Predictive Models of Neurodevelopmental Outcomes After Neonatal Hypoxic-Ischemic Encephalopathy

Abstract

OBJECTIVES: To develop predictive models for death or neurodevelopmental impairment (NDI) after neonatal hypoxic-ischemic encephalopathy (HIE) from data readily available at the time of NICU admission (“early”) or discharge (“cumulative”). METHODS: In this retrospective cohort analysis, we used data from the Children’s Hospitals Neonatal Consortium Database (2010–2016). Infants born at ≥35 weeks’ gestation and treated with therapeutic hypothermia for HIE at 11 participating sites were included; infants without Bayley Scales of Infant Development scores documented after 11 months of age were excluded. The primary outcome was death or NDI. Multivariable models were generated with 80% of the cohort; validation was performed in the remaining 20%. RESULTS: The primary outcome occurred in 242 of 486 infants; 180 died and 62 infants surviving to follow-up had NDI. HIE severity, epinephrine administration in the delivery room, and respiratory support and fraction of inspired oxygen of 0.21 at admission were significant in the early model. Severity of EEG findings was combined with HIE severity for the cumulative model, and additional significant variables included the use of steroids for blood pressure management and significant brain injury on MRI. Discovery models revealed areas under the curve of 0.852 for the early model and of 0.861 for the cumulative model, and both models performed well in the validation cohort (goodness-of-fit χ2: P = .24 and .06, respectively). CONCLUSIONS: Establishing reliable predictive models will enable clinicians to more accurately evaluate HIE severity and may allow for more targeted early therapies for those at highest risk of death or NDI.

Associations between fetal heart rate variability and umbilical cord occlusions‐induced neural injury: An experimental study in a fetal sheep model

“…The best way to define the relevant outcomes of intrapartum monitoring studies is an issue that has often been discussed in the literature and during expert panels 43 . There is a lack of clarity or consensus regarding the goals of intrapartum monitoring, especially regarding the role of intrapartum acidemia in the etiology of fetal neural injury 6,7,16 . Neurological outcome, as proposed in the INFANT trial, should be the gold standard 5…”

“…43 There is a lack of clarity or consensus regarding the goals of intrapartum monitoring, especially regarding the role of intrapartum acidemia in the etiology of fetal neural injury. 6,7,16 Neurological outcome, as proposed in the INFANT trial, should be the gold standard. 5 The only correlations found were between brainstem lesions and HRV.…”

“…Similarly, Ruth et al showed that fetal acid‐base status did not correlate with the risk of HIE and poor perinatal brain damage prediction by umbilical cord arterial pH 6 . More recent studies have confirmed that pH is a poor predictor of the long‐term outcome after perinatal asphyxia 6–8 …”

“…6 More recent studies have confirmed that pH is a poor predictor of the long-term outcome after perinatal asphyxia. [6][7][8] The intrapartum assessment of fetal hypoxic ischemia remains an important challenge in perinatal medicine, in which the aim is to screen for at-risk neonates and to prevent HIE during labor. One current approach is the analysis of the autonomic nervous system activity, which plays a major role in fetal homeostasis and which influences the FHR.…”

Research advances in the role of endogenous neurogenesis on neonatal hypoxic-ischemic brain damage

“…Neonatal hypoxic-ischemic brain damage (HIBD), which is caused by perinatal asphyxia, is a primary etiology for acute neonatal mortality and long-term infant neurological dysfunction (1)(2)(3). The incidence of neonatal HIBD is 1-3 per 1,000 in developed countries, while in developing countries the rate can be as high as 25 per 1,000 (4,5). HIBD can lead to irreversible neurological injuries including cerebral palsy, audiovisual impairment, memory difficulties, and cognitive dysfunction (6,7).…”