The accuracy of prenatal diagnosis of major congenital heart disease is increasing.

Regular audit of results of prenatal screening for congenital heart disease (CHD) is crucial to ensure reliable prenatal diagnosis. We aimed to assess the accuracy of prenatal diagnosis of major CHD between 1996 and 2013. During the study period, prenatal detection of major CHD improved from 4.5% to 71.0% (p<.001). Prenatal diagnoses on 628 live born children and terminated pregnancies were compared with postnatal findings or autopsy reports. The proportion of correct diagnoses increased throughout the study period from 42.9% in 1996 and reached 88.2% in 2013 (p<.001). A total of 32 foetuses with suspected major CHD were terminated though no major CHD was found at autopsy. In these pregnancies, termination was mainly performed due to other anomalies in the foetus.Along with improved detection of major CHD, the validity of a prenatal diagnosis is increasing. No cases of misinterpreted major CHD resulted in the termination of a healthy foetus in this study.Impact statementWhat is already known on this subject? Prenatal diagnosis of isolated congenital heart disease (CHD) correlates well with lesions found during autopsy performed in terminated foetuses. Few studies have assessed the accuracy of prenatal diagnosis of major CHD in live born children, cases with associated anomalies and the time trend in validity.What the results of this study add? This study illustrates that the validity of prenatal diagnosis of major CHD is increasing. Prenatal diagnoses in terminated pregnancies as well as in live born children is high except for coarctation of the aorta and atrioventricular septal defects. Chromosomal anomalies are associated with lower accuracy of prenatal diagnosis.What the implications are of these findings for clinical practice and/or further research? Prenatal diagnosis is an accurate tool for detecting major CHD. Misinterpretation has not led to the termination of a healthy foetus; however, this study illustrates that vigilant care should be placed on the cardiac evaluation when termination is considered due to the cardiac defect.

Mortality and morbidity of major congenital heart disease related to general prenatal screening for malformations.

BACKGROUND: Major congenital heart diseases (CHD) often demand intervention in the neonatal period. Prenatal diagnosis may improve mortality by eliminating the diagnostic delay; however, there is controversy concerning its true effect. We aimed to evaluate the effect of general prenatal screening on prognosis by comparing a period without general prenatal screening to a period with general prenatal screening. METHODS: We conducted a nationwide retrospective study including live born children and terminated fetuses diagnosed with major CHD. Prenatal screening was recommended only in high risk pregnancies between 1996 and 2004, whereas general prenatal screening was recommended between 2005 and 2013. We assessed the influence of general prenatal screening on all-cause mortality, cardiac death, preoperative and postoperative 30-day mortality and complication rate. RESULTS: 1-year mortality decreased over both periods, but the decrease was greater in the screening period (Odds ratio 0.92 (CI 0.83-1.00), p = 0.047). Prenatal detection of major CHD was associated with cardiac death in the period without general screening (Hazard Ratio 2.40 (CI 1.72-3.33), p < 0.001), whereas there was no significant association once general screening was implemented. Similarly, the association between prenatal diagnosis and pre- and postoperative mortality found in the period without general screening was insignificant after the implementation of general screening. CONCLUSION: Mortality in major CHD decreased throughout the study, especially in the period with general prenatal screening. However, comparing a prenatally diagnosed group with a postnatally diagnosed group is vulnerable to selection bias and proper interpretation is difficult.

Phenotypic spectrum associated with SPECC1L pathogenic variants: new families and critical review of the nosology of Teebi, Opitz GBBB, and Baraitser-Winter syndromes.

The SPECC1L protein plays a role in adherens junctions involved in cell adhesion, actin cytoskeleton organization, microtubule stabilization, spindle organization and cytokinesis. It modulates PI3K-AKT signaling and controls cranial neural crest cell delamination during facial morphogenesis. SPECC1L causative variants were first identified in individuals with oblique facial clefts. Recently, causative variants in SPECC1L were reported in a pedigree reported in 1988 as atypical Opitz GBBB syndrome. Six families with SPECC1L variants have been reported thus far. We report here eight further pedigrees with SPECC1L variants, including a three-generation family, and a further individual of a previously published family. We discuss the nosology of Teebi and GBBB, and the syndromes related to SPECC1L variants. Although the phenotype of individuals with SPECC1L mutations shows overlap with Opitz syndrome in its craniofacial anomalies, the canonical laryngeal malformations and male genital anomalies are not observed. Instead, individuals with SPECCL1 variants have branchial fistulae, omphalocele, diaphragmatic hernias, and uterus didelphis. We also point to the clinical overlap of SPECC1L syndrome with mild Baraitser-Winter craniofrontofacial syndrome: they share similar dysmorphic features (wide, short nose with a large tip, cleft lip and palate, blepharoptosis, retrognathia, and craniosynostosis), although intellectual disability, neuronal migration defect, and muscular problems remain largely specific to Baraitser-Winter syndrome. In conclusion, we suggest that patients with pathogenic variants in SPECC1L should not be described as "dominant (or type 2) Opitz GBBB syndrome", and instead should be referred to as "SPECC1L syndrome" as both disorders show distinctive, non overlapping developmental anomalies beyond facial communalities.

Live-Born Major Congenital Heart Disease in Denmark: Incidence, Detection Rate, and Termination of Pregnancy Rate From 1996 to 2013.

Importance: The occurrence of major congenital heart disease (CHD) is affected by several variables. Determining the development of the true incidence is critical to the establishment of proper treatment of these patients. Objective: To evaluate time trends in incidence, detection rate, and termination of pregnancy (TOP) rate of major CHD in fetuses in Denmark and assess the influence of the introduction of general prenatal screening in 2004. Design, Setting, and Participants: Nationwide, population-based, retrospective observational study in Denmark from 1996 to 2013 that included a consecutive sample of 14 688 live-born children and terminated fetuses diagnosed as having CHD. Patient records on TOP and children with major CHD were reviewed to validate the diagnoses. Major CHD included univentricular heart, transposition of the great arteries, congenitally corrected transposition of the great arteries, truncus arteriosus, interrupted aortic arch, atrioventricular septal defects, double outlet right ventricle, coarctatio of the aorta, Ebstein anomaly, pulmonary atresia with ventricular septal defect, pulmonary atresia with intact ventricular septum, and tetralogy of Fallot. Data were analyzed between January 2017 and March 2018. Main Outcomes and Measures: Temporal changes in incidence, detection rate, and TOP of major CHD. Results: Of 14 688 children and fetuses diagnosed with CHD, 2695 (18.4%; 95% CI, 17.8-19.1) had major CHD. A total of 7131 boys (1304 with major CHD) and 6926 girls (920 with major CHD) were included, with a median age of 11 years (interquartile range, 6-15 years). During the study period, the live-birth incidence of CHD was constant at 1.22% (95% CI, 1.18-1.26), whereas it decreased for major CHD. When including TOP, the incidence of major CHD did not change over time. The detection rate of major CHD increased from 4.5% (95% CI, 1.2-7.8) to 71.0% (95% CI, 63.3-78.7) (P < .001). At the end of the study, all cases of double outlet right ventricle, Ebstein anomaly, congenitally corrected transposition of the great arteries, and pulmonary atresia with ventricular septal defect were detected prenatally, whereas coarctation of the aorta had the lowest detection rate (21.7%; 95% CI, 3.5-40.0). The TOP rate increased from 0.6% (95% CI, -0.6 to 1.9) to 39.1% (95% CI, 30.9-47.4) (P < .001) among all major CHD. For prenatally diagnosed major CHD, 57.8% of cases were terminated and the proportion did not change significantly throughout the study. Diagnoses leading to TOP included all major CHD diagnoses. Conclusions and Relevance: Detection rates of major CHD improved during the study. This has led to increased TOP rates, with a subsequent 39% decrease in the live-birth incidence of major CHD.

A five year follow-up of women with obstetric anal sphincter rupture at their first delivery.

OBJECTIVES: Obstetric anal sphincter rupture (OASR) is considered a risk factor for subsequent fecal incontinence and suspected to be a risk factor for urinary incontinence and sexual dysfunction. The aims of this study were to assess risk factors for the different grades of OASR and to evaluate the clinical outcome five years after birth using validated questionnaires. STUDY DESIGN: A five year follow-up study was performed on 82 women with OASR during their first delivery in 2009. Case records were reviewed for known risk factors for OASR. Three questionnaires were mailed to the women: The St. Marks fecal incontinence score, The Danish anal sphincter rupture questionnaire (DASRQ) and a short supplemental questionnaire. The data were analyzed using Wilcoxon rank sum test, Fisher's exact test and Kruskal-Wallis test. RESULTS: Fifty percent had an OASR 3a, 32% an OASR 3b, and 18% OASR 4. None of the investigated risk factors showed statistically significant difference according to the degree of rupture. Seventy-four percent of the women had some degree of fecal incontinence with a significantly higher frequency of fecal incontinence in rupture group 4 than in 3a. Forty-four percent had urinary incontinence and 50% had some sort of sexual dysfunction with no significant differences between the rupture groups. CONCLUSION: None of the investigated risk factors increased the incidence of more severe grades of rupture. Ninety-one percent of women with OASR at their first delivery had some degree of fecal or urinary incontinence or sexual dysfunction five years after. The symptoms of fecal incontinence showed a tendency to be more severe in women with more advanced sphincter rupture.

Manual protection of the perineum reduces the risk of obstetric anal sphincter ruptures.

INTRODUCTION: During vaginal delivery, the risk of obstetric anal sphincter injuries (OASIS) is well-known. Despite sufficient repair, 30-50% of women will experience anal incontinence. Recent studies from Norway have shown a reduction in the incidence of OASIS when the perineum is supported manually. In Denmark, the frequency of OASIS is the highest in Scandinavia and it is increasing. The aim of this study was to reduce the incidence of OASIS through an interventional programme. METHODS: We conducted a study inspired by the Norwegian intervention. Our focus was on four points: 1) good communication between the delivering woman and the birth assistant, 2) visualisation of the perineum in the last stages of delivery, 3) support of the perineum during the final minutes of pushing and 4) episiotomy only on indication. A total of 768 primiparous and 1,175 multiparous women were enrolled in this quality improvement cohort study. Data were analysed for association with the occurrence of OASIS. RESULTS: The proportions of parturients with anal sphincter ruptures decreased significantly during the first year of the study from 4.4% to 1.7% (p < 0.001). The decrease was more pronounced for primiparous women: from 7.2% to 2.9% (p = 0.006). A similar decrease was observed for instrumental deliveries although this was not significant for primiparous women, probably due to the size of the study population. Episiotomies increased significantly from 4.4% to 7.1% for all deliveries. CONCLUSION: After the first year of intervention, our results demonstrate that manual protection of the perineum reduces the overall risk of OASIS significantly. FUNDING: not relevant. TRIAL REGISTRATION: not relevant.