Early pregnancy anxiety during the COVID-19 pandemic: preliminary findings from the UCSF ASPIRE study

This nationwide population-based study includes data from the University of California, San Francisco Assessing the Safety of Pregnancy in the Coronavirus Pandemic Prospective Cohort Study (UCSF ASPIRE). Only pregnant persons < 10 weeks’ gestation were eligible to enroll. Participants were recruited as two distinct samples: 1) a community sample and 2) Society for Assisted Reproductive Technology (SART) sample. The community sample included participants who acquired information about the study through either social media advertisement, the lay press, partnerships with online media companies focused on disseminating information to pregnant persons, traditional clinics providing prenatal care, or word of mouth. The SART sample comprised participants recruited from a network of fertility clinics nationwide with clinical encounters around the time of conception, allowing for precise gestational dating. Both cohorts of ASPIRE participants were prospectively followed throughout their pregnancy and postpartum courses. Prior to enrollment, written, informed consent was obtained. Participants completed baseline questionnaires regarding sociodemographic variables, history of COVID-19 exposure and/or infection, and mental health during the COVID-19 pandemic throughout their pregnancy. Study data were collected and managed using REDCap electronic data capture tools hosted at the University of California, San Francisco [24, 25]. Additionally, participants were sent routine short questionnaires to record their symptoms of COVID-19 infection. Participants were eligible for remuneration after survey completion at multiple time points during this longitudinal study. This study was approved by the UCSF Institutional Review Board.

From May 2020 through February 2021, 5,207 pregnant persons across 48 states were enrolled into the UCSF ASPIRE study and completed the baseline questionnaire. Of respondents, 4,303 (82%) completed the Generalized Anxiety Disorder 7 (GAD-7) questionnaire and were included in this analytic sample. The mean age of participants was 33 years of age with over 65% of participants between age 31–40. The regional distribution was similar with the highest recruitment in the West (29.7%) and lowest from the Northeast (19.5%); otherwise, 24.8% and 25.9% were recruited from the Midwest and South, respectively. Close to 26% of participants were recruited from fertility clinics and comprised the SART cohort while roughly 74% were recruited through community.

Upon enrollment, pregnant persons are asked to complete the GAD-7 questionnaire administered electronically. The GAD-7 is a validated 7-item scale which serves as a screening tool and severity indicator of generalized anxiety disorder and has been recommended to measure perinatal anxiety by the National Institute for Health and Care Excellence [26, 27]. The internal consistency of the GAD-7 has previously been demonstrated to be excellent (Cronbach alpha 0.92) with good test–retest reliability as well (intraclass correlation 0.83) [27]. The questionnaire requires respondents to identify how often they have been bothered by a list of symptoms over the last two weeks including “feeling nervous, anxious, or on edge, not being able to stop or control worrying, and trouble relaxing”, to name a few. The severity of symptoms are categorized as one of four options including “not at all”, “several days”, “more than half the days”, and “nearly every day” which corresponds to 0, 1, 2, or 3 points, respectively. Scoring for anxiety symptom severity is as follows: Minimal (0–4), Mild (5–9), Moderate (10–14), and Severe (15 +). A cut-off of 10 or more indicates clinically significant anxiety symptoms [27].

Characteristics interrogated for their association with anxiety during pregnancy include: maternal age stratified based on the distribution of anxiety in our study (18 to 30, 31 to 35, 36 to 40, 41 or greater years), maternal race/ethnicity (Hispanic, Non-Hispanic White, Black/African American, Asian, Native American, and Pacific Islander), maternal education (Less than a college degree, College degree, Master’s degree, or Professional degree), partner status (Married or partnered, other), income (Less than $99,999, $100,000 to 250,999, $251,000 or more), insurance status (private insurance, other), working outside of the home (none of the time, some of the time, all the time), employment in health care (yes, no), employment status (homemaker, part-time, full-time, unemployed), previous pregnancy and live birth (yes, no), prior miscarriage (yes, no), care through a fertility clinic this pregnancy (yes, no), history of anxiety (yes, no), and history of depression (yes, no).

We also investigated COVID-19 and economic-specific variables, including history of COVID-19 infection among oneself or household contacts (yes, no), COVID-19 death among friends or family residing in the same household (yes, no), job loss (yes, no), reduced hours at work (yes, no), inability to pay rent or mortgage (yes, no), and worry about the health of self or loved ones during the COVID-19 pandemic (yes, no). The Perceived Stress Scale (PSS) [28], a reliable measure of the degree of stress experienced based on situations occurring over the past month, was also investigated to determine the possible impact of COVID-19 related stress on early pregnancy anxiety symptoms. The PSS has an internal reliability of 0.6 and while there are no established cutoffs, we used our population norms to classify low (≤ 4) vs moderate to high (> 4) levels of stress [28].

An important strength of this work is the large cohort size and its national representation. Beyond the pandemic, this study represents one of the few studies to date to capture the prevalence and risk factors for anxiety symptoms during the first trimester. These results therefore represent novel information regarding a gestational time that has been historically difficult to access. We anticipate that future results from this longitudinal cohort will clarify the natural history and later pregnancy implications of anxiety initially identified in the first trimester. Nevertheless, there are several limitations to be considered as well. Although we utilized a gold-standard instrument for interrogating anxiety symptoms, questionnaire-based assessments lack the rigor of a clinical interview. Further, our cohort represents a population of persons interested and able to participate in a longitudinal seroprevalence study of COVID-19, and our recruitment scheme utilized both social media and fertility clinic-based recruitment and required enrollment prior to 10 weeks of gestation. As such, while this study is nationwide, it includes predominantly White, non-Hispanic women of higher socioeconomic status, thus, the generalizability of our findings should be considered with these factors in mind. We did not see a difference in anxiety symptoms based on the month enrolled into the cohort. However, as burden from the COVID-19 has differed by region throughout this period, it is possible there is an association between regional surge and anxiety symptoms we were unable to disentangle. While this could be a potential factor associated with the presence of anxiety symptoms, we do not feel this confounded the associations otherwise seen in this analysis. We sought to ascertain if working on-site differentially impacted anxiety symptoms when compared to employment that allowed some or completely virtual options. While this variable was not a significant predictor in our analysis, we acknowledge the structure of the question may have impacted any potential association. Finally, our findings likely do not accurately reflect the experience of persons with less interest in or capacity for research participation or the experience of those who did not become aware of their pregnancy until after 10 weeks.