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Therapeutic hypothermia is recommended for moderate and severe neonatal encephalopathy, but is being applied to a wider range of neonates than originally envisaged. To examine the clinical use of therapeutic hypothermia, data collected during the first 3 years (2012–2014) of the Baby Cooling Registry of Japan were analysed. Of 485 cooled neonates, 96.5% were ≥36 weeks gestation and 99.4% weighed ≥1,800 g. Severe acidosis (pH < 7 or base deficit ≥16 mmol/L) was present in 68.9%, and 96.7% required resuscitation for >10 min. Stage II/III encephalopathy was evident in 88.3%; hypotonia, seizures and abnormal amplitude-integrated electroencephalogram were observed in the majority of the remainder. In-hospital mortality was 2.7%; 90.7% were discharged home. Apgar scores and severity of acidosis/encephalopathy did not change over time. The time to reach the target temperature was shorter in 2014 than in 2012. The proportion undergoing whole-body cooling rose from 45.4% to 81.6%, while selective head cooling fell over time. Mortality, duration of mechanical ventilation and requirement for tube feeding at discharge remained unchanged. Adherence to standard cooling protocols was high throughout, with a consistent trend towards cooling being achieved more promptly. The mortality rate of cooled neonates was considerably lower than that reported in previous studies.

BackgroundVariants in the type IV collagen gene (COL4A1/2) cause early-onset cerebrovascular diseases. Most individuals are diagnosed postnatally, and the prenatal features of individuals with COL4A1/2 variants remain unclear.MethodsWe examined COL4A1/2 in 218 individuals with suspected COL4A1/2-related brain defects. Among those arising from COL4A1/2 variants, we focused on individuals showing prenatal abnormal ultrasound findings and validated their prenatal and postnatal clinical features in detail.ResultsPathogenic COL4A1/2 variants were detected in 56 individuals (n=56/218, 25.7%) showing porencephaly (n=29), schizencephaly (n=12) and others (n=15). Thirty-four variants occurred de novo (n=34/56, 60.7%). Foetal information was available in 47 of 56 individuals, 32 of whom (n=32/47, 68.1%) had one or more foetal abnormalities. The median gestational age at the detection of initial prenatal abnormal features was 31 weeks of gestation. Only 14 individuals had specific prenatal findings that were strongly suggestive of features associated with COL4A1/2 variants. Foetal ventriculomegaly was the most common initial feature (n=20/32, 62.5%). Posterior fossa abnormalities, including Dandy-Walker malformation, were observed prenatally in four individuals. Regarding extrabrain features, foetal growth restriction was present in 16 individuals, including eight individuals with comorbid ventriculomegaly.ConclusionsPrenatal observation of ventriculomegaly with comorbid foetal growth restriction should prompt a thorough ultrasound examination and COL4A1/2 gene testing should be considered when pathogenic variants are strongly suspected.