BACKGROUND:Previous work has shown pediatricians the neurological examination in newborn infants because they do not feel confident performing it. In a UK survey about the neurological examination in unwell newborns, 72% wanted a proforma to aid practice. Our aim was to develop a proforma to improve the neonatal neurological examination, alongside a flowchart to aid formulation of differential diagnoses and investigation plans. METHODS:Four perinatal neurologists and a graphic designer developed a proforma based on existing examinations and data on attitudes toward the examination in the unwell newborn. This was reviewed via qualitative focus groups and interviews with UK health professionals. Thematic analysis was used to gauge attitudes toward and improve the proforma. RESULTS:Two themes arose from the review and interviews: "Neurophobia" about the neurological assessment of the acutely unwell newborn, and ways of improving practice and confidence. Participants suggested improvements to the proforma. They reported it would allow the neurological examination to be performed consistently, and it would improve confidence, documentation, communication, and interpretation of findings. CONCLUSIONS:We have developed a proforma for documenting the neurological assessment of the unwell newborn, which participants report will improve reliable identification of abnormal signs, their neuroanatomical siting and significance, and confidence in assessing an unwell newborn neurologically. The proforma is not intended to replace current examinations for the stable term or preterm newborn, for whom appropriate validated tools should be chosen. We plan to undertake further validity testing, including interobserver agreement and data on the value of the interpretive flowchart.

AimsNeonatal hypoxic-ischemic encephalopathy (HIE) carries increased probability of neurodevelopmental difficulties. Parental birth-related stress is linked to poorer child outcomes; its role in HIE is unknown. We explored emotional-behavioural function in children with HIE and whether parental birth-related stress mediated this.MethodsFifty-one children with HIE (median age 6.4 years), 41 typically developing controls (median age 7.70 years) and their parents participated. Measurements included general cognitive abilities (FSIQ, Wechsler Intelligence Scales for Children); parent-report Child Behavior Checklist (CBCL) and the parallel Teacher Report-Form (TRF) for emotional-behavioural function; the Modified Perinatal Post-Traumatic Stress Disorder Questionnaire for parental birth-related stress. Group comparisons controlled for FSIQ and parental education. Mediation analyses tested whether birth-related stress mediated the relationship between HIE status and child emotional-behavioural function.ResultsParent-ratings, but not teacher-ratings, showed that children with HIE had significantly greater difficulties with Anxious/Depressed behaviour (p=0.022), Social Problems (p=0.021), Attention Problems (p=0.009). Parents of children with HIE reported significantly greater birth-related stress (p<0.001), which mediated the relationship between HIE and child Anxious/Depressed behaviour.InterpretationChildren with HIE experience greater emotional and behavioural difficulties than peers. Behaviour expresses differently in home and school. The long-term impact of birth-related stress highlights need for family-centred interventions.

With increased access to advanced prenatal neuroimaging and genetic testing, neurological disorders such as brain malformations, brain injuries, and genetic disorders, are increasingly being diagnosed during pregnancy. In this review, we address neonatal neurocritical care considerations for the population with prenatally identified neurological disorders. We identify antenatal considerations, including planning location of delivery, as well as postnatal considerations, including clinical phenotyping, neuromonitoring, neuroimaging, and genetic testing. The importance of interdisciplinary collaboration between obstetrics, maternal-fetal medicine, neonatology, pediatric neurology, neuroradiology, genetics, palliative care, early intervention and habilitative services is emphasized. We outline high-priority research gaps, and highlight the need for large, multicenter studies that capture diverse geographies, populations, care practices and settings longitudinally.

(Abstracted from BJOG 2024;131:1673–1683) Fetal growth restriction (FGR) occurs when a fetus grows slower than expected for gestational age. Severe early-onset cases are associated with stillbirth, neonatal death, and developmental disorders.

BACKGROUND:Neonatal Hypoxic-Ischaemic Encephalopathy (HIE) increases the risk for neurodevelopmental impairment. Information on school-age memory function is limited in children who received hypothermia treatment (TH) for neonatal HIE. OBJECTIVES:To evaluate memory function in school-aged children who had neonatal HIE and TH and survived without major neuromotor impairment. METHOD:Fifty-one children with neonatal HIE and 41 typically developing (TD) peers participated. At age 6-8 years general cognitive abilities (FSIQ) were assessed with Wechsler Intelligence Scale for Children (WISC-V), immediate and delayed visual and verbal memory with Children's Memory Scale (CMS), everyday memory with Rivermead Behavioural Memory Test for Children (RBMT-C), and working memory with WISC-V. Real-life implications were assessed with Behavior Rating Inventory for Executive Function (BRIEF; Parent and Teacher). Group differences were examined and correlations calculated to assess associations between memory measures. Relationship maps illustrate co-occurring impairments. RESULTS:FSIQ was in the normal range for both groups but significantly lower in the HIE group. Children with HIE had significantly more deficits in working memory (20.4 % vs 0 %), verbal immediate (20.0 % vs 2.5 %), verbal delayed (17.8 % vs 2.5 %), visual immediate (28.9 % vs 7.5 %), and everyday memory (38.8 % vs 5.6 %). Relationship maps identified more co-occurring clinical/borderline impairments in children with HIE (45.1 % vs 4.9 %) and more frequent clinical impairments in real-world memory measures. CONCLUSION:Despite hypothermia treatment, and with general cognitive abilities in the normal range, children with neonatal HIE are at risk of memory impairments in multiple domains, affecting everyday functioning at home and school. Timely identification is important for individually targeted support.

Agenesis of the corpus callosum is a common indication for fetal neurology consultation, increasingly identified through advances in fetal sonography and fetal magnetic resonance imaging. Despite improvements in diagnostic accuracy, prognostic counseling is challenging due to highly variable neurodevelopmental outcomes. Several factors contribute to neurodevelopmental outcome variability, including associated anomalies and etiologic considerations such as genetic, acquired, and environmental factors. This narrative review discusses existing literature on prenatal findings, postnatal outcomes, and comorbidities to provide practical guidelines for prenatal diagnosis, counseling, and postnatal management. Additionally, practice and research gaps are identified to advocate for guidelines to improve counseling, management, and optimization of outcomes for affected children and families.

Malformations of cortical development (MCDs) are a heterogeneous family of congenital brain malformations that originate from disturbed development of the cerebral cortex. MCDs can arise from primary genetic disorders that lead to dysfunction of the molecular processes controlling neuronal proliferation, neuronal migration, cortical folding or cortical organization. MCDs can also result from secondary, disruptive causes, such as congenital infection or other in utero brain injuries. Sequelae of MCDs can include epilepsy, intellectual disability and cerebral palsy, among other symptoms, with a high burden of paediatric morbidity. Advances in antenatal genetic testing and imaging have improved the ability to diagnose MCDs, yet limited literature exists to aid clinicians in prognostication of outcomes and perinatal management. These clinical realities can make it challenging for clinicians caring for fetal neurological conditions to counsel families and make recommendations for interdisciplinary care. We aim to review the literature on fetal MCDs and present practice guidelines for clinicians regarding the pre- and postnatal management of MCDs.

Fetal intracerebral hemorrhage is increasingly recognized on prenatal imaging. In this review, we discuss clinically relevant aspects of fetal intracerebral hemorrhage, including germinal matrix-intraventricular hemorrhage, as well as intraparenchymal hemorrhage. We discuss current clinical practice for prenatal counseling and postnatal management of fetal intracerebral hemorrhage, and offer practical recommendations for clinicians. We propose standardized terminology for classification of fetal intracerebral hemorrhage to be used in future research. We also highlight gaps in the literature and priorities for future research, namely the need for prospective large-scale studies to better understand underlying etiologies and neurodevelopmental outcomes in fetal intracerebral hemorrhage. IMPACT STATEMENT: We discuss the diverse etiologies and outcomes of fetal intracerebral hemorrhage, and propose standardized terminology for classification. We outline current practice and offer practical recommendations for management and counseling of fetal intracerebral hemorrhage, recognizing the need for capacity-building in the newly emerging subspecialty of fetal neurology. We highlight gaps in the literature and research priorities in fetal intracerebral hemorrhage to promote collaborative research, and the development of interventions to improve pregnancy and child outcomes.

Evaluation of the cavum septum pellucidum is required in standard second-trimester screening fetal anatomy ultrasound scans. The absence of septum pellucidum triggers further evaluation and referral for subspecialty counseling. Absence of septum pellucidum is linked to other midline anomalies including septo-optic dysplasia. The purpose of this narrative review on absent septum pellucidum and septo-optic dysplasia is to discuss the literature, including pre- and postnatal management and neurodevelopmental outcome, provide practical recommendations, and outline research gaps to advance this nascent field.

Susceptibility weighted imaging (SWI) of neonatal hypoxic-ischemic brain injury can provide assistance in the prognosis of neonatal hypoxic-ischemic encephalopathy (HIE). We propose a convolutional neural network model to classify SWI images with HIE. Due to the lack of a large dataset, transfer learning method with fine-tuning a pre-trained ResNet 50 is introduced. We randomly select 11 datasets from patients with normal neurology outcomes (n = 31) and patients with abnormal neurology outcomes (n = 11) at 24 months of age to avoid bias in classification due to any imbalance in the data. We develop a rule-based system to improve the classification performance, with an accuracy of 0.93 ± 0.09. We also compute heatmaps produced by the Grad-CAM technique to analyze which areas of SWI images contributed more to the classification patients with abnormal neurology outcome. Such regions that are important in the classification accuracy can interpret the relationship between the brain regions affected by hypoxic-ischemic and neurodevelopmental outcomes of infants with HIE at the age of 2 years.

Holoprosencephaly (HPE) is one of the most common malformations in embryonic development. It represents a continuum spectrum that involves the midline cleavage of forebrain structures. Facial malformations of varying degrees of severity are also observed. It is probable that HPE results from a combination of genetic mutations and environmental influences during the initial weeks of pregnancy. Some patients with HPE experience early death, while others go on to experience neurodevelopmental impairment. Accurate fetal imaging can facilitate diagnosis and prenatal counseling, though more subtle brain abnormalities can be difficult to diagnose prenatally. Fetal counseling can be complex, given that the etiopathogenesis remains unclear and variable penetrance is prevalent in inherited genetic mutations. The aim of this narrative review is to examine the literature on HPE and to offer recommendations for pediatric neurologists for fetal counseling and postnatal care

OBJECTIVE:Severe early-onset fetal growth restriction (FGR) causes stillbirth, neonatal death and neurodevelopmental impairment. Poor maternal spiral artery remodelling maintains vasoactive responsiveness but is susceptible to treatment with sildenafil, a phosphodiesterase type 5 (PDE5) inhibitor, which may improve perinatal outcomes. DESIGN:Superiority, double-blind randomised controlled trial. SETTING:A total of 20 UK fetal medicine units. POPULATION:Pregnancies affected by FGR, defined as an abdominal circumference below the tenth centile with absent end-diastolic flow in the umbilical artery between 22+0 and 29+6 weeks of gestation. METHODS:Treatment with sildenafil (25 mg three times/day) or placebo until delivery or 32 weeks of gestation. MAIN OUTCOME MEASURES:All infants alive at hospital discharge were assessed for cardiovascular function and cognitive, speech/language and neuromotor impairment at 2 years of age. The primary outcome was survival without cerebral palsy or neurosensory impairment, or a Bayley-III composite score of >85. RESULTS:In total, 135 women were randomised between November 2014 and July 2016 (70 to sildenafil and 65 to placebo). We previously published that there was no improvement in time to delivery or perinatal outcomes with sildenafil. In all, 75 babies (55.5%) were discharged alive, with 61 infants eligible for follow-up (32 sildenafil and 29 placebo). One infant died (placebo), three mothers declined and ten mothers were uncontactable. There was no difference in neurodevelopment or blood pressure following treatment with sildenafil. Infants who received sildenafil had a larger head circumference at 2 years of age (median difference 49.2 cm, IQR 46.4-50.3, vs 47.2 cm, 95% CI 44.7-48.9 cm). CONCLUSIONS:Sildenafil therapy did not prolong pregnancy or improve perinatal outcomes and did not improve infant neurodevelopment in FGR survivors. Therefore, sildenafil should not be prescribed for this condition.

Fetal cerebral ventriculomegaly is one of the most common fetal neurological disorders identified prenatally by neuroimaging. The challenges in the evolving landscape of conditions like fetal cerebral ventriculomegaly involve accurate diagnosis and how best to provide prenatal counseling regarding prognosis as well as postnatal management and care of the infant. The purpose of this narrative review is to discuss the literature on fetal ventriculomegaly, including postnatal management and neurodevelopmental outcome, and to provide practice recommendations for pediatric neurologists.

OBJECTIVE:To identify current practices in the management of selective fetal growth restriction (sFGR) in monochorionic diamniotic (MCDA) twin pregnancies. DESIGN:Cross-sectional survey. SETTING:International. POPULATION:Clinicians involved in the management of MCDA twin pregnancies with sFGR. METHODS:A structured, self-administered survey. MAIN OUTCOME MEASURES:Clinical practices and attitudes to diagnostic criteria and management strategies. RESULTS:Overall, 62.8% (113/180) of clinicians completed the survey; of which, 66.4% (75/113) of the respondents reported that they would use an estimated fetal weight (EFW) of <10th centile for the smaller twin and an inter-twin EFW discordance of >25% for the diagnosis of sFGR. For early-onset type I sFGR, 79.8% (75/94) of respondents expressed that expectant management would be their routine practice. On the other hand, for early-onset type II and type III sFGR, 19.3% (17/88) and 35.7% (30/84) of respondents would manage these pregnancies expectantly, whereas 71.6% (63/88) and 57.1% (48/84) would refer these pregnancies to a fetal intervention centre or would offer fetal intervention for type II and type III cases, respectively. Moreover, 39.0% (16/41) of the respondents would consider fetoscopic laser surgery (FLS) for early-onset type I sFGR, whereas 41.5% (17/41) would offer either FLS or selective feticide, and 12.2% (5/41) would exclusively offer selective feticide. For early-onset type II and type III sFGR cases, 25.9% (21/81) and 31.4% (22/70) would exclusively offer FLS, respectively, whereas 33.3% (27/81) and 32.9% (23/70) would exclusively offer selective feticide. CONCLUSIONS:There is significant variation in clinician practices and attitudes towards the management of early-onset sFGR in MCDA twin pregnancies, especially for type II and type III cases, highlighting the need for high-level evidence to guide management.

This editorial is linked to Letter to the editor by Gogou on pages 1106–1107 of this issue.