Outcome at early school age and adolescence after hypothermia-treated hypoxic-ischaemic encephalopathy: an observational, population-based study.

OBJECTIVE: We aimed to describe long-term outcomes following hypoxic-ischaemic encephalopathy (HIE) treated with therapeutic hypothermia (TH). DESIGN: Prospective, population-based observational study. SETTING: Tertiary level neonatal intensive care units and neonatal outpatient clinic, Karolinska University Hospital, Stockholm, Sweden. PATIENTS: Sixty-six infants treated with TH due to HIE between 2007 and 2009. INTERVENTIONS: At 6-8 years and 10-12 years of age, children were assessed using a standardised neurological examination, the Movement Assessment Battery for Children, Second Edition (MABC-2) and the Wechsler Intelligence Scales for Children IV/V. Parents completed the Five-to-Fifteen (FTF) questionnaire. MAIN OUTCOME MEASURES: Adverse outcome among survivors was defined as cerebral palsy (CP), epilepsy, hearing or visual impairment, full-scale IQ (FSIQ) below 85, attention deficit disorder with/without hyperactivity, autism spectrum disorder or developmental coordination disorder. RESULTS: Mortality was 12%. Seventeen per cent of survivors developed CP. Mean FSIQ was normal in children without major neuromotor impairment. Assessment in early adolescence revealed emerging deficits in 26% of children with a previously favourable outcome. The proportion of children exhibiting executive difficulties increased from 7% to 19%. This was reflected also by a significantly increased proportion of children with an FTF score >90th percentile compared with norms in early adolescence. The proportion of children with an MABC-2 score ≤5th percentile was also significantly increased compared with norms. CONCLUSIONS: Survivors without major neuromotor impairment have normal intelligence. The incidence of executive difficulties appears to be increased in this patient population. More subtle difficulties may go undetected at early school-age.

Kidney outcomes in early adolescence following perinatal asphyxia and hypothermia-treated hypoxic-ischaemic encephalopathy.

BACKGROUND: Acute kidney injury (AKI) remains common among infants with hypothermia-treated hypoxic-ischaemic encephalopathy (HIE). Little is known about long-term kidney outcomes following hypothermia treatment. We recently reported that 21% of survivors of hypothermia-treated HIE had decreased estimated glomerular filtration rate (eGFR) based on plasma creatinine in early adolescence. Here, we assessed kidney functions more comprehensively in our population-based cohort of children born in Stockholm 2007-2009 with a history of hypothermia-treated HIE. METHODS: At 10-12 years of age, we measured cystatin C (cyst C) to estimate GFR. Children with decreased cyst C eGFR also underwent iohexol clearance examination. We measured urine-albumin/creatinine ratio, blood pressure (BP) and kidney volume on magnetic resonance imaging. Fibroblast growth factor 23 (FGF 23) levels in plasma were assessed by enzyme-linked immunosorbent assay (ELISA). Outcomes were compared between children with and without a history of neonatal AKI. RESULTS: Forty-seven children participated in the assessment. Two children (2/42) had decreased cyst C eGFR, for one of whom iohexol clearance confirmed mildly decreased GFR. One child (1/43) had Kidney Disease Improving Global Outcomes (KDIGO) category A2 albuminuria, and three (3/45) had elevated office BP. Subsequent ambulatory 24-h BP measurement confirmed high normal BP in one case only. No child had hypertension. Kidney volume and FGF 23 levels were normal in all children. There was no difference in any of the parameters between children with and without a history of neonatal AKI. CONCLUSION: Renal sequelae were rare in early adolescence following hypothermia-treated HIE regardless of presence or absence of neonatal AKI. A higher resolution version of the Graphical abstract is available as Supplementary information.

Acute kidney injury in infants with hypothermia-treated hypoxic-ischaemic encephalopathy: An observational population-based study.

AIM: To describe incidence and outcome of acute kidney injury (AKI) in infants with hypothermia-treated hypoxic-ischaemic encephalopathy (HIE). METHODS: This observational population-based study included all term and near-term infants with hypothermia-treated HIE born between 2007 and 2009 in greater Stockholm. The KDIGO definition modified for neonatal patients was used to identify infants with AKI. We analysed association between AKI and neonatal morbidity/mortality. Furthermore, we calculated estimated glomerular filtration rate (eGFR) at the age of 10-12 years. RESULTS: Out of 83,939 live births in the Stockholm region, 66 infants underwent hypothermia treatment due to HIE. Out of 65 included infants, 45% suffered AKI. Degree of AKI correlated with HIE severity. One infant needed kidney replacement therapy; others were treated conservatively. AKI was associated with increased mortality and need for blood products (p < 0.05). eGFR at age 10-12 years was available for 72% of survivors. Nine children (21%) had subnormal eGFR, with no difference between those with and without a history of neonatal AKI. CONCLUSION: Despite therapeutic hypothermia, AKI remains a common complication in infants with HIE and is associated with increased neonatal mortality. Twenty-one per cent of children had subnormal eGFR at 10-12 years, highlighting the need for long-term follow-up of renal function.