The Effect of Steroids on Prenatally Diagnosed Lung Lesions.

BACKGROUND: Open fetal resection for large lung lesions has virtually been replaced by maternal steroid administration. Despite this paradigm shift, little is known about the effects steroids have on lung lesion growth in utero. METHODS: A 10-year retrospective review of all prenatally diagnosed lung lesions cared for at our fetal care center was performed. We evaluated the effects of prenatal steroids on congenital pulmonary airway malformation (CPAM)-volume-ratio (CVR), distinguishing change in CVR among CPAMs, bronchopulmonary sequestrations (BPS), and bronchial atresias. We also correlated fetal ultrasound and MRI findings with pathology to determine the accuracy of prenatal diagnosis. RESULTS: We evaluated 199 fetuses with a prenatal lung lesion. Fifty-four (27 %) were treated with prenatal steroids with a subsequent 21 % mean reduction in the CVR (2.1 ± 1.4 to 1.1 ± 0.4, p = 0.003). Fetuses with hydrops and mediastinal shift who were treated with steroids rarely had resolution of these radiographic findings. Postnatal pathology was available for 91/199 patients (45.7 %). The most common diagnosis was CPAM (42/91, 46 %), followed by BPS (30/91, 33 %), and bronchial atresia (14/91, 15 %). Fetuses who received steroids and had pathology consistent with CPAM were more likely to have a reduction in their CVR (p = 0.02). Fetal ultrasound correctly diagnosed the type of lung lesion in 75 % of cases and fetal MRI in 81 % of cases. CONCLUSIONS: Prenatally diagnosed CPAMs are more likely to respond to maternal steroids than BPS or bronchial atresias. Knowing the diagnosis in utero could aid to steward steroid usage, however, fetal imagining modalities are not perfect in distinguishing subtype. LEVEL OF EVIDENCE: III.

Dysregulation of miRNA-mRNA expression in fetal growth restriction in a caloric restricted mouse model.

Fetal growth restriction (FGR) is associated with aberrant placentation and accounts for a significant proportion of perinatal deaths. microRNAs have been shown to be dysregulated in FGR. The purpose of this study was to determine microRNA-regulated molecular pathways altered using a caloric restricted mouse model of FGR. Pregnant mice were subjected to a 50% caloric restricted diet beginning at E9. At E18.5, RNA sequencing of placental tissue was performed to identify differences in gene expression between caloric restricted and control placentas. Significant differences in gene expression between caloric restricted and control placentas were observed in 228 of the 1546 (14.7%) microRNAs. Functional analysis of microRNA-mRNA interactions demonstrated enrichment of several biological pathways with oxidative stress, apoptosis, and autophagy pathways upregulated and angiogenesis and signal transduction pathways downregulated. Ingenuity pathway analysis also suggested that ID1 signaling, a pathway integral for trophoblast differentiation, is also dysregulated in caloric restricted placentas. Thus, a maternal caloric restriction mouse model of FGR results in aberrant microRNA-regulated molecular pathways associated with angiogenesis, oxidative stress, signal transduction, apoptosis, and cell differentiation. As several of these pathways are dysregulated in human FGR, our findings suggest that this model may provide an excellent means to study placental microRNA derangements seen in FGR.