and Anxiety in during COVID-19: A Rapid Review and Meta-Analysis

Lianne M. TOMFOHR-MADSEN, PhD1,2,3 Nicole RACINE, PhD1,2 Gerald F GIESBRECHT PhD1,2 Catherine LEBEL, PhD2,4 Sheri MADIGAN, PhD1,2

1. Department of Psychology, University of Calgary, Calgary, AB 2. Alberta Children’s Hospital Research Institute (ACHRI), Calgary, AB 3. Department of Pediatrics, University of Calgary, Calgary, AB 4. Department of Radiology, University of Calgary, Calgary, AB

Disclosure Statement: The authors report no conflicts of interest.

Financial Support: Salary support for this project was provided by the Canadian Child Health Clinician Scientist Program (CCHCSP; LTM).

Address correspondence to: Lianne Tomfohr-Madsen, PhD, Department of Psychology, University of Calgary, 2500 University Drive, NW, Calgary, AB, T2N 1N4, [email protected]

1 Abstract

Objective: The present study rapidly reviewed and meta-analyzed the worldwide prevalence of depression and anxiety among pregnant women during the COVID-19 pandemic.

Methods: A systematic search of the literature and meta-analyses were conducted.

Results: Fifteen studies with 11,091 participants met inclusion criteria. Depression was assessed in 11 studies, with a pooled prevalence of .265 or 26.5% and anxiety in 12 studies, with a pooled prevalence of .335 or 33.5%.

Conclusions: Rates of depression and anxiety during pregnancy are elevated during the pandemic. There is an urgent need to ensure screening and treatment for depression and anxiety during pregnancy.

Keywords: Pregnancy, COVID-19, Mental Health, Depression, Anxiety, Meta-Analysis

2 Exposure to natural disasters and disease outbreaks increases the prevalence of mental health problems, including during pregnancy.1 Early reports from pregnant cohorts around the world suggest elevated depression and anxiety symptoms among pregnant individuals during the

COVID-19 pandemic; however, the exact prevalence is unknown. The aim of the current study was to conduct a rapid review of the prevalence of depression and anxiety experienced in pregnancy during the COVID-19 pandemic and examine moderators of these associations.

Study Design

This rapid review was registered with PROSPERO [CRD42020205186]. PRISMA guidelines were followed for search strategy, article screening, and data extraction.2 A health sciences librarian conducted electronic searches in PsycINFO, Cochrane Central Register of

Controlled Trails (CENTAL), EMBASE, and MEDLINE up to August 28th, 2020. The search strategy included terms from three themes: 1) mental health and illness (including depression and anxiety), 2) COVID-19, and 3) pregnancy. Terms were searched as subject headings and keywords. Adjacency operators and truncation symbols were used to capture variations in key terms. A database of prints pre-publication for studies that matched the key terms

“pregnan*” and “COVID-19” was also searched.

Inclusion criteria for the current study were: 1) study participants were pregnant; 2) a proportion of individuals in the study met clinical cut-offs for anxiety or depressive symptoms via a validated self-report measure or healthcare professional diagnosis; 3) data was obtained after the onset of COVID-19, 4) participants were > 18 years; 5) study was empirical; and 6) written in English. Qualitative or case study reports were excluded. Using Covidence software, one author reviewed all titles and abstracts emerging from the search strategy to determine inclusion eligibility. A second author reviewed 20% of titles and abstracts for

3 reliability with Cohen’s Kappa=.87. Disagreements were resolved via consensus. Subsequently, full text articles were reviewed by both coders and reliability for the full text review yielded

Cohen’s Kappa=.81. Disagreements were resolved by discussion.

Data Extraction

Prevalence data of clinically elevated anxiety and depressive symptoms were extracted by two coders. Each coder conducted 50% of the extractions and all included studies were double extracted for reliability purposes. All studies were examined to ensure those included represented independent samples. Moderators extracted were: 1) study quality; 2) participant age (mean); 3) geographic location, 4) gestation (weeks pregnant), and 5) % minority of the sample.

Study Quality

A short 6-item study quality measure was used based on modified versions of the

National Institute of Health Quality Assessment Tool for Observation Cohort and Cross-

Sectional Studies;3,4 scores ranged from 0-6.

Data Analysis

All data was entered into Comprehensive Meta-Analysis (CMA version 3.0)5 where pooled prevalence and 95% confidence intervals (CIs) were computed. Random-effects models were used. Pooled prevalences were weighted by the inverse of their variance, giving greater weight to studies with larger samples. Tests of heterogeneity were examined with and without outliers to determine if outliers influenced between-study heterogeneity, which was examined using Q and I2 statistics. A Q statistic or I2 statistic greater than 75% suggests moderator analyses should be explored. Categorical moderators were only conducted when k ≥

10 and with a minimum cell size of k > 3 were available. Random-effect meta-regressions were

4 calculated for continuous moderators. The Egger test and funnel plots were used to examine publication bias.

Results

The search yielded 361 non-duplicate records (Fig. 1a). 31 full text articles were reviewed and 15 met full inclusion criteria.

Study Characteristics

Across all 15 studies, mean participant age was 30.93 years (range, 29.2-32.98) and mean gestational age was 21.64 weeks (range 7.04-31.63) (Table 1). Ten countries were represented, across North America (n=5, 33.3%), East Asia (n=4; 26.7%), Europe (n=3, 20%), West Asia

(n=2, 13.3%), and South Asia (n=1, 7%).6-16 Mean study quality was 3.8 out of 6 (range: 2-5).

Pooled Prevalence of Clinically Elevated Prenatal Depressive Symptoms During COVID-19

A random-effects meta-analysis of 11 studies revealed a pooled event rate of .265 (95%

CI: .217, .319; Fig 1b). The funnel plot was asymmetrical; however, the Egger test was not significant (p < .20). There was significant between-study heterogeneity (Q = 203.47, p < .001, I2

= 95.09); thus, maternal age and gestational age were explored as potential moderators. The event rate of prenatal depression increased as maternal age increased (Z = 2.67; p < .01).

Gestational age was not a significant moderator of event rate (Z = 0.60; p < .55)

Pooled Prevalence of Clinically Elevated Prenatal Anxiety Symptoms During COVID-19

A random-effects meta-analysis of 12 studies revealed a pooled event rate of .335 (95%

CI: .230, .497); Fig 1c), indicating a prevalence of clinically significant prenatal anxiety across studies of 33.5%. The funnel plot was symmetrical and the Egger test was not significant (p =

45). There was significant between-study heterogeneity (Q = 1381.48, p < .001, I2 = 99.20); thus,

5 potential moderators were explored. The event rate of prenatal anxiety increased with maternal age (Z = 2.14; p < .05). Gestational age was not a significant moderator (Z = -0.73; p < .47).

Comment

In this rapid review and meta-analysis, we observed significantly elevated rates of antenatal depression and anxiety during the COVID-19 pandemic compared to historical norms.17,18 Older mothers were more likely to report elevated depression and anxiety symptoms.

Meta-analysis of the prevalence of depression and anxiety suggests elevated rates at levels relevant to clinicians and policy makers. In line with pre-pandemic practice guidelines, this study suggests the need for screening for depression and anxiety in pregnancy during the pandemic.19,20

When elevated rates of depression and anxiety are detected, it is imperative that women are offered services that meet their treatment preferences (i.e., pharmacological or psychological) and can be accessed remotely.21,22

6 Acknowledgment(s)

We would like thank Nicole Dunnewold, MLIS, from the University of Calgary, for her assistance with the search strategy. Funding was provided by the Canadian Child Clinician

Scientist Research Program (LTM), the Canada Research Chairs Program (SM, CL) and Alberta

Innovates (NR).

7 References

1. Lee DTS, Sahota D, Leung TN, Yip ASK, Lee FFY, Chung TKH. Psychological responses of pregnant women to an infectious outbreak: A case-control study of the 2003 SARS outbreak in Hong Kong. Journal of Psychosomatic Research. 2006;61(5):707-713. 2. Moher D, Shamseer L, Clarke M, et al. Preferred reporting items for and meta-analysis protocols (PRISMA-P) 2015 statement. Systematic Reviews. 2015;4(1):1. 3. Wells GA, Shea B, Higgins JP, Sterne J, Tugwell P, Reeves BC. Checklists of methodological issues for review authors to consider when including non-randomized studies in systematic reviews. Res Synth Methods. 2013;4(1):63-77. 4. National Heart L, and Blood Institute. Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. https://www.nhlbi.nih.gov/health-topics/study-quality- assessment-tools. Published 2014. Accessed. https://www.nhlbi.nih.gov/health-topics/study-quality-assessment-tools. 5. Compehensive Meta-Analysis Software (CMA) [computer program]. Version 3: Biostat; 2013. 6. Davenport MH, Meyer S, Meah VL, Strynadka MC, Khurana R. Moms Are Not OK: COVID-19 and Maternal Mental Health. Frontiers in Global Women's Health. 2020;1. 7. Cameron EE, Joyce KM, Delaquis CP, Reynolds K, Protudjer JLP, Roos LE. Maternal psychological distress & mental health service use during the COVID-19 pandemic. Journal of Affective Disorders. 2020;276:765-774. 8. Lebel C, MacKinnon A, Bagshawe M, Tomfohr-Madsen L, Giesbrecht G. Elevated depression and anxiety symptoms among pregnant individuals during the COVID-19 pandemic. J Affect Disord. 2020;277:5-13. 9. Durankus F, Aksu E. Effects of the COVID-19 pandemic on anxiety and depressive symptoms in pregnant women: a preliminary study. J Matern Fetal Neonatal Med. 2020;10.1080/14767058.2020.1763946:1-7. 10. Suzuki S. Psychological status during the first trimester of pregnancy under the COVID- 19 epidemic in Japan. The Journal of Maternal-Fetal & Neonatal Medicine. 2020;10.1080/14767058.2020.1793319:1-2. 11. Wu Y, Zhang C, Liu H, et al. Perinatal depressive and anxiety symptoms of pregnant women during the coronavirus disease 2019 outbreak in China. Am J Obstet Gynecol. 2020;223(2):240 e241-240 e249. 12. Ahorsu DK, Imani V, Lin C-Y, et al. Associations Between Fear of COVID-19, Mental Health, and Preventive Behaviours Across Pregnant Women and Husbands: An Actor- Partner Interdependence Modelling. International Journal of Mental Health and Addiction. 2020;10.1007/s11469-020-00340-x. 13. Ceulemans M, Hompes T, Foulon V. Mental health status of pregnant and breastfeeding women during the COVID-19 pandemic: A call for action. Int J Gynaecol Obstet. 2020;10.1002/ijgo.13295. 14. Patabendige M, Gamage MM, Weerasinghe M, Jayawardane A. Psychological impact of the COVID‐ 19 pandemic among pregnant women in Sri Lanka. International Journal of Gynecology & Obstetrics. 2020.

8 15. Dagklis T, Tsakiridis I, Mamopoulos A, Athanasiadis A, Pearson R, Papazisis G. The impact of the COVID ‐ 19 lockdown on antenatal mental health in Greece. Psychiatry and Clinical Neurosciences. 2020;10.1111/pcn.13135. 16. Silverman ME, Medeiros C, Burgos L. Early pregnancy mood before and during COVID-19 community restrictions among women of low socioeconomic status in New York City: a preliminary study. Archives of Women's Mental Health. 2020;10.1007/s00737-020-01061-9. 17. Dennis CLaF-HKaSR. Prevalence of antenatal and postnatal anxiety: Systematic review and meta-analysis. British Journal of Psychiatry. 2017;210(5):315--323. 18. Gavin NIaGBNaLKNaM-BSaGGaST. Perinatal depression: a systematic review of prevalence and incidence. Obstetrics \& Gynecology. 2005;106(5):1071--1083. 19. ACOG Committee Opinion No. 757: Screening for Perinatal Depression. Obstetrics & Gynecology. 2018;132(5):e208-e212. 20. Gynaecologists. RAaNZCoOa. Mental health care in the perinatal period (College Statement: C‐‐ Obs 48). Mar 2012; revised July 2018. . 21. Ride J, Lancsar E. Women’s Preferences for Treatment of Perinatal Depression and Anxiety: A Discrete Choice Experiment. 2016;11(6):e0156629. 22. Arch JJ. Cognitive behavioral therapy and pharmacotherapy for anxiety: Treatment preferences and credibility among pregnant and non-pregnant women. Behaviour research and therapy. 2014;52:53--60.

9 Tables

Table 1: Characteristics of Included Studies

First Author ,Year, Na Mean Age Mean % Country Mental Name of Data Collection Reference (years) Weeks Minorit Health Mental Health Date Gestation y Group Measures Measure (Anx, Dep) Anx, Dep HADS, HADS March/April Ahorsu, 2020 290 29.24 15.04 - Iran 2020 Cameron, 2020 61 32.98 25.09 14.30 Canada Anx, Dep PASS, EPDS April 2020 Ceulemans, 2020 2421 - - - Belgium Anx, Dep GAD-7, EPDS - 269-anxiety Anx, Dep STAI, EPDS 215- Dagklis, 2020 depression - - - Greece - Canada Anx, Dep STAI, EPDS 290-anxiety (73%) 148- International Davenport, 2020 depression 32.7 26.9 9.7 (27%) April/May 2020 Durankus, 2020 260 29.56 7.04 - Turkey Dep EPDS - 1757-anxiety Anx, Dep PROMIS, 1764- EPDS Lebel, 2020 depression 32.4 22.5 12.9 Canada April 2020 Liu, 2020 1947 - - - China Anx SAS February 2020 Mappa, 2020 178 33 18 1.1 Italy Anx STAI March 2020 Patabendige, 2020 257 29.2 23.3 - Sri Lanka Anx, Dep HADS, HADS April-May 2020 United Anx GAD-7 Preis, 2020 788 29.2 25.3 22.8 States April 2020 United Dep EPDS February-June Silverman, 2020 485 - - 10 States 2020 Suzuki, 2020 117 - - - Japan Anx, Dep GAD-2, March-April

10 Whooley-2 2020 Dep EPDS January-February Wu, 2020 1285 30 - 3.5 China 2020 Yue, 2020 308 31.02 31.63 - China Anx SAS February 2020 Note: BAI: Beck Anxiety Inventory; EPDS: Edinburgh Scale; GAD-2: Generalized Anxiety Disorder 2-Item;

GAD-7: Generalized Anxiety Disorder 7-Item; HADS: Hospital Anxiety and Depression Scale; PASS: Perinatal Anxiety Screening

Scale; PROMIS: Patient-Reported Outcomes Measurement Information System; SAS: Self-Rating Anxiety Scale; STAI: State-Trait

Anxiety Inventory. Anx: Anxiety, Dep: Depression, -: missing. aTotal sample size entered in the meta-analysis.

11 Figure Legend

Figure 1a: PRISMA diagram and forest plots.

12 Panel A

13