Early pregnancy sulfur dioxide exposure raises odds of congenital limb defects

By Priyanjana Pramanik, MSc.Reviewed by Susha Cheriyedath, M.Sc.Jan 20 2026

A large Chinese cohort study identifies early pregnancy as a sensitive window during which sulfur dioxide exposure is associated with higher odds of limb abnormalities, sharpening the focus on air quality and maternal health protection.

Study: Maternal exposure to ambient air pollution and risk of congenital limb defects in offspring. Image Credit chayanuphol / Shutterstock

In a recent article published in the journal Scientific Reports, researchers investigated whether women who are exposed to environmental air pollutants during the pre-conception and early pregnancy periods are more likely to have children with congenital limb defects (CLDs).

They found that women who were exposed to sulfur dioxide during the first three months after conception were more likely to have children with higher odds of being diagnosed with certain congenital limb defects, particularly limb shortening and polydactyly.

Congenital Limb Defects and Environmental Risk Factors

CLDs are common birth abnormalities involving missing, shortened, or abnormally formed limbs, including conditions such as polydactyly (the formation of extra fingers), syndactyly (webbed or fused toes or fingers), limb shortening, and clubfoot (feet that point downward at birth). They represent a common type of congenital disability globally and affect around 3.9 in 1,000 births in China.

CLDs can severely impact physical function, development, and quality of life, while also affecting caregivers and burdening health systems. Although genetic and chromosomal abnormalities explain some cases, about half of CLDs have no clearly identified cause, highlighting the potential role of environmental factors.

Increasing evidence suggests that exposure to ambient air pollution during pregnancy contributes to adverse pregnancy outcomes, including higher odds of certain congenital anomalies such as facial, oral, and cardiac defects. However, studies linking air pollution to CLDs remain scarce and inconsistent. Most previous research has relied on small case–control designs, focused on limited exposure windows, or examined single pollutants only.

Population-Based Cohort and Exposure Assessment

Researchers utilized data from the Wuhan Maternal and Child Health Management Information System, which contains detailed information on maternal, pregnancy, and birth outcomes collected through a government registration system. In addition to birth defect-related information, the dataset included sociodemographic variables, past medical histories, pregnancy-related complications, gestational histories, antenatal care utilization, delivery details, and postnatal care.

The study included 510,550 mother–infant pairs from January 2011 to September 2017. All stillbirths, live births, and pregnancy terminations due to congenital anomalies were considered. Congenital limb defects were identified through a standardized congenital disability surveillance system and classified into polydactyly, syndactyly, limb shortening, and clubfoot.

Researchers obtained daily concentrations of six major air pollutants from 21 monitoring stations across Wuhan. Individual exposure levels were estimated by incorporating the spatial distance between monitoring stations and maternal residential addresses. Exposure windows included three months before and three months after conception.

Multivariate logistic regression models were used to assess associations between pollutant exposure and CLD risk, adjusting for key maternal and infant characteristics. Stratified analyses and interaction tests were conducted to explore potential effect modification by selected sociodemographic and pregnancy-related factors.

Associations Between Pollutants and Limb Defects

Among the 510,550 births included, 1,864 infants were diagnosed with CLDs, corresponding to an incidence of 3.7 per 1,000 births. Sulfur dioxide exposure during each of the first three months after conception was significantly associated with a higher odds of the child being diagnosed with any CLD, with adjusted odds ratios ranging from 1.033 to 1.043 per 10 μg/m³ increase, indicating modest effect sizes at the individual level.

In contrast, no consistent associations were observed between overall CLD risk and exposure to other major pollutants, including particulate matter, nitrogen dioxide, carbon monoxide, or ozone, during either pre-conception or early pregnancy. However, ozone exposure during the third month of pregnancy was associated with a higher odds of syndactyly in subtype-specific analyses.

Subgroup analyses showed that sulfur dioxide exposure was particularly associated with higher odds of limb shortening and polydactyly, while no consistent associations were observed for clubfoot. Two-pollutant models confirmed the robustness of the sulfur dioxide-related findings, and sensitivity analyses yielded similar results after excluding infants with additional congenital anomalies.

Effect modification analyses suggested stronger associations among women whose occupation was classified as professional, as well as variation by maternal age, season of conception, and residential setting, although statistical evidence for interaction was not uniform across all exposure windows. Limited evidence of interaction was observed for preterm birth in specific exposure periods.

Public Health Implications and Study Limitations

Using data from a large population-based cohort, this study provides evidence that maternal sulfur dioxide exposure during early pregnancy, but not before conception, is associated with higher odds of congenital limb defects, particularly polydactyly and limb shortening. Other major air pollutants, such as ozone, carbon monoxide, nitrogen dioxide, and fine particulate matter, were not consistently associated with overall CLD risk.

The findings are consistent with several previous studies and suggest that early pregnancy may represent a biologically plausible window of increased vulnerability for limb development. Key strengths of the study include its large sample size, population-based design, detailed exposure assessment, and consideration of multiple exposure windows and potential sociodemographic modifiers.

However, limitations include potential exposure misclassification due to reliance on residential addresses and ambient monitoring stations, lack of personal exposure measurements, and limited information on indoor air pollution or maternal behavioral factors.

Despite these limitations, the study highlights the importance of reducing sulfur dioxide exposure among pregnant women and of considering potentially vulnerable subgroups in public health strategies. Although the absolute risk of CLDs at the individual level remains low, the findings provide evidence that may inform environmental policy discussions and preventive efforts to reduce congenital disabilities.