Clinical outcome is associated with the Urinary Tract Dilatation Classification System grade.

AIM: To assess the association between the Urinary Tract Dilatation (UTD) Antenatal (A) and Postnatal (P) Classification System grade and the outcome in term newborns. METHODS: This retrospective study enrolled 166 term newborns (71% boys, 206 ureterorenal units) evaluated for unilateral or bilateral UTD in the Neonatology Department of Ljubljana University Medical Center from 2012 to 2018. Data on family history, sex, gestational age, birth weight, head circumference, Apgar score, possible oligohydramnios, indication for and age at first postnatal ultrasound, time of follow-up, and clinical outcome were collected. Radiology records were reviewed to grade UTD according to the Multidisciplinary Consensus on the Classification of Prenatal and Postnatal UTD. RESULTS: The majority of ureterorenal units with UTD A 2-3 had UTD P 2 or 3. Spontaneous resolution, specific uropathy, the need for surgery, and the risk of urinary tract infection were all significantly associated with the UTD P grade. No patient experienced renal dysfunction at the end of follow-up (12-48 months, median 24 months), and therefore this parameter was not associated with the UTD P grade. CONCLUSIONS: The UTD grade was associated with the probability of spontaneous resolution, time to its occurrence, specific uropathies urinary tract infection, and risk for surgery. However, no association with renal dysfunction was established.

Molecular characteristics of thalassemia and hemoglobin variants in prenatal diagnosis program in northern Thailand.

Molecular analysis of globin genes is an essential process for prenatal diagnosis (PND) of severe thalassemia. This study aimed to describe the molecular characteristics of thalassemia and hemoglobin (Hb) variants in PND program in northern Thailand. The type and frequency of globin gene mutations from 1290 couples at risk of fetal severe thalassemia diseases that were tested at Thalassemia Laboratory at Chiang Mai University from 2012 to 2017 were retrospectively reviewed. The PND program detected 444 (34.4%), 196 (15.2%) and 642 (49.8%) couples at risk of fetal Hb Bart's hydrops fetalis, beta-thalassemia major (BTM) and beta-thalassemia/Hb E disease, respectively. Coinheritance of more than one type of thalassemia was common and eight (0.6%) couples were at risk of two types of severe thalassemia. There were two types of alpha0-thalassemia; 893 (99.7%) Southeast Asian and 3 (0.3%) Thai deletions. Twenty beta-globin gene mutations were found with 94.3% of beta0-thalassemia. The codon 41/42 (- TTCT), codon 17 (A>T), IVS-I-1 (G>T) and codon 71/72 (+ A) comprised 90% of beta-thalassemia mutations. The study shows a high percentage of couples at risk of fetal Hb Bart's hydrops fetalis and BTM. The percentage of beta0-thalassemia is higher than those seen in other regions of Thailand.

The antenatal urinary tract dilation classification system accurately predicts severity of kidney and urinary tract abnormalities.

BACKGROUND: Urinary tract dilation (UTD) is a commonly diagnosed prenatal condition; however, it is currently unknown which features lead to benign and resolving or pathologic abnormalities. A consensus UTD classification system (antenatal UTD classification, UTD-A) was created by Nguyen et al. in 2014 [1], but has not yet been validated. OBJECTIVE: To evaluate the ability of the UTD-A system to identify kidney and urinary tract (KUT) abnormalities, assess whether UTD-A can predict severity of KUT conditions, and perform a cost analysis of screening ultrasound (US). METHODS: A retrospective single-center study was conducted at an academic medical center. Inclusion criteria were: neonates in the well or sick nursery who had a complete abdominal or limited renal US performed in the first 30 days of life between January 01, 2011 and December 31, 2013. Data were collected on prenatal US characteristics from which UTD-A classification was retrospectively applied, and postnatal data were collected up to 2 years following birth. RESULTS: A total of 203 patients were identified. Of the 36 abnormal postnatal KUT diagnoses, 90% were identified prenatally as UTD A1 or UTD A2-3. The remaining 10% developed postnatal KUT abnormalities due to myelomeningocele, such as VUR or UTD, which were not evident prenatally. Overall sensitivity and specificity of the UTD-A system was 0.767 (95% CI 0.577, 0.901) and 0.836 (95% CI 0.758, 0.897), respectively, when resolved UTD was counted as a normal diagnosis. Postnatal diagnoses differed by UTD-A classification as shown in the Summary fig. Of all the obstructive uropathies, 90.9% occurred in the UTD A2-3 class and none occurred in UTD-A Normal. Rate of postnatally resolved UTD was significantly higher in the UTD A1 group (78%) compared with UTD A2-3 (31%) or UTD-A Normal (12%, all P < 0.001). There was a notable trend towards more UT surgeries, UTI, and positive VUR among UTD A2-3 patients, but statistical significance was limited by a small number of patients. CONCLUSIONS: This study found that the UTD-A classification system revealed important differences in the severity of UTD abnormalities. With repeated validation in larger cohorts, the UTD-A classification may be used to offer a prognosis for parents regarding prenatally diagnosed KUT conditions. Larger prospective studies should be designed to validate whether the UTD-A system can predict postnatal events related to UTD morbidity such as need for UT-related surgery or UTI.

The pathology of congenital lung lesions.

The spectrum of complications associated with congenital lung malformation is wide. They can range from fetal hydrops in utero to postnatal problems of ventilation, obstruction and infection; presentation may occur from the neonatal period to adulthood. Many lesions will remain asymptomatic while at the other end of the complication spectrum, there is a small risk of neoplasia associated with some forms of cystic lung. A better understanding of the pathology has shown that bronchial atresia/obstruction is the likely hidden pathology underlying many congenital lung lesions leading to downstream cystic maldevelopment. Earlier diagnosis has led to increasing difficulties in ascribing malformations to conventional categories that were originally described in postnatal lungs. It is probably more important to be aware of the potential combination of vascular and airway connections and complications than to try and prescribe a classification of pulmonary lesions associated with rigid definitions.

The diagnostic features of spina bifida: the role of ultrasound.

Myelomeningocele (MMC) is one of the most devastating, nonlethal congenital anomalies worldwide. The live birth prevalence of MMC changed dramatically in the 1980s with the introduction of maternal serum screening and the widespread use of prenatal ultrasound imaging. The high-resolution ultrasound affordable today with state-of-the-art equipment allows us to make a very accurate diagnosis of MMC, including details related to the entire fetal central nervous system. Ultrasound can accurately localize the site of the osseous and soft tissue defects. Congenital spinal defects can be characterized definitively as open or closed, which are treated very differently with in utero repair, which is done in some cases, compared to only conservative follow-up with postnatal therapy for occult defects. Additional findings of kyphosis, scoliosis and anomalous vertebrate and associated conditions such as cervical syrinx can be identified. The state of the intracranial structures, including the presence or absence of ventriculomegaly and hindbrain herniation, as well as unexpected complications such as intracranial hemorrhage can be diagnosed. The severity of neurological compromise in some fetuses can be estimated by detailed examination of the lower extremities. As well as searching for talipes, we also now routinely characterize flexion and extension motions at the hip, knee and ankle joints. The information provided by ultrasound plays a crucial role, now more than ever, in patient counseling and pregnancy management. This article emphasizes how we utilize ultrasound in the evaluation of patients with suspected MMC at the Center for Fetal Diagnosis and Treatment at the Children's Hospital of Philadelphia.

Fetal skeletal dysplasias in a tertiary care center: radiology, pathology, and molecular analysis of 112 cases.

Fetal skeletal dysplasias are a heterogeneous group of rare genetic disorders, affecting approximately 2.4-4.5 of 10,000 births. We performed a retrospective review of the perinatal autopsies conducted between the years 2002-2011 at our center. The study population consisted of fetuses diagnosed with skeletal dysplasia with subsequent termination, stillbirth and live-born who died shortly after birth. Of the 2002 autopsies performed, 112 (5.6%) were diagnosed with skeletal dysplasia. These 112 cases encompassed 17 of 40 groups of Nosology 2010. The two most common Nosology groups were osteogenesis imperfecta [OI, 27/112 (24%)] and the fibroblast growth factor receptor type 3 (FGFR3) chondrodysplasias [27/112 (24%)]. The most common specific diagnoses were thanatophoric dysplasia (TD) type 1 [20 (17.9%)], and OI type 2 [20 (17.9%)]. The combined radiology, pathology, and genetic investigations and grouping the cases using Nosology 2010 resulted in a specific diagnosis in 96 of 112 cases.

Multidisciplinary consensus on the classification of prenatal and postnatal urinary tract dilation (UTD classification system).

OBJECTIVE: Urinary tract (UT) dilation is sonographically identified in 1-2% of fetuses and reflects a spectrum of possible uropathies. There is significant variability in the clinical management of individuals with prenatal UT dilation that stems from a paucity of evidence-based information correlating the severity of prenatal UT dilation to postnatal urological pathologies. The lack of correlation between prenatal and postnatal US findings and final urologic diagnosis has been problematic, in large measure because of a lack of consensus and uniformity in defining and classifying UT dilation. Consequently, there is a need for a unified classification system with an accepted standard terminology for the diagnosis and management of prenatal and postnatal UT dilation. METHODS: A consensus meeting was convened on March 14-15, 2014, in Linthicum, Maryland, USA to propose: 1) a unified description of UT dilation that could be applied both prenatally and postnatally; and 2) a standardized scheme for the perinatal evaluation of these patients based on sonographic criteria (i.e. the classification system). The participating societies included American College of Radiology, the American Institute of Ultrasound in Medicine, the American Society of Pediatric Nephrology, the Society for Fetal Urology, the Society for Maternal-Fetal Medicine, the Society for Pediatric Urology, the Society for Pediatric Radiology and the Society of Radiologists in Ultrasounds. RESULTS: The recommendations proposed in this consensus statement are based on a detailed analysis of the current literature and expert opinion representing common clinical practice. The proposed UTD Classification System (and hence the severity of the UT dilation) is based on six categories in US findings: 1) anterior-posterior renal pelvic diameter (APRPD); 2) calyceal dilation; 3) renal parenchymal thickness; 4) renal parenchymal appearance; 5) bladder abnormalities; and 6) ureteral abnormalities. The classification system is stratified based on gestational age and whether the UT dilation is detected prenatally or postnatally. The panel also proposed a follow-up scheme based on the UTD classification. CONCLUSION: The proposed grading classification system will require extensive evaluation to assess its utility in predicting clinical outcomes. Currently, the grading system is correlated with the risk of postnatal uropathies. Future research will help to further refine the classification system to one that correlates with other clinical outcomes such as the need for surgical intervention or renal function.

Diagnostic and clinical classification of autoimmune myasthenia gravis.

Myasthenia gravis is characterized by muscle weakness and abnormal fatigability. It is an autoimmune disease caused by the presence of antibodies against components of the muscle membrane localized at the neuromuscular junction. In most cases, the autoantibodies are against the acetylcholine receptor (AChR). Recently, other targets have been described such as the MuSK protein (muscle-specific kinase) or the LRP4 (lipoprotein related protein 4). Myasthenia gravis can be classified according to the profile of the autoantibodies, the location of the affected muscles (ocular versus generalized), the age of onset of symptoms and thymic abnormalities. The disease generally begins with ocular symptoms (ptosis and/or diplopia) and extends to other muscles in 80% of cases. Other features that characterize MG include the following: variability, effort induced worsening, successive periods of exacerbation during the course of the disease, severity dependent on respiratory and swallowing impairment (if rapid worsening occurs, a myasthenic crisis is suspected), and an association with thymoma in 20% of patients and with other autoimmune diseases such as hyperthyroidism and Hashimoto's disease. The diagnosis is based on the clinical features, the benefit of the cholinesterase inhibitors, the detection of specific autoantibodies (anti-AChR, anti-MuSK or anti-LRP4), and significant decrement evidenced by electrophysiological tests. In this review, we briefly describe the history and epidemiology of the disease and the diagnostic and clinical classification. The neonatal form of myasthenia is explained, and finally we discuss the main difficulties of diagnosis.

Comparison of five classification systems for interpreting electronic fetal monitoring in predicting neonatal status at birth.

OBJECTIVE: To compare the accuracy of five different classification systems for interpreting electronic fetal monitoring (EFM) when predicting neonatal status at birth, as determined by the umbilical cord arterial pH. METHODS: Ninety-seven cardiotocography traces were retrospectively interpreted according to five classification systems for EFM: Dublin Fetal Heart Rate Monitoring Trial (DFHRMT), Royal College of Obstetricians and Gynecologists (RCOG), Society of Obstetricians and Gynaecologists of Canada (SOGC), National Institute of Child Health and Human Development (NICHD) and Parer & Ikeda's. For each classification system, sensitivity, specificity, positive and negative predictive values were calculated. The capacity of the classifications to predict neonatal pH was also evaluated by receiver-operating characteristic (ROC) curves. Agreement between the five systems was estimated using weighted kappa statistic. RESULTS: Considering pH ≤7.15 as the cutoff for low pH, the sensitivity and specificity values were 100 and 18% (DFHRMT); 100 and 15% (RCOG); 88 and 37% (SOGC); 67 and 92% (NICHD); 55 and 67% (Parer & Ikeda). The ROC curves showed that all classifications analyzed had a low discriminative capacity when predicting umbilical artery pH ≤7.15. An excellent agreement was observed between DFHRMT and RCOG (weighted κ value: 0.860). CONCLUSIONS: Parer & Ikeda and NICHD classifications had the highest specificity in detecting umbilical cord arterial pH ≤7.15. The high specificity of the NICHD classification is hindered by a high percentage of "intermediate" traces (80%). Parer & Ikeda classification is the one that best classify as pathological only the traces of fetuses that are truly at risk of acidemia, thus avoiding unnecessary intervention. It also showed the best trade-off between sensitivity and specificity and the lowest rate of traces considered "intermediate."

Diagnosis, treatment, and long-term outcomes of fetal hydrocephalus.

This study analyzed 156 cases of fetal hydrocephalus treated at Osaka National Hospital from 1992 to 2011 to review current methods for diagnosing and treating fetal hydrocephalus, and for estimating its clinical outcome. This was a retrospective study of a single institute (Osaka National Hospital). Of 156 cases in total, 37% were diagnosed as isolated ventriculomegaly, 50% as another type of malformation (36 cases of myelomeningocele, six of holoprosencephaly, three of Dandy-Walker syndrome, one case of Joubert syndrome, 12 of arachnoid cyst, nine of encephalocele, three of atresia of Monro and eight of corpus callosum agenesis, and 13% as secondary hydrocephalus. Diagnoses were made between 13 and 40 weeks of gestation (average 27 weeks). Diagnosis was made before 21 weeks of gestation in 24% of cases, from the first day of 22 weeks to the sixth day of 27 weeks in 27%, and after the first day of 28 weeks in 49%. With the exclusion of 17 aborted cases and 40 cases in which the patients were too young to evaluate or lost during follow-up, the final outcome was analyzed for 90 cases. Of these, 17% of the patients died, 21% showed severe retardation, 13% moderate retardation, 26% mild retardation, and 23% showed a good outcome. The long-term outcome was mostly influenced by the basic disease and accompanying anomaly. The time of diagnosis showed no correlation with outcome. Hydrocephalus associated with arachnoid cyst, atresia of Monro, and corpus callosum agenesis, and hydrocephalus due to fetal intracranial hemorrhage, resulted in good outcomes. By contrast, holoprosencephaly, hydrocephalus associated with encephalocele, syndromic hydrocephalus, and hydrocephalus due to fetal virus infection led to poor outcomes. For accurate diagnosis and proper counseling, established protocols are important for the diagnosis and treatment of fetal hydrocephalus, including not only fetal sonography, fetal magnetic resonance imaging, and TORCH (toxoplasma, rubella, cytomegalovirus, herpes simplex) screening test, but also chromosomal and gene testing.

Imaging diagnosis of congenital brain anomalies and injuries.

Fetal brain is rapidly developing and changing its appearance week by week during pregnancy. The brain is the most important organ but it is quite hard to observe detailed structure of this organ by conventional transabdominal sonography. Transvaginal high-resolution ultrasound and three-dimensional (3D) ultrasound has been a great diagnostic tool for evaluation of three-dimensional structure of fetal central nervous system (CNS). This method has contributed to the prenatal assessment of congenital CNS anomalies, intracranial vascular anomalies and acquired brain damage in utero. It is possible to observe the whole brain structure by magnetic resonance imaging in the post half of pregnancy but transvaginal high-resolution 3D ultrasound is certainly powerful modality as well for understanding brain anatomy. Longitudinally and carefully evaluation of neurological short- or long-term prognosis should be required according to precise prenatal diagnosis, for proper counseling and management based on precise evidence.

Isolated congenital megacystis without intestinal obstruction: a mild variant of chronic intestinal pseudoobstruction syndrome?

Megacystis is frequently involved with chronic intestinal pseudoobstruction syndrome; however, isolated megacystis without intestinal obstruction is extremely rare. We present the case of a female patient with isolated congenital megacystis without severe intestinal obstruction. In this case, barium enema did not reveal any significant findings; however, histologic evaluation of her rectum showed hypoganglionosis of the submucous and myenteric plexuses. These findings indicate that this case may be a mild variant of chronic intestinal pseudoobstruction syndrome. The presence of megacystis should alert the physician to the possibility of chronic intestinal pseudoobstruction syndrome.

[Specificities of neonatal hemostasis and implications in pathologic situations]. / Particularités de l'hémostase chez le nouveau-né et implications en pathologie.

The haemostasis of healthy newborn differs from those of normal adult but remains well balanced without bleeding or thrombosis. However, this equilibrium is unstable, and the neonate is exposed to acquired or inherited haemostasis disorders that necessitate to be early diagnosed in order to be appropriately treated. Several studies provided reference ranges for haemostatic components in the foetus, the newborn and throughout childhood. The particularities of neonatal haemostasis are therefore better defined and contribute to further understand the pathophysiology and characteristics of hemorrhagic and thrombotic disorders that occur in newborns. Some examples of the impact of age on haemostasis are: the risk of neonatal alloimmune thrombocytopenia is high in the first newborn of a woman at risk since the involved antigens are fully expressed by foetal platelets; the newborn is at risk for vitamin K deficiency with bleeding due to poor transport of vitamin K across the placenta and low levels of coagulation factors II, VII, IX, X; the diagnosis of some inherited coagulation deficiencies can be difficult in the newborn due to physiologically low levels of coagulation factors; thrombotic events are rare in the healthy neonate, despite physiologically very low levels of several coagulation inhibitors; the pharmacokinetic and effects of antithrombotic agents are influenced by the specificities of haemostasis in neonates. This review will discuss about the foetal development of haemostasis until birth, and some implications regarding the pathophysiology, the diagnosis and the treatment of bleeding disorders in the human neonate.

Diagnosing foetal atrioventricular heart blocks.

Foetal echocardiographic ultrasound techniques still remain the dominating modality for diagnosing foetal atrioventricular block (AVB). Foetal electrocardiography might become a valuable tool to measure time intervals, but magnetocardiography is unlikely to get a place in clinical practice. Assuming that AVB is a gradually progressing and preventable disease, starting during a critical period in mid-gestation with a less abnormal atrioventricular conduction before progressing to a complete irreversible AVB (CAVB), echocardiographic methods to detect first-degree AVB have been developed. The time intervals obtained with these techniques are all based on the identification of mechanical or hemodynamic events as markers of atrial (A) and ventricular (V) depolarizations and will accordingly include both electrical and mechanical components. Prospective observational studies have demonstrated a transient prolongation of AV time intervals in anti-Ro/SSA antibody-exposed foetuses, but it has not succeeded to identify a degree of AV time prolongation predicting irreversible cardiac damage and progression to CAVB. Causes of sustained bradycardia include CAVB, 2:1 AVB, sinus bradycardia and blocked atrial bigeminy (BAB). Using foetal echocardiographic techniques and a systematic approach, a correct diagnosis can be made in almost every case. Sinus bradycardia and CAVB are usually easy to diagnose, but BAB has a tendency to be sustained and shows a high degree of resemblance with 2:1 AVB when diagnosed during mid-gestational. As BAB resolves without treatment and 2:1 AVB may respond to treatment with fluorinated steroids, a correct diagnosis becomes an issue of major importance to avoid unnecessary treatment of harmless and spontaneously reversing conditions.

A developmental and genetic classification for midbrain-hindbrain malformations.

Advances in neuroimaging, developmental biology and molecular genetics have increased the understanding of developmental disorders affecting the midbrain and hindbrain, both as isolated anomalies and as part of larger malformation syndromes. However, the understanding of these malformations and their relationships with other malformations, within the central nervous system and in the rest of the body, remains limited. A new classification system is proposed, based wherever possible, upon embryology and genetics. Proposed categories include: (i) malformations secondary to early anteroposterior and dorsoventral patterning defects, or to misspecification of mid-hindbrain germinal zones; (ii) malformations associated with later generalized developmental disorders that significantly affect the brainstem and cerebellum (and have a pathogenesis that is at least partly understood); (iii) localized brain malformations that significantly affect the brain stem and cerebellum (pathogenesis partly or largely understood, includes local proliferation, cell specification, migration and axonal guidance); and (iv) combined hypoplasia and atrophy of putative prenatal onset degenerative disorders. Pertinent embryology is discussed and the classification is justified. This classification will prove useful for both physicians who diagnose and treat patients with these disorders and for clinical scientists who wish to understand better the perturbations of developmental processes that produce them. Importantly, both the classification and its framework remain flexible enough to be easily modified when new embryologic processes are described or new malformations discovered.

Prenatal stroke.

The main focus of this chapter is the comprehensive description of the neuropathology, the imaging correlates and underlying mechanisms of prenatal stroke. We describe established prenatal stroke in subgroups similar to postnatal stroke: arterial (forebrain or hindbrain) infarction, venous thrombosis, primary lobar haemorrhage. This longitudinal classification should facilitate the study of risk factors and mechanisms. Forebrain lesions of arterial type present as porencephaly, (hemi)hydranencephaly, multicystic encephalopathy or schizencephaly. Venous prenatal forebrain stroke presents as simple porencephaly (in some of genetic nature) and sinus thrombosis. A list of rare porencephaly-like conditions is added for differentiation from arterial and venous porencephaly. Hindbrain infarctions (so far the only reported variants seem to be of arterial nature) present as brainstem disconnection, focal brainstem destruction, uni- or bilateral cerebellar destruction and focal spinal cord ischaemia. Prenatal intracranial haemorrhage and congenital brain infection should be considered in the differential diagnosis of prenatal stroke.