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.

The international Perinatal Outcomes in the Pandemic (iPOP) study: protocol.

Preterm birth is the leading cause of infant death worldwide, but the causes of preterm birth are largely unknown. During the early COVID-19 lockdowns, dramatic reductions in preterm birth were reported; however, these trends may be offset by increases in stillbirth rates. It is important to study these trends globally as the pandemic continues, and to understand the underlying cause(s). Lockdowns have dramatically impacted maternal workload, access to healthcare, hygiene practices, and air pollution - all of which could impact perinatal outcomes and might affect pregnant women differently in different regions of the world. In the international Perinatal Outcomes in the Pandemic (iPOP) Study, we will seize the unique opportunity offered by the COVID-19 pandemic to answer urgent questions about perinatal health. In the first two study phases, we will use population-based aggregate data and standardized outcome definitions to: 1) Determine rates of preterm birth, low birth weight, and stillbirth and describe changes during lockdowns; and assess if these changes are consistent globally, or differ by region and income setting, 2) Determine if the magnitude of changes in adverse perinatal outcomes during lockdown are modified by regional differences in COVID-19 infection rates, lockdown stringency, adherence to lockdown measures, air quality, or other social and economic markers, obtained from publicly available datasets. We will undertake an interrupted time series analysis covering births from January 2015 through July 2020. The iPOP Study will involve at least 121 researchers in 37 countries, including obstetricians, neonatologists, epidemiologists, public health researchers, environmental scientists, and policymakers. We will leverage the most disruptive and widespread "natural experiment" of our lifetime to make rapid discoveries about preterm birth. Whether the COVID-19 pandemic is worsening or unexpectedly improving perinatal outcomes, our research will provide critical new information to shape prenatal care strategies throughout (and well beyond) the pandemic.

Changes in antibiotic prescribing following COVID-19 restrictions: Lessons for post-pandemic antibiotic stewardship.

AIMS: Public health responses to reduce SARS-CoV-2 transmission have profoundly affected the epidemiology and management of other infections. We examined the impact of COVID-19 restrictions on antibiotic dispensing in Australia. METHODS: We used national claims data to investigate antibiotic dispensing trends from November 2015 to October 2020 and whether changes reflected reductions in primary care consultations. We used interrupted time series analysis to quantify changes in monthly antibiotic dispensing and face-to-face and telehealth GP consultations and examined changes by recipient age, pharmacy State and prescriber specialty. RESULTS: Over the study period, an estimated 19 921 370 people had 125 495 137 antibiotic dispensings, 71% prescribed by GPs. Following COVID-19 restrictions, we observed a sustained 36% (95% CI: 33-40%) reduction in antibiotic dispensings from April 2020. Antibiotics recommended for managing respiratory tract infections showed large reductions (range 51-69%), whereas those recommended for non-respiratory infections were unchanged. Dispensings prescribed by GPs decreased from 63.5 per 1000 population for April-October 2019 to 37.0 per 1000 for April-October 2020. Total GP consultation rates remained stable, but from April 2020, 31% of consultations were telehealth. CONCLUSION: In a setting with a low COVID-19 incidence, restrictions were associated with a substantial reduction in community dispensings of antibiotics primarily used to treat respiratory infections, coincident with reported reductions in respiratory viral infections. Our findings are informative for post-pandemic antimicrobial stewardship and highlight the potential to reduce inappropriate prescribing by GPs and specialists for respiratory viral infections.

Changes in infection-related hospitalizations in children following pandemic restrictions: an interrupted time-series analysis of total population data.

BACKGROUND: Infectious diseases are a leading cause of hospitalization during childhood. The various mitigation strategies implemented to control the coronavirus disease (COVID-19) pandemic could have additional, unintended benefits for limiting the spread of other infectious diseases and their associated burden on the health care system. METHODS: We conducted an interrupted time-series analysis using population-wide hospitalization data for the state of Victoria, Australia. Infection-related hospitalizations for children and adolescents (aged <18 years, total source population ∼1.4 million) were extracted using pre-defined International Classification of Diseases 10th Revision Australian Modification (ICD-10-AM) codes. The change in weekly hospitalization rates (incidence rate ratio, IRR) for all infections following the introduction of pandemic-related restrictions from 15 March 2020 was estimated. RESULTS: Over 2015-19, the mean annual incidence of hospitalization with infection among children less than 18 years was 37 per 1000 population. There was an estimated 65% (95% CI 62-67%) reduction in the incidence of overall infection-related hospitalizations associated with the introduction of pandemic restrictions. The reduction was most marked in younger children (at least 66% in those less than 5 years of age) and for lower respiratory tract infections (relative reduction 85%, 95% CI 85-86%). CONCLUSIONS: The wider impacts of pandemic mitigation strategies on non-COVID-19 infection-related hospitalizations are poorly understood. We observed marked and rapid decreases in hospitalized childhood infection. In tandem with broader consequences, sustainable measures, such as improved hand hygiene, could reduce the burden of severe childhood infection post-pandemic and the social and economic costs of hospitalization.

Diabetes and Overweight/Obesity Are Independent, Nonadditive Risk Factors for In-Hospital Severity of COVID-19: An International, Multicenter Retrospective Meta-analysis.

OBJECTIVE: Obesity is an established risk factor for severe coronavirus disease 2019 (COVID-19), but the contribution of overweight and/or diabetes remains unclear. In a multicenter, international study, we investigated if overweight, obesity, and diabetes were independently associated with COVID-19 severity and whether the BMI-associated risk was increased among those with diabetes. RESEARCH DESIGN AND METHODS: We retrospectively extracted data from health care records and regional databases of hospitalized adult patients with COVID-19 from 18 sites in 11 countries. We used standardized definitions and analyses to generate site-specific estimates, modeling the odds of each outcome (supplemental oxygen/noninvasive ventilatory support, invasive mechanical ventilatory support, and in-hospital mortality) by BMI category (reference, overweight, obese), adjusting for age, sex, and prespecified comorbidities. Subgroup analysis was performed on patients with preexisting diabetes. Site-specific estimates were combined in a meta-analysis. RESULTS: Among 7,244 patients (65.6% overweight/obese), those with overweight were more likely to require oxygen/noninvasive ventilatory support (random effects adjusted odds ratio [aOR], 1.44; 95% CI 1.15-1.80) and invasive mechanical ventilatory support (aOR, 1.22; 95% CI 1.03-1.46). There was no association between overweight and in-hospital mortality (aOR, 0.88; 95% CI 0.74-1.04). Similar effects were observed in patients with obesity or diabetes. In the subgroup analysis, the aOR for any outcome was not additionally increased in those with diabetes and overweight or obesity. CONCLUSIONS: In adults hospitalized with COVID-19, overweight, obesity, and diabetes were associated with increased odds of requiring respiratory support but were not associated with death. In patients with diabetes, the odds of severe COVID-19 were not increased above the BMI-associated risk.

Infectious diseases in children and adolescents in China: analysis of national surveillance data from 2008 to 2017.

OBJECTIVES: To outline which infectious diseases in the pre-covid-19 era persist in children and adolescents in China and to describe recent trends and variations by age, sex, season, and province. DESIGN: National surveillance studies, 2008-17. SETTING: 31 provinces in mainland China. PARTICIPANTS: 4 959 790 Chinese students aged 6 to 22 years with a diagnosis of any of 44 notifiable infectious diseases. The diseases were categorised into seven groups: quarantinable; vaccine preventable; gastrointestinal and enteroviral; vectorborne; zoonotic; bacterial; and sexually transmitted and bloodborne. MAIN OUTCOME MEASURES: Diagnosis of, and deaths from, 44 notifiable infectious diseases. RESULTS: From 2008 to 2017, 44 notifiable infectious diseases were diagnosed in 4 959 790 participants (3 045 905 males, 1 913 885 females) and there were 2532 deaths (1663 males, 869 females). The leading causes of death among infectious diseases shifted from rabies and tuberculosis to HIV/AIDS, particularly in males. Mortality from infectious diseases decreased steadily from 0.21 per 100 000 population in 2008 to 0.07 per 100 000 in 2017. Quarantinable conditions with high mortality have effectively disappeared. The incidence of notifiable infectious diseases in children and adolescents decreased from 280 per 100 000 in 2008 to 162 per 100 000 in 2015, but rose again to 242 per 100 000 in 2017, largely related to mumps and seasonal influenza. Excluding mumps and influenza, the incidence of vaccine preventable diseases fell from 96 per 100 000 in 2008 to 7 per 100 000 in 2017. The incidence of gastrointestinal and enterovirus diseases remained constant, but typhoid, paratyphoid, and dysentery continued to decline. Vectorborne diseases all declined, with a particularly noticeable reduction in malaria. Zoonotic infections remained at low incidence, but there were still unpredictable outbreaks, such as pandemic A/H1N1 2009 influenza. Tuberculosis remained the most common bacterial infection, although cases of scarlet fever doubled between 2008 and 2017. Sexually transmitted diseases and bloodborne infections increased significantly, particularly from 2011 to 2017, among which HIV/AIDS increased fivefold, particularly in males. Difference was noticeable between regions, with children and adolescents in western China continuing to carry a disproportionate burden from infectious diseases. CONCLUSIONS: China's success in infectious disease control in the pre-covid-19 era was notable, with deaths due to infectious diseases in children and adolescents aged 6-22 years becoming rare. Many challenges remain around reducing regional inequalities, scaling-up of vaccination, prevention of further escalation of HIV/AIDS, renewed efforts for persisting diseases, and undertaking early and effective response to highly transmissible seasonal and unpredictable diseases such as that caused by the novel SARS-CoV-2 virus.