PMCC PMCC

Search tips
Search criteria

Advanced
Results 1-25 (1104964)

Clipboard (0)
None

Related Articles

1.  Association between breast feeding and asthma in 6 year old children: findings of a prospective birth cohort study 
BMJ : British Medical Journal  1999;319(7213):815-819.
Objectives
To investigate the association between the duration of exclusive breast feeding and the development of asthma related outcomes in children at age 6 years.
Design
Prospective cohort study.
Setting
Western Australia.
Subjects
2187 children ascertained through antenatal clinics at the major tertiary obstetric hospital in Perth and followed to age 6 years.
Main outcome measures
Unconditional logistic regression to model the association between duration of exclusive breast feeding and outcomes related to asthma or atopy at 6 years of age, allowing for several important confounders: sex, gestational age, smoking in the household, and early childcare.
Results
After adjustment for confounders, the introduction of milk other than breast milk before 4 months of age was a significant risk factor for all asthma and atopy related outcomes in children aged 6 years: asthma diagnosed by a doctor (odds ratio 1.25, 95% confidence interval 1.02 to 1.52); wheeze three or more times since 1 year of age (1.41, 1.14 to 1.76); wheeze in the past year (1.31, 1.05 to 1.64); sleep disturbance due to wheeze within the past year (1.42, 1.07 to 1.89); age when doctor diagnosed asthma (hazard ratio 1.22, 1.03 to 1.43); age at first wheeze (1.36, 1.17 to 1.59); and positive skin prick test reaction to at least one common aeroallergen (1.30, 1.04 to 1.61).
Conclusion
A significant reduction in the risk of childhood asthma at age 6 years occurs if exclusive breast feeding is continued for at least the 4 months after birth. These findings are important for our understanding of the cause of childhood asthma and suggest that public health interventions to optimise breast feeding may help to reduce the community burden of childhood asthma and its associated traits.
Key messagesAsthma is the leading cause of admission to hospital in Australian children and its prevalence is increasingWhether breast feeding protects against asthma or atopy, or both, is controversialAsthma is a complex disease, and the relative risks between breast feeding and asthma or atopy are unlikely to be large; this suggests the need for investigation in a large prospective birth cohort with timely assessment of atopic outcomes and all relevant exposuresExclusive breast feeding for at least 4 months is associated with a significant reduction in the risk of asthma and atopy at age 6 years and with a significant delay in the age at onset of wheezing and asthma being diagnosed by a doctorPublic health interventions to promote an increased duration of exclusive breast feeding may help to reduce the morbidity and prevalence of childhood asthma and atopy
PMCID: PMC314207  PMID: 10496824
2.  Effects of BMI, Fat Mass, and Lean Mass on Asthma in Childhood: A Mendelian Randomization Study 
PLoS Medicine  2014;11(7):e1001669.
In this study, Granell and colleagues used Mendelian randomization to investigate causal effects of BMI, fat mass, and lean mass on current asthma at age 7½ years in the Avon Longitudinal Study of Parents and Children (ALSPAC) and found that higher BMI increases the risk of asthma in mid-childhood.
Please see later in the article for the Editors' Summary
Background
Observational studies have reported associations between body mass index (BMI) and asthma, but confounding and reverse causality remain plausible explanations. We aim to investigate evidence for a causal effect of BMI on asthma using a Mendelian randomization approach.
Methods and Findings
We used Mendelian randomization to investigate causal effects of BMI, fat mass, and lean mass on current asthma at age 7½ y in the Avon Longitudinal Study of Parents and Children (ALSPAC). A weighted allele score based on 32 independent BMI-related single nucleotide polymorphisms (SNPs) was derived from external data, and associations with BMI, fat mass, lean mass, and asthma were estimated. We derived instrumental variable (IV) estimates of causal risk ratios (RRs). 4,835 children had available data on BMI-associated SNPs, asthma, and BMI. The weighted allele score was strongly associated with BMI, fat mass, and lean mass (all p-values<0.001) and with childhood asthma (RR 2.56, 95% CI 1.38–4.76 per unit score, p = 0.003). The estimated causal RR for the effect of BMI on asthma was 1.55 (95% CI 1.16–2.07) per kg/m2, p = 0.003. This effect appeared stronger for non-atopic (1.90, 95% CI 1.19–3.03) than for atopic asthma (1.37, 95% CI 0.89–2.11) though there was little evidence of heterogeneity (p = 0.31). The estimated causal RRs for the effects of fat mass and lean mass on asthma were 1.41 (95% CI 1.11–1.79) per 0.5 kg and 2.25 (95% CI 1.23–4.11) per kg, respectively. The possibility of genetic pleiotropy could not be discounted completely; however, additional IV analyses using FTO variant rs1558902 and the other BMI-related SNPs separately provided similar causal effects with wider confidence intervals. Loss of follow-up was unlikely to bias the estimated effects.
Conclusions
Higher BMI increases the risk of asthma in mid-childhood. Higher BMI may have contributed to the increase in asthma risk toward the end of the 20th century.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
The global burden of asthma, a chronic (long-term) condition caused by inflammation of the airways (the tubes that carry air in and out of the lungs), has been rising steadily over the past few decades. It is estimated that, nowadays, 200–300 million adults and children worldwide are affected by asthma. Although asthma can develop at any age, it is often diagnosed in childhood—asthma is the most common chronic disease in children. In people with asthma, the airways can react very strongly to allergens such as animal fur or to irritants such as cigarette smoke, becoming narrower so that less air can enter the lungs. Exercise, cold air, and infections can also trigger asthma attacks, which can be fatal. The symptoms of asthma include wheezing, coughing, chest tightness, and shortness of breath. Asthma cannot be cured, but drugs can relieve its symptoms and prevent acute asthma attacks.
Why Was This Study Done?
We cannot halt the ongoing rise in global asthma rates without understanding the causes of asthma. Some experts think obesity may be one cause of asthma. Obesity, like asthma, is increasingly common, and observational studies (investigations that ask whether individuals exposed to a suspected risk factor for a condition develop that condition more often than unexposed individuals) in children have reported that body mass index (BMI, an indicator of body fat calculated by dividing a person's weight in kilograms by their height in meters squared) is positively associated with asthma. Observational studies cannot prove that obesity causes asthma because of “confounding.” Overweight children with asthma may share another unknown characteristic (confounder) that actually causes both obesity and asthma. Moreover, children with asthma may be less active than unaffected children, so they become overweight (reverse causality). Here, the researchers use “Mendelian randomization” to assess whether BMI has a causal effect on asthma. In Mendelian randomization, causality is inferred from associations between genetic variants that mimic the effect of a modifiable risk factor and the outcome of interest. Because gene variants are inherited randomly, they are not prone to confounding and are free from reverse causation. So, if a higher BMI leads to asthma, genetic variants associated with increased BMI should be associated with an increased risk of asthma.
What Did the Researchers Do and Find?
The researchers investigated causal effects of BMI, fat mass, and lean mass on current asthma at age 7½ years in 4,835 children enrolled in the Avon Longitudinal Study of Parents and Children (ALSPAC, a long-term health project that started in 1991). They calculated an allele score for each child based on 32 BMI-related genetic variants, and estimated associations between this score and BMI, fat mass and lean mass (both measured using a special type of X-ray scanner; in children BMI is not a good indicator of “fatness”), and asthma. They report that the allele score was strongly associated with BMI, fat mass, and lean mass, and with childhood asthma. The estimated causal relative risk (risk ratio) for the effect of BMI on asthma was 1.55 per kg/m2. That is, the relative risk of asthma increased by 55% for every extra unit of BMI. The estimated causal relative risks for the effects of fat mass and lean mass on asthma were 1.41 per 0.5 kg and 2.25 per kg, respectively.
What Do These Findings Mean?
These findings suggest that a higher BMI increases the risk of asthma in mid-childhood and that global increases in BMI toward the end of the 20th century may have contributed to the global increase in asthma that occurred at the same time. It is possible that the observed association between BMI and asthma reported in this study is underpinned by “genetic pleiotropy” (a potential limitation of all Mendelian randomization analyses). That is, some of the genetic variants included in the BMI allele score could conceivably also increase the risk of asthma. Nevertheless, these findings suggest that public health interventions designed to reduce obesity may also help to limit the global rise in asthma.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001669.
The US Centers for Disease Control and Prevention provides information on asthma and on all aspects of overweight and obesity (in English and Spanish)
The World Health Organization provides information on asthma and on obesity (in several languages)
The UK National Health Service Choices website provides information about asthma, about asthma in children, and about obesity (including real stories)
The Global Asthma Report 2011 is available
The Global Initiative for Asthma released its updated Global Strategy for Asthma Management and Prevention on World Asthma Day 2014
Information about the Avon Longitudinal Study of Parents and Children is available
MedlinePlus provides links to further information on obesity in children, on asthma, and on asthma in children (in English and Spanish
Wikipedia has a page on Mendelian randomization (note: Wikipedia is a free online encyclopedia that anyone can edit; available in several languages)
doi:10.1371/journal.pmed.1001669
PMCID: PMC4077660  PMID: 24983943
3.  Association of Adenotonsillectomy with Asthma Outcomes in Children: A Longitudinal Database Analysis 
PLoS Medicine  2014;11(11):e1001753.
Rakesh Bhattacharjee and colleagues use data from a US private health insurance database to compare asthma severity measures in children one year before and one year after they underwent adenotonsillectomy with asthma measures in those who did not undergo adenotonsillectomy.
Please see later in the article for the Editors' Summary
Background
Childhood asthma and obstructive sleep apnea (OSA), both disorders of airway inflammation, were associated in recent observational studies. Although childhood OSA is effectively treated by adenotonsillectomy (AT), it remains unclear whether AT also improves childhood asthma. We hypothesized that AT, the first line of therapy for childhood OSA, would be associated with improved asthma outcomes and would reduce the usage of asthma therapies in children.
Methods and Findings
Using the 2003–2010 MarketScan database, we identified 13,506 children with asthma in the United States who underwent AT. Asthma outcomes during 1 y preceding AT were compared to those during 1 y following AT. In addition, 27,012 age-, sex-, and geographically matched children with asthma without AT were included to examine asthma outcomes among children without known adenotonsillar tissue morbidity. Primary outcomes included the occurrence of a diagnostic code for acute asthma exacerbation (AAE) or acute status asthmaticus (ASA). Secondary outcomes included temporal changes in asthma medication prescriptions, the frequency of asthma-related emergency room visits (ARERs), and asthma-related hospitalizations (ARHs). Comparing the year following AT to the year prior, AT was associated with significant reductions in AAE (30.2%; 95% CI: 25.6%–34.3%; p<0.0001), ASA (37.9%; 95% CI: 29.2%–45.6%; p<0.0001), ARERs (25.6%; 95% CI: 16.9%–33.3%; p<0.0001), and ARHs (35.8%; 95% CI: 19.6%–48.7%; p = 0.02). Moreover, AT was associated with significant reductions in most asthma prescription refills, including bronchodilators (16.7%; 95% CI: 16.1%–17.3%; p<0.001), inhaled corticosteroids (21.5%; 95% CI: 20.7%–22.3%; p<0.001), leukotriene receptor antagonists (13.4%; 95% CI: 12.9%–14.0%; p<0.001), and systemic corticosteroids (23.7%; 95% CI: 20.9%–26.5%; p<0.001). In contrast, there were no significant reductions in these outcomes in children with asthma who did not undergo AT over an overlapping follow-up period. Limitations of the MarketScan database include lack of information on race and obesity status. Also, the MarketScan database does not include information on children with public health insurance (i.e., Medicaid) or uninsured children.
Conclusions
In a very large sample of privately insured children, AT was associated with significant improvements in several asthma outcomes. Contingent on validation through prospectively designed clinical trials, this study supports the premise that detection and treatment of adenotonsillar tissue morbidity may serve as an important strategy for improving asthma control.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
The global burden of asthma has been rising steadily over the past few decades. Nowadays, about 200–300 million adults and children worldwide are affected by asthma, a chronic condition caused by inflammation of the airways (the tubes that carry air in and out of the lungs). Although asthma can develop at any age, it is often diagnosed in childhood—asthma is one of the commonest chronic diseases in children. In the US, for example, asthma affects around 7.1 million children under the age of 18 years and is the third leading cause of hospitalization of children under the age of 15 years. In people with asthma, the airways can react very strongly to allergens such as animal fur or to irritants such as cigarette smoke. Exercise, cold air, and infections can trigger asthma attacks, which can be fatal. The symptoms of asthma include wheezing, coughing, chest tightness, and shortness of breath. Asthma cannot be cured, but drugs can relieve its symptoms and prevent acute asthma attacks.
Why Was This Study Done?
Recent studies have found an association between severe childhood asthma and obstructive sleep apnea (OSA). In OSA, airway inflammation promotes hypertrophy (excess growth) of the adenoids and the tonsils, immune system tissues in the upper airway. During sleep, the presence of hypertrophic adenotonsillar tissues predisposes the walls of the throat to collapse, which results in apnea—a brief interruption in breathing. People with OSA often snore loudly and frequently wake from deep sleep as they struggle to breathe. Childhood OSA, which affects 2%–3% of children, can be effectively treated by removal of the adenoids and tonsils (adenotonsillectomy). Given the association between childhood OSA and severe asthma and given the involvement of airway inflammation in both conditions, might adenotonsillectomy also improve childhood asthma? Here, the researchers analyze data from the MarketScan database, a large database of US patients with private health insurance, to investigate whether adenotonsillectomy is associated with improvements in asthma outcomes and with reductions in the use of asthma therapies in children.
What Did the Researchers Do and Find?
The researchers used the database to identify 13,506 children with asthma who had undergone adenotonsillectomy and to obtain information about asthma outcomes among these children for the year before and the year after the operation. Because asthma severity tends to decrease with age, the researchers also used the database to identify 27,012 age-, sex-, and geographically matched children with asthma who did not have the operation so that they could examine asthma outcomes over an equivalent two-year period in the absence of complications related to adenotonsillar hypertrophy. Comparing the year after adenotonsillectomy with the year before the operation, adenotonsillectomy was associated with a 30% reduction in acute asthma exacerbations, a 37.9% reduction in acute status asthmaticus (an asthma attack that is unresponsive to the drugs usually used to treat attacks), a 25.6% reduction in asthma-related emergency room visits, and a 35.8% reduction in asthma-related hospitalizations. By contrast, among the control children, there was only a 2% reduction in acute asthma exacerbations and only a 7% reduction in acute status asthmaticus over an equivalent two-year period. Adenotonsillectomy was also associated with significant reductions (changes unlikely to have occurred by chance) in prescription refills for most types of drugs used to treat asthma, whereas there were no significant reductions in prescription refills among children with asthma who had not undergone adenotonsillectomy. The study was limited by the lack of measures of race and obesity, which are both associated with severity of asthma.
What Do These Findings Mean?
These findings show that in a large sample of privately insured children in the US, adenotonsillectomy was associated with significant improvements in several asthma outcomes. These results do not show, however, that adenotonsillectomy caused a reduction in the severity of childhood asthma. It could be that the children who underwent adenotonsillectomy (but not those who did not have the operation) shared another unknown factor that led to improvements in their asthma over time. To prove a causal link, it will be necessary to undertake a randomized controlled trial in which the outcomes of groups of children with asthma who are chosen at random to undergo or not undergo adenotonsillectomy are compared. However, with the proviso that there are some risks associated with adenotonsillectomy, these findings suggest that the detection and treatment of adenotonsillar hypertrophy may help to improve asthma control in children.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001753.
The US Centers for Disease Control and Prevention provides information on asthma, including videos, games, and links to other resources for children with asthma
The American Lung Association provides detailed information about asthma and a fact sheet on asthma in children; it also has information about obstructive sleep apnea
The National Sleep Foundation provides information on snoring and obstructive sleep apnea in children
The UK National Health Service Choices website provides information (including some personal stories) about asthma, about asthma in children, and about obstructive sleep apnea
The “Global Asthma Report 2014” will be available in October 2014
MedlinePlus provides links to further information on asthma, on asthma in children, on sleep apnea, and on tonsils and adenoids (in English and Spanish)
doi:10.1371/journal.pmed.1001753
PMCID: PMC4219664  PMID: 25369282
4.  Major Radiodiagnostic Imaging in Pregnancy and the Risk of Childhood Malignancy: A Population-Based Cohort Study in Ontario 
PLoS Medicine  2010;7(9):e1000337.
In a record-linkage study, Joel Ray and colleagues examine the association between diagnostic imaging during pregnancy and later childhood cancers.
Background
The association between fetal exposure to major radiodiagnostic testing in pregnancy—computed tomography (CT) and radionuclide imaging—and the risk of childhood cancer is not established.
Methods and Findings
We completed a population-based study of 1.8 million maternal-child pairs in the province of Ontario, from 1991 to 2008. We used Ontario's universal health care–linked administrative databases to identify all term obstetrical deliveries and newborn records, inpatient and outpatient major radiodiagnostic services, as well as all children with a malignancy after birth. There were 5,590 mothers exposed to major radiodiagnostic testing in pregnancy (3.0 per 1,000) and 1,829,927 mothers not exposed. The rate of radiodiagnostic testing increased from 1.1 to 6.3 per 1,000 pregnancies over the study period; about 73% of tests were CT scans. After a median duration of follow-up of 8.9 years, four childhood cancers arose in the exposed group (1.13 per 10,000 person-years) and 2,539 cancers in the unexposed group (1.56 per 10,000 person-years), a crude hazard ratio of 0.69 (95% confidence interval 0.26–1.82). After adjusting for maternal age, income quintile, urban status, and maternal cancer, as well as infant sex, chromosomal or congenital anomalies, and major radiodiagnostic test exposure after birth, the risk was essentially unchanged (hazard ratio 0.68, 95% confidence interval 0.25–1.80).
Conclusions
Although major radiodiagnostic testing is now performed in about 1 in 160 pregnancies in Ontario, the absolute annual risk of childhood malignancy following exposure in utero remains about 1 in 10,000. Since the upper confidence limit of the relative risk of malignancy may be as high as 1.8 times that of an unexposed pregnancy, we cannot exclude the possibility that fetal exposure to CT or radionuclide imaging is carcinogenic.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
In industrialized countries, childhood cancer (any form of cancer in a child aged 14 years or under) remains a major cause of death. With the exception of a few known risk factors, such as acquired genetic predisposition to cancer, which accounts for about 10% of all childhood cancers, the etiology of most childhood cancer remains unknown. There is thought to be an association between exposure to ionizing radiation in pregnancy and the subsequent risk of development of cancer in the exposed mother's child, but the evidence base to support this association is conflicting. For example, studies examining maternal exposure to plain radiographs in pregnancy and subsequent childhood cancer are inconsistent. Furthermore, although their use has dramatically increased over the past two decades, little is known about the cancer risk related to certain types of radiodiagnostic tests, such as CT and radionuclide imaging, both of which expose the fetus to considerably higher doses of radiation than plain radiographs administered at the same anatomical level.
Why Was This Study Done?
Many women could be exposed to major radiodiagnostic tests, such as those used in emergency situations, before they are aware that they are pregnant, as almost 50% of pregnancies are unplanned. This situation means that it is important to determine the subsequent cancer risk to any child exposed to maternal radiodiagnostic tests before birth.
What Did the Researchers Do and Find?
The researchers conducted a retrospective population-based cohort study of women who delivered a live infant in Ontario, Canada between April 1, 1992 and March 31, 2008. The basis of the research was an anonymized database for the whole province of Ontario, where universal health care, including prenatal care and radiodiagnostic testing, is available to all residents. Database characteristics allowed the researchers to link maternal radiation exposure (a major radiodiagnostic test performed on the mother up to one day before her delivery date) in a specific (index) pregnancy to a subsequent malignancy in the child. After birth, maternal-infant pairs were only followed up if the infant was delivered at term, weighed 2,500 g or more, and survived for at least 30 days.
The researchers were able to follow up 1,835,517 maternal-child pairs. The overall rate of exposure to major radiodiagnostic testing in pregnancy was 3.0 per 1,000 and occurred at an estimated mean gestational age of 15.7 weeks. A total of four childhood cancers occurred in the exposed group and 2,539 cancers in the unexposed group corresponding to a crude hazard ratio of 0.69, which did not significantly change after adjustments were made for potential confounding factors, such as maternal age, sex, and the presence of any chromosomal or congenital anomalies in the infant. The overall prevalence of childhood cancer following exposure to CT or radionuclide imaging in pregnancy is under 0.07%, giving an incidence rate of 1.13 per 10,000 person-years.
What Do These Findings Mean?
These findings can help inform clinicians and mothers about the risk of childhood malignancy following major radiodiagnostic testing in pregnancy. The absolute risk appears to be low, while the relative risk is not materially higher than that of unexposed controls. However, as the upper confidence limit of the relative risk of malignancy may be a maximum of 1.8 times that of an unexposed pregnancy, the possibility that fetal exposure to CT or radionuclide imaging is carcinogenic cannot be excluded. Because this finding means that a very slight risk may exist, beta hCG testing should continue to be done in all potentially pregnant women before undergoing major radiodiagnostic testing, and lead apron shielding used in all women of reproductive age, whether or not known to be pregnant. In addition, nonradiation-emitting imaging, such as MRI and ultrasonography, should be considered first, when clinically appropriate. However, some pregnant women will still be faced with the decision to undergo CT or nuclear imaging because the test is clinically warranted. The findings of this study suggest that when clinically indicated, major radiodiagnostic testing in pregnancy should be performed, along with brief counseling to help lessen the anxiety experienced by an expectant mother before and after the birth of her child.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000337.
For information for patients and caregivers on radiodiagnostic testing, see The Royal College of Radiologists
The National Cancer Institute provides information about childhood cancer
CureSearch for Children's Cancer provides additional information about research into childhood cancer
doi:10.1371/journal.pmed.1000337
PMCID: PMC2935460  PMID: 20838660
5.  Psychological Stress and Hospitalization for Childhood Asthma-a Nationwide Cohort Study in Two Nordic Countries 
PLoS ONE  2013;8(10):e78816.
Objective
Exposures to psychological stress in early life may contribute to the development or exacerbation of asthma. We undertook a cohort study based on data from several population-based registers in Denmark and Sweden to examine whether bereavement in childhood led to increased asthma hospitalization.
Methods
All singleton children born in Denmark during 1977-2008 and in Sweden during 1973-2006 were included in the study (N=5,202,576). The children were followed from birth to the date of first asthma hospitalization, emigration, death, their 18th birthday, or the end of study (31 December 2007 in Sweden and 31 December 2008 in Denmark), whichever came first. All the children were assigned to the non-bereaved group until they lost a close relative (mother, father or a sibling), from when they were included in the bereaved group. We evaluated the hazard ratio (HR) of first hospitalization for asthma in bereaved children using Cox proportional hazards regression models, compared to those who were in the non-bereaved group. We also did a sub-analysis on the association between bereavement and first asthma medication.
Results
A total of 147,829 children were hospitalized for asthma. The overall adjusted HR of asthma hospitalization in bereaved children was 1.10 (95% confidence interval (CI): 1.04-1.16), compared to non-bereaved children. The risk of asthma hospitalization was increased in those who lost a close relative at age of 14-17 years (HR=1.54, 95% CI: 1.23-1.92), but not in younger age groups. The association between bereavement and asthma hospitalization did not change over time since bereavement. In the sub-analysis in singleton live births during 1996-2008 recorded in the DMBR, bereavement was associated with a lower use of asthma medication (HR=0.87, 95% CI: 0.80-0.95).
Conclusions
Our data suggests that psychological stress following bereavement in late adolescence is associated with an increased risk of asthma hospitalization or lowers the threshold for asthma hospitalization.
doi:10.1371/journal.pone.0078816
PMCID: PMC3808299  PMID: 24205324
6.  Antibiotics in fetal and early life and subsequent childhood asthma: nationwide population based study with sibling analysis 
Objective To investigate the association between exposure to antibiotics in fetal and early life and asthma in childhood, with adjustment for confounding factors.
Design Nationwide prospective population based cohort study, including sibling control design.
Setting Swedish population identified from national demographic and health registers.
Participants 493 785 children born 2006-10; 180 894 of these were eligible for sibling analyses.
Main outcome measure Asthma defined as having both an asthma diagnosis and dispensed asthma drugs. The association between antibiotic exposure and asthma was investigated in the whole cohort with Cox proportional hazard regression. A stratified proportional hazards model conditional on sibling group was used to adjust for shared factors within families. Confounding by respiratory infections was assessed by investigating whether specific groups of antibiotics were associated with asthma.
Results Antibiotic exposure in fetal life was associated with an increased risk of asthma in cohort analyses (hazard ratio 1.28, 95% confidence interval 1.25 to 1.32), but not in sibling analyses (0.99, 0.92 to 1.07). In cohort analyses, antibiotics used to treat respiratory infections in childhood were associated with a more pronounced increased risk of asthma (4.12, 3.78 to 4.50) than antibiotics used for urinary tract and skin infections (1.54, 1.24 to 1.92). In sibling analyses, the excess risks after exposure to antibiotics for respiratory infections decreased (2.36, 1.78 to 3.13) and disappeared for antibiotics for urinary tract and skin (0.85, 0.47 to 1.55).
Conclusions Previous positive associations between exposure to antibiotics in fetal and early life and subsequent childhood asthma could have been caused by confounding by shared familial factors, in addition to confounding by respiratory infections.
doi:10.1136/bmj.g6979
PMCID: PMC4247260  PMID: 25432937
7.  Maternal Bereavement and Childhood Asthma—Analyses in Two Large Samples of Swedish Children 
PLoS ONE  2011;6(11):e27202.
Background
Prenatal factors such as prenatal psychological stress might influence the development of childhood asthma.
Methodology and Principal Findings
We assessed the association between maternal bereavement shortly before and during pregnancy, as a proxy for prenatal stress, and the risk of childhood asthma in the offspring, based on two samples of children 1–4 (n = 426 334) and 7–12 (n = 493 813) years assembled from the Swedish Medical Birth Register. Exposure was maternal bereavement of a close relative from one year before pregnancy to child birth. Asthma event was defined by a hospital contact for asthma or at least two dispenses of inhaled corticosteroids or montelukast. In the younger sample we calculated hazards ratios (HRs) of a first-ever asthma event using Cox models and in the older sample odds ratio (ORs) of an asthma attack during 12 months using logistic regression. Compared to unexposed boys, exposed boys seemed to have a weakly higher risk of first-ever asthma event at 1–4 years (HR: 1.09; 95% confidence interval [CI]: 0.98, 1.22) as well as an asthma attack during 12 months at 7–12 years (OR: 1.10; 95% CI: 0.96, 1.24). No association was suggested for girls. Boys exposed during the second trimester had a significantly higher risk of asthma event at 1–4 years (HR: 1.55; 95% CI: 1.19, 2.02) and asthma attack at 7–12 years if the bereavement was an older child (OR: 1.58; 95% CI: 1.11, 2.25). The associations tended to be stronger if the bereavement was due to a traumatic death compared to natural death, but the difference was not statistically significant.
Conclusions/Significance
Our results showed some evidence for a positive association between prenatal stress and childhood asthma among boys but not girls.
doi:10.1371/journal.pone.0027202
PMCID: PMC3210147  PMID: 22087265
8.  Rethinking race/ethnicity, income, and childhood asthma: racial/ethnic disparities concentrated among the very poor. 
Public Health Reports  2005;120(2):109-116.
OBJECTIVE: Past studies of the prevalence of childhood asthma have yielded conflicting findings as to whether racial/ethnic disparities remain after other factors, such as income, are taken into account. The objective of this study was to examine the association of race/ethnicity and family income with the prevalence of childhood asthma and to assess whether racial/ethnic disparities vary by income strata. METHODS: Cross-sectional data on 14,244 children aged <18 years old in the 1997 National Health Interview Survey were examined. The authors used logistic regression to analyze the independent and joint effects of race/ethnicity and income-to-federal poverty level (FPL) ratio, adjusting for demographic covariates. The main outcome measure was parental report of the child having ever been diagnosed with asthma. RESULTS: Bivariate analyses, based on weighted percentages, revealed that asthma was more prevalent among non-Hispanic black children (13.6%) than among non-Hispanic white children (11.2%; p<0.01), but the prevalence of asthma did not differ significantly between Hispanic children (10.1%) and non-Hispanic white children (11.2%; p=0.13). Overall, non-Hispanic black children were at higher risk for asthma than non-Hispanic white children (adjusted odds ratio [OR]=1.20; 95% confidence interval [CI] 1.03, 1.40), after adjustment for sociodemographic variables, including the ratio of annual family income to the FPL. Asthma prevalence did not differ between Hispanic children and non-Hispanic white children in adjusted analyses (adjusted OR=0.85; 95% CI 0.71, 1.02). Analyses stratified by income revealed that only among children from families with incomes less than half the FPL did non-Hispanic black children have a higher risk of asthma than non-Hispanic white children (adjusted OR=1.99; 95% CI 1.09, 3.64). No black vs. white differences existed at other income levels. Subsequent analyses of these very poor children that took into account additional potentially explanatory variables did not attenuate the higher asthma risk for very poor non-Hispanic black children relative to very poor non-Hispanic white children. CONCLUSIONS: Non-Hispanic black children were at substantially higher risk of asthma than non-Hispanic white children only among the very poor. The concentration of racial/ethnic differences only among the very poor suggests that patterns of social and environmental exposures must overshadow any hypothetical genetic risk.
PMCID: PMC1497701  PMID: 15842111
9.  Pregnancy exposures and risk of childhood asthma admission in a population birth cohort 
Pediatric Allergy and Immunology  2011;22(8):836-842.
Background
There is increasing interest in the potential for in utero exposures to affect the risk of asthma. We used population data to explore the associations between perinatal conditions and the risk of hospital admission with asthma between the 2nd and 5th birthday.
Methods
The study population was 240,511 singleton infants born during 2001–2003. Birth records and longitudinally linked hospital admissions were used to identify asthma admissions and to model potential risk factors.
Results
A total of 7245 children (3.0%) had one or more childhood admissions with asthma. In utero infectious exposures associated with childhood asthma were maternal antenatal admission with a urinary tract infection (UTI) [adjusted odds ratio (aOR) = 1.49, 95% confidence interval (1.23–1.79)] and pre-term pre-labor rupture of membranes (PROM) [aOR = 1.23 (1.04–1.45)]. There was no evidence that gestational age at time of first antenatal UTI admission (<28, ≥28 wks) affected the risk of asthma (homogeneity test p = 0.6). Pre-term birth was a risk factor for asthma admission, with the risk decreasing by 5.3% with each extra week of gestation. Autumn and winter conceptions were associated with an increased risk of childhood asthma admission: winter aOR = 1.15 (1.08–1.23), autumn aOR = 1.09 (1.02–1.16).
Conclusions
As in utero exposure to both UTI and PROM carry an increased risk of childhood asthma admission, this suggests that the immune system response generally is the relevant factor rather than a specific organism. The season-associated risk is consistent with early pregnancy exposures such as the winter flu season or low vitamin D.
doi:10.1111/j.1399-3038.2011.01206.x
PMCID: PMC3263424  PMID: 21929593
asthma; children; population; pregnancy; risk factors
10.  Gene-Environment Interaction in the Onset of Eczema in Infancy: Filaggrin Loss-of-Function Mutations Enhanced by Neonatal Cat Exposure  
PLoS Medicine  2008;5(6):e131.
Background
Loss-of-function variants in the gene encoding filaggrin (FLG) are major determinants of eczema. We hypothesized that weakening of the physical barrier in FLG-deficient individuals may potentiate the effect of environmental exposures. Therefore, we investigated whether there is an interaction between FLG loss-of-function mutations with environmental exposures (pets and dust mites) in relation to the development of eczema.
Methods and Findings
We used data obtained in early life in a high-risk birth cohort in Denmark and replicated the findings in an unselected birth cohort in the United Kingdom. Primary outcome was age of onset of eczema; environmental exposures included pet ownership and mite and pet allergen levels. In Copenhagen (n = 379), FLG mutation increased the risk of eczema during the first year of life (hazard ratio [HR] 2.26, 95% confidence interval [CI] 1.27–4.00, p = 0.005), with a further increase in risk related to cat exposure at birth amongst children with FLG mutation (HR 11.11, 95% CI 3.79–32.60, p < 0.0001); dog exposure was moderately protective (HR 0.49, 95% CI 0.24–1.01, p = 0.05), but not related to FLG genotype. In Manchester (n = 503) an independent and significant association of the development of eczema by age 12 mo with FLG genotype was confirmed (HR 1.95, 95% CI 1.13–3.36, p = 0.02). In addition, the risk increased because of the interaction of cat ownership at birth and FLG genotype (HR 3.82, 95% CI 1.35–10.81, p = 0.01), with no significant effect of the interaction with dog ownership (HR 0.59, 95% CI 0.16–2.20, p = 0.43). Mite-allergen had no effects in either cohort. The observed effects were independent of sensitisation.
Conclusions
We have demonstrated a significant interaction between FLG loss-of-function main mutations (501x and 2282del4) and cat ownership at birth on the development of early-life eczema in two independent birth cohorts. Our data suggest that cat but not dog ownership substantially increases the risk of eczema within the first year of life in children with FLG loss-of-function variants, but not amongst those without. FLG-deficient individuals may need to avoid cats but not dogs in early life.
In two independent cohorts of children, Hans Bisgaard and colleagues show an association between mutations in the filaggrin gene (FLG) and ownership of cats, but not dogs, with development of eczema.
Editors' Summary
Background.
Eczema is a skin condition characterized by dry, red, and itchy patches on the skin. Eczema is associated with asthma and allergy, though allergy rarely plays a role in development or severity of eczema. Eczema usually begins during infancy, typically on the face, scalp, neck, extensor sides of the forearms, and legs. Up to one in five infants develops eczema, but in more than half of them, the condition improves or disappears completely before they are 15 years old. If eczema persists into adulthood, it usually affects the face and the skin inside the knees and elbows. There is no cure for eczema but it can be controlled by avoiding anything that makes its symptoms worse. These triggers include irritants such as wool, strong soaps, perfumes, and dry environments. A good skin-care routine and frequent moisturizing can also help to keep eczema under control, but in many cases, corticosteroid creams and ointments may be necessary to reduce inflammation.
Why Was This Study Done?
Eczema tends to run in families. This suggests that eczema is caused by genetic factors as well as by environmental factors. Recently, researchers discovered that two common “loss-of-function” variants in the gene encoding filaggrin (FLG) predispose people to eczema. People who inherit one or two defective genes make no filaggrin, a protein that normally forms a physical barrier in the skin that protects the body from potentially harmful substances in the environment. Might the weakening of this barrier in filaggrin-deficient individuals affect their responses to environmental substances to which the skin is exposed? In this study, the researchers test this potential explanation for how genetic and environmental factors (in particular, exposure to pets) might interact to determine an individual's chances of developing eczema.
What Did the Researchers Do and Find?
To test their hypothesis, the researchers studied two independent groups of infants during their first year of life—a high-risk group consisting of infants born in Copenhagen, Denmark to mothers with asthma and a group of infants born to women from the general population in Manchester, United Kingdom. The researchers determined which FLG variants each child had inherited and classified those with either one or two defective copies of FLG as having an FLG mutation. They determined pet exposure in early life by asking whether a dog or a cat was living in the parental home when the child was born (“pet ownership”) and then analyzed how these genetic and environmental factors affected the age of onset of eczema. In both groups, children with FLG mutations were twice as likely to develop eczema during the first year of life as children without FLG mutations. For children without FLG mutations, cat ownership at birth had no effect on eczema risk but for children with FLG mutations, cat ownership at birth (but not dog ownership) further increased the risk of developing eczema.
What Do These Findings Mean?
These findings show that FLG mutations and cat ownership at birth interact to determine the chances of a child developing eczema during the first year of life. They provide support, therefore, for the researchers' suggestion that the weakening of the skin's protective barrier that is caused by filaggrin deficiency increases the child's susceptibility to factors associated with cat exposure. Only a small number of children in this study carried FLG mutations and were exposed to cats from birth, so these findings need confirming in independent studies. In addition, it is still not clear how exposure to cats drives the development of eczema. Allergy was not the mechanism as the FLG-deficient children exposed to cat and who developed eczema did not develop cat-specific immunoglobin E antibodies. Nevertheless, these findings suggest that, to reduce their risk of developing eczema, filaggrin-deficient individuals should avoid cats (but not dogs) during the first few months of life.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0050131.
The MedlinePlus Encyclopedia has a page on eczema (in English and Spanish); links to further information are provided by MedlinePlus
EczemaNet is a comprehensive online information resource about eczema provided by the American Academy of Dermatologists
The US National Institute of Arthritis and Musculoskeletal and Skin Diseases provides information on eczema
The UK National Health Service Direct health encyclopedia provides information for patients on eczema (in several languages)
The Copenhagen Studies on Asthma in Childhood (COPSAC) and Manchester Asthma and Allergy Study (MAAS) Web sites provide more information about the children involved in this research
doi:10.1371/journal.pmed.0050131
PMCID: PMC2504043  PMID: 18578563
11.  The Severity-Dependent Relationship of Infant Bronchiolitis on the Risk and Morbidity of Early Childhood Asthma 
Background
Infants hospitalized for bronchiolitis have a high rate of early childhood asthma. It is not known whether bronchiolitis severity correlates with the risk of early childhood asthma or with asthma-specific morbidity.
Objectives
To determine whether a dose-response relationship exists between severity of infant bronchiolitis and both the odds of developing early childhood asthma and asthma-specific morbidity.
Methods
We conducted a population-based retrospective birth cohort study of term, healthy infants born 1995-2000 and enrolled in a statewide Medicaid program. We defined bronchiolitis severity by categorizing infants into mutually exclusive groups based on most advanced level of healthcare for bronchiolitis. Healthcare visits, asthma-specific medications, and demographics were identified entirely from Medicaid and linked vital records files. Asthma was ascertained between 4-5.5 years, and one-year asthma morbidity (hospitalization, emergency department visit, or oral corticosteroid course) was determined between 4.5-5.5 years, among children with prevalent asthma.
Results
Among 90,341 children, 18% had an infant bronchiolitis visit, and these infants contributed to 31% of early childhood asthma diagnoses. Relative to children with no infant bronchiolitis visit, the adjusted odds ratios for asthma were 1.86 [95% confidence intervals 1.74-1.99], 2.41 (2.21-2.62) and 2.82 (2.61-3.03) in the Outpatient, Emergency Department, and Hospitalization groups respectively. Children hospitalized with bronchiolitis during infancy had increased early childhood asthma morbidity compared with children with no bronchiolitis visit.
Conclusion
To our knowledge, this is the first study to demonstrate the dose-response relationship between severity of infant bronchiolitis and the increased odds of both developing early childhood asthma and experiencing asthma-specific morbidity.
doi:10.1016/j.jaci.2009.02.021
PMCID: PMC2703291  PMID: 19361850
Bronchiolitis; asthma
12.  Association of Birth Weight With Asthma-Related Outcomes at Age 2 Years 
Pediatric pulmonology  2006;41(7):643-648.
Summary. Background: Although lower birth weight associated with prematurity raises the risk of asthma in childhood, few prospective studies have examined higher birth weight, and few have separated the two components of birth weight, fetal growth and length of gestation.
Objective. To examine the associations of fetal growth and length of gestation with asthma-related outcomes by age 2 years.
Methods. We studied 1,372 infants and toddlers born after 34 weeks’ gestation in Project Viva, a prospective cohort study of pregnant mothers and their children. The main outcome measures were parent report of (1) any wheezing (or whistling in the chest) from birth to age 2 years, (2) recurrent wheezing during the first 2 years of life, and (3) doctor’s diagnosis of asthma, wheeze or reactive airwaydisease (“asthma”) by age 2. We calculated gestational age from the last menstrual period or ultrasound examination, and determined birth weight for gestational age z-value (“fetal growth”) using US national reference data.
Results. Infants’ mean birth weight was 3,527 (SD, 517; range, 1,559–5,528) grams. By age 2 years, 34% of children had any wheezing, 14% had recurrent wheezing, and 16% had doctor-diagnosed asthma. After adjusting for several parent, child, and household characteristics in logistic regression models, we found that infants with birth weight ≥4,000 g were not more likely to have any wheezing (odds ratio (OR), 0.91; 95% confidence interval (CI): 0.62, 1.34) or doctor-diagnosed asthma (OR, 0.80; 95% CI: 0.49, 1.31) than infants with birth weight 3,500–3,999 g. In models examining length of gestation and fetal growth separately, neither the highest nor the lowest groups of either predictor were associated with the three outcomes. Boys had a higher incidence of asthma-related outcomes than girls, and exposure to passive smoking, parental history of asthma, and exposure to older siblings were all associated with greater risk of recurrent wheeze or asthma-related outcomes at age 2 years.
Conclusion. Although male sex, exposure to smoking, parental history of asthma, and exposure to older siblingswere associated with increased riskof wheezing and asthma-related outcomes in this prospective study of children born after 34 weeks gestation, fetal growth and length of gestation were not.
doi:10.1002/ppul.20427
PMCID: PMC1488724  PMID: 16703577
asthma; birth weight; fetal growth; length of gestation; wheezing
13.  Fluticasone propionate-salmeterol versus inhaled corticosteroids plus montelukast: outcomes study in pediatric patients with asthma 
Background
The purpose of this study (GSK ADA111194) was to compare asthma-related health care utilization and costs associated with fluticasone propionate (an inhaled corticosteroid [ICS]) and salmeterol (a long-acting beta-agonist) in a single inhalation device (fluticasone propionate-salmeterol) versus the combination of ICS + montelukast in the treatment of pediatric patients with asthma.
Methods
This was a retrospective, observational cohort study using a large health insurance claims database spanning January 1, 2000 to January 31, 2008. The target population was patients aged 4–11 years with at least one pharmacy claim for fluticasone propionate-salmeterol, any ICS, or montelukast during the study period. The date of first claim for the medication of interest was deemed the index date. Patients were required to be continuously eligible to receive health care services one year prior to and 30 days after the index date, and have at least one claim with an ICD-9-CM code for asthma (493.xx) in the one-year pre-index period. Patients with prescriptions for fluticasone propionate-salmeterol, ICS + montelukast, or long-acting beta-agonists during the pre-index period were excluded. Patients were matched on a 1:1 basis according to three variables, ie, pre-index use of oral corticosteroids, ICS, and presence of pre-index respiratory-related hospitalizations/emergency department visits. The risk of asthma-related hospitalization, combined hospitalization/emergency department visit, and monthly asthma-related costs were assessed using multivariate methods.
Results
Of the 3001 patients identified, 2231 patients were on fluticasone propionate-salmeterol and 770 were on ICS + montelukast. After matching, there were 747 pairs of fluticasone propionate-salmeterol and ICS + montelukast patients, which were well matched for baseline characteristics. Patients who started fluticasone propionate-salmeterol compared with patients on ICS + montelukast had a significantly (P < 0.02) lower rate of asthma-related hospitalizations (0.3% versus 3.5%) and asthma-related hospitalizations/emergency department visits (3.5% versus 5.7%). After controlling for baseline and patient characteristics, fluticasone propionate-salmeterol users were associated with a significantly lower risk of an asthma-related hospitalization (adjusted hazard ratio 0.039; 95% confidence interval 0.004–0.408) or hospitalization/emergency department visit (hazard ratio 0.441; 95% confidence interval 0.225–0.864), and $151 (95% confidence interval 67–346) lower asthma-related monthly costs compared with ICS + montelukast.
Conclusion
In patients aged 4–11 years with asthma, use of fluticasone propionate-salmeterol was associated with lower asthma-related health care utilization and costs compared with use of ICS + montelukast.
doi:10.2147/JAA.S34582
PMCID: PMC3536350  PMID: 23300347
fluticasone propionate; salmeterol; montelukast; inhaled corticosteroids; asthma; pediatric; outcomes; asthma
14.  Association of Prenatal and Childhood Blood Lead Concentrations with Criminal Arrests in Early Adulthood 
PLoS Medicine  2008;5(5):e101.
Background
Childhood lead exposure is a purported risk factor for antisocial behavior, but prior studies either relied on indirect measures of exposure or did not follow participants into adulthood to examine the relationship between lead exposure and criminal activity in young adults. The objective of this study was to determine if prenatal and childhood blood lead concentrations are associated with arrests for criminal offenses.
Methods and Findings
Pregnant women were recruited from four prenatal clinics in Cincinnati, Ohio if they resided in areas of the city with a high concentration of older, lead-contaminated housing. We studied 250 individuals, 19 to 24 y of age, out of 376 children who were recruited at birth between 1979 and 1984. Prenatal maternal blood lead concentrations were measured during the first or early second trimester of pregnancy. Childhood blood lead concentrations were measured on a quarterly and biannual basis through 6.5 y. Study participants were examined at an inner-city pediatric clinic and the Cincinnati Children's Hospital Medical Center in Cincinnati, Ohio. Total arrests and arrests for offenses involving violence were collected from official Hamilton County, Ohio criminal justice records. Main outcomes were the covariate-adjusted rate ratios (RR) for total arrests and arrests for violent crimes associated with each 5 μg/dl (0.24 μmol/l) increase in blood lead concentration. Adjusted total arrest rates were greater for each 5 μg/dl (0.24 μmol/l) increase in blood lead concentration: RR = 1.40 (95% confidence interval [CI] 1.07–1.85) for prenatal blood lead, 1.07 (95% CI 0.88–1.29) for average childhood blood lead, and 1.27 (95% CI 1.03–1.57) for 6-year blood lead. Adjusted arrest rates for violent crimes were also greater for each 5 μg/dl increase in blood lead: RR = 1.34 (95% CI 0.88–2.03) for prenatal blood lead, 1.30 (95% CI 1.03–1.64) for average childhood blood lead, and 1.48 (95% CI 1.15–1.89) for 6-year blood lead.
Conclusions
Prenatal and postnatal blood lead concentrations are associated with higher rates of total arrests and/or arrests for offenses involving violence. This is the first prospective study to demonstrate an association between developmental exposure to lead and adult criminal behavior.
Kim Dietrich and colleagues find an association between developmental exposure to lead and adult criminal behavior.
Editors' Summary
Background.
Violent crime is an increasing problem in many countries, but why are some people more aggressive than others? Being male has been identified as a risk factor for violent criminal behavior in several studies, as have exposure to tobacco smoke before birth, having antisocial parents, and belonging to a poor family. Another potential risk factor for antisocial behavior as an adult is exposure to lead during childhood, although few studies have looked directly at whether childhood lead exposure is linked with criminal behavior in adulthood. Lead is a toxic metal that damages the nervous system when ingested or inhaled. It is present throughout the environment because of its widespread use in the past in paint, solder for water pipes, and gasoline. In 1978, 13.5 million US children had a blood lead level above 10 μg/dl, the current US Centers for Disease Control and Prevention blood lead level of concern (the average US blood lead level is 2 μg/dl). Lead paint and solder were banned in 1978 and 1986, respectively, by the US federal government; leaded gasoline was finally phased out in 1996. By 2002, only 310,000 US children had a blood lead level above 10 μg/dl. However, children exposed to lower levels of lead than this—through ingesting flakes or dust residues of old lead paint, for example—can have poor intellectual development and behavioral problems including aggression.
Why Was This Study Done?
Although some studies have suggested that childhood lead exposure is associated with later criminal behavior, these studies have often relied on indirect measurements of childhood lead exposure such as bone lead levels in young adults or a history of lead poisoning. Other studies that have measured childhood lead exposure directly have not followed their participants into adulthood. In this new study, the researchers investigate the association between actual measurements of prenatal and childhood blood lead concentrations and criminal arrests in early adulthood to get a clearer idea about whether early lead exposure is associated with subsequent violent behavior.
What Did the Researchers Do and Find?
Between 1979 and 1984, the researchers recruited pregnant women living in poor areas of Cincinnati, which had a high concentration of older, lead-contaminated housing, into the Cincinnati Lead Study. They measured the women's blood lead concentrations during pregnancy as an indication of their offspring's prenatal lead exposure and the children's blood lead levels regularly until they were six and half years old. They then obtained information from the local criminal justice records on how many times each of the 250 offspring had been arrested between becoming 18 years old and the end of October 2005. The researchers found that increased blood lead levels before birth and during early childhood were associated with higher rates of arrest for any reason and for violent crimes. For example, for every 5 μg/dl increase in blood lead levels at six years of age, the risk of being arrested for a violent crime as a young adult increased by almost 50% (the “relative risk” was 1.48).
What Do These Findings Mean?
These findings provide strong evidence that early lead exposure is a risk factor for criminal behavior, including violent crime, in adulthood. One possibility, which the authors were unable to assess in this study, is that lead exposure impairs intelligence, which in turn makes it more likely that a criminal offender will be caught (i.e., arrested). The authors discuss a number of limitations in their study—for example, they probably did not capture all criminal behavior (since most criminal behavior does not lead to arrest). Although both environmental lead levels and crime rates have dropped over the last 30 years in the US, the overall reduction was not uniform—inner-city children remain particularly vulnerable to lead exposure. The findings therefore suggest that a further reduction in childhood lead exposure might be an important and achievable way to reduce violent crime.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0050101.
A PLoS Medicine Perspective article by David Bellinger further discusses this study and a related paper on childhood lead exposure and brain volume reduction in adulthood
Study researcher Kim Dietrich can be heard talking about “The Lethal Legacy of Lead”, a brief MP3 about lead exposure and violent crime
Toxtown, an interactive site from the US National Library of Medicine, provides information on environmental health concerns including exposure to lead (in English and Spanish)
The US Environmental Protection Agency provides information on lead in paint, dust, and soil and on protecting children from lead poisoning (in English and Spanish)
MedlinePlus provides a list of links to information on lead poisoning (in English and Spanish)
The US Centers for Disease Control and Prevention provides information about its Childhood Lead Poisoning Prevention Program
The UK Health Protection Agency also provides information about lead and its health hazards
doi:10.1371/journal.pmed.0050101
PMCID: PMC2689664  PMID: 18507497
15.  Examining the relationship between depression and asthma exacerbations in a prospective follow-up study 
Psychosomatic medicine  2013;75(3):305-310.
Background
While depression has been linked with asthma in numerous studies, its relationship with asthma exacerbations, including emergency room (ER) visits and oral steroid (OS) use has not been well documented. The main aim is to investigate whether comorbid depression increases exacerbations among patients with asthma.
Method
The study included 568 participants with asthma, who were between 18-56 years old, were taking an inhaled corticosteroid, and participated in both baseline and follow-up surveys. Surveys and medical records from a large, integrated health system were collected as part of the Adherence Feedback for Improving Respiratory Medication Use trial (ClinicalTrials.gov: NCT00459368). Number of ER visits and OS prescription fills for asthma were calculated for 12-month periods before and after the follow-up survey. Depression was measured using a standardized two-item instrument on both surveys. Negative binomial regression and modified proportional hazards models were used in the analyses.
Results
Among patients with asthma, those who had depression (n=187; 32.9%) were at increased risk of having an asthma-related ER visit (adjusted relative risk (aRR): 1.96, 95% confidence interval (CI): 1.02 - 3.75), but not an OS fill (aRR: 0.98; 95%CI: 0.72-1.32). Participants with depression and asthma, who also received psychiatric treatment via antidepressant medication (n=126; 22.2%) or psychotherapy (n=39; 6.9%), were more likely to have an ER visit (medication hazard ratio (HR): 2.09, 95%CI: 1.35-3.25; psychotherapy HR: 2.07, 95%CI: 1.38-3.22).
Conclusion
This study suggests a temporal relationship between depression and asthma-related ER visits. Research and practice must further consider the importance of these comorbid conditions.
doi:10.1097/PSY.0b013e3182864ee3
PMCID: PMC3706985  PMID: 23440228
asthma; depression; emergency care; oral steroid; mental health services
16.  Factors in childhood as predictors of asthma in adult life. 
BMJ : British Medical Journal  1994;309(6947):90-93.
OBJECTIVE--To determine which factors measured in childhood predict asthma in adult life. DESIGN--Prospective study over 25 years of a birth cohort initially studied at the age of 7. SETTING--Tasmania, Australia. SUBJECTS--1494 men and women surveyed in 1991-3 when aged 29 to 32 (75% of a random stratified sample from the 1968 Tasmanian asthma survey of children born in 1961 and at school in Tasmania). MAIN OUTCOME MEASURES--Self reported asthma or wheezy breathing in the previous 12 months (current asthma). RESULTS--Of the subjects with asthma or wheezy breathing by the age of 7, as reported by their parents 25.6% (190/741) reported current asthma as an adult compared with 10.8% (81/753) of subjects without parent reported childhood asthma (P < 0.001). Factors measured at the age of 7 that independently predicted current asthma as an adult were being female (odds ratio 1.57; 95% confidence interval 1.19 to 2.08); having a history of eczema (1.45; 1.04 to 2.03); having a low mild forced expiratory flow rate (interquartile odds ratio 1.40; 1.15 to 1.71); having a mother or father with a history of asthma (1.74 (1.23 to 2.47) and 1.68 (1.18 to 2.38) respectively); and having childhood asthma (1.59; 1.10 to 2.29) and, if so, having the first attack after the age of 2 (1.66; 1.17 to 2.36) or having had more than 10 attacks (1.70; 1.17 to 2.48). CONCLUSION--Children with asthma reported by their parents in 1968 were more likely than not to be free of symptoms as adults. The subjects who had more severe asthma (especially if it developed after the age of 2 and was associated with reduced expiratory flow), were female, or had parents who had asthma were at an increased risk of having asthma as an adult. These findings have implications for the treatment and prognosis of childhood asthma, targeting preventive and educational strategies and understanding the onset of asthma in adult life.
PMCID: PMC2540556  PMID: 8038673
17.  Changes in the Prevalence of Childhood Asthma in Seoul from 1995 to 2008 and Its Risk Factors 
Purpose
To investigate the prevalence of asthma and determine its risk factors in elementary school students in Seoul.
Methods
A modified International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire was used to survey 4,731 elementary school students from five areas in Seoul between April and October, 2008.
Results
In elementary school children, the lifetime and recent 12-month prevalence of wheezing were 11.7% and 5.6%, respectively. The lifetime prevalence of asthma diagnosis was 7.9%, and the recent 12-month prevalence of asthma treatment was 2.7%. Male sex (adjusted odds ratio [aOR], 1.90; 95% confidence interval [CI], 1.36-2.66), history of atopic dermatitis (AD) (aOR, 2.76; 95% CI, 1.98-3.84), history of allergic rhinitis (AR) (aOR, 3.71; 95% CI, 2.61-5.26), history of bronchiolitis before 2 years of age (aOR, 2.06; 95% CI, 1.39-3.07), use of antibiotics during infancy for >3 days (aOR, 1.88; 95% CI, 1.35-2.62), parental history of asthma (aOR, 2.83; 95% CI, 1.52-5.27), exposure to household molds during infancy (aOR, 1.84; 95% CI, 1.18-2.89), and the development or aggravation of asthma symptoms within 6 months after moving to a new house (aOR, 11.76; 95% CI, 5.35-25.86) were the independent risk factors for wheezing within 12 months.
Conclusions
The prevalence of wheezing and asthma in elementary school students in 2008 was similar to that in the past decade. Male sex, history of AD, history of AR, history of bronchiolitis before 2 years of age, parental asthma, use of antibiotics during infancy, exposure to molds in the house during infancy, and development or aggravation of asthma symptoms within 6 months after moving to a new house, could be risk factors for wheezing within 12 months.
doi:10.4168/aair.2011.3.1.27
PMCID: PMC3005315  PMID: 21217922
Asthma; prevalence; risk factor; childhood
18.  Eczema in early childhood is strongly associated with the development of asthma and rhinitis in a prospective cohort 
BMC Dermatology  2012;12:11.
Background
This study aimed to estimate the association between eczema in early childhood and the onset of asthma and rhinitis later in life in children.
Methods
A total of 3,124 children aged 1–2 years were included in the Dampness in Building and Health (DBH) study in the year 2000, and followed up 5 years later by a parental questionnaire based on an International Study of Asthma and Allergies in Childhood protocol. The association between eczema in early childhood and the incidence of asthma and rhinitis later in life was estimated by univariable and multivariable logistic regression modelling.
Results
The prevalence of eczema in children aged 1–2 years was 17.6% at baseline. Children with eczema had a 3-fold increased odds of developing asthma (adjusted odds ratio [aOR], 3.07; 95% confidence interval (CI) 1.79–5.27), and a nearly 3-fold increased odds of developing rhinitis (aOR, 2.63; 1.85–3.73) at follow-up compared with children without eczema, adjusted for age, sex, parental allergic disease, parental smoking, length of breastfeeding, site of living, polyvinylchloride flooring material, and concomitant allergic disease. When eczema was divided into subgroups, moderate to severe eczema (aOR, 3.56; 1.62–7.83 and aOR, 3.87; 2.37–6.33, respectively), early onset of eczema (aOR, 3.44; 1.94–6.09 and aOR, 4.05; 2.82–5.81; respectively), and persistence of eczema (aOR, 5.16; 2.62–10.18 and aOR, 4.00; 2.53–6.22, respectively) further increased the odds of developing asthma and rhinitis. Further independent risk factors increasing the odds of developing asthma were a parental history of allergic disease (aOR, 1.83; 1.29–2.60) and a period of breast feeding shorter than 6 months (aOR, 1.57; 1.03–2.39). The incidence of rhinitis was increased for parental history of allergic disease (aOR, 2.00; 1.59–2.51) and polyvinylchloride flooring (aOR, 1.60; 1.02–2.51).
Conclusion
Eczema in infancy is associated with development of asthma and rhinitis during the following 5-year period, and eczema is one of the strongest risk factors. Early identification is valuable for prediction of the atopic march.
doi:10.1186/1471-5945-12-11
PMCID: PMC3469362  PMID: 22839963
19.  Asthma in children born after infertility treatment: findings from the UK Millennium Cohort Study 
STUDY QUESTION
Is asthma more common in children born after subfertility and assisted reproduction technologies (ART)?
SUMMARY ANSWER
Yes. Asthma, wheezing in the last year and anti-asthmatic medication were all more common in children born after a prolonged time to conception (TTC). This was driven specifically by an increase in children born after ART.
WHAT IS KNOWN ALREADY
Few studies have investigated any association between ART and asthma in subsequent children, and findings to date have been mixed. A large registry-based study found an increase in asthma medication in ART children but suggests underlying infertility is the putative risk factor. Little is known about asthma in children after unplanned or mistimed conceptions.
STUDY DESIGN, SIZE, DURATION
The Millennium Cohort Study is a UK-wide, prospective study of 18 818 children recruited at 9 months of age. Follow-up is ongoing. This study analyses data from follow-up surveys at 5 and 7 years of age (response rates of 79 and 70%, respectively).
PARTICIPANTS/MATERIALS, SETTING, METHODS
Singleton children whose natural mothers provided follow-up data were included. Mothers reported whether their pregnancy was planned; planners provided TTC and details of any ART. The population was divided into ‘unplanned’ (unplanned and unhappy), ‘mistimed’ (unplanned but happy), ‘planned’ (planned, TTC < 12 months), ‘untreated subfertile’ (planned, TTC >12 months), ‘ovulation induced’ (received clomiphene citrate) and ‘ART’ (IVF or ICSI). The primary analysis used the planned children as the comparison group; secondary analysis compared the treatment groups to the children born to untreated subfertile parents. Outcomes were parent report of asthma and wheezing at 5 and 7 years, derived from validated questions in the International Study of Asthma and Allergies in Childhood, plus use of anti-asthmatic medications. A total of 13 041 (72%) children with full data on asthma and confounders were included at 5 years of age, and 11 585 (64%) at 7 years.
MAIN RESULTS AND THE ROLE OF CHANCE
Compared with planned children, those born to subfertile parents were significantly more likely to experience asthma, wheezing and to be taking anti-asthmatics at 5 years of age [adjusted odds ratio (OR): 1.39 (95% confidence interval (CI): 1.07, 1.80), OR: 1.27 (1.00, 1.63) and OR: 1.90 (1.32,2.74), respectively]. This association was mainly related to an increase among children born after ART (adjusted OR: 2.65 (1.48, 4.76), OR: 1.97, (1.10, 3.53) and OR: 4.67 (2.20, 9.94) for asthma, wheezing and taking anti-asthmatics, respectively). The association was also present, though reduced, at the age of 7 years.
LIMITATIONS, REASONS FOR CAUTION
The number of singletons born after ART was relatively small (n = 104), and as such the findings should be interpreted with caution. However, data on a wide range of possible confounding and mediating factors were available and analysed. The data were weighted for non-response to minimize selection bias.
WIDER IMPLICATIONS OF THE FINDINGS
The findings add to the growing body of evidence suggesting an association between subfertility, ART and asthma in children. Further work is needed to establish causality and elucidate the underlying mechanism. These findings are generalizable to singletons only, and further work on multiples is needed.
STUDY FUNDING/COMPETING INTEREST(S)
This study was funded by a Medical Research Council project grant. No competing interests.
doi:10.1093/humrep/des398
PMCID: PMC3545639  PMID: 23223378
infertility; assisted reproduction techniques; asthma; unplanned pregnancy
20.  Perinatal risk factors for asthma in Finnish adolescent twins 
Thorax  2000;55(1):25-31.
BACKGROUND—Previous studies have suggested that, in addition to genetic liability and environment in early childhood, intrauterine life also influences the risk for asthma beyond childhood. Low birth weight, prematurity, young maternal age, and maternal smoking have all shown an association with asthma. The effect of perinatal factors on the risk for asthma in relation to familial and social risk factors was studied in a nationwide population-based sample of adolescent twins. In addition to a distribution of birth characteristics among twins which differs from that of singletons, data on twins enable a distinction to be made between genetic and environmental sources of variation.
METHODS—Questionnaires were sent to five consecutive birth cohorts of Finnish 16 year old twins born in 1975-9 and to their parents (3065 families). The outcome measure was life time prevalence of doctor-diagnosed asthma in these adolescents. The association between asthma and potential risk factors was assessed by multiple logistic regression and discordant twin pair analysis.
RESULTS—Risk for asthma increased with increasing ponderal index (p for trend <0.01) and decreasing maternal age (p for trend <0.05). Among the 25% of twins with the highest ponderal index, the odds ratio for asthma was 1.82 (95% confidence interval 1.18 to 2.79) compared with those in the lowest 25%. Neither birth weight, gestational age, nor Apgar score was associated with asthma. When perinatal risk factors were combined with familial and social risk factors, ponderal index, maternal smoking, parental asthma, and sibship size were all significant independent determinants of asthma in these adolescents.
CONCLUSIONS—The risk for asthma in adolescent twins increases with increasing ponderal index when adjusted for familial and social factors.


doi:10.1136/thorax.55.1.25
PMCID: PMC1745589  PMID: 10607798
21.  Modifiable exposures to air pollutants related to asthma phenotypes in the first year of life in children of the EDEN mother-child cohort study 
BMC Public Health  2013;13:506.
Background
Studies have shown diverse strength of evidence for the associations between air pollutants and childhood asthma, but these associations have scarcely been documented in the early life. The purpose of this study was to evaluate the impacts of various air pollutants on the development of asthma phenotypes in the first year of life.
Methods
Adjusted odds ratios were estimated to assess the relationships between exposures to air pollutants and single and multi-dimensional asthma phenotypes in the first year of life in children of the EDEN mother-child cohort study (n = 1,765 mother-child pairs). The Generalized Estimating Equation (GEE) model was used to determine the associations between prenatal maternal smoking and in utero exposure to traffic-related air pollution and asthma phenotypes (data were collected when children were at birth, and at 4, 8 and 12 months of age). Adjusted Population Attributable Risk (aPAR) was estimated to measure the impacts of air pollutants on health outcomes.
Results
In the first year of life, both single and multi-dimensional asthma phenotypes were positively related to heavy parental smoking, traffic-related air pollution and dampness, but negatively associated with contact with cats and domestic wood heating. Adjusted odds ratios (aORs) for traffic-related air pollution were the highest [1.71 (95% Confidence Interval (CI): 1.08-2.72) for ever doctor-diagnosed asthma, 1.44 (95% CI: 1.05-1.99) for bronchiolitis with wheezing, 2.01 (95% CI: 1.23-3.30) for doctor-diagnosed asthma with a history of bronchiolitis]. The aPARs based on these aORs were 13.52%, 9.39%, and 17.78%, respectively. Results persisted for prenatal maternal smoking and in utero exposure to traffic-related air pollution, although statistically significant associations were observed only with the asthma phenotype of ever bronchiolitis.
Conclusions
After adjusting for potential confounders, traffic-related air pollution in utero life and in the first year of life, had a greater impact on the development of asthma phenotypes compared to other factors.
doi:10.1186/1471-2458-13-506
PMCID: PMC3671198  PMID: 23705590
Environment; Traffic-related air pollution; Environmental Tobacco Smoke (ETS); Pets; Moulds; Asthma; Children
22.  Bone mineral density and fractures in older men with chronic obstructive pulmonary disease or asthma 
Osteoporosis International  2009;21(8):1341-1349.
Summary
In 5,541 community dwelling men, chronic obstructive pulmonary disease, or asthma was associated with lower bone mineral density (BMD) at the spine and total hip and an increased risk of vertebral and nonvertebral fractures independent of age, body mass index, and smoking. Men prescribed with corticosteroids had the lowest BMD.
Introduction
It is unclear whether chronic obstructive pulmonary disease (COPD) is independently associated with BMD and fractures.
Methods
In 5,541 men from the Osteoporotic Fractures in Men Study, history of COPD or asthma, current treatment with corticosteroids, BMD, bone loss after 4.5 years and fractures were ascertained.
Results
Seven hundred fourteen (13%) men reported COPD or asthma, of which 103 were prescribed an oral steroid and 177 an inhaled steroid. Independent of confounders, men prescribed corticosteroids for COPD or asthma had the lowest BMD and a 2-fold increased risk of vertebral osteoporosis compared to men with no history of COPD or asthma (OR 2.13, 95% CI (confidence interval) 1.15–3.93 oral steroids; OR 2.05, 95% CI 1.27–3.31 inhaled steroids). During follow-up, BMD increased at the spine, but there was no difference in bone loss at the hip. However, men with COPD or asthma had a 2.6- and 1.4-fold increased risk of vertebral and nonvertebral fractures, respectively.
Conclusion
Chronic obstructive pulmonary disease or asthma was associated with lower BMD at the spine and hip and increased risk of vertebral and nonvertebral fractures independent of age, clinic site, BMI, and smoking. A history of COPD or asthma may be a useful clinical risk factor to identify patients with osteoporosis.
doi:10.1007/s00198-009-1076-x
PMCID: PMC2895883  PMID: 19816753
Bone loss; Bone mineral density; Elderly; Fractures; Pulmonary disease
23.  Statin Exposure Is Associated with Decreased Asthma-related Emergency Department Visits and Oral Corticosteroid Use 
Rationale: Statins, or HMG-CoA reductase inhibitors, may aid in the treatment of asthma through their pleiotropic antiinflammatory effects.
Objectives: To examine the effect of statin therapy on asthma-related exacerbations using a large population-based cohort.
Methods: Statin users aged 31 years or greater with asthma were identified from the Population-Based Effectiveness in Asthma and Lung population, which includes data from five health plans. Statin exposure and asthma exacerbations were assessed over a 24-month observation period. Statin users with a statin medication possession ratio greater than or equal to 80% were matched to non–statin users by age, baseline asthma therapy, site of enrollment, season at baseline, and propensity score, which was calculated based on patient demographics and Deyo-Charlson conditions. Asthma exacerbations were defined as two or more oral corticosteroid dispensings, asthma-related emergency department visits, or asthma-related hospitalizations. The association between statin exposure and each of the three outcome measures was assessed using conditional logistic regression.
Measurements and Main Results: Of the 14,566 statin users, 8,349 statin users were matched to a nonuser. After adjusting for Deyo-Charlson conditions that remained unbalanced after matching, among statin users, statin exposure was associated with decreased odds of having asthma-related emergency department visits (odds ratio [OR], 0.64; 95% confidence interval [CI], 0.53–0.77; P < 0.0001) and two or more oral corticosteroid dispensings (OR, 0.90; 95% CI, 0.81–0.99; P = 0.04). There were no differences in asthma-related hospitalizations (OR, 0.91; 95% CI, 0.66–1.24; P = 0.52).
Conclusions: Among statin users with asthma, statin exposure was associated with decreased odds of asthma-related emergency department visits and oral corticosteroid dispensings.
doi:10.1164/rccm.201306-1017OC
PMCID: PMC3863744  PMID: 24093599
HMG-CoA reductase inhibitors; asthma therapy; exacerbations
24.  Preterm Birth and Childhood Wheezing Disorders: A Systematic Review and Meta-Analysis 
PLoS Medicine  2014;11(1):e1001596.
In a systematic review and meta-analysis, Jasper Been and colleagues investigate the association between preterm birth and the development of wheezing disorders in childhood.
Please see later in the article for the Editors' Summary
Background
Accumulating evidence implicates early life factors in the aetiology of non-communicable diseases, including asthma/wheezing disorders. We undertook a systematic review investigating risks of asthma/wheezing disorders in children born preterm, including the increasing numbers who, as a result of advances in neonatal care, now survive very preterm birth.
Methods and Findings
Two reviewers independently searched seven online databases for contemporaneous (1 January 1995–23 September 2013) epidemiological studies investigating the association between preterm birth and asthma/wheezing disorders. Additional studies were identified through reference and citation searches, and contacting international experts. Quality appraisal was undertaken using the Effective Public Health Practice Project instrument. We pooled unadjusted and adjusted effect estimates using random-effects meta-analysis, investigated “dose–response” associations, and undertook subgroup, sensitivity, and meta-regression analyses to assess the robustness of associations.
We identified 42 eligible studies from six continents. Twelve were excluded for population overlap, leaving 30 unique studies involving 1,543,639 children. Preterm birth was associated with an increased risk of wheezing disorders in unadjusted (13.7% versus 8.3%; odds ratio [OR] 1.71, 95% CI 1.57–1.87; 26 studies including 1,500,916 children) and adjusted analyses (OR 1.46, 95% CI 1.29–1.65; 17 studies including 874,710 children). The risk was particularly high among children born very preterm (<32 wk gestation; unadjusted: OR 3.00, 95% CI 2.61–3.44; adjusted: OR 2.81, 95% CI 2.55–3.12). Findings were most pronounced for studies with low risk of bias and were consistent across sensitivity analyses. The estimated population-attributable risk of preterm birth for childhood wheezing disorders was ≥3.1%.
Key limitations related to the paucity of data from low- and middle-income countries, and risk of residual confounding.
Conclusions
There is compelling evidence that preterm birth—particularly very preterm birth—increases the risk of asthma. Given the projected global increases in children surviving preterm births, research now needs to focus on understanding underlying mechanisms, and then to translate these insights into the development of preventive interventions.
Review Registration
PROSPERO CRD42013004965
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Most pregnancies last around 40 weeks, but worldwide, more than 11% of babies are born before 37 weeks of gestation (the period during which a baby develops in its mother's womb). Preterm birth is a major cause of infant death—more than 1 million babies die annually from preterm birth complications—and the number of preterm births is increasing globally. Multiple pregnancies, infections, and chronic (long-term) maternal conditions such as diabetes can all cause premature birth, but the cause of many preterm births is unknown. The most obvious immediate complication that is associated with preterm birth is respiratory distress syndrome. This breathing problem, which is more common in early preterm babies than in near-term babies, occurs because the lungs of premature babies are structurally immature and lack pulmonary surfactant, a unique mixture of lipids and proteins that coats the inner lining of the lungs and helps to prevent the collapse of the small air sacs in the lungs that absorb oxygen from the air. Consequently, preterm babies often need help with their breathing and oxygen supplementation.
Why Was This Study Done?
Improvements in the management of prematurity mean that more preterm babies survive today than in the past. However, accumulating evidence suggests that early life events are involved in the subsequent development of non-communicable diseases (non-infectious chronic diseases). Given the increasing burden of preterm birth, a better understanding of the long-term effects of preterm birth is essential. Here, the researchers investigate the risks of asthma and wheezing disorders in children who are born preterm by undertaking a systematic review (a study that uses predefined criteria to identify all the research on a given topic) and a meta-analysis (a statistical method for combining the results of several studies). Asthma is a chronic condition that is caused by inflammation of the airways. In people with asthma, the airways can react very strongly to allergens such as animal fur and to irritants such as cigarette smoke. Exercise, cold air, and infections can also trigger asthma attacks, which can sometimes be fatal. The symptoms of asthma include wheezing (a high-pitched whistling sound during breathing), coughing, chest tightness, and shortness of breath. Asthma cannot be cured, but drugs can relieve its symptoms and prevent acute asthma attacks.
What Did the Researchers Do and Find?
The researchers identified 30 studies undertaken between 1995 and the present (a time span chosen to allow for recent changes in the management of prematurity) that investigated the association between preterm birth and asthma/wheezing disorders in more than 1.5 million children. Across the studies, 13.7% of preterm babies developed asthma/wheezing disorders during childhood, compared to only 8.3% of babies born at term. Thus, the risk of preterm babies developing asthma or a wheezing disorder during childhood was 1.71 times higher than the risk of term babies developing these conditions (an unadjusted odds ratio [OR] of 1.71). In analyses that allowed for confounding factors—other factors that affect the risk of developing asthma/wheezing disorders such as maternal smoking—the risk of preterm babies developing asthma or a wheezing disorder during childhood was 1.46 times higher than that of babies born at term (an adjusted OR of 1.46). Notably, compared to children born at term, children born very early (before 32 weeks of gestation) had about three times the risk of developing asthma/wheezing disorders in unadjusted and adjusted analyses. Finally, the population-attributable risk of preterm birth for childhood wheezing disorders was more than 3.1%. That is, if no preterm births had occurred, there would have been more than a 3.1% reduction in childhood wheezing disorders.
What Do These Findings Mean?
These findings strongly suggest that preterm birth increases the risk of asthma and wheezing disorders during childhood and that the risk of asthma/wheezing disorders increases as the degree of prematurity increases. The accuracy of these findings may be affected, however, by residual confounding. That is, preterm children may share other, unknown characteristics that increase their risk of developing asthma/wheezing disorders. Moreover, the generalizability of these findings is limited by the lack of data from low- and middle-income countries. However, given the projected global increases in children surviving preterm births, these findings highlight the need to undertake research into the mechanisms underlying the association between preterm birth and asthma/wheezing disorders and the need to develop appropriate preventative and therapeutic measures.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001596.
The March of Dimes, a nonprofit organization for pregnancy and baby health, provides information on preterm birth (in English and Spanish)
Nemours, another nonprofit organization for child health, also provides information (in English and Spanish) on premature babies and on asthma (including personal stories)
The UK National Health Service Choices website provides information about premature labor and birth and a real story about having a preterm baby; it provides information about asthma in children (including real stories)
The MedlinePlus Encyclopedia has pages on preterm birth, asthma, asthma in children, and wheezing (in English and Spanish); MedlinePlus provides links to further information on premature birth, asthma, and asthma in children (in English and Spanish)
doi:10.1371/journal.pmed.1001596
PMCID: PMC3904844  PMID: 24492409
25.  Home Dampness and Molds, Parental Atopy, and Asthma in Childhood: A Six-Year Population-Based Cohort Study 
Environmental Health Perspectives  2004;113(3):357-361.
Previous studies of how parental atopy and exposure to dampness and molds contribute to the risk of asthma have been mainly cross-sectional or prevalent case–control studies, where selection and information bias and temporality constitute problems. We assessed longitudinally the independent and joint effects of parental atopy and exposure to molds in dwellings on the development of asthma in childhood. We conducted a population-based, 6-year prospective cohort study of 1,984 children 1–7 years of age at the baseline in 1991 (follow-up rate, 77%). The study population included 1,916 children without asthma at baseline and complete outcome information. The data collection included a baseline and follow-up survey. The outcome of interest was development of asthma during the study period. The studied determinants were parental allergic diseases and four indicators of exposure at baseline: histories of water damage, presence of moisture and visible molds, and perceived mold odor in the home. A total of 138 (7.2%) children developed asthma during the study period, resulting in an incidence rate of 125 cases per 10,000 person-years [95% confidence interval (CI), 104–146]. In Poisson regression adjusting for confounding, parental atopy [adjusted incidence rate ratio (IRR) 1.52; 95% CI, 1.08–2.13] and the presence of mold odor in the home reported at baseline (adjusted IRR 2.44; 95% CI, 1.07–5.60) were independent determinants of asthma incidence, but no apparent interaction was observed. The results of this cohort study with assessment of exposure before the onset of asthma strengthen the evidence on the independent effects of parental atopy and exposure to molds on the development of asthma.
doi:10.1289/ehp.7242
PMCID: PMC1253765  PMID: 15743728
asthma; damp housing; effect modification; interaction; molds

Results 1-25 (1104964)