Chad A. Logan

Changing Societal and Lifestyle Factors and Breastfeeding Patterns Over Time

BACKGROUND: Breastfeeding is an important determinant of early infant immune function and potentially future health. Although numerous studies have reported rising breastfeeding initiation rates and duration, few longitudinally investigated the impact of shifting societal and lifestyle factors on breastfeeding patterns in developed nations. METHODS: The Ulm Birth Cohort Study (UBCS) and Ulm SPATZ Health Study (SPATZ) cohorts consist of newborns and their mothers recruited, respectively, from 2000 to 2001 and 2012 to 2013 at the University Medical Center Ulm, Germany. Cox proportional hazards models were used to estimate crude and mutually adjusted hazard ratios for study effect (time trend) and individual risk factors on noninitiation and duration of predominant and total breastfeeding. RESULTS: Compared with UBCS mothers, SPATZ mothers had lower cessation rates of both predominant breastfeeding by 4 months and total breastfeeding by 6 months: hazard ratio (95% confidence interval) 0.79 (0.67–0.93) and 0.71 (0.60–0.82), respectively. However, this crude time trend was limited to mothers with higher educational achievement. Similar time trend effects were observed among less educated mothers only after adjustment for early cessation risk factors. Mutually adjusted hazard ratios for individual risk factors were similar in both studies: low education, high BMI, smoking within 6 weeks of delivery, and cesarean delivery were associated with early breastfeeding cessation beginning at 6 weeks. In addition, actively abstaining from drinking alcohol was associated with lower rates of early cessation. CONCLUSIONS: Our results suggest widening socioeconomic disparity in breastfeeding and potentially subsequent child health, which may require new targeted interventions.

Delivery Mode, Duration of Labor, and Cord Blood Adiponectin, Leptin, and C-Reactive Protein: Results of the Population-Based Ulm Birth Cohort Studies

Background Numerous studies have reported associations between delivery mode and health outcomes in infancy and later life. Previous smaller studies indicated a relationship between delivery mode and newborn inflammation potentially constituting a mediating factor. We aimed to determine the influence of delivery mode and duration of labor on cord blood concentrations of adiponectin, leptin, and high-sensitivity C-reactive protein (hs-CRP). Methods In the Ulm SPATZ Health Study, 934 singleton newborns and their mothers were recruited during their hospital stay in the University Medical Center Ulm, Southern Germany, from 04/2012-05/2013. Inflammatory biomarkers were measured by ELISAs (n = 836). Delivery mode was analyzed categorically (elective cesarean (reference), active labor delivery: emergency cesarean, assisted vaginal, and spontaneous vaginal); duration of labor continuously. Following log-transformation, linear regression was used to estimate geometric means ratios (GMR) adjusted for potential confounders for the effects of delivery mode and duration of labor on each biomarker separately. Independent replication was sought in the similarly conducted Ulm Birth Cohort Study recruited from 11/2000-11/2001. Results Individually, active labor delivery modes as well as increasing duration of labor were associated with higher leptin and hs-CRP concentrations. After mutual adjustment, the associations with delivery modes were attenuated but those for duration of labor remained statistically significant (GMR (95%CI) 1.10 (1.00; 1.21) and 1.15 (1.04; 1.27) for leptin and hs-CRP per hour of labor, respectively). No significant adjusted associations were observed between delivery modes and adiponectin concentrations. These findings were replicated in an independent birth cohort study. Conclusions Cord blood leptin and hs-CRP concentrations were associated with duration of labor rather than delivery mode. Further research is warranted to investigate these associations with additional cytokines involved in inflammatory response to delineate the inflammatory profile. Subsequently, research on determinants of these associations and their role in development of chronic disease is needed.

Gestational Weight Gain and Fetal-Maternal Adiponectin, Leptin, and CRP: results of two birth cohorts studies

Gestational weight gain (GWG) is an important modifiable factor known to influence fetal outcomes including birth weight and adiposity. Unlike behaviors such as smoking and alcohol consumption, the effect of GWG throughout pregnancy on fetal development and other outcomes has not been extensively studied. The aim of this study was to investigate the relationship of GWG with endocrine factors such as adiponectin, leptin, and C-reactive protein which may be associated with inflammatory response, fetal growth, and adiposity later in life. Data were obtained from the Ulm Birth Cohort Study (UBCS) and the Ulm SPATZ Health Study, two methodologically similar birth cohort studies including newborns and their mothers recruited from 11/2000–11/2001 and 04/2012–05/2013. In the two included birth cohorts we consistently observed statistically significant positive associations between GWG beginning as early as the second trimester with fetal cord blood leptin and stronger association beginning as early as the first trimester with post-delivery maternal serum leptin. Total weight gain exceeding commonly accepted recommended guidelines was consistently associated with higher leptin levels in both cord blood and post-delivery maternal serum. These results suggest a potential pathomechanistic link between fetal environment and surrogate markers of long-term health.

Postpartum Smoking Relapse and Breast Feeding: Defining the Window of Opportunity for Intervention

Background Though many women spontaneously quit smoking during pregnancy, a large proportion relapse after delivery. Efforts aimed at reducing postpartum smoking relapse have been largely ineffective. Several studies have reported breast feeding as a primary factor influencing smoking abstinence duration. However, data on the potential role of breast feeding in smoking intervention efforts remain incomplete. Methods The Ulm SPATZ Health Study cohort consists of 1006 newborns of 970 mothers recruited in the University Medical Center Ulm, Germany. Kaplan-Meier plots, log-rank tests, and Cox proportional hazards models were used to assess differences in predominant and total breast-feeding duration stratified by smoking abstinence at 2 years and relapse period (by 6 weeks, 6 months, and 2 years postdelivery). Chi-square and Kruskal-Wallis tests were performed to identify significant differences in demographic and lifestyle factors across smoking categories. Results Approximately 70% of previous smokers who initiated breast feeding relapsed within 2 years. Relapse by 6 months was significantly associated with noninitiation of predominant breast feeding. Total breast-feeding duration rates among abstaining mothers and those who relapsed after 6 weeks mirrored those of nonsmokers respectively up to 1 year and 3 months. Lower age and education were mostly associated with smoking by 6 weeks. First parity and having a nonsmoking partner were associated with abstinence up to 2 years. Conclusions Interventions promoting breast feeding to incentivize continued smoking abstinence may be effective prior to weaning. Those promoting breast feeding longer than 6 months and partner smoking cessation may increase rates of long-term smoking abstinence lasting longer than 2 years postdelivery. Implications Most mothers who quit smoking during pregnancy relapse within 6 months of delivery. Though interventions targeting new mothers have been largely unsuccessful, relapse is often delayed until after weaning and targeted breast-feeding promotion has been suggested to enhance smoking cessation interventions. In this study, we assess the relationship between breast-feeding duration and long-term smoking abstinence by longitudinally investigating predominant and total breast-feeding patterns among mothers with a recent history of smoking stratified by period of relapse up to 2 years after delivery.

New approach shows no association between maternal milk fatty acid composition and childhood wheeze or asthma

Previous observational studies have implied breastmilk fatty acid composition may play a role in the development of atopic eczema or atopic sensitization in breastfed infants and toddlers. However, studies investigating associations with wheeze and asthma in later childhood are scarce and did not account for inherent correlation of compositional data. Our aim was to explore the association of maternal milk fatty acid composition with childhood wheezing phenotypes and asthma up to age 13 years using a new statistical approach.

Cord blood PRF1 methylation patterns and risk of lower respiratory tract infections in infants: findings from the Ulm Birth Cohort.

AbstractLower respiratory tract infections (LRTIs) are a major cause of morbidity in children. DNA methylation provides a mechanism for transmitting environmental effects on the genome, but its potential role in LRTIs is not well studied. We investigated the methylation pattern of an enhancer region of the immune effector gene perforin-1 (PRF1), which encodes a cytolytic molecule of cytotoxic T lymphocytes (CTLs) and natural killer cells (NK), in cord blood DNA of children recruited in a German birth cohort in association with LRTIs in the first year of life.Pyrosequencing was used to determine the methylation levels of target cytosine–phosphate–guanines (CpGs) in a 2-stage case–control design. Cases were identified as children who developed ≥2 episodes of physician-recorded LRTIs during the first year of life and controls as children who had none. Discovery (n = 87) and replication (n = 90) sets were arranged in trios of 1 case and 2 controls matched for sex and season of birth.Logistic regression analysis revealed higher levels of methylation at a CpG that corresponds to a signal transducer and activator of transcription 5 (STAT5) responsive enhancer in the discovery (odds ratio [OR] per 1% methylation difference 1.24, 95% confidence interval [CI] 1.03–1.50) and replication (OR per 1% methylation difference 1.25, 95% CI 1.04–1.50) sets. Adjustment for having siblings <5 years old in the discovery and replication sets produced ORs of 1.19 (95% CI 0.98–1.45) and 1.25 (95% CI 1.04–1.50), respectively. Adjustment for gestational age in the replication set had no influence on the results. Methylation levels at adjacent CpGs varied with maternal age, smoking, education, and having siblings <5 years old.Our data support an association between cord blood PRF1 enhancer methylation patterns and subsequent risk of LRTIs in infants. Methylation levels at specific CpGs of the PRF1 enhancer varied according to maternal and family environmental factors suggesting a role for DNA methylation in mediating environmental influences on gene function.

Reduced PRF1 enhancer methylation in children with a history of severe RSV bronchiolitis in infancy: an association study

BackgroundAcute lower respiratory tract infection is the commonest disease affecting children under five worldwide. Respiratory syncytial virus (RSV) is among the most common causative pathogens. Epidemiological data suggest an association between severe viral respiratory infections in infancy and increased incidence of childhood wheeze and asthma. DNA methylation is involved in immune cell differentiation and identity. It provides an avenue for environmental influences on the genome and therefore has potential as a marker for sustained effects of infectious insults. In this study we investigated the association between DNA methylation patterns in the perforin gene (PRF1) in childhood and a history of hospitalisation for severe RSV disease in the first two years of life.MethodsIn this retrospective study, we explored patterns of whole blood DNA methylation at a methylation sensitive region of the proximal PRF1 enhancer in a group of children with a record of hospitalisation for severe RSV disease during infancy (n = 43) compared to healthy controls matched for age and sex with no similar hospitalisation history, no allergy and no persistent wheeze (n = 43). Univariate and bivariate conditional logistic regression analyses were conducted to test the association between PRF1 enhancer methylation and record of hospitalisation for RSV disease.ResultsChildren with a record of hospitalisation for severe RSV bronchiolitis demonstrated markedly lower levels of DNA methylation at two cytosine-phosphate-guanine dinucleotide (CpG) loci of the PRF1 proximal enhancer, corresponding to a signal transducer and activator of transcription 5 (STAT5) responsive element, compared to controls, adjusted odds ratios of 0.82 (95% confidence interval [CI] 0.71, 0.94) and 0.73 (95% CI 0.58, 0.92) for each 1% increase in DNA methylation. Smoking in the household showed a significant influence on DNA methylation at the assayed positions.ConclusionsOur findings support an association between childhood DNA methylation patterns in PRF1 and a record of severe RSV infection in infancy. Longitudinal studies are required to establish the utility of PRF1 methylation as a marker of severe RSV disease.

Fetal growth and incidence of atopic dermatitis in early childhood: Results of the Ulm SPATZ Health Study

Fetal growth may be a precursory factor in observed association between birthweight and atopic dermatitis (AD), however, recent studies utilizing fetal ultrasound-based data have reported contradictory results. This study aims to clarify previous findings through comprehensive investigation of association between several trimester-specific ultrasound-based anthropometric measures with AD diagnosis by age 3 years. Measurements of 386 newborns in the Ulm SPATZ Health Study were converted into adjusted z-scores categorized as “low” (≤1 SD below mean), “normal,” or “high” (≥1 SD above mean). AD cases were defined using parent- or pediatrician-report of physician-diagnosis or clinical diagnosis. Adjusted risk ratios (RR) with 95% confidence intervals (95% CI) were calculated using modified Poisson regression. Compared to normal, both low and high 2nd trimester abdominal circumference [RR 1.51, (95% CI 1.01; 2.24) and 1.83 (1.21; 2.76)], high 2nd trimester head- abdominal circumference ratio [1.69 (1.16; 2.48)], and faltering 2nd to 3rd trimester [1.59 (1.04; 2.43)] head circumference were associated with greater AD risk. High 3rd trimester femur length [0.54 (0.31; 0.94)] was associated with lower risk. Using more inclusive exposure cut-points (0.8 SD), lower 1st trimester crown-rump length was also associated with greater AD risk. Our data suggest several different patterns of fetal growth may be differentially associated with AD.

Association of maternal uric acid and cystatin C serum concentrations with maternal and neonatal cardiovascular risk markers and neonatal body composition: The Ulm SPATZ Health Study

Purpose In utero exposure to cardiometabolic risk factors may determine health related outcomes at birth and in later life. The aim of this analysis was to describe the relationship of maternal serum uric acid (SUA) and cystatin C with maternal and neonatal cardiometabolic risk markers and with birth weight and risk of small-for-gestational age (SGA) as well as large-for gestational age (LGA). Material and methods In the Ulm SPATZ Health Study, 934 singleton newborns and their mothers were recruited during their hospital stay in the University Medical Center Ulm between 04/2012 and 05/2013 (overall response 49%). The association between SUA and cystatin C (both in quartiles and as continuous measures) with risk for SGA as well as with LGA was quantified by means of multivariable logistic regression. Results Overall, n = 885 mother-newborn pairs were included in the final analysis. Most of the mothers were of German nationality (85%) and were between 26 and 35 years of age at delivery (69%). Maternal SUA was associated with maternal age, body mass index, alcohol consumption and history of hypertension as well as with many other maternal and neonate cardiovascular risk markers. Cystatin C was associated with parity. No clear association of SUA with SGA and LGA was observed in fully adjusted models. However, cystatin C was negatively associated with SGA with an odds ratio (OR) of 0.35 (95% CI: 0.16–0.77; p for trend 0.04) comparing the top quartile vs. the bottom quartile and was positively associated with LGA with an OR of 5.92 (95% CI: 2.27–15.44; p for trend <0.0001) after adjustment for covariates. Conclusions We found a positive association of cystatin C with birth weight and a clearly increased risk for LGA with maternal increased cystatin C values in a population with fairly normal renal function.

Determinants of leptin in human breast milk: results of the Ulm SPATZ Health Study

BackgroundLeptin in human breast milk has been implicated as a potential regulator of early-life metabolic programming. We comprehensively investigated the influence of maternal body mass index (BMI) and non-adiposity associated determinants on breast milk leptin concentration at 6 weeks, 6 months, and 1 year postpartum.MethodsThe Ulm SPATZ Health Study consists of 1006 newborns and their mothers recruited from the general population in the University Medical Center Ulm, Southern Germany, in 2012/2013. Leptin concentration was measured in skimmed breast milk using commercially available ELISA (R&D System). Generalized estimating equations (GEE) accounting for repeated measures were used to calculate beta coefficients and 95% confidence intervals for association of potential demographic and lifestyle related determinants of hormone concentration with BMI-standardized leptin z-scores.ResultsLeptin concentration was measured in breast milk samples obtained from 694 mothers at approximately 6 weeks (n = 668), 6 months (n = 445), and 1 year (n = 69) postpartum. Differences in crude leptin concentrations between collection times were mostly explained by changes in BMI, breastfeeding frequency, and breast milk fat concentration. Positive associations between BMI and leptin were nonlinear and stronger among lower BMI subjects. Upon standardization, residual leptin concentrations were associated with maternal birth country, parity, age, and smoking history.ConclusionsBreast milk leptin concentration is primarily determined by adiposity-related factors. Studies using BMI as a proxy measure for adiposity should account for an observed nonlinear association with leptin, which may be especially important in determining causal associations with health outcomes from this and other adiposity-related hormones in breast milk.