This is to certify that the dissertation titled "A STUDY ON ANALYSIS OF VALIDITY OF LATERAL PLACENTAL LOCATION IN PREDICTION OF PRE ECLAMPSIA" submitted by Dr.N.Dhivya to the Faculty of Obstetrics and Gynaecology, The Tamilnadu Dr. M.G.R. Medical university, Chennai in partial fulfillment of the requirement for the award of M.D. Degree (Obstetrics and Gynaecology) is a bonafide research work carried out by her under our direct supervision and guidance
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Shallow endovascular cytotrophoblastic invasion in the spiral arteries, an exaggerated inflammatory response and inappropriate endothelial cell activation are key features in the pathogenesis of pre-eclampsia. The mechanisms behind these features are unknown. It is thought that certain women are more likely to develop pre-eclampsia by virtue of a genetic predisposition or an acquired disease associated with vascular injury such as Diabetes Mellitus (Chesley 1978) or a combination of both. This vascular injury may facilitate an increased influx of copies of the antigenic RhD gene into the maternal circulation. The vast increase in the number of antigenic fetal cells could lead to excessive stimulation o f the maternal inflammatory immune response, an immunological feature which has been proposed to be associated with pre-eclampsia (Redman et al 1999). In this way the surplus of allogenic material from the fetus can cause an immunological reaction in the mother leading to pre-eclampsia. With this evidence, the RhD gene is one possible candidate acting as a triggering factor with the antigenic potential to stimulate an inflammatory response leading to pre-eclampsia.
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However, a number of other studies, including that of Siddiqui et al., did not observe significant differences between HCT levels in pre-eclamptic women and women with normal pregnancies   . Pregnancy at high altitudes, compared to sea level, is characterized by an increased blood viscosity as a result of increased HCT and plasma viscosity . Some evidence suggests that the plasma volume in patients with pre-eclampsia is lower than normal  . Decreased plasma volume induces a high Hb concentration . These factors contributed to high maternal hemoglobin levels in our study, the question around absence of statistical signific- ance can be answered by increased Hb and HCT levels in control group as well as the low sample size.
The following data will be extracted from each included study: first author; year of publication; setting; number of participating centres; country of investigation; admission criteria for participants; baseline characteristics; inclusion period; study design characteristics; details of the index test measurement; details of the citation standard; num- bers of included subjects, proportion dropped out, pro- portion uninterpretable/indeterminate/intermediate test results; (pre-specified) cut-off values; incidence of pre- eclampsia within the study population; (mean) time of onset and severity of pre-eclampsia; numbers of subjects on which to base 2 × 2 data tables or necessary data for the construction of a 2 × 2 data table; correlation coefficients between tests; financial support of industry.
In present study we found that patients who had elevated uterine artery pulsatility index in second trimester developed pre-eclampsia later in pregnancy. Present study is supported by the following. Papageorghiou et al have studied the Doppler velocimetry of maternal uterine arteries between the 22nd and 24th weeks of gestation by the measurement of PI. 5
Results: We found that lower levels of serum PlGF concentration were associated with early-onset PE, whereas lower %hCG-h was associated with the late-onset PE. Serum PlGF was lower and hCG β higher in severe PE, while %hCG-h and serum PAPP-A were lower in non-severe PE. By using multivariate regression analyses the best prediction for all PE was achieved with the third model: AUC was 0.66, and sensitivity 36% at 90% specificity. Third model also gave the highest prediction accuracy for late-onset, severe and non-severe PE: AUC 0.66 with 32% sensitivity, AUC 0.65, 24% sensitivity and AUC 0.60, 22% sensitivity at 90% specificity, respectively. The best prediction for early-onset PE was achieved using the second model: AUC 0.68 and 20% sensitivity at 90% specificity. Conclusions: Although the multivariate models did not meet the requirements to be clinically useful screening tools, our results indicate that the biomarker profile in women with risk factors for PE is different according to the subtype of PE. The heterogeneous nature of PE results in difficulty to find new, clinically useful biomarkers for prediction of PE in early pregnancy in high-risk cohorts.
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Patients with multi organ failure such as hemolysis, elevated liver enzymes, low platelet count syndrome, eclampsia , placental abruption, acute renal failure, and pulmonary oedema exhibited highest urinary prolactin concentrations (P <0.028) and frequency of antiangiogenic prolactin fragments in urine (P <0.036). High serum prolactin levels were associated with severe preeclampsia independently of gestational age, proteinuria, and prolactinuria (P<0.032).
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According to ACOG incidence of preeclampsia -5 to 8%.Incidence of preeclampsia in KMC is 11%.Considering the age groups, the maximum number of patients were found between the ages of the 21-25 years, 44.5% and 42% in normotensive group& in PIH complicating pregnancy respectively. This shows that in this study the child bearing period is earlier when compared to advanced countries where number of elderly primigravidae are encountered. Young pts <20&>30yrs said to have increased incidence of preeclampsia(AMJ of O&G 1993).In 10 years, 1958-1967, in Aberdeen city, the incidence of severe pre-Eclampsia in first pregnancy was 4.8% varying from 4.2% in 15-19 years age group to 6.5% in those of 30 years of age and more.
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Methods: Study design: Retrospective study. Information was collected from hospital case records of high risk deliveries that took place from January 2008 to December 2008 in a teaching hospital in south India. A total of 648 high risk case sheets were analysed. Results: Of 1106 case records analysed, there were 648 cases of high risk deliveries and found that 161 were preterm deliveries, 150 cases were post dated, 120 cases of previous caesarian section, 90 cases of eclampsia, 49 cases of pre eclampsia. Outcomes of the deliveries are: Only one maternal death recorded and 207 babies born with low birth weight, 81 needed NICU care, and 30 had fetal complication, 24 Intra Uterine Deaths, 11 still births and one congenital anomaly.
intake is considered the cause of high blood pressure in 41% of cases. 84% of our population did not know that preeclampsia was a pregnancy-related condition. High maternal age, heredity, overweight and abnormal placentation may be the cause of preeclampsia reported by some patients. Other risk factors, such as the history of hypertension, pre-eclampsia, primiparity, primipaternity, and diabetes cited in the literature, are not known by patients. 14
populations had specific risk factors for vitamin D defi- ciency such as race or seasonal sun exposure. A nested case control study showed an association between EOSPE and vitamin D deficiency after the diagnosis of EOSPE. Serum 25(OH)D was measured at the time of diagnosis of EOSPE (~ 29 weeks of gestation). Controls were matched to cases according to gestational age at diagnosis with EOSPE and race. In patients with EOSPE (n = 50), 25(OH)D was significantly lower compared to the controls (n = 100) (44.9 vs. 79.9 nmol/L; p < 0.001). There was an adjusted odds ratio (aOR) of 3.6 [(95% CI 1.71–7.58), p < 0.001] for EOSPE when maternal 25(OH)D was less than or equal to 19.6 nmol/L. There was also a 12-fold increase in odds of diagnosis with EOSPE in African American women, who had the lowest mean 25(OH)D concentration among groups catego- rized by race . In an Iranian case control study conducted in the fall and winter months, 25(OH)D levels were measured at the time of delivery in 41 pre- eclamptic women, 50 normal women and from their umbilical cord samples immediately after birth. This study found mean 25(OH)D levels to be significantly lower in pre-eclamptic women versus normal women (37.9 ± 33.9 nmol/L vs. 58.2 ± 38.2 nmol/L, respectively, p = 0.001). There was a significant relationship between vitamin D levels in pre-eclamptic women with levels in their neonates (r = 0.901, p = 0.0001) .
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diseases in our society, as these diseases are more prevalent here than the west. In a study conducted in Jordan, it showed 38% consanguineous marriages in a total of 77 cases of both preeclampsia and eclampsia 7,8 . However, they found statistically no significant difference in the occurrence of severe pre-eclampsia/eclampsia between primipara married to a first cousin or a relative other than a first cousin and primipara married to a non-relative. On the other hand, in our study there is a marked increase in the number of patients having consanguineous marriage that developed the disease and also reflected a family history of the disease as well. In another study of Jordan by Obeidat et al showed a significant association with low birth weight delivery (13.9% vs. 10.1%), preterm delivery (19.9% vs. 12.3%), and births with congenital anomalies (4.1% vs. 0.8%) compared with non-consanguineous marriages 10 .
In addition to the failure to down-regulate TGFbeta3, placental hypoxia might also contribute to this defect. Evidence from experiments in vitro suggests that cytotrophoblast differentiation is significantly influenced by hypoxia. When cytotrophoblasts were cultured in hypoxic conditions (2% oxygen) they continued to proliferate without proper differentiation. However, when these cytotrophoblasts were cultured in 20% oxygen they stopped proliferating and differentiated normally (29,30). It appears that ischaemia or hypoxia during the second wave of invasion might restrict the development invasive properties by the cytotrophoblasts, consequently affecting the invasion of the myometrium by some segments of the placenta. In addition to poor angiogenesis and vasculogenesis, there is also a possibility that the hypothesized poor placental perfusion might be due to an imbalance of vaso- active factors in the placenta. The placenta lacks neural innervation and blood flow is principally regulated by humoral factors. An imbalance of these in favour of vasoconstrictors might compromise blood flow to and also in the placenta. Numerous vaso-active factors have been identified, some of which include the products of the renin- angiotensin system, kallikrienkinin-kininogen system, endothelins, nitric oxide, catecholamines, and vasodilatory and vasoconstrictive eicosanoids. Our observations of these have highlighted the existence of numerous abnormalities in some of these factors in the preeclamptic placentae. For example, placentae from women with pre-
Abstract: Pre-eclampsia is a significant, multifactorial, multiorgan disease affecting 5%–8% of all pregnancies in the US where it is the third leading cause of maternal mortality. Despite improvements in the diagnosis and management of pre-eclampsia, severe complications can occur in both the mother and the fetus, and there is no effective method of prevention. Early detection and identification of pregnant women most at risk of developing the disease have proven challenging, but recent efforts combining biochemical and biophysical markers are promising. Efforts at prevention of pre-eclampsia with aspirin and calcium have had limited success, but research on modifiable risk factors, such as obesity surgery, are encouraging. Obstetric management of severe pre-eclampsia focuses on medical management of blood pressure and prevention of seizures using magnesium sulfate, but the ultimate cure remains delivery of the fetus and placenta. Timing of delivery depends on several factors, including gestational age, fetal lung maturity, and most importantly, disease severity. Anesthetic management includes regional anesthesia with careful evaluation of the patient’s airway, volume status, and coagulation status to reduce morbidity and mortality. The potential complications of general anesthesia, including intracranial hemorrhage, in these patients make regional anesthesia the preferred choice in many cases. Nevertheless, it is important to be aware of the contraindications to neuraxial anesthesia and to prepare always for the possibility of encountering a difficult airway.
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[17-22]. It is reported that a history of previous pre-eclampsia is a known risk factor for a new event in a future pregnancy, with recurrence rate varying from less than 10% to 65%, depending on the population or methodology considered . For severe preeclamptic women in an initial pregnancy, recurrence rates for any type of pre-eclampsia are very high, approaching 50% in some studies . Patients who conceived through IVF usually had an infertility history, and were extremely nervous, this nervousness may lead to anxiety or depression during pregnancy . The stress experienced by patients may increase resistance of the uterine artery, which is one of the factors leading to pre-eclampsia . Conceiving twice ART and previous pre-eclampsia make our patient extremely anxious than other pregnant women and these may lead to the adverse maternal and neonatal outcome to her. So here comes to our question, our patient has at least two obvious high risks of recurrent pre-eclampsia( PCOS and pre-eclampsia history), although we had done what we could to prevent the recurrence, but according to the figures mentioned above we found the rapidly increasing of BP and decreasing of liver function at her 31 th week of gestation, can the risk decrease if she do fetus reducing in the first trimester of her pregnancy? Or if we transplant just one embryo to those patients who are having IVF and have high risks of pre-eclampsia like our patient, will the recurrent pre-eclampsia incidence decrease? As is well known, Multiple pregnancies are more likely to be associated with pregnancy-induced hypertension , Morris R KP reported that pregnancy outcome rates have improved following selective fetal reduction as experience with techniques have improved and the number of very high
sphygmomanometer validated for use in pregnancy and pre-eclampsia (Microlife WatchBP home). The women were asked to self-monitor, taking two measurements in both morning and evening following five minutes rest on 3 days a week (Monday, Wednesday and Friday). Women used a traffic light system (red – high BP, ur- gent action required; amber – raised BP, action required; green – normal BP) developed from our previous work to classify raised BP and were given written advice regarding actions in the light of persistently high read- ings . Optionally they could text their readings to a central server and receive automated responses via the NHS “Florence” Simple Telehealth system [19, 20], which also provided text prompts and reminders to the participants.
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It complicates around 6-8% of all pregnancies. How pregnancy incites or aggravates hypertension remains unsolved despite decades of intensive research. Studies have shown that LDH activity & gene expression are higher in placentae in Pre-eclampsia than normal pregnancy. Hypoxia induces LDH isoenzyme activity in trophoblasts resulting in higher lactate production. 
This is a nested prospective observational study of women from South Africa and Zimbabwe recruited in the CAP trial . The CAP trial is a multi-centre randomized, double-blind placebo-controlled clinical trial with the ob- jective to determine whether calcium supplementation be- fore conception and during the first half of pregnancy reduces the incidence of recurrent pre-eclampsia more ef- fectively than supplementation starting at 20 weeks, which is the current WHO recommendation. In the CAP trial, non-pregnant women with history of pre-eclampsia or eclampsia in their most recent pregnancy were invited to participate as they are at higher risk of developing pre-eclampsia in subsequent pregnancies. Once admitted in the trial, participants were required to attend study sites every 12 weeks for follow up until pregnancy occurred. Pregnant women were followed up throughout their preg- nancy and trial visits were scheduled at 8, 20 and 32 weeks´ gestation. Eligible women were randomized to receive either 500 mg of elemental calcium daily or pla- cebo from recruitment and blinded supplementation con- tinued while participants were non-pregnant or until 20 weeks’ gestation. From 20 weeks’ gestation, all partici- pants received calcium supplements in compliance with WHO guidelines . The CAP trial started in 2011 and recruitment was completed in September 2016.
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Increases in inflammatory cytokine production have been associated with endothelial dysfunction, increased placenta apoptosis, decreased angiogenesis and kidney abnormalities that are relevant to the pathophysiology of pre-eclampsia . Endothelial cell damage induces the production of ET-1 (endothelin-1) [111,112]. In pregnant mice, ET-1 was shown to cause hypertension, proteinuria and renal damage. Furthermore, IL-6 acts downstream of TNFα to induce the release of ET-1 in mice. In addition, in the presence of autoantibodies from pre-eclamptic women, IL-6 mediates the release of ET-1 from human placental villous explants . These studies validate the original in vitro observations of Collino et al. , which showed that pre-eclamptic sera induces nephrin shedding from podocytes through ET- 1 release by endothelial glomerular cells. These separate studies show an association between inflammation and ET-1 in rodents, and ET-1 may play an important role in pre- eclampsia, but pregnant women with excessive inflammation and high levels of inflammatory cytokines, such as those with infections, do not always develop pre-eclampsia.
We searched the electronic databases of MEDLINE (US National Library of Medicine), EBSCOhost research databases, BVS Bireme, and SciELO, assisted by a clinical librarian, to identify the principal obstetric disorders that significantly increase maternal and perinatal morbidity and mortality in our region, including: “proteomics and pre-eclampsia”, “pro- teomics and perinatal infections”, “proteomics and premature rupture of membranes”, “proteomics and preterm birth”, “pro- teomics and intrauterine growth restriction”, “proteomics and ectopic pregnancy”, and “proteomics and pregnancy”. Other obstetric disorders were excluded.