Doppler Ultrasound and Resistive Indices in the Diagnosis of Ureteropelvic Junction Obstruction in the Pediatric Population.

OBJECTIVES: Mercapto acetyl tri-glycine renogram (MAG3) scan has been the gold standard assessment of pediatric ureteropelvic junction obstruction (UPJO) but requires intravenous access and radiation exposure. While Doppler ultrasound measurements of resistive indices (RI) of the arcuate arteries have been proposed as an alternative assessment of obstruction, they have not been widely adopted in the pediatric population. We hypothesized that RI of the main renal artery (RA) is more strongly correlated with MAG3 findings than arcuate RI. METHODS: Pediatric patients with unilateral Society for Fetal Urology grade 3-4 hydronephrosis undergoing concomitant RUS and MAG3 were recruited. Doppler ultrasound peak systolic velocity (PSV); RI of bilateral RA at the origin, middle, and hilum; and RI of the superior, middle, and lower pole arcuate arteries were obtained. MAG3 differential renal function (DRF) and T½ were recorded. Differences in RI measurements (DRI) between the affected and normal kidney were calculated and compared with DRF and T½. RESULTS: 31 patients (median 4.6-month-old) were enrolled. Only RA RI at the origin differed between affected and normal kidneys (p < .001). DRI RA at the origin showed weak evidence for an association with MAG3 DRF < 40% (p .07). DRI was not associated with T½ > 20 minutes. CONCLUSION: There was weak evidence for an association between RA DRI at the origin and DRF but not with T½. These findings suggest that RA DRI may provide additional data in the evaluation of patients with UPJO to tailor the use of MAG3 and associated risk of radiation exposure to those patients most at risk for concomitant renal function impairment.

Reference Values for Fetal Cardiac Dimensions, Volumes, Ventricular Function and Left Ventricular Longitudinal Strain Using Doppler Ultrasound Gated Cardiac Magnetic Resonance Imaging in Healthy Third Trimester Fetuses.

BACKGROUND: Recent advances in hardware and software permit the use of cardiac MRI of late gestation fetuses, however there is a paucity of MRI-based reference values. PURPOSE: To provide initial data on fetal cardiac MRI-derived cardiac dimensions, volumes, ventricular function, and left ventricular longitudinal strain in healthy developing fetuses >30 weeks gestational age. STUDY TYPE: Prospective. POPULATION: Twenty-five third trimester (34 ± 1 weeks, range of 32-37 weeks gestation) women with healthy developing fetuses. FIELD STRENGTH/SEQUENCE: Studies were performed at 1.5 T and 3 T. Cardiac synchronization was achieved with a Doppler ultrasound device. The protocol included T2 single shot turbo spin echo stacks for fetal weight and ultrasound probe positioning, and multiplanar multi-slice cine balanced steady state free precession gradient echo sequences. ASSESSMENT: Primary analyses were performed by a single observer. Weight indexed right ventricular (RV) and left ventricular (LV) volumes and function were calculated from short axis (SAX) stacks. Cardiac dimensions were calculated from the four-chamber and SAX stacks. Single plane LV longitudinal strain was calculated from the four-chamber stack. Interobserver variability was assessed in 10 participants. Cardiac MRI values were compared against available published normative fetal echocardiogram data using z-scores. STATISTICAL TESTS: Mean and SDs were calculated for baseline maternal/fetal demographics, cardiac dimensions, volumes, ventricular function, and left ventricular longitudinal strain. Bland-Altman and intraclass correlation coefficient analysis was performed to test interobserver variability. RESULTS: The mean gestational age was 34 ± 1.4 weeks. The mean RV and LV end diastolic volumes were 3.1 ± 0.6 mL/kg and 2.4 ± 0.5 mL/kg respectively. The mean RV cardiac output was 198 ± 49 mL/min/kg while the mean LV cardiac output was 173 ± 43 mL/min/kg. DATA CONCLUSION: This paper reports initial reference values obtained by cardiac MRI in healthy developing third trimester fetuses. MRI generally resulted in slightly larger indexed values (by z-score) compared to reports in literature using fetal echocardiography. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 2.

Fetal lung volumes measured by MRI predict pulmonary morbidity among infants with giant omphaloceles.

OBJECTIVE: Giant omphaloceles (GO) have associated pulmonary hypoplasia and respiratory complications. Total lung volumes (TLV) on fetal MRI can prognosticate congenital diaphragmatic hernia outcomes; however, its applicability to GO is unknown. We hypothesize that late gestation TLV and observed-to-expected TLV (O/E TLV) on fetal MRI correlate with postnatal pulmonary morbidity in GO. METHOD: A single-institution retrospective review of GO evaluated between 2012 and 2022 was performed. Fetal MRI TLV between 32 and 36 weeks' gestation and O/E TLV throughout gestation were calculated and correlated with postnatal outcomes. RESULTS: 86 fetuses with omphaloceles were evaluated; however, only 26 met strict inclusion criteria. MRIs occurred between 18 and 36 weeks' gestation. Those requiring delivery room intubation had significantly lower late gestation TLV and O/E TLV. O/E TLV predicted tracheostomy placement and survival. Neither TLV nor O/E TLV predicted the length of hospitalization or supplemental oxygen after discharge. Three fetuses had a TLV less than 35 mL: one died of respiratory failure, and the other two required tracheostomy. CONCLUSIONS: Fetal MRI TLV measured between 32 and 36 weeks' gestation and O/E TLV predict the need for delivery room intubation and tracheostomy. O/E TLV correlated with survival. These data support fetal MRI as a prognostic tool to predict GO associated pulmonary morbidity.

Five siblings expand the spectrum of GPC6-related skeletal dysplasia.

Skeletal dysplasias broadly include disorders of cartilage or bone. Omodysplasia-1 is a type of skeletal dysplasia caused by biallelic loss of function variants in the GPC6 gene. GPC6 codes for the protein glypican 6 (GPC6) (OMIM *604404), which stimulates bone growth. We report a family in which five out of nine children were presented with a skeletal dysplasia characterized phenotypically by mild short stature and rhizomelia. All affected individuals were found to have homozygous missense variants in GPC6: c.511 C>T (p.Arg171Trp). Radiograph findings included rhizomelic foreshortening of all four extremities, coxa breva, and ulna minus deformity. Using a Hedgehog (Hh) reporter assay, we demonstrate that the variant found in this family results in significantly reduced stimulation of Hh activity when compared to the wild-type GPC6 protein, however protein function is still present. Thus, the milder phenotype seen in the family presented is hypothesized due to decreased GPC6 protein activity versus complete loss of function as seen in omodysplasia-1. Given the unique phenotype and molecular mechanism, we propose that this family's findings widen the phenotypic spectrum of GPC6-related skeletal dysplasias.

Multifocal Paraganglioma in Teenager Presenting With Hypertension.

Pediatric hypertension represents a rare though increasingly common medical problem. When encountered, a workup to determine the etiology should be conducted. In this report, we detail an unusual case in which a teenager presenting with hypertension was found to have multifocal primary paragangliomas. We illustrate important considerations in management which include appropriate preoperative labs and imaging, collaboration with endocrinology for preoperative alpha-blockade, surgical management with close perioperative hemodynamic control, and genetic evaluation for all patients with paragangliomas.

Third-trimester percentage predicted lung volume and percentage liver herniation as prognostic indicators in congenital diaphragmatic hernia.

BACKGROUND: Over the last two decades, fetal imaging has greatly improved, and new prenatal imaging measurements have been developed to characterize congenital diaphragmatic hernia (CDH) severity. OBJECTIVE: To determine the best prenatal imaging predictor of postnatal CDH outcomes, including use of extracorporeal membrane oxygenation (ECMO) and in-hospital mortality, with particular attention to the percentage of liver herniation (%LH) as a predictor. Additionally, we sought to guide best practices across hospital systems including improved models of prenatal risk assessment. MATERIALS AND METHODS: We conducted a retrospective review of infants with left CDH who were prenatally diagnosed. We analyzed prenatal imaging measurements including observed-to-expected (O/E) lung-to-head ratio (LHR) on US, percentage predicted lung volume (PPLV) on MRI, and O/E total fetal lung volume (TFLV) and %LH on MRI. We compared prenatal imaging characteristics for infants with (1) in-hospital postnatal mortality and (2) use of ECMO. Then we performed multivariate logistic regression to determine independent predictors of postnatal outcomes. RESULTS: We included 63 infants with a median gestation of 34 weeks at the time of prenatal MRI. Low O/E LHR (31.2 vs. 50, P < 0.0001), PPLV (14.7 vs. 22.6, P < 0.0001) and O/E TLFV (24.6 vs. 38.3, P < 0.0001) and high %LH (15.1 vs. 2.1, P = 0.0006) were associated with worse postnatal outcomes; however, only PPLV was predictive of survival and need for ECMO on multivariable analysis. PPLV survival to discharge model showed an area under the curve (AUC) of 0.93 (95% confidence interval [CI]: 0.86, 0.99), P < 0.0001; and an odds ratio of 68.7 (95% CI: 6.5-2,302), P = 0.003. PPLV need for ECMO model showed AUC = 0.87 (95% CI: 0.78, 0.96), P < 0.0001; and odds ratio = 20.1 (95% CI: 3.1-226.3), P = 0.011. CONCLUSION: Low O/E LHR, PPLV and O/E TFLV and high %LH in the third trimester are associated with worse postnatal outcomes. PPLV most strongly predicted outcome using a logistic regression model. Percentage of liver herniation was not an independent predictor of outcomes.

Megacystis Associated With an Underlying ACTA2 Variant and Diagnosis of Multisystemic Smooth Muscle Dysfunction Syndrome: A Case Report.

Fetal megacystis, or an enlarged fetal bladder, is most often attributed to embryological defects, occurring early in gestation. Recent investigations have demonstrated that the underlying etiology of megacystis may be more myriad than originally thought. We present the third reported patient with megacystis due to an ACTA2 Arg179 substitution variant causing Multisystemic Smooth Muscle Dysfunction Syndrome. We also provide a description of pediatric evaluation and follow up. The growing number of cases in which this ACTA2 variant has been identified in fetal megacystis suggests that molecular sequencing is an appropriate consideration, particularly prenatally, when other features of Multisystemic Smooth Muscle Dysfunction Syndrome cannot be detected.

Visualization of the Anal Dimple by Fetal MRI: Is It Feasible?

INTRODUCTION: The aim of this study was to determine the feasibility of fetal MRI in identifying the normal anal dimple (AD) and compare it with prenatal ultrasound (US). METHODS: Retrospective review of 130 patients with both fetal MRI and US. The gestational age (GA) was stratified into four groups: (1) 16 to 21 weeks-6 days; (2) 22 to 27 weeks-6 days; (3) 28 to 33 weeks-6 days; and (4) 34 weeks and beyond. Steady-state free precession (SSFP) and single shot fast spin echo (SSFSE) axial T2 MRI and transverse US images of the fetal perineum were analyzed, and visualization of the AD was determined. Clinical indication, gender, single versus multiple gestation, best MRI sequence where it was seen, and postnatal AD information were recorded. RESULTS: The AD was visualized in 125/130 fetal MRIs, and visualization was independent of GA (p 0.230). US visualized the AD in 67/130 cases, and the best GA for visualization was in group 3 (p < 0.001). There was no difference in AD visualization between SSFSE and SSFP sequences (p 0.167). CONCLUSION: Prenatal visualization of the AD by MRI is feasible and superior to US, independent of GA. Adding AD visualization to routine screening prenatal US and MRI may increase recognition of anorectal malformation.

Prenatally Diagnosed Posterior Urethral Valves: Ethical Dilemmas of Fetal Intervention.

Although anhydramnios due to in utero renal failure has traditionally been considered lethal, in utero interventions offer the potential for pulmonary survival. As fetal interventions become more common, questions arise about how to identify and counsel eligible candidates.  In this report we describe the presentation and management of a 17-year-old pregnant female who presented from out-of-state with severe lower urinary tract obstruction (LUTO) with associated anhydramnios, focusing on the ethical questions that this case raised.

The novel fetal MRI O/E CLV versus O/E LHR in predicting prognosis in congenital diaphragmatic hernias: can we teach an old dog new tricks?

PURPOSE: In congenital diaphragmatic hernia (CDH), ultrasound (U/S) measurements of the contralateral lung commonly provide the observed-to-expected lung-to-head ratio (O/E LHR) and are used to determine the severity of pulmonary hypoplasia. Fetal magnetic resonance imaging (MRI) measurement of the observed-to-expected total lung volume (O/E TLV) has been used as an adjunct to O/E LHR in predicting outcomes. Since O/E LHR only measures the contralateral lung, we sought to investigate if MRI measurements of the contralateral lung volume (O/E CLV) can accurately predict outcomes in CDH. We hypothesize that O/E CLV is a better predictor of CDH outcomes than O/E LHR. METHODS: We identified all infants with a prenatal diagnosis of CDH at our fetal center who had both MRI and U/S measurements. Using lung volume ratios of right-left 55:45, we calculated O/E CLV from O/E TLV. We used receiver-operating characteristic (ROC) curves to calculate the area under the curve (AUC) to compare the predictive accuracy of O/E CLV to O/E LHR for ECMO support, as well as survival to both discharge and 1 year. RESULTS: Seventy-four patients had complete prenatal imaging with 39% requiring ECMO support. The median O/E CLV was 48.0% and the median O/E LHR was 42.3%. O/E CLV was a better predictor of the need for ECMO support (AUC 0.81 vs. 0.74). O/E CLV was a better predictor of survival to discharge (AUC 0.84 vs. 0.64) and 1-year survival (AUC 0.83 vs. 0.63) than O/E LHR. CONCLUSION: O/E LHR is a well-validated standard for predicting outcomes and guiding prenatal counseling in CDH. We provide evidence that fetal MRI measurements of the contralateral lung volume corrected for gestational age were more accurate in predicting the need for ECMO and survival. Future prospective studies validating O/E CLV regarding outcomes and ECMO utilization are warranted. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

Visualization of the fetal anus by prenatal ultrasound for the diagnosis of anorectal malformations: is it feasible?

PURPOSE: The goal of this study was to determine the feasibility of identifying the anal dimple (AD) on routine prenatal ultrasound. Using the presence, absence, appearance, and location of the anal dimple as an indirect sign for possible underlying anorectal malformations (ARM), we hypothesize that evaluation of the anal dimple as part of the fetal anatomic survey may increase the sensitivity in detecting less severe ARMs. METHODS: In a prospective longitudinal observational study, pregnant women who underwent prenatal ultrasound (US) at the Colorado Fetal Care Center between January 2019 and 2020 were enrolled. The variables recorded included gestational age, singleton versus multiple pregnancy, gender of the fetus, visualization of the AD, and reason for non-visualization of the AD. RESULTS: A total of 900 ultrasounds were performed, evaluating 1044 fetuses, in 372 different pregnant women. Gestational ages ranged from 16 to 38 weeks. The AD was visualized in 612 fetuses (58.6%) and not seen in 432 (41.4%). The two most common reasons for non-visualization were extremes in gestational age (n = 155; 36%) and fetal position (n = 152; 35.3%). The optimal gestational age range for AD visualization was 28-33 weeks + 6 days, with 78.1% visualization rate. CONCLUSION: Visualization of the anal dimple by ultrasound is feasible and may aid in the detection of less severe ARMs, ultimately impacting pregnancy management and family counseling. The optimal timing for anal dimple visualization is late second and third trimester.

Imaging of fetal cystic kidney disease: multicystic dysplastic kidney versus renal cystic dysplasia.

With the advent of routine prenatal imaging, the number of renal anomalies identified prenatally has significantly increased; however, the underlying etiologies of these anomalies and the clinical significance of these findings remains unclear. This confusion is especially true for the prenatal diagnosis of cystic renal changes. The terms "cystic kidney disease" and "renal cystic dysplasia" encompass myriad renal diseases. Although renal cystic dysplasia in infants shares many similarities with multicystic dysplastic kidney (MCDK), it is important to distinguish MCDK from other etiologies that would lead to renal cysts, to ensure proper patient diagnosis and appropriate counseling regarding risks and to guide clinical management. The purpose of this review is to highlight the multiple etiologies of cystic kidney disease, including genetic associations, associations with underlying syndromes, and associations with underlying anatomical abnormalities. Here we focus on prenatal imaging, associated pathological findings, and clinical significance, with an emphasis on the defining characteristics of MCDK as compared to other forms of cystic renal disease.

Placental magnetic resonance imaging Part I: the normal placenta.

Mounting evidence suggests that the placenta is involved in nearly all abnormalities of pregnancy and fetal development. Traditional imaging evaluation of the placenta by ultrasound has more recently been complemented by MRI for complex cases requiring additional information, such as in the diagnosis of the placenta accreta spectrum (placenta accreta, increta and percreta). MRI can often help delineate the safest approach to delivery and adds diagnostic certainty to enable prognostication and to avoid potentially lethal complications. Increasingly, prenatal MRI has become the purview of the pediatric imager and is becoming the standard of care for select gestational indications. However, placental MRI might be unfamiliar to the radiologist. Thus, we provide a simple and systematic approach to evaluating the placenta by MRI, to enable delivery planning and family counseling.

Placental magnetic resonance imaging Part II: placenta accreta spectrum.

The human placenta remains an enigma to many. Its position as the point of communication between distinct maternal and fetal circulations means that it must act as both source of nourishment and gatekeeper for the developing pregnancy. In vivo assessment of the placenta is perhaps the greatest challenge, yet it is most essential for diagnostic and prognostic purposes. In particular, there is a need for improved diagnostic accuracy in recognizing the invasive forms of the placenta accreta spectrum that require surgical intervention at delivery and often cesarean hysterectomy. The costs of insufficient sensitivity and specificity are high, with well-documented cases of adverse outcomes ranging from unnecessary surgery to maternal hemorrhage and even death. In Part I of this pictorial essay series, we reviewed the appearance of the normal developing placenta across gestation by MRI. With this as a background, we here consider the varied appearances of the placenta accreta spectrum (placenta accreta, increta, percreta), which is a growing challenge given the rapidly expanding number of women worldwide with history of cesarean section delivery. Accurate prenatal imaging is crucial for recognizing cases of the placenta accreta spectrum and for planning the necessary surgery.

Differentiating presacral masses in anorectal malformations and isolated sacrococcygeal teratomas.

PURPOSE: Presacral masses associated with anorectal malformations (ARM) are most frequently dermoid or teratomas. Sacrococcygeal teratoma (SCT), in isolation, is a different condition. There are limited data comparing the two. The aim of this study was to compare presacral masses associated with ARM and isolated SCTs. METHODS: A retrospective review was performed from 1979 to 2018. Patients with presacral masses and associated ARM (n = 39) were identified and compared to patients with isolated SCTs (n = 32). RESULTS: Those with presacral mass and ARM had a lower proportion of immature and mixed teratomas by pathology and a longer time to mass resection. They had higher percentages of sacral anomalies (76% versus 9%), tethered cord (50% versus 6%), and other anomalies (51% versus 9%). For long-term bowel function, patients with presacral mass and ARM were more likely to be fecally incontinent and require enemas (59% versus 11%). Regarding isolated SCTs, 4% recurred with a time to recurrence of 7 months. CONCLUSIONS: Compared to patients with isolated SCT, patients with presacral mass and ARM had lower grade tumors. In addition, they had a higher proportion of sacral defects and other congenital defects, as well as worse bowel function outcomes.

Correction to: The spectrum of cloacal malformations: how to differentiate each entity prenatally with fetal MRI.

The published version of this article unfortunately contained a mistake. Author name Mariana Z. Meyers was incorrect. The correct middle initial is given above.

The Natural History of Wilms Tumor-A Case Comparison of Two Different Tumors.

Due to the rarity of Wilms tumor (WT) and the relative urgency with which pediatric renal tumors are treated, there is little reported data on the natural history and growth of WTs. Historical reports of estimated doubling times of WTs were based on time to disease recurrence after initial diagnosis and treatment, and were published before the current advancements in molecular biomarker testing. We compare 2 cases of WT with sequential imaging, and postulate how the growth parameters of these tumors may be associated with differing chromosomal traits.