End-of-life decisions in neonates and infants: a nationwide mortality follow-back survey.

OBJECTIVES: Neonatology has undergone important clinical and legal changes; however, the implications for end-of-life decision-making in seriously ill neonates to date are unknown. Our aim was to examine changes in prevalence and characteristics of end-of-life decisions (ELDs) in neonatology. METHODS: We performed a nationwide mortality follow-back survey in August 1999 to July 2000 and September 2016 to December 2017 in Flanders, Belgium. Data were linked to information from death certificates. For each death under the age of 1, physicians were asked to complete an anonymous questionnaire about which ELDs were made preceding death. RESULTS: The response rate was 87% in 1999-2000 (253/292) and 83% in 2016-2017 (229/276). The proportion of deaths of infants born before 26 weeks' gestation was increased (14% vs 34%, p=0.001). Prevalence of ELDs remained stable at 60%, with non-treatment decisions occurring in about 35% of all deaths. Use of medication with an explicit life-shortening intention was prevalent in 7%-10% of all deaths. In early neonatal death (<7 days old) medication with an explicit life-shortening intention decreased from 12% to 6%, in late neonatal death (7-27 days old), it increased from 0% to 26%, and in postneonatal death (>27 days old), it increased from 2% to 10%. CONCLUSIONS: Over a timespan of 17 year, the prevalence of neonatal ELDs has remained stable. A substantial number of deaths was preceded by the intentionally hastening of death by administrating medication. While surveying solely the physician perspective in this paper, there is a need for an open multidisciplinary debate, including, for example, nursing staff and family members, based on clinical as well as ethical and jurisdictional reflections to discuss the need for international guidelines.

Motor outcome after perinatal stroke and early prediction of unilateral spastic cerebral palsy.

BACKGROUND: Unilateral spastic cerebral palsy (USCP) occurs in 30%-68% of infants with perinatal stroke. Early detection of USCP is essential for referring infants to early intervention. The aims of this study were to report motor outcomes after perinatal stroke, and to determine the predictive value of the General Movements Assessment (GMA) and Hand Assessment for Infants (HAI) for detection of USCP. MATERIALS AND METHODS: This was a prospective observational study involving infants with perinatal stroke. GMA was conducted between 10 and 15 weeks post term-age (PTA). The HAI was performed between 3 and 5 months PTA. Motor outcome was collected between 12 and 36 months PTA. RESULTS: The sample consisted of 46 infants. Fifteen children (32.6%) were diagnosed with CP, two children with bilateral CP and 13 with USCP. Abnormal GMA had a sensitivity of 85% (95% confidence interval [CI] 55-98%) and a specificity of 52% (95% CI 33-71%) to predict USCP. When asymmetrically presented FMs were also considered as abnormal, sensitivity increased to 100%, hence the specificity declined to 43%. A HAI asymmetry index cut-off of 23, had both a sensitivity and a specificity of 100% to detect USCP. CONCLUSION: Using GMA and HAI can enable prediction of USCP before the age of 5 months in infants with perinatal stroke. Nevertheless, GMA must be interpreted with caution in this particular population. The HAI was found to be a very accurate screening tool for early detection of asymmetry and prediction of USCP.

Neurodevelopmental outcomes of very preterm and very-low-birthweight infants in a population-based clinical cohort with a definite perinatal treatment policy.

BACKGROUND: With constant changes in neonatal care practices, recent information is valuable for healthcare providers and for parental counselling. The aim of the study was to describe the neurodevelopmental outcome in a cohort of very preterm (VPT)/very-low-birthweight (VLBW) infants at 2 years corrected age (CA). MATERIAL AND METHODS: This is a population-based cohort study of all infants born with a GA <31 weeks and/or BW < 1500 g between 2014 and 2016 admitted to the Flemish (Belgium) neonatal intensive care units. Infants had routine clinical follow-up around 2 years CA. The diagnosis of cerebral palsy (CP), visual and hearing impairments were recorded. Motor, cognitive and language outcomes were assessed using the Bayley-III. Neurodevelopmental impairment (NDI) was classified as mild (<1 standard deviation [SD]) or moderate-severe (<2SD) based on the defined categories of motor, cognitive, hearing, and vision impairments. RESULTS: Of the 1941 admissions, 92% survived to discharge and follow-up data were available for 1089 infants (61.1%). Overall, 19.3%, 18.9% and 41.8% of infants had a motor, cognitive and language delay, respectively. CP was diagnosed in 4.3% of the infants. Mild and moderate-to-severe NDI was observed in 25.2% and 10.9% of the infants, respectively. The number of infants with a normal outcome increased from nearly 40% in the category of GA<26 weeks to 70% for infants in the category of 30─31 weeks GA. CONCLUSION: At 2 years CA, 64% were free from NDI and 90% were free from moderate-to-severe NDI. However, a lower GA and BW are associated with higher rates of adverse neurodevelopmental outcomes at 2 years CA.

Outcome of Infants with Therapeutic Hypothermia after Perinatal Asphyxia and Early-Onset Sepsis.

BACKGROUND: Animal models suggest that neuroprotective effects of therapeutic hypothermia (TH) after perinatal asphyxia are reduced in infants with early-onset sepsis. OBJECTIVES: To assess the outcome of infants with perinatal asphyxia, neonatal encephalopathy, and TH in the presence of early-onset sepsis. METHODS: In a retrospective cohort of 1,084 infants with perinatal asphyxia and TH, the outcome of 42 infants (gestational age 36.1-42.6 weeks and birth weight 2,280-5,240 g) with proven sepsis (n = 14) and probable sepsis (n = 28) was analyzed. Death, cerebral palsy, or a delayed development at 2 years was considered an adverse outcome. RESULTS: Sepsis was caused mostly by group B streptococci (n = 17), other Gram-positive bacteria (n = 5), and Candida albicans (n = 1). Of the 42 infants, 9 (21.4%) died, and 5 (11.9%) showed impairments on follow-up. The outcome is comparable to the previously reported outcome of infants with TH without early-onset sepsis. CONCLUSION: A good outcome was reported in the majority of infants with perinatal asphyxia, TH, and early-onset sepsis. Cooling should not be withheld from these infants.

Effect of treatment of subclinical neonatal seizures detected with aEEG: randomized, controlled trial.

OBJECTIVES: The goals were to investigate how many subclinical seizures in full-term neonates with hypoxic-ischemic encephalopathy (HIE) would be missed without continuous amplitude-integrated electroencephalography (aEEG) and whether immediate treatment of both clinical and subclinical seizures would result in a reduction in the total duration of seizures and a decrease in brain injury, as seen on MRI scans. METHODS: In this multicenter, randomized, controlled trial, term infants with moderate to severe HIE and subclinical seizures were assigned randomly to either treatment of both clinical seizures and subclinical seizure patterns (group A) or blinding of the aEEG registration and treatment of clinical seizures only (group B). All recordings were reviewed with respect to the duration of seizure patterns and the use of antiepileptic drugs (AEDs). MRI scans were scored for the severity of brain injury. RESULTS: Nineteen infants in group A and 14 infants in group B were available for comparison. The median duration of seizure patterns in group A was 196 minutes, compared with 503 minutes in group B (not statistically significant). No significant differences in the number of AEDs were seen. Five infants in group B received AEDs when no seizure discharges were seen on aEEG traces. Six of 19 infants in group A and 7 of 14 infants in group B died during the neonatal period. A significant correlation between the duration of seizure patterns and the severity of brain injury in the blinded group, as well as in the whole group, was found. CONCLUSIONS: In this small group of infants with neonatal HIE and seizures, there was a trend for a reduction in seizure duration when clinical and subclinical seizures were treated. The severity of brain injury seen on MRI scans was associated with a longer duration of seizure patterns.

Natural history of brain lesions in extremely preterm infants studied with serial magnetic resonance imaging from birth and neurodevelopmental assessment.

OBJECTIVES: The aim was to survey the range of cerebral injury and abnormalities of cerebral development in infants born between 23 and 30 weeks' gestation using serial MRI scans of the brain from birth, and to correlate those findings with neurodevelopmental outcome after 18 months corrected age. METHODS: Between January 1997 and November 2000, consecutive infants born at < 30 weeks' gestational age underwent serial MRI brain scans from birth until term-equivalent age. Infants were monitored after 18 months of age, corrected for prematurity, with the Griffiths Mental Development Scales and neurologic assessment. RESULTS: A total of 327 MRI scans were obtained from 119 surviving infants born at 23 to 30 weeks of gestation. Four infants had major destructive brain lesions, and tissue loss was seen at term for the 2 survivors. Fifty-one infants had early hemorrhage; 50% of infants with term scans after intraventricular hemorrhage had ventricular dilation. Twenty-six infants had punctate white matter lesions on early scans; these persisted for 33% of infants assessed at term. Early scans showed cerebellar hemorrhagic lesions for 8 infants and basal ganglia abnormalities for 17. At term, 53% of infants without previous hemorrhage had ventricular dilation and 80% of infants had diffuse excessive high signal intensity within the white matter on T2-weighted scans. Complete follow-up data were available for 66% of infants. Adverse outcomes were associated with major destructive lesions, diffuse excessive high signal intensity within the white matter, cerebellar hemorrhage, and ventricular dilation after intraventricular hemorrhage but not with punctate white matter lesions, hemorrhage, or ventricular dilation without intraventricular hemorrhage. CONCLUSIONS: Diffuse white matter abnormalities and post-hemorrhagic ventricular dilation are common at term and seem to correlate with reduced developmental quotients. Early lesions, except for cerebellar hemorrhage and major destructive lesions, do not show clear relationships with outcomes.

Selecting neonates with congenital cytomegalovirus infection for ganciclovir therapy.

OBJECTIVE: The objective of this study is to look for evidence based or scientific guidelines for selection of newborns with congenital cytomegalovirus (CMV) infection that might benefit from treatment with ganciclovir. MATERIALS AND METHODS: A literature search was conducted involving the MEDLINE database and the Cochrane Collaboration Library. Abstracts were reviewed to select pertinent articles dealing with ganciclovir therapy in neonates. References from selected articles as well as from reviews were screened for additional relevant articles. In total, 13 case reports (16 patients in all), three descriptive uncontrolled studies (20 patients in all), two randomized dose-comparative studies (54 patients in all) and one randomized controlled study (42 patients) were identified. OBSERVATIONS: All reported patients presented with central nervous system manifestation of CMV infection. Only the randomized controlled study showed a reduction of hearing deterioration in the treated group. Published predictors of hearing loss in congenitally CMV infected children allow identification of candidates that might benefit from treatment. Studies so far are promising but of insufficient number to make evidence based recommendations about indications for treatment of congenital CMV. As such, studies are very difficult to conduct and treatment of infants at high risk of hearing loss may appear justified. There is scientific data to help clinicians in selecting a subgroup of infants that is at higher risk of hearing deterioration and therefore might benefit the most from ganciclovir therapy.

Neurologic examination of preterm infants at term age: comparison with term infants.

OBJECTIVES: The aim was to establish the range of neurologic findings in preterm infants reaching term age, their relation to gestational age at birth, and the possible differences with healthy term newborns tested during the first days of life. STUDY DESIGN: The Dubowitz neonatal neurologic examination was performed at term age in 157 low-risk preterm infants born between 25 and 34 weeks' gestation who had cranial ultrasonograms that were normal or showed minor abnormalities. Infants were subdivided in 3 groups according to their gestational age at birth. RESULTS: Within the preterm cohort, the range of scores for the 3 gestational age subgroups was different from each other for 21 of the 34 items, although the median scores were different only in 10 of the 34 items. The range of scores and their median in preterm infants however was wider than that found in term infants. Preterm infants examined at term were also more hyperexcitable and tended to have less flexor tone in the limbs and less extensor tone in the neck in the sitting posture. CONCLUSIONS: The distribution of scores provides useful guidelines when a preterm infant is examined at term.

Prognostic value of the neurologic optimality score at 9 and 18 months in preterm infants born before 31 weeks' gestation.

OBJECTIVE: The Hammersmith Infant Neurological Examination was performed in a cohort of 74 preterm infants whose gestational age ranged between 24 and 30.5 weeks. The infants were examined between 9 and 18 months' chronologic age (6-15 months' corrected age) and scored with the optimality score system previously standardized in a cohort of low-risk term infants. The aim of the study was to establish the frequency distribution of the optimality scores in this cohort and to establish whether the scores can predict locomotor function at 2 years of age. RESULTS: The results showed that this standardized neurologic examination can be performed in preterm infants as early as 9 months' chronologic age to predict motor outcome at 2 years old. The scores showed no significant association with the degree of prematurity or the age of assessment. CONCLUSION: This examination should be particularly useful in very premature infants who are at high risk of severe neurologic and developmental disabilities and for whom the early prediction of motor function can be difficult.