Evidence Links Genetically Determined Asthma to Spontaneous Abortion and Gestational Diabetes: Study

"However, there is insufficient conclusive evidence supporting an elevated risk of spontaneous abortion and gestational diabetes in individuals diagnosed early with asthma or the interplay between asthma and preterm birth (PTB) or preeclampsia (PE). This suggests that confounding variables may have influenced findings in prior observational studies," the researchers wrote.

Mendelian randomization is a technique that uses genetic variants as instruments to explore causal relationships between exposures (like asthma) and outcomes (such as adverse pregnancy conditions). Unlike observational studies that can be affected by confounding factors, Mendelian randomization leverages genetic information to minimize bias and strengthen causal inference.

Several empirical studies have suggested a link between asthma and adverse pregnancy outcomes (APOs). However, the precise impact of asthma on APOs remains unclear. Considering this, Xinyu Han, Department of First Clinical Medical College, Heilongjiang University of Chinese Medicine, Harbin, China, and colleagues performed univariate Mendelian randomization (UVMR) and MVMR studies to identify the causal association between asthma and APOs.

Bi-directional UVMR analyses were performed using combined information obtained from genome-wide association studies (GWAS) data. The primary method employed to assess the causal relationship between asthma or age at diagnosis and adverse APOs was the inverse variance weighted (IVW) method.

The exposure data from two sources were obtained from the IEU Open GWAS project, comprising 56,167 and 47,222 European asthma patients, respectively. Data on four adverse pregnancy outcomes were extracted from the GWAS dataset of the FinnGen collaboration. To mitigate potential confounding effects, including smoking status, frequent drinking, body mass index (BMI), and number of live births, the researchers utilized multivariable Mendelian randomization (MVMR). Additionally, rigorous sensitivity analyses were conducted to validate the robustness of the Mendelian randomization findings.

The following were the key findings of the study:

• Following the implementation of the Bonferroni adjustment, the UVMR assessment revealed that in the IVW model, asthma was significantly linked to an elevated risk of spontaneous abortion (SA) (odds ratio [OR]: 1.115) and gestational diabetes mellitus (GDM) (OR: 1.125).
• There was no causal correlation between asthma and preterm birth (PTB) (OR: 0.979) or preeclampsia (PE) (OR: 1.059).
• After adjusting for confounding factors, including smoking status, frequent drinking, BMI, and live birth quantity, the MVMR analysis shows a statistically significant causal relationship between asthma and SA or GDM.
• The investigation's findings did not reveal a substantial correlation between the age of asthma onset based on genetics and the likelihood of SA or GDM.
• The inverse MR outcomes indicate a lack of causal connection linking APOs to the incidence of asthma.
• Sensitivity analyses verified the validity of these findings.

"The study provides evidence indicating a genetic predisposition to asthma is associated with an increased risk of spontaneous abortion and gestational diabetes mellitus," the researchers wrote. "Further exploration is required to elucidate the underlying mechanisms. However, our analysis did not find conclusive evidence linking an earlier diagnosis of asthma with heightened risks of SA and GDM, nor did it reveal a significant interaction between asthma and either preterm birth or preeclampsia."

"These findings suggest that previous observational research may have been influenced by confounding variables," they concluded.

Reference:

Han, Xinyu, et al. "Asthma and Risk of Adverse Pregnancy Outcomes: a Mendelian Randomization Study." Heliyon, vol. 10, no. 13, 2024, pp. e33857.