Perinatal outcomes after admission with COVID-19 in pregnancy: a UK national cohort

Perinatal outcomes after admission with COVID-19 in pregnancy: a UK national cohort | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Perinatal outcomes after admission with COVID-19 in pregnancy: a UK national cohort Marian Knight, Hilde Engjom, Rema Ramakrishnan, Nicola Vousden, and 8 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3785899/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 15 Apr, 2024 Read the published version in Nature Communications → Version 1 posted You are reading this latest preprint version Abstract BACKGROUND There are few population-based studies of sufficient size and follow-up duration to have reliably assessed perinatal outcomes for pregnant women admitted to hospital with SARS-CoV-2 infection. METHODS The United Kingdom Obstetric Surveillance System (UKOSS) includes all 194 consultant-led UK maternity units. From March 2020 to March 2022, pregnant women admitted with a positive SARS-CoV-2 PCR test within seven days before or during admission were included and categorised by dominant SARS-CoV-2 variant, severity of maternal COVID-19 and vaccination status. RESULTS In total, 16,351 infants were born to 16,627 women; women with symptomatic COVID-19 contributed 7,116 (43.3%) births, 111 of which were stillborn. Infection during the delta variant period was associated with increased risk of stillbirth irrespective of infection severity compared to mild wild-type infection (mild wildtype 0.8% vs. mild delta 3%, adjusted risk ratio [aRR] 3.57, 95% confidence interval [CI] 1.66 to 7.67; vs. moderate to severe delta, 1.9%, aRR2.41; 95%CI 1.03 to 5.60). All variants were associated with increased risk of preterm birth in women with moderate to severe infection compared to women with mild infection in the wildtype period. After introduction of vaccination during pregnancy, 91.2% (83/91) of stillbirths and 92.1% (422/459) of preterm births < 34 weeks’ gestation were in symptomatic women with no documented vaccination or with unknown vaccine status. CONCLUSION COVID-19 variant, severity, and no or unknown maternal vaccinations were key risk factors for adverse perinatal outcomes. There is strong evidence for continued recommendation of SARS-CoV-2 vaccination during pregnancy to protect women and their babies. Health sciences/Medical research/Epidemiology Health sciences/Diseases/Infectious diseases/Viral infection Figures Figure 1 Introduction During the course of the pandemic, evolving variants of SARS-CoV-2 were associated with higher risk of severe maternal disease and adverse perinatal outcomes, but short observation time and lack of outcome data for continuing pregnancies were likely to bias results towards pregnancies ending at an earlier gestation and with more severe perinatal outcomes. 1 – 4 The latest update of the World Health Organization (WHO) systematic review of coronavirus disease in pregnancy included studies published early in the alpha-dominant period. 5 Few of the studies in the WHO review were population-based or based on European data, and concerns have been raised about the conduct of other systematic reviews and the quality of included studies. 6 Several of the larger multinational registry studies of COVID-19 in pregnancy lacked information about the source population and relied on passive, voluntary reporting, 7 – 9 and studies linking national routine health registry data have been unclear whether hospital admission was related to COVID-19 or pregnancy complications. 10 – 13 Robust evidence is needed to inform the care of pregnant women and counselling regarding vaccination, 14 – 16 particularly given the current increase in hospitalisations due to the omicron (XBB) lineage viruses and new emerging variants such as “pirola“ (BA.2.86). 17 18 Therefore, this study aimed to assess perinatal outcomes for mothers admitted to hospital with SARS-CoV-2 infection using a population-based national cohort with comprehensive follow-up. Methods STUDY DESIGN AND OVERSIGHT The United Kingdom Obstetric Surveillance System (UKOSS) has a source population of all women giving birth or being admitted to one of the 194 consultant-led maternity units in England, Northern Ireland, Scotland and Wales, approximately 720,000 maternities annually. 19 – 22 A protocol for active surveillance of pregnant women admitted to hospital with viral infection was planned in 2012, approved by the ethical review board (HRA NRES Committee East Midlands, Nottingham 1 (Ref. Number: 12/EM/0365) and hibernated ( https://doi.org/10.1186/ISRCTN40092247 ). The protocol was activated for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) from March 1, 2020, and concluded on March 31, 2022. Routines were in place to ensure complete reporting (online supplementary), 3 and follow-up information about birth outcomes up to December 31, 2022, were retrieved from clinical records until April 24, 2023. Maternal and perinatal deaths were cross-checked with the MBRRACE-UK mortality surveillance. ( https://www.npeu.ox.ac.uk/mbrrace-uk ). The corresponding author vouches for the accuracy and completeness of the data and reporting. Patients and public were part of the UKOSS steering committee and involved in study design, oversight, reporting and dissemination of study findings but not in the conduct of the study. The funder played no role in study design; in the collection, analysis, and interpretation of data; in the writing of the report; nor in the decision to submit the paper for publication. STUDY POPULATION AND GROUPS Pregnant women were included if admitted to hospital with a positive SARS-CoV-2 reverse transcriptase polymerase chain reaction (PCR) test within seven days of admission, during admission or up to two days after giving birth. Women were further classified according to their SARS-CoV-2 symptoms (symptomatic/asymptomatic); severity of infection (mild/moderate to severe); and the dominant viral variant in UK at the time of the PCR test (wild-type March 1 to November 30 2020; alpha December 1 2020, to May 15 2021; delta May 16 to December 14 2021; omicron December 15 2021, to March 31 2022). 23 SEVERITY OF MATERNAL COVID-19 Moderate to severe maternal COVID-19 was defined according to modified WHO criteria as maternal death, maternal intensive care admission, peripheral oxygen saturation below 95% at admission, pneumonia on radiological imaging or need for respiratory support (either oxygen supplementation, non-invasive ventilation (high flow nasal oxygen or continuous positive airway pressure), mechanical ventilation or extracorporeal membrane oxygenation (ECMO)). 24 MATERNAL CHARACTERISTICS AND MEDICAL RISK FACTORS The sociodemographic characteristics and medical risk factors recorded were maternal age, maternal body mass index (kg/m 2 ), employment, ethnic background, smoking, pre-existing medical conditions (no medical conditions (reference) vs asthma, hypertension, cardiac disease or diabetes), preeclampsia, gestational diabetes, parity, plurality and gestational age at admission (categorised by completed weeks into < 22, 22 to 27, 28–33, 34–36 and ≥ 37 weeks). Vaccination status was recorded from January 2021 after vaccination was recommended for pregnant women in risk groups in the UK from December 22, 2020. 25 PREGNANCY AND PERINATAL OUTCOMES Pregnancy outcomes examined were pregnancy loss (< 24 weeks’ gestation), gestational age at birth, expedited birth due to COVID-19, and mode of birth (spontaneous vaginal, operative vaginal, caesarean section prior to or during labor). The perinatal outcomes were stillbirth at ≥ 24 weeks’ gestation, preterm birth (< 34 weeks’ and 34 + 0 to 36 + 6 weeks’ gestation), neonatal unit admission, and neonatal death within seven days after birth. STATISTICAL ANALYSES Percentages and frequencies were computed by symptom group, and for symptomatic women by severity of infection, dominant variant, and vaccination status. Where data were missing, percentages are presented as the proportion of cases known. Risk ratios (RR) with 95% confidence intervals (CI) for stillbirth, preterm birth and admission to neonatal unit for births to symptomatic women were computed using symptomatic mild infection during the wild-type period as the reference category with the lowest absolute risk. Since severity and variant were known risk factors, we included a preplanned interaction analysis to assess the combined effect of these factors. 2 , 4 Several models were run: models with dominant variant only (crude RR), disease severity only (crude RR), and with an interaction term for variant and severity (interaction without covariates (model 1); adjusted for selected covariates without vaccination status (model 2); and adjusted for selected covariates and vaccination status using mild infection during the alpha period as reference (model 3). Multilevel Poisson or multinomial regression model as appropriate was used with random intercept to account for clustering effect among multiple pregnancies. The multivariable model for stillbirth was adjusted for maternal age, ethnicity, employment status, body mass index, plurality, smoking, parity, medical conditions prior to or during pregnancy and gestational age at admission. The preterm birth model included the above except gestational age at admission, and the model for neonatal unit admission was adjusted for gestational age at birth, parity, and medical conditions. Statistical analyses were performed using STATA version 18 (Statacorp, TX, USA). Results Among a source population of approximately 1.5 million maternities, 20 – 22 16,627 women were included (Supplementary Figure S1 ). Their characteristics are shown by symptom status and severity in Table 1 . A higher proportion of women with moderate to severe COVID-19 were overweight or obese, had diabetes or asthma, and were of a minority ethnic background compared with women with asymptomatic or mild infection. Women with moderate to severe infection were more likely to be admitted prior to 37 weeks’ gestation (77.3%) compared with asymptomatic women (24.9%) and women with mild infection (51.3%). Vaccination coverage increased gradually amongst women admitted with SARS-CoV-2 from May 2021 onwards (Fig. 1 ). Table 1 Characteristics of pregnant women admitted with SARS-CoV-2, by symptom group, March 1, 2020, to March 31, 2022, United Kingdom. Symptom group Asymptomatic (N = 9374) Mild infection (N = 4901) Moderate to severe infection * (N = 2352) Age (years) - no. (%) < 20 231 (2.5) 100 (2.0) 21 (0.9) 20–34 6685 (71.5) 3583 (73.2) 1544 (65.8) ≥35 2438 (26.1) 1210 (24.7) 782 (33.3) Missing 20 8 5 Body Mass Index (BMI) (kg/m 2 ) - no. (%) Underweight (< 18.5) 229 (2.5) 101 (2.1) 17 (0.8) Normal (18.5 to < 25) 3599 (39.7) 1829 (38.5) 529 (23.4) Overweight (25 to < 30) 2702 (29.8) 1467 (30.9) 714 (31.6) Obese (≥ 30) 2528 (27.9) 1357 (28.5) 1000 (44.3) Missing 316 147 92 Woman or partner in paid work - no. (%) 7010 (74.8) 3788 (77.3) 1791 (76.2) Ethnic Group - no. (%) White 6107 (66.7) 3134 (65.4) 1350 (58.9) Asian 1689 (18.5) 934 (19.5) 519 (22.6) Black 825 (9.0) 418 (8.7) 254 (11.1) Chinese/Other 282 (3.1) 178 (3.7) 110 (4.8) Mixed 249 (2.7) 129 (2.7) 59 (2.6) Missing 222 108 60 Current smoking - no. (%) 1547 (17.0) 626 (13.1) 178 (7.8) Missing 294 138 68 Pre-existing medical conditions - no. (%) Asthma 552 (5.9) 375 (7.7) 231 (9.8) Hypertension 155 (1.7) 80 (1.6) 55 (2.3) Cardiac disease 114 (1.2) 68 (1.4) 38 (1.6) Diabetes 132 (1.4) 71 (1.5) 60 (2.6) Medical conditions during pregnancy - no. (%) Pre-eclampsia 141 (1.5) 73 (1.5) 49 (2.1) Gestational diabetes 595 (6.4) 354 (7.2) 263 (11.2) Multiparous - no. (%) 5749 (61.9) 3038 (62.4) 1626 (69.8) Missing 90 35 22 Multiple pregnancy - no. (%) 140 (1.5) 96 (2.0) 51 (2.2) Gestation at admission (weeks days ) - no. (%) < 22 463 (5.0) 468 (9.6) 194 (8.3) 22–27 + 6 300 (3.2) 445 (9.1) 415 (17.8) 28–33 + 6 639 (6.9) 863 (17.7) 738 (31.7) 34–36 + 6 915 (9.8) 729 (14.9) 455 (19.5) 37 or more 6987 (75.1) 2374 (48.7) 529 (22.7) Missing 70 22 21 Evidence of pneumonia on imaging - no. (%) - - 1695 (72.1) Respiratory support required - no. (%) - † - 1709 (76.2) Intensive Care Unit admission - no. (%) - † - 771 (32.8) Maternal Death - no. (%) 1 (0.01) - 38 (1.6) Vaccination status - no. (%) Unvaccinated 6099 (65.1) 3424 (69.9) 1785 (75.9) 1 dose 620 (6.6) 271 (5.5) 72 (3.1) 2 doses 835 (8.9) 290 (5.9) 41 (1.7) 3 doses 140 (1.5) 53 (1.1) 4 (0.2) Not known/ not documented 1680 (17.9) 863 (17.6) 450 (19.1) * Moderate to severe Covid-19 was defined as one or more of the following: maternal death, intensive care unit admission, peripheral oxygen saturation below 85% at admission, pneumonia on imaging, or need for respiratory support with either oxygen, high flow nasal cannula or continuous positive pressure mask, mechanical ventilation or extracorporeal membrane oxygenation. † 27 (0.3%) asymptomatic women needed respiratory support or were admitted to ICU for other reasons and one of them died from other causes than Covid-19. Of the 16,386 (98.6%) women with known pregnancy outcomes, 1.9% (n = 319) experienced a pregnancy loss (Supplementary Figure S1 ) and the remaining 16,067 women gave birth to 16,351 infants of whom 190 were stillborn. Pregnancy outcomes for symptomatic women are shown by variant and severity in Table 2 , and for asymptomatic women in Supplementary Table S1 . Women with moderate to severe COVID-19 were more likely to give birth prior to 37 weeks, have an expedited birth due to COVID-19 and a pre-labour caesarean birth than women with mild disease. Table 2 Maternal and pregnancy outcomes for women with symptomatic SARS-CoV-2 by severity, March 1, 2020 to March 31, 2022, United Kingdom. Severity Mild infection (N = 4901) Moderate to severe infection * (N = 2352) Pregnancy outcome - no. (%) Birth 4710 (96.1) 2264 (96.3) Pregnancy loss 92 (1.9) 26 (1.1) Birth outcome unknown 99 (2.0) 62 (2.6) Gestation at birth (weeks + days ) † - no. (%) 22 + 0 – 27 + 6 47 (1.0) 49 (2.2) 28 + 0 – 33 + 6 180 (3.8) 305 (13.6) 34 + 0 – 36 + 6 441 (9.4) 395 (17.6) 37 + 0 or more 4022 (85.8) 1490 (66.6) Missing 20 24 Birth expedited due to COVID-19 † - no. (%) 80 (1.7) 601 (26.6) Mode of birth † - no. (%) Pre-labour Caesarean 1246 (26.6) 1129 (50.4) Caesarean after labour onset 702 (15.0) 260 (11.6) Operative vaginal 491 (10.5) 141 (6.3) Spontaneous vaginal 2239 (47.9) 712 (31.8) Missing 32 21 *Moderate to severe Covid-19 defined as one or more of the following. maternal death, intensive care unit admission, peripheral oxygen saturation below 85% at admission, pneumonia on imaging, or need for respiratory support with oxygen, high flow nasal cannula or continuous positive pressure mask, mechanical ventilation or extracorporeal membrane oxygenation. † Pregnancy loss excluded from denominator The perinatal outcomes for births to symptomatic women are shown in Table 3 and for births to asymptomatic women in Supplementary Table S2. Amongst the 7,116 infants born to 6,974 symptomatic women, 1.6% (n = 111) were stillborn and 8.2% (n = 581) were born prior to 34 weeks’ gestation (Table 3 ). Table 3 Perinatal outcomes for babies of women admitted to hospital with symptomatic SARS-CoV-2 by dominant variant period and severity of maternal infection, March 1, 2020, to March 31, 2022, United Kingdom. SARS-CoV-2 dominant variant Wild-type period Alpha period Delta period Omicron period Severity* Mild (N = 1067) Moderate to severe * (N = 370) Mild (N = 1220) Moderate to severe * (N = 678) Mild (N = 1420) Moderate to severe * (N = 1055) Mild (N = 1098) Moderate to severe * (N = 208) Stillbirths - no. (%) 9 (0.8) 6 (1.6) 12 (1.0) 9 (1.3) 42 (3.0) 20 (1.9) 8 (0.7) 5 (2.4) Model 1 † : RR (95% CI [Ref] 1.93 (0.68–5.38) 1.17 (0.49–2.76) 1.57 (0.63–3.95) 3.49 (1.70–7.18) 2.25 (1.03–4.92) 0.86 (0.32–2.34) 2.86 (0.96–8.46) Model 2 ‡ : RR (95% CI) [Ref] 1.90 (0.61–5.88) 1.20 (0.49–2.97) 1.68 (0.63–4.51) 3.57 (1.66–7.67) 2.41 (1.03–5.60) 0.96 (0.35–2.66) 2.62 (0.79–8.69) Model 3 § : RR (95% CI) NA NA [Ref] 0.99 (0.33–3.01) 2.82 (1.29–6.16) 1.89 (0.81–4.40) 0.79 (0.25–2.47) 2.07 (0.64–6.76) Preterm live birth ¶ - no. (%) < 34 weeks’ GA 56 (5.3) 57 (15.5) 56 (4.6) 121 (18.1) 92 (6.5) 177 (16.9) 41 (3.7) 17 (8.2) Model 1 † : RR (95% CI) [Ref] 3.74 (2.52–5.55) 0.87 (0.59–1.27) 4.41 (3.15–6.17) 1.27 (0.90–1.79) 4.26 (3.10–5.85) 0.69 (0.46–1.04) 1.83 (1.04–3.24) Model 2 ‡ : RR (95% CI) [Ref] 3.46 (2.24–5.34) 0.84 (0.56–1.27) 5.03 (3.51–7.20) 1.37 (0.95–1.97) 4.94 (3.52–6.94) 0.66 (0.42–1.03) 2.02 (1.13–3.63) Model 3 § : RR (95% CI) NA NA [Ref] 6.84 (4.42–10.59) 1.92 (1.24–2.96) 7.01 (4.65–10.59) 0.98 (0.59–1.63) 2.98 (1.57–5.65) 34 + 0 – 36 + 6 weeks’ GA 104 (9.8) 65 (17.7) 120 (9.9) 105 (15.7) 153 (10.8) 201 (19.2) 101 (18.0) 41 (19.8) Model 1 † : RR (95% CI) [Ref] 2.30 (1.63–3.23) 1.00 (0.76–1.32) 2.06 (1.54–2.77) 1.14 (0.87–1.48) 2.60 (2.01–3.37) 0.92 (0.69–1.22) 2.38 (1.59–3.56) Model 2 ‡ : RR (95% CI) [Ref] 2.36 (1.62–3.42) 1.00 (0.74–1.34) 2.38 (1.73–3.26) 1.18 (0.89–1.57) 2.92 (2.22–3.86) 1.04 (0.77–1.42) 2.55 (1.67–3.87) Model 3 § : RR (95% CI) NA NA [Ref] 2.32 (1.63–3.31) 1.23 (0.90–1.67) 3.00 (2.21–4.06) 1.20 (0.85–1.69) 2.81 (1.81–4.35) Neonatal unit admission || - no. (%) 144 (13.6) 120 (33.1) 160 (13.3) 231 (34.5) 180 (13.1) 349 (33.7) 105 (9.6) 50 (24.5) Model 1 † : RR (95% CI) [Ref] 2.43 (1.97- 3.00) 0.98 (0.79–1.20) 2.53 (2.11–3.05) 0.96 (0.78–1.18) 2.47 (2.08–2.94) 0.71 (0.56–0.90) 1.80 (1.35–2.39) Model 2 ‡ : RR (95% CI) [Ref] 1.61 (1.32–1.96) 0.99 (0.81–1.21) 1.61 (1.35–1.93) 0.88 (0.73–1.08) 1.52 (1.28–1.81) 0.76 (0.61–0.95) 1.51 (1.16–1.97) Model 3 § : RR (95% CI) NA NA [Ref] 1.60 (1.30–1.97) 0.92 (0.73–1.14) 1.57 (1.28–1.94) 0.77 (0.60–0.99) 1.55 (1.16–2.07) Neonatal death ** - no. (%) †† 4 (0.4) 1 (0.3) 0 2 (0.3) 6 (0.4) 3 (0.3) 2 (0.2) 0 Abbreviations: gestational age (GA), risk ratio (RR), confidence interval (CI), Not available (NA) *Moderate to severe Covid-19 defined as one or more of the following. maternal death, intensive care unit admission, peripheral oxygen saturation below 85% at admission, pneumonia on imaging, or need for respiratory support with oxygen, high flow nasal cannula or continuous positive pressure mask, mechanical ventilation or extracorporeal membrane oxygenation. † Model 1: Variant + severity + interaction term for variant and severity. ‡ Model 2: Stillbirth: Model 1 + maternal age, ethnicity, employment status, body mass index, multiple pregnancy, smoking, parity, pre-existing medical conditions, pre-eclampsia, gestational diabetes, and gestational age at admission Preterm birth: Model 1 + maternal age, ethnicity, employment status, body mass index, multiple pregnancy, smoking, parity, pre-existing medical conditions, and pre-eclampsia. Neonatal admission: Model 1 + gestational age at birth, parity, and pre-existing medical conditions § Model 3: Model 2 + vaccination status. Vaccination started from January 1, 2021, so mild alpha infection was used as reference group. ¶ 45 infants born to symptomatic women had missing data for gestational age at birth. || 112 infants born to symptomatic women had missing data for admission to neonatal unit. ** 75 infants born to symptomatic women had missing data for neonatal death. †† risk ratios were not calculated due to low numbers. The absolute risk of stillbirth among symptomatic women was 0.8% for mild infection in the wild-type period and 1.6%, 1.3%, 1.9% and 2.4% with moderate to severe maternal infection in the wild-type, alpha, delta and omicron variant periods, respectively (Table 3 ). Compared to women with mild infection during the wild-type period, there was no evidence for a statistically significant increased risk of stillbirth for women with moderate to severe infection, except for during the delta period, noting that smaller numbers impacted the study power to detect differences as statistically significant. After adjusting for maternal risk factors, there was an increased risk of stillbirth during the delta period irrespective of infection severity (mild RR 3.57; 95%CI 1.66 to 7.67 and moderate to severe RR 2.41; 95%CI 1.03 to 5.60) when compared with mild infection during the wild-type period. (Table 3 , model 2). The risk of being born prior to 34 weeks’ gestation was 7.9% in the wild-type period and 9.4% with alpha (crude RR 1.21; 95%CI 0.94 to 1.55), 10.9% with delta (crude RR 1.49; 95%CI 1.18 to 1.87) and 4.5% with omicron (crude RR 0.53; 95%CI 0.38 to 0.74). The risk of being born at 34 + 0 -36 + 6 weeks’ gestation was 11.8% in the wild-type period and 11.9% with alpha (crude RR 1.03; 95%CI 0.83 to 1.87), 14.4% with delta (crude RR 1.31; 95%CI 1.07 to 1.59) and 10.9% with omicron (crude RR 0.87; 95%CI 0.69 to 1.11) (Supplementary Table S3). Compared with births among women with mild infection, infants born to women with moderate to severe infection had a fourfold increased risk of birth before 34 weeks’ gestation and a nearly doubled risk of birth at 34 + 0 -36 + 6 weeks’ gestation in the crude risk ratio analyses (Supplementary Table S4). When the association was examined by variant period and infection severity, the risk of being born preterm prior to 34 weeks’ gestation was 5.3% with mild maternal infection during the wild-type period, and 15.5%, 18.1%, 16.9% and 8.2% with moderate to severe maternal infection in the wild-type, alpha, delta and omicron variant periods, respectively. We found evidence of a multiplicative interaction between variant period and infection severity on the risk of preterm birth. The risk of birth before 34 weeks’ was five times higher among infants born to women with moderate to severe infection during the alpha and delta periods, compared with women with mild infection during the wild-type period, after adjusting for maternal risk factors (alpha RR 5.03; 95%CI 3.51 to 7.20; delta RR 4.94; 95%CI 3.52 to 6.94) (Table 3 , model 2) whereas this risk was doubled during the omicron period (RR 2.02; 95%CI 1.13 to 3.63) (Table 3 , model 2). The risk increase was two-to-threefold for birth between 34 + 0 to 36 + 6 weeks’ gestation among women with moderate to severe infection across all periods when compared to mild wild-type infection (Table 3 , model 2). We also found evidence of a multiplicative interaction between variant period and infection severity on neonatal unit admission. Compared with women with mild infection in the wild-type period, analyses accounting for both severity and variant in a model adjusted for maternal risk factors and gestational age at birth (model 2) showed 1.5 times higher risk of neonatal unit admission across all variant periods in neonates born to women with moderate to severe infection (Table 3 , model 2). These patterns for preterm birth and neonatal unit admission persisted after accounting for vaccination status (Table 3 , model 3). Neonatal deaths at less than seven days of age were rare, with a total of 18 deaths among babies born to symptomatic women (Table 3 ). Amongst 5,185 births to symptomatic women from January 1, 2021 onwards, when vaccination was recommended for pregnant women in risk groups, there were 91 stillbirths among symptomatic women; 91.2% (83/91) occurred to women with no documented vaccine or unknown vaccination status (Table 4 ). Women who were unvaccinated or had unknown vaccination status also gave birth to 92.1% (422/458) of the infants born before < 34 weeks’ gestation in the symptomatic group. Perinatal outcomes and maternal vaccination status for asymptomatic women are reported in online supplementary Table S5; 75% (49/65) of the stillbirths and 78.1% (249/319) of infants born prior to 34 weeks were born to women with no documented vaccination or unknown vaccination status. Table 4 Perinatal outcomes in births to women with symptomatic SARS-CoV-2 admitted to hospital by number of documented maternal vaccination doses, from January 1, 2021, to March 31, 2022, United Kingdom Vaccination status Unvaccinated (N = 3184) Vaccine status unknown (N = 1275) 1 dose (N = 347) 2 doses (N = 319) 3 doses (N = 60) Stillbirth - no. (%) 64 (2.0) 19 (1.5) 3 (0.9) 5 (0.6) 0 Preterm births * - no. (%) < 34 weeks 299 (9.5) 123 (9.7) 13 (3.8) 20 (6.3) 3 (5.0) 34 + 0 − 36 + 6 weeks’ 443 (14.0) 152 (12.0) 34 (9.9) 26 (8.2) 7 (11.7) Admission to Neonatal Unit † - no. (%) 620 (19.9) 270 (21.5) 40 (11.7) 40 (12.7) 9 (15.0) Neonatal Death ‡ - no. (%) 6 (0.2) 3 (0.2) 2 (0.6) 1 (0.3) 0 * 45 infants born to symptomatic women had missing data for gestational age at birth † 112 infants born to symptomatic women had missing data for admission to neonatal unit. ‡ 77 infants born to symptomatic women had missing data for neonatal death Discussion This national cohort study of pregnant women admitted to hospital with SARS-CoV-2 shows that compared with women with mild infection in the wild-type period there was increased risk of stillbirth for women with mild and moderate to severe infection during the delta period. The risk of preterm birth was increased for babies born to women with moderate to severe infection across all periods. Omicron was considered to be a variant with lower risk of adverse perinatal outcomes, 26 yet we observed a threefold increase in risk of birth prior to 34 weeks’ gestation for women with moderate to severe COVID-19 in this period compared with mild infection in the wild-type period, after accounting for vaccination status. Unvaccinated women were at higher risk of stillbirth and preterm birth. The key strengths of this study are that birth outcomes were available for almost all the included women. The large sample size provides sufficient statistical power to detect a difference in stillbirth during the delta period. We observed an increase in risk of preterm birth with moderate to severe maternal infection across all variant periods, demonstrating the merit of a nuanced analysis taking variant and severity into account. In addition, the availability of data about symptom status, severity of infection and vaccination status allowed robust regression models. The UKOSS system of active and uniform case identification across all pregnant women admitted to hospital in the UK that tested positive for SARS-CoV-2 reduces the risk of selection bias compared with other studies. Finally, the clinical information reduced the risk of misclassification bias, such as attributing adverse outcomes associated with pregnancy-related admission incorrectly to COVID-19. Several limitations also need to be considered. First, perinatal outcomes in births to pregnant women with SARS-CoV-2 who were not admitted to hospital at the time of infection could not be assessed. There would likely be few adverse outcomes in this group, as studies from other countries did not find an increased risk of adverse perinatal outcomes with a test-delivery interval exceeding ten days. 27 Second, we have included time periods when the variants of SARS-CoV-2 were dominant as proxy for individual variant sequencing data which were not available. Third, whilst providing robust data about the prevalence of stillbirth in women with COVID-19, we do not have clinical information to assess the cause of death and differentiate iatrogenic and spontaneous nature of the preterm birth We adjusted for known confounders, but there could be time-dependent changes that were unmeasured and may be important underlying causes of stillbirth and preterm birth. For example, indirect impacts of the pandemic such as competing hospital pressures, differing practice around intrapartum fetal monitoring for women with COVID-19, or delay in seeking care may contribute to the higher proportion of stillbirths observed in women with COVID-19 during the delta period, but this does not explain the increase in preterm births. The proportion of stillbirths observed in women with asymptomatic infection during the wild-type period was comparable to nationally-reported figures in the UK (4/1000 total births versus 3.5/1000 total births, respectively). 28 Recent UK-wide surveillance of perinatal deaths identified an increase in the perinatal mortality rate during 2021. 28 The current study indicates that COVID-19 in unvaccinated pregnant women could have contributed to this increase. This study significantly adds to the field since previous cohort studies that ended during earlier variant periods reported stillbirth rates comparable with pre-pandemic periods, 12 , 19 , 29 thus demonstrating the need for ongoing surveillance of perinatal outcomes during a pandemic to inform care. Similarly, other studies with shorter 30 or unclear 31 duration of follow up after admission with infection have had insufficient data to reliably compare severe perinatal outcomes and did not account for severity of maternal infection. By January 2022, 50.6% of the women who gave birth in England had received two vaccine doses. 32 Previous cohort studies have demonstrated the benefit of maternal SARS-CoV-2 vaccination to prevent hospital admission due to COVID-19 in pregnant women, 33 reduce moderate to severe maternal COVID-19, 2 , 4 and reduce infant hospitalization for COVID-19, severe neonatal morbidity and death. 3 , 34 , 35 The current study clearly demonstrates the benefit of maternal vaccination on perinatal outcomes, showing a large proportion of stillbirths in women with no documented vaccination in both those with and without any symptoms of COVID-19. Preterm birth is also associated with adverse short-term 36 and long-term 37 , 38 health outcomes and the need for neonatal unit admissions increases demand and economic impact on the health services. 39 With ongoing increasing SARS-CoV-2 infections, it is paramount to ensure that pregnant women are prioritised for vaccination, and that messaging around safety and access to vaccines is clear and readily available. Conclusion In this large national cohort comprising two years’ active surveillance over four SARS-CoV-2 variant periods and with near complete follow-up of pregnancy outcomes for included women, severe perinatal outcomes were more common in women with moderate to severe COVID-19, during the delta dominant period and among unvaccinated women. We provide strong evidence to recommend continuous surveillance of pregnancy outcomes in future pandemics and to continue to recommend vaccination in pregnancy to protect both mothers and babies. Declarations Study registration number: (https://doi.org/10.1186/ISRCTN40092247) Ethics approval: HRA NRES Committee East Midlands – Nottingham 1 (Ref. Number: 12/EM/0365). Information about ethnicity was self-determined according to the UK standard census categories (List of ethnic groups - GOV.UK (ethnicity-facts-figures.service.gov.uk) Rema Ramakrishnan, Hilde Engjom, Nicola Vousden and Marian Knight analysed the data. The study protocol was published at the study start and is available on the UKOSS website https://www.npeu.ox.ac.uk/ukoss/completed-surveillance/covid-19-in-pregnancy References Knight, M. , et al. Characteristics and outcomes of pregnant women admitted to hospital with confirmed SARS-CoV-2 infection in UK: national population based cohort study. BMJ 369 , m2107 (2020). Vousden, N. , et al. Severity of maternal infection and perinatal outcomes during periods in which Wildtype, Alpha and Delta SARS-CoV-2 variants were dominant: Data from the UK Obstetric Surveillance System national cohort. BMJ Medicine 1 (2022). Vousden, N. , et al. Management and implications of severe COVID-19 in pregnancy in the UK: data from the UK Obstetric Surveillance System national cohort. Acta Obstet Gynecol Scand 101 , 461-470 (2022). Engjom, H.M. , et al. Severity of maternal SARS-CoV-2 infection and perinatal outcomes of women admitted to hospital during the omicron variant dominant period using UK Obstetric Surveillance System data: prospective, national cohort study. BMJ Medicine 1 , e000190 (2022). Allotey, J. , et al. Clinical manifestations, risk factors, and maternal and perinatal outcomes of coronavirus disease 2019 in pregnancy: living systematic review and meta-analysis. BMJ 370 , m3320 (2020). D'Souza, R., Malhame, I. & Shah, P.S. Evaluating perinatal outcomes during a pandemic: A role for living systematic reviews. Acta Obstet Gynecol Scand 101 , 4-6 (2022). Woodworth, K.R. , et al. Birth and Infant Outcomes Following Laboratory-Confirmed SARS-CoV-2 Infection in Pregnancy - SET-NET, 16 Jurisdictions, March 29-October 14, 2020. MMWR Morb Mortal Wkly Rep 69 , 1635-1640 (2020). Villar, J. , et al. Association between fetal abdominal growth trajectories, maternal metabolite signatures early in pregnancy, and childhood growth and adiposity: prospective observational multinational INTERBIO-21st fetal study. Lancet Diabetes Endocrinol 10 , 710-719 (2022). Mullins, E. , et al. Pregnancy and neonatal outcomes of COVID-19: The PAN-COVID study. Eur J Obstet Gynecol Reprod Biol 276 , 161-167 (2022). Gurol-Urganci, I. , et al. Maternal and perinatal outcomes of pregnant women with SARS-CoV-2 infection at the time of birth in England: national cohort study. American journal of obstetrics and gynecology 225 , 522 e521-522 e511 (2021). Magnus, M.C. , et al. Pregnancy and risk of COVID-19: a Norwegian registry-linkage study. BJOG 129 , 101-109 (2022). Doyle, T.J. , et al. Maternal and Perinatal Outcomes Associated With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection During Pregnancy, Florida, 2020-2021: A Retrospective Cohort Study. Clin Infect Dis 75 , S308-S316 (2022). Magnus, M.C. , et al. Infection with SARS-CoV-2 during pregnancy and risk of stillbirth: a Scandinavian registry study. BMJ Public Health 1 , e000314 (2023). Perrotta, K. , et al. COVID-19 vaccine hesitancy and acceptance among pregnant people contacting a teratogen information service. J Genet Couns 31 , 1341-1348 (2022). Ceulemans, M. , et al. Vaccine Willingness and Impact of the COVID-19 Pandemic on Women's Perinatal Experiences and Practices-A Multinational, Cross-Sectional Study Covering the First Wave of the Pandemic. Int J Environ Res Public Health 18 (2021). Riley, L.E. mRNA Covid-19 Vaccines in Pregnant Women. N Engl J Med 384 , 2342-2343 (2021). Looi, M.K. Covid-19: Scientists sound alarm over new BA.2.86 "Pirola" variant. BMJ 382 , 1964 (2023). Centre for Disease Control and Prevention (CDC). Update on SARS CoV-2 Variant BA.2.86. (ed. Diseases, N.C.f.I.a.R.) (U.S. Department of Health and Human Services, Atlanta, 2023). Knight, M. , et al. Characteristics and outcomes of pregnant women admitted to hospital with confirmed SARS-CoV-2 infection in UK: national population based cohort study. BMJ 369 , m2107 (2020). National Records of Scotland. Monthly births Scotland. (2023). Northern Ireland Statistics and Research Agency. Monthly live births 2006 to 2023. (2023). Office for National Statistics. Births in England and Wales. (London, 2023). UK Health Security Agency. Investigation of SARS-CoV-2 variants: technical briefings. (ed. England, P.H.) (GOV.UK, London, 2023). World Health Organisation. COVID-19 Clinical Management: Living guidance 25 January 2021 (World Health Organisation, , Geneva, 2021). Joint Committee on Vaccination and Immunisation (JCVI). Pregnant women urged to come forward for COVID-19 vaccination. (ed. UK Health Security Agency) (UK, 2021). Stock, S.J. , et al. Pregnancy outcomes after SARS-CoV-2 infection in periods dominated by delta and omicron variants in Scotland: a population-based cohort study. Lancet Respir Med 10 , 1129-1136 (2022). Stephansson, O. , et al. SARS-CoV-2 and pregnancy outcomes under universal and non-universal testing in Sweden: register-based nationwide cohort study. BJOG 129 , 282-290 (2022). Draper ES, G.I., Smith LK, Matthews RJ, Fenton AC, Kurinczuk JJ, Smith PW, Manktelow BN, on behalf of the & Collaboration, M.-U. MBRRACE_UK Perinatal Mortality Surveillance UK perinatal deaths for births from 1 January 2021 to 31 December 2021 State of the Nation report. in The Infant Mortality and Morbidity Studies (ed. MBRRACE-UK, J.E.o.b.o.) (Department of Population Health Sciences, University of Leicester, Leicester, 2023). Donati, S., Corsi, E., Maraschini, A., Salvatore, M.A. & It, O.S.S.C.-W.G. SARS-CoV-2 infection among hospitalised pregnant women and impact of different viral strains on COVID-19 severity in Italy: a national prospective population-based cohort study. BJOG 129 , 221-231 (2022). Stock, S.J. , et al. SARS-CoV-2 infection and COVID-19 vaccination rates in pregnant women in Scotland. Nat Med 28 , 504-512 (2022). McClymont, E. , et al. Association of SARS-CoV-2 Infection During Pregnancy With Maternal and Perinatal Outcomes. JAMA 327 , 1983-1991 (2022). UK Health Security Agency. Vaccine uptake among pregnant women increasing but inequalitites persist. (ed. Agency, U.H.S.) (2022). Bosworth, M.L. , et al. Vaccine effectiveness for prevention of covid-19 related hospital admission during pregnancy in England during the alpha and delta variant dominant periods of the SARS-CoV-2 pandemic: population based cohort study. BMJ Med 2 , e000403 (2023). Halasa, N.B. , et al. Maternal Vaccination and Risk of Hospitalization for Covid-19 among Infants. N Engl J Med 387 , 109-119 (2022). Jorgensen, S.C.J. , et al. Newborn and Early Infant Outcomes Following Maternal COVID-19 Vaccination During Pregnancy. JAMA Pediatr (2023). Costeloe, K.L. , et al. Short term outcomes after extreme preterm birth in England: comparison of two birth cohorts in 1995 and 2006 (the EPICure studies). BMJ 345 , e7976 (2012). Pierrat, V. , et al. Neurodevelopmental outcomes at age 5 among children born preterm: EPIPAGE-2 cohort study. BMJ 373 , n741 (2021). Inder, T.E., Volpe, J.J. & Anderson, P.J. Defining the Neurologic Consequences of Preterm Birth. N Engl J Med 389 , 441-453 (2023). Khan, K.A. , et al. Economic costs associated with moderate and late preterm birth: a prospective population-based study. BJOG 122 , 1495-1505 (2015). Additional Declarations Yes there is potential Competing Interest. All authors have completed the ICMJE uniform disclosure form www.icmje.org/coi_disclosure.pdf and declare: MK, MQ, PB, PO’B, JJK received grants from the NIHR in relation to the submitted work. HME participated in this work as academic visitor to the NPEU with funding from The Norwegian Research Council, grant no 320181. KB, NV, RR, NS, CG have no conflicts of interest to declare. EM was Trustee and President of RCOG, Trustee of British Menopause Society and Chair of the Board of Trustees Group B Strep Support. PO’B was Vice President of RCOG and Co-Chair of the RCOG Vaccine Committee. No other relationships or activities that could appear to have influenced the submitted work. Supplementary Files SupplementaryUKOSSCovid19perinatal.docx Supplementary material nrreportingsummaryflat.pdf Article File - Reporting Summary signededitorialpolicychecklist.pdf Article File - Editorial Policy Checklist NatureMedicineSTROBEchecklistv4cohort.doc Article File - STROBE checklist Cite Share Download PDF Status: Published Journal Publication published 15 Apr, 2024 Read the published version in Nature Communications → Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3785899","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":265945667,"identity":"35721d3a-c114-4afe-8ada-8cf6e1776f78","order_by":0,"name":"Marian 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9JT","correspondingAuthor":false,"prefix":"","firstName":"Nigel","middleName":"","lastName":"Simpson","suffix":""},{"id":265945674,"identity":"48dd712a-0762-49e5-b818-1d4cd65e6bc8","order_by":7,"name":"Chris Gale","email":"","orcid":"","institution":"Neonatal Medicine, School of Public Health, Faculty of Medicine, Imperial College London, London, UK, SW7 2BX and Centre for Paediatrics and Child Health, Imperial College, London, UK, SW7 2AZ.","correspondingAuthor":false,"prefix":"","firstName":"Chris","middleName":"","lastName":"Gale","suffix":""},{"id":265945675,"identity":"ac34342c-b562-48fe-b1bb-28468ae2cf14","order_by":8,"name":"Pat O’Brien","email":"","orcid":"","institution":"Institute for Women’s Health, University College London, London, UK and Norfolk and Norwich University Hospital, Colney Lane, Norwich NR4 7UY, 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of Oxford, UK, OX3 7LF","correspondingAuthor":false,"prefix":"","firstName":"Jennifer","middleName":"","lastName":"Kurinczuk","suffix":""}],"badges":[],"createdAt":"2023-12-21 09:05:12","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3785899/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3785899/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1038/s41467-024-47181-z","type":"published","date":"2024-04-15T04:00:00+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":49385533,"identity":"69e3b5fd-af8f-44f2-8fc3-7e4be525b51b","added_by":"auto","created_at":"2024-01-09 19:51:08","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":144002,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eMonthly rate (%) of perinatal outcomes\u003c/strong\u003e: stillbirth, preterm birth (\u0026lt;34 weeks’ and 34\u003csup\u003e+0\u003c/sup\u003e –36\u003csup\u003e+6\u003c/sup\u003e weeks), and admission to neonatal unit, by symptom status; asymptomatic women in the upper panel and symptomatic women in the lower panel. Number of women admitted to hospital for each month from March 2020 to March 2022 is shown on Y axis to the right. Vaccination status among included women by minimum number of doses recorded; at least 1 dose, 2 doses or 3 doses (%) is shown in the dotted lines. The vertical dashed lines indicate key vaccination policies: First COVID-19 vaccine administered in the U.K. in December 31, 2020 and pregnant women were included as priority group by the Joint Committee on Vaccination and Immunisation (JCVI) in the U.K. The dominant SARS-CoV-2 variant is indicated by the background color.\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-3785899/v1/882015189818c6b0b28e2d5e.jpg"},{"id":54745301,"identity":"f7602e9b-27e3-461b-a1d8-91f5495a2393","added_by":"auto","created_at":"2024-04-16 07:07:57","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":542094,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3785899/v1/dfa68829-b023-4ee4-b72a-f7bae266f1f0.pdf"},{"id":49385536,"identity":"feea1e5c-f3ef-4afb-bb6b-f482f6950c5c","added_by":"auto","created_at":"2024-01-09 19:51:09","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":110118,"visible":true,"origin":"","legend":"\u003cp\u003eSupplementary material\u003c/p\u003e","description":"","filename":"SupplementaryUKOSSCovid19perinatal.docx","url":"https://assets-eu.researchsquare.com/files/rs-3785899/v1/d7e09ace187e7a61f5a06ef9.docx"},{"id":49385535,"identity":"ca1e5009-68ab-49b1-9786-fc4ca7081470","added_by":"auto","created_at":"2024-01-09 19:51:09","extension":"pdf","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":2738311,"visible":true,"origin":"","legend":"Article File - Reporting Summary","description":"","filename":"nrreportingsummaryflat.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3785899/v1/795dd0664d4664942cd9f665.pdf"},{"id":49385537,"identity":"39c75f69-5e81-492d-bd26-16d5ac5ef330","added_by":"auto","created_at":"2024-01-09 19:51:09","extension":"pdf","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":2310144,"visible":true,"origin":"","legend":"Article File - Editorial Policy Checklist","description":"","filename":"signededitorialpolicychecklist.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3785899/v1/6f30786a1a4c53f2d3f1ad6f.pdf"},{"id":49385534,"identity":"36bfcf8a-71cd-473c-b433-9473468f7651","added_by":"auto","created_at":"2024-01-09 19:51:09","extension":"doc","order_by":4,"title":"","display":"","copyAsset":false,"role":"supplement","size":87040,"visible":true,"origin":"","legend":"Article File - STROBE checklist","description":"","filename":"NatureMedicineSTROBEchecklistv4cohort.doc","url":"https://assets-eu.researchsquare.com/files/rs-3785899/v1/779b1de05d5e95b5b651fe63.doc"}],"financialInterests":"\u003cb\u003eYes\u003c/b\u003e there is potential Competing Interest.\nAll authors have completed the ICMJE uniform disclosure form www.icmje.org/coi_disclosure.pdf and declare: MK, MQ, PB, PO’B, JJK received grants from the NIHR in relation to the submitted work. HME participated in this work as academic visitor to the NPEU with funding from The Norwegian Research Council, grant no 320181. KB, NV, RR, NS, CG have no conflicts of interest to declare. EM was Trustee and President of RCOG, Trustee of British Menopause Society and Chair of the Board of Trustees Group B Strep Support. PO’B was Vice President of RCOG and Co-Chair of the RCOG Vaccine Committee. No other relationships or activities that could appear to have influenced the submitted work.","formattedTitle":"Perinatal outcomes after admission with COVID-19 in pregnancy: a UK national cohort","fulltext":[{"header":"Introduction","content":"\u003cp\u003eDuring the course of the pandemic, evolving variants of SARS-CoV-2 were associated with higher risk of severe maternal disease and adverse perinatal outcomes, but short observation time and lack of outcome data for continuing pregnancies were likely to bias results towards pregnancies ending at an earlier gestation and with more severe perinatal outcomes.\u003csup\u003e\u003cspan additionalcitationids=\"CR2 CR3\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eThe latest update of the World Health Organization (WHO) systematic review of coronavirus disease in pregnancy included studies published early in the alpha-dominant period.\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e Few of the studies in the WHO review were population-based or based on European data, and concerns have been raised about the conduct of other systematic reviews and the quality of included studies.\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eSeveral of the larger multinational registry studies of COVID-19 in pregnancy lacked information about the source population and relied on passive, voluntary reporting,\u003csup\u003e\u003cspan additionalcitationids=\"CR8\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e and studies linking national routine health registry data have been unclear whether hospital admission was related to COVID-19 or pregnancy complications.\u003csup\u003e\u003cspan additionalcitationids=\"CR11 CR12\" citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e Robust evidence is needed to inform the care of pregnant women and counselling regarding vaccination,\u003csup\u003e\u003cspan additionalcitationids=\"CR15\" citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e particularly given the current increase in hospitalisations due to the omicron (XBB) lineage viruses and new emerging variants such as \u0026ldquo;pirola\u0026ldquo; (BA.2.86).\u003csup\u003e17 18\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eTherefore, this study aimed to assess perinatal outcomes for mothers admitted to hospital with SARS-CoV-2 infection using a population-based national cohort with comprehensive follow-up.\u003c/p\u003e "},{"header":"Methods ","content":"\u003ch2\u003eSTUDY DESIGN AND OVERSIGHT\u003c/h2\u003e\n\u003cp\u003eThe United Kingdom Obstetric Surveillance System (UKOSS) has a source population of all women giving birth or being admitted to one of the 194 consultant-led maternity units in England, Northern Ireland, Scotland and Wales, approximately 720,000 maternities annually.\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e19\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e A protocol for active surveillance of pregnant women admitted to hospital with viral infection was planned in 2012, approved by the ethical review board (HRA NRES Committee East Midlands, Nottingham 1 (Ref. Number: 12/EM/0365) and hibernated (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1186/ISRCTN40092247\u003c/span\u003e\u003c/span\u003e). The protocol was activated for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) from March 1, 2020, and concluded on March 31, 2022. Routines were in place to ensure complete reporting (online supplementary),\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e and follow-up information about birth outcomes up to December 31, 2022, were retrieved from clinical records until April 24, 2023. Maternal and perinatal deaths were cross-checked with the MBRRACE-UK mortality surveillance. (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.npeu.ox.ac.uk/mbrrace-uk\u003c/span\u003e\u003c/span\u003e). The corresponding author vouches for the accuracy and completeness of the data and reporting. Patients and public were part of the UKOSS steering committee and involved in study design, oversight, reporting and dissemination of study findings but not in the conduct of the study. The funder played no role in study design; in the collection, analysis, and interpretation of data; in the writing of the report; nor in the decision to submit the paper for publication.\u003c/p\u003e\n\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\n\u003ch2\u003eSTUDY POPULATION AND GROUPS\u003c/h2\u003e\n\u003cp\u003ePregnant women were included if admitted to hospital with a positive SARS-CoV-2 reverse transcriptase polymerase chain reaction (PCR) test within seven days of admission, during admission or up to two days after giving birth. Women were further classified according to their SARS-CoV-2 symptoms (symptomatic/asymptomatic); severity of infection (mild/moderate to severe); and the dominant viral variant in UK at the time of the PCR test (wild-type March 1 to November 30 2020; alpha December 1 2020, to May 15 2021; delta May 16 to December 14 2021; omicron December 15 2021, to March 31 2022).\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e23\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e\n\u003ch2\u003eSEVERITY OF MATERNAL COVID-19\u003c/h2\u003e\n\u003cp\u003eModerate to severe maternal COVID-19 was defined according to modified WHO criteria as maternal death, maternal intensive care admission, peripheral oxygen saturation below 95% at admission, pneumonia on radiological imaging or need for respiratory support (either oxygen supplementation, non-invasive ventilation (high flow nasal oxygen or continuous positive airway pressure), mechanical ventilation or extracorporeal membrane oxygenation (ECMO)).\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\n\u003ch2\u003eMATERNAL CHARACTERISTICS AND MEDICAL RISK FACTORS\u003c/h2\u003e\n\u003cp\u003eThe sociodemographic characteristics and medical risk factors recorded were maternal age, maternal body mass index (kg/m\u003csup\u003e2\u003c/sup\u003e), employment, ethnic background, smoking, pre-existing medical conditions (no medical conditions (reference) vs asthma, hypertension, cardiac disease or diabetes), preeclampsia, gestational diabetes, parity, plurality and gestational age at admission (categorised by completed weeks into \u0026lt;\u0026thinsp;22, 22 to 27, 28\u0026ndash;33, 34\u0026ndash;36 and \u0026ge;\u0026thinsp;37 weeks).\u003c/p\u003e\n\u003cp\u003eVaccination status was recorded from January 2021 after vaccination was recommended for pregnant women in risk groups in the UK from December 22, 2020.\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e\n\u003ch2\u003ePREGNANCY AND PERINATAL OUTCOMES\u003c/h2\u003e\n\u003cp\u003ePregnancy outcomes examined were pregnancy loss (\u0026lt;\u0026thinsp;24 weeks\u0026rsquo; gestation), gestational age at birth, expedited birth due to COVID-19, and mode of birth (spontaneous vaginal, operative vaginal, caesarean section prior to or during labor). The perinatal outcomes were stillbirth at \u0026ge;\u0026thinsp;24 weeks\u0026rsquo; gestation, preterm birth (\u0026lt;\u0026thinsp;34 weeks\u0026rsquo; and 34\u003csup\u003e+\u0026thinsp;0\u003c/sup\u003e to 36\u003csup\u003e+\u0026thinsp;6\u003c/sup\u003e weeks\u0026rsquo; gestation), neonatal unit admission, and neonatal death within seven days after birth.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e\n\u003ch2\u003eSTATISTICAL ANALYSES\u003c/h2\u003e\n\u003cp\u003ePercentages and frequencies were computed by symptom group, and for symptomatic women by severity of infection, dominant variant, and vaccination status. Where data were missing, percentages are presented as the proportion of cases known.\u003c/p\u003e\n\u003cp\u003eRisk ratios (RR) with 95% confidence intervals (CI) for stillbirth, preterm birth and admission to neonatal unit for births to symptomatic women were computed using symptomatic mild infection during the wild-type period as the reference category with the lowest absolute risk. Since severity and variant were known risk factors, we included a preplanned interaction analysis to assess the combined effect of these factors.\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e2\u003c/span\u003e,\u003cspan class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e Several models were run: models with dominant variant only (crude RR), disease severity only (crude RR), and with an interaction term for variant and severity (interaction without covariates (model 1); adjusted for selected covariates without vaccination status (model 2); and adjusted for selected covariates and vaccination status using mild infection during the alpha period as reference (model 3).\u003c/p\u003e\n\u003cp\u003eMultilevel Poisson or multinomial regression model as appropriate was used with random intercept to account for clustering effect among multiple pregnancies. The multivariable model for stillbirth was adjusted for maternal age, ethnicity, employment status, body mass index, plurality, smoking, parity, medical conditions prior to or during pregnancy and gestational age at admission. The preterm birth model included the above except gestational age at admission, and the model for neonatal unit admission was adjusted for gestational age at birth, parity, and medical conditions. Statistical analyses were performed using STATA version 18 (Statacorp, TX, USA).\u003c/p\u003e\n\u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eAmong a source population of approximately 1.5\u0026nbsp;million maternities,\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e20\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e 16,627 women were included (Supplementary Figure \u003cspan class=\"InternalRef\"\u003eS1\u003c/span\u003e). Their characteristics are shown by symptom status and severity in Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e. A higher proportion of women with moderate to severe COVID-19 were overweight or obese, had diabetes or asthma, and were of a minority ethnic background compared with women with asymptomatic or mild infection. Women with moderate to severe infection were more likely to be admitted prior to 37 weeks\u0026rsquo; gestation (77.3%) compared with asymptomatic women (24.9%) and women with mild infection (51.3%). Vaccination coverage increased gradually amongst women admitted with SARS-CoV-2 from May 2021 onwards (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tab1\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eCharacteristics of pregnant women admitted with SARS-CoV-2, by symptom group, March 1, 2020, to March 31, 2022, United Kingdom.\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eSymptom group\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eAsymptomatic\u003c/p\u003e\n\u003cp\u003e(N\u0026thinsp;=\u0026thinsp;9374)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eMild infection\u003c/p\u003e\n\u003cp\u003e(N\u0026thinsp;=\u0026thinsp;4901)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eModerate to severe infection\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003e(N\u0026thinsp;=\u0026thinsp;2352)\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAge (years) - no. (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026lt;\u0026thinsp;20\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e231 (2.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e100 (2.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e21 (0.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e20\u0026ndash;34\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e6685 (71.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3583 (73.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1544 (65.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026ge;35\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2438 (26.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1210 (24.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e782 (33.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMissing\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e20\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e8\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e5\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eBody Mass Index (BMI) (kg/m\u003csup\u003e2\u003c/sup\u003e) - no. (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eUnderweight (\u0026lt;\u0026thinsp;18.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e229 (2.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e101 (2.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e17 (0.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNormal (18.5 to \u0026lt;\u0026thinsp;25)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3599 (39.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1829 (38.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e529 (23.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eOverweight (25 to \u0026lt;\u0026thinsp;30)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2702 (29.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1467 (30.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e714 (31.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eObese (\u0026ge;\u0026thinsp;30)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2528 (27.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1357 (28.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1000 (44.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMissing\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e316\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e147\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e92\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eWoman or partner in paid work - no. (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e7010 (74.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3788 (77.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1791 (76.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eEthnic Group - no. (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eWhite\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e6107 (66.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3134 (65.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1350 (58.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAsian\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1689 (18.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e934 (19.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e519 (22.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eBlack\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e825 (9.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e418 (8.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e254 (11.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eChinese/Other\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e282 (3.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e178 (3.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e110 (4.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMixed\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e249 (2.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e129 (2.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e59 (2.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMissing\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e222\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e108\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e60\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCurrent smoking - no. (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1547 (17.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e626 (13.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e178 (7.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMissing\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e294\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e138\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e68\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePre-existing medical conditions - no. (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAsthma\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e552 (5.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e375 (7.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e231 (9.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eHypertension\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e155 (1.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e80 (1.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e55 (2.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCardiac disease\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e114 (1.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e68 (1.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e38 (1.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eDiabetes\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e132 (1.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e71 (1.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e60 (2.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMedical conditions during pregnancy\u003c/p\u003e\n\u003cp\u003e- no. (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePre-eclampsia\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e141 (1.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e73 (1.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e49 (2.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eGestational diabetes\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e595 (6.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e354 (7.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e263 (11.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMultiparous - no. (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e5749 (61.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3038 (62.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1626 (69.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMissing\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e90\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e35\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e22\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMultiple pregnancy - no. (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e140 (1.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e96 (2.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e51 (2.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eGestation at admission\u003c/p\u003e\n\u003cp\u003e(weeks\u003csup\u003edays\u003c/sup\u003e) - no. (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026lt;\u0026thinsp;22\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e463 (5.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e468 (9.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e194 (8.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e22\u0026ndash;27\u003csup\u003e+\u0026thinsp;6\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e300 (3.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e445 (9.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e415 (17.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e28\u0026ndash;33\u003csup\u003e+\u0026thinsp;6\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e639 (6.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e863 (17.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e738 (31.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e34\u0026ndash;36\u003csup\u003e+\u0026thinsp;6\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e915 (9.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e729 (14.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e455 (19.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e37 or more\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e6987 (75.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2374 (48.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e529 (22.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMissing\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e70\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e22\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e21\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eEvidence of pneumonia on imaging - no. (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1695 (72.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eRespiratory support required - no. (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003csup\u003e\u0026dagger;\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1709 (76.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eIntensive Care Unit admission - no. (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003csup\u003e\u0026dagger;\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e771 (32.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMaternal Death - no. (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1 (0.01)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e38 (1.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eVaccination status - no. (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eUnvaccinated\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e6099 (65.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3424 (69.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1785 (75.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1 dose\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e620 (6.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e271 (5.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e72 (3.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2 doses\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e835 (8.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e290 (5.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e41 (1.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3 doses\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e140 (1.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e53 (1.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e4 (0.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNot known/\u003c/p\u003e\n\u003cp\u003enot documented\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1680 (17.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e863 (17.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e450 (19.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"4\" align=\"left\"\u003e\n\u003cp\u003e\u003csup\u003e*\u003c/sup\u003eModerate to severe Covid-19 was defined as one or more of the following: maternal death, intensive care unit admission, peripheral oxygen saturation below 85% at admission, pneumonia on imaging, or need for respiratory support with either oxygen, high flow nasal cannula or continuous positive pressure mask, mechanical ventilation or extracorporeal membrane oxygenation.\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e\u0026dagger;\u003c/sup\u003e 27 (0.3%) asymptomatic women needed respiratory support or were admitted to ICU for other reasons and one of them died from other causes than Covid-19.\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eOf the 16,386 (98.6%) women with known pregnancy outcomes, 1.9% (n\u0026thinsp;=\u0026thinsp;319) experienced a pregnancy loss (Supplementary Figure \u003cspan class=\"InternalRef\"\u003eS1\u003c/span\u003e) and the remaining 16,067 women gave birth to 16,351 infants of whom 190 were stillborn. Pregnancy outcomes for symptomatic women are shown by variant and severity in Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e, and for asymptomatic women in Supplementary Table \u003cspan class=\"InternalRef\"\u003eS1\u003c/span\u003e. Women with moderate to severe COVID-19 were more likely to give birth prior to 37 weeks, have an expedited birth due to COVID-19 and a pre-labour caesarean birth than women with mild disease.\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tab2\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eMaternal and pregnancy outcomes for women with symptomatic SARS-CoV-2 by severity, March 1, 2020 to March 31, 2022, United Kingdom.\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eSeverity\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eMild\u003c/p\u003e\n\u003cp\u003einfection\u003c/p\u003e\n\u003cp\u003e(N\u0026thinsp;=\u0026thinsp;4901)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eModerate to severe infection\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003e(N\u0026thinsp;=\u0026thinsp;2352)\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePregnancy outcome - no. (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eBirth\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e4710 (96.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2264 (96.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePregnancy loss\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e92 (1.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e26 (1.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eBirth outcome unknown\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e99 (2.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e62 (2.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eGestation at birth\u003c/p\u003e\n\u003cp\u003e(weeks\u003csup\u003e+\u0026thinsp;days\u003c/sup\u003e)\u003csup\u003e\u0026dagger;\u003c/sup\u003e - no. (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e22\u003csup\u003e+\u0026thinsp;0\u003c/sup\u003e \u0026ndash; 27\u003csup\u003e+\u0026thinsp;6\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e47 (1.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e49 (2.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e28\u003csup\u003e+\u0026thinsp;0\u003c/sup\u003e \u0026ndash; 33\u003csup\u003e+\u0026thinsp;6\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e180 (3.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e305 (13.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e34\u003csup\u003e+\u0026thinsp;0\u003c/sup\u003e \u0026ndash; 36\u003csup\u003e+\u0026thinsp;6\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e441 (9.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e395 (17.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e37\u003csup\u003e+\u0026thinsp;0\u003c/sup\u003e or more\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e4022 (85.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1490 (66.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cem\u003eMissing\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cem\u003e20\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cem\u003e24\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eBirth expedited due to COVID-19\u003csup\u003e\u0026dagger;\u003c/sup\u003e - no. (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e80 (1.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e601 (26.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMode of birth\u003csup\u003e\u0026dagger;\u003c/sup\u003e - no. (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePre-labour Caesarean\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1246 (26.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1129 (50.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCaesarean after labour onset\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e702 (15.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e260 (11.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eOperative vaginal\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e491 (10.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e141 (6.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSpontaneous vaginal\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2239 (47.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e712 (31.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cem\u003eMissing\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cem\u003e32\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cem\u003e21\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"3\" align=\"left\"\u003e\n\u003cp\u003e*Moderate to severe Covid-19 defined as one or more of the following. maternal death, intensive care unit admission, peripheral oxygen saturation below 85% at admission, pneumonia on imaging, or need for respiratory support with oxygen, high flow nasal cannula or continuous positive pressure mask, mechanical ventilation or extracorporeal membrane oxygenation.\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e\u0026dagger;\u003c/sup\u003e Pregnancy loss excluded from denominator\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eThe perinatal outcomes for births to symptomatic women are shown in Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e and for births to asymptomatic women in Supplementary Table S2. Amongst the 7,116 infants born to 6,974 symptomatic women, 1.6% (n\u0026thinsp;=\u0026thinsp;111) were stillborn and 8.2% (n\u0026thinsp;=\u0026thinsp;581) were born prior to 34 weeks\u0026rsquo; gestation (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tab3\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003ePerinatal outcomes for babies of women admitted to hospital with symptomatic SARS-CoV-2 by dominant variant period and severity of maternal infection, March 1, 2020, to March 31, 2022, United Kingdom.\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eSARS-CoV-2 dominant variant\u003c/p\u003e\n\u003c/th\u003e\n\u003cth colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eWild-type period\u003c/p\u003e\n\u003c/th\u003e\n\u003cth colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eAlpha period\u003c/p\u003e\n\u003c/th\u003e\n\u003cth colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eDelta period\u003c/p\u003e\n\u003c/th\u003e\n\u003cth colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eOmicron period\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSeverity*\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMild\u003c/p\u003e\n\u003cp\u003e(N\u0026thinsp;=\u0026thinsp;1067)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eModerate to severe\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003e(N\u0026thinsp;=\u0026thinsp;370)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMild\u003c/p\u003e\n\u003cp\u003e(N\u0026thinsp;=\u0026thinsp;1220)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eModerate to severe\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003e(N\u0026thinsp;=\u0026thinsp;678)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMild\u003c/p\u003e\n\u003cp\u003e(N\u0026thinsp;=\u0026thinsp;1420)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eModerate to severe\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003e(N\u0026thinsp;=\u0026thinsp;1055)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMild\u003c/p\u003e\n\u003cp\u003e(N\u0026thinsp;=\u0026thinsp;1098)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eModerate to severe\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003e(N\u0026thinsp;=\u0026thinsp;208)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eStillbirths - no. (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e9 (0.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e6 (1.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e12 (1.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e9 (1.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e42 (3.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e20 (1.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e8 (0.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e5 (2.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eModel 1\u003csup\u003e\u0026dagger;\u003c/sup\u003e: RR\u003c/p\u003e\n\u003cp\u003e(95% CI\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e[Ref]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.93\u003c/p\u003e\n\u003cp\u003e(0.68\u0026ndash;5.38)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.17\u003c/p\u003e\n\u003cp\u003e(0.49\u0026ndash;2.76)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.57\u003c/p\u003e\n\u003cp\u003e(0.63\u0026ndash;3.95)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3.49\u003c/p\u003e\n\u003cp\u003e(1.70\u0026ndash;7.18)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2.25\u003c/p\u003e\n\u003cp\u003e(1.03\u0026ndash;4.92)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.86\u003c/p\u003e\n\u003cp\u003e(0.32\u0026ndash;2.34)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2.86\u003c/p\u003e\n\u003cp\u003e(0.96\u0026ndash;8.46)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eModel 2\u003csup\u003e\u0026Dagger;\u003c/sup\u003e: RR\u003c/p\u003e\n\u003cp\u003e(95% CI)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e[Ref]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.90\u003c/p\u003e\n\u003cp\u003e(0.61\u0026ndash;5.88)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.20\u003c/p\u003e\n\u003cp\u003e(0.49\u0026ndash;2.97)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.68\u003c/p\u003e\n\u003cp\u003e(0.63\u0026ndash;4.51)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3.57\u003c/p\u003e\n\u003cp\u003e(1.66\u0026ndash;7.67)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2.41\u003c/p\u003e\n\u003cp\u003e(1.03\u0026ndash;5.60)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.96\u003c/p\u003e\n\u003cp\u003e(0.35\u0026ndash;2.66)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2.62\u003c/p\u003e\n\u003cp\u003e(0.79\u0026ndash;8.69)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eModel 3\u003csup\u003e\u0026sect;\u003c/sup\u003e: RR\u003c/p\u003e\n\u003cp\u003e(95% CI)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNA\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNA\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e[Ref]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.99\u003c/p\u003e\n\u003cp\u003e(0.33\u0026ndash;3.01)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2.82\u003c/p\u003e\n\u003cp\u003e(1.29\u0026ndash;6.16)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.89\u003c/p\u003e\n\u003cp\u003e(0.81\u0026ndash;4.40)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.79\u003c/p\u003e\n\u003cp\u003e(0.25\u0026ndash;2.47)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2.07\u003c/p\u003e\n\u003cp\u003e(0.64\u0026ndash;6.76)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePreterm live birth\u003csup\u003e\u0026para;\u003c/sup\u003e - no. (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026lt;\u0026thinsp;34 weeks\u0026rsquo; GA\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e56 (5.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e57 (15.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e56 (4.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e121 (18.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e92 (6.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e177 (16.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e41 (3.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e17 (8.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eModel 1\u003csup\u003e\u0026dagger;\u003c/sup\u003e: RR\u003c/p\u003e\n\u003cp\u003e(95% CI)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e[Ref]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3.74\u003c/p\u003e\n\u003cp\u003e(2.52\u0026ndash;5.55)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.87\u003c/p\u003e\n\u003cp\u003e(0.59\u0026ndash;1.27)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e4.41\u003c/p\u003e\n\u003cp\u003e(3.15\u0026ndash;6.17)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.27\u003c/p\u003e\n\u003cp\u003e(0.90\u0026ndash;1.79)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e4.26\u003c/p\u003e\n\u003cp\u003e(3.10\u0026ndash;5.85)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.69\u003c/p\u003e\n\u003cp\u003e(0.46\u0026ndash;1.04)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.83\u003c/p\u003e\n\u003cp\u003e(1.04\u0026ndash;3.24)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eModel 2\u003csup\u003e\u0026Dagger;\u003c/sup\u003e: RR\u003c/p\u003e\n\u003cp\u003e(95% CI)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e[Ref]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3.46\u003c/p\u003e\n\u003cp\u003e(2.24\u0026ndash;5.34)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.84\u003c/p\u003e\n\u003cp\u003e(0.56\u0026ndash;1.27)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e5.03\u003c/p\u003e\n\u003cp\u003e(3.51\u0026ndash;7.20)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.37\u003c/p\u003e\n\u003cp\u003e(0.95\u0026ndash;1.97)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e4.94\u003c/p\u003e\n\u003cp\u003e(3.52\u0026ndash;6.94)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.66\u003c/p\u003e\n\u003cp\u003e(0.42\u0026ndash;1.03)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2.02\u003c/p\u003e\n\u003cp\u003e(1.13\u0026ndash;3.63)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eModel 3\u003csup\u003e\u0026sect;\u003c/sup\u003e: RR\u003c/p\u003e\n\u003cp\u003e(95% CI)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNA\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNA\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e[Ref]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e6.84\u003c/p\u003e\n\u003cp\u003e(4.42\u0026ndash;10.59)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.92\u003c/p\u003e\n\u003cp\u003e(1.24\u0026ndash;2.96)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e7.01\u003c/p\u003e\n\u003cp\u003e(4.65\u0026ndash;10.59)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.98\u003c/p\u003e\n\u003cp\u003e(0.59\u0026ndash;1.63)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2.98\u003c/p\u003e\n\u003cp\u003e(1.57\u0026ndash;5.65)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e34\u003csup\u003e+\u0026thinsp;0\u003c/sup\u003e \u0026ndash; 36\u003csup\u003e+\u0026thinsp;6\u003c/sup\u003e weeks\u0026rsquo; GA\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e104 (9.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e65 (17.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e120 (9.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e105 (15.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e153 (10.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e201 (19.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e101 (18.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e41 (19.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eModel 1\u003csup\u003e\u0026dagger;\u003c/sup\u003e: RR\u003c/p\u003e\n\u003cp\u003e(95% CI)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e[Ref]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2.30\u003c/p\u003e\n\u003cp\u003e(1.63\u0026ndash;3.23)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.00\u003c/p\u003e\n\u003cp\u003e(0.76\u0026ndash;1.32)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2.06\u003c/p\u003e\n\u003cp\u003e(1.54\u0026ndash;2.77)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.14\u003c/p\u003e\n\u003cp\u003e(0.87\u0026ndash;1.48)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2.60\u003c/p\u003e\n\u003cp\u003e(2.01\u0026ndash;3.37)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.92\u003c/p\u003e\n\u003cp\u003e(0.69\u0026ndash;1.22)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2.38\u003c/p\u003e\n\u003cp\u003e(1.59\u0026ndash;3.56)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eModel 2\u003csup\u003e\u0026Dagger;\u003c/sup\u003e: RR\u003c/p\u003e\n\u003cp\u003e(95% CI)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e[Ref]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2.36\u003c/p\u003e\n\u003cp\u003e(1.62\u0026ndash;3.42)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.00\u003c/p\u003e\n\u003cp\u003e(0.74\u0026ndash;1.34)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2.38\u003c/p\u003e\n\u003cp\u003e(1.73\u0026ndash;3.26)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.18\u003c/p\u003e\n\u003cp\u003e(0.89\u0026ndash;1.57)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2.92\u003c/p\u003e\n\u003cp\u003e(2.22\u0026ndash;3.86)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.04\u003c/p\u003e\n\u003cp\u003e(0.77\u0026ndash;1.42)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2.55\u003c/p\u003e\n\u003cp\u003e(1.67\u0026ndash;3.87)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eModel 3\u003csup\u003e\u0026sect;\u003c/sup\u003e: RR\u003c/p\u003e\n\u003cp\u003e(95% CI)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNA\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNA\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e[Ref]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2.32\u003c/p\u003e\n\u003cp\u003e(1.63\u0026ndash;3.31)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.23\u003c/p\u003e\n\u003cp\u003e(0.90\u0026ndash;1.67)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3.00\u003c/p\u003e\n\u003cp\u003e(2.21\u0026ndash;4.06)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.20\u003c/p\u003e\n\u003cp\u003e(0.85\u0026ndash;1.69)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2.81\u003c/p\u003e\n\u003cp\u003e(1.81\u0026ndash;4.35)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNeonatal unit admission\u003csup\u003e||\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003e- no. (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e144 (13.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e120 (33.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e160 (13.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e231 (34.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e180 (13.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e349 (33.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e105 (9.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e50 (24.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eModel 1\u003csup\u003e\u0026dagger;\u003c/sup\u003e: RR\u003c/p\u003e\n\u003cp\u003e(95% CI)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e[Ref]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2.43\u003c/p\u003e\n\u003cp\u003e(1.97- 3.00)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.98\u003c/p\u003e\n\u003cp\u003e(0.79\u0026ndash;1.20)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2.53\u003c/p\u003e\n\u003cp\u003e(2.11\u0026ndash;3.05)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.96\u003c/p\u003e\n\u003cp\u003e(0.78\u0026ndash;1.18)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2.47\u003c/p\u003e\n\u003cp\u003e(2.08\u0026ndash;2.94)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.71\u003c/p\u003e\n\u003cp\u003e(0.56\u0026ndash;0.90)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.80\u003c/p\u003e\n\u003cp\u003e(1.35\u0026ndash;2.39)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eModel 2\u003csup\u003e\u0026Dagger;\u003c/sup\u003e: RR\u003c/p\u003e\n\u003cp\u003e(95% CI)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e[Ref]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.61\u003c/p\u003e\n\u003cp\u003e(1.32\u0026ndash;1.96)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.99\u003c/p\u003e\n\u003cp\u003e(0.81\u0026ndash;1.21)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.61\u003c/p\u003e\n\u003cp\u003e(1.35\u0026ndash;1.93)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.88\u003c/p\u003e\n\u003cp\u003e(0.73\u0026ndash;1.08)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.52\u003c/p\u003e\n\u003cp\u003e(1.28\u0026ndash;1.81)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.76\u003c/p\u003e\n\u003cp\u003e(0.61\u0026ndash;0.95)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.51\u003c/p\u003e\n\u003cp\u003e(1.16\u0026ndash;1.97)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eModel 3\u003csup\u003e\u0026sect;\u003c/sup\u003e: RR\u003c/p\u003e\n\u003cp\u003e(95% CI)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNA\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNA\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e[Ref]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.60\u003c/p\u003e\n\u003cp\u003e(1.30\u0026ndash;1.97)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.92\u003c/p\u003e\n\u003cp\u003e(0.73\u0026ndash;1.14)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.57\u003c/p\u003e\n\u003cp\u003e(1.28\u0026ndash;1.94)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.77\u003c/p\u003e\n\u003cp\u003e(0.60\u0026ndash;0.99)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.55\u003c/p\u003e\n\u003cp\u003e(1.16\u0026ndash;2.07)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNeonatal death\u003csup\u003e**\u003c/sup\u003e - no. (%)\u003csup\u003e\u0026dagger;\u0026dagger;\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e4 (0.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1 (0.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2 (0.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e6 (0.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3 (0.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2 (0.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"9\" align=\"left\"\u003e\n\u003cp\u003eAbbreviations: gestational age (GA), risk ratio (RR), confidence interval (CI), Not available (NA)\u003c/p\u003e\n\u003cp\u003e*Moderate to severe Covid-19 defined as one or more of the following. maternal death, intensive care unit admission, peripheral oxygen saturation below 85% at admission, pneumonia on imaging, or need for respiratory support with oxygen, high flow nasal cannula or continuous positive pressure mask, mechanical ventilation or extracorporeal membrane oxygenation.\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e\u0026dagger;\u003c/sup\u003eModel 1: Variant\u0026thinsp;+\u0026thinsp;severity\u0026thinsp;+\u0026thinsp;interaction term for variant and severity.\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e\u0026Dagger;\u003c/sup\u003eModel 2:\u003c/p\u003e\n\u003cp\u003eStillbirth: Model 1\u0026thinsp;+\u0026thinsp;maternal age, ethnicity, employment status, body mass index, multiple pregnancy, smoking, parity, pre-existing medical conditions, pre-eclampsia, gestational diabetes, and gestational age at admission\u003c/p\u003e\n\u003cp\u003ePreterm birth: Model 1\u0026thinsp;+\u0026thinsp;maternal age, ethnicity, employment status, body mass index, multiple pregnancy, smoking, parity, pre-existing medical conditions, and pre-eclampsia.\u003c/p\u003e\n\u003cp\u003eNeonatal admission: Model 1\u0026thinsp;+\u0026thinsp;gestational age at birth, parity, and pre-existing medical conditions\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e\u0026sect;\u003c/sup\u003eModel 3: Model 2\u0026thinsp;+\u0026thinsp;vaccination status. Vaccination started from January 1, 2021, so mild alpha infection was used as reference group.\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e\u0026para;\u003c/sup\u003e 45 infants born to symptomatic women had missing data for gestational age at birth.\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e||\u003c/sup\u003e 112 infants born to symptomatic women had missing data for admission to neonatal unit.\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e**\u003c/sup\u003e 75 infants born to symptomatic women had missing data for neonatal death.\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e\u0026dagger;\u0026dagger;\u003c/sup\u003e risk ratios were not calculated due to low numbers.\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eThe absolute risk of stillbirth among symptomatic women was 0.8% for mild infection in the wild-type period and 1.6%, 1.3%, 1.9% and 2.4% with moderate to severe maternal infection in the wild-type, alpha, delta and omicron variant periods, respectively (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e). Compared to women with mild infection during the wild-type period, there was no evidence for a statistically significant increased risk of stillbirth for women with moderate to severe infection, except for during the delta period, noting that smaller numbers impacted the study power to detect differences as statistically significant. After adjusting for maternal risk factors, there was an increased risk of stillbirth during the delta period irrespective of infection severity (mild RR 3.57; 95%CI 1.66 to 7.67 and moderate to severe RR 2.41; 95%CI 1.03 to 5.60) when compared with mild infection during the wild-type period. (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e, model 2).\u003c/p\u003e\n\u003cp\u003eThe risk of being born prior to 34 weeks\u0026rsquo; gestation was 7.9% in the wild-type period and 9.4% with alpha (crude RR 1.21; 95%CI 0.94 to 1.55), 10.9% with delta (crude RR 1.49; 95%CI 1.18 to 1.87) and 4.5% with omicron (crude RR 0.53; 95%CI 0.38 to 0.74). The risk of being born at 34\u003csup\u003e+\u0026thinsp;0\u003c/sup\u003e-36\u003csup\u003e+\u0026thinsp;6\u003c/sup\u003e weeks\u0026rsquo; gestation was 11.8% in the wild-type period and 11.9% with alpha (crude RR 1.03; 95%CI 0.83 to 1.87), 14.4% with delta (crude RR 1.31; 95%CI 1.07 to 1.59) and 10.9% with omicron (crude RR 0.87; 95%CI 0.69 to 1.11) (Supplementary Table S3). Compared with births among women with mild infection, infants born to women with moderate to severe infection had a fourfold increased risk of birth before 34 weeks\u0026rsquo; gestation and a nearly doubled risk of birth at 34\u003csup\u003e+\u0026thinsp;0\u003c/sup\u003e-36\u003csup\u003e+\u0026thinsp;6\u003c/sup\u003e weeks\u0026rsquo; gestation in the crude risk ratio analyses (Supplementary Table S4).\u003c/p\u003e\n\u003cp\u003eWhen the association was examined by variant period and infection severity, the risk of being born preterm prior to 34 weeks\u0026rsquo; gestation was 5.3% with mild maternal infection during the wild-type period, and 15.5%, 18.1%, 16.9% and 8.2% with moderate to severe maternal infection in the wild-type, alpha, delta and omicron variant periods, respectively. We found evidence of a multiplicative interaction between variant period and infection severity on the risk of preterm birth. The risk of birth before 34 weeks\u0026rsquo; was five times higher among infants born to women with moderate to severe infection during the alpha and delta periods, compared with women with mild infection during the wild-type period, after adjusting for maternal risk factors (alpha RR 5.03; 95%CI 3.51 to 7.20; delta RR 4.94; 95%CI 3.52 to 6.94) (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e, model 2) whereas this risk was doubled during the omicron period (RR 2.02; 95%CI 1.13 to 3.63) (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e, model 2). The risk increase was two-to-threefold for birth between 34\u003csup\u003e+\u0026thinsp;0\u003c/sup\u003e to 36\u003csup\u003e+\u0026thinsp;6\u003c/sup\u003e weeks\u0026rsquo; gestation among women with moderate to severe infection across all periods when compared to mild wild-type infection (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e, model 2).\u003c/p\u003e\n\u003cp\u003eWe also found evidence of a multiplicative interaction between variant period and infection severity on neonatal unit admission. Compared with women with mild infection in the wild-type period, analyses accounting for both severity and variant in a model adjusted for maternal risk factors and gestational age at birth (model 2) showed 1.5 times higher risk of neonatal unit admission across all variant periods in neonates born to women with moderate to severe infection (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e, model 2). These patterns for preterm birth and neonatal unit admission persisted after accounting for vaccination status (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e, model 3). Neonatal deaths at less than seven days of age were rare, with a total of 18 deaths among babies born to symptomatic women (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e\n\u003cp\u003eAmongst 5,185 births to symptomatic women from January 1, 2021 onwards, when vaccination was recommended for pregnant women in risk groups, there were 91 stillbirths among symptomatic women; 91.2% (83/91) occurred to women with no documented vaccine or unknown vaccination status (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e). Women who were unvaccinated or had unknown vaccination status also gave birth to 92.1% (422/458) of the infants born before \u0026lt;\u0026thinsp;34 weeks\u0026rsquo; gestation in the symptomatic group. Perinatal outcomes and maternal vaccination status for asymptomatic women are reported in online supplementary Table S5; 75% (49/65) of the stillbirths and 78.1% (249/319) of infants born prior to 34 weeks were born to women with no documented vaccination or unknown vaccination status.\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tab4\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003ePerinatal outcomes in births to women with symptomatic SARS-CoV-2 admitted to hospital by number of documented maternal vaccination doses, from January 1, 2021, to March 31, 2022, United Kingdom\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eVaccination status\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eUnvaccinated\u003c/p\u003e\n\u003cp\u003e(N\u0026thinsp;=\u0026thinsp;3184)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eVaccine status unknown\u003c/p\u003e\n\u003cp\u003e(N\u0026thinsp;=\u0026thinsp;1275)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e1 dose\u003c/p\u003e\n\u003cp\u003e(N\u0026thinsp;=\u0026thinsp;347)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e2 doses\u003c/p\u003e\n\u003cp\u003e(N\u0026thinsp;=\u0026thinsp;319)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e3 doses\u003c/p\u003e\n\u003cp\u003e(N\u0026thinsp;=\u0026thinsp;60)\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eStillbirth - no. (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e64 (2.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e19 (1.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3 (0.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e5 (0.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePreterm births\u003csup\u003e*\u003c/sup\u003e - no. (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026lt;\u0026thinsp;34 weeks\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e299 (9.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e123 (9.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e13 (3.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e20 (6.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3 (5.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e34\u003csup\u003e+\u0026thinsp;0\u003c/sup\u003e \u0026minus;\u0026thinsp;36\u003csup\u003e+\u0026thinsp;6\u003c/sup\u003e weeks\u0026rsquo;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e443 (14.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e152 (12.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e34 (9.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e26 (8.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e7 (11.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAdmission to Neonatal Unit\u003csup\u003e\u0026dagger;\u003c/sup\u003e -\u003c/p\u003e\n\u003cp\u003eno. (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e620 (19.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e270 (21.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e40 (11.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e40 (12.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e9 (15.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNeonatal Death\u003csup\u003e\u0026Dagger;\u003c/sup\u003e - no. (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e6 (0.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3 (0.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2 (0.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1 (0.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"6\" align=\"left\"\u003e\n\u003cp\u003e\u003csup\u003e*\u003c/sup\u003e 45 infants born to symptomatic women had missing data for gestational age at birth\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e\u0026dagger;\u003c/sup\u003e 112 infants born to symptomatic women had missing data for admission to neonatal unit.\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e\u0026Dagger;\u003c/sup\u003e 77 infants born to symptomatic women had missing data for neonatal death\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis national cohort study of pregnant women admitted to hospital with SARS-CoV-2 shows that compared with women with mild infection in the wild-type period there was increased risk of stillbirth for women with mild and moderate to severe infection during the delta period. The risk of preterm birth was increased for babies born to women with moderate to severe infection across all periods. Omicron was considered to be a variant with lower risk of adverse perinatal outcomes,\u003csup\u003e\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e yet we observed a threefold increase in risk of birth prior to 34 weeks\u0026rsquo; gestation for women with moderate to severe COVID-19 in this period compared with mild infection in the wild-type period, after accounting for vaccination status. Unvaccinated women were at higher risk of stillbirth and preterm birth.\u003c/p\u003e \u003cp\u003eThe key strengths of this study are that birth outcomes were available for almost all the included women. The large sample size provides sufficient statistical power to detect a difference in stillbirth during the delta period. We observed an increase in risk of preterm birth with moderate to severe maternal infection across all variant periods, demonstrating the merit of a nuanced analysis taking variant and severity into account.\u003c/p\u003e \u003cp\u003eIn addition, the availability of data about symptom status, severity of infection and vaccination status allowed robust regression models. The UKOSS system of active and uniform case identification across all pregnant women admitted to hospital in the UK that tested positive for SARS-CoV-2 reduces the risk of selection bias compared with other studies. Finally, the clinical information reduced the risk of misclassification bias, such as attributing adverse outcomes associated with pregnancy-related admission incorrectly to COVID-19.\u003c/p\u003e \u003cp\u003eSeveral limitations also need to be considered. First, perinatal outcomes in births to pregnant women with SARS-CoV-2 who were not admitted to hospital at the time of infection could not be assessed. There would likely be few adverse outcomes in this group, as studies from other countries did not find an increased risk of adverse perinatal outcomes with a test-delivery interval exceeding ten days.\u003csup\u003e\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u003c/sup\u003e Second, we have included time periods when the variants of SARS-CoV-2 were dominant as proxy for individual variant sequencing data which were not available. Third, whilst providing robust data about the prevalence of stillbirth in women with COVID-19, we do not have clinical information to assess the cause of death and differentiate iatrogenic and spontaneous nature of the preterm birth\u003c/p\u003e \u003cp\u003eWe adjusted for known confounders, but there could be time-dependent changes that were unmeasured and may be important underlying causes of stillbirth and preterm birth. For example, indirect impacts of the pandemic such as competing hospital pressures, differing practice around intrapartum fetal monitoring for women with COVID-19, or delay in seeking care may contribute to the higher proportion of stillbirths observed in women with COVID-19 during the delta period, but this does not explain the increase in preterm births.\u003c/p\u003e \u003cp\u003eThe proportion of stillbirths observed in women with asymptomatic infection during the wild-type period was comparable to nationally-reported figures in the UK (4/1000 total births versus 3.5/1000 total births, respectively).\u003csup\u003e\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u003c/sup\u003e Recent UK-wide surveillance of perinatal deaths identified an increase in the perinatal mortality rate during 2021.\u003csup\u003e\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u003c/sup\u003e The current study indicates that COVID-19 in unvaccinated pregnant women could have contributed to this increase.\u003c/p\u003e \u003cp\u003eThis study significantly adds to the field since previous cohort studies that ended during earlier variant periods reported stillbirth rates comparable with pre-pandemic periods,\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e,\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e,\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u003c/sup\u003e thus demonstrating the need for ongoing surveillance of perinatal outcomes during a pandemic to inform care. Similarly, other studies with shorter\u003csup\u003e\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u003c/sup\u003e or unclear\u003csup\u003e\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e\u003c/sup\u003e duration of follow up after admission with infection have had insufficient data to reliably compare severe perinatal outcomes and did not account for severity of maternal infection.\u003c/p\u003e \u003cp\u003eBy January 2022, 50.6% of the women who gave birth in England had received two vaccine doses.\u003csup\u003e\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e\u003c/sup\u003e Previous cohort studies have demonstrated the benefit of maternal SARS-CoV-2 vaccination to prevent hospital admission due to COVID-19 in pregnant women,\u003csup\u003e\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e\u003c/sup\u003e reduce moderate to severe maternal COVID-19,\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e,\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e and reduce infant hospitalization for COVID-19, severe neonatal morbidity and death.\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e,\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e,\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e\u003c/sup\u003e The current study clearly demonstrates the benefit of maternal vaccination on perinatal outcomes, showing a large proportion of stillbirths in women with no documented vaccination in both those with and without any symptoms of COVID-19.\u003c/p\u003e \u003cp\u003ePreterm birth is also associated with adverse short-term\u003csup\u003e\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e\u003c/sup\u003e and long-term\u003csup\u003e\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e,\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e\u003c/sup\u003e health outcomes and the need for neonatal unit admissions increases demand and economic impact on the health services.\u003csup\u003e\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e\u003c/sup\u003e With ongoing increasing SARS-CoV-2 infections, it is paramount to ensure that pregnant women are prioritised for vaccination, and that messaging around safety and access to vaccines is clear and readily available.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn this large national cohort comprising two years\u0026rsquo; active surveillance over four SARS-CoV-2 variant periods and with near complete follow-up of pregnancy outcomes for included women, severe perinatal outcomes were more common in women with moderate to severe COVID-19, during the delta dominant period and among unvaccinated women. We provide strong evidence to recommend continuous surveillance of pregnancy outcomes in future pandemics and to continue to recommend vaccination in pregnancy to protect both mothers and babies.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eStudy registration number: (https://doi.org/10.1186/ISRCTN40092247)\u003c/p\u003e\n\u003cp\u003eEthics approval: HRA NRES Committee East Midlands \u0026ndash; Nottingham 1 (Ref. Number: 12/EM/0365). Information about ethnicity was self-determined according to the UK standard census categories (List of ethnic groups - GOV.UK (ethnicity-facts-figures.service.gov.uk)\u003c/p\u003e\n\u003cp\u003eRema Ramakrishnan, Hilde Engjom, Nicola Vousden and Marian Knight analysed the data.\u003c/p\u003e\n\u003cp\u003eThe study protocol was published at the study start and is available on the UKOSS website https://www.npeu.ox.ac.uk/ukoss/completed-surveillance/covid-19-in-pregnancy\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eKnight, M.\u003cem\u003e, et al.\u003c/em\u003e Characteristics and outcomes of pregnant women admitted to hospital with confirmed SARS-CoV-2 infection in UK: national population based cohort study. \u003cem\u003eBMJ\u003c/em\u003e \u003cstrong\u003e369\u003c/strong\u003e, m2107 (2020).\u003c/li\u003e\n\u003cli\u003eVousden, N.\u003cem\u003e, et al.\u003c/em\u003e Severity of maternal infection and perinatal outcomes during periods in which Wildtype, Alpha and Delta SARS-CoV-2 variants were dominant: Data from the UK Obstetric Surveillance System national cohort. \u003cem\u003eBMJ Medicine\u003c/em\u003e \u003cstrong\u003e1\u003c/strong\u003e(2022).\u003c/li\u003e\n\u003cli\u003eVousden, N.\u003cem\u003e, et al.\u003c/em\u003e Management and implications of severe COVID-19 in pregnancy in the UK: data from the UK Obstetric Surveillance System national cohort. \u003cem\u003eActa Obstet Gynecol Scand\u003c/em\u003e \u003cstrong\u003e101\u003c/strong\u003e, 461-470 (2022).\u003c/li\u003e\n\u003cli\u003eEngjom, H.M.\u003cem\u003e, et al.\u003c/em\u003e Severity of maternal SARS-CoV-2 infection and perinatal outcomes of women admitted to hospital during the omicron variant dominant period using UK Obstetric Surveillance System data: prospective, national cohort study. \u003cem\u003eBMJ Medicine\u003c/em\u003e \u003cstrong\u003e1\u003c/strong\u003e, e000190 (2022).\u003c/li\u003e\n\u003cli\u003eAllotey, J.\u003cem\u003e, et al.\u003c/em\u003e Clinical manifestations, risk factors, and maternal and perinatal outcomes of coronavirus disease 2019 in pregnancy: living systematic review and meta-analysis. \u003cem\u003eBMJ\u003c/em\u003e \u003cstrong\u003e370\u003c/strong\u003e, m3320 (2020).\u003c/li\u003e\n\u003cli\u003eD\u0026apos;Souza, R., Malhame, I. \u0026amp; Shah, P.S. 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UK Health Security Agency) (UK, 2021).\u003c/li\u003e\n\u003cli\u003eStock, S.J.\u003cem\u003e, et al.\u003c/em\u003e Pregnancy outcomes after SARS-CoV-2 infection in periods dominated by delta and omicron variants in Scotland: a population-based cohort study. \u003cem\u003eLancet Respir Med\u003c/em\u003e \u003cstrong\u003e10\u003c/strong\u003e, 1129-1136 (2022).\u003c/li\u003e\n\u003cli\u003eStephansson, O.\u003cem\u003e, et al.\u003c/em\u003e SARS-CoV-2 and pregnancy outcomes under universal and non-universal testing in Sweden: register-based nationwide cohort study. \u003cem\u003eBJOG\u003c/em\u003e \u003cstrong\u003e129\u003c/strong\u003e, 282-290 (2022).\u003c/li\u003e\n\u003cli\u003eDraper ES, G.I., Smith LK, Matthews RJ, Fenton AC, Kurinczuk JJ, Smith PW, Manktelow BN, on behalf of the \u0026amp; Collaboration, M.-U. 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SARS-CoV-2 infection among hospitalised pregnant women and impact of different viral strains on COVID-19 severity in Italy: a national prospective population-based cohort study. \u003cem\u003eBJOG\u003c/em\u003e \u003cstrong\u003e129\u003c/strong\u003e, 221-231 (2022).\u003c/li\u003e\n\u003cli\u003eStock, S.J.\u003cem\u003e, et al.\u003c/em\u003e SARS-CoV-2 infection and COVID-19 vaccination rates in pregnant women in Scotland. \u003cem\u003eNat Med\u003c/em\u003e \u003cstrong\u003e28\u003c/strong\u003e, 504-512 (2022).\u003c/li\u003e\n\u003cli\u003eMcClymont, E.\u003cem\u003e, et al.\u003c/em\u003e Association of SARS-CoV-2 Infection During Pregnancy With Maternal and Perinatal Outcomes. \u003cem\u003eJAMA\u003c/em\u003e \u003cstrong\u003e327\u003c/strong\u003e, 1983-1991 (2022).\u003c/li\u003e\n\u003cli\u003eUK Health Security Agency. Vaccine uptake among pregnant women increasing but inequalitites persist. (ed. Agency, U.H.S.) (2022).\u003c/li\u003e\n\u003cli\u003eBosworth, M.L.\u003cem\u003e, et al.\u003c/em\u003e Vaccine effectiveness for prevention of covid-19 related hospital admission during pregnancy in England during the alpha and delta variant dominant periods of the SARS-CoV-2 pandemic: population based cohort study. \u003cem\u003eBMJ Med\u003c/em\u003e \u003cstrong\u003e2\u003c/strong\u003e, e000403 (2023).\u003c/li\u003e\n\u003cli\u003eHalasa, N.B.\u003cem\u003e, et al.\u003c/em\u003e Maternal Vaccination and Risk of Hospitalization for Covid-19 among Infants. \u003cem\u003eN Engl J Med\u003c/em\u003e \u003cstrong\u003e387\u003c/strong\u003e, 109-119 (2022).\u003c/li\u003e\n\u003cli\u003eJorgensen, S.C.J.\u003cem\u003e, et al.\u003c/em\u003e Newborn and Early Infant Outcomes Following Maternal COVID-19 Vaccination During Pregnancy. \u003cem\u003eJAMA Pediatr\u003c/em\u003e (2023).\u003c/li\u003e\n\u003cli\u003eCosteloe, K.L.\u003cem\u003e, et al.\u003c/em\u003e Short term outcomes after extreme preterm birth in England: comparison of two birth cohorts in 1995 and 2006 (the EPICure studies). \u003cem\u003eBMJ\u003c/em\u003e \u003cstrong\u003e345\u003c/strong\u003e, e7976 (2012).\u003c/li\u003e\n\u003cli\u003ePierrat, V.\u003cem\u003e, et al.\u003c/em\u003e Neurodevelopmental outcomes at age 5 among children born preterm: EPIPAGE-2 cohort study. \u003cem\u003eBMJ\u003c/em\u003e \u003cstrong\u003e373\u003c/strong\u003e, n741 (2021).\u003c/li\u003e\n\u003cli\u003eInder, T.E., Volpe, J.J. \u0026amp; Anderson, P.J. Defining the Neurologic Consequences of Preterm Birth. \u003cem\u003eN Engl J Med\u003c/em\u003e \u003cstrong\u003e389\u003c/strong\u003e, 441-453 (2023).\u003c/li\u003e\n\u003cli\u003eKhan, K.A.\u003cem\u003e, et al.\u003c/em\u003e Economic costs associated with moderate and late preterm birth: a prospective population-based study. \u003cem\u003eBJOG\u003c/em\u003e \u003cstrong\u003e122\u003c/strong\u003e, 1495-1505 (2015).\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"nature-portfolio","isNatureJournal":true,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"","title":"Nature Portfolio","twitterHandle":"","acdcEnabled":false,"dfaEnabled":false,"editorialSystem":"ejp","reportingPortfolio":"","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-3785899/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3785899/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBACKGROUND\u003c/h2\u003e \u003cp\u003eThere are few population-based studies of sufficient size and follow-up duration to have reliably assessed perinatal outcomes for pregnant women admitted to hospital with SARS-CoV-2 infection.\u003c/p\u003e\u003ch2\u003eMETHODS\u003c/h2\u003e \u003cp\u003eThe United Kingdom Obstetric Surveillance System (UKOSS) includes all 194 consultant-led UK maternity units. From March 2020 to March 2022, pregnant women admitted with a positive SARS-CoV-2 PCR test within seven days before or during admission were included and categorised by dominant SARS-CoV-2 variant, severity of maternal COVID-19 and vaccination status.\u003c/p\u003e\u003ch2\u003eRESULTS\u003c/h2\u003e \u003cp\u003eIn total, 16,351 infants were born to 16,627 women; women with symptomatic COVID-19 contributed 7,116 (43.3%) births, 111 of which were stillborn. Infection during the delta variant period was associated with increased risk of stillbirth irrespective of infection severity compared to mild wild-type infection (mild wildtype 0.8% vs. mild delta 3%, adjusted risk ratio [aRR] 3.57, 95% confidence interval [CI] 1.66 to 7.67; vs. moderate to severe delta, 1.9%, aRR2.41; 95%CI 1.03 to 5.60). All variants were associated with increased risk of preterm birth in women with moderate to severe infection compared to women with mild infection in the wildtype period. After introduction of vaccination during pregnancy, 91.2% (83/91) of stillbirths and 92.1% (422/459) of preterm births\u0026thinsp;\u0026lt;\u0026thinsp;34 weeks\u0026rsquo; gestation were in symptomatic women with no documented vaccination or with unknown vaccine status.\u003c/p\u003e\u003ch2\u003eCONCLUSION\u003c/h2\u003e \u003cp\u003eCOVID-19 variant, severity, and no or unknown maternal vaccinations were key risk factors for adverse perinatal outcomes. There is strong evidence for continued recommendation of SARS-CoV-2 vaccination during pregnancy to protect women and their babies.\u003c/p\u003e","manuscriptTitle":"Perinatal outcomes after admission with COVID-19 in pregnancy: a UK national cohort","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-01-09 19:51:04","doi":"10.21203/rs.3.rs-3785899/v1","editorialEvents":[],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"nature-communications","isNatureJournal":true,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"NCOMMS","sideBox":"Learn more about [Nature Communications](http://www.nature.com/ncomms/)","snPcode":"","submissionUrl":"https://mts-ncomms.nature.com/","title":"Nature Communications","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature Communications","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"e0041bb6-e919-4f27-b426-47e9b6a561c9","owner":[],"postedDate":"January 9th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":28018827,"name":"Health sciences/Medical research/Epidemiology"},{"id":28018828,"name":"Health sciences/Diseases/Infectious diseases/Viral infection"}],"tags":[],"updatedAt":"2024-04-16T07:07:52+00:00","versionOfRecord":{"articleIdentity":"rs-3785899","link":"https://doi.org/10.1038/s41467-024-47181-z","journal":{"identity":"nature-communications","isVorOnly":false,"title":"Nature Communications"},"publishedOn":"2024-04-15 04:00:00","publishedOnDateReadable":"April 15th, 2024"},"versionCreatedAt":"2024-01-09 19:51:04","video":"","vorDoi":"10.1038/s41467-024-47181-z","vorDoiUrl":"https://doi.org/10.1038/s41467-024-47181-z","workflowStages":[]},"version":"v1","identity":"rs-3785899","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3785899","identity":"rs-3785899","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}