Joseph Davidson

and 10 more

Objective: Hirschsprung is a congenital disorder affecting the gastrointestinal tract. However, pelvic colorectal surgery in infancy has been hypothesised to impact gynaecological outcomes in later life. Describe sexual function and fertility outcomes in women with Hirschsprung disease compared to population controls. Assess factors associated with poor outcomes (sexual dysfunction and subfertility). Design: International multicentre cross-sectional cohort study with population-matched controls Setting: Status post-discharge from paediatric services Population: Female patients aged > 20 years Methods: Validated questionnaire based survey with linkage to patient medical records. Comparison with controls using Mann-Whitney and Fisher’s Exact tests. Multivariable logistic regression using outcomes of sexual dysfunction and subfertility. Main Outcome Measures: Sexual Dysfunction (Female Sexual Function Index; FSFI ≤ 26), Subfertility at 1 and 2 years. Results: Sexual dysfunction as per the FSFI was more common in patients and associated with poor functional outcomes; sexual abstinence seemed to associate even moreso with poor bowel outcomes. Subfertility was higher in patients compared to controls (1 year: 21/45 (47%) vs 38/178 (21%), p=0.0008; 2 years: 12/45 (27%) vs 17/178 (10%), p=0.004). There was an increased proportion of patients who had accessed fertility services (20/45 (44%) vs 43/178 (24%); p=0.009), however the proportion of successful pregnancies in patients attempting to conceive with IVF (11/17 (65%) vs 27/43 (63%); p=1.0) were similar. Conclusions: This novel data suggests that women with Hirschsprung disease who have undergone reconstructive surgery may be at risk for adverse sexual functional and fertility outcomes.

Max Beesley

and 12 more

Background: While pregnant women have been identified as a potentially at-risk group concerning COVID-19 infection, little is known regarding the susceptibility of the fetus to infection. Co-expression of ACE2 and TMPRSS2 has been identified as a pre-requisite for infection, and expression across different tissues is known to vary between children and adults. However, the expression of these proteins in the fetus is unknown. Methods: We performed a retrospective analysis of single cell data repositories. This data was then validated at both gene and protein level by performing qRT-PCR and two-colour immunohistochemistry on a library of second-trimester human fetal tissues. Findings: TMPRSS2 is present at both gene and protein level in the predominantly epithelial fetal tissues analysed. ACE2 is present at significant levels, only in the fetal intestine and kidney and is not expressed in the fetal lung. The placenta is also negative for the two proteins both during development and at term. Interpretation: This dataset indicates that the lungs are unlikely to be a viable route of SARS-CoV2 fetal infection. The fetal kidney, despite presenting both the proteins required for the infection, is anatomically protected from the exposure to the virus. However, the GI tract is likely to be susceptible to infection due to its high co-expression of both proteins, as well as its exposure to potentially infected amniotic fluid. Funding: This work was made possible by an MRC / UKRI COVID-19 Rapid response initiative grant (MR/V028480/1).

Joseph Davidson

and 9 more

Abstract Objective:Evaluate deformable slice-to-volume registration (DSVR) to calculate 3D-segmented total lung volume (TLV) in fetuses with congenital diaphragmatic hernia, congenital lung lesions and healthy controls, with comparison to 2D-manual segmentation. Design:Pilot study Setting:Regional fetal medicine referral centre Sample:Fetal MRIs performed for clinical indications (abnormal cases) or as research participants (healthy controls) Methods:Sixteen MRI datasets of fetuses (22-32 weeks GA). Diagnosis: CDH(n=5), CPAM(n=2), CDH with BPS(n=1) and healthy control(n=8). DSVR was used for reconstruction of 3D isotropic (0.85 mm) volumes of fetal body followed by semi-automated lung segmentation. The resulting 3D TLV were compared to the traditional 2D-based volumetry, and a normogram of DSVR-derived fetal lung volumes from 100 cases was produced. Main Outcome Measures:Concordance with 2D-volumetry assessed with Bland-Altman analysis, results of segmentations presented visually. Observed/Expected values were calculated for abnormal cases based upon the normogram. Results:DSVR-derived TLV values have high correlation with the 2D-based measurements but with a consistently lower volume; bias -1.44cm3 [95% limits: -2.6 to -0.3] with improved resolution able to exclude hilar structures even in severe motion corruption or in cases of lung hypoplasia. Conclusions:Application of DSVR for fetal MRI provides a solution for analysis of motion corrupted scans and does not suffer from the interpolation error inherent in 2D-segmentation as per current clinical practice. It increases information content of acquired data in terms of visualising organs in 3D space and quantification of volumes, which we believe will have important value for counselling and surgical planning. Keywords:Fetal MRI; congenital diaphragmatic hernia; CPAM; lung volume