Dynamic discriminant model for predicting respiratory distress at birth based on mass volume ratio in fetuses with congenital lung malformation.

OBJECTIVES: The congenital lung malformation volume ratio (CVR) is a prenatal ultrasound measurement that parameterizes congenital lung malformation (CLM) size. The aims of this study were to use serial measurements to create estimated growth curves of fetal CVR for asymptomatic and symptomatic neonates with CLM and to investigate whether a discriminant prognostic model based on these measurements could predict accurately which fetuses with CLM will require invasive respiratory support at delivery and should therefore be delivered at a tertiary-care facility. METHODS: This was a retrospective study of fetuses diagnosed prenatally with CLM at three tertiary-care children's hospitals between 2009 and 2016. Those with two or more sonographic measurements of CVR were included. Serial fetal CVR measurements were used to create estimated growth curves for neonates with and those without respiratory symptoms at delivery, defined as requiring invasive respiratory support for the first 24 h after delivery. A discriminant model based on serial CVR measurements was used to calculate the dynamic probability of the need for invasive respiratory support. The performance of this model overall and in preterm and term neonates was compared with those using maximum CVR thresholds of 1.0 and 1.6. RESULTS: Of the 147 neonates meeting the inclusion criteria, 16 (10.9%) required postnatal invasive respiratory support. The estimated CVR growth curve models showed different growth trajectories for asymptomatic and symptomatic neonates, with significantly higher CVR in symptomatic neonates, and values peaking late in the second trimester at around 25 weeks' gestation in asymptomatic neonates. All prognostic methods had high accuracy for the prediction of the need for invasive respiratory support in term neonates, but the discriminant model had the best performance overall (area under the receiver-operating characteristics curve (AUC) = 0.88) and in the preterm population (AUC = 0.85). CONCLUSIONS: The estimated CVR growth curves showed different growth patterns in asymptomatic and symptomatic neonates with CLM. The dynamic discriminant model performed well overall and particularly in neonates that were carried to term. Development of an externally validated clinical tool based on this analysis could be useful in determining the site of delivery for fetuses with CLM. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Prenatal and postnatal markers of severity in congenital diaphragmatic hernia have similar prognostic ability.

OBJECTIVES: The purpose of this study was to compare prenatal versus postnatal markers of congenital diaphragmatic hernia (CDH) severity at a single fetal-care center. METHODS: A retrospective study was performed of patients having a complete prenatal evaluation and surgical repair (n = 55). Observed-to-expected lung-to-head ratio (o/eLHR), observed-to-expected total lung volume (o/eTLV), liver position (LP), a predictive dependent variable from logistic regression of o/eLHR and liver position (o/eLHR + LP), and diaphragmatic defect size per the CDH Study Group A-D classification were plotted into receiver-operating characteristics (ROC) curves. Survival and need for extracorporeal membrane oxygenation (ECMO) were primary outcomes. RESULTS: Survival was 69%, and ECMO utilization was 56%. Distribution was 80% left-sided defects. In the survival ROC curve, the area under the curve (AUC) for o/eLHR was 0.73, o/eTLV 0.74, LP 0.73, o/eLHR + LP 0.78, and defect size 0.84 (p = 0.23). The ROC curve for ECMO support showed o/eLHR had an AUC of 0.82, o/eTLV 0.89, LP 0.79, o/eLHR + LP 0.87, and defect size 0.90 (p = 0.19). The AUCs were similar when only left-sided CDH was analyzed. CONCLUSIONS: These data suggest that prenatal evaluation was equivalent to the postnatal diaphragmatic defect classification for predicting survival and need for ECMO in CDH patients.

Management of perinatal lung malformations.

This review uses the most up-to-date literature to help guide obstetrical providers through the diagnosis and management of perinatal lung malformations. These lesions, which include congenital pulmonary airway malformation [CPAM, formerly congenital cystic adenomatoid malformation (CCAM)] and bronchopulmonary sequestration (BPS), are relatively rare but are becoming increasingly common because of the improved resolution and enhanced sensitivity of fetal ultrasound. Serial assessment throughout pregnancy remains the norm rather than the exception. Perinatal management strategies can differ based on the sonographic characteristics and dynamic growth patterns of lung masses. Fetal magnetic resonance imaging and other diagnostic testing can sometimes be helpful in providing additional prognostic information. Over the last decade, the importance of echocardiography and utility of maternal steroids have been recognized in cases of non-immune hydrops. Fetal surgery is now rarely performed. Decisions regarding whether delivery of these fetuses should occur in a tertiary care center with pediatric surgery coverage versus delivery at a local community hospital are now highly relevant in most prenatal counseling discussions with families. Large lung malformations may require urgent surgical removal in the early postnatal period because of respiratory distress. Other complications, such as recurrent pneumonia, pneumothorax, and cancer, are indications for lung resection on an elective basis. In the vast majority of cases, the overall prognosis remains excellent.

Peripheral regulation of graft-versus-host alloreactivity in mixed chimeric miniature swine.

BACKGROUND: Despite the presence of circulating donor-derived T cells during the induction of mixed chimerism across MHC barriers in miniature swine, severe graft-versus-host disease was avoided in the majority of animals. In this study, we investigated the possible roles of recipient and donor lymphoid populations in the regulation of donor-anti-recipient alloreactivity. METHODS: Mixed chimerism across a full MHC-mismatch barrier was established in miniature swine using a high-dose allogeneic peripheral blood stem cell protocol. Peripheral blood mononuclear cells from mixed chimeric swine were co-cultured with naïve donor-matched responders and naïve recipient-matched stimulators in mixed lymphocyte reactions. RESULTS: Peripheral blood mononuclear cells from mixed chimeras inhibited donor-anti-recipient proliferation. This suppression was radioresistant to 25 Gy. Suppression of donor-anti-recipient alloreactivity was not observed in mixed lymphocyte co-cultures when donor-derived cells were added in the absence of recipient-derived cells. CONCLUSIONS: These results suggest an association between the presence of an active and relatively radioresistant cell population, demonstrable in vitro, and the regulation of graft-versus-host disease across MHC barriers in mixed chimeric miniature swine.