Experimental animal models have demonstrated that one of the primary consequences of prenatal stress is increased fear and anxiety in the offspring. Few prospective human studies have evaluated the consequences of prenatal stress on anxiety during preadolescence. The purpose of this investigation is to determine the consequences of prenatal exposure to both maternal biological stress signals and psychological distress on anxiety in preadolescent children. Participants included 178 mother-child pairs. Maternal psychological distress (general anxiety, perceived stress, depression and pregnancy-specific anxiety) and biological stress signals were evaluated at 19, 25, and 31 gestational weeks. Anxiety was evaluated in the children at 6 to 9 years of age using the Child Behavior Checklist. Analyses revealed that prenatal exposure to elevated maternal cortisol, depression, perceived stress and pregnancy-specific anxiety was associated with increased anxiety in children. These associations remained after considering obstetric, sociodemographic and postnatal maternal psychological distress; factors that could influence child development. When all of the prenatal measures were considered together, cortisol and pregnancy-specific anxiety independently predicted child anxiety. Children exposed to elevated prenatal maternal cortisol and pregnancy-specific anxiety were at an increased risk for developing anxiety problems during the preadolescent period. This project identifies prenatal risk factors associated with lasting consequences for child mental health and raises the possibility that reducing maternal distress during the prenatal period will have long term benefits for child well-being.
anxiety; development; fetal programming; prenatal; cortisol; stress; pregnancy
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.
Our aim is to explore (1) whether gestational medication use, mode of delivery, and early postnatal exposure correlate with childhood asthma, (2) the dose responsiveness of such exposure, and (3) their links to early- and late-onset asthma. We conducted a matched case-control study based on the Taiwan Children Health Study, which was a nationwide survey that recruited 12-to-14-year-old school children in 14 communities. 579 mothers of the participants were interviewed by telephone. Exclusive breastfeeding protected children from asthma. Notably, childhood asthma was significantly associated with maternal medication use during pregnancy, vacuum use during vaginal delivery, recurrent respiratory tract infections, hospitalization, main caregiver cared for other children, and early daycare attendance. Exposure to these factors led to dose responsiveness in relationships to asthma. Most of the exposures revealed a greater impact on early-onset asthma, except for vacuum use and daycare attendance.
Alcohol consumption in western pregnant women is not uncommon and could be a risk factor for childhood atopic disease. However, reported alcohol intake may be unreliable, and associations are likely to be confounded.
We aimed to study the relation between prenatal alcohol exposure and atopic phenotypes in a large population-based birth cohort with the use of a Mendelian randomization approach to minimize bias and confounding.
In white mothers and children in the Avon Longitudinal Study of Parents and Children (ALSPAC) we first analyzed associations between reported maternal alcohol consumption during pregnancy and atopic outcomes in the offspring measured at 7 years of age (asthma, wheezing, hay fever, eczema, atopy, and total IgE). We then analyzed the relation of maternal alcohol dehydrogenase (ADH)1B genotype (rs1229984) with these outcomes (the A allele is associated with faster metabolism and reduced alcohol consumption and, among drinkers, would be expected to reduce fetal exposure to ethanol).
After controlling for confounders, reported maternal drinking in late pregnancy was negatively associated with childhood asthma and hay fever (adjusted odds ratio [OR] per category increase in intake: 0.91 [95% CI, 0.82-1.01] and 0.87 [95% CI, 0.78-0.98], respectively). However, maternal ADH1B genotype was not associated with asthma comparing carriers of A allele with persons homozygous for G allele (OR, 0.98 [95% CI, 0.66-1.47]) or hay fever (OR, 1.11 [95% CI, 0.71-1.72]), nor with any other atopic outcome.
We have found no evidence to suggest that prenatal alcohol exposure increases the risk of asthma or atopy in childhood.
Alcohol; ADH1B; Mendelian randomization; prenatal exposure; ALSPAC; pregnancy; birth cohort; asthma; atopy; ADH, Alcohol dehydrogenase; ALSPAC, Avon Longitudinal Study of Parents and Children (ALSPAC); GWAS, Genome Wide Association Study; PCA, Principal Components Analysis
Studies exploring the relationship between prenatal vitamin D exposure and childhood asthma have yielded conflicting results. Higher vitamin D intake during pregnancy has been shown to lower the risk of childhood wheeze, yet a study of maternal late-pregnancy serum 25-hydroxyvitamin D suggested higher serum concentrations may be associated with increased childhood asthma.
To assess the relationship between mothers’ serum 25-hydroxyvitamin D status and asthma and wheeze phenotypes in their children at age 6 years. Secondly, to explore the relationship between maternal 25-hydroxyvitamin D status and objective measures of childhood atopy and lung function.
Serum 25-hydroxyvitamin D was measured at 34 weeks’ gestation in the mothers of 860 children born at term. Wheeze was classified as either transient or persistent/late using questionnaire data collated from 6, 12, 24 and 36 months and 6 years. At 6 years spirometry was performed and atopic status was determined by skin prick testing, exhaled nitric oxide was measured in 451 and bronchial hyperresponsiveness in 216 children.
There were no significant associations between maternal late-pregnancy 25-hydroxyvitamin D status and either asthma or wheeze at age 6 years. Maternal vitamin D status was not associated with transient or persistent/late wheeze; no significant association was found between persistent/late wheeze when subdivided according to atopic status. No associations were found with skin sensitisation or lung function.
This study provides no evidence that exposure to higher concentrations of 25-hydroxyvitamin D in maternal serum during late pregnancy increases the risk of childhood asthma, wheeze or atopy.
asthma epidemiology; asthma; paediatric asthma
Maternal antenatal anxiety is associated with an increased risk of behavioral disturbances in offspring. Recent work has suggested that the effect of maternal antenatal anxiety on infant temperament at 6 months is moderated by the serotonin transporter polymorphism 5-HTTLPR, with carriers of the short allele more susceptible to the adverse behavioral outcomes of maternal antenatal anxiety. These findings, however, are yet to be replicated and extended beyond infancy. The aim of the current study was to assess this same potential moderator (5-HTTLPR) in a large population-based cohort study, and to determine whether or not the effects persist into childhood and early adolescence.
Data from the Avon Longitudinal Study of Children and Parents (ALSPAC) cohort (N = 3,946) were used to assess whether the 5-HTTLPR genotype moderated the association between self-reported maternal antenatal anxiety (Crown Crisp Index) in pregnancy, and child temperament at 6 months (Infant Temperament Questionnaire), and also later behavioral and emotional problems on the Strengths and Difficulties Questionnaire from age 4 to 13 years.
We found no evidence to suggest that the 5-HTTLPR polymorphism moderated the effects of maternal antenatal anxiety on infant temperament at 6 months or infant behavioral and emotional problems from childhood through to adolescence.
Our results, based on a large prospective community sample that assessed children from infancy to early adolescence, provide a thorough test of, but no evidence for, a genetic moderation of the effects of maternal antenatal anxiety by 5-HTTLPR.
5-HTTLPR; antenatal anxiety; gene-by-environment interaction (G×E); fetal programming; serotonin transporter
Background. Maternal distress during pregnancy increases the intrauterine level of glucocorticoids, which may have long-term health consequences for the child.
Objective. To examine if distress as a combined measure of anxiety, depression, and stress of the mother during pregnancy was associated with offspring childhood overweight at age 7.
Methods. We performed a cohort study using prospective data from 37,764 women and child dyads from the Danish National Birth Cohort (1996–2002). At a telephone interview at approximately 30 weeks gestation, the women reported whether they felt anxious, depressed, or stressed. The 95 percentile for body mass index in an international reference defined childhood overweight at any given age. Logistic regression was used for the analyses. Results. The prevalence of overweight children at 7 years of age was 9.9%. Prenatal exposure to maternal distress during pregnancy was not associated with childhood overweight at 7 years of age (adjusted OR 1.06 (95% CI 0.96; 1.18)). In analyses stratified on sex, a small tendency of overweight was seen in boys (OR 1.15 (0.99; 1.33)), but not in girls (OR 0.98 (0.85; 1.13)). Conclusions. Maternal distress during pregnancy appeared to have limited, if any, influence on the risk of overweight in offspring at 7 years of age.
Exposure to maternal anxiety predicts offspring brain development. However, because children's brains are commonly assessed years after birth, the timing of such maternal influences in humans is unclear. This study aimed to examine the consequences of antenatal and postnatal exposure to maternal anxiety upon early infant development of the hippocampus, a key structure for stress regulation. A total of 175 neonates underwent magnetic resonance imaging (MRI) at birth and among them 35 had repeated scans at 6 months of age. Maternal anxiety was assessed using the State-Trait Anxiety Inventory (STAI) at week 26 of pregnancy and 3 months after delivery. Regression analyses showed that antenatal maternal anxiety did not influence bilateral hippocampal volume at birth. However, children of mothers reporting increased anxiety during pregnancy showed slower growth of both the left and right hippocampus over the first 6 months of life. This effect of antenatal maternal anxiety upon right hippocampal growth became statistically stronger when controlling for postnatal maternal anxiety. Furthermore, a strong positive association between postnatal maternal anxiety and right hippocampal growth was detected, whereas a strong negative association between postnatal maternal anxiety and the left hippocampal volume at 6 months of life was found. Hence, the postnatal growth of bilateral hippocampi shows distinct responses to postnatal maternal anxiety. The size of the left hippocampus during early development is likely to reflect the influence of the exposure to perinatal maternal anxiety, whereas right hippocampal growth is constrained by antenatal maternal anxiety, but enhanced in response to increased postnatal maternal anxiety.
antenatal anxiety; hippocampus; magnetic resonance imaging; neonatal brain; postnatal anxiety
To examine whether prenatal occupational exposures, especially to organic solvents, are associated with atopic diseases in childhood.
The study comprised children born in Odense or Aalborg, Denmark between 1984 and 1987. Occupational job titles were derived from questionnaires filled out by the mothers when attending midwife centres. Assessment of organic solvent exposures was based on job titles selected by occupational specialists. A follow up questionnaire to the parents provided data on medical diagnoses as well as wheezing symptoms for 7844 children aged 14–18. Multivariate logistic regression analyses were performed to estimate the cumulative risk for wheezing (early wheezing not diagnosed as asthma), asthma, hay fever, and atopic eczema during childhood by means of odds ratios (OR) and 95% confidence intervals (CI).
Explorative analyses by maternal job titles in pregnancy showed elevated odds ratios concerning different atopic diseases for occupational groups such as “bakers, pastry cooks, and confectionary makers”, “dental assistants”, “electrical and electronic assemblers”, “sewers and embroiders”, and “bookbinders and related workers”. An excess risk ratio for hay fever (OR 2.8, CI 1.1 to 7.5) was found following maternal gestational exposure to organic solvents. Furthermore, a slightly raised odds ratio for asthma was observed in children of shift workers (OR 1.2, CI 1.0 to 1.5).
The data suggest links between certain maternal occupations during pregnancy and atopic diseases, which merits further scrutiny. However, no consistent pattern was seen across the different atopic diseases.
solvents; prenatal exposure delayed effects; hypersensitivity
Recent studies have reported an association between maternal use of gastric acid-suppressive drugs during pregnancy and asthma in the offspring, but the association could have been confounded by unmeasured risk factors.
We assessed the association between the use of acid-suppressive drugs during pregnancy and the risk of developing childhood asthma using a bidirectional crossover design.
Mother–infant matched sets in the UK General Practitioners Research Database were used to identify children with a drug-treated asthma diagnosis during the years 2006–2010 who were matched to a sibling without asthma as controls. Primary exposure was use of any anti-suppressive drug during pregnancy, and subgroup analyses were conducted according to drug class (e.g. proton pump inhibitors or histamine 2 receptor antagonists) and trimester. Conditional logistic regression was used to estimate odds ratios (OR) with their corresponding 95 % confidence intervals (CIs).
A total of 1,874 children with asthma and 1,874 control siblings were included in the analysis. The exposure rate among case and control pregnancies was 22 and 20 %, respectively. After adjustments for gender, birth order, mother’s age and general practice visits, the exposure to any gastric-acid suppressive drug during pregnancy slightly increased the risk for developing asthma (OR 1.23, 95 % CI 1.01–1.51; p = 0.042). A trend towards increased risks was observed for those who used proton pump inhibitors and/or histamine 2 receptor antagonists (adjusted OR 1.72, 95 % CI 1.00–2.98; p = 0.048).
These findings lend support to the emerging evidence that exposure to acid-suppressive drugs during pregnancy is associated with childhood asthma. More basic research is now warranted to investigate the mechanisms.
Electronic supplementary material
The online version of this article (doi:10.1007/s40264-013-0093-z) contains supplementary material, which is available to authorized users.
Background: Maternal sex hormones in pregnancy can theoretically influence the developing fetal immune system and modulate the subsequent development of atopic disorders. Early onset of menarche has been linked to increased oestrogen levels in adult women. A study was undertaken to examine the association between early onset menarche in pregnant women and asthma and atopic status of their children at 7 years of age.
Methods: The Avon Longitudinal Study of Parents and Children (ALSPAC) is a longitudinal birth cohort study in which pregnant women, resident in Avon (UK), were recruited on the basis of an expected date of delivery between 1 April 1991 and 31 December 1992. Maternal age at menarche was assessed from prenatal questionnaires administered to the women. Clinical outcomes in the children were based on mothers' responses to self-completion questionnaires and included asthma, eczema, and hay fever. The atopic status of the child was objectively assessed by skin prick tests to a panel of common aeroallergens at the age of 7 years. Analyses used multivariable logistic regression with a diverse range of possible confounders.
Results: Complete data were available on 5765 woman and child pairs. The prevalence of ever reported asthma to 7 years was 20.4%, eczema 58.6%, hay fever 12.1%, and atopy (defined as any positive (>2 mm weal) response) was present in 20.6%. There were no significant differences in mean age of menarche between mothers of children with and without each of the primary outcomes. Adjusted odds ratios (95% CI) for the latest age of menarche (16+ years) compared with the lowest (<12 years) reference group were 1.41 (1.00 to 1.99) for asthma, 0.98 (0.73 to 1.91) for eczema, 0.95 (0.62 to 1.44) for hay fever, and 0.98 (0.68 to 1.42) for atopy.
Conclusion: No consistent association was found between maternal age at menarche and asthma, eczema, hay fever or atopy in their children during early childhood.
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
One of the mechanisms supposed to explain the increasing prevalence of asthma, among children in particular, is the use of antibiotics because they may modify natural microbial exposure and development of the immune system in early childhood. The aim of this study is to investigate the association between the use of various classes of antibiotics (penicillin, cephalosporin and macrolide derivatives) in early childhood and the medical diagnosis of asthma or wheezing reported by mothers over the follow-up after adjustment for potential confounders and respiratory infections. In a population-based sample of 5-year-olds, a part of the ongoing birth cohort study, the standardized interviews on health outcomes, potential confounders (child’s gender, maternal atopy, parity, prenatal and postnatal environmental tobacco smoke) and the use of antibiotics were gathered from mothers of 310 children. While the overall use of antibiotics during the early childhood was insignificantly associated with asthma (adjusted OR = 1.65, 95%CI: 0.93 – 2.93), the risk estimates were significant both for macrolide antibiotics (adjusted OR=2.14, 95%CI: 1.16–3.95) and cephalosporins (OR=1.98, 95%CI: 1.14–3.37). The significant excess in IRR (incident risk ratio) of wheezing episodes was related only to the use of macrolide antibiotics (adjusted IRR=1.91, 95%CI: 1.12–3.27). The use of other classes of antibiotics was found not to be associated with the medical diagnosis of asthma or wheezing episodes recorded in the study period. Conclusion: as early childhood use of broad spectrum antibiotics is associated with an increased risk of developing asthma in 5-year-olds, it may be hypothesized that the antibiotic- related suppression of allergic inflammatory responses in the course of treatment may later lead to greater than before atopic immune response in Th2 children or an impairment of Th1 immune responses in early childhood.
antibiotics; asthma; childhood; wheezing; Th1 immune responses; allergic reactions
To estimate whether prenatal exposure to acetaminophen is associated with risk of diagnosed asthma and asthma symptoms in children.
The authors prospectively followed 1,505 pregnant women and their children until 6 years (±3 months) of life. Acetaminophen use in the first and third trimesters of pregnancy was assessed before 24 weeks of gestation and within 1 month of delivery, and asthma in children was assessed when the child was 6 years old. Adjusted odds ratios (aORs) were derived from logistic regression models controlling for potential confounders.
Acetaminophen was used by 69% of women during pregnancy. Use of acetaminophen did not significantly increase the risk of asthma (aOR 0.76, 95% confidence interval [CI] 0.53–1). Acetaminophen use during both the first and the third trimester was associated with a significantly reduced risk of asthma (aOR 0.59, 95% CI 0.36–0.98). There was no evidence of a dose response, and consumption greater than 10,400 mg (32 tablets) a month did not increase risk (aOR 0.99, 95% CI 0.19–5.30).
Our results suggest that acetaminophen use during pregnancy does not increase risk of asthma in children.
Previous studies indicate that maternal anxiety is associated with asthma in the adolescent child, but mechanisms are unclear.
To investigate the association between maternal anxiety and maternal, self- and register-based report of asthma in the adolescent child, and whether the association remains after control of familial confounding (shared environmental and genetic factors).
From the Twin and Offspring Study of Sweden, 1691 mothers (1058 twins) and their adolescent child were included. The association between maternal self-reported anxiety (Beck Anxiety Inventory (BAI) and Karolinska Scales of Personality (KSP) somatic or psychic anxiety) and asthma based on subjective (maternal or child report) or objective (register-based diagnosis and medication) measures were analysed using logistic regression. The children-of-twins design was used to explore whether genes or environment contribute to the association.
Maternal BAI anxiety (OR 2.02, CI 1.15–3.55) was significantly associated with adolescent asthma reported by the mother. Maternal KSP somatic anxiety (OR 1.74, CI 1.04–2.91) and psychic anxiety (OR 1.74, CI 1.05–2.86) was significantly associated with breathlessness reported by the adolescent child. In contrast, maternal anxiety was not associated with increased risk for the register-based outcomes of asthma diagnosis or medication. The results remained also after adjusting for covariates and the children-of-twins analyses which indicate that the association was due to familial confounding.
We found some associations between maternal anxiety and subjectively reported offspring asthma or breathlessness which may be due to familial effects. A likely candidate for explaining this familial confounding is heritable personality traits associated with both anxiety and subjective measures of asthma.
Little is known about relationships between dietary patterns, n-3 polyunsaturated fatty acids (PUFA) intake and excessive anxiety during pregnancy.
To examine whether dietary patterns and n-3 PUFA intake from seafood are associated with high levels of anxiety during pregnancy.
Pregnant women enrolled from 1991–1992 in ALSPAC (n 9,530). Dietary patterns were established from a food frequency questionnaire using principal component analysis. Total intake of n-3 PUFA (grams/week) from seafood was also examined. Symptoms of anxiety were measured at 32 weeks of gestation with the Crown-Crisp Experiential Index; scores ≥9 corresponding to the 85th percentile was defined as high anxiety symptoms. Multivariate logistic regression models were used to estimate the OR and 95% CI, adjusted by socioeconomic and lifestyle variables.
Multivariate results showed that women in the highest tertile of the health-conscious (OR 0.77; 0.65–0.93) and the traditional (OR 0.84; 0.73–0.97) pattern scores were less likely to report high levels of anxiety symptoms. Women in the highest tertile of the vegetarian pattern score (OR 1.25; 1.08–1.44) were more likely to have high levels of anxiety, as well as those with no n-3 PUFA intake from seafood (OR 1.53; 1.25–1.87) when compared with those with intake of >1.5 grams/week.
The present study provides evidence of a relationship between dietary patterns, fish intake or n-3 PUFA intake from seafood and symptoms of anxiety in pregnancy, and suggests that dietary interventions could be used to reduce high anxiety symptoms during pregnancy.
The high prevalence of children's asthma symptoms, worldwide, is unexplained. We examined the relation between maternal pre-pregnancy weight and body mass index (BMI), and asthma symptoms in adolescents.
Data from 6945 adolescents born within the Northern Finland Birth Cohort 1986 were used. Prospective antenatal and birth outcome data, including maternal pre-pregnancy weight and BMI, and asthma symptoms in adolescent offspring at age 15–16 years, were employed. Logistic regression analyses were performed to examine the associations between relevant prenatal factors and asthma symptoms during adolescence.
Current wheeze (within the past year) was reported by 10.6% of adolescents, and physician-diagnosed asthma by 6.0%. High maternal pre-pregnancy BMI was a significant predictor of wheeze in the adolescents (increase per kilogram per square metre unit; 2.7%, 95% CI 0.9 to 4.4 for ever wheeze; 3.5%, 95% CI 1.3 to 5.8 for current wheeze), and adjusting for potential confounders further increased the risk (2.8%, 95% CI 0.5 to 5.1; 4.7%, 95% CI 1.9 to 7.7, respectively). High maternal pre-pregnancy weight, in the top tertile, also significantly increased the odds of current wheeze in the adolescent by 20% (95% CI 4 to 39), and adjusting for potential confounders further increased the risk (OR=1.52, 95% CI 1.19 to 1.95). Results were similar for current asthma. Furthermore, these significant associations were observed only among adolescents without parental history of atopy but not among those with parental history of atopy.
The association demonstrated here between maternal pre-pregnancy overweight and obesity, and asthma symptoms in adolescents suggests that increase in asthma may be partly related to the rapid rise in obesity in recent years.
Asthma; wheeze; prevalence; adolescent; maternal pre-pregnancy weight; BMI; obesity
While some evidence suggests that antigen sensitization may begin prenatally, the influence of maternal allergen exposure during pregnancy has not been fully elucidated.
We examined the relationship between prenatal maternal aeroallergen exposure and cord blood total immunoglobulin E (IgE) and the potential mediating/indirect effect of maternal immune response.
This study was performed in 301 mother-infant pairs enrolled in the Asthma Coalition on Community, Environment, and Social Stress (ACCESS) project, a study examining the effects of prenatal and early life social and physical environmental exposures on urban asthma risk. Dust samples collected prenatally from mothers’ bedrooms were analyzed for cockroach and dust mite allergens. Cord blood was analyzed for total IgE and maternal serum collected during pregnancy for total and specific IgE. We assessed the relationship between prenatal exposure and cord blood total IgE and the potential mediation effect adjusting for maternal age, race, education, smoking status and dust collection season; and child’s gender and season of birth.
In multivariate models, elevated prenatal dust mite levels (> 0.2 µg/g) increased cord blood IgE concentrations by 29% (p=0.08) and continuous dust mite concentration was associated with a significant non-linear increase in cord blood IgE (p=0.02). Elevated prenatal exposure to cockroach allergen (> 2 U/g) was not associated with cord blood IgE, but showed a significant indirect relationship through maternal total IgE (β=0.23; 95% CI: 0.08, 0.41).
These results demonstrate that maternal prenatal exposure to household allergens may impact cord blood IgE albeit the underlying mechanism may be allergen-specific.
Maternal prenatal inhalant allergen exposure may precipitate infant immune response although the pathway of the effect may differ by allergen.
Prenatal exposure to dust mite was associated with increased cord blood total IgE whereas the relationship between prenatal cockroach exposure and total cord blood IgE was only observed through the indirect effect of maternal allergic response.
Allergen; Dust Mite; Cockroach; Maternal; Prenatal; Cord Blood; Immunoglobulin E; IgE; Urban
Prenatal maternal stress could have permanent effects on the offspring’s tissue structure and function, which may predispose to cardiovascular diseases. We investigated whether maternal psychosocial stress is a prenatal factor affecting the blood pressure (BP) of offspring.
In the Amsterdam Born Children and their Development (ABCD) study, around gestational week 16, depressive symptoms, state-anxiety, pregnancy-related anxiety, parenting daily hassles and job strain were recorded by questionnaire. A cumulative stress score was also calculated (based on 80th percentiles). Systolic and diastolic BP and mean arterial pressure (MAP) were measured in the offspring at age 5–7 years. Inclusion criteria were: no use of antihypertensive medication during pregnancy; singleton birth; no reported cardiovascular problems in the child (N = 2968 included).
After adjustment for confounders, the single stress scales were not associated with systolic and diastolic BP, MAP and hypertension (p>0.05). The presence of 3–4 psychosocial stressors prenatally (4%) was associated with 1.5 mmHg higher systolic and diastolic BP (p = 0.046; p = 0.04) and 1.5 mmHg higher MAP in the offspring (p = 0.02) compared to no stressors (46%). The presence of 3–4 stressors did not significantly increase the risk for hypertension (OR 1.8; 95% CI 0.93.4). Associations did not differ between sexes. Bonferroni correction for multiple testing rendered all associations non-significant.
The presence of multiple psychosocial stressors during pregnancy was associated with higher systolic and diastolic BP and MAP in the child at age 5–7. Further investigation of maternal prenatal stress may be valuable for later life cardiovascular health.
Acetaminophen has been associated with asthma and is in part metabolised via the glutathione pathway. Inner-city minority children have high asthma morbidity and a relatively high frequency of a minor allele variant in the glutathione S transferase Pi gene (GSTP1). We hypothesised that prenatal acetaminophen exposure would predict wheeze at age 5 years in an inner-city minority cohort and examined whether this association was modified by common polymorphisms in genes related to the glutathione pathway.
An ongoing population-based birth cohort study of Dominican Republic and African-American children in New York prospectively assessed the use of analgesics during pregnancy and current wheeze at age 5 years in 301 children. Genotyping was conducted for GST polymorphisms. Binomial regression was used to adjust for potential confounders including postnatal acetaminophen use.
34% of mothers reported acetaminophen use during pregnancy and 27% of children had current wheeze at 5 years. Prenatal exposure to acetaminophen predicted current wheeze (multivariate relative risk 1.71; 95% CI 1.20 to 2.42; p=0.003), and the risk increased monotonically with increasing number of days of prenatal acetaminophen exposure (p trend <0.001). 68% of children had at least one copy of the GSTP1 minor allele (Val). The risk of wheeze was modified by GSTP1 (additive interaction p=0.009) and was observed only among children with the GSTP1 minor allele.
Prenatal exposure to acetaminophen predicted wheeze at age 5 years in an inner-city minority cohort. The risk was modified by a functional polymorphism in GSTP1, suggesting a mechanism involving the glutathione pathway.
Early-life experiences and environmental exposures have been associated with childhood asthma. To investigate further whether the timing of such experiences and exposures is associated with the occurrence of asthma by 5 years of age, we conducted a prevalence case-control study nested within the Children's Health Study, a population-based study of > 4,000 school-aged children in 12 southern California communities. Cases were defined as physician-diagnosed asthma by age 5, and controls were asthma-free at study entry, frequency-matched on age, sex, and community of residence and countermatched on in utero exposure to maternal smoking. Telephone interviews were conducted with mothers to collect additional exposure and asthma histories. Conditional logistic regression models were fitted to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Asthma diagnosis before 5 years of age was associated with exposures in the first year of life to wood or oil smoke, soot, or exhaust (OR = 1.74; 95% CI, 1.02-2.96), cockroaches (OR = 2.03; 95% CI, 1.03-4.02), herbicides (OR = 4.58; 95% CI, 1.36-15.43), pesticides (OR = 2.39; 95% CI, 1.17-4.89), and farm crops, farm dust, or farm animals (OR = 1.88; 95% CI, 1.07-3.28). The ORs for herbicide, pesticide, farm animal, and crops were largest among children with early-onset persistent asthma. The risk of asthma decreased with an increasing number of siblings (ptrend = 0.01). Day care attendance within the first 4 months of life was positively associated with early-onset transient wheezing (OR = 2.42; 95% CI, 1.28-4.59). In conclusion, environmental exposures during the first year of life are associated with childhood asthma risk.
The consequences of prenatal maternal stress for infant mental and motor development were examined in 125 full term infants at 3, 6 and12 months of age. Maternal cortisol and psychological state were evaluated five times during pregnancy and at 3, 6 and 12 months postpartum. Exposure to elevated concentrations of cortisol early in gestation was associated with a slower rate of development over the first postnatal year and lower scores on the mental development index of the Bayley Scales of Infant Development (BSID) at 12 months. Elevated levels of maternal cortisol late in gestation, however, were associated with accelerated development over the first year and higher scores on the BSID at 12 months. Elevated levels of maternal pregnancy specific anxiety early in pregnancy were independently associated with lower scores on the BSID at 12 months. These associations could not be explained by postnatal maternal psychological stress, stress related to parenting, prenatal medical history, socioeconomic factors or child race, sex or birth order. These data suggest that maternal cortisol and pregnancy specific anxiety have programming influences on the developing fetus. Prenatal exposure to the same signal, cortisol, had opposite associations with infant development based on the timing of exposure.
pregnancy; cortisol; stress; infant development; cognition; prenatal; depression; anxiety; fetal programming
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.
Little is known about paternal psychosocial factors and childhood asthma.
To examine the link between maternal and paternal psychosocial stress and asthma outcomes in young children.
Parents of 339 pairs of Puerto Rican twins were interviewed individually about their own psychosocial stress and about asthma in their children at age 1 and again about their child’s asthma at age 3. Fathers were asked about symptoms of post-traumatic stress disorder (PTSD), depression, and anti-social behavior. Mothers were asked about depressive symptoms. Outcomes assessed in children included recent asthma symptoms, oral steroid use and hospitalizations for asthma in the prior year, and asthma diagnosis. Generalized estimated equation models were used for the multivariate analysis of parental psychosocial stress and asthma morbidity in childhood.
After multivariable adjustment, paternal PTSD symptoms, depression, and anti-social behavior were each associated with increased asthma symptoms at age 1 (e.g., OR =1.08 for each 1-point increase in PTSD score, 95% CI=1.03–1.14). Maternal depressive symptoms were associated with an increased risk of asthma hospitalizations at age 1 year. At age 3 years, maternal depressive symptoms were associated with asthma diagnosis and hospitalizations for asthma (OR for each 1-point increase in symptoms=1.16, 95% CI=1.00–1.36]). In an analysis combining 1 and 3 year outcomes, paternal depression was associated with oral steroid use, maternal depressive symptoms were associated with asthma hospitalizations and asthma diagnosis, and parental depression was associated with hospitalizations for asthma.
Both paternal and maternal psychosocial factors may influence asthma morbidity in young Puerto Rican children.
psychosocial stress; childhood wheeze; Puerto Rico; parental stress; asthma; paternal stress
Asthma is one of the most common chronic diseases in children, with increasing morbidity and mortality. A genetic predisposition and exposure to allergens have been implicated as major risk factors for the development of asthma. However, increasing evidence indicates that the mother plays a crucial role in mediating the development of fetal-infant immune responses to inhaled allergens. The exact nature and mechanism of this maternal influence and how it might be associated with the development of allergic sensitization and asthma are not clear. Under normal conditions, the maternal environment during pregnancy promotes an initial Th2 skewed immune response in the offspring which transitions to a nonallergic Th1 type response after birth. However, the allergic mother’s influence may delay the normal transition to a nonallergic immune response to inhaled allergens in her children, thus increasing the risk for the development of allergic sensitization and/or asthma. Understanding the underlying mechanisms by which the maternal immune environment can influence the development of the fetal-infant immune response to inhaled allergens may lead to identifying new targets for the prevention of allergic sensitization and asthma.
in utero; postnatal; immune; development; allergy; lung