Early-life determinants of asthma from birth to age 20 years: a German birth cohort study.

BACKGROUND: The lack of longitudinal data analyses from birth to adulthood is hampering long-term asthma prevention strategies. OBJECTIVE: We aimed to determine early-life predictors of asthma incidence up to age 20 years in a birth cohort study by applying time-to-event analysis. METHODS: In 1990, the Multicenter Allergy Study included 1314 newborns in 5 German cities. Children were evaluated from birth to age 20 years at 19 time points. Using a Cox regression model, we examined the associations between 36 early-life factors and onset of asthma based on a doctor's diagnosis or asthma medication (primary outcome), typical asthma symptoms, or allergic asthma (including positive IgE measurements). RESULTS: Response at 20 years was 71.6%. Two hundred eighteen subjects met the primary outcome criteria within 16,257 person years observed. Asthma incidence was lower in participants who were vaccinated (measles, mumps, and rubella vaccine/tick-borne encephalitis vaccine/BCG vaccine: adjusted hazard ratio [HR], 0.66 [95% CI, 0.47-0.93]). Up to age 20 years, asthma incidence was higher in subjects who had parents with allergic rhinitis (adjusted HR, 2.24 [95% CI, 1.67-3.02]), started day care early or late (before 18 months: adjusted HR, 1.79 [95% CI, 1.03-3.10]; after 3 years: adjusted HR, 1.64 [95% CI, 0.96-2.79]), had mothers who smoked during pregnancy (adjusted HR, 1.79 [95% CI, 1.20-2.67]), had poor parents (adjusted HR, 1.55 [95% CI, 1.09-2.22]), and had parents with asthma (adjusted HR, 1.65 [95% CI, 1.17-2.31]). Not associated with asthma were aspects of diet and breast-feeding, pet ownership, presence of older siblings, and passive smoking. CONCLUSION: Parental asthma and nasal allergy increase asthma incidence in offspring up to adulthood. Avoiding tobacco smoke exposure during pregnancy, receiving vaccinations in early childhood, and starting day care between 1.5 and 3 years of age might prevent or delay the development of asthma.

How pre- and postnatal risk factors modify the effect of rapid weight gain in infancy and early childhood on subsequent fat mass development: results from the Multicenter Allergy Study 90.

BACKGROUND: It is unclear which exposures may cause or modify the adverse effect of rapid weight gain on fat mass development in term children whose birth weight is appropriate-for-gestational age (AGA). OBJECTIVE: To determine which intrauterine or postnatal exposures increase the risk of or modify the effect of rapid weight gain on body fat percentage (BF%) and body mass index (BMI) trajectories between 2 and 6 y of age. DESIGN: Term AGA singletons (n = 370) from the German Multicenter Allergy Study (MAS-90), a longitudinal birth cohort study, with repeated anthropometric measurements until 6 y, and data on breastfeeding status, exposure to smoking during pregnancy, and maternal anthropometric and socioeconomic characteristics were included in this analysis. RESULTS: A shorter gestation [multivariate-adjusted odds ratio (OR): 5.12; 95% CI: 2.22, 11.82; P = 0.0001], being firstborn (OR: 2.01; 95% CI: 1.10, 3.69; P = 0.02), and having been bottle-fed (OR: 3.02; 95% CI: 1.68, 5.43; P = 0.0002) all significantly increased a child's risk of gaining weight rapidly, whereas a larger BMI at birth was protective (OR: 0.54; 95% CI: 0.38, 0.77; P = 0.0006). Multilevel model analyses showed that rapid growers exposed to tobacco in utero subsequently gained more BF% between 2 and 6 y than did rapid growers who had not been exposed (beta +/- SE: 0.78 +/- 0.28%/y; P = 0.005). Similarly, change in BF% was greater in rapid growers with an overweight mother than in those with a normal-weight mother (1.01 +/- 0.30%/y; P = 0.0007). CONCLUSIONS: The occurrence of rapid weight gain between birth and 2 y and the magnitude of its effect on BF% development in AGA children is influenced by both intrauterine and postnatal exposures.

Undernutrition and growth restriction in pregnancy.

Newborn size is the result of intrauterine growth. Premature, low birthweight of <2,500 g, small for gestational age (SGA, <10th percentile), or intrauterine growth-restricted (IUGR) newborns may have similar weights. Serial fetal biometry (ultrasound), required for the diagnosis, timing and severity of intrauterine growth restriction in the individual infant, is still not common in epidemiological studies. SGA newborns have less lean body mass, but they particularly lack fat mass. The most important etiological determinants of intrauterine growth restriction in developed countries is cigarette smoking, while in developing countries it is usually longstanding food deprivation. Follow-up studies of SGA newborns consistently showed a positive association between birthweight and later lean body mass, whereas associations with adiposity were more variable. Most SGA infants had catch-up in length/height. Signs of the metabolic syndrome accompanied the catch-up in bodyweight and central adiposity. So far, no overarching model is available to explain how the epigenetic and hormonal tunings, which accompany intrauterine malnutrition from preconception through pregnancy, can program the regulatory systems of fundamental life processes. The theoretical concepts of a thrifty phenotype (Hales and Barker) and of a predictive adaptive response (Gluckman and Hanson) offer a comprehensive approach to understanding the empirical and experimental findings.

Secular trends in neonatal macrosomia in Berlin: influences of potential determinants.

To investigate the trend in the prevalence of neonatal macrosomia and to evaluate the influences of potential determinants, key features of 206 308 hospital deliveries (97% of all) in Berlin in the years 1993-99, collected by the Berlin Medical Board, were analysed using SPSS 10.0. After exclusion of multiple births and preterm infants, there was a significant increase over 7 years (P < 0.01) in the prevalence of birthweights >or= 4000 g, maternal age >or= 30 years, height of >or= 165 cm, prepregnancy BMI (body mass index) >or= 26 kg/m2 and pregnancy weight gain> 16 kg, but no substantial trend in the prevalence of recognised diabetes or maternal smoking. The adjusted model (OR [95% CI]) for delivering a newborn >or= 4000 g was statistically significant for post-term delivery (2.56 [2.39, 2.75]), women aged >or= 30 years (1.06 [1.02-1.11]), >or= 165 cm tall (1.94 [1.87,2.01]), multiparae (1.98 [1.91, 2.05]), not smoking in pregnancy (2.03 [1.93, 2.14]), prepregnancy BMI >or= 26 compared with < 20 (4.01 [3.77, 4.26]), pregnancy weight gain >or= 16 kg compared with < 10 kg (3.37.[3.22, 3.53]) and for recognised diabetes (1.85.[1.69, 2.04]). It is speculated that this increase in the prevalence of neonatal macrosomia may contribute to the secular trend of overweight and obesity under affluent living conditions.

The development of childhood asthma: lessons from the German Multicentre Allergy Study (MAS).

Epidemiological surveys have indicated that there has been a notable increase in the prevalence of both asthma and other allergic symptoms in children and young adults. Since it seems unlikely that genetic factors would contribute to the rising trend, environmental factors might play a major part in the development of childhood asthma. In a prospective birth-cohort study, we assessed the relevance of different exposures such as mite and cat allergen exposure, environmental tobacco smoke (ETS) exposure, early infectious diseases and vaccinations for the development of childhood asthma up to the age of 10 years. Data up to 7 years of age have been evaluated. Of 1314 newborn infants enrolled in five German cities in 1990, follow-up data at age 7 years were available for 939 children (72%). Assessments included repeated measurements of specific IgE to food and inhalant allergens, measurement of indoor allergen exposure at 6 months, 18 months and 3 years of age and yearly interviews by a paediatrician. At age 7 years, pulmonary function was tested and bronchial responsiveness was determined in 645 children. At age 7, the prevalence of wheezing in the past 12 months was 10% (94 out of 938), and 6.1% (57 out of 939) parents reported a doctor's diagnosis of asthma in their children. Sensitisation to indoor allergens was associated with asthma, wheeze and increased bronchial responsiveness. However, no relationship between early indoor allergen exposure and the prevalence of asthma, wheeze and bronchial responsiveness was seen. During the first 3 years of life, intra-uterine tobacco and consistent ETS exposure have an adjuvant effect on allergic sensitisation that is transient and restricted to children with a genetic predisposition for allergy. Children sensitised to any allergen early in life and sensitised to inhalant allergens by the age of 7 years were at a significantly increased risk of being asthmatic at this age (odds ratio (OR) = 10.12; 95% confidence interval (CI) = 3.81-26.88). Children with repeated episodes (> or =2) of runny nose before the age of 1 year were less likely to develop asthma by the age of 7 years (OR = 0.52; 95% CI = 0.29-0.92). Our data do not support the hypothesis that exposure to environmental allergens directly causes asthma in childhood but that induction of specific IgE responses and the development of childhood asthma are determined by independent factors. Indoor allergen avoidance is recommended as first line treatment in secondary and tertiary prevention; however, conclusions should be drawn with caution about the possible effect of primary preventative measures. Since allergic asthma seems to be a Th2-disease, immunomodulating factors such as early childhood infections, LPS-exposure or other factors influencing gene-environment interaction and individual susceptibility seem to be relevant for the development of childhood asthma.

Iron deficiency is prevalent in a sample of pregnant women at delivery in Germany.

OBJECTIVE: To determine the prevalence and risk factors of iron deficiency in pregnancy, since iron supplements are not routine in Germany. STUDY DESIGN: Soluble transferrin receptor (sTfR), ferritin, hemoglobin (Hb), C-reactive protein (CRP) and leucocyte counts were determined in venous blood samples of 378 women before delivery; 191 of them filled in a questionnaire. Statistical analysis was performed using SPSS 9.0.1. RESULTS: CRP and leucocyte count correlated significantly with ferritin values, while sTfR values were independent. Iron deficiency (sTfR >3.3 mg/dl) was found in 40.7% of pregnant women, and anemia (Hb<11.0 g/dl) in 13.6%. Non-German nationality, low educational level and young maternal age were significant risk factors for iron deficiency, while alcohol use in pregnancy, iron and folic acid supplements were protective. After adjusting for all other factors in a logistic regression equation, not taking any iron supplements in pregnancy (odd ratios (OR) 3.3 and 95% confidence interval (CI) 1.1-9.4), and young maternal age (OR 2.86 and 95% CI 1.1-7.7) remained significant risks. CONCLUSION: Iron deficiency in pregnant women in Germany is prevalent; it could be prevented by routine iron supplements.