Mortality risk after neonatal seizures in very preterm newborns

We analyzed clinical and instrumental data of 403 consecutive newborns with gestational age from 24 to 32 weeks, admitted to the University-Hospital of Parma between January 2000 and December 2007, to evaluate the possible relationship between neonatal mortality and occurrence of neonatal seizures in very preterm newborns. Seventy-four subjects died during hospital stay. Seizures were present in 35 neonates, in whom the mortality rate was 37.1%. Multivariate analysis revealed that birth-weight

Objective and psychophysical studies of infant visual development

Distortion or deprivation of vision during an early `critical' period of visual development can result in permanent visual impairment which indicates the need to identify and treat visually at-risk individuals early. A significant difficulty in this respect is that conventional, subjective methods of visual acuity determination are ineffective before approximately three years of age. In laboratory studies, infant visual function has been quantified precisely, using objective methods based on visual evoked potentials (VEP), preferential looking (PL) and optokinetic nystagmus (OKN) but clinical assessment of infant vision has presented a particular difficulty. An initial aim of this study was to evaluate the relative clinical merits of the three techniques. Clinical derivatives were devised, the OKN method proved unsuitable but the PL and VEP methods were evaluated in a pilot study. Most infants participating in the study had known ocular and/or neurological abnormalities but a few normals were included for comparison. The study suggested that the PL method was more clinically appropriate for the objective assessment of infant acuity. A study of normal visual development from birth to one year was subsequently conducted. Observations included cycloplegic refraction, ophthalmoscopy and preferential looking visual acuity assessment using horizontally and vertically oriented square wave gratings. The aims of the work were to investigate the efficiency and sensitivity of the technique and to study possible correlates of visual development. The success rate of the PL method varied with age; 87% of newborns and 98% of infants attending follow-up successfully completed at least one acuity test. Below two months monocular acuities were difficult to secure; infants were most testable around six months. The results produced were similar to published data using the acuity card procedure and slightly lower than, but comparable with acuity data derived using extended PL methods. Acuity development was not impaired in infants found to have retinal haemorrhages as newborns. A significant relationship was found between newborn binocular acuity and anisometropia but not with other refractive findings. No strong or consistent correlations between grating acuity and refraction were found for three, six or twelve months olds. Improvements in acuity and decreases in levels of hyperopia over the first week of life were suggestive of recovery from minor birth trauma. The refractive data was analysed separately to investigate the natural history of refraction in normal infants. Most newborns (80%) were hyperopic, significant astigmatism was found in 86% and significant anisometropia in 22%. No significant alteration in spherical equivalent refraction was noted between birth and three months, a significant reduction in hyperopia was evident by six months and this trend continued until one year. Observations on the astigmatic component of the refractive error revealed a rather erratic series of changes which would be worthy of further investigation since a repeat refraction study suggested difficulties in obtaining stable measurements in newborns. Astigmatism tended to decrease between birth and three months, increased significantly from three to six months and decreased significantly from six to twelve months. A constant decrease in the degree of anisometropia was evident throughout the first year. These findings have implications for the correction of infantile refractive error.

A scoring system for early prognostic assessment after neonatal seizures

OBJECTIVE: The aim of this study was to devise a scoring system that could aid in predicting neurologic outcome at the onset of neonatal seizures. METHODS: A total of 106 newborns who had neonatal seizures and were consecutively admitted to the NICU of the University of Parma from January 1999 through December 2004 were prospectively followed-up, and neurologic outcome was assessed at 24 months’ postconceptional age. We conducted a retrospective analysis on this cohort to identify variables that were significantly related to adverse outcome and to develop a scoring system that could provide early prognostic indications. RESULTS: A total of 70 (66%) of 106 infants had an adverse neurologic outcome. Six variables were identified as the most important independent risk factors for adverse outcome and were used to construct a scoring system: birth weight, Apgar score at 1 minute, neurologic examination at seizure onset, cerebral ultrasound, efficacy of anticonvulsant therapy, and presence of neonatal status epilepticus. Each variable was scored from 0 to 3 to represent the range from “normal” to “severely abnormal.” A total composite score was computed by addition of the raw scores of the 6 variables. This score ranged from 0 to 12. A cutoff score of =4 provided the greatest sensitivity and specificity. CONCLUSIONS: This scoring system may offer an easy, rapid, and reliable prognostic indicator of neurologic outcome after the onset of neonatal seizures. A final assessment of the validity of this score in routine clinical practice will require independent validation in other centers.

Preterm infants with video-EEG confirmed seizures:outcome at 30 months of age

Our aim was to identify early predictors of poor neurodevelopmental outcome and of subsequent epilepsy in very early preterm and late preterm newborns with neonatal seizures.

Neonatal seizures and post-neonatal epilepsy:a seven-year follow-up study

BACKGROUND: Seizures are one of the most common symptoms of acute neurological disorders in newborns. This study aims at evaluating predictors of epilepsy in newborns with neonatal seizures. METHODS: we recruited consecutively eighty-five neonates with repeated neonatal video-EEG-confirmed seizures between Jan 1999 and Dec 2004. The relationship between clinical, EEG and ultrasound data in neonatal period and the development of post-neonatal epilepsy was investigated at 7 years of age. RESULTS: Fifteen patients (17.6%) developed post-neonatal epilepsy. Partial or no response to anticonvulsant therapy (OR 16.7, 95% CI: 1.8-155.8, p= .01; OR 47, 95% CI: 5.2-418.1, p<.01 respectively), severely abnormal cerebral ultrasound scan findings (OR: 5.4; 95% CI: 1.1-27.4; p<.04), severely abnormal EEG background activity (OR: 9.5; 95% CI: 1.6-54.2; p= .01) and the presence of status epilepticus (OR: 6.1; 95% CI: 1.8-20.3; p<.01) were found to be predictors of epilepsy. However, only the response to therapy seemed to be an independent predictor of post-neonatal epilepsy. CONCLUSION: Neonatal seizures seem to be related to post-neonatal epilepsy. Recurrent and prolonged neonatal seizures may act on an epileptogenic substrate, causing further damage, which is responsible for the subsequent clinical expression of epilepsy.

Pulse oximetry as a screening test for congenital heart defects in newborn infants: a test accuracy study with evaluation of acceptability and cost-effectiveness

Background: Screening for congenital heart defects (CHDs) relies on antenatal ultrasound and postnatal clinical examination; however, life-threatening defects often go undetected. Objective: To determine the accuracy, acceptability and cost-effectiveness of pulse oximetry as a screening test for CHDs in newborn infants. Design: A test accuracy study determined the accuracy of pulse oximetry. Acceptability of testing to parents was evaluated through a questionnaire, and to staff through focus groups. A decision-analytic model was constructed to assess cost-effectiveness. Setting: Six UK maternity units. Participants: These were 20,055 asymptomatic newborns at = 35 weeks’ gestation, their mothers and health-care staff. Interventions: Pulse oximetry was performed prior to discharge from hospital and the results of this index test were compared with a composite reference standard (echocardiography, clinical follow-up and follow-up through interrogation of clinical databases). Main outcome measures: Detection of major CHDs – defined as causing death or requiring invasive intervention up to 12 months of age (subdivided into critical CHDs causing death or intervention before 28 days, and serious CHDs causing death or intervention between 1 and 12 months of age); acceptability of testing to parents and staff; and the cost-effectiveness in terms of cost per timely diagnosis. Results: Fifty-three of the 20,055 babies screened had a major CHD (24 critical and 29 serious), a prevalence of 2.6 per 1000 live births. Pulse oximetry had a sensitivity of 75.0% [95% confidence interval (CI) 53.3% to 90.2%] for critical cases and 49.1% (95% CI 35.1% to 63.2%) for all major CHDs. When 23 cases were excluded, in which a CHD was already suspected following antenatal ultrasound, pulse oximetry had a sensitivity of 58.3% (95% CI 27.7% to 84.8%) for critical cases (12 babies) and 28.6% (95% CI 14.6% to 46.3%) for all major CHDs (35 babies). False-positive (FP) results occurred in 1 in 119 babies (0.84%) without major CHDs (specificity 99.2%, 95% CI 99.0% to 99.3%). However, of the 169 FPs, there were six cases of significant but not major CHDs and 40 cases of respiratory or infective illness requiring medical intervention. The prevalence of major CHDs in babies with normal pulse oximetry was 1.4 (95% CI 0.9 to 2.0) per 1000 live births, as 27 babies with major CHDs (6 critical and 21 serious) were missed. Parent and staff participants were predominantly satisfied with screening, perceiving it as an important test to detect ill babies. There was no evidence that mothers given FP results were more anxious after participating than those given true-negative results, although they were less satisfied with the test. White British/Irish mothers were more likely to participate in the study, and were less anxious and more satisfied than those of other ethnicities. The incremental cost-effectiveness ratio of pulse oximetry plus clinical examination compared with examination alone is approximately £24,900 per timely diagnosis in a population in which antenatal screening for CHDs already exists. Conclusions: Pulse oximetry is a simple, safe, feasible test that is acceptable to parents and staff and adds value to existing screening. It is likely to identify cases of critical CHDs that would otherwise go undetected. It is also likely to be cost-effective given current acceptable thresholds. The detection of other pathologies, such as significant CHDs and respiratory and infective illnesses, is an additional advantage. Other pulse oximetry techniques, such as perfusion index, may enhance detection of aortic obstructive lesions.

Fetal growth restriction results in remodeled and less efficient hearts in children

Background— Fetal growth restriction (FGR) affects 5% to 10% of newborns and is associated with increased cardiovascular mortality in adulthood. The most commonly accepted hypothesis is that fetal metabolic programming leads secondarily to diseases associated with cardiovascular disease, such as obesity, diabetes mellitus, and hypertension. Our main objective was to evaluate the alternative hypothesis that FGR induces primary cardiac changes that persist into childhood. Methods and Results— Within a cohort of fetuses with growth restriction identified in fetal life and followed up into childhood, we randomly selected 80 subjects with FGR and compared them with 120 normally grown fetuses, matched for gender, birth date, and gestational age at birth. Cardiovascular assessment was performed in childhood (mean age of 5 years). Compared with control subjects, children with FGR had a different cardiac shape, with increased transversal diameters and more globular cardiac ventricles. Although left ejection fraction was similar among the study groups, stroke volume was reduced significantly, which was compensated for by an increased heart rate to maintain output in severe FGR. This was associated with subclinical longitudinal systolic dysfunction (decreased myocardial peak velocities) and diastolic changes (increased E/E' ratio and E deceleration time). Children with FGR also had higher blood pressure and increased intima-media thickness. For all parameters evaluated, there was a linear increase with the severity of growth restriction. Conclusions— These findings suggest that FGR induces primary cardiac and vascular changes that could explain the increased predisposition to cardiovascular disease in adult life. If these results are confirmed, the impact of strategies with beneficial effects on cardiac remodeling should be explored in children with FGR.

Phenobarbital for neonatal seizures:response rate and predictors of refractoriness

Background : Phenobarbital is the first-line choice for neonatal seizures treatment, despite a response rate of approximately 45%. Failure to respond to acute anticonvulsants is associated with poor neurodevelopmental outcome, but knowledge on predictors of refractoriness is limited. Objective : To quantify response rate to phenobarbital and to establish variables predictive of its lack of efficacy. Methods : We retrospectively evaluated newborns with electrographically confirmed neonatal seizures admitted between January 1999 and December 2012 to the neonatal intensive care unit of Parma University Hospital (Italy), excluding neonates with status epilepticus. Response was categorized as complete (cessation of clinical and electrographic seizures after phenobarbital administration), partial (reduction but not cessation of electrographic seizures with the first bolus, response to the second bolus), or absent (no response after the second bolus). Multivariate analysis was used to identify independent predictors of refractoriness. Results : Out of 91 newborns receiving phenobarbital, 57 (62.6%) responded completely, 15 (16.5%) partially, and 19 (20.9%) did not respond. Seizure type (p = 0.02), background electroencephalogram (EEG; p ≤ 0.005), and neurologic examination (p ≤ 0.005) correlated with response to phenobarbital. However, EEG (p ≤ 0.02) and seizure type (p ≤ 0.001) were the only independent predictors. Conclusion : Our results suggest a prominent role of neurophysiological variables (background EEG and electrographic-only seizure type) in predicting the absence of response to phenobarbital in high-risk newborns.

The effect of notch filtering on the waveform of the newborn auditory brainstem response

OBJECTIVE: To identify whether the use of a notch filter significantly affects the morphology or characteristics of the newborn auditory brainstem response (ABR) waveform and so inform future guidance for clinical practice. DESIGN: Waveforms with and without the application of a notch filter were recorded from babies undergoing routine ABR tests at 4000, 1000 and 500 Hz. Any change in response morphology was judged subjectively. Response latency, amplitude, and measurements of response quality and residual noise were noted. An ABR simulator was also used to assess the effect of notch filtering in conditions of low and high mains interference. RESULTS: The use of a notch filter changed waveform morphology for 500 Hz stimuli only in 15% of tests in newborns. Residual noise was lower when 4000 Hz stimuli were used. Response latency, amplitude, and quality were unaffected regardless of stimulus frequency. Tests with the ABR stimulator suggest that these findings can be extended to conditions of high level mains interference. CONCLUSIONS: A notch filter should be avoided when testing at 500 Hz, but at higher frequencies appears to carry no penalty.