Mitra Yousefi

Breastfeeding is associated with increased lung function at 18 years of age: a cohort study

Breastfeeding has been linked with increased forced vital capacity (FVC) in children but not in older adolescents. Our aim was to investigate the effects of breastfeeding duration and infant weight gain on FVC in both developmental periods. In a birth cohort, information on breastfeeding duration was collected at 1 and 2 yrs; spirometric tests were conducted at 10 and 18 yrs. To estimate the effect of breastfeeding duration on FVC at 18 yrs of age, we used linear models; to analyse repeated FVC measurements at 10 and 18 yrs of age, we used linear mixed models. Links between breastfeeding, infant weight gain and FVC at 10 and 18 yrs of age were analysed through path analyses. Among 808 breastfed children, 49% were breastfed for ≥4 months. At 18 yrs of age the augmenting effect of breastfeeding on FVC was reduced with increased height. Linear mixed models identified that breastfeeding duration was associated with increased FVC. Path analysis suggested a direct effect of breastfeeding on FVC at 10 yrs of age, but an indirect effect at 18 yrs of age via FVC at 10 yrs of age. Although inversely related to breastfeeding, a higher weight gain in infants led to taller adolescents and, in turn, resulted in increased FVC. In conclusion, a longer duration of breastfeeding contributes to lung health in childhood and adolescence.

Maternal immune markers in serum during gestation and in breast milk and the risk of asthma-like symptoms at ages 6 and 12 months: a longitudinal study

BackgroundThe role of breast milk on the risk of childhood asthma is in dispute. The aim of this prospective study is to determine the relationship of immune markers in maternal serum during gestation and breast milk to asthma-like symptoms (AS) in infancy.MethodsPregnant women were recruited in Columbia and Charleston, South Carolina. Blood (median: three weeks before delivery) and breast milk (three weeks after delivery) samples were collected. Concentrations of interferon (IFN)-γ, IFN gamma-induced protein 10 (IP-10 or CXCL10), CCL11, interleukin (IL) 1β, IL-4, IL-5, IL-6, CXCL8, IL-10, IL-12(p70), IL-13, transforming growth factor (TGF)-β1, and immunoglobulin (Ig) A in both maternal serum and milk whey were determined via immunoassays. Asthma-like symptoms (AS) of the infant were ascertained at 6 and 12 months, respectively. Generalized estimating equations assessed relative risks (RRs) of immune markers for repeated measurements of AS, considering intra-individual correlations and adjusting for confounders. To provide comparable risk estimates, quartiles of the immune markers were used, except for IL-5 in whey and IgA in serum, which were dichotomized.ResultsOf 178 women, 161 provided blood and 115 breast milk samples. IL-12(p70), IL-4, IL-10, IL-1β, and CCL11 in serum and in whey were not further considered for the statistical analyses since the proportion of non-detectable values was high. Most immune markers in serum and milk whey were moderately or highly correlated; however, IgA was negatively correlated. Infants in the highest quartile of IL-13 in both serum and whey were at a higher risk of AS (RR = 3.02 and 4.18; respectively) compared to infants in the first quartile. High levels of IL-5 in serum and whey was also identified as a risk. In addition, increased secretory IgA and TGF-β1 in breast milk reduced the risks of AS.ConclusionsMaternal serum and whey levels of IL-5 and IL-13 are risk markers for AS; whey IgA and TGF-β1 seem to be protective. Only focusing on breast milk portend that milk cytokines IL-5 and IL-13 have adverse effects. However, similar immune exposures during late gestation and via milk suggest that both may enhance AS among infants.

Interplay of filaggrin loss-of-function variants, allergic sensitization, and eczema in a longitudinal study covering infancy to 18 years of age.

Background Immune specific genes as well as genes regulating the formation of skin barrier are major determinants for eczema manifestation. There is a debate as to whether allergic sensitization and filaggrin gene (FLG) variants lead to eczema or FLG variants and eczema increase the risk of allergic sensitization. To investigate the time-order between eczema and allergic sensitization with respect to FLG variants, data from a large prospective study covering infancy to late adolescence were analyzed. Methodology/Principal Findings Repeated measurements of eczema and allergic sensitization (documented by skin prick tests) at ages 1, 2, 4, 10, and 18 years were ascertained in the Isle of Wight birth cohort (n = 1,456). Three transition periods were analyzed: age 1-or-2 to 4, 4 to 10, and 10 to 18 years. FLG variants were genotyped in 1,150 participants. Over the three transition periods, in temporal sequence analyses of initially eczema-free participants, the combined effect of FLG variants and allergic sensitization showed a 2.92-fold (95% CI: 1.47–5.77) increased risk ratio (RR) of eczema in subsequent examinations. This overall risk was more pronounced at a younger age (transition period 1-or-2 to 4, RR = 6.47, 95% CI: 1.96–21.33). In contrast, FLG variants in combination with eczema showed a weaker, but significant, risk ratio for subsequent allergic sensitization only up to 10 years of age. Conclusions/Significance Taking the time order into account, this prospective study demonstrates for the first time, that a combination of FLG variants and allergic sensitization increased the risk of eczema in subsequent years. Also FLG variants interacted with eczema and increased the risk of subsequent allergic sensitization, which, was limited to the younger age. Hence, early restoration of defective skin barrier could prevent allergic sensitization and subsequently reduce the risk of eczema development.

Relationships between age of puberty onset and height at age 18 years in girls and boys

BackgroundChanges during puberty may influence final adult height. Height is related to multiple health conditions, including lung function. We investigated the association between the age of onset of five puberty events and height at age 18 years, analyzing boys and girls separately.MethodsOf 1456 children recruited into the Isle of Wight birth cohort (1989–1990), 1313 were followed up at age 18 years. Height was measured, and age of pubertal onset was collected at age 18 years. Cluster analysis was performed on the five puberty events in boys and girls and linear regression was applied with the clusters predicting height at age 18 years. Individual linear regression analyses assessed the age of onset of each pubertal event as a potential predictor for height at age 18 years.ResultsOf the 1313 children followed up at age 18 years, 653 were males and 660 were females. All puberty variables had high internal consistency. In girls, earlier age of menarche, breast development, and growth spurt were related to shorter height. In boys, earlier age of growth spurt and slower progression through puberty were related to taller height at age 18 years.ConclusionsGiven that boys and girls may have opposing associations between pubertal timing and adult height and that height is an important predictor of lung function, the effect of pubertal timing on respiratory health should be explored.

Pre- and perinatal characteristics and breast milk immune markers

Background:Maternal allergy and gestational exposures can alter the concentration of type-1/type-2/T-regulatory markers in breast milk. We tested whether maternal risk factors are related to breast milk immune markers.Methods:Expecting mothers were enrolled in 2008–2010 in South Carolina in prenatal clinics and classes. Interferon (IFN)-γ–induced protein 10 (CXCL10), CCL11, interleukin (IL)-1β, IL-4, IL-5, IL-6, CXCL8, IL-10, IL-12(p70), IL-13, transforming growth factor (TGF)-β1, and immunoglobulin (Ig)A in 115 whey samples were measured by immunoassays. Maternal asthma, eczema, rhinitis, smoking, urogenital infections during gestation, pet exposure, education, race/ethnicity, age, body mass, and the child’s birth date and sex were ascertained. The effects of these risk factors on immune markers were estimated using general linear models.Results:Maternal asthma was linked to higher levels of IL-5, rhinitis to lower levels of IL-5 and INF-γ, and eczema to lower levels of IL-6. Gestational smoking was related to increased concentrations of CXCL8 and IL-6. African-American mothers had markedly higher levels of IL-6, IFN-γ, and CXCL8. Urogenital infections, maternal age, body mass, child’s sex, and season of birth contributed to the variation.Conclusion:The impact of maternal allergies on immune markers in breast milk was small compared with that of maternal nondisease characteristics.

Expression of CYP19 and CYP17 is associated with leg length, weight, and BMI.

This study investigates associations between gene expressions of aromatase (CYP19), 17α hydroxylase (CYP17), and estrogen receptors α and β and anthropometric measurements in offspring of the Michigan fish eater cohort. Leg and trunk length, height, weight, and BMI and gene expression in peripheral blood cells were measured in offspring of the Michigan fish eater cohort. The parental generation was followed between 1973 and 1991, and maternal age, height, and weight data were collected. Female offspring were contacted in 2001/2002 and followed up in 2006/2007; offspring information included age, education, reproductive history, smoking, and exercise. Gene expression was standardized against 18S ribosomal ribonucleic acid (18SrRNA) and RNA polymerase II (RNA PolII) expressions. Mixed models assessed the statistical effect of gene expression on anthropometric outcomes, accounting for multiple offspring from one mother. Anthropometric measurements and gene expression were measured in 139 female offspring. The two length and the height measurements were correlated, as were BMI and weight. CYP19 expression was correlated with the other gene expressions and both estrogen receptor expressions were associated. For every 1 unit of ΔCt (18SrRNA ‐ CYP19) or ΔCt (RNA PolII ‐ CYP19), BMI was increased by 0.9 (P = 0.03) and 0.87 kg/m2 (P = 0.04), respectively, and weight by 2.35 kg (P = 0.03) and 2.1 kg (P = 0.03), respectively. For every 1 unit of ΔCt (18SrRNA ‐ CYP17), leg length was increased by 0.84 cm (P = 0.04). The results suggest that CYP17 gene expression may influence growth during childhood and adolescence while CYP19 may be associated with the concurrent measures of weight and BMI.