Clostridium botulinum and sudden infant death syndrome: A 10 year prospective study

It has been proposed that sudden and unexpected death in infants due to intestinal infection with Clostridium botulinum may mimic the clinicopathological features of sudden infant death syndrome. Between 3.3 and 3.8% of infants in some series have had this neurotoxin-producing bacterium isolated on faecal culture. Prospective screening of 248 infants presenting with the sudden infant death syndrome to the Adelaide Children's Hospital over a 10 year period from 1981 to 1990 was conducted. Faecal samples were obtained from both small and large intestines and cultured specifically for C. botulinum. No samples were positive. The results of this study suggest that routine post-mortem culture of faeces for C. botulinum has been of limited use within the South Australian infant population over the last decade, and that occult botulism has not been a significant factor in the causation of sudden death.     

Adverse reactions in healthy and immunocompromised children under six years of age vaccinated with the Danish BCG vaccine, strain Copenhagen 1331: implications for the vaccination policy in Sweden

A retrospective analysis of the adverse reactions reported between 1979 and 1991, in the 139000 children under six years of age vaccinated in Sweden with the Danish BCG vaccine, strain Copenhagen 1331, showed an incidence of I.9 per 1000 vaccinated children. Regional lymphoglandular swellings and/or abscesses were most commonly reported in 1.4 per 1000. Serious, disseminated, BCG infections developed in four infants vaccinated neonatally. Three of the infants suffered from severe, combined, immunodeficiency syndrome, undiagnosed at the time of vaccination. The incidence of severe, combined, immunodeficiency syndrome was higher in the BCG-vaccinated population (4 per 100000 infants vaccinated within a year of their births), compared with all newborns in Sweden (1 per 100 000). The mean age at the onset of symptoms was 2.4 months for the seven non-BCG-vaccinated infants versus 1.3 months for the four BCG-vaccinated ones, while the immunodeficiency syndrome was diagnosed at an average age of 7.6 months in those who were not vaccinatedversus 5.3 months in those BCG-vaccinated. It is recommended that the selective BCG vaccination of infants at high risk of exposure to tuberculosis should be postponed to six months of age to reduce the risk of inoculating infants suffering from immunodeficiency syndromes.     

Effect of palivizumab prophylaxis in decreasing respiratory syncytial virus hospitalizations in premature infants

BACKGROUND: Respiratory syncytial virus (RSV) is a major cause of hospitalization in preterm infants and infants with chronic lung disease (CLD). Palivizumab, a humanized monoclonal antibody, was approved in Europe in 1999 as prophylaxis against severe RSV-related respiratory illness. No multiple season data have been published on palivizumab effectiveness in European populations. Data collected during 4 years in Spain compared RSV hospitalization rates and risk factors in a cohort of palivizumab-prophylaxed and nonprophylaxed preterm infants. METHODS: The first cohort was derived from 2 previous studies and included 1583 infants followed during 2 RSV seasons (1998 to 1999, 1999 to 2000) before palivizumab initiation in Spain. The second cohort included 1919 infants who received palivizumab prophylaxis for 2 subsequent respiratory seasons (2000 to 2001, 2001 to 2002). Both cohorts were preterm (< or =32 weeks gestational age) and < or =6 months old at onset of RSV season. RESULTS: The RSV hospitalization rate in the palivizumab-prophylaxed cohort was 3.95, and it was 13.25% in nonprophylaxed infants This 70% overall difference in RSV hospitalization was observed despite the palivizumab-prophylaxed group's lower gestational ages, more severe neonatal intensive care unit respiratory courses and higher incidence of CLD. Significant risk factors for RSV hospitalization in both cohorts included: lower gestational age; chronologic age <3 months at RSV season onset; school age siblings; and lower parental education. Nonprophylaxed children had a higher risk for RSV-related hospitalization than did prophylaxed patients (odds ratio, 3.86; 95% confidence interval, 2.83 to 5.25). CONCLUSION: Data from this study support the effectiveness of palivizumab in significantly modifying RSV-related hospitalizations in high risk preterm infants, with and without CLD, during two respiratory seasons.     

Infant botulism. Three cases in a small town

Through Dec 31, 1985, there have been six cases of infant botulism reported in Colorado. Three of these infants have lived in the same town of 800 people in western Colorado. Two of these three infants developed infant botulism within a six-month period in late 1981. The infants lived approximately 400 m apart; they had used the same crib at the time each developed botulism. A specimen from the crib yielded Clostridium botulinum, as did four soil samples from the town and house-dust samples from the home of a relative of the second infant. The third infant developed infant botulism in September 1984. This infant had not shared the crib. In this case, all seven samples of soil from various locations in the town yielded C botulinum, as did a sample of house dust from the home of this infant. The occurrence of these three cases in such a small town seems unlikely to be only coincidental. Investigations and reports of other such clusters may provide insight into modes of transmission of infant botulism.     

不同肠内营养开始时间对极低出生体重儿肠道菌群及代谢产物影响的前瞻性研究北大核心CSCD

目的 探讨不同肠内营养开始时间对极低出生体重儿肠道菌群及代谢产物的影响。方法 选取2020年6~12月重庆医科大学附属儿童医院新生儿科收治的29例极低出生体重儿为研究对象,根据生后肠内营养开始时间(开奶时间)不同分为<24 h组(n=15)和24~72 h组(n=14)。采集患儿住院第2周和第4周的粪便标本,采用16S rDNA高通量测序和气相色谱-质谱法分别分析粪便样本的菌群和短链脂肪酸(short-chain fatty acids,SCFAs)。结果 菌群结果显示,生后第2周和第4周2组间Chao指数(反映菌群丰富度)和Shannon指数(反映菌群多样性)差异无统计学意义(P>0.05)。菌群组成分析中,生后第2周和第4周2组间主要菌群在门、属水平上差异无统计学意义(P>0.05)。2组SCFAs比较显示,开奶时间<24 h组第4周丙酸高于24~72 h组(P<0.05),而2组SCFAs总量及其他各SCFAs含量差异无统计学意义(P>0.05)。结论 较早开始肠内营养对极低出生体重儿肠道菌群多样性和丰富度无影响,但24 h内开始肠内营养可以使代谢产物丙酸水平增高。     

A FOLLOW-UP STUDY OF INFANTS WITH ADVERSE REACTIONS TO COW'S MILK I. Serum IgE, Skin Test Reactions and RAST in Relation to Clinical Course

Abstract. 47 infants with cow's milk sensitivity were followed for a period varying between 6 months to 4 years (mean 28 months). The age at onset of symptoms varied between 14 days to 20 months. The clinical course was studied in relation to reaginic allergy by use of serum IgE, skin prick test and RAST. Infants with an immediate onset of symptoms from the gastrointestinal tract and the skin after cow's milk intake were discerned as a distinct entity having a high frequency of atopy in the family, positive skin tests and positive RASTs to milk (71%). Cases with delayed reactions to cow's milk seldom had a positive RAST or skin test. Most infants of both groups showed an increasing tolerance to milk. In RAST positive infants the RAST-titers increased significantly after onset of symptoms. After having reached a peak the titers subclined in several cases. The titers did not reflect the degree of milk sensitivity during the follow-up period. However, infants who developed high titers seemed to develop tolerance more slowly than infants with low titers.     

A follow-up study of infants with adverse reactions to cow's milk. I. Serum IgE, skin test reactions and RAST in relation to clinical course

47 infants with cow's milk sensitivity were followed for a period varying between 6 months to 4 years (mean 28 months). The age at onset of symptoms varied between 14 days to 20 months. The clinical course was studied in relation to reaginic allergy by use of serum IgE, skin prick test and RAST. Infants with an immediate onset of symptoms from the gastrointestinal tract and the skin after cow's milk intake were discerned as a distinct entity having a high frequency of atopy in the family, positive skin tests and positive RASTs to milk (71%). Cases with delayed reactions to cow's milk seldom had a positive RAST or skin test. Most infants of both groups showed an increasing tolerance to milk. In RAST positive infants the RAST-titers increased significantly after onset of symptoms. After having reached a peak the titers subclined in several cases. The titers did not reflect the degree of milk sensitivity during the follow-up period. However, infants who developed high titers seemed to develop tolerance more slowly than infants with low titers.     

Coronary aneurysms in infants and young children with acute febrile mucocutaneous lymph node syndrome.

In 1967, Kawasaki, in Japan, first described a new syndrome affecting infants and young children-an acute, febrile illness with mucocutaneous involvement associated with swelling of cervical lymph nodes. The prognosis is usually good but recently it has become evident that 1-2 percent of the patients die suddenly from acute heart failure. Infantile polyarteritis (nodosa-like arteritis) accompained by coronary aneurysm and thrombosis has been noted in postmortem examinations. Twenty patients surviving the illness were examined by coronary angiography; 12 of the 20 had abnormal coronary angiograms; seven patients had coronary aneurysms. Complete regression of the coronary aneurysms was proved in two patients at subsequent angiography. One patient developed mitral regurgitation as a result of papillary muscle dysfunction. One had a coronary aneurysm without symptoms two years after the onset of illness.     

婴儿肠道菌群与分娩方式、喂养方式及胆汁淤积性肝病的关系

目的分析分娩方式和喂养方式对健康婴儿肠道菌群的影响,探讨肠道相关分子微生态在胆汁淤积性肝病中的作用及意义。方法收集37例健康婴儿(其中阴道分娩21例,剖宫产16例;母乳喂养15例,人工喂养22例)及84例胆汁淤积性肝病婴儿粪便,提取粪便中细菌DNA并测量A260值;应用实时荧光定量PCR反应测定粪便中双歧杆菌、乳酸杆菌及大肠杆菌3种代表菌的数量。结果阴道分娩婴儿与剖宫产婴儿比较,母乳喂养婴儿与人工喂养婴儿比较,粪便标本中细菌DNA A260值和3种代表菌数量差异均无统计学意义(Pa>0.05)。健康对照组与胆汁淤积性肝病组粪便标本中细菌的DNA A260值分别为(1.94±0.47)g.L-1和(0.40±0.09)g.L-1,2组比较差异有统计学意义(t=8.91,P=0.00);健康对照组与胆汁淤积性肝病组3种细菌数(lg拷贝数/g湿便)的对数值比较差异均有统计学意义(双歧杆菌9.49±0.59 vs 7.68±0.57;t=15.96,P=0.00;乳酸杆菌8.58±0.32 vs 8.16±0.70;t=3.46,P=0.00;大肠杆菌6.87±0.67 vs 7.26±0.86;t=-2.41,P=0.02)。结论不同的分娩方式、喂养方式对婴儿期肠道菌群无影响;胆汁淤积性肝病婴儿肠道菌群与健康婴儿不同,粪便中细菌总量减少,双歧杆菌及乳酸杆菌数量明显减少,大肠杆菌的数量则明显增多,提示肠道菌群失调与婴儿胆汁淤积性肝病的发生、发展有一定关系。     

Rapid death of infant rhesus monkeys injected with Clostridium difficile toxins A and B: physiologic and pathologic basis

Clostridium botulinum can colonize and produce botulinal toxin in the human infant intestine, which the toxin then permeates to cause generalized flaccid paralysis, and occasionally, sudden death. This study was undertaken to test the hypothesis that toxins produced by other intestinal clostridia, e.g., C. difficile, might also cause systemic illness and sometimes death in infants (J Pediatr 100:568, 1982). Because this hypothesis could not be evaluated clinically until the systemic manifestations of C. difficile toxins in primates were known, infant rhesus monkeys were given 6 to 11 micrograms/kg of the recently purified C. difficile toxins A or B, either intravenously or intraperitoneally. The animals showed no abnormalities for several hours, but then developed lethargy, hypotonia, hypothermia, and, shortly before death, sudden elevation of serum concentrations of potassium, magnesium, and phosphorus and of enzymes that derived mainly from skeletal muscle, heart and brain. Five of six animals died quietly 3.5 to 8.0 hours after onset of symptoms. Death appeared to result from cessation of breathing, after which the sinus tachycardia then deteriorated to a flat ECG. Necropsy findings were insufficient to explain the cause of death. It appears that in infant monkeys microgram amounts of C. difficile toxins A and B can produce a rapid quiet death, the cause of which is undetectable at necropsy, a situation pathologically reminiscent of crib death in human infants, although the possible clinical identity of these two conditions has yet to be established.     

Honey and other environmental risk factors for infant botulism.

Infant botulism results from the in vivo production of toxin by Clostridium botulinum after it has colonized the infant's gut. Epidemiologic and laboratory investigations of this recently recognized disease were undertaken to identify risk factors and routes by which C. botulinum spores might reach susceptible infants. Clostridium botulinum organisms, but no preformed toxin, were identified in six different honey specimens fed to three California patients with infant botulism, as well as from 10% (9/90) of honey specimens studied. By food exposure history, honey was significantly associated with type B infant botulism (P = 0.005). In California, 29.2% (12/41) of hospitalized patients had been fed honey prior to onset of constipation; worldwide, honey exposure occurred in 34.7% (28/75) of hospitalized cases. Of all food items tested, only honey contained C. botulinum organisms. On household vacuum cleaner dust specimens and five soil specimens (three from case homes, two from control homes) contained Clostridium botulinum. The known ubiquitous distribution of C. botulinum implies that exposure to its spores is universal and that host factors contribute importantly to the pathogenesis of infant botulism. However, honey is now an identified and avoidable source of C. botulinum spores, and it therefore should not be fed to infants.     

Intestinal Lymphangiectasia in Children: A Study of Upper Gastrointestinal Endoscopic Biopsies

From 1980-1986 intestinal mucosal lymphangiectasia was diagnosed histologically in eight patients (6 weeks to 16 years; four males/Jour females; seven white). The presenting features were diarrhea (six/eight), vomiting (four/eight), and growth deficit (seven/eight). Additional conditions in these patients included asthma, urinary tract infection, esophageal atresia, hydrops fetalis, inflammatory bowel disease, malabsorption syndrome, and thymic hypoplasia. Hypoalbuminemia and edema (four/eight) were more prominent in those patients under 5 years of age. Two had systemic lymphangiectasia and lymphopenia. The patients responded variably to hyperalimentation and dietary supplements, depending on the extent of their lymphangiectasia and the age at onset of symptoms. Dilated lymphatics were seen in the small intestinal mucosa under the surface epithelium. Lesions were often focal, requiring several biopsies or serial sections for detection. Other common findings were mild to moderate lymphoplasmacytic inflammation and mild to moderate villous injury with blunting and edema. Mild inflammation without lymphangiectasia was also present in esophageal, gastric, or colonic biopsies. Diagnosis should be made on the basis of endoscopic findings or in small-intestinal inflammatory conditions even in the absence of a classic clinical picture. Histologic confirmation may require more than one serially sectioned biopsy. This study confirms the diversity of disorders that may be associated with intestinal lymphangiectasia and shows that the disease in infants is more severe and generalized.     

Intestinal lymphangiectasia in children: a study of upper gastrointestinal endoscopic biopsies

From 1980-1986 intestinal mucosal lymphangiectasia was diagnosed histologically in eight patients (6 weeks to 16 years; four males/four females; seven white). The presenting features were diarrhea (six/eight), vomiting (four/eight), and growth deficit (seven/eight). Additional conditions in these patients included asthma, urinary tract infection, esophageal atresia, hydrops fetalis, inflammatory bowel disease, malabsorption syndrome, and thymic hypoplasia. Hypoalbuminemia and edema (four/eight) were more prominent in those patients under 5 years of age. Two had systemic lymphangiectasia and lymphopenia. The patients responded variably to hyperalimentation and dietary supplements, depending on the extent of their lymphangiectasia and the age at onset of symptoms. Dilated lymphatics were seen in the small intestinal mucosa under the surface epithelium. Lesions were often focal, requiring several biopsies or serial sections for detection. Other common findings were mild to moderate lymphoplasmacytic inflammation and mild to moderate villous injury with blunting and edema. Mild inflammation without lymphangiectasia was also present in esophageal, gastric, or colonic biopsies. Diagnosis should be made on the basis of endoscopic findings or in small-intestinal inflammatory conditions even in the absence of a classic clinical picture. Histologic confirmation may require more than one serially sectioned biopsy. This study confirms the diversity of disorders that may be associated with intestinal lymphangiectasia and shows that the disease in infants is more severe and generalized.     

Urea utilization by the intestinal flora, of infants fed mother's milk and a formula diet, as measured with the 15N-tracer technique

15N-Incorporation by intestinal bacteria was measured under different feeding conditions in 16 infants after a single oral loading of 165 mg [15N2]urea X kg-1 body weight as a tracer. In five subjects on a mother's milk diet, the 15N-excess in the isolated intestinal bacteria was 1.08 (0.17-1.85) atom-%. The mean 15N-excess in the intestinal flora of five formula-fed subjects did not differ significantly from these values [0.63 (0.17-1.05) atom-%]. A trend to a higher incorporation of 15N from labeled urea by the intestinal flora was seen in four infants, who were adapted to an increased nutritional urea supply on a special formula, containing 14 g of milk protein, 80 g lactose, 36 g fat, and 0.35 g urea X L-1. The same observation was made in two infants with chronic renal failure. The incorporation of urea nitrogen by the putrefactive intestinal flora of infants on a formula diet as well as by the bifidobacterial flora of those on mother's milk feeding indicates the utilization of ureas as a source of bacterial protein and nucleic acid synthesis. The adaptive usage of urea for the bacterial metabolism can be considered as a sign of supportive detoxification by the intestinal flora.     

Prognostic value of immunological data, in vitro antibody production, and virus culture in vertical infection with HIV-1

The prognostic value of immunological indices, in vitro antibody production, and virus culture pattern at 3 months of age was estimated in 35 infants infected by HIV-1 from a cohort of 298 babies born to HIV-1 seropositive mothers and followed up from birth. At 1 year old, 15 of these infants were classified as stage P-1 (according to the Centers for Disease Control classification) seven were P-2A, and seven had AIDS. Significantly higher CD8 percentages, lower percentages and absolute value of CD4, and lower CD4/CD8 ratios at 3 months were observed in infants with severe symptoms at 1 year of age when compared with those who were asymptomatic at this age. Seventy seven per cent of infants with a 'rapid' virus culture when 3 months old had developed AIDS or had died by 1 year of age and only 8% of those with 'slow' virus culture had AIDS when 1 year old. Moreover, 100% of those who were asymptomatic at 1 year had a slow virus culture at 3 months. Significant statistical association was found between the virus replication pattern at 3 months and the clinical stage at 1 year of age.     

Necrotizing enterocolitis increases the bone resorption in premature infants

BACKGROUND: Necrotizing enterocolitis is a common neonatal gastrointestinal disease that affects approximately 10% of premature infants less than 1500 g. The average mortality is 20-40% and survivors may present with diarrhea or malabsorption, intestinal strictures and fistulas, feeding abnormalities and failure to thrive. It is not clear whether the higher incidence of this gastrointestinal disease in premature infants contributes to the risk of osteopenia of prematurity. AIM: To examine bone turnover state in premature infants who had a necrotizing enterocolitis attack during postnatal period. STUDY DESIGN AND SUBJECTS: We examine the bone turnover markers in infants with necrotizing enterocolitis and compare them with infants with sepsis. Forty-one premature infants participated in the study and were divided into three groups. In group I, there were 14 premature infants who developed necrotizing enterocolitis with negative blood culture during their hospitalization. In group II, there were 12 premature infants who developed sepsis during their hospitalization. Age-matched 15 premature infants who were given parenteral nutrition served as control group (group III). Blood samples and 6-h urine samples were obtained for bone turnover markers and calcium, phosphorous, creatinine and 25-hydroxy vitamin D between the day 20 and 25. Bone osteoblastic activity was assessed by measurement of serum osteocalcin. Bone resorption was assessed by measurement of serum levels of beta-CrossLaps and urinary deoxypyridinoline. RESULTS: There were no significant differences in bone osteoblastic activity among the groups, but bone resorption markers were significantly higher in infants with necrotizing enterocolitis compared to other groups (p < 0.016). CONCLUSION: Necrotizing enterocolitis increases the bone resorption in premature infants. It may be related with reduced glucagon like peptide-2 levels, a new intestinal hormone that is primary secreted from distal small intestine.     

Intestinal microflora in early infancy: composition and development

The neonatal intestinal microbiota is a complex ecosystem composed of numerous genera, species and strains of bacteria. This enormous cell mass performs a variety of unique activities that affect both the colonic and systemic physiology. Its primary activities include nutritive, metabolic, immunological and protective functions. Most studies of infants have been based on faecal samples using the classical plating techniques with culturing on specific media. The limitations of these methods must be taken into account when evaluating the varying results of the different studies. The establishment of the gut microbial population is not strictly a succession in the ecological sense; it is rather a complex process influenced by microbial and host interactions and by external and internal factors. The climax intestinal flora is attained in successive stages. The foetal intestine is sterile and bathed in swallowed amniotic fluid. Following delivery, multiple different antigens challenge the intestine of the newborn. The maternal intestinal flora is a source of bacteria for the neonatal gut. The bacterial flora is usually heterogeneous during the first few days of life, independently of feeding habits. After the first week of life, a stable bacterial flora is usually established. In full-term infants a diet of breast milk induces the development of a flora rich in Bifidobacterium spp. Other obligate anaerobes, such as Clostridium spp. and Bacteroides spp., are more rarely isolated and also enterobacteria and enterococci are relatively few. During the corresponding period, formula-fed babies are often colonized by other anaerobes in addition to bifidobacteria and by facultatively anaerobic bacteria; the development of a "bifidus flora" is unusual. In other studies the presence of a consistent number of bifidobacteria in infants delivered in large urban hospitals has not been demonstrated, whether the babies were bottle fed or exclusively breastfed. The predominant faecal bacteria were coliforms and bacteroides. According to these studies, environmental factors may be more important than breastfeeding in gut colonization after delivery. Environmental factors are indeed extremely important for the intestinal colonization of infants born by caesarean section. In these infants, the establishment of a stable flora characterized by a low incidence of Bacteroides spp. and by the isolation of few other bacteria is consistently delayed. In extremely low-birthweight infants, hospitalization in neonatal intensive care units, characterized by prolonged antibiotic therapy, parenteral nutrition, delayed oral feedings and intubation seems to affect the composition of the intestinal microbiota. The gut is colonized by a small number of bacterial species; Lactobacillus and Bifidobacteria spp. are seldom, if ever, identified. According to the few studies so far performed, the predominant species are Enterococcus faecalis, E. coli, Enterobacter cloacae, Klebsiella pneumoniae, Staphylococcus epidermidis and Staphylococcus haemolyticus. Hygienic conditions and antimicrobial procedures strongly influence the intestinal colonization pattern.     

Two cases of type A infant botulism in Grenoble, France: no honey for infants

We report two severe cases of infant botulism diagnosed at Grenoble University Hospital, France, respectively in 2006 and 2009. Both cases were characterized by a delay in diagnosis, severe neurological manifestations and extended period of hospitalization in intensive care unit, but a complete recovery. Infant botulism is a rare but life-threatening disease. It primarily affects infants, and the main risk factor is honey ingestion. Diagnosis should be systematically evoked by pediatricians in infants suffering from constipation, fatigue, muscle weakness, difficult feeding and altered cry, but before the onset of generalized flaccid paralysis, so as to administer specific treatment (BabyBIG?, a human derived botulinum antitoxin) at an early stage of the disease when it is most effective. In conclusion, parents should be aware of the role of honey as a source of spores of Clostridium botulinum and therefore infant botulism in the first year of life.     

Prognostic value of immunological data,in vitro antibody production,and virus culture in vertical infection with HIV-1.

The prognostic value of immunological indices, in vitro antibody production, and virus culture pattern at 3 months of age was estimated in 35 infants infected by HIV-1 from a cohort of 298 babies born to HIV-1 seropositive mothers and followed up from birth. At 1 year old, 15 of these infants were classified as stage P-1 (according to the Centers for Disease Control classification) seven were P-2A, and seven had AIDS. Significantly higher CD8 percentages, lower percentages and absolute value of CD4, and lower CD4/CD8 ratios at 3 months were observed in infants with severe symptoms at 1 year of age when compared with those who were asymptomatic at this age. Seventy seven per cent of infants with a ''rapid'' virus culture when 3 months old had developed AIDS or had died by 1 year of age and only 8% of those with ''slow'' virus culture had AIDS when 1 year old. Moreover, 100% of those who were asymptomatic at 1 year had a slow virus culture at 3 months. Significant statistical association was found between the virus replication pattern at 3 months and the clinical stage at 1 year of age.