The prevalence of mental ill-health in women during pregnancy and after childbirth during the Covid-19 pandemic: a Systematic review and Meta-analysis

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51 Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) is a respiratory disease 52 causing coronavirus. SARS-CoV has caused the Middle East Respiratory Syndrome 53 (MERS), SARS-CoV in Hong King and SARS-CoV-2 (COVID-19). COVID-19, to date, have 54 had the highest mortality and morbidity globally , thus reaching the pandemic status. In 55 comparison to research conducted to explore the impact of pandemics on the general 56 wellbeing, there appears to be a paucity on its association with women’s mental health. 57 Many pregnant women have reported that the pandemic negatively impacted their mental 58 health. 59 60 Aim 61 This study aimed is to explore the prevalenc e of the impact of the COVID-19, MERS and 62 SARS pandemics on the mental health of pregnant women. 63 64

65 A study protocol was developed and published in PROSPERO ( CRD42021235356) to 66 explore a number of key objectives. For the pur pose of this study PubMed, Science direct, 67 Ovid PsycINFO and EMBASE databases were searched from December 2000 – July 2021. 68 The search results were screened, first by title, and then by abstract. A meta-analysis was 69 conducted to report the findings. 70 71

72 There were no studies reporting the mental health impact due to MERS and SARS. We 73 systematically identified 316 studies that report ed on the mental health of women that were 74 pregnant and soon after birth. The meta-analysis indicated 24.9% (21.37%-29.02%) of 75 pregnant women reported symptoms of depressi on, 32.8% (29.05% to 37.21%) anxiety, 76 29.44% (18.21% - 47.61%) stress, 27.93% (9.05%-86.15 %) PTSD, and 24.38% (11.89%-77 49.96%) sleep disorders during the COVID-19 pandemic. Furthermore, the I 2 test showed a 78 high heterogeneity value. 79 80

81 The importance of managing the mental health during pregnancy and after-delivery 82 improves the quality of life and wellbeing of mothers. Developing an evidence based mental 83 health framework as part of pandemic preparedness to help pregnant women would improve 84 the quality of care received during challenging times. 85 86

Covid-19, Mental ill-health, Depression, Anxiety, Stress, Pregnancy, Antenatal 87 care, Postnatal care, Wellbeing 88 89 90 91 92 93 94 . CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted June 14, 2022. ; https://doi.org/10.1101/2022.06.13.22276327doi: medRxiv preprint 3

95 Since December 2019, the coronavirus disease 2019 (COVID-19) pandemic caused by 96 severe acute respiratory syndrome coronav irus 2 (SARS-Cov-2) has spread around the 97 world unprecedentedly, overwhelming healthcare systems around the world. On March 11, 98 2020, the World Health Organization (WHO) declared COVID-19 a global pandemic. This 99 led to a rippling impact of the virus on healthcare systems and patients who needed to 100 access care for both physical and mental health and wellbeing [1]. There was concern that 101 the acute intensive care services would not be able to cope with the growing volume of 102 affected individuals requiring ventilatory supp ort. To reduce viral transmission and relieve 103 pressure on healthcare systems, many countries, including the United Kingdom (UK), 104 entered lockdown. 105 People were ordered by law to stay at home. In many hospitals, staff were redeployed and 106 departments were adapted or converted to COVID-19 services. However, women who were 107 pregnant and needed to give birth were identified as a vulnerable group and the ability to 108 provide good quality maternity care during the Covid-19 pandemic was prioritised. 109 110 It is well documented that public health emergencies not only have a huge impact on the 111 physical health of a population but also results in an increase in mental ill-health including: 112 conditions such as depression; post-traumatic stress disorder (PTSD); substance use 113 disorder; behavioural disorders; noncomplianc e with public health directives, domestic 114 violence; and child abuse[5]. These can arise from triggers directly related to the infection, 115 for example, the neuroinvasive potential of SARS-CoV-2 may affect brain function and 116 mental health. The treatment for COVID-19 may also have adverse effects on mental health 117 and indirectly may contribute to anxiety. In addition, the imposition of unfamiliar and 118 undesired public health measures including social isolation strongly correlates with the 119 likelihood of clinically significant depression or anxiety [5,6]. These findings were echoed in 120 an evaluation of severe acute respiratory syndrome (SARS) epidemic with increases in 121 PTSD, stress, and psychological distress in both patients and clinicians. Affected individuals 122 and communities were motivated to comply with quarantine to reduce the risk of infecting 123 others and to protect their community’s health. However emotional distress tempted some to 124 consider violating the recommended public health measures[6]. 125 126 One such vulnerable group is women during their pregnancy and after childbirth. Maternal 127 mental ill-health has been an international public health concern for many years[ 1] with 128 millions of women experiencing mental il l-health during pregnancy and after childbirth[ 1, 2]. 129 Common mental disorders (depression, anxiety) rank third in the list of the burden of disease 130 globally and maternal mental ill-health affects up to 10% of women during pregnancy and 131 13% of women after childbirth[6, 7]. It is well documented that compromised maternal mental 132 ill-health is associated with adverse short and long-term consequences for the mother and 133 the baby[12, 13] . However, limited data exists on the prevalence of mental ill-health in 134 women who were pregnant and gave birth during the COVID-19 pandemic. This systematic 135 review and meta-analysis therefore assessed th e prevalence of mental ill-health in women 136 during pregnancy and after childbirth during the Covid-19 pandemic. We then compared our 137 findings in relation to other global pandemics including severe acute respiratory syndrome 138 (SARS) and Middle Eastern Respiratory Syndrome (MERS). 139 140 141 . CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted June 14, 2022. ; https://doi.org/10.1101/2022.06.13.22276327doi: medRxiv preprint 4 142 143

144 A systematic methodology was developed along with a relevant protocol that was peer 145 reviewed and published in PROSPERO (CRD42021235356). The developed method 146 focuses on the prevalence of mental ill-health in women during pregnancy and after 147 childbirth during the Covid-19 pandemic. 148 149 Search criteria 150 The search criteria was developed based upon the research question using PubMed, 151 Science direct, Ovid PsycINFO and EM BASE databases: PubMed, Science direct and 152 EMBASE. We developed a wide search criteri on to ensure the inclusion of any pregnant 153 women with existing gynaecological conditions. The MeSH terms used include (COVID) OR 154 (SARS-CoV-2) AND (SARS) AND (MERS) AND ((mental health) OR (depression) OR 155 (anxiety) OR (PTSD) OR (psychosis) OR (unipolar) OR (bipolar)) AND ((PCOS) OR (fibroid) 156 OR (endometriosis) OR (pre-eclampsia) OR (still birth) OR (GDM) OR (preterm birth) OR 157 (women's health) OR (pregnant women) OR (pregnancy)). 158 Screening eligibility criteria 159 All studies published in English were included from 20 th December 2019 to 31 st July 2021. 160 Screening and data extraction were performed by two authors independently. Initially, titles 161 and abstracts were reviewed to determine the relevance. A PRISMA diagram was 162 completed based on the eligibility steps completed. 163 164 Data extraction 165 Full texts of the included papers were reviewed carefully to extract data including time and 166 locations of the study, participants and sample size, mean age, gestation, days since 167 childbirth, prevalence of mental symptoms, data collection tools used, and cut-offs scores 168 applied. Any disagreement was discussed and resolved by consensus between two authors. 169 For studies with both COVID-19 cohort and non-COVID-19 cohort, we only used data of the 170 COVID-19 cohort and the p-value comparing them. Studies from SARS and MERS were 171 also reviewed in full to ensure the eligibility criteria was met. For studies reporting mean 172 (SD) or median (IQR) of the scales measuring mental symptoms instead of prevalence rates 173 were included and a simulation method assuming normal distribution was applied to 174 generate the corresponding prevalence rates. 175 Risk of bias assessment 176 A risk of bias assessment was completed with a RoB table. 177 Data analysis 178 Random effects model with restricted maximum-likelihood estimation method was applied 179 for meta-analysis and I-square statistic was used to evaluate heterogeneity across studies. 180 The pooled prevalence rates of anxiety, depressi on, PTSD, stress and sleep disorder with 181 95% confidence interval (CI) were computed. Subgroup analysis was conducted in terms of 182 trimester. Sensitivity analysis was performed to assess the robustness of the results. 183 Potential publication bias was assessed with funnel plot and Egger’s test. Analyses were 184 conducted with the R studio (version 1.4.17.17) and STATA 16.1. 185 . CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted June 14, 2022. ; https://doi.org/10.1101/2022.06.13.22276327doi: medRxiv preprint 5 186

187 188 Our initial search identified a total of 1603 papers and 523 studies were excluded after 189 screening by titles and abstracts. After full-text evaluation, 217 and 99 studies were included 190 in the systematic review and meta-analysis, respectively. The PRISMA (Preferred Reporting 191 Items for Systematic Reviews and Meta-analyses) flowchart was illustrated in Figure 1. 192 Inclusion and exclusion criteria 193 All COVID-19, SARS and MERS studies that evaluated the mental health of pregnant 194 women that may or may not have gynaecological conditions that were reported in English 195 between December 2000 – July 2021 were included. All other studies were excluded from 196 this analysis. 197 Characteristics of studies 198 A total of 217 COVID-19 studies were included and 99 studies were meta-analysed. These 199 studies were reported from various parts of t he world, as indicated in the characteristics 200 Table 1. We did not identify SARS and MERS studies that were suitably aligned to the 201 eligibility criteria of our study. 202 Study design, source of data, data collection method and sample size 203 All 217 studies used different study designs; 107 cross-sectional, 7 cohort and 7 case 204 controlled. A total of 23 qualitative studies us ed self-reported methods of data collection. All 205 studies reported a variety of mental health symptoms. Real-world data from hospital 206 admissions were used in 5 studies whilst 2 extracted data from patient medical records. The 207 217 study pool comprised of a sample of 638,889 pregnant women whilst 6898 were within 208 90 days of delivery. The sample sizes used within the studies varied considerably; 129 209 comprised of approximately 500, 40 with 500–999, 18 with 1000–1999 and 24 ≥ 2000 210 women. 211 Stages of pregnancy assessed 212 A total of 99 studies reported pregnant women during their first, second and third trimester. 213 Site of data collection 214 Many studies reported that data collection took place during routine antenatal or postnatal 215 visits in outpatient departments, tertiary/provincial hospitals, secondary level or district 216 hospitals and primary healthcare facility level. 217 Of the 217 systematically included studies, 64 reported data on depression, 82 on anxiety, 218 20 on stress, 7 on PTSD, and 8 on sleep disorder. Detailed characteristics of the 219 systematically included studies and those meta-analysed are listed in Table 1 and 2 (table 2 220 supplementary material). 221 222 223 224 . CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted June 14, 2022. ; https://doi.org/10.1101/2022.06.13.22276327doi: medRxiv preprint 6 225 Table 1. 217 studies in systematic review and meta-analysis 226 227 ID Authors Publication Year Country Sample size p-value 1 Wu Y 2020 China 1285 0.01 2 Duranku ş F 2020 Turkey 260 N/A 3 Moyer CA 2020 United States 2740 p<0.001 4 Zanardo V 2020 Italy 91 p<0.001 5 López-Morales H 2021 Argentina 43 N/A 6 Salehi L 2020 Iran 220 N/A 7 Pariente G 2020 Israel 223 0.002 8 Ostacoli L 2020 Italy 163 N/A 9 Ravaldi C 2021 Italy 200 p<0.001 10 Zhou Y 2020 China 544 N/A 11 Kahyaoglu Sut H 2021 Turkey 403 N/A 12 Hui PW 2021 Hong Kong (China) 925 p<0.05 13 Oskovi-Kaplan ZA 2021 Turkey 223 N/A 14 Sinaci S 2020 Turkey 246 N/A 15 Dong H 2021 China 156 N/A 16 Hocaoglu M 2020 Turkey 283 p=0.01 17 Liang P 2020 China 845 N/A 18 Preis H 2020 US 4451 N/A 19 Yue C 2021 China 308 N/A 20 Maharlouei N 2020 Iran 540 N/A 21 Medina-Jimenez V 2020 Mexico 503 N/A 22 Ceulemans M 2020 Belgium 3445 N/A 23 Milne SJ 2020 Ireland 70 N/A 24 Matsushima M 2020 Japan 1777 N/A 25 Ceulemans M 2021 Ireland, Norway, Switzerland, the Netherlands, and the UK 3545 N/A 26 Gildner TE 2020 US 1856 N/A 27 Shayganfard M 2020 Iran 103 N/A 28 Yassa M 2020 Turkey 203 N/A 29 Silverman ME 2020 US 516 p<0.001 30 Muhaidat N 2020 Jordan 944 N/A 31 Thayer ZM 2021 US 2099 N/A 32 Jiang H 2021 China 1873 N/A 33 Zhang Y 2021 China 560 N/A 34 Mayeur A 2020 France 88 N/A 35 Lin W 2021 China 751 N/A 36 Zhang CJP 2020 China 1901 N/A 37 Yang X 2021 Chinese 19515 N/A 38 Khamees RE 2021 Egypt 120 p<0.001 39 Lorentz MS 2021 Brazil 50 p=0.004 (comparing scores) p=0.062 (comparing prevalence) 40 Silverman ME 2020 US 485 N/A 41 Akgor U 2021 Turkey 297 N/A . CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted June 14, 2022. ; https://doi.org/10.1101/2022.06.13.22276327doi: medRxiv preprint 7 42 Shahid A 2020 Pakistan 552 N/A 43 Preis H 2020 US 788 N/A 44 Dagklis T 2020 Greece 269 p<0.001 45 Ionio C 2021 Italy 40 N/A 46 Esteban-Gonzalo S 2021 Spain 353 N/A 47 Koyucu RG 2021 Turkey 729 N/A 48 Overbeck G 2021 Denmark 330 0.2209 49 Kachi Y 2021 Japan 270 N/A 50 Mariño-Narvaez C 2021 Spain 75 p=0.038 51 Liu J 2021 US 715 N/A 52 Smith CL 2021 USA 83 N/A 53 Cao Y 2021 China 298 N/A 54 Mappa I 2021 Italy 161 p<0.0001 55 Mehdizadehkashi A 2021 Iran 300 N/A 56 Yirmiya K 2021 Israel 1114 N/A 57 Xie M 2021 China 689 p=0.03 58 Ge Y 2021 China 446 N/A 59 López-Morales H 2021 Argentina 102 N/A 60 Puertas-Gonzalez JA 2021 Spain 100 p=0.025 61 Çolak S 2021 Turkey 149 N/A 62 Xu K 2021 China 274 N/A 63 Zilver SJM 2021 Netherlands 1102 p=0.14(compa ring prevalence)/p =0.03(compari ng score) 64 Maharlouei N 2021 Iran 540 N/A 65 Harrison V 2021 UK 205 N/A 66 Saadati N 2021 Iran 300 N/A 67 Wang Q 2021 China 15428 N/A 68 Behmard V 2021 Iran 801 N/A 69 King LS 2021 US 725 p<0.001 70 Nurrizka RH 2021 Indonesia 120 N/A 71 Jelly P 2021 India 333 N/A 72 Wang Q 2021 China 19515 N/A 73 Zhang Y 2021 China 1794 N/A 74 Masjoudi M 2021 Iran 215 N/A 75 Shangguan F 2021 China 2120 N/A 76 T sakiridis I 2021 Greece 505 N/A 77 Brik M 2021 Spain 164 N/A 78 Effati-Daryani F 2021 Iran 437 N/A 79 Boekhorst MGBM 2021 Netherlands 265 N/A 80 An R 2021 China 209 N/A 81 Lubián López DM 2021 Spain 514 N/A 82 Maleki A 2021 Iran 2336 N/A 83 Khoury JE 2021 Canada 304 N/A 84 Suárez-Rico BV 2021 Mexico 293 N/A 85 Korukcu O 2021 Turkey 497 p<0.0001 86 Obata S 2021 Japan 4798 N/A 87 Sakalidis VS 2021 Australia and New Zealand 233 N/A 88 Basu A 2021 64 countries 6894 N/A . CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted June 14, 2022. ; https://doi.org/10.1101/2022.06.13.22276327doi: medRxiv preprint 8 89 Kara P 2021 Turkey 445 N/A 90 Fallon V 2021 UK 614 p<0.001 91 Mo PKH 2021 China 4087 N/A 92 Wu F 2021 Shenzhen 3434 N/A 93 Ding W 2021 Wuhan 817 N/A 94 Chrzan-D ę tkoś M 2021 Poland 78 p=0.025 95 Janevic T 2021 New York 228 N/A 96 Thompson KA 2021 US 232 N/A 97 Mirzaei N 2021 Iran 200 N/A 98 Hiiragi K 2021 Japan 279 p=0.17 99 McFarland MJ 2021 US 2402 N/A 100 Zhou Y 2021 China 1266 N/A 101 Gluska H 2021 Israel 421 N/A 102 Liu CH 2021 US 628 p<0.01 103 Ramirez Biermann C 2021 US 162 N/A 104 Palalioglu RM 2021 Turkey 526 N/A 105 Molgora S 2020 Italian 389 N/A 106 Patabendige M 2020 Sri Lanka 257 N/A 107 Mollard E 2021 US 885 N/A 108 Wang J 2021 China 2235 N/A 109 Zeng X 2020 China 625 N/A 110 Miranda AR MD 2021 Argentina 305 N/A 111 Nomura R 2021 Brazil 1662 N/A 112 Davis JA 2021 US 31 N/A 113 Provenzi L 2021 Italy 163 N/A 114 Kotabagi P 2020 UK 11 N/A 115 Berthelot N 2020 Canada 1258 0.001 116 Corbett GA 2020 NA 71 N/A 117 Farrell T 2020 Qatar 288 N/A 118 Stepowicz A 2020 Poland 210 N/A 119 Mayopoulos GA 2021 United States 637 0.008 120 Liu CH 2021 United States 1123 N/A 121 Farewell CV 2020 United States 27 N/A 122 Haruna M 2020 Japan 2872 N/A 123 Bender WR 2020 United States 318 N/A 124 Aksoy Derya Y 2021 Turkey 48 N/A 125 Nodoushan RJ 2020 Iran 560 N/A 126 Mortazavi F 2021 Iran 484 N/A 127 Chasson M 2021 Israel 233 N/A 128 T aubman-Ben-Ari O 2020 Israel 233 N/A 129 Moyer CA 2021 Ghana 71 N/A 130 Dib S 2020 UK 1329 N/A 131 Qi M 2020 China 298 N/A 132 Kassaw C 2020 Ethiopia 178 N/A 133 Zheng QX 2020 China 331 N/A 134 0 2021 Brazil 1041 N/A 135 Perzow SED 2021 US 135 p<0.001 136 Pope J 2021 US,Ireland,UK 573 N/A 137 Kotabagi P 2020 UK 14 p=0.9 . CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted June 14, 2022. ; https://doi.org/10.1101/2022.06.13.22276327doi: medRxiv preprint 9 138 Naurin E 2021 Sweden 0 N/A 139 Bo HX 2021 China 1309 N/A 140 Barbosa-Leiker C 2021 US 162 N/A 141 Stampini V 2021 Italy 600 N/A 142 Li C 2021 China 2201 N/A 143 Bradfield Z 2021 Australia 2840 N/A 144 Kinser PA 2021 US 524 N/A 145 Özkan Ş at S 2021 Turkey 376 N/A 146 Kawamura H 2021 Japan 297 N/A 147 Silverio SA 2021 UK 710 N/A 148 Ahlers-Schmidt CR 2020 US 114 N/A 149 de Arriba-García M 2021 Spain 754 N/A 150 Chaves C 2021 Spain 724 N/A 151 Wdowiak A 2021 Poland 50 N/A 152 Ravaldi C 2020 Italy 2448 N/A 153 Wyszynski DF 2021 64 countries 7185 N/A 154 Sbrilli MD 2021 US 199 N/A 155 Davenport MH 2020 Canada 900 p<0.01 156 Di Mascio D 2020 China,Saudia Arabia,South Korea,United Arab,Jordan,Canada,USA 19 157 Juan J 2020 USA,Iran,China,Italy,Spain,Pe ru,Sweden,Turkey,Korea,Aust ralia,Canada and France 24 158 Amaral WND 2020 China,France,US,Iran,Italy,Sp ain,EUA,Peru,UK, Switzerland,Netherlands,Irela nd,Sweden,Canada,Korea 1457 159 Di Mascio D 2020 Argentina,Australia,Belgium,B razil,Colombia,Czech Republic,Finland,Germany,Gr eece,Israel,Italy, North Macedonia,Peru,Portugal,Re public of Kosovo,Romania,Russia,Ser bia,Slovenia,Spain,Turkey,US 388 160 Sentilhes L 2020 Europe,Sub-Saharan Africa,North Africa 38 161 Sahin D 2021 Turkey 533 162 Kayem G 2020 France 617 163 Adhikari EH 2020 T exas,US 252 164 Garcia Rodriguez A 2020 N/A 1 165 Islam MM 2020 N/A 235 166 Hansen JN 2021 N/A 1 167 Oltean I 2021 N/A 315 168 Wei SQ 2021 N/A 438548 169 Singh V 2021 India 132 170 Della Gatta AN 2021 China 51 171 Di Toro F 2021 N/A 1104 172 Bellos I 2021 China 158 173 Abou Ghayda R 2020 China,Italy,Iran 104 174 Remaeus K 2020 Sweden 67 175 Mullins E 2020 N/A 1606 176 Zaigham M 2020 China,Sweden,US,Korea,Hon duras 108 . CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted June 14, 2022. ; https://doi.org/10.1101/2022.06.13.22276327doi: medRxiv preprint 10 177 Yu N 2020 China 7 178 Galang RR 2020 N/A 12 179 Capobianco G 2020 N/A 44 180 Berthelot N 2020 Canada 1258 181 Mappa I 2020 Italy 178 182 Ayaz R 2020 N/A 63 183 Dubey P 2020 N/A 790 184 Pierce-Williams RAM 2020 USA 44 185 Gao YJ 2020 N/A 236 186 Yang R 2020 China 65 187 Yee J 2020 N/A 9032 188 Liu X 2020 China 1947 189 Novoa RH 2020 N/A 322 190 Matar R 2020 China,US,Republic of Korea,Honduras 136 191 Gur RE 2020 America 787 192 Sakowicz A 2020 America 1317 193 T aubman-Ben-Ari O 2020 Israel 336 194 Ng QJ 2020 Singapore 324 195 Hamzehgardeshi Z 2020 Iran 318 196 Ozsurmeli M 2020 Turkey 24 197 Makvandi S 2020 N/A 68 198 Guo Y 2020 China 20 199 Karimi L 2020 N/A 571 200 Waratani M 2020 Japan 1 201 Savasi VM 2020 Italy 11 202 Effati-Daryani F 2020 Iran 205 203 Smith V 2020 N/A 92 204 Chen H 2020 China 9 205 Wang Y 2020 China 72 206 Janevic T 2021 USA 3731 207 Cao D 2020 China 10 208 Lebel C 2020 Canada 1764/175 7 209 Marín Gabriel MA 2020 Spain 11 210 Lokken EM 2020 America 155 211 Ashraf MA 2020 N/A 90 212 de Vasconcelos Gaspar A 2021 Portugal 7 213 Huntley BJF 2020 N/A 538 214 Khoury R 2020 USA 241 215 Diriba K 2020 N/A 1316 216 Assiri A 2016 N/A 5 217 Malik A 2016 N/A 1 228 229 230 231 232 233 234 235 236 . CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted June 14, 2022. ; https://doi.org/10.1101/2022.06.13.22276327doi: medRxiv preprint 11 Table 2. 99 studies selected for meta-analysis of depression, anxiety, stress, PTSD and sleep disorders 237 238 Authors Country Sample Size Publication Year Symptoms Measure Name Lebel C Canada 1757/ 1764 2020 Anxiety,Depression PROMIS,EPDS Ayaz R Turkey 63 2020 Anxiety BAI Durankuş F Turkey 260 2020 Anxiety,Depression BAI,EPDS Liu X China 1947 2020 Anxiety SAS Mappa I Italy 178 2020 Anxiety STAI-T ,STAI-S López-Morales H Argentina 72 2021 Anxiety,Depression STAI-S,BDI-II Salehi L Iran 220 2020 Anxiety CDAS Gur RE United States 787 2020 Anxiety,Depression GAD-7,PHQ-2 Ng QJ Singapore 324 2020 Anxiety,Depression,Str ess DASS21-A, DASS21-D, DASS21-S Effati-Daryani F Iran 205 2020 Anxiety,Depression,Str ess DASS21-A, DASS21-D, DASS21-S Ravaldi C Italy 200 2021 Anxiety COVID-ASSESS questionnaire Zhou Y China 544 2020 Anxiety,Depression,PT SD,Sleep orders GAD-7,PHQ- 9,PCL-5,ISI Kahyaoglu Sut H Turkey 403 2021 Anxiety,Depression HADS-A, HADS-D Sinaci S Turkey 200 2020 Anxiety STAI-T ,STAI-S Dong H China 156 2021 Anxiety,Depression SAS,SDS Hocaoglu M Turkey 283 2020 Anxiety,PTSD STAI-T ,STAI- S/IES-R Yue C China 308 2021 Anxiety SAS Taubman-Ben-Ari O Israel 336 2020 Anxiety self-designed questionnaire Maharlouei N Iran 540 2020 Anxiety self-designed questionnaire Milne SJ Ireland 70 2020 Anxiety N/A Ceulemans M Ireland, Norway, Switzerland, the Netherlands, and the UK 3545 2021 Anxiety,Depression,Str ess GAD-7,EDS, PSS-10 Yassa M Turkey 203 2020 Anxiety STAI-S,STAI-T Jiang H China 1873 2021 Anxiety,Depression,Str ess SAS,EDS, CPSS-14 Mayeur A France 88 2020 Anxiety self-designed questionnaire Lin W China 751 2021 Anxiety,Depression SAS,PHQ-9 Yang X Chinese 19515 2021 Anxiety,Depression GAD-7,PHQ-9 Akgor U Turkey 297 2021 Anxiety,Depression HADS-A, HADS-D Preis H US 788/4451 2020 Anxiety,Stress GAD-7,PREPS Dagklis T Greece 269/215 2020 Anxiety,Depression STAI-S,STAI- T/EPDS Esteban-Gonzalo S Spain 353 2021 Anxiety STAI-S Koyucu RG Turkey 729 2021 Anxiety,Depression,Str ess DASS21-A, DASS21-D, . CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted June 14, 2022. ; https://doi.org/10.1101/2022.06.13.22276327doi: medRxiv preprint 12 DASS21-S Liu J US 715 2021 Anxiety,Depression GAD-7,EPDS Cao Y China 298 2021 Anxiety,Depression N/A Mappa I Italy 161 2021 Anxiety STAI-T ,STAI-S Mehdizadehkashi A Iran 300 2021 Anxiety self-designed questionnaire Yirmiya K Israel 1114 2021 Anxiety,Depression,Str ess GAD-7,PHQ- 2,PREPS Xie M China 689 2021 Anxiety,Depression,Sl eep disorders SCL90-R,PSQI Ge Y China 446 2021 Anxiety SAS López-Morales H Argentina 102 2021 Anxiety,Depression STAI-S,BDI-II Puertas-Gonzalez JA Spain 100 2021 Anxiety,Depression,Str ess SCL-90-R,PSS-14 Çolak S Turkey 149 2021 Anxiety,Depression,Str ess BAI,BDI,PSQI Xu K China 274 2021 Anxiety,Depression,Str ess,Sleep disorders SAS,EPDS,CPSS, PSQI Zilver SJM Netherlands 1102 2021 Anxiety,Depression,Str ess HADS-A,HADS- D,PSS-10 Maharlouei N Iran 540 2021 Anxiety,Depression,Str ess DASS21-A, DASS21-D, DASS21-S Harrison V UK 205 2021 Anxiety,Depression PASS,EPDS Saadati N Iran 300 2021 Anxiety HAQ Wang Q China 15428 2021 Anxiety,Depression GAD-7,PHQ-9 Behmard V Iran 801 2021 Anxiety CDAS Hamzehgardeshi Z Iran 318 2021 Anxiety,Depression PRAQ,EPDS Jelly P India 333 2021 Anxiety GAD-7 Wang Q China 19515 2021 Anxiety,Depression GAD-7,PHQ-9 Zhang Y China 1794/560 2021 Anxiety,Stress SAS,IES Masjoudi M Iran 215 2021 Anxiety,Stress CDAS,PSS-14 Shangguan F China 2120 2021 Anxiety,Stress GAD-7,PSS Tsakiridis I Greece 505 2021 Anxiety,Depression STAI-S,STAI- T/EPDS Brik M Spain 109/164 2021 Anxiety STAI-S,STAI- T/EPDS Effati-Daryani F Iran 437 2021 Anxiety,Depression,Str ess DASS21-A, DASS21-D, DASS21-S Lubián López DM Spain 514 2021 Anxiety STAI-S,STAI- T/EPDS Maleki A Iran 2336 2021 Anxiety GAD-7 Khoury JE Canada 304 2021 Anxiety,Depression,Str ess,Sleep disorders GAD-7,CES- D,PSS-10,ISI Suárez-Rico BV Mexico 293 2021 Anxiety STAI-T Obata S Japan 4798 2021 Anxiety,Depression K6,EPDS Mo PKH China 4087 2021 Anxiety,Depression GAD-7,PHQ-9 Wu F Shenzhen 3434 2021 Anxiety,Depression GAD-7,PHQ-9 Ding W Wuhan 817 2021 Anxiety SAS Mirzaei N Iran 200 2021 Anxiety,Depression HADS-A, HADS-D Ramirez Biermann C US 162 2021 Anxiety,Depression self-designed questionnaire Palalioglu RM Turkey 526 2021 Anxiety self-designed questionnaire Molgora S Italian 389 2020 Anxiety,Depression STAI-S,STAI- T/EPDS Patabendige M Sri Lanka 257 2020 Anxiety,Depression HADS-A, . CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted June 14, 2022. ; https://doi.org/10.1101/2022.06.13.22276327doi: medRxiv preprint 13 HADS-D Zeng X China 516 2020 Anxiety,Depression,Sl eep disorders GAD-7,EPDS, DSM-IV Nurrizka RH Indonesia 36 2021 Anxiety DASS-21-A Wu Y China 1285 2020 Depression EPDS Wang Y China 72 2020 Depression,PTSD EPDS,PCL-C Medina-Jimenez V Mexico 503 2020 Depression,Stress EPDS,PSS Matsushima M Japan 1777 2020 Depression EPDS Gildner TE US 1856 2020 Depression EPDS Shayganfard M Iran 66 2020 Depression,Stress EPDS,PSS-14 Silverman ME US 516 2020 Depression EPDS Muhaidat N Jordan 944 2020 Depression self-designed questionnaire Thayer ZM US 2099 2021 Depression EPDS Zhang CJP China 1901 2020 Depression,PTSD EPDS,PCL-S Khamees RE Egypt 120 2021 Depression EPDS Silverman ME US 485 2020 Depression EPDS Shahid A Pakistan 552 2020 Depression,Sleep disorders EPDS,self- designed questionnaire Ionio C Italy 75 2021 Depression EPDS Overbeck G Denmark 330 2021 Depression MDI Kachi Y Japan 270 2021 Depression EPDS Smith CL USA 83 2021 Depression,Stress EPDS,PSS-10 King LS US 725 2021 Depression EPDS Korukcu O Turkey 497 2021 Depression EDS Zhou Y China 1266 2021 Depression PHQ-9 Chaves C Spain 450 2021 Depression EPDS Davis JA US 31 2021 Stress PSS-10 Ionio C Italy 75 2021 PTSD IES-R Basu A 64 countries 5712 2021 PTSD IES-6 Kara P Turkey 445 2021 PTSD PCL-5 Wang J China 2235 2021 Sleep disorders ISI 239 240 241 242 243 244 245 246 247 248 249 250 251 252 253 254 255 256 257 258 259 260 . CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted June 14, 2022. ; https://doi.org/10.1101/2022.06.13.22276327doi: medRxiv preprint 14 261 Meta-analysis 262 Edinburgh Postnatal Depression Scale (EPDS), the Patient Health Questionnaire 9-item 263 (PHQ-9), the depression subscale of the Hospital Anxiety and Depression Scale (HADS-D) 264 were the commonly used data collection tools to assess symptoms of depression in women 265 during pregnancy and after childbirth. The pooled prevalence of depression was 24.91% 266 with a 95% CI of 21.37%- 29.02% (Figure 2). 267 Figure 2. Forest plot of depression 268 . CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted June 14, 2022. ; https://doi.org/10.1101/2022.06.13.22276327doi: medRxiv preprint 15 269 270 271 272 273 . CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted June 14, 2022. ; https://doi.org/10.1101/2022.06.13.22276327doi: medRxiv preprint 16 Anxiety symptoms were commonly measured by the State-Trait Anxiety Inventory (STAI, 274 with two subscales STAI-T and STAI-S), the General Anxiety Disorder 7-item (GAD-7) and 275 Self-rating Anxiety Scale (SAS). Anxiety prevalence was 32.88% with a 95% CI of 29.05% to 276 37.21% (Figure 3). 277 Figure 3. Forest plot of anxiety 278 . CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted June 14, 2022. ; https://doi.org/10.1101/2022.06.13.22276327doi: medRxiv preprint 17 279 280 281 . CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted June 14, 2022. ; https://doi.org/10.1101/2022.06.13.22276327doi: medRxiv preprint 18 Tools like the Perceived Stress Scale (PSS, wi th 10-item and 14-item versions), the stress 282 subscale of the 21-item Depression Anxiety and Stress Scale (DASS21-S) were frequently 283 used to evaluate stress symptoms. The pooled prevalence of stress among perinatal women 284 was 29.44% (95% CI: 18.21% - 47.61%) as demonstrated in Figure 4. 285 Figure 4. Forest plot of stress 286 287 288 289 PTSD symptoms were typically measured by the DSM-V Post-Traumatic Stress Disorder 290 Checklist (PCL-5) and the Impact of Events Scale (IES). The studies reporting PTSD 291 symptoms were heterogeneous (Figure 5) resulting in a pooled prevalence of 27.93% with a 292 95%CI of 9.05%-86.15%. 293 Figure 5. Forest plot of PTSD 294 295 296 297 The Insomnia Severity Index (ISI) and the Pittsburgh Sleep Quality Index (PSQI) were to 298 assess and report symptoms associated with sleep disorders. The pooled prevalence was 299 24.38% with a 95% CI of 11.89%-49.96% (Figure 6 supplementary material). 300 301 . CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted June 14, 2022. ; https://doi.org/10.1101/2022.06.13.22276327doi: medRxiv preprint 19 Figure 6. Forest plot of sleep disorders 302 303 304 305 306 307 The I 2 evaluated for depression, anxiety, PTSD, stress and sleep issues were over 98%, 308 which demonstrates a high heterogeneity among the studies. Therefore, a subgroup 309 analysis was conducted to further evaluate the heterogeneity. 310 Subgroup analysis 311 Women were assessed at different stages of their pregnancy. To determine the rates of 312 depression, anxiety, PTSD, stress and sleep problems, the dataset was categorised based 313 on the trimesters;1 st trimester (<12 weeks), 2 nd trimester (13-27 weeks), 3 rd trimester (28-41 314 weeks)] and the immediate post-partum period (immediately after childbirth and up to six 315 weeks) for studies that reported follow-up details. 316 The heterogeneity of depression is lower in comparison to anxiety, PTSD, stress and sleep 317 problems. Heterogeneity within the 1 st trimester was 89.47%. I 2 of the anxiety group during 318 the 1st trimester and 2 nd trimester were 88.91% and 92.35%, respectively. These appear to 319 similar to the I 2 values of depression. I 2 for stress associated with the 2 nd and 3rd trimesters 320 were 78.57% and 64.65%, respectively, indicating mild heterogeneity. Intuitively, Maharlouei 321 and colleagues study reported a small prevalence, thus could be an influencing factor for the 322 heterogeneity reported. I 2 for PTSD across three trimesters were 24.67%, 89.47% and 323 81.62%, respectively. I 2 was 0% during the 1 st trimester within the groups of participants 324 reporting sleep disturbance. 1 st trimester group showed relatively low heterogeneity across 325 mental health symptoms, thus strictly sti pulating the gestational weeks of the included 326 pregnancy helped reduce the heterogeneity. 327 328 329 330 331 332 . CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted June 14, 2022. ; https://doi.org/10.1101/2022.06.13.22276327doi: medRxiv preprint 20 [Figure 7] 333 Figure 7 Subgroup analysis of depression 334 335 336 337 338 . CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted June 14, 2022. ; https://doi.org/10.1101/2022.06.13.22276327doi: medRxiv preprint 21 [Figure 8] 339 Figure 8 Subgroup analysis of anxiety 340 . CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted June 14, 2022. ; https://doi.org/10.1101/2022.06.13.22276327doi: medRxiv preprint 22 341 342 . CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted June 14, 2022. ; https://doi.org/10.1101/2022.06.13.22276327doi: medRxiv preprint 23 [Figure 9] 343 Figure 9 Subgroup analysis of stress 344 345 346 347 348 349 [Figure 10] 350 Figure 10 Subgroup analysis of PTSD 351 352 . CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted June 14, 2022. ; https://doi.org/10.1101/2022.06.13.22276327doi: medRxiv preprint 24 353 354 355 356 357 [Figure 11] 358 Figure 11 Subgroup analysis of sleep disorders 359 360 . CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted June 14, 2022. ; https://doi.org/10.1101/2022.06.13.22276327doi: medRxiv preprint 25 361 362 363 Figure 12. Funnel plot of depression 364 . CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted June 14, 2022. ; https://doi.org/10.1101/2022.06.13.22276327doi: medRxiv preprint 26 365 366 367 368 Figure 13. Funnel plot of anxiety 369 370 371 372 373 374 375 376 377 378 379 380 381 382 Figure 14. Funnel plot of stress 383 . CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted June 14, 2022. ; https://doi.org/10.1101/2022.06.13.22276327doi: medRxiv preprint 27 384 385 Figure 15. Funnel plot of PTSD 386 387 388 389 390 391 392 393 394 395 396 397 398 399 400 401 402 403 404 Figure 16. Funnel plot of sleep disorders 405 . CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted June 14, 2022. ; https://doi.org/10.1101/2022.06.13.22276327doi: medRxiv preprint 28 406 407 408 Publication bias and sensitivity analysis 409 Publication bias and a sensitivity analysis was conducted to assess the reliability of the data 410 as some studies had large standard errors that would produce undesirable effects. Copas 411 selection model was used to select studies for the sensitivity analysis. The p-values of 412 residual selection bias were evaluated as demonstrated in Figure 17-21. Studies with a p-413 value of >0.1 indicated that the residual selection had minimal bias and, the selected studies 414 can be represented. The proportions ident ified were 67.84%, 100% and 59.49% for 415 depression, anxiety and sleep disorders, respec tively. Studies reporting stress and PTSD, 416 the copas selection model could not provide a decision indicating the previous conclusions 417 of high heterogeneity is accurate. 418 419 Figure 17. P-value for residual selection bias of depression 420 421 Figure 18. P-value for residual selection bias of anxiety 422 423 . CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted June 14, 2022. ; https://doi.org/10.1101/2022.06.13.22276327doi: medRxiv preprint 29 424 425 426 Figure 19. P-value for residual selection bias of stress 427 428 429 430 431 Figure 20. P-value for residual selection bias of PTSD 432 433 Figure 21. P-value for residual selection bias of sleep disorders 434 435 . CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted June 14, 2022. ; https://doi.org/10.1101/2022.06.13.22276327doi: medRxiv preprint 30 436 437 A summary of studies used within the Copas selection model and random effects model has 438 been demonstrated in Table 3, which indicates that the two models have no significant 439 difference. P-value of the changes between these conclusions are 0.1108, 0.638 and 0.1042 440 for depression, anxiety and sleep disorders, res pectively. The p-value of the Egger’s test 441 was 0.0256 ( Table 4. supplementary material ) for studies of depression, revealing the 442 existence of publication bias. The p-values of 0.256 and 0.998 (Table 4. supplementary 443 material) indicates that it is challenging to detect publication bias for studies associated with 444 anxiety and sleep disturbances. 445 446 Table 3. Summary of sensitivity analysis 447 448 Outcome N of stud y Model Probability of publishing study with largest standard error Proporti on(%) lower(%) upper(%) p-value for differences between two

Depressio n 64 copas selecion model 67.84% 27.1 1 24.3 2 30.22 0.1108 random effects model 24.9 1 21.3 7 29.02 anxiety 82 copas selecion model 100.00% 32.8 8 29.0 8 37.18 0.638 random effects model 32.8 8 29.0 5 37.21 Sleep disorders 8 copas selecion model 59.49% 27.1 1 14.9 4 49.21 0.1042 random effects model 24.3 8 11.8 9 49.95 449 Table 4. P-value of Egger Test for the five mental health symptoms 450 451 Outcome N of studies p-value of Egger test depression 64 0.0256* anxiety 82 0.256 stress 20 0.069 PTSD 7 0.742 sleep disorders 8 0.998 Note: ( * ) : p<0.05 indicates significance 452 453 . CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted June 14, 2022. ; https://doi.org/10.1101/2022.06.13.22276327doi: medRxiv preprint 31

454 455 Main findings 456 Our study demonstrates that depression, anxiety, PTSD, stress and sleep problems were 457 common throughout the pregnancy period and after childbirth during the COVID-19 458 pandemic with 24.9% of women reporting symptoms of depression, 32.8% anxiety, 29.44% 459 stress, 27.93% PTSD, and 24.38% sleep disorders. The lack of research conducted to 460 assess the mental health impact of SARS and MERS on pregnant women is a significant 461

as such data could have supported preparation for similar pandemics in the future. 462 Our meta-analyses indicated a clear-cut mental health impact of COVID on pregnant and 463 post-partum mothers with a pooled prevalence of multiple symptomatologies of depression, 464 anxiety, PTSD, stress and insomnia. 465 466 Strengths and weakness 467 468 To our knowledge, this is the first systematic review and meta-analysis to focus on mental 469 health outcomes in women during pregnancy and after childbirth during the Covid-19 470 pandemic. The searches were not limited by geographical location or language, therefore, 471 further increasing the chances for all relevant literature to be identified. The MESH terms 472 used did not consider all types of obstetri c or gynaecology conditions but did include the 473 common conditions. The variety of screening tools used across the included studies must be 474 considered when interpreting the results of this review. Direct comparisons cannot be made 475 where the same screening tool was not used. Furthermore, most studies used self-reported 476 questionnaires, with no clinical follow-up to c onfirm diagnoses. Therefore, the results cannot 477 be interpreted as prevalence of mental illness, but rather prevalence of symptomatology. 478 479 Interpretation 480 481 Some studies have demonstrated that the extent and severity of mental health impact 482 increased in women during pregnancy and after childbirth during humanitarian disasters and 483 pandemics which is similar to our study [11]. 484 485 The subgroup analysis showed that the prevalenc e of depression is identical during the first 486 trimester of pregnancy [24.61% (95% CI 17.12 – 35.37)] and after childbirth [24.96 (95% CI 487 20.26 – 30.76)] compared to the second and third trimesters when the prevalence of 488 depression is much lower at 16.52 (95% CI 9.31 – 29.33), and 22.49 (95% CI 18.91 – 489 26.74), respectively. This is suggestive of women who became pregnant and gave birth 490 during the pandemic suffered from depression more frequently in the early stage and after 491 birth, which appears to have been plateaued during the latter part of their pregnancy. It is 492 unclear as to the reason for this observation, and the impact of this in a real-time scenario. 493 The prevalence of anxiety, on the other hand, is higher among women after childbirth [32.09 494 (95% CI 25.55 – 40.30)], compared to an identic al prevalence of anxiety during all the three 495 trimesters of pregnancy [1st trimester 22.06 (95% CI 16.08 – 30.25), 2nd trimester 23.37 (95% 496 CI 17.36 – 31.45), 3 rd trimester 26.02 (95% CI 19.36 – 34.96)]. This finding suggests that 497 women after childbirth suffered more from anxiety during the Covid-19 pandemic. The stress 498 level was significantly higher in women during the 1 st trimester of pregnancy 70.58% (95% 499 CI 49.46 – 100.72), compared to 47.81% (95% CI 36.32 – 62.94). 500 . CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted June 14, 2022. ; https://doi.org/10.1101/2022.06.13.22276327doi: medRxiv preprint 32 501 This could be due to some of these women bei ng first-time mothers or, general stress and 502 health anxiety regarding how and when to access care from midwives and obstetricians as 503 part of routine and emergency maternity care due to the Covid-19 pandemic. The findings of 504 high level of stress amongst pregnant women is in keeping with other studies carried out 505 during the Covid-19 pandemic that reported up to 70% of pregnant women suffered from 506 stress during the pandemic[8]. Being pregnant and giving birth are known triggers for women 507 to develop anxiety, and depression and pregnancy is a known risk factor for exacerbations 508 or decline in pre-existing mental ill-health[9 ,10]. Other possible reasons for the increase in 509 mental ill-health in women during pregnancy or after childbirth may be because of the 510 massive clinical changes that took place regar ding how women could access maternity care 511 during the Covid-19 pandemic. As pregnant women were at higher risk of severe illness if 512 they become infected with severe acute respiratory syndrome (SARS)-CoV-2 and develop 513 COVID-19, pregnant women were advised to be stringent with public health measures such 514 as social distancing and self-isolation to lower their risk of COVID-19 exposure. This led to 515 the rapid implementation of virtual access to antenatal care to minimising the need for travel 516 to antenatal clinics and in-person contact with healthcare staff, and antenatal care changed 517 immediately from face-to-face consultations to telephone or video consultations. Birth 518 partners were limited in number and visiting hour s for partners were restricted resulting in 519 less emotional and psychological support for women during labour in the delivery room, and 520 after childbirth on the postnatal wards. Furthermore, as the Covid-19 vaccination was 521 developed and the implementation programme initiated, there was uncertainty regarding the 522 effectiveness and safety of the Covid-19 vaccine in women who were pregnant, which may 523 have contributed and exacerbated stress and anxiety. 524 525 Recommendations 526 527 All women should be risk assessed for maternal mental health at their booking visit and 528 screened at every contact during pregnancy and after childbirth. All healthcare systems 529 need to invest in perinatal mental health services delivered from a multi-disciplinary team 530 including mental health nurses, specialist midwives, obstetricians with specialist interest in 531 mental health and perinatal psychologists and psychi atrist. Maternity mental health services 532 should be delivered in a way that meets the specific needs of the individual patient, including 533 face-to-face consultations, telephone calls and/or video consultations. Up to date information 534 regarding the impact of Covid-19 on maternity services needs to be available and easily 535 accessible for women during pregnancy and after childbirth, for example by using social 536 media campaigns and hospital websites. Learning from this data derived from COVID 537 pandemic and consideration of the special n eeds of the pregnant and postnatal mothers 538 should be imperative in strategies to implemen t early to improve preparedness of the health 539 service in future pandemics. 540 541

542 543 This study highlights that maternity mental ill-health was common during the Covid-19 544 pandemic and highlights the need to understand the complexity of factors associated with 545 maternal mental health. Maternity mental health services need further investment and 546 prioritisation and clear effective referral pat hways and support for women who report mental 547 health concerns during and after pregnancy are needed and require further research as to 548 . CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted June 14, 2022. ; https://doi.org/10.1101/2022.06.13.22276327doi: medRxiv preprint 33 how best provide this care in a way that meets the specific needs of each women, across 549 different healthcare systems. 550 551 552 553 554 555 556 List of abbreviations: 557 MERS- Middle Eastern Respiratory Syndrome 558 SARS- Severe acute respiratory syndrome 559 EPDS- Edinburgh Postnatal Depression Scale 560 SAS- Self-rating Anxiety Scale 561 IES- Impact of Events Scale 562 ISI - Insomnia Severity Index 563 PSQI- Pittsburgh Sleep Quality Index 564 IAPT- Improving Access to Psychological Therapy 565 566 Declarations: 567 Ethics approval and consent to participate 568 Not applicable for this review? 569 570 Consent for publication 571 Not applicable? 572 573 Availability of data and materials 574 Data availability statement goes here. 575 Competing interests 576 Financial and non-financial competing interests should be mentioned here. 577 578 Funding 579 Source(s) of funding should be mentioned here. Role of the funding source in the design of 580 the study and data collection/analysis/interpretation should be declared. 581 582 Authors’ contributions 583 Authors’ individual contributions should be mentioned here. 584 585

586 Authors should obtain permission from everyone to be acknowledged in this section. 587 588 589 590 591 592 593 594 . CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted June 14, 2022. ; https://doi.org/10.1101/2022.06.13.22276327doi: medRxiv preprint 34 595 596 597 598 599 600

601 1. Odejinmi F, Egbase E, Clark TJ, Mallick R. COVID-19 in Women's health reducing the risk 602 of infection to patients and staff during acute and elective hospital admission for 603 gynaecological surgery. Best Pract Res Clin Obstet Gynaecol. 2021; 73 : 40-55 [PMID: 604 7970477 DOI: 10.1016/j.bpobgyn.2021.03.005]. 605 2. Royal College of Obstetricians and Gynaecologists Restoration and Recovery: Priorities 606 for Obstetrics and Gynaecology. Royal College of Obstetricians and Gynaecologists . 2020. 607 https://www.rcog.org.uk/globalassets/documents/guidelines/2020-05-29-restoration-and-608 recovery---priorities-for-obstetrics-and-gynaecology.pdf 609 3. The Lancet Rheumatology. Too long to wait: the impact of COVID-19 on elective surgery. 610 Lancet Rheumatol . 2021 Feb.; 3: e83 [PMID: 33778775 DOI: 10.1016/s2665-611 9913(21)00001-1] 612 4. Soares-Júnior JM, Sorpreso ICE, Motta EV, Utiyama EM, Baracat EC. Gynecology and 613 women's health care during the COVID-19 pandemic: Patient safety in surgery and 614 prevention. Clinics (Sao Paulo). 2020 Jun 22; 75: e2063 [PMID: 32578830 DOI: 615 10.6061/clinics/2020/e2063] 616 5. Galea S, Merchant RM, Lurie N. The Mental Health Consequences of COVID-19 and 617 Physical Distancing: The Need fo r Prevention and Early Intervention. JAMA Intern 618 Med. 2020 Jun 1;180: 817-818 [PMID: 32275292 DOI: 10.1001/jamainternmed.2020.1562] 619 6. Pfefferbaum B, North CS. Mental Health and the Covid-19 Pandemic. N Engl J Med. 2020 620 Aug 6; 383: 510-512 [PMID: 32283003 DOI: 10.1056/nejmp2008017] 621 7. Loades ME, Chatburn E, Higson-Sweeney N, Reynolds S, Shafran R, Brigden A, et al. 622 Rapid Systematic Review: The Impact of Social Isolation and Loneliness on the Mental 623 Health of Children and Adolescents in the Context of COVID-19. J Am Acad Child Adolesc 624 Psychiatry. 2020; 59:1218-1239.e3 [PMID: 32504808 DOI: 10.1016/j.jaac.2020.05.009] 625 8. Yan H, Ding Y, Guo W. Mental Health of Pregnant and Postpartum Women During the 626 Coronavirus Disease 2019 Pandemic: A Systematic Review and Meta-Analysis. Front 627 Psychol. 2020; 11: 617001 [PMID: 33324308 DOI: 10.3389/fpsyg.2020.617001] 628 . CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted June 14, 2022. ; https://doi.org/10.1101/2022.06.13.22276327doi: medRxiv preprint 35 9. Woody CA, Ferrari AJ, Siskind DJ, Whiteford HA, Harris MG. A systematic review and 629 meta-regression of the prevalence and incidence of perinatal depression. J affect disord . 630 2017; 219: 86-92 [PMID: 28531848 DOI: 10.1016/j.jad.2017.05.003] 631 10. Dennis C-L, Falah-Hassani K, Shiri R. Prevalence of antenatal and postnatal anxiety: 632 systematic review and meta-analysis. Br J Psychiatry. 2017; 210: 315-323 [PMID: 28302701 633 DOI: 10.1192/bjp.bp.116.187179] 634 11. Harville E, Xiong X, Buekens P. Disasters and perinatal health:a systematic review. 635 Obstet Gynecol Surv . 2010; 65: 713-28 [PMID: 21375788 DOI: 636 10.1097/ogx.0b013e31820eddbe] 637 638 639 Figure 1. PRISMA Flow Diagram 640 Table 1. 217 studies in systematic review and meta-analysis 641 Table 2. (Supplementary material) 99 studies selected for meta-analysis of 642 depression, anxiety, stress, PTSD and sleep disorders 643 Figure 2. Forest plot of depression 644 Figure 3. Forest plot of anxiety 645 Figure 4. Forest plot of stress 646 Figure 5. Forest plot of PTSD 647 Figure 6 (supplementary material) 648 Figure 7 Subgroup analysis of depression (supplementary material) 649 Figure 8 Subgroup analysis of anxiety (supplementary material) 650 Figure 9 Subgroup analysis of stress (supplementary material) 651 Figure 10 Subgroup analysis of PTSD (supplementary material) 652 Figure 11 Subgroup analysis of sleep disorders (supplementary material) 653 Figure 12. Funnel plot of depression 654 Figure 13. Funnel plot of anxiety 655 Figure 14. Funnel plot of stress 656 Figure 15. Funnel plot of PTSD 657 Figure 16. Funnel plot of sleep disorders (supplementary material) 658 Figure 17. P-value for residual selection bias of depression 659 Figure 18. P-value for residual selection bias of anxiety 660 Figure 19. P-value for residual selection bias of stress 661 Figure 20. P-value for residual selection bias of PTSD 662 Figure 21. P-value for residual selection bias of sleep disorders (supplementary 663 material) 664 Table 3. Summary of sensitivity analysis (supplementary material) 665 . CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted June 14, 2022. ; https://doi.org/10.1101/2022.06.13.22276327doi: medRxiv preprint 36 Table 4. P-value of Egger Test for the five mental health symptoms (supplementary 666 material) 667 . CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted June 14, 2022. ; https://doi.org/10.1101/2022.06.13.22276327doi: medRxiv preprint PRISMA Flow Diagram Relevant records identified through database (n = 975 ) Screening Included Eligibility Identification Additional records identified through other sources (n = 628) Records after duplicates removed (n =1376) Records screened (n =523) Records excluded (n =853) Full-text articles assessed for eligibility (n = 309) Full-text articles excluded, with reasons (n = 95) - Duplicated (n=4) - Not relative objective (n=2) - No mental health outcome (n = 55) - No pregnancy group specified (n =15) - Study unpublished or incomplete (n = ) - With other interventions (n=1) - wrong publication type (n=17) - missed data (n=1) Final sample size (n = 217) Studies included for the systematic review (n =217) Studies included for the meta- analysis (n =99) Initial review (n = 6750) . CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted June 14, 2022. ; https://doi.org/10.1101/2022.06.13.22276327doi: medRxiv preprint