Mean WRAML2 Index Scores for Boys and Girls Stratified by Prenatal Stress and Black Carbon Exposure.

<p>Low and high prenatal stress are defined as negative life event domain scores ≤ 1 (lowest tertile) and >3 (highest tertile), respectively; BC is dichotomized using a median split (0.4 μg/m³). Error bars represent one standard deviation above and below the mean. Abbreviations: BC: black carbon; WRAML2: Wide Range Assessment of Memory and Learning-2nd edition. <i>P</i>_<i>int</i> represents the p-value from the 3-way interaction between child sex × prenatal stress × prenatal BC.</p

Detection of long non-coding RNAs in human breastmilk extracellular vesicles: Implications for early child development

<p>Breastmilk has many documented beneficial effects on the developing human infant, but the components of breastmilk that influence these developmental pathways have not been fully elucidated. Increasing evidence suggests that non-coding RNAs encapsulated in extracellular vesicles (EVs) represent an important mechanism of communication between the mother and child. Long non-coding RNAs (lncRNAs) are of particular interest given their key role in gene expression and development. However, it is not known whether breastmilk EVs contain lncRNAs. We used qRT-PCR to determine whether EVs isolated from human breastmilk contain lncRNAs previously reported to be important for developmental processes. We detected 55 of the 87 screened lncRNAs in EVs from the 30 analyzed breastmilk samples, and CRNDE, DANCR, GAS5, SRA1 and ZFAS1 were detected in >90% of the samples. GAS5, SNHG8 and ZFAS1 levels were highly correlated (Spearman's rho > 0.9; <i>P</i> < 0.0001), which may indicate that the loading of these lncRNAs into breastmilk EVs is regulated by the same pathways. The detected lncRNAs are important epigenetic regulators involved in processes such as immune cell regulation and metabolism. They may target a repertoire of recipient cells in offspring and could be essential for child development and health. Further experimental and epidemiological studies are warranted to determine the impact of breastmilk EV-encapsulated lnRNAs in mother to child signaling.</p

General descriptive statistics for paired maternal-cord blood samples included in the analysis.

<p>General descriptive statistics for paired maternal-cord blood samples included in the analysis.</p

Disrupted Prenatal Maternal Cortisol, Maternal Obesity, and Childhood Wheeze. Insights into Prenatal Programming

<p><em>Rationale</em>: Exploring prenatal factors influencing childhood wheeze may inform programming mechanisms.</p> <p><em>Objectives</em>: We examined associations among prenatal maternal cortisol profiles, maternal obesity, and repeated wheeze up to age 2 years (n = 261).</p> <p><em>Methods</em>: Salivary cortisol was collected five times per day over 3 days at 29.0 ± 4.9 weeks gestation. Mothers were categorized as obese (body mass index ≥ 30 kg/m²) versus nonobese (body mass index < 30 kg/m²). Using logistic regression, we examined the influence of log-transformed cortisol metrics (level at each time point, morning rise, diurnal and afternoon slopes) and obesity on wheeze adjusting for covariates. Linear mixed models were implemented to examine associations between cortisol trajectories and wheezing. Interactions between maternal cortisol and obesity were considered.</p> <p><em>Measurements and Main Results</em>: Mothers were primarily minority (56.5% Hispanic, 24.1% African American), 61% had less than or equal to 12 years of education, 34% were obese, and 8.4% of children had repeated wheeze. An interquartile range increase in mean log cortisol at bedtime (odds ratio, 2.2; 95% confidence interval, 1.09–4.09) and maternal obesity (odds ratio, 3.43; 95% confidence interval, 1.26–9.35) were independently associated with wheeze. Linear mixed models revealed an association between a flatter afternoon slope (slower decline in log cortisol per hour) and repeated wheeze in children of obese mothers (children with [−0.017 change] and without [−0.061 change] wheeze [<em>P</em> = 0.009 for time × wheeze interaction]), but not in children of nonobese mothers (with [−0.050 change] and without [−0.061 change] wheeze [<em>P</em> = 0.51]).</p> <p><em>Conclusions</em>: Maternal prenatal cortisol disruption and obesity were independently associated with children’s wheeze. Obese women with adverse cortisol profiles were most likely to have children with repeated wheeze.</p

Spearman correlation coefficients between umbilical cord blood and maternal blood for each epigenetic marker.

‡<p>0.05≥p≥0.01.</p>†<p>0.01>p>0.0001.</p

Primers used for DNA methylation analysis.

a<p>Nucleotides at which DNA methylation was measured are underlined.</p

Localization of gene promoters and regions amplified and of the CpG dinucleotide positions at which DNA methylation was quantified.

<p>Localization of gene promoters and regions amplified and of the CpG dinucleotide positions at which DNA methylation was quantified.</p

Examples of pyrograms.

<p>A) <i>LINE-1</i>, B) <i>Alu</i>, C) <i>p16</i>, and D) <i>p53</i>.</p

Determining Prenatal, Early Childhood and Cumulative Long-Term Lead Exposure Using Micro-Spatial Deciduous Dentine Levels

<div><p>The aim of this study was to assess the validity of micro-spatial dentine lead (Pb) levels as a biomarker for accurately estimating exposure timing over the prenatal and early childhood periods and long-term cumulative exposure to Pb. In a prospective pregnancy cohort sub-sample of 85 subjects, we compared dentine Pb levels measured using laser ablation-inductively coupled plasma mass spectrometry with Pb concentrations in maternal blood collected in the second and third trimesters, maternal bone, umbilical cord blood, and childhood serial blood samples collected from the ages of 3 months to ≥6 years. We found that Pb levels (as ²⁰⁸Pb:⁴³Ca) in dentine formed at birth were significantly associated with cord blood Pb (Spearman ρ = 0.69; n = 27; p<0.0001). The association of prenatal dentine Pb with maternal patella Pb (Spearman ρ = 0.48; n = 59; p<0.0001) was stronger than that observed for tibia Pb levels (Spearman ρ = 0.35; n = 41; p<0.03). When assessing postnatal exposure, we found that Pb levels in dentine formed at 3 months were significantly associated with Pb concentrations in children’s blood collected concurrently (Spearman ρ = 0.64; n = 55; p<0.0001). We also found that mean Pb concentrations in secondary dentine (that is formed from root completion to tooth shedding) correlated positively with cumulative blood lead index (Spearman ρ = 0.38; n = 75; p<0.0007). Overall, our results support that micro-spatial measurements of Pb in dentine can be reliably used to reconstruct Pb exposure timing over the prenatal and early childhood periods, and secondary dentine holds the potential to estimate long-term exposure up to the time the tooth is shed.</p></div

Timing of collection of Pb biomarkers used in the present study^a.

a<p>additional measures are available in ELEMENT but not relevant for analyses presented in this study.</p