Clinical Pharmacist and Master’s student in Clinical Pharmacy with research interests in pharmacovigilance, behavioral interventions in mental health, and AI applications in clinical decision support. Experience includes digital health research with Bloomsbury Health (London) and pharmacovigilance practice in patient support programs. Published work covers drug awareness among healthcare providers, postpartum depression management, and patient safety reporting. 
Clinical Pharmacist and Master’s student in Clinical Pharmacy with research interests in pharmacovigilance, behavioral interventions in mental health, and AI applications in clinical decision support. Experience includes digital health research with Bloomsbury Health (London) and pharmacovigilance practice in patient support programs. Published work covers drug awareness among healthcare providers, postpartum depression management, and patient safety reporting. What was studied?
This study investigated the relationship between maternal nickel exposure and congenital heart defects (CHDs) in offspring using a multi-center case-control design across five Chinese cities. Nickel levels in maternal hair and fetal placental tissue markers of chronic exposure were quantified using ICP-MS. Logistic regression, adjusted for confounders such as maternal age, BMI, gestational age, smoking, folic acid use, education, and co-exposure to cadmium, lead, and arsenic, assessed the association with CHDs. Unlike previous research focused on other heavy metals, this study addressed the underexplored role of nickel in CHD risk.
Who was studied?
The study population consisted of 399 cases (pregnant women carrying fetuses diagnosed with CHDs) and 490 controls (pregnant women with no fetal malformations). All participants were recruited from maternal and child hospitals in Zhengzhou, Shenzhen, Fuzhou, Xi’an, and Wuhan between August 2010 and July 2013. Cases were defined by prenatal diagnosis of structural heart defects, confirmed by postnatal examination or autopsy if relevant. Controls were matched by time and location, excluding any with chromosomal abnormalities, hereditary syndromes, multifetal pregnancies, or family history of CHDs. The gestational ages ranged from 14 to 40 weeks. Biological samples included 587 maternal hair samples and 395 placental tissue samples. Comprehensive demographic data and behavioral information were collected via structured questionnaires.
Most Important Findings
| Finding | Details |
|---|---|
| Maternal hair nickel concentration | Higher in CHD group (0.629 ng/mg) vs. controls (0.443 ng/mg), P <0.001 |
| Fetal placental tissue nickel concentration | Higher in CHD group (0.178 ng/mg) vs. controls (0.148 ng/mg), P <0.05 |
| Risk association – Total CHDs | Highest tertile of hair nickel linked with increased CHD risk (aOR 2.672, 95% CI 1.623–4.399; P <0.001) |
| CHD subtypes (hair nickel) | Septal defects (aOR 2.919, 95% CI 1.647–5.175); Conotruncal defects (aOR 2.305, 95% CI 1.209–4.733); RV outflow obstruction (aOR 2.396, 95% CI 1.213–4.733) |
| CHD subtypes (placental nickel) | Strongest for “other heart defects” (aOR 4.538, 95% CI 1.153–17.853) |
| Trend | Clear dose–response relationship observed, supporting causality |
| Certification relevance | Study establishes empirical nickel exposure ranges in pregnancy, critical for heavy metal certification benchmarks |
Key implications
This study provides critical evidence for Heavy Metal Tested and Certified (HTMC) programs, showing that even low-level, non-occupational nickel exposure can increase the risk of congenital heart defects (CHDs). Findings highlight the need for stricter monitoring of nickel in consumer products, water, food, and maternal environments. Maternal hair and placental tissue are validated as effective biomarkers, supporting their inclusion in certification and surveillance protocols. Establishing exposure thresholds can guide health-based reference values, while the dose-response trend and identified CHD subtypes justify targeted preventive measures. Given possible synergistic effects with other metals, multi-metal testing is also recommended for certification schemes.
Citation
Zhang N, Chen M, Li J, et al. Metal nickel exposure increase the risk of congenital heart defects occurrence in offspring: A case-control study in China. Medicine (Baltimore). 2019;98(18):e15352. doi:10.1097/MD.0000000000015352
Nickel is a widely used transition metal found in alloys, batteries, and consumer products that also contaminates food and water. High exposure is linked to allergic contact dermatitis, organ toxicity, and developmental effects, with children often exceeding EFSA’s tolerable daily intake of 3 μg/kg bw. Emerging evidence shows nickel crosses the placenta, elevating risks of preterm birth and congenital heart defects, underscoring HMTC’s stricter limits to safeguard vulnerable populations.
Cadmium is a persistent heavy metal that accumulates in kidneys and bones. Dietary sources include cereals, cocoa, shellfish and vegetables, while smokers and industrial workers receive higher exposures. Studies link cadmium to kidney dysfunction, bone fractures and cancer.
Lead is a neurotoxic heavy metal with no safe exposure level. It contaminates food, consumer goods and drinking water, causing cognitive deficits, birth defects and cardiovascular disease. HMTC’s rigorous lead testing applies ALARA principles to protect infants and consumers and to prepare brands for tightening regulations.
Heavy metals are high-density elements that accumulate in the body and environment, disrupting biological processes. Lead, cadmium, arsenic, mercury, nickel, tin, aluminum, and chromium are of greatest concern due to persistence, bioaccumulation, and health risks, making them central to the HMTC program’s safety standards.
