Search

The objective of our study was to compare microcystic and macrocystic congenital cystic adenomatoid malformation (CCAMs) through prenatal characteristics, perinatal outcome, postnatal management and development after consultation in our prenatal diagnosis centre. We conducted a retrospective cohort study of 227 cases prenatally diagnosed as CCAM in our hospital within three years. One hundred and eighty-one cases continued their pregnancy and 46 pregnancies were terminated. One hundred and fifteen of 227 cases were microcystic and 112 were macrocystic. The prenatal ultrasound characteristics of two types showed no statistically significant differences, despite that CVR of macrocystic CCAMs was mildly greater than microcystic. None of recorded cases received surgical intervention in utero . Compared with healthy foetuses, CCAMs presented with higher percentage of polyhydramnios and male foetuses, larger amount of postpartum blood loss and longer duration of NICU hospitalisation. Compared with 46 legal abortions, continued pregnancy cases had a smaller CVR, less polyhydramnios, cardiac shift and hydrops. One hundred and seventy-nine cases were followed up after birth and 174 babies were asymptomatic. Thirty one cases received successful surgical resection. In conclusion, the prenatally diagnosed CCAMs have a good short-term prognosis and conservative management is a reasonable option in asymptomatic fetuses. Microcystic and macrocystic CCAMs both presented similar prenatal courses and perinatal prognoses. Conservative management, prenatally and postnatally, could be accepted in selected cases.Impact statement What is already known on this subject? Congenital cystic adenomatoid malformation is a well-known developmental abnormality of the lung. The prognosis for most CCAMs is good, but the prenatal and postnatal management remains controversial. What do the results of this study add? This study is one of the largest case cohorts to conclude that microcystic and macrocystic CCAMs both presented similar prenatal courses and perinatal prognoses. Conservative management is a reasonable option in asymptomatic babies. What are the implications of these findings for clinical practice and/or further research? A comprehensive assessment by an experienced multidisciplinary team is necessary to forbid blinding abortions of CCAMs. Conservative management prenatally and postnatally could be accepted in most asymptomatic cases.

Inroduction:  The aim of this study is to assess the changes in prevalence, mortality and termination pregnancy of omphalocele, and to identify associated anomalies., Materials and Methods:  A population-based nationwide register study. All cases with omphalocele were identified in the Finnish Register of Congenital Malformations and the Care Register for Health Care from 1993 to 2014 including live births, stillbirths, and terminations of pregnancy due to fetal anomalies. Associated anomalies were recorded and analyzed, and perinatal and infant mortality and prevalence were calculated., Results:  There were 600 cases with omphalocele including 229 live births, 39 stillbirths, and 332 (55%) abortions. Birth prevalence in Finland was 1.96 per 10,000 births with no consistent trend over time. However, total prevalence was much higher (4.71/10,000) because more than half of these families chose option for the termination of pregnancy. Omphalocele is often complicated with other anomalies; most commonly chromosomal abnormalities (9.3%), heart defects (6.3%), central nervous system anomalies (3.0%), gastrointestinal, and urogenital malformations (both 2.0%). Proportion of chromosomal and central nervous system abnormalities were even higher in terminated pregnancies. Overall infant mortality was 22%. Total 1-year survival rates for isolated omphalocele, cases with multiple anomalies and neonates with chromosomal defects were 80, 88, and 17%, respectively., Conclusion:  Omphalocele is a rare congenital anomaly, often associated with other malformations. Our data suggest that isolated cases may be more common than previously thought. In the absence of chromosomal defects, survival is reasonably good. Regardless, more than half of these pregnancies are often terminated., Competing Interests: None declared., (Thieme. All rights reserved.)

Background: To assess the indications and complications of late amniocentesis and the advanced genetic test results in a tertiary university fetal medical medicine unit., Methods: In this retrospective study, women that underwent amniocentesis at 24 + 0 to 39 + 4 weeks, between January 2014 and December 2019, were recruited. Indications, complications, genetic test results, and pregnancy outcomes were reported for each pregnancy and compared with those who underwent the traditional amniocentesis at 16 + 0 to 23 + 6 weeks (control group). Information was retrieved from patient medical records, checked by research staff, and analyzed., Results: Of the 1287 women (1321 fetuses) included in the late amniocentesis group, late detected sonographic abnormalities (85.5%) were the most common indication. The overall incidence of preterm birth and intrauterine demise after amniocentesis were 2.5 and 1.3%, respectively. Sixty-nine fetuses with aneuploidy (5.3%) and seventy-two fetuses with pathogenic copy number variations (5.5%) were identified by chromosomal microarray analysis. The maximal diagnostic yield (70%) was in the subgroup of fetuses with the abnormal diagnostic test results, followed by abnormal NIPT results (35.7%) and multiple abnormalities (23.8%). And 35.4% of the pregnancies were finally terminated., Conclusions: Due to the high detection rates of advanced genetic technologies and the safety of the invasive procedure (3.9% vs 4.0%), it is reasonable to recommend late amniocentesis as an effective and reliable method to detect late-onset fetal abnormalities. However, chromosomal microarray and whole-exome sequencing may result in uncertain results like variants of uncertain significance. Comprehensive genetic counseling is necessary.

Introduction:  The study aims to assess the changes in prevalence and mortality of gastroschisis, and to identify associated anomalies., Materials and Methods:  It is a population-based nationwide study. All gastroschisis cases were identified in the Finnish Register of Congenital Malformations and the Care Register for Health Care from 1993 to 2014 including live births, stillbirths, and terminations of pregnancy due to fetal anomalies. Associated anomalies were recorded, and analyzed, and prevalence and infant mortality were calculated., Results:  There were 320 cases of gastroschisis; 235 (73%) live births, 16 (5%) stillbirths, and 69 (22%) terminations of pregnancy. Live birth prevalence of gastroschisis in Finland was lower than generally reported (1.73 in 10,000). However, due to relatively high rates of abortion, our total prevalence of 2.57/10,000 was similar with other reports. The most common risk factor was young maternal age. Babies with gastroschisis were born prematurely, on average on the 36th week and most are delivered by caesarean section. There was a significant increasing trend in live birth prevalence ( p  = 0.0018). Overall infant mortality was 7.7% (18/235), 7.2% (16/222) in simple gastroschisis and 15% (2/13) in complex gastroschisis. Associated anomalies were rare both in aborted fetuses and neonates, and there was only one case with a chromosomal abnormality., Conclusion:  Gastroschisis is usually an isolated anomaly with increasing birth prevalence and excellent survival rates. Regardless of the good prognosis, the abortion rates in Finland are higher than previously reported, and we hypothesize this to be due to lack of appropriate antenatal counselling., Competing Interests: A.R. reports grants from Clinical Research Institute HUCH, during the conduct of the study. All the other authors report no conflict of interest., (Thieme. All rights reserved.)

Background and Aims: Severe congenital heart defects (CHDs) still represent one of the main causes of infant death. The risk factors associated with cardiac surgery and postoperative mortality are well known. We aimed to describe the rates, causes and time trends of mortality before surgery-including termination of pregnancies and palliative care-in fetuses and children below 2 years of age with severe CHDs., Methods and Results: Data concerning all 789 345 pregnancies in Norway from 2004 to 2016 were retrieved from the Medical Birth Registry of Norway, the Oslo University Hospital's Clinical Registry for Congenital Heart Defects, the Norwegian Cause of Death Registry, the National Registry, Statistics Norway, autopsy reports and medical records. When including termination of pregnancy and stillbirths, the number of fetuses and children with severe CHDs that did not reach the age of 2 years was 31%. Mortality among the 2359 live-born infants with severe CHDs was 10%, of whom 58% died before surgery. Of the preoperative deaths, 81% died in a palliative care setting, and comorbidity and univentricular CHDs were common among these infants. Together, palliative care and termination of pregnancy accounted for 86% of deaths in cases of severe CHDs, and this proportion increased during the study period (annual percent changes 1.3, 95% CI 0.4 to 2.1, p<0.001), mainly due to an increased termination rate., Conclusions: Termination of pregnancy accounted for the majority of the deaths in fetuses and children with severe CHDs. Among live-born children, most preoperative deaths occurred in a palliative care setting and were strongly related to comorbidities and/or univentricular hearts., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: The aim of this study was to analyse the characteristics of the prenatal diagnosis (PD) of birth defects (BDs) and termination of pregnancy (TOP) for fetal anomalies and to suggest perinatal management., Methods: BD surveillance data were collected from 52 registered hospitals in Hunan between 2015 and 2018. The PD and TOP rates of BDs were calculated to examine the associations between infant sex, maternal age, and region., Results: From 2015 to 2018, a total of 18 931 fetuses with BDs were identified, of which 10 299 fetuses (54.4%) were diagnosed prenatally and 9343 pregnancies (90.7% among PDs and 49.3% among BDs) were terminated. The mean gestational age at diagnosis for fetuses with BDs was 25.1 ± 5.9 weeks and showed a downward trend over the study period. The average PD rate of the BDs was higher in rural areas than in urban areas (58.1% vs 50.3%), higher for female than male fetuses (57.25% vs 48.92%), and higher for mothers older than age 35 than for those younger (58.62% vs 53.69%). The average TOP rate of fetuses with BDs in rural areas was higher than that in urban areas (91.99% vs 89.12%) and decreased with increasing maternal age ( x trend 2 = 7.926, P = .005). The five BDs with the highest PD rates were conjoined twins (100%), anencephaly (97.87%), congenital hydrocephalus (97.66%), chromosomal malformation (96.07%), and encephalocele (95.54%). The five BDs with the highest TOP rates among the PDs were conjoined twins (100%), exstrophy of the urinary bladder (100%), chromosomal malformation (98.09%), encephalocele (98%), and anencephaly (97.28%)., Conclusions: More than half of BDs were diagnosed prenatally, with the majority diagnosed at less than 28 gestational weeks. The TOP rates following PD in Hunan Province were high, especially for rural and younger mothers. The findings suggest a need for high-quality, targeted counselling following PD., (© 2020 John Wiley & Sons, Ltd.)

Objective: To study changes in the reasons for third-trimester termination of pregnancy (TOP) for fetal anomalies over a 20-year period in France., Study Design: We compared a consecutive series of third-trimester TOPs from a single centre in 2005-2014 to those performed by Dommergues et al. in a similar centre in 1986-1994, using the same criteria., Main Outcome Measures: The process leading to late TOP, using the same categories in both studies., Results: In the present series, 205 of 1409 TOPs were performed in the third trimester, vs. 305/956 in the historical series. There were 33 (16.1 %) diagnoses missed at the screening before the third trimester, 55 (26.8 %) cases in which the anomaly was impossible to diagnose until the third trimester, 86 (42 %) cases in which fetal prognosis could not be established until the third trimester despite earlier diagnosis, 31 (15.1 %) TOPs postponed to allow more time for the women/couples to contemplate, versus respectively 113 (37 %), 55 (18 %), 122 (40 %), and 15 (5%) in the historical series., Conclusion: There was a significant drop in the rate of anomalies missed earlier. The increase in late TOP due to couples requiring additional time for contemplation might result from changes in counselling processes., Competing Interests: Declaration of Competing Interest No conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Non-invasive prenatal testing (NIPT) can determine the sex of the fetus very accurately and very early in gestation. There are concerns that the ease, timing, and accuracy of NIPT sex determination will facilitate sex-selective termination of pregnancy (TOP). Here, we review current practices, the evidence for a link between NIPT and sex-selective TOP, and associated ethical issues. Sex-selective TOP, usually motivated by son preference, has had serious demographic consequences in countries such as India and China. Currently, ultrasound is the primary method by which parents determine the sex of the fetus. The diffusion of ultrasound technology has had a direct impact on the rates of sex-selective TOP. Although NIPT is currently more costly, it is feasible that increased uptake of this technology could have a similar effect. Partly because NIPT is a relatively recent development in prenatal screening, there is little data on the impact of NIPT on sex selection practices. Evidence that NIPT is playing a role in sex-selective TOP remains largely anecdotal. Further research is required to assess and quantify TOP resulting from NIPT sex determination. The use of these technologies for sex selection raises a number of ethical issues, in addition to practical demographic consequences., (© 2019 The Authors. Prenatal Diagnosis published by John Wiley & Sons Ltd.)

Background: Public health organisations use public health indicators to guide health policy. Joint analysis of multiple public health indicators can provide a more comprehensive understanding of what they are intended to evaluate., Objective: To analyse variaitons in the prevalence of congenital anomaly-related perinatal mortality attributable to termination of pregnancy for foetal anomaly (TOPFA) and prenatal diagnosis of congenital anomaly prevalence., Methods: We included 55 363 cases of congenital anomalies notified to 18 EUROCAT registers in 10 countries during 2008-12. Incidence rate ratios (IRR) representing the risk of congenital anomaly-related perinatal mortality according to TOPFA and prenatal diagnosis prevalence were estimated using multilevel Poisson regression with country as a random effect. Between-country variation in congenital anomaly-related perinatal mortality was measured using random effects and compared between the null and adjusted models to estimate the percentage of variation in congenital anomaly-related perinatal mortality accounted for by TOPFA and prenatal diagnosis., Results: The risk of congenital anomaly-related perinatal mortality decreased as TOPFA and prenatal diagnosis prevalence increased (IRR 0.79, 95% confidence interval [CI] 0.72, 0.86; and IRR 0.88, 95% CI 0.79, 0.97). Modelling TOPFA and prenatal diagnosis together, the association between congenital anomaly-related perinatal mortality and TOPFA prevalence became stronger (RR 0.70, 95% CI 0.61, 0.81). The prevalence of TOPFA and prenatal diagnosis accounted for 75.5% and 37.7% of the between-country variation in perinatal mortality, respectively., Conclusion: We demonstrated an approach for analysing inter-linked public health indicators. In this example, as TOPFA and prenatal diagnosis of congenital anomaly prevalence decreased, the risk of congenital anomaly-related perinatal mortality increased. Much of the between-country variation in congenital anomaly-related perinatal mortality was accounted for by TOPFA, with a smaller proportion accounted for by prenatal diagnosis., (© 2020 The Authors. Paediatric and Perinatal Epidemiology published by John Wiley & Sons Ltd.)

Objective: To define the predictive value (PV) of known prognostic factors of fetal infection with Cytomegalovirus following maternal primary infection <14 weeks of gestation, at different time points of pregnancy: the end of the second trimester; following prenatal magnetic resonance imaging (MRI) at 32 weeks of gestation; and using all ultrasound scans performed in the third trimester (US3rdT)., Design: A retrospective study., Setting: Reference fetal medicine unit., Population: Sixty-two fetuses infected <14 weeks of gestation., Methods: We defined second-trimester assessment (STA) as the combination of ultrasound findings <28 weeks of gestation and fetal platelet count at cordocentesis. Three groups were defined: normal, extracerebral, and cerebral STA., Main Outcome Measures: For each group, the PV of STA alone, STA + MRI, and STA + US3rdT were assessed retrospectively. Outcome at birth and at follow-up were reported., Results: The STA was normal, and with extracerebral and cerebral features, in 43.5, 42.0, and 14.5%, respectively. The negative PV of normal STA and MRI for moderate to severe sequelae was 100%. The residual risk was unilateral hearing loss in 16.7% of cases. Of pregnancies with cerebral STA, 44% were terminated. Following extracerebral STA, 48% of neonates were symptomatic and 30% had moderate to severe sequelae. In those cases, the positive and negative PV of MRI for sequelae were 33 and 73%, respectively. STA + US3rdT had a lower negative PV than MRI for symptoms at birth and for moderate to severe sequelae. Any false-positive findings at MRI were mostly the result of hypersignals of white matter., Conclusions: Serial assessment in the second and third trimesters by ultrasound and MRI is necessary to predict the risk of sequelae occurring in 35% of pregnancies following fetal infection in the first trimester of pregnancy., Tweetable Abstract: Serial ultrasound prognostic assessment following fetal CMV infection in the 1st trimester is improved by MRI at 32 weeks., (© 2019 Royal College of Obstetricians and Gynaecologists.)

Background Research focused on adolescents' attitudes towards abortion is limited, and validated scales are not routinely used. A greater understanding of adolescents' attitudes towards abortion could better inform the sexuality education strategies targeted at this age group., Methods: A cross-sectional survey was completed by 1470 adolescents (437 males, 1033 females) aged 12-19 years and living in Perth, Australia. Participants were recruited from secondary schools, antenatal clinics and termination clinics to capture varying experiences of sexual activity and pregnancy. Survey items investigated abortion attitudes, sexual behaviour and pregnancy history alongside other demographic and psychosocial factors. Analyses included comparative means and adjusted linear regressions., Results: Sexually active participants (n = 554) and females reporting a previous abortion (n = 196) held more supportive attitudes towards abortion (P < 0.001 for both). Among sexually active females, more supportive attitudes were held by those reporting a previous abortion (β = 2.60, 95% confidence interval 0.93-4.27, P = 0.002), later age (≥16 years) at first vaginal intercourse (P < 0.001), use of oral contraception at last sex (P = 0.029), previous condom use (P < 0.001) and/or three or more oral sex partners in the previous 12 months (P = 0.005). For sexually active males, more supportive attitudes were reported by those whose female partners had used oral contraception at last sex (P = 0.013) or ever (P = 0.017). Multivariable analyses indicated that other correlates, including risky sexual behaviour, had minimal or no effect on attitudes., Conclusions: Adolescents' attitudes towards abortion appear to be influenced by their ability to personalise and contextualise the effect of a pregnancy. Associations between less-effective contraceptive use and reduced support for abortion may be explained by a diminished perceived risk of parenthood. Educational strategies should acknowledge and respond to differences in abortion attitudes as adolescents commence and navigate sexual relationships.

Anencephaly is a malformation characterized by the total or partial absence of the brain, and Brazil records the fourth largest number of births of anencephalic fetuses in the world. Fetal anencephaly is associated with a more significant number of maternal complications. As of 2012, women with anencephalic gestation were empowered with the right to carry the pregnancy to term or terminate it, if they so desired, without any judicial authorization. Objectives: to understand the experiences of women with fetal anencephaly and to identify the determinant factors for interrupting the gestation or not. This is a qualitative study using the Life Narratives method with 12 women over 18 years old diagnosed with an anencephalic fetus, who interrupted gestation or delivery in a public maternity hospital in Rio de Janeiro. Data were collected between June and November 2016, and the process was finalized when the narrative patterns reached progressive saturation from the recurrences. The statements that emerged following floating and in-depth reading were articulated in Narrative Nuclei, and data comparative and comprehensive analysis was performed. The reports brought to light the intense experiences of these women, as well as the weaknesses existing concerning care and the pregnancy termination issue.

Objective: As prenatal diagnostic services expand throughout low-income countries, an important consideration is the appropriateness of these services for patients. In these countries, services now include prenatal ultrasound and occasionally genetic testing. To assess patient interest, we surveyed pregnant patients at a hospital in Addis Ababa, Ethiopia, on their preferences for prenatal testing and termination of affected pregnancies for congenital anomalies and genetic diseases., Method: One hundred one pregnant patients were surveyed on their preferences for prenatal testing and termination of affected pregnancies using a survey covering various congenital anomalies and genetic diseases., Results: Eighty-nine percent of patients reported interest in testing for all conditions. Three percent of patients were not interested in any testing. Over 60% of patients reported interest in termination for anencephaly, early infant death, severe intellectual disability, hemoglobinopathy, and amelia. Patients were more likely to express interest in prenatal testing and termination for conditions associated with a shortened lifespan., Conclusion: Ethiopian patients were interested in prenatal testing and termination of pregnancy for many conditions. Advancing prenatal diagnostic capacities is a potential strategy for addressing the incidence of congenital anomalies and genetic disease in Ethiopia. Importantly, there exist many factors and technological limitations to consider before implementation., (© 2019 John Wiley & Sons, Ltd.)

The prenatal genetic counseling process may be influenced by the patient's insurance coverage for both prenatal testing and termination. Major commercial insurance providers have different policies. TRICARE is the United States Department of Defense health program for uniformed service members. TRICARE provides coverage to approximately 9.4 million beneficiaries, including health plans, special programs, prescriptions, and dental plans. TRICARE's covered medical expenses are outlined in their policies, including those pertaining to genetic testing and termination. This qualitative study aimed to explore the extent to which insurance coverage of prenatal genetic testing and termination of pregnancy affect the genetic counseling process by exploring genetic counselors' experience with TRICARE. The majority of counselors stated that they did not change their overall counseling process for TRICARE patients. However, several counselors expressed that they changed the way they discussed cost with TRICARE patients, specifically in regard to genetic testing. Additionally, counselors provided their perceptions of their patients' emotional experiences. With the recent consolidation of the three TRICARE regions into two TRICARE Regional Office (TRO) regions and the renewal of the Laboratory Developed Tests Demonstration Project, the findings of this study are valuable in the evaluation of TRICARE's coverage of prenatal genetic services., (© 2019 John Wiley & Sons, Ltd.)

Background: Fetal structural anomalies, which are detected by ultrasonography, have a range of genetic causes, including chromosomal aneuploidy, copy number variations (CNVs; which are detectable by chromosomal microarrays), and pathogenic sequence variants in developmental genes. Testing for aneuploidy and CNVs is routine during the investigation of fetal structural anomalies, but there is little information on the clinical usefulness of genome-wide next-generation sequencing in the prenatal setting. We therefore aimed to evaluate the proportion of fetuses with structural abnormalities that had identifiable variants in genes associated with developmental disorders when assessed with whole-exome sequencing (WES)., Methods: In this prospective cohort study, two groups in Birmingham and London recruited patients from 34 fetal medicine units in England and Scotland. We used whole-exome sequencing (WES) to evaluate the presence of genetic variants in developmental disorder genes (diagnostic genetic variants) in a cohort of fetuses with structural anomalies and samples from their parents, after exclusion of aneuploidy and large CNVs. Women were eligible for inclusion if they were undergoing invasive testing for identified nuchal translucency or structural anomalies in their fetus, as detected by ultrasound after 11 weeks of gestation. The partners of these women also had to consent to participate. Sequencing results were interpreted with a targeted virtual gene panel for developmental disorders that comprised 1628 genes. Genetic results related to fetal structural anomaly phenotypes were then validated and reported postnatally. The primary endpoint, which was assessed in all fetuses, was the detection of diagnostic genetic variants considered to have caused the fetal developmental anomaly., Findings: The cohort was recruited between Oct 22, 2014, and June 29, 2017, and clinical data were collected until March 31, 2018. After exclusion of fetuses with aneuploidy and CNVs, 610 fetuses with structural anomalies and 1202 matched parental samples (analysed as 596 fetus-parental trios, including two sets of twins, and 14 fetus-parent dyads) were analysed by WES. After bioinformatic filtering and prioritisation according to allele frequency and effect on protein and inheritance pattern, 321 genetic variants (representing 255 potential diagnoses) were selected as potentially pathogenic genetic variants (diagnostic genetic variants), and these variants were reviewed by a multidisciplinary clinical review panel. A diagnostic genetic variant was identified in 52 (8·5%; 95% CI 6·4-11·0) of 610 fetuses assessed and an additional 24 (3·9%) fetuses had a variant of uncertain significance that had potential clinical usefulness. Detection of diagnostic genetic variants enabled us to distinguish between syndromic and non-syndromic fetal anomalies (eg, congenital heart disease only vs a syndrome with congenital heart disease and learning disability). Diagnostic genetic variants were present in 22 (15·4%) of 143 fetuses with multisystem anomalies (ie, more than one fetal structural anomaly), nine (11·1%) of 81 fetuses with cardiac anomalies, and ten (15·4%) of 65 fetuses with skeletal anomalies; these phenotypes were most commonly associated with diagnostic variants. However, diagnostic genetic variants were least common in fetuses with isolated increased nuchal translucency (≥4·0 mm) in the first trimester (in three [3·2%] of 93 fetuses)., Interpretation: WES facilitates genetic diagnosis of fetal structural anomalies, which enables more accurate predictions of fetal prognosis and risk of recurrence in future pregnancies. However, the overall detection of diagnostic genetic variants in a prospectively ascertained cohort with a broad range of fetal structural anomalies is lower than that suggested by previous smaller-scale studies of fewer phenotypes. WES improved the identification of genetic disorders in fetuses with structural abnormalities; however, before clinical implementation, careful consideration should be given to case selection to maximise clinical usefulness., Funding: UK Department of Health and Social Care and The Wellcome Trust., (Copyright © 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

The present study aimed to examine the value of ultrasonic soft markers in prenatal screening by analyzing the clinical outcome of fetuses with ultrasonic soft markers during the second trimester of pregnancy. A retrospective analysis was performed to evaluate the outcome of 591 fetuses with ultrasonic soft markers from January 2015 to August 2016 in Zhongnan Hospital of Wuhan University, China. It was found that 591 fetuses showed ultrasonic soft markers in 4927 cases with the occurrence rate being 12.0%. Among them, 564 fetuses (95.4%) were delivered and the remaining 27 cases (4.6%) were aborted. Five hundred and sixty-seven cases had single ultrasonic soft marker, including echogenic intracardiac focus (n=343), mild renal pelvis dilatation (n=116), short long bones (n=72), single umbilical artery (n=31), mild lateral ventriculomegaly (n=21), choroid plexus cysts (n=19), and echogenic bowel (n=13), with the disappearing rates in pregnancy being 97.1% (333/343), 77.6% (90/116), 0% (0/72), 0% (0/31), 57.1% (12/21), 89.5% (17/19) and 61.5% (8/13) respectively. The rate of pregnancy termination due to single ultrasonic soft marker was 3.4% (19/567), and that was 33.3% (8/24) due to two ultrasonic soft markers with the difference being statistically significant (P<0.05). The reasons of pregnancy termination included malformations (polycystic kidney, cleft lip and palate, congenital heart diseases, pcromphalus, hypospadias, hydrocephalus), chromosome abnormality, and stillbirth. It was concluded that single ultrasonic soft marker is usually transient manifestation in pregnancy. Without the other structural defects, single ultrasonic soft marker usually disappears spontaneously with favorable prognosis in a low-risk population. It is suggested that ultrasonic soft markers should be appropriately interpreted to avoid unnecessary invasive examination.

Background: Cytomegalovirus (CMV) infection during pregnancy is the most common cause of intrauterine infection, and is a common cause of sensorineural hearing loss and mental retardation., Objectives: To evaluate trends in amniocentesis and pregnancy outcome in women with suspected cytomegalovirus (CMV) infection during the first trimester., Methods: All blood tests for CMV immunoglobulin M (IgM) done between 2008 and 2009 on pregnant women who were enrolled in the Maccabi Healthcare Services were retrieved from laboratory database. Immunoglobulin G (IgG) avidity was measured and women were classified according to the risk of acquiring CMV infection. For each patient, performance of amniocentesis and whether pregnancy came to term were recorded., Results: Of 109,439 pregnant women evaluated during the study period, 76,712 (70.1%) were tested for CMV IgM, and 792 (1.03%) were found to be positive. Among women with positive IgM, only 205 (25.9%) underwent amniocentesis. When compared with women with negative CMV IgM, the rate of pregnancy cessation was doubled in women with positive CMV IgM (28.3% vs. 14.3%, P < 0.05) and mostly elevated in women with a high risk of acquiring CMV (42.3% pregnancy cessation). Among women with positive CMV IgM, those who did not undergo amniocentesis were more likely to abort than those who performed amniocentesis (35.6% vs. 7.3%, P < 0.05)., Conclusions: More women with suspected CMV infection during the first trimester of pregnancy aborted before all means of detection were utilized to rule out or confirm fetal infection with CMV.

There are few reports on the prognosis of prenatally diagnosed trisomy 13 in relation to postnatal management. The aim of this study was to report on the prenatal and postnatal outcomes and postnatal management of trisomy 13 fetuses that were prenatally diagnosed at our center between 2003 and 2015. The data were retrospectively reviewed from medical records. Of the 31 cases of trisomy 13, 12 patients were diagnosed before 22 weeks of gestation, and 19 were diagnosed at or after 22 weeks of gestation. Nine families opted for termination of the pregnancy, 14 fetuses died, and 8 were born alive. Aggressive treatment was requested in two of the live births, with one patient achieving long-term survival (7 years). The other died during infancy (Day 61). One out of four who received palliative treatment is alive at two years of age with only nutrition supplementation. These three patients who achieved neonatal survival had few structural anomalies. Fetal death and early neonatal death are common in trisomy 13; however, fetuses that receive medical treatment for cases without major ultrasound abnormalities may achieve neonatal survival. Therefore, it is useful to provide comprehensive information, including precise ultrasound findings and treatment options, to parents with trisomy 13 fetuses during genetic counseling., (© 2017 Wiley Periodicals, Inc.)

Edwards syndrome (trisomy 18) and Patau syndrome (trisomy 13) both have high natural fetal loss rates. The aim of this study was to provide estimates of these fetal loss rates by single gestational week of age using data from the National Down Syndrome Cytogenetic Register. Data from all pregnancies with Edwards or Patau syndrome that were prenatally detected in England and Wales from 2004 to 2014 was analyzed using Kaplan-Meier survival estimates. Pregnancies were entered into the analysis at the time of gestation at diagnosis, and were considered "under observation" until the gestation at outcome. There were 4088 prenatal diagnoses of trisomy 18 and 1471 of trisomy 13 in the analysis. For trisomy 18, 30% (95%CI: 25-34%) of viable fetuses at 12 weeks will result in a live birth and at 39 weeks gestation 67% (60-73%) will result in a live birth. For trisomy 13 the survival is 50% (41-58%) at 12 weeks and 84% (73-90%) at 39 weeks. There was no significant difference in survival between males and females when diagnosed at 12 weeks for trisomy 18 (P-value = 0.27) or trisomy 13 (P-value = 0.47). This paper provides the most precise gestational age-specific estimates currently available for the risk of fetal loss in trisomy 13 and trisomy 18 pregnancies in a general population., (© 2017 Wiley Periodicals, Inc.)

Objective: The article aimed to assess the spectrum of fetal renal tract abnormalities as a major finding leading to termination of pregnancy (TOP)., Method: The study population included all pregnant women with singleton pregnancy who underwent TOP in our institute because of fetal renal tract indications between 1998 and 2015. We specifically excluded TOPs performed because of multiple pregnancies, multisystem defects, abnormal karyotype and chromosomal or genetic defect not related to renal tract abnormalities. The patients were stratified into late TOP (≥24 weeks' gestation) and early TOP (<24 weeks' gestation)., Results: There were 97 (3.5%) cases of TOP because of fetal renal abnormalities and are the subjects of this study. Of these cases, 19 (19.6%) were at ≥24 weeks' gestation. Renal cystic disease was the leading indication for late TOP compared with early TOP group (31.8% vs 21.8%, respectively, p = 0.001). Routine prenatal care raised suspicion of abnormalities in 11 (50.9%) cases, and diagnosis was established by additional tests. Abnormal findings were either missed in one (5.3%) case or developed later in two (10.5%) cases. No routine prenatal screening was performed in the remaining five (26.3%) cases., Conclusions: We found a different distribution for fetal renal tract abnormalities leading to late versus early TOP. As many of renal tract malformations could have been diagnosed earlier (~32%), timely scanning may reduce the need for late TOPs in some cases. © 2016 John Wiley & Sons, Ltd., (© 2016 John Wiley & Sons, Ltd.)

Objective: To assess fetal abnormalities leading to termination of pregnancy (TOP) performed in twin pregnancies., Method: The current study consisted of all women with dichorionic twin pregnancies (study group) who underwent TOP due to fetal abnormalities in our institute from 1999 to 2015. The data were compared to our registry of all parturient women with a singleton pregnancy (control group) that underwent TOP due to fetal anomalies at the same period., Results: There were 2495 cases of TOP because of fetal indications during the study period. Of them, 86 (3.4%) and 2409 (96.6%) were from the study and control group, respectively. Structural anomalies were the leading indication for TOP in twins compared with singleton pregnancies (81.4% versus 50.9%, respectively, p < 0.0001). For twins, the leading indication for TOP was central nervous system (CNS) abnormalities and it was more common compared with singleton pregnancies (26.1% versus 12.2%, respectively, p < 0.0001). This was followed by chromosomal/genetic abnormalities (16.3% versus 40.4%, respectively, p < 0.0001)., Conclusions: We found a different distribution for fetal anomalies leading to TOP in twins versus singleton pregnancies. The main indication for TOP in the study group was structural malformations, with a predominance of CNS abnormalities.

Aim: To analyze the impact of counseling on antenatal congenital surgical anomalies (ACSA)., Methods: Cases presenting with ACSA for fetal counseling and those presenting in post-natal period following diagnosis of ACSA (PACSA) for surgical opinion were analyzed for spectrum, presentation and outcome., Results: 117 cases including ACSA(68);PACSA(49) were analyzed. Gestational age at diagnosis of ACSA;PACSA was 17-37;17-39 weeks (median 24;32 weeks). Diagnoses in ACSA;PACSA included urological (26;31), neurological (10;5), congenital diaphragmatic hernia (CDH)(5;1), gastrointestinal (5;5), lung and chest anomalies (5;1), intraabdominal cysts (4;1), abdominal wall defects (4;0), tumors (3;3), limb anomaly (1;1), esophageal atresia (1;1), conjoint twins (1;0), hepatomegaly (1;0), and major cardiac anomalies (2;0). Two antenatal interventions were done for ACSA; vesicoamniotic shunt and amnioinfusion for oligohydramnios. 17;24 ACSA;PACSA required early surgical intervention in post-natal period. Nine ACSA underwent medical termination of pregnancy and 4 had intrauterine demise. Nine ACSA babies died including two CDH, one gastroschisis, one duodenal atresia, one conjoint twins, one megacystitis with motility disorder and three posterior urethral valves. All PACSA babies survived., Conclusion: Fetal counseling for CSA portrays true outcome of ACSA with 32.3% (22/68) mortality versus 0% for PACSA due to selection bias. However, fetal counseling ensures optimal perinatal care.

Previous studies have demonstrated the influence of changes in the age at which women give birth, and of developments in prenatal screening and diagnosis on the number of pregnancies diagnosed and terminated with chromosomal anomalies. However, we are unaware of any population studies examining pregnancy terminations after diagnosis of chromosomal anomalies that has included all aneuploidies and the influence of maternal factors. The aims of this study were to examine the association between results of prenatal tests and pregnancy termination, and the proportion of foetuses with and without chromosomal anomalies referred for invasive diagnostic tests over time. Diagnostic information of 26,261 prenatal invasive tests from all genetic service laboratories in Scotland from 2000 to 2011 was linked to Scottish Morbidity Records to obtain details on pregnancy outcome. Binary logistic regression was carried out to test the associations of year and type of diagnosis with pregnancy termination, while controlling for maternal age, neighbourhood deprivation and parity. There were 24,155 (92.0%) with no chromosomal anomalies, 1,483 (5.6%) aneuploidy diagnoses, and 623 (2.4%) diagnoses of anomaly that was not aneuploidy (including translocations and single chromosome deletions). In comparison with negative test results, pregnancies diagnosed with trisomy were most likely to be terminated (adjusted OR 437.40, 95% CI 348.19-549.46) followed by other aneuploid anomalies (adjusted OR 95.94, 95% CI 69.21-133.01). During the study period, fewer pregnancies that were diagnosed with aneuploidy were terminated, including trisomy diagnoses (adjusted OR 0.44, 95% CI 0.26-0.73). Older women were less likely to terminate (OR 0.35, 95% CI 0.28, 0.42), and parity was also an independent predictor of termination. In keeping with previous findings, while the number of invasive diagnostic tests declined, the proportion of abnormal results increased from 6.09% to 10.88%. Systematic advances in prenatal screening have improved detection rates for aneuploidy. This has been accompanied by a reduction in the rate of termination for aneuploidy. This may reflect societal changes with acceptance of greater diversity, but this is speculation, and further research would be needed to test this., Competing Interests: The authors have declared that no competing interests exist.

Objective: To assess the maternal complications in pregnant women with fetuses with several congenital anomaly as well as the predictor variables for the termination of pregnancy., Methods: We performed a retrospective cohort study with 94 medical records of pregnant women with fetal infeasibility confirmed in the postnatal period by clinical, radiological or anatomopathological exams. To compare the categorical variables regarding the termination and nontermination of pregnancy, we used analysis of variance (ANOVA) and the Mann-Whitney U-test. To assess the variables that were more associated with the judicial request for the termination of pregnancy, we used logistic regression., Results: The termination of pregnancy was performed in 41 (43.6%) and nontermination of pregnancy in 53 (56.4%) pregnant women. Pregnant women who did not terminate the pregnancy had more complications in the gestational period (p < 0.0001) and in the postpartum period (p  =  0.0088). After multiple logistic regressions, the following variables influenced the decision to terminate the pregnancy: type of congenital anomaly (OR: 18.59; 95%CI: 1.96; 175.87) and living children (OR: 0.45; 95%CI: 0.25; 0.80)., Conclusion: Most of the pregnant women with fetal infeasibility opted for nontermination of pregnancy and these patients had more obstetrical complications. The type of congenital anomaly and living children were the factors most associated with the choice for the termination of pregnancy.

Objective: Decision-making for pregnancies complicated by severe congenital anomalies of the kidneys and urinary tract (CAKUT) are ethically challenging, partly because the outcomes are not well studied., Study Design: Retrospective cohort study of severe cases of CAKUT over 14 years., Results: Seventy-one of the 108 cases could be completely analyzed. Forty-six percent (n=33) infants were live-born; one-third (n=11) survived to 12 months. Twice as many non-surviving infants received a trial of therapy vs comfort care only. Two-thirds of non-survivors who received a trial of therapy died within the first 9 h of life. Live-born infants faced morbidities such as pneumothorax and neonatal dialysis., Conclusions: Over half of pregnancies complicated by severe CAKUT ended in termination or stillbirth, but one-third of live-born infants survived to 12 months and the majority of non-survivors died within hours. This may allay concerns about prolonged and futile intensive care for parents considering a trial of therapy.

Objectives: A fetal persistent intrahepatic right umbilical vein has been linked to anomalies and genetic disorders but can be a normal variant. We conducted a retrospective review to determine other sonographic findings that can stratify fetuses for further evaluation., Methods: A total of 313 fetuses had a persistent intrahepatic right umbilical vein identified on 17- to 24-week sonography. The outcome was any major congenital anomaly or an adverse neonatal outcome, which was defined as aneuploidy, fetal demise, or neonatal death., Results: A total of 217 patients (69.3%) had a normal neonatal outcome. Sixty-nine patients (22.0%) were lost to follow-up. Five fetuses (2.1%) had aneuploidy; 4 of the 5 had additional sonographic findings, and 1 had an isolated persistent intrahepatic right umbilical vein. Twenty-four fetuses had a major anomaly in association with the persistent right umbilical vein; 26 additional fetuses had soft sonographic markers associated with karyotypic abnormalities but were chromosomally normal. Of those with adverse neonatal outcomes, 12 had a congenital heart defect (57%). An additional sonographic finding with a persistent intrahepatic right umbilical vein was predictive of a congenital anomaly or an adverse neonatal outcome (P < .001), with a positive predictive value of 44.0% (95% confidence interval, 30.0%-58.7%). An isolated persistent intrahepatic right umbilical vein had a 0.4% risk for a congenital anomaly or an adverse neonatal outcome., Conclusions: A persistent intrahepatic right umbilical vein should prompt an extended anatomic survey and a fetal cardiac evaluation. If the survey and cardiac anatomy are reassuring, no further follow-up is needed. If additional findings are identified, genetic counseling and invasive testing should be considered.

Objective: A prenatal ultrasound examination and a postmortem examination provide the basis for correct diagnosis in fetuses terminated due to congenital anomalies. The aim of this study was to correlate fetal anomalies detected by ultrasound examination with those identified at autopsy following termination of pregnancy (TOP) over a 30-year period, and to evaluate the correlation between findings at different gestational ages and assess these trends over time., Methods: The study group consisted of 1029 TOPs performed over a 30-year period, from 1985 to 2014. The gestational age ranged between 11 and 33 weeks. Prenatal ultrasound examinations were performed at the National Center for Fetal Medicine, St Olavs Hospital, Trondheim, Norway. Autopsies were performed at the Department of Pathology and Medical Genetics at the same hospital or a collaborating hospital., Results: There was full agreement between ultrasound and autopsy findings in 88.1% (907/1029) of TOPs, and the main diagnosis was correct in 97.9% (1007/1029). When comparing the 15-year period of 2000-2014 with that of 1985-1999, the difference in the rates of full agreement and agreement in the main diagnosis was statistically significant. In 1.3% (13/1029) of cases, ultrasound findings were not confirmed at autopsy. There were no false-positive diagnoses leading to TOP. Throughout the 30-year period, there was an increase in early TOPs, whereas late TOPs declined., Conclusions: Our study demonstrates that there is a clear correlation between ultrasound and autopsy findings, which is continuously improving. Despite this high correlation, there is reason to continue the practice of validation to ensure the safety of the diagnostic process leading to TOP. The trend towards an earlier termination emphasizes the necessity of such a practice. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.)

Background: The number of affected infants and the types of malformations identified by a malformation surveillance programs can be impacted if elective terminations for malformations are not included., Methods: The occurrence of malformations in all newborn infants was determined in a daily review of the findings in the pediatricians' examinations and those of all consultants. In addition, the findings in autopsies of all elective terminations were reviewed to identify all fetuses with structural abnormalities. A severity scale was used to subdivide the malformations. To establish the impact of elective termination, the malformed infants identified in the Active Malformations Surveillance Program at Brigham and Women's Hospital in Boston were analyzed for the 2 years before and after the hospital decreased significantly the number of elective terminations temporarily (1999-2000 vs. 2001-2002). The effect on the number of malformations identified at birth, as well as malformations of greater severity, was determined., Results: The number of terminated fetuses with malformations decreased dramatically after termination services were interrupted (p < 0.0001). There were no differences in the prevalence rates of all malformations in the 2 years before and after the change in access to elective terminations. However, there were significant decreases in the number of infants identified with lethal/life-limiting and severe/handicapping malformations., Conclusion: In the surveillance for malformations among newborn infants, the inclusion of malformed fetuses from elective terminations had a significant effect on the number of infants with the more severe malformations identified. Birth Defects Research (Part A) 106:659-666, 2016. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Background: With the increased accuracy of non-invasive prenatal testing (NIPT) based on cell-free DNA (cfDNA) techniques, the likelihood of false-positive screening results has been reduced for high-risk populations. Following a positive screening test, a diagnostic procedure to confirm the result is strongly recommended, although some patients have terminated pregnancies because of a positive NIPT alone. Chorionic villus sampling (CVS), the diagnostic procedure of choice in the first trimester, is not available in all locations. Amniocentesis before 15 weeks, referred to as early amniocentesis (EA), is associated with a 1% rate of talipes and an increased rate of early pregnancy loss compared with CVS. Our objective was to compare the level of risk for euploid pregnancies following a positive NIPT based on the invasive procedure chosen., Method: Using data from a 2003 meta-analysis, we estimated the rates of adverse pregnancy outcome in euploid pregnancies based on the positive predictive value (PPV) of NIPT and the invasive procedure used-that is, CVS, EA, or termination of pregnancy (TOP)., Results: Following NIPT, we found that the rate of adverse fetal outcomes in euploid pregnancies was lower for CVS than for EA at all PPV levels. As the PPV of NIPT increased, the difference in risk between EA and CVS decreased. The risk to euploid pregnancies of TOP was excessive at all PPVs., Conclusion: CVS is the recommended diagnostic test in the first trimester because it is safer than EA for the fetus. However, EA is better than no testing when early TOP is planned. Patients should be strongly counselled against TOP without confirmatory testing., (Copyright © 2016. Published by Elsevier Inc.)

Objective: To study the efficacy of 100 μg intravenous shot of carbetocin compared to 20 IU oxytocin intravenous infusion to prevent placental retention in second trimester medical termination of pregnancy., Methods: A double-blinded randomized controlled trial was conducted at Ain Shams University Maternity Hospital from 1 April 2013 to 30 November 2013. A total of 132 women between 14 and 24 weeks gestation indicated for termination were randomized to receive either 20 IU oxytocin infusion (n = 66) or 100 μg carbetocin shot (n = 66) after fetal expulsion. Patients were observed for time elapsed between fetal and placental expulsion, presence of placental retention and blood loss., Results: Third stage was 33.4 ± 20.4 min in oxytocin group & 23.1 ± 16.8 min in carbetocin group (p = 0.002). Eight patients (12.1%) in oxytocin group had complete placental retention versus two patients (3.0%) in carbetocin group (p = 0.05). Eight patients (13.8%) received oxytocin had remnants of placenta compared to four patients (6.2%) received carbetocin (p = 0.04). Sixteen patients (24.2%) received oxytocin and six patients (9%) received carbetocin needed surgical curettage (p = 0.04). Third stage blood loss was 87.2 ± 33.7 ml in carbetocin and 206.9 ± 35.2 ml in oxytocin groups (p = 0.001)., Conclusion: Carbetocin is superior to oxytocin infusion for management of placental delivery in second trimester abortion.

Context: Termination of pregnancy (TOP) is regulated by French law for decades. Indications of TOP may vary depending on progress performed in perinatal medicine and in diagnosis of fetal anomalies, and also according to the way malformations are perceived in society., Objectives: To determine whether the frequency and indications of TOP had varied in the Lorraine Centre for Perinatal Diagnosis from 2000 to 2012., Subjects and Methods: Retrospective study performed on a randomized sample of medical files presented in the Lorraine Centre for Perinatal Diagnosis in years 2000, 2006 and 2012. We analyzed the number of files presented by parents-to-be, the indication motivating TOP, general characteristics of both pregnancies and mothers. We also performed a prospective enquiry among the French Centres for Perinatal Diagnosis in order to determine national rates., Results: General characteristics of mothers and pregnancies were similar from 2002 to 2012. No modification in indications of TOP was measured. In Lorraine, most TOPs were performed for chromosomal abnormality. On the national level, centres for perinatal diagnosis received more requests for TOPs in the study period. There were also more TOPs for non-lethal fetal anomalies, and parents refusing TOPs though the centres had agreed with its indication., Conclusion: The national trends were not measured in Lorraine region., (Copyright © 2016. Published by Elsevier Masson SAS.)

Infants with limb reduction deficiencies (LRD) often have other associated congenital anomalies. The purpose of this investigation was to assess the prevalence and the types of associated anomalies in a defined population. The associated anomalies in infants with LRD were collected in all livebirths, stillbirths and terminations of pregnancy during 29 years in 387,067 consecutive births in the area covered by our population-based registry of congenital malformations. Of the 317 infants bom with LRD during this period, representing a prevalence of 8.2 per 10,000, 59.9% had associated anomalies. There were 27 (8.5%) cases with chromosomal abnormalities including 17 trisomies 18, and 73 (23.0%) nonchromosomal recognized dysmorphic conditions including 19 VA(C)TER(L) association and 15 Poland syndrome. However, numerous other recognized dysmorphic conditions were registered. Ninety (28.4%) of the cases had multiple congenital anomalies (MCA). Anomalies in the musculoskeletal, the cardiac, the urogenital, and the central nervous system were the most common other anomalies. This study included special strengths: each affected child was examined by a geneticist, all elective terminations were ascertained, and the surveillance for anomalies was continued until 2 years of age. Therefore the overall prevalence of associated anomalies, which was more than one in two infants, emphasizes the need for a thorough investigation of infants with LRD. A routine screening for other anomalies especially in the musculoskeletal system, the cardiovascular system, the urogenital system, the central nervous system, and the digestive system may be considered in infants and in fetuses with LRD.

Study Question: What are the long term trends in the total (live births, fetal deaths, and terminations of pregnancy for fetal anomaly) and live birth prevalence of neural tube defects (NTD) in Europe, where many countries have issued recommendations for folic acid supplementation but a policy for mandatory folic acid fortification of food does not exist?, Methods: This was a population based, observational study using data on 11,353 cases of NTD not associated with chromosomal anomalies, including 4162 cases of anencephaly and 5776 cases of spina bifida from 28 EUROCAT (European Surveillance of Congenital Anomalies) registries covering approximately 12.5 million births in 19 countries between 1991 and 2011. The main outcome measures were total and live birth prevalence of NTD, as well as anencephaly and spina bifida, with time trends analysed using random effects Poisson regression models to account for heterogeneities across registries and splines to model non-linear time trends., Summary Answer and Limitations: Overall, the pooled total prevalence of NTD during the study period was 9.1 per 10,000 births. Prevalence of NTD fluctuated slightly but without an obvious downward trend, with the final estimate of the pooled total prevalence of NTD in 2011 similar to that in 1991. Estimates from Poisson models that took registry heterogeneities into account showed an annual increase of 4% (prevalence ratio 1.04, 95% confidence interval 1.01 to 1.07) in 1995-99 and a decrease of 3% per year in 1999-2003 (0.97, 0.95 to 0.99), with stable rates thereafter. The trend patterns for anencephaly and spina bifida were similar, but neither anomaly decreased substantially over time. The live birth prevalence of NTD generally decreased, especially for anencephaly. Registration problems or other data artefacts cannot be excluded as a partial explanation of the observed trends (or lack thereof) in the prevalence of NTD., What This Study Adds: In the absence of mandatory fortification, the prevalence of NTD has not decreased in Europe despite longstanding recommendations aimed at promoting peri-conceptional folic acid supplementation and existence of voluntary folic acid fortification., Funding, Competing Interests, Data Sharing: The study was funded by the European Public Health Commission, EUROCAT Joint Action 2011-2013. HD and ML received support from the European Commission DG Sanco during the conduct of this study. No additional data available., (© Khoshnood et al 2015.)

Objectives: To report the management of carriers of haemophilia in a French university hospital and assess different issues of these patients., Patients and Methods: Retrospective study of the carriers of haemophilia who consulted at the university hospital of Montpellier, France, between 1995 and 2011. Information were obtained from medical records and from a questionnaire sent to carriers. We recorded data about biological characteristics, bleeding tendency and management of pregnancies., Results: Sixty-four carriers of haemophilia A or B were included. Their median FVIII or FIX level was 52 % (range, 15-137 %). Menstrual bleeding lasted more than 7 days in 31 % of carriers. A total of 142 pregnancies started in 54 carriers, and 101 resulted in live births with 26 boys with haemophilia. Sixty-two prenatal diagnoses carried out, 15 have terminated their pregnancy because of a hemophiliac male fetus. Seventy-six percent of deliveries were vaginal delivery and 49 % took place in a level-3 maternity. There were 10.8 % and 8.5 % primary and secondary post-partum hemorrhage, respectively., Conclusion: The risk of bleeding among carriers of haemophilia is associated with their antihemophilic factor level. To improve the management of carriers, a multidisciplinary and standardized medical record, with a specific questionnaire to evaluate bleedings, could be considered. A regional register that lists all carriers, regardless of their antihemophilic factor level, would also be useful., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

Objectives: To investigate the perinatal outcome of cases with a prenatal diagnosis of single-ventricle cardiac defects, single ventricle being defined as a dominant right ventricle (RV) or left ventricle (LV), in which biventricular circulation was not possible., Methods: We reviewed patients with a prenatal diagnosis of single-ventricle cardiac defects, made at one institution between 1995 and 2008. Cases diagnosed with double-inlet LV, tricuspid atresia, pulmonary atresia with intact ventricular septum and severe RV hypoplasia and those with hypoplastic left heart syndrome (HLHS) were included in the study population. Patients with HLHS were identified prenatally as being standard risk or high risk (HLHS with highly restrictive or intact atrial septum, mitral stenosis with aortic atresia and/or LV coronary artery sinusoids). Patients with an address over 200 miles from the hospital, diagnosed with heterotaxy syndrome or referred for fetal intervention, were excluded., Results: We identified 312 cases of single-ventricle cardiac defect (208 dominant RV; 104 dominant LV) that were diagnosed prenatally. Most (96%) patients with a dominant RV had HLHS. Among the total 312 cases there were 98 (31%) elective terminations of pregnancy (TOP), 12 (4%) cases of spontaneous fetal demise, 12 (4%) cases lost to prenatal follow-up and 190 (61%) live births. Among the 199 patients that underwent fetal echocardiography before 24 weeks' gestation, there were 97 (49%) cases of elective TOP. There was no difference in prenatal outcome between those with a dominant RV and those with a dominant LV (P = 0.98). Of the 190 live births, five received comfort care. With an average of 7 years' follow-up (to obtain data on the Fontan procedure), transplantation-free survival was lower in those with a dominant RV than in those with a dominant LV (standard-risk HLHS odds ratio (OR), 3.0 (P = 0.01); high-risk HLHS OR, 8.8 (P < 0.001))., Conclusions: The prenatal outcome of cases with single-ventricle cardiac defects was similar between those with a dominant RV and those with a dominant LV, however postnatal intermediate-term survival favored those with a dominant LV. High-risk HLHS identified prenatally was associated with the lowest transplantation-free survival., (Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd.)

The number of male per 100 female live births (defined as the sex ratio at birth, SRB) has been shown to be consistently stable in human populations irrespective of time and geographical location. All over the globe approximately 105 boys are born for every 100 girls and any significant deviation from this 'global average' is considered to be unnatural and is attributed to sex-selective under-reporting of births, sex-selective abortion, sex-selective infanticide or other man-made factors. The present paper uses data on civil registration from 2004-2011 to investigate the sex ratio at birth in modern Greece. It was found that the SRB is extremely masculine when the parents originate from the Indian sub-continent and China. The SRB is also unnaturally high (more than 113 boys per 100 girls) in the case of legitimate births born to Greek mothers who are illiterate. These findings are strong evidence that sex-selective abortions are taking place in Greece within population groups with a certain ethnic and social profile. Other parameters, such as age of mother at birth, birth order, legal status of birth and geographical location, were also investigated and they were found to play a role in the variation of SRB, but not to the extent education and ethnic group do.

The present and future live birth prevalence of Down syndrome (DS) is of practical importance for planning services and prioritizing research to support people living with the condition. Live birth prevalence is influenced by changes in prenatal screening technologies and policies. To predict the future impact of these changes, a model for estimating the live births of people with DS is required. In this study, we combine diverse and robust datasets with validated estimation techniques to describe the non-selective and live birth prevalence of DS in the United States from 1900-2010. Additionally, for the period 1974-2010, we estimate the impact of DS-related elective pregnancy terminations (following a prenatal diagnosis of DS) on the live births with DS. The live birth prevalence for DS in the most recent years (2006-2010) was estimated at 12.6 per 10,000 (95% CI 12.4-12.8), with around 5,300 births annually. During this period, an estimated 3,100 DS-related elective pregnancy terminations were performed in the U.S. annually. As of 2007, the estimated rates at which live births with DS were reduced as a consequence of DS-related elective pregnancy terminations were 30% (95% CI: 27.3-31.9) for the U.S. as a whole. Our results and our model provide data on the impact of elective pregnancy terminations on live births with DS and may provide a baseline from which future trends for live births with DS can be estimated., (© 2015 Wiley Periodicals, Inc.)

Objective: To compare the policy of prenatal diagnosis versus first trimester screening of trisomy 21 among pregnant women of advanced age., Methods: A retrospective study was conducted on patients aged ≥35 divided in two groups: patients who requested first trimester combined test and only in case of screen-positive result underwent invasive testing (group A); patients undergoing chorionic villous sampling or amniocentesis as first investigation (group B). The following outcome variables were compared: antenatal detection of trisomy 21, occurrence of trisomy 21 at birth, miscarriage rate, hospitals' costs., Results: 4527 women were included. Of these, 534 (11.80%) underwent T21 screening whereas 3993 (88.20%) requested primary invasive testing. In group A, 64 combined test were positive (11.99%) and 8 trisomy 21 cases were diagnosed (1.50%); the loss of euploid fetuses after invasive procedure was 4.55% (2/44). No false-negative case was observed. In group B 57 cases of trisomy 21 were diagnosed (1.43%), and pregnancy loss rate of chromosomally normal fetuses was 0.45% (17/3806). The estimated cost was, respectively, 67.720€ for the primary screening versus 1.996.500€ for direct prenatal diagnosis., Conclusion: First trimester screening of trisomy 21 is highly accurate and cost saving among women ≥35.

Objectives: to estimate prevalence, mortality and lethality of congenital heart defects (CHDs), and to evaluate time trend by comparing two birth cohorts (1992- 2000 vs. 2001-2009)., Design: descriptive study using a population-based registry: the Tuscan Registry of congenital defects (RTDC), which is a member of the European network of surveillance of congenital anomalies (EUROCAT) since 1979., Setting and Participants: CHD cases were collected by the RTDC between 1992 and 2009., Main Outcome Measures: prevalence and mortality rates were calculated for all and non-chromosomal CHDs. The non-chromosomal cases were classified in three severity classes (SI, SII, SIII), according to decreasing perinatal mortality. It was estimated prevalence of: live births, foetal deaths (stillbirths and spontaneous abortions from 20 weeks gestation), terminations of pregnancy for foetal anomaly (TOPFAs) at any gestational age, and of prenatally diagnosed cases. Perinatal, neonatal and infant mortality were calculated. Early-neonatal, neonatal and infant lethality were calculated for the non-chromosomal cases., Results: 3,653 cases were identified out of 486,947 live births and 1,883 stillbirths, 95% of which were non-chromosomal cases. The total average prevalence was 7.47/1,000 births. The overall prevalence decreased significantly in all CHDs (Prevalence ratio - PR: 0.86; 95%CI 0.80-0.91) as well as in non-chromosomal (PR: 0.86; 95%CI 0.80-0.92), while in the more severe defects (SI/SII combined cases) the total prevalence was stable over time. In more severe cases, prevalence of live births decreased significantly (PR: 0.83; 95%CI 0.71-0.97), while the greater increase of TOPFAs and of diagnosed cases was observed in the prenatal period. All three mortality rates reduced significantly over time. In the more severe cases, the greatest rate mortality reduction was observed for neonatal mortality (Mortality ratio - MR: 0.29; 95%CI 0.16-0.49) than perinatal (MR: 0.37; 95%CI 0.19-0.70) and infant mortality (MR: 0,40; 95%CI 0.28-0.56). In this group of CHDs, early neonatal lethality decreased from 10% to 3%, neonatal lethality from 17% to 6%, and infant lethality from 24% to 10%., Conclusions: the results suggest that the improvements in prenatal diagnosis and in foetal and neonatal treatment and care have reduced the burden of congenital heart defects on the health of the Tuscany population.

Aims: This study evaluated the evolution of the prenatal diagnosis of congenital heart disease (CHD) between 2003 and 2008 and its repercussion for the CHD prevalence rate at birth in a well-defined population (Canton of Vaud, Switzerland)., Methods and Results: All 572 cases of CHD reported in the Eurocat Registry of Vaud-Switzerland between 1.5.2003 and 31.12.2008 were analysed and compared with the cases in our clinical database. CHD cases were divided into five different groups according to heart disease severity. The prenatal detection rates increased significantly between 2003 and 2008, with a mean detection rate of 25.2%. There was a significantly higher rate of prenatal diagnosis in the first four groups of CHD severity, with the highest detection rate (87.5%) found in the group with the most severe CHD (group 1). In this group, 85.7% of cases resulted in a termination of pregnancy, and there was a consequent 75% reduction in the prevalence of severe major cardiac malformation at birth. Detection rates were 66% in group 2, 68.6% in group 3, and the lowest in groups 4 and 5, with rates of 25.9% and 12.9%, respectively., Conclusion: This study shows that the prenatal detection rate for CHD increased in a well-defined population over the study period. Prenatal diagnosis thus has had a major impact on patients with the most severe types of CHD and has resulted in a significant reduction in severe CHD at birth.

Background: The difficulty many birth defects registries have in identifying early pregnancy terminations can lead to significant underreporting of certain types of malformations. This study was designed to determine the potential benefit of using maternal ICD-9 codes relating to management of pregnancy due to fetal anomaly in surveillance of central nervous system (CNS) defects (655.0)., Methods: Women assigned the ICD-9/ICD-9-CM (henceforth termed ICD-9) code 655.0 between 1990 and 2000 were ascertained from two administrative health databases in Manitoba, Canada, one relating to maternal serum screening and one based on hospital discharges. Information was collected on the type of CNS defect identified and whether it was isolated or associated with other anomalies. The relationship of these variables to pregnancy outcome and its potential impact on surveillance for these types of defects was explored., Results: Neural tube defects were the most common finding (67%) identified in the fetuses/infants of women assigned code 655.0, followed by hydrocephaly (20%) and Dandy-Walker anomaly (6%), but the proportion of neural tube defect cases declined after food fortification with folic acid. Termination of pregnancy occurred in ∼50% of neural tube defect cases, 18% before 20 weeks of gestation, but was rare for other CNS defects., Conclusion: The maternal ICD-9 code 655.0 had a very high (97%) positive predictive value for identifying fetuses with a CNS defect; 655.00 was particularly effective in identifying neural tube defects pregnancies terminated before 20 weeks gestation that would be difficult to ascertain, especially by passive surveillance systems using infant related data alone., (© 2014 Wiley Periodicals, Inc.)

Background: Exomphalos occurs in 2.2 per 10,000 births with 76% of these babies surviving to discharge. The aim of this study was to determine the birth prevalence and survival of babies with this anomaly in England and Wales., Methods: Six BINOCAR regional congenital anomaly registers in England and Wales (covering 36% of births) between 2005 and 2011 provided cases for this study. Cases included live births, stillbirths (24+ weeks' gestation), late miscarriages (20-23 weeks' gestation), and terminations of pregnancy with fetal anomaly., Results: The overall birth prevalence was 3.8 (95% confidence interval [CI]: 3.6-4.0) per 10,000 births; 1.4 (1.2-1.6) for isolated cases, 1.2 (1.1-1.4) for cases with multiple anomalies, and 1.2 (1.1-1.4) for cases with chromosomal anomalies. The live birth prevalence was 0.8 (0.7-0.9), 0.5 (0.4-0.6), and 0.1 (0.0-0.1) per 10,000 live births, respectively. Edwards syndrome, congenital heart defects, and nervous system anomalies were the most common anomalies associated with exomphalos. A prenatal diagnosis was made in 83% of isolated, 95% of multiple, and 99% of chromosomal cases. Fifty-five percent of isolated and multiple cases were live born, whereas 85% of cases with chromosomal anomalies resulted in a termination of pregnancy with fetal anomaly. The 1-year survival of live born babies with an isolated exomphalos was 92% compared with 81% in cases with multiple anomalies and 27% in cases with chromosomal anomalies (p < 0.001)., Conclusion: We report a higher birth prevalence than has previously been reported. The proportion of infants surviving with exomphalos remained unchanged over the time period., (© 2014 Wiley Periodicals, Inc.)

Introduction: Trisomy 18 and 13 are the most common autosomal trisomies, after trisomy 21, and their frequency is rising due to the increased maternal age of pregnant women. The fetuses suffer from multi-organ damage that may lead to many gestational complications as well as short life expectancy., Objective: To assess the indications for prenatal karyotyping of trisomy 13 (T-13, Patau syndrome) and trisomy 18 (T-18, Edwards syndrome) during pregnancy in our medical center., Methods: This retrospective cohort study involved all singleton pregnancies locally diagnosed or referred to our Institute because of T-13 and T-18, during the years 1998-2011., Results: There were 1879 cases of termination of pregnancies (TOPs) because of fetal indications, of them 53 cases of T-18 and 10 cases of T-13. The main indications for prenatal karyotyping in our study group were abnormal sonographic findings during anomaLy scans. In addition, 7 newborns with T-18 and 3 infants with T-13 were born in our hospital during the same period of time. We examined all cases that led to the Live birth of newborns with chromosomal anomalies, stemming from the Lack of extraction of the tests mentioned above and/or ignoring findings that raise suspicion that requires performing prenatal karyotyping during pregnancy., Discussion: Our findings corresponded with other studies and showed that prenatal diagnosis of T-13/T-18 due to abnormal sonographic finding is rising., Conclusions: Our study shows that it was possible to identify the vast majority of T-13/T-18 among the pregnant women who had an increased risk based on a combination of the routine screening tests applied in Israel.

Objectives: To evaluate in a population-based cohort the effect of the introduction of the 20-week ultrasound scan in 2007 on the time of diagnosis, pregnancy outcome and total prevalence and liveborn prevalence of cases with selected congenital heart defects (CHDs) in The Netherlands., Methods: We included children and fetuses diagnosed with selected severe CHD, born in the 11-year period from 2001 to 2011. Two groups of CHD were defined: those associated with an abnormal four-chamber view at ultrasound (Group 1), and those associated with a normal four-chamber view at ultrasound (Group 2). The time of diagnosis, pregnancy outcome and total liveborn prevalence were compared for both groups over two 5-year periods, before and after the introduction of the 20-week ultrasound scan. Trends in total and liveborn prevalence were examined over 2001 to 2011., Results: Information was collected on 269 children and fetuses. After the introduction of the 20-week ultrasound scan, the prenatal detection rate of CHDs increased in both groups (Group 1, 34.6% in 2001-2005 vs 84.8% in 2007-2011 (P < 0.001); Group 2, 14.3% in 2001-2005 vs 29.6% in 2007-2011 (P = 0.037)). The rate of termination of pregnancy (TOP) increased significantly only for Group 1 (15.4% vs 51.5% (P < 0.001)). The total prevalence of CHD in Group 1 increased over time from 2.9 per 10 000 births in 2001 to 6.4 per 10 000 births in 2011 (P = 0.016). The liveborn prevalence did not show a trend over time. For Group 2, no trends in total or liveborn prevalence could be detected over time., Conclusions: Since the implementation of the routine 20-week ultrasound scan in The Netherlands, prenatal detection rate of selected severe CHDs increased significantly. Improved prenatal detection was accompanied by a more than three-fold increase in TOP, although only in those CHDs with an abnormal four-chamber view at prenatal ultrasound., (Copyright © 2013 ISUOG. Published by John Wiley & Sons Ltd.)

Objective: To document outcome following prenatal diagnosis of ventricular septal defects (VSDs), particularly associated anomalies and the requirement for surgical closure of the defect., Methods: All cases of prenatal diagnosis of a VSD made by fetal cardiologists at a tertiary fetal medicine referral center in the period January 2002 to December 2011 were extracted from our database. Data regarding fetal cardiac diagnosis, extracardiac anomalies, nuchal translucency thickness and karyotype were noted., Results: A total of 171 cases fulfilled our selection criteria. Of these, 69% were diagnosed with a perimembranous VSD and 31% with a muscular defect. The median gestational age at diagnosis was 21 + 6 (range, 12 + 0 to 37 + 3) weeks. Owing to severe extracardiac or genetic conditions, pregnancy resulted in intrauterine death or termination in 49% cases, and postnatal death occurred in 9% of cases. Seventy-two babies were liveborn, and were regarded as potential surgical candidates if hemodynamics suggested that surgery was indicated. Surgical closure of the VSD proved necessary in 50% of the patients with a perimembranous VSD and 13% of those with a muscular VSD. All patients operated on survived surgical repair. No karyotypic abnormalities were identified in fetuses with VSDs that had normal first-trimester screening and no other sonographic abnormalities., Conclusions: A high proportion of VSDs diagnosed during fetal life (29%) require postnatal surgical intervention. The assessment of hemodynamic significance from fetal echocardiography is imperfect. The presence of extracardiac abnormalities or abnormal results on first-trimester screening has a major impact on the incidence of karyotypic abnormalities in affected fetuses. This should inform discussions with parents about invasive testing., (Copyright © 2013 ISUOG. Published by John Wiley & Sons Ltd.)

Objective: The authors conducted a prospective, comparative observational study to evaluate the risk of major anomalies following exposure to lithium during pregnancy., Method: A total of 183 lithium-exposed pregnancies of women who contacted the Israeli Teratology Information Service were followed up (90.2% in the first trimester) and compared with 72 disease-matched and 748 nonteratogenic-exposed pregnancies., Results: There were significantly more miscarriages (adjusted odds ratio=1.94, 95% CI=1.08-3.48) and elective terminations of pregnancy (17/183 [9.3%] compared with 15/748 [2.0%]) in the lithium-exposed group compared with the nonteratogenic exposure group. The rate of major congenital anomalies after exclusion of genetic or cytogenetic anomalies was not significantly different between the three groups (lithium-exposed in the first trimester: 8/123 [6.5%]; bipolar: 2/61 [3.3%]; nonteratogenic: 19/711 [2.7%]). Cardiovascular anomalies occurred more frequently in the lithium group exposed during the first trimester when compared with the nonteratogenic exposure group (5/123 [4.1%] compared with 4/711 [0.6%]) but not after excluding anomalies that spontaneously resolved (3/123 [2.4%] compared with 2/711 [0.3%]). Ebstein's anomaly was diagnosed in one lithium-exposed fetus and in two retrospective lithium cases that were not included because contact with the information service was made after the prenatal diagnosis by ultrasound. The rate of noncardiovascular anomalies was not significantly different between the groups. The rate of preterm deliveries was higher in the lithium group compared with the nonteratogenic exposure group (18/131 [13.7%] compared with 41/683 [6.0%])., Conclusions: Lithium treatment in pregnancy is associated with a higher rate of cardiovascular anomalies. Women who are treated with lithium during organogenesis should undergo fetal echocardiography and level-2 ultrasound.

Sporadic cases of rubella infection are reported each year in France due to insufficient vaccination coverage. Rubella virus is a very unstable enveloped RNA virus. For this reason, transportation and storage of samples collected for its detection require particular conditions. The genetic stability of rubella virus has allowed the development of very effective vaccines. During the recent rubella outbreaks in Algeria and Tunisia, an unusual high rate of encephalitis was reported. The role of the laboratory is crucial in the management of rubella infection during pregnancy. Rubella serological results must be interpreted with caution. Congenital rubella is a severe disease that should already be eliminated thanks to a very effective vaccine that has been developed. All women of childbearing age should be vaccinated. Rubella vaccination of an unknowingly pregnant woman is not an indication for abortion., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

Objective: To investigate different cut-off levels of nuchal translucency (NT) to predict abnormal cardiac findings (ACF) in second trimester ultrasound examination and confirmed postnatal congenital heart defects (CHD) in euploid pregnancies., Methods: A retrospective analysis was performed on singleton pregnancies examined in our ultrasound units from 2006 to 2011. Fetuses with an abnormal karyotype were excluded. Different cut-off levels of NT thickness were analyzed to evaluate its performance to detect the ACF on second trimester ultrasound (2nd US) examination and also the CHD detected in neonatal follow-up evaluation of ACF cases., Results: Of the 12,840 cases, a total number of 8541 euploid pregnancies were included in the study. Thirty-three had ACFs detected by 2nd US (3.86/1000). The mean NT thickness was found to be higher in fetuses with ACFs (p < 0.0001). Of 33 ACFs, 17 (52%, 1.99/1000) had major CHDs in neonatal follow-up. The area under the ROC curves for NT thickness to predict ACFs and CHDs were 0.67 and 0.65, respectively., Conclusions: Higher NT thickness is associated with higher risk of ACF. NT is a weak predictor of ACF and major CHD; however, fetuses with an unexplained increase in NT measurement should be referred for further cardiac investigations.

Objectives: To highlight the value of 3D ultrasound in the prenatal assessment of fetal cardiovascular abnormalities., Patients and Methods: A retrospective offline analysis of volume datasets of fetuses diagnosed with cardiovascular anomalies by 2D ultrasound was performed., Results: Thirty-four fetuses with 38 cardiac malformations were evaluated. Mean gestational age at diagnosis was 26 weeks. Isolated cardiovascular malformations were detected in 23 fetuses. Extracardiac abnormalities were identified in eight fetuses. Ten terminations of pregnancy were performed., Conclusion: Offline analysis of cardiovascular anomalies conferred significant diagnostic advantages over 2D ultrasound. 3D ultrasound is a valuable tool for the prenatal diagnosis and the management of congenital heart diseases., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)