Prenatal screening after preimplantation genetic testing for aneuploidy: time to evaluate old strategies.

RESEARCH QUESTION: How does first-trimester aneuploidy screening perform in pregnancies achieved through IVF with preimplantation genetic testing for aneuploidy (PGT-A) in a medical setting? DESIGN: This retrospective cohort study was undertaken in a single tertiary care centre between January 2013 and June 2022. In total, 20,237 women had prenatal follow-up at the study centre and were included in the study. The women were divided into three groups: singleton pregnancies conceived through the transfer of a PGT-A-screened euploid embryo (n = 510); singleton pregnancies conceived through IVF without PGT-A (n = 3291); and singleton pregnancies conceived naturally (n = 16,436). RESULTS: The conventional combined screening test for pregnancies conceived through IVF with PGT-A had specificity of 91%; sensitivity could not be calculated as there were no cases of fetal aneuploidy in this group. In 89.1% of pregnancies conceived through IVF with PGT-A with high risk for trisomy 21, 18 or 13, the result was related to advanced maternal age (>35 years at time of screening). CONCLUSIONS: The current screening strategy for trisomies 21, 18 and 13 can generate unnecessary tests in pregnancies achieved through IVF with PGT-A. A new protocol is needed for these patients, with greater weight given to ultrasound markers.

Prevalence of corpus callosum pathology in an unselected population. Should assessment of the corpus callosum be included in the routine 20 weeks scan?

OBJECTIVES: To determine the prevalence of abnormalities of the corpus callosum (AbnCC) in a non-selected population, to propose a systematic screening protocol for AbnCC in all populations through direct assessment, and to describe the follow-up and prognosis of all AbnCC cases diagnosed in our clinical setting. METHODS: This was a retrospective review of the prevalence of AbnCC over 11 years. We included a sagittal assessment of the corpus callosum (CC) in the second-trimester scan. AbnCC was classified into complete agenesis of CC (ACC) and dysgenesis of CC (DCC; including small, partial agenesis, thick and with lipoma). RESULTS: Of the 38,586 second-trimester scans performed during our screening, 43 cases of AbnCC were detected (prevalence of 0.8/1000). Of the AbnCC cases, 10 cases were identified as ACC (29.40%) and 24 as DCC (70.59%). Follow-up investigations showed that in the 43 cases with AbnCC, 76.5% had other associated ultrasound abnormalities, 26.5% had genetic abnormalities, 11.8% had other MRI abnormalities, and 25% of the children had neurodevelopmental delays (8.8% of the total), which were severe in only one case. CONCLUSIONS: AbnCC is found in approximately 0.8/1000 of cases in an unselected population. The findings suggest that systematic and direct assessment of the CC as part of screening ultrasound in the second trimester of gestation should be recommended as a routine practice.

Fetal Megacystis: Associated Structural Abnormalities and Obstetric Outcomes.

Purpose: We evaluated the obstetrical outcomes, ultrasonographic characteristics, and final diagnosis in pregnancies with fetal megacystis (FM). Methods: We evaluated the obstetrical outcomes and associated structural abnormalities of fetuses with FM detected between FM between 2000 and 2021. Results: 17 FM were diagnosed, 16 had follow up. 16 were early megacystis. 14/16 (87.5%) of pregnancies were terminated, 1/16 (6.25%) resulted in intrauterine death, and 1/16 (6.25%) survived. FM was associated with 13 other abnormal sonographic findings in 12/16 (75%) pregnancies. The most common associated ultrasound abnormality was umbilical cord cyst in 3/16 (18.75%). Recognized etiologies included posterior urethral valves (2), trisomy 18 (2), trisomy 13 (1), Prune Belly syndrome (1), and Megacystis-Microcolon-Hypoperistalsis syndrome (1). Conclusion: Most FM are detected in the 2nd trimester, most are electively terminated, are associated with other ultrasonic abnormalities in 75%, most commonly umbilical cord cyst, and have an identifiable cause in 44%.

"Screening for small-for-gestational age neonates at early third trimester in a high-risk population for preeclampsia".

BACKGROUND: Strategies to improve prenatal detection of small-for-gestational age (SGA) neonates are necessary because its association with poorer perinatal outcome. This study evaluated, in pregnancies with first trimester high risk of early preeclampsia, the performance of a third trimester screening for SGA combining biophysical and biochemical markers. METHODS: This is a prospective longitudinal study on 378 singleton pregnancies identified at high risk of early preeclampsia according to a first trimester multiparametric algorithm with the cutoff corresponding to 15% false positive rate. This cohort included 50 cases that delivered SGA neonates with birthweight < 10th centile (13.2%) and 328 cases with normal birthweight (86.8%). At 27-30 weeks' gestation, maternal weight, blood pressure, estimated fetal weight, mean uterine artery pulsatility index and maternal biochemical markers (placental growth factor and soluble FMS-Like Tyrosine Kinase-1) were assessed. Different predictive models were created to evaluate their performance to predict SGA neonates. RESULTS: For a 15% FPR, a model that combines maternal characteristics, estimated fetal weight, mean uterine artery pulsatility index and placental growth factor achieved a detection rate (DR) of 56% with a negative predictive value of 92.2%. The area under receiver operating characteristic curve (AUC) was 0.79 (95% confidence interval (CI), 0.72-0.86). The DR of a model including maternal characteristics, estimated fetal weight and mean uterine artery pulsatility index was 54% (AUC, 0.77 (95% CI, 0.70-0.84)). The DR of a model that includes maternal characteristics and placental growth factor achieved a similar performance (DR 56%, AUC 0.75, 95% CI (0.67-0.83)). CONCLUSIONS: The performance of screening for SGA neonates at early third trimester combining biophysical and biochemical markers in a high-risk population is poor. However, a high negative predictive value could help in reducing maternal anxiety, avoid iatrogenic interventions and propose a specific plan for higher risk patients.

Prenatal Evaluation of the Fetal Conus Medullaris on a Routine Scan.

OBJECTIVE: To assess the ability to identify the conus medullaris (CM) and measure the conus-sacrum distance (CS distance) on a routine scan and the relationship with maternal and fetal factors. METHODS: This was a prospective study. The assessment of the CM and the CS distance and the influence of the body mass index (BMI), gestational age (GA) and fetal position were analyzed. The correlation between the femur length (FL) and the GA with the CS distance was evaluated. RESULTS: A total of 696 fetuses were analyzed. The CM could be visualized in 82.3% of the cases, and the CS distance could be analyzed in 81.2% of the cases. The CM assessment was statistically associated with BMI and fetal position but not with GA. The CS distance assessment was statistically associated with BMI and GA but not with fetal position. We determined a significant association between the FL/CS distance and between the GA/CS distance. CONCLUSIONS: Assessment of the CM is possible on most routine scans. The CS distance could be introduced to routine scans for the assessment of prenatal skin-covered spinal dysraphism. High BMI, advanced GA and breech presentation could be potential factors limiting the feasibility of evaluating the CM.

Systematic review of screening for trisomy 21 in twin pregnancies in first trimester combining nuchal translucency and biochemical markers: a meta-analysis.

AIM: This article is a systematic review of the literature to establish the detection rate and false-positive rate of the combined test for the screening of trisomy 21 in twins. MATERIAL AND METHODS: We conducted a literature search (MEDLINE, EMBASE and ScienceDirect and Cochrane) to identify studies between 1995 and 2013 that provided data on the combined test in twins. Selected studies included data on maternal age, number of fetuses affected by Down syndrome, test strategy, sensitivity and specificity of the test. RESULTS: The combined test in twins had a pooled sensitivity of 0.893 [95% confidence interval (CI) 0.797-0.947] and a pooled specificity of 0.946 (95% CI 0.933-0.957). The performance of the test was good (summary receiver operating characteristic area under the curve: 0.817). In dichorionic twins, sensitivity and specificity were 0.862 (95% CI 0.728-0.936) and 0.952 (95% CI 0.942-0.96), respectively. In monochorionic twins, the sensitivity and specificity were 0.874% (95% CI 0.526-0.977) and 0.954% (95% CI 0.943-0.963), respectively. CONCLUSIONS: The results of this meta-analysis show that the accumulative evidence on the performance of the combined test in twin pregnancies is good. Nowadays, it seems to be the best first-trimester screening test available for twin pregnancies.

Concordance between prenatal ultrasound and autopsy findings in a tertiary center.

OBJECTIVE: The aim of this study was to evaluate the ultrasound (US)/autopsy concordance in elective termination of pregnancies (TOP) due to fetal causes. METHODS: We performed a retrospective evaluation of elective TOP from 2004 to 2012. Inclusion criteria were gestational age at termination <24 weeks, fetal pathology and availability of US/autopsy data. Based on the US-autopsy concordance, cases were divided into four groups: Group 1: agreement; Group 2: autopsy confirmed all US findings but provided additional information; Group 3: autopsy didn't confirm all US findings; Group 4: disagreement. RESULTS: One hundred and fifty-one patients fulfilled the inclusion criteria during the study period. Central nervous system malformations (91.5%), cardiovascular anomalies (90.2%) and renal system malformations (91.3%) were confirmed by autopsy. We found less concordance in the abdominal and musculoskeletal anomalies (61.5% and 66.7%, respectively). There were 130 (86%) fetuses in group 1, 7 in group 2 (4.6%), 3 in group 3 (1.9%) and 11 in group 4 (7.2%). In 5.29% of cases, the autopsy added relevant information to the diagnosis and counselling. CONCLUSIONS: Diagnosis concordance between US and necropsy is achieved in almost 90% of cases. An autopsy may help to adjust the diagnosis and help in counselling the parents for a future pregnancy.

Sonographic evaluation of the fetal conus medullaris.

OBJECTIVE: The aim of this study is to determine the most reproducible method in the sonographic evaluation of the conus medullaris (CM) and its relationship with gestational age (GA). METHODS: This is a prospective study of singleton structurally normal fetuses between 20 and 30 weeks' gestation. Sonographic evaluation of the CM was performed using two methodologies: a qualitative assessment of the CM level in relation to the lumbar vertebrae and a quantitative measurement of the distance from the CM to the last spine ossification centre (conus-sacrum or CS distance). Both parameters were analysed offline by two operators using 3D stored volumes. Interobserver variability of methods, the relationship between CS and femur length (FL) or GA was evaluated. RESULTS: We analysed 101 3D volumes. Interobserver concordance was low for the CM level (k = 0.4, P < 0.05) and high for CS distance (ICC = 0.950). A significant correlation between CS and both FL and GA was observed. CONCLUSIONS: CS distance but not CM level is reproducible. CS distance is significantly correlated with both FL and GA. CS distance could be useful in the assessment of prenatal skin-covered spinal dysraphism.

Assessment of fetal cardiac function in early fetal life: feasibility, reproducibility, and early fetal nomograms.

BACKGROUND: Fetal cardiology has shown a rapid development in the past decades. Fetal echocardiography is not only used for the detection of structural anomalies but also to assess fetal cardiac function. Assessment of the fetal cardiac function is performed mostly in the second and third trimesters. The study of fetal cardiac function at the end of first trimester has not been investigated properly, and there is a lack of reference values at early gestational weeks. OBJECTIVE: This study aimed to assess if the measurement of time-related parameters of cardiac function in the left ventricle of the fetal heart is feasible and reproducible at the end of the first trimester. If possible, we provide nomograms of these parameters from 11 to 13+6 gestational weeks. STUDY DESIGN: We conducted a prospective observational study from March to September 2022. The study was carried out in 2 hospitals (Hospital Universitari Dexeus, Barcelona, and Hospital VITAHS 9 Octubre, Valencia, Spain). The scans were performed by 3 specialists in fetal medicine. The exclusion criteria were fetal cardiac rhythm abnormalities, abnormal nuchal translucency, abnormal ductus venosus, fetal malformations, stillbirth, estimated fetal weight <10 percentile, diabetes, and gestational hypertensive disorders. The cardiac function parameters studied in the left ventricle were isovolumetric contraction time, isovolumetric relaxation time, ejection time, filling time, cycle time, myocardial performance index, ejection time fraction, and filling time fraction. We study the feasibility and intra- and interobserver reproducibility of these parameters using the interclass correlation coefficient. Nomograms were created and the percentiles of the values of the different parameters were calculated. RESULTS: A total of 409 cases were recruited but only 296 could be included in the statistical analysis once the exclusion criteria were applied. The intraobserver reproducibility study was excellent (interclass correlation coefficient >0.900), and the interobserver reproducibility study was good (interclass correlation coefficient >0.700). The data regression analysis showed that cycle time, filling time, isovolumetric contraction time, and filling time fraction increased with gestational age, whereas ejection time fraction decreased with gestational age and myocardial performance index (mean, 0.43±0.08), isovolumetric relaxation time (mean, 0.04±0.01), and ejection time (mean, 0.16±0.01) remained constant from 11 to 13 weeks. CONCLUSION: The study of fetal cardiac function is feasible and reproducible at 11 to 13+6 gestational weeks. Nomograms of the studied parameters are provided.

Angiogenic factors assessment in pre-eclampsia high-risk population for the prediction of small-for-gestational age neonates: A prospective longitudinal study.

OBJECTIVE: The authors aimed to compare cross-sectional versus longitudinal models for prediction of small-for-gestational age (SGA) neonates among pregnancies with high risk of early pre-eclampsia (PE). METHODS: A prospective longitudinal study was performed in Hospital Universitari Dexeus, Barcelona. The study population included 390 pregnancies with a high risk of early PE according to the first trimester algorithm. Cross-sectional models combining first trimester risk plus placental growth factor and FMS-like tyrosine kinase 1/placental growth factor ratio, respectively, were created at 19-22, 24-26, and 27-30 weeks and compared with a model assessing longitudinal changes of these parameters. Models adding mean uterine artery pulsatility index and abdominal circumference were evaluated. SGA neonates were defined as having a birth weight less than the tenth centile. RESULTS: The predictive performance of a model assessing longitudinal changes of angiogenic factors was similar to that of single evaluations at the second and early third trimesters. The performance of the models combining angiogenic factors with mean uterine artery pulsatility index and abdominal circumference was better than those using only biochemical markers. However, the longitudinal evaluation of biochemical and biophysical parameters did not perform better than cross-sectional evaluations. CONCLUSIONS: Evaluation of angiogenic factors are useful for prediction of SGA neonates in a high-risk population for early PE. However, longitudinal models do not increase their predictive capacity.

Early first-trimester free-ß-hCG and PAPP-A serum distributions in monochorionic and dichorionic twins.

OBJECTIVE: To examine the distribution of first-trimester biochemical markers of aneuploidy in twins according to chorionicity. METHODS: Maternal serum free-ß-human chorionic gonadotropin (hCG) and pregnancy-associated plasma protein A (PAPP-A) were measured between 8-13 + 6 weeks as a part of a routine first-trimester screening program in conjunction with fetal nuchal translucency measured at 11 to 13 + 6 weeks' gestation. Data from 279 twin pregnancies were extracted from our fetal databases. Down syndrome cases were excluded. Individual marker concentrations were expressed as weight, ethnicity, smoking and maternal diabetes corrected. To compare the distributions of the biochemical parameters, a generalized additive model was used adjusted to a smoothing regression model with the values transformed with base 10'' logarithm using R software (generalized additive model-smoothing spline regression). RESULTS: Free-ß-hCG and PAPP-A distributions, analyzed with a generalized additive model adjusted to a smoothing regression model, were significantly different depending on the chorionicity. We graphically displayed the relationship between the predicted concentration of the free-ß-hCG and PAPP-A and the gestational age in days for monochorionic and dichorionic twins adjusted by weight. CONCLUSION: Pregnancy-associated plasma protein A and free-ß-hCG values are gestational age specific. It is necessary to make a distinction between monochorionic and dichorionic twins because biochemical markers are lower in monochorionic than in dichorionic twins.

First trimester risk assessment for trisomy 21 in twin pregnancies combining nuchal translucency and first trimester biochemical markers.

OBJECTIVE: The aim is to describe the performance of first-trimester combined risk assessment in twin pregnancies. METHODS: Maternal serum free beta-human chorionic gonadotrophin and pregnancy-associated plasma protein A (PAPP-A) were determined at 8 to 12 weeks and fetal nuchal translucency (NT) was measured at 11 to 13+6 weeks. The individual risk was estimated for each fetus using the combined test in dichorionic twins. In monochorionic twins, the mean risk assessment of the two fetuses was used. An invasive diagnostic procedure was offered when the risk was ≥ 1 : 270 in either one of the fetuses. RESULTS: From February 2007 to June 2011, 447 twin pregnancies were enrolled in this study. There were 402 (89.9%) dichorionic and 45 (10.1%) monochorionic twins. In dichorionic twins, mean crown-rump length (CRL) was 63.9 mm; median NT multiples of the median (MoM) was 0.97; median Β-hCG was MoM 1.74; median PAPP-A was 1.72. In monochorionic twins, mean CRL was 61.9 mm; median NT MoM was 0. 98; median Β-hCG MoM was 1.44; and median PAPP-A was 1.51. Two pregnancies with Down syndrome were detected by first trimester screening, both in dichorionic twins. The false positive rate was 5.7% (95% confidence interval 4.1-7.3) and 4.4% (95% confidence interval 0.1-8.8%) in dichorionic and monochorionic twins, respectively. CONCLUSIONS: The combined test in twins appears to be a good method for Down syndrome screening with a high detection rate and an acceptable false-positive rate.

Is the addition of the ductus venosus useful when screening for aneuploidy and congenital heart disease in fetuses with normal nuchal translucency?

OBJECTIVE: The aim of this study was to examine the possible role of Doppler ultrasound assessment of ductus venosus (DV) blood flow at 11⁺°-13⁺6 weeks' gestation in fetuses with normal nuchal translucency (NT) in screening for autosomal trisomies (AT) and for congenital heart diseases (CHD) in chromosomally normal fetuses. METHODS: First-trimester combined screening for trisomy 21 (T21) was carried out prospectively for 7 years in singleton pregnancies. NT and the pulsatility index for DV (DVPI) were calculated. The DV was analyzed according to its association with AT and CHD. The detection rate (DR), false-positive rate (FPR), positive predictive value (PPV), and odds ratio (OR) for abnormal DV were calculated. RESULTS: Abnormal DV as an early marker of euploid CHD gives a DR of 12.5%, an FPR of 4.3%, a PPV of 1.4%, and a negative predictive value (NPV) of 99.5%, with an OR of 3.1 (95% CI 1.3-7.4). Moreover, abnormal DV as an early marker of AT shows a DR of 35.7%, an FPR of 4.3%, a PPV of 1.2%, an NPV of 99.9%, and an OR of 12.3 (95% CI 4.1-36), and the values are 33.3, 4.3, 0.97, and 99.9% and 11 (95% CI 3.2-36.9), respectively, for T21. CONCLUSIONS: Our data supports the association between increased DVPI and CHD or AT. The sensitivity of this marker is not strong enough to be used a screening test.

Outcome in a series of 1135 twin pregnancies: does the type of conception play a role?

BACKGROUND: The rate of twin pregnancies conceived via assisted reproductive technology has increased markedly in recent years. The elevated number of multiple pregnancies is the most serious and frequent complication of assisted reproductive technology. Twin pregnancies are associated with higher rates of obstetrical complications, preterm delivery, and perinatal morbidity and mortality than singleton pregnancies. OBJECTIVE: This study aimed to investigate the association between the mode of conception and obstetrical and perinatal outcomes in twin pregnancies, adjusting for parity, age, and chorionicity. STUDY DESIGN: This was a retrospective cohort study of 1135 twin pregnancies between May 2006 and April 2021. All spontaneous (n=369) and assisted reproductive technology-conceived (n=766) twin pregnancies with antenatal care and delivery in the Universitari Quiron-Dexeus Hospital, Barcelona, Spain, a tertiary obstetrical care center, were studied according to chorionicity. RESULTS: The mean maternal age was higher among assisted reproductive technology twin pregnancies than among naturally conceived ones, and there were also less parous women in the assisted reproductive technology twin group. The global survival rates in both groups of twins were practically identical, namely 744 of 766 (97.1%) assisted reproductive technology twins and 357 of 369 (96.8%) spontaneously conceived twins. Patients with dichorionic assisted reproductive technology twins had a higher incidence of gestational diabetes (relative risk, 1.69; 95% confidence interval, 1.10-2.59) and gestational hypertension or preeclampsia (relative risk, 2.75; 95% confidence interval, 1.60-4.729). Monochorionic diamniotic assisted reproductive technology twins had a higher risk for gestational diabetes (relative risk, 4.12; 95% confidence interval, 1.35-12.56). We analyzed the gestational age at delivery, onset of labor, type of delivery, rate of preterm births, weight discordance, rate of small for gestational age neonates and intrauterine growth restriction, and admission to the neonatal intensive care unit. We could not find any statistical differences between monochorionic diamniotic assisted reproductive technology twins and spontaneously conceived twins. Among dichorionic twins, those conceived by assisted reproductive technology had an earlier gestational age at delivery (36.3±2.29 vs 36.6±2; P<.05) and we found statistical differences in the onset of labor with more cesarean deliveries (relative risk, 1.27; 95% confidence interval, 1.06-1.51). When adjusting for cofounding factors (maternal age, parity, chorionicity), the type of conception remained an independent risk factor for gestational hypertension and preeclampsia but not for gestational diabetes or cesarean delivery. CONCLUSION: Pregnancy outcomes are comparable between assisted reproductive technology and spontaneously conceived twins, and when adjusted for confounding factors, only the risk for gestational hypertension and preeclampsia remained increased in the assisted reproductive technology group.

Gestational diabetes prevalence and outcomes in women undergoing assisted reproductive techniques (ART).

Infertility affects millions worldwide and use of assisted reproductive techniques (ART) is in high demand. AIMS: To investigate whether women that underwent ART at our hospital had a higher incidence of GDM than women who conceived spontaneously, if the ART subtype affects the GDM rate and to study obstetrical outcomes in women with GDM in both groups. METHODS: This was a retrospective analysis of prospectively collected data of singleton pregnancies attended at Hospital Universitari Dexeus between 2008 and 2019. Age<18 years, pregestational diabetes, metformin prior to pregnancy and multiple pregnancies were excluded. RESULTS: A total of 29,529 patients were included. Pregnancy was achieved by ART in 2596 (8.8%): in vitro fertilisation (IVF/ICSI) 32.8%, frozen embryo transfer (FET) 37.7%, oocyte donor receptors (ODR) 17.2% and insemination 12.2%. The GDM rate was 8.9% (12.7% in ART vs 8.5% in non-ART, p<0.001). The GDM was 11.2% in IVF/ICSI, 17.7% in ODR, 13% in FET and 9.1% in the insemination group (p=0.001). In a multivariable analysis adjusting for age, parity and BMI, ART was not associated with GDM [OR 1.03 (0.90-1.19)], nor was type of ART. Pregnancy outcomes in GDM patients were similar in both groups except for C-section rates (30.0% in ART vs 15.9% in non-ART (p<0.001). CONCLUSIONS: Despite a higher prevalence of GDM in ART pregnancies, ART was not associated with an increased risk of GDM when adjusting for age, parity and BMI. The prognosis of GDM in ART and non-ART was similar except for C-section rates.

Maternal high-dose valacyclovir and its correlation with newborn blood viral load and outcome in congenital cytomegalovirus infection.

BACKGROUND/OBJECTIVE: Currently, there is no validated treatment for fetal cytomegalovirus (CMV). Two studies suggest that high-dose maternal valacyclovir decreases fetal viral load and improves outcomes in moderately-symptomatic fetuses. We offered valacyclovir in cases of fetal infection lacking ultrasound abnormalities or with non-severe infection. Maternal tolerability, fetal outcome and newborn blood viral load were evaluated in pregnancies of mothers receiving valacyclovir. STUDY DESIGN: We performed a case series including 8 pregnancies with fetal CMV classified as unaffected/mildly-moderately affected. Mothers received valacyclovir (8 g/24h) from fetal infection diagnosis to delivery. Standard newborn evaluation was performed, and viremia was determined in the first 48 h of life and compared according to length of maternal treatment and presence/absence of prenatal anomalies. RESULTS: Valacyclovir was administered at a median gestational age of 26.5 weeks (23.8-33.1) in 3 cases without fetal abnormalities, and 5 with mild/moderate abnormalities. Three were 3 first trimester primary infections, one non-primary infection, and in 4 the type of infection was unknown. Valacyclovir was well-tolerated. Fetal features did not progress. Three newborns were asymptomatic, and one was severely affected (bilateral chorioretinitis). The median newborn viral load (IQR) was 502 IU/mL (231-191781) with lower levels when maternal treatment was administered ≥10 weeks, and in cases without fetal abnormalities [median 234 IU/mL (228-711) vs. 4061 (292-510500) p = .18; and 234 IU/mL (228-379500) vs. 711 IU/mL (292-4061) p = .65, respectively], these differences being non-significant. CONCLUSIONS: Fetal CMV lesions remained stable with high-dose maternal valacyclovir. Newborn viral load was unchanged despite treatment duration and fetal/neonatal abnormalities. SUMMARY: Fetal cytomegalovirus lesions remained stable with high-dose maternal valacyclovir. Newborn viral load was unchanged despite treatment duration and fetal/newborn abnormalities.

Effects of angiotensin-converting enzyme inhibitors (ACE i) on zinc metabolism in patients with heart failure.

The aim of this study is to investigate the effects of angiotensin-converting enzyme (ACE) inhibitors and furosemide on zinc metabolism by assessing serum zinc and urine levels in hospitalized subjects. We recruited 11 patients with heart failure from the Internal Medicine Department; these patients had been hospitalized less than 72 h before. Heart failure was defined using clinical and radiological signs. Serum zinc concentrations were measured using an air/acetylene flame atomic absorption spectrophotometer. Urine zinc levels were analyzed by inductively coupled plasma mass spectrometry (ICP-MS). Data were obtained from the 11 patients and 24 healthy controls matched for age and sex. Results indicate higher urine zinc levels and lower concentrations of zinc in serum in heart failure patients vs matched controls (p<0.05). This study suggests that treating heart failure patients with ACE inhibitors may result in zinc deficiency.

Initial experience with non-invasive prenatal testing of cell-free DNA for major chromosomal anomalies in a clinical setting.

OBJECTIVE: To evaluate non-invasive prenatal testing (NIPT) of cell-free DNA (cfDNA) as a screening method for major chromosomal anomalies (CA) in a clinical setting. METHODS: From January to December 2013, Panorama™ test or Harmony™ prenatal test were offered as advanced NIPT, in addition to first-trimester combined screening in singleton pregnancies. RESULTS: The cohort included 333 pregnant women with a mean maternal age (MA) of 37 years who underwent testing at a mean gestational age of 14.6 weeks. Eighty-four percent were low-risk pregnancies. Results were provided in 97.3% of patients at a mean reporting time of 12.9 calendar days. Repeat sampling was performed in six cases and results were obtained in five of them. No results were provided in four cases. Four cases of Down syndrome were detected and there was one discordant result of Turner syndrome. We found no statistical differences between commercial tests except in reporting time, fetal fraction and MA. The cfDNA fraction was statistically associated with test type, maternal weight, BMI and log ßhCG levels. CONCLUSIONS: NIPT has the potential to be a highly effective screening method for major CA in a clinical setting.

Analysis of three different strategies in prenatal screening for Down's syndrome in twin pregnancies.

OBJECTIVES: To compare the performance of three different strategies in prenatal screening for Down's syndrome in twins [nuchal translucency, the combined test, the combined test + ductus venosus pulsatility index (DVPI)]. METHODS: We included 277 twin pregnancies with two cases of trisomy 21 (both dichorionic). We performed a computer simulation of Down's syndrome NT screening, combined test screening and the combined test with the addition of DVPI screening using the commercialized software SsdwLab6. The strategies were compared using the area under the receiver operating characteristic curve. RESULTS: NT screening false-positive rate (FPR) was 10.9% (95% CI: 8.3-13.5). The combined test FPR was 6.2% (95% CI: 4.1-8.2%) and the combined test plus DVPI was 6% (95% CI: 4-8). FPR was higher in advanced maternal age patients. Detection rate was 100% in all cases. The area under the curve was 0.987 (95% CI: 0.972-0.994) in NT screening; 0.987 (95% CI: 0.978-0.997) in the combined test and 0.983 (95% CI: 0.977-0.996) in the combined test + DVPI. CONCLUSIONS: Down's syndrome screening is feasible in twins with low FPR. The results of this study are similar to the results achieved in singletons. The combined test appears to be the most effective. The addition of DVIP does not significantly improve the prenatal screening for trisomy 21.