Impact of GDM on Asthma During Pregnancy and Postpartum

New research from Cleveland Clinic highlights the importance of early, universal screening for asthma and gestational diabetes mellitus (GDM) during pregnancies.

The study, which appears in The Journal of Allergy and Clinical Immunology: In Practice, indicates that GDM is associated with an increased risk of asthma exacerbations during pregnancy and underscores the need for timely and effective interventions to manage blood glucose levels in pregnant patients with pre-existing asthma.

"Both conditions are linked to numerous maternal and perinatal adverse outcomes — longer hospital stays, pregnancy loss, lower birth weights, preterm birth and preeclampsia, for example," says Peng Zhang, MD, MSc, the study's lead author and a critical care specialist at Cleveland Clinic.

She continues, “We know that insulin resistance in nonpregnant individuals is associated with worse asthma outcomes, and given the fact that pregnant patients with asthma have a higher risk of developing GDM, we wanted to learn more about the impact GDM has on asthma and the risk of asthma exacerbation.”

Study design and findings

The retrospective, cohort study included the electronic health records of pregnant patients at Cleveland Clinic between 2010 and 2023. The authors excluded patients with pre-existing diabetes mellitus or chronic lung diseases. Asthma exacerbations were defined as the need for an oral corticosteroid (OCS) prescription.

The study cohort was comprised of 10,985 pregnant patients with asthma. Of these, 1,492 patients (13.6%) were diagnosed with GDM and 9,493 did not have GDM. In the study, pregnant patients with GDM tended to be older (median age 30.0 vs 27.5 years, bootstrap estimated difference 2.5 years, 95% CI: 2.2-2.9), had higher BMIs at the start of pregnancy (mean BMI: 31.2 vs 28.3 kg/m², bootstrap estimated difference 2.7, 95% CI: 2.0-3.3) and had higher blood glucose levels (median level 92.00 vs 86.00 mg/dL, bootstrap estimated difference 5.72 mg/dL, 95% CI: 4.00-7.00). Patients with GDM also tended to be white (74.3% vs 69.2%, P < .001) and privately insured at the time of delivery (private insurance 68.8% vs 64.0%, P < .001).

“One of the other important findings from this study was that patients who developed GDM during their pregnancy were more likely than their non-GDM counterparts to have received at least one course of OCS prescription in the year before pregnancy [(14.3% vs 9.8%, P < .001)],” says Dr. Zhang. “This showed us that patients who developed GDM were more likely to have a history of pre-pregnancy asthma exacerbations.”

The authors found that GDM was associated with a higher risk of asthma exacerbations during pregnancy (adjusted odds ratio [OR] = 1.36, 95% CI: 1.10-1.67), but the association was less so postpartum (adjusted OR = 1.11, 95% CI: 0.92-1.33).

The group also performed subgroup analyses for 4,331 individuals with documented blood glucose levels during pregnancy. After adjusting for other covariates, they found a positive association between blood glucose levels and a higher risk of asthma exacerbation during pregnancy. For each doubling of the blood glucose level, the risk of asthma exacerbations during pregnancy increased 2.02 times (adjusted OR = 2.02 for log₂[-blood glucose level], 95% CI: 1.45-2.81).

Key factors associated with increased asthma exacerbations

Patients with a prepregnancy history of asthma (during pregnancy: adjusted OR = 3.05, 95% CI: 2.53-3.66; first year postpartum: adjusted OR = 2.98, 95% CI: 2.53-3.49) were found to have a higher likelihood of asthma exacerbations during pregnancy and postpartum. Older age is another risk factor, and the group found that the risk of asthma exacerbation increased by 4% during pregnancy with each 1-year increment of maternal age (adjusted OR = 1.04, 95% CI: 1.02-1.05) and increased by 1% in the postpartum period (adjusted OR = 1.01, 95% CI: 1.00-1.03). Medicaid coverage at the time of delivery (adjusted OR = 1.35, 95% CI: 1.09-1.66 during pregnancy, and adjusted OR = 1.25, 95% CI: 1.05-1.49 postpartum, respectively) was also associated with higher risk.

“There were a couple of factors that were associated with a higher risk of asthma exacerbations during pregnancy but weren’t as strong during postpartum,” says Dr. Zhang. “For example, Medicaid coverage was associated with a higher number of OCS prescriptions during pregnancy, but not postpartum.”

She continues, “Additionally, a higher BMI at the onset of the pregnancy was associated with a higher risk during pregnancy, but this association was no longer meaningful after controlling for blood glucose levels. This indicated to us that the severity of GDM is directly correlated with the risk of asthma exacerbations during pregnancy – which is different than just being a confounding variable associated with prepregnancy obesity.”

The authors believe their study is the first to provide real-world data to characterize the association between GDM and asthma and that is also the largest to date to assess the factors that contribute to asthma exacerbation during pregnancy and the first year postpartum.

"We know there is a link between insulin and asthma in our non-pregnant patients with asthma and Type 2 diabetes (T2DM),” says Dr. Zhang. “We don’t fully understand the exact pathobiological mechanisms at play, but at least with our pregnant patients, we can surmise that the physiological surge of local and placental hormones during pregnancy leads to a state of mild insulin resistance. I hope our study helps providers recognize that our pregnant patients need better asthma management and the importance of early intervention.”