Development and clinical validation of real-time artificial intelligence diagnostic companion for fetal ultrasound examination.

OBJECTIVE: Prenatal diagnosis of a rare disease on ultrasound relies on a physician's ability to remember an intractable amount of knowledge. We developed a real-time decision support system (DSS) that suggests, at each step of the examination, the next phenotypic feature to assess, optimizing the diagnostic pathway to the smallest number of possible diagnoses. The objective of this study was to evaluate the performance of this real-time DSS using clinical data. METHODS: This validation study was conducted on a database of 549 perinatal phenotypes collected from two referral centers (one in France and one in the UK). Inclusion criteria were: at least one anomaly was visible on fetal ultrasound after 11 weeks' gestation; the anomaly was confirmed postnatally; an associated rare disease was confirmed or ruled out based on postnatal/postmortem investigation, including physical examination, genetic testing and imaging; and, when confirmed, the syndrome was known by the DSS software. The cases were assessed retrospectively by the software, using either the full phenotype as a single input, or a stepwise input of phenotypic features, as prompted by the software, mimicking its use in a real-life clinical setting. Adjudication of discordant cases, in which there was disagreement between the DSS output and the postnatally confirmed ('ascertained') diagnosis, was performed by a panel of external experts. The proportion of ascertained diagnoses within the software's top-10 differential diagnoses output was evaluated, as well as the sensitivity and specificity of the software to select correctly as its best guess a syndromic or isolated condition. RESULTS: The dataset covered 110/408 (27%) diagnoses within the software's database, yielding a cumulative prevalence of 83%. For syndromic cases, the ascertained diagnosis was within the top-10 list in 93% and 83% of cases using the full-phenotype and stepwise input, respectively, after adjudication. The full-phenotype and stepwise approaches were associated, respectively, with a specificity of 94% and 96% and a sensitivity of 99% and 84%. The stepwise approach required an average of 13 queries to reach the final set of diagnoses. CONCLUSIONS: The DSS showed high performance when applied to real-world data. This validation study suggests that such software can improve perinatal care, efficiently providing complex and otherwise overlooked knowledge to care-providers involved in ultrasound-based prenatal diagnosis. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Pathological and sonographic review of early isolated severe lower urinary tract obstruction and implications for prenatal treatment.

OBJECTIVE: To identify favorable renal histology in fetuses with early severe lower urinary tract obstruction (LUTO) and determine the best timing and selection criteria for prenatal surgery. METHODS: This multicenter, retrospective study included male fetuses with severe LUTO which died before 24 weeks of gestation during the period January 2000 to December 2018. Age-matched controls were used as reference standard for renal histology. Prenatal ultrasound features and fetal serum and/or urine ß2microglobulin level were retrieved and kidney histology slides (hematein-eosin-safran and α-smooth-muscle-actin (αSMA) immunostaining) were prepared and reviewed. αSMA-positive staining of the blastema is due to its aberrant differentiation into myofibroblastic cells. Cases were sorted into histopathologic groups (favorable or unfavorable) according to the blastema's morphology and αSMA labeling and the data of these groups were compared. RESULTS: Included in the study were 74 fetuses with a median gestational age at outcome of 17 + 6 (range, 13 + 0 to 23 + 5) weeks. Parenchymal organization was preserved in 48% of the kidneys. A blastema was present in 90% of the kidneys, but it was morphologically normal in only 9% and αSMA-negative in only 1% of them. Most (82%) fetuses had an unfavorable prognosis, and 36% of fetuses died ≤ 18 weeks and had severe renal lesions detected on histology (early unfavorable prognosis). A favorable renal prognosis was associated with an earlier gestational age (P = 0.001). Fetuses with LUTO had a significantly lower number of mature glomeruli (P < 0.001) compared with controls. However, there was no significant difference in the number of glomeruli generations between the early-unfavorable-prognosis group (≤ 18 weeks) and the group with a favorable prognosis (P = 0.19). A comparison of prenatal ultrasound features and biochemical markers between groups could not identify any prenatal selection criteria. CONCLUSIONS: Before 18 weeks, around 30% of fetuses with severe LUTO still have potential for kidney development. Identification of these cases would enable them to be targeted for prenatal therapy. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Preterm premature rupture of membranes is a collateral effect of improvement in perinatal outcomes following fetoscopic coagulation of chorionic vessels for twin-twin transfusion syndrome: a retrospective observational study of 1092 cases.

OBJECTIVES: Preterm premature rupture of membranes (PPROM) is a leading complication following fetoscopic laser coagulation (FLC) for twin-twin transfusion syndrome (TTTS). Our primary objective was to describe the impact of improvements in surgical technique on survival and rate of PPROM over time. The secondary objective was to assess potential risk factors for PPROM. DESIGN AND SETTING: Single-centre retrospective observational study. POPULATION: 1092 consecutive cases of TTTS operated by FLC between 2000 and 2016, with a 6.8% rate of loss to follow up. METHODS: The incidence of PPROM and potential risk factors were analysed using competing risks models. MAIN OUTCOME MEASURES: PPROM, neonatal survival and neurological damage at 28 days. RESULTS: PPROM <32 weeks increased from 15 to 40% between 2000 and 2016 along with an overall improvement of perinatal outcomes: dual survival rose from 42 to 66% whereas dual losses dropped two-fold, from 19 to 9%. Gestational age at surgery at <17 weeks was a significant risk-factor for PPROM, with an additional risk of 10% within the first week of surgery. Although early PPROM at <20 weeks carried a 56% risk of miscarriage, the occurrence of PPROM at >20 weeks did not affect survival, despite an increase in preterm birth at <32 weeks. CONCLUSIONS: With significant improvement in perinatal outcomes, possibly related to improvements in surgical technique, postoperative complications have shifted to non-lethal obstetric complications such as PPROM, with rather reassuring postnatal outcomes, despite an increase in preterm birth and, potentially, morbidity. Early surgeries (<17 weeks) are at higher risk of postoperative PPROM. TWEETABLE ABSTRACT: Following laser/TTTS, rates of PPROM increased with perinatal survival; surgeries at <17 weeks are at highest risk.

Sequential fetal serum ß2-microglobulin to predict postnatal renal function in bilateral or low urinary tract obstruction.

OBJECTIVE: Fetal serum ß2-microglobulin has been shown to predict postnatal renal outcome in cases of fetal obstructive uropathy. We assessed the value of serial measurements of fetal serum ß2-microglobulin in the prediction of postnatal renal outcome. METHODS: We retrospectively studied renal outcome in 42 fetuses with bilateral or low urinary tract obstruction that had fetal blood sampling on at least two occasions to assay serum levels of ß2-microglobulin. Amniotic fluid volume at the time of each sampling was recorded. We classified renal outcome as either favorable (when postnatal renal function was normal) or adverse (when postnatal chronic renal failure occurred or when renal dysplasia at autopsy was noted). A ß2-microglobulin cut-off of 5 mg/L and amniotic fluid index of 5 cm were used to predict postnatal renal outcome. RESULTS: Renal outcome was adverse in 28 cases and favorable in 14. In 12 (28.6%) cases, fetal serum ß2-microglobulin concentration differed between the first and last measurement. Prediction of postnatal renal outcome was correct in 11 of these cases based on the last ß2-microglobulin measurement. The sensitivity of ß2-microglobulin in predicting renal outcome was significantly higher (P = 0.005) when using the last rather than the first measurement (96.4% vs 64.3%), with similar specificity for both measurements (85.7% vs 78.6%, non-significant). The sensitivity of amniotic fluid volume was also significantly higher (P = 0.005) when using the last rather than the first measurement (75.0% vs 35.7%), with similar specificity for both measurements (64.3% vs 71.4%, non-significant). CONCLUSION: Sequential measurement of serum ß2-microglobulin, performed for adverse ultrasound findings, such as renal parenchymal abnormality or decreasing amniotic fluid volume, predicts postnatal renal outcome more accurately than does a single assay. This may be due to possible worsening of renal injury with increasing duration of urinary tract obstruction. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Prenatal prediction of pulmonary arterial hypertension in congenital diaphragmatic hernia.

OBJECTIVE: To evaluate the role of prenatal prognostic markers obtained routinely by ultrasound examination and magnetic resonance imaging (MRI) in the prediction of development of postnatal pulmonary arterial hypertension (PAH) in isolated congenital diaphragmatic hernia (CDH). METHODS: One hundred and ten cases of isolated CDH were referred to our fetal medicine unit between January 2004 and April 2013. Mortality and morbidity rates were reviewed for those presenting with postnatal PAH. The following prenatal markers were evaluated as potential predictive factors of PAH: liver position, side of the CDH defect, lung area to head circumference ratio (LHR) and observed/expected LHR (o/e-LHR), which were measured by ultrasound, and observed/expected total fetal lung volume (o/e-TFLV), which was measured by MRI. Univariable logistic regression was used to assess associations. RESULTS: PAH was significantly associated with perinatal mortality and morbidity (P < 0.001). The occurrence of PAH decreased significantly with an increasing LHR, o/e-LHR and o/e-TFLV and was significantly increased for cases with an intrathoracic liver, but not for those with right-sided defects. Univariable regression revealed that o/e-TFLV (odds ratio (OR), 0.9 (95% CI, 0.86-0.95); P < 0.05 for percentage unit change in o/e), LHR (OR, 0.19 (95% CI, 0.09-0.40); P < 0.05 for unit change), o/e-LHR (OR, 0.95 (95% CI, 0.93-0.98); P < 0.05 for percentage unit change in o/e) and liver position (OR, 2.82 (95% CI, 1.13-7.00); P < 0.05 for intrathoracic liver) were significant predictors of subsequent PAH. No differences were found after adjusting for gestational age at delivery. The areas under the receiver-operating characteristics curve were 0.80 and 0.75 for o/e-TFLV and o/e-LHR, respectively. CONCLUSION: In cases of CDH, PAH is associated with high rates of mortality and morbidity. Routinely obtained prenatal markers, usually used for the assessment of pulmonary hypoplasia, are also relevant for the postnatal prediction of PAH.

Prognostic value of a hernia sac in congenital diaphragmatic hernia.

OBJECTIVE: To investigate the prognostic value of a hernia sac in isolated congenital diaphragmatic hernia (CDH). METHODS: Our database was searched to identify all consecutive cases of CDH referred to our fetal medicine unit between January 2004 and August 2011. Presence or absence of a hernia sac was assessed in liveborn cases using surgery or postnatal autopsy reports. We studied the correlation between the presence of a hernia sac and prenatal findings and perinatal morbidity and mortality. RESULTS: Over the study period, there were 70 cases with isolated CDH born alive in which either a surgery or autopsy report was available. Neonatal death, either preoperative or postoperative, occurred in 1/18 (5.6%) infants with a hernia sac and in 17/52 (32.7%) cases without a hernia sac (P = 0.03). Patients with a hernia sac had a significantly higher observed to expected pulmonary volume on prenatal magnetic resonance imaging (51.9 vs 39.3%, P = 0.01). Neonatal morbidity in surviving infants was lower in the group with a hernia sac, although not significantly. CONCLUSION: The presence of a hernia sac is associated with a higher pulmonary volume and a better overall prognosis for CDH.

Fetal obstructive uropathy complicated by urinary ascites: outcome and prognostic value of fetal serum ß-2-microglobulin.

OBJECTIVES: To determine whether the prognostic value of fetal serum ß-2-microglobulin is altered and whether the occurrence of fetal urinary ascites prevents kidney damage in cases of fetal obstructive uropathy with urinary ascites. METHODS: This was a retrospective study of cases of fetal bilateral obstructive uropathy that occurred between 2006 and 2010, for which both fetal serum and ascites samples were sent to our laboratory for analysis. ß-2-microglobulin was assayed in both fetal serum and the corresponding ascites. Renal outcome was analyzed. Histological features of the kidney in cases of termination of pregnancy and renal function of liveborn infants were recorded. RESULTS: Fourteen cases with analysis of fetal serum and fetal ascites in a context of urinary obstruction were included. Renal outcome was unfavorable in eight cases (57%) and favorable in six (43%). When fetal serum ß-2-microglobulin was < 5 mg/L, renal outcome was favorable in all cases (4/4). When fetal serum ß-2-microglobulin was ≥ 5 mg/L, 8/10 cases (80%) had an unfavorable renal outcome (sensitivity, 100%; specificity, 66%). CONCLUSION: Fetal serum ß-2-microglobulin reliably predicts postnatal renal outcome in obstructive uropathy complicated by urinary ascites. Moreover, urine extravasation does not seem to protect fetal renal function.

Outcome in fetuses with isolated congenital diaphragmatic hernia with increased nuchal translucency thickness in first trimester.

OBJECTIVE: To examine the possible association between increased nuchal translucency (NT) thickness in the first trimester and perinatal outcome in isolated congenital diaphragmatic hernia (CDH). METHODS: We conducted a retrospective study between January 2004 and June 2010. The database was searched to identify all consecutive cases of CDH referred to the fetal medicine center of Necker Hospital in Paris. Enlarged NT was defined above the 95th centile. Only children born alive with an isolated CDH were selected for the analysis of prognostic factors. We also studied the correlation between NT thickness in the first trimester and lung-to-head ratio, observed to expected lung area-to-head ratio, lung volume estimated by magnetic resonance imaging, and other prenatal features of intrathoracic compression. RESULTS: Seventy-one cases of isolated CDH were available. The fetal NT was above the 95th centile in 9 of the 71 cases. Neonatal death occurred in 7/9 (78%) cases with enlarged NT, compared with 24/62 (38%) with normal NT (P = 0.035). Enlarged NT was significantly associated with prenatal features of intrathoracic compression. CONCLUSION: Enlarged NT thickness in CDH is associated with a poor outcome and is related to an early intrathoracic compression.

[The use of ondansetron in acute gastroenteritis. Its impact in a pediatric emergency department]. / L'impiego dell'ondansentron nella gastroenterite acuta e la sua efficacia in un pronto soccorso pediatrico.

BACKGROUND: Ondansentron is in consideration in literature for its use in vomiting secondary to acute gastroenteritis in children. OBJECTIVE: To evaluate its usefulness in children with acute gastroenteritis referred to a paediatric emergency department. METHODS: A retrospective study considered 967 children treated with ondansetron (0,06 mg/kg IM) plus oral rehydration, with a control group of 286 children who received only oral rehydration. RESULTS: The time spent into the short-stay observation unit and the total emergency department stay were significantly reduced in children receiving ondansentron. No adverse reactions to the drug were recorded.

[The use of ondansetron in acute gastroenteritis. Its impact in a pediatric emergency department]. / L'impiego dell'ondansentron nella gastroenterite acuta e la sua efficacia in un pronto soccorso pediatrico.

BACKGROUND: Ondansentron is in consideration in literature for its use in vomiting secondary to acute gastroenteritis in children. OBJECTIVE: To evaluate its usefulness in children with acute gastroenteritis referred to a paediatric emergency department. METHODS: A retrospective study considered 967 children treated with ondansetron (0,06 mg/kg IM) plus oral rehydration, with a control group of 286 children who received only oral rehydration. RESULTS: The time spent into the short-stay observation unit and the total emergency department stay were significantly reduced in children receiving ondansentron. No adverse reactions to the drug were recorded.

The study of visual evoked potentials in patients with thyroid-associated ophthalmopathy identifies asymptomatic optic nerve involvement.

In the present study we have recorded visual evoked cortical potentials (VECP) in 88 patients affected by autoimmune thyroid disease and thyroid-associated ophthalmopathy (TAO) without clinical signs of optic neuropathy. At the time of ophthalmological examination, 37 of these patients were hyperthyroid, 41 were euthyroid, and 8 were hypothyroid; 2 were not assessed. Twenty-nine normal subjects served as controls. We performed pattern reversal visual stimulation and recorded the amplitude and latency of the cortical electric response at 100 ms (P100 wave). There were no differences in the mean P100 amplitude of TAO patients and normal subjects. The mean P100 latency in patients was 105.6 +/- 0.5 ms, significantly higher than that in normal subjects (102.0 +/- 0.5 ms; P < 0.00003). Latency in euthyroid patients did not differ from that in either hypo- or hyperthyroid patients. The VECP test was positive (latency, > or = 110.0 ms) in 21 (23.8%) TAO patients. In patients with proptosis greater than 21 mm, latency was 106.7 +/- 0.7 ms, significantly higher than that in patients with normal Hertel measurements (104.3 +/- 0.6 ms; P < 0.01). Latency was not increased in patients with acute inflammatory signs compared to those with inactive eye disease and in patients with altered extrinsic motility. In patients with an abnormal visual field study, the mean latency was 110.3 +/- 1.5 ms, significantly higher than that in patients with a normal visual field (104.7 +/- 0.4; by t test, P < 0.000003). In conclusion, we observed a prolongation of the latency of the evoked cortical response in patients with TAO without subjective visual complaints and without optic nerve compression. We believe that the study of VECP in TAO is complementary to the study of the visual field in identifying early optic nerve dysfunction in the absence of decreased visual acuity.

Focal Castleman disease of the lung: MRI findings.

Castleman disease is an uncommon benign disorder mainly affecting mediastinal lymph nodes and rarely visceral organs. The most typical structural finding is hypervascularity which can be well demonstrated both by CT and MRI. We report MR findings of an unusual case of solitary parenchymal lung involvement.

Early smoking-induced lung lesions in asymptomatic subjects. Correlations between high resolution dynamic CT and pulmonary function testing.

PURPOSE: To evaluate the prevalence and significance of the pathological effects of cigarette smoking on the lung and the sensitivity of high-resolution CT (HRCT) in the recognition of early smoking-induced lesions in asymptomatic former or current smokers. MATERIALS AND METHODS: We performed a prospective and consecutive analysis of 36 volunteers (16 males, 20 females), 10 non-smokers (3 males; 7 females) and 26 smokers (13 males; 13 females / 17 current smokers; 9 former smokers), all asymptomatic and with normal respiratory flows. These subjects underwent lung function testing and HRCT, after providing written informed consent for the study. The HRCT scans were obtained at three pre-selected levels (aortic arch, tracheal carina and venous hilum). The same scans were obtained in post-expiration phase. At the level of the apical segmental bronchus of the right upper lobe, we measured on the monitor wall thickening, and the total and internal diameters using the techniques reported in literature. Each study was independently evaluated by two radiologists that were blinded to all clinical and functional data; they also evaluated the presence, prevalence and type of emphysema, areas of patchy hyperlucency and oligoemia in the inspiration phase and areas of expiratory air trapping. The extension was evaluated with the visual score method. The data obtained were analysed with the Windows SPSS package for statistical analysis. RESULTS: The two groups (non smokers and smokers) showed significant differences in some functional tests such as FEV1 (p<0.005) and Tiffeneau index (p<0.005), which were lower in current-smokers or former-smokers, although still within the normal range. The HRCT study did not show areas of emphysema or air trapping in non smokers. In the smokers' group, air trapping was observed in 30.7% of cases: 33.3% former-smokers and 29.4% current smokers (mean extension was 21.36% in former smokers and 9.48% in current smokers). Mean extension in the smokers' group was 13.94%. Pulmonary emphysema was found in 34.6% of cases in the smokers' group: 33.3% former-smokers and 35.2% current-smokers. Emphysema was prevalent in the upper lobes (88.8%). Mean extension was 8.76% in the former smokers group and 18.81% in current-smokers, with a total mean extension of 15.47% in the smokers' group. Statistically, there was a significant difference between non-smokers and smokers as regards emphysema extension and expiratory air trapping (p=0.034 and p=0.050, respectively). The smokers' group had a significantly wider diameter of the apical segmental bronchus of the right upper lobe than the controls. There was no significant statistical correlation between this dilatation and the emphysema score (r=0.051; p=0.81). The entity of smoking history did not correlate with emphysema extension or air trapping or with the size of the apical segmental bronchus of the right upper lobe. CONCLUSIONS: Our study demonstrates that HRCT is more sensitive and specific than commonly-used functional tests for the evaluation of initial emphysema in asymptomatic smokers. We observed expiratory air trapping only in the smokers' group, and only of the lobular type, without evidence of disease in inspiratory scans. Among the smokers and former-smokers, air trapping was found in 30.7% of subjects, with a mean extension lower than 10%. Our results therefore suggest that, even in asymptomatic subjects, expiratory air trapping is probably pathological and, once bronchial asthma has been excluded, it may be related to cigarette smoking and indicate early inflammatory bronchiolar damage. HRCT may therefore be regarded as a useful tool in the early diagnosis of smoking-related lung disease.