Mortality in infantile spasms: A hospital-based study.

OBJECTIVE: To determine risk factors and causes for mortality during childhood in patients with infantile spasms (IS). We describe the overall goals of care for those who died. METHODS: This is a retrospective chart review of IS patients born between 2000 and 2011. We examined potential risk factors for mortality, including etiology, neurologic impairment, medication use, persistence of epileptic spasms, and comorbid systemic involvement (requirement for G-tube feedings, respiratory interventions). For patients who died, we describe cause of death and resuscitation status or end-of-life care measures. RESULTS: We identified 150 IS patients with median follow-up of 12 years. During the study period, 25 (17%) patients died, 13 before 5 years of age. Univariate analysis demonstrated that developmental delay, identifiable etiology, hormonal use for IS, persistence of epileptic spasms, polypharmacy with antiseizure medications, refractory epilepsy, respiratory system comorbidity, and the need for a G-tube were significant risk factors for mortality. In a multivariate analysis, mortality was predicted by persistence of epileptic spasms (odds ratio [OR] = 4.30, 95% confidence interval [CI] = 1.11-16.67, P = .035) and significant respiratory system comorbidity (OR = 12.75, 95% CI = 2.88-56.32, P = .001). Mortality was epilepsy-related in one-third of patients who died with sudden unexpected death in epilepsy (SUDEP), accounting for 88% of epilepsy-related deaths. Most deaths before age 5 years were related to respiratory failure, and SUDEP was less common (17%) whereas SUDEP was more common (45%) with deaths after 5 years. For the majority (67%) of patients with early mortality, an end-of-life care plan was in place (based on documentation of resuscitation status, comfort measures, or decision not to escalate medical care). SIGNIFICANCE: Mortality at our single-center IS cohort was 17%, and persistence of epileptic spasms and comorbid respiratory system disorders were the most important determinants of mortality. Early deaths were related to neurological impairments/comorbidities. SUDEP was more common in children who died after 5 years of age than in those who died younger than 5 years.

Clinical report and biochemical analysis of a patient with fumarate hydratase deficiency.

Fumarate hydratase deficiency (FHD) is a rare metabolic disease caused by two defective copies of the FH gene, which encodes the Krebs cycle enzyme fumarase. FHD is associated with brain and developmental abnormalities, seizures, and high childhood mortality. We describe the symptoms and treatment of a patient with FHD. While infantile spasms are common in FHD, the patient presented with epileptic spasms later in childhood. Also unexpectedly, the patient responded excellently to lacosamide for her non-convulsive status epilepticus and epileptic spasms after three first-line medication trials failed. We biochemically analyzed the patient's two fumarase variants (E432Kfs*17 and D65G). While E432Kfs*17 was extremely enzymatically defective, D65G exhibited only a mild defect, possibly playing a role in the patient's longer survival.

Causes of mortality in early infantile epileptic encephalopathy: A systematic review.

INTRODUCTION: Early infantile epileptic encephalopathy syndrome (EIEE), also known as Ohtahara syndrome, is an age-dependent epileptic encephalopathy syndrome defined by clinical features and electroencephalographic findings. Epileptic disorders with refractory seizures beginning in the neonatal period and/or early infancy have a potential risk of premature mortality, including sudden death. We aimed to identify the causes of death in EIEE and conducted a literature survey of fatal outcomes. METHODS: We performed a literature search in MEDLINE, EMBASE, and Web of Science for data from inception until September 2017. The terms "death sudden," "unexplained death," "SUDEP," "lethal," and "fatal" and the medical subject heading terms "epileptic encephalopathy," "mortality," "death," "sudden infant death syndrome," and "human" were used in the search strategy. The EIEE case report studies reporting mortality were included. RESULTS: The search yielded 1360 articles. After screening for titles and abstracts and removing duplicate entries, full texts of 15 articles were reviewed. After reading full texts, 11 articles met the inclusion criteria (9 articles in English and 2 in Japanese, dated from 1976 to 2015). The review comprised 38 unique cases of EIEE, 17 of which had death as an outcome. In all cases, the suppression-burst pattern on electroencephalographies (EEGs) was common. Most cases (55%) involved male infants. The mean (standard deviation [SD]) age at onset of seizure was 19.6 ±â€¯33 days. The mean (SD) age at death was 12.9 ±â€¯14.1 months. Most infants (58.8%) survived less than one year. The cause of death was described only in eight (47%) patients; the cause was pneumonia/respiratory illness or sudden unexpected death in epilepsy (SUDEP). DISCUSSION: The results show EIEE as a severe disease associated with a premature mortality, evidenced by a very young age at death. Increasing interest in the detection of new molecular bases of EIEE is leading us to a better understanding of this severe disease, but well-reported data are lacking to clarify EIEE-related causes of death.

Early Seizure Freedom Is a Prognostic Factor for Survival in Patients with West Syndrome.

INTRODUCTION: West syndrome (WS) is a devastating epileptic encephalopathy with substantial mortality. After a study by Riikonen in 1996, further data on mortality and prognostic factors for survival has been scarce. We aimed to study mortality in patients with WS and identify prognostic factors for survival. METHODS: We performed a single-center retrospective study in a tertiary referral clinic (Erasmus University Hospital/Sophia Children's Hospital). This study obtained data from deceased patients regarding the age of death and cause of death. Seizure outcome was assessed at 8 weeks after the start of treatment and at 1 year after the onset of WS. At 1 year of follow-up seizure frequency, number of antiepileptic drugs and seizure type were evaluated. RESULTS: With a mean follow-up of 60 months (range 8-314 months), 162 patients met the inclusion criteria. At 8 weeks and 1 year of follow-up, 64 patients (40%) were seizure free. Overall, 37 patients (23%) died. The cumulative mortality percentage was 31%. Seizure freedom was an independent predictor of survival (p = 0.01). CONCLUSION: In this study, remission of seizures at 8 weeks of follow-up was significantly associated with reduced mortality in patients with WS.

Unexpected relationship between tympanometry and mortality in children with nontraumatic coma.

OBJECTIVE: We sought to further examine the relationship between tympanometry and mortality after noting an unexpected association on assessment of baseline data of a study whose primary aim was to investigate the utility of noninvasive tympanic membrane displacement measurement for monitoring intracranial pressure in childhood coma. METHODS: We recruited children who presented with acute nontraumatic coma to the high-dependency unit of Kilifi District Hospital on the rural coast of Kenya. We excluded children with sickle cell disease, epilepsy, and neurodevelopmental delay. We performed tympanometry on the right ear before tympanic membrane displacement analyzer measurements. All children were managed according to standard World Health Organization guidelines. RESULTS: We recruited 72 children with a median age of 3.2 years (interquartile range [IQR]: 2.0-4.3 years); 31 (43%) were female. Thirty-eight (53%) had cerebral malaria, 8 (11%) acute bacterial meningitis, 4 (6%) sepsis, and 22 (30%) encephalopathy of unknown etiology. Twenty (28%) children died. Tympanometry was normal in 25 (35%) children. Adjusting for diagnosis and clinical features of increased intracranial pressure, both associated with death on univariable analysis, children with abnormal tympanometry had greater odds of dying than did those with normal tympanometry (adjusted odds ratio: 17.0; 95% confidence interval: 1.9-152.4; P = .01). Children who died had a lower compliance (0.29 mL; IQR: 0.09-0.33 mL) compared with those who survived (0.48 mL; IQR: 0.29-0.70 mL) (P < .01). CONCLUSIONS: Abnormal tympanometry appears to be significantly associated with death in children with acute nontraumatic coma. This finding needs to be explored further through a prospective study that incorporates imaging and intensive physiologic monitoring.

Balancing clinical benefits of vigabatrin with its associated risk of vision loss.

Vigabatrin is an effective and well-tolerated antiepileptic drug (AED) for the treatment of refractory complex partial seizures (rCPS) and infantile spasms (IS), but its benefits must be evaluated in conjunction with its risk of retinopathy with the development of peripheral visual field defects (pVFDs). Vigabatrin should be considered for rCPS if a patient has failed appropriate trials of other AEDs or is not a suitable candidate for other AEDs, is not an optimal surgical candidate, and continues to experience debilitating effects from seizures. Vigabatrin is indicated as monotherapy for pediatric patients with IS. Its efficacy in achieving improved seizure control should be apparent within 12 weeks in patients with rCPS and within 2-4 weeks after attaining appropriate dosage for patients with IS. Because 12 weeks is well less than the known time of onset of visual defects, the risk of developing pVFDs may be minimized by discontinuing vigabatrin early during the course of therapy for patients with inadequate response. Appropriate vision screening is recommended at baseline, every 3 months during continued vigabatrin treatment, and at 3-6 months after discontinuation (if therapy has spanned more than a few months). If a pVFD is detected at any point and the decision is made to discontinue therapy, the pVFD is not likely to progress after discontinuation of vigabatrin. Although some patients will be at risk of retinopathy, vigabatrin is an appropriate treatment option for patients who achieve substantial clinical benefit, especially given the severe consequences of rCPS and uncontrolled IS. While retinopathy with the development of pVFDs is a serious adverse event, it is not life-threatening and its risk can be effectively managed.

Increased risk of death among children with Lennox-Gastaut syndrome and infantile spasms.

The magnitude and causes of death among a cohort of children with epilepsy were determined. A follow-up study with a population-based cohort of 10-year-old children in the metropolitan Atlanta area with epilepsy was conducted. The National Death Index and linkage to State of Georgia death certificates were used to identify deaths. The authors estimated the expected numbers of deaths by applying mortality rates adjusted by age, race, and sex for the entire state of Georgia to the population for the follow-up period. Among the 688 children who were in the final epilepsy cohort, 64 deaths occurred; 20.6 deaths were expected (mortality ratio adjusted for age, race, and sex = 3.11). The mortality ratios for children with Lennox-Gastaut syndrome and infantile spasms were 13.92 and 11.91, respectively. Children and adolescents with epilepsy, especially those with Lennox-Gastaut syndrome or infantile spasms, have an increased risk of death.

Early-onset neonatal seizures: types, risk factors and short-term outcome.

UNLABELLED: In a large majority of term newborns, early-onset neonatal seizures (EONS) are believed to relate to perinatal risk factors. AIM: To identify risk factors for EONS. METHODS: Among a cohort of 1293 newborns admitted over a period of 2 years to the neonatal intensive care unit of Tikur Anbasa Hospital, Addis Ababa, 93 had seizures. The case control study method was used to identify risk factors associated with EONS. Univariate analysis was used to further examine risk factors after adjusting for the effect of severe perinatal asphyxia (Apgar < or = 3). RESULTS: A total of 78 (85%) term newborns had EONS. Hypoxic-ischaemic encephalopathy (OR 3.46, 95% CI 2.74-7.42) and shock (OR 2.53, 95% CI 1.51-4.76) were significantly associated with EONS. Multifocal clonic (66%) followed by focal clonic (22%) were the most common types of EONS. Nine (11%) of the newborns with EONS died. During follow-up, 37 (53%) of the 69 surviving newborns with EONS had psychomotor delay with or without neurological deficit. CONCLUSION: Hypoxic-ischaemic encephalopathy and shock are important causes of EONS.

Fetal stroke.

Fetal stroke, or that which occurs between 14 weeks of gestation and the onset of labor resulting in delivery, has been associated with postnatal epilepsy, mental retardation, and cerebral palsy. The entity is caused by antenatal ischemic, thrombotic, or hemorrhagic injury. We present seven new cases of fetal stroke diagnosed in utero and review the 47 cases reported in the literature. Although risk factors could not be assigned to 50% of the fetuses with stroke, the most common maternal conditions associated with fetal stroke were alloimmune thrombocytopenia and trauma. Magnetic resonance imaging was optimal for identifying fetal stroke, and prenatal imaging revealed hemorrhagic lesions in over 90% of studies; porencephalies were identified in just 13%. Seventy-eight percent of cases with reported outcome resulted in either death or adverse neurodevelopmental outcome at ages 3 months to 6 years. Fetal stroke appears to have different risk factors, clinical characteristics, and outcomes than other perinatal or childhood stroke syndromes. A better understanding of those risk factors predisposing a fetus to cerebral infarction may provide a basis for future therapeutic intervention trials. Ozduman K, Pober BR, Barnes P, Copel JA, Ogle EA, Duncan CC, Ment LR. Fetal stroke.

Long-term outcome of patients with West syndrome.

The long-term outcome of Finnish children with West syndrome was evaluated. Two hundred and fourteen patients were followed up for 20-35 years or until death. A third of the patients died before the age of 3 years. The most common cause of death was infection. Autopsy revealed brain anomalies in 25 of 38 (66%) autopsied patients. Intellectual outcome was normal or slightly impaired in a quarter of the patients. All of them completed their education at a normal school or in a school for the educationally impaired children. Another fourth were taught in special training schools. Specific cognitive deficits were seen in some patients with normal intelligence. Nine attended secondary schools and seven of them had a professional occupation. Ten were married and five had children. One third of the patients were seizure-free, another third had seizures daily or monthly, and the remaining patients had seizures less frequently. Factors associated with a good prognosis were cryptogenic etiology, normal development before the onset of the spasms, a short treatment lag, and a good response to adrenocorticotropic hormone; this was seen in both the symptomatic and the cryptogenic group, and there were no relapses. In this study, the late appearance of focal abnormalities in electroencephalography was not associated with an unfavorable outcome. Focal abnormalities in temporal region were often seen in patients with autism. The location of an abnormality may be of importance for the prognosis. In this study, all the patients (100%) could be followed, which may be due to the special circumstances characteristic of Finland. The outcome in children with West syndrome seems to be better than is generally believed.

West syndrome in tuberous sclerosis complex.

West syndrome occurs commonly in children with tuberous sclerosis complex and is associated with a grave prognosis for cognitive and seizure outcomes. We sought to determine the epilepsy outcome of children with tuberous sclerosis complex and West syndrome and whether EEG, MRI, or steroid therapy duration were different in those whose epilepsy improved compared with those with intractable seizures. Seventeen patients with tuberous sclerosis complex and West syndrome were identified. For each patient, two sets of clinical evaluations, EEG and MRI data, and treatment information separated by at least 12 months were obtained. The patients were divided into two seizure outcome groups. EEG, MRI, and treatment data were compared between the groups. The intellectual deficiency was either severe (76%) or moderate (24%). Seizure control improved in 10 and worsened in seven, without mortality (follow-up range = 12-216 months). No significant differences in EEG background, MRI findings, or steroid treatment duration were evident between the groups. The difference in EEG-sleep approached statistical significance (P = 0.06). Our findings did not confirm reports of high mortality and poor epilepsy outcome in intellectually deficient children with West syndrome and tuberous sclerosis complex. EEG sleep was the best indicator of seizure control and approached statistical significance. The duration of steroid therapy had no influence on seizure control.

Childhood generalized and mesial temporal epilepsies demonstrate different amounts and patterns of hippocampal neuron loss and mossy fibre synaptic reorganization.

In this study, we determined whether childhood seizures were associated with hippocampal neuron loss and mossy fibre synaptic reorganization and if hippocampal sclerosis evolved from longer seizure histories. Children undergoing surgical treatment for catastrophic epilepsy were grouped into the following pathology categories: (i) those with generalized seizures and extra-hippocampal congenital pathologies (i.e. prenatal cortical dysplasia; n = 17); (ii) cases of generalized seizures and extra-hippocampal acquired lesions. (i.e. postnatal ischaemic injuries and encephalitis; n = 7); (iii) children with complex partial hippocampal epilepsy (n = 4). Further, to determine whether the epileptogenic location influenced hippocampal pathology, the seizure focus was classified as (i) hippocampal, (ii) temporal (n = 13) or (iii) extra-temporal (n = 11). Surgical and autopsy (n = 23) hippocampi were studied for (i) fascia-dentata (FD) and Ammon's horn (AH) neuron densities; (ii) thickness; height or length of the FD molecular layer, stratum granulosum (SG) and stratum pyramidale; and (iii) grey value (GV) densities of supragranular neo-Timm's staining. Statistically significant results (P < 0.05) showed the following. (i) Autopsy hippocampal neuron densities for the hilus (H), AH and prosubiculum (Pro) decreased logarithmically at the same time as the thickness of the stratum pyramidale and Pro increased. By contrast, autopsy granule cell densities and thickness did not significantly change with age; however, the SG lengthened-expanding around the enlarging H. Further, the supragranular molecular layer height increased logarithmically, and took longer than the increase in stratum pyramidale thickness. (ii) Compared with age-matched autopsies, young children with a history of hippocampal seizures showed decreased granule cell, hilar and regio superior neuron densities similar to adults with hippocampal sclerosis (average loss 70%). By contrast, children with extra-hippocampal congenital or acquired pathologies showed only decreased granule cell densities, along with a thinner and shorter SG. Compared with extra-temporal locations, those with temporal lobe lesions showed decreased hilar and AH neuron densities, but averaged 20-30% less than autopsies and not in the pattern typical of hippocampal sclerosis. (iii) The neo-Timm's GV densities, when compared with autopsies, showed supragranular mossy fibre sprouting in children with congenital pathologies and temporal lobe lesions; however, the greatest GVs were in children with hippocampal seizures. (iv) Of the children with extra-hippocampal congenital or acquired pathologies there were no statistical correlations between longer duration of seizures with changes in neuron densities, hippocampal heights, or mossy fibre sprouting. These results indicate the following. (i) In the human there is anatomical evidence for postnatal maturation of the hippocampus and our results are consistent with the notion that AH pyramids are a stable population; however, there are probably increases in granule cell numbers. Further, compared with the AH, dendritic maturation of the FD granule cells appears to take longer. (ii) Extra-hippocampal childhood seizures whether from prenatal or postnatal aetiologies are associated with moderate FD and minimal AH neuron losses and signs of aberrant mossy fibre sprouting. (iii) By contrast, young children with the syndrome of mesial temporal epilepsy show patterns of neuron loss and mossy fibre sprouting, typical of hippocampal sclerosis. (iv) Repeated extra-hippocampal childhood seizures are not associated with progressive evolution of hippocampal damage or mossy fibre sprouting. These findings support the hypothesis that childhood seizures can damage or alter the postnatally developing granule cells of the human hippocampus, and that early neuron loss and aberrant axon circuits may contribute to chronic hippocampal seizures. However, repeated childhood generalized seiz

Long-term otucome of West syndrome: a study of adults with a history of infantile spasms.

To our knowledge, ours is the first study to evaluate the outcome of infantile spasms (IS) in adult patients. We analyzed 214 children born between 1960 and 1976 who had been followed for 20-35 years or until death at 3 months to 30 years of age. Mortality was 31% (67 of 214 patients). Thirty-six of the surviving patients (24%) had normal (25 patients) or only slightly impaired (11 patients) intelligence as assessed by their educational abilities. Four had academic occupations. Eight were married or living unmarried with a partner. Five had healthy children. At follow-up, the EEGs of the 25 normal persons were either normal or slightly abnormal, demonstrated focal findings in 9 (36%), and had unspecific changes in 1. Focal abnormalities were not more common in patients with less good outcomes (37%). In patients with normal neurological outcomes, IS had been classified as cryptogenic only in 9 of 25 (36%) cases. Therefore, some patients with IS apparently have normal intelligence and socioeconomic status as adults, including patients whose spasms were either symptomatic or associated with focal EEG findings.

Early childhood surveillance of developmental disorders by a birth defects surveillance system: methods, prevalence comparisons, and mortality patterns.

The prevalence of developmental disabilities in early childhood is not well documented. An established birth defects registry extended surveillance to identify cases of developmental disorders in early childhood by adding all known sources of diagnosis and service to case-finding methods. Residents of a northwest Arkansas region born during 1985 to 1987 and diagnosed with either a birth defect or a developmental disorder by the 4th birthday comprised the studied cohort. Case records were linked with death certificates to examine the influence of mortality on prevalence ratios. Prevalence ratios estimated were 64.5/1000 resident live births (60.9/1000 among survivors to age 4 years) for either birth defect or developmental disorder, 33.4/1000 for developmental disorder, 37.0/1000 for birth defect, and 9.5/1000 for both developmental disorder and birth defect. Prevalence ratios of specific developmental disorders and the role of mortality in decreasing population prevalence are reported. The most common diagnostic categories in this age group were developmental delay, seizures, and failure to thrive. Overlap of birth defect categories with a diagnosed developmental disability was examined; 68.8% of children diagnosed with neural tube defects and 45.5% of those with chromosomal abnormalities who survived to age 4 years had clinically diagnosed developmental disorders. An anticipated high degree of overlap (77%) for other central nervous system defects was found. For other birth defect categories, developmental disorder diagnosis was present in 20 to 30% of the study group. Death before age 4 years occurred most often when the diagnosis was newborn seizures (17.1%) or "conditions of the brain" (13.6%); the mortality rate was 6 to 8% for epilepsy or seizure disorders, mental retardation, and vision loss. The large number of developmental diagnoses among this cohort indicates that surveillance of these disorders in early childhood, even with tentative diagnoses, is feasible. Data obtained indicate that many birth defects are associated with developmental disorders; potentially, this association can contribute to earlier identification of developmental disorders in childhood.

Low risk of seizure recurrence after early withdrawal of antiepileptic treatment in the neonatal period.

The risk of seizure recurrence within the first year of life was evaluated in infants with neonatal seizures diagnosed with a combination of clinical signs, amplitude-integrated electroencephalogram (EEG) monitoring, and standard EEG. Fifty eight of 283 (4.5%) neonates in tertiary level neonatal intensive care had seizures. The mortality in the infants with neonatal seizures was 36.2%. In 31 surviving infants antiepileptic treatment was discontinued after one to 65 days (median 4.5 days). Three infants received no antiepileptic treatment, two continued with prophylactic antiepileptic treatment. Seizure recurrence was present in only three cases (8.3%)--one infant receiving prophylaxis, one treated for 65 days, and in one infant treated for six days. Owing to the small number of infants with seizure recurrence, no clinical features could be specifically related to an increased risk of subsequent seizures. When administering antiepileptic treatment, one aim was to abolish both clinical and electrographical seizures. Another goal was to minimise the duration of treatment and to keep the treatment as short as possible. It is suggested that treating neonatal seizures in this way may not only reduce the risk of subsequent seizure recurrence, but may also minimise unnecessary non-specific prophylactic treatment for epilepsy.

Aicardi syndrome: natural history and possible predictors of severity.

Aicardi syndrome is defined by the clinical triad of infantile spasms, agenesis of the corpus callosum, and pathognomonic chorioretinal lacunae. Almost all patients are girls with severe cognitive and physical handicaps, and epilepsy. Fourteen patients with Aicardi syndrome, seen at The Hospital for Sick Children, Toronto, Ontario, Canada, between 1975 and 1992, were reviewed to document the natural history of the disease and obtain life-table estimates of survival. The relationship between 28 neurologic features present in infancy and clinical outcome, as measured by mobility and cognitive function also was examined. Life-table analysis indicated that the estimated survival rate was 76% at 6 years of age and 40% at 15 years of age. Three of the 14 girls (21%) could walk or crawl and 4 (29%) had some language ability. None of the 28 neurologic features was predictive of ultimate clinical outcome. This information should be discussed with parents of children with Aicardi syndrome.

Natural history and outcome of neonatal hypocalcemic and hypomagnesemic seizures.

The clinical characteristics and neurologic outcome of 15 newborn infants with seizures due to hypocalcemia and hypomagnesemia have been studied with careful exclusion of those patients who had other possible etiologies for seizures. Associated diagnoses included severe congenital heart disease in 7 of 15 (47%) patients. Possible causes for this association with congenital heart disease include a forme fruste of DiGeorge syndrome, hypocalcemia and hypomagnesemia due to critical illness, and subtle embolic cerebral ischemia. In contrast with previous studies, no abnormalities of formula milk feeding were observed. Five patients (36%) died of causes unrelated to seizures. Follow-up in 8 of 9 patients who had no cerebral insults other than neonatal seizures at a mean age of 57.8 +/- 10.5 months found neurologic abnormalities in 2 (22%), both with an endocrine etiology for hypocalcemia. We conclude that infants with severe congenital heart disease should be investigated for hypocalcemia and hypomagnesemia. Previous observations of a universally favorable neurologic outcome in newborns with hypocalcemic or hypomagnesemic seizures may be valid for those who have a nutritional etiology for the metabolic disturbance but are less relevant to the current population in whom hypocalcemia or hypomagnesemia due to errors in formula milk feeding is seldom observed. In this group, neurologic prognosis may be more related to associated medical conditions.

Differential postmorbidity mortality in observational studies of risk factors for neurologic disorders.

Selection bias may be introduced in case-control or cross-sectional studies, and the impact on the observed associations may be dramatic. Many authors have examined this issue primarily in the context of subject source (e.g. referral bias). The potential bias encountered when a risk factor associated with outcome is also associated with an increase in mortality among cases greater than that among those not developing the disease (e.g. selective survival) is examined here. The potential for selective survival bias arising in observational studies is demonstrated in studies of the etiology of neonatal seizures and Parkinson's disease.

[Complications of two series of 1000 each heart catheterization studies in childhood]. / Komplikationen bei zwei Serien von je 1000 Herzkatheteruntersuchungen im Kindesalter.

Two series of 1,000 consecutive cardiac catheterizations in neonates, infants and older children were prospectively investigated with respect to catheter-induced complications. These were categorized into arrhythmias, vascular complications, catheter and contrast perforations, central nervous (CNS) complications, clinical deterioration and catheter-related death. Comparing series 1 and 2, the number of arrhythmias decreased from 7.6% to 5.0%, acute vascular complications decreased from 2.1% to 1.4%, the number of patients showing clinical deterioration from 2.6% to 0.6% and CNS complications from 0.4% to 0.1%, whereas catheter or contrast perforations-remained virtually constant at 0.4% and 0.5% respectively. Catheter-induced mortality decreased from 2.0% to 0.7%. The group of neonates showed the greatest reduction in serious complications and catheter-induced mortality (31.3% to 12.4% and 11.0% to 4.4%, respectively). Increasing experience of the investigators, introduction of two-dimensional echocardiography as a supplementary investigation or even catheter substitute, use of percutaneous catheterization and sheath techniques, introduction of E-type prostaglandins and increased use of intubation and anaesthesia for catheterization all played an important role in the improvement shown in this investigation. Complications are still mainly seen in the group of neonates and cyanotic patients.

Perinatal factors influencing the outcome of 501- to 1000-gm newborns.

This article is a review of the various factors relating to fetal and neonatal mortality in infants of a particular birth weight. Factors influencing survival positively also are considered, including various presentations and some specific maternal factors.