Use of hypoallergenic formula in the prevention of atopic disease among Asian children

OBJECTIVE: To determine the effect of a partially hydrolysed formula on genetically predisposed children, with respect to the development of atopic clinical manifestations and in vitro testing of serum IgE levels (total and milk-specific). METHODS: One hundred and ten infants were randomly assigned to receive either partially hydrolysed formula or standard infant formula, and were prospectively monitored from birth for clinical atopic symptoms and serum IgE levels. RESULTS: Eczema occurred less frequently in infants receiving partially hydrolysed formula. This was significant (P < 0.05) at 3, 6, 9, 12, 18 and 24 months. However, the significance decreased with time, although it almost reached statistical significance at 30 months by the Kaplan-Meier survival function (log-rank statistic, 3.46; P = 0.063). Although wheezing occurred less frequently in infants receiving partially hydrolysed formula, compared to those receiving standard infant formula, the difference did not reach statistical significance (P > 0.05). CONCLUSIONS: Exclusive feeding of hypoallergenic milk formula in the first 4 months of life has a protective effect in terms of the development of atopic dermatitis in the first 2 years of life, compared to feeding with cow's milk formula.     

Role of atopy in the natural history of wheeze and bronchial hyper-responsiveness in childhood

The role of atopy in the development of asthma has become increasingly recognised. We have been prospectively following a birth cohort of children of atopic parents to document the development of atopic disease. Our aim in this study was to document the natural history of BHR and wheeze at 10 years of age and to relate this to atopy. We reviewed 47 of our original cohort of 79 infants at 10 years of age and documented their clinical history of atopic disease and performed allergen skin prick tests and BHR to histamine. Thirty-three (70%) children wheezed at some time during their 10 years of life, with 13 commencing in infancy. Twenty-two children (47%) had current wheeze at 10 years of age. Wheeze in infancy was a poor predictor (RR 1.23, Cl₉₅ 0.66–2.23) of current wheeze while wheeze commencing after infancy was a good predictor (RR 2.89, Cl₉₅ 1.45–5.2). In contrast both atopy in infancy (RR 2.94, Cl₉₅ 1.92–4.53) and current atopy (RR 3.58, Cl₉₅ 1.43–9.03) were strong predictors of current wheeze. Analysis of BHR confirmed the importance of atopy in predicting its occurrence and severity. Sensitisation to D. pteronyssinus appeared to be the strongest predictor of both current wheeze and BHR. These observations confirm the importance of atopy in predicting outcome in children with asthma and suggest that wheezing in infancy and wheezing in later childhood may have different pathogenetic mechanisms.     

Development of atopic disease in early childhood--predisposing factors

In this study, we attempted to find factors which predispose infants to atopy. 200 unselected newborns were followed up to 3 years of age. Children with elevated cordblood IgE or positive family history developed atopic disease significantly more frequent (p less than 0.05, p less than 0.01). Parental smoking or formula feeding alone did not influence the frequency of subsequent atopic disorders. However, in combination with reduced cordblood CD8-cells atopy was observed significantly more often (p less than 0.05, p less than 0.025). Similar results were found in children with reduced cordblood CD3-cells, whose parents were smokers (p less than 0.01). These results suggest that factors which alone do not influence atopy can enhance each other to predispose atopic disease in early childhood.     

Preliminary data on a field study with a new hypo-allergic formula

The incidence of atopic manifestations due to cow's milk proteins was analysed in five groups of 15 newborns considered to be at risk for atopy because of a positive family history. All infants were studied over a 4-month period. The infants received either an adapted formula (AdFo), breast milk or a new hypo-allergic formula (HAF). Atopic manifestations appeared in 1 out of 15 breast-fed infants compared with 18 out of 45 infants fed with an AdFo. None of the infants receiving the HAF (exclusively from birth for 2–4 months) developed symptoms of atopy. Symptoms in each infant receiving an AdFo (n=18) disappeared with the HAF. Although the results of this study are promising, data on a larger population and double-blind investigations are needed before firm conclusions can be drawn.Abbreviations AdFo adapted formula - HAF hypo-allergic formula - IgE immunoglobulin E - RAST radioallergosorbent test     

Fish oil supplementation in pregnancy modifies neonatal progenitors at birth in infants at risk of atopy

Dietary n-3 polyunsaturated fatty acids (PUFA) may represent a mode of allergy prevention. Cord blood (CB) CD34+ hemopoietic progenitors are altered in infants at risk of atopy. We therefore studied the effects of dietary n-3 PUFA supplementation during pregnancy on numbers and function of progenitors in neonates at high risk of atopy. In a double-blind study, atopic, pregnant women were randomized to receive fish oil capsules or placebo from 20 wk gestation until delivery. At birth, CB CD34+ cells were isolated and analyzed by flow cytometry for expression of cytokine (IL-5Ralpha, IL-3Ralpha, granulocyte/macrophage colony-stimulating factor Ralpha) or chemokine (CXCR4 and CCR3) receptors. CB cells were also cultured in methylcellulose assays for eosinophil/basophil colony-forming cells. At age 1 y, infants were clinically assessed for atopic symptoms and skin tests. Percentages of CB CD34+ cell numbers were higher after n-3 PUFA than placebo. Co-expression of cytokine or chemokine receptors on CD34 cells was not altered by n-3 PUFA supplementation. However, there were significantly more IL-5-responsive CB eosinophil/basophil colony forming units (Eo/B-CFU) in the fish oil, compared with the control, group. Overall, there was a positive association between CD34+ cells and IL-5-responsive Eo/B-CFU in CB and 1 y clinical outcomes, including atopic dermatitis and wheeze. Dietary n-3 PUFA supplementation during pregnancy in atopic mothers alters infant cord blood hemopoietic progenitor phenotype. This may have an impact on development of atopic disease.     

氟康唑预防极低出生体重儿侵袭性真菌感染疗效和安全性的Meta分析

目的 系统评价使用氟康唑预防极低出生体重儿（VLBWI）侵袭性真菌感染的疗效和安全性,为临床更好地预防性使用氟康唑提供依据。方法 计算机检索PubMed、Embase、Cochrane图书馆、万方数据库、中国科技期刊数据库（维普）和中国知网,纳入VLBWI预防性使用氟康唑的随机对照试验（RCT）研究。采用Review Manager 5.3统计软件对符合纳入标准的临床研究进行Meta分析。结果 共纳入12篇RCT研究,合计1 679例VLBWI。Meta分析结果显示：试验组（使用氟康唑）侵袭性真菌感染的发生率显著低于安慰剂对照组（RR=0.44,95% CI：0.27~0.71,P < 0.001）;真菌定植率低于对照组（RR=0.31,95% CI：0.24~0.40,P < 0.001）;住院期间病死率低于对照组（RR=0.74,95% CI：0.58~0.94,P=0.01）。使用不同预防剂量氟康唑的两组侵袭性真菌感染发生率和真菌定植率比较差异均无统计学意义（P > 0.05）;耐药情况及并发症发生率在试验组和对照组组间比较差异均无统计学意义（P > 0.05）。结论 氟康唑预防VLBWI侵袭性真菌感染有效且相对安全。小剂量给药可取得类似预防效果。     

IgA antibodies, TGF-beta1 and -beta2, and soluble CD14 in the colostrum and development of atopy by age 4

Specific defense factors in breast milk together with length of breast-feeding and genetic predisposition may modulate the development of allergy. We studied whether IgA, soluble CD14 (sCD14), or transforming growth factor (TGF)-beta in colostrum could affect the development of atopy in children up to age 4. From a cohort of 4676, we selected four groups of children with either long or short exclusive breast-feeding (>3.5 or <0.5 mo); these groups further differed in the presence or absence of atopic heredity. In colostrum from mothers, we measured total IgA, IgA antibodies to cow's milk (CM) and casein, sCD14, and TGF-beta1 and -beta2. The children were divided into three groups: those with no atopic symptoms or IgE, those with allergic symptoms, and those with both outcomes. Mothers of infants later showing atopic symptoms or, in addition, having IgE sensitization (verified atopy) had a lower concentration of IgA casein antibodies in their colostrum than did mothers of infants with no indication of atopy at age 4. Low concentration of IgA casein antibodies was a significant risk for verified atopy. sCD14 levels were lower in colostrum of mothers with infants developing atopic symptoms and IgE sensitization than of those of infants with no atopy. Specific IgA antibodies to CM antigens and sCD14 in colostrum significantly associated with the appearance of both symptomatic and verified atopy by age 4.     

益生菌预防极低出生体重儿迟发型败血症的Meta分析

目的 评估益生菌预防极低出生体重儿迟发型败血症(late-onset sepsis,LOS)的有效性.方法 检索PubMed、Web of Science、Cochrane Library、万方数据库、中国知网、中国生物医学文献数据库等数据库中关于益生菌预防极低出生体重儿LOS的临床随机对照试验.LOS类型包括临床败血...     

Comparison of a partially hydrolyzed infant formula with two extensively hydrolyzed formulas for allergy prevention:A prospective, randomized study

The aim of this study was to compare the allergy‐preventive effect of a partially hydrolyzed formula with two extensively hydrolyzed formulas, in infants with a high risk for development of allergic disease. High‐risk infants from four Danish centres were included in the period from June 1994 to July 1995. Five‐hundred and ninety‐five high‐risk infants were identified. High‐risk infants were defined as having bi‐parental atopy, or a single atopic first‐degree relative combined with cord blood immunoglobulin E (IgE) ≥ 0.3 kU/l. At birth all infants were randomized to one of three different blinded formulas. All mothers had unrestricted diets during pregnancy and lactation and were encouraged to breast‐feed exclusively. If breast‐feeding was insufficient, one of the three formulas, according to randomization, was given during the first 4 months. It was recommended not to introduce cow's milk, cow's milk products, and solid foods until the age of 4 months. After the age of 4 months a normal unrestricted diet and conventional cow's milk‐based formula were given when needed. All infants were followed‐up prospectively with interview and physical examination at the age of 6, 12, and 18 months, and if any possible atopic symptoms were reported. If food allergy was suspected, controlled elimination/challenge procedures were performed in a hospital setting. Of 550 infants included in the study, 514 were seen at all visits and 36 were excluded owing to non‐compliance. Of 478 infants who completed the study, 232 were exclusively breast‐fed, 79 received an extensively hydrolyzed casein formula (Nutramigen), 82 an extensively hydrolyzed whey formula (Profylac), and 85 a partially hydrolyzed whey formula (Nan HA), during the first 4 months of life. These four groups were identical in regard to atopic predisposition, cord blood IgE, birthplace, and gender. Exclusively breast‐fed children were exposed less to tobacco smoke and pets at home and belonged to higher social classes, whereas the three formula groups were identical concerning environmental factors. The frequency of breast‐feeding was high; only eight (2%) children were not breast‐fed at all. The three formula groups were identical in regard to duration of breast‐feeding and age at introduction of formula and solid foods. No significant differences were found in the three groups of infants receiving formula milk regarding the cumulative incidence of atopic dermatitis or respiratory symptoms. The cumulative incidence of parental‐reported cow's milk allergy was significantly higher in children fed partially hydrolyzed formula (Nan HA) compared with extensively hydrolyzed formula (Nutramigen or Profylac) at 12 and 18 months (NanHA, 7.1%; Nutramigen, 2.5%; Profylac, 0%; p = 0.033). The cumulative incidence of confirmed cow's milk allergy was 1.3% (three of 232) in exclusively breast‐fed infants, 0.6% (one of 161) in infants fed extensively hydrolyzed formula (Nutramigen or Profylac), and 4.7% (four of 85) in infants fed partially hydrolyzed formula (Nan HA). Partially hydrolyzed formula was found to be less effective than extensively hydrolyzed formula in preventing cow's milk allergy, 0.6% vs. 4.7% (p = 0.05), but because of the small number of cases the results should be interpreted with caution. Compared with other similar studies the frequency of atopic symptoms was low, even though the dietetic intervention did not include either maternal diet during lactation or dietary restrictions to the children after the age of 4 months.     

Expression of the T-cell markers CD2 and CD28 in healthy and atopic children during the first 18 months of life

Atopy may be associated with a reduced T-cell function early in life, particularly regarding maturation of Th1 responses. The T-cell surface molecules CD2 and CD28 are involved in important T-cell activation pathways. Stimulation via the CD2 receptor increases the responsiveness to interleukin (IL)-12, which is a potent inducer of Th1 responses, whereas CD28 stimulation is critical for Th2 differentiation. Our aim was to prospectively study the expression of the cell-surface markers CD2 and CD28 on T-cells in relation to development of atopic disease. Children (n = 172) were followed from birth to 18 months and the cumulative history of atopic disease was recorded. Blood samples were obtained at birth and at 18 months, and in a subgroup of 78 infants also at 3, 6 and 12 months. Flow cytometry was used to analyze the T-cell markers CD2 and CD28, the latter also within the subsets of T-helper (CD4+) and T-cytotoxic (CD8+) cells. At 18 months, 31 children had and 118 did not have atopic symptoms. At this age, skin prick test (SPT) positive children with atopic symptoms with or without an atopic family history (AFH) showed a lower expression of CD2 mode fluorescence intensity (FI) as well as a lower proportion of CD2+ cells, as compared with non-sensitized children with neither atopic symptoms nor AFH. This was accompanied by a higher expression of CD28 FI on CD2+CD8+CD28+ cells. No significant differences were seen at time points before 18 months, although the proportion of CD2+ tended to be low also earlier in life. In conclusion, the observed reduced expression of CD2 in atopic infants may support previous findings that atopy is associated with a reduced CD2 function. The high CD28 FI in SPT positive children with atopic symptoms may possibly be a consequence of a TH2-skewed immune system.     

Asthma, lung function and allergy in 12-year-old children with very low birth weight: A prospective study

We assessed the relationship between very low birth weight (VLBW) (≤1500 g) and the development of asthma, lung function and atopy. The study groups comprised 74 of all 86 (86%) VLBW and 64 of all 86 (74%) matched term children who were prospectively followed for 12 years. A questionnaire on asthmatic and allergic symptoms was completed and skin prick tests, spirometry and hypertonic saline provocation tests were performed at 12 years of age. Cytokine secretion was analysed in stimulated blood leukocyte cultures in 28 VLBW and 23 term children. A history of asthma was more frequent among the VLBW children, as compared with the term children at age 12 (22% vs. 9%, p = 0.046). Among the VLBW children, very preterm birth (gestational age: week 25 to 29) (RR 2.5, 95%CI 1.1–5.8), neonatal mechanical ventilation (RR 2.8, 95%CI 1.2–6.4) and neonatal oxygen supplementation (RR 4.3, 95%CI 1.3–14.0) were significantly associated with a history of asthma by the age of 12 years in univariate analyses. In multivariate logistic regression, neonatal oxygen supplementation ≥ 9 days was the only remaining significant risk factor for a history of asthma (adjusted OR 6.7, 95%CI 1.0–44). The VLBW children who required mechanical ventilation during the neonatal period were more likely to have bronchial hyperresponsiveness than those not requiring mechanical ventilation (60% vs. 28%, p = 0.050). The spirometric values were similar among the VLBW and the term children at 12 years. Very low birth weight was not significantly related to allergic rhinoconjunctivitis, eczema or positive skin prick tests. Furthermore, the levels of IL‐4, IL‐5 and IFN‐γ in stimulated cell cultures were similar in the VLBW and the term children. A history of asthma by 12 years of age was twice as common among the VLBW as the term children, and neonatal oxygen supplementation seemed to be associated with the increased risk. Furthermore, mechanical ventilation during the neonatal period was associated with bronchial hyperresponsiveness at age 12. Very low birth weight per se was not, however, related to atopy.     

Soluble CD30 and CD23 in cord blood are not related to atopy in early childhood

Atopic disease, including atopic dermatitis (AD), is associated with a T-helper 2 (Th2)-dependent immune response. The cytokine receptor CD30 appears to be preferentially expressed on, and its soluble form (sCD30) released by, Th2 cells. Therefore, sCD30 may be a potential marker for atopic disorders. The aim of this study was to test the hypothesis that the sCD30 level in cord blood could be used to predict the development of atopy or AD in early childhood. In a case-control study, levels of sCD30, as well as soluble low-affinity immunoglobulin E (IgE) receptor (sCD23), interleukin-4 (IL-4) and IgE, were measured in cord blood in 35 children who subsequently developed allergic sensitization and AD before the age of three, and the results were compared to those of 35 matched children without a history of atopy. There was no difference in cord blood levels of sCD30 between controls (32.5 U/ml; 19.7–80.1) and children with subsequent atopy and AD (32.2 U/ml; 22–75.9) (median; quartiles). The concentration of sCD30 showed no relation to the levels of total IgE, sCD23 or IL-4. Levels of sCD23 were similar in children with subsequent atopy (60.2 U/ml; 44.5–76.8) and controls (55.2 U/ml; 38.3–72.5), whereas IL-4 was detectable in 10 of the atopic children and in only two of the controls (p < 0.05). In conclusion, cord blood levels of sCD30 or sCD23 do not seem to be related to the subsequent development of atopy or AD at the age of three.     

A mixture of prebiotic oligosaccharides reduces the incidence of atopic dermatitis during the first six months of age.

BACKGROUND: Oligosaccharides may alter postnatal immune development by influencing the constitution of gastrointestinal bacterial flora. AIMS: To investigate the effect of a prebiotic mixture of galacto- and long chain fructo-oligosaccharides on the incidence of atopic dermatitis (AD) during the first six months of life in formula fed infants at high risk of atopy. METHODS: Prospective, double-blind, randomised, placebo controlled trial; 259 infants at risk for atopy were enrolled. A total of 102 infants in the prebiotic group and 104 infants in the placebo group completed the study. If bottle feeding was started, the infant was randomly assigned to one of two hydrolysed protein formula groups (0.8 g/100 ml prebiotics or maltodextrine as placebo). All infants were examined for clinical evidence of atopic dermatitis. In a subgroup of 98 infants, faecal flora was analysed. RESULTS: Ten infants (9.8%; 95 CI 5.4-17.1%) in the intervention group and 24 infants (23.1%; 95 CI 16.0-32.1%) in the control group developed AD. The severity of the dermatitis was not affected by diet. Prebiotic supplements were associated with a significantly higher number of faecal bifidobacteria compared with controls but there was no significant difference in lactobacilli counts. CONCLUSION: Results show for the first time a beneficial effect of prebiotics on the development of atopic dermatitis in a high risk population of infants. Although the mechanism of this effect requires further investigation, it appears likely that oligosaccharides modulate postnatal immune development by altering bowel flora and have a potential role in primary allergy prevention during infancy.     

深度水解蛋白配方奶喂养对极低/超低出生体重儿生长发育的影响

目的探讨深度水解蛋白配方奶喂养对极低出生体重(VLBW)和超低出生体重(ELBW)婴儿生长发育的影响。方法选取VLBW和ELBW婴儿375例作为研究对象,根据随机数字表法将其分为观察组(n=187)和对照组(n=188)。观察组给予深度水解蛋白配方奶喂养,当喂养达10 mL/次后,改用标准早产儿配方奶喂养。对照组给予标准早产儿配方奶喂养。两组持续喂养4周,比较两组喂养不耐受发生率、达全肠道喂养时间、胎便排净时间、自主排便次数、生长发育情况、喂养后第4天和第10天胃动素水平以及感染发生情况。结果观察组喂养不耐受率低于对照组(P0.05);观察组达全肠道喂养时间和胎便排净时间均短于对照组(P0.05);观察组平均每日自主排便次数多于对照组(P0.05);观察组婴儿体重、头围和身长均大于对照组(分别是1 793±317 g vs 1 621±138 g、30.5±1.1 cm vs 30.0±1.6 cm和43.9±1.2 cm vs 42.1±2.0 cm;均P0.05);观察组婴儿喂养第4天和第10天胃动素水平均高于对照组(P0.05);观察组婴儿感染率低于对照组(P0.05)。结论深度水解蛋白配方奶可提高胃动素水平,增加胃肠道喂养耐受性,促进VLBW和ELBW婴儿早期生长发育,降低感染发生率。     

Randomized, double-blind comparison of growth in infants receiving goat milk formula versus cow milk infant formula

OBJECTIVE: To compare growth of infants fed goat milk infant formula (GMF) or cow milk infant formula (CMF) and to compare tolerability and safety of the two formulas. METHODS: The study was conducted in Auckland, New Zealand. This was a double-blind randomized controlled trial. Newborn term infants were randomized within 72 h of birth to GMF or CMF. Milk formula powder in single serve sachets were reconstituted and fed to infants from trial commencement until age 168 days. No other formula given from randomization until age 168 days. Infant weight, length and head circumference were measured at birth and age 14, 28, 56, 84, 112, 140 and 168 days. Bowel motion frequency and consistency, sleeping and crying patterns and adverse events were also measured. RESULTS: Seventy-two infants were randomized, 36 each to GMF or CMF, with 62 infants completing the intervention. At enrollment the average weight of infants in the GMF group (mean +/- SD) was 3.33 +/- 0.43 kg and in the CMF group 3.43 +/- 0.47 kg; and at study completion 8.07 +/- 0.90 kg (GMF) and 7.87 +/- 0.99 kg (CMF). The difference in average weight gain over the study period for the GMF group versus the CMF group was not significant (+309 g; 95% CI = -49 to +668, P = 0.09). Median daily bowel motion frequency was greater in the GMF group than the CMF group (2.4 vs 1.7, P = 0.01). There were no group differences in bowel motion consistency, duration of crying, ease of settling, or frequency of adverse events. CONCLUSION: Growth of infants fed GMF is not different to that of infants-fed CMF.     

Prediction of atopic disease in infancy by determination of immunological parameters: IgE, IgE- and IgG-antibodies to food allergens, skin prick tests and T-lymphocyte subsets

The possibility of predicting the development of atopic diseases up to 18 months of age, by using IgE, IgE- and IgG-antibodies (Ab) to food allergens, skin prick tests (SPT) and T-lymphocyte subsets, was prospectively studied in 163 infants with atopic heredity. IgE determinations in cord blood showed a positive allergy-predictive value of only 21%, using an optimal cut-off limit (≥ 0.9 kU/l). The corresponding figure for a weakly positive RAST (≥ 0.15 < 0.35 PRU/ml) to ovomucoid (OVO) or β-lactoglobulin (BLG) at 6 months of age was 25% and for a positive RAST ≥ 0.35 PRU/ml 100%. The predictive value of positive SPT to ovalbumin (OA), OVO, BLG and whole cow's milk varied between 67 and 100% and for IgG-Ab levels to the same food allergens the predictability did not exceed 30%. Total numbers of T cells (CD2, CD3) were higher (p < 0.05) at delivery among atopic infants, but neither in cord blood nor in blood samples, taken at 2 and 6 months of age, could absolute T-cell subset numbers or the CD4/CD8 ratios predict atopic diseases in more than 45% of the cases. A low sensitivity was observed in most of the parameters studied. Thus, none of the tests used in the present study seems suitable for predicting the development of atopic diseases during early infancy.     

Associations between atopic markers in asthma and intestinal helminth infections in Cuban schoolchildren

Total serum IgE (tIgE), allergen-specific IgE (sIgE), and skin prick test (SPT) are commonly used markers for atopy and atopic disease. The association between these measures and their relationship to clinical symptoms differs in affluent and non-affluent countries. We investigated the role of intestinal helminth infections in observed variations in atopic markers and asthma, and possible diagnostic and epidemiological consequences. A cross-sectional study was conducted in Cuban schoolchildren (n = 1285; 4-14 yrs). Atopy was determined by SPT, sIgE, and tIgE; asthma by International Study of Asthma and Allergies in Childhood questionnaire; and intestinal helminth infections by stool examination. Percentages of tIgE, sIgE, and SPT positives were 88.9%, 25.5%, and 16.5%, respectively. Asthma was found in 20.8%, and helminth infections in 20.9% of the children. All three atopic markers were significantly associated with each other and with asthma. Median tIgE levels were higher in helminth-infected than in uninfected children, irrespective of their status of atopy/asthma. Discordant results between SPT and sIgE were observed in 22.6% of the children. Among SPT positives, 41% were sIgE negative. The proportion of SPT negatives among sIgE positives was 74% in helminth-infected and 58.4% in uninfected children (p < 0.05). Helminth infections affected tIgE levels, reconfirming the limited value of tIgE for diagnosis of atopy and asthma in tropical areas. Higher frequencies of sIgE than positive SPTs were observed, especially in helminth-infected children. This corresponds with current hypothesis on the role of helminths in atopy. However, the observed proportion of sIgE negatives among children with positive SPT suggests that other mechanisms may also be involved.     

Birth size effect on pulmonary functions and atopic sensitization in preadolescence

Background: The purpose of the present paper was to examine whether low birth size is associated with reduced pulmonary function and increased atopic sensitization in preadolescence. Methods: A cohort of 25 small‐for‐gestational‐age (SGA) infants and an age‐ and sex‐matched comparison group of 29 appropriate‐for‐gestational‐age (AGA) infants born in 1993/94 were studied in preadolescence. Forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), and forced expiratory flow when 25–75% of FVC is expired (FEF_25–75%) were measured using a spirometer. Atopic sensitization was assessed on serum total IgE levels and skin prick tests (SPT) to common allergens. Results: There were positive correlations among FEV1 (r = 0.30, P = 0.001), FVC (r = 0.20, P = 0.03), and FEF_25–75% (r = 0.5, P = 0.001) and ponderal index (PI), although the FEV1/FVC ratio was not correlated with birth size. Mean value of serum total IgE was higher in SGA (106.0 ± 73.4 IU/mL) than AGA children (71.4 ± 67.1 IU/mL; P = 0.02). PI under 10th centile was associated with high IgE levels (P = 0.04, odds ratio, 3.2; 95%CI: 1.0–9.8). The overall prevalence of atopy was 14.8% and there was no significant difference between the groups (P > 0.05). Conclusion: Preadolescents who were born SGA with low birth size compared to controls had reduced pulmonary function. In preadolescence the prevalence of atopy is not higher in SGA than AGA children, although low PI at birth is associated with high IgE levels. Further follow up of this cohort is required to establish the pattern of pulmonary functions and atopic sensitizations in relation to birth size.     

Subclinical hypothyroidism in atopic South Italian children

AIM: To verify if subclinical hypothyroidism (SCH) could be associated to atopy in children. METHODS: Seven hundred and thirty-two Caucasian children from South Italy presenting symptoms of allergic disease were enrolled and submitted to atopy, obesity, chronic low grade inflammation, and SCH work up. RESULTS: Four hundred and forty-five out of 705 (63.12%) children affected by allergic disease were diagnosed as atopic and 260 (36.88%) as not atopic. The SCH prevalence was 6.3%. Significant higher prevalence of SCH among atopic children with average (group 2) and high (group 3) low grade chronic inflammation compared to atopic children with mild (group 1) low grade chronic inflammation was present. Moreover, group 1 and group 2 presented an OR to show SCH of 2.57 (95%CI: 1.55-6.26) and 2.96 (95%CI: 1.01-8.65), respectively. Both in atopic and not atopic children we found C3 serum levels significantly higher in group 3 respect to group 2 and group 1. Noteworthy, among atopic patients, also total immunoglobulin E (IgE) serum levels, were significantly higher in group 3 compared to group 2 and group 1 children. In atopic children, C3 and total IgE serum values increased in parallel with the increase of C-reactive protein values, while in not atopic children this phenomenon was not evident. CONCLUSION: The possibility exists that an increasing atopic inflammation contributes to SCH occurrence. So far this is the first report in literature showing an association between SCH and atopy but further studies are needed to confirm our data.     

Genetic and environmental factors affecting the development of atopy through age 4 in children of atopic parents: a prospective randomized study of food allergen avoidance

The effect of food allergen avoidance, as well as other environmental and genetic factors, on the development of atopy were determined in this follow-up report of a prospective randomized controlled study of 288 infants of atopic parents, in which 78% were available for evaluation at age 4 years. The prophylactictreated group consisted of mothers who avoided cow milk. egg. and peanut during the last trimester of pregnancy and lactation and of infants who avoided cow milk until 1 year (casein hydrolysate supplementation prior to 1 year) and egg, peanut, and fish until after 2 years. The control group consisted of maternal/infant pairs who followed standard feeding practices. The cumulative prevalence of food allergy and food sensitization remained lower in the prophylactic treated group from 1 to 4 years of age. However, the period (current) prevalence of food allergy in both study groups was similar (about 5%) at 3 and 4 years. Such findings suggest that period prevalence may represent the more appropriate measure to assess the impact of intervention measures on the development of atopic disease at older ages. Prophylactic-treated children evidenced lower levels of IgG beta lacloglobulin (BLG) at 4 months and I and 2 years (p < 0.0001) and lower IgG ovalbumen/ovomucoid (OVA) levels only at 2 years (p < 0.001). Both groups evidenced similar prevalences of asthma, allergic rhinitis, and positive inhalant skin tests from birth to 4 years. Children with food allergy evidenced higher 4 year cumulative prevalences of allergic rhinitis and asthma (p < 0.05). Risk factors for atopic disease by age 4 years were shown by multivariate analysis (p < 0.05) to include (1) unrestricted diet and elevated cord blood IgE with food allergy, (2) male gender and lower paternal level of education with asthma, and (3) non-caucasian ethnicity and spring/summer birth with atopic dermatitis and allergic rhinitis. Serum IgE levels were not significantly different between groups at 3 and 4 years, despite their being a trend towards lower serum IgE levels in the prophylactic-treated group at 4 months (p < 0.07). In the control group, formula feeding prior to 4 months was associated with higher 4 month serum IgE levels (p < 0.05). Stepwise linear regression revealed that serum IgE variability from birth to 4 years was influenced by male gender, non-caucasian ethnicity, maternal and paternal serum IgE levels, 4 month IgG BLG levels, positive food and inhalant skin tests, and the development of atopic dermatitis, food allergy, asthma, and allergic rhinitis. These findings demonstrate the strength of genetic factors and their modulation by dietary and envi-ronmental influences in the development of atopy and reveal that the reduction in food allergy in infancy by maternal/infant food allergen avoidance fails to affect respiratory allergy development from birth to 4 years.