Key Takeaways
- In a study of 4,695 pregnant women, higher exposure to PM2.5, PM10 and nitrogen dioxide around conception was associated with higher odds of congenital heart defects in their children.
- Nitrogen dioxide, or NO2, showed the strongest association. Periconception exposure was associated with 62% higher odds of congenital heart defects in the adjusted analysis.
- Ventricular septal defects, which involve an opening between the heart’s lower chambers, showed associations with all three pollutants.
- Researchers also identified protein patterns in maternal and umbilical cord blood associated with pollution exposure and congenital heart defects, providing clues for future research into possible biological pathways.
- The study was observational and cannot establish that air pollution caused the heart defects.
Introduction
Air pollution around conception was associated with higher odds of congenital heart defects in a study of 4,695 pregnant women in China.
Exposure to air pollution around the time of conception may be associated with higher odds of congenital heart defects, according to research that also identified circulating proteins that could help scientists investigate the biology behind the association.
The study, published September 9, 2026, in Nature Communications, examined exposure to fine particulate matter, larger particulate matter, ozone and nitrogen dioxide before conception and during early pregnancy.
Among 4,695 participants, higher exposure to PM2.5, PM10 and nitrogen dioxide was associated with greater odds of congenital heart defects. Nitrogen dioxide showed the strongest association during the periconception period (Liang et al., 2026).
Researchers also identified pollution-related protein patterns in maternal and umbilical cord serum that were associated with congenital heart defect outcomes.
The results add biological clues to an association investigated in earlier epidemiological studies, but they do not establish that pollution caused the heart defects.
What the Study Examined
The researchers conducted a nested case-control study using participants from the China Birth Cohort Study, a prospective birth cohort designed to investigate environmental, genetic and lifestyle influences on maternal and child health.
The primary analysis included 4,695 participants.
Researchers estimated exposure to four common outdoor air pollutants: PM2.5, PM10, ozone and nitrogen dioxide, or NO2.
PM2.5 consists of particulate matter no more than 2.5 micrometers in diameter, while PM10 includes particles no more than 10 micrometers across. NO2 is a gaseous pollutant produced by combustion and is commonly associated with sources such as traffic.
The researchers examined exposure before conception, during the first trimester and across a broader periconception period combining the two.
Their statistical models accounted for numerous factors that could influence the results, including maternal age, body mass index, pre-pregnancy health conditions, household income, education, ethnicity, season of conception, adverse pregnancy history, parity, geographic region and urban or rural residence.
Three Pollutants Were Associated With Congenital Heart Defects
PM2.5, PM10 and NO2 were each associated with higher odds of congenital heart defects during the periconception period.
For PM2.5, the adjusted odds ratio was 1.13, with a 95% confidence interval of 1.08 to 1.19. This corresponds to 13% higher relative odds for the exposure comparison used in the study.
For PM10, the corresponding odds ratio was 1.07, representing 7% higher relative odds.
NO2 showed the largest association, with an odds ratio of 1.62 and a 95% confidence interval of 1.47 to 1.79, corresponding to 62% higher relative odds.
Ozone was not significantly associated with overall congenital heart defect risk in these analyses.
These estimates describe relative odds associated with the study-defined exposure comparisons. They do not represent equivalent increases in a child’s absolute probability of having a congenital heart defect. For example, 62% higher odds does not mean an absolute risk increase of 62 percentage points.
The associations remained similar in sensitivity analyses that additionally accounted for factors including conception year, proximity to major arterial roads and pre-existing diabetes.
Ventricular Septal Defects Showed a Consistent Pattern
Researchers also examined specific types of congenital heart defects.
Ventricular septal defects, or VSDs, showed one of the clearest patterns. A VSD is an opening in the wall separating the heart’s two lower chambers.
During the periconception period, PM2.5 exposure was associated with 22% higher odds of VSD, PM10 with 9% higher odds and NO2 with 38% higher odds.
The same consistent pattern was not observed across atrial septal defects, tetralogy of Fallot or persistent left superior vena cava.
That distinction is important because congenital heart defects encompass different structural abnormalities that may have different developmental pathways and environmental influences.
Earlier Research Supports the Association, but the Evidence Has Been Mixed
The new findings build on previous research examining air pollution and congenital heart defects.
A 2023 nationwide Chinese study analyzed 1,434,998 births, including 7,335 congenital heart defects. Researchers estimated maternal PM2.5 exposure from three months before conception through the first three months of pregnancy.
For every 10 μg/m³ increase in PM2.5 exposure during the periconception period, the odds of congenital heart defects were approximately 2% higher. Septal defects showed a somewhat stronger association, with approximately 4% higher odds per 10 μg/m³ increase. The association between PM2.5 and congenital heart defects was more pronounced during the preconception period (Yuan et al., 2023).
That study’s very large sample provided substantial statistical power, but it remained observational and used satellite-based outdoor PM2.5 estimates rather than direct measurements of each woman’s personal exposure.
A 2020 systematic review and meta-analysis illustrates why the broader literature remains less straightforward.
Hu and colleagues analyzed 26 epidemiological studies. They found statistically significant associations for several specific pollutant and heart defect combinations. For example, higher categorical NO2 exposure was associated with coarctation of the aorta, while PM10 and ozone were associated with atrial septal defects in analyses based on specified increases in pollutant concentrations (Hu et al., 2020).
Many other pollutant and congenital heart defect combinations were not statistically significant, and the studies varied in how they measured pollution, defined heart defects and accounted for potential confounders.
The earlier evidence therefore supports concern about air pollution without establishing one uniform relationship across every pollutant and every type of congenital heart defect.
Blood Proteins Offer Clues for Future Research
The new study went beyond examining pollution exposure and diagnoses.
Researchers analyzed circulating proteins in maternal serum collected during early pregnancy and in umbilical cord serum. Their models identified pollutant-specific protein signatures that reflected pollution exposure and were also associated with congenital heart defect outcomes.
Four proteins received particular attention: FGF-4, VEGF-D, macrophage stimulating protein and angiogenin.
These proteins participate in biological processes relevant to development, including cell signaling and blood vessel formation. Their associations with pollution exposure and congenital heart defects provide leads for investigating pathways that might connect environmental exposures with fetal cardiovascular development.
The results are hypothesis-generating rather than proof of a mechanism. The study did not experimentally demonstrate that pollution altered these proteins and that the resulting changes caused heart defects.
What the Results May Mean
The exposure period examined is important because cardiovascular development begins early in pregnancy. The findings also add to evidence that environmental exposures before conception may deserve attention alongside exposures occurring after pregnancy begins.
The 2023 nationwide Chinese study similarly reported a more pronounced association between PM2.5 and congenital heart defects during the preconception period (Yuan et al., 2023).
Neither study, however, establishes a precise exposure threshold below which congenital heart defects can be guaranteed not to occur.
Congenital heart defects have complex origins. Genetic factors and multiple maternal and environmental influences may contribute, and many cases have no single identifiable cause.
The results should therefore be understood as population-level associations. They cannot determine whether pollution caused an individual child’s heart defect or assign responsibility to a pregnant person or family.
Limitations
The observational design is the most important limitation. Researchers measured associations between estimated pollution exposure and congenital heart defects rather than experimentally manipulating exposure, so the study cannot establish causation.
Exposure assessment also introduces uncertainty. Estimates of outdoor air pollution do not perfectly represent what an individual actually inhales. People spend different amounts of time indoors and outdoors, travel through different environments and encounter different household exposures.
Residual confounding remains possible. Although the researchers accounted for numerous maternal, socioeconomic and geographic characteristics, observational analyses cannot fully eliminate the influence of other factors associated with both pollution exposure and pregnancy outcomes.
The protein analysis is exploratory. Associations among pollutants, circulating proteins and congenital heart defects do not establish a causal molecular pathway.
Finally, the study was conducted in China. Pollution concentrations, pollutant mixtures, environmental conditions and population characteristics differ between countries, so the magnitude of the reported associations may not apply directly to other populations.
Final Thoughts
The new study strengthens evidence connecting air pollution around conception with congenital heart defects.
Among 4,695 participants, higher exposure to PM2.5, PM10 and NO2 was associated with higher odds of congenital heart defects, with NO2 showing the strongest association. Ventricular septal defects showed associations with all three pollutants.
The findings are consistent with earlier large-scale evidence linking periconception PM2.5 exposure with congenital heart defects (Yuan et al., 2023), while a previous meta-analysis shows that associations have varied by pollutant and heart defect subtype (Hu et al., 2020).
The new contribution is the addition of maternal and umbilical cord protein data, which provides possible biological leads for future research.
The evidence does not yet show that these pollutants directly cause congenital heart defects or that the identified proteins form the causal pathway. Establishing those connections will require further research with stronger exposure assessment and studies capable of testing the proposed biological mechanisms.
Funding and Disclosures
The primary study received support from the National Key Research and Development Program of China and the Beijing Natural Science Foundation. The authors declared no competing interests. See Liang et al. (2026) for the complete funding statement.
References
Hu, C. Y., Huang, K., Fang, Y., Yang, X. J., Ding, K., Jiang, W., Hua, X. G., Huang, D. Y., Jiang, Z. X., & Zhang, X. J. (2020). Maternal air pollution exposure and congenital heart defects in offspring: A systematic review and meta-analysis. Chemosphere, 253, 126668. https://doi.org/10.1016/j.chemosphere.2020.126668
Liang, C., Ding, R., Su, S., Xie, S., Liu, J., Li, T., Sun, Z., Liu, R., Duan, J., & Yin, C. (2026). A nested case-control study of air pollution and congenital heart defects via circulating proteins. Nature Communications. https://doi.org/10.1038/s41467-026-77623-9
Yuan, X., Liang, F., Zhu, J., Huang, K., Dai, L., Li, X., Wang, Y., Li, Q., Lu, X., Huang, J., Liao, L., Liu, Y., Gu, D., Liu, H., & Liu, F. (2023). Maternal exposure to PM2.5 and the risk of congenital heart defects in 1.4 million births: A nationwide surveillance-based study. Circulation, 147(7), 565–574. https://doi.org/10.1161/CIRCULATIONAHA.122.061245
