الفهرس 
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Abstract
Pre-eclampsia (PE) a pregnancy-associated disorder remains one of the main causes of maternal and perinatal morbidity and mortality. Several pathophysiological mechanisms have been implicated in the pathogenesis of preeclampsia which mainly occur in early pregnancy due to a variety of immune and genetic factors, placental ischemia, oxidative stress and other factors resulting in vascular anomalies and placental site trophoblastic cell dysfunction, shallow implantation of the placenta, and increased resistance of uterine artery blood flow. Considering the importance of PE, the development of an efficient management system for the disorder is crucial to tackle the problem of PE. However, currently the diagnosis, screening and management of PE remains controversial and no single standard has so far been agreed upon. Firsttrimester screening may be a major advantage over a second-trimester approach since it opens prospects for early and more efficient interventions. The existence of a screening process would be essential to improve both pregnancy outcome and optimize the utilization of resources in antenatal care. An early detection of PE would allow a chance to plan the appropriate monitoring and for clinical management to be immediately done following early detection of the disease thus making prophylactic strategies much more effective. Doppler ultrasound provides a noninvasive method for the assessment of the uteroplacental circulation. The finding that impaired placental perfusion reflected in increased uterine artery pulsatility index (PI) is associated with the development of PE is compatible with the hypothesis that PE is the consequence of impaired placentation. Unfortunately, this finding is nonspecific, so it is not diagnostically useful if used alone. Invasive cytotrophoblasts express vascular endothelial growth factor (VEGF), placental growth factor (PlGF), and vascular endothelial growth factor recepter -1 (VEGFR-1), this expression is altered in preeclampsia. Placental growth factor (PlGF) has been considered as one of the key biomarkers to predict preeclampsia, as it has a very high specificity and is thus more useful to rule in preeclampsia. Hence, patients with low PlGF levels have a high likelihood of developing preeclampsia and warrant intensive surveillance to enable its prompt and early recognition. Today, PlGF is used as part of several larger prediction algorithms where it has been shown to increase the overall prediction rate. Most current screening methods of effective screening for the development of early onset preeclampsia (PE) can be provided in the firsttrimester of pregnancy. Screening by a combination of maternal risk factors, uterine artery Doppler, mean arterial pressure and biochemical markers. Two common methods used to identify women at high-risk for developing PE are defined by the American College of Obstetricians and Gynecologists (ACOG) and the National Institute for Health and Care Excellence (NICE) guidelines. An alternative approach to screening for preeclampsia has been developed by the Fetal Medicine Foundation. (FMF) which is the most frequently used predictive algorithm for PE, it has been reported that mean arterial pressure (MAP) and mean uterine artery pulsatility index (UtA-PI) between 11 and 13 weeks’ gestation are higher in women that will later develop PE, and are particularly raised in those who develop early-onset PE, compared with unaffected pregnancies. The aim of this study is to investigate whether the measurement of maternal serum placental growth factor (PlGF) combined with uterine artery Doppler ultrasound, are useful in early predicting preeclampsia and to examine the diagnostic accuracy of the Fetal Medicine Foundation Algorithm for the early screening and prediction of the high risk preeclampsia at 11-13 weeks gestation in a group of pregnant women. This study included 120 primigravida women with a live, singleton fetus at 11-13 weeks gestation without risk factors attending antenatal care clinic at Tanta University Hospitals. The methods of the whole study process were initially posed in a committee established in the Department of Obstetrics and Gynecology at Tanta University Hospitals, and all procedures were assessed and approved ethically by Local Ethics Committee of Tanta University Hospitals. The duration of the study was from June 2021 till 2022, after fulfilling the Research and Ethics Committee guidelines. Inclusion criteria: 1. Age between 22-35 years. 2. Gestational age between 11 and 13 weeks (assessed by the first day of the last menstrual period and confirmed by ultrasound). 3. Primigravida 4. Single viable intrauterine pregnancy (confirmed by ultrasound). Exclusion criteria: Cases excluded from this study are those with; pre-existing maternal diseases such as renal diseases and diabetes, autoimmune diseases, hypertension, intrauterine fetal death, fetal anomalies, and pelvic pathology, for example, uterine fibroid. All case s were subjected to the following: 1) A signed informed written consent: All cases signed an informed written consent before the study. 2) History taking: • Personal history: include name, age, occupation, address, special habits, marital status and parity. • Complaint: was taken from patients’ own words. No complaint other than coming for routine antenatal care. • Menstrual history: include age of menarche, length of the cycle, duration, amount of bleeding and 1st day of last menstrual period. • Past history: cases were asked for the presence of medical diseases especially chronic hypertension, diabetes mellitus, thyroid disease, systemic lupus erythematosus, renal dysfunction, hepatic dysfunction, hematological disorders, heart disease and local or systemic infection. 3) General examination: This was done to assess the vital signs including the pulse, blood pressure, temperature and respiratory rate. General look and body areas were examined including face, neck, chest, back and limbs. 4) Estimation of Body mass index (BMI): BMI is one of the main risk factors for pre-eclampsia, calculated as weight in kilograms divided by height in cm squared) at first antenatal care. 5) Blood Pressure measurement and determination of mean arterial blood pressure: According to standardized protocols, MAP = SBP + 2 (DBP) 36) Ultrasound: Transabdominal ultrasound (TAS) was done for all cases to confirm viability, gestational age and any anomalies. Gestational age was derived from the fetal crown-rump length (CRL). 7) Determination of Uterine Artery Doppler Ultrasound (UtAD) according to standardized protocols. 8) Routine laboratory investigations: Basic investigations were done for all cases in the first antenatal care visit including Hb concentration, platelet cell count, liver functions, renal functions, thyroid profile, glycated hemoglobin HbAIC and urine analysis. 9) Specific laboratory investigations: Determination of maternal serum placental growth factor (PlGF) by specific immunoassay (ELISA) method using Human PlGF ELISA Kit instructions (Catalogue No. 201- 12-0139) in the Central Lab of Faculty of medicine, Tanta University Hospitals. 10) The measured values of mean arterial pressure, uterine artery pulsatility index, and placental growth factor were converted into multiples of the median (MoM). 11) The Fetal Medicine Foundation model was used for the determination of patient-specific risk of preeclampsia at 11-13 weeks gestation in each case. • Cases that didn’t complete the study were replaced by new ones from the obstetric clinics. • Preeclampsia was determined by the new detection of hypertension and proteinuria after 20 weeks gestation. • Diagnosis of hypertension, when systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg measured twice 6 h apart. • Proteinuria was also determined when 24-h urine collection contained ≥300 mg protein, or two readings >+1 proteinuria by the use of dipstick method. • Gestational age was determined from the fetal crown-rump length (CRL). The main results of the present study revealed; A. Only 11 of 120 normal pregnant women were categorized as a high preeclampsia risk group with a percentage of 9.2 % and the rest 109 cases were low preeclampsia risk group with a percentage of 90.8 % by application of fetal medicine foundation algorithm (FMF). B. The demographic data and the clinical features of the pregnant women showed no statistical significant differences between low and high risk groups as regards maternal age, weight, height, BMI and gestational age either by last menstrual period (LMP) and by ultrasound (US) at sampling. C. There were no significant differences between the two studied groups regarding systolic, diastolic and mean arterial blood pressures respectively. Also, there was no significant difference between the two studied groups regarding the multiple of median (MoM) of blood pressure. Also, there were no significant differences between the two groups as regards the routine laboratory investigations including; Liver function tests, kidney functions, hemoglobin concentration, platelets count, thyroid profile, and Hb AIC %. D. Fetal crown -rump length showed no significant difference between the two studied groups. Regarding right and left and mean uterine artery pulsatility indices (PI) and multiple of median (MoM), there was statistical significant increase of their values in high preeclampsia risk group when compared to low preeclampsia risk one E. As regards serum human placental growth factor and its multiple of median (MoM) in the two studied groups, they showed statistically significant lower values in high preeclampsia risk group when compared to the low preeclampsia risk one. F. Receiver operating characteristic curve (ROC) demonstrate to what extent it can be depended on placental growth factor, mean uterine artery PI and mean arterial blood pressure as a predictor for preeclampsia denoting the significant diagnostic performance for PIGF and mean uterine artery PI . The optimal cutoff value of PlGF value using the ROC curve was ≤40 resulting in a sensitivity of 90.91%, a specificity of 96.33 %, a positive predictive value of 71.4, a negative predictive value of 99.1% and an accuracy of 95.83%. While the optimal cutoff value of mean uterine artery PI value using the ROC curve was >1.91 resulting in a sensitivity of 90.91%, a specificity of 96.33 %, a positive predictive value of 71.4, a negative predictive value of 99.1% and an accuracy of 95.83%.