Pre-eclampsia and risk of early-childhood asthma: a register study with sibling comparison and an exploration of intermediate variables.

BACKGROUND: We aimed to study whether pre-eclampsia is associated with childhood asthma, allergic and non-allergic asthma, accounting for family factors and intermediate variables. METHODS: The study population comprised 779 711 children born in 2005-2012, identified from Swedish national health registers (n = 14 823/7410 exposed to mild/moderate and severe pre-eclampsia, respectively). We used Cox regression to estimate the associations of mild/moderate and severe pre-eclampsia with incident asthma, before and after age 2 years. Cox regressions were controlled for familial factors using sibling comparisons, then stratified on high and low risk for intermediate variables: caesarean section, prematurity and small for gestational age. We used logistic regression for allergic and non-allergic prevalent asthma at 6 years as a measure of more established asthma. RESULTS: The incidence of asthma in children was 7.7% (n = 60 239). The associations varied from adjusted hazard ratio (adjHR) 1.11, 95% confidence interval (CI): 1.00, 1.24 for mild/moderate pre-eclampsia and asthma at >2 years age, to adjHR 1.78, 95% CI: 1.64, 1.95 for severe pre-eclampsia and asthma at <2 years age. Sibling comparisons attenuated most estimates except for the association between severe pre-eclampsia and asthma at <2 years age (adjHR 1.45, 95% CI: 1.10, 1.90), which also remained when stratifying for the risk of intermediates. Mild/moderate and severe pre-eclampsia were associated with prevalent non-allergic (but not allergic) asthma at 6 years, with adjusted odds ratio (adjOR) 1.17, 95% CI: 1.00, 1.36 and adjOR 1.51, 95% CI: 1.23, 1.84, respectively. CONCLUSIONS: We found evidence that severe, but not mild/moderate, pre-eclampsia is associated with asthma regardless of familial factors and confounders.

Adipokines in adolescence; the associations with lung function and atopy - A cross-sectional study.

Both inflammatory and mechanical effects have been proposed to explain the increased risk of asthma and reduced lung function observed in obese children and adults. The evidence regarding the potential role of obesity in the aetiology of atopy and allergy is more conflicting. The adipokines leptin and adiponectin are inflammatory markers of fat metabolism which may be involved in explaining the increased risk of asthma and reduced lung function in obese children and adults. In this cross-sectional study, we aimed to study how adiponectin and leptin were associated with lung function and atopic sensitisation in adolescents. The study included 384 children at mean age 12.9 years with measurements of adiponectin, leptin, lung function and atopic sensitisation. Adiponectin and leptin levels were measured in serum, lung function was measured by spirometry and atopic sensitisation was measured by serum specific Immunoglobulin E. In linear regression models, leptin was negatively associated with forced vital capacity (FVC) (Beta: -4.13; 95% Confidence Interval: -5.83, -2.44, P < 0.001) and forced expiratory volume in the first second (FEV1) (-3.74; -5.39, -2.09, P < 0.001) after adjusting for body mass index (BMI) and other covariates. No associations were observed between adiponectin and lung function or between leptin or adiponectin and atopic sensitisation. In this cross-sectional analysis of adolescents in all weight classes, leptin was negatively associated with FEV1 and FVC independent of BMI, but no associations were found between adiponectin and lung function. The results suggest that leptin may have a functional role in the airways of healthy children.

The associations between weight-related anthropometrics during childhood and lung function in late childhood: a retrospective cohort study.

BACKGROUND: An association between body weight in childhood and subsequent lung function and asthma has been suggested, but few longitudinal studies exist. Our aim was to explore whether weight-related anthropometric measurements through childhood were associated with lung function in late childhood. METHODS: From an original nested case-control study, a cohort study was conducted, where lung function was measured in 463 children aged 12.8 years, and anthropometry was measured at several ages from birth through 12.8 years of age. Associations between anthropometrics and lung function were analysed using multiple linear and fractional polynomial regression analysis. RESULTS: Birthweight and body mass index (BMI; kg/m2) at different ages through childhood were positively associated with forced vital capacity in percent of predicted (FVC %) and forced expiratory volume in the first second in percent of predicted (FEV1%) at 12.8 years of age. BMI, waist circumference, waist-to-height ratio and skinfolds at 12.8 years of age and the change in BMI from early to late childhood were positively associated with FVC % and FEV1% and negatively associated with FEV1/FVC and forced expiratory flow at 25-75% of FVC/FVC. Interaction analyses showed that positive associations between anthropometrics other than BMI and lung function were mainly found in girls. Inverse U-shaped associations were found between BMI at the ages of 10.8/11.8 (girls/boys) and 12.8 years (both genders) and FVC % and FEV1% at 12.8 years of age. CONCLUSIONS: Weight-related anthropometrics through childhood may influence lung function in late childhood. These findings may be physiological or associated with air flow limitation. Inverse U-shaped associations suggest a differential impact on lung function in normal-weight and overweight children. TRIAL REGISTRATION: This study was observational without any health care intervention for the participants. Therefore, no trial registration number is available.

Exposure to preeclampsia in utero affects growth from birth to late childhood dependent on child's sex and severity of exposure: Follow-up of a nested case-control study.

BACKGROUND AND OBJECTIVE: An adverse intrauterine environment may affect offspring growth and development. Our aim was to explore whether preeclampsia (PE) exposure in utero influences growth from birth to 13 years. METHODS: In a nested case-control study, 229 children were exposed to PE (mild/moderate: n = 164, severe: n = 54) and 385 were unexposed. Length/height and weight were abstracted from records at birth, 3 and 6 months, 1 and 4 years, and measured along with waist circumference and skinfolds at follow-up at 11/12 (girls/boys) and 13 years (both sexes). Associations between PE and z-scores for growth were analyzed by multiple linear and fractional polynomial regression with adjustment for potential confounders. RESULTS: In boys, exposure to mild/moderate PE was positively associated with linear growth after 0.5 years, but severe PE was negatively associated with linear growth in all ages. In girls, both exposure to mild/moderate and severe PE were negatively associated with linear growth. Exposure to PE was negatively associated with weight and body mass index (BMI) during infancy, but positively associated with weight and BMI thereafter, except that boys exposed to severe PE consistently had a lower weight and BMI compared to the unexposed. Exposure to severe PE only was positively associated with waist-to-height ratio at 11/12 (girls/boys) and 13 years (both sexes). CONCLUSIONS: From birth to adolescence, linear growth, weight and BMI trajectories differed between the sexes by severity of exposure to PE. In general, PE exposure was negatively associated with linear growth, while in girls; positive associations with weight and BMI were observed. This underlines fetal life as a particularly sensitive period affecting subsequent growth and this may have implications for targeted approaches for healthy growth and development.

Body mass index and physical activity in early childhood are associated with atopic sensitization, atopic dermatitis and asthma in later childhood.

BACKGROUND: The results of studies on the associations of childhood excessive weight/obesity and physical activity with atopic sensitization and atopic diseases are inconsistent. We studied the associations of anthropometry and physical activity in childhood with atopic sensitization and atopic diseases in late childhood. METHODS: In a cohort study including cases exposed to preeclampsia during pregnancy and controls, anthropometry and physical activity were assessed at several ages in 617 children. Associations with atopic sensitization and atopic diseases in late childhood were analysed using multiple logistic regression. RESULTS: Body mass index standard deviation score (BMI SDS) at 1 year and low physical activity at 3-6 years were positively associated with atopic sensitization at 12.8 years [adjusted odds ratio (OR) 1.22; 95 % confidence interval (1.00, 1.49) and OR 2.36; (1.15, 4.81), respectively]. Change in BMI SDS from 1 to 4 years, BMI SDS at 4 years, and high physical activity at 6-10 years were positively associated with atopic dermatitis by 10.8 years [OR 1.46; (1.11, 1.92); OR 1.32; (1.06, 1.65) and OR 1.94; (1.16, 3.24); respectively]. Low physical activity at 3-6 and 6-10 years were positively associated with asthma by 10.8 years [OR 3.61; (1.56, 8.36) and OR 2.52; (1.24, 5.12), respectively]. CONCLUSIONS: BMI and physical activity in early childhood were associated with atopic sensitization, atopic dermatitis and asthma in later childhood. Larger cohorts with repeated measurements of both predictors and outcomes are required to further elucidate this issue. Trial registration Our study was observational without any clinical intervention on the participants. Therefore, no trial registration number is available.

Birth after preeclamptic pregnancies: association with allergic sensitization and allergic rhinoconjunctivitis in late childhood; a historically matched cohort study.

BACKGROUND: The development of allergic sensitization and allergic disease may be related to factors during intrauterine life, but the role of maternal preeclampsia is not known.We studied if maternal preeclampsia is associated with long-term allergic sensitization, allergic rhinoconjunctivitis, atopic dermatitis, asthma and with altered lung function in late childhood. METHODS: 617 children participated in a 1:2 matched and controlled historical cohort study; 230 born after preeclamptic pregnancies and 387 born after normotensive pregnancies. Specific IgE in serum and lung function were measured at the age of 12.8 years and questionnaires on maternal and adolescent data were completed at the ages of 10.8 years (girls) and 11.8 years (boys), and at 12.8 years (both genders). The association between birth after preeclampsia and the main outcome measures allergic sensitization, allergic rhinoconjunctivitis, atopic dermatitis, asthma and lung function in late childhood were analysed with multiple regression analyses, including possible confounders. RESULTS: Severe maternal preeclampsia was associated with high level allergic sensitization (sum of specific IgE in serum ≥ 3.9 kU/l; the 25 percentile for all children being sensitized); odds ratio (OR): 3.79; 95% confidence interval (CI): (1.54, 9.32); p = 0.015 and with allergic rhinoconjunctivitis in offspring; OR: 2.22, 95% CI: (1.19, 4.14), p = 0.047. Preeclampsia was not associated with atopic dermatitis, asthma or altered lung function in late childhood. CONCLUSION: Maternal preeclampsia was associated with allergic sensitization and allergic rhinoconjunctivitis in offspring in late childhood, but not with other atopic diseases.

Fatty acids in cord blood plasma, the relation to soluble CD23 and subsequent atopy.

Atopy is suggested to be linked to the balance between levels of n-6 and n-3 series of long chain polyunsaturated fatty acids (PUFAs) in the diet. In a nested case-control study, levels of fatty acids, IgE and soluble low affinity IgE receptor (sCD23) were measured in cord blood in 35 children who subsequently developed allergic sensitisation and atopic dermatitis before the age of 3, and similarly in 35 matched children without a history of atopy. We found a tendency to lower levels of the n-3 PUFAs eicosapentaenoic acid (EPA) and alpha-linolenic acid (ALA) in the cord blood plasma of atopics compared to non-atopics. Levels of sCD23 were negatively correlated to levels of n-3 series of PUFAs and n-9 eicosenoic acid, and levels of n-9 eicosenoic acid was negatively correlated to levels of IgE. There was no association between the levels of sCD23 and n-6 PUFAs. Lower levels of n-3 PUFAs in cord blood may be associated with the development of atopy in children. A possible mechanism may be through the regulation of CD23, thereby influencing IgE synthesis.