Applying citizen science to engage families affected by ovarian cancer in developing genetic service outreach strategies.

Citizen science (CS) approaches involving non-professional researchers (citizens) as research collaborators has been used infrequently in health promotion generally and specifically, in cancer prevention. Standardized CS approaches may be especially useful for developing communication interventions to encourage families to consider cancer genetic services. We engaged survivors of ovarian cancer and their close relatives as CS collaborators to collect and help interpret data to inform content for a website, printed invitation materials, and short-message reminders. We applied an implementation quality framework, and posed four research questions regarding the feasibility of CS: recruitment, data collection, data quality and evaluation of the experience. CS members were recruited through three networks: clinical sites, local and national cancer support organizations, and online ovarian cancer patient support groups. The professional research team operationalized theory-aligned CS tasks, five data collection options, question banks/scripts for creating surveys, structured interviews, online training and ongoing support from research coaches. 14 CS members agreed to the 12-week and 20-hour commitment for an honorarium. CS members opted to do both qualitative and quantitative assessments. CS members collected 261 surveys and 39 structured interviews. The largest number of surveys were collected for Task 1 (n = 102) to assess survivors' reactions to different possible options for motivating survivors to visit a study website; 77% of this data were complete (i.e., no missing values). Data collected for tasks 2, 3, 4, and 5 (e.g., assessment of survivors' and relatives' respective communication preferences) ranged from 10 to 58 surveys (80% to 84% completeness). All data were collected within the specified time frame. CSs reported 17 hours of work on average and regarded the experience positively. Our experience suggests that CS engagement is feasible, can yield comprehensive quantitative and qualitative data, and is achievable in a relatively a short timeline.

Barriers to Sonographer Screening for Fetal Heart Defects: A U.S. National Survey.

OBJECTIVE: We surveyed obstetric sonographers, who are at the forefront of the screening process to determine how barriers to prenatal cardiac screening impacted screening abilities. METHODS: We performed a cross-sectional national survey of obstetric sonographers in the United States using a sampling frame from American Registry of Diagnostic Medical Sonography mailing lists. The web survey measured the ability to obtain and interpret fetal heart images. Several cognitive, sociodemographic, and system-level factors were measured, including intention to perform cardiac imaging. Regression and mediation analyses determined factors associated with intention to perform and ability to obtain and interpret cardiac images. Subgroup analyses of sonographers in tertiary versus nontertiary centers were also performed. RESULTS: Survey response rate either due to noncontact or nonresponse was 40%. Of 480 eligible sonographers, ~30% practiced in tertiary settings. Sonographers had lower intention to perform outflow views compared to 4 chambers. Higher self-efficacy and professional expectations predicted higher odds of intention to perform outflow views (OR 2.8, 95% CI 1.9-4.2 and 1.9, 95% CI 1.1-3.0, respectively). Overall accuracy of image interpretation was 65% (±14%). For the overall cohort and nontertiary subgroup, higher intention to perform outflows was associated with increased accuracy in overall image interpretation. For the tertiary subgroup, self-efficacy and feedback were strongly associated with accuracy. CONCLUSIONS: We identified several modifiable (some heretofore unrecognized) targets to improve prenatal cardiac screening. Priorities identified by sonographers that are associated with screening success should guide future interventions.

Etiology and clinical presentation of birth defects: population based study.

Objective To assess causation and clinical presentation of major birth defects.Design Population based case cohort.Setting Cases of birth defects in children born 2005-09 to resident women, ascertained through Utah's population based surveillance system. All records underwent clinical re-review.Participants 5504 cases among 270 878 births (prevalence 2.03%), excluding mild isolated conditions (such as muscular ventricular septal defects, distal hypospadias).Main outcome measures The primary outcomes were the proportion of birth defects with a known etiology (chromosomal, genetic, human teratogen, twinning) or unknown etiology, by morphology (isolated, multiple, minors only), and by pathogenesis (sequence, developmental field defect, or known pattern of birth defects).Results Definite cause was assigned in 20.2% (n=1114) of cases: chromosomal or genetic conditions accounted for 94.4% (n=1052), teratogens for 4.1% (n=46, mostly poorly controlled pregestational diabetes), and twinning for 1.4% (n=16, conjoined or acardiac). The 79.8% (n=4390) remaining were classified as unknown etiology; of these 88.2% (n=3874) were isolated birth defects. Family history (similarly affected first degree relative) was documented in 4.8% (n=266). In this cohort, 92.1% (5067/5504) were live born infants (isolated and non-isolated birth defects): 75.3% (4147/5504) were classified as having an isolated birth defect (unknown or known etiology).Conclusions These findings underscore the gaps in our knowledge regarding the causes of birth defects. For the causes that are known, such as smoking or diabetes, assigning causation in individual cases remains challenging. Nevertheless, the ongoing impact of these exposures on fetal development highlights the urgency and benefits of population based preventive interventions. For the causes that are still unknown, better strategies are needed. These can include greater integration of the key elements of etiology, morphology, and pathogenesis into epidemiologic studies; greater collaboration between researchers (such as developmental biologists), clinicians (such as medical geneticists), and epidemiologists; and better ways to objectively measure fetal exposures (beyond maternal self reports) and closer (prenatally) to the critical period of organogenesis.

Risk factors for Dandy-Walker malformation: a population-based assessment.

Dandy-Walker malformation (DWM) is the most common congenital malformation of the cerebellum, but its causes are largely unknown. An increasing number of genes associated with congenital cerebellar malformations have been identified; however, few studies have examined the potential role of non-genetic, potentially modifiable risk factors. From the National Birth Defects Prevention Study, we examined maternal, paternal, and infant characteristics and maternal conditions and periconceptional exposures (from 1 month before to 3 months after conception) among infants with DWM (n = 160) and unaffected controls (n = 10,200), delivered between 1997 and 2009. Odds ratios, crude (cOR) and adjusted (aOR) were computed using logistic regression. Maternal factors associated with DWM included non-Hispanic black race/ethnicity (aOR = 2.0, 95%CI: 1.3-3.2). Among maternal conditions, a history of infertility increased the risk for DWM (all: aOR = 2.4, 95%CI: 1.3-4.6; multiple: aOR = 3.9, 95%CI: 1.7-8.9). The lack of association with many maternal exposures supports the hypothesis of a major contribution of genetic factors to the risk for DWM; however, the observed associations with maternal non-Hispanic black race/ethnicity and maternal history of infertility indicate that further research into factors underlying these characteristics may uncover potentially modifiable risk factors, acting alone or as a component of gene-environment interactions.

Admission to a dedicated cardiac intensive care unit is associated with decreased resource use for infants with prenatally diagnosed congenital heart disease.

Many factors in the delivery and perinatal care of infants with a prenatal diagnosis of congenital heart disease (CHD) have an impact on outcome and costs. This study sought to determine the modifiable factors in perinatal management that have an impact on postnatal resource use for infants with CHD. The medical records of infants with prenatally diagnosed CHD (August 2006-December 2011) who underwent cardiac surgery before discharge were reviewed. The exclusion criteria ruled out prematurity and intervention or transplantation evaluation before surgery. Clinical characteristics, outcomes, and cost data were collected. Multivariate linear regression models were used to determine the impact of perinatal decisions on hospitalization cost and surrogates of resource use after adjustment for demographic and other risk factors. For the 126 patients who met the study criteria, the median hospital stay was 22 days (range 4-122 days), and the median inflation-adjusted total hospital cost was $107,357 (range $9,746-602,320). The initial admission to the neonatal versus the cardiac intensive care unit (NICU vs. CICU) was independently associated with a 19 % longer hospital stay, a 26 % longer ICU stay, and 47 % more mechanical ventilation days after adjustment for Risk Adjustment for Congenital Heart Surgery, version 1 score, gestation age, genetic abnormality, birth weight, mode of delivery, and postsurgical complications. Weekend versus weekday delivery was not associated with hospital cost or length of hospital stay. For term infants with prenatally diagnosed CHD undergoing surgery before discharge, preoperative admission to the NICU (vs. the CICU) resulted in a longer hospital stay and greater intensive care use. Prenatal planning for infants with CHD should consider the initial place of admission as a modifiable factor for potential lowering of resource use.

Analysis of skeletal dysplasias in the Utah population.

The Utah Birth Defect Network (UBDN) collects population-based data for Utah on births from all resident women. The prevalence of skeletal dysplasias and epidemiologic characteristics/outcomes were evaluated. Cases categorized as a skeletal dysplasia from all live births, stillbirths, and pregnancy terminations (TAB) between 1999 and 2008 were reviewed by three clinical geneticists. After case review, 153 were included for analysis (88% live births, 3% stillborn, 9% TAB), and categorized by groupings defined by molecular, biochemical, and/or radiographic criteria as outlined in the 2010 Nosology and Classification of Genetic Skeletal Disorders. The overall prevalence for skeletal dysplasias was 3.0 per 10,000 births, and 20.0 per 10,000 stillbirths. The most common diagnostic groups were osteogenesis imperfecta (OI; n = 40; 0.79 per 10,000), thanatophoric dysplasia (n = 22; 0.43 per 10,000), achondroplasia (n = 18; 0.35 per 10,000), and cleidocranial dysplasia (n = 6; 0.12 per 10,000). The most common groups based on the 2010 Nosology and Classification of Genetic Skeletal Disorders were the FGFR3 chondrodysplasia group (n = 41; 0.81 per 10,000), the OI/decreased bone density group (n = 40; 0.79 per 10,000), and the type 2 collagen group (n = 10; 0.2 per 10,000). Median age of postnatal diagnosis was 30 days (range 1-2,162). Of those deceased, 88% were prenatally suspected; of those alive 29% prenatally suspected. Median age of death for live born individuals was 1 day (range 1-1,450 days). Previously reported prevalence rates vary, but our data provide a population-based approach not limited to the perinatal/neonatal period. Understanding the range for survival within each group/diagnosis is beneficial for health care providers when counseling families.

Autosomal recessive hypophosphatasia manifesting in utero with long bone deformity but showing spontaneous postnatal improvement.

CONTEXT: Hypophosphatasia (HPP) is a heritable metabolic disorder of the skeleton that includes variable expressivity conditioned by gene dosage effect and the variety of mutations in the tissue nonspecific alkaline phosphatase (TNSALP) gene. Patient age when skeletal problems first manifest generally predicts the clinical course, with perinatal HPP causing bone disease in utero with postnatal lethality. OBJECTIVE: Our objective was to identify TNSALP mutations and characterize the inheritance pattern of a family with clinically variable HPP with one child manifesting in utero with long bone deformity but showing spontaneous prenatal and postnatal improvement. DESIGN: TNSALP enzyme and substrate analysis and TNSALP mutation analysis were performed on all family members. PATIENTS: A boy with HPP showing long bone deformity that spontaneously improved in utero and after birth is described. His older brother has the childhood form of HPP without findings until after infancy. His parents and twin sister are clinically unaffected. RESULTS: Both boys are compound heterozygotes for the same missense mutations in TNSALP, documenting autosomal recessive inheritance for their HPP. The parents each carry one defective allele. CONCLUSIONS: The patient is an autosomal recessive case of HPP with prenatal long bone deformity but with spontaneous prenatal and postnatal improvement. Thus, prenatal detection by sonography of bowing of long bones from HPP, even with autosomal recessive inheritance, does not necessarily predict lethality but can represent variable expressivity or the effects of modifiers on the TNSALP defect(s).

Unilateral short femur--what does this mean? Report of 3 cases.

OBJECTIVES: This study aims to: (1) characterize the prenatal diagnosis of short femur; (2) describe typical findings of proximal focal femoral deficiency; and (3) review the most common differential diagnoses for short femur(s). METHODS: We present 3 examples of prenatally diagnosed proximal focal femoral deficiency and briefly reviewed the differential diagnosis of short femur(s) in utero and associations such as ethnic variation, trisomy 21, and diabetic embryopathy. RESULTS: Multiple cases are presented in which a short femur (unilateral or bilateral) is the dominant finding on prenatal ultrasound. The fetuses were extensively examined for other skeletal anomalies, and global skeletal dysplasias are excluded from the differential diagnosis. Prenatal imaging findings are correlated with postnatal history and imaging. CONCLUSION: Prenatal sonography is now widely used as a screening tool, and at times, subtle findings such as an isolated short femur can be seen without other significant anatomic abnormalities. Counseling for the parents can be difficult without some knowledge of the range of associations seen with short femur(s). Proximal focal femoral dysplasia should be considered in the differential diagnosis when a short femur is discovered.

Brachymesomelic dysplasia with Peters anomaly of the eye results from disruptions of the X chromosome near the SHOX and SOX3 genes.

We report on a mother and son affected with an unusual skeletal dysplasia and anterior segment eye abnormalities. Their skeletal phenotype overlaps with the SHOX-related skeletal dysplasias and is intermediate between Leri-Weill dyschondrosteosis (LWD) and Langer Mesomelic dysplasia (LMD). The mother has bilateral Peters anomaly of the eye and was reported as having a new syndrome; the son had severe bilateral sclerocornea. Chromosome analysis showed that the mother has a pericentric inversion of the X chromosome [46,X,inv(X)(p22.3q27)] and the son, a resultant recombinant X chromosome [46,Y,rec(X)dup(Xq)inv(X)(p22.3q27)]. The observed skeletal and ophthalmologic abnormalities in both patients were similar in severity. The additional features of developmental delay, growth retardation, agenesis of the corpus callosum, cryptorchidism and hypoplastic scrotum in the son are consistent with Xq28 duplication. Analysis of the son's recombinant X chromosome showed that the Xp22.33 breakpoint lies 30-68 kb 5' of the SHOX gene. This finding suggests that the skeletal dysplasia in both mother and son is allelic with LWD and LMD and results from a novel misexpression of SHOX. Analysis of the Xq27.1 breakpoint localized it to a 90 kb interval 3' of the SOX3 gene, supporting a novel role of SOX3 misexpression in the development of Peters anomaly of the eye.