Delay in childhood vaccinations during the COVID-19 pandemic.

OBJECTIVES: In many jurisdictions, routine medical care was reduced in response to the COVID-19 pandemic. The objective of this study was to determine whether the frequency of on-time routine childhood vaccinations among children age 0-2 years was lower following the COVID-19 declaration of emergency in Ontario, Canada, on March 17, 2020, compared to prior to the pandemic. METHODS: We conducted a longitudinal cohort study of healthy children aged 0-2 years participating in the TARGet Kids! primary care research network in Toronto, Canada. A logistic mixed effects regression model was used to determine odds ratios (ORs) for delayed vaccination (> 30 days vs. ≤ 30 days from the recommended date) before and after the COVID-19 declaration of emergency, adjusted for confounding variables. A Cox proportional hazards model was used to explore the relationship between the declaration of emergency and time to vaccination. RESULTS: Among 1277 children, the proportion of on-time vaccinations was 81.8% prior to the COVID-19 declaration of emergency and 62.1% after (p < 0.001). The odds of delayed vaccination increased (odds ratio = 3.77, 95% CI: 2.86-4.96), and the hazard of administration of recommended vaccinations decreased after the declaration of emergency (hazard ratio = 0.75, 95% CI: 0.60-0.92). The median vaccination delay time was 5 days (95% CI: 4-5 days) prior to the declaration of emergency and 17 days (95% CI: 12-22 days) after. CONCLUSION: The frequency of on-time routine childhood vaccinations was lower during the first wave of the COVID-19 pandemic. Sustained delays in routine vaccinations may lead to an increase in rates of vaccine-preventable diseases.

RéSUMé: OBJECTIFS: Dans plusieurs juridictions, les soins médicaux systématiques étaient réduits à cause de la pandémie de COVID-19. L'objectif de cette étude était de déterminer si la fréquence de donner les vaccinations systématiques aux enfants de l'âge de 0 à 2 ans était réduite en conséquence de la déclaration d'urgence de COVID-19 en Ontario, Canada dès le 17 mars 2020, comparer avec la fréquence avant la pandémie. MéTHODES: Nous avons mené une étude de cohorte longitudinale des enfants en bonne santé âgés de 0 à 2 ans qui participent dans le réseau de recherche en soins primaires TARGet Kids! à Toronto, Canada. Un modèle de régression logistique à effets mixtes était utilisé pour déterminer le rapport de cotes (RC) pour les vaccinations retardées (> 30 jours c. ≤ 30 jours de la date recommandée) et était équilibré pour les variables confondantes. Le modèle à risques proportionnels de Cox était utilisé pour examiner le lien entre la déclaration d'urgence et le temps jusqu'à la vaccination. RéSULTATS: Parmi 1 277 enfants, la proportion de vaccination à l'heure était 81,8 % avant la déclaration d'urgence de COVID-19 et 62,1 % après (p < 0,001). La possibilité de vaccination retardée était augmentée (RC = 3,77; IC95% : 2,86­4,96), et le taux d'administration recommandé pour les vaccinations était réduit après la déclaration d'urgence (ratio de hasard = 0,75; IC95% : 0,60­0,92). Le médian temps de retard pour les vaccinations était 5 jours (IC95% : 4­5 jours) avant la déclaration d'urgence et 17 jours (IC95% : 12­22 jours) après. CONCLUSION: La fréquence de vaccinations systématiques aux enfants à l'heure était inférieure pendant la première vague de la pandémie COVID-19. Des retards soutenus pour recevoir les vaccinations systématiques peuvent entrainer une augmentation des taux de maladies évitables par la vaccination.

Delay in childhood vaccinations during the COVID-19 pandemic

Objectives In many jurisdictions, routine medical care was reduced in response to the COVID-19 pandemic. The objective of this study was to determine whether the frequency of on-time routine childhood vaccinations among children age 0–2 years was lower following the COVID-19 declaration of emergency in Ontario, Canada, on March 17, 2020, compared to prior to the pandemic. Methods We conducted a longitudinal cohort study of healthy children aged 0–2 years participating in the TARGet Kids! primary care research network in Toronto, Canada. A logistic mixed effects regression model was used to determine odds ratios (ORs) for delayed vaccination (> 30 days vs. ≤ 30 days from the recommended date) before and after the COVID-19 declaration of emergency, adjusted for confounding variables. A Cox proportional hazards model was used to explore the relationship between the declaration of emergency and time to vaccination. Results Among 1277 children, the proportion of on-time vaccinations was 81.8% prior to the COVID-19 declaration of emergency and 62.1% after (p < 0.001). The odds of delayed vaccination increased (odds ratio = 3.77, 95% CI: 2.86–4.96), and the hazard of administration of recommended vaccinations decreased after the declaration of emergency (hazard ratio = 0.75, 95% CI: 0.60–0.92). The median vaccination delay time was 5 days (95% CI: 4–5 days) prior to the declaration of emergency and 17 days (95% CI: 12–22 days) after. Conclusion The frequency of on-time routine childhood vaccinations was lower during the first wave of the COVID-19 pandemic. Sustained delays in routine vaccinations may lead to an increase in rates of vaccine-preventable diseases. Supplementary Information The online version contains supplementary material available at 10.17269/s41997-021-00601-9.

Vitamin D supplementation to prevent acute respiratory infections: a systematic review and meta-analysis of aggregate data from randomised controlled trials.

BACKGROUND: A 2017 meta-analysis of data from 25 randomised controlled trials (RCTs) of vitamin D supplementation for the prevention of acute respiratory infections (ARIs) revealed a protective effect of this intervention. We aimed to examine the link between vitamin D supplementation and prevention of ARIs in an updated meta-analysis. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, Web of Science, and the ClinicalTrials.gov registry for studies listed from database inception to May 1, 2020. Double-blind RCTs of vitamin D3, vitamin D2, or 25-hydroxyvitamin D (25[OH]D) supplementation for any duration, with a placebo or low-dose vitamin D control, were eligible if they had been approved by a research ethics committee, and if ARI incidence was collected prospectively and prespecified as an efficacy outcome. Studies reporting results of long-term follow-up of primary RCTs were excluded. Aggregated study-level data, stratified by baseline 25(OH)D concentration and age, were obtained from study authors. Using the proportion of participants in each trial who had one or more ARIs, we did a random-effects meta-analysis to obtain pooled odds ratios (ORs) and 95% CIs to estimate the effect of vitamin D supplementation on the risk of having one or more ARIs (primary outcome) compared with placebo. Subgroup analyses were done to estimate whether the effects of vitamin D supplementation on the risk of ARI varied according to baseline 25(OH)D concentration (<25 nmol/L vs 25·0-49·9 nmol/L vs 50·0-74·9 nmol/L vs >75·0 nmol/L), vitamin D dose (daily equivalent of <400 international units [IU] vs 400-1000 IU vs 1001-2000 IU vs >2000 IU), dosing frequency (daily vs weekly vs once per month to once every 3 months), trial duration (≤12 months vs >12 months), age at enrolment (<1·00 years vs 1·00-15·99 years vs 16·00-64·99 years vs ≥65·00 years), and presence versus absence of airway disease (ie, asthma only, COPD only, or unrestricted). Risk of bias was assessed with the Cochrane Collaboration Risk of Bias Tool. The study was registered with PROSPERO, CRD42020190633. FINDINGS: We identified 1528 articles, of which 46 RCTs (75 541 participants) were eligible. Data for the primary outcome were obtained for 48 488 (98·1%) of 49 419 participants (aged 0-95 years) in 43 studies. A significantly lower proportion of participants in the vitamin D supplementation group had one or more ARIs (14 332 [61·3%] of 23 364 participants) than in the placebo group (14 217 [62·3%] of 22 802 participants), with an OR of 0·92 (95% CI 0·86-0·99; 37 studies; I2=35·6%, pheterogeneity=0·018). No significant effect of vitamin D supplementation on the risk of having one or more ARIs was observed for any of the subgroups defined by baseline 25(OH)D concentration. However, protective effects of supplementation were observed in trials in which vitamin D was given in a daily dosing regimen (OR 0·78 [95% CI 0·65-0·94]; 19 studies; I2=53·5%, pheterogeneity=0·003), at daily dose equivalents of 400-1000 IU (0·70 [0·55-0·89]; ten studies; I2=31·2%, pheterogeneity=0·16), for a duration of 12 months or less (0·82 [0·72-0·93]; 29 studies; I2=38·1%, pheterogeneity=0·021), and to participants aged 1·00-15·99 years at enrolment (0·71 [0·57-0·90]; 15 studies; I2=46·0%, pheterogeneity=0·027). No significant interaction between allocation to the vitamin D supplementation group versus the placebo group and dose, dose frequency, study duration, or age was observed. In addition, no significant difference in the proportion of participants who had at least one serious adverse event in the vitamin supplementation group compared with the placebo group was observed (0·97 [0·86-1·07]; 36 studies; I2=0·0%, pheterogeneity=0·99). Risk of bias within individual studies was assessed as being low for all but three trials. INTERPRETATION: Despite evidence of significant heterogeneity across trials, vitamin D supplementation was safe and overall reduced the risk of ARI compared with placebo, although the risk reduction was small. Protection was associated with administration of daily doses of 400-1000 IU for up to 12 months, and age at enrolment of 1·00-15·99 years. The relevance of these findings to COVID-19 is not known and requires further investigation. FUNDING: None.

Public health preventive measures and child health behaviours during COVID-19: a cohort study.

OBJECTIVE: The primary objective was to determine the association between public health preventive measures and children's outdoor time, sleep duration, and screen time during COVID-19. METHODS: A cohort study using repeated measures of exposures and outcomes was conducted in healthy children (0 to 10 years) through The Applied Research Group for Kids (TARGet Kids!) COVID-19 Study of Children and Families in Toronto, Canada, between April 14 and July 15, 2020. Parents were asked to complete questionnaires about adherence to public health measures and children's health behaviours. The primary exposure was the average number of days that children practiced public health preventive measures per week. The three outcomes were children's outdoor time, total screen time, and sleep duration during COVID-19. Linear mixed-effects models were fitted using repeated measures of primary exposure and outcomes. RESULTS: This study included 554 observations from 265 children. The mean age of participants was 5.5 years, 47.5% were female and 71.6% had mothers of European ethnicity. Public health preventive measures were associated with shorter outdoor time (-17.2; 95% CI -22.07, -12.40; p < 0.001) and longer total screen time (11.3; 95% CI 3.88, 18.79; p = 0.003) during COVID-19. The association with outdoor time was stronger in younger children (<5 years), and the associations with total screen time were stronger in females and in older children (≥5 years). CONCLUSION: Public health preventive measures during COVID-19 were associated with a negative impact on the health behaviours of Canadian children living in a large metropolitan area.

RéSUMé: OBJECTIF: L'objectif principal était de déterminer la relation entre les mesures préventives de la santé publique et le temps passé en plein air, la durée du sommeil ainsi que le temps passé devant l'écran par les enfants pendant COVID-19. MéTHODES: Une étude de cohorte utilisant des mesures répétées des expositions et des effets a été menée chez des enfants en bonne santé (0 à 10 ans) par l'entremise de l'Étude COVID-19 sur les Enfants et Familles du Groupe de Recherche Appliquée pour les Enfants (TARGet Kids!) à Toronto, au Canada, entre le 14 avril et le 15 juillet 2020. Les parents ont été invités à remplir des questionnaires sur adhésion aux mesures préventives de la santé publique et les comportements de santé des enfants. La principale exposition était le nombre moyen de jours par semaine durant lesquels les enfants pratiquaient des mesures préventives de la santé publique. Les trois effets étaient le temps passé en plein air par les enfants, le temps total passé devant l'écran et la durée du sommeil pendant le COVID-19. Des modèles linéaires à effets mixtes ont été ajustés en utilisant des mesures répétées d'exposition primaire et des effets. RéSULTATS: Cette étude comprend 554 observations sur 265 enfants. L'âge moyen des participants était de 5,5 ans, 47,5 % étaient des femmes et 71,6 % avaient des mères d'origine européenne. Les mesures préventives de la santé publique ont été associées à un temps passé en plein air plus court (-17,2 ; IC 95% -22,07, -12,40; p < 0,001) et à un temps total devant l'écran plus long (11,3 ; IC 95% 3,88, 18,79; p = 0,003) pendant la COVID-19. La relation avec le temps passé en plein air était plus importante chez les jeunes enfants (<5 ans), et les relations avec le temps total passé devant l'écran étaient plus importantes chez les enfants de sexe féminin et les enfants plus âgés (≥5 ans). CONCLUSION: Les mesures préventives de la santé publique prises lors de COVID-19 ont été associées à un impact négatif sur les comportements de santé des enfants canadiens vivant dans une grande région métropolitaine.

Vitamin D supplementation to prevent acute respiratory infections: systematic review and meta-analysis of aggregate data from randomised controlled trials.

BACKGROUND: A 2017 meta-analysis of data from 25 randomised controlled trials of vitamin D supplementation for the prevention of acute respiratory infections revealed a protective effect of the intervention. Since then, 20 new RCTs have been completed. METHODS: Systematic review and meta-analysis of data from randomised controlled trials (RCTs) of vitamin D for ARI prevention using a random effects model. Pre-specified sub-group analyses were done to determine whether effects of vitamin D on risk of ARI varied according to baseline 25-hydroxyvitamin D (25[OH]D) concentration or dosing regimen. We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science and the ClinicalTrials.gov registry from inception to 1st May 2020. Double-blind RCTs of supplementation with vitamin D or calcidiol, of any duration, were eligible if they were approved by a Research Ethics Committee and if ARI incidence was collected prospectively and pre-specified as an efficacy outcome. Aggregate data, stratified by baseline 25(OH)D concentration, were obtained from study authors. The study was registered with PROSPERO (no. CRD42020190633). FINDINGS: We identified 45 eligible RCTs (total 73,384 participants). Data were obtained for 46,331 (98.0%) of 47,262 participants in 42 studies, aged 0 to 95 years. For the primary comparison of vitamin D supplementation vs. placebo, the intervention reduced risk of ARI overall (Odds Ratio [OR] 0.91, 95% CI 0.84 to 0.99; P for heterogeneity 0.01). No statistically significant effect of vitamin D was seen for any of the sub-groups defined by baseline 25(OH)D concentration. However, protective effects were seen for trials in which vitamin D was given using a daily dosing regimen (OR 0.75, 95% CI 0.61 to 0.93); at daily dose equivalents of 400-1000 IU (OR 0.70, 95% CI 0.55 to 0.89); and for a duration of ≤12 months (OR 0.82, 95% CI 0.72 to 0.93). No significant interaction was seen between allocation to vitamin D vs. placebo and dose frequency, dose size, or study duration. Vitamin D did not influence the proportion of participants experiencing at least one serious adverse event (OR 0.97, 95% CI 0.86 to 1.09). Risk of bias within individual studies was assessed as being low for all but three trials. A funnel plot showed left-sided asymmetry (P=0.008, Egger's test). INTERPRETATION: Vitamin D supplementation was safe and reduced risk of ARI, despite evidence of significant heterogeneity across trials. Protection was associated with administration of daily doses of 400-1000 IU vitamin D for up to 12 months. The relevance of these findings to COVID-19 is not known and requires investigation. FUNDING: None.