Optimal non-invasive diagnosis of fetal achondroplasia combining ultrasonography with circulating cell-free fetal DNA analysis.

OBJECTIVES: To assess the performance of non-invasive prenatal testing (NIPT) for achondroplasia using high-resolution melting (HRM) analysis, and to propose an optimal diagnostic strategy combining ultrasound examination and cell-free fetal DNA (cffDNA) analysis. METHODS: In this prospective multicenter study, cffDNA was extracted from blood of pregnant women at risk for fetal achondroplasia (owing to paternal achondroplasia, previous affected child or suspected rhizomelic shortening) and of pregnant low-risk controls. The presence of either one of the two main fibroblast growth factor receptor 3 gene (FGFR3) mutations was determined using HRM combined with confirmation by SNaPshot minisequencing. Results were compared with phenotypes obtained using three-dimensional computed tomography or postnatal examination, and/or molecular diagnosis by an invasive procedure. Fetal biometry (head circumference and femur length) was analyzed in order to develop a strategy in which cffDNA analysis for diagnosis of achondroplasia is offered only in selected cases. RESULTS: Eighty-six blood samples from women at risk for fetal achondroplasia and 65 from controls were collected. The overall sensitivity and specificity of NIPT were 1.00 (95% CI, 0.87-1.00) and 1.00 (95% CI, 0.96-1.00), respectively. Critical reduction in femur length of affected fetuses could be observed from 26 weeks' gestation. CONCLUSIONS: HRM combined with SNaPshot minisequencing is a reliable method for NIPT for achondroplasia. Its implementation in routine clinical care combined with ultrasonography is an efficient strategy for the non-invasive diagnosis of achondroplasia. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Is training sufficient for ultrasound operators to diagnose deep infiltrating endometriosis and bowel involvement by transvaginal ultrasound?

OBJECTIVES: To assess and compare the diagnostic accuracy of transvaginal ultrasonography (TVUS) by trained or untrained ultrasound operators in deep infiltrating endometriosis (DIE) imaging, for diagnosing DIE and bowel involvement. METHODS: This was an observational study of patients with clinically suspected DIE operated in a reference center. TVUS was performed pre-operatively by a trained or/and untrained ultrasound operator to search for DIE and rectal involvement. During surgery, DIE was diagnosed according to macroscopic and histological criteria. Sensitivity (Se), specificity (Sp) and c-index were calculated with 95% confidence intervals for trained and untrained operators, if TVUS results were significantly predictive of DIE and rectal involvement at p<0.05. RESULTS: 115 patients were included: 100 (87%) had DIE and 34 (29.6%) had bowel involvement. TVUS was performed by a trained ultrasound operator for 70 patients and by an untrained one for 56 patients. When performed by a trained operator, TVUS significantly predicted DIE with a Se of 58% (95% CI, 46-70), a Sp of 87.5% (95% CI, 63-100) and a c-index of 0.73 (95% CI, 0.59-0.87). TVUS performed by an untrained operator was not significantly predictive of DIE (p=0.58). Rectal involvement was significantly predicted by TVUS performed by a trained operator with a Se of 40% (95% CI, 23-59), a Sp of 93% (95% CI, 86-100) and a c-index of 0.67 (95% CI, 0.56-0.77). None of the untrained ultrasound operators diagnosed a bowel involvement. CONCLUSION: TVUS is not sufficient to diagnose DIE and bowel involvement, in particular when performed by untrained ultrasound operators.

Maternal periconceptional undernutrition in Merinos d'Arles sheep: 1. Effects on pregnancy and reproduction results of dams and offspring growth performances.

Maternal undernutrition during gestation can condition offspring adult health, with the periconceptional period pointed out as a key period. The aim of this study was to evaluate the effects of maternal periconceptional undernutrition on pregnancy and offspring growth performance in sheep. 52 Merinos d'Arles ewes were fed to requirements (control group, C), whereas 64 ewes received 50% of their dietary needs from -15 to +30 days post-conception (restricted group, R). Thereafter, both groups were fed according to needs. Maternal body weight (BW), body condition score (BCS) and Non Esterified Fatty Acids (NEFA), progesterone, leptin and cortisol plasma concentrations were monitored weekly during the restriction period and the following month, then monthly until weaning. Lambs were weighed weekly until weaning at 22 kg BW, then monthly. Plasma leptin was monitored monthly in lambs. The BW, BCS, and leptin concentrations were significantly decreased, whereas NEFA and cortisol concentrations were increased in R dams. Maximum progesterone concentration was higher in R ewes that had a high (10-25%) vs. low (0-10%) BW loss during restriction (27.9 ± 2.59 vs. 20.8 ± 2.00 ng/mL, P < 0.05). Overall, gestation was significantly longer in the R group (151.0 ± 0.3 vs. 149.4 ± 0.4 days, P < 0.001). There was no difference between groups for pregnancy rates, prolificacy, birth weight and lamb mortality, but the proportion of male lambs was significantly higher in the R group, only for singletons (16/26 vs. 9/26, P < 0.05). Lamb growth was not significantly modified by treatment. Leptin concentrations at birth were significantly lower in R vs. C males (6.15 ± 0.13 ng/mL vs. 7.42 ± 0.36 ng/mL, P < 0.05), whereas in females, leptin concentrations were significantly higher in R vs. C lambs at 4 mo of age (7.31 ± 0.27 ng/mL vs. 6.41 ± 0.29 ng/mL, P < 0.05). These results indicate that maternal periconceptional undernutrition in a hardy breed does not significantly affect lamb birth weight and growth rates, in contrast to previous reports in other breeds, suggesting that caution must be taken when extrapolating programming data between breeds and breeding conditions.