Risk factors for neonatal hypoxic ischemic encephalopathy and therapeutic hypothermia: a matched case-control study.

BACKGROUND: Peripartum asphyxia is one of the main causes of neonatal morbidity and mortality. In moderate and severe cases of asphyxia, a condition called hypoxic-ischemic encephalopathy (HIE) and associated permanent neurological morbidities may follow. Due to the multifactorial etiology of asphyxia, it may be difficult prevent, but in term neonates, therapeutic cooling can be used to prevent or reduce permanent brain damage. The aim of this study was to assess the significance of different antenatal and delivery related risk factors for moderate and severe HIE and the need for therapeutic hypothermia. METHODS: We conducted a retrospective matched case-control study in Helsinki University area hospitals during 2013-2017. Newborn singletons with moderate or severe HIE and the need for therapeutic hypothermia were included. They were identified from the hospital database using ICD-codes P91.00, P91.01 and P91.02. For every newborn with the need for therapeutic hypothermia the consecutive term singleton newborn matched by gender, fetal presentation, delivery hospital, and the mode of delivery was selected as a control. Odds ratios (OR) between obstetric and delivery risk factors and the development of HIE were calculated. RESULTS: Eighty-eight cases with matched controls met the inclusion criteria during the study period. Maternal and infant characteristics among cases and controls were similar, but smoking was more common among cases (aOR 1.46, CI 1.14-1.64, p = 0.003). The incidence of preeclampsia, diabetes and intrauterine growth restriction in groups was equal. Induction of labour (aOR 3.08, CI 1.18-8.05, p = 0.02) and obstetric emergencies (aOR 3.51, CI 1.28-9.60, p = 0.015) were more common in the case group. No difference was detected in the duration of the second stage of labour or the delivery analgesia. CONCLUSIONS: Smoking, induction of labour and any obstetric emergency, especially shoulder dystocia, increase the risk for HIE and need for therapeutic hypothermia. The decisions upon induction of labour need to be carefully weighed, since maternal smoking and obstetric emergencies can hardly be controlled by the clinician.

Outcomes of the First Pregnancy After Fertility-Sparing Surgery for Early-Stage Ovarian Cancer.

OBJECTIVE: To evaluate the outcomes of the first pregnancy after fertility-sparing surgery in patients treated for early-stage ovarian cancer. METHODS: We performed a retrospective study of women aged 18-45 years with a history of stage IA or IC ovarian cancer reported to the California Cancer Registry for the years 2000-2012. These data were linked to the 2000-2012 California Office of Statewide Health Planning and Development birth and discharge data sets to ascertain oncologic characteristics and obstetric outcomes. We included in the case group ovarian cancer patients who conceived at least 3 months after fertility-sparing surgery. The primary outcome was preterm birth, and only the first pregnancy after cancer diagnosis was considered. Secondary outcomes included small-for-gestational-age (SGA) neonates, neonatal morbidity (respiratory support within 72 hours after birth, hypoxic-ischemic encephalopathy, seizures, infection, meconium aspiration syndrome, birth trauma, and intracranial or subgaleal hemorrhage), and severe maternal morbidity as defined by the Centers for Disease Control and Prevention. Propensity scores were used to match women in a 1:2 ratio for the case group and the control group. Wald statistics and logistic regressions were used to evaluate outcomes. RESULTS: A total of 153 patients who conceived after fertility-sparing surgery were matched to 306 women in a control group. Histologic types included epithelial (55%), germ-cell (37%), and sex-cord stromal (7%). Treatment for ovarian cancer was not associated with preterm birth before 37 weeks of gestation (13.7% vs 11.4%; odds ratio [OR] 1.23, 95% CI 0.69-2.20), SGA neonates (birth weight less than the 10th percentile: 11.8% vs 12.7%; OR 0.91, 95% CI 0.50-1.66), severe maternal morbidity (2.6% vs 1.3%; OR 2.03, 95% CI 0.50-8.25), or neonatal morbidity (both 5.9% OR 1.00, 95% CI 0.44-2.28). CONCLUSION: Patients who conceived at least 3 months after surgery for early-stage ovarian cancer did not have an increased risk of adverse obstetric outcomes.

Antenatal and Perioperative Mechanisms of Global Neurological Injury in Congenital Heart Disease.

Congenital heart defects (CHD) is one of the most common types of birth defects. Thanks to advances in surgical techniques and intensive care, the majority of children with severe forms of CHD survive into adulthood. However, this increase in survival comes with a cost. CHD survivors have neurological functioning at the bottom of the normal range. A large spectrum of central nervous system dysmaturation leads to the deficits seen in critical CHD. The heart develops early during gestation, and CHD has a profound effect on fetal brain development for the remainder of gestation. Term infants with critical CHD are born with an immature brain, which is highly susceptible to hypoxic-ischemic injuries. Perioperative blood flow disturbances due to the CHD and the use of cardiopulmonary bypass or circulatory arrest during surgery cause additional neurological injuries. Innate patient factors, such as genetic syndromes and preterm birth, and postoperative complications play a larger role in neurological injury than perioperative factors. Strategies to reduce the disability burden in critical CHD survivors are urgently needed.

Neurologic Injury in Neonates Undergoing Cardiac Surgery.

Neurodevelopmental outcomes after neonatal congenital heart surgery are significantly influenced by brain injury detectable by MRI imaging techniques. This brain injury can occur in the prenatal and postnatal periods even before cardiac surgery. Given the significant incidence of new MRI brain injury after cardiac surgery, much work is yet to be done on strategies to detect, prevent, and treat brain injury in the neonatal period in order to optimize longer-term neurodevelopmental outcomes.

Characteristics and outcomes of children with acute myeloid leukemia and Down syndrome who are ineligible for clinical trials due to severe comorbidities.

BACKGROUND: High survival rates of 80-90% have been reported in recent clinical trials of reduced-intensity chemotherapies for children with acute myeloid leukemia and Down syndrome (AML-DS). However, a certain number of children with AML-DS have complicating comorbidities, including congenital heart disease (CHD), and are therefore ineligible for enrolment in clinical trials. METHODS: We retrospectively analyzed the clinical characteristics and outcomes of children with AML-DS who were excluded from Japanese clinical trials conducted between 2000 and 2015. RESULTS: Twelve children (six males and six females) were identified and were ineligible for CHD (n = 8) and other comorbidities, including hyperleukocytosis complicated with coagulopathy, severe hemophagocytosis, pulmonary fibrosis, and hypoxic-ischemic encephalopathy (n = 1 each). The median age at the diagnosis was 14 months (range, 5 months to 11.5 years). Among all cases, 11 patients were treated with curative intent. Four patients were considered intolerant to intensive chemotherapy and received only low-dose cytarabine-based chemotherapy: three failed to achieve remission and died of disease, while one successfully achieved remission but eventually died of infection. Seven cases underwent regular-intensive chemotherapy for AML-DS: six were alive and in remission; one had relapsed disease. One patient who received the best supportive care died of disease. Finally, six patients remained in continuous complete remission, while six died. The 5-year overall survival rate was 51%. CONCLUSIONS: The prognosis of AML-DS patients who received insufficient treatment due to severe complication was poor. The optimal dose intensity of curative chemotherapy for such cases should be explored.

Biomarkers of impaired placentation at 35-37 weeks' gestation in the prediction of adverse perinatal outcome.

OBJECTIVE: To investigate the potential value of uterine artery pulsatility index (UtA-PI) and serum levels of the angiogenic placental growth factor (PlGF) and the antiangiogenic factor soluble fms-like tyrosine kinase-1 (sFlt-1) in the prediction of adverse perinatal outcome in small-for-gestational-age (SGA) and non-SGA neonates at 35-37 weeks' gestation. METHODS: This was a prospective observational study of 19 209 singleton pregnancies attending for a routine hospital visit at 35 + 0 to 36 + 6 weeks' gestation. This visit included recording of maternal demographic characteristics and medical history, sonographic estimation of fetal weight, color Doppler ultrasound for measurement of mean UtA-PI, and measurement of serum concentrations of PlGF and sFlt-1. Multivariable logistic regression analysis was carried out to determine which of the factors from maternal or pregnancy characteristics and measurements of UtA-PI, PlGF and sFlt-1 provided a significant contribution in the prediction of each of four adverse outcome measures: first, stillbirth; second, Cesarean delivery for suspected fetal compromise in labor; third, neonatal death or hypoxic ischemic encephalopathy Grade 2 or 3; and, fourth, admission to the neonatal unit (NNU) for ≥ 48 h. Predicted probabilities from logistic regression analysis were used to construct receiver-operating characteristics curves to assess the performance of screening for these adverse outcomes. RESULTS: First, 83% of stillbirths, 82% of Cesarean sections for presumed fetal compromise in labor, 91% of cases of neonatal death or hypoxic ischemic encephalopathy and 86% of NNU admissions for ≥ 48 h occurred in pregnancies with a non-SGA neonate. Second, UtA-PI > 95th percentile, sFlt-1 > 95th percentile and PlGF < 5th percentile were associated with increased risk of Cesarean delivery for suspected fetal compromise in labor and NNU admission for ≥ 48 h; the number of stillbirths and cases of neonatal death or hypoxic ischemic encephalopathy was too small to demonstrate significance in the observed differences from cases without these adverse outcomes. Third, multivariable logistic regression analysis demonstrated that, in the prediction of Cesarean delivery for suspected fetal compromise in labor, there was no significant contribution from biomarkers; the prediction of NNU admission for ≥ 48 h by maternal demographic characteristics and medical history was only marginally improved by the addition of sFlt-1 or PlGF. Fourth, for each biomarker, the detection rate of adverse outcome was higher in SGA than in non-SGA neonates, but this increase was accompanied by an increase in false-positive rate. Fifth, the relative risk of UtA-PI > 95th , sFlt-1 > 95th and PlGF < 5th percentiles for most adverse outcomes was < 2.5 in both SGA and non-SGA neonates. CONCLUSIONS: In pregnancies undergoing routine antenatal assessment at 35-37 weeks' gestation, measurements of UtA-PI, sFlt-1 or PlGF provide poor prediction of adverse perinatal outcome in both SGA and non-SGA fetuses. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Factors associated with neonatal hypoxic ischemic encephalopathy in infants with an umbilical artery pH less than 7.00.

OBJECTIVE: Our objective was to identify factors associated with hypoxic-ischemic encephalopathy (HIE) among newborns with an umbilical pH < 7.00. STUDY DESIGN: Case-control study during a four-year study period in a single academic tertiary-center, including all neonates ≥35 weeks with an umbilical pH < 7.00. Cases were neonates with HIE, regardless of Sarnat classification, and controls were neonates without signs of HIE. We used univariate and multivariate analysis to compare the maternal, obstetric, and neonatal characteristics of cases and controls. RESULTS: Among 21,211 births, 179 neonates≥35 weeks (0.84%) had an umbilical pH < 7.00. One hundred and forty-seven(82.1%) newborns had severe asphyxia without HIE, 32(17.9%) had HIE and 21(11.7%) needed therapeutic hypothermia. Neonates with HIE were significantly more likely to have 5-minute Apgar score<7(75% versus 15.7% P < 0.01), together with a lower mean umbilical arterial pH (6.84 versus 6.95, P < 0.01) and lower mean base deficits (-17.0 versus -12.7, P < 0.01). Factors significantly associated with HIE were the mother being overweight(28.1% for cases versus 14.3% for controls, adjusted OR=4.6[1.4-15.2]) or obese(25.0% versus 13.6%, aOR=15.5[1.1-12.5]), smoking(18.7% versus 5.4%, aOR=5.8[1.6-21.2]), a sentinel event as cord prolaps or placenta abruption (34.4% versus 13.6%, aOR=2.7[1.1-7.2]), and decreased fetal heart rate variability(68.7% versus 44.2%, aOR=2.8[1.1-6.9]). CONCLUSION: Among neonates with an umbilical cord pH < 7.00, those with HIE had a more severe metabolic acidosis. Maternal factors associated with HIE among newborns with an umbilical pH < 7.00, were being overweight or obese, and smoking, and the associated obstetric factors were a sentinel event and decreased fetal heart rate variability.

Risk management and provider liabilities in infantile cerebral palsy based on malpractice litigation cases.

AIM: Infantile cerebral palsy (CP) severely affects the survival and quality of life of infants. CP is typically caused by multiple factors, leading to causal uncertainty of the role of medical errors in CP and resulting in frequent medical disputes. No relevant research exists on risk management and malpractice liabilities in CP, including in China. METHOD: A retrospective analysis of 400 CP malpractice litigation cases from 18th June 1999 to 23rd November 2017, collected from China Judgments Online, included basic case information, CP risk factors, medical errors, medical malpractice liability determination, and compensation. RESULTS: Up to 63.5% of infants with CP were affected by asphyxia, followed by hypoxic-ischemic encephalopathy (63.3%), neonatal infection (52.3%) and intracranial hemorrhage (36.0%). Most (89.1%) of civil judgments resulted in liability for medical errors, with the highest proportion of ultimate liability. The three most frequent medical errors were failure of completing delivery in time (30.2%), incomplete assessment of birth process detection (28.8%), and nonstandard medical records (25.3%). Each case involved 2.5 medical errors on average. No difference in the distribution of medical errors between premature and full-term CP infants (P > 0.05) was found. Compensation for damage was awarded in 91.4% of claims, and the mean value of compensation was $73,506. The mean value of the total actual loss of the family was $128,198. INTERPRETATION: Contradictions between the doctors and patients were prominent in malpractice CP litigation cases, with a total loss of $3.97 billion attributable to new CP cases in China in 2017. Asphyxia was the most frequent risk factor for CP since it may easily draw the attention of the sufferer's family. Medical service providers did not pay attention to risk management in preterm infants. The importance of fetal monitoring and standardized medical record writing should be emphasized.

Encefalopatía hipóxica-isquémica neonatal / Neonatal hypoxic-ischemic encephalopathy

La encefalopatía hipóxica-isquémica es un síndrome bien definido que afecta a los recién nacidos a término debido a asfixia fetal al nacer. La incidencia es 1-8 de cada 1000 nacidos en países desarrollados y asciende hasta 25 cada 1000 nacidos en países en desarrollo. Las causas más frecuentes son desprendimiento de la placenta, prolapso del cordón umbilical y rotura uterina. El criterio diagnóstico incluye incapacidad parcial o total del recién nacido para llorar y respirar al ser estimulado que requiere ventilación asistida en la sala de partos, Apgar < 5 en 5 y 10 minutos, acidemia (pH ≤ 7 y/o déficit de bases ≥ 12 mmol/l), alteraciones del estado de vigilia/sueño, de los reflejos primitivos y estiramiento muscular y tono muscular. En la forma leve la recuperación es total en tres días y sin (o con mínimas) secuelas de neurodesarrollo. En las formas moderadas y graves existen déficits neurológicos permanentes y alteraciones del neurodesarrollo (48%), 27% mueren y 25% son normales. El EEG regular o amplitud integrada y la resonancia magnética y espectroscópica realizados entre las 24 y las 96 horas y los 7 y 21 días de nacido respectivamente tienen un gran valor diagnóstico y pronóstico. Se recomienda hipotermia corporal (33.5 °C por 72 horas) antes de las 6 horas de nacido en las formas moderadas y graves. El resultado es una disminución de la mortalidad (de 35% a 27%) y de la morbilidad (de 48% a 27%).

Hypoxic-ischemic encephalopathy is a clearly recognizable clinical syndrome of in term newborns due to fetal asphyxia at birth. The incidence is 1.5 (95% CI 1.3 to 1.7) but it ranges from 1-8 and 25 out of every 1000 born in developed and developing countries, respectively. The most frequent causes are detachment of the placenta, prolapse of the umbilical cord and uterine rupture. The diagnostic criteria include partial or total incapacity for the newborn to cry and breath at birth even when stimulated, requiring assisted ventilation in the delivery room, Apgar < 5 in 5 and 10 minutes, acidemia (pH ≤ 7 and / or bases deficit ≥ 12 mmol/l), alterations of the conscience and the reflexes of Moro, grasping and suction, muscular stretching and muscle tone. The clinical forms are mild, moderate and severe. In the mild forms, the recovery is total in three days without, or with minimal, neurodevelopmental alterations. The moderate and severe forms cause permanent neurological deficits and neurodevelopmental alterations (48%) or death (27%). The regular or amplitude integrated EEG and the magnetic and spectroscopic magnetic resonance imaging performed between 24 and 96 hours and 7 and 21 days after birth, respectively, have a high diagnostic and prognostic value. Induced hypothermia (33.5° C for 72 hours) is recommended before 6 hours old. The result is a decrease in mortality (from 35% to 27%) and morbidity (from 48% to 27%).

Infant outcome after complete uterine rupture.

BACKGROUND: Complete uterine rupture is a rare peripartum complication often associated with a catastrophic outcome for both mother and child. However, little has been written based on large data sets about maternal and infant outcome after complete ruptures. This is partly due to the rarity of the event and the serious maternal and infant outcome; it is also partly due to the use of international diagnostic codes that do not differentiate between the less catastrophic partial rupture and more catastrophic complete uterine rupture. As uterine rupture is expected to increase due to increased cesarean delivery rates worldwide, it is important to know more completely about the outcome following complete uterine rupture. OBJECTIVE: We sought to explore risk factors associated with poor infant outcome in cases of complete uterine rupture. STUDY DESIGN: This population-based study used data from the Medical Birth Registry of Norway, the Patient Administration System, and medical records. We included births with complete uterine rupture after start of labor in all maternity units in Norway during the period 1967 through 2008 (n = 244 births), identified among 2,455,797 births. Uterine ruptures were identified and further studied through a review of medical records. We estimated the associations between infant outcomes and demographic and labor risk factors using logistic regression analyses. Odds ratios with 95% confidence intervals for each risk factor were determined after adjustment for demographic factors and period of birth. The main outcome measure was infant outcome: healthy infant, intrapartum/infant deaths, hypoxic ischemic encephalopathy, and admission to the neonatal intensive care unit. RESULTS: We identified 109 (44.7%) healthy infants, 56 (23.0%) infants needing neonatal intensive care unit admission, 64 (26.2%) intrapartum/infant deaths, and 15 (6.1%) infants with hypoxic ischemic encephalopathy. The highest number of intrapartum/infant deaths occurred in 1967 through 1977 (51.6%) and the fewest in 2000 through 2008 (15.0%). Unscarred uterine ruptures did not significantly increase intrapartum/infant deaths compared to scarred uterine ruptures. Placental separation and/or fetal extrusion had the highest odds ratio for intrapartum/infant deaths (odds ratio, 17.9; 95% confidence interval, 7.5-42.4). Time-to-delivery interval <20 minutes resulted in fewest intrapartum/infant deaths (9.9%), although there were 2 deaths at 10-minute interval. Time to delivery >30 minutes vs <20 minutes increased risk of death (odds ratio, 16.7; 95% confidence interval, 6.4-43.5). CONCLUSION: Intrapartum/infant death after complete uterine rupture decreased significantly over the decades. Time to delivery >30 minutes and placental separation and/or fetal extrusion had the highest association with intrapartum/infant deaths after complete uterine rupture. Time to delivery <20 minutes limited the incidence of intrapartum/infant deaths.

Association of Catastrophic Neonatal Outcomes With Increased Rate of Subsequent Cesarean Deliveries.

OBJECTIVE: To evaluate whether full-term deliveries resulting in neonates diagnosed with hypoxic-ischemic encephalopathy are associated with a significant increase in the rate of subsequent unscheduled cesarean deliveries. METHODS: We conducted a retrospective chart review study and examined all deliveries in the Department of Obstetrics and Gynecology at Hadassah University Hospital, Mt. Scopus campus, Jerusalem, Israel, during 2009-2014. We reviewed all cases of hypoxic-ischemic encephalopathy in singleton, term, liveborn neonates and identified seven such cases, three of which were attributed to obstetric mismanagement and four that were not. We measured the rate of unscheduled cesarean deliveries before and after the events and their respective hazard ratio. RESULTS: Before a mismanaged delivery resulting in hypoxic-ischemic encephalopathy, the baseline rate of unscheduled cesarean deliveries was approximately 80 unscheduled cesarean deliveries for every 1,000 deliveries. In the first 4 weeks immediately after each of the three identified cases, there was a significant increase in the rate of unscheduled cesarean deliveries by an additional 48 unscheduled cesarean deliveries per 1,000 deliveries (95% confidence interval [CI] 27-70/1,000). This increase was transient and lasted approximately 4 weeks. We estimated that each case was associated with approximately 17 additional unscheduled cesarean deliveries (95% CI 8-27). There was no increase in the rate of unscheduled cesarean deliveries in cases of hypoxic-ischemic encephalopathy that were not associated with mismanagement. CONCLUSION: The increase in the rate of unscheduled cesarean deliveries after a catastrophic neonatal outcome may result in short-term changes in obstetricians' risk evaluation.

¿Es posible disminuir la incidencia de encefalopatía hipóxico isquémica? / Is it possible to reduce the incidence of hypoxic-ischemic encephalopathy?

Objetivo: Determinar si una política local, establecida en la Maternidad del Hospital Padre Hurtado (HPH), para bajar la incidencia de Encefalopatía Hipóxico Isquémica es efectiva, sin incrementar en forma relevante la tasa de cesáreas. Diseño: Estudio de cohorte. Escenario: Unidad de Gestión Clínica de la Mujer y el Recién Nacido del Hospital Padre Hurtado. Población: Neonatos mayores de 33 semanas de edad gestacional, nacidos en el Hospital Padre Hurtado durante los años 1999 y 2015. Método: Se revisaron los resultados de una política de intervención para prevención de asfixia neonatal establecida en la Maternidad del Hospital Padre Hurtado durante un periodo de 14 años. Resultados: Al analizar los datos de un total de 102.612 nacidos vivos, se constató una disminución en la incidencia de EHI en sus 3 grados de una tasa de 4.75/1.000 nacidos vivos previo a la intervención (grupo control) a una tasa de 1.46 por 1.000 nacidos vivos post intervenciones, con alta significancia estadística (p=0,008), llegando en los últimos 6 años a tasa promedio de 0.87/1.000 nacidos vivos. La tasa de EHI moderada y severa bajó de 1.15 por mil nacidos vivos a 0.62, también con alta significancia estadística (p=0.02). La tasa de cesáreas oscilo entre 26-29 % en estos años. Conclusión: La introducción de intervenciones protocolizadas y sistematizadas por medio de la implementación de guías de manejo del trabajo de parto, la capacitación del equipo de profesionales y la auditoría continua de los casos de EHI en el Servicio de Maternidad del Hospital Padre Hurtado se asoció a una disminución significativa de EHI, manteniendo la tasa de cesáreas bajo 30%.

Objectives: Determine whether a local policy to reduce the incidence of neonatal hypoxic-ischemic encephalopathy (HIE), established at the Maternity Unit of Hospital Padre Hurtado (HPH), is effective without significantly increasing the cesarean rate. Design: Cohort study. Setting: Maternity unit of Hospital Padre Hurtado. Population: Newborns older than 33 weeks born at Hospital Padre Hurtado between 1999 and 2015. Methods: The results of a training policy to prevent HIE and perinatal asphyxia established at the Maternity unit of Hospital Padre Hurtado were reviewed during a period of 14 years. Results: From a total of 102.612 newborns analyzed, results showed a decrease in all grades of HIE incidence, from a rate of 4.75 / 1,000 live births prior to intervention (control group) to a rate of 1.46 per 1,000 live births after interventions, with high statistically significance (p=0.008), it reached an average rate of 0.87/1000 for the last 6 years. The moderate and severe HIE rate decreased from 1.15/1000 to 0.62/1000, also with high statistically significance (p=0.02). During the same period of time, the cesarean rate varied between 26-29%. Conclusion: The introduction of protocolized and systematized interventions trough the implantation of Management guides, obstetrics emergency trainings to the professional team and continues audit of the HIE cases at the Maternity unit Hospital Padre Hurtado was associated to a significant decrease of HIE, maintaining the rate of cesareans below 30%.

Safety of Early High-Dose Recombinant Erythropoietin for Neuroprotection in Very Preterm Infants.

OBJECTIVE: To investigate the safety and short term outcome of high dose recombinant human erythropoietin (rhEpo) given shortly after birth and subsequently over the first 2 days for neuroprotection to very preterm infants. STUDY DESIGN: Randomized, double masked phase II trial. Preterm infants (gestational age 26 0/7-31 6/7 weeks) were given rhEpo (nt = 229; 3000 U/kg body weight) or NaCl 0.9% (nc = 214) intravenously at 3, 12-18, and 36-42 hours after birth. RESULTS: There were no relevant differences between the groups for short-term outcomes such as mortality, retinopathy of prematurity, intraventricular hemorrhage, sepsis, necrotizing enterocolitis, and bronchopulmonary dysplasia. At day 7-10, we found significantly higher hematocrit values, reticulocyte, and white blood cell counts, and a lower platelet count in the rhEpo group. CONCLUSIONS: Early high-dose rhEpo administration to very premature infants is safe and causes no excess in mortality or major adverse events. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00413946.

Effects of neonatal hypoxic-ischemic episodes on late seizure outcomes in C57 black mice.

We examined brain injury and seizures in adult C57 black mice (C57/BL6) that underwent neonatal hypoxic-ischemic (HI) episodes. Mouse pups of 7 days-old underwent a ligation of the right common carotid artery and a subsequent hypoxic challenge (8% O2 for 45min). Post-HI mice were implanted with intracranial electrodes at 2-3 months of age, subjected to behavioral/EEG recordings and hippocampal electrical stimulation in next several months and then euthanized for brain histological assessments at ages of 11-12 months. Histological assessment revealed ipsilateral brain infarctions in 9 post-HI animals. Evident motor seizures were found to occur in only 2 animals with histologically identified cystic infarctions but not in the 21 post-HI animals with or without infarctions. In response to the hippocampal stimulation, post-HI animals were less prone than sham controls to evoked motor seizures. We thus suggest that adult C57 black mice may have low propensity of developing epileptic seizures following the neonatal HI episode. Our present observations may be relevant to future investigation of post-HI epileptogenesis in mouse models.

Indications for caesarean sections at ≥34 weeks among nulliparous women and differential composite maternal and neonatal morbidity.

OBJECTIVE: To compare composite maternal and neonatal morbidities (CMM, CNM) among nulliparous women with primary indications for caesarean section (CS) as acute clinical emergency (group I; ACE), non-reassuring fetal heart rate (group II) and arrest disorder (group III). DESIGN: A multicentre prospective study. SETTING: Nineteen academic centres in the USA, with deliveries in 1999-2002. POPULATION: Nulliparous women (n = 9829) that had CS. METHODS: Nulliparous women undergoing CS for three categories of indications were compared using logistic regression model, adjusted for five variables. MAIN OUTCOME MEASURES: CMM was defined as the presence of any of the following: intrapartum or postpartum transfusion, uterine rupture, hysterectomy, cystotomy, ureteral or bowel injury or death; CNM was defined as the presence of any of the following: umbilical arterial pH <7.00, neonatal seizure, cardiac, hepatic, renal dysfunction, hypoxic ischaemic encephalopathy or neonatal death. RESULTS: The primary reasons for CS were ACE in 1% (group I, n = 114) non-reassuring FHR in 29% (group II; n = 2822) and failed induction/dystocia in the remaining 70% (group III; n = 6893). The overall risks of CMM and CNM were 2.5% (95% confidence intervals, CI, 2.2-2.8%) and 1.9% (95% CI 1.7-2.2), respectively. The risk of CMM was higher in group I than in group II (RR 4.1, 95% CI 3.1, 5.3), and group III (RR 3.2, 95% CI 2.7, 3.7). The risk of CNM was also higher in group I than in group II (RR 2.8, 95% CI 2.3, 3.4) and group III (RR 14.1, 95% CI 10.7, 18.7). CONCLUSIONS: Nulliparous women who have acute clinically emergent caesarean sections are at the highest risks of both composite maternal and neonatal morbidity and mortality.

Pineal cysts - a benign consequence of mild hypoxia in a near-term brain?

BACKGROUND: Pineal cysts are benign glial uniloculated or multiloculated fluid-filled sacs located in the pineal gland region. Small pineal cysts are often found incidentally in healthy adults in 1.5-10.8%. Large cysts may cause neurological problems due to pressure exertion on adjacent structures. METHODS: We have used prospective, observational study of an inception cohort of 16 adolescents of mean age 21.69 years (SD=±0.87) with mild (68.7%) to moderate (31.3%) HIE: 7 girls (43.8%) and 9 (56.3%) boys, born with mean gestational age of 35.75 weeks (SD=±3.80) and mean birthweight of 2 644 g (SD=±815). HIE was confirmed by presence of abnormal CTG and/or meconium and/or Apgar scores less than 7 at 5 minutes and/or need for resuscitation and/or cord pH less than 7.2 and /or BE more than -15. The clinical assessment of HIE was done according to the Sarnat-Sarnat scoring. Neonatal data, including EEG and imaging data, were collected. Adolescents were scanned with 3T Magnetom Trio Tim, Siemens, head coil 12 channels, regular sequences and sagittal 3D magnetization-prepared rapid acquisition gradient echo (MPRAGE) sequence with voxel size 1 mm3. Neurological outcome was determined. RESULTS: In 1 patient we found cortical dysplasia and 1 had a panic attack hence their data were omitted. In the group of 14 we have incidentally found in 5 patients a larger, asymptomatic pineal cysts with the overall incidence of 36%. Other MR findings in the group were in 50% white matter injury, in 50% thinner corpus callosum. No statistically significant difference between neonatal cUS and late follow-up MRI (p=0.881) was found. Correlation was not significant with Spearman correlation coefficient 0.201. Presence of pineal cysts was linked to thinner corpus callosum (p=0.005). CONCLUSIONS: We propose that larger pineal cyst, in the absence of other imaging findings except for thinner corpus callosum, is a benign consequence of mild hypoxia in a near-term brain. Our findings warrant a larger study.

Risk factors and treatment of stroke in Chinese young adults.

OBJECTIVE: To evaluate the risk factors and treatment status of Chinese stroke patients aged 35-45 years old. METHODS: We collected data from 1988 in-hospital stroke patients aged 35-45 years old from 36 hospitals in mainland China and compared it to 12,260 health controls with the same age. Information about stroke risk factors was obtained through a questionnaire. Multiple logistic regression and chi-square test were performed to explore the association between risk factors and stroke in young patients. RESULTS: Of the stroke patients, 94.3% had an ischemic stroke and 73.0% were male. Frequencies of stroke risk factors were significantly higher in patients than those in controls, including history of hypertension (41.0% versus 9.0%, p<0.05), diabetes (5.2% versus 1.7%, p<0.05), hypercholesterolemia (4.2% versus 2.9%, p<0.05), heart diseases (7.2% versus 1.6%, p<0.05), stroke (14.9% versus 1.3%, p<0.05), smoking (38.8% versus 33.3%, p<0.05) and drinking (38.0% versus 24.9%, p<0.05). Furthermore, only 12.8% of patients with hypertension took antihypertensive drugs regularly, and 27.9% of diabetic patients took hypoglycemic drugs regularly. Risk factors when compared between male and female patients were as follows: history of heart diseases (5.9 versus 10.8, p<0.05), smoking (50.9 versus 6.5, p<0.05) and drinking (50.4 versus 5.8, p<0.05). CONCLUSION: Majority of the Chinese stroke patients aged 35-45 years were male and had suffered an ischemic stroke. The history of stroke, heart disease and hypercholesterolemia could increase the risk of stroke in young adults, and the risk factors in the order of importance were hypertension, smoking, alcohol drinking, previous stroke, heart disease, diabetes mellitus and hyperlipidemia. Hypertension, smoking and alcohol drinking were found to be the main risk factors; treatment state and lifestyle should be improved for young stroke patients.

Circulating biochemical markers of brain damage in infants complicated by ischemia reperfusion injury.

Hypoxia-ischemia constitutes a risk in infants by altering cerebral blood flow regulatory mechanisms and causing loss of cerebral vascular auto-regulation. Hypotension, cerebral ischemia, and reperfusion are the main events involved in vascular auto-regulation leading to cell death and tissue damage. Reperfusion could be critical since organ damage, particularly of the brain, may be amplified during this period. An exaggerated activation of vasoactive agents of calcium mediated effects could be responsible for reperfusion injury, which, in turns, leads to cerebral hemorrhage and damage. These dramatic phenomena represent a common repertoire in infants complicated by perinatal acute or chronic hypoxia or cardiovascular disorders treated by risky procedures such as open heart surgery and cardiopulmonary by-pass (CPB). To date, despite accurate perinatal and intra-operative monitoring, the post-insult period is crucial, since clinical symptoms and monitoring parameters may be of no avail and therapeutic window for pharmacological intervention (6-12 hours) may be limited, at a time when brain damage is already occurring. Therefore, the measurement of circulating biochemical markers of brain damage, such as vasoactive agents and nervous tissue peptides is eagerly awaited in clinical practice to detect high risk infants. The present review is aimed at investigating the role as circulating biochemical markers such as adrenomedullin, a vasoactive peptide; S100B, a calcium binding protein, activin A, a glycoprotein; neuronal specific enolase (NSE), a dimeric isoenzyme; glial fibrillary acid protein (GFAP), a astroglial protein, in the cascade of events leading to ischemia reperfusion injury in infants complicated by perinatal asphyxia or cardiovascular disorders requiring risky therapeutic strategies such as CPB and/or extracorporeal membrane oxygenation.