Gestation In Normal Pregnancies Research Articles

Cervicovaginal Fetal Fibronectin Levels in Preterm Labor: Just Association or Reliable Screening Biomarker

Background: Preterm birth (PTB) is a chief reason for neonatal illness and death. Prediction of PTB can prevent complications. The cervico-vaginal fetal fibronectin (fFN) test is a good predictor for preterm labor (PTL) within 7 to 14 days from testing. The levels of fFN are high during the first 16 to 22 weeks of gestation in normal pregnancy before it drops to very low values and rises over again as the gestation reaches term. The current work aimed to assess the association and reliability of cervicovaginal fFN in predicting PTL. Patient and method: The study was cross-sectional that included hundred pregnant (aging from 20–34 years), gestational age ranging (from 24–34 weeks), and presented with abdominal pain. All applicants’ Detailed medical history regarding age, gravidity, and parity were taken from all applicants. Gestational age was calculated through general examination and abdominal and vaginal examination. During speculum vaginal examination, fFN samples were taken from the cervix and were examined for fFN using the quick check for assay. Statistical scrutiny was carried out by SPSS version 17. A p ≤ 0.05 was measured as significant. Result: The mean age was (27.53 ± 4.23), range (of 20–34). Positive fFN results were detected in only (22%) of patients. Around two-thirds of the women end their pregnancy by normal vaginal delivery. Less than half (45.5%) of the included women delivered within one week after presentation, around 1/3rd (31.8%) delivered after the second week, and only 22.2% delivered during the first day of presentation. There was a significant association between pregnancy outcome and fFN results. A majority (90.9%) of patients end with preterm labor during 2 weeks of follow-up were presented with positive fetal fibronectin. The majority (90.9%) of patients end with preterm labor during 2 weeks of follow-up were presented with positive fFN results. There were non-significant variations between means of gestational ages, parity, and gestational age/weeks between those with positive and negative fFN results. Conclusion: Among pregnant women with uterine contraction before advanced cervical dilatation, the presence of cervicovaginal fFN is an associated and reliable screening test in predicting the risk of PTL.

Gestational Age Dependence of the Maternal Circulating Long Non-Coding RNA Transcriptome During Normal Pregnancy Highlights Antisense and Pseudogene Transcripts.

In the post-genomic era, our understanding of the molecular regulators of physiologic and pathologic processes in pregnancy is expanding at the whole-genome level. Longitudinal changes in the known protein-coding transcriptome during normal pregnancy, which we recently reported (Gomez-Lopez et al., 2019), have improved our definition of the major operant networks, yet pregnancy-related functions of the non-coding RNA transcriptome remain poorly understood. A key finding of the ENCODE (Encyclopedia of DNA Elements) Consortium, the successor of the Human Genome Project, was that the human genome contains approximately 60,000 genes, the majority of which do not encode proteins. The total transcriptional output of non-protein-coding RNA genes, collectively referred to as the non-coding transcriptome, is comprised mainly of long non-coding RNA (lncRNA) transcripts (Derrien et al., 2012). Although the ncRNA transcriptome eclipses its protein-coding counterpart in abundance, it has until recently lacked a comprehensive, unbiased, genome-scale characterization over the timecourse of normal human pregnancy. Here, we annotated, characterized, and selectively validated the longitudinal changes in the non-coding transcriptome of maternal whole blood during normal pregnancy to term. We identified nine long non-coding RNAs (lncRNAs), including long intergenic non-coding RNAs (lincRNAs) as well as lncRNAs antisense to or otherwise in the immediate vicinity of protein-coding genes, that were differentially expressed with advancing gestation in normal pregnancy: AL355711, BC039551 (expressed mainly in the placenta), JHDM1D-AS1, A2M-AS1, MANEA-AS1, NR_034004, LINC00649, LINC00861, and LINC01094. By cross-referencing our dataset against major public pseudogene catalogs, we also identified six transcribed pseudogenes that were differentially expressed over time during normal pregnancy in maternal blood: UBBP4, FOXO3B, two Makorin (MKRN) pseudogenes (MKRN9P and LOC441455), PSME2P2, and YBX3P1. We also identified three non-coding RNAs belonging to other classes that were modulated during gestation: the microRNA MIR4439, the small nucleolar RNA (snoRNA) SNORD41, and the small Cajal-body specific ncRNA SCARNA2. The expression profiles of most hits were broadly suggestive of functions in pregnancy. These time-dependent changes of the non-coding transcriptome during normal pregnancy, which may confer specific regulatory impacts on their protein-coding gene targets, will facilitate a deeper molecular understanding of pregnancy and lncRNA-mediated molecular pathways at the maternal-fetal interface and of how these pathways impact maternal and fetal health.

Contrast-enhanced ultrasound evaluation of placental perfusion in brachicephalic bitches

The present study aimed to investigate placental hemodynamics to determine quantitative and qualitative parameters for pregnant brachycephalic bitches as well as describe placental vascularization and perfusion in females with fetal abnormalities close to delivery. Forty-four healthy fetuses from 22 brachycephalic bitches and 9 fetuses with gestational abnormalities (anasarca and hydrocephalus) from 8 brachycephalic bitches were evaluated. All female dogs were artificially inseminated intravaginally and underwent cesarean section at the end of gestation. Pregnancy diagnosis was made on the 25th day and experimental evaluations were performed on Days 25 (M1), 45 (M2), and 58 (M3) of gestation in normal pregnancies. Fetuses with gestational abnormalities were evaluated at the last time point. Biometric values of the fetuses were determined by B-mode and vascular indices by Doppler fluxometry of the umbilical artery, whereas qualitative assessment of contrast filling and quantitative parameters of placental perfusion were performed using CEUS. Parameter comparisons among the examined fetuses (normal and abnormal) and between the moments (M1, M2, and M3) were performed by Student's t-test and ANOVA tests, and then correlated using the Spearman test. In healthy fetuses, systolic and diastolic velocities as well as the time averages of minimum and maximum velocities increased significantly from M2 to M3 (P < 0.05), whereas the pulsatility index (P < 0.043) and vascular resistance (P < 0.001) decreased. Contrast distribution was always homogeneous in placental tissues and CEUS filling parameters remained constant during the evaluated periods (P < 0.05). In fetuses with hydrops, Doppler values were similar to those obtained in healthy subjects (P > 0.05), but CEUS evaluation demonstrated a heterogeneous distribution with lower intensity of placental tissue filling and a delay in perfusion time (P < 0.05) with a diagnostic accuracy of 75%. The association of dopplerfluxometry and CEUS allowed evaluation of qualitative and quantitative parameters of physiological pregnancy hemodynamics in all gestational thirds without evidence of significant changes in the physiology of the maternal-fetal binomial, and CEUS was shown to be applicable in the detection of failures in placental vascular filling (tissue dysfunction) in fetuses with anasarca and hydrocephaly.

Placental function and fetal weight are associated with maternal hemodynamic indices in uncomplicated pregnancies at 35–37 weeks of gestation

Over the years, there has been an increasing interest in the assessment of maternal hemodynamic responses during pregnancy. With the use of both noninvasive devices and/or maternal echocardiography, it has been shown that mothers who have pregnancy complications have altered hemodynamics compared with those who have uncomplicated pregnancies. It also has been suggested that preexisting maternal cardiac changes might drive the development of complications in pregnancy that are associated with impaired placentation. To understand, however, this potential link in complicated pregnancies, it is important to clarify whether placental function is associated with maternal cardiac functional indices in normal pregnancies. To determine whether placental function, perfusion, and fetal weight are associated with maternal cardiac hemodynamic responses at 35-36 weeks of gestation in normal pregnancies. Prospective screening of women attending Kings' College Hospital for routine hospital visit at 35-37 weeks' gestation. We recorded maternal characteristics and measured mean arterial pressure, uterine artery pulsatility index, sonographic estimated fetal weight, and serum placental growth factor and soluble fms-like tyrosine kinase 1. We also performed maternal echocardiogram to assess cardiac output and peripheral vascular resistance as well as indices of diastolic and systolic function, including global longitudinal systolic function and left ventricular mass indexed to body surface area. We studied 1386 women. Maternal characteristics were associated with both maternal hemodynamics and functional and structural indices. Uterine artery pulsatility index was associated with left ventricular mass (P=.03) and global longitudinal systolic function (P=.017). There were significant nonlinear associations between placental growth factor and cardiac output and peripheral vascular resistance (P<.001 for both) and between soluble fms-like tyrosine kinase 1 and peripheral vascular resistance (P=.018). Estimated fetal weight was associated with maternal cardiac output (mean increase=0.186, 95% confidence interval, 0.133-0.238, P<.001) and peripheral vascular resistance (mean decrease=-0.164, 95% confidence interval, -0.217 to -0.111, P<.001). No association was noted between placental and fetal parameters and maternal cardiac functional and structural indices. In multivariable analysis, placental growth factor remained strongly associated with maternal cardiac output and peripheral vascular resistance (P=.002 for both) over and above maternal characteristics and estimated fetal weight. Estimated fetal weight was associated with left ventricular mass (0.102, 95% confidence interval, 0.044-0.162, P=.001). The results of this study suggest a strong link between maternal hemodynamic responses and fetoplacental needs across the whole spectrum in normal pregnancies. These findings would also indicate that to diagnose maternal cardiac dysfunction in pregnancies complicated by impaired placentation a more extensive echocardiographic assessment might be needed rather than relying on hemodynamics which are strongly associated with fetoplacental indices.

217: Longitudinal assessment of placental tissue homogeneity in normal pregnancies using a novel ultrasound tool

Pathologic studies suggest a change in placental tissue structure in complicated pregnancies. Intensity Analysis (IA) is a novel noninvasive technology that measures tissue homogeneity by analyzing the statistical value of the acquired echo signal amplitude within a certain region of interest (ROI). The measurement is compared to an estimated variance of normal or reference tissue. Normalized Local Variance [NLV], is quantified and displayed in color maps, representing distribution of intensities within the ROI. As IA-NLV increases, homogeneity of tissue decreases. To our knowledge, IA of placental tissue has not been measured longitudinally in normal pregnancies. Our objective was to longitudinally evaluate IA of placental tissue in normal pregnancies. Normal pregnant women with singletons were consented for serial US exams starting between 12 0/7 and 13 6/7 weeks. US was performed every 2 weeks until 16 weeks, then every 4 weeks until delivery. IA of placenta was longitudinally measured on sagittal section of the placenta at level of cord insertion. The average of 3 measurements per US examination was used for analysis. Women with BMI > 30 Kg/m2 at enrollment or who developed any maternal or fetal complication were excluded. Linear and polynomial models assessed for best fit of data. 54 women were included in this analysis. 8 US were performed per pregnancy. The change in longitudinal NLV of the IA throughout gestation is shown in Figure 1. Cubic polynomial model represented the best fit of NLV with gestational age. NLV increased with advancing gestation. Non-invasive assessment of placental tissue structure with IA is feasible. Our data show reduction in homogeneity of placental tissue with advancing gestation in normal pregnancies. This NLV nomogram can be used as a reference to assess placental tissue homogeneity in complicated pregnancies.

Variations of plasma D-dimer level at various points of normal pregnancy and its trends in complicated pregnancies: A retrospective observational cohort study.

D-Dimer (DD) is the smallest fragment of plasmin-mediated cleavage of fibrin. There is a progressive increase in DD concentration with advancing gestation in normal pregnancies, making the upper limit of 0.5 μg/ml used in non-pregnant population an unfavorable marker during pregnancy. Coagulation and fibrinolysis parameters are also markedly disturbed in pregnancies complicated by various pathologies.We designed this retrospective observational cohort study to investigate the trimester specific reference range for DD throughout normal pregnancy, and to compare the distribution of DD in third trimester healthy pregnancies and those complicated by preeclampsia (PE), severe preeclampsia (SPE), gestational diabetes mellitus (GDM), premature rupture of membranes (PROM) and preterm premature rupture of membranes (PPROM). In addition, we aimed to determine the diagnostic value of DD in PE and SPE.In this retrospective observational cohort study, 250 normal and 178 complicated pregnancies were included. Normal pregnancies included 88-first trimester, 101-second trimester and 61-third trimester pregnancies. Complicated pregnancy included 34 PE, 44 SPE, 32 GDM, 33 PROM, and 35 PPROM cases during the third trimester. Predefined exclusion criteria were used.The period of gestation (POG) accounted for 41.9% of the variance in DD, with strong correlation between the POG and DD. The trimester specific reference intervals were computed. The distribution for severe preeclampsia was statistically different compared to other categories in the third trimester. This exceptional distribution led to the generation of a receiver operating characteristic (ROC) curve with an area under curve of 0.828, attesting its possible role in predicting severe preeclampsia.We determined trimester specific reference intervals of DD. The role of DD has been explored, and it may be of diagnostic value in severe preeclampsia.

Insulin Stimulates GLUT4 Trafficking to the Syncytiotrophoblast Basal Plasma Membrane in the Human Placenta.

Placental transport capacity influences fetal glucose supply. The syncytiotrophoblast is the transporting epithelium in the human placenta, expressing glucose transporters (GLUTs) and insulin receptors (IRs) in its maternal-facing microvillous plasma membrane (MVM) and fetal-facing basal plasma membrane (BM). The objectives of this study were to (i) determine the expression of the insulin-sensitive GLUT4 glucose transporter and IR in the syncytiotrophoblast plasma membranes across gestation in normal pregnancy and in pregnancies complicated by maternal obesity, and (ii) assess the effect of insulin on GLUT4 plasma membrane trafficking in human placental explants. Placental tissue was collected across gestation from women with normal body mass index (BMI) and mothers with obesity with appropriate for gestational age and macrosomic infants. MVM and BM were isolated. Protein expression of GLUT4, GLUT1, and IR were determined by western blot. GLUT4 was exclusively expressed in the BM, and IR was predominantly expressed in the MVM, with increasing expression across gestation. BM GLUT1 expression was increased and BM GLUT4 expression was decreased in women with obesity delivering macrosomic babies. In placental villous explants, incubation with insulin stimulated Akt (S473) phosphorylation (+76%, P = 0.0003, n = 13) independent of maternal BMI and increased BM GLUT4 protein expression (+77%, P = 0.0013, n = 7) in placentas from lean women but not women with obesity. We propose that maternal insulin stimulates placental glucose transport by promoting GLUT4 trafficking to the BM, which may enhance glucose transfer to the fetus in response to postprandial hyperinsulinemia in women with normal BMI.

Apparent systemic 11ß-dehydroxysteroid dehydrogenase 2 activity is increased in preeclampsia but not in intrauterine growth restriction.

The enzyme 11ß-dehydroxysteroid dehydrogenase 2 (11ß-HSD2) converts active cortisol (F) to inactive cortisone (E). A reduced 11ß-HSD2 activity in the placenta has been demonstrated for prematurity, low birth weight, and preeclampsia. We hypothesized that disturbed placental function rather than a maternal response contributes to decreased 11ßHSD2 activity as reflected by a diminished conversion of F to E. Hence, the aim of the present study was to estimate the systemic activity of 11ß-HSD2 throughout gestation and in pregnancies complicated by preeclampsia (PE) and intrauterine growth restriction (IUGR) by calculating maternal serum F/E ratios. A total of 188 maternal serum samples were analyzed for nine glucocorticoid metabolites by gas chromatography-mass spectrometry (GC-MS) and F/E ratios were calculated. Study Group A: In a longitudinal set 33 healthy pregnant women were analyzed at three different time points throughout gestation and one postpartum. Study Group B: Cross-sectionally additional 56 patients were enrolled. We compared patients with PE (N = 14) and IUGR (N = 14) with gestational age matched healthy controls (CTRL = 28). Group A: The apparent 11β-HSD2 activity dropped in the second trimester being restored to first trimester levels (P value = 0.016). Group B: The 11β-HSD2 activity was high in PE (P value < 0.05) but not in the IUGR group as compared to CTRL. The increased apparent serum 11β-HSD2 activity observed with advancing gestation in normal pregnancy may reflect an elevated general increase in enzyme activity due to a higher placental mass. The high systemic 11β-HSD2 activity in PE but not in IUGR however suggests an increased F deactivation in maternal tissue in PE rather than in the placenta since placental insufficiency in the absence of PE does not significantly alter F/E ratio.

Dlx3 and GCM-1 functionally coordinate the regulation of placental growth factor in human trophoblast-derived cells.

Placental growth factor (PGF) is abundantly expressed by trophoblast cells within human placentae and is important for trophoblast development and placental vascularization. Circulating maternal serum levels of PGF are dynamically upregulated across gestation in normal pregnancies, whereas low circulating levels and placental production of PGF have been implicated in the pathogenesis of preeclampsia and other gestational diseases. However, the underlying molecular mechanism of regulating PGF expression in the human placenta remains poorly understood. In this study, we demonstrated that transcription factors Distal-less 3 (DLX3) and Glial cell missing-1 (GCM1) were both sufficient and required for PGF expression in human trophoblast-derived cells by overexpression and knockdown approaches. Surprisingly, while DLX3 and GCM1 were both positive regulators of PGF, co-overexpression of DLX3 and GCM1 led to an antagonist effect on PGF expression on the endogenous gene and a luciferase reporter. Further, deletion and site-directed mutagenesis studies identified a novel regulatory element on the PGF promoter mediating both DLX3- and GCM1-dependent PGF expression. This regulatory region was also found to be essential for the basal activity of the PGF promoter. Finally, Chromatin-immunoprecipitation (ChIP) assays revealed colocalization of DLX3 and GCM1 at the identified regulatory region on the PGF promoter. Taken together, our studies provide important insights into intrinsic regulation of human placental PGF expression through the functional coordination of DLX3 and GCM1, and are likely to further the understanding of pathogenesis of PGF dysregulation in preeclampsia and other disease conditions.

Serum levels of GDF15 are reduced in preeclampsia and the reduction is more profound in late-onset than early-onset cases

BackgroundPreeclampsia is a pregnancy specific disorder affecting 3–5% of pregnancies worldwide. It is clinically divided into early-onset and late-onset subtypes. Placental factors are involved in the pathogenesis of preeclampsia. Growth differentiation factor 15 (GDF15), a protein of the transforming growth factor beta superfamily, is highly expressed in the placenta. However, it is unclear whether the circulating levels of GDF15 are altered in preeclampsia at the time of or prior to disease presentation. MethodsSerum samples across three trimesters from 29 healthy pregnancies, third trimester sera from 34 women presenting with preeclampsia (early-onset n=16, late-onset n=18) and 66 gestation-age-matched controls, and sera at 11–13weeks of pregnancy from women who later did (n=36) or did not (n=33) develop late-onset preeclampsia, were examined for GDF15 by ELISA. ResultsSerum GDF15 levels increased significantly with gestation in normal pregnancy. Serum GDF15 was significantly reduced in the third trimester in women presenting with preeclampsia compared to their gestation-age-matched controls. This reduction was apparent in both early-onset and late-onset subtypes, but it was more profound in late-onset cases. At 11–13weeks of gestation, however, serum levels of GDF15 were similar between women who subsequently did and did not develop late-onset preeclampsia. ConclusionSerum GDF15 increased with gestation age, reaching the highest level in the third trimester. Serum GDF15 was significantly reduced in the third trimester in women presenting with preeclampsia, especially in late-onset cases. However, serum GDF15 was not altered in the first trimester in women destined to develop late-onset preeclampsia.

Gender-specific reference charts for cardiotocographic parameters throughout normal pregnancy: a retrospective cross-sectional study of 9701 fetuses

ObjectiveTo establish reference values for cardiotocographic (CTG) parameters from 24 to 41 weeks of gestation in normal pregnancies. Study designRetrospective cross-sectional study, using the first antepartum tracing of singleton fetuses with normal pregnancy outcomes (term birth, normal birthweight, normal umbilical artery pH and Apgar scores, no intensive care unit admission). Cases were consecutively selected from a hospital electronic patient record, and analyzed using the OmniviewSisPorto 3.7 system. Variables were compared between male and female fetuses, by gestational age, and percentile curves were constructed. ResultsA total of 9701 tracings (corresponding to 9701 fetuses) were analyzed. All CTG parameters changed significantly throughout gestation in both genders, with a decrease in baseline and decelerations, and an increase in average long-term variability (LTV), average short-term variability (STV), accelerations and uterine contractions. The mean baseline value decreased 9bpm, and its range almost doubled from 24 to 40 weeks. Until 30 weeks the lower percentiles for average LTV were below 5bpm, and the minimum value for average STV was never below 1bpm. The proportion of tracings without accelerations decreased from 30.1% at 24-25 weeks to 0.5% at 39 weeks. The median number of decelerations was practically zero for all gestational ages. All CTG variables, except decelerations and uterine contractions, showed statistically significant gender differences: baseline was consistently higher in females, while average LTV and average STV tended to be lower in females throughout most of pregnancy. Separate percentile curves were constructed for male and female fetuses. ConclusionThis study provides reference values for CTG parameters throughout pregnancy, derived from the largest dataset of healthy fetuses published to date. For the first time, gender differences were clearly demonstrated in fetal life, and percentile curves constructed separately for male and female fetuses.

Serum HtrA1 is differentially regulated between early-onset and late-onset preeclampsia

HtrA1 (high temperature requirement A1) is a serine protease of the HtrA family. We have previously shown that the placenta expresses the highest level of HtrA1 mRNA compared to other tissues in the human. Others have reported that placental HtrA1 is significantly up-regulated in preeclampsia (PE), a pregnancy-specific multi-systemic disorder associated with new onset hypertension and proteinuria. However, it is unclear how serum HtrA1 changes in a normal pregnancy and whether it is altered in PE pregnancies. A sandwich ELISA highly specific to human HtrA1 and suitable for serum detection was developed and thoroughly validated. This assay was then applied to serum samples from different stages of normal pregnancy, as well as early-onset (<34 weeks) and late-onset (>34 weeks) PE pregnancies. Serum HtrA1 increased progressively with increasing gestation in normal pregnancies. However, this trend was perturbed in women with PE. Compared to respective gestation-age-matched normal pregnancies, HtrA1 serum levels were significantly increased in early-onset PE, but significantly reduced in late-onset PE. This is the first report to show a clear increase of HtrA1 in the maternal circulation during normal pregnancy, consistent with HtrA1 being highly expressed in the placenta. Importantly, this study identified that serum HtrA1 was altered differently in early-onset and late-onset PE pregnancies, highlighting the complex regulation of HtrA1 in the different subtypes. The significant increase of serum HtrA1 in early-onset PE suggests that it may be a potential biomarker for the diagnosis of early-onset PE at disease presentation.

736: Placental tumor necrosis factor-α levels throughout gestation in normal pregnancy

736: Placental tumor necrosis factor-α levels throughout gestation in normal pregnancy

A quantitative investigation of hemodynamic adaptation to pregnancy using uterine artery Doppler ultrasonography and finger photoplethysmography

Objective: Normal pregnancy is characterized by maternal hemodynamic adaptations of cardiovascular system and uterine artery. We aimed to investigate quantitatively the relationship between uterine artery Doppler (Ut AD) ultrasonography and finger photoplethysmography (PPG) in each of the three trimesters. Methods: Eighty normal pregnancy subjects were recruited from the nulliparous women with uncomplicated singleton pregnancy presenting for a routine ultrasound scan and divided into three groups according to their trimester. Comparative analysis were conducted between Ut AD ultrasonography and finger PPG within and across trimesters, particularly with focus on the relationship between Uterine Artery Resistance Index (UtA RI) and photoplethysmographic reflection index (PPG RI) throughout pregnancy. Additional 10 preeclampsia patients in third trimester were enrolled for comparison. Results: Both UtA RI and PPG RI were markedly decreased with gestation in normal pregnancy and generally consistent with each other in trend. The preeclampsia patients of third trimester were significantly higher in both indices, even more than normal pregnancy subjects of first trimester. Conclusions: The results of this study revealed clear relationship between UtA RI and PPG RI throughout pregnancy which could be exploited to enhance the potential ability in early recognition of pathophysiologic process in maternal adaptation and prediction of complicated pregnancy.

Reference Ranges for Ductus Venosus Velocity Ratios in Pregnancies With Normal Outcomes

The purpose of this study was to establish reference ranges for ductus venosus velocity ratios. Singleton pregnancies from 11 to 38 weeks with exactly established gestational ages (GAs) were recruited for the study. Pregnancies with fetal anomalies, growth abnormalities, maternal medical complications, stillbirth, birth weight below the 10th or above the 90th percentile, and neonatal anomalies were excluded. The ductus venosus pulsatility index for veins (PIV) and velocity ratios (S/v, S/D, v/D, S/a, v/a, and D/a, where S indicates ventricular systole [s-wave], v, ventricular end-systolic relaxation [v-descent], D, passive diastolic ventricular filling [D-wave], and a, active ventricular filling during atrial systole [a-wave]) were calculated. Separate regression models were fitted to estimate the mean and standard deviation at each GA for each ratio. A total of 902 velocity wave ratios and ductus venosus PIVs were used for reference ranges. The S/v, S/D, and v/D ratios were not changed with GA (P > .05 for all). The PIV and S/a, v/a, and D/a ratios were reduced with GA (P < .0001 for all). Significant reductions in the means and standard deviations of the PIV and S/a, v/a, and D/a ratios were observed between 17 and 18 weeks' gestation. Therefore, nomograms were separately created between 11 and 17 weeks and 18 and 38 weeks. We created reference ranges for ductus venosus velocity ratios between 11 and 38 weeks' gestation in normal pregnancies. These reference ranges may prove beneficial for evaluation of fetal conditions that are associated with cardiovascular abnormalities.

Fetal circulatory redistribution in normal and intra-uterine growth restriction (IUGR) pregnancies by volume blood flow (VBF)

IntroductionA number of studies have reported that ‘sparing’ or redistribution occurs in various vascular beds in IUGR. We took a global approach to assessing this redistribution using VBF.MethodWomen booking at...

Serum Concentrations of Soluble Flt-1 Are Decreased among Women with a Viable Fetus and No Symptoms of Miscarriage Destined for Pregnancy Loss

Miscarriage is the most common complication of pregnancy. Pre-clinical miscarriage has an estimated incidence of 30%, whilst clinical miscarriage has an incidence of 12-15%. Two thirds of pregnancies lost to miscarriage are believed to be attributable to defective placentation, thus a number of studies have sought to identify markers of defective placentation that could be used as clinical biomarkers of miscarriage. Decreased soluble FMS-like tyrosine kinase-1 (sFlt1), placental growth factor (PlGF), and soluble endoglin (sEng) in the maternal circulation during the first trimester have recently been proposed as potential markers of pregnancy loss. However, in these studies clinical samples were only obtained once women had presented with symptoms of miscarriage. In this study we prospectively screened serum samples collected from asymptomatic women with a viable fetus. We assessed maternal serum levels of sFlt1, PlGF and sEng across the first trimester of normal pregnancy and compared levels between women who continued to a live birth, to those who subsequently miscarried. Both sFlt1 and PlGF significantly (p≤0.05) increased across gestation in normal pregnancy with serum levels rising from 0.65±0.12 ng/ml at 6 weeks to 1.85±0.24 ng/ml at 12 weeks for sFlt1, and 57.2±19.2 pg/ml to 106±22.7 pg/ml for PlGF. sEng remained unchanged throughout the the first trimester. Importantly we detected a significant (35%, p≤0.05) decrease in sFlt1 levels between our control and miscarriage cohort, however there was significant overlap between cases and controls, suggesting serum sFlt1 is unlikely to be useful as a clinical biomarker in asymptomatic women. Nevertheless, our data suggests a dysregulation of angiogenic factors may be involved in the pathophysiology of miscarriage.

Established preeclampsia risk factors are related to patterns of blood pressure change in normal term pregnancy

Hypertension during pregnancy is one of the diagnostic criteria for preeclampsia. We investigated the pattern of blood pressure (BP) change across pregnancy and associations of risk factors for preeclampsia with BP changes in normal pregnancy. We examined repeat antenatal BP measurements (median 14 per woman) of 11,789 women from the Avon Longitudinal Study of Parents and Children cohort with a live-term birth and no evidence of preeclampsia or previous hypertension. Linear spline random effects models with knots at 18, 30 and 36 weeks gestation described changes in BP with gestational age. On average, SBP and DBP decreased slowly until 18 weeks and rose from 18 weeks onwards, with increasing rate at 30 weeks and then again at 36 weeks. In obese women, BP was higher at 8 weeks and rose more slowly between 18 and 30 weeks and more rapidly between 30 and 36 weeks than in normal-weight women. Nulliparous women had higher BP at 8 weeks and faster increases in DBP from 30 weeks and SBP from 36 weeks onwards than multiparas. Women who smoked throughout pregnancy had lower BP at 8 weeks and throughout pregnancy; women who only smoked in the first trimester soon attained the same pattern of change as never smokers. In twin pregnancies, BP rose more rapidly from 30 weeks onwards than in singleton pregnancies. Established preeclampsia risk factors are associated with higher BP in early pregnancy and faster BP increases later in gestation in normal pregnancy, suggesting a continuum of risk.

Maternal small arterial elasticity decreases with gestation in normal pregnancy

Changes in maternal blood pressure are seen in normal pregnancy. Mean arterial pressure falls until the end of the second trimester and then rises again to prepregnancy levels in the...

Potential mri biomarkers for placental structure and function at 1.5 T

MRI provides quantitative indices including relaxation time measurements, T1 and T2, which theoretically relate to placental composition and indices relating to perfusion, measured by Intra-Voxel Incoherent Motion (IVIM); related variables...