Changes in infant morbidity associated with decreases in neonatal mortality

Neonatal mortality and morbidity among infants surviving to 1 year of age in eight geographic areas have been compared to determine whether recent decreases in mortality have affected the risk of infants having congenital anomalies or developmental delay. Mortality was obtained from birth and death records in 1976 and either 1978 or 1979; morbidity through home interviews with mothers of random samples of infants and developmental observations on the children. It is concluded that the decrease in mortality was not offset by increases in children with defects. Neonatal mortality decreased by 18% in this 2- to 3-year period; risk of congenital anomalies or developmental delay (all types combined) declined by 16% among the surviving infants. The reduction in risk was concentrated in the minor congenital anomalies or developmental delay category; the proportion of children with severe or moderate congenital anomalies or developmental delay did not change. Decreases occurred at every birth weight including the very low birth weights of 1,500 g or less, a subgroup with especially high mortality and morbidity resulting from perinatal events.     

Perirenal hemorrhage as first presentation of Wilms tumor

Wilms tumor typically presents as an abdominal mass, though occasionally patients present with other manifestations. We report a case of a child presenting with a perirenal hemorrhage and an initially occult Wilms tumor, found only on subsequent renal arteriography. Symptoms in this patient were caused by the presence of perirenal and subcapsular hemorrhage rather than the tumor itself. Despite an unusual presentation, we need to consider underlying neoplasia in children with renal hemorrhage and the absence of a history of trauma. Follow-up studies might help clarify initial negative imaging results.     

Brain and ocular abnormalities in infants with in utero exposure to cocaine and other street drugs.

We describe 10 infants with developmental delay and congenital cerebral anomalies who were found to have had in utero exposure to vasoactive drugs. Nine infants had ophthalmological abnormalities; these included strabismus, nystagmus, and/or hypoplastic optic discs. Six mothers used cocaine, one used cocaine and heroin, one used only heroin, one used amphetamine, and one used phenylpropanolamine. Each of these cerebral anomalies (agenesis of the corpus callosum, septo-optic dysplasia, schizencephaly, hydranencephaly, congenital hydrocephalus, porencephaly, and cerebral infarctions) can be attributed to insults at different stages of development. There appears to be a relationship between the time of prenatal drug exposure and the type of cerebral anomaly, evoking malformations, disruptions, or fetal strokes. Since many or possibly all of these anomalies are thought to have a vascular origin, it seems appropriate to implicate prenatal exposure to vasoactive drugs.     

Clinicopathologic review of twelve children with nephropathy, Wilms tumor, and genital abnormalities (Drash syndrome)

The clinicopathologic and radiologic features of 12 children with complete and incomplete forms of Drash syndrome are reported. Their common denominator was a nephropathy. Four had the full triad, consisting of nephropathy, Wilms tumor, and genital abnormalities; five had nephropathy and genital abnormalities, and three had nephropathy and Wilms tumor. Of the 11 children who had proteinuria, eight had the nephrotic syndrome. Of the 10 whose condition progressed to end-stage renal failure, seven were less than 3 years of age. The histologic features of Wilms tumor were favorable in all seven children, and the tumor was bilateral in three. Of the nine patients who had genital abnormalities, eight had 46,XY karyotype and either ambiguous genitalia (six patients) or normal female phenotype (two). One other patient had a normal 46,XX female karyotype and phenotype but had both müllerian and wolffian structures and a streak ovary. Nine patients had a distinct pelvicaliceal abnormality not previously reported as a feature of this syndrome. Other congenital abnormalities were aniridia, mental retardation, deafness, nystagmus, and cleft palate. This syndrome must be considered in any infant with unexplained nephropathy, particularly in young phenotypic female infants and in those children with ambiguous genitalia or Wilms tumor with an early presentation.     

A CASE OF JARCHO-LEVIN SYNDROME ASSOCIATED WITH BILATERAL CYSTIC RENAL DISEASE AND WILMS TUMOR: MR Imaging Findings

Jarcho-Levin syndrome (JLS) is a congenital disorder characterized by a variety of vertebral and costal anomalies that result in thoracic deformity. Hitherto, a plethora of associated anomalies have been described in several reports. In this report, the authors describe a case of JLS who has Wilms tumor and bilateral cystic renal disease. To the authors’ knowledge, there is only a single case of JLS who presented with multiple renal cortical cysts, but none with an associated Wilms tumor in the literature. Additional anomalies seen in the present case that are related with this syndrome are also discussed.     

Case report: WT1 exon 6 truncation mutation and ambiguous genitalia in a patient with Denys-Drash syndrome

Denys-Drash syndrome is a rare genetic disorder featuring the triad of congenital nephropathy, Wilms tumor, and intersex disorders (XY under-virilization or XY female). Denys-Drash syndrome is associated with constitutional mutations in the Wilms tumor suppressor gene WT1. Unlike WAGR (Wilms tumor, aniridia, genitourinary anomalies, and mental retardation) syndrome, with its complete deletion of one copy of WT1, Denys-Drash syndrome is generally caused by a dominant-negative mutation. We present a new case of Denys-Drash syndrome in a patient initially diagnosed with XY ambiguous genitalia/partial androgen insensitivity syndrome, who was found to have a novel nonsense mutation in exon 6 leading to a stop codon and hence a truncated protein. Based on lessons learned from this patient, the diagnosis of Denys-Drash syndrome should be considered in the presence of ambiguous genitalia and partial androgen insensitivity.     

Neurological outcome in twins

Twins are at greater risk of death and severe morbidity than singletons which is in excess of that attributable to their greater prematurity. Monozygous, specifically monochorionic, twins are at greater risk than dichorionic twins. The major morbidity is neurological impairment usually presenting as cerebral palsy or severe learning disability and frequently, but not always, associated with fetal death of a co-twin. The likely pathogenesis of the neurological impairment is ischaemia attributable to haemodynamic imbalance via placental vascular anastomoses. In addition to the neurological impairment, congenital cardiac, renal, intestinal and other anomalies are more common but discordant in monozygous twins. It has been hypothesized that cerebral palsy and other neurological impairment in apparently singleton infants is attributable to early loss of a twin, the ‘vanishing’ twin phenomenon. It is also postulated that other congenital anomalies in singletons may be attributable to the same phenomenon.     

A case report of simultaneous occurrence of wilms tumor and acute lymphoblastic leukemia

Acute lymphoblastic leukemia (ALL) is the most and Wilms tumor is the sixth most common malignancy in childhood. Genetic changes in WT1 or WT2 in Wilms tumor and a wide range of chromosomal mutations are reported in ALL that may predispose them to other congenital anomalies especially in Wilms tumor patients. Hospitalized patient was a 3-year-old girl with high-grade fever, petechia, and solid abdominal mass. The patient had anemia, thrombocytopenia, and leukocytosis in her initial homogram, and a large renal mass originated from left kidney in abdominal imagings. Bone marrow aspiration revealed ALL, and simultaneous kidney biopsy uncovered her Wilms tumor. Leukemia and Wilms tumor are 2 independent malignancies but occurred together in this patient. It is reasonable to investigate cellular and genetic relation of these 2 independent malignancies.     

Screening for Wilms tumor and hepatoblastoma in children with Beckwith-Wiedemann syndromes: a cost-effective model

BACKGROUND: We undertook a cost-benefit analysis of screening for Wilms tumor and hepatoblastoma in children with Beckwith-Wiedemann syndrome (BWS), a known cancer predisposition syndrome. The purpose of this analysis was twofold: first, to assess whether screening in children with BWS has the potential to be cost-effective; second, if screening appears to be cost-effective, to determine which parameters would be most important to assess if a screening trial were initiated. PROCEDURES: We used data from the BWS registry at the National Cancer Institute, the National Wilms Tumor Study (NWTS), and large published series to model events for two hypothetical cohorts of 1,000 infants born with BWS. One hypothetical cohort was screened for cancer until a predetermined age, representing the base case. The other cohort was unscreened. For our base case, we assumed: (a) sonography examinations three times yearly (triannually) from birth until 7 years of age; (b) screening would result in one stage shift downward at diagnosis for Wilms tumor and hepatoblastoma; (c) 100% sensitivity and 95% specificity for detecting clinical stage I Wilms tumor and hepatoblastoma; (d) a 3% discount rate; (e) a false positive result cost of $402. We estimated mortality rates based on published Wilms tumor and hepatoblastoma stage specific survival. RESULTS: Using the base case, screening a child with BWS from birth until 4 years of age results in a cost per life year saved of $9,642 while continuing until 7 years of age results in a cost per life-year saved of $14,740. When variables such as cost of screening examination, discount rate, and effectiveness of screening were varied based on high and low estimates, the incremental cost per life-year saved for screening up until age four remained comparable to acceptable population based cancer screening ranges (< $50,000 per life year saved). CONCLUSIONS: Under our model's assumptions, abdominal sonography examinations in children with BWS represent a reasonable strategy for a cancer screening program. A cancer screening trial is warranted to determine if, when, and how often children with BWS should be screened and to determine cost-effectiveness in clinical practice.     

Survival of children born with congenital anomalies

Aim: To describe the survival to age 5 years of children born with congenital anomalies. Methods: Between 1980 and 1997, 6153 live born cases of congenital anomaly were diagnosed and registered by the population based Glasgow Register of Congenital Anomalies. They were retrospectively followed to assess their survival status from birth up to the age of 5 years. Results: The proportions of all live born infants with congenital anomalies surviving to the end of the first week, and first and fifth year were 94%, 89%, and 88%, respectively. Survival to age 5, the end point of follow up, was significantly poorer for infants with chromosomal anomalies (48%) compared to neural tube defects (72%), respiratory system anomalies (74%), congenital heart disease (75%), nervous system anomalies (77%), and Down''s syndrome (84%). Conclusion: Although almost 90% of all live born infants with congenital anomalies survive to 5 years, there are notable variations in survival between anomaly types. Our findings should be useful for both clinicians and geneticists to assess the prognosis of congenital anomalies. This information is also important for affected families and for the planning of health care needs for this high risk population.     

Survival of children born with congenital anomalies.

AIM: To describe the survival to age 5 years of children born with congenital anomalies. METHODS: Between 1980 and 1997, 6153 live born cases of congenital anomaly were diagnosed and registered by the population based Glasgow Register of Congenital Anomalies. They were retrospectively followed to assess their survival status from birth up to the age of 5 years. RESULTS: The proportions of all live born infants with congenital anomalies surviving to the end of the first week, and first and fifth year were 94%, 89%, and 88%, respectively. Survival to age 5, the end point of follow up, was significantly poorer for infants with chromosomal anomalies (48%) compared to neural tube defects (72%), respiratory system anomalies (74%), congenital heart disease (75%), nervous system anomalies (77%), and Down's syndrome (84%). CONCLUSION: Although almost 90% of all live born infants with congenital anomalies survive to 5 years, there are notable variations in survival between anomaly types. Our findings should be useful for both clinicians and geneticists to assess the prognosis of congenital anomalies. This information is also important for affected families and for the planning of health care needs for this high risk population.     

Non calcific vasculopathy in the basal ganglia.

Stripes of high echogenicity in the basal ganglia of infants have been rarely observed on cerebral ultrasound. These lesions, which appear to be due to a non calcific vasculopathy, are caused, in the majority of cases, by congenital infections and trisomy 13. We describe four infants with the characteristic ultrasonic appearance of this vasculopathy. Two children had cytomegalovirus (CMV) infection, one a human immunodeficiency virus (HIV) infection. The fourth child who presented a malformation of the skull and eye anomalies had no definitive diagnosis. Of the three surviving children one was developing normally. One had mild and one severe psychomotor retardation.     

Association of wilms tumor with spinal dysraphism

Previous data suggested an association of vertebral anomalies with Wilms tumor. At the same time, vertebral midline fusion defects are often indicated by dermal anomalies over the spine. In the present study the prevalence of both occult spina bifida and cutaneous signs of spinal dysraphism was significantly higher in 50 Wilms patients than in 180 control children (18.0 versus 4.4%, p <.01, and 35.9 versus 17.5%, p <.02, respectively). Family investigations are needed to answer the question whether signs of spinal dysraphism in parents and sibs of patients may be regarded as indicators of an increased risk of Wilms tumor in the family.     

Cavoatrial tumor extension in children with wilms tumor: a retrospective review of 17 children in a single center

The aim of this study was to evaluate the clinical characteristics and treatment results of 17 children with cavoatrial tumor extension of Wilms tumor. Of the 360 Wilms tumors diagnosed between 1980 and 2000, 17 patients with intracaval thrombus were identified from the medical records at the pediatric oncology department of Hacettepe University. The following data were collected and reviewed: age, sex, presenting symptoms, tumor site, presence of anaplasia, stage, associated congenital anomalies, localization of tumor thrombus, radiologic findings, type and duration of preoperative chemotherapy, response to preoperative chemotherapy, recurrences, and survival. The frequency of cavoatrial extension in this group was 4.7% (15 in the inferior vena cava and 2 in the right atrium). Fourteen patients received preoperative chemotherapy consisting of two-drug regimen (vincristine and actinomycin D) ranging from 1 to 12 weeks (median 4 weeks). Since intravascular invasion is often asymptomatic, a careful radiologic examination to detect tumor thrombus before surgery is essential. There is no need for aggressive surgery in the presence of tumor thrombus. It may be resolved by preoperative chemotherapy. Surgical removal of the thrombus should be considered in the presence of life-threatening tumor thrombosis at diagnosis and in patients who had residual thrombus after chemotherapy.     

Relationship between pressure passivity and subependymal/intraventricular hemorrhage as assessed by pulsed Doppler ultrasound

A prospective study was undertaken using a range-gated, pulsed Doppler velocimeter to study flowpressure relationships in the anterior cerebral artery. Serial velocity and pressure studies were performed with each infant serving as his or her own control. The hypothesis tested was that ill preterm infants sustaining subependymal/intraventricular hemorrhage would have absent autoregulation. The hypothesis has been tested in 88 studies on 32 infants. Of 32 infants studied, 15 were judged to be pressure passive; nine of these children bled. The other 17 infants were not pressure passive; eight of these children bled (P greater than .05). From these studies, it may be concluded that the pressure passive state is not the final common link in the genesis of subependymal/intravertricular hemorrhage. Pulsed Doppler ultrasound may provide an extremely useful noninvasive technique for studying both the arterial and venous sides of the cerebral circulation.     

Hemorrhagic stroke associated with pulmonary edema and catastrophic cardiac failure

Cerebral arteriovenous fistula (AVF) is a vascular malformation that is rare in the pediatric population. Older children with cerebral AVF tend to present with neurologic problems related to intracranial venous hypertension or intracranial hemorrhage. Cardiac and pulmonary complications following acute neurologic injury such as subarachnoid hemorrhage are common in adults, but are rarely reported in children. However, complications have been reported in cases of enterovirus 71 rhombencephalitis in infants and children and can cause high morbidity and mortality. Here, we report a 14-year-old boy who presented with cardiac failure associated with pulmonary edema following cerebral hemorrhagic stroke due to AVF. After aggressive investigation and management, we intervened before significant hypoxia and hypotension developed, potentially reducing the risk of long-term adverse neurologic consequences in this patient.     

Long-term prognosis of asphyctic neonates from an intensive care unit: intrauterine retarded infants at high risk of cerebral palsy

The surviving asphyctic infants born during the three-year period 1977 to 1979 and admitted to the regional neonatal intensive care unit were prospectively followed up to 2 and 4 years of age. According to outcome the children were divided into three subgroups: 1 who did not show any consequence of asphyxia; 2 who showed syndromes classified as cerebral palsy; 3 whose psychomotor functions were found to be retarded. The cerebral palsy group mainly consisted of children who were born with a weight deficit after 37 weeks gestation. Only 4 out of the 15 children were premature and among them only 1 was of very low birth weight. Thus, dysmaturity was the main somatic characteristic of the severely handicapped children. In addition to intrauterine growth retardation, the high rate of congenital anomalies was a further feature of the cerebral palsy group. Gestational complications (toxaemia, haemorrhage, threatening abortion or premature delivery), as well as the distortions of the most important biochemical variables (pH, calcium, bilirubins and glucose level) either in themselves or in combination had a similar incidence in the three subgroups. Among postnatal conditions, only the incidence of convulsions seemed to be important prognostically. On the basis of the great difference in outcome it is concluded that there is no simple relationship between asphyxia and eventual handicap. There are certainly some other noxious factors (e.g., dysmaturity, congenital anomalies, etc.) associated with, or related to asphyxia which can be of great aetiological significance.     

PHACES Association: A Vasculocutaneous Syndrome

PHACES association is a spectrum of anomalies that might occur in infants with large facial hemangiomas. Most infants with PHACES association have segmental hemangiomas of the head or neck. Cardiac and cerebrovascular anomalies might be the most important association, as they carry a significant risk of complications. This article summarizes the dermatologic, cardiac, and cerebral vascular findings in a cohort of infants diagnosed with PHACES association. All had large segmental facial hemangiomas and aortic arch abnormalities. Four of the five were not suspected of having arch obstruction prior to imaging studies because of the aberrant origin of both subclavian arteries, and 4/5 required either interventional or surgical repair for arch obstruction. In contrast to classic aortic coarctation, the aortic anomalies found in the cohort had unusually complex and unpredictable anatomic involvement. Cerebral vascular anomalies were identified in 5/5, and 2/5 had neurologic complications secondary to abnormal cerebral vascular supply. It is important for care providers to recognize this association that presents with a cutaneous stigma, as it is associated with potentially lethal and often unrecognized vascular anomalies. Earlier recognition of the associated vascular pathologies might enable preemptive treatments before potentially devastating and irreversible sequelae.     

Vascular Tumors of the Heart in Infants and Children: Case Series and Review of the Literature

Primary tumors of the heart are rare in children, of which vascular tumors comprise a small subgroup. We present the clinical, histopathologic, and imaging findings in six children with vascular tumors of the heart and review the findings of 36 previously published cases. We observed three intramuscular hemangiomas of the small-vessel type in older children, two congenital hemangiomas in infants, and one malignant polymorphous hemangioendothelioma. Intramuscular hemangiomas did not respond to corticosteroid and were biologically distinct from the congenital hemangiomas, both of which exhibited regression with pharmacotherapy. Age at diagnosis appears to predict histologic type, tumor location, and clinical presentation.     

Nonimmunologic hydrops fetalis--a review of 31 cases

Non-immunologic hydrops fetalis-a review of 31 cases: 31 Patients with non-immunologic hydrops fetalis (NIHF) seen between 1984 and 1987 are described. 13 infants survived. The infants with major congenital malformations and connatal infections died. In 8 of the patients who died a cause for NIHF could not be identified. 10 of the survivors presented chylous ascites and/or chylothorax without major congenital anomalies. 2 infants had fetal tachyarrhythmia and 1 patient showed severe anemia due to fetomaternal hemorrhage.