Superior Vena Cava Syndrome and Hypoxic Ischemic Encephalopathy Secondary to a Massive, Right-Sided Immature Cervical Teratoma.

Cervical teratomas are a rare form of fetal teratoma that can grow to massive size. Generally, these masses can be surgically excised after birth with excellent physical and functional prognosis because the benign variants respect anatomical borders. The primary complications of these masses are associated with compromise of the trachea and esophagus: upper airway obstruction and polyhydramnios. We report the first documented occurrence of superior vena cava syndrome and hypoxic ischemic encephalopathy associated with a massive, right-sided cervical teratoma. This case highlights that when cervical teratomas are right-sided and sufficiently large, they can extend inferiorly and compromise central venous return to the heart. This unique presentation would likely have required fetal surgical excision to avoid catastrophic cerebral injury.

Expression of the Nrf2-system at the blood-CSF barrier is modulated by neonatal inflammation and hypoxia-ischemia.

Transcription factor NF-E2-related factor-2 (Nrf2) is a key regulator of endogenous anti-oxidant systems shown to play a neuroprotective role in the adult by preserving blood-brain barrier function. The choroid plexus, site for the blood-CSF barrier, has been suggested to be particularly important in maintaining brain barrier function in development. We investigated the expression of Nrf2- and detoxification-system genes in choroid plexus following systemic LPS injections, unilateral cerebral hypoxia-ischemia (HI) as well as the combination of LPS and HI (LPS/HI). Plexuses were collected at different time points after LPS, HI and LPS/HI in 9-day old mice. mRNA levels of Nrf2 and many of its target genes were analyzed by quantitative PCR. Cell death was analyzed by caspase-3 immunostaining and TUNEL. LPS caused down-regulation of the Nrf2-system genes while HI increased expression at earlier time points. LPS exposure prior to HI prevented many of the HI-induced gene increases. None of the insults resulted in any apparent cell death to choroidal epithelium. These data imply that the function of the inducible anti-oxidant system in the choroid plexus is down-regulated by inflammation, even if choroid cells are not structurally damaged. Further, LPS prevented the endogenous antioxidant response following HI, suggesting the possibility that the choroid plexus may be at risk if LPS is united with an insult that increases oxidative stress such as hypoxia-ischemia.

Mood disorders in children following neonatal hypoxic-ischemic encephalopathy.

BACKGROUND: Few studies on the consequences following newborn hypoxic-ischemic encephalopathy (NHIE) assess the risk of mood disorders (MD), although these are prevalent after ischemic brain injury in adults. OBJECTIVE: To study the presence of MD in children survivors of NHIE. METHODS: 14 children survivors of NHIE treated with hypothermia and without cerebral palsy and 15 healthy children without perinatal complications were studied aged three to six years for developmental status (Ages and Stages Questionnaire 3 [ASQ-3]) and for socio-emotional status (Preschool Symptom Self-Report [PRESS] and Child Behavior Checklist [CBCL] 1.5-5 tests). Maternal depression was assessed using Montgomery-Asberg Depression Rating Scale (MADRS). Socio-economic factors such as parental educational level or monthly income were also studied. RESULTS: NHIE children did not present delay but scored worse than healthy children for all ASQ3 items. NHIE children showed higher scores than healthy children for PRESS as well as for anxious/depressive symptoms and aggressive behavior items of CBCL. In addition, in three NHIE children the CBCL anxious/depressive symptoms item score exceeded the cutoff value for frank pathology (P = 0.04 vs healthy children). There were no differences in the other CBCL items as well as in maternal MADRS or parental educational level or monthly income. Neither ASQ3 scores nor MADRS score or socio-economic factors correlated with PRESS or CBCL scores. CONCLUSIONS: In this exploratory study children survivors of NHIE showed increased risk of developing mood disturbances, in accordance with that reported for adults after brain ischemic insults. Considering the potential consequences, such a possibility warrants further research.

Preconditioning and postinsult therapies for perinatal hypoxic-ischemic injury at term.

Perinatal hypoxic-ischemic encephalopathy can be a devastating complication of childbirth. Herein, the authors review the pathophysiology of hypoxic-ischemic encephalopathy and the current status of neuroprotective strategies to ameliorate the injury centering on four themes: (1) monitoring in the perinatal period, (2) rapid identification of affected neonates to allow timely institution of therapy, (3) preconditioning therapy (a therapeutic that reduces the brain vulnerability) before hypoxic-ischemic encephalopathy, and (4) prompt institution of postinsult therapies to ameliorate the evolving injury. Recent clinical trials have demonstrated the significant benefit for hypothermic therapy in the postnatal period; furthermore, there is accumulating preclinical evidence that adjunctive therapies can enhance hypothermic neuroprotection. Advances in the understanding of preconditioning may lead to the administration of neuroprotective agents earlier during childbirth. Although most of these neuroprotective strategies have not yet entered clinical practice, there is a significant hope that further developments will enhance hypothermic neuroprotection.

Cost-effectiveness of therapeutic hypothermia to treat neonatal encephalopathy.

OBJECTIVE: To estimate the cost-effectiveness (CE) of total body hypothermia plus intensive care versus intensive care alone to treat neonatal encephalopathy. METHODS: Decision analytic modeling was used to synthesize mortality and morbidity data from three randomized controlled trials, the Total Body Hypothermia for Neonatal Encephalopathy Trial (TOBY), National Institute of Child Health and Human Development (NICHD), and CoolCap trials. Cost data inputs were informed by TOBY, the sole source of prospectively collected resource utilization data for encephalopathic infants. CE was expressed in terms of incremental cost per disability-free life year (DFLY) gained. Probabilistic sensitivity analysis was performed to generate CE acceptability curves (CEACs). RESULTS: Cooling led to a cost increase of £3787 (95% confidence interval [CI]: -2516, 12,360) (€5115; 95% CI: -3398-16,694; US$5344; 95% CI: -3598, 26,356; using 2006 Organisation for Economic Co-operation and Development (OECD) purchasing power parities) and a DFLY gain of 0.19 (95%CI: 0.07-0.31) over the first 18 months after birth. The incremental cost per DFLY gained was £19,931 (€26,920; US$28,124). The baseline CEAC showed that if decision-makers are willing to pay £30,000 for an additional DFLY, there is a 69% probability that cooling is cost-effective. The probability of CE exceeded 99% at this threshold when the throughput of infants was increased to reflect the national incidence of neonatal encephalopathy or when the time horizon of the economic evaluation was extended to 18 years after birth. CONCLUSIONS: The probability that cooling is a cost-effective treatment for neonatal encephalopathy is finely balanced over the first 18 months after birth but increases substantially when national incidence data or an extended time horizon are considered.

Small molecule biomarkers for neonatal hypoxic ischemic encephalopathy.

Hypoxic Ischemic Encephalopathy (HIE) is one of the most deleterious conditions in the perinatal period and the access to small molecule biomarkers aiding accurate diagnosis and disease staging, progress monitoring, and early outcome prognosis could provide relevant advances towards the development of personalized therapies. The emergence of metabolomics, the "omics" technology enabling the holistic study of small molecules, for biomarker discovery employing different analytical platforms, animal models and study populations has drastically increased the number and diversity of small molecules proposed as candidate biomarkers. However, the use of very few compounds has been implemented in clinical guidelines and authorized medical devices. In this work we review different approaches employed for discovering HIE-related small molecule biomarkers. Their role in associated biochemical disease mechanisms as well as the way towards their translation into the clinical practice are discussed.

Neonatal encephalopathy and hypoxic-ischemic encephalopathy.

Acute hypoxic-ischemic encephalopathy around the time of birth remains a major cause of death and life-long disability. The key insight that led to the modern revival of studies of neuroprotection was that, after profound asphyxia, many brain cells show initial recovery from the insult during a short "latent" phase, typically lasting approximately 6h, only to die hours to days later after a "secondary" deterioration characterized by seizures, cytotoxic edema, and progressive failure of cerebral oxidative metabolism. Studies designed around this framework showed that mild hypothermia initiated as early as possible before the onset of secondary deterioration and continued for a sufficient duration to allow the secondary deterioration to resolve is associated with potent, long-lasting neuroprotection. There is now compelling evidence from randomized controlled trials that mild to moderate induced hypothermia significantly improves survival and neurodevelopmental outcomes in infancy and mid-childhood.

Biomarkers in neonatal hypoxic-ischemic encephalopathy-Review of the literature to date and future directions for research.

The widespread introduction of therapeutic hypothermia as a standard of care in hypoxic-ischemic encephalopathy (HIE) has brought increasing pressure on clinicians to make an early and accurate assessment of the degree of hypoxic injury (HI) that has occurred and the severity of the encephalopathy that will ensue. No single blood-based marker is currently robust enough to detect significant HI or predict outcome. However, research in the field has been active in the last 10 years and we know that HIE is associated with predictable alterations in the expression of a number of inflammatory proteins, neuron-specific proteins, metabolite pathways, and microRNA. These alterations evolve quickly over the first hours and days of life. Predictive power varies depending on the timing of measurement of the biomarker, the sample type, and the case mix of the cohort examined. Combining clinical data with biochemical measurements is currently the most likely path toward improved detection and prediction of outcome in neonatal HIE.

Early identification of neonatal mild hypoxic-ischemic encephalopathy by amide proton transfer magnetic resonance imaging: A pilot study.

PURPOSE: This study aimed to evaluate the amide proton transfer (APT) values in neonates with mild hypoxic-ischemic encephalopathy (HIE) using APT imaging. METHOD: A total of 30 full-term neonates with mild HIE (16 males and 14 females; mean postnatal age 4.2 days, age range 2-7 days) and 12 normal neonates (six males and six females; mean postnatal age 3.3 days, age range 2-5 days) underwent conventional magnetic resonance imaging and APT imaging. APT measurements were performed in multiple regions of interest (ROIs) in the brain. APT values were statistically analyzed to assess for significant differences between the mild HIE and normal neonates in different regions of the brain, and correlation with neonatal gestational age. RESULTS: In 30 neonates with mild HIE, 10% (3/30) of the HIE patients had normal conventional MRI. There were significant differences in APT values of the HIE group in bilateral caudate, bilateral thalamus, bilateral centrum semiovale and left globus pallidus/putamen (p < 0.05), and no statistical difference was observed in right globus pallidus/putamen (p = 0.051) and brainstem (p = 0.073) between the two groups. Furthermore, APT values in bilateral caudate, bilateral globus pallidus/putamen, bilateral thalamus, and brainstem regions (p < 0.05) exhibited positive linear correlations with gestational age in the control group, except for bilateral centrum semiovale (right: Pearson's r = 0.554, p = 0.062; left: Pearson's r = 0.561, p = 0.058). In the mild HIE groups, no significant correlation with gestational age was found in all regions. CONCLUSIONS: APT imaging is a feasible and useful technique with diagnostic capability for neonatal HIE.

Neonatal hypoxic-ischemic encephalopathy: emerging therapeutic strategies based on pathophysiologic phases of the injury.

Neonatal hypoxic ischemic encephalopathy (HIE) is an important cause of neonatal death and disability. At present, there is no unified standard and specialized treatment method for neonatal HIE. In clinical practice, we have found that a gap remains between preclinical medical research and clinical application in the treatment of neonatal HIE. To promote an organic combination of preclinical research and clinical application, we propose the different phases as intervention targets, based on the pathophysiologic changes in phases I, II, and III of neonatal HIE; moreover, we suggest transformative medicine as a principle that may improve the therapeutic effect by blocking the progression of the disease to an irreversible stage. For instance, in phase I, mild hypothermia, free radical scavenger (erythropoietin, hydrogen-rich saline), excitatory amino acid receptor blocker, and neuroprotective agents should be administered to neonates with moderate/severe HIE; in phase II, following phase I treatment, anti-inflammatory agents, neuroprotective or nerve regeneration agents, and stem cell transplantation should be administered to patients; in phase III, anti-inflammatory agents, neuroprotective or nerve regeneration agents, and stem cell transplantation should be administered to patients. As soon as the patient's condition has stabilized, acupuncture, massage, and rehabilitation training should be performed. Following further study of stem cells, stem cell transplantation is expected to become the most promising therapeutic candidate for treatment of severe neonatal HIE with its sequelae.

MRI in paediatric hypoxic-ischemic disease, metabolic disorders and malformations-a review.

MRI has become the most important modality in paediatric neuroimaging. It provides an excellent anatomical overview with good spatial and temporal resolution, allows investigations of the blood vessels, and - using technologies such as diffusion-weighted imaging and magnetic resonance spectroscopy - it allows quick and exact differentiation of ischemic, hypoxic, inflammatory, oncologic, traumatic and metabolic diseases. This review presents an overview of brain MRI in infants and children with suspected hypoxic-ischemic disease, metabolic disorders or (vascular) malformations, illustrating these issues by some MRI findings in selected important conditions and discussing some major clinical and pathophysiological aspects important for imaging.

Neurokinin A level in hypoxic-ischemic encephalopathy.

BACKGROUND: The present study was performed to investigate the effect of neonatal hypoxic-ischemic encephalopathy (HIE) on the neurotransmitter neurokinin A (NKA) and determine its relation to the severity of neonatal hypoxia. METHODS: Eighteen neonates suffering from HIE were compared to 10 clinically healthy full-term neonates acting as the control group. Maternal history of each neonate was collected, then deliveries were attended, resuscitation details including the Apgar score and thorough clinical examination of the neonates were performed. Routine laboratory work-up was done for the enrolled neonates, including complete blood count and C-reactive protein as well as estimation of NKA by enzyme-linked immunosorbent assay in the cord blood and after clinical stabilization. RESULTS: NKA was significantly lower in HIE patients compared to the controls at delivery with improvement in the follow-up sample. Additionally, the maximum decrease was detected in the neonates who suffered severe hypoxia compared to those who suffered mild hypoxia. Significant positive correlations were demonstrated between NKA at birth and Apgar scores at the 10th and 15th min. Regression showed that stage of HIE was the strongest determinant factor for the level of NKA at birth. CONCLUSION: NKA levels are decreased in HIE and this is more profound in the severe degrees of hypoxia compared to the mild ones. This emphasizes its role in pathogenesis of HIE and further proves that an imbalance in the central neuropeptide system results from HIE in the neonatal period.

Impacts of therapeutic hypothermia on cardiovascular hemodynamics in newborns with hypoxic-ischemic encephalopathy: a case control study using echocardiography.

PURPOSE: The effects of therapeutic hypothermia (TH) on hemodynamics in newborns with hypoxic-ischemic encephalopathy (HIE) were evaluated. MATERIALS AND METHODS: Thirty-two neonates (gestational age, 39.4 ± 1.3 weeks) who had TH for HIE and echocardiographic hemodynamic assessments during TH and post-TH period were studied. Gestational-age-matched 34 healthy neonates were enrolled for comparison. RESULTS: During TH, patients had significantly decreased left ventricular cardiac output (LVCO), descending aorta blood flow (DABF), and DABF/LVCO ratio, and increased resistive index of DA compared to controls. Upper body blood flow (UBBF) remained unchanged but UBBF/LVCO ratio significantly increased during TH. Urine output decreased significantly during TH and increased after rewarming, and showed significant positive correlation with DABF/LVCO ratio. Sixteen patients (50%) showed hypoxic-ischemic (HI) lesions on brain magnetic resonance imaging (MRI) and had significantly increased UBBF/LVCO ratio during TH compared to patients without HI lesions. Patients with UBBF/LVCO ratio >55% had significantly higher risk of having HI lesions on brain MRI (odds ratio 13.0; 95% CI, 2.4-70.2). CONCLUSIONS: Decrease in cardiac output and descending aorta blood flow, and preferential cerebral redistribution of cardiac output along with an increase in systemic peripheral vascular resistance may affect systemic organ perfusion and cerebral metabolism.

Progesterone as a Postnatal Prophylactic Agent for Encephalopathy Caused by Prenatal Hypoxic Ischemic Insult.

Brain damage caused by hypoxic ischemic insult during the perinatal period causes hypoxic ischemic encephalopathies (HIEs). Therapeutic hypothermia is indicated for HIE, but because the therapeutic burden is large for its limited therapeutic effectiveness, another strategy is needed. Progesterone (P4) plays a neuroprotective role through the actions of its metabolite, allopregnanolone (Allo), on P4 receptor, γ-aminobutyric acid type A receptors or both. We examined the therapeutic potential of P4 using a newborn rat model of HIE. Fetal rats were exposed to transient ischemic hypoxia by 30-minute bilateral uterine artery clamping on gestational day 18. After spontaneous birth, newborn pups were subcutaneously injected with P4 (0.10 or 0.01 mg), medroxyprogesterone acetate (MPA; 0.12 mg), or Allo (0.10 mg) through postnatal days (PDs) 1 to 9. Brain damage in the rats was assessed using the rotarod test at PD50. The HIE insult reduced the rats' ability in the rotarod task, which was completely reversed by P4 and Allo, but not by MPA. Histological examination revealed that the HIE insult decreased neuronal (the cortex and the hippocampal CA1 region) and oligodendroglial cell density (the corpus callosum) through PD0 to PD50. The axon fiber density and myelin sheath thickness in the corpus callosum were also reduced at PD50. The time-course study revealed that P4 restored oligodendroglial cells by PD5, which was followed by neuroprotective action of P4 that lasted long over the injection period. These results suggest that P4 protects the neonatal brain from HIE insult via restoration of oligodendroglial cells.

Perinatal Brain Injury: Mechanisms, Prevention, and Outcomes.

Perinatal brain injury may lead to long-term morbidity and neurodevelopmental impairment. Improvements in perinatal care have resulted in the survival of more infants with perinatal brain injury. The effects of hypoxia-ischemia, inflammation, and infection during critical periods of development can lead to a common pathway of perinatal brain injury marked by neuronal excitotoxicity, cellular apoptosis, and microglial activation. Various interventions can prevent or improve the outcomes of different types of perinatal brain injury. The objective of this article is to review the mechanisms of perinatal brain injury, approaches to prevention, and outcomes among children with perinatal brain injury.

Gerard W. Ostheimer Lecture 2006: What's New in Obstetric Anaesthesia? Contributions from the 2005 literature.

The Gerard W. Ostheimer lecture is given every year at the annual meeting of the Society for Obstetric Anesthesia and Perinatology by an obstetric anaesthesiologist who has reviewed the scientific literature for the previous calendar year. This article is based on the 2006 Ostheimer lecture and reviews three areas of interest in neonatology: resuscitation of the newborn, neonatal encephalopathy and the influence of epidural analgesia on breastfeeding.

Prediction of Outcome in Neonates with Hypoxic-Ischemic Encephalopathy II: Role of Amplitude-Integrated Electroencephalography and Cerebral Oxygen Saturation Measured by Near-Infrared Spectroscopy.

BACKGROUND: Few data have been published on the combined use of amplitude-integrated electroencephalography (aEEG) and near-infrared spectroscopy (NIRS) for outcome prediction in neonates cooled for hypoxic-ischemic encephalopathy (HIE). OBJECTIVE: Our aim was to evaluate the predictive values and the most powerful predictive combinations of single aEEG and NIRS parameters and the respective cut-off values with regard to short-term outcomes in HIE II. METHODS: aEEG and NIRS were prospectively studied at the Medical University of Vienna in the first 102 h of life with regard to magnetic resonance imaging (MRI). Thirty-two neonates diagnosed with HIE II treated with hypothermia were investigated. The measurement period was divided into 6-h epochs. According to MRI, 2 outcome groups were defined and predictive values of aEEG parameters, regional cerebral oxygen saturation (rScO2), and the additional value of both methods combined were studied. Receiver operating curves (ROC) were obtained and area under the curve (AUC) values were calculated. ROC were then used to detect the optimal cut-off points, sensitivity, specificity, positive predictive values, and negative predictive values. RESULTS: At all time epochs, combined parameter scores were more predictive than single parameter scores. The highest AUC were observed between 18 and 60 h of cooling for the aEEG summation score (0.72-0.84) and for (background pattern + seizures) × rScO2 (0.79-0.85). At 42-60 h sensitivity was similar between those 2 scores (87.5-90.0%), but the addition of NIRS to aEEG led to an increase in specificity (from 52.4-59.1% to 72.7-90.5%). CONCLUSIONS: In HIE II, aEEG and NIRS are important predictors of short-term outcome. The combination of both methods improves prognostication. The highest predictive abilities were observed between 18 and 60 h of cooling.

Proton MR spectroscopy in neonates with perinatal cerebral hypoxic-ischemic injury: metabolite peak-area ratios, relaxation times, and absolute concentrations.

BACKGROUND: Results from cerebral proton (1)H-MR spectroscopy studies of neonates with perinatal hypoxic-ischemic injury have generally been presented as metabolite peak-area ratios, which are T1- and T2-weighted, rather than absolute metabolite concentrations. We hypothesized that compared with (1)H-MR spectroscopy peak-area ratios, calculation of absolute metabolite concentrations and relaxation times measured within the first 4 days after birth (1) would improve prognostic accuracy and (2) enhance the understanding of underlying neurochemical changes in neonates with neonatal encephalopathy. METHODS: Seventeen term infants with neonatal encephalopathy and 10 healthy controls were studied at 2.4T at 1 (1-3) and 2 (2-4) (median [interquartile range]) days after birth, respectively. Infants with neonatal encephalopathy were classified into 2 outcome groups (normal/mild and severe/fatal), according to neurodevelopmental assessments at 1 year. The MR spectroscopy peak-area ratios, relaxation times, absolute concentrations, and concentration ratios of lactate (Lac), creatine plus phosphocreatine (Cr), N-acetylaspartate (NAA), and choline-containing compounds (Cho) from a voxel centered on the thalami were analyzed according to outcome group. RESULTS: Comparing the severe/fatal group with the controls (significance assumed with P < 0.05), we found that Lac/NAA, Lac/Cho, and Lac/Cr peak-area ratios increased and NAA/Cr and NAA/Cho decreased; Lac, NAA, and Cr T2s were increased; [Lac] was increased and [Cho], [Cr], and [NAA] decreased; and among the concentration ratios, only [Lac]/[NAA] was increased. Comparison of the normal/mild group with controls revealed no differences in peak-area ratios, relaxation times, or concentration ratios but decreased [NAA], [Cho], and [Cr] were observed in the infants with normal/mild outcome. Comparison of the normal/mild and severe/fatal groups showed increased Lac/NAA and Lac/Cho and decreased NAA/Cr and NAA/Cho peak-area ratios, reduced [NAA], and increased Lac T2 in the infants with the worse outcome. CONCLUSIONS: Metabolite concentrations, in particular [NAA], enhance the prognostic accuracy of cerebral (1)H-MR spectroscopy-[NAA] was the only measurable to discriminate among all (control, normal/mild, and severe/fatal outcome) groups. However, peak-area ratios are more useful prognostic indicators than concentration ratios because they depend on metabolite concentrations and T2s, both of which are pathologically modulated. Concentration ratios depend only on the concentrations of the constituent metabolites. Increased Cr T2 may provide an indirect marker of impaired cellular energetics, and similarly, NAA T2 may constitute an index of exclusively neuronal energy status. Our recommendation is to collect data that enable calculation of brain metabolite concentrations. However, if time constraints make this impossible, metabolite peak-area ratios provide the next best method of assigning early prognosis in neonatal encephalopathy.

Circulating Dickkopf-1 in hypoxic ischemic neonates.

OBJECTIVE: The current study aimed to determine the serum level of Dickkopf-1 (Dkk-1) in peripheral blood of neonates with hypoxic ischemic encephalopathy (HIE). METHODS: We measured serum levels of Dkk-1 by ELISA in neonates with HIE (n = 20) within 24 h from symptom onset and in healthy controls (n = 20). RESULTS: Dkk-1 serum levels increased significantly in HIE neonates than in healthy control. DKK-1 serum levels increased significantly in HIE neonates with convulsion, using multiple anti-convulsant drugs and those complicated with cranial ultrasound changes. Serum DKK-1 levels increased significantly in severe HIE patients. CONCLUSION: Our study provides for the first time the evidence of releasing Dkk-1 into the circulation of neonates with HIE with higher level in severe degree.

Hypoxic ischemic encephalopathy in newborns linked to placental and umbilical cord abnormalities.

OBJECTIVE: Birth asphyxia and hypoxic ischemic encephalopathy (HIE) of the newborn remain serious complications. We present a study investigating if placental or umbilical cord abnormalities in newborns at term are associated with HIE. MATERIALS AND METHODS: A prospective cohort study of the placenta and umbilical cord of infants treated with hypothermia (HT) due to hypoxic brain injury and follow-up at 12 months of age has been carried out. The study population included 41 infants treated for HT whose placentas were submitted for histopathological analysis. Main outcome measures were infant development at 12 months, classified as normal, cerebral palsy, or death. A healthy group of 100 infants without HIE and normal follow-up at 12 months of age were used as controls. RESULTS: A velamentous or marginal umbilical cord insertion and histological abruption was associated with the risk of severe HIE, OR = 5.63, p = 0.006, respectively, OR = 20.3, p = 0.01 (multiple-logistic regression). Velamentous or marginal umbilical cord insertion was found in 39% among HIE cases compared to 7% in controls. CONCLUSIONS: Placental and umbilical cord abnormalities have a profound association with HIE. A prompt examination of the placentas of newborns suffering from asphyxia can provide important information on the pathogenesis behind the incident and contribute to make a better early prognosis.