Critical windows of exposure to air pollution and gestational diabetes: assessing effect modification by maternal pre-existing conditions and environmental factors.

BACKGROUND: Ambient air pollution has been associated with gestational diabetes (GD), but critical windows of exposure and whether maternal pre-existing conditions and other environmental factors modify the associations remains inconclusive. METHODS: We conducted a retrospective cohort study of all singleton live birth that occurred between April 1st 2006 and March 31st 2018 in Ontario, Canada. Ambient air pollution data (i.e., fine particulate matter with a diameter ≤ 2.5 µm (PM2.5), nitrogen dioxide (NO2) and ozone (O3)) were assigned to the study population in spatial resolution of approximately 1 km × 1 km. The Normalized Difference Vegetation Index (NDVI) and the Green View Index (GVI) were also used to characterize residential exposure to green space as well as the Active Living Environments (ALE) index to represent the active living friendliness. Multivariable Cox proportional hazards regression models were used to evaluate the associations. RESULTS: Among 1,310,807 pregnant individuals, 68,860 incident cases of GD were identified. We found the strongest associations between PM2.5 and GD in gestational weeks 7 to 18 (HR = 1.07 per IQR (2.7 µg/m3); 95% CI: 1.02 - 1.11)). For O3, we found two sensitive windows of exposure, with increased risk in the preconception period (HR = 1.03 per IQR increase (7.0 ppb) (95% CI: 1.01 - 1.06)) as well as gestational weeks 9 to 28 (HR 1.08 per IQR (95% CI: 1.04 -1.12)). We found that women with asthma were more at risk of GD when exposed to increasing levels of O3 (p- value for effect modification = 0.04). Exposure to air pollutants explained 20.1%, 1.4% and 4.6% of the associations between GVI, NDVI and ALE, respectively. CONCLUSION: An increase of PM2.5 exposure in early pregnancy and of O3 exposure during late first trimester and over the second trimester of pregnancy were associated with gestational diabetes whereas exposure to green space may confer a protective effect.

Canadian Healthcare Access in Parkinson's Disease and COVID-19: A Cross-Sectional Survey.

BACKGROUND: Parkinson's disease (PD) is a common chronic neurodegenerative condition. As a result of the COVID-19 pandemic, healthcare provision faced challenges worldwide. We aimed to explore how the COVID-19 pandemic changed healthcare experiences for people living with Parkinson's disease (PwP) in Canada. METHODS: We conducted a national cross-sectional online survey about healthcare access for PwP in 2020. Participants (n = 298) were recruited through Parkinson Canada, the national patient association and its provincial partners, that advertised the study in a monthly newsletter. We used descriptive statistics and multivariate regression modelling to test associations of interest. A P < 0.05 was deemed statistically significant. RESULTS: During the COVID-19 pandemic, PwP reported greater difficulty obtaining PD-related healthcare services and lesser satisfaction with healthcare provision compared to pre-pandemic experiences. Dissatisfaction with care was associated with the presence of barriers to access services, a lack of confidence in accessing services remotely, pre-pandemic care dissatisfaction, and difficulty in obtaining care during the COVID-19 pandemic. Unmet care needs were associated with a lack of confidence in accessing services remotely, dissatisfaction with pre-pandemic care, difficulty obtaining pre-pandemic care, and communication challenges. CONCLUSION: Our results suggest that healthcare experiences for PwP significantly changed during the COVID-19 pandemic, with challenges in access to virtual care. Poorer pre-pandemic care experiences were amplified during the pandemic.

'It doesn't happen any other way': relationship-building and reflexivity for equity-focused intersectoral practice (EquIP).

Intersectoral processes that bring together public institutions, civil society organizations and affected community members are essential to tackling complex health equity challenges. While conventional wisdom points to the importance of human relationships in fostering collaboration, there is a lack of practical guidance on how to do intersectoral work in ways that support authentic relationship-building and mitigate power differentials among people with diverse experiences and roles. This article presents the results of RentSafe EquIP, a community-based participatory research initiative conducted in Owen Sound, Canada, in the midst of a housing crisis. The research explored the potential utility of equity-focused intersectoral practice (EquIP), a novel approach that invests in human relationships and knowledge co-creation among professionals and affected members of the community. The three-phase EquIP methodology centred the grounded expertise of community members with lived/living experience of housing inadequacy to catalyze reflexive thinking by people in professional roles about the institutional gaps and barriers that prevent effective intersectoral response to housing-related inequities. The research demonstrated that EquIP can support agency professionals and community members to (i) engage in (re)problematization to redefine the problem statement to better include upstream drivers of inequity, (ii) support reflexivity among those in professional roles to identify institutional practices, policies and norms that perpetuate stigma and impede effective intersectoral response and (iii) spark individual and collective agency and commitment towards a more equity-focused intersectoral system. We conclude that the EquIP methodology is a promising approach for communities seeking to address persistent health equity and social justice challenges.

Ambient air pollution and incidence of early-onset paediatric type 1 diabetes: A retrospective population-based cohort study.

BACKGROUND: Studies have reported increasing incidence rates of paediatric diabetes, especially among those aged 0-5 years. Epidemiological evidence linking ambient air pollution to paediatric diabetes remains mixed. OBJECTIVE: This study investigated the association between maternal and early-life exposures to common air pollutants (NO2, PM2.5, O3, and oxidant capacity [Ox; the redox-weighted average of O3 and NO2]) and the incidence of paediatric diabetes in children up to 6 years of age. METHODS: All registered singleton births in Ontario, Ca nada occurring between April 1st, 2006 and March 31st, 2012 were included through linkage from health administrative data. Monthly exposures to NO2, PM2.5, O3, and Ox were estimated across trimesters, the entire pregnancy period and during childhood. Random effects Cox proportional hazards models were used to assess the relationships with paediatric diabetes incidence while controlling for important covariates. We also modelled the shape of concentration-response (CR) relationships. RESULTS: There were 1094 children out of a cohort of 754,698 diagnosed with diabetes before the age of six. O3 exposures during the first trimester of pregnancy were associated with paediatric diabetes incidence (hazard ratio (HR) per interquartile (IQR) increase = 2.00, 95% CI: 1.04-3.86). The CR relationship between O3 during the first trimester and paediatric diabetes incidence appeared to have a risk threshold, in which there was little-to-no risk below 25 ppb of O3, while above this level risk increased sigmoidally. No other associations were observed. CONCLUSION: O3 exposures during a critical period of development were associated with an increased risk of paediatric diabetes incidence.

Spatiotemporal Variations in Ambient Ultrafine Particles and the Incidence of Childhood Asthma.

Rationale: Little is known regarding the impact of ambient ultrafine particles (UFPs; <0.1 µm) on childhood asthma development. Objectives: To examine the association between prenatal and early postnatal life exposure to UFPs and development of childhood asthma. Methods: A total of 160,641 singleton live births occurring in the City of Toronto, Canada between April 1, 2006, and March 31, 2012, were identified from a birth registry. Associations between exposure to ambient air pollutants and childhood asthma incidence (up to age 6) were estimated using random effects Cox proportional hazards models, adjusting for personal- and neighborhood-level covariates. We investigated both single-pollutant and multipollutant models accounting for coexposures to particulate matter ≤2.5 µm in aerodynamic diameter (PM2.5) and NO2. Measurements and Main Results: We identified 27,062 children with incident asthma diagnosis during the follow-up. In adjusted models, second-trimester exposure to UFPs (hazard ratio per interquartile range increase, 1.09; 95% confidence interval, 1.06-1.12) was associated with asthma incidence. In models additionally adjusted for PM2.5 and nitrogen dioxide, UFPs exposure during the second trimester of pregnancy remained positively associated with childhood asthma incidence (hazard ratio per interquartile range increase, 1.05; 95% confidence interval, 1.01-1.09). Conclusions: This is the first study to evaluate the association between perinatal exposure to UFPs and the incidence of childhood asthma. Exposure to UFPs during a critical period of lung development was linked to the onset of asthma in children, independent of PM2.5 and NO2.

Effect modification of perinatal exposure to air pollution and childhood asthma incidence.

Perinatal exposure to ambient air pollution has been associated with childhood asthma incidence, however, less is known regarding the potential effect modifiers in this association. We examined whether maternal and infant characteristics modified the association between perinatal exposure to air pollution and development of childhood asthma.761 172 births occurring between 2006 and 2012 were identified in the province of Ontario, Canada. Associations between exposure to ambient air pollutants and childhood asthma incidence (up to age 6) were estimated using Cox regression models.110,981 children with asthma were identified. In models adjusted for postnatal exposures, second trimester exposures to particulate matter with a diameter ≤2.5 µm (PM2.5) (Hazard Ratio (HR) per interquartile (IQR) increase=1.07, 95% CI: 1.06-1.09) and nitrogen dioxide (NO2) (HR per IQR increase=1.06, 95% CI: 1.03-1.08) were associated with childhood asthma development. Enhanced impacts were found among children born to mothers with asthma, those who smoked during pregnancy, boys, those born preterm, of low birth weight and among those born to mothers living in urban areas during pregnancy.Prenatal exposure to air pollution may have a differential impact on the risk of asthma development according to maternal and infant characteristics.

Maternal Exposure to Aeroallergens and the Risk of Early Delivery.

BACKGROUND: Daily changes in aeroallergens during pregnancy could trigger early labor, but few investigations have evaluated this issue. This study aimed to investigate the association between exposure to aeroallergens during the week preceding birth and the risk of early delivery among preterm and term pregnancies. METHODS: We identified data on 225,234 singleton births that occurred in six large cities in the province of Ontario, Canada, from 2004 to 2011 (April to October) from a birth registry. We obtained daily counts of pollen grains and fungal spores from fixed-site monitoring stations in each city and assigned them to pregnancy period of each birth. Associations between exposure to aeroallergens in the preceding week and risk of delivery among preterm (<37 gestational weeks), early-term (37-38 weeks), and full-term (≥39 weeks) pregnancies were evaluated with Cox regression models, adjusting for maternal characteristics, meteorologic parameters, and air pollution concentrations, and pooled across the six cities. RESULTS: The risk of delivery increased by 3% per interquartile range width (IQRw = 22.1 grains/m) increase in weed pollen the day before birth among early-term (hazard ratio [HR] = 1.03; 95% confidence interval [CI]: 1.01, 1.05) and full-term pregnancies (HR = 1.03; 95% CI: 1.01, 1.04). Exposure to fungal spores cumulated over 0 to 2 lagged days was associated with increased risk of delivery among full-term pregnancies only (HR = 1.07; 95% CI: 1.01, 1.12). We observed no associations among preterm deliveries. CONCLUSIONS: Increasing concentrations of ambient weed pollen and fungal spores may be associated with earlier delivery among term births.

Progression from Asthma to Chronic Obstructive Pulmonary Disease. Is Air Pollution a Risk Factor?

RATIONALE: Individuals with asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS), have more rapid decline in lung function, more frequent exacerbations, and poorer quality of life than those with asthma or COPD alone. Air pollution exposure is a known risk factor for asthma and COPD; however, its role in ACOS is not as well understood. OBJECTIVES: To determine if individuals with asthma exposed to higher levels of air pollution have an increased risk of ACOS. METHODS: Individuals who resided in Ontario, Canada, aged 18 years or older in 1996 with incident asthma between 1996 and 2009 who participated in the Canadian Community Health Survey were identified and followed until 2014 to determine the development of ACOS. Data on exposures to fine particulate matter (PM2.5) and ozone (O3) were obtained from fixed monitoring sites. Associations between air pollutants and ACOS were evaluated using Cox regression models. MEASUREMENTS AND MAIN RESULTS: Of the 6,040 adults with incident asthma who completed the Canadian Community Health Survey, 630 were identified as ACOS cases. Compared with those without ACOS, the ACOS population had later onset of asthma, higher proportion of mortality, and more frequent emergency department visits before COPD diagnosis. The adjusted hazard ratios of ACOS and cumulative exposures to PM2.5 (per 10 µg/m(3)) and O3 (per 10 ppb) were 2.78 (95% confidence interval, 1.62-4.78) and 1.31 (95% confidence interval, 0.71-2.39), respectively. CONCLUSIONS: Individuals exposed to higher levels of air pollution had nearly threefold greater odds of developing ACOS. Minimizing exposure to high levels of air pollution may decrease the risk of ACOS.

A spatial analysis of COPD prevalence, incidence, mortality and health service use in Ontario.

BACKGROUND: Risk factors for chronic obstructive pulmonary disease (COPD) include smoking, occupational exposure and air pollution, which vary geographically, but relatively little is known about how COPD varies spatially. DATA AND METHODS: This population-based ecological analysis examines physician-diagnosed COPD prevalence, incidence, mortality, and health care services use in Ontario over a 10-year period. Data were mapped and analyzed at the sub-Local Health Integration Network level (n = 141). Comparative morbidity figures were calculated and analyzed for local clusters of high and low rates of COPD health and health service use outcomes. RESULTS: A total of 722,494 individuals were identified as having COPD over the study period. Clusters of high rates in health outcomes and in most indicators of health service use emerged in northern parts of Ontario and in industrial and more rural agricultural areas. Clusters of low rates were centered on major urban and suburban areas. An exception was COPD-specific physician visits, which were lower in northern areas suggesting greater reliance on acute care. INTERPRETATION: This study highlights the need for research focused on explaining the spatial patterns identified here.

Patterns and determinants of health care utilization among people with Parkinson's disease: A population-based analysis in Ontario, Canada.

In Ontario, despite the increasing prevalence of Parkinson's disease (PD), barriers to access-to-care for people with Parkinson's disease (PwP) and their caregivers are not well understood. The objective of this study is to examine spatial patterns of health care utilization among PwP and identify factors associated with PD-related health care utilization of individuals in Ontario. We employed a retrospective, population-based study design involving administrative health data to identify PwP as of March 31, 2018 (N = 35,482) using a previously validated case definition. An enhanced 2-step floating catchment area method was used to measure spatial accessibility to PD care and a descriptive spatial analysis was conducted to describe health service utilization by geographic area and specialty type. Negative binomial regression models were then conducted to identify associated geographic, socioeconomic, comorbidity and demographic factors. There was marked spatial variability in PD-related service utilization, with neurology and all provider visits being significantly higher in urban areas (CMF>1.20; p<0.05) and family physician visits being significantly higher (CMF >1.20; p<0.05) in more rural areas and remote areas. More frequent visits to family physicians were associated with living in rural areas, while less frequent visitation was associated with living in areas of low spatial accessibility with high ethnic concentration. Visits to neurologists were positively associated with living in areas of high spatial accessibility and with high ethnic concentration. Visits to all providers were also positively associated with areas of high spatial accessibility. For all outcomes, less frequent visits were found in women, older people, and those living in more deprived areas as years living with PD increased. This study demonstrates the importance of geographic, socioeconomic and individual factors in determining PwP's likelihood of accessing care and type of care provided. Our results can be expected to inform the development of policies and patient care models aimed at improving accessibility among diverse populations of PwP.

Exploring COVID-19 from the perspectives of healthcare personnel in Malawi.

Background: The Coronavirus 2019 disease (COVID-19) brought many healthcare systems around the world to the point of collapse all the while putting the lives of healthcare workers at risk. This study forgoes an institutional look at healthcare to center individual healthcare personnel in Malawi to better understand (1) how the worldviews of healthcare workers impact their work in the context of COVID-19, (2) how COVID-19 impacted healthcare workers, and (3) the unique conditions faced by being a healthcare worker in a low-income nation. Methods: This research uses a hermeneutic phenomenological approach to qualitative methodology involving in-depth interviews (n = 15) with healthcare workers, traditional healers, and hospital leadership. The data collected were inductively coded and analyzed using the framework method, producing rich descriptions on how COVID-19 impacted the lifeworlds of healthcare workers in Malawi. Results: The findings reveal many of the struggles healthcare workers faced due to misaligned government policy and perceived proximity to COVID-19; outline their needs such as wanting better resources, funds, wages, and public health communication; and, exemplify the significant role that personal biases, worldviews, and sense of fear played in how healthcare workers perceived and interacted with COVID-19. Conclusion: Much of what was said echoes beyond borders, reflecting common global sentiments felt by healthcare personnel, and offers directions to explore building policies, strategies, and plans in preparation for any future disease outbreaks.

Impact of the COVID-19 pandemic on perceived access and quality of care in German people with parkinsonism.

Due to the heterogeneous clinical presentation, people with Parkinsonism (PwP) develop individual healthcare needs as their disease progresses. However, because of limited health resources during the COVID-19 pandemic, many patients were put at risk of inadequate care. All this occurred in the context of inequitable healthcare provision within societies, especially for such vulnerable populations. This study aimed to investigate factors influencing satisfaction and unmet need for healthcare among PwP during the COVID-19 pandemic in Germany. Analyses relied on an anonymous online survey with a 49-item questionnaire. We aimed at describing access to health services before and during the early stages of the pandemic. To this end, a generalized linear model was used to derive significant predictors and a stepwise regression to subsummarize the main factors of perceived inadequate care. In total, 551 questionnaires showed that satisfaction with Parkinsonism-related care decreased significantly during the pandemic (p < 0.001). In particular, factors such as lower educational level, lower perceived expertise of healthcare providers, less confidence in remote care, difficulties in obtaining healthcare, and restricted access to care before the pandemic but also lower densities of neurologists at residence and less ability to overcome barriers were indicative of higher odds to perceive unmet needs (p < 0.05). The results unveil obstacles contributing to reduced access to healthcare during the COVID-19 pandemic for PwP. These findings enable considerations for improved provision of healthcare services to PwP.

Fine particulate matter concentration and composition and the incidence of childhood asthma.

BACKGROUND: Several studies have found positive associations between outdoor fine particulate air pollution (≤2.5 µm, PM2.5) and childhood asthma incidence. However, the impact of PM2.5 composition on children's respiratory health remains uncertain. OBJECTIVE: We examined whether joint exposure to PM2.5 mass concentrations and its major chemical components was associated with childhood asthma development. METHODS: We conducted a population-based cohort study by identifying 1,130,855 singleton live births occurring between 2006 and 2014 in the province of Ontario, Canada. Concentrations of PM2.5 and its seven major chemical components were assigned to participants based on their postal codes using chemical transport models and remote sensing. The joint impact of outdoor PM2.5 concentrations and its major components and childhood asthma incidence (up to age 6) were estimated using Cox proportional hazards models, allowing for potential nonlinearity. RESULTS: We identified 167,080 children who developed asthma before age 6. In adjusted models, outdoor PM2.5 mass concentrations during childhood were associated with increased incidence of childhood asthma (Hazard Ratio (HR) for each 1 µg/m3 increase = 1.026, 95% CI: 1.021-1.031). We found that the joint effects of PM2.5 and its components on childhood asthma incidence may be 24% higher than the conventional approach. Specific components/source markers such as black carbon, ammonium, and nitrate appeared to play an important role. CONCLUSIONS: Early life exposure to PM2.5 and its chemical components is associated with an increased risk of asthma development in children. The heterogeneous nature of PM2.5 should be considered in future health risk assessments.

Evidence-based performance indicators of primary care for asthma: a modified RAND Appropriateness Method.

PURPOSE: To develop evidence-based performance indicators that measure the quality of primary care for asthma. DATA SOURCES: Cochrane Database of Systematic Reviews, MEDLINE, EMBASE and CINAHL for peer-reviewed articles published in 1998-2008 and five national/global asthma management guidelines. STUDY SELECTION: Articles with a focus on current asthma performance indicators recognized or used in community and primary care settings. Data extraction Modified RAND Appropriateness METHOD: was used. The work described herein was conducted in Canada in 2008. Five clinician experts conducted the systematic literature review. Asthma-specific performance indicators were developed and the strength of supporting evidence summarized. A survey was created and mailed to 17 expert panellists of various disciplines, asking them to rate each indicator using a 9-point Likert scale. Percentage distribution of the Likert scores were generated and given to the panellists before a face-to-face meeting, which was held to assess consensus. At the meeting, they ranked all indicators based on their reliability, validity, availability and feasibility. RESULTS: Literature search yielded 1228 articles, of which 135 were used to generate 45 performance indicators in five domains: access to care, clinical effectiveness, patient centeredness, system integration and coordination and patient safety. The top five ranked indicators were: Asthma Education from Certified Asthma Educator, Pulmonary Function Monitoring, Asthma Control Monitoring, Controller Medication Use and Asthma Control. CONCLUSION: The top 15 ranked indicators are recommended for implementation in primary care to measure asthma care delivery, respiratory health outcomes and establish benchmarks for optimal health service delivery over time and across populations.

The relationship between socio-economic and geographic factors and asthma among Canada's Aboriginal populations.

OBJECTIVES: To examine the prevalence, exacerbations and management of asthma among Canada's Aboriginal populations, and its relationship to socio-economic and geographic factors. STUDY DESIGN: Secondary analysis of a national cross-sectional questionnaire survey. METHODS: Data were collected in 2000 and 2001 through a survey of Aboriginal children and adults residing on- and off-reserve as part of the 2001 Aboriginal People's Survey (APS). The asthma related outcome variables - physician-diagnosed asthma, attack in past year and regular use of inhalants - were examined in relation to socio-economic and geographic factors such as income, education, housing and location of residence. Statistical analyses were based on weighted univariate and multivariate logistic regressions. RESULTS: The results show variations in asthma diagnosis, attacks and inhalant use across geographic location, socio-economic and demographic characteristics. Geographic location was found to be significantly associated with asthma for both adults and children, with those living in the northern territories, on-reserve or rural locations being the least likely to be diagnosed. Geographic location and Aboriginal identity were also found to be significantly associated with asthma medication use. CONCLUSIONS: While these findings may suggest a "healthier" population in more remote locations, they alternatively point to a general pattern of under-diagnosis, potentially due to poor health care access, as is typical in more remote locations.

Ambient ultrafine particle concentrations and incidence of childhood cancers.

BACKGROUND: Ambient air pollution has been associated with childhood cancer. However, little is known about the possible impact of ambient ultrafine particles (<0.1 µm) (UFPs) on childhood cancer incidence. OBJECTIVE: This study aimed to evaluate the association between prenatal and childhood exposure to UFPs and development of childhood cancer. METHODS: We conducted a population-based cohort study of within-city spatiotemporal variations in ambient UFPs across the City of Toronto, Canada using 653,702 singleton live births occurring between April 1, 1998 and March 31, 2017. Incident cases of 13 subtypes of paediatric cancers among children up to age 14 were ascertained using a cancer registry. Associations between ambient air pollutant concentrations and childhood cancer incidence were estimated using random-effects Cox proportional hazards models. We investigated both single- and multi-pollutant models accounting for co-exposures to PM2.5 and NO2. RESULTS: A total of 1,066 childhood cancers were identified. We found that first trimester exposure to UFPs (Hazard Ratio (HR) per 10,000/cm3 increase = 1.13, 95% CI: 1.03-1.22) was associated with overall cancer incidence diagnosed before 6 years of age after adjusting for PM2.5, NO2, and for personal and neighborhood-level covariates. Association between UFPs and overall cancer incidence exhibited a linear shape. No statistically significant associations were found for specific cancer subtypes. CONCLUSION: Ambient UFPs may represent a previously unrecognized risk factor in the aetiology of cancers in children. Our findings reinforce the importance of conducting further research on the effects of UFPs given their high prevalence of exposure in urban areas.

Spatial variations in ambient ultrafine particle concentrations and risk of congenital heart defects.

BACKGROUND: Cardiovascular malformations account for nearly one-third of all congenital anomalies, making these the most common type of birth defects. Little is known regarding the influence of ambient ultrafine particles (<0.1 µm) (UFPs) on their occurrence. OBJECTIVE: This population-based study examined the association between prenatal exposure to UFPs and congenital heart defects (CHDs). METHODS: A total of 158,743 singleton live births occurring in the City of Toronto, Canada between April 1st 2006 and March 31st 2012 were identified from a birth registry. Associations between exposure to ambient UFPs between the 2nd and 8th week post conception when the foetal heart begins to form and CHDs identified at birth were estimated using random-effects logistic regression models, adjusting for personal- and neighbourhood-level covariates. We also investigated multi-pollutant models accounting for co-exposures to PM2.5, NO2 and O3. RESULTS: A total of 1468 CHDs were identified. In fully adjusted models, UFP exposures during weeks 2 to 8 of pregnancy were not associated with overall CHDs (Odds Ratio (OR) per interquartile (IQR) increase = 1.02, 95% CI: 0.96-1.08). When investigating subtypes of CHDs, UFP exposures were associated with ventricular septal defects (Odds Ratio (OR) per interquartile (IQR) increase = 1.13, 95% CI: 1.03-1.33), but not with atrial septal defect (Odds Ratio (OR) per interquartile (IQR) increase = 0.89, 95% CI: 0.74-1.06). CONCLUSION: This is the first study to evaluate the association between prenatal exposure to UFPs and the risk of CHDs. UFP exposures during a critical period of embryogenesis were associated with an increased risk of ventricular septal defect.