Background: Bisphenol A (BPA), an endocrine-disrupting chemical that is routinely detected in > 90% of Americans, promotes experimental asthma in mice. The association of prenatal BPA exposure and wheeze has not been evaluated in humans.
Objective: We examined the relationship between prenatal BPA exposure and wheeze in early childhood.
Methods: We measured BPA concentrations in serial maternal urine samples from a prospective birth cohort of 398 mother–infant pairs and assessed parent-reported child wheeze every 6 months for 3 years. We used generalized estimating equations with a logit link to evaluate the association of prenatal urinary BPA concentration with the dichotomous outcome wheeze (wheeze over the previous 6 months).
Results: Data were available for 365 children; BPA was detected in 99% of maternal urine samples during pregnancy. In multivariable analysis, a one-unit increase in log-transformed creatinine-standardized mean prenatal urinary BPA concentration was not significantly associated with child wheeze from birth to 3 years of age, but there was an interaction of BPA concentration with time (p = 0.003). Mean prenatal BPA above versus below the median was positively associated with wheeze at 6 months of age [adjusted odds ratio (AOR) = 2.3; 95% confidence interval (CI): 1.3, 4.1] but not at 3 years (AOR = 0.6; 95% CI: 0.3, 1.1). In secondary analyses evaluating associations of each prenatal BPA concentration separately, urinary BPA concentrations measured at 16 weeks gestation were associated with wheeze (AOR = 1.2; 95% CI: 1.0, 1.5), but BPA concentrations at 26 weeks of gestation or at birth were not.
Conclusions: Mean prenatal BPA was associated with increased odds of wheeze in early life, and the effect diminished over time. Evaluating exposure at each prenatal time point demonstrated an association between wheeze from 6 months to 3 years and log-transformed BPA concentration at 16 weeks gestation only.
bisphenol A; BPA; child; cotinine; prenatal; tobacco; wheeze
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.
asthma; birth weight; fetal growth; length of gestation; wheezing
Background: In the UK and other developed countries the prevalence of asthma symptoms has increased in recent years. This is likely to be the result of increased exposure to environmental factors. A study was undertaken to investigate the association between maternal use of chemical based products in the prenatal period and patterns of wheeze in early childhood.
Methods: In the population based Avon Longitudinal Study of Parents and Children (ALSPAC), the frequency of use of 11 chemical based domestic products was determined from questionnaires completed by women during pregnancy and a total chemical burden (TCB) score was derived. Four mutually exclusive wheezing patterns were defined for the period from birth to 42 months based on parental questionnaire responses (never wheezed, transient early wheeze, persistent wheeze, and late onset wheeze). Multinomial logistic regression models were used to assess the relationship between these wheezing outcomes and TCB exposure while accounting for numerous potential confounding variables. Complete data for analysis was available for 7019 of 13 971 (50%) children.
Results: The mean (SD) TCB score was 9.4 (4.1), range 0–30. Increased use of domestic chemical based products was associated with persistent wheezing during early childhood (adjusted odds ratio (OR) per unit increase of TCB 1.06 (95% confidence interval (CI) 1.03 to 1.09)) but not with transient early wheeze or late onset wheeze. Children whose mothers had high TCB scores (>90th centile) were more than twice as likely to wheeze persistently throughout early childhood than children whose mothers had a low TCB score (<10th centile) (adjusted OR 2.3 (95% CI 1.2 to 4.4)).
Conclusion: These findings suggest that frequent use of chemical based products in the prenatal period is associated with persistent wheezing in young children. Follow up of this cohort is underway to determine whether TCB is associated with wheezing, asthma, and atopy at later stages in childhood.
The majority of infants in the United States are in non-parental child care, yet little is known about the effect of child care on development of obesity.
To examine the relationship between child care attendance from birth to 6 months and adiposity at 1 and 3 years of age.
We studied 1138 children from a prospective cohort of pregnant women and their offspring. The main exposure was time in child care from birth to 6 months of age, overall and by type of care: (1) child care center; (2) someone else’s home; and (3) child’s own home by nonparent. The main outcomes were weight-for-length (WFL) z score at 1 year and BMI z score at 3 years of age.
A total of 649 (57%) infants attended child care; 17% were cared for in a center, 27% in someone else’s home, and 21% in their own home by a nonparent. After adjustment for confounders, overall time in child care was associated with an increased WFL z score at 1 year and BMI z score at 3 years of age but not skinfold thicknesses. Center and own home care were not associated with the outcomes, but care in someone else’s home was associated with an increase in both the 1- and 3-year outcomes.
Child care in the first 6 months of life, especially in someone else’s home, was associated with an increased WFL z score at 1 year and BMI z score at 3 years of age.
child care; childhood obesity; nutrition; physical activity; infancy
Prenatal maternal smoking and prematurity independently affect wheezing and asthma in childhood.
We sought to evaluate the interactive effects of maternal smoking and prematurity upon the development of early childhood wheezing.
We evaluated 1448 children with smoke exposure data from a prospective urban birth cohort in Boston. Maternal antenatal and postnatal exposure was determined from standardized questionnaires. Gestational age was assessed by the first day of the last menstrual period and early prenatal ultrasound (preterm<37 weeks gestation). Wheezing episodes were determined from medical record extraction of well and ill/unscheduled visits. The primary outcome was recurrent wheezing, defined as ≥ 4 episodes of physician documented wheezing. Logistic regression models and zero inflated negative binomial regression (for number of episodes of wheeze) assessed the independent and joint association of prematurity and maternal antenatal smoking on recurrent wheeze, controlling for relevant covariates.
In the cohort, 90 (6%) children had recurrent wheezing, 147 (10%) were exposed to in utero maternal smoke and 419 (29%) were premature. Prematurity (odds ratio [OR] 2.0; 95% CI, 1.3-3.1) was associated with an increased risk of recurrent wheezing, but in utero maternal smoking was not (OR 1.1, 95% CI 0.5-2.4). Jointly, maternal smoke exposure and prematurity caused an increased risk of recurrent wheezing (OR 3.8, 95% CI 1.8-8.0). There was an interaction between prematurity and maternal smoking upon episodes of wheezing (p=0.049).
We demonstrated an interaction between maternal smoking during pregnancy and prematurity on childhood wheezing in this urban, multiethnic birth cohort.
Smoking; Prematurity; Wheeze
To examine the relation between pertussis vaccination and the prevalence of wheezing illnesses in young children.
Prospective cohort study.
Three former health districts comprising Avon Health Authority.
9444 of 14 138 children enrolled in the Avon longitudinal study of pregnancy and childhood and for whom data on wheezing symptoms, vaccination status, and 15 environmental and biological variables were available.
Main outcome measures
Episodes of wheezing from birth to 6 months, 7-18 months, 19-30 months, and 31-42 months. These time periods were used to derive five categories of wheezing illness: early wheezing (not after 18 months); late onset wheezing (after 18 months); persistent wheezing (at every time period); recurrent wheezing (any combination of two or more episodes for each period); and intermittent wheezing (any combination of single episodes of reported wheezing). These categories were stratified according to parental self reported asthma or allergy.
Unadjusted comparisons of the defined wheezing illnesses in vaccinated and non-vaccinated children showed no significant association between pertussis vaccination and any of the wheezing outcomes regardless of stratification for parental asthma or allergy. Wheeze was more common in non-vaccinated children at 18 months, and there was a tendency for late onset wheezing to be associated with non-vaccination in children whose parents did not have asthma, but this was not significant. After adjustment for environmental and biological variables, logistic regression analyses showed no significant increased relative risk for any of the wheezing outcomes in vaccinated children: early wheezing (0.99, 95% confidence interval 0.80 to 1.23), late onset wheezing (0.85, 0.69 to 1.05), persistent wheezing (0.91, 0.47 to 1.79), recurrent wheezing (0.96, 0.72 to 1.26), and intermittent wheezing (1.06, 0.81 to 1.37).
No evidence was found that pertussis vaccination increases the risk of wheezing illnesses in young children. Further follow up of this population with objective measurement of allergy and bronchial responsiveness is planned to confirm these observations.
Key messagesPertussis vaccination has been proposed as a risk factor for the development of asthma and atopyThere was no evidence for increased wheezing illnesses in young children who were vaccinated against pertussis compared with non-vaccinated childrenFollow up studies of this population will help to further clarify the relation between early infections and vaccination and the development of atopic diseases, including asthmaLarge scale longitudinal studies beginning in pregnancy offer the opportunity to examine complex interactions between genetics and the environment in the cause of common childhood diseases
Our aim was to determine the extent to which infant growth – in weight-for-length – from birth to 6 months is associated with systolic blood pressure (SBP) at 3 years, and to determine whether this association varies with birth size.
In 530 children from the prospective cohort Project Viva, we measured birth length and 6-month weight and length with research standard instruments and SBP at age 3 years with a Dinamap automated recorder. We derived weight-for-length z-scores (WFL-z) and analyzed data with mixed effect regression models.
Mean (SD) WFL-z was 0.47(0.75) at birth and 0.70(0.96) at 6 months. Mean (SD) SBP at 3 years was 91.7(9.4) mmHg. After adjusting for confounding variables and birth WFL-z, child SBP was 1.0mmHg (95% CI 0.2, 1.8) higher for each z-score increment in 6-month WFL-z. SBP of children in the lowest birth WFL-z quartile and the highest 6-month WFL-z quartile was 5.5mmHg (95% CI 2.6, 8.4) higher than of children in the highest birth and lowest 6-month WFL-z quartiles.
More rapid increase in weight-for-length, a measure of adiposity, in the first 6 months of life is associated with higher early childhood systolic blood pressure, particularly in children who are thin at birth.
Little is known about mouse allergen exposure in home environments and the development of wheezing, asthma and atopy in childhood.
To examine the relation between mouse allergen exposure and wheezing, atopy, and asthma in the first 7 years of life.
Prospective study of 498 children with parental history of allergy or asthma followed from birth to age 7 years, with longitudinal questionnaire ascertainment of reported mouse exposure and dust sample mouse urinary protein allergen levels measured at age 2–3 months.
Parental report of mouse exposure in the first year of life was associated with increased risk of transient wheeze and wheezing in early life. Current report of mouse exposure was also significantly associated with current wheeze throughout the first 7 years of life in the longitudinal analysis (P = 0.03 for overall relation of current mouse to current wheeze). However, early life mouse exposure did not predict asthma, eczema or allergic rhinitis at age 7 years. Exposure to detectable levels of mouse urinary protein in house dust samples collected at age 2–3 months was associated with a twofold increase in the odds of atopy (sensitization to >=1 allergen) at school age (95% confidence interval for odds ratio = 1.1–3.7; P = 0.03 in a multivariate analysis.
Among children with parental history of asthma or allergies, current mouse exposure is associated with increased risk of wheeze during the first 7 years of life. Early mouse exposure was associated with early wheeze and atopy later in life.
childhood asthma; indoor allergens; mouse allergen
AIMS: To document the prevalence of, and identify risk factors for, recurrent wheezing treated with bronchodilators in the first year of life. METHODS: Parental history and neonatal data were collected prospectively in a regional cohort of very preterm infants (< 33 weeks). Data on maternal smoking, siblings at home, breast feeding, respiratory symptoms, and hospital re-admissions were documented at 12 months. RESULTS: Outcome data were available for 525/560 (95%) of survivors. The incidence of recurrent wheeze was 76/525 (14.5%) in very preterm infants and 20/657 (3%) in a cohort of term newborns. Significant risk factors for recurrent wheeze in very preterm infants were parental history of asthma, maternal smoking, siblings at home, neonatal oxygen supplementation at 28 days, 36, and 40 weeks of gestation. CONCLUSIONS: Wheezing respiratory illnesses are common in very preterm infants. The factors involved are similar to those in more mature infants, with the addition of immaturity and neonatal lung injury.
Prematurity (<37 weeks) has been inconsistently associated with asthma and wheezing. Chorioamnionitis may promote both prematurity and inflammatory pathways in infants’ airways.
To investigate the relationship of prematurity and chorioamnionitis with the development of early childhood recurrent wheezing.
The Boston Birth Cohort (n=1096) were followed prospectively from birth to a mean age of 2.2±2 years. Perinatal and postnatal clinical data and placental pathology were collected. The primary outcome was recurrent wheezing (≥2 physician documented episodes). Secondary outcomes included physician diagnosed asthma, food allergy and eczema. Preterm children were grouped by gestational age into moderately (33-36.9 weeks) and very preterm (<33 weeks) with and without chorioamnionitis, and compared to term children without chorioamnionitis (reference group). Chorioamnionitis was diagnosed either by intrapartum fever or by placental histology findings. Logistic regression models were preformed to investigate the independent and joint associations of degree of prematurity and chorioamnionitis.
Prematurity was associated with recurrent wheezing (OR:1.7, 95%CI:1.2-2.6). However, when subjects were grouped by degree of prematurity with or without chorioamnionitis, the highest risk of wheezing (OR:4.0, 95%CI:2.0-8.0) and physician diagnosed asthma (OR:4.4 95%CI:2.2-8.7) was present in the very preterm children with chorioamnionitis. The effect on both wheezing (OR:5.4, 95%CI:2.4-12.0) and asthma (OR:5.2, 95%CI:2.3-11.9) was greater in African Americans. Neither prematurity nor chorioamnionitis were associated with food allergy or eczema.
We found a strong joint effect of prematurity and chorioamnionitis on early childhood wheezing. This effect was stronger in African Americans.
Chorioamnionitis may increase the risk of recurrent wheezing in very low birth weight infants.
Chorioamnionitis; prematurity; recurrent wheezing
Respiratory syncytial virus (RSV) infection in infancy is associated with subsequent recurrent wheezing.
A retrospective cohort study examined children born at ≥32 weeks gestation between 1996–2004. All children were enrolled in an integrated health care delivery system in Northern California and were followed through the fifth year of life. The primary endpoint was recurrent wheezing in the fifth year of life and its association with laboratory-confirmed, medically-attended RSV infection during the first year, prematurity, and supplemental oxygen during birth hospitalization. Other outcomes measured were recurrent wheezing quantified through outpatient visits, inpatient hospital stays, and asthma prescriptions.
The study sample included 72,602 children. The rate of recurrent wheezing in the second year was 5.6% and fell to 4.7% by the fifth year. Recurrent wheezing rates varied by risk status: the rate was 12.5% among infants with RSV hospitalization, 8% among infants 32–33 weeks gestation, and 18% in infants with bronchopulmonary dysplasia. In multivariate analyses, increasing severity of respiratory syncytial virus infection was significantly associated with recurrent wheezing in year 5; compared with children without RSV infection in infancy, children who only had an outpatient RSV encounter had an adjusted odds ratio of 1.38 (95% CI,1.03–1.85), while children with a prolonged RSV hospitalization had an adjusted odds ratio of 2.59 (95% CI, 1.49–4.50).
Laboratory-confirmed, medically attended RSV infection, prematurity, and neonatal exposure to supplemental oxygen have independent associations with development of recurrent wheezing in the fifth year of life.
Respiratory syncytial virus; Recurrent wheezing; Prematurity
Background: The hygiene hypothesis states that insufficient exposure to certain infectious agents during childhood increases the risk of developing asthma and atopic diseases. Improvements in hygiene levels may be partly responsible for this decline in exposure.
Aims: To assess whether hygiene levels in infancy are associated with wheeze and/or atopic eczema, independent of a number of possible confounding factors.
Methods: Data were gathered from the Avon Longitudinal Study of Parents and Children (ALSPAC). Parental self completion questionnaires provided symptom data on infant wheeze and atopic eczema at 0–6 months and 30–42 months, respectively. A simple hygiene score was derived using questionnaire responses at 15 months, which ranged from least hygienic to most hygienic. Multivariable logistic regression models analysed the effect of hygiene scores on health outcomes, while adjusting for a number of important confounding variables.
Results: Increasing hygiene scores were independently associated with wheezing (OR = 1.04; 95% CI: 1.00 to 1.08) and atopic eczema (OR = 1.04; 95% CI: 1.01 to 1.07) between 30 and 42 months, but not in the first six months. The odds ratio was higher for atopic eczema if the rash was reported to have become sore and oozy (OR = 1.09; 95% CI: 1.02 to 1.16).
Conclusions: High levels of hygiene at 15 months of age were independently associated with wheeze and atopic eczema reported between 30 and 42 months, and there was an increased risk for children with more severe eczema during this period. The importance of hygiene in public health should not be dismissed; however, the creation of a sterile environment through excessive cleanliness may potentially be harmful to the immune system.
Wheezing during infancy has been linked to early loss of pulmonary function. We prospectively investigated the relation between bronchial hyperresponsiveness (BHR) and progressive impairment of pulmonary function in a cohort of asthmatic infants followed until age 9 years. We studied 129 infants who had had at least three episodes of wheezing. Physical examinations, baseline lung function tests and methacholine challenge tests were scheduled at ages 16 months and 5, 7 and 9 years. Eighty-three children completed follow-up. Twenty-four (29%) infants had wheezing that persisted at 9 years of age. Clinical outcome at age 9 years was significantly predicted by symptoms at 5 years of age and by parental atopy. Specific airway resistance (sRaw) was altered in persistent wheezers as early as 5 years of age, and did not change thereafter. Ninety-five per cent of the children still responded to methacholine at the end of follow-up. The degree of BHR at 9 years was significantly related to current clinical status, baseline lung function, and parental atopy. BHR at 16 months and 5 years of age did not predict persistent wheezing between 5 and 9 years of age, or the final degree of BHR, but it did predict altered lung function. Wheezing that persists from infancy to 9 years of age is associated with BHR and to impaired lung function. BHR itself is predictive of impaired lung function in children, strongly pointing to early airway remodeling in infantile asthma.
The incidence of wheeze is unknown and the role of early life wheeze in subsequent health is not clearly understood. Our goal was to calculate the age-specific incidence of wheeze and determine whether wheezing at particular times in early life was predictive of abnormal airway hyperresponsiveness (AHR), percent predicted FEV1 and current asthma at age 6 years.
Using data from a birth cohort study with annual report of wheezing (Childhood Allergy Study) and spirometry and methacholine challenge at age 6 years, the age-specific incidence of wheeze was determined using Kaplan-Meier estimates. Logistic and linear regression models were used to assess the associations between the presence of age-specific wheezing and the outcomes of current asthma, AHR and percent predicted FEV1 at age 6 years.
The 6-year cumulative incidence of wheezing was higher for boys (66.2%, 95% CI 59.8%, 72.6%) than girls (47.6% 95% CI 41.4%, 53.8%). There was no age when wheezing was more strongly associated with either AHR or percent predicted FEV1 at 6 years. Only wheeze in the fifth year among males and in females, both wheezing in the fourth and fifth years were positively predictive of current asthma at age 6. This is likely due to the definition of current asthma (ever doctor diagnosis and either medication or symptoms in last year). Eczema, parental asthma history and total cord blood IgE did not affect these associations.
Wheezing at any particular time in early life may not be predictive of early childhood lung function.
Obesity and asthma have increased in westernised countries. Maternal obesity may increase childhood asthma risk. If this relation is causal it may be mediated through factors associated with maternal adiposity, such as fetal development, pregnancy complications or infant adiposity. We investigated the relationships of maternal BMI and fat mass with childhood wheeze and examined the influences of infant weight gain and childhood obesity.
Maternal pre-pregnancy BMI and estimated fat mass (from skinfold thicknesses) were related to asthma, wheeze and atopy in 940 children. Transient or persistent/late wheeze was classified using questionnaire data collected at ages 6, 12, 24 and 36 months and 6 years. At 6 years, skin prick testing was conducted and exhaled nitric oxide and spirometry measured. Infant adiposity gain was calculated from skinfold thickness at birth and 6 months.
Greater maternal BMI and fat mass were associated with increased childhood wheeze (RR 1.08 per 5 kg m−2, p=0.006; RR 1.09 per 10 kg, p=0.003); these reflected associations with transient wheeze (RR 1.11, p=0.003; RR 1.13, p=0.002, respectively) but not with persistent wheeze or asthma. Infant adiposity gain was associated with persistent wheeze but not significantly. Adjusting for infant adiposity gain or BMI at 3 or 6 years did not reduce the association between maternal adiposity and transient wheeze. Maternal adiposity was not associated with offspring atopy, exhaled nitric oxide, or spirometry.
Greater maternal adiposity is associated with transient wheeze but not asthma or atopy, suggesting effects upon airway structure/function but not allergic predisposition.
adiposity; body mass index; obesity; asthma; allergic sensitisation
Paracetamol (PCM) and antibiotic (ATB) use have been associated with risk for wheezing and asthma in children. The aim of this study was to verify the association of recurrent wheezing (≥3 episodes) in infancy and use of ATB or PCM in the first year of life.
Cross-sectional study using a standardized and validated questionnaire (EISL: Estudio Internacional sobre Sibilancias en Lactantes) with questions: Has your baby had wheezing or whistling in the chest area or bronchitis in the first 12 months of life? Has your baby had 3 or more wheezing episodes in the first year of life? How often has your baby used antibiotics in the first year of life? How often has your baby used paracetamol in the first year of life? Parents of infants, ages 12 to 15 months that attended to Health Centers for routine immunization were interviewed between September 2009 to September 2010 (EISL Phase III). Risk was demonstrated using Odds ratio and 95% CI.
One thousand and 3 parents participated in the survey and 19.8% of infants had recurrent wheezing starting at 6.1 ± 3 months. The use of PCM was not related to the presence of recurrent wheezing [No PCM (OR = 0.91; 95% CI, 0.38-2.19; P = 0.83), PCM 1–3 times (OR = 1.21; 95% CI, 0.77-1.91; P = 0.4), PCM 4–6 times (OR = 1.21; 95% CI, 0.77-1.9; P = 0.41) and PCM ≥7 times (OR = 0.76; 95% CI, 0.51-1.13; P = 0.17)], while more frequent use of ATB reduced the risk of recurrent wheezing in the first year of life [No ATB (OR = 2.18; 95% CI, 1.35-3.51; P = 0.001), ATB 1–3 times (OR = 1.39; 95% CI, 0.93-2.07; P = 0.1), ATB 4–6 times (OR = 0.37; 95% CI, 0.22-0.62; P = 0.001) and PCM≥7 times (OR = 0.22; 95% CI, 0.07-0.66; P = 0.001)].
The frequent use of ATB reduced the risk of recurrent wheezing in the first year of life unlike PCM that was not associated with recurrent wheezing in this study population.
A number of studies have linked obesity with asthma in adults and children. Few longitudinal studies have evaluated the effect of maternal pre-pregnancy obesity on either asthma or early childhood respiratory morbidity, and these have not been in urban, nonwhite populations. We sought to determine whether pre-pregnancy obesity was associated with recurrent wheezing in an urban, nonwhite population. This study includes 1,191 children from the Boston Birth Cohort (1998–present) followed prospectively to a mean age of 3.0 ± 2.4 years with study visits aligned with the pediatric primary care schedule. Multivariate logistic regression was used to evaluate the associations of maternal pre-pregnancy obesity (body mass index ≥30) with recurrent wheezing (≥4 lifetime episodes). Secondary outcomes included log-transformed cord-blood immunoglobulin E (Phadia), and physician diagnoses of eczema and food allergy. Pre-pregnancy obesity was present in 20.7% of mothers. Of the 1,191 children, 60 (5%) developed recurrent wheezing. Children of obese mothers had an increased risk of recurrent wheezing (adjusted odds ratio, 95% confidence interval: 3.51, 1.68–7.32). These associations persisted even after adjustment for fetal growth status. In contrast, maternal obesity was not associated with eczema or food allergy, and was inversely associated with log cord-blood immunoglobulin E (β, 95% confidence interval: −0.34, −0.66 to −0.02). In this predominantly urban, multiracial/ethnic birth cohort, maternal pre-pregnancy obesity was associated with an increased risk of recurrent wheezing. This association was not explained by fetal growth or increased atopy. Maternal pre-pregnancy obesity is a prevalent risk factor for respiratory morbidity in this urban, nonwhite population.
Some studies show that greater parental control over children’s eating habits predicts later obesity, but it is unclear whether parents are reacting to infants who are already overweight.
To examine the longitudinal association between maternal feeding restriction at age 1 and body mass index (BMI) at age 3 and the extent to which the association is explained by weight for length (WFL) at age 1.
We studied 837 mother–infant pairs from a prospective cohort study. The main exposure was maternal feeding restriction at age 1, defined as agreeing or strongly agreeing with the following question: “I have to be careful not to feed my child too much.” We ran multivariable linear regression models before and after adjusting for WFL at age 1. All models were adjusted for parental and child sociodemographic characteristics.
100 (12.0%) mothers reported feeding restriction at age 1. Mean (SD) WFL z-score at age 1 was 0.32 (1.01), and BMI z-score at age 3 was 0.43 (1.01). Maternal feeding restriction at age 1 was associated with higher BMI z-score at age 3 before (β 0.26 (95% CI 0.05 to 0.48)) but not after (β 0.00 (95% CI −0.17 to 0.18)) adjusting for WFL z-score at age 1. Each unit of WFL z-score at age 1 was associated with an increment of 0.57 BMI z-score units at age 3 (95% CI 0.51 to 0.62).
We found that maternal feeding restriction was associated with children having a higher BMI at age 3 before, but not after, adjusting for WFL at age 1. One potential reason may be that parents restrict the food intake of infants who are already overweight.
Rationale: Critical periods for programming early wheeze risk may include pregnancy and infancy. Effects of timing remain poorly understood.
Objectives: Associations among prenatal and postnatal maternal stress and children’s wheeze were prospectively examined in 653 families. Effect modification by maternal sensitization was also examined.
Methods: Stress was indexed by a maternal negative life events (NLEs) score (range, 0–9) ascertained during pregnancy and between 1 and 2 years postpartum. Mothers reported child wheeze every 3 months up to age 2 years. Relationships of prenatal and postnatal maternal NLEs with repeated wheeze (≥2 episodes) were examined using logistic regression adjusting for covariates. Penalized splines were implemented to explore possible nonlinear associations. We also examined the interaction between prenatal stress and maternal sensitization indexed by allergen-specific IgE from maternal prenatal serum.
Measurements and Main Results: Adjusted models considering prenatal or postnatal NLEs alone both showed an exposure-response relationship between higher stress and child wheeze. When considering prenatal and postnatal stress concurrently, only children of mothers with high stress in both periods were significantly more likely to wheeze (adjusted odds ratio, 3.04; 95% confidence interval, 1.67–5.53) than children of mothers reporting low stress in both periods. Associations between high prenatal stress and wheeze were significant in children born to nonsensitized mothers (any IgE <0.35 kU/L) but not in the sensitized group (P for interaction = 0.03).
Conclusions: Although children have heightened sensitivity to maternal stress in utero and in early childhood, those with higher stress in both periods were particularly at risk for wheeze. The prenatal maternal immune milieu modified effects.
negative life events; stress; pregnancy; maternal sensitization; childhood wheeze
Breastfeeding clearly protects against early wheezing, but recent data suggest that it may increase later risk of atopic disease and asthma.
To examine the relationship between breastfeeding and later asthma and allergy outcomes using data from the Avon Longitudinal Study of Parents and Children, a large birth cohort in the United Kingdom.
We used adjusted logistic regression models to evaluate the association between breastfeeding and atopy at age 7 years, bronchial responsiveness to methacholine at age 8 years, and wheeze at ages 3 and 7½ years. Bayesian methods were used to assess the possibility of bias due to an influence of early wheezing on duration of breastfeeding as well as selection bias.
Breastfeeding was protective for wheeze in the first 3 years of life (OR =0.80, 95% CI 0.70-0.90 for 6+ months relative to never) but not wheeze (OR=0.98, 95% CI 0.79-1.22), atopy (OR=1.12, 95% CI 0.92-1.35) or BHR (1.07, 95% CI 0.82-1.40) at ages 7-8 years. Bayesian models adjusting for the longer duration of breastfeeding among children with wheezing in early infancy gave virtually identical results.
We did not find consistent evidence for either a deleterious effect or a protective effect of breastfeeding on later risk of allergic disease in a large prospective birth cohort of children with objective outcome measures and extensive data on potential confounders and effect modifiers. Neither reverse causation nor loss to follow-up appears to have materially biased our results.
Breastfeeding does not increase the risk of asthma or atopy in children, even when their mothers are asthmatic.
This study supports the evidence that breastfeeding does not adversely affect children with regard to asthma and other allergic outcomes. Breastfeeding’s protective role against early wheezing is a benefit for respiratory health.
asthma; atopy; breastfeeding; bronchial hyperresponsiveness; allergy
Tobacco smoke and genetic susceptibility are risk factors for asthma and wheezing. The aim of this study was to investigate whether there is a combined effect of interleukin-13 gene (IL13) polymorphisms and tobacco smoke on persistent childhood wheezing and asthma.
In the Isle of Wight birth cohort (UK, 1989–1999), five IL13 single nucleotide polymorphisms (SNPs): rs1800925 (-1112C/T), rs2066960, rs1295686, rs20541 (R130Q) and rs1295685 were genotyped. Parents were asked whether their children had wheezed in the last 12 months at ages 1, 2, 4 and 10 years. Children who reported wheeze in the first 4 years of life and also had wheezing at age 10 were classified as early-onset persistent wheeze phenotype; non-wheezers never wheezed up to age 10. Persistent asthma was defined as having a diagnosis of asthma both during the first four years of life and at age 10. Logistic regression methods were used to analyze data on 791 children with complete information. Potential confounders were gender, birth weight, duration of breast feeding, and household cat or dog present during pregnancy.
Maternal smoking during pregnancy was associated with early-onset persistent wheeze (OR 2.93, p < 0.0001); polymorphisms in IL13 were not (OR 1.15, p = 0.60 for the common haplotype pair). However, the effect of maternal smoking during pregnancy was stronger in children with the common IL13 haplotype pair compared to those without it (OR 5.58 and OR 1.29, respectively; p for interaction = 0.014). Single SNP analysis revealed a similar statistical significance for rs20541 (p for interaction = 0.02). Comparable results were observed for persistent childhood asthma (p for interaction = 0.03).
This is the first report that shows a combined effect of in utero exposure to smoking and IL13 on asthma phenotypes in childhood. The results emphasize that genetic studies need to take environmental exposures into account, since they may explain contradictory findings.
The rise in asthma prevalence over the last few decades may be due changes in pre-natal or early life environment including maternal diet during pregnancy. Previous studies have found associations between individual foods or nutrients consumed during pregnancy and asthma or wheeze in children, but these may be confounded by overall dietary pattern.
To determine if overall maternal dietary pattern during pregnancy is associated with recurrent wheeze in children.
1376 mother-infant pairs from Project Viva, a longitudinal pre-birth cohort, who had responses for food frequency questionnaires in the 1st and 2nd trimester and outcome data at 3 years of age were included. Multivariable logistic regression was used to look at associations between dietary pattern and the primary outcome of recurrent wheeze at 3 years. Overall dietary pattern was examined using Mediterranean diet score, Alternate Healthy Eating Index modified for pregnancy (AHEI-P), and principal components analysis to look at Western and Prudent diets.
None of these dietary patterns was associated with the primary outcome of recurrent wheeze in children in either the crude or in the multivariable models (multivariable model: OR per one point increase Mediterranean diet 0.98 [95% CI 0.89, 1.08] AHEI-P 1.07 [0.87, 1.30] Prudent 1.02 [0.83, 1.26] Western 0.98 [0.81, 1.19]).
Overall dietary pattern during pregnancy is not associated with recurrent wheeze in this cohort. Maternal intake of individual nutrients may be more important determinants ofoffspring wheeze-associated illness than is dietary pattern.
asthma; dietary pattern; Mediterranean diet; healthy diet; principal components; childhood wheeze; pregnancy
Studies have found that exposure to mice is highly prevalent among children with asthma living in urban areas.
To examine the relationship between exposure to mice and wheeze in the first year of life.
We conducted an ongoing prospective birth cohort study of 498 children with a history of allergy or asthma in at least 1 parent living in metropolitan Boston (the Home Allergens and Asthma Study).
In a multivariate analysis, infants whose parents reported exposure to mice in the household had nearly twice the odds of developing any wheeze in the first year of life as children without exposure (odds ratio [OR], 1.83; 95% confidence interval [CI], 1.14–2.95; P = .01). Other variables associated with wheeze in the first year of life included low birth weight (OR, 1.77; 95% CI, 1.06–2.95; P = .03), having at least 1 lower respiratory tract illness (OR, 5.59; 95% CI, 3.46–9.04; P < .001), exposure to high levels of endotoxin at age 2 to 3 months (fourth quartile compared with first quartile: OR, 2.32; 95% CI, 1.19–4.54; P = .01), and exposure to cockroach allergen of 0.05 U/g of dust or more at age 2 to 3 months (OR, 1.83; 95% CI, 1.09–3.08; P = .02).
Among children with a parental history of asthma or allergies, exposure to mice is associated with wheeze in the first year of life, independent of other factors.
relationship between infant feeding and childhood asthma is
controversial. This study tested the hypothesis that the relation between breast feeding and childhood asthma is altered by the presence
of maternal asthma.
non-selected newborn infants (n=1246) were enrolled at birth. Asthma
was defined as a physician diagnosis of asthma plus asthma symptoms
reported on ⩾2 questionnaires at 6, 9, 11or 13 years. Recurrent
wheeze (⩾4 episodes in the past year) was reported by questionnaire
at seven ages in the first 13 years of life. Duration of exclusive
breast feeding was based on prospective physician reports or parental
questionnaires completed at 18 months. Atopy was assessed by skin test
responses at the age of 6years.
relationship between breast feeding, asthma, and wheeze differed with
the presence or absence of maternal asthma and atopy in the child.
After adjusting for confounders, children with asthmatic mothers were
significantly more likely to have asthma if they had been exclusively
breast fed (OR 8.7, 95% CI 3.4 to 22.2). This relationship was only
evident for atopic children and persisted after adjusting for
confounders. In contrast, the relation between recurrent wheeze and
breast feeding was age dependent. In the first 2 years of life
exclusive breast feeding was associated with significantly lower rates
of recurrent wheeze (OR 0.45, 95% CI 0.2 to 0.9), regardless of the
presence or absence of maternal asthma or atopy in the child. Beginning
at the age of 6 years, exclusive breast feeding was unrelated to
prevalence of recurrent wheeze, except for children with asthmatic
mothers in whom it was associated with a higher odds ratio for wheeze
(OR 5.7, 95% CI 2.3 to 14.1), especially if the child was atopic.
relationship between breast feeding and asthma or recurrent wheeze
varies with the age of the child and the presence or absence of
maternal asthma and atopy in the child. While associated with
protection against recurrent wheeze early in life, breast feeding is
associated with an increased risk of asthma and recurrent wheeze
beginning at the age of 6 years, but only for atopic children with
investigate the relation between total serum IgE at 0.5-3 and 3-6
years, and the risk of allergic sensitisation and persistent wheezing
up to 8 years of age.
follow up study of 45 infants with highly recurrent wheezing, no
allergic symptoms, and negative skin tests.
RESULTS—In the last
follow up year, 15 children still suffered from wheezing. Five
wheeze-free and four episodically wheezing children had become
sensitised. No association was found between early (0.5-3 years) IgE z
scores and the recurrence of wheezing during follow up, or atopic
sensitisation. IgE z scores at 3-6 years were significantly higher in
children with positive skin tests (p = 0.013), but were still not
associated with recurrence of wheezing.
subjects with frequent early wheezing and no signs of atopy, early
total serum IgE measurements are not predictive of outcome.