Seizures after initiation of rewarming in cooled infants with hypoxic ischaemic encephalopathy.

BACKGROUND: Seizures after initiation of rewarming from therapeutic hypothermia for neonatal encephalopathy are well recognised but not easy to predict. METHODS: A secondary analysis was performed of NEOLEV2 trial data, a multicentre randomised trial of levetiracetam versus phenobarbital for neonatal seizures. Enrolled infants underwent continuous video EEG (cEEG) monitoring. The trial data were reviewed for 42 infants with seizures during therapeutic hypothermia and 118 infants who received therapeutic hypothermia but had no seizures on cEEG. RESULTS: Overall, 112 of 160 (70%) had cEEG monitoring continued until rewarming was completed. Of the 42 infants with prior seizures, there were 30 infants with valid cEEG available and seizures occurred following the initiation of rewarming in 8 (26.6%). For the 118 seizure-naive infants, 82 (69.5%) continued cEEG until either rewarming was completed or 90 h of age and none had documented seizures. CONCLUSION: Overall, just over a quarter of infants with prior seizures had cEEG evidence of at least one seizure in the 24 h after initiation of rewarming but no seizure-naive infant had cEEG evidence of seizure(s) on rewarming. Critically, by reporting the two groups separately, the data can provide guidance on the duration of EEG monitoring. IMPACT: Infants with hypoxic ischaemic encephalopathy who have cEEG evidence of seizures during therapeutic hypothermia have a significant risk of further seizures on rewarming. For infants with hypoxic ischaemic encephalopathy but no cEEG evidence of seizures during therapeutic hypothermia, there is very little risk of de novo seizures. Ongoing work utilising large cohorts may generate EEG criteria that refine estimates of risk for rewarming seizures. Based on current experience, if seizures have occurred during therapeutic hypothermia for hypoxic ischaemic encephalopathy, the EEG monitoring should be continued during rewarming and for 12 h thereafter to minimise the risk of missing an event.

COHESION: a core outcome set for the treatment of neonatal encephalopathy.

BACKGROUND: Heterogeneity in outcomes reported in trials of interventions for the treatment of neonatal encephalopathy (NE) makes evaluating the effectiveness of treatments difficult. Developing a core outcome set for NE treatment would enable researchers to measure and report the same outcomes in future trials. This would minimise waste, ensure relevant outcomes are measured and enable evidence synthesis. Therefore, we aimed to develop a core outcome set for treating NE. METHODS: Outcomes identified from a systematic review of the literature and interviews with parents were prioritised by stakeholders (n = 99 parents/caregivers, n = 101 healthcare providers, and n = 22 researchers/ academics) in online Delphi surveys. Agreement on the outcomes was achieved at online consensus meetings attended by n = 10 parents, n = 18 healthcare providers, and n = 13 researchers/ academics. RESULTS: Seven outcomes were included in the final core outcome set: survival; brain injury on imaging; neurological status at discharge; cerebral palsy; general cognitive ability; quality of life of the child, and adverse events related to treatment. CONCLUSION: We developed a core outcome set for the treatment of NE. This will allow future trials to measure and report the same outcomes and ensure results can be compared. Future work should identify how best to measure the COS. IMPACT: We have identified seven outcomes that should be measured and reported in all studies for the treatment of neonatal encephalopathy. Previously, a core outcome set for neonatal encephalopathy treatments did not exist. This will help to reduce heterogeneity in outcomes reported in clinical trials and other studies, and help researchers identify the best treatments for neonatal encephalopathy.

Shoulder dystocia, umbilical cord blood gases and neonatal encephalopathy.

The interpretation of umbilical cord gases may not be straightforward following shoulder dystocia. We reviewed Perinatal and Maternal Mortality Review Committee data from New Zealand infants with moderate and severe neonatal encephalopathy (NE) for 2010-2017 inclusive. If one or more of: pH of ≤7.1; base excess of ≤-12 mmol/L; or lactate of ≥6 mmol/L were present it was considered an abnormal result. One-third (12/36) of infants born following shoulder dystocia had documented umbilical cord gases within the normal range. It is important for clinicians to be aware of this possibility when assessing newborn infants with NE.

How do neonatal units within the Australian and New Zealand Neonatal Network manage ex-preterm infants with severe chronic lung disease still requiring major respiratory support at term?

AIM: The aim was to survey the Australian and New Zealand Neonatal Network (ANZNN) member units regarding current services and management guidelines for the ex-premature infant with severe chronic lung disease (CLD) still requiring significant respiratory support at term. METHODS: A 16-question survey was sent to clinical directors of all Level 3 units in Australia and New Zealand via the network. Reminder emails were sent, as required, to prompt a satisfactory response rate. RESULTS: Survey responses were received from 26 of the 29 (90%) ANZNN Level 3 units. At 37 weeks' corrected gestation, over 90% of the units provide ongoing respiratory support in the neonatal intensive care unit (NICU). However, by 50 weeks, ongoing care is provided in several settings, including NICU, high dependency unit (HDU)/paediatric intensive care unit or respiratory wards. The majority (76%) of units arrange transfer on an ad hoc basis, but six units (24%) have set criteria for transfer based on gestation, workload and respiratory requirement. Three units declared a maximum age in NICU (44, 46 or 48 weeks). A variety of approaches were used to identify infants who were likely to require transfer, and 78% of units had a staff member assigned to assist transition. Three units stated that they had a home ventilation programme suitable for these infants. No unit supplied a guideline on tracheostomy or specific respiratory management post-term. CONCLUSION: Despite a significant number of babies requiring ongoing support for severe CLD, the location of the service appears very variable, and there is a lack of specific written guidelines.

Contributory factors and potentially avoidable neonatal encephalopathy associated with acute peripartum events: An observational study.

BACKGROUND: In 25% of affected babies, neonatal encephalopathy results from acute peripartum events, but rigorous review of these cases for quality improvement is seldom reported. New Zealand has maintained a national database of all babies diagnosed with Sarnat moderate and severe neonatal encephalopathy since 2010 under the Perinatal and Maternal Mortality Review Committee. AIMS: To determine the rate of contributory factors, potentially avoidable mortality or morbidity, and to identify key areas for improvements to maternity and neonatal care among cases of neonatal encephalopathy following an acute peripartum event. MATERIALS AND METHODS: Sarnat moderate and severe cases identified from the national collection of neonatal encephalopathy with a history of an acute peripartum event were reviewed using a standardised independent multidisciplinary methodology and a tool for assessing contributory factors and potential avoidability, with the addition of a human factors lens. RESULTS: Forty-seven cases from 2013 to 2015 were reviewed. The most common acute peripartum events were placental abruption (12) and shoulder dystocia (11). Contributory factors were identified in 89%, and the severity of outcome was potentially avoidable in 66%. Key modifiable areas included dynamic risk assessment, preparedness for obstetric and neonatal emergencies, best practice for maternal and fetal surveillance in labour, and documentation. CONCLUSIONS: There is significant potential to improve quality and safety in acute peripartum care to reduce the risk of neonatal encephalopathy. Human factors were not well captured by the clinical notes or review tool. Attention to human factors by improved methodology can enhance review of neonatal encephalopathy.

Contributory factors and potentially avoidable neonatal encephalopathy associated with perinatal asphyxia.

BACKGROUND: The recently published monograph, Neonatal encephalopathy and neurologic outcome, from the American College of Obstetricians and Gynecologists calls for a root cause analysis to identify components of care that contributed to cases of neonatal encephalopathy to design better practices, surveillance mechanisms, and systems. All cases of infants born in New Zealand with moderate and severe neonatal encephalopathy were reported to the New Zealand Perinatal and Maternal Mortality Review Committee from 2010. A national clinical review of these individual cases has not previously been undertaken. OBJECTIVES: The objective of the study was to undertake a multidisciplinary structured review of all cases of neonatal encephalopathy that arose following the onset of labor in the absence of acute peripartum events in 2010-2011 to determine the frequency of contributory factors, the proportion of potentially avoidable morbidity and mortality and to identify themes for quality improvement. STUDY DESIGN: National identification of, and collection of clinical records on, cases of moderate or severe neonatal encephalopathy occurring after the onset of labor in the absence of an acute peripartum event, excluding those with normal gases and Apgar scores at 1 minute, among all cases of moderate and severe neonatal encephalopathy at term in New Zealand in 2010-2011 was undertaken. Cases were included if they had abnormal gases as defined by any of pH of ≤ 7.2, base excess of ≤ -10, or lactate of ≥ 6 or if there were no cord gases, an Apgar score at 1 minute of ≤ 7. A clinical case review was undertaken by a multidisciplinary team using a structured tool to record contributory factors (organization and/or management, personnel, and barriers to access and/or engagement with care), potentially avoidable morbidity and mortality and to identify themes to guide quality improvement. RESULTS: Eighty-three babies fulfilled the inclusion criteria for the review, 56 moderate (67%) and 27 severe (33%), 21 (25%) of whom were deceased prior to hospital discharge. Eighty-four percent of 64 babies with cord gas results had one of pH of ≤ 7.0, base excess of ≤ -12, or lactate of ≥ 6; and 42% (8 of 19) without cord gases had 5 minute Apgar scores < 5. Excluding 5 babies who died within a day of birth, all but 1 baby were admitted to a neonatal unit within 1 day of birth. Contributory factors were identified in 84% of 83 cases, most commonly personnel factors (76%). Fifty-five percent of cases with morbidity or mortality were considered to be potentially avoidable, and 52% of cases were considered potentially avoidable because of personnel factors. The most frequently identified theme related to the use and interpretation of cardiotocography in labor. CONCLUSION: A multidisciplinary case review of neonatal encephalopathy following apparently uncomplicated labor identified a high rate of potentially avoidable morbidity and mortality and issues amenable to quality improvement such as multidisciplinary training of staff in fetal surveillance in labor.

Blood pressure measurement at two years in offspring of women randomized to a trial of metformin for GDM: follow up data from the MiG trial.

BACKGROUND: Offspring born following maternal gestational diabetes are at risk of excessive childhood weight gain and Type 2 diabetes in childhood, which in turn is associated with an increased rate of hypertension. We aimed to determine the systolic and diastolic blood pressure at two years of age in a cohort of children exposed to gestational diabetes mellitus using data from the MiG trial of metformin use in gestational diabetes. The secondary aim was to analyze these data by randomization of treatment to insulin or metformin. METHODS: The offspring of women who had gestational diabetes and had been assigned to either open treatment with metformin (with supplemental insulin if required) or insulin in the MiG trial were followed up at 2 years of age. Oscillometric measurement of BP in the right arm was performed by a researcher using an appropriately sized cuff. RESULTS: A total of 489 measurement blood pressure measurements were obtained in 170 of the 222 children who were seen at a median (range) age of 29 (22-38) months corrected gestational age. At the time of assessment the mean (SD) weight and height was 13.8(2) kg and 90 (4.2) cm respectively. For the whole group the mean (SD) systolic pressure was 90.9 (9.9) mmHg and mean (SD) diastolic pressure was 55.7 (8.1) mmHg. No difference was found between the metformin and insulin treatment arms. In a regression model, height and weight were only two factors associated with the levels of systolic blood pressure. For each additional kg the systolic blood pressure increased by 1.0 mmHg. For each additional cm of height the systolic blood pressure increased by 0.42 mmHg. CONCLUSIONS: Blood pressure data was obtained at approximately two years of age in a substantial cohort of children whose mothers received treatment for GDM. These novel data compare favorably with published norms. CLINICAL TRIALS REGISTRY: This study was registered under the Australian New Zealand Clinical Trials Registry ( ACTRN12605000311651 ).

Randomized controlled trial of oxygen saturation targets in very preterm infants: two year outcomes.

OBJECTIVE: To assess whether an oxygen saturation (Spo2) target of 85%-89% compared with 91%-95% reduced the incidence of the composite outcome of death or major disability at 2 years of age in infants born at <28 weeks' gestation. STUDY DESIGN: A total 340 infants were randomized to a lower or higher target from <24 hours of age until 36 weeks' gestational age. Blinding was achieved by targeting a displayed Spo2 of 88%-92% using a saturation monitor offset by ±3% within the range 85%-95%. True saturations were displayed outside this range. Follow-up at 2 years' corrected age was by pediatric examination and formal neurodevelopmental assessment. Major disability was gross motor disability, cognitive or language delay, severe hearing loss, or blindness. RESULTS: The primary outcome was known for 335 infants with 33 using surrogate language information. Targeting a lower compared with a higher Spo2 target range had no significant effect on the rate of death or major disability at 2 years' corrected age (65/167 [38.9%] vs 76/168 [45.2%]; relative risk 1.15, 95% CI 0.90-1.47) or any secondary outcomes. Death occurred in 25 (14.7%) and 27 (15.9%) of those randomized to the lower and higher target, respectively, and blindness in 0% and 0.7%. CONCLUSIONS: Although there was no benefit or harm from targeting a lower compared with a higher saturation in this trial, further information will become available from the prospectively planned meta-analysis of this and 4 other trials comprising a total of nearly 5000 infants.

A survey of the management of neonatal hypoglycaemia within the Australian and New Zealand Neonatal Network.

BACKGROUND: Neonatal hypoglycaemia is a common problem linked to both brain damage and death. There is controversy regarding both the definition of and best treatment for neonatal hypoglycaemia. AIM: To determine current management of neonatal hypoglycaemia within the Australian and New Zealand Neonatal Network (ANZNN). METHODS: Four questionnaires were sent to the Director of each of the 45 nurseries within the ANZNN. The Director was asked to complete one questionnaire and give the remaining three to other doctors involved with the management of babies with hypoglycaemia in the nursery. RESULTS: One hundred and eighty surveys were sent and 127 were returned (71%), including at least one from each nursery. Almost all respondents (120, 94%) reported using a protocol to treat hypoglycaemia. Only 2 (2%) reported screening all babies for neonatal hypoglycaemia, with the remainder screening babies at risk. Only 67, (53%) reported that blood glucose levels were tested on an analyser generally considered to be reliable at low levels. Most respondents (99, 78%) reported the clinical threshold for treatment was <2.6 mmol/L. However, when provided with clinical scenarios, respondents reported a variety of interventions, including no treatment. CONCLUSION: Doctors within the ANZNN are consistent about definition and screening for neonatal hypoglycaemia. However, frequently, the diagnosis is made using unreliable analysers. There is also wide variation in treatment, suggesting a lack of reliable evidence on which to base practice.

Fluid recovery during lung lavage in meconium aspiration syndrome.

UNLABELLED: Lung lavage using two aliquots of 15 mL/kg of dilute surfactant was performed in 30 ventilated infants with severe meconium aspiration syndrome (MAS). Mean recovery of instilled lavage fluid was 46%, with greater fluid return associated with lower mean airway pressure at 24 h and a shorter duration of respiratory support. CONCLUSION: Recovery of instilled lavage fluid is paramount in effective lung lavage in MAS and must be afforded priority in the lavage technique.

Ossification of sacral vertebral bodies in neonates born 24 to 38 weeks' gestational age and its relevance to spinal ultrasonography.

OBJECTIVE: Determination of gestational age and/or birth weight at which sacral ossification centers appear. STUDY DESIGN: Radiographs were reviewed of newborns admitted to Auckland City Hospital between January 2008 and December 2010. Infants were divided into weight clusters increasing in 100-g increments from 400 g to 3000 g and 500-g increments thereafter, for a total of 29 weight clusters. Adequate images were available for at least five newborns per cluster. RESULTS: Images of 163 newborns were reviewed. All but six newborns had five sacral ossification centers by 32 weeks' gestation and a birth weight of 1800 g. Five of the six infants had a congenital anomaly and associated growth restriction. CONCLUSIONS: Infants can be expected to have all five sacral ossification centers present by the time they reach a gestational age of 32 weeks and/or a birth weight of 1800 g. Variation from this can be associated with congenital anomalies and growth restriction.

Deep-Learning Markerless Tracking of Infant General Movements using Standard Video Recordings.

Monitoring spontaneous General Movements (GM) of infants 6-20 weeks post-term age is a reliable tool to assess the quality of neurodevelopment in early infancy. Abnormal or absent GMs are reliable prognostic indicators of whether an infant is at risk of developing neurological impairments and disorders such as cerebral palsy (CP). Therapeutic interventions are most effective at improving neuromuscular outcomes if administered in early infancy. Current clinical protocols require trained assessors to rate videos of infant movements, a time-intensive task. This work proposes a simple, inexpensive, and broadly applicable markerless pose-estimation approach for automatic infant movement tracking using conventional video recordings from handheld devices (e.g., tablets and mobile phones). We leverage the enhanced capabilities of deep-learning technology in image processing to identify 12 anatomical locations (3 per limb) in each video frame, tracking a baby's natural movement throughout the recordings. We validate the capability of resnet152 and a mobile-net-v2-1 to identify body-parts in unseen frames from a full-term male infant, using a novel automatic unsupervised approach that fuses likelihood outputs of a Kalman filter and the deep-nets. Both deep-net models were found to perform very well in the identification of anatomical locations in the unseen data with high average Percentage of Correct Keypoints (aPCK) performances of >99.65% across all locations.Clinical relevance-Results of this research confirm the feasibility of a low-cost and publicly accessible technology to automatically track infants' GMs and diagnose those at higher risk of developing neurological conditions early, when clinical interventions are most effective.

A Population Model of Time-Dependent Changes in Serum Creatinine in (Near)term Neonates with Hypoxic-Ischemic Encephalopathy During and After Therapeutic Hypothermia.

The objective was to apply a population model to describe the time course and variability of serum creatinine (sCr) in (near)term neonates with moderate to severe encephalopathy during and after therapeutic hypothermia (TH). The data consisted of sCr observations up to 10 days of postnatal age in neonates who underwent TH during the first 3 days after birth. Available covariates were birth weight (BWT), gestational age (GA), survival, and acute kidney injury (AKI). A previously published population model of sCr kinetics in neonates served as the base model. This model predicted not only sCr but also the glomerular filtration rate normalized by its value at birth (GFR/GFR0). The model was used to compare the TH neonates with a reference full term non-asphyxiated population of neonates. The estimates of the model parameters had good precision and showed high between subject variability. AKI influenced most of the estimated parameters denoting a strong impact on sCr kinetics and GFR. BWT and GA were not significant covariates. TH transiently increased [Formula: see text] in TH neonates over the first days compared to the reference group. Asphyxia impacted not only GFR, but also the [Formula: see text] synthesis rate. We also observed that AKI neonates exhibit a delayed onset of postnatal GFR increase and have a higher [Formula: see text] synthesis rate compared to no-AKI patients. Our findings show that the use of [Formula: see text] as marker of renal function in asphyxiated neonates treated with TH to guide dose selection for renally cleared drugs is challenging, while we captured the postnatal sCr patterns in this specific population.

Multi-Round versus Real-Time Delphi survey approach for achieving consensus in the COHESION core outcome set: a randomised trial.

BACKGROUND: Delphi surveys are commonly used to prioritise critical outcomes in core outcome set (COS) development. This trial aims to compare a three-round (Multi-Round) Delphi (MRD) with a Real-Time Delphi (RTD) in the prioritisation of outcomes for inclusion in a COS for neonatal encephalopathy treatments and explore whether 'feedback', 'iteration', and 'initial condition' effects may occur in the two survey methods. METHODS: We recruited 269 participants (parents/caregivers, healthcare providers and researchers/academics) of which 222 were randomised to either the MRD or the RTD. We investigated the outcomes prioritised in each survey and the 'feedback', 'iteration', and 'initial condition' effects to identify differences between the two survey methods. RESULTS: In the RTD, n = 92 participants (83%) fully completed the survey. In the MRD, n = 60 participants (54%) completed all three rounds. Of the 92 outcomes presented, 26 (28%) were prioritised differently between the RTD and MRD. Significantly fewer participants amended their scores when shown stakeholder responses in the RTD compared to the MRD ('feedback effect'). The 'iteration effect' analysis found most experts appeared satisfied with their initial ratings in the RTD and did not amend their scores following stakeholder response feedback. Where they did amend their scores, ratings were amended substantially, suggesting greater convergence. Variance in scores reduced with subsequent rounds of the MRD ('iteration effect'). Whilst most participants did not change their initial scores in the RTD, of those that did, later recruits tended to align their final score more closely to the group mean final score than earlier recruits (an 'initial condition' effect). CONCLUSION: The feedback effect differed between the two Delphi methods but the magnitude of this difference was small and likely due to the large number of observations rather than because of a meaningfully large difference. It did not appear to be advantageous to require participants to engage in three rounds of a survey due to the low change in scores. Larger drop-out through successive rounds in the MRD, together with a lesser convergence of scores and longer time to completion, indicate considerable benefits of the RTD approach. TRIAL REGISTRATION: NCT04471103. Registered on 14 July 2020.

Improvement in mortality of very low birthweight infants and the changing pattern of neonatal mortality: the 50-year experience of one perinatal centre.

AIM: Neonatology is a relatively new sub-specialty so we aimed to review survival data in the context of advances in neonatal care. METHOD: Review of neonatal survival for very low birthweight babies over the last 50 years. RESULTS: In the data collected from a single tertiary neonatal unit, survival for babies 501-1000 g improved from below 10% in 1959 to over 60% in 2009. Similarly, survival for babies 1001 to 1500 g has improved from approximately 50% to over 90%. During the study period, death due to extreme prematurity or cardiorespiratory problems, namely respiratory distress syndrome, fell from 90% in 1964 to only 45% of neonatal deaths in 2008. CONCLUSION: In addition to reporting the remarkable improvement in neonatal survival over this period, we have highlighted items of historical context.

Neonatal Neuroimaging in Neonatal Intensive Care Graduates Who Subsequently Develop Cerebral Palsy.

Cerebral palsy is a common cause of physical disability. The New Zealand Cerebral Palsy Register (NZCPR) was established in 2015 and reports national data. Internationally, an early CP diagnosis has been a focus, with imaging and clinical tools used to enable early accurate detection. Accordingly, guidelines are being developed for New Zealand, including a specific pathway for high-risk neonatal intensive care (NICU) graduates, reflecting the high rate of CP in this group. To inform this work, we reviewed imaging data from a retrospective NICU cohort identified from the NZCPR. In these 140 individuals with CP and a confirmed NICU admission during 2000-2019 inclusive, imaging frequency, modality, and rate of abnormality was determined. Overall, 114 (81.4%) had imaging performed in the NICU, but the frequency and modality used varied by gestational subgroup. For infants born at less than 32 weeks gestation, 53/55 had routine imaging with ultrasound, and IVH was graded as none or mild (grade 1-2) in 35 or severe (grade 3-4) in 18 infants. For the 34 infants born between 32-36 weeks gestation, only 13/19 imaged in the NICU were reported as abnormal. For 51 term-born infants, 41/42 imaged in the NICU with MRI had abnormal results.