Sequelae In Infants Research Articles

Abstract PCCLB-38: SUPPORTING NEURODEVELOPMENTAL OUTCOMES FOR NEONATES IN THE PAEDIATRIC INTENSIVE CARE SETTING

Aims & Objectives: Neurological sequelae in infants with congenital heart disease (CHD) emulate those in premature infants. Developmentally supportive practices are seen as a strategy to mitigate some of the effects of the critical care environment on the vulnerable brain. Aims: To establish a framework of developmentally supportive care beyond the Neonatal Intensive Care Unit (NICU) in the Paediatric Intensive Care Unit (PICU) setting. Methods Based on the success of established neurodevelopmental care initiates in the NICU, we constituted a governance committee and conducted a feasibility survey on PICU staff knowledge and attitudes towards the concept. Targeted multidisciplinary education sessions were undertaken to capture the majority of PICU staff. With a clinical developmental round to support practice and provide practical ongoing education for staff implemented. We plan to conduct a subsequent post-implementation survey in the next six months to gain feedback for evaluation and comparison. Results Twenty four percent of 150 PICU staff completed the survey. 90% of respondents indicated they understood the benefits of neurodevelopmental care while 64% felt confident in implementing developmentally supportive strategies. 45% identified there was adequate resources to support this initiative in the PICU. Conclusions Developmentally supportive practices for young infants are well recognised in the NICU setting. Research indicates this approach may also be helpful in high risk infants and those with CHD, both in pre and postoperative periods in the PICU. The governance committee have formulated a proactive strategy for ongoing staff education, evaluation, and implementation of neuro-protective practice in the PICU designed to support neurodevelopmental outcomes.

No evidence of obstetrical adverse events after hyperimmune globulin application for primary cytomegalovirus infection in pregnancy: experience from a single centre

To determine the frequency of obstetrical adverse events and clinical outcome in infants following antenatal hyperimmune globulin (HIG) treatment for primary cytomegalovirus (CMV) infection in pregnancy. Data from 50 women including three twin pregnancies were retrospectively evaluated. Primary infection was defined by seroconversion or the presence of CMV-specific IgM and low IgG avidity. All women received two or more infusions of HIG (200U/kg). Congenital CMV (cCMV) infection was diagnosed by detection of CMV in amniotic fluid and/or neonatal urine. We compared gestational age (GA) at birth, head circumference (HC) and birth weight (BW) of infants in our study cohort with those of live-born infants delivered in our clinic between 2015 and 2016. Median gestational age at time of maternal CMV diagnosis was 13weeks. One-hundred-forty-one maternal HIG doses were given. No HIG-related severe adverse reactions occurred. Preterm birth rate was 4.2% (2/47) in singleton pregnancies. None of the neonates had birth weight or head circumference<3rd percentile (<3P) for gestational age. There was no statistically significant difference regarding GA, BW and HC between our study cohort and the total population of live-born infants. The frequency of CMV-related sequelae in infants with cCMV infection was 10.5% (2/19) (one with bilateral hearing loss and one with mild motoric delay), both cases following first trimester maternal infection. Antenatal HIG treatment was well tolerated and not associated with prematurity or decreased birth weight. HIG application might have a favorable effect on the clinical course of congenital CMV infection.

Co-infection of human herpesvirus type 2 (HHV-2) and human immunodeficiency virus (HIV) among pregnant women in Rio de Janeiro, Brazil

ABSTRACTPregnant women who are infected with the Human Immunodeficiency Virus (HIV) are particularly vulnerable to severe and recurrent infections with Human Herpesvirus 2 (HHV-2). Neonatal transmission of HHV-2 has been associated with malformations and neurological sequelae in infants, which makes it very important to perform antenatal monitoring for genital herpes. In the study, 134 pregnant women infected with HIV were tested for HHV-2 IgM and IgG using an enzyme-linked immunosorbent assay (ELISA) and had HHV-2 DNA analyzed by Real Time Polymerase Chain Reaction (qPCR). Fisher’s exact test was applied to analyze the epidemiological dates (p < 0.05). A total of 59.7% of the pregnant women infected with HIV had HHV-2 IgG and 3.75% of them showed HHV-2 viremia. HHV-2 IgM was found in 6% of the pregnant women and 25% of them had HHV-2 viremia. The risk factors associated with HHV-2 seropositive were age under 20 and a CD4/CD8 ratio > 1. Our study found high HHV-2/HIV coinfection prevalence and HHV-2 viremia among patients with recurrent and primary genital infection, reinforcing the need of prevention and control of HHV-2 infection in order to avoid this virus transmission.

Is lenticulostriated vasculopathy an unfavorable prognostic finding in infants with congenital cytomegalovirus infection?

BackgroundLenticulostriated vasculopathy (LSV) detected in head ultrasound (HUS) has been related to neurological and hearing sequelae in infants with congenital cytomegalovirus (cCMV) infection. ObjectiveTo assess the role of LSV in predicting neurodevelopmental and hearing outcomes in infants with cCMV infection. Study designWe enrolled consecutive infants who were affected by cCMV infection and underwent HUS within the first month of life. Data on clinical onset and course, laboratory findings, visual/hearing functions and neurodevelopmental outcome were collected. As controls, infants with suspected intrauterine exposure to Toxoplasma and with no confirmed congenital toxoplasmosis were considered. ResultsData from 161 infants with cCMV infection (105 symptomatic) and 133 controls were analyzed. HUS was normal in 66 (41%) cCMV patients. Among these, 28 (42.4%) were symptomatic and 38 (57.6%) asymptomatic infants. The percentage of patients with no HUS abnormalities was higher in asymptomatic (38/56, 67.9%) than in symptomatic infants (28/105, 26.7%) (p<0.05). LSV, as isolated or associated with other brain abnormalities, was diagnosed in 64/161 (39.7%) patients with cCMV compared to 24/133 (18%) controls (p<0.05). In cCMV group, LSV was found in 51 (48.6%) symptomatic infants and in 13 (72.2%) asymptomatic patients (p>0.05). Overall, in the whole population of 95 patients with cCMV and abnormal HUS results, LSV (alone or with other findings) did not represent a risk factor for unfavorable neurological and hearing outcome. Similar results were obtained when we limited the analysis to the group of symptomatic cCMV patients. ConclusionsAlthough LSV is a common HUS finding in infants with cCMV infection, its presence is not predictive of an adverse outcome. Our data suggest that HUS as a single neuroimaging investigation is unreliable in selecting candidates to antiviral therapy, mainly in presence of LSV as isolated finding.

Tumor Necrosis Factor Alpha-Induced Recruitment of Inflammatory Mononuclear Cells Leads to Inflammation and Altered Brain Development in Murine Cytomegalovirus-Infected Newborn Mice.

Congenital human cytomegalovirus (HCMV) infection is a significant cause of abnormal neurodevelopment and long-term neurological sequelae in infants and children. Resident cell populations of the developing brain have been suggested to be more susceptible to virus-induced cytopathology, a pathway thought to contribute to the clinical outcomes following intrauterine HCMV infection. However, recent findings in a newborn mouse model of the infection in the developing brain have indicated that elevated levels of proinflammatory mediators leading to mononuclear cell activation and recruitment could underlie the abnormal neurodevelopment. In this study, we demonstrate that treatment with tumor necrosis factor alpha (TNF-α)-neutralizing antibodies decreased the frequency of CD45+ Ly6Chi CD11b+ CCR2+ activated myeloid mononuclear cells (MMCs) and the levels of proinflammatory cytokines in the blood and the brains of murine CMV-infected mice. This treatment also normalized neurodevelopment in infected mice without significantly impacting the level of virus replication. These results indicate that TNF-α is a major component of the inflammatory response associated with altered neurodevelopment that follows murine CMV infection of the developing brain and that a subset of peripheral blood myeloid mononuclear cells represent a key effector cell population in this model of virus-induced inflammatory disease of the developing brain.IMPORTANCE Congenital human cytomegalovirus (HCMV) infection is the most common viral infection of the developing human fetus and can result in neurodevelopmental sequelae. Mechanisms of disease leading to neurodevelopmental deficits in infected infants remain undefined, but postulated pathways include loss of neuronal progenitor cells, damage to the developing vascular system of the brain, and altered cellular positioning. Direct virus-mediated cytopathic effects cannot explain the phenotypes of brain damage in most infected infants. Using a mouse model that recapitulates characteristics of the brain infection described in human infants, we have shown that TNF-α plays a key role in brain inflammation, including recruitment of inflammatory mononuclear cells. Neutralization of TNF-α normalized neurodevelopmental abnormalities in infected mice, providing evidence that virus-induced inflammation is a major component of disease in the developing brain. These results suggest that interventions limiting inflammation associated with the infection could potentially improve the neurologic outcome of infants infected in utero with HCMV.

Limitations in the Activity of Mobility at Age 6 Years After Difficult Birth at Term: Prospective Cohort Study.

A difficult birth at term (DBAT) may manifest as fetal acidosis and low Apgar scores and is often referred to as "perinatal asphyxia," especially when infants show signs of neonatal encephalopathy (NE). In contrast to DBAT resulting in moderate-to-severe NE, which is associated with neurodevelopmental disorders, little is known about the prognosis of less severe forms of DBAT, with or without NE. The purpose of this study was to evaluate the International Classification of Functioning, Disability and Health, Children & Youth Version activity "mobility" and other neurodevelopmental sequelae in infants with DBAT at age 6 years. The index cohort (n=62; 35 boys, 27 girls) consisted of consecutive term infants with DBAT based on clinical criteria in a Dutch nonacademic hospital from 1999 to 2005. Neonatal encephalopathy was assessed according to the Sarnat grading system and excluded infants with severe NE. The matched reference cohort (n=81; 49 boys, 32 girls) consisted of healthy term infants. The primary outcome at 6 years was limited mobility (Movement Assessment Battery for Children score ≤15th percentile). Secondary outcomes included learning and behavioral problems and the presence of minor neurological dysfunction. Three children developed cerebral palsy and were excluded from analyses. Children with DBAT more often had limited mobility than children without DBAT (risk ratio [RR]=2.44; 95% confidence interval [95% CI]=1.16, 5.14). The risk of limited mobility rose with increasing severity of NE (mild NE: RR=3.38; 95% CI=1.40, 8.16; moderate NE: RR=4.00; 95% CI=1.54, 10.40), and manual abilities especially were affected (RR=4.12; 95% CI=1.40, 12.14). Learning problems, need for physical therapy, and complex minor neurological dysfunction were more common in children with DBAT than in children without DBAT. Term infants who develop mild or moderate NE following DBAT are at increased risk for limited mobility at age 6 years. Routine monitoring of neuromotor development in these children is warranted.

Molecular tests in diagnosis of Cytomegalovirus (CMV), human herpesvirus 6 (HHV-6) and Epstein-Barr virus (EBV) using real-time PCR in HIV positive and HIV-negative pregnant women in Ouagadougou, Burkina Faso

IntroductionLes herpès virus EBV, CMV et HHV-6 sont des virus qui évoluent sous le modèle pandémique et sont responsables d’infections congénitales pouvant provoquer des séquelles graves chez les nouveau-nés. L’objectif de cette étude était de déterminer les prévalences de CMV, EBV et HHV-6 chez les femmes enceintes VIH(+) et VIH(-) à Ouagadougou.MéthodesDans cette étude 200 échantillons de plasma sanguin de femmes enceintes dont 100 femmes VIH(+) et 100 femmes VIH(-) ont été diagnostiqués par PCR multiplex en temps réel pour les trois infections (EBV, CMV et HHV-6).RésultatsSur l’ensemble des 200 échantillons analysés, 18 (9,0%) étaient positifs à au moins un des trois virus, 12 (6,0%) étaient positifs au EBV, 13 (6,5%) au CMV et 12 (6,0%) positifs au HHV-6. Parmi les 18 cas d’infections, nous avons trouvé 10 cas (55,6%) de coïnfections dont 90,0% (9/10) d’infection multiple EBV/CMV/HHV6 et 10,0% de coinfection EBV/HHV6. Le taux d’infection HHVs était plus élevé chez les femmes VIH(-) que celles VIH(+) (12,0% versus 6,0%). Parmi les VIH(+), la PCR a révélé 7,1% (soit 6/85) d’infection HHVs chez celles qui n’étaient pas sous ARV contre 0% chez celles sous ARV.ConclusionLes herpès virus sont fréquents chez les femmes enceintes au Burkina Faso et pourraient constituer une menace chez ces dernières à cause des complications et des risques d’infection pour le nouveau-né.

Distribution of cytomegalovirus gN variants and associated clinical sequelae in infants

BackgroundHuman cytomegalovirus (HCMV) is the most widespread cause of congenital infection. The effects of various viral strains and viral loads on the infection outcome have been under debate. ObjectivesTo determine the distribution of gN variants in HCMV strains isolated from children with congenital or postnatal infection and to establish the relationship between the viral genotype, the viral load, and the sequelae. Study designThe study population included congenitally HCMV-infected newborns and children with postnatal or unproven congenital HCMV infection. The genotyping was performed by RFLP analysis of PCR-amplified fragments, and the viral load was measured by quantitative real-time PCR. ResultsOur results demonstrated that the HCMV genotypes gN3b, gN4b, and gN4c were prevalent in the patients examined. There were no differences in the distributions of gN genotypes in the congenitally and postnatally infected children. Multiple HCMV strains were detected in both groups of children. A significant association between the HCMV gN4 genotype and the incidence of neurological disorders was observed (p=0.045). Our results suggest that the detection of the gN2 or the gN4 genotype may be indicative of serious manifestations in children. In contrast, the gN3b and the gN1 genotypes represent less pathogenic HCMV strains. The HCMV load in urine was significantly higher in children with congenital infection compared with children with postnatal infection. No correlation was found between the viral load and the genotype. ConclusionOur results suggest that the gN genotype may be a virological marker of symptomatic HCMV infection in newborns.

New Pharmacological Approaches in Infants with Hypoxic-Ischemic Encephalopathy

New knowledge of the pathophysiology and evolution of hypoxic-ischemic brain injuries has made feasible interventions to improve clinical outcomes for newborns surviving birth asphyxia. Brain injury following hypoxic-ischemic insult is a complex process evolving over hours to days, which provides a unique window of opportunity for neuroprotective treatment interventions. The specific pathologic processes preceding the onset of irreversible cerebral injury appear to be a combination of several mechanisms that are variable according to the severity and duration of the insult and to biochemical modifications in the brain. Advances in neuroimaging, brain monitoring techniques, and tissue biomarkers have improved the ability to diagnose, monitor, and care for newborn infants with neonatal encephalopathy, as well as to predict their outcome. The role of oxidative stress in newborn morbidity with respect to the higher risk of free radical damage in these babies is growing. However, challenges remain in early identification of infants at risk for neonatal encephalopathy, determination of timing and extent of hypoxic-ischemic brain injury, as well as optimal management and treatment duration. Potential neuroprotective strategies targeting different pathways leading to neuronal cell death in response to hypoxic-ischemic insult have been investigated: hypothermia, erythropoietin, iminobiotin, deferioxamine, magnesium, allopurinol, xenon, melatonin and statins. Hypothermia is currently the only recognized beneficial therapy. However, many infants still develop significant adverse outcomes. It is becoming evident that the association of moderate hypothermia with neuroprotective drugs may enhance the outcome. By virtue of their pleiotropic effects without toxic effects, melatonin and statins may act at different levels of the multiple mechanisms responsible for the progression of the neurodegenerative process and represent promising neuroprotectants, alone or as additional adjunctive therapy, for reducing brain injury and its long-term sequelae in infants. More clinical studies are needed to clarify the role of these potential neuroprotective drugs.

Glycerol and Bacterial Meningitis

Scientific efforts aimed at improving the prognosis of patients affected by severe diseases deserve to be highlighted and thoroughly evaluated for potential impact. Despite modern intensive care management and the advent of potent broadspectrum antimicrobial agents bacterial meningitis is still associated with unacceptably high rates of long-term-morbidity and case fatality. During the past 20 years comprehensive experimental and clinical studies have been performed to define the molecular pathophysiologic events involved in bacterial meningitis that are responsible for clinical manifestations and adverse outcomes. These studies have demonstrated that administration of dexamethasone before the first effective parenteral antibiotic dose reduced neurologic and/or audiologic sequelae in infants and children with Haemophilus influenzae meningitis and possibly in those infected with Streptococcus pneumoniae. Recently the benefit of corticosteroid therapy was confirmed in adults with pneumococcal meningitis. Nevertheless the favorable effects of treatment with dexamethasone are far from ideal and in selected situations they can be marginal or nonexistent. Children with delayed medical attention profound malnutrition HIV infection or treatment with suboptimal antibiotics (based on current bacterial drug-resistance profiles) are less likely than others to respond to adjunctive antiinflammatory therapy. These situations are commonly seen in poor regions of the world as illustrated in a clinical trial conducted in Malawi. Consequently novel and accessible forms of adjuvant therapy are clearly needed for the unique challenges faced by countries with limited economic and technical resources. (excerpt)

Iodine and thyroid hormones during pregnancy and postpartum

Iodine is a trace element essential for synthesis of the thyroid hormones, triiodothyronine and thyroxine. These hormones play a vital role in the early growth and development stages of most organs, especially the brain. The World Health Organization (WHO) has declared that, after famine, iodine deficiency is the most avoidable cause of cerebral lesions including different degrees of mental retardation and cerebral paralysis. The main function of iodine in vertebrates is to interact with the thyroid hormones. During pregnancy sufficient quantities of iodine are required to prevent the appearance of hypothyroidism, trophoblastic and embryonic or fetal disorders, neonatal and maternal hypothyroidism, and permanent sequelae in infants. Thyroid hormone receptors and iodothyronine deiodinases are present in placenta and central nervous tissue of the fetus. A number of environmental factors influence the epidemiology of thyroid disorders, and even relatively small abnormalities and differences in the level of iodine intake in a population have profound effects on the occurrence of thyroid abnormalities. The prevalence of disorders related to iodine deficit during pregnancy and postpartum has increased. Iodine supplementation is an effective measure in the case of pregnant and lactating women. However, it is not implemented and the problem is still present even in societies with theoretically advanced health systems. During pregnancy and postpartum, the WHO recommends iodine intake be increased to at least 200 μg/day. Side-effects provoked by iodine supplementation are rare during pregnancy at the recommended doses.

Death from cerebrovascular infarction in a patient with PHACES syndrome

Death from cerebrovascular infarction in a patient with PHACES syndrome

Reflux esophagitis: sequelae and differential diagnosis in infants and children including eosinophilic esophagitis.

Gastroesophageal reflux disease (GERD) is a common condition in infants and children and has many clinical mimics. Most pediatric pathology departments process many mucosal biopsies from the proximal gastrointestinal tract to evaluate the presence or absence of reflux esophagitis. Since this subject was last reviewed in the 1997 edition of Perspectives in Pediatric Pathology devoted to gastrointestinal diseases in children (Dahms BB. Reflux esophagitis and sequelae in infants and children. In: Dahms BB, Qualman SJ, eds. Gastrointestinal Disease. Perspectives in Pediatric Pathology, vol. 20. Basel: Karger, 1997;14-34), progress in the field has allowed recognition of additional presenting symptoms and treatments of GERD. Histologic criteria for diagnosing reflux esophagitis have not changed. However, the entity of eosinophilic esophagitis has emerged since 1997 and has been defined well enough to allow it to be distinguished from reflux esophagitis, with which it was probably previously confused. Refinements (though not simplification!) in the definition of Barrett esophagus are still in evolution. This review will summarize these newer concepts and briefly review the standards of diagnosis of reflux esophagitis.

Cranial Doppler ultrasonography as a predictor of neurologic sequelae in infants with bacterial meningitis.

To perform transcranial Doppler sonography in newborns and infants with bacterial meningitis to evaluate predictive value of neurologic sequelae. Thirty-three patients (15 newborn, 18 infant patients) with bacterial meningitis underwent cranial Doppler ultrasonography during acute phase and 3rd and 6th months after disease. Patients were examined regularly for neurologic outcome with electroencephalography and magnetic resonance imaging. The age-matched control group consisted of 20 healthy children underwent cranial Doppler sonography only. To compare with the healthy controls, the mean blood flow velocity was significantly increased (P < 0.001), and pulsatility index was higher than those control group (P < 0.05) during acute bacterial meningitis. None of the patients were diagnosed with stenosis of cerebral artery. According to neurologic outcome, 14 of 33 patients had neurologic sequelae. The mean cerebral blood flow was significantly higher (P < 0.01) in patients without neurologic sequelae; pulsatility index was significantly higher (P < 0.05) in patients with neurologic sequelae when compared with the healthy controls. There was no significant difference between mean cerebral blood flow velocities and mean pulsatility index values of newborn and infant patients, regarding to neurologic outcome (P < 0.05). Cranial Doppler ultrasonography is useful for prediction of neurologic sequelae in infants with bacterial meningitis.

PROPORTIONAL ASSIST VENTILATION IN INFANTS

Proportional assist ventilation and respiratory mechanical unloading is a new mode of respiratory assistance that produces similar gas exchange with lower airway pressures than conventional ventilation in infants. This is achieved by tailoring the ventilator pressure contour to the specific derangements in lung mechanics and by a near perfect synchronization with the infant's own inspiratory effort. In contrast to conventional ventilation, PAV only amplifies the effect on ventilation of the spontaneous respiratory effort and relies on the subject's respiratory control. Whether PAV will reduce the incidence of acute complications and chronic pulmonary sequelae in infants needs to be evaluated in randomized controlled trials.

Preterm delivery for maternal or fetal indications: maternal morbidity, neonatal outcome and late sequelae in infants.

To assess maternal morbidity, and neonatal outcome and especially long term sequelae in infants born preterm due to maternal or fetal indications. Analysis of retrospective cohort. Oulu University Central Hospital, Finland. One hundred and three women, who were between the 24th and the 33rd week of pregnancy, delivered by caesarean delivery because of maternal or fetal indications. They were matched with 103 women who had spontaneous preterm delivery at corresponding gestational weeks between 1990-1997. Maternal morbidity, reasons for caesarean delivery, neonatal mortality and morbidity rates, and later development of the infants. Pre-eclampsia was diagnosed in 57% of the women in the indicated group and only in one woman in the control group. All infants in the indicated group and almost a third in the control group were born by caesarean birth; the main indication was threatening fetal asphyxia. There was a significant difference in neonatal mortality rates between the groups (175 vs 78 per thousand live births in the indicated vs control infants; RR 2.3, 95% CI 1.02, 4.9) and the main cause of death was respiratory insufficiency: 64% in the indicated group and 22% in the controls; RR 2.9, 95% CI 0.8, 10. Respiratory distress syndrome occurred more often (73% vs 53%, RR 1.4, 95% CI 1.1, 1.7) and it was more severe and more complicated in infants in the indicated group, compared with those in the control group. Symptomatic chronic lung disease at one year of age was more common in infants in the indicated group than in the control group (15% vs 3%; RR 4.6, 95% CI 1.4, 15.9). Not only the risks of neonatal mortality and morbidity but also long term pulmonary consequences, appear to be greater in infants born preterm by indicated delivery than in preterm infants born spontaneously at corresponding weeks.

An approach to the diagnosis of congenital infections

An approach to the diagnosis of congenital infections

Perinatal and neonatal outcome and late pulmonary sequelae in infants born after preterm premature rupture of membranes

Objective: To evaluate fetal outcome and long-term impact of very early preterm premature rupture of membranes (PROM). Methods: In a retrospective cohort study, 78 women with singleton pregnancies who delivered at the Oulu University Central Hospital between 1990 and 1996 and who had early PROM, between the 17th and 30th gestational weeks, were matched with 78 women with spontaneous preterm delivery during the same time (control group). The main outcome measures were maternal morbidity, interval from early PROM to delivery, perinatal and neonatal mortality rates and neonatal morbidity, need for primary and recurrent hospitalization and later pulmonary complications of the infants, and growth and neurologic findings at 1 year of corrected age. Results: The perinatal mortality was 282 per 1000 births in the early PROM group and 256 per 1000 births in the control group. Histopathologically defined chorioamnionitis and puerperal infections were significantly more common in the early PROM group than in controls (51 versus 29%, odds ratio [OR] 2.5, 95% confidence interval [CI] 1.3, 4.9 and 38 versus 22%, OR 2.3, 95% CI 1.1, 5.1, respectively). There were no differences in neonatal infections between groups. Pulmonary hypoplasia was detected more often in the early PROM group (in nine infants) compared with the control group (no infants). The duration of rehospitalization up to 1 year of age due to respiratory problems was a mean of 5 days in the early PROM group and a mean of 1 day in the control group ( P = .01; 95% CI 0.9, 6.9). Symptomatic chronic lung disease at 1 year of age was detected more often in the early PROM group than in controls (22 versus 9%; OR 2.4, 95% CI 0.9, 6.5). Conclusion: Early PROM seems to be a major obstetric and neonatal problem with pulmonary ramifications extending beyond the neonatal period. However, most of these infants can be saved.

Cerebral vasculopathy and neurologic sequelae in infants with cervicofacial hemangioma: report of eight patients.

To determine the association of cerebral arterial anomalies and progressive cerebral arterial occlusive disease in infants with facial hemangiomas. The cases of eight infants (seven girls and one boy) with the diagnosis of cervicofacial hemangioma and intracranial arterial anomalies were reviewed retrospectively. Findings from clinical and imaging examinations--including cranial computed tomography, magnetic resonance imaging and angiography, and catheter angiography--were evaluated. Serial imaging findings were studied to document progressive intracranial vascular changes. Five patients had additional associated congenital anomalies. Seven were treated with corticosteroids, interferon alfa-2a, or both. Progressive cerebrovascular occlusive changes were documented in four of the seven patients with serial imaging findings. Four other patients (all treated pharmacologically) had MR imaging documentation of cerebral infarction, and all had consistent, acquired neurologic symptoms. Intracranial arterial anomalies can coexist with cervicofacial hemangioma. Aneurysmal and occlusive changes are potentially progressive and can result in cerebral infarction. A causative association between occlusive cerebrovascular disease and pharmacologic treatment has not been excluded.

Perinatal Brain Iron Deficiency Predisposes the Rat Hippocampus to Long-term Damage following Hypoxic-ischemic Insult • 1566

The offspring of pregnancies complicated by diabetes mellitus or intrauterine growth retardation are at increased risk for perinatal asphyxia and for long-term neurocognitive sequelae. Both gestational conditions are characterized by an increased prevalence of brain iron deficiency. The hippocampus is important for a variety of cognitive functions (e.g., recognition memory) and is susceptible to hypoxicischemic (HI) injury. To evaluate the hypothesis that brain iron deficiency increases the vulnerability of the hippocampus to HI injury and to assess whether iron induced reperfusion injury has any role in such injuries, we ligated the right common carotid artery in 15 perinatally iron-deficient and 15 iron-sufficient 7-day-old rat pups,and exposed them to 2.5 hours of 8% FIO2(Levine model). The non-ligated left side served as the undamaged internal control. On day 14, neuronal injury was quantified histochemically by assessing intensity of staining for Nissl substance in 4 hippocampal subareas in both hemispheres using optical densitometry in gray scale units (range: 1/white-254/black). To assess iron induced reperfusion injury, sections were stained for iron by modified Perl's reaction. The brain iron concentration of the iron-deficient group was 55% of control (p<0.001). In the iron-deficient group,there was significant loss of Nissl substance on the ligated right side in subareas CA1 (124 ± 14 v. 112 ± 15, p=0.002), CA3ab (144 ± 10 v. 129 ± 15, p=0.001) and the dentate gyrus (136 ± 14 v. 128 ± 13, p=0.012), when compared with the unligated left side.The iron-sufficient group had significant right sided Nissl loss only in CA1 (111 ± 14 v. 106± 15, p = 0.05). The mean number of subareas with detectable right sided Nissl loss per animal was greater in the iron-deficient group than the iron-sufficient group (2.9 ± 1.0 v. 2.0 ± 1.2, p<0.05). The degree of right-sided Nissl substance loss per animal in the iron-deficient group was also greater in CA1(p=0.042), CA3ab(p=0.003) and the dentate gyrus(p=0.037)when compared with the iron-sufficient group. There were no side-to-side differences in the number of iron stained cells in either group. Perinatal iron deficiency increases the vulnerability of hippocampal subareas of CA1, CA3ab and dentate to HI injury. Iron deposition is not involved in the pathophysiology of this injury. These findings may explain the increased risk of perinatal asphyxia and its neurocognitive sequelae in infants born of pregnancies complicated by perinatal iron deficiency.