Regional differences in milk and complementary feeding patterns in infants participating in an international nutritional type 1 diabetes prevention trial

Differences in breastfeeding, other milk feeding and complementary feeding patterns were evaluated in infants at increased genetic risk with and without maternal type 1 diabetes (T1D). The Trial to Reduce IDDM in the Genetically at Risk is an international nutritional primary prevention double‐blinded randomized trial to test whether weaning to extensively hydrolyzed vs. intact cow's milk protein formula will decrease the development of T1D‐associated autoantibodies and T1D. Infant diet was prospectively assessed at two visits and seven telephone interviews between birth and 8 months. Countries were grouped into seven regions: Australia, Canada, Northern Europe, Southern Europe, Central Europe I, Central Europe II and the United States. Newborn infants with a first‐degree relative with T1D and increased human leukocyte antigen‐conferred susceptibility to T1D were recruited. A lower proportion of infants born to mothers with than without T1D were breastfed until 6 months of age in all regions (range, 51% to 60% vs. 70% to 80%). Complementary feeding patterns differed more by region than by maternal T1D. In Northern Europe, a higher proportion of infants consumed vegetables and fruits daily compared with other regions. Consumption of meat was more frequent in all European regions, whereas cereal consumption was most frequent in Southern Europe, Canada and the United States. Maternal T1D status was associated with breastfeeding and other milk feeding patterns similarly across regions but was unrelated to the introduction of complementary foods. Infant feeding patterns differed significantly among regions and were largely inconsistent with current recommended guidelines.     

Prospective cohort studies using hydrolysed formulas for allergy prevention in atopy-prone newborns: a systematic review

The aim of this study is to give a systematic overview on publications having investigated the allergy preventive effect of extensively and/or partially hydrolysed infant formulas. Publications were searched by several strategies. Inclusion criteria were: prospective cohort study, randomisation, family history of atopy of the subjects, follow-up for at least the 1st year of life. Studies were described systematically as to methods, study participants, interventions and co-interventions, and study outcomes. The methodological quality was judged according to an instrument assessing the reduction of bias (score between 0 and 7 points). Data of studies having examined partial hydrolysates are presented as odds ratios. Of 16 studies found, 10 fulfilled the inclusion criteria. Study designs showed considerable differences as to methods, intervention and co-intervention procedures and definition of outcomes. Methodological quality varied between 0 and 6 points. The comparison of exclusively test- and control formula-fed groups showed a uniform tendency towards allergy protection in studies with partial hydrolysates. Study results on the effect of extensive hydrolysates were not comparable because of major differences in study designs. Conclusion More well-designed studies with an adequate statistical power are needed to compare the allergy preventive effect of partially and extensively hydrolysed formulas with a standard infant formula. Received: 17 May 2000 / Accepted: 30 January 2001     

Prediction and prevention of type 1 diabetes

Clinical type 1 diabetes represents end-stage insulitis resulting from progressive β-cell destruction over an asymptomatic period that may last for years. This knowledge and recent advances in our ability to identify individuals at increased risk for clinical disease have paved the way for trials aimed at preventing or delaying the clinical onset of type 1 diabetes. Individuals at risk for type 1 diabetes can be identified by a positive family history, or by genetic, immunological or metabolic markers. These markers can also be combined to achieve a higher positive predictive value. As long as there is no effective preventive modality available for clinical use, screening for the identification of risk individuals can be considered ethically acceptable only in the context of sound research protocols. Prevention of type 1 diabetes can be implemented at three different levels, out of which primary prevention includes all strategies aimed at decreasing the risk of developing type 1 diabetes in individuals without any signs of β-cell damage. Secondary prevention aims to reduce the incidence of type 1 diabetes by stopping β-cell destruction in individuals with signs of such a process, while the objective of tertiary prevention is to restore β-cell function or prevent complications in patients with overt type 1 diabetes. At present, one primary prevention trial and four comprehensive secondary prevention trials are in progress. Common features of these intervention trials are that the recruitment of patients fulfilling the inclusion criteria is time-consuming and the trials must proceed for a long time, as clinical disease is the end point. The secondary prevention trials also require extensive screening for the identification of eligible patients. The ongoing intervention trials may, however, represent a new era in type 1 diabetes, i.e. the beginning of the end of this complicated disease.     

Parental reactions to information about increased genetic risk of type 1 diabetes mellitus in infants

OBJECTIVE: To assess the anxiety, emotions, thoughts, and coping behaviors of parents 1 week after they receive the results of screening of their infant's genetic risk of type 1 diabetes mellitus. DESIGN: Survey. SETTING: The population-based Type 1 Diabetes Prediction and Prevention project conducted in Turku. PARTICIPANTS: Parents of 443 consecutive high-risk infants and 506 next-born low-risk infants. INTERVENTIONS: An infant's genetic risk of type 1 diabetes mellitus was measured from cord blood. High-risk information was delivered by telephone and low-risk information by mail 4 weeks later. MAIN OUTCOME MEASURES: Anxiety measured using the state anxiety scale of the State-Trait Anxiety Inventory, and feelings, thoughts, and coping behaviors extracted from the questionnaire. RESULTS: One week after obtaining the results, 67% of mothers and 63% of fathers of high-risk children and 58% of mothers and 54% of fathers of low-risk children had returned the questionnaire. Anxiety levels of parents of high-risk infants were similar to those of parents of low-risk infants (P = .86). More than 90% of the parents thought that it was good to know about the risk. Fifty-five percent of mothers and 37% of fathers of high-risk infants expressed modest worry. Increased anxiety was connected with other stressful life events, catastrophizing thoughts of diabetes mellitus risk, and emotion-focused or avoiding coping attitudes. CONCLUSIONS: Learning about their infant's genetic diabetes mellitus risk induces only mild anxiety in most parents. Identifying the few parents with stronger anxiety helps focus intensified counseling.     

Is affluence a risk factor for bronchial asthma and type 1 diabetes?

In the last decades, an increase in bronchial asthma and type 1 diabetes occurrence has been observed in affluent countries, and a positive association between the two disorders has been demonstrated at the population level. This association could be explained by common risk factors predisposing to both disorders. Altered environmental and lifestyle conditions, possibly related to socio-economic status, might account for the rising trend of the two disorders. To test this hypothesis, we calculated the correlation between the occurrence of type 1 diabetes and asthma, the gross national product (GNP) and the infant mortality rate, in several European and extra-European countries. GNP was positively correlated with the incidence of type 1 diabetes and with symptoms of asthma in European (r(sp): 0.53 and 0.69; p = 0.001 and p < 0.0001, respectively) and extra-European countries (r(sp): 0.44 and 0.46; p = 0.04 for both diseases). Infant mortality rate was inversely correlated with GNP and with the occurrences of the two diseases in Europe (r(sp): -0.66, p < 0.0001 for type 1 diabetes; r(sp):- 0.51, p = 0.01 for asthma). In extra-European countries, a significant relationship was found between infant mortality and asthma (r(sp): -0.46; p = 0.03); a trend towards a negative correlation between infant mortality and type 1 diabetes was also found, although no statistical significance was reached (r(sp): -0.21; p = 0.31). This analysis indicates that type 1 diabetes and asthma are positively associated with the GNP at the population level. Similarly, countries with low infant mortality rates tend to have a higher incidence of these immune-mediated diseases. Although GNP reflects many societal and lifestyle differences, it is notable that a high socio-economic status implies a reduced or delayed exposure to infectious agents. The reduced pressure of infectious agents on the immune system throughout life might contribute to increase the susceptibility to bronchial asthma and type 1 diabetes.     

Prediction and prevention of type 1 diabetes: update on success of prediction and struggles at prevention

Type 1 diabetes mellitus (T1DM) is the archetypal example of a T cell‐mediated autoimmune disease characterized by selective destruction of pancreatic β cells. The pathogenic equation for T1DM presents a complex interrelation of genetic and environmental factors, most of which have yet to be identified. On the basis of observed familial aggregation of T1DM, it is certain that there is a decided heritable genetic susceptibility for developing T1DM. The well‐known association of T1DM with certain human histocompatibility leukocyte antigen (HLA) alleles of the major histocompatibility complex (MHC) was a major step toward understanding the role of inheritance in T1DM. Type 1 diabetes is a polygenic disease with a small number of genes having large effects (e.g., HLA) and a large number of genes having small effects. Risk of T1DM progression is conferred by specific HLA DR/DQ alleles [e.g., DRB1*03‐DQB1*0201 (DR3/DQ2) or DRB1*04‐DQB1*0302 (DR4/DQ8)]. In addition, the HLA allele DQB1*0602 is associated with dominant protection from T1DM in multiple populations. A concordance rate lower than 100% between monozygotic twins indicates a potential involvement of environmental factors on disease development. The detection of at least two islet autoantibodies in the blood is virtually pre‐diagnostic for T1DM. The majority of children who carry these biomarkers, regardless of whether they have an a priori family history of the disease, will develop insulin‐requiring diabetes. Facilitating pre‐diagnosis is the timing of seroconversion which is most pronounced in the first 2 yr of life. Unfortunately the significant progress in improving prediction of T1DM has not yet been paralleled by safe and efficacious intervention strategies aimed at preventing the disease. Herein we summarize the chequered history of prediction and prevention of T1DM, describing successes and failures alike, and thereafter examine future trends in the exciting, partially explored field of T1DM prevention.     

枸橼酸咖啡因与氨茶碱治疗早产儿原发性呼吸暂停的比较

目的 探讨枸橼酸咖啡因与氨茶碱治疗早产儿原发性呼吸暂停的疗效与安全性.方法 回顾性分析2013 年3 月至2014 年3 月收治的125 例诊断有原发性呼吸暂停的早产儿的临床资料,根据治疗措施不同分为枸橼酸咖啡因组(n=65)和氨茶碱组(n=60).比较两组治疗的有效率及不良反应发生率.结果 枸橼酸咖啡因组有效56 例(86%),氨茶碱组有效43 例(72%),两组比较差异有统计学意义(PP结论 枸橼酸咖啡因治疗早产儿原发性呼吸暂停疗效优于氨茶碱,不良反应发生率较低.     

Age at first introduction to complementary foods is associated with sociodemographic factors in children with increased genetic risk of developing type 1 diabetes

Infant's age at introduction to certain complementary foods (CF) has in previous studies been associated with islet autoimmunity, which is an early marker for type 1 diabetes (T1D). Various maternal sociodemographic factors have been found to be associated with early introduction to CF. The aims of this study were to describe early infant feeding and identify sociodemographic factors associated with early introduction to CF in a multinational cohort of infants with an increased genetic risk for T1D. The Environmental Determinants of Diabetes in the Young study is a prospective longitudinal birth cohort study. Infants (N = 6404) screened for T1D high risk human leucocyte antigen‐DQ genotypes (DR3/4, DR4/4, DR4/8, DR3/3, DR4/4, DR4/1, DR4/13, DR4/9 and DR3/9) were followed for 2 years at six clinical research centres: three in the United States (Colorado, Georgia/Florida, Washington) and three in Europe (Sweden, Finland, Germany). Age at first introduction to any food was reported at clinical visits every third month from the age of 3 months. Maternal sociodemographic data were self‐reported through questionnaires. Age at first introduction to CF was primarily associated with country of residence. Root vegetables and fruits were usually the first CF introduced in Finland and Sweden and cereals were usually the first CF introduced in the United States. Between 15% and 20% of the infants were introduced to solid foods before the age of 4 months. Young maternal age (<25 years), low educational level (<12 years) and smoking during pregnancy were significant predictors of early introduction to CF in this cohort. Infants with a relative with T1D were more likely to be introduced to CF later.     

Risk assessment, prediction and prevention of type 1 diabetes

Circulating antibodies to pancreatic beta-cell antigens are markers of islet autoimmunity. In first-degree relatives of persons with type 1 diabetes, the levels and range of antigen specificities of these islet antibodies reflect the risk for clinical diabetes. However, in the general population, in which the disease prevalence is up to 30-fold lower, the predictive value of islet antibodies is correspondingly less. Islet antibody assays are primarily research tools to identify 'prediabetic' individuals for secondary prevention trials, but can also discriminate type 1 diabetes in several clinical situations. Loss of first-phase insulin response (FPIR) to intravenous glucose signifies imminent diabetes, but FPIR is normal in most islet-antibody-positive individuals. The contribution of a single FPIR measurement to risk assessment is therefore limited, but rate of fall of FPIR may be a useful predictor. Although beta cells are destroyed by autoreactive T cells, the assay of islet antigen-reactive T cells is not routine. Genetically, the major histocompatibility complex encoding human leukocyte antigen (HLA) alleles accounts for about 50% of familial clustering of type 1 diabetes. HLA typing is not diagnostic, but can be used to differentiate high- from low-risk individuals, e.g. at birth. While 'preclinical' diagnosis raises important medical and ethical questions, an optimized screening strategy provides a basis for counselling and follow-up. Recent knowledge of disease mechanisms and 'proof-of-principle' in the non-obese diabetic (NOD) mouse model justify expectations that type 1 diabetes is preventable, and even intervention that only delays onset of clinical diabetes is likely to be cost-effective.     

Insulin in human milk and the prevention of type 1 diabetes

Abstract: Although controversial, exclusive breast milk feeding was shown to exert a protective effect in preventing type 1 diabetes. In contrast, an early introduction of cow's milk-based formula in young infants may enhance the risk of disease, especially in genetically susceptible children, presumably by an increase of intestinal permeability to macromolecules such as bovine serum albumin and β-casein, which may arouse autoimmunity. We have shown that human milk contains insulin in substantial concentrations, while insulin is barely detectable (if at all) in infant formulas. Orally administered insulin was demonstrated to promote gut maturation and to reduce intestinal permeability to macromolecules. Furthermore, oral insulin may induce tolerance to insulin and protect against the development of type 1 diabetes. We herewith raise a hypothesis that human milk is protective against the development of type 1 diabetes by virtue of the effects of its substantial content of insulin.     

UK health visitors' role in identifying and intervening with infants at risk of developing obesity

Childhood obesity is associated with a number of modifiable risk factors that can be identified during infancy or earlier. In the UK, health visitors advise parents about infant feeding, but little is known about their role in obesity prevention. The aim of this study was to investigate the beliefs and current practices of UK health visitors in relation to recognising and intervening with infants at risk of developing obesity. Thirty members of the health visiting team were interviewed. The interviews were audio‐recorded and transcribed verbatim. Thematic analysis was applied using an interpretative, inductive approach. Health visitors were aware of some of the modifiable risk factors for childhood obesity such as infant feeding practices. They felt they had a role in advising parents about diet but did not formally identify and/or intervene with larger infants. Infant overweight was considered a sensitive issue that was difficult to raise with parents. They believed some parents preferred larger infants and were unaware that their feeding practices might be contributing to obesity risk. A need for training and guidance was identified together with strategies to overcome system barriers. Health visitors do not currently target parents of infants at risk of obesity largely because they do not perceive they have appropriate guidance and skills to enable them to do so. There is an urgent need for tools and training to enable all health care professionals to recognise and manage infants at risk of developing obesity without creating a sense of blame.     

早产儿贫血现状及防治研究进展

随着现代医疗技术水平的不断提高,早产儿存活率也在不断提高,但早产儿贫血目前仍是早产儿营养管理上的常见问题之一。防治早产儿贫血的主要方法有不同途径的补充铁剂、红细胞输注及合理使用重组人红细胞生成素等,但上述防治方法各有利弊。文章就早产儿贫血的现状及防治方面进展进行论述。     

早产儿侵袭性真菌感染的防治

侵袭性真菌感染是早产儿致死和致残的重要原因,近年来,国内相关报道日益增多.该文对早产儿侵袭性真菌感染的国内外发生现状及诊断、治疗和预防方面的进展作一简要介绍.     

Incidence and significance of primary abnormalities of cardiac rhythm in infants at high risk for sudden infant death syndrome

Summary The exact relationship between cardiac arrhythmias and sudden infant death syndrome (SIDS) is uncertain. Several reports have implicated both ventricular and supraventricular arrhythmias in isolated cases, but there have been no studies of the incidence or type of arrhythmias that occur in populations at risk for SIDS. Of 1699 infants at high risk for SIDS, 60 (4%) were found to have a primary cardiac arrhythmia (i.e., not associated with disordered respiration or apnea). The incidence of atrial and ventricular premature beats, supraventricular tachycardia, and Wolff-Parkinson-White syndrome was similar to the incidence found in normal infants. Primary bradycardia (defined as a heart rate less than 60 for greater than 10 s not associated with abnormal respiration) was the most common arrhythmia, occurring with a frequency and severity not seen in normal infants. Thirty-two infants experienced periodic bradycardia. In 19 of these latter infants, there were symptoms associated with these bradyarrhythmias that necessitated treatment. Heart rates as low as 20 beats/min were recorded. One infant presented with an episode of ventricular fibrillation and on further evaluation was noted to have recurrent bradyarrhythmias. In no infant was there abnormal prolongation of the QT interval. Primary bradyarrhythmias are seen at an increased incidence in infants at high risk for SIDS and may play a causal role in this syndrome. Most symptomatic infants can be adequately controlled with sympathomimetic or parasympatholytic therapy. Other cardiac arrhythmias occur at a rate similar to that in normal infants and are therefore unlikely to play a major role in SIDS.     

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.     

Breastfeeding and catch-up growth in infants born small for gestational age

Postnatal growth was prospectively measured from birth to 1 y in 54 term infants born small for gestational age (SGA), fed either breast milk or a standard term infant formula. Breastfeeding was associated with a 0.36 and 0.64 standard deviation (SD) increase in weight at 2 weeks and 3 months of age. respectively, which persisted beyond the breastfeeding period (0.64 SD at 1 y). Breastfed infants also showed greater catch-up growth in head circumference [SD score (SDS) 0.53 higher at 3 months], and greater body length gain (SDS 0.68 higher at 6 months). This increased growth was independent of potentially confounding obstetric, social and demographic factors. Our findings suggest that breastfeeding may promote faster growth in infants compromised by poor growth in utero. SGA infants may be programmed for a number of adverse outcomes; the possibility that such events are altered by choice of postnatal diet is a key issue for future research.     

Early hypoadrenalism in premature infants at risk for bronchopulmonary dysplasia or death

AIM: To study the relationship between serum cortisol and dehydroepiandrosterone sulphate (DHEAS) concentrations and death or bronchopulmonary dysplasia at 36 weeks of postmenstrual age in preterm infants. METHODS: Prospective measurement of cord, day of birth (D0) and day 4 (D4) serum cortisol and DHEAS concentrations and performance of low-dose (LD) ACTH tests in 89 preterm infants with gestational age <34 weeks at birth and in need of mechanical ventilation. RESULTS: Serum DHEAS levels correlated negatively with gestational age. At all sampling times, basal serum cortisol levels correlated positively with gestation-adjusted DHEAS levels (r = 0.39-0.46, p = 0.0032-<0.0001). The mean cord, D0 basal and stimulated cortisol, and cord and D0 DHEAS adjusted for gestational age were lower in the poor than good outcome infants (p < 0.02 for all). In the multiple logistic regression analyses, gestational age was the most significant factor affecting outcome, but low cord and D0 basal and stimulated cortisol and gestation-adjusted DHEAS levels also predicted poor outcome (OR 5.7-22; p = 0.049-0.014). CONCLUSIONS: Low cord and first day serum cortisol and DHEAS levels associated with poor outcome in preterm infants, which suggests general relative adrenocortical insufficiency in some premature newborns.