Impact of a prenatal exposure mixture of metals on DNA

Overview

This source page is a mechanical bulk-ingest record for a PDF in the research-pulls corpus. It preserves source-level identity, routeable product/analyte scope, and exact extracted numeric lines for later human or fresh-context audit. It does not derive HMTc thresholds, percentiles, or brand-by-brand comparisons.

Key numbers

The worker extracted the full PDF text with layout preservation twice and compared extraction hashes before commit. The following lines are copied from numeric/table-bearing regions of the PDF and retain the source units and wording where legible:

senic, cadmium) and DNA methylation-derived cell-type composition from cord blood (n = 428). We used the novel Dirichlet Bayesian
4.85% (95% credible intervals (CrI): 1.11%, 8.81%) increase in GR proportion, driven by arsenic. Conversely, a one-quartile increase in
metal mixture in women carrying a male was marginally associated with a 3.44% (95% CrI: −7.08%, 0.37%; 80%CrI: −5.83%, −1.01%)
economic status (SES) at recruitment (52%) (Table 1). Mothers had
on average 28 years at recruitment and gave birth to 54% males.
tributions also indicate that 42% Mexican pregnant women were
had abnormal levels of urinary As (>50 μg/L) (76), 63% for uri-
nary Cd (>0.185 μg/L) (77), and 67% for blood Mn (>15 μg/L) (78).
granulocytes (mean (SD): 45 (11)) followed by CD4+ T-cells (mean
(SD): 15 (6)) (Table 1; Fig. 1). Furthermore, although levels of metal
fects induced by prenatal exposure to toxicants including heavy overall sample population (Table 2; Fig. 2), or after stratifying by
metals (64–66). To our knowledge, no previous study has examined median levels of maternal FA supplementation (Table S3; Fig. S2).
ical exposures in relation to cell-type composition (67). To our carrying a female was associated with a 4.85% (95% credible inter-
knowledge, no study has investigated to date the effect of metal vals (CrI): (1.11%, 8.81%)) increase in cell proportion of cord blood
exposure mixtures on cell-type composition in humans. For the granulocytes (Table 2; Fig. 3). This association was primarily driven
come framework to accommodate for multiple cell-type propor- women carrying a male was marginally associated with a 3.44%
tions. We selected a priori a combined mixture of heavy metals (95% CrI: (−7.08%, 0.37%); 80% CrI: (−5.83%, −1.01%)) decrease in
Growth, Environment and Social Stressors (PROGRESS) birth co- higher cell proportion of CD8+ T-cells (β (80% CrI): 7.19% (1.51%,
hort of child–mother pairs with high levels but variable expo- 13.1%)) in mothers carrying a male, and a lower cell proportion of
sure to metals, we hypothesize that a prenatal exposure mixture natural killer (NK) cells (β (80% CrI): −12.0% (−20.6%, −3.02%)) and
of toxic metals is linked to alterations of cell-type composition, nucleated red blood cells (nRBCs) (β (80% CrI): −6.82% (−12.8%,
which was estimated from cord blood DNA methylation. More- −0.77%)) in mothers carrying a female. Consistent results were
fetal sex. Given that we previously elucidated protective effects ers carrying a female (NK β (95% CrI): −0.18 (−0.34, −0.02); nRBCs
from FA supplementation during pregnancy mitigating the effects β (95% CrI): −0.12 (−0.24, −0.01)) (Table S4).
Male 230 (54%)
Female 198 (46%)
Pb > 35 μg/L 178 (42%)
Pb ≤ 35 μg/L 250 (58%)
Cd > 0.185 μg/L 268 (63%)
Cd ≤ 0.185 μg/L 160 (37%)
As > 50 μg/L 35 (8.2%)
As ≤ 50 μg/L 393 (92%)
Missing data for n = 59 participants (14%) and restricted in stratified analyses by folic acid.
Concentrations measured in blood. No concentrations below 4 μg/L for manganese.
Mean SE SD 95th CrI (low) 95th CrI (high) 80th CrI (low) 80th CrI (high) ESS Rhat
Overall (n = 428)
Fetal sex male (n = 230)
Fetal sex female (n = 198)
Figure 1. Blood cell-type composition in cord blood of PROGRESS children (N = 428). Proportions are shown for granulocytes (GR), CD4+ T-cells (CD4),
(n = 428). Visual summary of the DBWQS regression results showing the high arsenic-driving effects may be related to Hg, a common co-
Figure 3. DBWQS absolute proportion results in PROGRESS cord blood stratified by fetal sex in n = 230 male (A, B) and n = 198 female (C, D) carriers.
use of steroids, consumption of one or more alcoholic drinks removed n = 5 observations that had missing measures for some

Methods (brief)

which sample composition has not been accounted for (47, 48).
fects induced by prenatal exposure to toxicants including heavy overall sample population (Table 2; Fig. 2), or after stratifying by
metal exposure. On a similar note, our study also highlights the in Heiss et al. (125), which included removing poor quality samples
high prevalence of heavy metal toxicity in this population, which and probes, sex-mismatched samples, single-nucleotide polymor-
chronic conditions, including a history of infertility, heart or re- An initial sample size of 433 observations had metals measured
per day, or drug addiction at recruitment. Information on socio- of the metals in the mixture, yielding a final sample size of n = 428.
demographic, lifestyle, and environmental factors was collected Our subset population had similar baseline characteristics as
through validated questionnaires, along with biological samples compared to the main PROGRESS cohort with the 948 mother–
(119, 120). Briefly, PROGRESS collected information on maternal urinary As and Cd, and blood Pb and Mn—and DNA methylation-
ternal blood and urine were collected in trace element-free tubes.
tection (LOD) with LOD/ 2. Specific gravity was used to correct
for urinary dilution for metals collected in urine (As and Cd). We
Umbilical cord blood samples were collected at the time of deliv-
1. Bjørklund G, Chartrand MS, Aaseth J. Manganese exposure and - 00592- z
1. Goodman CV, Green R, DaCosta A et al. Sex difference of pre- 72. Aung MT, Meeker JD, Boss J et al. Manganese is associated
1. Gervin K, Page CM, Aass HC et al. Cell type specific DNA methy- differential strategies of fetal growth and survival. Placenta
nary cadmium excretion in spot urine samples, first morning /nutrition- facts- label/folate- and- folic- acid- nutrition- and- s

Implications

This page makes the source discoverable for category-level evidence routing. Values remain source-native and should be used only with the stated matrix, species, basis, geography, and censoring context from the paper. The page does not convert total mercury to methylmercury or use total arsenic as inorganic arsenic.

Wiki pages this source may touch

Verification notes

Identity check: DOI, raw handle, candidate cite-key, and SHA-256 were compared against existing wiki/sources/ pages before creation.
Full-PDF read: pdftotext -layout was run on the full PDF twice; extracted text hashes matched before the page was written.
Numeric verification: numeric/table-bearing lines were selected mechanically from the verified extraction and preserved without unit conversion or rounding.
Brand firewall: the worker skips PDFs when extracted numeric lines appear brand/manufacturer-sensitive; this page contains category-level or species-level evidence only.
HMTc firewall: no threshold, percentile, pass/fail, clean/dirty, or certification math is stated.

Update history

The five most recent substantive edits to this page, classified major (evidence or structure moved), correction (a published value or statement was wrong and has been fixed), or minor (narrative rewritten without changing the underlying evidence). Each description is derived from what the edit did to this page; the linked commit is the authoritative record, routine regeneration passes are excluded, and the full version history lives in git. When DOI minting comes online (see schema docs), each entry below will also link to a version-pinned DataCite DOI.

Commit	Date	Change	Description
b01ec52c	2026-08-04	major	2 sections added
d49e450f	2026-08-03	major	5 sections added; narrative text revised