Low 5‐min Apgar score in moderately preterm infants; association with subsequent death and cerebral palsy: a register based Danish national study

Perinatal hypoxic ischemic encephalopathy (HIE) occurs in 1–6 ⁄ 1000 newborns and is associated with a high risk of death or subsequent neurodevelopmental disabilities (1,2). A recent meta-analysis including datasets on 1320 born at term infants suffering from HIE confirms that treating mature infants with moderate hypothermia therapy is associated with a reduction in death and neurological impairment at 18 months (3). The entry criteria for therapy were based on evidence of birth asphyxia combined with signs of moderate or severe encephalopathy. Therapeutic hypothermia is feasible in clinical practice and has a good safety record with only few and benign side effects (4). Currently, there is no other brain protective treatments available for infants suffering from HIE, and moderate hypothermia therapy have recently been implemented in many neonatal departments. Animal studies support that preterm infants with a perinatal hypoxic ischemic brain injury may also benefit from moderate hypothermia therapy, (5) but as human clinical trials have only included infants with a gestational age ‡36 weeks there are no human data to support this. The Apgar scoring system is used for rapid assessment of newborns and the score is included as an entry criterion for hypothermia therapy, as a marker of perinatal asphyxia in the newborn. The value of the Apgar score in predicting outcome has been questioned (6,7) although there is a strong association between a low Apgar score and death or later neurological impairments (8,9). In a Norwegian population based study including 235,000 mature newborns, infants with 5-min Apgar scores of 0–3 had a 386-fold increased risk of neonatal death and an 81-fold increased risk of cerebral palsy compared with infants who had 5-min Apgar scores of 7–10 (10). Similarly, a Swedish population based study of 1,028,705 term newborns found an increase in the risk of cerebral palsy with decreasing 5-min Apgar score (11). However, the association between Apgar score and outcome in moderately preterm infants (gestational age 32– 35 weeks) has not been well investigated. The present study is a register-based study from Denmark including all infants born in the period 1982–2002. We used the 5-min Apgar score as a marker of perinatal asphyxia and investigated (i) the incidence of a low 5-min Apgar score (Apgar score £5) in moderately preterm infants and (ii) the association between a low 5-min Apgar score and subsequent death or cerebral palsy in these infants. Using the Danish Central Person Registry (CPR) to gain information on the CPR numbers of all live born infants in the period 1982–2002, data were then extracted from registries held by Statistics Denmark. From the national birth registry, data on birth weight, gestational age, gender and Apgar score were obtained. Birth weight and gestational age were evaluated by calculating a birth weight Z-score using the normal foetal growth data of Marsál (12). We tried to eliminate misclassifications by excluding (i) infants with a birth weight three standard deviations or more from the mean, and (ii) infants with a 5-min Apgar score of 0 or 1 who were not admitted to the neonatal department within the first day of life. Infants without a registered Apgar score were also excluded. Mortality (death before year 2009) was investigated through the Cause-of-Death Registry held by the National Board of Health. Diagnoses of neurological disease were extracted from the National Patients Registry. Diagnoses were coded according to the ICD-10 (since 1993) and the ICD-8 (before 1993) classification, and for the purpose of this study we determined the prevalence of cerebral palsy (CP) using ICD-8: 34.30–34.50 and ICD-10: G80–G82. Logistic Regression was used to estimate associations between a low 5-min Apgar score and subsequent death or Acta Pædiatrica ISSN 0803–5253