Mads Langager Larsen

Introduction: Magnesium sulfate (MgSO ₄ ) administered before very preterm birth reduces the risk of cerebral palsy in surviving infants and is recommended in international guidelines. In April 2020, a national guideline for MgSO ₄ for fetal neuroprotection was introduced in Denmark. We evaluated clinical uptake and adherence following guideline implementation. Material and Methods: This retrospective medical chart review study included women who delivered at gestational age 24 + 0 to 31 + 6 weeks of gestation at nine different Danish hospitals between April 2020 and December 2023. These departments handled around 50% of all deliveries in Denmark in this period. Data were obtained from electronic medical records. The primary outcome was administration of MgSO ₄ for fetal neuroprotection among eligible women. Secondary outcomes included temporal trends in uptake, differences by gestational age and hospital size, and documented reasons for non‐administration. Descriptive statistics were used to summarize uptake rates and patient characteristics, and comparisons were performed using appropriate statistical tests. Results: A total of 583 eligible women were included. Overall, 481 women (83%) received MgSO ₄ for fetal neuroprotection; of these, 340 women (71%) received MgSO ₄ within 24 h of birth. Uptake was highest among women delivering before 28 weeks of gestation, where MgSO ₄ was administered in nearly all eligible cases. Among women delivering between 28 + 0 and 31 + 6 weeks, approximately one in five did not receive treatment. Uptake did not increase over the study period, suggesting early adoption followed by stable implementation. Large‐volume hospitals demonstrated higher treatment rates compared with smaller hospitals. The most frequent reasons for non‐administration were lack of guideline awareness/oversight at later gestational ages and rapid delivery or maternal/fetal instability at earlier gestations. Conclusions: Following the implementation of the national guideline, uptake of MgSO ₄ for fetal neuroprotection in Denmark was high but incomplete. Persistent gaps in treatment, particularly among women delivering after 28 weeks of gestation, indicate a need for targeted implementation strategies to improve adherence and ensure equitable neuroprotective care.

Background: Smallness for gestational age and reduced head circumference at birth are consistently associated with later neurodevelopmental disorders (NDD), but it is unclear whether similar associations are present at foetal biometry in mid‐gestation. Objectives: To investigate associations between second‐trimester foetal biometric measurements and later NDD. Methods: We conducted a population‐based cohort study using data from routine second‐trimester ultrasound scans (gestational weeks 18–21) in Denmark. We included all singleton euploid live births from 2008 to 2015. Foetal biometrics included head circumference, biparietal diameter (BPD), abdominal circumference (AC), femur length, estimated foetal weight (EFW), and the head‐abdomen ratio. NDD comprised cerebral palsy (CP), epilepsy, intellectual disability, and autism spectrum disorders (ASD). Children were followed from birth until diagnosis, death, emigration, or 31 December 2022. Associations were examined using multivariable Cox proportional hazards models, and cumulative incidence through age 10 years was estimated accounting for death as a competing risk. Adjusted mean differences in biometric Z ‐scores were examined using multivariable linear regression. Results: Among 337,028 children, 13,414 (4.0%; 69.7% males) were diagnosed with at least one NDD. Larger BPD was associated with higher hazards of epilepsy, intellectual disability, and ASD. Larger AC and EFW were associated with lower hazard of intellectual disabilities. Individuals with epilepsy, ASD, and intellectual disabilities had slightly larger mean BPD Z ‐score at their second–trimester scans, compared to children without NDD. Furthermore, smaller HC was associated with lower hazards and cumulative incidence of epilepsy, whereas shorter FL was associated with higher hazards of CP and epilepsy. Conclusions: Mid‐gestation head size did not follow the expected risk pattern. These findings propose a rethinking of the relationship between restricted brain growth and neurodevelopmental impairment, suggesting that atypical early brain development may be reflected in accelerated rather than reduced growth, or that restricted growth‐related causes of NDD act later in pregnancy.

Aim: To give a comprehensive overview of genetic findings in children with cerebral palsy, including a description of subtype, comorbidities and neuroimaging, providing insight into the clinical utility of genetics. Method: A systematic review of previous literature using Embase and Medline as databases. All studies were published between 2000 and 2022, each including at least 10 individuals with cerebral palsy. Results: A total of 19 studies were included, comprising a total of 3707 individuals with cerebral palsy. The overall diagnostic yield was 22.2%, with the highest yield (up to 55%) in cryptogenic cerebral palsy. Variants in a total of 377 unique genes were identified, most frequently CTNNB1 , SPAST and ATL1 . In addition, 59 different CNVs were identified, of which 32 were in known (micro)duplication/−deletion syndromes such as 22q11.2 microdeletion/−duplication and 14q12 microdeletion. Spastic and dyskinetic cerebral palsy were the most common phenotypes among genetically diagnosed cases. Findings also included variants in genes linked to epilepsy, specific neuroimaging patterns and potentially treatable conditions. Conclusion: These results highlight the importance of genetic evaluation for diagnostic clarification, targeted treatment, monitoring of comorbidities and genetic counseling. We recommend offering genetic testing to individuals with cryptogenic cerebral palsy to optimize management and prevention.

Aim: To estimate the cumulative risk of epilepsy after neonatal seizures and identify subpopulations at increased risk.Method: This was a nationwide register‐based cohort study including all children born in Denmark between 1997 and 2018. The cumulative risk of epilepsy in children with and without neonatal seizures was compared. Furthermore, neonatal seizures were stratified according to aetiology.Results: We followed 1 294 377 children and identified 1998 neonatal survivors with neonatal seizures. The cumulative risk of epilepsy was 20.4% (95% confidence interval [CI] = 18.5–22.3) among children with neonatal seizures, compared to 1.15% (95% CI = 1.12–1.18) among children without. Epilepsy was diagnosed before 1 year of age in 11.4% of children with neonatal seizures, in an additional 4.5% between 1 year and 5 years, 3.1% between 5 years and 10 years, and 1.4% between 10 years and 22 years. The aetiologies of neonatal cerebral infarction, haemorrhage, or malformations (adjusted hazard ratio = 2.49, 95% CI = 1.98–3.14) and low Apgar score (1.49, 95% CI = 1.12–1.98) were associated with the highest risk of epilepsy, compared to children with seizures of unknown aetiology.Interpretation: Epilepsy after neonatal seizures is common and remains a substantial risk throughout childhood. Aetiological risk factors are identifiable and relevant when planning appropriate information for parents and follow‐up.

This commentary is on the original article by Suzuki et al. on pages 475–485 of this issue.