Gestational Age In Normal Pregnancies Research Articles

Longitudinal assessment of placental perfusion in normal and hypertensive pregnancies using pseudo-continuous arterial spin-labeled MRI: preliminary experience.

To evaluate longitudinal placental perfusion using pseudo-continuous arterial spin-labeled (pCASL) MRI in normal pregnancies and in pregnancies affected by chronic hypertension (cHTN), who are at the greatest risk for placental-mediated disease conditions. Eighteen normal and 23 pregnant subjects with cHTN requiring antihypertensive therapy were scanned at 3T using free-breathing pCASL-MRI at 16-20 and 24-28weeks of gestational age. Mean placental perfusion was 103.1 ± 48.0 and 71.4 ± 18.3mL/100g/min at 16-20 and 24-28weeks respectively in normal pregnancies and 79.4 ± 27.4 and 74.9 ± 26.6mL/100g/min in cHTN pregnancies. There was a significant decrease in perfusion between the first and second scans in normal pregnancies (p = 0.004), which was not observed in cHTN pregnancies (p = 0.36). The mean perfusion was not statistically different between normal and cHTN pregnancies at both scans, but the absolute change in perfusion per week was statistically different between these groups (p = 0.044). Furthermore, placental perfusion was significantly lower at both time points (p = 0.027 and 0.044 respectively) in the four pregnant subjects with cHTN who went on to have infants that were small for gestational age (52.7 ± 20.4 and 50.4 ± 20.9mL/100g/min) versus those who did not (85 ± 25.6 and 80.0 ± 25.1mL/100g/min). pCASL-MRI enables longitudinal assessment of placental perfusion in pregnant subjects. Placental perfusion in the second trimester declined in normal pregnancies whereas it remained unchanged in cHTN pregnancies, consistent with alterations due to vascular disease pathology. Perfusion was significantly lower in those with small for gestational age infants, indicating that pCASL-MRI-measured perfusion may be an effective imaging biomarker for placental insufficiency. pCASL-MRI enables longitudinal assessment of placental perfusion without administering exogenous contrast agent and can identify placental insufficiency in pregnant subjects with chronic hypertension that can lead to earlier interventions. • Arterial spin-labeled (ASL) magnetic resonance imaging (MRI) enables longitudinal assessment of placental perfusion without administering exogenous contrast agent. • ASL-MRI-measured placental perfusion decreased significantly between 16-20 week and 24-28 week gestational age in normal pregnancies, while it remained relatively constant in hypertensive pregnancies, attributed to vascular disease pathology. • ASL-MRI-measured placental perfusion was significantly lower in subjects with hypertension who had a small for gestational age infant at 16-20-week gestation, indicating perfusion as an effective biomarker of placental insufficiency.

A biomarker for bacteremia in pregnant women with acute pyelonephritis: soluble suppressor of tumorigenicity 2 or sST2

Objective Sepsis is a leading cause of maternal death, and its diagnosis during the golden hour is critical to improve survival. Acute pyelonephritis in pregnancy is a risk factor for obstetrical and medical complications, and it is a major cause of sepsis, as bacteremia complicates 15–20% of pyelonephritis episodes in pregnancy. The diagnosis of bacteremia currently relies on blood cultures, whereas a rapid test could allow timely management and improved outcomes. Soluble suppression of tumorigenicity 2 (sST2) was previously proposed as a biomarker for sepsis in non-pregnant adults and children. This study was designed to determine whether maternal plasma concentrations of sST2 in pregnant patients with pyelonephritis can help to identify those at risk for bacteremia. Study design This cross-sectional study included women with normal pregnancy (n = 131) and pregnant women with acute pyelonephritis (n = 36). Acute pyelonephritis was diagnosed based on a combination of clinical findings and a positive urine culture. Patients were further classified according to the results of blood cultures into those with and without bacteremia. Plasma concentrations of sST2 were determined by a sensitive immunoassay. Non-parametric statistics were used for analysis. Results The maternal plasma sST2 concentration increased with gestational age in normal pregnancies. Pregnant patients with acute pyelonephritis had a higher median (interquartile range) plasma sST2 concentration than those with a normal pregnancy [85 (47–239) ng/mL vs. 31 (14–52) ng/mL, p < .001]. Among patients with pyelonephritis, those with a positive blood culture had a median plasma concentration of sST2 higher than that of patients with a negative blood culture [258 (IQR: 75–305) ng/mL vs. 83 (IQR: 46–153) ng/mL; p = .03]. An elevated plasma concentration of sST2 ≥ 215 ng/mL had a sensitivity of 73% and a specificity of 95% (area under the receiver operating characteristic curve, 0.74; p = .003) with a positive likelihood ratio of 13.8 and a negative likelihood ratio of 0.3 for the identification of patients who had a positive blood culture. Conclusion sST2 is a candidate biomarker to identify bacteremia in pregnant women with pyelonephritis. Rapid identification of these patients may optimize patient care.

Use of intravoxel incoherent motion MRI to assess placental perfusion in normal and Fetal Growth Restricted pregnancies on their third trimester.

Intravoxel Incoherent Motion (IVIM) MRI is a non-invasive, in vivo techniques which can assess placental perfusion quantitatively, and be useful for evaluating placental microcirculation. Our primary aim was to investigate whether fetal growth restriction (FGR) pregnancies have different placental perfusion and diffusion compared with normal pregnancies using IVIM. A secondary aim was to investigate correlations between placental IVIM parameters and gestational age in normal pregnancy. This study population included 17 FGR pregnancies and 36 normal pregnancies between 28+3 to 38+0 weeks. All women underwent a MRI examination including an IVIM sequence with 9b-values on a 3.0T MRI system. The standard diffusion coefficeint (D), pseudodiffusion (D*) and perfusion fraction (f) were calculated. Placental f was significantly lower in the FGR group than that in the normal group (33.96±2.62(%) vs 38.48±5.31(%), p=0.002). Placental D and D* in two groups showed no statistical significance (P>0.05). Placental f moderately increased with increasing gestational age in normal pregnancies (r=0.411, p=0.013), and there existed a negative correlation between D values and gestational age (r=-0.390, p=0.019). The f values are able to distinguish FGR from normal pregnancies. It can be uses as a feasible index to evaluate placenta perfusion. Gestational age-associated changes in placental IVIM parameters likely reveal trajectories of microvascular perfusion fraction and diffusion characteristics in the normal developing placenta.

Evaluation of Correlation and Variability between Transcerebellar Diameter and Gestation age in Normal pregnancies

Background: Transcerebellar diameter is emerging as a promising indicator for assessment of the Gestational age. Present study was done with the objective to evaluate the Correlation and estimate the Variability between Transcerebellar Diameter and Gestation age in Normal pregnancies. Material and Methods: This Prospective Cross-sectional study was conducted on antenatal women of gestational age 15-40 weeks with normal singleton pregnancies cases attending the antenatal clinic and admitted in the Department of Obstetrics and gynecology, and sent to Department of Radiology KNSH MandC and IGMC Shimla for Antenatal USG Scan. In every patient TCD was measured. Data was analysed by appropriate statistical test using EPI INFO Version 7.2 software. Correlation coefficients were then used to compare TCD with Gestational age in normal pregnancies. Results: In this study 100 were normal pregnancies were studied. Mean age of study participants was 24.8±3.25years. Maximum number of patients (54%) was between 21-25 years followed by 26-30 years (32%). Maximum number of patients (44%) was between 30-36 weeks of gestation and least number of patients (5%) was between 12- 18weeks. It was noted that minimum variability was seen during 12-18 weeks i.e±0.34weeks and maximum variability in estimation of gestational age by transcerebellar diameter was seen between 24-30 weeks i.e.±1.38 weeks. It was observed that during second trimester TCD had the highest correlation with gestational age i.e.0.987 .It is also noted that TCD has relatively lesser correlation with gestational age in third trimester. i.e.0.788. Conclusion: Overall it was noted that TCD had a strong correlation with gestational age throughout the pregnancy which was statistically significant.

The amniotic fluid proteome changes with gestational age in normal pregnancy: a cross-sectional study

The cell-free transcriptome in amniotic fluid (AF) has been shown to be informative of physiologic and pathologic processes in pregnancy; however, the change in AF proteome with gestational age has mostly been studied by targeted approaches. The objective of this study was to describe the gestational age-dependent changes in the AF proteome during normal pregnancy by using an omics platform. The abundance of 1310 proteins was measured on a high-throughput aptamer-based proteomics platform in AF samples collected from women during midtrimester (16–24 weeks of gestation, n = 15) and at term without labor (37–42 weeks of gestation, n = 13). Only pregnancies without obstetrical complications were included in the study. Almost 25% (320) of AF proteins significantly changed in abundance between the midtrimester and term gestation. Of these, 154 (48.1%) proteins increased, and 166 (51.9%) decreased in abundance at term compared to midtrimester. Tissue-specific signatures of the trachea, salivary glands, brain regions, and immune system were increased while those of the gestational tissues (uterus, placenta, and ovary), cardiac myocytes, and fetal liver were decreased at term compared to midtrimester. The changes in AF protein abundance were correlated with those previously reported in the cell-free AF transcriptome. Intersecting gestational age-modulated AF proteins and their corresponding mRNAs previously reported in the maternal blood identified neutrophil-related protein/mRNA pairs that were modulated in the same direction. The first study to utilize an aptamer-based assay to profile the AF proteome modulation with gestational age, it reveals that almost one-quarter of the proteins are modulated as gestation advances, which is more than twice the fraction of altered plasma proteins (~ 10%). The results reported herein have implications for future studies focused on discovering biomarkers to predict, monitor, and diagnose obstetrical diseases.

PREDICTIVE VALUE OF SERUM TUMOR NECROSIS FACTOR-Α LEVEL AND UTERINE ARTERY DOPPLER INDICES AT 11-13 WEEKS' GESTATION IN CASES OF PREECLAMPSIA

Background: Cytokines are involved in fetoplacental development, and have been suggested to be the placental factor capable of damaging endothelial cells and contributing to many of the pathophysiological changes associated with preeclampsia. Uterine artery Doppler measurements show that impedance to flow in the uterine arteries decreases with gestational age in normal pregnancies. That impedance to flow is increased in established pre-eclampsia and fetal growth restriction (FGR), and this increased impedance predates the onset of the clinical syndrome of pre-eclampsia or FGR. Objective: To determine the validity of using combined biophysical (uterine artery Doppler) and biochemical (TNf- α) markers at 11-13 weeks for early screening for pre-eclampsia. Patients and methods: This study was conducted at the outpatient clinic at Sayed Galal Hospital, Al-Azhar University. This was a prospective cohort study that carried out on three hundred pregnant women who attended to outpatient clinic for antenatal care at 11-13 weeks of pregnancy with 48 missed cases (in the form of 2 IUFDs, 3 preterm labors, 30 miscarriages, and inability to follow 13 cases up). Results: There were no statistically significant differences between women who developed pre-eclampsia and who did not develop pre-eclampsia as regard maternal age and BMI. The mean concentration of sTNF- α, was higher in women who developed pre-eclampsia than in women who did not develop pre-eclampsia, and the differences were statistically significant. The best cut off value of the serum TNF- α is ≥14 pg/ml and at this value, we have sensitivity 67.8%; specificity 98%; PPV 79.4%; NPV 96.4%. The mean PI of the right and the left uterine arteries was higher in women who developed pre-eclampsia than in women who did not develop pre-eclampsia, and the differences were statistically significant. The best cutoff value of the mean uterine arteries was 1.7 and at this value we have 100% sensitivity, 84.4% specificity, 41.7% PPV, 100% NPV. Conclusion: The combination of TNF-α and UA Doppler waveforms almost invariably predicts PET and other adverse pregnancy outcomes; therefore, when used together, biochemistry and ultrasound screening have the ability to improve the sensitivity of screening for PET.

Diagnosis of fetal asphyxia depending on the change of blood flow of fetal middle cerebral artery and umbilical artery using color Doppler ultrasonography

Introduction: Ultrasonography has been used in the medical field for more than 50 years and estimated to be safe. The aim of the study was to set the criteria for the diagnosis of fetal asphyxia depending on the indices of fetal middle cerebral artery (FMCA) and umbilical artery (UA). Subjects and Methods: Color Doppler ultrasound (ALOKA-SSD1700) was used to confirm the dynamics of blood flow indices in fetal arteries. Among 417 pregnant women (327 normal and 90 with fetal distress), various arterial velocimetric parameters (ratio of systole to diastole and pulsatility and resistance indexes) were evaluated in the FMCA and UA. t-test and Chi-square test were used for the comparison of average and ratios, respectively, and Ridit test for grading of data. Results: The normal values of blood flow indices of FMCA with gestational age in normal pregnancy reached their peak at the 30th week and then gradually decreased. As for funicular artery, the indices reached their peak at the 28th week and then gradually decreased. The criterion for the diagnosis of fetal asphyxia depending on the blood flow of FMCA and UA is the ratio of resistance indices in the MCA or UA =.10, and the sensitivity, specificity, and accuracy of diagnosis were 86.7%, 98.8%, and 96.2%, respectively. Conclusion: The study confirmed the normal values and dynamics of the blood flow indices of FMCA and UA according to the number of weeks of normal pregnancy and determined criteria for the diagnosis of fetal asphyxia depending on those indices.

Fetal Gestational Age Determination using Ultrasound Placental Thickness.

Background:The purposes of this study are to sonographically measure the placental thickness (PT) in normal fetuses; to correlate it with gestational age (GA), fetal growth parameters, and estimated fetal weight (EFW); and to design a nomogram for the derived PT measurements.Methods:This was a hospital-based cross-sectional study on 400 women with apparently normal pregnancy within the age range of 18–45 years recruited from the Antenatal Clinic of our hospital. The fetal GA was estimated by the last menstrual period (LMP). The fetal growth parameters were determined using standard sonographic methods while the PT was measured at the level of the umbilical cord insertion site. PT was then correlated with GA, fetal growth parameters, and the EFW.Results:The mean PT (mean ± standard deviation) in the 1st, 2nd, 3rd trimesters and the whole duration of pregnancy were 14.5 ± 0.3 mm, 24.6 ± 3.9 mm, 34.8 ± 2.8 mm, and 29.6 ± 7.1 mm, respectively. PT ranged from 13.5 ± 1.9 mm at 11 weeks to 39.1 ± 0.6 mm at 40 weeks. PT (in mm) had a linear relationship and a statistically significant positive correlation with GA (in weeks) in all the trimesters, with most significant correlation recorded in the 2nd trimester (r = 0.79). There was also a statistically significant positive correlation between PT and the fetal growth parameters (biparietal diameter, head circumference, abdominal circumference, femur length and crown-rump length), and EFW. PT nomogram was developed from 11 to 40 weeks of gestation using a scatter plot with 95% confidence interval for our locality.Conclusion:PT has a linear relationship with GA, fetal growth parameters, and EFW and it can be used along with other fetal growth parameters to increase the accuracy for predicting GA in normal pregnancies, especially when the subject is not sure of or does not know her LMP.

Serum cytokine patterns in first half of pregnancy

IntroductionHuman pregnancy is a state of elevated maternal systemic inflammation, and pregnancy complications are often associated with a dysfunctional immune response. The network of cytokines reflects this complex immune activity, and broad serum cytokine profiling provides a new tool to understand the changes in immune status during pregnancy. ObjectiveThis study aimed to determine how maternal serum cytokine patterns change during the first half of pregnancy. MethodsMaternal peripheral serum samples collected at a mean gestation of 10, 13, 18 and 24 weeks were included from a prospective clinical study of healthy women (n = 110) in first half of normal pregnancy. The serum samples were analysed for 27 different cytokines using multiplex magnetic bead-based immunoassays, and high sensitivity C-reactive protein (CRP) was analysed by ELISA. Serum cytokine and CRP patterns were explored with linear mixed effects models (LMM) and multilevel partial least squares discriminant analysis (PLS-DA). ResultsSerum cytokine profiling provided partial overview of the maternal immune status and corresponding reference values for serum cytokine levels during the first half of pregnancy. Several cytokines decreased in concentration from first to second trimester. Cytokine pattern analysis revealed that chemokines provided the most sensitive measurement of variation with gestational age in normal pregnancies. The nine inflammatory cytokines showed the highest intra-group correlation during pregnancy, while CRP levels did not correlate with changes in the inflammatory cytokines. ConclusionChemokines showed the greatest gestational variation and inflammatory cytokines showed a strong intra-group correlation during the first half of pregnancy.

Serum Calcium and Magnesium Levels in Normal Ghanaian Pregnant Women: A Comparative Cross-Sectional Study.

BACKGROUND:Pregnancy is described as a normal physiologic state associated with various biochemical changes. Magnesium and calcium are essential macronutrients required for foetal growth. Complications associated with their deficiency during normal pregnancy include; low neonatal birth weight, pre-eclampsia, eclampsia and preterm labour. Changes in serum levels of magnesium and calcium in normal pregnancy have not been extensively studied among Ghanaian women.AIM:To determine the variation in serum magnesium and calcium levels with gestational age in normal pregnancy in Ghanaian women.METHODS:A hospital-based comparative cross-sectional study was conducted among 32 normal non-pregnant women (Group A) and 100 normal pregnant women (Group B) attending the clinic at the Korle-Bu Teaching hospital. The group B pregnant women were further divided into Group B1 (n = 33), Group B2 (n = 37) and Group B3 (n = 30) based on their pregnancy gestation as first, second and third trimester respectively. Blood samples were obtained from the antecubital vein of subjects and total serum calcium, magnesium, protein and albumin were estimated. Data obtained were analysed using SPSS for windows version 20. Analysis of variance (ANOVA) was employed to determine the statistical differences between the groups. A p-value of ≤ 0.05 was considered significant.RESULTS:Mean serum total calcium and magnesium in first, second and third trimester normal pregnant women were 2.14 ± 0.16, 2.13 ± 0.44, 2.13 ± 0.35 mmol/L and 0.77 ± 0.11, 0.77 ± 0.16 and 0.76 ± 0.14 mmol/L respectively. Mean serum total calcium and magnesium levels in non-pregnant women were 2.20 ± 0.16 and 0.80 ± 0.10 mmol/L respectively. There was a statistically non-significant difference in serum total calcium and magnesium between non-pregnant and normal pregnant women, with p-values of 0.779 and 0.566 respectively. Mean total serum protein and albumin in first, second and third-trimester normal pregnant women were 68.42 ± 10.37, 70.46 ± 6.84, 66.70 ± 7.83 g/L and 39.92 ± 3.22, 40.75 ± 8.06, 38.26 ± 3.02 g/L respectively. Mean total serum protein and albumin in non-pregnant women were 73.13 ± 7.02 and 42.94 ± 3.03 g/L respectively. Mean total serum protein and albumin levels were lower in pregnant women as compared to non-pregnant women with the difference being significant in the third trimester (p-values of 0.012 and 0.002).CONCLUSION:Total serum calcium and magnesium levels in normal pregnancy were non-significantly lower compared to non-pregnant women in Ghana. There was a reduction in total serum protein, and albumin levels during pregnancy with a significant reduction noticed during the third trimester compared to the non-pregnant state.

Foeto-placental parameters in normal pregnancy and factors affecting them.

The aim of this study was to evaluate foeto-placental (F/P) parameters, namely foetal birth weight, placental weight (PW) and F/P weight ratio, in normal pregnancy and factors affecting them. A retrospective study was conducted on labour ward data obtained over a period of 3 years (2015-2017). Only deliveries above 28-week gestational age which met other selection criteria were included in the study. Their sociodemographic parameters, PW, foetal birth weight, foetal outcome and Apgar scores were extracted from the delivery registers. The F/P weight ratio was calculated from the values obtained. All data collected were subjected to statistical analysis using SPSS version 20. The mean age ± standard error of mean of parturient was 31.84 ± 0.18 years. A larger proportion, 1455 (80.7%) of the women were booked. The mean gestational age ± standard deviation at delivery was 37.81 ± 2.72 weeks. Foetal weight (FW), PW and F/P weight ratio rise progressively with advancing gestational age in normal pregnancy, the FW rising faster than the placenta which gains weight slowly. The F/P ratio rises steadily initially and then abruptly from 42-week gestational age as the foetus outgrows the placenta, after which there is a sharp decline from 43-week gestational age. FW, PW and F/P ratio are significantly affected by gestational age and booking status (P = 0.000). Parity and foetal sex were found to have significant influence on FW alone (P = 0.026 and P = 0.000, respectively). This study clarifies the need to avoid undue prolongation of pregnancy beyond 42 weeks to avert adverse consequences which may be related to the differential growth in the foetus and placenta.

Placental thickness estimation by ultrasonography and its correlation with gestational age in normal pregnancies in late 2nd and 3rd trimester

Placental thickness estimation by ultrasonography and its correlation with gestational age in normal pregnancies in late 2nd and 3rd trimester

The maternal plasma proteome changes as a function of gestational age in normal pregnancy: a longitudinal study

Pregnancy is accompanied by dramatic physiological changes in maternal plasma proteins. Characterization of the maternal plasma proteome in normal pregnancy is an essential step for understanding changes to predict pregnancy outcome. The objective of this study was to describe maternal plasma proteins that change in abundance with advancing gestational age and determine biological processes that are perturbed in normal pregnancy. A longitudinal study included 43 normal pregnancies that had a term delivery of an infant who was appropriate for gestational age without maternal or neonatal complications. For each pregnancy, 3to6 maternal plasma samples (median, 5) were profiled to measure the abundance of 1125 proteins using multiplex assays. Linear mixed-effects models with polynomial splines were used to model protein abundance as a function of gestational age, and the significance of the association was inferred via likelihood ratio tests. Proteins considered to be significantly changed were defined as having the following: (1) >1.5-fold change between 8 and 40 weeks of gestation; and (2) a false discovery rate-adjusted value of P < .1. Gene ontology enrichment analysis was used to identify biological processes overrepresented among the proteins that changed with advancing gestation. The following results were found: (1) Ten percent (112 of 1125) of the profiled proteins changed in abundance as a function of gestational age; (2) of the 1125 proteins analyzed, glypican-3, sialic acid-binding immunoglobulin-type lectin-6, placental growth factor, C-C motif-28, carbonic anhydrase 6, prolactin, interleukin-1 receptor 4, dual-specificity mitogen-activated protein kinase 4, and pregnancy-associatedplasma protein-A had more than a 5-fold change in abundance across gestation (these 9 proteins are known to be involved in a wide range of both physiological and pathological processes, such as growth regulation, embryogenesis, angiogenesis immunoregulation, inflammation etc); and (3) biological processes associated with protein changes in normal pregnancy included defense response, defense response to bacteria, proteolysis, and leukocyte migration (false discovery rate, 10%). The plasma proteome of normal pregnancy demonstrates dramatic changes in both the magnitude of changes and the fraction of the proteins involved. Such information is important to understand the physiology of pregnancy and the development of biomarkers to differentiate normal vs abnormal pregnancy and determine the response to interventions.

Comparison of Amniotic Fluid Index at Different Gestational Age in Normal Pregnancy

Sonographic assessment of amniotic fluid has formed an integral and important component of pregnancy assessment of fetal wellbeing. Changes in amniotic fluid volume are associated with variable outcome of the fetus. Amniotic fluid index which is an objective means of assessing adequacy of amniotic fluid volume does not only vary with gestational age but also differs from population to population. The study determined the reference values of amniotic fluid index and compared the values with the established ranges throughout gestation in uncomplicated singleton pregnancies among women attending our antenatal care facility. This was a longitudinal prospective assessment of amniotic fluid index in eighty six healthy pregnant women with singleton pregnancies recruited at 20 to 22 weeks of gestation and followed up to 41 weeks and 3 days. The patients recruited at 20 weeks had amniotic fluid measurements at recruitment and 4 weeks apart until 40 weeks gestation. Those recruited at 22 weeks had it also at recruitment and 4 weekly with the last estimation at 41 weeks +3 days. These measurements were plotted against their respective gestational ages. The graph was then analyzed using statistical and graphical packages of SPSS version 21. The study populations mean, 5th and 95th percentiles was documented and discussed appropriately. A total of 414 readings were obtained from 81 subjects who underwent more than 3 measurements. Analysis of the data obtained shows a rising AFI with a mean 28 weeks and, thereafter gradually fell till term. The mean age obtained in the study group compared with that of Caucasians showed statistically significant difference (P=0.014). Also, comparison with Chama et al. showed obvious statistical difference at the lower limit (5th percentile; P=0.007, 50th percentile; P=0.006) but no differences at the upper limit (95th percentile; P=0.726). Amniotic fluid index values appear to be differing in different population. The reference range of AFI used in clinical practice should therefore be based on data obtained from local population.

Mitochondrial – Endoplasmic reticulum interactions in the trophoblast: Stress and senescence

Placental stress has been implicated in the pathophysiology of complications of pregnancy, including growth restriction and pre-eclampsia. Initially, attention focused on oxidative stress, but recently mitochondrial and endoplasmic reticulum stress have been identified. Complex molecular interactions exist among these different forms of stress, making it unlikely that any occurs in isolation. In part, this is due to close physiological connections between the two organelles principally involved, mitochondria and the endoplasmic reticulum (ER), mediated through Ca2+ signalling. Here, we review the involvement of the mitochondria-ER unit in the generation of stress within the trophoblast, and consider consequences for obstetric outcome. Mild stress may induce adaptive responses, including upregulation of antioxidant defences and autophagy, while moderate levels may affect stem cell behaviour and reduce cell proliferation, contributing to the growth-restricted phenotype. High levels of stress can stimulate release of pro-inflammatory cytokines and anti-angiogenic factors, increasing the risk of pre-eclampsia. In addition, chronic stress may promote senescence of the trophoblast, which in other cell types leads to a pro-inflammatory senescence-associated secretory phenotype. Evidence from rodents suggests that a degree of trophoblastic stress develops with increasing gestational age in normal pregnancies. The increase in maternal concentrations of soluble fms-like tyrosine kinase-1 (sFlt-1) and reduction in placental growth factor (PlGF) suggest the same may occur in the human, starting around 30 weeks of pregnancy. Placental malperfusion, or co-existing maternal conditions, such as diabetes, will exacerbate that stress. Amelioration of trophoblastic stress should remain a research priority, but will be difficult due to the complexity of the molecular pathways involved.

Trends of vital signs with gestational age in normal pregnancies: a systematic review protocol

IntroductionVital signs (blood pressure, heart rate, temperature, oxygen saturation and respiratory rate) are thought to undergo changes during and immediately after pregnancy. However, these physiological changes are not taken into...

Evaluación del crecimiento fetal mediante la medida ultrasonográfica del cerebelo. Estudio en el Hospital Nacional Cayetano Heredia

OBJETIVO: Obtener un nomograma que relaciones la curva de crecimiento transverso del cerebelo fetal con la edad gestacional en gestantes normales. DISEÑO: Estudio de tipo transversal, entre marzo y julio de 2000, en el Departamento de Obstetricia y Ginecología del Hospital Nacional Cayetano Heredia de Lima. MATERIAL Y MÉTODOS: Se evaluó 198 gestantes entre 15 y 38 semanas de gestación normal. Se realizó las medidas biométricas múltiples fetales para determinar la edad gestacional, incluyendo el diámetro transverso del cerebelo. Los datos fueron sometidos un programa de regresión cuadrática para el diámetro transverso del cerebelo. RESULTADOS: Con la determinación del diámetro transverso del cerebelo fetal por ultrasonido, se obtiene un nomograma, para la edad gestacional, siendo válido para su estimación (R2=0,9511, P&lt;0,0005). CONCLUSIONES: La medida ultrasonográfica del diámetro transverso del cerebelo fetal proporciona una buena información para determinar la edad gestacional en el embarazo normal y sus medidas en milímetros concuerdan con edad gestacional entre las 19 y 25 semanas.

Difference between Vascularization Indexes of the Placenta in Severe Pre-eclampsia and Normal Pregnancy by Three-dimensional Power Doppler Ultrasound

ABSTRACT Aim The object of this study was to analyze the vascularization index of three-dimensional (3D) power Doppler ultrasound (PDUS) of the placenta in severe pre-eclampsia compared with normal pregnancy conditions by vascular biopsy sampling sphere. Subjects and methods This study is a prospective longitudinal observational study on 80 pregnant women which divided into 2 groups: Group I (study group) were 40 pregnant women with severe pre-eclampsia, group II (control group) were 40 pregnant women without disorder. Variables examined in this study were vascular index (VI), flow index (FI) and vascular flow index (VFI) of the 3D-PD placental perfusion. Its correlation to gestational age in normal pregnancy compared with the condition of preeclampsia were obtained by taking multiple biopsy sampling vascular sphere. All pregnant women underwent 3D PD-US examination (single examination only), data volume recorded of the placenta allows for off-line analysis without the presence of the patient, thus allowing the data analysis done anywhere and anytime by observers for the comparative analysis of interobserver reliability. Results The placenta can be visualized perfectly in both of the study group and also the control group. Average Kappa value for the acquisition of placental vascularization index measurements with 3D PD-US was 0.72 (0.61-0.82), 0.73 (0.65-0.82) and 0.71 (0.61-0.81) for VI, FI and VFI in the range of 20 to 38 weeks showed good interobserver reliability. All 3D power Doppler indices had a significant association with gestational age, with VI showed a less significant relationship (r = 0.207, p = 0.0139) and FI has the most significant relationship (r = 0.582, p &lt; 0.001). FI index increased progressively with gestational age, while the VI index values indicate dispersion pattern and reached a plateau from week 30 onwards. Entering week 37th, there was a decrease in the value of the index VI until the end of pregnancy. Meanwhile, VFI index appears to resemble the pattern of a combination of both VI and FI index (r = 0.692, p &lt;0.001). Conclusion All parameters of 3D power Doppler index was lower in the severe pre-eclampsia compared with normal pregnancy. 3D PD-US can be used to assess the vascularization of the placenta and the intensity of intra-placental blood flow. Placental vascular biopsy method is fairly efficient way to perform routine evaluations evolution of placental vascular branch during pregnancy. How to cite this article Andonotopo W, Kristanto H, Dewantiningrum J, Pramono BA. Difference between Vascularization Indexes of the Placenta in Severe Pre-eclampsia and Normal Pregnancy by Three-dimensional Power Doppler Ultrasound. Donald School J Ultrasound Obstet Gynecol 2014;8(4):329-335.

In vivo31P-MR spectroscopy in normal pregnancy, early and late preeclampsia: A study of placental metabolism

IntroductionPreeclampsia affects about 3% of pregnancies and the placenta is believed to play a major role in its pathophysiology. Lately, the role of the placenta has been hypothesised to be more pronounced in preeclampsia of early (<34 weeks) rather than late (≥34 weeks) onset. 31P Magnetic Resonance Spectroscopy (MRS) enables non-invasive, in vivo studies of placental metabolism. Our aim was to study placental energy and membrane metabolism in women with normal pregnancies and those with early and late onset preeclampsia. MethodsThe study population included fourteen women with preeclampsia (five with early onset and nine with late onset preeclampsia) and sixteen women with normal pregnancy (seven with early and nine with late pregnancy). All women underwent a 31P-MRS examination of the placenta. ResultsThe phosphodiester (PDE) spectral intensity fraction of the total 31P signal and the phosphodiester/phosphomonoester (PDE/PME) spectral intensity ratio was higher in early onset preeclampsia than in early normal pregnancy (p = 0.03 and p = 0.02). In normal pregnancy the PDE spectral intensity fraction and the PDE/PME spectral intensity ratio increased with increasing gestational age (p = 0.006 and p = 0.001). DiscussionSince PDE and PME are related to cell membrane degradation and formation, respectively, our findings indicate increased cell degradation and maybe also decreased cell proliferation in early onset preeclampsia compared to early normal pregnancy, and with increasing gestational age in normal pregnancy. ConclusionsOur findings could be explained by increased apoptosis due to ischaemia in early onset preeclampsia and also increased apoptosis with increasing gestational age in normal pregnancy.

Placental perfusion in normal pregnancy and early and late preeclampsia: A magnetic resonance imaging study

ObjectiveOur primary aim was to investigate if women with early or late preeclampsia have different placental perfusion compared with normal pregnancies. A secondary aim was to investigate if placental perfusion changes with increasing gestational age in normal pregnancy. MethodsThe study population included thirteen women with preeclampsia (five with early and eight with late preeclampsia) and nineteen women with normal pregnancy (ten with early and nine with late pregnancy). Early was defined as <34 weeks and late as ≥34 weeks gestation. All women underwent a magnetic resonance imaging (MRI) examination including a diffusion weighted sequence at 1.5 T. The perfusion fraction was calculated. ResultsWomen with early preeclampsia had a smaller placental perfusion fraction (p = 0.001) and women with late preeclampsia had a larger placental perfusion fraction (p = 0.011), compared to women with normal pregnancies at the corresponding gestational age. The placental perfusion fraction decreased with increasing gestational age in normal pregnancies (p = 0.001). ConclusionBoth early and late preeclampsia differ in placental perfusion from normal pregnant women. Observed differences are however in the opposite direction, suggesting differences in pathophysiology. Placental perfusion decreases with increasing gestational age in normal pregnancy.