Challenges of Developing Robust AI for Intrapartum Fetal Heart Rate Monitoring.

Background: CTG remains the only non-invasive tool available to the maternity team for continuous monitoring of fetal well-being during labour. Despite widespread use and investment in staff training, difficulty with CTG interpretation continues to be identified as a problem in cases of fetal hypoxia, which often results in permanent brain injury. Given the recent advances in AI, it is hoped that its application to CTG will offer a better, less subjective and more reliable method of CTG interpretation. Objectives: This mini-review examines the literature and discusses the impediments to the success of AI application to CTG thus far. Prior randomised control trials (RCTs) of CTG decision support systems are reviewed from technical and clinical perspectives. A selection of novel engineering approaches, not yet validated in RCTs, are also reviewed. The review presents the key challenges that need to be addressed in order to develop a robust AI tool to identify fetal distress in a timely manner so that appropriate intervention can be made. Results: The decision support systems used in three RCTs were reviewed, summarising the algorithms, the outcomes of the trials and the limitations. Preliminary work suggests that the inclusion of clinical data can improve the performance of AI-assisted CTG. Combined with newer approaches to the classification of traces, this offers promise for rewarding future development.

Range of UK practice regarding thresholds for phototherapy and exchange transfusion in neonatal hyperbilirubinaemia.

OBJECTIVE: To establish the range of opinion regarding thresholds at which phototherapy and exchange transfusion are used to treat neonatal hyperbilirubinaemia in the UK. DESIGN: A survey of existing charts and guidelines collected from around the UK. Threshold levels were extracted from the charts and entered into an Excel spreadsheet. Filters were applied to analyse subsets of guidelines, and calculations were carried out to analyse the rate of rise of bilirubin (in micromol/l/h) between the origin and the plateau, where this was possible. RESULTS: Of 263 hospitals contacted, 163 submitted guidelines, of which most were in the form of individual charts. There was wide variation in the choice of the threshold levels at which treatment was recommended, particularly in preterm babies. At 28 weeks, for example, the range at which phototherapy was recommended extended from 100 micromol/l to 250 micromol/l, and the upper limit was even higher if data from units which used a single guideline for preterm babies of all gestations were included. There was variation in the choice of the origin of the graph and the time at which the plateau commenced (and hence the slope), whether "sickness" criteria should be adopted, and what those criteria should be. Many charts were confusing, poorly presented, sketchily drawn and lacked proper gridlines or axis labels. CONCLUSIONS: For such a vitally important topic it is disappointing that there is little existing consensus and no national guidance in the UK. Guidelines for England, Wales and Northern Ireland will be available from 2010, when the National Institute for Health and Clinical Excellence completes its review.

The relationship between the onset of electrographic seizure activity after birth and the time of cerebral injury in utero.

In the fetal lamb model of hypoxic-ischaemic injury, the insult is followed by EEG depression, after which seizures emerge at 7-13 hours. We explored the relationship between the emergence of electrographic seizures and our estimate of the time of the cerebral injury in nine babies who underwent continuous video-EEG monitoring from soon after birth. Babies with prelabour insults had their first seizures before 12 hours of age, whereas those whose insult was peripartum had seizure onset at 18-20 hours of age. EEG seizure onset time could have important clinical and medico-legal applications, and be related to the time or severity of the insult, or both.

Second-line anticonvulsant treatment of neonatal seizures: a video-EEG monitoring study.

The authors conducted a randomized trial of second-line anticonvulsant treatments for neonates. The response to treatment was assessed using continuous video-EEG because the clinical diagnosis of seizure in neonates is known to be unreliable. Of 27 neonates with EEG-confirmed seizures, 5 were excluded because of protocol violations, and 11 responded to phenobarbitone in a dose of 40 mg/kg as first line. Three of five neonates treated with lignocaine responded. Six neonates were treated with benzodiazepines as second line: None responded, and their neurodevelopmental outcome was poor.

Non-expert use of the cerebral function monitor for neonatal seizure detection.

BACKGROUND: The cerebral function monitor (CFM) is widely used to detect neonatal seizures, but there are very few studies comparing it with simultaneous electroencephalography (EEG). OBJECTIVE: To determine the accuracy of non-expert use of the CFM and to assess interobserver agreement of CFM seizure detection. PATIENTS: Babies admitted to the neonatal intensive care unit at King's College Hospital who were at high risk of seizure and had video-EEG monitoring. METHODS: Video-EEG was used to detect seizures. Each baby had CFM recordings at speeds of 6, 15, and 30 cm/h during the EEG. Four neonatologists, trained in CFM seizure recognition, independently rated one hour CFM samples at three speeds from each baby. Interobserver agreement was quantified using Cohen's kappa. RESULTS: CFM traces from 19 babies with EEG seizures and 21 babies without EEG seizures were analysed. Overall non-expert interpretation of the CFM performed poorly as a seizure detector compared with simultaneous EEG (sensitivities 38% at 6 cm/h; 54% at 15 cm/h; 55% at 30 cm/h). Although babies with seizures were more likely to be correctly classified at higher speeds (p = 0.02), babies without seizures were also more likely to be misclassified (p < 0.001). Agreement between observers was not good at any speed (kappa values from 0.01 to 0.39). The observers usually detected generalised seizures but often missed seizures that were focal, low amplitude, or lasted less than one minute. CONCLUSION: Approximately half of all neonatal seizures may be missed using CFM alone. Neonatal seizures need to be diagnosed, characterised, and quantified first using EEG. The CFM may then be useful for long term monitoring.

Neonatal murmurs: are senior house officers good enough?

AIM: To show that, given appropriate guidelines, senior house officers (SHOs) have the clinical skills required to assess neonatal murmurs. METHODS: Neonatal SHOs identified babies with a cardiac murmur at routine neonatal examination. The SHOs assessed whether the murmur was significant or innocent and decided between immediate further assessment or echocardiogram as an outpatient. RESULTS: A total of 112 babies had murmurs at routine neonatal examination. The incidence of cardiac murmurs was 13.8 per 1000. Twelve babies were referred for immediate further assessment. Eleven had structurally abnormal hearts. One had a normal heart with pulmonary hypoplasia. One hundred babies were referred, and 78 attended for outpatient follow up. Of these, the SHO assessed nine babies as having a significant murmur and 69 as having an innocent murmur. Twenty two babies failed to attend for follow up; all were thought to have innocent murmurs. Of the nine murmurs assessed as significant, four were confirmed as such and five were found to be innocent. Of the 91 murmurs assessed as innocent, 63 were proven to be innocent, six had abnormalities on echocardiogram, and 22 defaulted to follow up. Five of the serious murmurs were small ventricular septal defects, which had resolved by 6 months of age; the other had mild pulmonary stenosis. None of these babies were clinically symptomatic at outpatient review. CONCLUSION: Given appropriate guidelines, SHOs have the skills to assess the significance of, and decide on appropriate management for, neonatal murmurs. Electrocardiograms and chest radiographs are not necessary.

Phenobarbitone, neonatal seizures, and video-EEG.

AIMS: To evaluate the effectiveness of phenobarbitone as an anticonvulsant in neonates. METHODS: An observational study using video-EEG telemetry. Video-EEG was obtained before treatment was started, for an hour after treatment was given, two hours after treatment was given, and again between 12 and 24 hours after treatment was given. Patients were recruited from all babies who required phenobarbitone (20-40 mg/kg intravenously over 20 minutes) for suspected clinical seizures and had EEG monitoring one hour before and up to 24 hours after the initial dose. An EEG seizure discharge was defined as a sudden repetitive stereotyped discharge lasting for at least 10 seconds. Neonatal status epilepticus was defined as continuous seizure activity for at least 30 minutes. Seizures were categorised as EEG seizure discharges only (electrographic), or as EEG seizure discharges with accompanying clinical manifestations (electroclinical). Surviving babies were assessed at one year using the Griffiths neurodevelopmental score. RESULTS: Fourteen babies were studied. Four responded to phenobarbitone; these had normal or moderately abnormal EEG background abnormalities and outcome was good. In the other 10 babies electrographic seizures increased after treatment, whereas electroclinical seizures reduced. Three babies were treated with second line anticonvulsants, of whom two responded. One of these had a normal neurodevelopmental score at one year, but the outcome for the remainder of the whole group was poor. CONCLUSION: Phenobarbitone is often ineffective as a first line anticonvulsant in neonates with seizures in whom the background EEG is significantly abnormal.

Early serial EEG in hypoxic ischaemic encephalopathy.

OBJECTIVES: To perform early serial EEGs in infants with hypoxic ischaemic encephalopathy (HIE) and compare the findings with neurodevelopmental outcome. METHODS: Nine full-term neonates with HIE had simultaneous video-EEG polygraphic studies within 8 h of birth. The EEG was repeated at 12-24 h intervals. All surviving infants had a neurodevelopmental assessment at 1 year. RESULTS: Two infants had a normal or mildly abnormal EEG within 8 h of birth and neurodevelopmental outcome was normal. Seven infants had severely depressed background activity in the first 8 h of life. In 3 infants the EEG activity recovered within 12-24 h showing continuous activity with no or only minor abnormalities. All these infants had a normal outcome. The remaining 4 infants, who also had an initially inactive recording, subsequently developed severe background abnormalities. At follow-up, two infants had died and the remainder developed major neurological sequelae. CONCLUSIONS: Early EEG is an excellent prognostic indicator for a favourable outcome if normal within the first 8 h of life and for a poor outcome if the background activity continues to be inactive or grossly abnormal beyond 8-12 h of life. However, an inactive or very depressed EEG within the first 8 h of life can be associated with good outcome if the EEG activity recovers within 12 h.

Grading of cerebral autoregulation in preterm and term neonates.

The response of cerebral blood flow velocity to a single spontaneous transient rise in blood pressure was studied to grade the cerebral autoregulatory response of newborns. Blood pressure was measured continuously through an umbilical or peripheral arterial catheter; continuous flow velocity recordings were taken from the middle cerebral artery using continuous wave Doppler ultrasound. From a cohort of 62 healthy term and preterm neonates, 325 transients in mean arterial blood pressure and mean cerebral blood flow velocity were identified for analysis using a foot-seeking algorithm. An initial classification of active or impaired autoregulation was given to each transient using a self-clustering technique. The grading of the transients was studied by examining the slope of the return of the cerebral blood flow velocity to baseline. Negative slopes indicate a normal autoregulation; slopes of 0 or greater indicate an absence of autoregulation. This classification was in agreement with the self-clustering method (Cohen's kappa = 0.94, P<0.0001). The relationship between the autoregulatory response assessed by the grading method and gestational age, postnatal age, and PCO(2) was examined using linear regression analysis. A significant relationship with gestational age (P = 0.002) but not PCO(2) (P = 0.06) or postnatal age (P = 0.14) was evident.

Dynamic cerebral autoregulation in sick newborn infants.

The sick newborn infant is vulnerable to brain injury and impaired cerebral autoregulation is thought to contribute to this. Coherent averaging is a method of measuring the dynamic cerebral autoregulatory response that is particularly suitable for neonates. We used this method in combination with a measure of the gradient of the cerebral blood flow velocity (CBFV) response following transient blood pressure (BP) peaks to study dynamic autoregulation in infants undergoing intensive care. Term and preterm infants at high risk of neurologic injury were compared with a control group of infants, also undergoing intensive care. Simultaneous video-EEG, CBFV (using transcranial Doppler), and arterial blood pressure measurements were obtained intermittently during a study period of at least 2 h. Cerebral autoregulatory response curves were constructed for high risk and control groups. Intact cerebral autoregulation produces a characteristic response consisting of a brief period when CBFV follows arterial blood pressure but quickly returns to baseline value. An impaired autoregulatory response shows CBFV mirroring the arterial blood pressure curve closely. Thirteen high-risk infants, who also had seizures (10 term and 3 preterm) and 12 control infants (6 term and 6 preterm) were studied. Autoregulation was absent in high-risk term and preterm infants. It was also absent in preterm control infants. Term, neurologically healthy infants undergoing intensive care have an intact autoregulatory response. The constant passive response seen in high-risk infants may reflect the severity of the underlying neurologic disease.

Investigation of prolonged neonatal jaundice.

UNLABELLED: Jaundice persisting beyond 14 d of age (prolonged jaundice) can be a sign of serious underlying liver disease. Protocols for investigating prolonged jaundice vary in complexity and the yield from screening has not been assessed. In order to address these issues, we carried out a prospective study of term infants referred to our neonatal unit with prolonged jaundice over an 18 mo period. Infants were examined by a paediatrician and had the following investigations: a total and conjugated serum bilirubin, liver function tests, full blood count, packed cell volume, group and Coombs' test, thyroid function tests, glucose-6-phosphate dehydrogenase levels and urine for culture. One-hundred-and-fifty-four infants were referred with prolonged jaundice out of 7,139 live births during the study period. Nine infants were referred to other paediatric specialties. One infant had a conjugated hyperbilirubinaemia, giving an incidence of conjugated hyperbilirubinaemia of 0.14 per 1,000 live births. Diagnoses included: giant cell hepatitis (n = 1), hepatoblastoma (n = 1), trisomy 9p (n = 1), urinary tract infections (n = 2), glucose-6-phosphate dehydrogenase deficiency (n = 3) and failure to regain birthweight (n = 1). CONCLUSIONS: In conclusion, a large number of infants referred to hospital for prolonged jaundice screening had detectable problems. The number of investigations may safely be reduced to: a total and conjugated bilirubin, packed cell volume, glucose-6-phosphate dehydrogenase level (where appropriate), a urine for culture and inspection of a recent stool sample for bile pigmentation. Clinical examination by a paediatrician has a vital role in the screening process.

Perinatal infection is an important risk factor for cerebral palsy in very-low-birthweight infants.

Sixty-nine very-low-birthweight infants out of a population of 923 had cerebral palsy (CP) at an 18-month follow-up. Thirty-nine of these had cranial ultrasound abnormalities in the neonatal period and 30 had normal cranial ultrasounds. The distribution of subtypes of CP differed markedly between the two groups, with hemiplegia predominating in those with abnormal cranial ultrasounds and diplegia in those with normal cranial ultrasounds. Regardless of ultrasound appearance, the relative risk of CP increased approximately fourfold with a neonatal history of sepsis.

Outcome predictors in nitric oxide treated preterm infants.

UNLABELLED: Our aim was to identify factors predictive of death in preterm infants in whom inhaled nitric oxide was administered in response to poor oxygenation (oxygenation index > or =15). Of the 23 (median gestational age 28 weeks, range 24-36) infants consecutively so treated, 15 died. Non-survival was commoner in infants with air leaks (12 of 12, P < 0.002) and/or a change in their oxygenation index of less than 30% in response to inhaled nitric oxide administration (P < 0.05). CONCLUSION: In preterm infants given inhaled nitric oxide because of poor oxygenation, a diagnosis of airleak and a lack of initial response are predictive of death.

Cerebral blood flow velocity during neonatal seizures.

AIM: To determine if cerebral blood flow velocity increases during all types of neonatal seizure, and whether the effect is due solely to an increase in blood pressure, transmitted to the cerebral circulation when autoregulation is impaired. METHODS: Seizures were diagnosed in 11 high risk neonates using cotside 16 channel video-EEG polygraphy. EEG, cerebral blood flow velocity (CBFV) using transcranial Doppler ultrasound, and arterial blood pressure (ABP) measurements were made. At least two 5-10 minute epochs of simultaneous measurements were performed on each infant. These epochs were then reviewed to eliminate artefacts, and one minute data periods containing a clear seizure onset were created. Each period contained 20 seconds before the seizure. Data periods without seizures from the same infants were also analysed and compared with seizure periods. RESULTS: Four infants had purely electrographic seizures-without clinical manifestations. Six infants had electroclinical seizures. One infant displayed both seizure types. A random effects linear regression analysis was used to determine the effect of seizures on CBFV and ABP. A significant increase was found in mean CBFV in those periods containing seizures. The mean percentage change in velocity for all infants was 15.6%. Three infants showed a significant increase in mean ABP after seizures but the overall increase in ABP for all infants was not significant. CONCLUSION: Electroclinical and electrographic neonatal seizures produce an increase in CBFV. In some infants the increase is not associated with an increase in blood pressure. These preliminary results suggest that electrographic seizures are associated with disturbed cerebral metabolism. Treatment of neonatal seizures until electrographic seizure activity is abolished may improve outcome for these infants.

Outcome of electroclinical, electrographic, and clinical seizures in the newborn infant.

Three seizure types have been described in the neonate: electroclinical, electrographic, and clinical only. Controversy still exists about whether the episodic abnormal movements seen in some infants, which are not accompanied by simultaneous ictal discharges on the EEG, are true seizures. Twenty-four infants with seizures were studied, 17 had purely electrographic and/or electroclinical seizures, seven had clinical-only seizures; six of these seven had clonic seizures, without facial manifestations or autonomic change. The three seizure types were investigated using video-EEG and a Griffiths neurodevelopmental assessment was performed in each seizure group. Of the seven infants with clinical-only seizures, six had clonic seizures with a normal background EEG, neuroimaging studies and neurodevelopmental follow-up assessment were normal in five. In the remaining 17 infants with electrographic and/or electroclinical seizures, seizure discharges were often associated with ocular phenomena, apnoea, or tonic posturing, and the background EEG was abnormal in all but one subject. Neurodevelopmental follow-up assessments revealed a poor outcome (14 of 17) in this group. In otherwise healthy infants, purely clonic seizures involving only the limbs may be a benign phenomenon and an EEG should be obtained to avoid unnecessary treatment. Infants with seizures superimposed on an abnormal background EEG pattern had a poor outcome.