Evidence map›Paper›PMID 34090432›Full record

ArticleEnvironmental health : a global access science source2021

Associations between prenatal exposure to cadmium and lead with neural tube defect risks are modified by single-nucleotide polymorphisms of fetal MTHFR and SOD2: a case-control study.

Mengyuan Liu, Jinhui Yu, Zaiming Su, Ying Sun, Yaqiong Liu, Qing Xie, Zhiwen Li, Linlin Wang, Jie Zhang, Lei Jin and 1 more

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in Environmental health : a global access science source, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 8 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed, 1 pooled it
1.3field-weighted citation impact, top 23% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

8 citing papers in PubMed, 1 synthesis or guideline pooled it, 18 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Frontiers in nutrition · 2025
    Article
  5. Article
  6. Advances in neural organoid systems and their application in neurotoxicity testing of environmental chemicals.Genes and environment : the official journal of the Japanese Environmental Mutagen Society · 2021
    Review
  7. Article
  8. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 1 institution in 1 country.

Mengyuan LiuInstitute of Reproductive and Child Health/Key Laboratory of Reproductive Health, National Health Commission of the People's Republic of China, Peking University, Beijing, China.
Jinhui YuInstitute of Reproductive and Child Health/Key Laboratory of Reproductive Health, National Health Commission of the People's Republic of China, Peking University, Beijing, China.
Zaiming SuInstitute of Reproductive and Child Health/Key Laboratory of Reproductive Health, National Health Commission of the People's Republic of China, Peking University, Beijing, China.
Ying SunInstitute of Reproductive and Child Health/Key Laboratory of Reproductive Health, National Health Commission of the People's Republic of China, Peking University, Beijing, China.
Yaqiong LiuInstitute of Reproductive and Child Health/Key Laboratory of Reproductive Health, National Health Commission of the People's Republic of China, Peking University, Beijing, China.
Qing XieInstitute of Reproductive and Child Health/Key Laboratory of Reproductive Health, National Health Commission of the People's Republic of China, Peking University, Beijing, China.
Zhiwen LiInstitute of Reproductive and Child Health/Key Laboratory of Reproductive Health, National Health Commission of the People's Republic of China, Peking University, Beijing, China.
Linlin WangInstitute of Reproductive and Child Health/Key Laboratory of Reproductive Health, National Health Commission of the People's Republic of China, Peking University, Beijing, China.
Jie ZhangInstitute of Reproductive and Child Health/Key Laboratory of Reproductive Health, National Health Commission of the People's Republic of China, Peking University, Beijing, China.
Lei JinInstitute of Reproductive and Child Health/Key Laboratory of Reproductive Health, National Health Commission of the People's Republic of China, Peking University, Beijing, China. jinlei@bjmu.edu.cn.
Aiguo RenInstitute of Reproductive and Child Health/Key Laboratory of Reproductive Health, National Health Commission of the People's Republic of China, Peking University, Beijing, China. renag@bjmu.edu.cn.ORCID 0000-0001-9115-5638
Peking University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundPrenatal exposure to heavy metals is implicated in the etiology of birth defects. We investigated whether concentrations of cadmium (Cd) and lead (Pb) in umbilical cord tissue are associated with risk for neural tube defects (NTDs) and whether selected genetic variants of the fetus modify their associations.

methodsThis study included 166 cases of NTD fetuses/newborns and 166 newborns without congenital malformations. Umbilical cord tissue was collected at birth or elective pregnancy termination. Cd and Pb concentrations were assessed by inductively coupled plasma-mass spectrometry, and 20 single-nucleotide polymorphisms (SNPs) in 9 genes were genotyped. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to estimate the risk for NTDs in association with metal concentrations or genotype using logistic regression. Multiplicative-scale interactions between the metals and genotypes on NTD risk were assessed with logistic regression, and additive-scale interactions were estimated with a non-linear mixed effects model.

resultsHigher concentrations of Cd were observed in the NTD group than in the control group, but no difference was found for Pb. Concentrations of Cd above the median level showed a risk effect, while the association between Pb and NTD risk was not significant in univariate analyses. The association of Cd was attenuated after adjusting for periconceptional folic acid supplementation. Fetuses with the AG and GG genotypes of rs4880 in SOD2 (superoxide dismutase 2) tended to have a lower risk, but fetuses with the CT and TT genotypes of rs1801133 in MTHFR (5,10-methylenetetrahydrofolatereductase) have a higher risk for NTDs when compared to their respective wild-type. rs4880 and Cd exhibited a multiplicative-scale interaction on NTD risk: the association between higher Cd and the risk for NTDs was increased by over fourfold in fetuses carrying the G allele [OR 4.43 (1.30-15.07)] compared to fetuses with the wild-type genotype. rs1801133 and Cd exposure showed an additive interaction, with a significant relative excess risk of interaction [RERI 0.64 (0.02-1.25)].

conclusionsPrenatal exposure to Cd may be a risk factor for NTDs, and the risk effect may be enhanced in fetuses who carry the G allele of rs4880 in SOD2 and T allele of rs1801133 in MTHFR.

Indexed as

AdultCadmiumCase-Control StudiesChinaEnvironmental PollutantsFemaleFetusGenotypeHumansInfant, NewbornLeadMaternal ExposureMaternal-Fetal ExchangeMethylenetetrahydrofolate Reductase (NADPH2)Neural Tube DefectsPolymorphism, Single NucleotideCadmiumEnvironmental PollutantsLeadMethylenetetrahydrofolate Reductase (NADPH2)MTHFR protein, humanSuperoxide DismutaseSuperoxide Dismutase 25,10-methylenetetrahydrofolatereductase (MTHFR)CadmiumLeadNeural tube defectsSingle-nucleotide polymorphismsSuperoxide dismutase 2 (SOD2)

Identifiers

PMID34090432
PMCPMC8180011
OpenAlexW3170207017

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.