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1.  Effects of trimester-specific and total gestational weight gain on children’s anthropometrics 
Gestational weight gain (GWG) has been shown to be a risk factor for overweight in offspring.
Aim of this study was to quantify the contributions of trimester-specific and total GWG on offspring’s BMI and waist circumference (WC). This is of interest for the design of interventions targeted at women showing a high GWG in early pregnancy.
In a retrospective cohort study data on GWG (total and by trimester, exposure), a number of potential confounders, and children’s BMI z-scores and WC (outcomes) were analyzed using structural equation models to disentangle the trimester-specific direct effects of GWG and indirect effects mediated via total GWG.
7313 mother child pairs with a children’s mean age of 5.81 years were analyzed. Total effects (indirect + direct) of GWG (kg/week) on children’s BMI z-score and WC (cm) were observed in all trimesters, most prominently in the second. The longitudinal effect of GWG is a composite of trimester-specific direct effects (on BMI: 0.105, 0.255, 0.002, on WC: 0.538, 1.64, 0.308) and total GWG (on BMI 0.608, on WC: 1.03) at the end of pregnancy.
Both trimester-specific priming and total GWG explained offspring’s anthropometrics. The results indicate, that reversal from additional weight gain attained early in pregnancy resulting in normal total GWG at the end of pregnancy might still contribute to a substantial reduction of offspring’s BMI and WC.
PMCID: PMC4287554  PMID: 25296625
Gestational weight gain; Pregnancy; Priming; Children; Overweight; Obesity; Structural equation models
2.  Differences in BMI z-Scores between Offspring of Smoking and Nonsmoking Mothers: A Longitudinal Study of German Children from Birth through 14 Years of Age 
Environmental Health Perspectives  2014;122(7):761-767.
Background: Children of mothers who smoked during pregnancy have a lower birth weight but have a higher chance to become overweight during childhood.
Objectives: We followed children longitudinally to assess the age when higher body mass index (BMI) z-scores became evident in the children of mothers who smoked during pregnancy, and to evaluate the trajectory of changes until adolescence.
Methods: We pooled data from two German cohort studies that included repeated anthropometric measurements until 14 years of age and information on smoking during pregnancy and other risk factors for overweight. We used longitudinal quantile regression to estimate age- and sex-specific associations between maternal smoking and the 10th, 25th, 50th, 75th, and 90th quantiles of the BMI z-score distribution in study participants from birth through 14 years of age, adjusted for potential confounders. We used additive mixed models to estimate associations with mean BMI z-scores.
Results: Mean and median (50th quantile) BMI z-scores at birth were smaller in the children of mothers who smoked during pregnancy compared with children of nonsmoking mothers, but BMI z-scores were significantly associated with maternal smoking beginning at the age of 4–5 years, and differences increased over time. For example, the difference in the median BMI z-score between the daughters of smokers versus nonsmokers was 0.12 (95% CI: 0.01, 0.21) at 5 years, and 0.30 (95% CI: 0.08, 0.39) at 14 years of age. For lower BMI z-score quantiles, the association with smoking was more pronounced in girls, whereas in boys the association was more pronounced for higher BMI z-score quantiles.
Conclusions: A clear difference in BMI z-score (mean and median) between children of smoking and nonsmoking mothers emerged at 4–5 years of age. The shape and size of age-specific effect estimates for maternal smoking during pregnancy varied by age and sex across the BMI z-score distribution.
Citation: Riedel C, Fenske N, Müller MJ, Plachta-Danielzik S, Keil T, Grabenhenrich L, von Kries R. 2014. Differences in BMI z-scores between offspring of smoking and nonsmoking mothers: a longitudinal study of German children from birth through 14 years of age. Environ Health Perspect 122:761–767;
PMCID: PMC4080541  PMID: 24695368
3.  Overweight in Adolescence Can Be Predicted at Age 6 Years: A CART Analysis in German Cohorts 
PLoS ONE  2014;9(3):e93581.
To examine, whether overweight in adolescents can be predicted from the body mass index (BMI) category, at the age of 6, the mother's education level and mother's obesity and to quantify the proportion of overweight at the age of 14 that can be explained by these predictors.
Pooled data from three German cohorts providing anthropometric and other relevant data to a total of 1 287 children. We used a classification and regression tree (CART) approach to identify the contribution of BMI category at the age of 6 (obese: BMI>97th percentile (P97); overweight: P90P90) at the age of 14.
While 4.8% [95%CI: 3.2;7.0] of 651 boys and 4.1% [95%CI: 2.6;6.2] of 636 girls with a BMIP97 (similar results for girls). BMI≥P75 at the age of 6 explained 63.5% [95%CI: 51.1;74.5]) and 72.0% [95%CI: 60.4;81.8] of overweight/obesity at the age of 14 in boys and girls, respectively.
Overweight/obesity in adolescence can be predicted by BMI category at the age of 6 allowing for parent counselling or risk guided interventions in children with BMI≥P75, who accounted for >2/3 of overweight/obesity in adolescents.
PMCID: PMC3968156  PMID: 24676281
4.  High diagnostic stability of confirmed migraine and confirmed tension-type headache according to the ICHD-3 beta in adolescents 
Stable headache diagnosis classification is a prerequisite for identification of headache type specific risk factors. Does the stability of a headache diagnosis over time vary between migraine and tension-type headache (TTH)? Are there differences in diagnosis stability between a probable and a definite headache diagnosis?
In a sample of 783 students (ages 12 to 18 years) participating in a headache intervention study in greater Munich, the stability of headache classification according to the International Classification of Headache Disorder - third edition (beta version) (ICHD-3 beta) after a follow-up of 7 months was examined. Differences in stability of probable or definite migraine and probable or definite TTH were assessed. The stability of the headache diagnosis was assessed as predictive value of headache diagnosis with regard to confirmation of the headache type using the same diagnostic instrument 7 months later. Predictive values with 95% confidence intervals (CI) are reported.
Of students with initial migraine, a diagnosis of migraine was confirmed in 65.71% of students after 7 months (95%-CI [59.40-71.64]). A clear distinction between probable (44.71%, 95%-CI [33.91-53.89]) and confirmed diagnosis (76.88% 95%-CI [69.56-83.17]) of migraine was observed. For TTH the predictive value was 62.66% (95%-CI [57.07-68.01]) overall with a lower stability for probable (46.10%, 95%-CI [37.68-54.69]) compared to the confirmed diagnosis (69.71%, 95%-CI [23.58-37.67]).
While confirmed migraine and confirmed TTH diagnoses seem stable over time, stability of a probable diagnosis for either headache type was lower.
Trial registration
The trial was registered at the German Clinical Trial Register with the ID DRKS00003308.
PMCID: PMC4075938  PMID: 24916858
Headache; Migraine; Tension-type headache; Adolescents; Stability; Tracking; Headache type; Probable diagnosis; Confirmed diagnosis
5.  Understanding interventions for improving routine immunization coverage in children in low- and middle-income countries: a systematic review protocol 
Systematic Reviews  2013;2:106.
Virtually all low- and middle-income countries are dependent on the World Health Organization’s Expanded Program on Immunization for delivery of vaccines to children. The Expanded Program on Immunization delivers routine immunization services from health facilities free of charge. Understanding interventions for improving immunization coverage remains key in achieving universal childhood immunization.
We will conduct a systematic review that aims to assess the effectiveness of the full range of potential interventions to improve routine immunization coverage in children in low- and middle-income countries. We will include intervention studies, as well as observational studies. We will search the Cochrane Database of Systematic Reviews (CDSR), Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, electronic databases for eligible studies published by 31 August 2013. At least two authors will independently screen search outputs, select studies, extract data and assess the risk of bias (using separate criteria for interventions and observational studies); resolving any disagreements by discussion and consensus. The use of logic models and the Cochrane Complexity Matrix will be explored in order to better understand and contextualize studies. We will express the result of each study as a risk ratio with its corresponding 95% confidence intervals for dichotomous data, or mean difference with its standard deviation for continuous data. We will conduct meta-analysis for the same type of participants, interventions, study designs, and outcome measures where homogeneity of data allows. Use of harvest plots may be explored as an alternative. Heterogeneity will be assessed using the χ2 test of heterogeneity, and quantified using the I2 statistic. This protocol has not been registered with PROSPERO.
This review will allow us to document evidence across a broad range of intervention types for improving routine immunization coverage in children and also distinguish between those that are well supported by evidence (to direct policy recommendations) and those that are not well supported (to direct research agenda).
PMCID: PMC3843560  PMID: 24262139
Expanded Program on Immunization (EPI); Routine immunization; Routine vaccination; Children; Low- and middle-income countries
6.  Breastfeeding and Its Prospective Association with Components of the GH-IGF-Axis, Insulin Resistance and Body Adiposity Measures in Young Adulthood – Insights from Linear and Quantile Regression Analysis 
PLoS ONE  2013;8(11):e79436.
Breastfeeding may lower chronic disease risk by long-term effects on hormonal status and adiposity, but the relations remain uncertain.
To prospectively investigate the association of breastfeeding with the growth hormone- (GH) insulin-like growth factor- (IGF) axis, insulin sensitivity, body composition and body fat distribution in younger adulthood (18–37 years).
Data from 233 (54% female) participants of a German cohort, the Dortmund Nutritional and Anthropometric Longitudinally Designed (DONALD) Study, with prospective data on infant feeding were analyzed. Multivariable linear as well as quantile regression were performed with full breastfeeding (not: ≤2, short: 3–17, long: >17 weeks) as exposure and adult IGF-I, IGF binding proteins (IGFBP) -1, -2, -3, homeostasis model assessment of insulin resistance (HOMA-IR), fat mass index, fat-free mass index, and waist circumference as outcomes.
After adjustment for early life and socio-economic factors, women who had been breastfed longer displayed higher adult IGFBP-2 (ptrend = 0.02) and lower values of HOMA-IR (ptrend = 0.004). Furthermore, in women breastfeeding duration was associated with a lower mean fat mass index (ptrend = 0.01), fat-free mass index (ptrend = 0.02) and waist circumference (ptrend = 0.004) in young adulthood. However, there was no relation to IGF-I, IGFBP-1 and IGFBP-3 (all ptrend>0.05). Associations for IGFBP-2 and fat mass index were more pronounced at higher, for waist circumference at very low or high percentiles of the distribution. In men, there was no consistent relation of breastfeeding with any outcome.
Our data suggest that breastfeeding may have long-term, favorable effects on extremes of adiposity and insulin metabolism in women, but not in men. In both sexes, breastfeeding does not seem to induce programming of the GH-IGF-axis.
PMCID: PMC3827372  PMID: 24236134
7.  Unchanged Severity of Influenza A(H1N1)pdm09 Infection in Children during First Postpandemic Season 
Emerging Infectious Diseases  2012;18(11):1755-1762.
Improvement is needed in preventing severe disease and nosocomial transmission in children beyond pandemic situations.
We conducted a nationwide hospital-based prospective study in Germany of influenza A(H1N1)pdm09 cases among children <15 years of age admitted to pediatric intensive care units and related deaths during the 2009–10 pandemic and the 2010–11 postpandemic influenza seasons. We identified 156 eligible patients: 112 in 2009–10 and 44 in 2010–11. Although a shift to younger patients occurred in 2010–11 (median age 3.2 vs. 5.3 years), infants <1 year of age remained the most affected. Underlying immunosuppression was a risk factor for hospital-acquired infections (p = 0.013), which accounted for 14% of cases. Myocarditis was predictive of death (p = 0.006). Of the 156 case-patients, 17% died; the difference between seasons was not significant (p = 0.473). Our findings stress the challenge of preventing severe postpandemic influenza infection in children and the need to prevent nosocomial transmission of influenza virus, especially in immunosuppressed children.
PMCID: PMC3559159  PMID: 23092713
influenza A(H1N1)pdm09 virus; influenza; children; critically ill; postpandemic; hospital-acquired infection; nosocomial transmission; viruses
8.  Identified risk factors and adolescents’ beliefs about triggers for headaches: results from a cross-sectional study 
The Journal of Headache and Pain  2012;13(8):639-643.
Although there are few studies on adolescents’ beliefs about triggers of headache, none of these compared the associations between perceived and observed triggers. This study aimed at comparing the prevalence of self-perceived and observed risk factors for headache among adolescents. Adolescents from the 10th and 11th grades of high schools answered questionnaires on their headaches and on potential risk factors regarding lifestyle, stress and muscle pain. Individuals reporting to have experienced headache in the preceding 6 months were asked to report what they believed to cause their headache (self-perceived triggers). 1,047 (83 %) of 1,260 adolescents reported headaches. Stress, lack of sleep and too much school work were the most frequently reported self-perceived triggers of headache; in contrast the statistical analysis identified alcohol and coffee consumption, smoking, neck pain, stress and physical inactivity as risk factors for headache. Among individuals with headache, 48 % believed that stress might trigger their headaches, while increased stress scores were only observed in 23 %. In contrast, while 7, 4, 0.3 and 0 % of individuals reporting headache considered consumption of too much alcohol, neck pain, physical inactivity and consumption of coffee might trigger their headache, 56, 51, 36 and 14 %, respectively, were exposed to these risk factors. The prevalence of self-perceived triggers of headache does not correspond to the prevalence of identified risk factors for headaches. While the role of stress was overestimated, the high prevalence of the other confirmed risk factors in adolescents with headache suggests potential for prevention by increasing awareness for these risk factors and appropriate interventions.
PMCID: PMC3484252  PMID: 23064890
Headache; Adolescents; Trigger factors; Risk factors; Lifestyle factors
9.  Gestational Weight Gain and Body Mass Index in Children: Results from Three German Cohort Studies 
PLoS ONE  2012;7(3):e33205.
Previous studies suggested potential priming effects of gestational weight gain (GWG) on offspring’s body composition in later life. However, consistency of these effects in normal weight, overweight and obese mothers is less clear.
We combined the individual data of three German cohorts and assessed associations of total and excessive GWG (as defined by criteria of the Institute of Medicine) with offspring’s mean body mass index (BMI) standard deviation scores (SDS) and overweight at the age of 5–6 years (total: n = 6,254). Quantile regression was used to examine potentially different effects on different parts of the BMI SDS distribution. All models were adjusted for birth weight, maternal age and maternal smoking during pregnancy and stratified by maternal pre-pregnancy weight status.
In adjusted models, positive associations of total and excessive GWG with mean BMI SDS and overweight were observed only in children of non- overweight mothers. For example, excessive GWG was associated with a mean increase of 0.08 (95% CI: 0.01, 0.15) units of BMI SDS (0.13 (0.02, 0.24) kg/m2 of ‘real’ BMI) in children of normal-weight mothers. The effects of total and excessive GWG on BMI SDS increased for higher- BMI children of normal-weight mothers.
Increased GWG is likely to be associated with overweight in offspring of non-overweight mothers.
PMCID: PMC3310864  PMID: 22457745
10.  Post-Pandemic Seroprevalence of Pandemic Influenza A (H1N1) 2009 Infection (Swine Flu) among Children <18 Years in Germany 
PLoS ONE  2011;6(9):e23955.
We determined antibodies to the pandemic influenza A (H1N1) 2009 virus in children to assess: the incidence of (H1N1) 2009 infections in the 2009/2010 season in Germany, the proportion of subclinical infections and to compare titers in vaccinated and infected children.
Methodology/Principal Findings
Eight pediatric hospitals distributed over Germany prospectively provided sera from in- or outpatients aged 1 to 17 years from April 1st to July 31st 2010. Vaccination history, recall of infections and sociodemographic factors were ascertained. Antibody titers were measured with a sensitive and specific in-house hemagglutination inhibition test (HIT) and compared to age-matched sera collected during 6 months before the onset of the pandemic in Germany. We analyzed 1420 post-pandemic and 300 pre-pandemic sera. Among unvaccinated children aged 1–4 and 5–17 years the prevalence of HI titers (≥1∶10) was 27.1% (95% CI: 23.5–31.3) and 53.5% (95% CI: 50.9–56.2) compared to 1.7% and 5.5%, respectively, for pre-pandemic sera, accounting for a serologically determined incidence of influenza A (H1N1) 2009 during the season 2009/2010 of 25,4% (95% CI : 19.3–30.5) in children aged 1–4 years and 48.0% (95% CI: 42.6–52.0) in 5–17 year old children. Of children with HI titers ≥1∶10, 25.5% (95% CI: 22.5–28.8) reported no history of any infectious disease since June 2009. Among vaccinated children, 92% (95%-CI: 87.0–96.6) of the 5–17 year old but only 47.8% (95%-CI: 33.5–66.5) of the 1–4 year old children exhibited HI titers against influenza A virus (H1N1) 2009.
Serologically determined incidence of influenza A (H1N1) 2009 infections in children indicates high infection rates with older children (5–17 years) infected twice as often as younger children. In about a quarter of the children with HI titers after the season 2009/2010 subclinical infections must be assumed. Low HI titers in young children after vaccination with the AS03B-adjuvanted split virion vaccine need further scrutiny.
PMCID: PMC3168498  PMID: 21915270
11.  Genetic Markers of Obesity Risk: Stronger Associations with Body Composition in Overweight Compared to Normal-Weight Children 
PLoS ONE  2011;6(4):e19057.
Genetic factors are important determinants of overweight. We examined whether there are differential effect sizes depending on children's body composition.
We analysed data of n = 4,837 children recorded in the Avon Longitudinal Study of Parents and Children (ALSPAC), applying quantile regression with sex- and age-specific standard deviation scores (SDS) of body mass index (BMI) or with body fat mass index and fat-free mass index at 9 years as outcome variables and an “obesity-risk-allele score” based on eight genetic variants known to be associated with childhood BMI as the explanatory variable.
The quantile regression coefficients increased with increasing child's BMI-SDS and fat mass index percentiles, indicating larger effects of the genetic factors at higher percentiles. While the associations with BMI-SDS were of similar size in medium and high BMI quantiles (40th percentile and above), effect sizes with fat mass index increased over the whole fat mass index distribution. For example, the fat mass index of a normal-weight (50th percentile) child was increased by 0.13 kg/m2 (95% confidence interval (CI): 0.09, 0.16) per additional allele, compared to 0.24 kg/m2 per allele (95% CI: 0.15, 0.32) in children at the 90th percentile. The genetic associations with fat-free mass index were weaker and the quantile regression effects less pronounced than those on fat mass index.
Genetic risk factors for childhood overweight appear to have greater effects on fatter children. Interaction of known genetic factors with environmental or unknown genetic factors might provide a potential explanation of these findings.
PMCID: PMC3078148  PMID: 21526213
12.  Severe Cases of Pandemic (H1N1) 2009 in Children, Germany 
Emerging Infectious Diseases  2011;17(2):186-192.
In a hospital-based observational study in Germany, we investigated children admitted to pediatric intensive care units and deaths caused by confirmed pandemic (H1N1) 2009 to identify risk factors and outcomes in critically ill children. Ninety-three children were eligible for our study, including 9 with hospital-acquired infections. Seventy-five percent had underlying chronic medical conditions; neurodevelopmental disorders were most prevalent (57%). The proportion of patients having >1 risk factor increased with age in years (odds ratio 1.21, p = 0.007). Of 15 deaths, 11 occurred in a pediatric intensive care unit (case-fatality rate 12%, 95% confidence interval 6%–21%). Only 9% of the children had been vaccinated against pandemic (H1N1) 2009; all survived. Our results stress the role of underlying risk factors, especially neurodevelopmental disorders, and the need for improving preventive measures to reduce severe disease and adverse outcomes of pandemic (H1N1) 2009 in children.
PMCID: PMC3204773  PMID: 21291587
Pandemic (H1N1) 2009; influenza; viruses; infants; children; critical illness; risk factors; Germany; research
13.  Risk Factors for Obesity: Further Evidence for Stronger Effects on Overweight Children and Adolescents Compared to Normal-Weight Subjects 
PLoS ONE  2011;6(1):e15739.
We recently showed that in preschoolers risk factors for overweight show stronger associations with BMI in children with high BMI values. However, it is unclear whether these findings might also pertain to adolescents.
We extracted data on 3–10 year-old (n = 7,237) and 11–17 year-old (n = 5,986) children from a representative cross-sectional German health survey (KiGGS) conducted between 2003 and 2006 and calculated quantile regression models for each age group. We used z-scores of children's body mass index (BMI) as outcome variable and maternal BMI, maternal smoking in pregnancy, low parental socioeconomic status, exclusive formula-feeding and high TV viewing time as explanatory variables.
In both age groups, the estimated effects of all risk factors except formula-feeding on BMI z-score were greatest for children with the highest BMI z-score. The median BMI z-score of 11–17 year-old children with high TV viewing time, for example, was 0.11 [95% CI: 0.03, 0.19] units higher than the median BMI z-score of teenage children with low TV viewing time. This risk factor was associated with an average difference of 0.18 [0.06, 0.30] units at the 90th percentile of BMI z-score and of 0.20 [0.07, 0.33] units at the 97th percentile.
We confirmed that risk factors for childhood overweight are associated with greater shifts in the upper parts of the children's BMI distribution than in the middle and lower parts. These findings pertain also to teenagers and might possibly help to explain the secular shift in the upper BMI percentiles in children and adolescents.
PMCID: PMC3024393  PMID: 21283747
14.  Association between exposure to radiofrequency electromagnetic fields assessed by dosimetry and acute symptoms in children and adolescents: a population based cross-sectional study 
Environmental Health  2010;9:75.
The increase in numbers of mobile phone users was accompanied by some concern that exposure to radiofrequency electromagnetic fields (RF EMF) might adversely affect acute health especially in children and adolescents. The authors investigated this potential association using personal dosimeters.
A 24-hour exposure profile of 1484 children and 1508 adolescents was generated in a population-based cross-sectional study in Germany between 2006 and 2008 (participation 52%). Personal interview data on socio-demographic characteristics, self-reported exposure and potential confounders were collected. Acute symptoms were assessed twice during the study day using a symptom diary.
Only few of the large number of investigated associations were found to be statistically significant. At noon, adolescents with a measured exposure in the highest quartile during morning hours reported a statistically significant higher intensity of headache (Odd Ratio: 1.50; 95% confidence interval: 1.03, 2.19). At bedtime, adolescents with a measured exposure in the highest quartile during afternoon hours reported a statistically significant higher intensity of irritation in the evening (4th quartile 1.79; 1.23, 2.61), while children reported a statistically significant higher intensity of concentration problems (4th quartile 1.55; 1.02, 2.33).
We observed few statistically significant results which are not consistent over the two time points. Furthermore, when the 10% of the participants with the highest exposure are taken into consideration the significant results of the main analysis could not be confirmed. Based on the pattern of these results, we assume that the few observed significant associations are not causal but rather occurred by chance.
PMCID: PMC3006375  PMID: 21108839
15.  Asthma in changing environments - chances and challenges of international research collaborations between South America and Europe - study protocol and description of the data acquisition of a case-control-study 
Asthma in children is an emerging public health problem in South America. So far, research in this part of the world is limited. This paper presents the methodology and description of the data acquisition of an asthma case-control study conducted in the Central South of Chile.
A hospital-based case-control study about asthma (188 cases, 294 controls) in children (6-15 years) was carried out in Valdivia, Chile between November 2008 and December 2009. Data on asthma risk factors were collected by computer-assisted personal interview using validated questions from e.g. ISAAC phase II. Data on household dust exposure (endotoxin, allergen analyses), skin prick tests to most common allergens, stool examinations for parasitic infection, and blood samples (total IgE, genetics) were collected. Additionally, 492 randomly chosen blood donors were recruited in order to assess allele frequencies in the population of Valdivia.
Overall 1,173 participants were contacted. Response was 82% among cases and 65% among controls. Atopic sensitization was high (78% among cases, 47% among controls). Cases had a statistically significantly (p < .0001) increased self-reported 12-month prevalence of symptoms of rhinitis (82% vs. 51%) and wheeze (68% vs. 16%). The study is well placed to address current hypotheses about asthma and its correlates in the South American context. Results of this study might help develop novel, innovative and individualized prevention strategies in countries in transition with respect to the South American context.
PMCID: PMC2930633  PMID: 20718949
16.  Maternal postnatal depression and child growth: a European cohort study 
BMC Pediatrics  2010;10:14.
Previous studies have reported postpartum depression to be associated with both positive and negative effects on early infant growth. This study examined the hypothesis that maternal postnatal depression may be a risk factor for later child growth faltering or overweight.
A total of 929 women and their children participating in a European multicenter study were included at a median age of 14 days. Mothers completed the Edinburgh postnatal depression scale (EPDS) at 2, 3 and 6 months after delivery. EPDS scores of 13 and above at any time were defined as maternal depression. Weight, length, triceps and subscapular skinfold thicknesses were measured, and body mass index (BMI) were calculated when the children were two years old and converted to standard deviation scores based on the WHO Multicentre Growth Reference Study (MGRS).
Z-scores for weight-for-length at inclusion of infants of mothers with high EPDS scores (-0.55, SD 0.74) were lower than of those with normal scores (-0.36, SD 0.74; p = 0.013). BMI at age 24 months did not differ in the high (16.3 kg/m2, SD 1.3) and in the normal EPDS groups (16.2 kg/m2, SD 1.3; p = 0.48). All other anthropometric indices also did not differ between groups, with no change by multivariate adjustment.
We conclude that a high maternal postnatal depression score does not have any major effects on offspring growth in high income countries.
PMCID: PMC2850333  PMID: 20226021
17.  The association between use of electronic media and prevalence of headache in adolescents: results from a population-based cross-sectional study 
BMC Neurology  2010;10:12.
Use of electronic media, i.e. mobile phones, computers, television, game consoles or listening to music, is very common, especially amongst adolescents. There is currently a debate about whether frequent use of these media might have adverse effects on health, especially on headaches, which are among the most-reported health complaints in adolescents. The aim of the present study was to assess associations between frequent use of electronic media and the prevalence of different types of headache in adolescents.
Data were derived from a population-based sample (n = 1,025, ages 13-17 years). Type of headache (i.e. migraine, tension-type headache, unclassifiable headache) was ascertained by standardized questionnaires for subjects reporting headache episodes at least once per month during the last six months. Duration of electronic media use was assessed during personal interviews. Associations were estimated with logistic regression models adjusted for age group, sex, family condition and socio-economic status.
Most of the adolescents used computers (85%), watched television (90%) or listened to music (90%) daily, otherwise only 23% of the participants used their mobile phones and only 25% played with game consoles on a daily basis. A statistically significant association between listening to music and any headache (odds ratio 1.8; 95% confidence interval 1.1-3.1 for 30 minutes per day, 2.1; 1.2-3.7 for 1 to 2 hours per day; 2.0; 1.2-3.5 for 3 hours and longer listening to music per day) was observed. When stratifying for type of headache, no statistically significant association was seen.
Apart from an association between listening to music on a daily basis and overall headache, no consistent associations between the use of electronic media and different types of headache were observed.
PMCID: PMC2834664  PMID: 20144204
18.  Effect of heptavalent pneumococcal conjugate vaccination on invasive pneumococcal disease in preterm born infants 
Evidence for protection of preterm born infants from invasive pneumococcal disease (IPD) by 7-valent pneumococcal conjugate vaccination (PCV7) is relatively sparse. Data from randomized trials is based on relatively small numbers of preterm born children.
We report data from active prospective surveillance of IPD in children in Germany. The cohorts of preterm born children in 2000 and 2007 and the respective whole birth cohorts are compared regarding occurrence of IPD.
After introduction of PCV7 we observed a reduction in the rate of IPD in preterm born infants comparing the 2000 and 2007 birth cohort. The rate of IPD among the whole birth cohorts was reduced from 15.0 to 8.5 notifications per 100,000 (P < .001). The impact among the preterm birth cohort was comparable: A reduction in notification rate from 26.1 to 16.7 per 100,000 comparing the 2000 with the 2007 preterm birth cohort (P = .39). Preterm born infants with IPD were either unvaccinated or vaccinated delayed or incomplete.
This adds to evidence that PCV7 also protects preterm born infants effectively from IPD. Preterm born infants should receive pneumococcal vaccination according to their chronological age.
PMCID: PMC2823613  PMID: 20085656
19.  Prenatal and Postnatal Tobacco Exposure and Behavioral Problems in 10-Year-Old Children: Results from the GINI-plus Prospective Birth Cohort Study 
Environmental Health Perspectives  2009;118(1):150-154.
Prenatal and postnatal tobacco exposure have been reported to be associated with behavioral problems. However, the magnitude of the association with tobacco exposure at specific periods of exposure is unclear.
We assessed the relative risk of behavioral problems in children who had been exposed to tobacco smoke in utero and postnatally.
We analyzed data from a prospective birth cohort study in two cities in Germany: the German Infant Nutrition Intervention. Our sample included 5,991 children born between 1995 and 1998 as well as their parents. We measured behavioral problems using the Strength and Difficulties Questionnaire (SDQ) at follow-up 10 years after birth. According to prespecified SDQ cutoff values, children were classified as “normal,” “borderline,” or “abnormal” according to the subscales “emotional symptoms,” “conduct problems,” “hyperactivity/inattention,” “peer-relationship problems,” and a total difficulties score. Smoke exposure and further covariates were assessed using parent questionnaires.
Compared with children not exposed to tobacco smoke, children exposed both pre- and postnatally to tobacco smoke had twice the estimated risk [95% confidence interval (CI), 1.4–3.1] of being classified as abnormal according to the total difficulties score of the SDQ at 10 years of age. Children who were only prenatally exposed had a 90% higher relative risk (95% CI, 0.9–4.0), whereas children who were only postnatally exposed had a 30% higher relative risk (95% CI, 0.9–1.9). These results could not be explained by confounding by parental education, father’s employment, child’s time spent in front of computer or television screen, being a single father or mother, or mother’s age.
Prenatal exposure to tobacco smoke is associated with behavioral problems in school-age children. Although our findings do not preclude the influence of postnatal exposure, prenatal exposure seems to be more important.
PMCID: PMC2831960  PMID: 20056582
adolescent health; behavioral problems; cohort study; environmental tobacco smoke exposure; strengths and difficulties questionnaire
20.  Incidence and classification of pediatric diffuse parenchymal lung diseases in Germany 
Diffuse parenchymal lung diseases (DPLD) in children represent a rare and heterogeneous group of chronic pulmonary disorders. Despite substantial advances in genetics and pathomechanisms, these often lethal diseases are still under-diagnosed. This is due to the fact that (i) the incidence is low, and (ii) clinical presentation, (iii) disease classification and (iv) specific treatment options are largely unknown.
Here we systematically assessed the incidence, the presentation, the diagnostic yield and treatments of pediatric DPLD in Germany, using the Surveillance Unit for Rare Paediatric Disorders (ESPED).
The incidence of DPLD was 1.32 new cases per 1 million of children per year. The majority of these children were diagnosed within the first year of life. Overall survival was 87%. Using centralized data entry and stratification tools, the patients were categorized into an advanced classification system based on diagnostic algorithms, including clinical presentations, genetics and/or histology. Combining molecular and clinical information, this survey provides an etiological overview and specific diagnostic recommendations for children with DPLD.
Standardized surveys and systematic classifications are valuable tools for the clinical handling of children with DPLD and aim to improve the disease understanding and the prognosis of these rare detrimental lung diseases.
PMCID: PMC2800105  PMID: 20003372
21.  Invasive Haemophilus influenzae infections in Germany: impact of non-type b serotypes in the post-vaccine era 
Haemophilus influenzae type b (Hib) vaccination led to a significant decrease in invasive bacterial infections in children. The aim of this study was to assess a potential shift to more non-type b invasive infections in a population with high Hib vaccination coverage and to compare the burden of suffering between children with Hib, capsulated non-b and non-capsulated Hi infections.
Cases with confirmed invasive Hi infections were ascertained through two independent nationwide active surveillance systems in 1998–2005. Information on possible predisposing conditions and clinical information was available from 2001 onwards.
The total number of reported non-type b Hi cases varied between 10 cases in 1998, 27 in 2000 and 14 in 2005. In each year, non-capsulated serotypes outnumbered capsulated non-type b ones. 192 cases were detected in 2001–2005, more than one half was non-type b and 88% of the non-type b cases were non-capsulated. For cases with Hib/capsulated non-type b infections the most common clinical presentation was meningitis (67% each); 89%/78% had no potential predisposing condition, 75%/72% completely recovered from disease and 6% (each) died. In contrast, meningitis was diagnosed in 34% of the non-capsulated Hi infections, septicaemia in 28% and pneumonia 21%; 62% had no potential predisposing condition, 83% completely recovered and 3% died.
There was no increase in non-type b Hi invasive infections during 8 years of active surveillance in Germany. Invasive disease due to non-type b Hi is not confined to children with risk factors. In patients with capsulated non-type b Hi infections the proportion of meningitis cases is similar to Hib, but double as high as in non-capsulated Hi.
PMCID: PMC2678273  PMID: 19379490
22.  An illustration of and programs estimating attributable fractions in large scale surveys considering multiple risk factors 
Attributable fractions (AF) assess the proportion of cases in a population attributable to certain risk factors but are infrequently reported and mostly calculated without considering potential confounders. While logistic regression for adjusted individual estimates of odds ratios (OR) is widely used, similar approaches for AFs are rarely applied.
Different methods for calculating adjusted AFs to risk factors of cardiovascular disease (CVD) were applied using data from the National Health and Nutrition Examination Survey (NHANES). We compared AFs from the unadjusted approach using Levin's formula, from Levin's formula using adjusted OR estimates, from logistic regression according to Bruzzi's approach, from logistic regression with sequential removal of risk factors ('sequential AF') and from logistic regression with all possible removal sequences and subsequent averaging ('average AF').
AFs following the unadjusted and adjusted (using adjusted ORs) Levin's approach yielded clearly higher estimates with a total sum of more than 100% compared to adjusted approaches with sums < 100%. Since AFs from logistic regression were related to the removal sequence of risk factors, all possible sequences were considered and estimates were averaged. These average AFs yielded plausible estimates of the population impact of considered risk factors on CVD with a total sum of 90%. The average AFs for total and HDL cholesterol levels were 17%, for hypertension 16%, for smoking 11%, and for diabetes 5%.
Average AFs provide plausible estimates of population attributable risks and should therefore be reported at least to supplement unadjusted estimates. We provide functions/macros for commonly used statistical programs to encourage other researchers to calculate and report average AFs.
PMCID: PMC2636839  PMID: 19166593
23.  Exposure to mobile telecommunication networks assessed using personal dosimetry and well-being in children and adolescents: the German MobilEe-study 
Environmental Health  2008;7:54.
Despite the increase of mobile phone use in the last decade and the growing concern whether mobile telecommunication networks adversely affect health and well-being, only few studies have been published that focussed on children and adolescents. Especially children and adolescents are important in the discussion of adverse health effects because of their possibly higher vulnerability to radio frequency electromagnetic fields.
We investigated a possible association between exposure to mobile telecommunication networks and well-being in children and adolescents using personal dosimetry. A population-based sample of 1.498 children and 1.524 adolescents was assembled for the study (response 52%). Participants were randomly selected from the population registries of four Bavarian (South of Germany) cities and towns with different population sizes. During a Computer Assisted Personal Interview data on participants' well-being, socio-demographic characteristics and potential confounder were collected. Acute symptoms were assessed three times during the study day (morning, noon, evening).
Using a dosimeter (ESM-140 Maschek Electronics), we obtained an exposure profile over 24 hours for three mobile phone frequency ranges (measurement interval 1 second, limit of determination 0.05 V/m) for each of the participants. Exposure levels over waking hours were summed up and expressed as mean percentage of the ICNIRP (International Commission on Non-Ionizing Radiation Protection) reference level.
In comparison to non-participants, parents and adolescents with a higher level of education who possessed a mobile phone and were interested in the topic of possible adverse health effects caused by mobile telecommunication network frequencies were more willing to participate in the study. The median exposure to radio frequency electromagnetic fields of children and adolescents was 0.18% and 0.19% of the ICNIRP reference level respectively.
In comparison to previous studies this is one of the first to assess the individual level of exposure to mobile telecommunication networks using personal dosimetry, enabling objective assessment of exposure from all sources and longer measurement periods. In total, personal dosimetry was proofed to be a well accepted tool to study exposure to mobile phone frequencies in epidemiologic studies including health effects on children and adolescents.
PMCID: PMC2614418  PMID: 18983641
24.  Risk factors for childhood obesity: shift of the entire BMI distribution vs. shift of the upper tail only in a cross sectional study 
BMC Public Health  2008;8:115.
Previous studies reported an increase of upper body mass index (BMI) quantiles for formula fed infants compared to breastfed infants, while corresponding mean differences were low. The aim of this study was to assess the impact of known risk factors for childhood obesity on the BMI distribution.
Data on 4,884 children were obtained at obligatory school entry health examinations in Bavaria (Germany). Exposure variables were formula feeding, maternal smoking in pregnancy, excessive TV-watching, low meal frequency, poor parental education, maternal overweight and high infant weight gain. Cumulative BMI distributions and Tukey mean-difference plots were used to assess possible shifts of BMI distributions by exposure.
Maternal overweight and high infant weight gain shifted the entire BMI-distribution with an accentuation on upper quantiles to higher BMI values. In contrast, parental education, formula feeding, high TV consumption, low meal frequency and maternal smoking in pregnancy resulted in a shift of upper quantiles only.
The single shifts among upper parts of the BMI distribution might be due to effect modification of the corresponding exposures by another environmental exposure or genetic predisposition. Affected individuals might represent a susceptible subpopulation of the exposed.
PMCID: PMC2322977  PMID: 18402677
25.  Vaccination coverage in children can be estimated from health insurance data 
BMC Public Health  2008;8:82.
The introduction of new vaccines for young children requires instruments for a rapid and timely assessment of the progressively increasing vaccination coverage. We assessed whether routine data generated by statutory health insurances (SHI) might be used to monitor vaccination coverage in young children.
For 90% of the population Germany's healthcare system is premium-funded through SHI. Specific medical codes on childhood vaccination are used for billing. These were used to analyse vaccine uptake up to 24 months in children born in Bavaria between 2001–10–01 and 2002–12–31. For children insured in the biggest SHI, vaccination coverage estimates based on billing data were compared to estimates considering only continuously insured children since birth, based on additional data provided by this SHI.
Definition of an appropriate denominator from the billing data was a major challenge: defining the denominator by any consultation by children with different ID numbers yielded 196,732 children, exceeding the number of births in Bavaria by a factor of 1.4. The main causes for this inflated denominator were migration and change of health insurance number. A reduced dataset based on at least one physician's visit in the first six months and 2nd year of life yielded 111,977 children. Vaccination coverage estimates for children in the biggest SHI were at maximum 1.7% higher than in the data set based on continuously insured children.
With appropriate adjustments to define the denominator physician's billing data provide a promising tool to estimate immunisation coverage. A slight overestimation based on these data was explained by children never seeing a physician.
PMCID: PMC2268683  PMID: 18312683

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