Published on 05.04.24 in Vol 10, No 1 (2024): Jan-Dec
Original Paper
Mutual Associations of Exposure to Ambient Air Pollutants in the First 1000 Days of Life With Asthma/Wheezing in Children: Prospective Cohort Study in Guangzhou, China
ABSTRACT
Background: The first 1000 days of life, encompassing pregnancy and the first 2 years after birth, represent a critical period for human health development. Despite this significance, there has been limited research into the associations between mixed exposure to air pollutants during this period and the development of asthma/wheezing in children. Furthermore, the finer sensitivity window of exposure during this crucial developmental phase remains unclear.
Objective: This study aims to assess the relationships between prenatal and postnatal exposures to various ambient air pollutants (particulate matter 2.5 [PM2.5], carbon monoxide [CO], sulfur dioxide [SO2], nitrogen dioxide [NO2], and ozone [O3]) and the incidence of childhood asthma/wheezing. In addition, we aimed to pinpoint the potential sensitivity window during which air pollution exerts its effects.
Methods: We conducted a prospective birth cohort study wherein pregnant women were recruited during early pregnancy and followed up along with their children. Information regarding maternal and child characteristics was collected through questionnaires during each round of investigation. Diagnosis of asthma/wheezing was obtained from children’s medical records. In addition, maternal and child exposures to air pollutants (PM2.5, CO, SO2, NO2, and O3) were evaluated using a spatiotemporal land use regression model. To estimate the mutual associations of exposure to mixed air pollutants with the risk of asthma/wheezing in children, we used the quantile g-computation model.
Results: In our study cohort of 3725 children, 392 (10.52%) were diagnosed with asthma/wheezing. After the follow-up period, the mean age of the children was 3.2 (SD 0.8) years, and a total of 14,982 person-years were successfully followed up for all study participants. We found that each quartile increase in exposure to mixed air pollutants (PM2.5, CO, SO2, NO2, and O3) during the second trimester of pregnancy was associated with an adjusted hazard ratio (HR) of 1.24 (95% CI 1.04-1.47). Notably, CO made the largest positive contribution (64.28%) to the mutual effect. After categorizing the exposure according to the embryonic respiratory development stages, we observed that each additional quartile of mixed exposure to air pollutants during the pseudoglandular and canalicular stages was associated with HRs of 1.24 (95% CI 1.03-1.51) and 1.23 (95% CI 1.01-1.51), respectively. Moreover, for the first year and first 2 years after birth, each quartile increment of exposure to mixed air pollutants was associated with HRs of 1.65 (95% CI 1.30-2.10) and 2.53 (95% CI 2.16-2.97), respectively. Notably, SO2 made the largest positive contribution in both phases, accounting for 50.30% and 74.70% of the association, respectively.
Conclusions: Exposure to elevated levels of mixed air pollutants during the first 1000 days of life appears to elevate the risk of childhood asthma/wheezing. Specifically, the second trimester, especially during the pseudoglandular and canalicular stages, and the initial 2 years after birth emerge as crucial susceptibility windows.
Trial Registration: Chinese Clinical Trial Registry ChiCTR-ROC-17013496; https://www.chictr.org.cn/showprojEN.html?proj=22475
JMIR Public Health Surveill 2024;10:e52456
doi:10.2196/52456
KEYWORDS
Introduction
Asthma is one of the major respiratory diseases. It is also the most common noncommunicable disease in children and imposes a huge economic and disease burden worldwide [
]. Asthma is estimated to affect around 14% of children worldwide, with its prevalence reported to be on the rise [ ]. It is well-known that childhood asthma increases the burden on society in terms of disruption to children’s lives, reduced physical ability, increased caregiver strain, and various direct medical costs. Wheezing during early childhood is frequently regarded as the primary symptom linked to asthma later in life [ ]. Research has shown that the intricate interplay of environmental exposures and genetic susceptibility can contribute to the onset of wheezing and asthma [ ].The first 1000 days of life, encompassing pregnancy and the initial 2 years after birth, represent a crucial period for human health development and interventions [
]. Lung and airway development commences between the 4th and 7th weeks of pregnancy, reaching the alveolar stage by 36 weeks. During pregnancy, fetal cells exhibit more rapid replication and differentiation compared with mature cells, making them highly responsive to external signals [ ]. Consequently, they are particularly susceptible to external exposure events. Air pollution, for instance, can disrupt alveolarization, leading to compromised lung development and function postnatally [ , ]. The lungs undergo growth from conception through early adulthood, with the prenatal and early postnatal phases being particularly critical [ ]. There is evidence suggesting that exposure to air pollution during early life can trigger the onset of asthma or wheezing and exacerbate preexisting conditions [ , , ]. A review, which has consolidated the link between exposure to air pollutants throughout the first 1000 days of life and the occurrence of asthma or wheezing in childhood, concluded that exposure to particulate matter (PMx) and nitrogen oxide (NOx) during pregnancy and the initial 2 years of life correlated with a heightened risk of developing asthma. Notably, the second trimester of pregnancy emerged as a particularly significant period [ ]. In addition, numerous studies have established connections between exposure to other pollutants such as ozone (O3), carbon monoxide (CO), and sulfur dioxide (SO2) during pregnancy or childhood and the onset of asthma in children [ , ]. For instance, Lin et al [ ] investigated the correlation between long-term exposure to ambient O3 and hospital admissions for asthma in children. They discovered a positive association between asthma admissions and increased levels of ambient O3 exposure. However, many of these studies solely explored the connection between individual pollutants and childhood asthma, without accounting for the combined impact of outdoor pollutants.Outdoor air pollution typically arises as a blend of various pollutants, yet many previous studies in both humans and animals have concentrated on the influence of individual pollutants on asthma or wheezing [
, ]. This narrow focus often obscures the comprehensive health implications of the pollutant mixture. Recognizing that air pollution comprises a combination of PM and gaseous pollutants, whose collective impact on health may diverge from that of individual pollutants, we characterized the collective influence of 5 pollutants (PM2.5, SO2, nitrogen dioxide [NO2], CO, and O3) on childhood asthma development as their mutual association. Guarnieri and Balmes [ ] have underscored the correlation between traffic-related air mixture pollutants (TRAPs) and asthma exacerbation, with a particular emphasis on the effects of TRAP as a mixture. Their review concluded that exposure to TRAP mixtures was not only accountable for triggering new asthma attacks but also for exacerbating existing asthma conditions. Research that examines multiple air pollutants collectively can contribute to a thorough and structured comprehension of the health hazards posed by air pollutants on asthma occurrence. Such studies offer a scientific foundation for potential public health interventions. With the ongoing global climate change, the composition of air pollutants is anticipated to become increasingly intricate. Consequently, estimating the combined impacts of air pollutants on asthma incidence is crucial for implementing early prevention measures against asthma and allergies in children.In this study, we undertook a prospective birth cohort investigation into the prenatal environment and offspring health in Guangzhou, China. Our objective was to assess the relationships between prenatal and postnatal exposures to various ambient air pollutants (PM2.5, CO, SO2, NO2, and O3) and the onset of childhood asthma or wheezing. Furthermore, we aimed to pinpoint the potential sensitivity window for the effects of air pollution.
Methods
Study Settings and Participants
All participant data were sourced from the Prenatal Environments and Offspring Health (PEOH) cohort study conducted at Panyu Central Hospital in Guangzhou, China. Detailed descriptions of this cohort study have been provided in previous publications [
, , ]. Further information regarding the population within the hospital’s catchment area, along with some basic demographic details concerning the broader populations of Guangzhou and China, can be found in . Pregnant women were enrolled in the study at the antenatal care unit, adhering to the following inclusion criteria: (1) gestational age <13 weeks; (2) between 18 and 50 years of age; and (3) absence of significant medical conditions, including hyperthyroidism, hypertension, chronic kidney disease, tuberculosis, and mental illness. All eligible women underwent face-to-face interviews to collect baseline information, and they were subsequently followed up during hospital delivery. Furthermore, we administered follow-up surveys on the children during their hospital visits. Throughout the follow-up period, we excluded cases involving multiple pregnancies and study participants with missing key variables. Recruitment for our study commenced in January 2016 and continued until July 31, 2020, when the follow-up concluded.Baseline Investigation
The baseline survey for the study was initiated in January 2016 and concluded in December 2017. A total of 4928 pregnant women were successfully recruited and their personal profiles were established. The collected information encompassed their demographic characteristics, lifestyle behaviors, changes in home address, living environment at home, work environment, activity patterns, medical history, diet during pregnancy, and antenatal care records.
Follow-Up Investigation
As illustrated in
, of the 4928 pregnant women enrolled in the baseline survey, 4279 were effectively followed up during their hospitalization for delivery. Throughout this period, maternal information was gathered via a follow-up questionnaire, while neonatal birth records were extracted from maternal medical records. Following the exclusion of cases involving multiple births (n=79) and those with missing key variables (n=10), a total of 4190 mother-child pairs were included in the follow-up. All children who attended child health clinics, pediatric outpatient clinics, or emergency departments were tracked for follow-up. Clinical symptoms, diagnostic disorders, and anthropometric data were extracted from their medical records, and questionnaires were administered to their parents or accompanying individuals. Throughout the follow-up process, a total of 465 infants were not successfully followed up. The final follow-up survey was concluded by July 31, 2020, with a total of 3725 children enrolled in the study ( ).