Neonatal BCG vaccination and atopic dermatitis before 13 months of age: A randomized clinical trial.

BACKGROUND: Studies have suggested that Bacillus Calmette-Guérin (BCG) vaccination may reduce the risk of allergic diseases, including atopic dermatitis. METHODS: The Danish Calmette Study was conducted 2012-2015. Within 7 days of birth new-borns were randomised 1:1 to BCG or no BCG. Exclusion criteria were gestational age <32 weeks, birth weight <1000 g, known immunodeficiency or no Danish-speaking parent. Data were collected through telephone interviews and clinical examinations until 13 months. RESULTS: Clinical atopic dermatitis was diagnosed in 466/2,052 (22.7%) children in the BCG group and 495/1,952 (25.4%) children in the control group (RR = 0.90 [95% confidence intervals 0.80-1.00]). The effect of neonatal BCG vaccination differed significantly between children with atopic predisposition (RR 0.84 (0.74-0.95)) and children without atopic predisposition (RR 1.09 [0.88-1.37]) (test of no interaction, P = .04). CONCLUSION: Among children with atopic predisposition, the number-needed-to-treat with BCG to prevent one case of atopic dermatitis was 21 (12-76).

Bacillus Calmette-Guérin vaccination at birth and in vitro cytokine responses to non-specific stimulation. A randomized clinical trial.

Several studies have shown increased in vitro cytokine responses to non-related pathogens after Bacillus Calmette-Guérin (BCG) vaccination. A total of 158 infants (80 BCG administered within 7 days of birth; 78 controls) were bled 4 days post-randomization, and at age 3 and 13 months. Geometric mean concentrations of IL-1ß, TNF-α, IL-6 (24 h stimulation) and IFN-γ, IL-10, IL-17, IL-22 (96 h stimulation) in response to in vitro stimulation with RPMI, LPS, PHA, Escherichia coli, Streptococcus pneumoniae, Candida albicans and BCG were compared among BCG vaccinated children and controls. BCG vaccination did not affect in vitro cytokine production, except IFN-γ and IL-22 response to BCG. Stratifying for 'age at randomization' we found a potentiating effect of BCG on cytokine production (TNF-α, IL-6, IL-10) in the 4 days post randomization stimulations, among children who were vaccinated at age 2-7 days versus age 0-1 days. BCG vaccination did not potentiate cytokine production to non-BCG antigens. At 4 days post randomization, BCG was associated with higher cytokine production in the later randomized children.

Low thymic size in preterm infants in the neonatal intensive care unit, a possible marker of infection? A prospective study from birth to 1 year of age.

AIM: To study the growth of the thymus in preterm infants. METHODS: Ultrasonographic thymic size (Ti) was studied in 80 preterm infants (gestational age 24-36 weeks) from birth to discharge from the neonatal intensive care unit (NICU). Thirty-three of these infants were followed to 1 year of age. RESULTS: At birth, the median Ti was 5.2 compared with 11.8 in term infants. At discharge, the median Ti was 10.0 and not significantly different from Ti in term infants at birth (p = 0.22). The size of the thymus was significantly associated with postmenstrual age and weight (both p < 0.01). Infections during admission were negatively associated with the size of the thymus (p < 0.01). During the first 3 months after discharge, preterm infants had a significantly higher frequency of infections than did term infants (p = 0.002); hereafter, the preterm infants had significantly fewer infections than term infants (p = 0.002). The median Ti in preterm infants and term infants at 1 year of age was 21.1 and 17.3, respectively. This difference was not statistically significant (p = 0.41). CONCLUSIONS: Growth of thymus was not compromised by preterm birth. Ti is negatively associated with the frequency of infections in preterm neonates submitted to NICU.

The size of the thymus: an important immunological diagnostic tool?

UNLABELLED: The report on the influence of seasonal factors on thymic size in early life describes a pattern of ultrasonographically measured thymic growth in Gambian infants including the finding of a smaller thymus in the hungry season. These factors raise a number of important questions: Is the size of the thymus relevant to its function and could measurement of the thymus be a useful immunological diagnostic tool in the investigation of thymic function in humans with a depressed immune system? CONCLUSION: Studies using the size of the thymus as an immunological diagnostic tool should be encouraged.

Thymic size in preterm neonates: a sonographic study.

AIM: To assess the variation in size of the thymus in vivo in preterm neonates and to identify relations between thymic size and gestational age (GA), birthweight, occurrence of postnatal infections and maternal alcohol and tobacco intake during pregnancy. METHODS: Eighty preterm neonates with a GA between 24 and 36 wk, and a birthweight between 490 and 4110 g were examined between days 0 and 19 after birth. The thymic size was assessed by sonography as a volume estimate, the so-called thymic index (Ti). The median Ti was 5.2 (1.2-17.9). Ti was positively correlated with birthweight and GA and negatively correlated with occurrence of postnatal infection (p < 0.01, p = 0.03, p = 0.05, R2 = 0.68). A correlation between thymic size and maternal alcohol and tobacco intake was not demonstrated. CONCLUSION: It is possible to assess the size of the thymus by sonography in very low-birthweight and preterm neonates. A normal range for Ti in preterm neonates has been established. The sonographic method is a safe and effective technique for measuring the size of the thymus in preterm infants.

Thymus size and head circumference at birth and the development of allergic diseases.

BACKGROUND: The positive association between a large head circumference at birth and total serum IgE levels has been suggested to be due to negative associations between head circumference at birth and thymus development and between thymus development and total serum IgE levels. OBJECTIVES: To examine the associations between head circumference and thymus size at birth and the development of allergic disease. METHODS: The size of the thymus was assessed by sonography during the first week of life in 149 healthy term infants. Information on birth characteristics and mode of delivery was collected at delivery. The presence of allergic disease was assessed 5 years later by mailed questionnaires, which were returned by 85% of the eligible families. RESULTS: At birth, head circumference was positively associated with thymus size (P < 0.001). In all, 27 (23%) of the children had developed at least one allergic disease. Multivariate analysis revealed that both parental allergy (Prevalence Ratio and 95% CI) = 3.18 (1.49-6.78)) and caesarean delivery (2.62 (1.48-4.64)) were independently correlated with allergic disease, whereas thymus size was not. CONCLUSIONS: Our study does not support that a large head circumference is associated with a small thymus size, nor that a small thymus size is associated with allergic disease. Whether thymus size at birth is related to total serum IgE levels still remains to be elucidated.

Impaired progenitor cell function in HIV-negative infants of HIV-positive mothers results in decreased thymic output and low CD4 counts.

Hematologic and immunologic functions were examined in 19 HIV-negative infants of HIV-positive mothers and 19 control infants of HIV-negative mothers. Control infants were selected to match for gestational age, weight, and mode of delivery. Cord blood was obtained from all infants and used for flow cytometric determination of lymphocyte subsets, including the naive CD4 count. Furthermore, to determine thymic output, cord blood mononuclear cells were used for determination of T-cell receptor excision circles (TRECs). Evaluation of progenitor cell function was done by means of colony-forming cell assay and fetal thymic organ cultures (FTOCs). Lower naive CD4 counts (459.3 +/- 68.9 vs 1128.9 +/- 146.8 cells/microL, P <.001) and reduced thymic output in infants of HIV-positive mothers were found (frequency of CD4(+) cells with TRECs was 3.6% +/- 0.7% compared with 14.3% +/- 2.2% in controls, P <.001). In combination with lower red blood cell counts in infants of HIV-positive mothers, this finding suggested impairment of progenitor cell function. Indeed, progenitors from infants of HIV-positive mothers had decreased cloning efficiency (15.7% +/- 2.6% vs 55.8% +/- 15.9%, P =.009) and seemed to generate fewer T cells in FTOCs. In conclusion, lower numbers of naive CD4(+) cells and reduced thymic output in HIV-negative infants of HIV-positive mothers may be due to impaired progenitor cell function.

Breast-feeding influences thymic size in late infancy.

We have previously shown that breast-fed infants have a considerably larger thymus at 4 months than formula-fed infants. The aim of the present study was to investigate whether breast-feeding also influences the thymic size in late infancy. In a cohort of 50 infants, all being partially breast-fed when recruited at 8 months, ultrasound assessment of the thymic index (a volume estimate) was performed at both 8 and 10 months of age. At 10 months the thymic index was significantly higher in those still being breast-fed compared to infants who had stopped breast-feeding between 8 and 10 months of age (P=0.05). This difference became more significant when controlled for the influence of infectious diseases (P=0.03). In infants still breast-fed at 10 months there was a significant correlation between the number of breast-feeds per day and their thymic index (P=0.01). Conclusion The effect of breast-feeding on thymus size is likely to be caused by immune modulating factors in breast milk. Breast milk influences thymic size in late infancy.

Thymus size in preterm infants evaluated by ultrasound. A preliminary report.

PURPOSE: To sonographically evaluate the thymic size in preterm infants. MATERIAL AND METHODS: In 6 healthy infants, born in gestational weeks 34-37, and 6 infants born in weeks 24-32, the thymic volume estimate (the thymic index) was assessed. The measurements were compared to the estimates calculated from the prediction model for neonates. RESULTS: The slightly preterm infants fit the prediction model. In cases where the results failed to fit into the model, it was adjusted in order to cover lower birth rates. The extremely preterm infants initially had a very low thymic index but, when healthy, they reached the normal range. CONCLUSION: With the knowledge of the birth weight it is now possible to predict the thymic size in healthy infants weighing 2,070 g or more.

Thymus size in infants from birth until 24 months of age evaluated by ultrasound. A longitudinal prediction model for the thymic index.

PURPOSE: To do a follow-up sonography assessment of the thymic size in infants at an age of 24 months, and to create a longitudinal prediction model for the thymic index covering all ages from birth to 24 months. MATERIAL AND METHODS: Of 37 infants examined in an earlier investigation, 34 attended a 24-month follow-up examination. The thymic index, a volume estimate, was assessed by sonography and compared to clinical variables, breast-feeding status and illness. The longitudinal prediction model was based on data throughout 2 years. RESULTS: There was no significant relation between the thymic index and the clinical variables, breast-feeding status or illness at 24 months. An overall test for the effect of breast-feeding status at 4 months for infants from 0-24 months was significant, as was the actual body length of the infants from 0-8 months. Prediction models were estimated. CONCLUSION: Based on a 24-month longitudinal sonography study, prediction models are presented whereby the thymic size, as an index, can be predicted at all times from birth to 24 months of age.

Thymus size evaluated by sonography. A longitudinal study on infants during the first year of life.

OBJECTIVE: To use sonography in a follow-up study aimed at assessing the size of the thymus in healthy infants, and to search for a possible relation to clinical variables, breast-feeding status, and illness. MATERIAL AND METHODS: Forty-seven healthy infants were examined as neonates and re-examined at 4 months of age. Thirty-seven of the infants were also re-examined at 8, 10, and 12 months of age. The thymus size was measured with the sonographic thymic index used as a volume estimate. The correlations between the thymic index and the sex, weight, length, illness, and breast-feeding status of the infants were analysed. RESULTS: At birth the median thymic index was 12 (range 4-29). At 4 months the median thymic index was 28 (range 12-83). The thymic index was positively correlated to the body length of the infant and to its breast-feeding status (p < 0.0001). At 8 months the median thymic index was 29 (range 6-55) and most of the variation could be explained by the length of the infant (p = 0.0018, r = 0.50). At 10 months the median thymic value had decreased to 19 (range 9-49), and at 12 months to 17 (range 7-53). Infants exclusively breast-fed during the first 4 months of their lives had a larger thymic index at 10 months than formula-fed infants (p = 0.0024). Infants with fever episodes from 10 to 12 months had a smaller thymic index at 12 months (p = 0.0241). CONCLUSION: The thymus size in healthy infants increases from birth to 4 and 8 months of age and then decreases. Most of the individual variation can be explained by breast-feeding status and body size, and to a lesser extent by illness. We propose statistical models by which the normal variation/distribution of the thymic size can be estimated in infants up to one year of age.

Sonographic measurement of thymic size in healthy neonates. Relation to clinical variables.

PURPOSE: To assess the variation in thymic size in healthy neonates by sonography and to study the possible correlation to clinical variables. MATERIAL AND METHODS: A study was made of 149 healthy term infants, at less than one week of age. The size of the thymus was assessed by sonography as a volume estimate, the thymic index. This index was compared to sex, weight, length, gestational age, and level of perinatal asphyxia of the infant. T-cell subsets (percentages of CD4 and CD8 receptor-positive T-lymphocytes in peripheral blood) were determined in 83 of the infants and compared to the sonographic thymic index. RESULTS: The thymic index varied between 4 and 29, and was positively correlated to the weight of the infant (p = 0.0003). There was no correlation to sex, length, gestational age or slight perinatal asphyxia. We found no correlation between the size of the thymus and the CD4 percentage, the CD8 percentage, or the CD4/CD8 ratio. CONCLUSION: The size of the thymus in healthy neonates as measured by sonography is significantly correlated to the weight of the infant. For a given weight of an infant it is possible to predict the normal range of thymic size.

Decreased thymus size in formula-fed infants compared with breastfed infants.

The objective of this research was to investigate if breastfeeding affects the size of the thymus. Ultrasound assessment of the thymic index (a volume estimate) at birth and age 4 months in 47 healthy infants born in the hospital were used. History of feeding mode, body size and illness were registered. At 4 months the geometric mean thymic index (range) was 38.3 (16.2-83.2) in exclusively breastfed infants (n = 21), 27.3 (15.6-50.0) in partially breastfed infants (n = 13) and 18.3 (12.2-32.6) in formula fed infants (n = 13; p = 0.0001, ANOVA). This finding was independent of weight, length, sex and previous or current illness. There was no significant difference in mean thymic index at birth between the three feeding groups and mean thymic index had increased in all three groups from birth to 4 months. For the formula-fed infants it seems that the thymus remains large for a period and then decreases in size after breastfeeding has been terminated. We conclude that the thymus is considerably larger in breastfed than in formula-fed infants at the age of 4 months. The cause of this difference is unknown but human milk contains many immune modulating factors that might cause this effect.