Objective:: Asthma is one of the most common comorbid conditions in pregnancy. While asthma has been identified as an independent risk factor for cardiovascular disease in the general population, the influence of active asthma during pregnancy on future cardiac risk is unclear. Growing evidence has linked maternal active asthma to adverse pregnancy outcomes (APOs), such as hypertensive disorders of pregnancy (HDP), including preeclampsia which is a well-defined risk factor for future cardiovascular disease including altered cardiac structure and diastolic dysfunction. A thorough understanding of the relationship between pre-existing asthma and APOs may be instrumental in identifying upstream factors contributing to lifetime maternal cardiovascular risk. However, current knowledge of these relationships has been largely derived from retrospective clinical studies, which limit the precision of capturing APOs. Therefore, we investigated associations between pre-existing asthma and individual subtypes of APOs in a secondary analysis of a prospective multi-center cohort of nulliparous individuals with rigorously adjudicated pregnancy outcomes.
Study design:: We included participants from the multisite Nulliparous Outcomes in Pregnancy: Monitoring Mothers to be (nuMom2b) cohort, which recruited nulliparous individuals with a viable, singleton gestation between 60/7 and 136/7 weeks. Details of the study design have been previously described, which included medical histories in standardized interviews. This secondary analysis included individuals aged 18 years or older with a live birth and excluded those with a history of pre-pregnancy hypertension or diabetes. For the purposes of this analysis, we defined active asthma as a self-reported history of asthma and on current asthma treatment, including use of bronchodilator, inhaled steroid, or immune modulator, captured at the first trimester visit. The primary outcome was HDP and secondary outcomes included other APOs. Characteristics between participants who did and did not have asthma were compared. Univariate and multivariate logistic regression, described using odds ratios (ORs) and adjusted ORs (aORs) and 95% confidence intervals (95% CI), was used to determine risk of APOs. Models were adjusted for maternal age, study site, insurance type (marker of socioeconomic status), and smoking status at the first trimester visit. Race/ethnicity and body mass index (BMI) were excluded from fully adjusted models as race/ethnicity was considered as a factor reflective of the social determinants of health and BMI was conceptualized as within the casual pathway for developing HDP. The study was approved by all local institutional review boards, and participants gave written informed consent. Analyses were conducted using STATA (MP 17, College Station, TX).
Results: Of 8,741 individuals included, 1,521 (17.4%) reported a diagnosis of asthma at the first trimester visit, of whom 588 (38.7%) reported the use of any asthma medication. When comparing participants with and without asthma, a higher proportion of those with asthma reported smoking tobacco in the three months prior to pregnancy (20.7% vs 16.5%) (Table 1). Univariate logistic regression revealed that a diagnosis of asthma was associated with a significantly higher risk of HDP (OR: 1.21 [1.04, 1.42]). Following adjustment, risk of HDP remained significantly higher (aOR: 1.23 [1.06, 1.42]), specifically preeclampsia (aOR: 1.21, [1.02, 1.45]). Secondary analyses in participants with active asthma (ie additional reported use of asthma medication during or before the first trimester) demonstrated a significantly higher risk of HDP (aOR 1.32 [1.06–1.65]) including preeclampsia (aOR 1.27 [1.07–1.51]; in addition to spontaneous preterm birth (aOR 1.60 [1.30–1.96]).
Conclusions: In a diverse, nationally representative sample of nulliparous individuals,, a diagnosis of asthma was associated with a significantly higher risk of HDP. Active asthma increased the risk of both spontaneous preterm birth and HDP. This analysis supports the importance of identifying active asthma as a risk factor for APOs associated with a higher risk of future cardiovascular disease.