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Introduction Outcome predictions of patients with congenital diaphragmatic hernia (CDH) still have some limitations in the prenatal estimate of postnatal pulmonary hypertension (PH). We propose applying Machine Learning (ML), and Deep Learning (DL) approaches to fetuses and newborns with CDH to develop forecasting models in prenatal epoch, based on the integrated analysis of clinical data, to provide neonatal PH as the first outcome and, possibly: favorable response to fetal endoscopic tracheal occlusion (FETO), need for Extracorporeal Membrane Oxygenation (ECMO), survival to ECMO, and death. Moreover, we plan to produce a (semi)automatic fetus lung segmentation system in Magnetic Resonance Imaging (MRI), which will be useful during project implementation but will also be an important tool itself to standardize lung volume measures for CDH fetuses. Methods and analytics Patients with isolated CDH from singleton pregnancies will be enrolled, whose prenatal checks were performed at the Fetal Surgery Unit of the Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico (Milan, Italy) from the 30th week of gestation. A retrospective data collection of clinical and radiological variables from newborns’ and mothers’ clinical records will be performed for eligible patients born between 01/01/2012 and 31/12/2020. The native sequences from fetal magnetic resonance imaging (MRI) will be collected. Data from different sources will be integrated and analyzed using ML and DL, and forecasting algorithms will be developed for each outcome. Methods of data augmentation and dimensionality reduction (feature selection and extraction) will be employed to increase sample size and avoid overfitting. A software system for automatic fetal lung volume segmentation in MRI based on the DL 3D U-NET approach will also be developed. Ethics and dissemination This retrospective study received approval from the local ethics committee (Milan Area 2, Italy). The development of predictive models in CDH outcomes will provide a key contribution in disease prediction, early targeted interventions, and personalized management, with an overall improvement in care quality, resource allocation, healthcare, and family savings. Our findings will be validated in a future prospective multicenter cohort study. Registration The study was registered at ClinicalTrials.gov with the identifier NCT04609163.

Congenital diaphragmatic hernia is a rare disease with high mortality and morbidity due to pulmonary hypoplasia and pulmonary hypertension. The aim of the study is to investigate the relationship between radiographic lung area and systolic pulmonary artery pressure (sPAP) on the first day of life, mortality, and hernia recurrence during the first year of life in infants with a congenital diaphragmatic hernia (CDH). A retrospective data collection was performed on 77 CDH newborns. Echocardiographic sPAP value, deaths, and recurrence cases were recorded. Lung area was calculated by tracing the lung's perimeter, excluding mediastinal structures, and herniated organs, on the preoperative chest X-ray performed within 24 h after birth. Logistic and linear regression analyses were performed. Deceased infants showed lower areas and higher sPAP values. One square centimeter of rising in the total, ipsilateral, and contralateral area was associated with a 22, 43, and 24% reduction in mortality risk. sPAP values showed a decreasing trend after birth, with a maximum of 1.84 mmHg reduction per unitary increment in the ipsilateral area at birth. Recurrence patients showed lower areas, with recurrence risk decreasing by 14 and 29% per unit increment of the total and ipsilateral area. In CDH patients, low lung area at birth reflects impaired lung development and defect size, being associated with increased sPAP values, mortality, and recurrence risk.Clinical Trial Registration: The manuscript is an exploratory secondary analysis of the trial registered at ClinicalTrials.gov with identifier NCT04396028.

In newborns with congenital diaphragmatic hernia (CDH), the radiographic lung area is correlated with functional residual capacity (FRC) and represents an alternative method to estimate lung hypoplasia. In a cohort of newborn CDH survivors, we retrospectively evaluated the relationship between radiographic lung area measured on the 1st day of life and long-term respiratory function. As a secondary analysis, we compared radiographic lung areas and respiratory function between patients undergoing fetal endoscopic tracheal occlusion (FETO) and patients managed expectantly (non-FETO). Total, ipsilateral, and contralateral radiographic areas were obtained by tracing lung perimeter as delineated by the diaphragm and rib cage, excluding mediastinal structures and herniated organs. Tidal volume (VT), respiratory rate (RR), and their Z-Scores when compared to the norm were collected from pulmonary function tests (PFTs) performed at 12 ± 6 months of age. Linear regression analyses using the absolute Z-Score values for each parameter were performed. In CDH survivors, an increase in total and ipsilateral lung area measured at birth was related to a reduction in the absolute Z-Score for VT in PFTs (p = 0.046 and p = 0.023, respectively), indicating a trend toward an improvement in pulmonary volumes and VT normalization. Radiographic lung areas were not significantly different between FETO and non-FETO patients, suggesting a volumetric lung increase due to prenatal intervention. However, the mean Z-Score value for RR was significantly higher in the FETO group (p < 0.001), probably due to impaired diaphragmatic motility in the most severe cases. Further analyses are necessary to better characterize the role of the radiographic pulmonary area in the prognostic evaluation of respiratory function in patients with CDH. Clinical Trial Registration: This trial was registered at ClinicalTrials.gov with the identifier NCT04396028.

The interleukin-1 (IL-1) gene family has been associated with susceptibility to periodontal diseases, including aggressive periodontitis (AgP); however, the results are still conflicting. The present study investigated the association between IL-1 genes and AgP using 70 markers spanning the 1.1-Mb region, where the IL-1 gene family maps, and exploring both the linkage disequilibrium (LD) and the haplotype structure in a case-control study including 95 patients and 121 control individuals. No association between AgP and IL1A, IL1B, and IL1RN genes was found in either single-point or haplotype analyses. Also, the LD map of the region 2q13–14 under the Malécot model for multiple markers showed no causal association between AgP and polymorphisms within the region (p = 0.207). In conclusion, our findings failed to support the existence of a causative variant for generalized AgP within the 2q13–14 region in an Italian Caucasian population.