Hypoxemic Ischemic Encephalopathy Research Articles

Complex end-of-life decision-making during neonatal retrieval: A retrospective cohort study.

The aim of this study was to compare patients referred to our retrieval service who were palliated before transfer, versus those transferred who were palliated within 7 days of birth. We conducted a retrospective chart review of infants referred to our neonatal retrieval service between 1 December 2015 and 31 March 2022 who died during retrieval or within 7 days of referral. Demographic and clinical data were collected from the service database and electronic medical records. Data on 60 infants were analysed; 25 (42%) infants were not transported and were palliated at the referring hospital, 35 (58%) infants were transported and later palliated at the accepting hospital. The most common primary diagnoses were prematurity (42%) and hypoxemic ischemic encephalopathy (HIE) (42%). Infants palliated at the referring hospital were more likely than those transported and later palliated to require resuscitation including chest compressions (52% vs. 23%, P = 0.02), management for hypotension (72% vs. 20%, P < 0.001) and management for pneumothorax (28% vs. 0%, P = 0.001) and less likely to require management for seizures (8% vs. 43%, P = 0.003). Palliation at the referring hospital should be considered as an option when escalating care is predicted to not affect outcome. In this cohort the infants least likely to be transported required significant management during stabilisation. Determining the infants for whom transport is non-beneficial remains difficult.

Institutional and Regional Variation in Opioid Prescribing for Hospitalized Infants in the US

High-risk infants, defined as newborns with substantial neonatal-perinatal morbidities, often undergo multiple procedures and require prolonged intubation, resulting in extended opioid exposure that is associated with poor outcomes. Understanding variation in opioid prescribing can inform quality improvement and best-practice initiatives. To examine regional and institutional variation in opioid prescribing, including short- and long-acting agents, in high-risk hospitalized infants. This retrospective cohort study assessed high-risk infants younger than 1 year from January 1, 2016, to December 31, 2022, at 47 children's hospitals participating in the Pediatric Health Information System (PHIS). The cohort was stratified by US Census region (Northeast, South, Midwest, and West). Variation in cumulative days of opioid exposure and methadone treatment was examined among institutions using a hierarchical generalized linear model. High-risk infants were identified by International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes for congenital heart disease surgery, medical and surgical necrotizing enterocolitis, extremely low birth weight, very low birth weight, hypoxemic ischemic encephalopathy, extracorporeal membrane oxygenation, and other abdominal surgery. Infants with neonatal opioid withdrawal syndrome, in utero substance exposure, or malignant tumors were excluded. Any opioid exposure and methadone treatment. Regional and institutional variations in opioid exposure. Overall, 132 658 high-risk infants were identified (median [IQR] gestational age, 34 [28-38] weeks; 54.5% male). Prematurity occurred in 30.3%, and 55.3% underwent surgery. During hospitalization, 76.5% of high-risk infants were exposed to opioids and 7.9% received methadone. Median (IQR) length of any opioid exposure was 5 (2-12) cumulative days, and median (IQR) length of methadone treatment was 19 (7-46) cumulative days. There was significant hospital-level variation in opioid and methadone exposure and cumulative days of exposure within each US region. The computed intraclass correlation coefficient estimated that 16% of the variability in overall opioid prescribing and 20% of the variability in methadone treatment was attributed to the individual hospital. In this retrospective cohort study of high-risk hospitalized infants, institution-level variation in overall opioid exposure and methadone treatment persisted across the US. These findings highlight the need for standardization of opioid prescribing in this vulnerable population.

Frequency of Acute Kidney Injury with Hypoxic Ischemic Encephalopathy Staging in Neonates with Perinatal Asphyxia: An Observational Study (Descriptive Case Series)

Perinatal asphyxia affects almost all the organs in neonates, kidneys being one of commonly affected organs. Early recognition of disturbances in renal function is important for early intervention to prevent irreversible damage to kidneys. Objective: In this study we observed the frequency of acute kidney injury (AKI) in neonates with clinical staging of hypoxemic ischemic encephalopathy (HIE) in neonates with perinatal asphyxia. Methodology: An overall number of 145 term neonates with perinatal asphyxia admitted at nursery of Liaquat University Hospital, Hyderabad from February-2019 to july-2019 were included in this study. Urine output was monitored from day one and serum creatinine was sent on third day of life. Serum creatinine was sent early of those neonates having low urine output. Results: The average birth weight was 2.72±2.67 kg. There were 106 (73.1%) males and 39 (26.9%) females. Most neonates were born via simple vaginal delivery 100 (68.97%) and few via caesarian section 45 (31.03%). Out of 145 neonates 38 (26.21%) were in stage I, 95 (65.52%) in stage II and 12 (8.28%) in stage III HIE. Frequency of AKI in neonates with perinatal asphyxia was 55 (37.93%). Incidence of AKI was significantly high in stage II 45(81.8%) as compare to stage I 0(0%) and stage III 10(18.2%) (p=0.0005). Conclusion: AKI is a common complication of perinatal asphyxia. Further multicenter based and studies on large scale need to be done to identify the inter-relationship between maternal factors and perinatal asphyxia associated AKI to prevent neonatal morbidity and mortality. Keywords: Acute kidney injury, perinatal asphyxia, hypoxic ischemic encephalopathy.

To feed or not to feed during therapeutic hypothermia in asphyxiated neonates: a systematic review and meta-analysis.

The practice of withholding feed during therapeutic hypothermia (TH) in neonates with hypoxemic ischemic encephalopathy (HIE) is based on conventions rather than evidence. Recent studies suggest that enteral feeding might be safe during TH. We systematically compared the benefits and harms of enteral feeding in infants undergoing TH for HIE. We searched electronic databases and trial registries (MEDLINE, CINAHL, Embase, Web of Science, and CENTRAL) until December 15, 2022, for studies comparing enteral feeding and non-feeding strategies. We performed a random-effects meta-analysis using RevMan 5.4 software. The primary outcome was the incidence of stage II/III necrotizing enterocolitis (NEC). Other outcomes included the incidence of any stage NEC, mortality, sepsis, feed intolerance, time to full enteral feeds, and hospital stay. Six studies ((two randomized controlled trials (RCTs) and four nonrandomized studies of intervention (NRSIs)) enrolling 3693 participants were included. The overall incidence of stage II/III NEC was very low (0.6%). There was no significant difference in the incidence of stage II/III NEC in RCTs (2 trials, 192 participants; RR, 1.20; 95% CI: 0.53 to 2.71, I2, 0%) and NRSIs (3 studies, no events in either group). In the NRSIs, infants in the enteral feeding group had significantly lower sepsis rates (four studies, 3500 participants, RR, 0.59; 95% CI: 0.51 to 0.67, I2-0%) and lower all-cause mortality (three studies, 3465 participants, RR: 0.43; 95% CI: 0.33 to 0.57, I2-0%) than the infants in the "no feeding" group. However, no significant difference in mortality was observed in RCTs (RR: 0.70; 95% CI: 0.28 to 1.74, I2-0%). Infants in the enteral feeding group achieved full enteral feeding earlier, had higher breastfeeding rates at discharge, received parenteral nutrition for a shorter duration, and had shorter hospital stays than the control group. Conclusion: In late preterm and term infants with HIE, enteral feeding appears safe and feasible during the cooling phase of TH. However, there is insufficient evidence to guide the timing of initiation, volume, and feed advancement. What is Known: • Many neonatal units withhold enteral feeding during therapeutic hypothermia, fearing an increased risk of complications (feed intolerance and necrotizing enterocolitis). • The overall risk of necrotizing enterocolitis in late-preterm and term infants is extremely low (< 1%). What is New: • Enteral feeding during therapeutic hypothermia is safe and does not increase the risk of necrotizing enterocolitis, hypoglycemia, or feed intolerance. It may reduce the incidence of sepsis and all-cause mortality until discharge.

NEONATAL SEIZURES: ETIOLOGY, TREATMENT AND PROGNOSIS

Introduction: Seizures are one of the most common pathologies in newborns. Their incidence is 1.5–3.5/1000 for term infants and 10–130/1000 for preterms. The most common causes of seizures in term infants are hypoxic-ischemic encephalopathy (HIE), cerebrovascular insult (CVI), cerebral malformations (CM), and metabolic disorders. For preterm infants: intraventricular hemorrhage (IVH), periventricular leukomalacia (PVL) and infections. Clinical characteristics are diverse and subtle, and subclinical forms are common. The drug of the first choice is phenobarbitone. Newborns with seizures are more prone to developing neurological disturbances such as epilepsy and cerebral palsy.&#x0D; Methods: This is a clinical, observational research, one-year, retrospective, cross-sectional study conducted in the Department of neonatal intensive care and neonatology of the Clinic of Pediatrics KCUS. The study included 43 newborns who met the inclusion criteria.&#x0D; Results: We found that 7.19% of hospitalized newborns had seizures. A number of seizures were recorded in the group of term infants with an earlier time of seizures. The most common etiological causes were: HIE, IVH, infections, and CM. There was a frequent occurrence of metabolic disorders such as acidosis, blood sugar, and mineral (Ca, K, Na, and Mg) disorders. The median of the first day of onset of seizures in full-term infants is on the fourth day, while in premature infants it is on the sixth day of life. Phenobarbitone was mainly used to stop seizures, with great success. Overall mortality in children with seizures was 37.21%.&#x0D; Conclusions: Seizures are common in newborns, which, depending on the etiological cause, increase mortality, especially in preterm infants. Seizures in term infants occur earlier than in premature infants. The most common etiology of seizures in term infants are infections, hypoxemic-ischemic encephalopathy, intracranial hemorrhage, cerebral malformations, and cerebrovascular insult. In premature infants these are hypoxemic-ischemic encephalopathy, intracranial bleeding, and infections. In the initial treatment of neonatal convulsions, phenobarbitone is most often used, which has proven to be successful in the majority of cases.

Impact of interval between induction of spinal anesthesia to delivery on umbilical arterial cord ph of neonates delivered by elective cesarean section

BackgroundTo evaluate the impact of interval between induction of spinal anesthesia to delivery of the fetus by elective cesarean section on umbilical arterial pH and neonatal outcome.Patients and methodsTwo hundred and twenty pregnant women who were planned for elective cesarean section at term under spinal anesthesia were recruited. Minimum systolic, diastolic and mean arterial blood pressures (SBP, DBP, MAP) and largest pressure decrease (SBP, DBP, MPA) were also recorded. Induction of spinal anesthesia to delivery interval was measured. Following delivery, umbilical arterial cord analysis for pH and base deficit were done. Apgar scores at 1 min and at 5 min, neonatal intensive care unit (NICU) admission, need for mechanical ventilation and incidence of hypoxemic-ischemic encephalopathy were recorded.ResultsInduction of spinal anesthesia to delivery interval was 25.7 ± 5.6 min. Lowest SBP and MAP reached during cesarean delivery were 88.9 ± 7.3 mmHg and 60.4 ± 5.6 mmHg, respectively. MAP < 65 mmHg was reached in 136 (62%) patients with a decrease of MAP of > 20% in 149 (68%) patients. Duration of the longest hypotension episode was 3.3 ± 2.2 min. All patients required ephedrine administration for hypotensive episodes with an average dosage of 11.4 ± 3.2 mg. Umbilical pH of 7.3 ± 0.1 and base deficit of 8.3 ± 4.4 mmol/l were recorded. Apgar scores at 5 min were 8.5 ± 1.2. Eight (3.6%) neonates were admitted in the NICU. One neonate needed mechanical ventilation. There were no cases of hypoxemic-ischemic encephalopathy. There were inverse correlations between induction of spinal anesthesia to delivery interval, body mass index (BMI) and duration of longest hypotension episode in relation to umbilical pH (r = -0.817, -0.395 and -0.268, respectively). Cut off value for induction of spinal anesthesia to delivery interval greater than 27 min predicted an umbilical pH of < 7.2. Cut off value for the duration of the longest hypotension episode greater than 5 min predicted an umbilical pH of < 7.2. Cut off value for BMI greater than 35 kg/m2 predicted an umbilical pH of < 7.2.ConclusionProlonged interval between induction of spinal anesthesia to delivery could be associated with neonatal acidosis. This could be aggravated by maternal obesity and prolonged duration of hypotension episodes during cesarean delivery.

454 Pregnancy outcome after cesarean section following a failed vacuum attempt

To compare pregnancy outcome of women who underwent cesarean section (CS) in second stage of labor, with or without a following failed vacuum extraction attempt (VE). A retrospective cohort study of women who underwent cesarean section during the second stage of labor in a single tertiary university affiliated medical center (2012-2019). Pregnancy outcome was compared for women who underwent cesarean section following a failed vacuum extraction to women who had cesarean section during the second stage of labor with no vacuum extraction attempt. Neonatal outcomes included umbilical artery pH less than 7.1, Apgar at 5 minutes < 7, hypoxemic ischemic encephalopathy and NICU admission. Maternal outcomes included duration of hospitalization, need for blood transfusion and need for re-surgery in 45 days. Overall, 88,375 women delivered during the study period. Of them, 120 women had a cesarean section following failed vacuum (study group). Another 551 women underwent cesarean section in the second stage of labor without VE attempt (control group). The groups were similar with regard to obstetrical and demographic characteristics. The rates of umbilical artery pH<7.1 (17.50% vs 6.53%, p<0.001), NICU admission (13.33% vs 2.90%, p<0.001), hypoxemic ischemic encephalopathy (5.83% vs 0.18%, p<0.001) and epicranial sub-aponeurotic hemorrhage (16.67% vs 2.18%, p<0.001) were significantly higher in the study group. No significant differences were found in maternal outcomes. In a sub-analysis including only labor with reassuring fetal heart tracing, failed vacuum attempt was associated with higher rate of NICU admission and epicranial hemorrhage (16.67% vs 3.13%, p=0.009, 27.78% vs. 3.41, p=0.001, respectively). Failed vacuum attempt is associated with a significant increased neonatal morbidity, but not increased maternal morbidityView Large Image Figure ViewerDownload Hi-res image Download (PPT)

Pregnancy outcome after cesarean section following a failed vacuum attempt

Objective To compare the pregnancy outcome of women who underwent cesarean section in the second stage of labor, with or without a vacuum extraction attempt Methods A retrospective cohort study of women who underwent a cesarean section during the second stage of labor in a single tertiary university-affiliated medical center (2012–2019). Pregnancy outcome was compared for women who underwent cesarean section following a failed vacuum extraction to women who had cesarean section during the second stage of labor with no vacuum extraction attempt. Neonatal outcomes included umbilical artery pH less than 7.1, Apgar at 5 min < 7, hypoxemic ischemic encephalopathy and NICU admission. Maternal outcomes included duration of hospitalization, need for blood transfusion and need for re-surgery in 45 days. Results Overall, 88,375 women delivered during the study period. Of them, 120 women had a cesarean section following a failed vacuum (study group). Another 551 women underwent a cesarean section in the second stage of labor without a VE attempt (control group). The groups were similar with regard to obstetrical and demographic characteristics. The rates of umbilical artery pH < 7.1 (17.50% vs 6.53%, p < .001), NICU admission (13.33% vs 2.90%, p < .001), hypoxemic ischemic encephalopathy (5.83% vs 0.18%, p < .001) and epicranial sub-aponeurotic hemorrhage (16.67% vs 2.18%, p < .001) were significantly higher in the study group. No significant differences were found in maternal outcomes. In a sub-analysis including only labor with reassuring fetal heart tracing, failed vacuum attempt was associated with higher rate of NICU admission and epicranial hemorrhage (16.67% vs 3.13%, p = .009, 27.78% vs. 3.41, p = .001, respectively). Conclusion Failed vacuum attempt is associated with a significant increased neonatal morbidity, but not increased maternal morbidity

Frequency, causes, and findings of brain CT scans of neonatal seizure at Ardabil City Hospital, Ardabil, Iran

Background: Neonatal seizures are the primary and most important signs of neurologic function disorders that often lead to serious complications. However, this disorder is predictable and manageable with suitable diagnostic and therapeutic methods. The aim of this study was to investigate the frequency, causes, and findings of brain CT scans of neonatal seizure.Methods: This descriptive cross-sectional study has been done on 70 neonates with seizures who hospitalized in Ardabil city hospital during 2016-2017. CT scans were done for all patients. Necessary information for each patient was recorded in a checklist including demographic data, history of diabetes mellitus, hypertension, and maternal endocrine disorders, and history of resuscitation and clinical data including type of seizure and its duration, Cause of seizure and CT scan findings (cerebral hemorrhage, local ischemic lesions, hypoxemic-ischemic encephalopathy, and anatomical cerebral malformations).Results: The mean age of neonates was 12.41±9.33 days. Of them, 61.4% were boys, 3.24% LBW and 40% were preterm at birth time. Of all neonates, 21.4% had history of seizure in their relative degree family members. Fever was the most common symptom accompanying seizures (40%). The most common form was tonic seizure (n=30, 42.9%) and its duration time was 4.99 minute. A total of 41.4% of neonates (29 cases) had abnormal CT scan reports. Hypoxic-ischemic encephalopathy (47%) was the most common findings in the CT scans of neonates with seizures.Conclusions: Results showed that, a considerable number of neonates had abnormal CT findings and the most common abnormal form was hypoxemic-ischemic encephalopathy.

Population Pharmacokinetics of Gentamicin in Neonates with Hypoxemic-Ischemic Encephalopathy Receiving Controlled Hypothermia.

Identify population pharmacokinetics and pharmacodynamic target attainment of gentamicin in neonates with hypoxic-ischemic encephalopathy (HIE) undergoing controlled hypothermia (CH). Prospective open-label pharmacokinetic study. Gentamicin concentrations were modeled and dosing regimens simulated for a 5000-patient neonatal population with HIE receiving CH using PMetrics, a nonparametric, pharmacometric modeling, and simulation package for R. A 189-bed children's tertiary care teaching hospital. Twelve patients, 5 (42%) females and 7 (58%) males, met inclusion criteria with a median gestation age of 39.9weeks (interquartile range [IQR] 38.5-40.2wks) and a median birthweight (BW) of 3.3 kg (IQR 3.1-3.7 kg). Gentamicin concentrations were best described by a two-compartment model with first-order elimination with BW as a covariate on volume of distribution (Vd). The mean total body population clearance (CL) was 2.2±0.7ml/minute/kg, and the volume of the central compartment was 0.44±0.06L/kg. The R2 , bias, and precision for the observed versus population predicted model were 0.917, 1.15, and 10.9μg/ml; the R2 , bias, and precision for the observed versus individual predicted model were 0.982, -0.132, and 0.932μg/ml, respectively. The calculated mean population estimate for the total Vd was 0.96±0.4L/kg. The dosing regimen that most consistently produced a maximum concentration (Cmax ) in the range of 10-12mg/L with a minimum concentration (Cmin ) level less than 2mg/L was 5mg/kg/dose given every 36hours. These data suggest the population pharmacokinetics of gentamicin in neonates with HIE receiving CH have an increase in gentamicin CL and are different from previous reports in neonates with HIE not receiving CH and/or neonates without HIE. This analysis suggests a dosing regimen of 5mg/kg/dose every 36hours results in a gentamicin Cmax within the range of 10-12mg/L with a Cmin lower than 2mg/L, which is appropriate for treating susceptible gram-negative organisms with minimum inhibitory concentrations of 1mg/L or lower.

Population Pharmacokinetics and Pharmacodynamic Target Attainment of Ampicillin in Neonates with Hypoxemic-Ischemic Encephalopathy in the Setting of Controlled Hypothermia.

To describe the population pharmacokinetics and pharmacodynamic target attainment of ampicillin in neonates with hypoxic-ischemic encephalopathy (HIE) undergoing controlled hypothermia (CH). Prospective, open-label pharmacokinetic study. A 189-bed, freestanding children's tertiary care teaching hospital. Thirteen neonates (three females and 10 males) with HIE encephalopathy receiving CH and ampicillin 100 mg/kg/dose intravenously every 8 hours who were admitted to the neonatal intensive care unit between May 2013 and June 2014. Blood (0.5 ml) was collected at 8, 10, and 14 hours of life coinciding with other scheduled laboratory investigations for ampicillin concentration analysis, providing a total of three ampicillin serum concentrations/patient. The patients had a median gestational age of 39 weeks, mean ± SD birth weight of 3.34 ± 0.61 kg, and mean ± SD estimated glomerular filtration rate of 43 ± 12.6 ml/minute/1.73 m2 . Ampicillin concentrations were best described by a two-compartment model with gestational age as a covariate with allometric scaling on total body clearance. The mean ± SD total body clearance for the population was 0.43 ± 0.12 ml/minute/kg (median 0.36 ml/min/kg), volume of the central compartment was 0.35 ± 0.46 L/kg, and the calculated population estimate for the total volume of distribution (Vd ) was 0.52 ± 0.28 L/kg. The R2 , bias, and precision were 0.497, 0.538, and 10.5 μg/ml and 0.972, -0.125, and 0.938 μg/ml for the observed versus population and observed versus individual predicted concentrations, respectively. Monte Carlo simulation was conducted to determine the probability of target attainment for 12 simulated ampicillin dosing regimens using 50% and 100% of the dosing interval that free drug concentration remains above the minimum inhibitory concentration (fT > MIC) in 5000 simulated neonates with HIE receiving CH. Dosing regimens of 25 and 50 mg/kg/dose every 24 hours provided for an appropriate pharmacodynamic target attainment of 50% and 100% fT > MIC. To our knowledge, this study describes the first pharmacokinetic data of ampicillin in neonates with HIE receiving CH and demonstrates a reduced total body clearance and an increased Vd for ampicillin. Based on these data, modifications to the ampicillin dosing regimens seem appropriate during the period of CH. Dosing regimens of ampicillin 25 and 50 mg/kg/day were able achieve optimal probability of target attainment against all susceptible gram-negative and gram-positive bacteria in a population of neonates with HIE receiving CH for 50% and 100% fT > MIC.

The effect of controllable moderate hypothermia on hemostasis in newborns with hypoxemic ischemic encephalopathy.

To study effect of controllable moderate hypothermia on system of hemostasis in newborns with hypoxemic ischemic encephalopathy. The retrospective analysis was carried out concerning 38 medical records of newborns with acute hypoxia of fetus (group I), 12 medical records of newborns with acute hypoxia of fetus against the background of chronic hypoxia of fetus (group II), 20 healthy newborns (group III) and 20 healthy adults. The thromboelastography was implemented in three stages: at first, third and sixth days of life of newborns. The thromboelastography is to be implemented in newborns with hypoxemic ischemic encephalopathy due to occurrence of of hemostasis shifting to hypocoagulation and high risk of bleeding. In healthy full-term children a physiological hypercoagulation was established as compared with adults without alterations of processes of lysis of clots. In newborns with chronic hypoxia of fetus against the background of applied medical hypothermia, in comparison with healthy newborns, decreasing of number of thrombocytes are observed and possibly lower functional activity of thrombocytes up to third day and also lower activity of plasma component of hemostasis at retained elasticity and strength of developed clots. The sixth day, after heating, the system of hemostasis is normalized and number of thrombocytes is restored. In newborns, having acute hypoxia of fetus against the background of chronic hypoxia of fetus higher risk of bleeding is noted at minimal difference according results of thromboelastography.

Clinico-Biochemical Profile of Neonates with Birth Asphyxia in Eastern Nepal

Introduction: Perinatal asphyxia is a common problem with the incidence varying from 0.5 – 2% of live births. It is an important cause of neonatal mortality and is a frequent cause for admission to neonatal intensive care units (NICU). The aims of this study were to find out the clinical and biochemical alterations in different stages of HIE. Materials and Methods: This was a prospective hospital based observational study performed during the period of February, 2010 to January, 2011. Results: Sixty inborn neonates satisfying the criteria for birth asphyxia requiring admission to pediatric wards and neonatal intensive care unit were studied. There were 13(21.7%) cases of mild hypoxemic ischemic encephalopathy (HIE), 27 (45%) moderate and 20 (33.3%) severe HIE. Seizures 41(68.3%), respiratory distress 32(53.3%) and shock 29(48.3%) were predominant manifestations observed. Meconium aspiration syndrome was found in 13.3% of neonates. Hypoglycemia 11(18.3%), hypocalcaemia 7(11.7%), hyponetremia 14 (23.3%) and hyperbilirubinemia 9(15%) were associated biochemical abnormalities. Twenty cases (33.3%) had acute renal failure and they belonged to moderate and severe stages of HIE. Seizures (P&lt; 0.001), respiratory distress (P=0.015), shock (P&lt;0.001) and serum creatinine (P=0.004) were found to be significant among different HIE stages. Conclusion: Neonates having birth asphyxia had HIE, seizures, respiratory distress, shock, hypoglycemia hypocalcaemia, hyponetremia, hyperbilirubinemia and acute renal failure mostly in moderate and severe stages. DOI: http://dx.doi.org/10.3126/jnps.v32i3.7626 J. Nepal Paediatr. SocVol.32(3) 2012 206-209

283: Two center RCT of outpatient versus inpatient cervical ripening for induction of labour with PGE2

cervical ripening for induction of labour with PGE2 Chris Wilkinson, Robert Bryce, Pamela Adelson, Judy Coffey, John Coomblas, Philip Ryan, Georgina Stamp, Deborah Turnbull Women’s and Children’s Hospital, Maternal Fetal Medicine, North Adelaide South Australia, Australia, Flinders Medical Centre, Perinatal Medicine, South Australia, Australia, University of Adelaide, Psychology, South Australia, Australia, Women’s and Children’s Hospital, Midwifery, North Adelaide South Australia, Australia, Flinders Medical Centre, Midwifery, South Australia, Australia, University of Adelaide, Public Health, South Australia, Australia, University of South Australia, Nursing and Midwifery, Adelaide, South Australia, Australia OBJECTIVE: To compare inpatient to outpatient cervical ripening for induction of labour with PGE2. STUDY DESIGN: Two centre RCT. Women were low risk, induced for post dates or social reasons. Consent and randomisation (stratified for parity) was performed when decision for induction of labour was made. RESULTS: 827 eligible consenting women from 2 tertiary centres were randomised to an experimental (411) and a control (416) arm. 215 experimental group and 210 control group received PGE2 cervical ripening, with the rest labouring spontaneously or not needing PGE2 by the induction date. There were no significant differences in oxytocin use (60% v 57%, p 0.28), spontaneous birth (53% v 51%, p 0.34), instrumental birth (23% v 22%, p 0.41) or cesarean section (24% v 27% p 0.24). Patient preference and patient satisfaction were also assessed, and will be reported. There were 11 serious outcomes/ incidents in the control group, of which 3 resulted in HIE (hypoxemic ischemic encephalopathy). 2 of these cases were plausibly related to PGE2 administration. Of 16 serious outcomes/incidents in the experimental group, 3 cases of HIE occurred. One of these cases was plausibly related to PGE2 administration. When this case was reported to the data monitoring committee, the trial was temporarily suspended, and further restrictions were imposed on recruitment eligibility regarding glucose intolerance and maternal BMI. 27 women (13%) in the experimental group receiving the outpatient intervention experienced hyperstimulation or non reassuring CTG monitoring within the 1 hour surveillance period and were not discharged. Another 13 (6%) in this group changed their minds and decided not to go home, despite being eligible. 7 (3%) remained in hospital for other reasons. Overall, 22% of women receiving PGE2 as an intended outpatient procedure did not go home. CONCLUSION: There were similar clinical outcomes in each group, including adverse outcomes. Strict adherence to clinical protocols identified almost all cases of hyperstimulation prior to discharge, but resulted in 1 in 5 women in the outpatient group not being discharged.

Cooling for Neonatal Hypoxic Ischemic Encephalopathy: Do We Have the Answer?

The neonatal community deserves congratulations for responding vigorously to Silverman's1 call for randomized controlled trials (RCTs) to evaluate neonatal therapies. Although more trials are still needed,2 existing RCTs present new challenges in interpretation. One of the most vexing is when to proclaim innovative therapies as “standard of care.” The neonatal critical care community faces this challenge in evaluation of hypothermia as treatment for hypoxemic-ischemic encephalopathy (HIE).3–5 National bodies have made declarations that the neonatal community should consider hypothermia experimental pending completion of current ongoing trials.6–9 Although the influence of these bodies is considerable, individual physicians and sites apparently feel pressure to “do something” in the very dire circumstances of HIE in the newborn. In an informal sample of convenience, we have found that some centers are performing cooling, either with or without informed consent. Although many clinicians concur with the leading bodies that state there is a need for additional trials, it is confusing for practicing neonatologists when some members of these bodies also publicly state that they are actively providing cooling therapy. If leading centers are promoting active cooling, they have, in effect, adopted cooling as a standard of care. This may not only have legal implications but also raises ethical issues for those who believe the right thing to do currently is to continue performing RCTs. The countervailing argument is that to not offer cooling as standard therapy for such a devastating disease as HIE is itself, unethical. These opposing viewpoints are not easily resolvable except by considering what the overall benefit of eliminating residual doubt, one way or the other, would be. Our concern is that advocacy of hypothermia as a standard of care represents an excessively low threshold for accepting promising therapies and will ultimately lead to resources … Address correspondence to Haresh Kirpalani, BM, MSc, Division of Neonatology, Children's Hospital of Philadelphia, 34th Street and Civic Center Boulevard, Philadelphia, PA 19104. E-mail: kirpalanih{at}email.chop.edu

Predicting Outcomes of Neonates Diagnosed With Hypoxemic-Ischemic Encephalopathy

The goals were to identify predictor variables and to develop scoring systems and classification trees to predict death/disability or death in infants with hypoxic-ischemic encephalopathy. Secondary analysis of data from the multicenter, randomized, controlled, National Institute of Child Health and Human Development Neonatal Research Network trial of hypothermia in hypoxic-ischemic encephalopathy was performed. Data for 205 neonates diagnosed as having hypoxic-ischemic encephalopathy were studied. Logistic regression analysis was performed by using clinical and laboratory variables available within 6 hours of birth, with death or moderate/severe disability at 18 to 22 months or death as the outcomes. By using the identified variables and odds ratios, scoring systems to predict death/disability or death were developed, weighting each predictor in proportion to its odds ratio. In addition, classification and regression tree analysis was performed, with recursive partitioning and automatic selection of optimal cutoff points for variables. Correct classification rates for the scoring systems, classification and regression tree models, and early neurologic examination were compared. Correct classification rates were 78% for death/disability and 71% for death with the scoring systems, 80% and 77%, respectively, with the classification and regression tree models, and 67% and 73% with severe encephalopathy in early neurologic examination. Correct classification rates were similar in the hypothermia and control groups. Among neonates diagnosed as having hypoxic-ischemic encephalopathy, the classification and regression tree model, but not the scoring system, was superior to early neurologic examination in predicting death/disability. The 3 models were comparable in predicting death. Only a few components of the early neurologic examination were associated with poor outcomes. These scoring systems and classification trees, if validated, may help in assessments of prognosis and may prove useful for risk-stratification of infants with hypoxic-ischemic encephalopathy for clinical trials.