Clinical practice guideline for the diagnosis and treatment of neonatal arterial ischemic stroke (2026)

Neonatal arterial ischemic stroke (NAIS) refers to pathological brain tissue damage caused by focal cerebral arterial infarction within the first 28 days after birth.^[1] NAIS accounts for approximately 80% of perinatal strokes.^[2] The reported incidence of NAIS is 18.51/100,000 live births^[3] and 32/100,000 in preterm infants.^[4] The early symptoms of NAIS are atypical, making it prone to misdiagnosis or missed diagnosis.^[5] NAIS is a significant cause of childhood hemiplegia, cerebral palsy, and cognitive dysfunction. In 2017, China issued the Experts’ consensus on the diagnosis and treatment of neonatal arterial ischemic stroke (in Chinese), which provided preliminary clinical diagnoses and treatment suggestions.^[6] However, limited by insufficient evidence at the time of the consensus, many disagreements remain regarding the risk factors, diagnosis, treatment, and prognosis of this disease. These guidelines, formulated based on the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology and currently available evidence, provides a comprehensive clinical diagnosis and treatment plan for NAIS.

The quality and strength of evidence were graded according to the GRADE methodology.^[7,8] For questions lacking direct evidence or relying solely on expert opinions sourced from clinical guidelines, recommendations were formulated using the Delphi technique, with the evidence strength categorized as a Good Practice Statement. The target users of this guideline include neonatologists (covering both neonatology and neonatal surgery), radiologists, rehabilitation physicians, and nursing staff, and the target population comprises neonates. The full text of these guidelines is provided in the Supplementary full text, http://links.lww.com/CM9/C973. List of members in drafting and steering committee, and working, secretary and external review group is shown in Supplement File 1, http://links.lww.com/CM9/C973.

Recommendations

Clinical question 1: What perinatal risk factors are associated with NAIS?

Recommendation 1: Primary maternal and intrapartum risk factors for NAIS include chorioamnionitis, emergency cesarean delivery, prolonged second stage of labor, antenatal fever, multiple gestations, preeclampsia/gestational hypertension, assisted vaginal delivery, maternal smoking, and a family history of thromboembolic events. (Level C evidence)

Recommendation 2: Neonatal risk factors include abnormal fetal heart rate, fetal growth restriction, oligohydramnios, meconium-stained amniotic fluid, neonatal asphyxia, need for resuscitation in the delivery room, birth trauma, prematurity, male sex, meningitis, neonatal sepsis, hypoglycemia, congenital heart disease, etc. (Level C evidence)

Clinical question 2: What clinical manifestation can occur in NAIS?

Recommendation 3: Early clinical manifestations of NAIS are atypical and may appear with seizures, respiratory distress, apnea, feeding difficulties, muscle tone abnormalities, and diminished or asymmetric Moro or grasp reflexes, etc. (Level C evidence)

Clinical question 3: What auxiliary examinations are required for neonates with NAIS?

Recommendation 4: Cranial magnetic resonance imaging (MRI) is the preferred auxiliary examination for diagnosing NAIS. (Good Practice Statement)

Recommendation 5: For NAIS occurring within 1 week of stroke onset, diffusion-weighted imaging (DWI) is the first-line choice (Level C evidence, strong recommendation); for NAIS with a stroke onset of 1 week or longer, T1- and T2-weighted imaging are recommended (Level D evidence, strong recommendation); performing diffusion tensor imaging (DTI) at 3 months of age can help predict long-term prognosis. (Level C evidence, weak recommendation)

Recommendation 6: Magnetic resonance angiography (MRA) is recommended to identify occluded vessels in NAIS and predict prognosis (Level C evidence, strong recommendation); three-dimensional time-of-flight magnetic resonance angiography (3D-TOF-MRA) may be used for a more accurate assessment of affected vessels. (Level C evidence, weak recommendation)

Recommendation 7: Cranial ultrasound can be used for initial assessment and dynamic bedside monitoring in neonates with high-risk factors or critically ill neonates with clinical suspicion of NAIS, and for serial monitoring of NAIS progression. (Level C evidence, weak recommendation)

Recommendation 8: Routine brain computed tomography (CT) scanning is not recommended and should only be performed in critically ill neonates when MRI is unavailable or to differentiate intracranial hemorrhage. (Good Practice Statement)

Recommendation 9: Video amplitude-integrated electroencephalography (aEEG) or continuous video EEG monitoring is recommended to assess cerebral electrical activity. (Level C evidence, strong recommendation)

Recommendation 10: Routine cardiac ultrasonography (echocardiography) is recommended for neonates with NAIS to rule out congenital heart disease. (Level C evidence, weak recommendation)

Recommendation 11: Screening for prothrombotic risk factors is recommended for neonates with NAIS who present with multiple thromboses or have a family history of thromboembolic events. (Level C evidence, weak recommendation)

Clinical question 4: What are the acute-phase therapeutic interventions for NAIS?

Recommendation 12: Neonates with suspected NAIS should be promptly transferred to a neonatal intensive care unit (NICU) with adequate diagnostic and therapeutic capabilities. (Good Practice Statement)

Recommendation 13: Acute-phase management should prioritize symptomatic and supportive care, including the optimization of cerebral perfusion, maintenance of internal homeostasis, and preservation of normal oxygen saturation. (Good Practice Statement)

Recommendation 14: Routine anticoagulation therapy is not recommended for the first-episode of NAIS (Level C evidence, weak recommendation). Anticoagulation therapy with unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH) should be considered only if systemic or cardioembolic thrombosis is confirmed. (Good Practice Statement)

Recommendation 15: Routine thrombolytic therapy is not recommended for NAIS. (Level C evidence, weak recommendation)

Recommendation 16: Phenobarbital is recommended as the first-line antiepileptic therapy for NAIS with seizures. If phenobarbital is ineffective, levetiracetam or midazolam may be added as adjunctive therapy. (Good Practice Statement)

Clinical question 5: What are the long-term adverse outcomes of NAIS?

Recommendation 17: Long-term sequelae of NAIS may include cerebral palsy as well as cognitive, language, visual, and auditory impairments, with cerebral palsy being the most common. (Level C evidence)

Clinical question 6: How should cerebral palsy be evaluated following NAIS?

Recommendation 18: For neonates with NAIS, clinical neurological assessment, neuroimaging, and motor testing should be conducted as early as possible, preferably within five months of corrected age, to evaluate the risk of developing cerebral palsy. (Level B evidence, strong recommendation)

Recommendation 19: A comprehensive evaluation of functional impairments should be performed in children with NAIS-related cerebral palsy to develop individualized rehabilitation interventions. (Good Practice Statement)

Clinical question 7: How should rehabilitation be conducted in children with cerebral palsy following NAIS?

Recommendation 20: For children with cerebral palsy, rehabilitation interventions, including goal-directed training (GDT) (Level C evidence, weak recommendation), goal-activity-motor enrichment (GAME) therapy (Level B evidence, strong recommendation), and core stability training (CST) (Level B evidence, strong recommendation), may be selected based on the child’s age and Gross Motor Function Classification System (GMFCS) level to improve motor and cognitive functions.

Recommendation 21: For children with hemiplegia, rehabilitation therapies such as Hand–Arm Bimanual Intensive Therapy (HABIT) including the lower extremities (HABIT-ILE), constraint-induced movement therapy (CIMT), modified CIMT (mCIMT), action observation training, and mirror therapy may be used to improve limb function. (Level B evidence, strong recommendation)

Recommendation 22: The combined use of assistive devices or pharmacological interventions may be considered. For ambulatory children with cerebral palsy and equinus gait, ankle–foot orthoses may be used to improve step length and ankle dorsiflexion angle (Level B evidence, weak recommendation). For children with cerebral palsy and focal symptomatic muscle spasticity, botulinum toxin type A injections may be used to improve gait and limb function. (Level B evidence, weak recommendation)

Recommendation 23: For children with cerebral palsy aged >2 years, repetitive transcranial magnetic stimulation (rTMS) may be considered to improve motor function. (Level B evidence, weak recommendation)

Clinical question 8: What preventive measures are available for NAIS?

Recommendation 24: Early intervention for neonatal hypoglycemia is recommended. (Level C evidence, strong recommendation)

Recommendation 25: Folate and B vitamins may be supplemented in neonates with methylenetetrahydrofolate reductase (MTHFR) gene mutations to prevent NAIS. (Level D evidence, weak recommendation)

Recommendation 26: Routine anticoagulation therapy is not recommended for preventing recurrent stroke after NAIS. (Level C evidence, weak recommendation)

Recommendation 27: For NAIS concurrent with congenital heart disease (CHD), aspirin or LMWH should be used to prevent recurrent stroke. (Level D evidence, weak recommendation)

All recommendation notes corresponding to the recommendations can be found in the Supplementary full text, http://links.lww.com/CM9/C973.

The NAIS diagnosis and treatment flowchart was shown in Supplementary Figure 1, http://links.lww.com/CM9/C973.

Funding

This guideline was supported by grants from the National Key R&D Program of China (No. 2024YFC2707700), the National Natural Science Foundation of China (Nos. 82171710, 82530056, and 82271749), the Sichuan Provincial Natural Science Foundation (No. 2025ZNSFSC0693), the Fundamental Research Funds for the Central University (No. SCU2025D005), and the Key R&D Program of Zhejiang Provincial Department of Science and Technology (No. 2025C02081).

Conflicts of interest

None.

Supplementary Material

cm9-139-2687-s001.docx ^{(1.6MB, docx)}