DNA methylation at birth potentially mediates the association between prenatal lead (Pb) exposure and infant neurodevelopmental outcomes

Early-life lead (Pb) exposure has been linked to adverse neurodevelopmental outcomes. Recent evidence has indicated a critical role of DNA methylation (DNAm) in cognition, and Pb exposure has also been shown to alter DNAm. However, it is unknown whether DNAm is part of the mechanism of Pb neurotoxicity. This longitudinal study investigated the associations between trimester-specific (T1, T2, and T3) maternal blood Pb concentrations, gene-specific DNAm in umbilical cord blood, and infant neurodevelopmental outcomes at 12 and 24 months of age (mental development index, psychomotor development index, and behavioral rating scale of orientation/engagement and emotional regulation) among 85 mother–infant pairs from the Early Life Exposure in Mexico to Environmental Toxicants (ELEMENT) study. In the mediation analysis for this pilot study, P < 0.1 was considered significant. DNAm at a locus in CCSER1 (probe ID cg02901723) mediated the association between T2 Pb on 24-month orientation/engagement [indirect effect estimate 4.44, 95% confidence interval (−0.09, 10.68), P = 0.06] and emotional regulation [3.62 (−0.05, 8.69), P = 0.05]. Cg18515027 (GCNT1) DNAm mediated the association of T1 Pb [−4.94 (−10.6, −0.77), P = 0.01] and T2 Pb [−3.52 (−8.09, −0.36), P = 0.02] with 24-month EMOCI, but there was a positive indirect effect estimate between T2 Pb and 24-month psychomotor development index [1.25 (−0.11, 3.32), P = 0.09]. The indirect effect was significant for cg19703494 (TRAPPC6A) DNAm in the association between T2 Pb and 24-month mental development index [1.54 (0, 3.87), P = 0.05]. There was also an indirect effect of cg23280166 (VPS11) DNAm on T3 Pb and 24-month EMOCI [2.43 (−0.16, 6.38), P = 0.08]. These associations provide preliminary evidence for gene-specific DNAm as mediators between prenatal Pb and adverse cognitive outcomes in offspring.

The Bayley-III scale may underestimate neurodevelopmental disability after cardiac surgery in infants

OBJECTIVES Neurodevelopmental disability is the most common complication among congenital heart surgery survivors. The Bayley scales are standardized instruments to assess neurodevelopment. The most recent edition (Bayley Scales of Infant and Toddler Development 3rd Edition, Bayley-III) yields better-than-expected scores in typically developing and high-risk infants than the second edition (Bayley Scales of Infant Development 2nd Edition, BSID-II). We compared BSID-II and Bayley-III scores in infants undergoing cardiac surgery. METHODS We evaluated 2198 infants who underwent operations with cardiopulmonary bypass between 1996 and 2009 at 26 institutions. We used propensity score matching to limit confounding by indication in a subset of patients (n = 705). RESULTS Overall, unadjusted Bayley-III motor scores were higher than BSID-II Psychomotor Development Index scores (90.7 ± 17.2 vs 77.6 ± 18.8, P < 0.001), and unadjusted Bayley-III composite cognitive and language scores were higher than BSID-II Mental Development Index scores (92.0 ± 15.4 vs 88.2 ± 16.7, P < 0.001). In the propensity-matched analysis, Bayley-III motor scores were higher than BSID-II Psychomotor Development Index scores [absolute difference 14.1, 95% confidence interval (CI) 11.7–17.6; P < 0.001] and the Bayley-III classified fewer children as having severe [odds ratio (OR) 0.24; 95% CI 0.14–0.42] or mild-to-moderate impairment (OR 0.21; 95% CI 0.14–0.32). The composite of Bayley-III cognitive and language scores was higher than BSID-II Mental Development Index scores (absolute difference 4.0, 95% CI 1.4–6.7; P = 0.003), but there was no difference between Bayley editions in the proportion of children classified as having severe cognitive and language impairment. CONCLUSIONS The Bayley-III yielded higher scores than the BSID-II and classified fewer children as severely impaired. The systematic bias towards higher scores with the Bayley-III precludes valid comparisons between early and contemporary cardiac surgery cohorts.

Gangguan Kognitif pada Anemia Defisiensi Besi

Anemia defisiensi besi masih merupakan masalah kesehatan terutama di negara yangsedang berkembang. Zat besi banyak dibutuhkan otak karena metabolisme oksidasinyayang tinggi. Beberapa enzim dalam proses oksidasi dan metabolisme sel membutuhkanbesi. Gangguan kognitif pada anemia defisiensi besi telah banyak diteliti. Beberapa halyang berhubungan dengan gangguan kognitif pada anemia defisiensi telah dikemukakan;terganggunya enzim-enzim yang berperan dalam metabolisme otak, gangguan dalammielinisasi dan terganggunya oksigenasi sel. Pada pemeriksaan terhadap bayi yangmenderita anemia defisiensi besi didapatkan skor Mental Development Index (MDI)yang rendah dan Infant Behavior Record (IBR) memperlihatkan perbedaan emosi. Padaanak usia sekolah didapatkan prestasi belajar yang rendah dan konsentrasi belajar yangsingkat.

Effect of Zinc Intake on Mental and Motor Development in Infants: A Meta-Analysis

A systematic review and meta-analysis of available randomized controlled trials (RCTs) was conducted to evaluate the effect of zinc (Zn) intake on mental and motor development in infants. Out of 5500 studies identified through electronic searches and reference lists, 5 RCTs were selected after applying the exclusion/inclusion criteria. The influence of Zn intake on mental and motor development was considered in the overall meta-analysis. Other variables were also taken into account as possible effect modifiers: doses of Zn intake, intervention duration, nutritional situation, and risk of bias. Indices of mental and motor development assessed were the Mental Development Index (MDI) and Psychomotor Development Index (PDI). Additionally we carried out a sensitivity analysis. The pooled β was -0.01 (95 %CI -0.02, 0) for MDI and 0 (95 %CI -0.03, 0.02) for PDI, with a substantial heterogeneity in both analyses. When we performed a meta-regression, the effect of Zn supplementation on MDI changed depending on the dose of supplementation. Regarding PDI, there was a differential effect of Zn intake depending on intervention duration, dose of supplementation, nutritional situation, and risk of bias. Zn supplementation showed a negative, weak and significant effect on PDI score in those studies with a length of 4 to 20 weeks (β= -0.05; CI 95 % -0.06 to -0.04). In conclusion, no association was found between Zn intake and mental and motor development in infants. Further standardized research is urgently needed to clarify the role of Zn supplementation upon infant mental and motor development, particularly in Europe.

Neurocognitive Development and Behavioral Outcome of 2-Year-Old Children with Univentricular Heart

Recent advances in the treatment of children with severe congenital heart defects, such as hypoplastic left heart syndrome (HLHS) and other forms of univentricular heart (UVH), have significantly improved their survival rates. However, these children are at risk for various neurodevelopmental deficits. The aim of the present study was to assess cognitive development, expressive language, and behavior in 30-month-old children with univentricular heart. The participants were 22 children with HLHS, 14 with UVH, and 41 healthy control subjects. The Bayley Scales of Infant Development II, MacArthur Communicative Development Inventories, and Child Behavior Checklist were used for assessments. The results revealed that children with HLHS exhibited a significantly lower mean mental development index, more delays in expressive language functions, and more behavioral problems than did the control children. Two children with HLHS (9%) had mental development indexes below 50, indicating significantly delayed performance. The children with UVH differed from the control children with respect to their lower mean mental development index. These findings suggest that at the age of 30 months, neurodevelopmental deficits are especially prevalent in children with HLHS. Thus, early developmental screening, intervention, and neuropsychological follow-up until school age is recommended particularly for the children with HLHS. (JINS, 2011, 17, 1094–1103)