Fetal volume measurements in the first trimester of pregnancy with three-dimensional ultrasound

Preterm birth and a low birth weight are major complications with significant consequences for families and society. It is expected that these complications are the result of the intra-uterine conditions in the first trimester of pregnancy. If it would be possible to detect the fetus at risk early in pregnancy, then the obstetric care can be adjusted accordingly. Earlier reports suggested that fetal growth in the first trimester of pregnancy is of significant value in assessing these complications in pregnancy, the clinical value of these findings is unknown because of the small differences between normal and abnormal growth (Chapter 1). If the fetal size is measured with routine two-dimensional ultrasound, the differences between normal and abnormal fetal size are small. The extra third dimension with three-dimensional ultrasound is expected to give more information about fetal development. The fetal volume rises seven times faster than the crown-rump-length (routine two-dimensional measurement), so impaired fetal growth will be more obvious. This thesis describes in vitro and in vivo studies in order to analyze the still rather complex volume measurements with three-dimensional ultrasound. Furthermore the predictive value of fetal volume measurements in relation to pregnancy outcome is discussed. In vitro studies Three-dimensional volume measurements are expected to be of diagnostic value in general gynecologic and obstetric practice. Despite that the introduction of volume measurements with VOCAL (Volume Organ Computer Aided AnaLysis) was an advancement, the volume measurements are still rather time consuming and complex, as explained in Chapter 1. The learning curve for volume measurements with three-dimensional ultrasound and VOCAL were analyzed in Chapter 2. There is no significant learning curve for volume measurements with three-dimensional ultrasound. In addition, the measurements from inexperienced sonographers were similar to those of an expert. Chapter 3 describes the relation between the volume of an object and the measurement error in vitro for a range of volumes that are comparable to actual fetal volumes in the first trimester of pregnancy. The results show that the percentage error, i.e. absolute measurement error expressed as a percentage of the actual volume, was smaller for larger objects. One should be aware of the volume-dependent absolute and percentage measurement error when interpreting the measured values. Explorative research in order to develop and verify a more practical semi-automated method for volume calculations with 3DUS images is evaluated in Chapter 4. The results of this study show that mathematical volume calculations are possible with the newly developed semi-automated method. This method was successfully applied on a first trimester fetus, where the points of interest at the contour of the fetal head and body were detected. We also succeeded in detecting voxels in the whole contour, including the limbs, of a first trimester fetus with a gestational age of 12 weeks. In vivo studies The high inter- and intra-observer reliability of abdominal fetal volume measurements with three-dimensional ultrasound measurements of the fetal head and rump, i.e. an inter- and intra-class correlation of 0.934 and 0.994, respectively is discussed in Chapter 5. Because of all these promising results, a prospective cohort study was performed to determine whether it is possible to detect a fetus at risk for preterm birth and/or low birth weight by measuring the fetal volume with three-dimensional ultrasound in the first trimester of pregnancy, of which the study protocol is described in Chapter 6. The results of this prospective cohort study are reported in Chapter 7. The difference in mean percentage error between normal and complicated pregnancies (preterm birth and/or low birth weight) was neither significant nor clinically relevant. The fetal volumes of the neonates born after preterm birth and/or low birth weight are distributed throughout the range of the neonates born a normal birth weight, indicating that it is hard to distinguish the complicated pregnancies from the normal ones by fetal volume alone. Analysis for CRL as a predictor of a low birth weight and the analysis with the individual growth curves showed results similar to the original analysis, i.e. no significant or clinically relevant differences between the normal and complicated group. In conclusion, the measurement of the three-dimensional fetal volume in the first trimester of pregnancy is, by itself, not useful for detecting pregnancies at risk for preterm birth and/or low birth weight. The combination with biochemical markers can be subject of future research. If fetal volume measurements appears to be useful after all, then we know that there is no learning curve for the volume measurements with three-dimensional ultrasound and that the inter- and intraobserver reliability of these measurements are good. Further research concerning automated volume measurements or automated detection of the expected fetal shape might be helpful in pregnancy dating and detection of congenital anomalies

The Application of First‑Trimester Volumetry in Predicting Pregnancy Complications

The application of first trimester volumetry in predicting pregnancy complications is a promising and interesting field in Obstetrics and Radiology. This was a descriptive review of first trimester volumetry in predicting pregnancy complications over a period of 6 months (January 1st, 2013 to June 30th, 2013). A search of literature on first trimester volumetry published in English was conducted. Relevant materials on first trimester volumetry were selected. Placenta volumes (PV) and embryo volume/fetal volume ratios in the first trimester are correlated with crown rump length (CRL) or gestational age (GA). Measurement of PV or placental quotient (PV/CRL ratio) is an early assessment to identify impaired trophoblast invasion and predict subsequent development of intrauterine growth restriction (IUGR) or pre‑eclampsia (PE). In early onset IUGR due to triploidy, or trisomy 13 or 18, a larger deficit in fetal volume is observed compared to CRL. In obstetric sonography, standardization of the 3D volumetric methodology is needed to improve reproducibility of measurement. The accuracy of these measurements is uncertain and current applicability to practice is not fully accepted, therefore, the current methods are yet to be standardized and general applicability is uncertain. Volumetry holds a good promise as an extra method for predicting IUGR, PE, aneuploidy, miscarriages, or stillbirth but lack of standardization currently limits its applicability.Keywords: 3D ultrasound, first trimester, pregnancy complications, volumetr

Feasibility of three-dimensional reconstruction and automated measurement of fetal long bones using 5D Long Bone™

의과대학/석사Objective: To evaluate the feasibility of 5D Long Bone™ (5D LB™), a new technique that automatically archives, reconstructs images, and measures lengths of fetal long bones, to assess whether the direction of volume sweep influences fetal long bone measurements in three-dimensional (3D) ultrasound and 5D LB™, and to compare measurements of fetal long bone lengths obtained with 5D LB™ and those obtained with conventional two-dimensional (2D) and manual 3D techniques. Methods: This prospective study included 39 singleton pregnancies at 26+0 to 32+0 weeks of gestation. Multiple pregnancies, fetuses with multiple congenital anomalies, and mothers with underlying medical diseases were excluded. Fetal long bones of the lower extremities―the femur, tibia, and fibula were measured by 2D and 3D ultrasound, and 5D LB™, by an expert and non-expert examiner. First, we analyzed the 3D ultrasound and 5D LB™ data according to 2 different sweeping angles. We analyzed intra- and interobserver variability and agreement between ultrasound techniques. Paired t-test, interclass correlation coefficient (ICC), Bland-Altman plot and Passing-Bablok regression were used for statistical analysis. Results: There was no statistical difference between long bone measurements analyzed according to 2 different volume-sweeping angles by 3D ultrasound and 5D LB™. Intra- and interobserver variability were not significantly different among all 3 ultrasound techniques. Comparing 2D ultrasound and 5D LB™, the ICC for femur, tibia, and fibula was 0.91, 0.92, and 0.89, respectively. Conclusion: 5D LB™ is reproducible and comparable with conventional 2D and 3D ultrasound techniques for fetal long bone measurement.ope

Second trimester serum tests for Down's Syndrome screening

Background Down's syndrome occurs when a person has three copies of chromosome 21 - or the specific area of chromosome 21 implicated in causing Down's syndrome - rather than two. It is the commonest congenital cause of mental retardation. Noninvasive screening based on biochemical analysis of maternal serum or urine, or fetal ultrasound measurements, allows estimates of the risk of a pregnancy being affected and provides information to guide decisions about definitive testing. Objectives To estimate and compare the accuracy of second trimester serum markers for the detection of Down’s syndrome. Search methods We carried out a sensitive and comprehensive literature search of MEDLINE (1980 to May 2007), EMBASE (1980 to 18 May 2007), BIOSIS via EDINA (1985 to 18 May 2007), CINAHL via OVID (1982 to 18 May 2007), The Database of Abstracts of Reviews of Effectiveness (The Cochrane Library 2007, Issue 1), MEDION (May 2007), The Database of Systematic Reviews and Meta-Analyses in Laboratory Medicine (May 2007), The National Research Register (May 2007), Health Services Research Projects in Progress database (May 2007). We studied reference lists and published review articles. Selection criteria Studies evaluating tests of maternal serum in women at 14-24 weeks of gestation for Down's syndrome, compared with a reference standard, either chromosomal verification or macroscopic postnatal inspection. Data collection and analysis Data were extracted as test positive/test negative results for Down's and non-Down's pregnancies allowing estimation of detection rates (sensitivity) and false positive rates (1-specificity). We performed quality assessment according to QUADAS criteria. We used hierarchical summary ROC meta-analytical methods to analyse test performance and compare test accuracy. Analysis of studies allowing direct comparison between tests was undertaken. We investigated the impact of maternal age on test performance in subgroup analyses. Main results Fifty-nine studies involving 341,261 pregnancies (including 1,994 with Down's syndrome) were included. Studies were generally high quality, although differential verification was common with invasive testing of only high-risk pregnancies. Seventeen studies made direct comparisons between tests. Fifty-four test combinations were evaluated formed from combinations of 12 different tests and maternal age; alpha-fetoprotein (AFP), unconjugated oestriol (uE3), total human chorionic gonadotrophin (hCG), free beta human chorionic gonadotrophin (βhCG), free alpha human chorionic gonadotrophin (αhCG), Inhibin A, SP2, CA125, troponin, pregnancy-associated plasma protein A (PAPP-A), placental growth factor (PGF) and proform of eosinophil major basic protein (ProMBP). Meta-analysis of 12 best performing or frequently evaluated test combinations showed double and triple tests (involving AFP, uE3, total hCG, free βhCG) significantly outperform individual markers, detecting six to seven out of every 10 Down's syndrome pregnancies at a 5% false positive rate. Tests additionally involving inhibin performed best (eight out of every 10 Down's syndrome pregnancies) but were not shown to be significantly better than standard triple tests in direct comparisons. Significantly lower sensitivity occurred in women over the age of 35 years. Women who miscarried in the over 35 group were more likely to have been offered an invasive test to verify a negative screening results, whereas those under 35 were usually not offered invasive testing for a negative screening result. Pregnancy loss in women under 35 therefore leads to under ascertainment of screening results, potentially missing a proportion of affected pregnancies and affecting the accuracy of the sensitivity. Authors' conclusions Tests involving two or more markers in combination with maternal age are significantly more sensitive than those involving one marker. The value of combining four or more tests or including inhibin have not been proven to show statistically significant improvement. Further study is required to investigate reduced test performance in women aged over 35 and the impact of differential pregnancy loss on study findings

Nové ultrazvukové markery aneuploidií v prvém trimestru gravidity

Prenatální diagnostika se ubírá několika směry - vizualizací plodů a laboratorní biochemickou, cytogenetickou a molekulárně genetickou diagnostikou. Zatímco vizualizace neznamená a priori pro těhotenství přímé riziko, nezpůsobí zvyšení počtu komplikací, u laboratorních vyšetření tomu tak vždy není. Známá jsou rizika, která jsou spojena s invazivními metodami prenatální diagnostiky. Množství potenciálních nechtěnych těhotenskych komplikací a ztrát, technická a také ekonomická náročnost invazivní prenatální diagnostiky vedou ke snaze vyhledávat potenciálně afektované jedince metodami skríningu a tím minimalizovat nežádoucí dopad invazivní diagnostiky na těhotnenskou populaci. Čím přesnější vyhledávací kriteria jsou nalezena, tím menší bude počet těhotnych exponovanych invazivními vykony. Další možností, jak snížit počet nechtěnnych komplikací v souvislosti s invazivními vykony, je zjednodušení a zlepšení techniky odběrů fetálních vzorků v průběhu gravidity. V práci jsme se prioritně zabyvali dvěma oblastmi: zjištění vztahu mezi frakčním zkrácením levé a pravé komory a chromozomální vybavou plodu a zjištěním spolehlivosti nové metody odběru vody plodové a biopsie choria pomocí vakuovych zkumavek. Prokázali jsme, že vyšetření funkčních parametrů fetálního srdce již na konci I. trimestru je nejen...Prenatal diagnostics is headed in several directions - towards visualization of fetuses and biochemical, cytogenetic and molecular genetic diagnostics in laboratories. Whereas visualization of fetuses does not a priori represent any direct risk for pregnancy and does not increase the number of potential pregnancy complications, this is not always the case with the laboratory testing. There are known risks connected with invasive methods of prenatal diagnostics. The number of potential unintentional pregnancy complications and losses as well as the technical and economic aspects of invasive prenatal diagnostics lead to attempts of identifying ways of detecting any potentially affected individuals by screening methods, thus minimizing the undesirable impact of invasive diagnostics on the pregnant population. The more precise the selective criteria, the lesser the number of pregnant women exposed to invasive exams. Another way of decreasing the number of unintentional complications in relation to invasive diagnostics is to simplify and improve the fetal samples harvesting methods during pregnancy. The work primarily focused on two areas: Determination of the relation between fraction shortening of the left and right ventricles and a fetal chromosomal complement, and verification of reliability of a new method...Gynekologicko-porodnická klinika 1. LF UK a VFNDepartment of Obstetrics and Gynaecology First Faculty of Medicine and General University HospitalFirst Faculty of Medicine1. lékařská fakult