Left-sided Congenital Diaphragmatic Hernia Research Articles

Comparison of current to past outcomes in congenital diaphragmatic hernia using mri observed-to-expected total fetal lung volume.

Fetal Centers use imaging studies to predict congenital diaphragmatic hernia (CDH) prognosis and the need for fetal therapy. Given improving CDH survival, we hypothesized that current fetal imaging severity predictions no longer reflect true outcomes and fail to justify the risks of fetal therapy. We analyzed our single-center contemporary data in a left-sided CDH cohort (n = 58) by prognostic criteria determined by MRI observed-to-expected total fetal lung volumes: severe <25%, moderate 25-35%, and mild >35%. We compared contemporary survival to prior studies and the TOTAL trials. Contemporary survival was significantly higher than past studies for all prognostic classifications (mild 100% vs 80-94%, moderate 95% vs 59-75%, severe 79% vs 13-25%; P < 0.01), and to either control or fetal therapy arms of the TOTAL trials. Current fetal imaging criteria are overly pessimistic and may lead to unwarranted fetal intervention. Fetal therapies remain experimental. Future studies will require updated prognostic criteria.

Self-reported respiratory and gastrointestinal outcomes in children with isolated congenital diaphragmatic hernia: A prospective multicentre study.

To evaluate medium-term self-reported respiratory and gastrointestinal (GI) outcomes in children with congenital diaphragmatic hernia (CDH). Self-reported respiratory and GI outcomes correlated with prenatal severity indicators. Prospective study at three fetal medicine units. Families of children prenatally diagnosed with isolated, left-sided CDH surviving for >1 year. Families received validated questionnaires for GI outcomes (Infant Gastroesophageal Reflux Questionnaire Revised, I-GERQ-R, for infants aged <2 years, or Paediatric Gastro-oesophageal Symptom and Quality of Life Questionnaire, PGSQ, for children aged aged 2-8 years or >9 years) and respiratory outcomes (preschool respiratory outcome questionnaire, for children aged ≤5 years, or the International Study of Asthma and Allergies in Childhood asthma questionnaire, for children aged 6-8 years or ≥9 years). Prenatal data collected from the medical records included lung size (percentage observed/expected lung-to-head ratio, O/E LHR %), liver position, fetal endoluminal tracheal occlusion (FETO) gestational age (GA) at delivery, and perinatal data included birthweight, location, patch repair and respiratory support. The GI and respiratory scores were correlated with O/E LHR using linear and logistic regression models. Univariate analysis was used to evaluate associations with perinatal variables. We obtained 142 responses from 342 families (representing a response rate of 45%). The baseline characteristics of participants and non-participants were comparable. No correlations between perinatal variables and respiratory or GI scores were identified. Children aged ≤5 years with lower O/E LHR values reported higher respiratory scores (P = 0.0175); this finding was not reported in older children. Overall, the children who underwent FETO (n = 51) had GI (P = 0.290) and respiratory (P = 0.052) scores that were comparable with those of children who were expectantly managed. Families and children with prenatally diagnosed CDH reported fewer respiratory symptoms with increasing age. There was no correlation between O/E LHR or the use of FETO and self-reported outcomes.

Multicentre, randomised controlled trial of physiological-based cord clamping versus immediate cord clamping in infants with a congenital diaphragmatic hernia (PinC): statistical analysis plan

BackgroundInfants born with congenital diaphragmatic hernia (CDH) are at high risk of respiratory insufficiency and pulmonary hypertension. Routine practice includes immediate clamping of the umbilical cord and endotracheal intubation. Experimental animal studies suggest that clamping the umbilical cord guided by physiological changes and after the lungs have been aerated, named physiological-based cord clamping (PBCC), could enhance the fetal-to-neonatal transition in CDH. We describe the statistical analysis plan for the clinical trial evaluating the effects of PBCC versus immediate cord clamping on pulmonary hypertension in infants with CDH (PinC trial).DesignThe PinC trial is a multicentre, randomised controlled trial in infants with isolated left-sided CDH, born ≥ 35.0 weeks of gestation. The primary outcome is the incidence of pulmonary hypertension in the first 24 h after birth. Maternal outcomes include estimated maternal blood loss. Neonatal secondary outcomes include mortality before discharge, extracorporeal membrane oxygenation therapy, and number of days of mechanical ventilation. Infants are 1:1 randomised to either PBCC or immediate cord clamping using variable random permutated block sizes (4–8), stratified by treatment centre and estimated severity of pulmonary hypoplasia (i.e. mild/moderate/severe). At least 140 infants are needed to detect a relative reduction in pulmonary hypertension by one third, with 80% power and 0.05 significance level. A chi-square test will be used to evaluate the hypothesis that PBCC decreases the occurrence of pulmonary hypertension. This plan is written and submitted without knowledge of the collected data. The trial has been ethically approved.Trial registrationClinicalTrials.gov NCT04373902 (registered April 2020).

Prenatal diagnosis of intrathoracic kidney and adrenal gland in left-sided congenital diaphragmatic hernia.

A 29-year-old primigravida at 31weeks of gestation was referred for intrathoracic kidney (ITK). Ultrasound revealed left kidney intrathoracic placement with an anteriorly positioned ectopic adrenal gland. Magnetic resonance imaging confirmed diaphragmatic interruption and colon herniation. A female neonate, delivered at 37weeks, underwent successful thoracoscopic repair for a left Bochdalek hernia. Despite compression of the left lung, notably optimistic lung-to-head ratio (LHR) values were observed, correlating with favorable outcomes. This case underscores the rare occurrence of ITK, its association with Bochdalek hernia, and the importance of comprehensive prenatal evaluations.

Long-Term Evaluation of the Shape of the Reconstructed Diaphragm in Patients with Left-Sided Congenital Diaphragmatic Hernia Using Serial Chest Radiographs and Correlation to Further Complications.

Background: Defining risk factors for long-term comorbidities in patients after neonatal repair of congenital diaphragmatic hernia (CDH) is an important cornerstone of the implementation of targeted longitudinal follow-up programs. Methods: This study systematically assessed serial chest radiographs of 89 patients with left-sided CDH throughout a mean follow-up of 8.2 years. These geometrical variables for the left and right side were recorded: diaphragmatic angle (LDA, RDA), diaphragmatic diameter (LDD, RDD), diaphragmatic height (LDH, RDH), diaphragmatic curvature index (LDCI, RDCI), lower lung diameter (LLLD, RLLD) and thoracic area (LTA, RTA). Results: It was demonstrated that the shape of the diaphragm in patients with large defects systematically differs from that of patients with small defects. Characteristically, patients with large defects present with a smaller LDCI (5.1 vs. 8.4, p < 0.001) at 6 months of age, which increases over time (11.4 vs. 7.0 at the age of 15.5 years, p = 0.727), representing a flattening of the patch and the attached rudimentary diaphragm as the child grows. Conclusions: Multiple variables during early follow-up were significantly associated with comorbidities such as recurrence, scoliotic curves of the spine and a reduced thoracic area. Some geometrical variables may serve as surrogate parameters for disease severity, which is associated with long-term comorbidities.

Prenatal Predictors of Survival, Pulmonary Hypertension, and ECMO in Isolated CDH Undergoing Expectant Management, A Systematic Review and Meta-analysis

Background and Hypothesis: Congenital diaphragmatic hernia (CDH) is a severe developmental defect affecting 1-4 per 10,000 births, characterized by left/right-sided defect, or mixed with herniation of abdominal contents into thorax, with resultant lung hypoplasia and persistent pulmonary hypertension (PHTN). The study investigates prenatal predictors of survival to hospital discharge, PHTN and the need for ECMO in fetuses with isolated CDH undergoing prenatal expectant management.&#x0D; Project Methods: We performed a systematic literature review on prenatal diagnostic tests in fetuses with isolated CDH undergoing expectant management. Primary outcomes included survival-to-hospital discharge, persistent PHTN within 28 days, and ECMO need. Newcastle Ottawa Scale assessed quality of studies. Meta-analysis performed when two or more studies reported on the same test. Subgroup analysis performed according to CDH side.&#x0D; Results: 161 full-text articles between 2000-2022 were assed for eligibility; 48 met inclusion criteria. 45 reported on survival, 12 on ECMO need, 8 on PHTN; quality of studies was moderate. Studies included were retrospective (81%) or prospective (19%) regarding fetuses undergoing expectant management (77%), or mixed tracheal occlusion and expectant management (20%). Most studies included mixed (41%) or left-sided (47%) CDH. Survival predicted by TFLV, o/e-TFLV, o/e-TFLV &lt;30%, LiTR, o/e-LHR, o/e-LHR &lt;25%, percentage herniated liver, MSA, stomach position in mid-chest, and liver up. ECMO need predicted by o/e-TFLV, o/e-LHR, and PPLV. These results were confirmed through subgroup analysis of only left-sided lesions. PHTN was predicted by presence of intrathoracic liver (OR-1.96, 95%CI 1.14,3.37, I2-0%); this was not significant after left-sided subgroup analysis.&#x0D; Conclusion and Potential Impact: In fetuses with CDH, FLV and presence/percentage of intrathoracic liver predict survival. FLV measurements predict ECMO need. Presence of intrathoracic liver may predict persistent PHTN; further studies are needed. Accurate prognostication of CDH severity would aid patient triage, resource mobilization, and identification of high-risk CDH infants in need of advanced treatment including ECMO or identification of candidates for fetal intervention procedures.

The Delivery Room Resuscitation of Infants with Congenital Diaphragmatic Hernia Treated with Fetoscopic Endoluminal Tracheal Occlusion: Beyond the Balloon

Introduction: Randomized controlled trials found that fetoscopic endoluminal tracheal occlusion (FETO) resulted in increased fetal lung volume and improved survival for infants with isolated, severe left-sided congenital diaphragmatic hernia (CDH). The delivery room resuscitation of these infants is particularly unique, and the specific delivery room events are largely unknown. The objective of this study was to compare the delivery room resuscitation of infants treated with FETO to standard of care (SOC) and describe lessons learned. Methods: Retrospective single-center cohort study of infants treated with FETO compared to infants who met FETO criteria during the same period but who received SOC. Results: FETO infants were more likely to be born prematurely with 8/12 infants born <35 weeks gestational age compared to 3/35 SOC infants. There were 5 infants who required emergent balloon removal (2 ex utero intrapartum treatment and 3 tracheoscopic removal on placental bypass with delayed cord clamping) and 7 with prenatal balloon removal. Surfactant was administered in 6/12 FETO (50%) infants compared to 2/35 (6%) in the SOC group. Extracorporeal membrane oxygenation use was lower at 25% and survival was higher at 92% compared to 60% and 71% in the SOC infants, respectively. Conclusion: The delivery room resuscitation of infants treated with FETO requires thoughtful preparation with an experienced multidisciplinary team. Given increased survival, FETO should be offered to infants with severe isolated left-sided CDH, but only in high-volume centers with the experience and capability of removing the balloon, emergently if needed. The neonatal clinical team must be skilled in managing the unique postnatal physiology inherent to FETO where effective interdisciplinary teamwork is essential. Empiric and immediate surfactant administration should be considered in all FETO infants to lavage thick airway secretions, particularly those delivered <48 h after balloon removal.

Pulmonary artery diameter ratio as a prognostic indicator of congenital diaphragmatic hernia

BackgroundFollowing on from an earlier study published in 2008 about left pulmonary artery (LPA) flow measured on serial echocardiography being strongly prognostic in left-sided congenital diaphragmatic hernia (CDH) and the...

Comparison of the Surgical Outcomes in Neonates with Left-sided Congenital Diaphragmatic Hernia with Only Skin Closure versus Abdominal Muscle Closure.

This study aims to compare the outcome of neonatal left congenital diaphragmatic hernia (CDH, Bochdalek type) repair through laparotomy with and without abdominal muscle closure. This retrospective study was conducted between January 2012 and May 2021 at a neonatal surgical unit of a Tertiary Care Center. Demographic details, preoperative management, Two-dimensional-echo, intra-operative findings, postoperative course, and follow-up data were collected and analyzed. The study group comprised 50 neonates with a mean standard deviation (SD) age at admission: 4.44 (5.12) days, male: female ratio of 3:2, and mean (SD) weight: 2.73 (0.51) kg. Following repair of the diaphragmatic defect through laparotomy, 26 (52%) underwent skin closure alone, whereas 24 (48%) underwent abdominal muscle closure. Postoperatively, there was a significant fall in the level of platelets (P = 0.021), increase in pressure support by at least 4-5 cm H2O (P = 0.027), and increase in the blood urea (P < 0.001), creatinine (P = 0.005), lactate (P = 0.019), and acidosis (P = 0.048) in the muscle closure group. Although not statistically significant, there was a fall in the urine output and blood pressure in this group. There was no significant difference in the duration of inotropes. Mortality was 8 (32%) in the skin closure group, and 14 (61%) in the muscle closure group (P = 0.05). Neonates undergoing left CDH repair through the abdominal route with skin closure alone, had better survival, as well as hematological, renal, and ventilatory parameters than those who underwent muscle closure. It is a useful surgical modification to improve outcome in centers with limited facilities.

Fetoscopic endoluminal tracheal occlusion vs expectant management for fetuses with severe left-sided congenital diaphragmatic hernia

BackgroundThe therapy of fetuses with congenital diaphragmatic hernia (CDH) is challenging, but there is evidence that fetoscopic endoluminal tracheal occlusion (FETO) has a benefit over expectant care. Additionally, standardisation and expertism have a great impact on survival, probably the key of centers relying on expectant management and extracorporeal membrane oxygenation (ECMO) after birth. ObjectiveTo examine the survival and morbidity rates of fetuses with severe isolated left-sided CDH (LCDH) who underwent FETO versus expectant management in high-volume centers. Study DesignThis was a multicenter retrospective study including all consecutive fetuses with severe isolated LCDH who were expectantly managed in a German center or underwent FETO in three other European centers (Belgium, France and Italy). Severe CDH was defined as observed-expected total fetal lung volume (o/e TFLV) ≤35% with intrathoracic position of the liver, using magnetic resonance images (MRI). All MRI were centralized and lung volumes were measured by two experienced operators, who were blinded to the pre- and postnatal data. Multiple logistic regression analyses were performed to examine the effect of the management in the two groups on the short- and long-term outcomes. Results147 patients with expectant management and 47 patients who underwent FETO were analyzed. Fetuses who were expectantly managed had lower o/e TFLV (20.6% ± 7.5% versus 23.7% ± 6.8%, p=0.013), higher gestational age at delivery (median weeks of gestation: 37.4 [IQR: 36.6, 38.00] versus 35.1 [IQR: 33.1, 37.2], p<0.001) and a more frequent use of ECMO (55.8% versus 4.3%, p<0.001) in comparison to the fetuses who underwent FETO. The survival rates at discharge and at two years of age of the expectant management group were higher compared to the survival rates of the FETO group (74.3% versus 44.7%, p=0.001 and 72.8% versus 42.5%, p=0.001, respectively). After adjustment for maternal age, gestational age at birth, o/e TFLV and birthweight Z-score, the odds ratios were 4.65 (95%CI: 1.9-11.9, p=0.001) and 4.37 (95%CI: 1.8-11.0, p=0.001) respectively. The morbidity was comparable between both groups. ConclusionFetuses with severe isolated LCDH had a higher survival rate when treated in an experienced center in Germany with an antenatal expectant management and frequent use of ECMO during the postnatal period in comparison to fetuses treated with FETO in 3 centers in Belgium, France and Italy, without the expense of higher morbidity.

Vascular reactivity is altered in the placentas of fetuses with congenital diaphragmatic hernia

IntroductionInfants with congenital diaphragmatic hernia (CDH) often develop pulmonary hypertension but frequently fail to respond to vasodilator therapy, for instance because of an altered pulmonary vasoreactivity. Investigating such alterations in vivo is impossible. We hypothesised that these alterations are also present in fetoplacental vessels, since both vasculatures are exposed to the same circulating factors (e.g. endothelin-1) and respond similarly to certain stimuli (e.g. hypoxia). As proof-of-concept, we compared fetoplacental vasoreactivity between healthy and CDH-affected placentas. MethodsFetoplacental vascular function of healthy and antenatally diagnosed left-sided CDH fetuses was assessed by wire myography. Placental expression of enzymes and receptors involved in the altered vasoreactive pathways was measured using quantitative PCR. ResultsCDH arteries (n = 6) constricted more strongly to thromboxane A2 agonist U46619 (p < 0.001) and dilated less to bradykinin (p = 0.01) and nitric oxide (NO)-donor sodium nitroprusside (p = 0.04) than healthy arteries (n = 8). Vasodilation to prostacyclin analogue iloprost and adenylate cyclase stimulator forskolin, and vasoconstriction to endothelin-1 were not different between both groups. Angiotensin II did not induce vasoconstriction. Phosphodiesterase inhibitors sildenafil and milrinone did not affect responses to sodium nitroprusside, forskolin, or U46619. The mRNA expression of guanylate cyclase 1 soluble subunit alpha 1 (p = 0.003) and protein kinase cyclic guanine monophosphate (cGMP)-dependent 1 (p = 0.02) were reduced in CDH versus healthy placentas. DiscussionThe identified changes in the thromboxane and NO-cGMP pathways in the fetoplacental vasculature correspond with currently described alterations in the pulmonary vasculature in CDH. Therefore, fetoplacental arteries may provide an opportunity to predict pulmonary therapeutic responses in infants with CDH.

Characterization of the congenital diaphragmatic hernia model in C57BL/6J fetal mice: a step toward lineage tracing experiments.

Lineage tracing is key to study the fate of individual cells and their progeny especially in developmental biology. To conduct these studies, we aimed to establish a reproducible model of CDH in the most commonly used genetic background strain that is C57BL/6J mice. CDH was induced in C57BL/6J dams by maternal administration of nitrofen + bisdiamine at E8.5. Fetuses from olive oil-gavaged mothers served as controls. Lungs from CDH and control fetuses were compared for (1) growth via radial airspace count (RAC), mean linear intercept (MLI) and gene expression for Fgf10, Nrp1, and Ctnnb1; (2) maturation (Pdpn, Spc, Ager, Abca3, Eln, Acta2, Pdgfra) via gene and protein expression; (3) vascularization via gene and protein expression (CD31, Vegfa, Vegfr1/2, Epas1, Enos). unpaired t-test or Mann-Whitney test. Nitrofen + bisdiamine administration resulted in 36% left-sided CDH (31% mortality). CDH fetuses had hypoplastic lungs and impaired growth (lower RAC, higher MLI, lower Fgf10, Nrp1, Ctnnb1), maturation (decreased Pdpn, Ager, Eln gene expression), and vascularization (decreased Cd31, Vegfr1/2; Epas1 and Enos). Lower protein expression was confirmed for PDPN, ELN and CD31. Modeling CDH in C57BL/6J mouse fetuses is effective in reproducing the classical CDH hallmarks. This model will be critical for lineage tracing experiments.

MRI prediction of fetal lung volumes and the impact on counselling

To assess whether lung volume percentages in congenital diaphragmatic hernia (CDH) differ depending on which formula is used to calculate the expected volume for gestation and any potential impact this may have on perinatal counselling. Forty-seven patients with left-sided CDH who had undergone fetal magnetic resonance imaging (MRI) at Sheffield Teaching Hospitals were reviewed. The lung volumes were measured on MRI and compared with the volumes that would be expected at the given gestation for each patient. Expected values were calculated using four formulae from the literature and the authors' in-house method. These measurements were used to calculate the percentage total lung volume observed compared with the expected lung volume in a healthy fetus of the same gestation. The differences in percentage lung volumes using these five methods were then compared with how they relate to predicted rates of survival. How predicted survival would change depending on which formula was used to calculate the percentage lung volume was investigated with a view to how this may change the counselling given to a family. In 10/47 (21%) patients, there was no change in the predicted percentage chance of survival depending on which formula was used to calculate the predicted lung volume. In 37/47 (79%), the predicted chance of survival changed depending on which formula was used to calculate the expected lung volume at the given gestation. In 20 (47%) of these cases, the change in predicted survival depending on which formula used was 45% (i.e., from 25% to 70% survival in four and from 50% to 95% survival in 16) and in two cases (4%) this difference was 70% (i.e., from 25% predicted survival to 95% predicted survival). There are several different methods for calculating expected lung volumes for any given gestation. When used to estimate the percentage lung volume in patients with CDH, there is a large difference in values depending on which method is used. This in turn leads to a large variation in predicted survival with some patients in this study having either a 25% or 95% chance of survival depending on which method is used. This has a huge impact on perinatal counselling and the difficult decisions made by families.

Lung proliferation is dependent on the duration not thetimepoint of tracheal occlusion in nitrofen rats with diaphragmatic hernia.

Prenatal tracheal occlusion (TO) promotes lung growth and is applied clinically in fetuses with congenital diaphragmatic hernia (CDH). Limited data are available regarding the effect of duration versus timepoint of TO. Our objective was to document the impact of TO on lung development in the near-term period in rats with nitrofen-induced CDH. Nitrofen was administered on embryonic day (ED)9 and fetal TO was performed on ED18.5, 19, or 20 (term=ED22). Sham-operated and untouched littermates served as controls. Lungs were harvested in 0.5-day steps and only fetuses with a left-sided CDH were included in further analyses. Healthy fetuses provided a reference for normal near-term lung development. Duration of TO in the nitrofen rat model for CDH predicts lung growth in terms of lung-body-weight ratio as well as an increased mRNA level of the proliferation marker Ki67. Longer TO also induced a more complex airway architecture. The timepoint of TO was not predictive of lung growth. In the nitrofen rat model of CDH, a longer period of TO leads to enhanced lung growth and more refined airway architecture.

Assessment of pulmonary artery size at birth as a prognostic factor in congenital diaphragmatic hernia: results of a multicenter study in Japan.

To assess the reliability of pulmonary artery (PA) parameters as a prognostic marker in neonates with isolated left-sided congenital diaphragmatic hernia (IL-CDH). A retrospective cohort study conducted by the Japanese CDH Study Group (JCDHSG). 323 IL-CDH patients registered with the JCDHSG were included. 272 patients survived to 90 days of age. Right PA (RPA) and left PA (LPA) diameters and pulmonary artery index (PAIndex) at birth were significantly larger in survivors. The cutoff values of RPA and LPA diameters and PAIndex for survival up to 90 days were 3.2 mm, 2.8 mm and 83.7, respectively, and logistic regression analysis showed that these were significantly related to survival. Multiple logistic regression analysis showed that both the PA parameters and liver herniation were significantly related to survival. The three PA parameters at birth can predict clinical outcomes and are considered as independent risk factors of liver herniation.

Clinical assessment of the fetal right Quantitative Lung Index

Objectives We have previously described gestational-age-independent sonographic indices to assess fetal lung size in the right and left lungs: The Quantitative Lung Index for the right lung (QLI-R) and for the left lung (QLI-L), respectively. The purpose of this study was to evaluate the clinical cutoff point of the QLI-R to predict pulmonary hypoplasia and neonatal death. Materials and Methods Retrospective assessment of the QLI-R in patients with left-sided congenital diaphragmatic hernia (CDH-L) and other fetal conditions at risk for fetal pulmonary hypoplasia. Cross-section and longitudinal assessment of the behavior of the QLI-R in untreated and treated patients. ROC curve analysis to determine the optimal cutoff point of the QLI-R in predicting neonatal death. Results One hundred eighteen patients with CDH-L and other fetal conditions at risk for pulmonary hypoplasia had QLI-R measurements done. Seventeen patients were excluded for various reasons. Eleven patients with conditions other than CDH-L but at risk for pulmonary hypoplasia were used for intraclass coefficient measurements of the QLI-R. Ninety patients had CDH-L, of which 78 did not undergo antenatal intervention and in which the cutoff point for pulmonary hypoplasia and neonatal demise was assessed. Stent tracheal occlusion was performed in the remaining 12 patients with CDH-L, in which the behavior of the QLI after surgery was assessed. Analysis of the ICC showed an overall intra-rater reliability of 0.985 (Cronbach’s Alpha-based). There was no correlation between gestational age and QLI-R (-0.73, Pearson correlation, p = .72). Twenty-six of the 78 patients (33%) with CDH-L managed expectantly had a neonatal demise. A QLI-R equal to or less than 0.45 was significantly predictive of neonatal demise (area under the curve 0.64, p = .046, sensitivity 77%). Nine of the 12 patients (75%) that underwent tracheal occlusion had neonatal survival. Of these, 10 had serial assessments of the QLI-R after surgery. An increase in the QLI-R of 0.11 was associated with a tendency for neonatal survival (p = .056). Conclusion Our study confirms that the QLI-R is a gestational-age-independent measurement of fetal lung size, with a high degree of reproducibility. In a population of expectantly managed CDH-L patients, a cutoff value of the QLI-R of 0.45 or lower is predictive of neonatal death from pulmonary hypoplasia. The QLI-R can be used to monitor fetal lung growth after tracheal occlusion, and an increase in the QLI-R is suggestive of neonatal survival. Further prospective studies are needed to confirm these findings and to explore the use of the QLI in other populations at risk for pulmonary hypoplasia and consequent neonatal demise.

INDIAMAN-20 (INstant DIAgnosis of 20 Major ANomalies) protocol: application of IOTA diagnostic strategy to fetal anomalies.

To compile a list of instant diagnoses of major fetal anomalies, and to present their sonographic descriptors and test them in a retrospective series of fetuses with congenital anomalies managed at our center. The first step was to identify major anomalies that meet the following criteria: (1) can be diagnosed directly and unequivocally on the basis of a set of descriptors evident on a single sonographic view; (2) are among those more commonly diagnosed in utero; (3) represent major lethal or life-threatening malformations or anomalies for which no or only palliative surgery can be performed. For each of these anomalies, a sonographic descriptor was produced. The second step was to test the descriptors of the instant diagnoses in all cases with these anomalies evaluated since January 2000 in our Fetal Medicine Unit, retrieved from our electronic database. For each congenital anomaly-sonographic descriptor pair we then evaluated the presence vs absence of an unequivocal relationship between anomaly and descriptor, assessing: whether a particular descriptor in a set reference plane identified unequivocally the anomaly, i.e. the same descriptor could not be found in any other malformation; and whether a particular anomaly presented the corresponding descriptor in all cases. Finally, we evaluated whether the sonographic descriptors could be applied in all trimesters or only selectively, considering the natural history of the 20 instant diagnoses. Of the 20 instant diagnoses, five involved the central/peripheral nervous system (exencephaly/anencephaly, alobar/semilobar holoprosencephaly, cephalocele, open spinal dysraphism, complete agenesis of corpus callosum), five involved the heart (hypoplastic left heart syndrome, complete atrioventricular septal defect, severe Ebstein's anomaly, critical aortic stenosis, transposition of the great arteries), five involved the abdominal wall (left-sided congenital diaphragmatic hernia, exomphalos, gastroschisis, body-stalk anomaly) or gastrointestinal tract (duodenal atresia), and five involved the remaining systems (three urinary (autosomal recessive polycystic kidney disease, multicystic dysplastic kidney, lower urinary tract obstruction), two skeletal (transverse limb defect, radial ray defect)). All of the descriptors were found to identify unequivocally the related malformations, whereas four of the malformations were not associated with their reference descriptors in every case. For example, congenital diaphragmatic hernia (left-sided) presented without the stomach in the thorax in 42/93 (45.2%) cases. Due to the natural history of the condition, not all signs were recognizable in the first trimester, some becoming evident only from the second trimester onwards. We have defined sonographic descriptors that enable an unequivocal instant diagnosis for a list of 20 major congenital anomalies: the 'INDIAMAN-20' (INstant DIAgnosis of Major ANomalies) protocol. We believe that using this approach may facilitate focused training of less experienced operators and that it may be incorporated into artificial intelligence and deep learning protocols, further boosting the instant prenatal recognition of these lethal or life-threatening malformations. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

The grading of stomach position for postnatal outcomes in isolated left-sided congenital diaphragmatic hernia: Asystematic review and meta-analysis.

To evaluate the correlation between stomach position (SP) grading and postnatal outcomes in fetuses with isolated left-sided congenital diaphragmatic hernias (CDHs). A literature search was conducted using the PubMed, Embase, and Cochrane Library databases. The corresponding 95% confidence intervals (CIs) were used to assess the differences in the odds of mortality according to the SP graded as level 0 to level 3. To evaluate the reliability of our results, a sensitivity analysis was also conducted. Nine papers with a total of 542 fetuses with isolated left-sided CDH were included. Congenital diaphragmatic hernia pregnancies complicated by an intrathoracic stomach had higher odds of neonatal mortality when compared with intraabdominal stomach (odds ratio [OR] 2.86; 95% CI 1.38-5.94). Four papers with SP grading from level 0 to level 3 were included in a subgroup analysis. Stomach position at level 1 and level 2 had lower odds of neonatal mortality when separately compared to level 3 (OR 0.12; 95% CI 0.04-0.33) and (OR 0.30; 95% CI 0.16-0.54). Stomach position at level 1 had lower odds of neonatal mortality when compared with level 2+3 (OR 0.25; 95% CI 0.09-0.66). Survival of fetuses with isolated left-sided CDH is correlated with the SP.

Characterization of Suboptimal Responses to Fetoscopic Endoluminal Tracheal Occlusion in Congenital Diaphragmatic Hernia

Introduction: The aim of the study was to characterize the changes in fetal lung volume following fetoscopic endoluminal tracheal occlusion (FETO) that are associated with infant survival and need for extracorporeal membrane oxygenation (ECMO) in congenital diaphragmatic hernia (CDH). Methods: Fetuses with CDH who underwent FETO at a single institution were included. CDH cases were reclassified by MRI metrics [observed-to-expected total lung volume (O/E TLV) and percent liver herniation]. The percent changes of MRI metrics after FETO were calculated. ROC-derived cutoffs of these changes were derived to predict infant survival to discharge. Regression analyses were done to determine the association between these cutoffs with infant survival and ECMO need, adjusted for site of CDH, gestational age at delivery, fetal sex, and CDH severity. Results: Thirty CDH cases were included. ROC analysis demonstrated that post-FETO increases in O/E TLV had an area under the curve of 0.74 (p = 0.035) for the prediction of survival to hospital discharge; a cutoff of less than 10% was selected. Fetuses with a <10% post-FETO increase in O/E TLV had lower survival to hospital discharge [44.8% vs. 91.7%; p = 0.018] and higher ECMO use [61.1% vs. 16.7%; p = 0.026] compared to those with an O/E TLV increase ≥10%. Similar results were observed when the analyses were restricted to left-sided CDH cases. A post-FETO <10% increase in O/E TLV was independently associated with lower survival at hospital discharge (aOR: 0.073, 95% CI: 0.008–0.689; p = 0.022) and at 12 months of age (aOR: 0.091, 95% CI: 0.01–0.825; p = 0.036) as well as with higher ECMO use (aOR: 7.88, 95% CI: 1.31–47.04; p = 0.024). Conclusion: Fetuses with less than 10% increase in O/E TLV following the FETO procedure are at increased risk for requiring ECMO and for death in the postnatal period when adjusted for gestational age at delivery, CDH severity, and other confounders.

Surgical Risk Factors for Delayed Oral Feeding Autonomy in Patients with Left-Sided Congenital Diaphragmatic Hernia.

Congenital diaphragmatic hernia (CDH) is a rare disease associated with major nutritional and digestive morbidities. Oral feeding autonomy remains a major issue for the care and management of these patients. The aim of this study was to specify the perinatal risk factors of delayed oral feeding autonomy in patients treated for CDH. This monocentric cohort study included 138 patients with CDH. Eighty-four patients were analyzed after the exclusion of 54 patients (11 with delayed postnatal diagnosis, 5 with chromosomal anomaly, 9 with genetic syndrom, 13 with right-sided CDH, and 16 who died before discharge and before oral feeding autonomy was acquired). They were divided into two groups: oral feeding autonomy at initial hospital discharge (group 1, n = 51) and nutritional support at discharge (group 2, n = 33). Antenatal, postnatal, and perisurgical data were analyzed from birth until first hospital discharge. To remove biased or redundant factors related to CDH severity, statistical analysis was adjusted according to the need for a patch repair. After analysis and adjustment, delayed oral feeding autonomy was not related to observed/expected lung-to-head ratio (LHR o/e), intrathoracic liver and/or stomach position, or operative duration. After adjustment, prophylactic gastrostomy (OR adjusted: 16.3, IC 95%: 3.6-74.4) and surgical reoperation (OR adjusted: 5.1, IC 95% 1.1-23.7) remained significantly associated with delayed oral feeding autonomy. Delayed oral feeding autonomy occurred in more than one third of patients with CDH. Both prophylactic gastrostomy and surgical reoperation represent significant risk factors. Bowel obstruction might also impact oral feeding autonomy. Prophylactic gastrostomy seems to be a false "good idea" to prevent failure to thrive. This procedure should be indicated case per case. Bowel obstruction and all surgical reoperations represent decisive events that could impact oral feeding autonomy.