Human milk, breastfeeding, and early neurodevelopmental outcomes for infants with critical CHD.

Human milk improves neurodevelopment for preterm infants, but relationships between human milk and neurodevelopment for infants with critical CHD are unknown. We aimed to (1) explore associations between human milk/direct breastfeeding and neurodevelopment at 1-year and 2-year follow-up and (2) describe patterns of human milk (maternal, donor) and commercial formula during hospitalisation in the first year of life.This retrospective cohort study included infants who underwent surgery for CHD < 6 months old. The primary outcome was neurodevelopment via Bayley Scales of Infant Development-IV. Analysis included adjusted linear regression for associations between exclusive human milk while inpatient during the first 6 months or any direct breastfeeding while inpatient during the first year of life and 1-year Bayley-IV scores. Models were adjusted for race, insurance type, genetic diagnosis, and length of stay.Of 98 eligible infants, 40% followed up at 1 year; 27% at 2 years. There were differences in follow-up related to demographics (race, ethnicity) and social determinants of health (insurance type, distance from clinic). In adjusted models, infants who directly breastfed had 13.18 points higher cognition (95% CI: 0.84-25.53, p = 0.037); 14.04 points higher language (2.55-25.53, p = 0.018); and 15.80 points higher motor scores (3.27-28.34, p = 0.015) at 1-year follow-up. Infants fed exclusive human milk had 12.64 points higher cognition scores (-0.53-25.82, p = 0.059).Future investigation into nutrition and neurodevelopment in the context of critical CHD is warranted. As neurodevelopmental follow-up becomes standard of care in this population, efforts are needed to mitigate disparities in access to this care.

Reduced Hippocampal Volumes in Children with History of Hypoxic Ischemic Encephalopathy after Therapeutic Hypothermia.

Hypoxic ischemic encephalopathy (HIE) remains a significant cause of disability despite treatment with therapeutic hypothermia (TH). Many survive with more subtle deficits that affect daily functioning and school performance. We have previously shown an early indication of hippocampal changes in infants with HIE despite TH. The aim of this study was to evaluate the hippocampal volume via MRI and memory function at 5 years of age. A cohort of children followed from birth returned for a 5-year follow-up (n = 10 HIE treated with TH, n = 8 healthy controls). The children underwent brain MRI and neurodevelopmental testing to assess their brain volume, general development, and memory function. Children with HIE had smaller hippocampal volumes than the controls despite no differences in the total brain volume (p = 0.02). Children with HIE generally scored within the average range on developmental testing. Though there was no difference in the memory scores between these groups, there was a positive within-group correlation between the hippocampal volume and memory scores in children with HIE (sentence recall r = 0.66, p = 0.038). There was no relationship between newborn memory function and 5-year hippocampal size. Children with HIE treated with TH experienced significant and lasting changes to the hippocampus despite improvements in survival and severe disability. Future studies should target diminishing injury to the hippocampus to improve overall outcomes.

Preserved speed of processing and memory in infants with a history of moderate neonatal encephalopathy treated with therapeutic hypothermia.

OBJECTIVE: Survivors of neonatal encephalopathy (NE) are at risk for impaired cognition. The objective of this study was to assess speed of processing (SOP) and memory in infants with moderate NE. STUDY DESIGN: Sample consisted of 17 infants with NE and 23 healthy controls. Visual-evoked potentials (VEP) were assessed at 8 months to assess SOP. Memory was assessed at 12 months using elicited imitation (EI). Memory and SOP had previously been assessed in this cohort in the newborn period. RESULTS: Infants with NE had similar SOP and EI performance as controls. Newborn SOP correlated with 8-month SOP in infants with NE, however, neonatal ERP memory measures were not correlated with EI performance at 12 months. CONCLUSIONS: Infants with moderate NE treated with TH show preserved memory and SOP through 12 months. Early behavioral and electrophysiologic assessments of memory and SOP provide insight into developing cognitive functions in this risk group.

Early body composition changes are associated with neurodevelopmental and metabolic outcomes at 4 years of age in very preterm infants.

BACKGROUND: Very preterm (VPT) infants are at-risk for altered growth, slower speed of processing (SOP), and hypertension. This study assesses the relationship between postnatal body composition (BC), neurodevelopment (indexed by SOP), and blood pressure (BP) in VPT infants. METHODS: Thirty-four VPT infants underwent weekly measurements and BC testing until discharge and post-discharge at 4 mos CGA and 4 yrs. At post-discharge visits, SOP was assessed using visual evoked potentials and the NIH Toolbox; BP was also measured. RESULTS: In-hospital rate of weight, length and fat-free mass (FFM) gains were associated with faster SOP at 4 yrs. Higher rate of gains in weight and FFM from discharge to 4 mos CGA were associated with faster SOP at 4 mos CGA, while higher fat mass (FM) gains during the same time were positively associated with BP at 4 yrs. BC at 4 yrs nor gains beyond 4 mos CGA were associated with outcomes. CONCLUSIONS: In VPT infants, early FFM gains are associated with faster SOP, whereas post-discharge FM gains are associated with higher BPs at 4 yrs. This shows birth to 4 mos CGA is a sensitive period for growth and its relation to neurodevelopmental and metabolic outcomes. Close monitoring and early nutritional adjustments to optimize quality of gains may improve outcomes.

ERP evidence of preserved early memory function in term infants with neonatal encephalopathy following therapeutic hypothermia.

BACKGROUND: Neonatal encephalopathy (NE) carries high risk for neurodevelopmental impairments. Therapeutic hypothermia (TH) reduces this risk, particularly for moderate encephalopathy (ME). Nevertheless, these infants often have subtle functional deficits, including abnormal memory function. Detection of deficits at the earliest possible time-point would allow for intervention during a period of maximal brain plasticity. METHODS: Recognition memory function in 22 infants with NE treated with TH was compared to 23 healthy controls using event-related potentials (ERPs) at 2 wk of age. ERPs were recorded to mother's voice alternating with a stranger's voice to assess attentional responses (P2), novelty detection (slow wave), and discrimination between familiar and novel (difference wave). Development was tested at 12 mo using the Bayley Scales of Infant Development, Third Edition (BSID-III). RESULTS: The NE group showed similar ERP components and BSID-III scores to controls. However, infants with NE showed discrimination at midline leads (P = 0.01), whereas controls showed discrimination in the left hemisphere (P = 0.05). Normal MRI (P = 0.05) and seizure-free electroencephalogram (EEG) (P = 0.04) correlated positively with outcomes. CONCLUSION: Infants with NE have preserved recognition memory function after TH. The spatially different recognition memory processing after early brain injury may represent compensatory changes in the brain circuitry and reflect a benefit of TH.

Linear growth and neurodevelopmental outcomes.

Despite advances in care, preterm infants exhibit disproportionate growth and neurodevelopmental delay attributable to both nutritional and nonnutritional factors. These infants have prolonged linear stunting and decreased fat-free mass compared with their term counterparts. These 2 metrics index organ growth and development (including the brain) and protein accretion. Protein, along with carbohydrates, fats, and zinc, plays key roles in brain development, and deficiencies can lead to linear growth failure, abnormalities in the growth hormone axis, and developmental delay. Optimization of nutrition, including protein intake, decreasing inflammatory episodes, and enhancing the growth hormone axis will likely improve long-term outcomes.

Exploratory study of the relationship of fat-free mass to speed of brain processing in preterm infants.

BACKGROUND: Preterm infants are at risk for long-term neurodevelopmental impairment as a function of postnatal nutritional status. Despite adequate neonatal weight gain, preterm infants have altered body composition, with lower fat-free mass (FFM) and higher adiposity at term corrected gestational age (CGA) than their term counterparts. The relationship between postnatal body composition and speed of brain processing in preterm infants is unknown. METHODS: Anthropometric measurements and body composition testing via air displacement plethysmography were performed on 16 appropriate-for-gestational age (GA) preterm (mean GA: 30.4 ± 2.8 wk) infants at term and 4 mo CGA. Infant visual pathway development was assessed at 4 mo CGA using pattern-reversal visual evoked potential (VEP); P100 (positive peak) latency was used to index neuronal speed of processing. RESULTS: Increased FFM at discharge (P = 0.02) and 4 mo CGA (P = 0.006) was associated with shorter latencies to the P100 peak. P100 latency was not related to total body weight, fat mass, or body fat percentage. CONCLUSION: FFM reflects protein accretion and indexes growth of organs, including the brain. The association of shorter VEP latency (i.e., faster neuronal processing) with higher FFM (i.e., better protein status) may be attributed to the positive effects of protein status on neuronal growth and differentiation.