Outcomes following the detection of fetal edema in early pregnancy prior to non-invasive prenatal testing.

OBJECTIVE: To investigate the incidence of structural and chromosomal abnormalities in cases of fetal edema on early ultrasound prior to non-invasive prenatal testing (NIPT). METHODS: A retrospective study of women undergoing pre-NIPT ultrasound with fetal crown-rump length (CRL) of 28 to 44 mm was conducted at a tertiary obstetric ultrasound clinic in Melbourne, Australia. Cases of reported fetal edema were included, and subclassified as isolated nuchal edema (>2.2 mm) or generalized edema/hydrops by two operators blinded to outcomes. RESULTS: We identified 104 cases of fetal edema. Nuchal edema and generalized edema were present in 40 (38.5%) and 64 (61.5%) cases, respectively. Relevant chromosomal anomalies were identified in 19.2% (20/104), occurring in 10.0% (4/40) of the nuchal edema and 25.0% (16/64) of the generalized edema/hydrops cases. Structural anomalies with normal karyotype occurred in four (3.8%) additional cases. Miscarriage occurred in four cases (3.8%) and termination of pregnancy in 18 cases (17.3%). Among cases that reached the 11 to 13+6 weeks ultrasound, the edema resolved in 81.9% and these cases had less adverse outcomes than those with NT≥3.5 mm (10.9% vs 76.5%, P < .001). CONCLUSIONS: Fetal edema in early pregnancy is associated with a high incidence of structural and/or chromosomal abnormalities; these rates increase with progressive severity.

Genetics experience impacts attitudes towards germline gene editing: a survey of over 1500 members of the public.

CRISPR-Cas9 has revolutionised genome engineering and has the potential to radically change our approach to genetic disease. However, the potential for genetic modification of embryos has raised significant and complex ethical and social concerns. The scientific community have called for ongoing stakeholder consultation about Germline Gene Editing (GGE), in particular lay publics, to help guide policy, education, research and regulatory priorities. In response, we conducted a survey to gauge public support for GGE and describe the demographic, experiential and contextual factors that influence individual attitudes. Respondent support was measured across nine hypothetical medical and enhancement GGE applications. We received responses from 1537 participants across 67 countries. Respondents were generally supportive of GGE, particularly for medical applications. While the most opposition observed was among religious respondents, those with work experience in genetics or genomics also reported greater resistance to GGE. Personal or family-related experience with genetics or genomics, identifying as female and tertiary education were also associated with less support for GGE. Further research needs to explore a diverse range of community and group attitudes towards GGE; the reasons underlying demographic and experiential differences; and to determine where the public and genetics professionals draw the line on ethical implementation respectively.

Cranial sonographic markers of fetal open spina bifida at 11 to 13 weeks of gestation.

OBJECTIVES: To compare the sonographic signs of spina bifida obtained on axial and sagittal views of the fetal head between 11 and 13+6 weeks of gestation. METHODS: This was a retrospective study including 27 cases of spina bifida and 1003 randomly selected controls. Indirect markers of spina bifida were evaluated on stored ultrasound images. Intracranial translucency (IT), ratio between the brainstem and the brainstem-occipital bone distance (BS/BSOB), and maxillo-occipital (MO) line were assessed on sagittal view, whereas biparietal diameter (BPD), BPD to abdominal circumference ratio (BPD/AC), and aqueduct to occipital bone (aqueduct of Sylvius [AoS]) distance were measured on the axial plane. Reference ranges were developed, and cases of spina bifida were examined in relation to the reference range. RESULTS: On the sagittal view, detection rates for IT below the fifth percentile, BS/BSOB above the 95th percentile, and an abnormal MO line were 52.3%, 96.3%, and 96.3%, respectively. On the axial view, detection rates for BPD, BPD/AC, and AoS below the fifth percentile were 66.7%, 70.4%, and 77.8%, respectively. CONCLUSION: The MO line and the BS/BSOB ratio appear to be the best indirect ultrasound markers of spina bifida and can be easily obtained during the routine first-trimester scan.

Influence of Body Mass Index on Fetal Fraction Increase With Gestation and Cell-Free DNA Test Failure.

OBJECTIVE: To assess the influence of body mass index (BMI) on fetal fraction increase with gestational age and on the rates of test failure. METHODS: We performed a cross-sectional study of consecutive singleton pregnancies in which cell-free DNA screening for fetal aneuploidies was performed from 10 weeks of gestation, between May 2013 and January 2018, at two fetal medicine clinics in Australia using one of two different platforms. Maternal characteristics, fetal fraction, and failure after a first attempt ("no-call") and after resampling ("test failure") were recorded. Body mass index was classified as normal (BMI less than 25.0), overweight (BMI 25.0-29.9), obesity class I (BMI 30.0-34.9), and obesity classes II and III (BMI 35.0 or greater). Fetal fraction and proportions of no-call results and test failure were compared between the groups. RESULTS: Of 14,223 singleton pregnancies included, 8,583 (60.3%) were screened with platform A and 5,640 (39.7%) with platform B. Median fetal fraction values were lower, and no-call and failure rates were higher in increased BMI groups across both platforms (P<.001 in both). When compared with women with normal BMIs, women with BMIs of 35 or greater had a significantly smaller increase in fetal fraction (0.1 vs 0.3 units/wk, P<.001, in both platforms). In this subgroup, when compared with women with normal BMIs, the odds ratios for a no-call result were 22.0 (95% CI 13.8-35.3, 16.6% vs 0.9%) and 8.0 (95% CI 4.1-15.6, 7.8% vs 1.0%) and for a failed test were 25.0 (95% CI 11.2-55.7, 6.4% vs 0.3%) and 5.8 (95% CI 2.0-17.3, 2.7% vs 0.5%) using platforms A and B, respectively. CONCLUSION: The increase in fetal fraction throughout gestation in women with BMIs of 35 or above is minimal. Postponing the test is unlikely to reduce test failure rates in this population.

"There's a whole different way of working with adolescents": interviews with Australian Genetic Counselors about their experiences with adolescent clients.

Adolescence is a developmental period marked by unique physical, psychological and social changes. Guidelines about working with adolescents are available to health professionals in other fields, yet few resources are tailored specifically to genetic counselors. The current qualitative study explored the experiences of genetic counselors who work with adolescent clients to determine whether challenges exist and if further training and support are needed. Semi-structured interviews were conducted with 11 genetic counselors from Australia. Interview transcripts were analyzed using thematic analysis from which 7 key themes emerged: 1) Adolescents: A distinct client group? 2) Characteristics of adolescents; 3) Strategies for working with adolescents; 4) Confidentiality; 5) Parental involvement and presence in sessions; 6) Benefits of working with adolescents; and 7) The effectiveness of past training and education. The findings hold important implications for clinical practice and may inform future training programs and guidelines for genetic counselors internationally.