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.
Our results showed some evidence for a positive association between prenatal stress and childhood asthma among boys but not girls.
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.
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.
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).
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.
asthma; children; population; pregnancy; risk factors
This study used a Cox proportional hazards model to determine whether neighborhood characteristics are associated with risk of readmission for childhood asthma independently of individual characteristics.
Rhode Island Hospital Discharge Data from 2001 to 2005 were used to identify children younger than 19 years of age at the time of the index (i.e., first) asthma admission, defined as a primary diagnosis of asthma or a primary diagnosis of respiratory illness with a secondary or tertiary diagnosis of asthma (n=2,919). Hazard ratios of repeat hospitalizations for childhood asthma from 2001 to 2005 were estimated, controlling for individual- and neighborhood-level variables.
During the study period, 15% of the sample was readmitted for asthma (n=451). In the unadjusted cumulative hazard curves, children residing in the census tracts with the highest proportion of crowded housing conditions, racial minority residents, or neighborhood-level poverty had higher cumulative hospital readmission rates as compared with children who resided in less disadvantaged neighborhoods. In the fully adjusted models, children insured by Medicaid at the time of their index admission had readmission rates that were 33% higher than children who were privately insured.
Our findings suggest that differences in health-care coverage are associated with higher readmission rates for pediatric asthma, but the relationship between neighborhood inequality and repeat hospitalizations for pediatric asthma requires further exploration. Social indicators such as minority race, Medicaid health insurance, and neighborhood markers of economic disadvantage are tightly interwoven in the U.S. and teasing these relationships apart is important in asthma disparities research.
In a large population-based study among adults in northern Europe the relation between occupational exposure and new-onset asthma was studied.
The study comprised 13 284 subjects born between 1945 and 1973, who answered a questionnaire 1989–1992 and again 1999–2001. Asthma was defined as ‘Asthma diagnosed by a physician’ with reported year of diagnose. Hazard ratios (HR), for new-onset adult asthma during 1980–2000, were calculated using a modified job-exposure matrix as well as high-risk occupations in Cox regression models. The analyses were made separately for men and women and were also stratified for atopy.
During the observation period there were 429 subjects with new-onset asthma with an asthma incidence of 1.3 cases per 1000 person-years for men and 2.4 for women. A significant increase in new-onset asthma was seen for men exposed to plant-associated antigens (HR = 3.6; 95% CI [confidence interval] = 1.4–9.0), epoxy (HR = 2.4; 95% CI = 1.3–4.5), diisocyanates (HR = 2.1; 95% CI = 1.2–3.7) and accidental peak exposures to irritants (HR = 2.4; 95% CI = 1.3–4.7). Both men and women exposed to cleaning agents had an increased asthma risk. When stratifying for atopy an increased asthma risk were seen in non-atopic men exposed to acrylates (HR = 3.3; 95% CI = 1.4–7.5), epoxy compounds (HR = 3.6; 95% CI = 1.6–7.9), diisocyanates and accidental peak exposures to irritants (HR = 3.0; 95% CI = 1.2–7.2). Population attributable risk for occupational asthma was 14% for men and 7% for women.
This population-based study showed that men exposed to epoxy, diisocyanates and acrylates had an increased risk of new-onset asthma. Non-atopics seemed to be at higher risk than atopics, except for exposure to high molecular weight agents. Increased asthma risks among cleaners, spray painters, plumbers, and hairdressers were confirmed.
Atopics and non-atopics; high molecular weight agent; high-risk occupations; irritating agents; job-exposure matrix; low molecualr weight agent; occupational asthma; population attributable risk
Chorioamnionitis is associated with preterm delivery and involution of the fetal thymus. Women at risk of preterm delivery receive antenatal corticosteroids which accelerate fetal lung maturation and improve neonatal outcome. However, the effects of antenatal corticosteroids on the fetal thymus in the settings of chorioamnionitis are largely unknown. We hypothesized that intra-amniotic exposure to lipopolysaccharide (LPS) causes involution of the fetal thymus resulting in persistent effects on thymic structure and cell populations. We also hypothesized that antenatal corticosteroids may modulate the effects of LPS on thymic development.
Time-mated ewes with singleton fetuses received an intra-amniotic injection of LPS 7 or 14 days before preterm delivery at 120 days gestational age (term = 150 days). LPS and corticosteroid treatment groups received intra-amniotic LPS either preceding or following maternal intra-muscular betamethasone. Gestation matched controls received intra-amniotic and maternal intra-muscular saline. The fetal intra-thoracic thymus was evaluated.
Intra-amniotic LPS decreased the cortico-medullary (C/M) ratio of the thymus and increased Toll-like receptor (TLR) 4 mRNA and CD3 expression indicating involution and activation of the fetal thymus. Increased TLR4 and CD3 expression persisted for 14 days but Foxp3 expression decreased suggesting a change in regulatory T-cells. Sonic hedgehog and bone morphogenetic protein 4 mRNA, which are negative regulators of T-cell development, decreased in response to intra-amniotic LPS. Betamethasone treatment before LPS exposure attenuated some of the LPS-induced thymic responses but increased cleaved caspase-3 expression and decreased the C/M ratio. Betamethasone treatment after LPS exposure did not prevent the LPS-induced thymic changes.
Intra-amniotic exposure to LPS activated the fetal thymus which was accompanied by structural changes. Treatment with antenatal corticosteroids before LPS partially attenuated the LPS-induced effects but increased apoptosis in the fetal thymus. Corticosteroid administration after the inflammatory stimulus did not inhibit the LPS effects on the fetal thymus.
Preterm prelabor rupture of membrane (PPROM) causes maternal and neonatal complications. Prophylactic antiobiotics were used in the management of PPROM. The objectives of this retrospective study were to compare clinical course and outcome of PPROM managed expectantly with prophylactic antibiotics and antenatal corticosteroids with those without prophylactic antibiotics and antenatal corticosteroids.
A total of 170 cases of singleton pregnant women with gestational age between 28–34 weeks suffering from PROM during January 1998 to December 2009 were included; 119 cases received prophylactic antibiotics and antenatal corticosteroids while 51 cases did not received prophylactic antibiotics and antenatal corticosteroids. Median latency period in the study group was significantly longer than in the control group (89.8 vs. 24.3 hours, P < 0.001). The percentage of patients who did not deliver within 48 hours and within 7 days in the study group were also significantly higher than in control group (64.7 vs. 31.4%, P < 0.001 and 29.4 vs. 7.8%, P = 0.002, respectively). Maternal infectious morbidity was comparable between groups (17.6% vs. 13.7%, P = 0.52). Neonatal infectious morbidity was significantly lesser in study group than control group (21% vs. 35.3%, p = 0.04).
Latency period of PPROM after using prophylactic antibiotics and antenatal corticosteroids increased while neonatal infectious morbidity was low. But maternal infectious morbidity was not increased. This retrospective study confirms the benefit of prophylactic antibiotics and antenatal corticosteroids in management of PPROM.
Preterm; Prelabor rupture of membranes; Latency; Prophylactic antibiotic; Corticosteroids
Many studies have reported that antibiotic use may be associated with increased risk of childhood asthma. Respiratory tract infections in small children may be difficult to distinguish from early symptoms of asthma, and studies may have been confounded by “protopathic” bias, where antibiotics are used to treat early symptoms of asthma. These analyses of a cohort including 1,401 US children assess the association between antibiotic use within the first 6 months of life and asthma and allergy at 6 years of age between 2003 and 2007. Antibiotic exposure was associated with increased risk of asthma (adjusted odds ratio = 1.52, 95% confidence interval (CI): 1.07, 2.16). The odds ratio if asthma was first diagnosed after 3 years of age was 1.66 (95% CI: 0.99, 2.79) and, in children with no history of lower respiratory infection in the first year of life, the odds ratio was 1.66 (95% CI: 1.12, 3.46). The adverse effect of antibiotics was particularly strong in children with no family history of asthma (odds ratio = 1.89, 95% CI: 1.00, 3.58) (Pinteraction = 0.03). The odds ratio for a positive allergy blood or skin test was 1.59 (95% CI: 1.10, 2.28). The results show that early antibiotic use was associated with asthma and allergy at 6 years of age, and that protopathic bias was unlikely to account for the main findings.
anti-bacterial agents; asthma; child; cohort studies; hypersensitivity
The “fetal origins of adult disease” hypothesis suggests the uterine environment can influence a fetus’ susceptibility to future disease. We examine whether the fetal environment, as reflected by birthweight, could modulate an individual’s future risk of rheumatoid arthritis (RA).
The relationship between birthweight and the risk of incident RA was studied in 87,077 women followed prospectively in the Nurses’ Health Study cohort. New cases of RA diagnosed between 1976 and 2002 were confirmed in 619 women. The association between birthweight and the future development of RA was studied in age-adjusted and Cox proportional hazard models adjusting for age and potential confounders, including history of maternal diabetes, childhood socioeconomic status, prematurity, maternal and paternal smoking, as well as additionally adjusting for risk factors for RA including smoking, age at menarche, use of oral contraceptives, use of post-menopausal hormones, total lifetime breast feeding, and body mass index at age 18.
In an age-adjusted model, birthweight > 4.54 kg vs. birthweight 3.2–3.85 kg was associated with a two-fold increased risk of RA (RR=2.1; 95% CI 1.4–3.3). Further adjusting for potential confounders and risk factors did not change this relationship (RR=2.0; 95% CI 1.3–3.0). Findings were similar when we limited cases to those with rheumatoid factor positive RA, (RR=2.1; 95%CI= 1.2–3.6).
In this large prospective cohort, birthweight > 4.54 kg was associated with a twofold increased risk of adult onset RA, compared with those of average birthweight. Further study of this observation may provide insight into the pathogenesis of RA.
rheumatoid arthritis; birthweight; risk factors
Rationale: Factors predicting the development of wheeze may differ between sexes and between childhood and adolescence. Methods: A New Zealand birth cohort of 1,037 children was followed to age 26. For this analysis, those reporting recurrent wheezing at two or more assessments were classified as “wheezers.” We examined risk factors for development of wheeze before age 10 (childhood) and subsequently (adolescent-onset) for males and for females separately using Cox regression modeling. Results: Males more often developed childhood wheeze (p = 0.002) and females adolescent-onset wheeze (p < 0.001). Maternal atopy (asthma or hay fever) was a risk factor for childhood wheeze in both sexes (hazard ratio [HR], 1.48, p < 0.05 for males; HR, 2.37, p < 0.001 for females). Paternal atopy also influenced childhood wheeze, significantly for males (HR, 1.72; p = 0.01), and similarly but not significantly for females (HR, 1.70; p = 0.08). For adolescent-onset wheeze, neither maternal (HR, 1.41; p = 0.19) nor paternal history (HR, 0.73; p = 0.42) was a risk factor in males, but maternal history (HR, 2.08; p < 0.01) was a significant risk factor for females. When both age ranges were combined, providing greater power for analysis, paternal history was a stronger risk factor for wheeze in females (HR, 1.62; p = 0.02) than in males (HR, 1.35; p = 0.12). Conclusion: The influence of parental atopy on the development for wheeze differs between males and females and between childhood- and adolescent-onset wheeze.
age of onset; asthma; parental history; risk factors; sex
With the goal of preventing open neural tube defects (NTDs), recommendations for folic acid supplementation before conception were introduced in Canada in 1994, and by November 1998 Canadian grain products were being fortified with folic acid. We wished to determine whether the annual incidence of open NTDs in Nova Scotia, including those in stillbirths and terminated pregnancies, changed after the introduction of either folic acid supplementation or fortification.
For the 10-year period from Jan. 1, 1991, to Dec. 31, 2000, we retrospectively extracted the total number of births in Nova Scotia and the number of live births and stillbirths with open NTDs from the Nova Scotia Atlee Perinatal Database as well as the number of terminated pregnancies affected by NTDs from the Fetal Anomaly Database. We determined the total annual incidence of all open NTDs, and of the subgroups spina bifida and anencephaly, per 1000 births in the province during the periods before (1991–1994) and after (1995–1998) folic acid supplementation initiatives were begun but before folic acid fortification of grain products was implemented, and during the periods before (1991–1997) and after (1998–2000) fortification.
In the period after supplementation initiatives were begun but before fortification was implemented, the incidence of open NTDs did not change significantly: the mean annual rate was 2.55 per 1000 births during 1991–1994 and 2.61 per 1000 births during 1995–1997 (relative risk [RR] 1.02, 95% confidence interval [CI] 0.77–1.35). After the fortification was implemented the incidence of open NTDs decreased by more than 50%: the mean annual rate was 2.58 per 1000 births during 1991–1997 and 1.17 per 1000 births during 1998–2000 (relative risk 0.46, 95% CI 0.32–0.66).
The recommendations for folic acid supplementation alone did not appear to succeed in reducing the incidence of open NTDs in Nova Scotia, whereas the fortification of grain products with folic acid did result in a significant reduction in the incidence.
Safety concerns surround the use of long-acting beta agonists (LABA) for the treatment of asthma, even in combination with inhaled corticosteroids (ICS) and particularly in high-risk subgroups.
To estimate the effect ICS therapy and fixed-dose ICS/LABA combination therapy on severe asthma exacerbations in a racially diverse population.
Inhaled corticosteroid and ICS/LABA exposure was estimated from pharmacy data for patients with asthma age 12 to 56 years who were members of a large health maintenance organization. Inhaled corticosteroid and ICS/LABA use was estimated for each day of follow-up to create a moving window of exposure. Proportional hazard models were used to assess the relationship between ICS and ICS/LABA combination therapy and severe asthma exacerbations (i.e., use of oral corticosteroids, asthma-related emergency department visit, or asthma-related hospitalization).
Among the 1,828 patients who met the inclusion criteria, 37% were African American, 46% were treated with ICS therapy alone, and 54% were treated with an ICS/LABA combination. Models assessing the risk of severe asthma exacerbations among individuals using ICS treatment alone and ICS/LABA combination therapy suggested that the overall protective effect was as good or better for ICS/LABA combination therapy when compared with ICS treatment alone (hazard ratio [HR]=0.65 vs. HR=0.72, respectively). Analyses in several subgroups, including African American patients, showed a similar statistically significant protective association for combination therapy.
Treatment with ICS/LABA fixed combination therapy appeared to perform as well or better than ICS alone in reducing severe asthma exacerbations; this included multiple high-risk subgroups.
Long-acting beta-agonist; inhaled corticosteroid; severe asthma exacerbation; safety; racially and ethnically diverse population; observational study
We hypothesized that the joint effect of genetic propensity to asthma and exposure to environmental tobacco smoke on the risk of childhood asthma is greater than expected on the basis of their independent effects. We performed a population-based 4-year cohort study of 2,531 children born in Oslo, Norway. We collected information on the child's health and environmental exposures at birth and when the child was 6, 12, 18, and 24 months and 4 years of age. The outcomes of interest were bronchial obstruction during the first 2 years and asthma at the age of 4 years. Parental atopy was defined as a history of maternal or paternal asthma or hay fever. Exposure to environmental tobacco smoke was defined on the basis of questionnaire information on household smokers at birth. In logistic regression analysis adjusting for confounding, parental atopy alone increased the risk of bronchial obstruction [odds ratio 1.62; 95% confidence interval (CI) 1.10-2.40] and asthma (1.66; 95% CI, 1.08-2.54). In children without parental atopy, there was little effect of exposure to environmental tobacco smoke on bronchial obstruction (1.29; 95% CI, 0.88-1.89) and asthma (0.84; 95% CI, 0.53-1.34). The presence of parental atopy and exposure had a substantial effect both on bronchial obstruction (2.88; 95% CI, 1.91-4.32) and asthma (2.68; 95% CI, 1.70-4.22). The results are consistent with the hypothesized joint effect of parental atopy and exposure to environmental tobacco smoke. This phenomenon--denoted as effect modification of environmental exposure by genetic constitution, or gene by environment interaction--suggests that some genetic markers could indicate susceptibility to environmental factors.
Most pertinent studies of inadequate antenatal care concentrate on the risk profile of women booking late or not booking at all to antenatal care. The objective of this study was to assess the outcome of pregnancies when free and easily accessible antenatal care has been either totally lacking or low in number of visits.
This is a hospital register based cohort study of pregnancies treated in Kuopio University Hospital, Finland, in 1989 – 2001. Pregnancy outcomes of women having low numbers (1–5) of antenatal care visits (n = 207) and no antenatal care visits (n = 270) were compared with women having 6–18 antenatal visits (n = 23137). Main outcome measures were: Low birth weight, fetal death, neonatal death. Adverse pregnancy outcomes were controlled for confounding factors (adjusted odds ratios, OR: s) in multiple logistic regression models.
Of the analyzed pregnant population, 1.0% had no antenatal care visits and 0.77% had 1–5 visits. Under- or non-attendance associated with social and health behavioral risk factors: unmarried status, lower educational level, young maternal age, smoking and alcohol use. Chorio-amnionitis or placental abruptions were more common complications of pregnancies of women avoiding antenatal care, and pregnancy outcome was impaired. After logistic regression analyses, controlling for confounding, there were significantly more low birth weight infants in under- and non-attenders (OR:s with 95% CI:s: 9.18 (6.65–12.68) and 5.46 (3.90–7.65), respectively) more fetal deaths (OR:s 12.05 (5.95–24.40) and 5.19 (2.04–13.22), respectively) and more neonatal deaths (OR:s 10.03 (3.85–26.13) and 8.66 (3.59–20.86), respectively).
Even when birth takes place in hospital, non- or under-attendance at antenatal care carries a substantially elevated risk of severe adverse pregnancy outcome. Underlying adverse health behavior and possible abuse indicate close surveillance of the newborn.
Asthma is the most common chronic condition affecting Aboriginal youth aged 8 to 12 years in Canada. Research investigating psychosocial challenges associated with asthma is limited. This study examines support resources, support-seeking strategies, support and education needs, and intervention preferences of Aboriginal youth with asthma and their caregivers in an effort to encourage community-wide, health-promoting behaviors.
We employed a community-based participatory research design to conduct interviews with 21 youths aged 8 to 12 years and 17 caregivers from 5 Mi’kmaq communities in Unama’ki (Cape Breton) Nova Scotia, Canada. After conducting interviews that explored existing and desired social, educational, and health support in participating communities, we held a 2-day asthma camp to engage participants in asthma education, social support networking, and cultural activities. At the camp, we collected data through participant observation, sharing circles, focus groups, and youth drawings of their experiences living with asthma.
Our study yielded 4 key findings: 1) asthma triggers included household mold, indoor smoking, pets, season change, strenuous exercise, extreme cold, and humidity; 2) social and educational support is lacking in Mi’kmaq communities despite a strong desire for these services; 3) cultural, linguistic, and geographic barriers to accessing support exist; and 4) family members are primary support resources.
Improved support and educational resources are needed to foster effective Mi’kmaq asthma support networks. Future asthma interventions for marginalized populations must be culturally meaningful and linguistically accessible to those using and providing asthma support.
Background: Inflammatory bowel disease (IBD) is known to be associated with reduced bone density but the extent to which this results in an increased risk of fracture and the contribution of corticosteroid therapy are unclear. We have conducted a large cohort study to address these issues.
Methods: We selected subjects within the General Practice Research Database (GPRD) with a diagnosis of IBD and up to five matched controls for each patient. We derived dates of recorded hip fractures and also information on smoking, use of corticosteroids, and a number of other drugs. We calculated the absolute risk of fracture and the relative risk as a hazard ratio corrected for available confounders by Cox regression.
Results: Seventy two hip fractures were recorded in 16 550 IBD cases and 223 in 82 917 controls. Cox modelling gave an unadjusted relative risk of hip fracture of 1.62 (95% confidence interval (CI) 1.24–2.11) for all IBD, 1.49 (1.04–2.15) for ulcerative colitis (UC) and 2.08 (1.36–3.18) for Crohn’s disease (CD). Multivariate modelling showed that both current and cumulative use of corticosteroids and use of opioid analgesics confounded this relationship. After adjusting for confounding, the relative risk was 1.41 (0.94–2.11) for UC and 1.68 (1.01–2.78) for CD.
Conclusion: The risk of hip fracture is increased approximately 60% in IBD patients. Corticosteroid use is a contributor to this, both in the long term as previously recognised and also in an acute reversible manner. The majority of hip fracture risk in IBD patients however cannot be attributed to steroid use.
corticosteroids; fracture; inflammatory bowel disease
This study compares the Bayesian and frequentist (non-Bayesian) approaches in the modelling of the association between the risk of preterm birth and maternal proximity to hazardous waste and pollution from the Sydney Tar Pond site in Nova Scotia, Canada.
The data includes 1604 observed cases of preterm birth out of a total population of 17559 at risk of preterm birth from 144 enumeration districts in the Cape Breton Regional Municipality. Other covariates include the distance from the Tar Pond; the rate of unemployment to population; the proportion of persons who are separated, divorced or widowed; the proportion of persons who have no high school diploma; the proportion of persons living alone; the proportion of single parent families and average income. Bayesian hierarchical Poisson regression, quasi-likelihood Poisson regression and weighted linear regression models were fitted to the data.
The results of the analyses were compared together with their limitations.
The results of the weighted linear regression and the quasi-likelihood Poisson regression agrees with the result from the Bayesian hierarchical modelling which incorporates the spatial effects.
The “fetal origins hypothesis” or concept of “developmental programming” suggests that faltering fetal growth and subsequent catch-up growth are implicated in the aetiology of cardiovascular disease. Associations between reduced birth weight, rapid postnatal weight gain, and asthma suggest that there are fetal origins to respiratory disease. The present paper first summarises the literature relating birth weight and post natal growth trajectories to asthma outcomes. Second, issues regarding the interpretation of antenatal fetal ultrasound measurements are discussed. Finally, recent reports linking antenatal measurement and growth trajectory to early childhood asthma outcomes are discussed. Understanding the nature and timing of factors which influence antenatal growth may give important insight into the antecedents of early-onset asthma with implications for interventions.
During the 2009 influenza pandemic, pregnant women were at particular risk of serious influenza illness. This concern was further complicated by questions about vaccine safety in pregnant women raised by anecdotal reports of fetal deaths following vaccination.
We explored the safety of influenza vaccination of pregnant women by linking Norwegian national registries and medical consultation data to determine influenza diagnosis, vaccination status, birth outcomes, and background information for pregnant women before, during, and after the pandemic. We used Cox regression models to estimate hazard ratios of fetal death, with gestational day as the time metric and vaccination and pandemic exposure as time-dependent exposure variables.
There were 117,347 eligible pregnancies in Norway in 2009–2010. Fetal mortality was 4.9/1000. 54% of pregnant women in their second or third trimester during the pandemic were vaccinated. Vaccination in pregnancy substantially reduced the risk of influenza diagnosis (adjusted hazard ratio, 0.30; 95% confidence interval [CI], 0.25 to 0.34). A clinical diagnosis of influenza in the mother increased the risk of fetal death (adjusted hazard ratio, 1.91; 95% CI, 1.07 to 3.41). Among pregnant women, the risk of fetal death was lower with vaccination, although this reduction was not statistically significant (adjusted hazard ratio, 0.88; 95% CI, 0.66 to 1.17).
Pandemic influenza in pregnancy was associated with increased risk of fetal death. Vaccination during pregnancy reduced the risk of influenza diagnosis. Vaccination itself did not increase fetal mortality, and may have reduced the risk of influenza-related fetal death during the pandemic.
Pandemic vaccination; influenza; influenza A(H1N1)pdm09; pandemic; pregnancy; fetal death; miscarriage; abortions; stillbirth; Norway; registry; register; population
Detailed data were provided by the Oxford Survey of Childhood Cancer OSCC on deaths from childhood cancer in Britain after irradiation of the fetus during diagnostic radiology of the mother. In each age group at death, 0-5, 6-9 and 10-15 years, excess cancer deaths decreased suddenly for births in and after 1958. A major factor was concerted action initiated in 1956 to reduce radiation exposure of fetal gonads for fear of genetic hazards. Dose reduction was achieved during 1957 and early 1958 by reducing the rising rate of obstetric radiography and by virtually abandoning pelvimetry as that had been understood. In the 1970s the rate of X-raying increased again and so did cancer risk but not significantly. Direct evidence that diagnostic X-rays can cause childhood cancer is the similar excess rate per X-ray in twins and singleton births when X-raying rate is 5-6 times higher in twins. In the past a dose-response for cancer in OSCC data based on number of films per X-ray examination was taken to be evidence for causation but dose per film varies with kind of X-ray examination. Fixed values for dose per film were mistakenly assumed by UNSCEAR (1972) and used by it and others when deriving risk co-efficients. In updated OSCC data cancer risk is independent of film number. The odds ratio for childhood cancer deaths after X-raying in birth years 1958-61 (1.23 with 95% confidence intervals CI 1.04-1.48) and the mean fetal whole body dose from obstetric radiography in 1958 (0.6 cGy) can each be derived from nationwide surveys in Britain. The corresponding risk coefficient for irradiation in the third trimester for childhood cancer deaths at ages 0-15 years = 4-5 x 10(-4) per cGy fetal whole body dose (95% CI 0.8-9.5 x 10(-4) per cGy). It is the same for cancer incidence and mortality. A lower risk in bomb survivors exposed in utero is not incompatible since its CI are wide. There is no dependable evidence that radiosensitivity is greater in early pregnancy. A significantly raised cancer rate after diagnostic X-raying supports the hypothesis that carcinogenesis by ionising radiation has no threshold.
Epidemiological studies have suggested that female hormones might play a role in asthma and that menopausal hormone therapy (MHT or HRT) might increase the risk of asthma in postmenopausal women. The only prospective study addressing this issue reports an increase in the risk of developing asthma which was similar for estrogen alone and estrogen/progestagen treatment.
The association between the use of different types of MHT and the risk of asthma onset in postmenopausal women was investigated prospectively from 1990 to 2002 by biennial questionnaire as part of the French E3N cohort study. Asthma onset was considered to be the time of medical diagnosis of asthma cases occurring during the follow up of women who were asthma free at baseline. Cox proportional hazards models were used, adjusting for potential confounding factors.
Among 57,664 women free of asthma at menopause 569 incident cases of asthma were identified during 495,448 years of follow-up. MHT was related to an increased risk of asthma onset (HR= 1.20, 95% CI 0.98–1.46) among recent users. The increase in risk of asthma onset was only significant among women reporting the use of estrogen alone (HR= 1.54, 95% CI 1.13–2.09).particularly in never smokers (HR= 1.80 95% CI 1.15–2.80) and women reporting allergic disease prior to asthma onset (HR= 1.86 95% CI 1.18–2.93). A small increase in the risk of asthma onset associated with the use of estrogen/progestagen was also observed in these subgroups.
Postmenopausal use of estrogen alone was associated with an increased rate of newly diagnosed asthma in menopausal women.
Asthma; Epidemiology; Menopausal hormone therapy (MHT); Hormone replacement therapy (HRT); Asthma; chemically induced; epidemiology; Body Mass Index; Drug Combinations; Estrogen Replacement Therapy; adverse effects; utilization; Estrogens; adverse effects; Female; France; epidemiology; Humans; Middle Aged; Postmenopause; Progesterone; adverse effects; Prospective Studies; Risk Factors
Study objective: The Vesta project aims to assess the role of traffic related air pollution in the occurrence of childhood asthma.
Design and setting: Case-control study conducted in five French metropolitan areas between 1998 and 2000. A set of 217 pairs of matched 4 to 14 years old cases and controls were investigated. An index of lifelong exposure to traffic exhausts was constructed, using retrospective information on traffic density close to all home and school addresses since birth; this index was also calculated for the 0–3 years age period to investigate the effect of early exposures.
Main results: Adjusted on environmental tobacco smoke, personal and parental allergy, and several confounders, lifelong exposure was not associated with asthma. In contrast, associations before age of 3 were significant: odds ratios for tertiles 2 and 3 of the exposure index, relative to tertile 1, exhibited a positive trend (1.48 (95%CI = 0.7 to 3.0) and 2.28 (1.1 to 4.6)), with greater odds ratios among subjects with positive skin prick tests.
Conclusions: These results suggest that traffic related pollutants might have contributed to the asthma epidemic that has taken place during the past decades among children.
The association between smoking and asthma or wheeze has been extensively studied in cross sectional studies, but evidence from large prospective cohort studies on the incidence of asthma during adolescence is scarce.
We report data from a cohort study in two German cities, Dresden and Munich. The study population (n = 2936) was first studied in 1995/6 at age 9–11 years as part of phase II of the International Study of Asthma and Allergies in Childhood (ISAAC II) and followed up in 2002/3. At baseline the parents completed a questionnaire and children underwent clinical examination and blood sampling. At follow up the young adults completed questionnaires on respiratory health, living, and exposure conditions. Incidence risk ratios (IRR) were calculated and adjusted for potential confounders using a modified Poisson regression approach.
The adjusted IRR for incident wheeze for active smokers compared with non‐smokers was 2.30 (95% confidence interval (CI) 1.88 to 2.82). The adjusted IRR was slightly higher for incident wheeze without a cold (2.76, 95% CI 1.99 to 3.84) and the incidence of diagnosed asthma (2.56, 95% CI 1.55 to 4.21). Analysis of duration and intensity of active smoking indicated dose dependent associations. Stratified analyses showed that the risk of incident wheeze without a cold in atopic smokers increased with decreasing plasma α1‐antitrypsin levels at baseline (1.64, 95% CI 1.22 to 2.20 per interquartile range).
Active smoking is an important risk factor for the incidence of asthma during adolescence. Relatively lower plasma levels of α1‐antitrypsin, although well above currently accepted thresholds, may increase susceptibility to respiratory disease among atopic smokers.
asthma; incidence; smoking; adolescence; α1‐antitrypsin
Results from studies of traffic and childhood asthma have been inconsistent, but there has been little systematic evaluation of susceptible subgroups. In this study, we examined the relationship of local traffic-related exposure and asthma and wheeze in southern California school children (5–7 years of age). Lifetime history of doctor-diagnosed asthma and prevalent asthma and wheeze were evaluated by questionnaire. Parental history of asthma and child’s history of allergic symptoms, sex, and early-life exposure (residence at the same home since 2 years of age) were examined as susceptibility factors. Residential exposure was assessed by proximity to a major road and by modeling exposure to local traffic-related pollutants. Residence within 75 m of a major road was associated with an increased risk of lifetime asthma [odds ratio (OR) = 1.29; 95% confidence interval (CI), 1.01–1.86], prevalent asthma (OR = 1.50; 95% CI, 1.16–1.95), and wheeze (OR = 1.40; 95% CI, 1.09–1.78). Susceptibility increased in long-term residents with no parental history of asthma for lifetime asthma (OR = 1.85; 95% CI, 1.11–3.09), prevalent asthma (OR = 2.46; 95% CI, 0.48–4.09), and recent wheeze (OR = 2.74; 95% CI, 1.71–4.39). The higher risk of asthma near a major road decreased to background rates at 150–200 m from the road. In children with a parental history of asthma and in children moving to the residence after 2 years of age, there was no increased risk associated with exposure. Effect of residential proximity to roadways was also larger in girls. A similar pattern of effects was observed with traffic-modeled exposure. These results indicate that residence near a major road is associated with asthma. The reason for larger effects in those with no parental history of asthma merits further investigation.
air pollution; asthma; child; epidemiology; traffic
Poorly controlled asthma can lead to maternal and fetal complications. Despite the known risks of poorly controlled asthma during pregnancy and the need for stepping up therapy when appropriate, there are concerns that management is suboptimal in primary care.
Our objective was to investigate the management of asthma during pregnancy by general practitioners providing shared maternity care.
A pre-piloted, anonymous mail survey was sent to all general practitioners (n = 842) involved in shared maternity care at six maternity hospitals in Victoria, Australia. Respondents were asked about their perceived safety of individual asthma medications during pregnancy. Approach to asthma management during pregnancy was further explored using scenarios of pregnant women with stable and deteriorating asthma and poor medication adherence.
Inhaled corticosteroids (ICS) were perceived to be the safest and were the preferred preventive medication in first trimester (74.1%), whilst leukotriene receptor antagonists were the least preferred (2.9%). A quarter (25.8%) of respondents would stop or decrease patients' ICS doses during pregnancy, even when their asthma was well controlled by current therapy. In addition, 12.1% of respondents were not sure how to manage deteriorating asthma during pregnancy and opted to refer to another health professional. Almost half the respondents (48.9%) reported encountering medication nonadherence during pregnancy.
A lack of confidence and/or knowledge among general practitioners in managing deteriorating asthma in pregnancy was observed despite a good understanding of the safety of asthma medications during pregnancy, compliance with evidence-based guidelines in the selection of preventive medications, and self reported good asthma knowledge.
Improved survival after childhood cancer raises concerns over the possible long-term reproductive health effects of cancer therapies. We investigated whether children of female childhood cancer survivors are at elevated risk of being born preterm or exhibiting restricted fetal growth and evaluated the associations of different cancer treatments on these outcomes.
Using data from the Childhood Cancer Survivor Study, a large multicenter cohort of childhood cancer survivors, we studied the singleton live births of female cohort members from 1968 to 2002. Included were 2201 children of 1264 survivors and 1175 children of a comparison group of 601 female siblings. Data from medical records were used to determine cumulative prepregnancy exposures to chemotherapy and radiotherapy. Logistic regression was used to estimate odds ratios (ORs) for the association between quantitative therapy exposures and preterm (<37 weeks) birth, low birth weight (<2.5 kg), and small-for-gestational-age (SGA) (lowest 10th percentile) births. All statistical tests were two-sided.
Survivors’ children were more likely to be born preterm than the siblings’ children (21.1% versus 12.6%; OR = 1.9, 95% confidence interval [CI] = 1.4 to 2.4; P<.001). Compared with the children of survivors who did not receive any radiotherapy, the children of survivors treated with high-dose radiotherapy to the uterus (>500 cGy) had increased risks of being born preterm (50.0% versus 19.6%; OR = 3.5, 95% CI = 1.5 to 8.0; P = .003), low birth weight (36.2% versus 7.6%; OR = 6.8, 95% CI = 2.1 to 22.2; P = .001), and SGA (18.2% versus 7.8%; OR = 4.0, 95% CI = 1.6 to 9.8; P = .003). Increased risks were also apparent at lower uterine radiotherapy doses (starting at 50 cGy for preterm birth and at 250 cGy for low birth weight).
Late effects of treatment for female childhood cancer patients may include restricted fetal growth and early births among their offspring, with risks concentrated among women who receive pelvic irradiation.