Reduction in Spontaneous and Iatrogenic Preterm Births in Twin Pregnancies During COVID-19 Lockdown in Melbourne, Australia: A Multicenter Cohort Study (preprint)

Background: Melbourne, Australia, recorded one of the longest and most stringent pandemic lockdowns in 2020, which was associated with an increase in preterm stillbirths among singleton pregnancies. Twin pregnancies may be particularly susceptible to the impacts of pandemic disruptions to maternity care due to their higher background risk of adverse perinatal outcomes. Objective: To compare the rates of adverse perinatal outcomes in twin pregnancies exposed and unexposed to lockdown restrictions in Melbourne. Study Design: Multicenter retrospective cohort study of all twin pregnancies birthing in public maternity hospitals in Melbourne. We compared perinatal outcomes between a pre-pandemic group ('unexposed') and two lockdown-exposed groups: exposure 1 from 22 March 2020 to 21 March 2021 and exposure 2 from 22 March 2021 to 27 March 2022. We analyzed routinely-collected maternity data on all twin births >20 weeks where outcomes were available for both infants. The primary outcomes were rates of preterm birth<37 weeks and all-cause stillbirth. Multivariable log-binomial regression models were used to compare perinatal outcomes between the pre-pandemic group and women in whom weeks 20+0 to 40+0 of their pregnancy occurred entirely during each lockdown-exposure period. Perinatal outcomes were calculated per infant; maternal outcomes were calculated per pregnancy. Results: We included 2267 women birthing twins. Total preterm births<37 weeks were significantly lower in the exposure 1 group compared with the pre-pandemic group (63.1% vs 68.3% respectively; adjusted risk ratio, aRR 0.92 95% CI 0.87-0.98, p=0.01). This was driven by both fewer iatrogenic preterm births (44.1% vs 48.1%; aRR 0.97 95% CI 0.92-1.03, p=0.39) and fewer spontaneous preterm births (18.9% vs 20.3%; aRR 0.95 95% CI 0.90-0.99, p=0.04). There were also significantly lower rates of preterm birth<34 weeks in the exposure 1 group compared with the pre-pandemic group (19.9% vs 23.0%, aRR 0.93 95% CI 0.89-0.98 p=0.01). Total iatrogenic births for fetal compromise were significantly lower (13.4% vs 20.4%; aRR 0.94 95% CI 0.89-0.98, p=0.01). There were fewer special care nursery admissions (38.5% vs 43.4%; aRR 0.91 95% CI 0.87-0.95, p<0.001). There was no associated difference in all-cause stillbirths (1.5% vs 1.6%; aRR 1.00 95% CI 0.99-1.01, p=0.82), adjusted stillbirths, birthweight<3rd centile (5.7% vs 6.0%; aRR 1.00, 95% CI 0.98-1.02 p=0.74) or neonatal intensive care unit admissions in the exposure 1 group compared to the pre-pandemic group. In contrast, when comparing the pre-pandemic group with exposure 2 group, there was no significant difference in the rates of preterm birth<37 or <34 weeks (p>0.05). However, during exposure 2 the rate of preterm birth<28 weeks was significantly higher (7.2% vs 4.8%; aRR 1.03 95% CI 1.01-1.05, p=0.04) and infants were more likely to be admitted to a neonatal intensive care unit (25.0% vs 19.6%; aRR 1.06 95% CI 1.03-1.10, p<0.0001) compared with the pre-pandemic period. Conclusions: Melbourne's first lockdown-exposure period was associated with fewer twin preterm births<34 and <37 weeks without significant differences in stillbirths or adverse newborn outcomes. These lower rates were not sustained into the second exposure period. Pandemic conditions may provide important lessons for future antenatal care of twin pregnancies, including prevention of preterm birth and optimal timing of birth.

Prevalence of iatrogenic CNS inflammation at a tertiary neuroimmunology clinic.

BACKGROUND: Various vaccines, tumor-necrosis-factor-alpha inhibitors (TNFAIs), immune-checkpoint inhibitors (ICIs), and other immunomodulators have been linked to inflammatory CNS events. The prevalence of iatrogenic events in the neuroimmunology clinic is unknown. OBJECTIVE: To evaluate the prevalence and clinical characteristics of iatrogenic CNS inflammation in a tertiary neuroimmunology clinic. METHODS: We analyzed 422 consecutive patients seen over five years at a tertiary neuroimmunology clinic who were systematically screened for exposure to vaccines, TNFAIs, ICIs, or other immunomodulators. In patients with suspected iatrogenic events, the Naranjo Adverse Drug Reaction Probability Scale was used to score the probability of iatrogenicity. RESULTS: In total, 27 potential iatrogenic events were observed, accounting for 6.4% of all new referrals. The average Naranjo score was 5.78 +/- 1.65 with 74% of the cases scored as probable and 26% scored as possible. The clinical phenotypes included MS relapses (37%); autoimmune encephalitis (30%); NMOSD attacks (15%); transverse myelitis (11%); optic neuritis (4%); and MOGAD attacks (4%). A monophasic course was observed in 44% of cases while 41% had a relapsing course. All patients stopped or interrupted treatment with the offending agent. In addition, 41% of the iatrogenic events were fully responsive to corticosteroids; 22% were partially responsive; and 15% resolved spontaneously. The most common potential triggers were vaccines (37%) followed by TNFAIs (33%) then ICIs (26%). A significantly higher number of probable iatrogenic events were observed among the ICI and vaccine groups compared to a higher number of possible events among the TNFAI group. The latter group also had a significantly longer interval since exposure. The ICI group was more likely to present with monophasic autoimmune encephalitis. CONCLUSION: Iatrogenic CNS inflammation is rare and typically involves steroid-responsive monophasic events. A subset of iatrogenic events can unmask or worsen relapsing disorders. The probability of iatrogenicity was higher in vaccine and ICI-related events compared to TNFAI-related events.

What the COVID-19 Pandemic Teaches Us About Pediatric Iatrogenic Risk.

Iatrogenic morbidity and mortality are pediatric public health risks. This article considers how the COVID-19 pandemic illuminates these risks, as clinicians have been forced to navigate increased diagnostic uncertainty and changes to pediatric health care systems, including closures, limited staffing, and new infection control guidelines.

The effect of COVID-19 on the pressure injury reporting gap.

Responsibilities placed on nurses increased during the COVID-19 pandemic. Hospital-acquired PI monitoring was deferred in favor of more critical patient needs. It was hypothesized that a counterintuitive dip in HAPI reporting would be observed despite maximum hospital capacity across much of the United States. The electronic medical records of patients treated in the YNHH System between December 2017 and February 2021 were retrospectively reviewed to identify patients with HAPIs, defined as PIs not documented upon admission but subsequently present during the patient's hospital stay. Paired t test revealed a significantly lower number of reported incidents mid-pandemic than during the prepandemic baseline months (P <.0001). The data in this report show interdisciplinary clinician-led teams must continue to monitor for HAPIs and congruous conditions to minimize reporting gaps and progression in PI severity despite COVID-19 pandemic-related conditions and additional related responsibilities.

Investigating service delivery and perinatal outcomes during the low prevalence first year of COVID-19 in a multiethnic Australian population: a cohort study.

OBJECTIVE: Investigate the impact of the COVID-19 pandemic on perinatal outcomes in an Australian high migrant and low COVID-19 prevalent population to identify if COVID-19 driven health service changes and societal influences impact obstetric and perinatal outcomes. DESIGN: Retrospective cohort study with pre COVID-19 period 1 January 2018-31 January 2020, and first year of global COVID-19 period 1 February 2020-31 January 2021. Multivariate logistic regression analysis was conducted adjusting for confounders including age, area-level socioeconomic status, gestation, parity, ethnicity and body mass index. SETTING: Obstetric population attending three public hospitals including a major tertiary referral centre in Western Sydney, Australia. PARTICIPANTS: Women who delivered with singleton pregnancies over 20 weeks gestation. Ethnically diverse women, 66% overseas born. There were 34 103 births in the district that met inclusion criteria: before COVID-19 n=23 722, during COVID-19 n=10 381. MAIN OUTCOME MEASURES: Induction of labour, caesarean section delivery, iatrogenic and spontaneous preterm birth, small for gestational age (SGA), composite neonatal adverse outcome and full breastfeeding at hospital discharge. RESULTS: During the first year of COVID-19, there was no change for induction of labour (adjusted OR, aOR 0.97; 95% CI 0.92 to 1.02, p=0.26) and a 25% increase in caesarean section births (aOR 1.25; 95% CI 1.19 to 1.32, p<0.001). During the COVID-19 period, we found no change in iatrogenic preterm births (aOR 0.94; 95% CI 0.80 to 1.09) but a 15% reduction in spontaneous preterm birth (aOR 0.85; 95% CI 0.75 to 0.97, p=0.02) and a 10% reduction in SGA infants at birth (aOR 0.90; 95% CI 0.82 to 0.99, p=0.02). Composite adverse neonatal outcomes were marginally higher (aOR 1.08; 95% CI 1.00 to 1.15, p=0.04) and full breastfeeding rates at hospital discharge reduced by 15% (aOR 0.85; 95% CI 0.80 to 0.90, p<0.001). CONCLUSION: Despite a low prevalence of COVID-19, both positive and adverse obstetric outcomes were observed that may be related to changes in service delivery and interaction with healthcare providers. Further research is suggested to understand the drivers for these changes.

Association between COVID-19 lockdown measures and the incidence of iatrogenic versus spontaneous very preterm births in the Netherlands: a retrospective study.

BACKGROUND: The COVID-19 pandemic led to regional or nationwide lockdowns as part of risk mitigation measurements in many countries worldwide. Recent studies suggest an unexpected and unprecedented decrease in preterm births during the initial COVID-19 lockdowns in the first half of 2020. The objective of the current study was to assess the effects of the two months of the initial national COVID-19 lockdown period on the incidence of very and extremely preterm birth in the Netherlands, stratified by either spontaneous or iatrogenic onset of delivery, in both singleton and multiple pregnancies. METHODS: Retrospective cohort study using data from all 10 perinatal centers in the Netherlands on very and extremely preterm births during the initial COVID-19 lockdown from March 15 to May 15, 2020. Incidences of very and extremely preterm birth were calculated using an estimate of the total number of births in the Netherlands in this period. As reference, we used data from the corresponding calendar period in 2015-2018 from the national perinatal registry (Perined). We differentiated between spontaneous versus iatrogenic onset of delivery and between singleton versus multiple pregnancies. RESULTS: The incidence of total preterm birth < 32 weeks in singleton pregnancies was 6.1‰ in the study period in 2020 versus 6.5‰ in the corresponding period in 2015-2018. The decrease in preterm births in singletons was solely due to a significant decrease in iatrogenic preterm births, both < 32 weeks (OR 0.71; 95%CI 0.53 to 0.95) and < 28 weeks (OR 0.53; 95%CI 0.29 to 0.97). For multiple pregnancies, an increase in preterm births < 28 weeks was observed (OR 2.43; 95%CI 1.35 to 4.39). CONCLUSION: This study shows a decrease in iatrogenic preterm births during the initial COVID-19-related lockdown in the Netherlands in singletons. Future studies should focus on the mechanism of action of lockdown measures and reduction of preterm birth and the effects of perinatal outcome.

The prevalence of AstraZeneca COVID-19 vaccine side effects among Nigist Eleni Mohammed memorial comprehensive specialized hospital health workers. Cross sectional survey.

INTRODUCTION: The best way to eradicate corona virus disease (COVID-19) viral infection is mass vaccination. Many studies demonstrate vaccination is associated with some local and systemic side effects. This study aimed to provide evidence on AstraZeneca COVID-19 vaccine side effects. METHODOLOGY: Institutional based cross-sectional survey was conducted among 254 health workers at Nigist Eleni Mohammed memorial comprehensive specialized hospital (from July 01/ 2021 to July 30/2021). Data were collected consecutively through self-administered online survey created on Google Forms of platform which had been randomly delivered via (Facebook or telegram pages). Demographic data of participants, side effect after first and second dose of vaccine were covered. RESULT: The prevalence of at least one side effect after first dose was 91.3% and after second dose was 67%. Injection site pain (63.8% vs. 50.4%), headache (48.8% vs. 33.5%), fever (38.8% vs. 20.9%), muscle pain (38.8% vs. 21.7%), fatigue (26% vs. 28.7%, tenderness at the site (27.6% vs. 21.7%), and joint pain (27.6% vs. 20.9%) were the most commonly reported side effects after first and second dose vaccine respectively. Most of participants reported that their symptoms emerged after 6hr of vaccination and only less than 5% of participant's symptoms lasted more than 72hr of post vaccination. The younger age (≤29 year) were more susceptible to at least one side effect (χ 2 = 4.2; p = 0.04) after first dose. CONCLUSION: The prevalence of side effect after first and second dose vaccine was higher. Most of the symptoms were short lived and mild. This result might help to solve an emerging public health challenge (vaccine hesitancy) nurtured by misinformation related to vaccines safety.

Spontaneous hemothorax in a 10-year-old boy with COVID-19. (preprint)

Spontaneous hemothorax occurs in the absence of trauma or iatrogenic causes. Etiologies of spontaneous hemothorax in children include connective tissue disease, neoplasia and coagulopathy which is associated with thromboembolic events. We present the case of a 10-year-old chronic hemodialysis patient with spontaneous hemothorax with a concurrent COVID 19 infection.

Increase in preterm stillbirths in association with reduction in iatrogenic preterm births during COVID-19 lockdown in Australia: a multicenter cohort study.

BACKGROUND: The COVID-19 pandemic has been associated with a worsening of perinatal outcomes in many regions around the world. Melbourne, Australia, had one of the longest and most stringent lockdowns worldwide in 2020 while recording only rare instances of COVID-19 infection in pregnant women. OBJECTIVE: This study aimed to compare the stillbirth and preterm birth rates in women who were exposed or unexposed to lockdown restrictions during pregnancy. STUDY DESIGN: This was a retrospective, multicenter cohort study of perinatal outcomes in Melbourne before and during the COVID-19 lockdown. The lockdown period was defined as the period from March 23, 2020 to March 14, 2021. Routinely-collected maternity data on singleton pregnancies ≥24 weeks gestation without congenital anomalies were obtained from all the 12 public hospitals in Melbourne. We defined the lockdown-exposed cohort as those women for whom weeks 20 to 40 of gestation occurred during the lockdown and the unexposed control group as women from the corresponding calendar periods 12 and 24 months before. The main outcome measures were stillbirth, preterm birth, fetal growth restriction (birthweight < third centile), and iatrogenic preterm birth for fetal compromise. We performed multivariable logistic regression analysis to compare the odds of stillbirth, preterm birth, fetal growth restriction, and iatrogenic preterm birth for fetal compromise, adjusting for multiple covariates. RESULTS: There were 24,817 births in the exposed group and 50,017 births in the control group. There was a significantly higher risk of preterm stillbirth in the exposed group than the control group (0.26% vs 0.18%; adjusted odds ratio, 1.49; 95% confidence interval, 1.08-2.05; P=.015). There was also a significant reduction in the preterm birth of live infants <37 weeks (5.68% vs 6.07%; adjusted odds ratio, 0.93; 95% confidence interval, 0.87-0.99; P=.02), which was largely mediated by a significant reduction in iatrogenic preterm birth (3.01% vs 3.27%; adjusted odds ratio, 0.91; 95% confidence interval, 0.83-0.99; P=.03), including iatrogenic preterm birth for fetal compromise (1.25% vs 1.51%; adjusted odds ratio, 0.82; 95% confidence interval, 0.71-0.93; P=.003). There were also significant reductions in special care nursery admissions during lockdown (11.53% vs 12.51%; adjusted odds ratio, 0.90; 95% confidence interval, 0.86-0.95; P<.0001). There was a trend to fewer spontaneous preterm births <37 weeks in the exposed group of a similar magnitude to that reported in other countries (2.69% vs 2.82%; adjusted odds ratio, 0.95; 95% confidence interval, 0.87-1.05; P=.32). CONCLUSION: Lockdown restrictions in Melbourne, Australia were associated with a significant reduction in iatrogenic preterm birth for fetal compromise and a significant increase in preterm stillbirths. This raises concerns that pandemic conditions in 2020 may have led to a failure to identify and appropriately care for pregnant women at an increased risk of antepartum stillbirth. Further research is required to understand the relationship between these 2 findings and to inform our ongoing responses to the pandemic.

The impact of mitigation measures on perinatal outcomes during the first nine months of the COVID-19 pandemic: A systematic review with meta-analysis.

Worldwide reports have produced conflicting data on perinatal outcomes during the COVID-19 pandemic. This systematic review and meta-analysis addressed the effect of mitigation measures against COVID-19 on preterm birth, stillbirth, low birth weight, and NICU admission during the first nine months of the pandemic. A search was performed using MEDLINE, Embase and SCOPUS for manuscripts published up until 24th May 2021. Studies that reported perinatal outcomes (preterm birth, stillbirth, low birth weight, NICU admission) during the COVID-19 pandemic with a pre-pandemic control period were included. Risk of bias assessment was performed using ROBINS-I tool. RevMan5 was used to perform meta-analysis with random-effects models. A score of the stringency of mitigation measures was calculated from the Oxford COVID-19 Government Response Tracker. Thirty-eight studies of moderate to serious risk of bias were included, with varied methodology, analysis and regional mitigation measures, using stringency index scores. There was no overall effect on preterm birth at less than 37 weeks (OR 0.96, 95% CI 0.92-1.00). However, there was a reduction in preterm birth at less than 37 weeks (OR 0.89, 95% CI 0.81-0.98) and 34 weeks (OR 0.56, 95% CI 0.37-0.83) for iatrogenic births and in singleton pregnancies. There was also a significant reduction in preterm births at less than 34 weeks in studies with above median stringency index scores (OR 0.71, 95% CI 0.58-0.88). There was no effect on risk of stillbirth (OR 1.04, 95% CI 0.90-1.19) or birth weight. NICU admission rates were significantly reduced in studies with above median stringency index scores (OR 0.87, 95% CI 0.78-0.97). The reduction in preterm births in regions with high mitigation measures against SARS-CoV-2 infection is likely driven by a reduction in iatrogenic births. Variability in study design and cohort characteristics need to be considered for future studies to allow further investigation of population level health measures of perinatal outcomes.

Prevalence, risk factors, treatment and outcome of multidrug resistance Candida auris infections in Coronavirus disease (COVID-19) patients: A systematic review.

BACKGROUND: Candida auris is an emerging multidrug-resistant pathogen in intensive care settings (ICU). During the coronavirus disease 19 (COVID-19) pandemic, ICU admissions were overwhelmed, possibly contributing to the C. auris outbreak in COVID-19 patients. OBJECTIVES: The present systematic review addresses the prevalence, underlying diseases, iatrogenic risk factors, treatment and outcome of C. auris infections in COVID-19 patients. METHODS: MEDLINE, Scopus, Embase, Web of Science and LitCovid databases were systematically searched with appropriate keywords from 1 January 2020 to 31 December 2021. RESULTS: A total of 97 cases of C. auris were identified in COVID-19 patients. The pooled prevalence of C. auris infections (encompassing candidemia and non-candidemia cases) in COVID-19 patients was 14%. The major underlying diseases were diabetes mellitus (42.7%), hypertension (32.9%) and obesity (14.6%), followed by the iatrogenic risk factors such as a central venous catheter (76.8%%), intensive care unit (ICU) stay (75.6%) and broad-spectrum antibiotic usage (74.3%). There were no significant differences in underlying disease and iatrogenic risk factors among C. auris non-candidemia/colonisation and C. auris candidemia cases. The mortality rate of the total cohort is 44.4%, whereas, in C. auris candidemia patients, the mortality was 64.7%. CONCLUSION: This study shows that the prevalence of C. auris infections remains unchanged in the COVID-19 pandemic. Hospital-acquired risk factors may contribute to the clinical illness. Proper infection control practices and hospital surveillance may stop future hospital outbreaks during the pandemic.

Outcomes of hospital-acquired SARS-CoV-2 infection in the Canadian first wave epicentre: a retrospective cohort study.

BACKGROUND: During the first wave of the COVID-19 pandemic, a substantial number of Quebec hospitals were hit by hospital-acquired (HA) SARS-CoV-2 infections. Our objective was to assess whether mortality is higher in HA cases than in non-hospital-acquired (NHA) cases and determine the prevalence of HA-SARS-CoV-2 infection in our hospital. METHODS: This retrospective single-centre cohort study included all adults (≥ 18 yr) who had COVID-19, admitted to Hôpital Maisonneuve-Rosemont (Montréal, Canada) from Mar. 1 to June 30, 2020. We collected data on demographic characteristics, comorbidities, treatment, admission to the intensive care unit (ICU) and mechanical ventilation requirements from electronic health records. We adjudicated hospital acquisition based on the timing of symptom onset, and polymerase chain reaction testing for and exposures to SARS-CoV-2. To evaluate the association between HA-SARS-CoV-2 infection and in-hospital mortality, we computed a multivariable logistic regression analysis including known risk factors for death in patients with COVID-19 as covariates. RESULTS: Among 697 patients with SARS-CoV-2 infection, 253 (36.3%) were classified as HA. The mortality rate was higher in the HA group than in the NHA group (38.2% v. 26.4%, p = 0.001), while the rates of ICU admission (8.3% v. 19.1%, p = 0.001) and requirement for mechanical ventilation (3.6% v. 13.0%, p = 0.001) were lower. Multivariable logistic regression analysis showed that HA-SARS-CoV-2 infection in patients younger than 75 years is an independent risk factor for death (odds ratio 2.78, 95% confidence interval 1.44-5.38). INTERPRETATION: Our results show that HA-SARS-CoV-2 infection in younger patients was associated with higher mortality. Future studies need to evaluate relevant patient-centred long-term outcomes in this population.