Ductus venosus as a marker of fetal growth in first trimester in a population of Colombian pregnant women / Ductus venoso como marcador de crecimiento fetal en primer trimestre en una población de gestantes colombianas

Abstract Objectives: to evaluate the relationship between the ductus venosus (DV) and the variables of fetal growth in the first trimester in a Colombian pregnant population. Methods: a descriptive cross-sectional study was carried out with secondary data obtained from a multicenter study.526 patients were included between weeks 11 and 14 for gestational ultrasound follow-up attended in three health care institutions in Bogotá, Colombia, between May 2014 and October 2018. A bivariate descriptive analysis was carried out where the relationship between the characteristics of the DV in the first trimester and ultrasound findings. Results: the flow wave of the DV in the first trimester was normal in the entire sample, with a pulsatility index of the ductus venosus (DVPI) of 0.96±0.18. In addition, a negative correlation was found between the crown-rump length (CRL) and the DVPI (p<0.05). Conclusion: there is a relationship between the DVPI regarding the CRL, indicating an interest in this early marker in relation to fetal growth alterations; however, more studies are required to determine the usefulness of this variable with respect to fetal growth.

Resumen Objetivos: evaluar la relación entre el ductus venoso (DV) y las variables del crecimiento fetal en primer trimestre en una población de gestantes colombianas. Métodos: se realizó un estudio transversal descriptivo con datos secundarios obtenidos de un estudio multicéntrico. Se incluyeron 526 pacientes entre las semanas 11 a 14 para seguimiento ecográfico gestacional atendidas en tres instituciones prestadoras de salud en Bogotá, Colombia, entre mayo del 2014 y octubre del 2018. Se realizó un análisis descriptivo bivariado donde se evaluó la relación entre las características del DV en primer trimestre y los hallazgos ecográficos. Resultados: la onda de flujo del DV en primer trimestre fue normal en la totalidad de la muestra, con un índice medio de pulsatilidad del ductus venoso (IPDV) de 0,96±0.18. Se encontró una correlación negativa entre la longitud cefalocaudal (LCC) y el IPDV (p<0.05). Conclusión: existe una relación entre el IPDV respecto a la LCC, señalando un interés de este marcador temprano en relación con las alteraciones del crecimiento fetal, sin embargo, se requieren más estudios para determinar la utilidad entre esta variable respecto al crecimiento fetal

The Application of Crown-Chin Length to Crown-Rump Length Ratio in Predicting Fetal Skeletal Dysplasia at First Trimester.

OBJECTIVE: To examine the feasibility of using crown-chin length (CCL) to crown-rump length (CRL) ratio in screening for skeletal dysplasia in the first trimester. METHODS: Four hundred and eighteen singleton pregnant women were recruited and the ratio of CCL to CRL was calculated according to gestational age. Fetuses with skeletal dysplasia were collected from database in the last 10 years. The CCL/CRL ratios were then calculated and the unpaired Student's t-test was to determine the significance of differences between normal fetuses and fetuses with skeletal dysplasia. Receiver operating characteristic curve was used to show the clinical sensitivity and specificity. RESULTS: In 418 normal fetuses, CCL increased linearly with gestation from a mean of 20 mm at 11+0 weeks to 37 mm at 13+6 weeks (CCL [mm] = 0.51-4 CRL, R2  = 0.824, P = .000). There was also a significant linear association between fetal CCL/CRL ratio and CRL, from a mean of 0.48 at 11+0 weeks to 0.41 at 13+6 weeks (CCL/CRL = 0.63-3 CRL, R2  = 0.108, P = .000). In 154 skeletal dysplasia cases, early pregnancy ultrasound images were available in only 16 cases. The CCL/CRL ratio in 10 of 16 fetuses with skeletal dysplasia was above the 95th percentile. Using the 95th percentile as a cut-off, the detection rate, specificity, false-positive rate, and positive likelihood ratio are 62.5, 72.6, 5, and 17.5%, respectively. CONCLUSIONS: Increased fetal CCL/CRL ratio at 11-14 weeks' gestation is associated with an increased risk of skeletal dysplasia and may be useful in first-trimester screening for this condition.

Crown-Rump Length Discordance, Increased Nuchal Translucency, and Detection of Fetal Structural Anomalies in Twin Pregnancies in the First Trimester: 5 Years of Experience in a Tertiary Hospital in China.

OBJECTIVE: To evaluate the efficacy of the first-trimester ultrasound scan in the detection of fetal structural anomalies in twin pregnancies. To examine the association between increased nuchal translucency (NT) thickness, crown-rump length (CRL) or NT discordance, and detection of structural anomalies in a large twin series in China. METHODS: We performed retrospective analysis of twin pregnancies who underwent 11-13+6 -week and second-trimester anomaly scan and booked at Beijing Obstetrics and Gynecology Hospital between January 2012 and December 2016. Measurement of fetal CRL/NT and assessment of fetal anatomic structures were based on standard (not detailed) protocols. Conjoined twins and twin-reversed arterial perfusion sequence (TRAPS) were excluded from structural anomalies. The diagnostic performance of first-trimester ultrasound in detection of fetal structural anomalies in twins was determined and compared with that of second trimester. The accuracy of independent variates associated with structural anomaly detection was calculated. RESULTS: A total of 1442 women with twin pregnancies were included. In 40 women and 45 fetuses, structural anomalies were found. Fetal structural anomalies verified at delivery were detected in 42.5% (17/40) of affected pregnancies in the first trimester and 92.5% (37/40) of affected pregnancies when added second trimester (P = .13). The survival rate of pregnancies detected in second trimester was higher than that of pregnancies detected in first trimester (11.8% vs 65.2%). The mean value of intertwin CRL/NT discordance in cases with fetal structural anomalies was larger in monochorionic twins than dichorionic twins, but monochorionicity was not associated with structural anomalies. CRL discordance ≥10% (OR 3.1, 95%CI 1.5-6.3) and NT ≥95th centile (OR 20.0, 95%CI 9.0-44.2) were associated with fetal structural anomalies. In both dichorionic (DC) and monochorionic (MC) twins, the percentages of CRL discordance ≥10% was larger in twins with structural anomalies than those without structural anomalies (37.5% vs 13.4% in DC twins and 50.0% vs 12.5% in MC twins), and this was also true for NT ≥95th centile (31.3% vs 1.7% in DC twins and 37.5% vs 2.2% in MC twins). In the setting of CRL discordance ≥10%, 40.0% (16/40) of twins with structural anomalies were found, in which the predominant fetal structural anomalies were cardiovascular defects, abdominal wall defects, and central nervous system defects. The AUC for detecting structural anomalies by CRL discordance ≥10% was 0.63. In the setting of NT ≥95th centile, 32.5% (13/40) of twins with structural anomalies were found, in which the predominant fetal structural anomalies were cardiovascular defects, cystic hygroma, and abdominal wall defects. The AUC for detecting structural anomalies by NT ≥95th centile was 0.65. CONCLUSIONS: The detection rate of twins with fetal structural anomalies was 42.5% per pregnancy in the first trimester. CRL discordance ≥10% and NT ≥95th centile may indicate higher risk of fetal structural anomalies in twins, but their efficacy was limited.

Fetal loss after chorionic villus sampling in twin pregnancy.

OBJECTIVE: To estimate the chorionic villus sampling (CVS)-related risk of fetal loss in twin pregnancy after adjustment for chorionicity, nuchal translucency thickness (NT), intertwin discordance in crown-rump length (CRL), maternal demographic characteristics and serum pregnancy-associated plasma protein-A (PAPP-A) and free ß-human chorionic gonadotropin (ß-hCG). METHODS: This was a multicenter study from eight fetal medicine units in which the leadership were trained at the Harris Birthright Research Centre for Fetal Medicine in London, UK, and in which the protocols for screening, invasive testing and pregnancy management are similar. Data were obtained prospectively from women with twin pregnancy undergoing routine ultrasound examination at 11-13 weeks' gestation. Multivariable logistic regression analysis with backward stepwise elimination was used to examine whether CVS provided a significant independent contribution to the prediction of risk of fetal loss after adjusting for maternal and pregnancy characteristics, including maternal age, racial origin and weight, method of conception, smoking status, parity, chorionicity, intertwin discordance in CRL, fetal NT ≥ 95th percentile and free ß-hCG and PAPP-A multiples of the median. Similarly, within the CVS group, multivariable logistic regression analysis was used to investigate the effect of the number of intrauterine needle insertions and size of the needle on the risk of fetal loss. RESULTS: The study population of 8581 twin pregnancies undergoing ultrasound examination at 11-13 weeks' gestation included 316 dichorionic and 129 monochorionic twins that had CVS. First, in twin pregnancies undergoing CVS, compared to those not undergoing CVS, there was a 2-fold increased risk of fetal loss at < 24 weeks' gestation and of loss at any stage in pregnancy. Second, the factors providing a significant independent contribution to the prediction of miscarriage or fetal loss in twin pregnancy were increased maternal weight, black racial origin, monochorionicity, and more so monoamnionicity, large intertwin discordance in CRL and increased fetal NT, and, in the case of fetal loss at any stage, there was also a contribution from assisted conception and low serum PAPP-A. Third, after adjustment for maternal and pregnancy characteristics, CVS did not provide a significant contribution to the risk of fetal loss. Fourth, in twin pregnancies that had CVS, there was no significant contribution to fetal loss from the number of intrauterine needle insertions or needle size. CONCLUSION: The 2-fold increased risk of fetal loss following CVS in twin pregnancy can, to a great extent, be explained by maternal and pregnancy characteristics rather than the invasive procedure itself. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

The significance of low first trimester serum progesterone in ongoing early pregnancies presenting as pregnancies of unknown location.

OBJECTIVES: The primary objective of this study was to ascertain whether there is association between low initial serum progesterone, sonographic parameters and clinical outcomes in women presenting with pregnancies of unknown location (PUL), which are found to be ongoing at their follow up scans in the first trimester. STUDY DESIGN: This was a non-interventional retrospective cohort study of 1056 patients spanning a 14-year period, conducted in the Early Pregnancy Unit (EPU) of an inner-city teaching hospital. Patients who had an ongoing singleton first trimester pregnancy after presenting with PUL were identified and categorised as having low progesterone if it was 32 nmol/l or lower. The crown-rump length (CRL), mean gestational sac diameter (MGSD) and gestational sac volume (GSV) were measured when the embryo was first seen, and the pregnancy outcome recorded. RESULTS: Pregnancies with low progesterone tended to have smaller gestational sacs (GS) on follow up scan (p = 0.001) and the sac was smaller than expected for a given CRL (p = 0.000). There was no ultrasound parameter that was characteristic of low progesterone. The observation of a smaller than expected MGSD for a given CRL remained even when only pregnancies with normal outcomes were analysed. Clinical outcome data were available for 854 (80.9 %) women. Overall, 81.4 % (n = 34/43) of pregnancies with low progesterone resulted in livebirth, compared to 91.7 % (n = 744/811) livebirths in pregnancies with higher levels (p = 0.0454). CONCLUSION: Pregnancies with low progesterone tend to have a smaller GS compared to those with a higher progesterone, and the GSs are smaller than expected for a given CRL. The current study shows that women with low progesterone at the start of pregnancy remain at higher risk of miscarriage, even when the pregnancy is initially found to be viable in the first trimester. These pregnancies also tend to be associated with the sonographic finding of a smaller GS than expected for a given gestational age, regardless of eventual outcome.

The effects of progesterone treatment on nuchal translucency in women with threatened miscarriage.

This study aims to investigate the effects of progesterone on the possible changes in nuchal translucency (NT) levels for patients diagnosed with threatened miscarriage. The study group was composed of 125 patients diagnosed with threatened miscarriage and taking 400 mg/day micronized orally progesterone at least for two weeks, the control group was composed of 160 healthy pregnant women not taking any progesterone. Crown rump length (CRL) NT thickness, Pregnancy-associated plasma protein-A (PAPP-A), free beta human chorionic gonadotropin (Beta-HCG) levels of patients were measured for assessment of aneuploidy risk. Both of the groups were divided into four subgroups to determine the relationship between thickness of NT and progesterone use for specific CRL measurements. CRL in the first, second, third and fourth group was 45-55 mm, 55-65 mm, 65-75 mm, 75-84 mm, respectively. The two groups were age and BMI matched. In all groups of CRL there were no significant difference in Mom levels of NT thickness, PAPP-A and free Beta-HCG between the study and control groups. There havent been any relation between NT thickness and progesterone use.IMPACT STATEMENTWhat is already known about this subject? Recently some studies have claimed that progesterone use might have caused atypical blood flow pattern on foetal circulation, which could possibly increase NT. If the NT thickness is affected by the use of progesterone, then the false positive rate of detecting Down Syndrome screening tests would increase.What the results of this study add? In this study we did not found any relation between NT thickness and progesterone use.What the implications are of these findings for clinical practice and/or further research? Using orally progesterone due to threatened miscarriage do not change NT thickness levels. Further studies have to be done with a large number of participants.

The effect of endometrial thickness and pattern on the success of frozen embryo transfer cycles and gestational age accuracy.

OBJECTIVE: To evaluate the relationship between endometrial thickness measured before embryo transfer, and pregnancy outcomes in frozen-thawed embryo transfer (FET). METHODS: We retrospectively analyzed outcomes of all consecutive FET cycles, from January 2012 to August 2018. Based on ROC analysis for endometrial thickness, we found 8 mm was a reliable cutoff point to predict pregnancy prior to embryo transfer. Accordingly, the cycles were divided into Group A: cycles with endometrial thickness ≤ 8 mm and Group B: > 8 mm. RESULTS: Group A included 485 FET cycles and group B included 626 cycles. Compared with group A, Group B had significantly higher chemical and clinical pregnancy rates (30.3 vs. 24.6%; p = .046, and 24.0 vs. 18.6%; p = .036), respectively. In multivariate analysis, endometrial thickness and the protocols used were the only parameters influencing the chance to achieve pregnancy, with odds ratio 1.54 (95%CI 1.07-2.22, p = .019) for the endometrium and odds ratio 1.95 (95%CI 1.31-2.9; p = .001) to the protocol used. Endometrial thickness might predict crown-rump length (CRL) discordancy with odds ratio 4.61 (p = .001; 95% CI 1.42-14.92). Compared with group B, Group A had more cases of overt discordancy (13.3 vs. 4%; p = .016). CONCLUSIONS: For patients undergoing FET cycles, endometrial thickness and treatment protocol may predict the chemical and clinical pregnancy rates, as well as CRL discordancy. SUMMARY: Endometrial thickness and preparation improved pregnancy rate in FET cycles and significantly greater crown-rump length discordancy was observed with thinner endometria.

Twin pregnancies, crown-rump length and birthweight discordancy: the influence of chorionicity / Gestações gemelares, comprimento craniocaudal e discordância de peso ao nascimento: a influência da corionicidade

Abstract Objective The purpose of the present study was to analyze the influence of chorionicity in the biometric parameters crown-rump length (CRL), birthweight (BW), crown-rump length discordancy (CRLD) and birthweight discordancy (BWD), determine the correlation between these latter two in cases of intertwin discordancy, and to analyze the influence of chronicity in the presence of these discordancies with clinical relevance (> 10% and > 15%, respectively). Methods The present study was a retrospective study based on the twin pregnancy database of the Centro Hospitalar S. João (2010-2015), including 486 fetuses among 66 monochorionic (MC) and 177 dichorionic gestations (DC). The inclusion criteria were multiple pregnancies with 2 fetuses and healthy twin gestations. The exclusion criteria were trichorionic gestations and pregnancies with inconclusive chorionicity, multiple pregnancy with ≥ 3 fetuses and pathological twin gestations. Results No statistically significant difference was found in BW (p = 0.09) and in its discordancy (p = 0.06) nor in CRL (p = 0.48) and its discordancy (p = 0.74) between MCs and DCs. Crown-rump length discordancy and birthweight discordancy were correlated by the regression line "BWD = 0.8864 x CRLD + 0.0743," with r2 = 0.1599. Crown-rump length discordancy > 10% was found in 7.58% of monochorionic and in 13.56% of dichorionic twins. Birthweight discordancy > 15% was detected in 16.67% of monochorionic and in 31.64% of dichorionic twins. Conclusion No statistically significant influence of chorionicity was identified in both birthweight and birthweight discordancy, as in crown-rump length and crown-rump length discordancy. Birthweight discordancy was correlated to crown-rump length discordancy in 20% of cases.

Resumo Objetivo O objetivo do presente estudo foi analisar a influência da corionicidade nos parâmetros biométricos comprimento craniocaudal, peso ao nascimento, discordância de comprimento craniocaudal e discordância de peso ao nascimento, determinar a correlação entre estes dois últimos caso haja discordância intergemelar e analisar a influência da corionicidade na presença destas discordâncias com relevância clínica (> 10% e > 15%, respectivamente). Métodos O presente estudo foi um estudo retrospectivo baseado na base de dados de gestações gemelares do Centro Hospitalar S. João (2010-2015), incluindo 486 fetos de 66 gestações monocoriônicas e 177 dicoriônicas. Os critérios de inclusão foram gestações múltiplas de 2 fetos e gestações gemelares saudáveis. Os critérios de exclusão foram gestações tricoriônicas ou de corionicidade inconclusiva, gestações múltiplas com ≥ 3 fetos e gestações gemelares patológicas. Resultados Não se encontrou diferença estatisticamente significativa no peso ao nascimento (p =0,09) e sua discordância (p = 0,06) nem no comprimento craniocaudal (p = 0,48) e sua discordância (p = 0,74) entre gestações monocoriônicas e dicoriônicas. Considerando todas as gestações, as discordâncias de comprimento craniocaudal e peso ao nascimento foram correlacionadas pela reta de regressão "discordância de peso ao nascimento = 0.8864 x discordância de comprimento craniocaudal + 0.0743," com r2 = 0,1599. A discordância de comprimento craniocaudal > 10% descobriu-se em 7.58% das gestações monocoriônicas e em 13.56% das dicoriônicas. A discordância de peso ao nascimento > 15% detectou-se em 16.67% das gestações monocoriônicas e em 31.64% das dicoriônicas. Conclusão Não se identificou influência estatisticamente significativa no peso ao nascimento e sua discordância, bem como no comprimento craniocaudal e sua discordância. A discordância de peso ao nascimento correlacionou-se com a discordância de comprimento craniocaudal em 20% dos casos.

Predictors of complete miscarriage after expectant management or misoprostol treatment of non-viable early pregnancy in women with vaginal bleeding.

PURPOSE: To identify predictors of complete miscarriage after expectant management or misoprostol treatment of non-viable early pregnancy in women with vaginal bleeding. METHODS: This was a planned secondary analysis of data from a published randomized controlled trial comparing expectant management with vaginal single dose of 800 µg misoprostol treatment of women with embryonic or anembryonic miscarriage. Predefined variables-serum-progesterone, serum-ß-human chorionic gonadotropin, parity, previous vaginal deliveries, gestational age, clinical symptoms (bleeding and pain), mean diameter and shape of the gestational sac, crown-rump-length, type of miscarriage, and presence of blood flow in the intervillous space-were tested as predictors of treatment success (no gestational sac in the uterine cavity and maximum anterior-posterior intracavitary diameter was ≤ 15 mm as measured with transvaginal ultrasound on a sagittal view) in univariable and multivariable logistic regression. RESULTS: Variables from 174 women (83 expectant management versus 91 misoprostol) were analyzed for prediction of complete miscarriage at ≤ 17 days. In patients managed expectantly, the rate of complete miscarriage was 62.7% (32/51) in embryonic miscarriages versus 37.5% (12/32) in anembryonic miscarriages (P = 0.02). In multivariable logistic regression, the likelihood of success increased with increasing gestational age, increasing crown-rump-length and decreasing gestational sac diameter. Misoprostol treatment was successful in 80.0% (73/91). No variable predicted success of misoprostol treatment. CONCLUSIONS: Complete miscarriage after expectant management is significantly more likely in embryonic miscarriage than in anembryonic miscarriage. Gestational age, crown-rump-length, and gestational sac diameter are independent predictors of success of expectant management. Predictors of treatment success may help counselling women with early miscarriage.

Successful use of an artificial placenta-based life support system to treat extremely preterm ovine fetuses compromised by intrauterine inflammation.

BACKGROUND: Ex vivo uterine environment therapy is an experimental intensive care strategy for extremely preterm infants born between 21 and 24 weeks of gestation. Gas exchange is performed by membranous oxygenators connected by catheters to the umbilical vessels. The fetus is submerged in a bath of synthetic amniotic fluid. The lungs remain fluid filled, and pulmonary respiration does not occur. Intrauterine inflammation is strongly associated with extremely preterm birth and fetal injury. At present, there are no data that we are aware of to show that artificial placenta-based systems can be used to support extremely preterm fetuses compromised by exposure to intrauterine inflammation. OBJECTIVE: To evaluate the ability of our ex vivo uterine environment therapy platform to support extremely preterm ovine fetuses (95-day gestational age; approximately equivalent to 24 weeks of human gestation) exposed to intrauterine inflammation for a period of 120 hours, the following primary endpoints were chosen: (1) maintenance of key physiological variables within normal ranges, (2) absence of infection and inflammation, (3) absence of brain injury, and (4) gross fetal growth and cardiovascular function matching that of age-matched in utero controls. STUDY DESIGN: Ten ewes with singleton pregnancies were each given a single intraamniotic injection of 10-mg Escherichia coli lipopolysaccharides under ultrasound guidance 48 hours before undergoing surgical delivery for adaptation to ex vivo uterine environment therapy at 95-day gestation (term=150 days). Fetuses were adapted to ex vivo uterine environment therapy and maintained for 120 hours with constant monitoring of key vital parameters (ex vivo uterine environment group) before being killed at 100-day equivalent gestational age. Umbilical artery blood samples were regularly collected to assess blood gas data, differential counts, biochemical parameters, inflammatory markers, and microbial load to exclude infection. Ultrasound was conducted at 48 hours after intraamniotic lipopolysaccharides (before surgery) to confirm fetal viability and at the conclusion of the experiments (before euthanasia) to evaluate cardiac function. Brain injury was evaluated by gross anatomic and histopathologic investigations. Eight singleton pregnant control animals were similarly exposed to intraamniotic lipopolysaccharides at 93-day gestation and were killed at 100-day gestation to allow comparative postmortem analyses (control group). Biobanked samples from age-matched saline-treated animals served as an additional comparison group. Successful instillation of lipopolysaccharides into the amniotic fluid exposure was confirmed by amniotic fluid analysis at the time of administration and by analyzing cytokine levels in fetal plasma and amniotic fluid. Data were tested for mean differences using analysis of variance. RESULTS: Six of 8 lipopolysaccharide control group (75%) and 8 of 10 ex vivo uterine environment group fetuses (80%) successfully completed their protocols. Six of 8 ex vivo uterine environment group fetuses required dexamethasone phosphate treatment to manage profound refractory hypotension. Weight and crown-rump length were reduced in ex vivo uterine environment group fetuses at euthanasia than those in lipopolysaccharide control group fetuses (P<.05). There were no biologically significant differences in cardiac ultrasound measurement, differential leukocyte counts (P>.05), plasma tumor necrosis factor α, monocyte chemoattractant protein-1 concentrations (P>.05), or liver function tests between groups. Daily blood cultures were negative for aerobic and anaerobic growth in all ex vivo uterine environment group animals. No cases of intraventricular hemorrhage were observed. White matter injury was identified in 3 of 6 lipopolysaccharide control group fetuses and 3 of 8 vivo uterine environment group fetuses. CONCLUSION: We report the use of an artificial placenta-based system to support extremely preterm lambs compromised by exposure to intrauterine inflammation. Our data highlight key challenges (refractory hypotension, growth restriction, and white matter injury) to be overcome in the development and use of artificial placenta technology for extremely preterm infants. As such challenges seem largely absent from studies based on healthy pregnancies, additional experiments of this nature using clinically relevant model systems are essential for further development of this technology and its eventual clinical application.

Is Cisterna Magna Width a Useful First-Trimester Marker of Aneuploidy?

OBJECTIVE: To assess whether the cisterna magna (CM) width measured in first-trimester fetuses is a useful marker for aneuploidy detection. METHODS: This was a prospective study in 2 different cohorts in a tertiary referral center. The first cohort comprised 913 fetuses from the general pregnancy population during the period 2012-2016 and was used to construct the CM reference ranges applying the λ-µ-σ (LMS) method. The second cohort included 714 high-risk fetuses undergoing chorionic villus sampling during the period 2012-2016. Mean detection rates using the 95th percentile for CM width observed in chromosomal anomaly groups were compared with those obtained in chromosomally normal fetuses. RESULTS: The 50th percentile for CM ranged from 1.66 to 2.75 mm when crown-rump length (CRL) increased from 45 to 84 mm. Among high-risk fetuses, the following chromosomal anomalies were diagnosed in 125 (17%) fetuses: trisomy 21 (n = 63), trisomy 18 or 13 (n = 21), monosomy X (n = 9), submicroscopic anomalies (n = 11), and other anomalies (n = 22). The mean CM width for euploid fetuses was 2.4 mm (1.13 multiples of the median, MoM). While CM width was significantly increased in trisomy 21 (mean 2.7 mm; 1.23 MoM; p > 0.05), no differences were found in the other anomaly groups. Among the 63 fetuses with trisomy 21, a CM width above the 99th percentile was observed in 23 fetuses (37%). CONCLUSIONS: The new reference range for CM width at 11-13 weeks of gestation did not differ from previous studies. In first-trimester fetuses with trisomy 21, CM width appears to be increased, although its value as an ultrasound marker is limited, because of its detection rate of 37%.

Fetal fraction and noninvasive prenatal testing: What clinicians need to know.

The fetal fraction (FF) is a function of both biological factors and bioinformatics algorithms used to interpret DNA sequencing results. It is an essential quality control component of noninvasive prenatal testing (NIPT) results. Clinicians need to understand the biological influences on FF to be able to provide optimal post-test counseling and clinical management. There are many different technologies available for the measurement of FF. Clinicians do not need to know the details behind the bioinformatics algorithms of FF measurements, but they do need to appreciate the significant variations between the different sequencing technologies used by different laboratories. There is no universal FF threshold that is applicable across all platforms and there have not been any differences demonstrated in NIPT performance by sequencing platform or method of FF calculation. Importantly, while FF should be routinely measured, there is not yet a consensus as to whether it should be routinely reported to the clinician. The clinician should know what to expect from a standard test report and whether reasons for failed NIPT results are revealed. Emerging solutions to the challenges of samples with low FF should reduce rates of failed NIPT in the future. In the meantime, having a "plan B" prepared for those patients for whom NIPT is unsuccessful is essential in today's clinical practice.

Intertwin discordance in fetal size at 11-13 weeks' gestation and pregnancy outcome.

OBJECTIVE: To investigate the value of intertwin discordance in fetal crown-rump length (CRL) at the 11-13-week scan in the prediction of adverse outcome in dichorionic (DC), monochorionic diamniotic (MCDA) and monochorionic monoamniotic (MCMA) twin pregnancies. METHODS: This was a retrospective analysis of prospectively collected data on twin pregnancies undergoing routine ultrasound examination at 11-13 weeks' gestation between 2002 and 2019. In pregnancies with no major abnormalities, we examined the value of intertwin discordance in fetal CRL in DC, MCDA and MCMA twins in the prediction of fetal loss at < 20 and < 24 weeks' gestation, perinatal death at ≥ 24 weeks, preterm delivery at < 32 and < 37 weeks, birth of at least one small-for-gestational-age (SGA) neonate with birth weight < 5th percentile and intertwin birth-weight discordance of ≥ 20% and ≥ 25%. RESULTS: First, the study population of 6225 twin pregnancies included 4896 (78.7%) DC, 1274 (20.4%) MCDA and 55 (0.9%) MCMA twin pregnancies. Second, median CRL discordance in DC twin pregnancies (3.2%; interquartile range (IQR), 1.4-5.8%) was lower than in MCDA twins (3.6%; IQR, 1.6-6.2%; P = 0.0008), but was not significantly different from that in MCMA twins (2.9%; IQR, 1.2-5.1%; P = 0.269). Third, compared to CRL discordance in DC twin pregnancies with two non-SGA live births at ≥ 37 weeks' gestation, there was significantly larger CRL discordance in both DC and MCDA twin pregnancies complicated by fetal death at < 20 and < 24 weeks' gestation, perinatal death at ≥ 24 weeks, preterm birth at < 32 and < 37 weeks, birth of at least one SGA neonate and birth-weight discordance ≥ 20% and ≥ 25%, and in MCDA twin pregnancies undergoing endoscopic laser surgery. Fourth, the predictive performance of CRL discordance for each adverse pregnancy outcome was poor, with areas under the receiver-operating-characteristics curves ranging from 0.533 to 0.624. However, in both DC and MCDA twin pregnancies with large CRL discordance, there was a high risk of fetal loss. Fifth, in DC twin pregnancies, the overall rate of fetal loss at < 20 weeks' gestation was 1.3% but, in the small subgroup with CRL discordance of ≥ 15%, which constituted 1.9% of the total, the rate increased to 5.3%. Sixth, in MCDA twin pregnancies, the rate of fetal loss or endoscopic laser surgery at < 20 weeks was about 11%, but, in the small subgroups with CRL discordance of ≥ 10%, ≥ 15% and ≥ 20%, which constituted 9%, < 3% and < 1% of the total, the risk was increased to about 32%, 49% and 70%, respectively. Seventh, in MCMA twin pregnancies, there were no significant differences in CRL discordance for any of the adverse outcome measures, but this may be the consequence of the small number of cases in the study population. CONCLUSIONS: In both DC and MCDA twin pregnancies, increased CRL discordance is associated with an increased risk of fetal death at < 20 and < 24 weeks' gestation, perinatal death at ≥ 24 weeks, preterm birth at < 37 and < 32 weeks, birth of at least one SGA neonate and birth-weight discordance ≥ 20% and ≥ 25%, but CRL discordance is a poor screening test for adverse pregnancy outcome. However, in DC twins, CRL discordance of ≥ 15% is associated with an increased risk of fetal loss at < 20 and < 24 weeks' gestation and, in MCDA twins, CRL discordance of ≥ 10%, and more so discordance of ≥ 15% and ≥ 20%, is associated with a very high risk of fetal loss or endoscopic laser surgery at < 20 and < 24 weeks and this information is useful in counseling women and defining the timing for subsequent assessment and possible intervention. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

The role of first trimester fetal heart rate in the prediction of gestational diabetes: A multicenter study.

OBJECTIVE: Early pregnancy models for prediction of GDM have been proposed, mostly using anamnestic and biochemical parameters. The aim of our study was to evaluate the strength of association of first trimester fetal heart rate (FHR) in predicting the development of gestational diabetes (GDM). STUDY DESIGN: We considered in our analysis singleton non-diabetic pregnant women who underwent a first trimester screening at 11-14 weeks. Data on maternal age, BMI, cigarette smoking, NT, FHR, CRL, DV-PVI, ß-hCG and PAPP-A were included in the analysis. Multivariate logistic regression analysis was used to estimate the association between maternal characteristics and first-trimester ultrasound measurements and GDM. We evaluated the efficacy of different models for the prediction of GDM. RESULTS: We considered 603 women, of whom 199 (33%) were subsequently diagnosed with GDM. ROC analysis showed that first trimester FHR was highly predictive of GDM (AUC 0.809, 95% CI 0.769-0.849, p < 0.001). At FPR of 20%, first trimester FHR had a detection rate of 65.2% for GDM (positive likelihood ratio: 3.26; negative likelihood ratio: 0.43), which increased to 89.5% at FPR of 40% (positive likelihood ratio: 2.24; negative likelihood ratio: 0.17). When considering as threshold 162 bpm, FHR showed detection rate of 76.9%, specificity of 67.1% and negative predictive value of 85.5% for GDM. CONCLUSION: This is the first study to highlight the potential role of first trimester FHR as early predictor of GDM. In our cohort, a threshold of 162 bpm has shown high detection rate and NPV for GDM.

Successful use of an artificial placenta to support extremely preterm ovine fetuses at the border of viability.

BACKGROUND: Ex vivo uterine environment therapy is an experimental life support platform designed to reduce the risk of morbidity and mortality for extremely preterm infants born at the border of viability (21-24 weeks' gestation). To spare the functionally immature lung, this platform performs gas exchange via a membranous oxygenator connected to the umbilical vessels, and the fetus is submerged in a protective bath of artificial amniotic fluid. We and others have demonstrated the feasibility of extended survival with ex vivo uterine environment therapy therapy in late preterm fetuses; however, there is presently no evidence to show that the use of such a platform can support extremely preterm fetuses, the eventual translational target for therapy of this nature. OBJECTIVE: The objective of the study was to use our ex vivo uterine environment therapy platform to support the healthy maintenance of 600-700 g/95 days gestational age (equivalent to 24 weeks of human gestation) sheep fetuses. Primary outcome measures were as follows: (1) maintenance of key physiological variables; (2) absence of infection; (3) absence of brain injury; and (4) growth and cardiovascular function patterns matching that of noninstrumented, age-matched in utero controls. STUDY DESIGN: Singleton fetuses from 8 ewes underwent surgical delivery at 95 days' gestation (term, 150 days). Fetuses were adapted to ex vivo uterine environment therapy and maintained for 120 hours with real-time monitoring of key physiological variables. Umbilical artery blood samples were regularly collected to assess blood gas data, differential counts, inflammation, and microbial load to exclude infection. Brain injury was evaluated by gross anatomical and histopathological approaches after euthanasia. Nine pregnant control animals were euthanized at 100 days' gestation to allow comparative postmortem analyses. Data were tested for mean differences with an analysis of variance. RESULTS: Seven of 8 ex vivo uterine environment group fetuses (87.5%) completed 120 hours of therapy with key parameters maintained in a normal physiological range. There were no significant intergroup differences (P > .05) in final weight, crown-rump length, and body weight-normalized lung and brain weights at euthanasia compared with controls. There were no biologically significant differences in hematological parameters (total or differential leucocyte counts and plasma concentration of tumor necrosis factor-α and monocyte chemoattractant protein 1) (P > .05). Daily blood cultures were negative for aerobic and anaerobic growth in all ex vivo uterine environment animals. There was no difference in airspace consolidation between control and ex vivo uterine environment animals, and there was no increase in the number of lung cells staining positive for the T-cell marker CD3. There were no increases in interleukin-1, interleukin-6, interleukin-8, tumor necrosis factor-α, and monocyte chemoattractant protein 1 mRNA expression in lung tissues compared with the control group. No cases of intraventricular hemorrhage were observed, and white matter injury was identified in only 1 ex vivo uterine environment fetus. CONCLUSION: For several decades, there has been little improvement in outcomes of extremely preterm infants born at the border of viability. In the present study, we report the use of artificial placenta technology to support, for the first time, extremely preterm ovine fetuses (equivalent to 24 weeks of human gestation) in a stable, growth-normal state for 120 hours. With additional refinement, the data generated by this study may inform a treatment option to improve outcomes for extremely preterm infants.

Spina bifida screening in the first trimester using ultrasound biparietal diameter measurement adjusted for crown-rump length or abdominal circumference.

OBJECTIVE: Compare the performance of first trimester ultrasound biparietal diameter (BPD) screening for open spina bifida (OSB) when BPD is adjusted for crown-rump length (CRL) or abdominal circumference (AC). METHODS: For 63 OSB and 24 265 unaffected pregnancies, BPD was expressed as multiple of the normal median (MoM) based on CRL and on AC, and as the ratio BPD/AC. Screening performance was assessed by the Mahalanobis distance, the observed detection rate with normal fifth and 10th percentile cut-offs and the area under the receiver-operator characteristic curve (AUC). RESULTS: Mahalanobis distance for BPD MoM was considerably higher when based on AC than on CRL: 1.69 versus 1.14. Screening performance was also higher: using a fifth percentile cut-off, the detection rate was 59% compared with 41%; using a 10th percentile cut-off, the rates were 63% and 51%. Whilst the false-positives rates were slightly higher too-5.3% versus 5.1% and 10.8% versus 9.9%-the AUC was statistically significantly higher: 0.872 (95% CI, 0.816-0.928) compared with 0.735 (95% CI, 0.664-0.806). BPD/AC had intermediate performance. CONCLUSION: The best results are obtained when AC, rather than CRL, is used to express BPD values in MoMs. First trimester OSB screening can detect half to two-thirds of cases.

The correlation between birth weight and insulin-like growth factor-binding protein-1 (IGFBP-1), kisspeptin-1 (KISS-1), and three-dimensional fetal volume.

PURPOSE: This study aimed to determine the relationship between birth weight, and maternal serum insulin-like growth factor-binding protein-1 (IGFBP-1) and kisspeptin-1 (KISS-1) levels, and first-trimester fetal volume (FV) based on three-dimensional ultrasonography. MATERIALS AND METHODS: The study included 142 pregnant women at gestational week 11°-136. All fetuses were imaged ultrasonographically by the same physician. Maternal blood samples were collected at the time of ultrasonographic evaluation and analyzed for IGFBP-1 and KISS-1 levels via enzyme-linked immunosorbent assay (ELISA). Maternal and neonatal weights were recorded at birth. Birth weight ≤10th and the >90th percentiles was defined as small and large for gestational age (SGA and LGA), respectively. RESULTS: Median crown-rump length (CRL), FV, and maternal serum IGFBP-1 and KISS-1 levels were 58.2 mm (35.3-79.2 mm), 16.3 cm3 (3.8-34.4 cm3), 68.1 ng mL-1 (3.8-377.9 mL-1), and 99.7 ng L-1 (42.1-965.3 ng L-1), respectively. First-trimester IGFBP-1 levels were significantly lower in the mothers with LGA neonates (p < .05). There was a significant positive correlation between CRL and FV, and between the IGFBP-1 and KISS-1 levels. IGFBP-1 levels and maternal weight at delivery were negatively correlated with neonatal birth weight. There was no correlation between CRL or FV and maternal IGFBP-1 or KISS1 levels (p > .05). The maternal IGFBP-1 level during the first trimester was a significant independent factor for SGA and LGA neonates (Odds ratio (OR): 0.011, 95%CI: 1.005-1.018, p < .001; and OR: 1.297, 95%CI: 1.074-1.566, p = .007, respectively). There was no significant relationship between SGA or LGA, and CRL, FV, or the KISS-1 level. CONCLUSIONS: As compared to the maternal KISS-1 level, the maternal IGFBP-1 level during the first trimester might be a better biomarker of fetal growth. Additional larger scale studies are needed to further delineate the utility of IGFBP-1 as a marker of abnormal birth weight.

Robotic distal pancreatectomy with selective closure of pancreatic duct: surgical outcomes.

Pancreatic fistula is the main post-operative complication of distal pancreatectomy associated with other further complications, such as intra-abdominal abscesses, wound infection, sepsis, electrolyte imbalance, malabsorption and hemorrhage. Surgeons have tried various techniques to close the stump of the remaining pancreas, but the controversy regarding the impact of stapler closure and suture closure of the pancreatic stump is far from resolved. In this study, we reported our technique and results of robotic assisted distal pancreatectomy with ultrasound identification and consequent selective closure of pancreatic duct. Twenty-one patients underwent consecutive robotic-assisted distal pancreatectomy were included in our study. We describe our technique and analyzed the operative and peri-operative data including mean operative time, intra-operative bleeding, blood transfusions necessity, conversion rate, mortality and morbidity rate, pancreatic fistula rate and grade, time of refeeding and canalization, length of hospital stay and readmission. Median operative time was 260 min. No conversion occurred. Estimated blood loss was 100 mL (range 50-200). No blood transfusions were performed. Mortality rate was 0%. One (5%) patient had a major complication, while 9 (43%) patients had minor complications (grade I). Three (14%) patients developed pancreatic fistula (grade B), while two (10%) patients had a biochemical leak. No late pancreatic fistula and re-operation occurred. The refeeding was started at second day (range 1^-6^) and the median canalization time was 4 days (range 2-7). The median hospital stay was 6 days (range 3-25) with a readmission rate of 0%. Robotic distal pancreatectomy can be considered safe and feasible. Our technique is easily reproducible, with good surgical results.

Effect of GnRH or hCG administration on Day 4 post insemination on reproductive performance in Merino sheep of North Patagonia.

Different therapeutic strategies have been used with the objective of improve luteal function to reduce embryonic losses. The objective of this work was to study the effect of the administration of GnRH or hCG at Day 4 post fixed time artificial insemination (FTAI) on reproductive efficiency in Merino sheep during the breeding season in North Patagonia. Estrus of multiparous Merino ewes (n = 288) was synchronized by two injections of prostaglandins (PG; 125 µg, Cloprostenol), 14 days apart. Cervical FTAI was performed 53-56 h after the second PG with a dose of fresh semen (100 × 106 spermatozoa) from five Merino rams. In all ewes body condition score (BCS) was determined at FTAI. At 4 days post FTAI ewes were randomly assigned into three experimental groups: GnRH group (4 µg, Buserelin; n = 99), hCG group (300 IU, hCG; n = 92) and Control group (1 ml, saline solution; n = 97). Pregnancy and pregnancy losses were evaluated by ultrasonography on Days 33 and 90 post FTAI. Additionally, embryo crown-rump length (CRL) was measured by ultrasonography (n = 12 single-pregnant ewes by experimental group) at the first ultrasound. Date of birth, litter size and lamb weight were recorded (n = 111 pregnant ewes). Pregnancy rate on Days 33 and 90 post FTAI did not differ among treatment groups (P > 0.05). Pregnancy losses at Day 33 post FTAI were lower in the hCG group compared to the GnRH and Control groups (0, 3, 7.2%, respectively; P < 0.05). Pregnancy losses between Days 33 and 90 after FTAI were negligible (P > 0.05). The embryo CRL at Day 33 post FTAI was not increased by the hormonal treatments (P > 0.05). Moreover, it was lower in GnRH group compared to Control group (P < 0.05). Litter size tended to be greater in the GnRH group compared to the hCG and Control groups (P < 0.1). The birth weight of twin lambs tended to be higher in the GnRH group compared to the Control group (P < 0.1). The birth weight of single lambs was not affected by treatments (P > 0.05). Ram fertility and BCS of ewes at FTAI influenced the effect of hormonal treatments on reproductive parameters. In conclusion, administration of hCG or GnRH at Day 4 post FTAI does not improve pregnancy rate but treatment with hCG reduces pregnancy loss on Day 33 post FTAI. GnRH treatment improves litter size and twin lambs birth weight.