis included 655 'healthy' pregnancies (uncomplicated by pre-eclampsia, diabetes, pre-term delivery or low birth weight) and a sub-set of 106 'low-risk' pregnancies defined using Intergrowth criteria. The 'healthy' study subjects showed lower mean CRL Z-score [-0.45 SD (95% CI:-0.54,-0.37)] at 11-14 weeks, and BPD Z-score [-1.2 SD (-1.28,-1.11) and -1.17 SD (-1.23,-1.1)] at 18-22 and 32-35 weeks respectively. Mean HC Z-score was comparable to the Intergrowth standard at 18-22 weeks [-0.08 SD (-0.16, 0.02)] but smaller at 32-35 weeks [-0.25 SD (-0.32,-0.19)]. Mean AC Z-score was lower at 18-22 weeks [-0.32 SD (-0.41,-0.23)] but comparable at 32-35 weeks [0.004 SD (-0.07, 0.07)]. FL was comparable to or larger than the Intergrowth standard at both time points [0.05 SD (-0.05, 0.14); 0.82 SD (0.75, 0.89), respectively]. These findings were similar, though measurements were slightly larger, in the 'low-risk' sample. CONCLUSIONS: This data from healthy and low-risk pregnant women in urban western India indicates that some fetal dimensions and growth trajectories differ significantly from the Intergrowth-21st. Our data suggest the need for a larger representative study to define a population-specific fetal growth reference for India, for identification of fetal growth restriction.

Maternal angiogenic factor disruptions prior to clinical diagnosis of preeclampsia: insights from the REVAMP study.

Preeclampsia is characterized by impaired angiogenesis and assessment of angiogenic factors can play a crucial role in the early diagnosis of preeclampsia. The current study reports the levels of angiogenic factors longitudinally from early pregnancy in women with preeclampsia and in the subtypes of preeclampsia, to identify their role in early prediction of preeclampsia. A total of 1154 women with singleton pregnancies were recruited in early pregnancy from 2 hospitals. Blood samples were collected, plasma samples were separated and stored at four time points across gestation: V1 = 11-14 weeks, V2 = 18-22 weeks, V3 = 26-28 weeks, and V4 = at delivery. The current study includes a total of 108 women developed preeclampsia (PE), and 216 matched controls. Angiogenic factors were estimated using commercially available ELISA kits. Receiver operating characteristic (ROC) curves were used to evaluate the potential diagnostic value in the prediction of PE. Lower levels of VEGF, PlGF, and higher levels of sEng and sEng/PlGF ratio (p < 0.05 for all) predate clinical diagnosis in women with preeclampsia. sEng levels and sEng/PlGF ratio showed significant correlation with odds of preeclampsia at all the timepoints. This study identifies a cut off of 33.5 for sFlt-1/PlGF and 25.9 for sEng/PlGF for prediction of early onset preeclampsia. This study reports various angiogenic factors serially across gestation in a general population to identify women at risk of developing preeclampsia and its subtypes. The study also reports a potential biomarker and a pragmatic window for estimation of angiogenic markers to identify women at risk.

Longitudinal Assessment of Oxidative Stress Markers in Women with Preeclampsia.

Preeclampsia (PE) is a pregnancy-specific disorder and a major contributor to maternal and fetal morbidity and mortality. Role of oxidative stress in early pregnancy with the pathophysiology of the disorder is unclear. The current study aims to analyse maternal levels of oxidative stress markers (MDA and protein carbonyl) longitudinally across gestation and placental levels of oxidative stress markers (MDA, protein carbonyl and 8-oxo-2'-deoxyguanosine) in women with PE and compare them with non-PE women. 324 pregnant women (216 non-PE and 108 PE women) were longitudinally followed during pregnancy. Women with preeclampsia were stratified as early onset preeclampsia (EOP) and late onset preeclampsia (LOP) Maternal blood at four time points across gestation (11-14 weeks, 18-22 weeks, 26-28 weeks, and at delivery) and placenta were collected. Maternal and placental levels of oxidative stress markers were assessed using commercially available kits. Maternal plasma MDA and protein carbonyl levels were comparable between the PE and non-PE group at all timepoints across gestation. Maternal plasma MDA were significantly higher levels at 26-28 weeks in EOP women when compared to non-PE women (p < 0.05). Placental 8-oxo-dG levels were lower in the EOP group as compared to non-PE (p < 0.05). Elevated plasma MDA levels were positively associated with birth length at 18-22 weeks and 26-28 weeks in the PE group (p < 0.05 for both). Maternal plasma MDA levels were positively associated with systolic blood pressure at 18-22 weeks. Oxidative stress in early pregnancy is not associated with risk of PE.

Fatty acids and their metabolites (resolvins) are altered in women with gestational diabetes mellitus (GDM).

The maternal fatty acid status plays a key role in influencing pregnancy outcomes. Omega-3 fatty acids are the precursors for E-series (RvE) and D-series resolvins (RvD) and possess anti-inflammatory properties. Pregnancy complications like gestational diabetes mellitus (GDM) are associated with excess maternal inflammation. This study reports the levels of maternal fatty acids across gestation in GDM and non-GDM women, placental fatty acids, resolvins and their association with the maternal fatty acid status. Pregnant women were recruited at 11-14 (V1) weeks and followed at 18-22 (V2) and 26-28 (V3) weeks and at delivery (V4). A total of 209 women who were diagnosed as GDM and 207 non-GDM women were included in this study. Fatty acids were estimated using gas chromatography. The protein levels of resolvins (RvE1, RvE2, RvD1 and RvD2) were measured using ELISA kits. Total PUFAs, eicosapentaenoic acid (EPA), omega-6 fatty acids, linoleic acid (LA) and arachidonic acid (AA) were lower, while saturated fatty acid (SFA) and alpha-linolenic acid (ALA) levels were higher in GDM women at 18-22 weeks. Placental AA was lower (p < 0.05) in women with GDM. Placental protein levels of RvE1, RvD1 and RvD2 were lower (p < 0.001 for all) in the GDM group. The maternal delta 5 desaturase index was positively associated, while erythrocyte omega-3 and omega-6 fatty acids were negatively associated with RvE2 at 11-14 weeks. Placental LA and ALA were positively associated with RvD1 and RvD2 (p < 0.05, for both), respectively. Our findings suggest that the maternal fatty acid status influences pro-resolving mediators which may lead to increased inflammation in GDM.

Altered expression of nutrient transporters in syncytiotrophoblast membranes in preeclampsia placentae.

INTRODUCTION: Expression of nutrient transporters in the placenta affects fetal growth. This study reports the protein expression of nutrient transporters in the syncytial membranes [microvillous membrane (MVM) and basal membrane (BM)] of normotensive control and preeclampsia placentae. METHODS: Placentae were collected from fourteen normotensive control women and fourteen women with preeclampsia. The syncytiotrophoblast MVM and BM membranes were isolated. The protein expression of glucose transporter (GLUT1), vitamin B12 transporter (CD320) and fatty acid transporters (FATP2, FATP4) was assessed in both the membranes. RESULTS: Comparison between membranes demonstrates similar CD320 protein expression in normotensive group whereas, in preeclampsia placentae it was higher in the BM as compared to MVM (p < 0.05). FATP2&4 protein expression was higher in the BM as compared to their respective MVM fraction in both the groups (p < 0.01 for both). Comparison between groups demonstrates higher GLUT1 expression in the MVM (p < 0.05) and BM (p < 0.05) whereas lower CD320 expression in the MVM (p < 0.05) of preeclampsia placentae as compared to their respective membranes in normotensive control. Furthermore, GLUT1 protein expression was positively associated and CD320 protein expression was negatively associated with maternal body mass index (BMI) (p < 0.05 for both). No difference was observed in the FATP2&4 protein expression. However, FATP4 protein expression was negatively associated with maternal blood pressure (p < 0.05 for MVM; p = 0.060 for BM) and birth weight (p < 0.05 for both membranes). DISCUSSION: The current study for the first time demonstrates differential expression of various transporters in the syncytiotrophoblast membranes of the preeclampsia placentae which may influence fetal growth.

Longitudinal profile of high-sensitivity C-reactive protein in women with pre-eclampsia.

PROBLEM: C-reactive protein (CRP) is a marker for inflammation and its role as a possible biomarker for an early prediction of pre-eclampsia (PE) is unclear. The present study investigates the levels of high-sensitivity CRP (hs-CRP) longitudinally across pregnancy in women with PE and compares them to women without PE (non-PE). METHOD OF STUDY: A total of 324 pregnant women [216 non-PE and 108 PE women] were included in this study. Maternal blood was taken at four different intervals (V1 = 11-14 weeks, V2 = 18-22 weeks, V3 = 26-28 weeks, and V4 = at delivery). RESULTS: Maternal serum hs-CRP levels were higher at V1, V2, and V3 (p < .05 for all) in the PE group compared to the non-PE group. The hs-CRP levels were associated with maternal blood pressure throughout pregnancy. Maternal hs-CRP levels did not differ among early and late onset PE. Higher maternal hs-CRP levels were associated with the increased risk of PE in unadjusted model in early pregnancy. However, there was no significance after adjusting for confounding factors. CONCLUSIONS: Our findings suggest although the levels of hs-CRP were higher in PE in early pregnancy, they are not associated with an increased risk of PE.

Association between proNGF receptors and apoptotic factors in human placentae.

INTRODUCTION: Earlier studies have shown higher apoptosis in the pre-term placenta as compared to term. However, the exact mechanisms triggering these are not completely understood. Studies in neuronal and non-neuronal tissues have shown that the precursor form of NGF (proNGF) triggers apoptosis through preferential activation of p75NTR and sortilin receptors. We therefore, investigated placental expression of proNGF, mature NGF, p75NTR, co-receptor sortilin and their association with apoptosis. We further compared the levels of pro-protein convertase, furin between samples having high and low proNGF: mature NGF ratio. METHODS: Placenta samples were collected from women delivering at term (≥37 weeks; n = 41) and preterm (<37 weeks; n = 44). The protein levels of NGF, proNGF, p75NTR, Bax, Bcl-2 and furin were estimated by ELISA. Mean values of variables between different groups were compared using the independent sample t-test and associations were studied by Pearson correlation analysis. RESULTS: The placental mature NGF, proNGF and p75NTR protein levels were comparable between groups. Bax: Bcl-2 ratio was higher in preterm (p < 0.05) compared to term placenta. p75NTR was positively associated with Bax levels and sortilin levels were positively associated with p75NTR in whole cohort as well as individual groups. DISCUSSION: The higher Bax: Bcl-2 ratio in preterm placenta suggests the sensitivity to apoptosis. There were no differences in levels of NGF, proNGF, p75NTR, sortilin, and furin between groups. The observed associations between p75NTR, sortilin and Bax suggest that p75NTR and sortilin mediated signalling may be involved in the mechanisms leading to higher apoptosis in preterm placentae.

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.

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.

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.

Relative risk of postpartum maternal morbidity among cesarean-delivered women: A multisite prospective cohort study in a large district, India.

Introduction: Family doctors manage mild to moderate postpartum morbidities that do not receive attention. The morbidities are higher after cesareans, which are increasing in number. The aim was to calculate the relative risk of various maternal morbidities occurring during 6 months postpartum among cesarean-delivered women in Pune District, India. Material and Methods: This was a large multisite study, which included all 11 non-teaching government hospitals performing at least five cesarean sections per month, one teaching government hospital, and one private teaching hospital. All eligible cesarean delivered and an equal number of age and parity matched vaginally delivered women were the participants. The obstetricians interrogated women before discharge, after 4 weeks, 6 weeks, and 6 months. Results: In this study 3,112 women participated. At any visit and among any group lost to follow-up proportion was <10%. There was no major intra-operative complication among vaginally delivered women. The relative risks of acute and severe morbidity as intensive care unit admission and blood transfusion among cesarean-delivered women were 2.59 [95% confidence interval (CI) = 1.96 to 3.44], 4.33 (95% CI = 2.17 to 8.92), respectively. The adjusted relative risk of surgical site pain and infection at 4 weeks; surgical site pain at 6 weeks; and lower abdominal pain, breast engorgement/mastitis, urinary incontinence, and weakness at 6 months among cesarean-delivered women was higher (P < 0.05). Vaginally delivered women resumed family activities earlier. Conclusion: Health care workers, including family doctors, during follow-up of cesarean-delivered women, must assess for pain, induration/discharge at the surgical site, urinary incontinence, and breast engorgement/mastitis.

A review of conventional and sustained-release formulations of oral natural micronized progesterone in obstetric indications.

BACKGROUND: Exogenous progesterone is a treatment option for obstetric indications associated with reduced progesterone activity. Oral natural micronized progesterone (NMP) is effective, although it requires multiple daily doses and may cause adverse events due to its active metabolites. A sustained-release formulation of NMP (NMP-SR) has been developed to overcome the limitations of conventional oral NMP. METHODS: This narrative review examines the available evidence for oral NMP and NMP-SR in several obstetric indications of interest. RESULTS: Literature searches identified 17 studies of oral NMP (luteal phase support during assisted reproduction, prevention of threatened miscarriage, prevention of preterm delivery), and clinical studies supporting use of NMP-SR (luteal phase support during intrauterine insemination, maintenance of high-risk pregnancy). Oral NMP was effective for luteal phase support during in vitro fertilization and intrauterine insemination, prevention of threatened miscarriage, and prevention of preterm delivery. NMP-SR was comparable to dydrogesterone for luteal phase support during intrauterine insemination and effectively maintained high-risk pregnancies. Oral NMP-SR was well tolerated. CONCLUSIONS: By releasing progesterone gradually and circumventing first-pass metabolism, NMP-SR elicits the desired therapeutic effect with benefits over conventional oral NMP in terms of bioavailability, once-daily dosing and improved tolerability. Oral NMP-SR appears to be a valuable option for treating obstetric conditions associated with insufficient progesterone exposure.

Assessment of difference in postpartum depression among caesarean and vaginally delivered women at 6-week follow-up in hospitals in Pune District, India: an observational cohort study.

OBJECTIVES: To compare the proportion of postpartum depression at 6 weeks among women who had caesarean delivery and women who had vaginal delivery and to assess its association with some sociodemographic factors. DESIGN: This is a descriptive comparative study with prospective enrolment. We followed the enrolled women and assessed them for postpartum depression 6 weeks after delivery. SETTING: We conducted the study in Pune District, India from July 2017 to December 2018. The study sites were all non-teaching government hospitals performing five or more caesarean sections per month and two teaching hospitals: one government and one private. PARTICIPANTS: We included in the study group women who have undergone caesarean section in the participating hospitals and were residents of Pune District. Women who delivered vaginally and matched in age and parity were included in the comparison group. We followed 1556 women in each group. MAIN OUTCOME MEASURES: An Edinburgh Postnatal Depression Scale score of 10 or more for each woman was the primary outcome. χ2 test and multivariable binary logistic regression were performed to assess the effect of mode of delivery on postpartum depression. RESULTS: The proportion of postpartum depression at 6 weeks was 3.79% among women who had caesarean delivery and 2.35% among those who had vaginal delivery (χ2=4.50, p=0.03). The adjusted OR was 1.86 (95% CI 1.14 to 3.03). Women of age less than 25 years had higher risk of postpartum depression. The adjusted OR was 2.10 (95% CI 1.21 to 3.65). The study did not observe any association between postpartum depression and income, education, occupation or sex of the newborn child. CONCLUSIONS: We conclude that young women particularly those who had caesarean delivery should be screened 6 weeks after delivery.

Risk of non-resumption of vaginal sex and dyspareunia among cesarean-delivered women.

CONTEXT: Many women have postpartum sexual dysfunction. The mode of delivery is an important determinant. AIMS: To calculate the risk ratio of non-resumption of vaginal sex and dyspareunia during the postpartum period among cesarean-delivered women. SETTINGS AND DESIGN: This large multisite study was conducted in 13 selected hospitals in Pune District during 2017-19. METHODS AND MATERIAL: A total of 3,112 women (half cesarean delivered and half vaginally) were interviewed by trained health workers using a structured questionnaire. Women were interviewed at 4 weeks, 6 weeks, and 6 months. STATISTICAL ANALYSIS USED: Chi-square test was applied. A risk ratio with a 95% confidence interval was calculated. RESULTS: At 6 weeks, the risk ratio of non-resumption of vaginal sex was significantly high among cesarean-delivered participants (1.14). Cesarean-delivered women had a lesser risk ratio of dyspareunia at both follow-ups (0.59, 0.49). Even at 6 months, about one-third vaginally delivered women had dyspareunia. The proportion of women non-resuming vaginal sex gradually decreased from 6 weeks to 6 months. The proportion of women having dyspareunia also decreased from 6 weeks to 6 months following childbirth. Residence in the rural area and cesarean delivery were the significant determinants of an early resumption of vaginal sex. Dyspareunia was significantly high among vaginal delivered than cesarean. About 25% of women continued to have dyspareunia up to 6 months. CONCLUSIONS: A large number of women suffer from dyspareunia; hence antenatal and postnatal care should include some counseling and management about the resumption of sex and dyspareunia.

Placental apoptotic markers are associated with placental morphometry.

INTRODUCTION: Preeclampsia is a hypertensive disorder affecting both mother and the fetus and is a major cause of maternal and neonatal morbidity and mortality. Abnormal placentation is a common feature in preeclampsia that contributes to placental dysfunction. It is likely that increased homocysteine and oxidative stress influence apoptosis in preeclampsia. Increased placental apoptosis may aggravate the symptoms of preeclampsia through disruption of the placental structure. The current study aims to examine the association between various placental apoptotic markers with placental dimensions and maternal and neonatal characteristics in women with preeclampsia. METHODS: A total of 80 pregnant women [preeclampsia (n = 40); normotensive control (n = 40)] were included in the study. Placental characteristics such as its major axis, minor axis, breadth, thickness (at centre, cord insertion and periphery) and trimmed placental weight were recorded.Placental protein levels of caspase-3, caspase-8, BAX and Bcl-2 were estimated by ELISA and gene expression were examined by real time quantitative PCR. RESULT: Protein levels of proapoptotic markers such as caspase-8 and 3 were higher (p < 0.01) in the preeclampsia group compared to control whereas, the level of antiapoptotic marker Bcl-2 (p < 0.05) was lower in the preeclampsia group. Caspase-3 and Bcl-2 protein levels were negatively associated with thickness of placenta at cord insertion (p < 0.01). Protein levels of caspase-8 and caspase-3 were positively associated with placental MDA levels (p < 0.01). Caspase-8 was negatively associated with baby length (p = 0.055). DISCUSSION: This study demonstrates the association of various apoptotic markers with oxidative stress and placental dimensions.

Maternal vitamin D deficiency influences long-chain polyunsaturated fatty acids and pregnancy outcome in association with alterations in one-carbon metabolism.

Preeclampsia is a pregnancy-specific disorder, leading to maternal and infant morbidity and mortality. Abnormal placentation has been reported in preeclampsia. Nutrients like vitamin D and long-chain polyunsaturated fatty acids (LCPUFA) are known to play a role in placental development. In an animal model, we have previously demonstrated that maternal vitamin D deficiency increases the thromboxane/prostacyclin ratio and contributes to inflammation and vasoconstriction. We hypothesize that maternal vitamin D status influences placental LCPUFA metabolism through alterations in one carbon metabolism in women with preeclampsia. To test this hypothesis, we recruited 69 normotensive control (NC) women and 50 women with preeclampsia. Women with preeclampsia had lower placental protein and mRNA levels of cystathionine-ß-synthase (CBS), higher plasma malondialdehyde (MDA) levels and higher levels of arachidonic acid (AA) and total omega-6 fatty acids in the placenta. Women with preeclampsia also demonstrated higher placental mRNA levels of cyclooxygenase-2 (COX-2) as compared to NC women. Maternal 25(OH)D levels were negatively associated with maternal plasma MDA levels. Placental vitamin D receptor (VDR) levels were positively associated with CBS while maternal MDA levels were positively associated with serum levels of thromboxane-B2 (TXB2) levels. Our findings indicate that vitamin D deficiency increases oxidative stress through alterations in one carbon metabolism to influence pro-inflammatory omega-6 metabolic pathway in the placenta. This study demonstrates a possible mechanism through which vitamin D deficiency can result in an imbalance in the LCPUFA metabolites and contribute to placental inflammation and endothelial dysfunction in preeclampsia.

Placental lipid metabolism in preeclampsia.

OBJECTIVES: The current study examines the placental and maternal lipid profile and expression of genes involved in placental lipid metabolism in women with preeclampsia. METHODS: The current study includes normotensive control women (n = 40) and women with preeclampsia (n = 39). Preeclampsia women were further classified into women delivering at term preeclampsia (T-PE; n = 15) and preterm preeclampsia (PT-PE; n = 24). RESULTS: There were no significant differences in maternal lipid profile between the T-PE and normotensive control groups. Maternal plasma VLDL (P < 0.05) and ratios of total cholesterol : HDL (P < 0.05), atherogenic index [log (triglycerides/HDL)] (P < 0.01) and apolipoprotein B : apolipoprotein A (P < 0.05) were higher in the PT-PE group as compared with the normotensive control group. Placental total cholesterol and HDL levels were higher (P < 0.05) in the T-PE as compared with the normotensive control group. Higher placental triglycerides (P < 0.05) were observed in PT-PE group compared with T-PE group. Placental mRNA levels of peroxisome proliferator activated receptor α, carnitine palmitoyl transferase-1, cluster of differentiation 36 and lipoprotein lipases were lower (P < 0.05) in the PT-PE than normotensive control group. A negative association of mRNA levels of peroxisome proliferator activated receptor α (r = -0.246, P = 0.032; r = -0.308, P = 0.007, respectively), carnitine palmitoyl transferase-1 (r = -0.292, P = 0.011; r = -0.366, P = 0.001), lipoprotein lipases (r = -0.296, P = 0.010; r = -0.254, P = 0.028) with SBP and DBP was observed. There was a positive association of placental triglycerides (r = 0.244, P = 0.031) with DBP. CONCLUSION: Women with preeclampsia exhibit higher lipid : lipoprotein ratios suggesting an atherogenic state particularly in women delivering preterm. Lower expression of genes involved in placental fatty acid oxidation and transport was also observed in preeclampsia.

Region-specific changes in the mRNA and protein expression of LCPUFA biosynthesis enzymes and transporters in the placentae of women with preeclampsia.

The biosynthesis and transport of long chain polyunsaturated fatty acids (LCPUFA) require the activity of fatty acid desaturase (FADS) enzymes, fatty acid transport proteins (FATP) and fatty acid binding proteins (FABP). In a previous study we have demonstrated region-specific changes in the LCPUFA levels in preeclampsia (PE) as compared to the normotensive control (NC) placentae. AIM: To understand the region-specific changes in the mRNA levels and protein expression of biosynthesis enzymes and transporters of LCPUFA in PE and NC placentae. METHODS: In this cross-sectional study, 20 NC women and 44 women with PE (23 term (TPE) and 21 preterm PE (PTPE)) were recruited. The samples were collected from four regions of the placentae considering cord insertion as the center (CM, central maternal/basal; CF, central fetal/chorionic; PM, peripheral maternal/basal and PF, peripheral fetal/chorionic). The mRNA levels were estimated using qRT-PCR. Statistical analysis was done using both post hoc least significant difference (LSD) test and Benjamini Hochberg correction in the analysis of covariance. Preliminarily, localization and expression of proteins were studied by immunohistochemistry (n = 3/group). RESULTS: The mRNA levels of FADS1, FADS2 and FATP1 were lower in the central regions (CM and CF) of the PE placentae (both TPE and PTPE) as compared to NC. These differences in the mRNA levels were observed by the LSD test and were not significant after the Benjamini Hochberg correction. Preliminary findings of IHC indicate that the protein expression of FADS1 and FATP4 was higher in the basal regions (CM and PM) of the PE placentae as compared to NC. FADS1, FADS2 and FATP4 proteins were localized in the syncytiotrophoblasts, cytotrophoblasts, mesenchymal cells, endothelial cells of the fetal capillaries and extravillous trophoblasts of the placenta. CONCLUSION: FADS enzymes are detected in the placentae of Indian women. In PE placentae, there are region-specific alterations in the mRNA and protein levels of LCPUFA biosynthesis enzymes (FADS1 and FADS2) and transporters (FATP1, FATP4 and FABP3) as compared to term NC. These changes were more pronounced toward the basal side and region around the cord insertion.

Differential Expression of Nerve Growth Factor (NGF) and Brain Derived Neurotrophic Factor (BDNF) in Different Regions of Normal and Preeclampsia Placentae.

Background: Our recent study indicates differential protein levels of neurotrophins and angiogenic factors in various regions of the normotensive and preeclampsia (PE) placenta. These changes may be in a response to differential mRNA expression of neurotrophins.Methods: This study examines the mRNA levels of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) in different regions of the placenta in normotensive control (NC) women and women with PE. Thirty NC women and forty one women with PE (18 delivered at term [T-PE] and 23 delivered preterm [PT-PE]) were included in the study. Placental samples were taken from four regions: central basal (CM), central chorionic (CF), peripheral basal (PM), and peripheral chorionic (PF). The mRNA levels of neurotrophins were measured by quantitative real-time PCR.Results: The BDNF mRNA levels were higher in peripheral fetal region as compared to peripheral basal region in NC (p < 0.05) group, PE group (p < 0.05) and term PE group (p < 0.01). The BDNF mRNA levels were lower in the central basal region of preterm PE group (p < 0.05) as compared to the NC group.Conclusion: The present study indicates that NGF and BDNF are expressed differentially across various regions of the placenta. This has implications for selection of the sampling site in the placenta while carrying out placental studies.

Evaluate the Feasibility of Surgical Transversus Abdominis Plane Block for Postoperative Analgesia After Cesarean Section.

BACKGROUND: Transversus abdominis plane (TAP) block is a fascial plane block providing postoperative analgesia after lower abdominal surgeries including Cesarean section. Conventionally, it is administered under ultrasound guidance or by blind technique. We studied a novel transperitoneal surgical TAP block for providing safe and effective analgesia after Cesarean section through transverse incision. METHODS: A hundred patients who fulfilled the inclusion criteria were included in the study after obtaining informed written consent. They were randomized in two groups: Group A with surgical TAP block and Group B without TAP block as control. Surgical TAP block was administered by transperitoneal route before the closure of peritoneum with 0.25% bupivacaine (dose adjusted with weight of the patient), and visual analogue score was assessed by a blind assessor. Time for rescue analgesia was noted and analyzed with the 'two independent sample t test.' RESULTS: The duration of postoperative analgesia in hours was significantly longer in the TAP block group compared with the control group (5.14 ± 1.63 vs 2.61 ± 0.89, p < 0.001). There was no reported complication of the surgical technique or any adverse effect of the used drug. CONCLUSION: Surgical TAP block via the transperitoneal route is a safe, easy and effective mode of providing postoperative analgesia after Cesarean section. This technique does not need any costly specialist equipment, overcomes the technical limitations of ultrasound-guided TAP block and can be used in obese patients also. It has almost no side effects, and the technique can be easily mastered.