Fetal hyperechoic kidneys: Diagnostic considerations and genetic testing strategies.

Isolated bilateral hyperechoic kidneys (HEK) on prenatal ultrasound presents diagnostic, prognostic, and counseling challenges. Prognosis ranges from normal outcome to lethal postnatally. Presence/absence of extra-renal malformations, gestational age at presentation, amniotic fluid volume, and renal size may distinguish underlying etiologies and thereby prognosis, as prognosis is highly dependent upon underlying etiology. An underlying genetic diagnosis, clearly impactful, is determined in only 55%-60% of cases. We conducted a literature review of chromosomal (aneuploidies, copy number variants [CNVs]) single genes and other etiologies of fetal bilateral HEK, summarized how this information informs prognosis and recurrence risk, and critically assessed laboratory testing strategies. The most commonly identified etiologies are autosomal recessive and autosomal dominant polycystic kidney disease and microdeletions at 17q12 involving HNF1b. With rapid gene discovery, alongside advances in prenatal imaging and fetal phenotyping, the growing list of single gene diagnoses includes ciliopathies, overgrowth syndromes, and renal tubular dysgenesis. At present, microarray and gene panels or whole exome sequencing (WES) are first line tests employed for diagnostic evaluation. Whole genome sequencing (WGS), with the ability to detect both single nucleotide variants (SNVs) and CNVs, would be expected to provide the highest diagnostic yield.

Can Dynamic Magnetic Resonance Images Improve Prenatal Diagnosis of Robin Sequence.

BACKGROUND: Robin sequence (RS) is a triad of micrognathia, glossoptosis, and airway obstruction. Prenatal diagnosis of RS improves delivery planning and postnatal care, but the process for prenatal diagnosis has not been refined. The purpose of this study was to determine if dynamic cine magnetic resonance imaging (MRI) can improve the reliability of prenatal diagnosis for RS compared to current static imaging techniques. MATERIALS AND METHODS: This is a retrospective cross-sectional study including fetuses with prenatal MRIs obtained in a single center from January 2014 to November 2019. Fetuses were included if they: 1) had a prenatal MRI with cine dynamic sequences of adequate quality, 2) were live born, and 3) had postnatal craniofacial evaluation to confirm RS. Patients without postnatal confirmation of their prenatal findings were excluded. The primary predictor variable was imaging type (cine or static MRI). Outcome variables were tongue and airway measurements: 1) tongue height, 2) length and width, 3) tongue shape index, 4) observation of tongue touching the posterior pharyngeal wall, and 5) measurement of oropharyngeal space. All measurements were made independently on the cine images and on static MRI sequences for the same cohort of subjects by a pediatric radiologist. Data were analyzed using paired samples t tests and Fisher exact tests, and significance was set as P < .05. RESULTS: A total of 11 patients with RS were included in the study. The smallest airway space consistently demonstrated complete collapse on the cine series compared to partial collapse on static images (0 mm vs 1.7 ± 1.4 mm, P = .002). No other imaging variable was statistically significantly different between techniques. CONCLUSIONS: Cine imaging sequences on prenatal MRI were superior to static images in discerning complete collapse of the smallest airway space, an important marker of RS. This suggests a possible benefit to adding dynamic MRI evaluation for prenatal diagnosis of this condition.

Regional Brain Growth Trajectories in Fetuses with Congenital Heart Disease.

OBJECTIVE: Congenital heart disease (CHD) is associated with abnormal brain development in utero. We applied innovative fetal magnetic resonance imaging (MRI) techniques to determine whether reduced fetal cerebral substrate delivery impacts the brain globally, or in a region-specific pattern. Our novel design included two control groups, one with and the other without a family history of CHD, to explore the contribution of shared genes and/or fetal environment to brain development. METHODS: From 2014 to 2018, we enrolled 179 pregnant women into 4 groups: "HLHS/TGA" fetuses with hypoplastic left heart syndrome (HLHS) or transposition of the great arteries (TGA), diagnoses with lowest fetal cerebral substrate delivery; "CHD-other," with other CHD diagnoses; "CHD-related," healthy with a CHD family history; and "optimal control," healthy without a family history. Two MRIs were obtained between 18 and 40 weeks gestation. Random effect regression models assessed group differences in brain volumes and relationships to hemodynamic variables. RESULTS: HLHS/TGA (n = 24), CHD-other (50), and CHD-related (34) groups each had generally smaller brain volumes than the optimal controls (71). Compared with CHD-related, the HLHS/TGA group had smaller subplate (-13.3% [standard error = 4.3%], p < 0.01) and intermediate (-13.7% [4.3%], p < 0.01) zones, with a similar trend in ventricular zone (-7.1% [1.9%], p = 0.07). These volumetric reductions were associated with lower cerebral substrate delivery. INTERPRETATION: Fetuses with CHD, especially those with lowest cerebral substrate delivery, show a region-specific pattern of small brain volumes and impaired brain growth before 32 weeks gestation. The brains of fetuses with CHD were more similar to those of CHD-related than optimal controls, suggesting genetic or environmental factors also contribute. ANN NEUROL 2021;89:143-157.

Ocular Ultrasound: Review of Bioeffects and Safety, Including Fetal and Point of Care Perspective: Review of Bioeffects and Safety, Including Fetal and Point-of-Care Perspective.

Ocular ultrasound is an invaluable tool for the evaluation of the eye and orbit. However, the eye and orbit are potentially sensitive to the thermal and mechanical effects of ultrasound. When performing B-mode imaging, dedicated ocular settings should be used. If these settings are not available, limiting the acoustic output to Food and Drug Administration (FDA) recommended maximum levels is strongly advised. Especially important is the acoustic output in spectral (pulsed) and color Doppler modes, which can exceed the FDA's maximum recommended levels for the eye. Adjusting settings to decrease acoustic output and limiting the time of the examination should be done when performing a Doppler examination. The acoustic output of shear wave elastography is significantly higher than FDA guidelines for the eye and should be considered experimental.

A role for abdominal ultrasound in discriminating suspected necrotizing enterocolitis in congenital heart disease patients.

PURPOSE: We evaluated the diagnostic utility of abdominal ultrasound (AUS), an adjunct to abdominal X-ray (AXR), for necrotizing enterocolitis (NEC) in congenital heart disease (CHD) patients. METHODS: 86 patients with suspected NEC from 2009 to 2018 were classified as with CHD (n = 18) if they required cardiac intervention versus without CHD (n = 68). Clinical and radiological data were collected, including AXR and AUS concordance. Wilcoxon rank-sum test and Fisher's exact test were performed. RESULTS: CHD patients had higher birth weights (p < 0.001) and gestational ages (p < 0.001) than non-CHD patients. CHD patients presented more frequently with hypotension (p = 0.041) and less frequently with bilious emesis (p < 0.001). Overall, CHD patients were less likely to have AUS findings of pneumatosis (33.3 vs. 72.1%; p = 0.005) and decreased mural flow (0 vs. 20.6%; p = 0.035) compared to non-CHD patients. On concordance analysis, CHD patients had 3.9-fold more discordant studies with pneumatosis on AXR but not on AUS (33.3 vs. 8.8%; p = 0.016) compared to non-CHD patients. Urgent surgery was required in 5.6% of CHD patients versus 16.2% of non-CHD patients. CONCLUSION: CHD patients with suspected NEC represent a distinct clinical population. AUS has particular utility in assessing findings of bowel viability in the CHD NEC population, reflecting reduced rates of surgical NEC.

Genetic diagnoses and associated anomalies in fetuses prenatally diagnosed with esophageal atresia.

Esophageal atresia (EA) is a congenital anomaly occurring in 2.3 per 10,000 live births. Due to advances in prenatal imaging, EA is more readily diagnosed, but data on the associated genetic diagnoses, other anomalies, and postnatal outcome for fetuses diagnosed prenatally with EA are scarce. We collected data from two academic medical centers (n = 61). Our data included fetuses with suspected EA on prenatal imaging that was confirmed postnatally and had at least one genetic test. In our cohort of 61 cases, 29 (49%) were born prematurely and 19% of those born alive died in the first 9 years of life. The most commonly associated birth defects were cardiac anomalies (67%) and spine anomalies (50%). A diagnosis was made in 61% of the cases; the most common diagnoses were vertebral defects, anal atresia, cardiac anomalies, tracheoesophageal fistula with esophageal atresia, radial or renal dysplasia, and limb anomalies association (43%, although 12% met only 2 of the criteria), trisomy 21 (5%), and CHARGE syndrome (5%). Our findings suggest that most fetuses with prenatally diagnosed EA have one or more additional major anomaly that warrants a more comprehensive clinical genetics evaluation. Fetuses diagnosed prenatally appear to represent a cohort with a worse outcome.

Can Robin Sequence Be Predicted From Prenatal Ultrasonography?

PURPOSE: Prenatal diagnosis of Robin sequence (RS) could promote safe delivery and improve perinatal care. The purpose of this study was to evaluate the correlation between prenatal ultrasonography (US) and magnetic resonance imaging (MRI) studies for assessing micrognathia to determine if US alone can be used to reliably screen for RS. MATERIALS AND METHODS: This was a retrospective case-control study of fetuses evaluated in the Advanced Fetal Care Center at Boston Children's Hospital from 2002 to 2017. To be included, 1) prenatal MRI and US must have been performed during the same visit, 2) the infant must have been live-born, and 3) the diagnosis must have been confirmed postnatally. Patients with images of inadequate quality for analysis were excluded. Patients were divided into 4 groups based on postnatal diagnosis: 1) RS (micrognathia, glossoptosis, and airway obstruction) (RS group), 2) micrognathia without RS (micrognathia group), 3) cleft lip and palate (CLP) without micrognathia (CLP group), and 4) gestational age-matched controls with normal craniofacial morphology (control group). The inferior facial angle (IFA) was measured using both imaging modalities and compared. Receiver operating characteristic curves were applied to identify a threshold for the diagnosis of RS from US. The sensitivity, specificity, positive predictive value, negative predictive value, and odds ratio were calculated. RESULTS: A total of 94 patients were included (mean gestational age at imaging, 24.9 ± 5.2 weeks), with 25 in the RS group (26.6%), 29 in the micrognathia group (30.9%), 23 in the CLP group (24.5%), and 17 in the control group (18.1%). The IFA was significantly smaller in the RS group than in all other groups on both US and MRI (P < .001). A moderate correlation was found between IFA measurements on US and MRI (intraclass correlation coefficient, 0.729). An IFA threshold on US of 45.5° maximized sensitivity (84%) and specificity (81%) for the diagnosis of RS. CONCLUSIONS: We suggest incorporating the IFA into routine prenatal US and referring patients for confirmatory MRI when the US IFA is lower than 45.5°.

Prenatal imaging throughout gestation in Beckwith-Wiedemann syndrome.

PURPOSE: Prenatal occurrence and timing of appearance of associated features in Beckwith-Wiedemann syndrome (BWS) are unknown. We reviewed our BWS patients with serial fetal imaging and correlated these with postnatal findings. METHODS: All BWS patients with fetal ultrasound (US) or magnetic resonance imaging (MRI) from 2000 to 2016 were reviewed to determine the presence of polyhydramnios, placentamegaly, macrosomia, macroglossia, retrognathia, omphalocele, visceromegaly, and hemihypertrophy. These observations were correlated with postnatal findings. Data were analyzed by Mann-Whitney U test. RESULTS: Nine BWS patients underwent 42 fetal imaging studies with median of five (range of two to six) studies per patient between 13 and 35 weeks gestation. All prenatal findings were confirmed postnatally with complete concordance. All patients with omphalocele were detected early in gestation but other postnatal findings less predictably so. All omphaloceles were small, and were found significantly earlier in gestation than macrosomia (P = 0.004) and macroglossia (P = 0.012). Visceromegaly and retrognathia were less frequent, with no significant differences in median gestational age from omphalocele when prenatally identified. CONCLUSIONS: In BWS, omphalocele is the most common prenatal finding and routinely observed in early gestation with 100% accuracy. Associated findings of macrosomia, macroglossia, visceromegaly, and retrognathia, when present, are detected later in gestation. Imaging in later gestation may reveal additional abnormalities that support a BWS diagnosis.

An algorithm for predicting Robin sequence from fetal MRI.

BACKGROUND: Infants with Robin sequence (RS) may present with airway compromise at delivery. Prenatal diagnosis would improve preparation and postnatal care. The purpose of this study was to devise a predictive algorithm for RS based on fetal magnetic resonance imaging (MRI). METHODS: Retrospective case-control study including fetal MRIs from 2002 to 2017. Inclusion criteria were (1) MRI of adequate quality, (2) live-born infant, and (3) postnatal evaluation. Subjects were grouped on the basis of postnatal diagnosis: (1) RS (micrognathia, glossoptosis, airway obstruction), (2) micrognathia without airway obstruction ("micrognathia"), (3) cleft lip and palate ("CLP"), and (4) gestational age-matched controls. A series of possible predictive variables were assessed on MRI. Receiver operator curves were applied to identify cut-off values, and a multivariable algorithm was developed. RESULTS: A total of 162 subjects with mean gestational age at MRI of 25.6 ± 4.9 weeks were included: RS, n = 27 (17%); micrognathia, n = 35 (22%); CLP, n = 46 (28%); control, n = 54 (33%). Three variables were independent predictors of RS: (1) Veau I/II cleft palate (OR = 38.8), (2) tongue shape index (>80%; OR = 8.7), and (3) inferior facial angle (<48°; OR = 14.5). CONCLUSION: MRI findings of cleft palate, TSI >80% and IFA <48° indicate a 98% probability of RS, whereas a lack of all 3 features denotes a likelihood of 1%.

Micrognathia and Oropharyngeal Space in Patients With Robin Sequence: Prenatal MRI Measurements.

PURPOSE: Micrognathia is the initiating feature of Robin sequence (RS) and leads to airway obstruction. Prenatal identification of micrognathia is currently qualitative and has not correlated with postnatal findings in previous studies. Oropharyngeal airway space has not been evaluated prenatally. The purposes of this study were to 1) quantitate mandibular characteristics and oropharyngeal size at prenatal magnetic resonance imaging (MRI) and 2) identify differences in fetuses with postnatal RS compared with those with micrognathia (without RS) and normal controls. MATERIALS AND METHODS: This is a retrospective case-control study of fetuses with prenatal MRIs performed from 2002 through 2017 who were live born and evaluated postnatally for craniofacial findings. Postnatal findings were used to divide patients into 3 groups: 1) RS (micrognathia, glossoptosis, and airway obstruction), 2) micrognathia without RS ("micrognathia"), and 3) a gestational-age matched control group with normal craniofacial morphology ("control"). Inferior facial angle (IFA), jaw index, and oropharyngeal space (OPS) were calculated and compared among groups. RESULTS: Of 116 patients in this study, 27 had RS (23%), 35 had micrognathia (30%), and 54 were control subjects (47%). IFA, jaw index, and OPS were statistically significantly smaller in the RS group compared with the comparison groups (P < .0001). CONCLUSIONS: Prenatal MRI measurements of micrognathia and OPS are considerably different in patients with RS compared with other groups, including those with micrognathia alone. These measurements might serve as reliable prenatal predictors of RS.

Pathogenesis of Cleft Palate in Robin Sequence: Observations From Prenatal Magnetic Resonance Imaging.

PURPOSE: The etiology of the palatal cleft in Robin sequence (RS) is unknown. The purpose of this study was to assess the position of the fetal tongue at prenatal magnetic resonance imaging (MRI) and to suggest a potential relation between tongue position and development of the cleft palate seen in most patients with RS. MATERIALS AND METHODS: This is a retrospective case-and-control study including fetuses with prenatal MRIs performed in the authors' center from 2002 to 2017. Inclusion criteria were 1) prenatal MRI of adequate quality, 2) liveborn infant, and 3) postnatal diagnosis of RS (Robin group) or cleft lip and palate (CLP group). Patients with postnatal RS without a palatal cleft were excluded. A control group with normal facial morphology was matched by gestational age. The outcome variable was tongue position at fetal MRI, described as within the cleft, along the floor of the mouth (normal), other, or indeterminate. RESULTS: One hundred twenty-two patients with mean gestational age at MRI of 25.8 ± 4.9 weeks were included (Robin, n = 21 [17%]; CLP, n = 47 [39%]; control, n = 54 [44%]). The tongue was visualized within the palatal cleft in 76.2% of the Robin group and 4.3% of the CLP group. The tongue was found along the floor of the mouth (normal) in the remainder of the Robin and CLP groups and in 100% of the control group. CONCLUSION: These findings suggest a relation between in utero tongue position and the development of cleft palate in RS.

Constant inhibition in congenital lower extremity shortening: does it begin in utero?

BACKGROUND: Limb-length discrepancy (LLD) in children with congenital lower extremity shortening is constant in proportion from birth to skeletal maturity (known as constant inhibition), but its developmental pattern in utero is unknown. The popular prenatal multiplier method to predict LLD at birth assumes constant inhibition in utero to be true. Verifying the in utero developmental pattern of LLD, and thus confirming the validity of the prenatal multiplier method, is crucial for meaningful prenatal parental counseling. OBJECTIVE: To elucidate the in utero developmental pattern of LLD in fetuses with congenital lower extremity shortening. MATERIALS AND METHODS: Clinical indications for 3,605 lower extremity radiographs performed on infants (<1 year old) at a large tertiary hospital over a 17-year period were reviewed. Inclusion criteria were (1) diagnosis of congenital lower extremity shortening, (2) bilateral lower limb postnatal radiographs documenting LLD and (3) fetal ultrasound (US) documenting LLD. Available measurements of femoral, tibial and fibular lengths on fetal US and postnatal radiographs were collected. Prenatal and postnatal length ratios of shorter-to-longer bones were calculated and compared. RESULTS: Eighteen infants met inclusion criteria. Diagnoses were proximal focal femoral deficiency=4, congenital short femur=2, tibial hemimelia=3, posteromedial tibial bowing=6 and fibular hemimelia=3. The correlations between postnatal and prenatal length ratios were high for the femur, tibia and fibula (R>0.98, P<0.0001). The relative differences in the postnatal and prenatal length ratios of these bones were small (|average|<0.026, standard deviation <0.068). CONCLUSION: Our data indicate that the postnatal and prenatal length ratios were equivalent, supporting the constant inhibition pattern of LLD in utero, thus validating the prenatal multiplier method for predicting LLD.

Maternal CD4+ T cells protect against severe congenital cytomegalovirus disease in a novel nonhuman primate model of placental cytomegalovirus transmission.

Elucidation of maternal immune correlates of protection against congenital cytomegalovirus (CMV) is necessary to inform future vaccine design. Here, we present a novel rhesus macaque model of placental rhesus CMV (rhCMV) transmission and use it to dissect determinants of protection against congenital transmission following primary maternal rhCMV infection. In this model, asymptomatic intrauterine infection was observed following i.v. rhCMV inoculation during the early second trimester in two of three rhCMV-seronegative pregnant females. In contrast, fetal loss or infant CMV-associated sequelae occurred in four rhCMV-seronegative pregnant macaques that were CD4(+) T-cell depleted at the time of inoculation. Animals that received the CD4(+) T-cell-depleting antibody also exhibited higher plasma and amniotic fluid viral loads, dampened virus-specific CD8(+) T-cell responses, and delayed production of autologous neutralizing antibodies compared with immunocompetent monkeys. Thus, maternal CD4(+) T-cell immunity during primary rhCMV infection is important for controlling maternal viremia and inducing protective immune responses that prevent severe CMV-associated fetal disease.

In Utero Glossoptosis in Fetuses With Robin Sequence: Measurements From Prenatal MRI.

OBJECTIVE: Glossoptosis causes airway obstruction in patients with Robin sequence (RS), but little is known about the in-utero tongue. The purpose of this study was to assess shape and position of the fetal tongue on prenatal magnetic resonance imaging (MRI) to determine if this is predictive of postnatal RS. DESIGN: Retrospective case-control study including fetuses with prenatal MRIs performed from 2002 to 2017. Inclusion criteria were (1) prenatal MRI of adequate quality, (2) live born and evaluated postnatally for craniofacial findings. Subjects were divided into groups based on postnatal findings: (1) RS, (2) micrognathia without RS, and (3) a gestational-age-matched control group with normal craniofacial morphology. Outcome variables were based on the prenatal MRI and included fetal tongue height, length, and width, tongue shape index (TSI, ratio of height to length), and observation of tongue touching the posterior pharyngeal wall. RESULTS: A total of 116 subjects with mean gestational age at MRI of 25.6 ± 5.1 weeks were included: RS, n = 27 (23%); micrognathia, n = 35 (30%); control, n = 54 (47%). Tongue length was significantly shorter ( P = .009) and TSI was significantly larger in the RS group ( P < .0001). The tongue touched the posterior pharyngeal wall in 5 (19%) of the RS group and in no subjects in the other groups ( P < .0001). CONCLUSION: In utero tongue shape and position were significantly different in fetuses with postnatal RS compared to those with isolated micrognathia and controls. Prenatal MRI tongue characteristics may be predictors for postnatal RS.

Temporal slice registration and robust diffusion-tensor reconstruction for improved fetal brain structural connectivity analysis.

Diffusion weighted magnetic resonance imaging, or DWI, is one of the most promising tools for the analysis of neural microstructure and the structural connectome of the human brain. The application of DWI to map early development of the human connectome in-utero, however, is challenged by intermittent fetal and maternal motion that disrupts the spatial correspondence of data acquired in the relatively long DWI acquisitions. Fetuses move continuously during DWI scans. Reliable and accurate analysis of the fetal brain structural connectome requires careful compensation of motion effects and robust reconstruction to avoid introducing bias based on the degree of fetal motion. In this paper we introduce a novel robust algorithm to reconstruct in-vivo diffusion-tensor MRI (DTI) of the moving fetal brain and show its effect on structural connectivity analysis. The proposed algorithm involves multiple steps of image registration incorporating a dynamic registration-based motion tracking algorithm to restore the spatial correspondence of DWI data at the slice level and reconstruct DTI of the fetal brain in the standard (atlas) coordinate space. A weighted linear least squares approach is adapted to remove the effect of intra-slice motion and reconstruct DTI from motion-corrected data. The proposed algorithm was tested on data obtained from 21 healthy fetuses scanned in-utero at 22-38 weeks gestation. Significantly higher fractional anisotropy values in fiber-rich regions, and the analysis of whole-brain tractography and group structural connectivity, showed the efficacy of the proposed method compared to the analyses based on original data and previously proposed methods. The results of this study show that slice-level motion correction and robust reconstruction is necessary for reliable in-vivo structural connectivity analysis of the fetal brain. Connectivity analysis based on graph theoretic measures show high degree of modularity and clustering, and short average characteristic path lengths indicative of small-worldness property of the fetal brain network. These findings comply with previous findings in newborns and a recent study on fetuses. The proposed algorithm can provide valuable information from DWI of the fetal brain not available in the assessment of the original 2D slices and may be used to more reliably study the developing fetal brain connectome.

Fetal lung apparent diffusion coefficient measurement using diffusion-weighted MRI at 3 Tesla: Correlation with gestational age.

PURPOSE: To evaluate the feasibility of using diffusion-weighted magnetic resonance imaging (DW-MRI) to assess the fetal lung apparent diffusion coefficient (ADC) at 3 Tesla (T). MATERIALS AND METHODS: Seventy-one pregnant women (32 second trimester, 39 third trimester) were scanned with a twice-refocused Echo-planar diffusion-weighted imaging sequence with 6 different b-values in 3 orthogonal diffusion orientations at 3T. After each scan, a region-of-interest (ROI) mask was drawn to select a region in the fetal lung and an automated robust maximum likelihood estimation algorithm was used to compute the ADC parameter. The amount of motion in each scan was visually rated. RESULTS: When scans with unacceptable levels of motion were eliminated, the lung ADC values showed a strong association with gestational age (P < 0.01), increasing dramatically between 16 and 27 weeks and then achieving a plateau around 27 weeks. CONCLUSION: We show that to get reliable estimates of ADC values of fetal lungs, a multiple b-value acquisition, where motion is either corrected or considered, can be performed. J. Magn. Reson. Imaging 2016;44:1650-1655.

Normative biometrics for fetal ocular growth using volumetric MRI reconstruction.

OBJECTIVE: To determine normative ranges for fetal ocular biometrics between 19 and 38 weeks gestational age (GA) using volumetric MRI reconstruction. METHOD: The 3D images of 114 healthy fetuses between 19 and 38 weeks GA were created using super-resolution volume reconstructions from MRI slice acquisitions. These 3D images were semi-automatically segmented to measure fetal orbit volume, binocular distance (BOD), interocular distance (IOD), and ocular diameter (OD). RESULTS: All biometry correlated with GA (Volume, Pearson's correlation coefficient (CC) = 0.9680; BOD, CC = 0.9552; OD, CC = 0.9445; and IOD, CC = 0.8429), and growth curves were plotted against linear and quadratic growth models. Regression analysis showed quadratic models to best fit BOD, IOD, and OD and a linear model to best fit volume. CONCLUSION: Orbital volume had the greatest correlation with GA, although BOD and OD also showed strong correlation. The normative data found in this study may be helpful for the detection of congenital fetal anomalies with more consistent measurements than are currently available. © 2015 John Wiley & Sons, Ltd.

Human fetal sacrococcygeal extension or 'tail' in the second trimester: prenatal diagnosis, associated findings, and clinical outcome.

BACKGROUND: There are over 30 cases of prenatally diagnosed sacral extensions or human 'tails' in the literature, including isolated and syndromic etiologies. Most cases were reported to resolve by the second trimester and postnatal course was benign. Our objective was to describe the prenatal findings, associated anomalies, and clinical outcome of a series of seven fetuses diagnosed prenatally with fetal sacrococcygeal extension. METHODS: In a prospective study on a series of 4040 consecutive patients seen through our clinic in a 10-year period, 7 patients had a sacrococcygeal extension identified on fetal imaging. Fetal sonographic and magnetic resonance imaging findings, results of genetic testing, and clinical outcomes were analyzed. RESULTS: All seven fetuses had associated anomalies, including neurologic, craniofacial, cardiac, spinal, renal, and musculoskeletal abnormalities, or abnormal ultrasound findings including growth restriction and abnormal umbilical cord Doppler. There were two cases of trisomy 13 and one case of Pfeiffer syndrome. The mean gestational age at diagnosis was 19.3 weeks. CONCLUSION: When a sacrococcygeal extension is seen on fetal imaging, work-up should include detailed fetal imaging and karyotype, and fetal growth should be monitored. Our experience with fetal sacrococcygeal extension demonstrates variability in the underlying presentation and etiology, making counseling in a prenatal setting challenging.

Prospective evaluation of a prenatal sonographic clubfoot classification system.

BACKGROUND: The purpose of this study was to prospectively evaluate our recently described fetal sonographic classification system for prenatal diagnosis of clubfoot. METHODS: Over 18 months, we prospectively enrolled consecutive pregnant patients evaluated for a prenatally diagnosed clubfoot. Prenatal sonographic scores assigned by a radiologist were compared to final clinical diagnosis and severity given by a pediatric orthopedic surgeon. Pearson's χ(2) test and logistic regression were used in statistical analyses on the subject level. Generalized estimating equations were used in analyses on the foot level to account for intrasubject correlation. RESULTS: There were 50 subjects, with 26 unilateral and 24 bilateral clubfeet, according to the prenatal ultrasound (US). A total of 51 (69%) of 74 feet and 36 (72%) of 50 subjects had a postnatal diagnosis of clubfoot. The accuracy of diagnosis in cases of a severe, moderate, and mild US score was 94, 70, and 25%, respectively (p = 0.003 comparing moderate-severe vs. mild). US severity correlated with the Dimeglio classification scoring system (Spearman's correlation 0.30). CONCLUSION: The fetal sonographic scoring system is predictive of clinical severity after birth, and improves the ability to counsel families with a prenatal diagnosis of clubfoot.