The Covid-19 pandemic had an upside for lockdown babies: substantially less wheezing and bronchiolitis, according to an Italian retrospective cohort study, with the researchers suggesting this was probably due to the social distancing measures in place at the time.
One or more wheezing episode by age 30 months was observed in a noteworthy 44% fewer babies born while stay-at-home orders were in effect compared than those born during the same months in 2016 and 2017 (9.4% vs 15%, P<0.001), reported researchers led by Carlo Giaquinto, MD, of the University of Padua, Italy.
Wheezing episodes occurred at a rate of 67.6 per 10 000 person-months among the lockdown group and 110.0 per 10 000 person-months in the historical group, according to the research letter published in JAMA Network Open.
Bronchiolitis cases, one of the most common reasons for hospital admissions among infants, dropped drastically during lockdown as well, from 82.4 episodes per 10 000 person-months in the historical cohort to just 6.6 episodes per 10 000 person-months for lockdown babies.
This decline in cases is probably tied to the social distancing measures that were in place at the time, reducing exposure to pathogens like respiratory syncytial virus (RSV), which accounts for anywhere from 50%-80% of bronchiolitis cases, the researchers noted. RSV is also a known risk factor for asthma and similar wheezing illnesses.
For wheezing, 30% of the reduced risk was estimated to be due to the lockdown preventive measures alone.
Medpage Today reports that the findings add weight to the recent US-based INSPIRE population-cohort study showing that dodging RSV infection within the first year of life was linked to a 26% lower risk of asthma over five years.
The new study “underscores the potential role of a universal RSV immunoprophylaxis in preventing post-bronchiolitis wheezing”, Giaquinto’s group argued.
After decades without an option for protecting most infants against the annual respiratory scourge, a spate of RSV prophylaxis options has become available in recent years.
The maternal RSV prefusion F protein vaccine (Abrysvo) gained a recommendation last year for mothers at 32 to 36 weeks’ gestation to prevent lower respiratory tract RSV infection in infants.
And around the same time, the monoclonal antibody nirsevimab (Beyfortus) gained official recommendation for all infants younger than eight months born during or entering their first RSV season.
Giaquinto’s study utilised the Pedianet database for all patients seen by 150 participating family paediatricians in Italy. Wheezing and anti-asthma medication use were identified through administrative codes.
The analysis included 2 192 births during the lockdown period, spanning February to April in 2020, and 3 889 births in the historical winter bronchiolitis seasons from February to April in both 2016 and 2017.
There were no differences in sex, area deprivation index, gestational age, or family history of atopic disease between the two cohorts.
Incidence curves for 30-month cumulative wheezing revealed a significant difference between the lockdown and historical cohorts, which was confirmed in a sensitivity to account for possible delayed diagnosis during lockdowns.
At 45 months, children in the historical group had a cumulative wheezing risk of 16% compared with a risk of 13% for those in the lockdown group (P=0.002).
Additionally, children who were born during lockdown received less nebulised β2 agonists at a rate of 5.1 per 1 000 person-months, compared with 7.9 per 1 000 person-months in the historical control group (P<0.001). The same was true for nebulised glucocorticosteroids (19.5 vs 23.5 per 1 000 person-months, P<0.001).
Limitations of the study included its retrospective design, as well as an inability to assess possible RSV infection among participants.
Study details
Wheeze among children born during covid-19 lockdown
Elisa Barbieri, Anna Cantarutti, Riccardo Boracchini, Eugenio Baraldi, et al.
Published in JAMA Network Open on 9 July 2024
Introduction
During the Covid-19 lockdown, bronchiolitis nearly disappeared. Bronchiolitis, caused by respiratory syncytial virus (RSV) in 50% to 80% of cases, is a recognised risk factor for wheezing illnesses and asthma. We compared rates of wheezing and respiratory medication use in children born during the 2020 lockdown vs those born in prepandemic winter bronchiolitis seasons.
Methods
This cohort study included all children born between February and April in 2020 (lockdown cohort) and the same months in 2016 and 2017 (historical cohort) enrolled in Pedianet, a comprehensive database of 150 family paediatricians in Italy. Wheezing was identified by ICD-9-CM codes (519.11 and 786.07). Antiasthma medications were identified with Anatomical Therapeutic Chemical codes (R03A* and R03BA*).
We calculated cumulative wheezing incidence using the Kaplan-Meier estimator and assessed significant differences using a log-rank test. P < .05 was used to indicate significance. Person-months were summed until 30 months of age. We conducted mediation analyses to evaluate the association between exposure period (lockdown vs historical) and wheezing onset and whether bronchiolitis mediated this association. The percentage mediated and percentage eliminated were calculated. All models were adjusted for sex, geographic location, and area deprivation index (ADI; to account for socioeconomic status). A sensitivity analysis up to 45 months was conducted to account for potential delays in wheezing onset during lockdown. Statistical analyses were conducted in March 2023 and April 2024 using SAS, version 9.4 (SAS Institute). We followed the STROBE reporting guideline. The Internal Scientific Committee of Società Servizi Telematici Srl, the legal owner of Pedianet, approved the study and access to the database. According to Italian law, observational, retrospective, non-interventional studies do not require the approval by an ethics committee in Italy. Written informed consent was provided by participants’ legal guardians or next of kin.
Results
There were 2 192 births during the lockdown period and 3 889 in the historical period, with no differences in sex, ADI, gestational age, and presence of atopic disease in the family. During the 30-month follow-up, 206 children (9.4%) in the lockdown cohort experienced at least one wheezing episode, vs 582 (15.0%) in the historical cohort (P < .001). Wheezing episode rates were 67.6 (95% CI, 61.2-74.0) and 110.0 (95% CI, 103.8-117.8) per 10 000 person-months in the lockdown and historical cohorts, respectively. Bronchiolitis cases were nearly absent during lockdown (6.6 [95% CI, −0.9 to 14.0] vs 82.4 [95% CI, 62.7 to 102.2] episodes per 10 000 person-months in the lockdown and historical cohorts, respectively). Thirty-month cumulative wheezing incidence curves showed a significant difference between cohorts), confirmed at 45 months with a cumulative wheezing risk of 16% (95% CI, 15%-18%) in historical cohort and 13% (95% CI, 12%-15%) in the lockdown cohort (log-rank test, P = .002).
Wheezing risk dropped by 44% in children born during lockdown. Thirty percent of wheezing was eliminated by the lockdown preventive measures alone, assuming bronchiolitis had no additional positive association with wheezing risk (HR, 4.43; 95% CI, 3.50-5.60; P = .01). Children in the lockdown cohort received fewer nebulised β2 agonists (5.1 [95% CI, 4.6-5.7] vs 7.9 [95% CI, 7.4-8.5] per 1000 person-months; P < .001) and nebulised glucocorticosteroids (19.5 [95% CI, 18.4-20.5] vs 23.5 [95% CI, 22.6-24.4] per 1 000 person-months; P < .001) vs the historical cohort during follow-up.
Discussion
In this study, children born during the Covid-19 lockdown had fewer wheezing episodes and less use of respiratory medicines compared with the prepandemic cohort. Limitations include the study’s retrospective nature and the impossibility of assessing RSV infection. In line with a large birth cohort study demonstrating that not being infected with RSV during the first year of life is associated with a 26% lower risk of five-year current asthma, this study underscores the potential role of a universal RSV immunoprophylaxis in preventing postbronchiolitis wheezing.
JAMA Network Open article – Wheeze Among Children Born During COVID-19 Lockdown (Open access)
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