Trends in severe postpartum haemorrhage among nulliparous women with spontaneous onset of labour: A population-based cohort study.

OBJECTIVE: To investigate the incidence of severe postpartum haemorrhage among nulliparous women with a spontaneous onset of labour at term from 2000 to 2020. DESIGN: Population-based cohort study. SETTING: National, using the Medical Birth Registry of Norway. POPULATION: Women (n = 330 244) who gave birth to their first singleton child in a cephalic presentation after a spontaneous onset of labour at term. METHODS: Cross-tabulations and regression analysis with generalised linear models were used to assess time trends and adjust for potential confounding factors. We also stratified the analyses by maternal age groups, obstetric interventions, mode of delivery and institution size. Time trends were analysed using periods of 5 or 6 years as a unit, and the period from 2000 to 2004 was used as the reference. MAIN OUTCOME MEASURES: Severe postpartum haemorrhage (PPH) was defined as blood loss of >1500 mL within 24 h and/or in combination with blood transfusion. RESULTS: Severe PPH occurred in 7601/330 244 (2.30%) women. The incidence increased from 1.24% in 2000-2004 to 3.83% in 2015-2020 (adjusted relative risk, aRR 2.90; 95% CI 2.70-3.12). Changes in maternal characteristics or obstetric interventions did not explain the increase, and we found similar increases across institutions of all sizes. CONCLUSIONS: The incidence of severe PPH among nulliparous women increased almost threefold over 21 years. The current high incidence warrants urgent efforts to assess unknown risk factors, the health care provided and health system factors that may contribute to the increase, to inform improvements in care.

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

There are few population-based studies of sufficient size and follow-up duration to have reliably assessed perinatal outcomes for pregnant women hospitalised with SARS-CoV-2 infection. The United Kingdom Obstetric Surveillance System (UKOSS) covers all 194 consultant-led UK maternity units and included all pregnant women admitted to hospital with an ongoing SARS-CoV-2 infection. Here we show that 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 16,627 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 SARS-CoV-2 vaccination in pregnancy to protect both mothers and babies.

Early suppression policies protected pregnant women from COVID-19 in 2020: A population-based surveillance from the Nordic countries.

INTRODUCTION: The Coronavirus 2019 Disease (COVID-19) pandemic reached the Nordic countries in March 2020. Public health interventions to limit viral transmission varied across different countries both in timing and in magnitude. Interventions indicated by an Oxford Stringency Index ≥50 were implemented early (March 13-17, 2020) in Denmark, Finland, Norway and Iceland, and on March 26, 2020 in Sweden. The aim of the current study was to assess the incidence of COVID-19-related admissions of pregnant women in the Nordic countries in relation to the different national public health strategies during the first year of the pandemic. MATERIAL AND METHODS: This is a meta-analysis of population-based cohort studies in the five Nordic countries with national or regional surveillance in the Nordic Obstetric Surveillance System (NOSS) collaboration: national data from Denmark, Finland, Iceland and Norway, and regional data covering 31% of births in Sweden. The source population consisted of women giving birth in the included areas March 1-December 31, 2020. Pregnant women with a positive SARS-CoV-2 PCR test ≤14 days before hospital admission were included, and admissions were stratified as either COVID-19-related or non-COVID (other obstetric healthcare). Information about public health policies was retrieved retrospectively. RESULTS: In total, 392 382 maternities were considered. Of these, 600 women were diagnosed with SARS-CoV-2 infection and 137 (22.8%) were admitted for COVID-19 symptoms. The pooled incidence of COVID-19 admissions per 1000 maternities was 0.5 (95% confidence interval [CI] 0.2 to 1.2, I2 = 77.6, tau2 = 0.68, P = 0.0), ranging from no admissions in Iceland to 1.9 admissions in the Swedish regions. Interventions to restrict viral transmission were less stringent in Sweden than in the other Nordic countries. CONCLUSIONS: There was a clear variation in pregnant women's risk of COVID-19 admission across countries with similar healthcare systems but different public health interventions to limit viral transmission. The meta-analysis indicates that early suppression policies protected pregnant women from severe COVID-19 disease prior to the availability of individual protection with vaccines.

Variations across Europe in hospitalization and management of pregnant women with SARS-CoV-2 during the initial phase of the pandemic: Multi-national population-based cohort study using the International Network of Obstetric Survey Systems (INOSS).

INTRODUCTION: The majority of data on COVID-19 in pregnancy are not from sound population-based active surveillance systems. MATERIAL AND METHODS: We conducted a multi-national study of population-based national or regional prospective cohorts using standardized definitions within the International Network of Obstetric Survey systems (INOSS). From a source population of women giving birth between March 1 and August 31, 2020, we included pregnant women admitted to hospital with a positive SARS-CoV-2 PCR test ≤7 days prior to or during admission and up to 2 days after birth. The admissions were further categorized as COVID-19-related or non-COVID-19-related. The primary outcome of interest was incidence of COVID-19-related hospital admission. Secondary outcomes included severe maternal disease (ICU admission and mechanical ventilation) and COVID-19-directed medical treatment. RESULTS: In a source population of 816 628 maternities, a total of 2338 pregnant women were admitted with SARS-CoV-2; among them 940 (40%) were COVID-19-related admissions. The pooled incidence estimate for COVID-19-related admission was 0.59 (95% confidence interval 0.27-1.02) per 1000 maternities, with notable heterogeneity across countries (I2 = 97.3%, P = 0.00). In the COVID-19 admission group, between 8% and 17% of the women were admitted to intensive care, and 5%-13% needed mechanical ventilation. Thromboprophylaxis was the most frequent treatment given during COVID-19-related admission (range 14%-55%). Among 908 infants born to women in the COVID-19-related admission group, 5 (0.6%) stillbirths were reported. CONCLUSIONS: During the initial months of the pandemic, we found substantial variations in incidence of COVID-19-related admissions in nine European countries. Few pregnant women received COVID-19-directed medical treatment. Several barriers to rapid surveillance were identified. Investment in robust surveillance should be prioritized to prepare for future pandemics.

Evolution of National Guidelines on Medicines Used to Treat COVID-19 in Pregnancy in 2020-2022: A Scoping Review.

The lack of inclusion of pregnant women in clinical trials evaluating the effectiveness of medicines to treat COVID-19 has made it difficult to establish evidence-based treatment guidelines for pregnant women. Our aim was to provide a review of the evolution and updates of the national guidelines on medicines used in pregnant women with COVID-19 published by the obstetrician and gynecologists' societies in thirteen countries in 2020-2022. Based on the results of the RECOVERY (Randomized Evaluation of COVID-19 Therapy) trial, the national societies successively recommended against prescribing hydroxychloroquine, lopinavir-ritonavir and azithromycin. Guidelines for remdesivir differed completely between countries, from compassionate or conditional use to recommendation against. Nirmatrelvir-ritonavir was authorized in Australia and the UK only in research settings and was no longer recommended in the UK at the end of 2022. After initial reluctance to use corticosteroids, the results of the RECOVERY trial have enabled the recommendation of dexamethasone in case of severe COVID-19 since mid-2020. Some societies recommended prescribing tocilizumab to pregnant patients with hypoxia and systemic inflammation from June 2021. Anti-SARS-CoV-2 monoclonal antibodies were authorized at the end of 2021 with conditional use in some countries, and then no longer recommended in Belgium and the USA at the end of 2022. The gradual convergence of the recommendations, although delayed compared to the general population, highlights the importance of the inclusion of pregnant women in clinical trials and of international collaboration to improve the pharmacological treatment of pregnant women with COVID-19.

Changes in preterm birth and stillbirth during COVID-19 lockdowns in 26 countries.

Preterm birth (PTB) is the leading cause of infant mortality worldwide. Changes in PTB rates, ranging from -90% to +30%, were reported in many countries following early COVID-19 pandemic response measures ('lockdowns'). It is unclear whether this variation reflects real differences in lockdown impacts, or perhaps differences in stillbirth rates and/or study designs. Here we present interrupted time series and meta-analyses using harmonized data from 52 million births in 26 countries, 18 of which had representative population-based data, with overall PTB rates ranging from 6% to 12% and stillbirth ranging from 2.5 to 10.5 per 1,000 births. We show small reductions in PTB in the first (odds ratio 0.96, 95% confidence interval 0.95-0.98, P value <0.0001), second (0.96, 0.92-0.99, 0.03) and third (0.97, 0.94-1.00, 0.09) months of lockdown, but not in the fourth month of lockdown (0.99, 0.96-1.01, 0.34), although there were some between-country differences after the first month. For high-income countries in this study, we did not observe an association between lockdown and stillbirths in the second (1.00, 0.88-1.14, 0.98), third (0.99, 0.88-1.12, 0.89) and fourth (1.01, 0.87-1.18, 0.86) months of lockdown, although we have imprecise estimates due to stillbirths being a relatively rare event. We did, however, find evidence of increased risk of stillbirth in the first month of lockdown in high-income countries (1.14, 1.02-1.29, 0.02) and, in Brazil, we found evidence for an association between lockdown and stillbirth in the second (1.09, 1.03-1.15, 0.002), third (1.10, 1.03-1.17, 0.003) and fourth (1.12, 1.05-1.19, <0.001) months of lockdown. With an estimated 14.8 million PTB annually worldwide, the modest reductions observed during early pandemic lockdowns translate into large numbers of PTB averted globally and warrant further research into causal pathways.

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.

Objectives: To describe the severity of maternal infection when the omicron SARS-CoV-2 variant (B.1.1.529) was dominant (15 December 2021 to 14 March 2022) and describe outcomes by symptoms and vaccination status. Design: Prospective, national cohort study using the UK Obstetric Surveillance System. Setting: 94 hospitals in the UK with a consultant led maternity unit. Participants: Pregnant women admitted to hospital for any cause with a positive SARS-CoV-2 test. Main outcome measures: Symptomatic or asymptomatic infection, vaccination status by doses before admission, and severity of maternal infection (moderate or severe infection according to modified World Health Organization's criteria). Results: Of 3699 women who were admitted to hospital, 986 (26.7%, 95% confidence interval 25.3% to 28.1%) had symptoms; of these, 144 (14.6%, 12.5% to 17.0%) had a moderate to severe infection, 99 (10.4%, 8.6% to 12.5%) of 953 received respiratory support, and 30 (3.0%, 2.1% to 4.3%) were admitted to an intensive care unit. Covid-19 specific drug treatment was given to 13 (43.3%) of the 30 women in intensive care. Four women with symptoms died (0.4%, 0.1% to 1.1%). Vaccination status was known for 845 (85.6%) women with symptoms; 489 (58.9%) were unvaccinated and only 55 (6.5%) had three doses. Moderate to severe infection was reported for 93 (19.0%) of 489 unvaccinated women with symptoms, decreasing to three (5.5%) of 55 after three doses. Among the 30 women with symptoms who were admitted to intensive care, 23 (76.7%) were unvaccinated and none had received three doses. Conclusion: Most women with severe covid-19 disease were unvaccinated and vaccine coverage among pregnant women admitted to hospital with SARS-CoV-2 was low. Ongoing action to prioritise and advocate for vaccine uptake in pregnancy is essential. A better understanding of the persistent low use of drug treatments is an urgent priority. Trial registration: ISRCTN 40092247.

COVID-19 in pregnancy-characteristics and outcomes of pregnant women admitted to hospital because of SARS-CoV-2 infection in the Nordic countries.

INTRODUCTION: Population-based studies about the consequences of SARS-CoV-2 infection (COVID-19) in pregnancy are few and have limited generalizability to the Nordic population and healthcare systems. MATERIAL AND METHODS: This study examines pregnant women with COVID-19 in the five Nordic countries. Pregnant women were included if they were admitted to hospital between 1 March and 30 June 2020 and had a positive SARS-CoV-2 PCR test ≤14 days prior to admission. Cause of admission was classified as obstetric or COVID-19-related. RESULTS: In the study areas, 214 pregnant women with a positive test were admitted to hospital, of which 56 women required hospital care due to COVID-19. The risk of admission due to COVID-19 was 0.4/1000 deliveries in Denmark, Finland and Norway, and 3.8/1000 deliveries in the Swedish regions. Women hospitalized because of COVID-19 were more frequently obese (p < 0.001) and had a migrant background (p < 0.001) compared with the total population of women who delivered in 2018. Twelve women (21.4%) needed intensive care. Among the 56 women admitted due to COVID-19, 48 women delivered 51 infants. Preterm delivery (n = 12, 25%, p < 0.001) and cesarean delivery (n = 21, 43.8%, p < 0.001) were more frequent in women with COVID-19 compared with women who delivered in 2018. No maternal deaths, stillbirths or neonatal deaths were reported. CONCLUSIONS: The risk of admission due to COVID-19 disease in pregnancy was low in the Nordic countries. A fifth of the women required intensive care and we observed higher rates of preterm and cesarean deliveries. National public health policies appear to have had an impact on the risk of admission due to severe COVID-19 disease in pregnancy. Nordic collaboration is important in collecting robust data and assessing rare outcomes.

Risk of eclampsia or HELLP-syndrome by institution availability and place of delivery - A population-based cohort study.

OBJECTIVE: To examine the association between availability of obstetric institutions and risk of eclampsia, HELLP-syndrome, or delivery before 35 gestational weeks in preeclamptic pregnancies. STUDY DESIGN: National population-based retrospective cohort study of deliveries in Norway, 1999-2009 (n = 636738) using data from The Medical Birth Registry of Norway and Statistics Norway. Main exposures were institution availability, measured by travel time to the nearest obstetric institution, and place of delivery. We computed relative risks (RR) with 95% confidence intervals (CI) using travel time ≤1 h as reference. We stratified analyses by parity and preeclampsia, and adjusted for socio-demographic and medical risk factors. Successive deliveries were linked using the national identification number. RESULTS: We identified 1387 eclampsia/HELLP cases (0.2%) and 3004 (0.5%) deliveries before 35 weeks in preeclamptic pregnancies. Nulliparous women living >1 h from any obstetric institution had 50% increased risk of eclampsia/HELLP (0.50 versus 0.35%, adjusted RR 1.5; 95 %CI 1.1-1.9). Parous women living >1 h from emergency institutions had a doubled risk of eclampsia (0.6‰ versus 0.3‰, adjusted RR 2.0; 1.2-3.3). Women without preeclampsia in the present pregnancy or history of preeclampsia constituted all eclampsia/HELLP cases in midwife-led institutions, 39-50% of cases in emergency institutions, and 78% of cases (135/173) in subsequent deliveries. Women with risk factors delivered in the emergency institutions, indicating well-implemented selective referral. CONCLUSION: The study shows the importance of available obstetric institutions. Policymakers and clinicians should consider the distribution of potential benefits and burdens when planning and evaluating the obstetric health service structure.

Increased risk of peripartum perinatal mortality in unplanned births outside an institution: a retrospective population-based study.

BACKGROUND: Births in midwife-led institutions may reduce the frequency of medical interventions and provide cost-effective care, while larger institutions offer medically and technically advanced obstetric care. Unplanned births outside an institution and intrapartum stillbirths have frequently been excluded in previous studies on adverse outcomes by place of birth. OBJECTIVE: The objective of the study was to assess peripartum mortality by place of birth and travel time to obstetric institutions, with the hypothesis that centralization reduces institution availability but improves mortality. STUDY DESIGN: This was a national population-based retrospective cohort study of all births in Norway from 1999 to 2009 (n = 648,555) using data from the Medical Birth Registry of Norway and Statistics Norway and including births from 22 gestational weeks or birthweight ≥500 g. Main exposures were travel time to the nearest obstetric institution and place of birth. The main clinical outcome was peripartum mortality, defined as death during birth or within 24 hours. Intrauterine fetal deaths prior to start of labor were excluded from the primary outcome. RESULTS: A total of 1586 peripartum deaths were identified (2.5 per 1000 births). Unplanned birth outside an institution had a 3 times higher mortality (8.4 per 1000) than institutional births (2.4 per 1000), relative risk, 3.5 (95% confidence interval, 2.5-4.9) and contributed 2% (95% confidence interval, 1.2-3.0%) of the peripartum mortality at the population level. The risk of unplanned birth outside an institution increased from 0.5% to 3.3% and 4.5% with travel time <1 hour, 1-2 hours, and >2 hours, respectively. In obstetric institutions the mortality rate at term ranged from 0.7 per 1000 to 0.9 per 1000. Comparable mortality rates in different obstetric institutions indicated well-functioning routines for referral. CONCLUSION: Unplanned birth outside an institution was associated with increased peripartum mortality and with long travel time to obstetric institutions. Structural determinants have an important impact on perinatal health in high-income countries and also for low-risk births. The results show the importance of skilled birth attendance and warrant attention from clinicians and policy makers to negative consequences of reduced access to institutions.