Neonatal herpes: case series in two obstetric centres over a 10-year period (2013-2023), France.

Neonatal herpes simplex virus (HSV) infection (HSV infection in infants less than 6 weeks of age) is rare but mortality and morbidity rates are high after disseminated disease and encephalitis. In France, the epidemiology is poorly described, and two decades ago, incidence was estimated to be 3 per 100,000 live births a year. We describe determinants, epidemiologic and clinical characteristics of neonatal HSV infection in a managed-care population attending in two major obstetric and paediatric centres, Paris, France, over a 10-year period. This retrospective case series study was conducted from 2013 to 2023, in infants less than 42 days of age who had virologically confirmed HSV infection. We report an overall rate of neonatal herpes of 5.5 per 100,000 live births a year and an incidence of symptomatic cases of 1.2 per 100,000 live births a year. HSV-1 was the major serotype involved (84.2%) and post-natal acquisition through the orolabial route reached 63.2%. All neonates who had neonatal HSV PCR screening (owing to clinical signs in parents) and who received prompt acyclovir treatment remained asymptomatic. Symptomatic forms accounted for 21.1% cases of the total and mortality was high (62.5% of symptomatic forms).   Conclusion: This case series confirms that neonates at risk for HSV disease and poor outcome are those born to HSV-seronegative mothers, preterm infants, and those who received acyclovir after onset of symptoms (mainly because mothers did not present evidence of acute HSV infection). Our study confirms the major role of HSV-1 and the frequency of its early post-natal acquisition. What is known: • Neonatal herpes simplex virus infection is rare but motality and morbidity rates are high after disseminted disease and encephalitis. National recommendations exist worldwide but mangement of this disease is not always easy. What is new: • As in France epidemiology of neonatal herpes is poorly described, our report is potentially an important addition to the existing literature. Moreover, we describe local practice that may be useful to physicians.

[Antenatal care for fetuses with congenital diaphragmatic hernia]. / Prise en charge anténatale des fœtus porteurs d'une hernie de coupole diaphragmatique.

Congenital diaphragmatic hernia (CDH) can be diagnosed prenatally and its severity assessed by fetal imaging. The prognosis of a fetus with CDH is based on whether or not the hernia is isolated, the measurement of lung volume on ultrasound and MRI, and the position of the liver. The birth of a child with CDH should take place in a center adapted to the care of such children, and in accordance with the recommendations defined by the French National Diagnosis and Care Protocol. It has recently been demonstrated that for moderate and severe forms of CDH, tracheal occlusion using a balloon placed in utero by fetoscopy (FETO) increases survival until discharge from the neonatal unit, but at the cost of an increased risk of prematurity. At the same time, advances in neonatal resuscitation and the standardization of follow-up of these children within the framework of the "Centre de référence maladies rares: hernie de coupole diaphragmatique" have improved the prognosis of these children and young adults.

Management and survival of foetuses with trisomy 18 in a French retrospective cohort.

OBJECTIVES: The main objective of this study was to evaluate parents' current demands following the announcement of trisomy 18 and maternal risks. MATERIAL AND METHODS: A single-centre retrospective study was performed in the Paris Saclay Foetal Medicine Department from 2018 to 2021. All patients followed up in the department who had cytogenetic confirmation of trisomy 18 were included. RESULTS: 89 patients were recruited. The most common malformations at ultrasound examination were cardiac or brain abnormalities, distal arthrogryposis as well as severe intrauterine growth retardation. 29% of foetuses with trisomy 18 had more than three malformations. 77.5% of patients requested medical termination of pregnancy. Among the 19 patients who chose to continue their pregnancy, 10 (52.6%) presented with obstetrical complications, of which 7 (41.2%) experienced stillbirth; five babies were born alive with no survival at 6 months. CONCLUSION: In France, in the case of foetal trisomy 18, most women request termination of pregnancy. In the post-natal period, the management of a newborn with trisomy 18 is oriented towards palliative care. The mother's risk of obstetrical complications should be part of counselling. Follow-up, support and safety should be the goal of management of these patients, regardless of the patient's choice.

Impact of the 1st Wave of the COVID-19 Pandemic and Lockdown on In Utero Transfer Activity in the Paris Area, France.

BACKGROUND: To assess changes in the number and profile of in utero transfer requests during the first lockdown. METHODS: An observational, retrospective, cohort study. All pregnant women, from the Paris area (France), for whom a request for in utero transfer to the transfer unit was made during the first lockdown in France (from 17 March to 10 May 2020) or during a mirror period (years 2016 to 2019) were included. We compared the numbers and proportions of various indications for in utero transfer, the rates of in utero transfer acceptance and the proportion of outborn deliveries. RESULTS: 206 transfer requests were made during the lockdown versus 227, 236, 204 and 228 in 2016, 2017, 2018 and 2019, respectively. The relative proportion of requests for threatened preterm births and for fetal growth restriction decreased from 45% in the mirror period to 37% and from 8 to 3%, respectively. The transfer acceptance rates and outborn deliveries did not differ between time periods. CONCLUSIONS: Although a reduction in in utero transfer requests was observed for certain indications, the first lockdown was not associated with a decrease in acceptance rates nor in an increase in outborn births of pregnancies with a high risk of prematurity in the Paris area.

Risk of hypoglycemia by anthropometric measurements in neonates of mothers with diabetes.

Macrosomia in neonates of diabetic women is a risk factor for neonatal hypoglycemia, with an over-risk for asymmetric macrosomia. This study aimed to study the association between anthropometric measurements and hypoglycemia in neonates of mothers treated for gestational diabetes. This is a secondary analysis of the INDAO trial study conducted between May 2012 and November 2016 in 13 French tertiary care university hospitals in 890 pregnant women with gestational diabetes treated with either insulin or glyburide. Neonatal anthropometric measurements were birthweight and weight-length ratio (WLR, defined as birth weight/length). Neonatal hypoglycemia was defined as capillary blood glucose below 36 mg/dL (2 mmol/L) or below 45 mg/dL (2.5 mmol/L) associated with clinical signs after 2 h of life. Their relationships were modeled with logistic regressions using fractional polynomials. Extreme categories of birthweight or WLR adjusted for gestational age at birth and sex were defined as Z-score < -1.28 or > 1.28. These categories were compared to Z-score between -1.28 and 1.28 by estimating odds ratios and confidence intervals for neonatal hypoglycemia. Neonatal hypoglycemia occurred in 9.1% of cases. The relationship between birthweight and WLR Z-scores and neonatal risk of hypoglycemia adjusted for maternal treatment was a U-shaped curve. Adjusted odds ratios for the risk of hypoglycemia were 9.6 (95% CI 3.5, 26.8) and 2.3 (95% CI 1.1, 4.9) for WLR Z-score below -1.28 and above 1.28, respectively, compared with WLR Z-score between -1.28 and 1.28.    Conclusion: Birthweight Z-score was associated with the risk of neonatal hypoglycemia in neonates from mothers treated for gestational diabetes. The risk of neonatal hypoglycemia was increased for both extreme birthweight Z-scores, regardless of maternal treatment. Small for gestational age neonates of diabetic mothers require special attention for the risk of neonatal hypoglycemia. What is Known: • Macrosomia in neonates of diabetic women is a risk factor for neonatal hypoglycemia, with an over-risk for asymmetric macrosomia. Few retrospective studies have assessed the risk for neonatal hypoglycemia among small for gestational age neonates born to diabetic mothers. What is New: • The risk of neonatal hypoglycemia among neonates of diabetic mothers increased for both low and high weight-length ratio, regardless of maternal medicinal treatment, gestational age at birth, and sex of the newborn.

Hypoglycemia and Glycemic Control With Glyburide in Women With Gestational Diabetes and Genetic Variants of Cytochrome P450 2C9 and/or OATP1B3.

Glyburide is mainly metabolized by the cytochrome P450 2C9 (CYP2C9) enzyme and enters the liver via the transporter OATP1B3. The variants OATP1B3*4 (699 G>A; rs7311358) and CYP2C9*2 and *3 are known to have a significant influence on the hepatic uptake and metabolism of glyburide, with lower clearance than in the wild type. In an ancillary study of the INDAO trial, we selected 117 pregnant women with gestational diabetes treated by glyburide and assessed the role of the combined CYP2C9 and OATP1B3 genetic polymorphisms in hypoglycemia and glycemic control. Three groups were constituted: (1) the wild-type genotype group (wild-type allele genotype for both CYP2C9*1 and OATP1B3*1 (699G)), (2) the intermediate group (carriers of CYP2C9*2 allele or OATP1B3*4 (699G>A) heterozygous), and (3) the variant group (carriers of CYP2C9*3 allele and/or OATP1B3*4 (699G>A) homozygous variant). We found that the risk of hypoglycemia was significantly higher in the variant genotype at the second week of treatment: 20.0% (4/20) vs. 8.1% (3/37) in the intermediate group and 4.1% (2/49) in the wild-type genotype group (P = 0.03). The last daily dose of glyburide during pregnancy was lower for patients in the variant genotype group: 4.7 mg (SD 3.5) vs. 8.7 mg (SD 5.7) in the wild-type group and 5.7 mg (SD 3.7) in the intermediate group (P < 0.01). In conclusion, the no-function variants CYP2C9*3 and OATP1B3*4 are associated with a higher risk of hypoglycemia and a lower dose of glyburide in women with gestational diabetes treated with glyburide, which is consistent with the pharmacokinetic roles of both CYP2C9 and OATP1B3.

Glyburide therapy for gestational diabetes: Glycaemic control, maternal hypoglycaemia, and treatment failure.

AIMS: The recommended first-line treatment for women with gestational diabetes mellitus (GDM) in the case of failure of diet is insulin. Recent results suggest that there is a potential role for glyburide therapy and highlight the need for better knowledge of glycaemic control with glyburide. The objective of this study was to describe and quantify in women with GDM the quality of glycaemic control, including the risk of maternal hypoglycaemia and of therapy failure. METHODS: This is a secondary analysis of the French INDAO non-inferiority trial from 2012 to 2016, in which 890 women with GDM randomized to receive glyburide or insulin treatment were compared for perinatal outcomes. Blood glucose concentrations were assessed prospectively during pregnancy. Optimal glycaemic control was defined as less than 20% of blood glucose values exceeding the targets. RESULTS: More than 50% of the women had optimal glycaemic control with glyburide, similar to that with insulin. Around 40% of the women had at least one episode of hypoglycaemia, more than with insulin. However, those hypoglycaemic episodes were mostly moderate and the rate of severe hypoglycaemia decreased significantly during the course of the trial. Failure of glyburide treatment (switch to insulin therapy) occurred in 18% of women and had few predictors. However, when failure occurred, glycaemic control was improved after switching to insulin. CONCLUSIONS: Glyburide is an effective treatment for reaching glycaemic goals during pregnancy in women with GDM. The risk of maternal hypoglycaemia may be minimized by clinical practice experience. These findings could be taken into account in the management of GDM.

Impact of simulation-based prenatal invasive procedure training on professional practice, a preliminary study.

INTRODUCTION: Amniocentesis and chorionic villus sampling remain the cornerstone of prenatal diagnosis. These procedures are associated with a risk of miscarriage estimated at approximately 0.5 %. Our team has developed a training model for performing simulation-based prenatal invasive procedures. Several simulation sessions are offered each year to obstetricians-gynecologists involved in fetal medicine in France and abroad. This simulation-based learning has already been conclusively evaluated according to levels I and II of the Kirkpatrick model. Here, we carried out a preliminary study according to level III: does participation in training in prenatal invasive procedures through simulation have an influence on professional practice? METHODS: An anonymous online survey was sent to 82 obstetricians-gynecologists who participated in the training in prenatal invasive procedures at the Antoine Béclère maternity hospital between January 1st, 2014 and December 31, 2018. This questionnaire, entitled "Evaluation of the professional impact of training in invasive procedures through simulation", included 20 quantitative and qualitative items. RESULTS: 48 (59 %) obstetricians-gynecologists responded to the questionnaire. 98 % of the participants considered that participation in the training had a significant impact on their professional practice. Half considered this impact to be major. 60 % of the former participants are now attached to a Multidisciplinary Center for Prenatal Diagnosis. CONCLUSION: Participation in training is considered by former participants to have a significant impact on their professional practice. In order to finalize the evaluation of this learning, a study of the benefits for patients and their pregnancy should be discussed.

Post lockdown COVID-19 seroprevalence and circulation at the time of delivery, France.

BACKGROUND: To fight the COVID-19 pandemic, lockdown has been decreed in many countries worldwide. The impact of pregnancy as a severity risk factor is still debated, but strict lockdown measures have been recommended for pregnant women. OBJECTIVES: To evaluate the impact of the COVID-19 pandemic and lockdown on the seroprevalence and circulation of SARS-CoV-2 in a maternity ward in an area that has been significantly affected by the virus. STUDY DESIGN: Prospective study at the Antoine Béclère Hospital maternity ward (Paris area, France) from May 4 (one week before the end of lockdown) to May 31, 2020 (three weeks after the end of lockdown). All patients admitted to the delivery room during this period were offered a SARS-CoV-2 serology test as well concomitant SARS-CoV-2 RT-PCR on one nasopharyngeal sample. RESULTS: A total of 249 women were included. Seroprevalence of SARS-CoV-2 was 8%. The RT-PCR positive rate was 0.5%. 47.4% of the SARS-CoV-2-IgG-positive pregnant women never experienced any symptoms. A history of symptoms during the epidemic, such as fever (15.8%), myalgia (36.8%) and anosmia (31.6%), was suggestive of previous infection. CONCLUSIONS: Three weeks after the end of French lockdown, SARS-CoV-2 infections were scarce in our region. A very high proportion of SARS-CoV-2-IgG-negative pregnant women, which is comparable to that of the general population, must be taken into consideration in the event of a resurgence of the pandemic. The traces of a past active circulation of the virus in this fragile population during the spring wave should encourage public health authorities to take specific measures for this independent at-risk group, in order to reduce viral circulation in pregnant patients.

Feticide in second- and third-trimester termination of pregnancy for fetal anomalies: Results of a national survey.

OBJECTIVE: To conduct an audit of the practice of feticide in second- and third-trimester termination of pregnancy for fetal anomalies (TOPFA) in prenatal diagnosis (PD) centers in France. RESULTS: A questionnaire was sent out to the 49 French PD centers and completed by 39/49 centers; 5350 TOPFAs were performed. The gestational age after which feticide was performed was 20 weeks in two centers (5%), 22 weeks in 28 centers (72%), 23 weeks in four centers (10%), and 24 weeks in five centers (13%). Fifteen of 39 centers reported that feticide was not performed in all cases, because of a fetal abnormality associated with a high probability of rapid neonatal death (13 centers), pregnant woman's refusal (11 centers), and technical impossibility of performing feticide (one center). Feticide was done using xylocaine in 38 of the 39 centers and using KCl in the remaining center. All but one of the centers before feticide used fetal anesthesia. Feticide was done on the day of induction of labor in 35/39 centers (90%), after maternal epidural analgesia in 33 centers, or after maternal subcutaneous local anesthesia in two centers. Feticide was done the day before induction of labor in two centers. CONCLUSION: In France, most TOPFAs performed in second and third trimesters are associated with feticide, which is most often done after fetal anesthesia.

Cell-Free DNA Analysis in Maternal Blood: Differences in Estimates between Laboratories with Different Methodologies Using a Propensity Score Approach.

OBJECTIVES: To evaluate the failure rate and performance of cell-free DNA (cfDNA) testing, mainly in terms of detection rates for trisomy 21, performed by 2 laboratories using different analytical methods. METHODS: cfDNA testing was performed on 2,870 pregnancies with the HarmonyTM Prenatal Test using the targeted digital analysis of selected regions (DANSR) method, and on 2,635 pregnancies with the "Cerba test" using the genome-wide massively parallel sequencing (GW-MPS) method, with available outcomes. Propensity score analysis was used to match patients between the 2 groups. A comparison of the detection rates for trisomy 21 between the 2 laboratories was made. RESULTS: In all, 2,811 patients in the Harmony group and 2,530 patients in the Cerba group had no trisomy 21, 18, or 13. Postmatched comparisons of the patient characteristics indicated a higher no-result rate in the Harmony group (1.30%) than in the Cerba group (0.75%; p = 0.039). All 41 cases of trisomy 21 in the Harmony group and 93 cases in the Cerba group were detected. CONCLUSIONS: Both methods of cfDNA testing showed low no-result rates and a comparable performance in detecting trisomy 21; yet GW-MPS had a slightly lower no-result rate than the DANSR method.

Autoimmune disorders but not heparin are associated with cell-free fetal DNA test failure.

BACKGROUND: Recent studies have suggested a possible association between heparin treatment at the time of cell-free DNA (cfDNA) testing and a non-reportable result. However, these studies lack of proper methodology and had a low level of proof to firmly incriminate heparin. Our objective was to investigate further the relationship between heparin treatment and cfDNA test results. METHODS: Two complementary approaches were used for the demonstration. First, we conducted a retrospective analysis of a cohort of patients with a singleton pregnancy, screened for aneuploidies by using cfDNA, but with a non-reportable cfDNA result. We included patients between 2013 and 2016 including the patients from the DEPOSA study as controls. CfDNA testing was performed by massive parallel sequencing by using a whole-genome approach. A multiple logistic regression was used to account for the influence of the variables included. Second, we performed in vitro experiments on mimic samples containing increased concentrations of heparin. RESULTS: Of 9867 singleton pregnancies tested during the inclusion period, 58 (0.59%) had a non-reportable result and were compared to 295 control patients. Fifteen (25.9%) and 20 (6.8%) patients were treated with heparin in the group with a non-reportable cfDNA result and with a successful assay, respectively. In multivariable analysis, an increased calculated risk at the first-trimester combined screening (OR 28.8 CI 9.76-85.15, p < 0.001), maternal weight (OR 1.03, CI 1.01-1.06, p = 0.01), and the presence of an autoimmune disease (OR 10.38, CI 1.62-66.53, p = 0.01) were the only characteristics associated with a non-reportable result. In vitro experiments showed that heparin had no impact on fetal fraction measurement or the final result, no matter what the dose tested. CONCLUSIONS: Treatment by heparin had no impact on cfDNA screening test for aneuploidies, while the presence of an autoimmune disorder is an independent predictor of a non-reportable result.

Myoepithelial cell-driven acini contraction in response to oxytocin receptor stimulation is impaired in lacrimal glands of Sjögren's syndrome animal models.

The purpose of the present studies was to investigate the impact of chronic inflammation of the lacrimal gland, as occurs in Sjögren's syndrome, on the morphology and function of myoepithelial cells (MECs). In spite of the importance of MECs for lacrimal gland function, the effect of inflammation on MECs has not been well defined. We studied changes in MEC structure and function in two animal models of aqueous deficient dry eye, NOD and MRL/lpr mice. We found a statistically significant reduction in the size of MECs in diseased compared to control lacrimal glands. We also found that oxytocin receptor was highly expressed in MECs of mouse and human lacrimal glands and that its expression was strongly reduced in diseased glands. Furthermore, we found a significant decrease in the amount of two MEC contractile proteins, α-smooth muscle actin (SMA) and calponin. Finally, oxytocin-mediated contraction was impaired in lacrimal gland acini from diseased glands. We conclude that chronic inflammation of the lacrimal gland leads to a substantial thinning of MECs, down-regulation of contractile proteins and oxytocin receptor expression, and therefore impaired acini contraction. This is the first study highlighting the role of oxytocin mediated MEC contraction on lacrimal gland function.

Effect of Glyburide vs Subcutaneous Insulin on Perinatal Complications Among Women With Gestational Diabetes: A Randomized Clinical Trial.

Importance: Randomized trials have not focused on neonatal complications of glyburide for women with gestational diabetes. Objective: To compare oral glyburide vs subcutaneous insulin in prevention of perinatal complications in newborns of women with gestational diabetes. Design, Settings, and Participants: The Insulin Daonil trial (INDAO), a multicenter noninferiority randomized trial conducted between May 2012 and November 2016 (end of participant follow-up) in 13 tertiary care university hospitals in France including 914 women with singleton pregnancies and gestational diabetes diagnosed between 24 and 34 weeks of gestation. Interventions: Women who required pharmacologic treatment after 10 days of dietary intervention were randomly assigned to receive glyburide (n=460) or insulin (n=454). The starting dosage for glyburide was 2.5 mg orally once per day and could be increased if necessary 4 days later by 2.5 mg and thereafter by 5 mg every 4 days in 2 morning and evening doses, up to a maximum of 20 mg/d. The starting dosage for insulin was 4 IU to 20 IU given subcutaneously 1 to 4 times per day as necessary and increased according to self-measured blood glucose concentrations. Main Outcomes and Measures: The primary outcome was a composite criterion including macrosomia, neonatal hypoglycemia, and hyperbilirubinemia. The noninferiority margin was set at 7% based on a 1-sided 97.5% confidence interval. Results: Among the 914 patients who were randomized (mean age, 32.8 [SD, 5.2] years), 98% completed the trial. In a per-protocol analysis, 367 and 442 women and their neonates were analyzed in the glyburide and insulin groups, respectively. The frequency of the primary outcome was 27.6% in the glyburide group and 23.4% in the insulin group, a difference of 4.2% (1-sided 97.5% CI, -∞ to 10.5%; P=.19). Conclusion and Relevance: This study of women with gestational diabetes failed to show that use of glyburide compared with subcutaneous insulin does not result in a greater frequency of perinatal complications. These findings do not justify the use of glyburide as a first-line treatment. Trial Registration: clinicaltrials.gov Identifier: NCT01731431.

Lung Ultrasound Findings in Congenital Pulmonary Airway Malformation.

BACKGROUND AND OBJECTIVE: Congenital pulmonary airway malformation (CPAM) is a group of rare congenital malformations of the lung and airways. Lung ultrasound (LU) is increasingly used to diagnose neonatal respiratory diseases since it is quick, easy to learn, and radiation-free, but no formal data exist for congenital lung malformations. We aimed to describe LU findings in CPAM neonates needing neonatal intensive care unit (NICU) admission and to compare them with a control population. METHODS: A retrospective review of CPAM cases from three tertiary academic NICUs over 3 years (2014-2016) identified five patients with CPAM who had undergone LU examination. LU was compared with chest radiograms and computed tomography (CT) scans that were used as references. RESULTS: CPAM lesions were easily identified and corresponded well with CT scans; they varied from a single large cystic lesion, multiple hypoechoic lesions, and/or consolidation. The first two LU findings have not been described in other respiratory conditions and were not found in controls. CONCLUSION: We provide the first description of LU findings in neonates with CPAM. LU may be used to confirm antenatally diagnosed CPAM and to suspect CPAM in infants with respiratory distress if cystic lung lesions are revealed. Further studies are necessary to define the place of LU in the management of CPAM.

Cell-free fetal DNA versus maternal serum screening for trisomy 21 in pregnant women with and without assisted reproduction technology: a prospective interventional study.

PURPOSE: Cell-free DNA (cfDNA) as a primary screening test has been available for years but few studies have addressed this option in a prospective manner. The question is of interest after reports that maternal serum screening (MSS) is less accurate for pregnancies resulting from assisted reproduction technologies (ART) than for spontaneous pregnancies (SP). METHODS: A prospective interventional study was designed to address the performances of cfDNA compared with MSS in pregnancies with or without ART. Each patient was offered both MSS and cfDNA testing. The primary analysis cohort ultimately included 794 patients with a spontaneous pregnancy (SP) (n = 472) or pregnancy obtained after ART (n = 322). RESULTS: Overall, the false-positive rate and positive predictive value were 6.6% and 8.8% for MSS but 0% and 100% for cfDNA. MSS false-positive rate and positive predictive values were clearly poorer in the ART group (11.7% and 2.6%) than in the SP group (3.2% and 21.1%). The global rates of invasive procedures were 1.9% (15/794) with cfDNA but 8.4% (65/794) if MSS alone was proposed. CONCLUSION: cfDNA achieved better performance than MSS in both spontaneous and ART pregnancies, thus decreasing the number of invasive procedures. Our findings suggest that cfDNA should be considered for primary screening, especially in pregnancies obtained after ART.

Teaching invasive prenatal procedures: effectiveness of two simple simulators in training.

BACKGROUND: Chorionic villus sampling (CVS) and amniocentesis are the major tools of invasive prenatal diagnosis. We studied the effectiveness of two simulators in training in invasive procedures. METHODS: Two affordable and simple simulators were developed, modelling the maternal abdomen and the different tissue layers crossed by the needle. The trainees were evaluated before and after practical and theoretical training. A score evaluating five criteria for technical quality in performing a procedure safely was established. Initial score of 9 or 10 was excluded. The primary endpoint was improvement defined as the change between pre-test and post-test, expressed as a percentage of the pre-test. RESULTS: A total of 54 residents and 63 specialists in obstetrics and gynaecology participated. Residents improved their scores in the practice of amniocentesis (80% [43-167]) and CVS (100% [29-150]), as well as specialists (100% [25-233] and 67% [33-122]). Specialists who earlier performed one CVS or more than five amniocentesis procedures had a lower increase during training than those who had performed fewer than five procedures (p < 0.01). Being inexperienced in CVS was associated with greater improvement (27% vs 56%, p = 0.003). CONCLUSION: A simple simulator improves the ability of physicians to perform invasive procedures in particular when initial experience is low. © 2016 John Wiley & Sons, Ltd.

Cell-free DNA analysis in maternal plasma in cases of fetal abnormalities detected on ultrasound examination.

OBJECTIVE: To evaluate the utility of noninvasive prenatal testing using cell-free circulating fetal DNA for detection of the three main autosomal fetal trisomies in the setting of ultrasonographically identified fetal anomalies. METHODS: Nine hundred patients at risk for fetal aneuploidy with or without ultrasonography anomalies and who underwent invasive procedures were included in the study. Cell-free DNA analysis was performed by massive parallel sequencing during a multicenter, noninterventional, prospective study and the results were compared with a fetal karyotype. RESULTS: Among all 900 pregnancies, cell-free DNA identified 76 of 76 (100%) fetal Down syndrome, 22 of 25 (88%) trisomy 18, and 12 of 12 (100%) trisomy 13. In those with a normal ultrasonogram and normal cell-free DNA analysis, karyotype identified 2 of 483 (0.4%) additional aneuploidies other than trisomies 13, 18, and 21. In those with an abnormal ultrasonogram and a normal cell-free DNA analysis, there were 23 of 290 (7.9%) additional pathogenic karyotypes. These additional aneuploidies included sex chromosome abnormalities and triploidy. The rates of additional aneuploidies not identifiable by standard cell-free DNA screening in the two groups is significantly different at P<.01. CONCLUSION: In women with fetal abnormalities by ultrasonography, the rate of pathogenic chromosome abnormalities missed by cell-free DNA was 8%. Noninvasive prenatal testing should not be offered to women with fetal abnormalities because a negative result is falsely reassuring. LEVEL OF EVIDENCE: III.