Chromosomal microarray analysis in the investigation of prenatally diagnosed congenital heart disease.

BACKGROUND: Chromosomal microarray analysis has emerged as a primary diagnostic tool in prenatally diagnosed congenital heart disease and other structural anomalies in clinical practice. OBJECTIVE: Our study aimed to investigate the diagnostic yield of microarray analysis as a first-tier test for chromosomal abnormalities in fetuses with both isolated and nonisolated congenital heart disease and to identify the association of different pathogenic chromosomal abnormalities with different subgroups of congenital heart disease. STUDY DESIGN: Retrospective data from 217 pregnancies that were diagnosed with congenital heart disease between 2011 and 2016 were reviewed. All pregnancies were investigated with the use of microarray analysis during the study period. Classification of chromosomal abnormalities was done based on American College of Medical Genetics and Genomics guidelines into (1) pathogenic chromosomal abnormalities that included numeric chromosomal abnormalities (aneuploidy and partial aneuploidy) and pathogenic copy number variants (22q11.2 deletion and other microdeletions/microduplications), (2) variants of uncertain significance, and (3) normal findings. RESULTS: Our study found a detection rate for pathogenic chromosomal abnormalities (numeric and pathogenic copy number variants) of 36.9% in pregnancies (n=80) that were diagnosed prenatally with congenital heart disease who underwent invasive testing with chromosomal microarray. The detection rate for numeric abnormalities was 29.5% (n=64) and for pathogenic copy number variants was 7.4% (n=16) of which 4.2% were 22q11.2 deletion and 3.2% were other pathogenic copy number variants, most of which theoretically could have been missed by the use of conventional karyotype alone. Pathogenic copy number variants were most common in conotruncal defects (19.6%; 11/56) that included 42.9% in cases of interrupted aortic arch, 23.8% in cases of tetralogy of Fallot, 13.3% in cases of transposition of the great arteries, and 8.3% in cases of double outlet right ventricle. Of these changes, 81.8% were 22q11.2 deletion, and 18.2% were other microdeletions/microduplications. After conotruncal defects, pathogenic copy number variants were most common in right ventricular outflow tract and left ventricular outflow tract groups (8% and 2.2%, respectively) in which none were 22q11.2 deletion. Pathogenic chromosomal abnormalities (numeric and pathogenic copy number variants) detected by chromosomal microarray analysis were significantly more common in the nonisolated congenital heart disease group (64.5%; n=49) compared with the isolated group (22%; n=31; P<.001). CONCLUSION: In pregnancies that were diagnosed with congenital heart disease and had undergone diagnostic genetic testing, our study showed that chromosomal microarray analysis has an added value in the detection of pathogenic chromosomal abnormalities compared with conventional karyotype, particularly in cases of pathogenic copy number variants. This yield is influenced not only by the type of congenital heart disease but also by the presence of extracardiac anomalies.

Preterm Birth of Infants Prenatally Diagnosed with Congenital Heart Disease, Characteristics, Associations, and Outcomes.

There are limited data on the relation between congenital heart disease (CHD) and preterm birth (PTB). We aimed to estimate the risk of PTB in newborns with CHD, to study associations and risk factors (modifiable and non-modifiable) as well as investigate postnatal outcomes. This was a retrospective cohort study of 336 pregnancies diagnosed with CHD between 2011 and 2016. Groups consisted of those delivered at or after 37 weeks, and those who delivered prior to 37 weeks. Collected data included maternal and fetal characteristics as well postnatal outcomes. Complete data were obtained from 237 singleton pregnancies. The overall proportion of PTB was 23.2% for all CHD, of which 38.2% were spontaneous PTB which was almost unchanged after excluding extracardiac anomalies and pathogenic chromosomal abnormalities. Significant non-modifiable risk factors were pregnancy-related HTN disorders (P < 0.001), fetal growth restriction (P = 0.01), and pathogenic chromosomal abnormalities (P = 0.046). Significant PTB modifiable risk factors included prenatal marijuana use (P = 0.01). Pregnancies delivered at 37-38 weeks had significantly more newborns with birthweight < 2500 g (P < 0.001), required more pre-operative NICU support including intubation (P = 0.049), vasopressors (P = 0.04), prostaglandins (P = 0.003), antibiotics (P = 0.01), and had longer hospital stay (P = 0.001) than those delivered at ≥ 39 weeks. Prenatally diagnosed pregnancies with CHD had higher PTB rate compared to the general population, with spontaneous PTB comprising 38.2% of these preterm deliveries. Most PTB risk factors were non-modifiable, however, significant modifiable factors included marijuana use in pregnancy. Outcomes were favorable in neonates delivered at or beyond 39 weeks.

Severe Maternal Morbidity and Mortality Among Indigenous Women in the United States.

OBJECTIVE: To describe delivery-related severe maternal morbidity and mortality among indigenous women compared with non-Hispanic white (white) women, distinguishing rural and urban residents. METHODS: We used 2012-2015 maternal hospital discharge data from the National Inpatient Sample to conduct a pooled, cross-sectional analysis of indigenous and white patients who gave birth. We used weighted multivariable logistic regression and predictive population margins to measure health conditions and severe maternal morbidity and mortality (identified using International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis and procedure codes) among indigenous and white patients, to test for differences across both groups, and to test for differences between rural and urban residents within each racial category. RESULTS: We identified an estimated 7,561,729 (unweighted n=1,417,500) childbirth hospitalizations that were included in the analyses. Of those, an estimated 101,493 (unweighted n=19,080) were among indigenous women, and an estimated 7,460,236 (unweighted n=1,398,420) were among white women. The incidence of severe maternal morbidity and mortality was greater among indigenous women compared with white women (2.0% vs 1.1%, respectively; relative risk [RR] 1.8, 95% CI 1.6-2.0). Within each group, incidence was higher among rural compared with urban residents (2.3% for rural indigenous women vs 1.8% for urban indigenous women [RR 1.3, 95% CI 1.0-1.6]; 1.3% for rural white women vs 1.2% for urban white women [RR 1.1, 95% CI 1.1-1.2]). CONCLUSION: Severe maternal morbidity and mortality is elevated among indigenous women compared with white women. Incidence is highest among rural indigenous residents. Efforts to improve maternal health should focus on populations at greatest risk, including rural indigenous populations.

Robotic Versus Laparoscopic Hysterectomy for Benign Disease: A Systematic Review and Meta-Analysis of Randomized Trials.

We conducted a systematic review and meta-analysis to assess the safety and effectiveness of robotic vs laparoscopic hysterectomy in women with benign uterine disease, as determined by randomized studies. We searched MEDLINE, EMBASE, the Cochrane Library, ClinicalTrials.gov, and Controlled-Trials.com from study inception to October 9, 2014, using the intersection of the themes "robotic" and "hysterectomy." We included only randomized and quasi-randomized controlled trials of robotic vs laparoscopic hysterectomy in women for benign disease. Four trials met our inclusion criteria and were included in the analyses. We extracted data, and assessed the studies for methodological quality in duplicate. For meta-analysis, we used random effects to calculate pooled risk ratios (RRs) and weighted mean differences. For our primary outcome, we used a modified version of the Expanded Accordion Severity Grading System to classify perioperative complications. We identified 41 complications among 326 patients. Comparing robotic and laparoscopic hysterectomy, revealed no statistically significant differences in the rate of class 1 and 2 complications (RR, 0.66; 95% confidence interval [CI], 0.23-1.89) or in the rate of class 3 and 4 complications (RR, 0.99; 95% CI, 0.22-4.40). Analyses of secondary outcomes were limited owing to heterogeneity, but showed no significant benefit of the robotic technique over the laparoscopic technique in terms of length of hospital stay (weighted mean difference, -0.39 day; 95% CI, -0.92 to 0.14 day), total operating time (weighted mean difference, 9.0 minutes; 95% CI, -31.27 to 47.26 minutes), conversions to laparotomy, or blood loss. Outcomes of cost, pain, and quality of life were reported inconsistently and were not amenable to pooling. Current evidence demonstrates neither statistically significant nor clinically meaningful differences in surgical outcomes between robotic and laparoscopic hysterectomy for benign disease. The role of robotic surgery in benign gynecology remains unclear.

Cutting xylem under tension or supersaturated with gas can generate PLC and the appearance of rapid recovery from embolism.

We investigated the common assumption that severing stems and petioles under water preserves the hydraulic continuity in the xylem conduits opened by the cut when the xylem is under tension. In red maple and white ash, higher percent loss of conductivity (PLC) in the afternoon occurred when the measurement segment was excised under water at native xylem tensions, but not when xylem tensions were relaxed prior to sample excision. Bench drying vulnerability curves in which measurement samples were excised at native versus relaxed tensions showed a dramatic effect of cutting under tension in red maple, a moderate effect in sugar maple, and no effect in paper birch. We also found that air injection of cut branches (red and sugar maple) at pressures of 0.1 and 1.0 MPa resulted in PLC greater than predicted from vulnerability curves for samples cut 2 min after depressurization, with PLC returning to expected levels for samples cut after 75 min. These results suggest that sampling methods can generate PLC patterns indicative of repair under tension by inducing a degree of embolism that is itself a function of xylem tensions or supersaturation of dissolved gases (air injection) at the moment of sample excision. Implications for assessing vulnerability to cavitation and levels of embolism under field conditions are discussed.