Regression in Early Childhood Development: An Unintended Outcome of Prolonged Hospitalization?

This brief review outlines a novel case study with targeted literature search. Patient X was a 21-month-old male who was receiving ongoing treatment for stage M MYCN-amplified high-risk neuroblastoma. Patient X's mother was considering refusal of further cancer-directed therapy because of the child's developmental regression noted during his prolonged hospitalization. Given the underlying malleability of the developing brain in early childhood, access to supportive services that facilitate ongoing neurodevelopment in hospitalized young children is of utmost importance; such services further reduce parental stress and likely enhances parental and medical team efficacy of care.

Delayed iron does not alter cognition or behavior among children with severe malaria and iron deficiency.

BACKGROUND: Malaria and iron deficiency (ID) in childhood are both associated with cognitive and behavioral dysfunction. The current standard of care for children with malaria and ID is concurrent antimalarial and iron therapy. Delaying iron therapy until inflammation subsides could increase iron absorption but also impair cognition. METHODS: In this study, Ugandan children 18 months to 5 years old with cerebral malaria (CM, n = 79), severe malarial anemia (SMA, n = 77), or community children (CC, n = 83) were enrolled and tested for ID. Children with ID were randomized to immediate vs. 28-day delayed iron therapy. Cognitive and neurobehavioral outcomes were assessed at baseline and 6 and 12 months (primary endpoint) after enrollment. RESULTS: All children with CM or SMA and 35 CC had ID (zinc protoporphyrin concentration ≥80 µmol/mol heme). No significant differences were seen at 12-month follow-up in overall cognitive ability, attention, associative memory, or behavioral outcomes between immediate and delayed iron treatment (mean difference (standard error of mean) ranged from -0.2 (0.39) to 0.98 (0.5), all P ≥ 0.06). CONCLUSIONS: Children with CM or SMA and ID who received immediate vs. delayed iron therapy had similar cognitive and neurobehavioral outcomes at 12-month follow-up. IMPACT: The optimal time to provide iron therapy in children with severe malaria is not known. The present study shows that delay of iron treatment to 28 days after the malaria episode, does not lead to worse cognitive or behavioral outcomes at 12-month follow-up. The study contributes new data to the ongoing discussion of how best to treat ID in children with severe malaria.

Beyond stimulus deprivation: iron deficiency and cognitive deficits in postinstitutionalized children.

Children adopted from institutions have been studied as models of the impact of stimulus deprivation on cognitive development (Nelson, Bos, Gunnar, & Sonuga-Barke, 2011), but these children may also suffer from micronutrient deficiencies (Fuglestad et al., 2008). The contributions of iron deficiency (ID) and duration of deprivation on cognitive functioning in children adopted from institutions between 17 and 36 months of age were examined. ID was assessed in 55 children soon after adoption, and cognitive functioning was evaluated 11-14.6 months postadoption when the children averaged 37.4 months old (SD = 4.9). ID at adoption and longer duration of institutional care independently predicted lower IQ scores and executive function (EF) performance. IQ did not mediate the association between ID and EF.

Iron deficiency after arrival is associated with general cognitive and behavioral impairment in post-institutionalized children adopted from Eastern Europe.

To investigate the role of iron deficiency in general cognitive and behavioral development in post-institutionalized (PI) children during the early post-adoption period. PI children (N = 57) adopted from Eastern Europe or Central Asia (9-46 months of age) were seen at baseline around 1 month after arrival into the US and at follow-up 6 months later. Measures included anthropometry, iron status, the Toddler Behavior Assessment Questionnaire-R (TBAQ-R), the Mullen Scales of Early Learning, and examiner-rated behaviors during testing. 26 % were iron deficient at baseline; 18 % were iron deficient at follow-up. There was a trend for those with iron deficiency at baseline to be more fearful on the TBAQ-R. Those with iron deficiency at follow-up displayed more hyperactivity on both the TBAQ-R and the examiner-rated behaviors. Those with iron deficiency at follow-up were more likely to score below average on the Mullen Early Learning Composite (iron deficient: 80 %; good iron status: 32 %). The association between iron status at follow-up and the Mullen Early Learning Composite was mediated by inattention and hyperactivity behaviors during testing. Iron deficiency is associated with neurobehavioral alterations months after arrival, mediated by the effect on attention and activity levels. Iron status needs to be monitored at least through the first half-year post-adoption, particularly in children exhibiting rapid catch-up growth. Additionally, developmental evaluation is recommended in those with iron deficiency, even in children with good iron status at arrival.

Iron deficiency in international adoptees from Eastern Europe.

OBJECTIVE: To assess iron deficiency (ID) in international adoptees after adoption. STUDY DESIGN: Participants (n = 37) were adopted into the United States from Eastern Europe before they were 24 months of age. Baseline (within 1 month post-adoption) and follow-up (6 months post-adoption) assessments included routine post-adoption clinical evaluations, anthropometrics, dietary intakes, and iron measures (hemogram and serum analysis). RESULTS: At adoption and follow-up, mean percent transferrin saturation and mean corpucuscular volume were low compared with the US population. Mean serum ferritin concentration became lower than the US population at follow-up, although the mean daily iron intake was more than the Recommended Dietary Allowance. Participants with Giardia lamblia at baseline had more compromised iron status at baseline and follow-up. Growth rate (change in z-score/months between assessments) was negatively correlated with change in serum ferritin concentrations between baseline and follow-up (r = -0.34; P < .05). CONCLUSIONS: International adoptees had compromised iron status, with ID more prevalent in participants with G lamblia, a parasite that may interfere with iron absorption. The persistent ID at follow-up was likely caused by the erythropoietic demands of catch-up growth.