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.

Correlation of maternal abuse during pregnancy with infant temperament and development

ObjectiveTo investigate the effects of domestic violence (DV) against pregnant women on their infant's development in China.Design247 mothers were interviewed using the Chinese version of the Abuse Assessment Screen, and all participants underwent postnatal assessment with the Edinburgh Postpartum Depression Scale (EDPS). Plasma glutamate (Glu), γ-aminobutyric acid (GABA) and cortisol levels of the neonates were measured. After a 10-month follow-up, the infants were assessed using the Revised Infant Temperament Questionnaire (RITQ) and Bayley Scales of Infant Development (BSID).Results86 infants of abused mothers (DV group) and 137 infants of non-abused mothers (non-DV group) completed the 10-month follow-up. Neonate levels of plasma Glu, GABA and cortisol were significantly higher in the DV group than in the non-DV group. Scores for the temperament factors, rhythmicity, approach/withdrawal, mood, distractibility and persistence, of the RITQ were rated significantly higher, and results for the Psychomotor Development Index (PDI) of the BSID were significantly lower in the DV group than in the non-DV group at 10 months. After adjustment for the EPDS as a covariate, only distractibility of the RITQ showed a statistically significant difference between the two groups. In correlation analysis, infant mood correlated significantly with levels of plasma Glu (β=0.2345) and GABA (β=0.2554), whether or not the EPDS scores were adjusted. Infant persistence and threshold of stimuli scores did not correlate significantly with DV during pregnancy after adjustment for the EPDS.ConclusionsDV against pregnant women may be associated with impaired temperament and development in their infants.

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.

Bronchopulmonary dysplasia as a predictor factor for motor alteration at 6 months corrected age in premature infants

OBJECTIVE: The study aimed to assess bronchopulmonary dysplasia (BPD) as a predisposing factor for alteration in the psychomotor development index (PDI) in premature infants and verify the incidence of neuromotor alterations at 6 months corrected age. METHOD: This was a prospective cohort study that followed the neuromotor development of 152 very low birth weight premature infants, with psychomotor development index as the outcome. The study used the Bayley Scale of Infant Development at 6 months corrected age, and neurological examination. RESULTS: Incidence of BPD was 13.2% (n=20). Logistic regression analysis showed an association between BPD and altered psychomotor development index (OR 3.98; 95%CI: 1.04-15.1) after adjusting for confounding variables. Neurological examination was altered in 67.1% of the 152 infants. CONCLUSION: Bronchopulmonary dysplasia acted as an independent predisposing factor for alteration in the psychomotor development index in premature infants at 6 months corrected age.

The Kent Infant Development Scale: Concurrent and Predictive Validity of a Modified Administration

A modified administration of the Kent Infant Development Scale for infants 6 to 8 mo. old was used in a prospective study of risk factors in infant development. The Mental Development Index and Psychomotor Development Index of the Bayley Scales of Infant Development were also administered at 6 mo., the Mental Index only at 1 and 2 yr. and the Stanford-Binet Intelligence Scale at age 3. The modified administration is described. Concurrent validity with the 6-mo. Bayley scales was substantial. Adequate predictive validity for 1- and 2-yr. Bayley scores and 3-yr. Stanford-Binet IQ was achieved with the Kent as compared to the predictive ability of the 6-mo. Bayley index.