Impact of introducing cell-free DNA screening into clinical care on first trimester ultrasound.

OBJECTIVE: First-trimester ultrasound is an important component of prenatal care. We investigated the impact of introducing cell-free DNA (cfDNA) aneuploidy screening into routine care, on performance of first-trimester ultrasound. METHODS: Retrospective study of patients who had prenatal care at a tertiary referral center. We compared the performance of any first-trimester ultrasound between three different aneuploidy screening protocols, used consecutively during the study period: (1) combined first-trimester screening (FTS); (2) FTS and cfDNA offered together; (3) patients requested to choose between FTS and cfDNA. Secondary outcomes included performance of nuchal translucency (NT), aneuploidy screens and diagnostic genetic procedures. RESULTS: The number of patients undergoing first-trimester ultrasound remained similar with the second protocol but decreased in the third (68.7% vs. 40.9%, OR 0.32, 95% CI 0.25-0.4, p < 0.001). Diagnostic procedures decreased between protocol 1 and 2 (7.6% vs. 4.4%, OR 0.59, 95% CI 0.37-0.93, p = 0.02) while NT scans decreased between protocol 2 and 3 (6.8% vs. 1.3%, OR 0.18, 95% CI 0.09-0.4, p < 0.001). The rate of FTS decreased over the study period and less women had cfDNA when they had to choose one method (p < 0.001). CONCLUSIONS: Introducing cfDNA screening as an alternative to FTS, resulted in fewer patients receiving ultrasound in the first-trimester.

Combination of "Markers" and the Consequent Importance of Fetal Abdominal Circumference in the First Trimester for Predicting Complications Specific to Monochorionic Twin Pregnancies.

BACKGROUND: Multifetal pregnancies are considered high-risk pregnancies compared to singleton pregnancies. Monochorionic diamniotic (MCDA) twin pregnancies tend to have a more complicated intrauterine course than their dichorionic counterparts. The most common complications are twin-to-twin transfusion syndrome (TTTS), selective fetal growth restriction (sFGR), and unexplained intrauterine fetal demise (IUFD). Early recognition of pregnancies at risk of developing complications will be helpful for counselling the parents and preparing them for necessary interventions in case a complication arises. OBJECTIVES: The aim of our study was to assess the role of discordant crown-rump length (dCRL), discordant nuchal translucency (dNT), and discordant abdominal circumference (dAC) measurements in isolation and in combination at the 11-13+6 weeks' scan in predicting the development of TTTS, sFGR, and IUFD. METHODS: All MCDA twin pregnancies with structurally normal, both live fetuses at the 11-13+6 weeks' scan were followed up by FMF (Fetal Medicine Foundation)-certified operators for development of TTTS, sFGR, and single/double IUFD until delivery. Discordance of CRL, NT, and AC of more than or equal to 10% was considered a "marker," and its presence was correlated with the occurrence of specific antenatal complications, i.e., TTTS, sFGR, and single or double IUFD. RESULTS: Combination of two markers predicted MCDA-related complications in the majority of cases (70.8% positive predictive value). Combination of dNT and dAC was the strongest predictor (80% positive predictive value). CONCLUSIONS: In our population of MC twin pregnancies, dCRL, dNT, and dAC at the 11+0-13+6 weeks' scan, in isolation, had a low predictive value for antenatal complications, i.e., TTTS, sFGR, and single/double IUFD. However, the presence of at least two markers in the first trimester could predict complications in the majority of these pregnancies. The combination of dNT and dAC appears to be the best.

Recent Development in Three and Four Dimension Fetal Echocardiography.

Since its introduction >15 years ago, the use of spatial and temporal image correlation (STIC) technology has contributed substantially to fetal echocardiography. Moreover, significant advances have occurred in 3- and 4-dimensional (3D/4D) echocardiography over the past several years including the matrix probe along with advances in gray scale and color Doppler post processing, resulting in improved display of ultrasound images. In this article, we provide examples to show these recent developments including the use of color Doppler with STIC in the glass-body mode and the matrix probe thus enabling the demonstration of cardiac anomalies of the 4-chamber-view and great arteries. The use of the matrix probe allows the examination of cardiac structures in 2 orthogonal planes simultaneously, which can help in display of anatomy side by side (Biplane mode). In addition, the rapid image reconstruction of the matrix probe allows for the display of live 4D and the rapid acquisition of a STIC volume. The display of multiplanar images of the heart in 3D/4D has also been used to automate the display of ultrasound images, resulting in standardization of the image display and thus minimizing the operation dependency of the ultrasound examination. Future addition of image recognition software can also provide assistance in image review.

The Impact of Technology on the Diagnosis of Congenital Malformations.

As technology improves and becomes more widely accessible, more subclinical congenital malformations are being detected. Using a cohort of 1,780,156 pregnant women and their offspring nested in the 2000-2013 US Medicaid Analytic eXtract, we contrasted time trends in malformations which do not necessarily present with overt clinical symptoms early in life and are more likely to be diagnosed via imaging (secundum atrial septal defect, patent ductus arteriosus, ventricular septal defect, pulmonary artery anomalies, pulmonary valve stenosis, hydrocephalus) with trends in malformations that are unlikely to escape clinical diagnosis (tetralogy of Fallot, coarctation of the aorta, transposition of the great vessels, hypoplastic left heart syndrome, oral cleft, abdominal wall defect). Logistic regression was used to account for trends in risk factors while assessing the impact of increased screening intensity. Prevalence of the diagnosis of secundum atrial septal defect rose from 2.3‰ in 2000-2001 to 7.5‰ in 2012-2013, of patent ductus arteriosus from 1.9‰ to 4.1‰, and of ventricular septal defect from 3.6‰ to 4.5‰. Trends were not explained by changes in the prevalence of risk factors but were attenuated when accounting for screening tests. The other malformations showed no temporal trends. Findings suggest that increased screening partially explains the observed increase in diagnosis of milder cases of select common malformations.

Zika virus infection: A correlation between prenatal ultrasonographic and postmortem neuropathologic changes.

This study presents a correlation between prenatal ultrasonographic images and neuropathologic findings of postmortem tissue samples from five confirmed cases of perinatal Zika virus (ZIKV) infection belonging to the cohort of the ZEN Initiative in Bucaramanga, Colombia. Deaths occurred between June 2016 and March 2017. Mothers consulted with ZIKV infection clinical manifestations or fetal central nervous system (CNS) abnormalities or both. A detailed ultrasound scan and neurosonographic protocol was performed by maternal fetal specialists. Perinatal autopsies were performed following the Colombian National Health Institute's ZIKV protocol. The autopsies were from two fetal deaths, and three early neonatal deaths. Gestational age was between 262/7 and 382/7 weeks. Two cases were classified as mild microcephaly. Few findings by ultrasound and pathology were found in case 1 because it was a late infection; the other cases presented findings corresponding to congenital Zika syndrome: craniofacial malformations, cerebellar hypoplasia, anomalies of the corpus callosum and ventriculomegaly, all confirmed in autopsy specimens. By ultrasonography, hyperechogenicities were seen in several brain structures, which correspond to cortical and periventricular calcifications, subependymal glial reactivity and perivascular rings. The ultrasound and pathological findings show a wide spectrum of CNS anomalies that confirm the neurotropic effect of the ZIKV, recognizing the neuroimaging findings of this disease (unilateral ventriculomegaly, alterations in the corpus callosum and cerebellum, and calcifications) are highly suggestive of ZIKV infection.

Preoperative Ultrasound Prediction of Essential Landmarks for Successful Fetoscopic Laser Treatment of Twin-Twin Transfusion Syndrome.

INTRODUCTION: The insertion site of the fetoscope for laser occlusion (FLOC) treatment of twin-twin transfusion syndrome (TTTS) determines the likelihood of treatment success. We assessed a standardized preoperative ultrasound approach for its ability to identify critical landmarks for successful FLOC. METHODS: Three surgeons independently performed preoperative ultrasound and deduced the likely orientation of the intertwin membrane (ITM) and vascular equator (VE) based on the sites of the cord insertion, the lie of the donor, and the size discordance between twins. At FLOC, these landmarks were visually verified and compared to preoperative assessments. RESULTS: Fifty consecutive FLOC surgeries had 127 preoperative assessments. Basic ITM and VE orientation were accurately predicted in 115 (90.6%), 109 (85.8%), and 105 (82.7%) assessments. Predictions were anatomically correct in 96 (75.6%), 70 (55.1%), and 58 (45.7%) assessments with no differences in accuracy between operators of different training level. The ITM/VE relationship was most poorly predicted in stage-3 TTTS (χ2, p = 0.016). CONCLUSION: In TTTS, preoperative ultrasound identification of placental cord insertion sites, lie of the donor twin, and size discordance enables preoperative prediction of key landmarks for successful FLOC.

Is Four-Dimensional (4D) Ultrasound Entering a New Field of Fetal Psychiatry?

The aim of is to explore whether by observing the fetus by 4D US it is possible to enter fetal behavior, emotions, mental status, consciousness, awareness and other states connected with fetal mind and ability of self-regulation. It is well known that fetal motoric activity is enabling the development of central and peripheral nervous system and the muscles. It is 4D US which enabled to investigate fetal movement patterns from the first trimester of pregnancy throughout the whole pregnancy. Based on the evaluation of fetal spontaneous motor activity by 4D US, a prenatal neurologic scoring test named Kurjak Antenatal Neurodevelopmental Test (KANET) was created. This test has been used to assess almost 2000 fetuses and our results have indicated that KANET has an ability to recognize normal, borderline, and abnormal behavior in fetuses from normal and abnormal pregnancies. The fetus is able to process tactile, vestibular, taste, olfactory, auditory and visual sensations. The fetus responds to painful stimuli with a wide spectrum of reactions. Important external signs of emotion are facial expressions. The existence of a wide range of facial expressions, including grimacing, smiling, crying, similar to emotional expressions in adults, has been revealed by 4D sonography in the 2nd and 3rd trimesters of pregnancy. It is questionable if mental, emotional and behavioral conditions of the fetus were covered in this paper and whether we are able to perceive the fetus as the patient who may develop communication or some other psychiatric disorders which we will be hopefully able to recognize prenatally. Although it seems as the speculation from the point of view of our recent diagnostic possibilities, it is apparent that the day when this will be a reality is rapidly approaching.

Outcome and Treatment of Antenatally Diagnosed Nonimmune Hydrops Fetalis.

INTRODUCTION: The objectives of this study were to evaluate the outcome of nonimmune hydrops fetalis in an attempt to identify independent predictors of perinatal mortality. MATERIAL AND METHODS: A retrospective cohort study was conducted including all cases of nonimmune hydrops from two tertiary care centers. Perinatal outcome was evaluated after classifying nonimmune hydrops into ten etiological groups. We examined the effect of etiology, site of fluid accumulation, and gestational age at delivery on postnatal survival. Neonatal mortality and hospital discharge survival were compared between the expectant management and fetal intervention groups among those with idiopathic etiology. RESULTS: A total of 142 subjects were available for analysis. Generally, nonimmune hydrops carried 37% risk of neonatal mortality and 50% chance of survival to discharge, which varies markedly based on the underlying etiology. Ascites was an independent predictor of perinatal mortality (p value = 0.003). There was nonsignificant difference in neonatal mortality and hospital discharge survival among idiopathic cases that were managed expectantly versus those in whom fetal intervention was carried out. DISCUSSION: The outcome of nonimmune hydrops varies largely according to the underlying etiology and the presence of ascites is an independent risk factor for perinatal mortality. In our series, fetal intervention did not offer survival advantage among fetuses with idiopathic nonimmune hydrops.

Perinatal Outcomes of Non-Primary Maternal Cytomegalovirus Infection: A 15-Year Experience.

OBJECTIVE: To evaluate perinatal outcomes in case of non-primary maternal cytomegalovirus (CMV) infection. METHODS: We performed a retrospective cohort study of pregnant women with active CMV infection referred to our unit over a 15-year period (January 2000 to December 2014). Non-primary infection was diagnosed on the basis of the results of confirmatory serological and virological tests (avidity test, immunoblotting, real-time PCR-DNA). The vertical transmission rate and the percentage of symptomatic congenital infection were determined in this group of patients. RESULTS: A total of 205 pregnant women were enrolled. Congenital infection occurred in 7 (3.4%) fetuses/neonates. Symptomatic disease was present at birth in 3 of the 7 congenitally infected neonates (1.5%). Two out of 3 symptomatic newborns presented a pathologic second-trimester ultrasound scan. CONCLUSION: Maternal immunity offers substantial protection against intrauterine transmission of CMV infection, but not against disease once the fetus is infected.

Diagnosis of fetal syndromes by three- and four-dimensional ultrasound: is there any improvement?

With all of our present knowledge, high technology diagnostic equipment, electronic databases and other available supporting resources, detection of fetal syndromes is still a challenge for healthcare providers in prenatal as well as in the postnatal period. Prenatal diagnosis of fetal syndromes is not straightforward, and it is a difficult puzzle that needs to be assembled and solved. Detection of one anomaly should always raise a suspicion of the existence of more anomalies, and can be a trigger to investigate further and raise awareness of possible syndromes. Highly specialized software systems for three- and four-dimensional ultrasound (3D/4D US) enabled detailed depiction of fetal anatomy and assessment of the dynamics of fetal structural and functional development in real time. With recent advances in 3D/4D US technology, antenatal diagnosis of fetal anomalies and syndromes shifted from the 2nd to the 1st trimester of pregnancy. It is questionable what can and should be done after the prenatal diagnosis of fetal syndrome. The 3D and 4D US techniques improved detection accuracy of fetal abnormalities and syndromes from early pregnancy onwards. It is not easy to make prenatal diagnosis of fetal syndromes, so tools which help like online integrated databases are needed to increase diagnostic precision. The aim of this paper is to present the possibilities of different US techniques in the detection of some fetal syndromes prenatally.

Ultrasound in Africa: what can really be done?

Today we are living in a globalized world in which information on what is happening in one part of the world is easily communicated to other parts of the world. This happens thanks to advancement in science and technology. One area where technology has made the greatest impact is heath care provision. Ultrasound technology is now playing a critical role in health care provision particularly in Obstetrics and Gynaecology. This has significantly assisted in provision of quality health care to pregnant women and their unborn infants and in reducing maternal and neonatal morbidity and mortality in the developed world. Africa the continent with greatest health care challenges and with the highest maternal and neonatal mortalities is yet to fully utilize this important technology. The need for this technology is great as the conditions requiring its application abound. The effective application of Ultrasound however faces serious challenges in Africa. To successfully entrench Ultrasound in quality Obstetrics and Gynaecology care various approaches must be adopted to overcome the challenges. The aim of this paper is to identify the benefits and the challenges inimical to the application Ultrasound in Obstetrics and Gynecology in Africa. It also examines what needs to be done to achieve better application of Ultrasound in Obstetrics and Gynecology.

Prenatal diagnosis of transposition of the great arteries over a 20-year period: improved but imperfect.

OBJECTIVE: To evaluate temporal trends in the prenatal diagnosis of transposition of the great arteries with intact ventricular septum (TGA/IVS) and its impact on neonatal morbidity and mortality. METHODS: We included in this study cohort newborns with TGA/IVS who were referred for surgical management to our center over a 20-year period (1992-2011). The study period was divided into five 4-year periods and the primary outcome was rate of prenatal diagnosis. Secondary outcomes included neonatal preoperative status and perioperative survival. RESULTS: Of the 340 patients with TGA/IVS, 81 (23.8%) had a prenatal diagnosis. The rate of prenatal diagnosis increased over the study period, from 6% in 1992-1995 to 41% in 2008-2011 (P < 0.001). Compared to patients with a postnatal diagnosis, balloon atrial septostomy (BAS) was performed earlier in patients with a prenatal diagnosis (0 days after delivery vs 1 day after delivery, respectively; P < 0.001) and fewer prenatally diagnosed neonates required mechanical ventilation (55.6% vs 68.0%; P = 0.03). Between patients with a prenatal or postnatal diagnosis of TGA/IVS, there were no statistically significant differences in the incidence of preoperative acidosis (16.0% vs 25.5%; P = 0.1), need for preoperative extracorporeal membrane oxygenation (2.5% vs 2.7%; P = 1.0) or mortality (one preoperative and no postoperative deaths among prenatally diagnosed patients compared with four preoperative and six postoperative deaths among postnatally diagnosed patients). CONCLUSIONS: The prenatal detection rate of TGA/IVS has improved but still remains below 50%, suggesting the need for strategies to increase detection rates. The mortality rate was not statistically significantly different between prenatally and postnatally diagnosed patients, however, there were significant preoperative differences with regard to earlier BAS and fewer neonates that required mechanical ventilation. Ongoing work is required to ascertain whether prenatal diagnosis confers long-term benefits.

Uptake of Noninvasive Prenatal Testing in Chinese Women following Positive Down Syndrome Screening.

OBJECTIVES: To investigate how the introduction of noninvasive prenatal testing (NIPT) influenced women's testing choices following a positive Down syndrome screening. METHODS: A retrospective study was conducted to compare differences in the uptake rates of invasive prenatal diagnosis (IPD) or no testing in one public hospital 1 year before (pre-NIPT) and 1 and 2 years after the introduction of NIPT in private in August 2011 using descriptive analysis and a χ² test. Conventional screening was funded publicly, but NIPT was not. Multivariable binary logistic regression was used to determine factors affecting choices. RESULTS: In pre-NIPT and in years 1 and 2 after the introduction of NIPT, 306, 362 and 401 women who screened positive were seen, respectively. In year 1 and year 2, 12.6 and 26.7% of them underwent NIPT while IPD was decreased by 16.3 and 25.6%, respectively (p < 0.001). Both chorionic villus sampling and amniocentesis decreased in year 1, but only the former in year 2. However, the rate of declining further testing was similar before and after NIPT (p = 0.213). In multivariable analysis, first trimester screening, nulliparity and working women were significant predictors of accepting NIPT, while only nulliparity was a predictor of declining IPD (OR = 0.61). CONCLUSIONS: Introduction of NIPT resulted in a significant decrease in IPD for 2 consecutive years..

The history of imaging in obstetrics.

During the past century, imaging of the pregnant patient has been performed with radiography, scintigraphy, computed tomography, magnetic resonance imaging, and ultrasonography (US). US imaging has emerged as the primary imaging modality, because it provides real-time images at relatively low cost without the use of ionizing radiation. This review begins with a discussion of the history and current status of imaging modalities other than US for the pregnant patient. The discussion then turns to an in-depth description of how US technology advanced to become such a valuable diagnostic tool in the obstetric patient. Finally, the broad range of diagnostic uses of US in these patients is presented, including its uses for distinguishing an intrauterine pregnancy from a failed or ectopic pregnancy in the first trimester; assigning gestational age and assessing fetal weight; evaluating the fetus for anomalies and aneuploidy; examining the uterus, cervix, placenta, and amniotic fluid; and guiding obstetric interventional procedures.

Normative data for fetal cisterna magna length measurement between 18 and 24 weeks of pregnancy.

PURPOSE: The aim of this study was to determine normative data for fetal cisterna magna length (CML) measurement in a Brazilian population. METHODS: This was a retrospective cross-sectional study on 3,862 normal singleton pregnancies between the 18th and 24th weeks of pregnancy. Fetal CML was measured in the axial plane of the fetal head, at lateral ventricle level, including the cavum septum pellucidum, thalamus, third ventricle, and transverse cerebellar diameter. The anteroposterior measurement was made between the posterior border of the cerebellar vermis and the internal face of the occipital bone. To assess the correlation between CML and gestational age (GA), polynomial equations were calculated, with adjustments using determination coefficient (R2). RESULTS: The mean CML ranged from 4.29±0.93 mm at 18 to 18+6 weeks to 5.58±1.23 mm at 24 to 24+6 weeks of pregnancy. There was a good correlation between CML and GA, best represented by a linear equation: CML=0.535+0.208*GA (R2=0.084). CONCLUSION: We established normative data for fetal CML in the second trimester of pregnancy, in a large Brazilian population.

Levels of maternal serum angiogenic factors in third-trimester normal pregnancies: reference ranges, influence of maternal and pregnancy factors and fetoplacental Doppler indices.

AIM: To establish normal ranges of maternal placental growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1) and sFlt-1/PlGF ratio at 32-41 weeks' gestation and to evaluate the influence of maternal characteristics, and of fetoplacental Doppler. MATERIAL AND METHODS: Serum levels of PlGF, sFlt-1 and sFlt-1/PlGF ratio were measured in 300 noncomplicated pregnancies (30 at each gestational week between 32 and 41). Quantile regression analysis was used to derive gestational age (GA)-adjusted normal ranges, and to account for characteristics that might influence serum levels. The relationship with Doppler indices was tested, including umbilical artery pulsatility index and middle cerebral artery pulsatility index. RESULTS: PlGF decreased with GA from 32 weeks, while sFlt-1 and sFlt-1/PlGF ratio increased steadily. None of the factors evaluated showed any significant influence on the levels of angiogenic factors. PlGF multiple of the median significantly correlated with mean uterine artery Doppler (R -0.17; p = 0.029). CONCLUSIONS: In normal pregnancies during the third trimester, serum PlGF decreases, sFlt-1 increases and sFlt-1/PlGF ratio increases with GA. Angiogenic factor levels needed no adjustment for factors such as smoking, body mass index, blood pressure or parity.

Past and present in omphalocele treatment in Romania.

BACKGROUND: Omphalocele is a congenital abnormality whose prognosis has improved significantly over the last few decades, reaching a survival rate of 80-90% in developed countries. Currently, in Romania no comprehensive study on the incidence, treatment, and survival of patients with this defect of the anterior abdominal wall has been carried out. METHODS: This retrospective analytical study was conducted over a period of 23 years and included 105 children with omphalocele. Prenatal diagnosis, referral to our hospital, children age upon admission, associated diseases, medical and surgical management, early and late postoperative complications, and the length of hospital stay were analysed. RESULTS: The low rate of antenatal diagnosis (13.3%), the high frequency of associated congenital malformations (71.4%) and chromosomal abnormalities (27.6%), inadequate and delayed transport to a specialized pediatric surgery center together with an increased rate of sepsis (37.1%)resulted in a high mortality rate (54.3%). CONCLUSIONS: The significantly reduced length of hospital stay and higher survival rate despite the apparently more frequent medical complications plead for the surgical treatment of omphalocele whenever not contraindicated by the presence of severe pulmonary hypoplasia, cardiac defects, immaturity and other severe congenital anomalies, when conservative treatment is indicated.