The application of late amniocentesis: a retrospective study in a tertiary fetal medicine center in China.

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.

Omphalocele in Finland from 1993 to 2014: Trends, Prevalence, Mortality, and Associated Malformations-A Population-Based Study.

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.

The prenatal ultrasonic character and postnatal follow-up of 227 microcystic and macrocystic congenital cystic adenomatoid malformations.

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 statementWhat 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.

Evolution of third-trimester pregnancy terminations in France.

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.

Multilevel analyses of related public health indicators: The European Surveillance of Congenital Anomalies (EUROCAT) Public Health Indicators.

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.

Severe congenital heart defects: incidence, causes and time trends of preoperative mortality in Norway.

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.

On the way to interrupting the gestation or not: experiences of pregnant women with anencephalic fetuses. / Nas vias de interromper ou não a gestação: vivências de gestantes de fetos com anencefalia.

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.

A anencefalia é uma malformação caracterizada pela ausência total ou parcial do encéfalo e o Brasil é o quarto colocado em número de nascimentos de fetos anencéfalos no mundo. Existe associação entre anencefalia fetal e maior número de complicações maternas. A partir de 2012 a mulher com gestação de anencéfalo poderá manter ou interromper a gestação, se assim o desejar, sem necessidade de autorização judicial. Objetivos: compreender as vivências das mulheres de fetos com anencefalia e identificar os fatores determinantes para a escolha de interromper ou não interromper a gestação. Estudo qualitativo e método das narrativas de vida, com 12 mulheres, maiores de 18 anos e com diagnóstico de feto anencéfalo, que realizaram a interrupção da gestação ou o parto em uma maternidade pública do Rio de Janeiro. A coleta dos dados foi entre junho e novembro de 2016 e encerrada quando os padrões narrativos alcançaram a saturação progressiva, a partir das recorrências. Os enunciados emergidos após leitura flutuante e aprofundada foram articulados em Núcleos Narrativos e realizada análise comparativa e compreensiva dos dados. Os relatos trouxeram à tona as vivências intensas dessas mulheres, como também as fragilidades existentes em relação ao cuidado e a problemática da interrupção da gestação.

Nas vias de interromper ou não a gestação: vivências de gestantes de fetos com anencefalia / On the way to interrupting the gestation or not: experiences of pregnant women with anencephalic fetuses

Resumo A anencefalia é uma malformação caracterizada pela ausência total ou parcial do encéfalo e o Brasil é o quarto colocado em número de nascimentos de fetos anencéfalos no mundo. Existe associação entre anencefalia fetal e maior número de complicações maternas. A partir de 2012 a mulher com gestação de anencéfalo poderá manter ou interromper a gestação, se assim o desejar, sem necessidade de autorização judicial. Objetivos: compreender as vivências das mulheres de fetos com anencefalia e identificar os fatores determinantes para a escolha de interromper ou não interromper a gestação. Estudo qualitativo e método das narrativas de vida, com 12 mulheres, maiores de 18 anos e com diagnóstico de feto anencéfalo, que realizaram a interrupção da gestação ou o parto em uma maternidade pública do Rio de Janeiro. A coleta dos dados foi entre junho e novembro de 2016 e encerrada quando os padrões narrativos alcançaram a saturação progressiva, a partir das recorrências. Os enunciados emergidos após leitura flutuante e aprofundada foram articulados em Núcleos Narrativos e realizada análise comparativa e compreensiva dos dados. Os relatos trouxeram à tona as vivências intensas dessas mulheres, como também as fragilidades existentes em relação ao cuidado e a problemática da interrupção da gestação.

Abstract 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.

Attitudes towards abortion in male and female adolescents with diverse sexual and pregnancy experiences: a cross-sectional study.

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 (ß = 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.

Gastroschisis in Finland 1993 to 2014-Increasing Prevalence, High Rates of Abortion, and Survival: A Population-Based Study.

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.

Prenatal diagnosis of birth defects and termination of pregnancy in Hunan Province, China.

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.

Refining the prognosis of fetuses infected with Cytomegalovirus in the first trimester of pregnancy by serial prenatal assessment: a single-centre retrospective study.

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.

Sex selection and non-invasive prenatal testing: A review of current practices, evidence, and ethical issues.

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.

Patient preferences for prenatal testing and termination of pregnancy for congenital anomalies and genetic diseases in Ethiopia.

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.

The impact of insurance coverage on the prenatal genetic counseling process: An exploration of genetic counselors' experiences with TRICARE.

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.

Prenatal exome sequencing analysis in fetal structural anomalies detected by ultrasonography (PAGE): a cohort study.

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.

Prognosis of 591 fetuses with ultrasonic soft markers during mid-term pregnancy.

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.

Trends in Continuity of Pregnancy in Women with Positive Cytomegalovirus IgM during the First Trimester, 2008-2009.

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.

The outcomes of 31 cases of trisomy 13 diagnosed in utero with various management options.

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.