Recurrent late-onset sepsis in the neonatal intensive care unit: incidence,clinical characteristics and risk factors

We aimed to characterize the incidence, clinical features, risk factors and outcomes of recurrent late-onset sepsis (LOS) in the neonatal intensive care unit (NICU). All neonates with LOS from the NICU of a tertiary-level teaching hospital in northern Taiwan between 2004 and 2011 were enrolled for analyses. A case-control study was performed to determine risk factors for recurrence. Of 713 neonates with LOS, 150 (21.0%) experienced recurrence and 48 (6.7%) had >1 recurrences; c. two-thirds of recurrent LOS occurred in infants with birth weight (BW) ≦ 1500 g or gestational age (GA) ≦ 30 weeks. The recurrent LOS episodes were significantly more severe and had a higher sepsis-attributable mortality rate than the first episodes. The overall in-hospital mortality rate was 30.7% for neonates with recurrent LOS and 7.8% for those with single LOS (odds ratio (OR), 5.22; 95% CI, 3.28–8.30). When both BW and GA were controlled, neonates with recurrent LOS had a significantly prolonged hospitalization compared with the controls (median 109 vs. 84 days, p <0.001). After multivariate logistic regression, longer duration of total parenteral nutrition (TPN; OR, 1.30; 95% CI, 1.10–1.52 for every 10-day increment), presence of congenital anomalies (OR, 2.64; 95% CI, 1.10–6.35) and neurological co-morbidities (OR, 4.14; 95% CI, 1.14–15.10) were identified as the independent risk factors for LOS recurrence. We concluded that c. one-fifth of neonates with LOS had recurrence, which significantly resulted in prolonged hospitalization and increased mortality. Longer TPN administration, presence of congenital anomalies and neurological co-morbidities are independently associated with recurrent LOS.     

Sensitization to human milk

Background Allergy to milk is one of the earliest manifestations of IgE‐mediated allergies and affects about 2.5% of newborn children. Several reports indicate that milk‐allergic patients may be sensitized also to human milk proteins. Objective To analyse the specificity and possible biological relevance of IgE reactivity to human milk antigens in milk‐allergic patients. Methods The specificity of IgE reactivity to cow's milk and human milk antigens was analysed with sera from milk‐allergic children and adults by IgE immunoblotting. IgE cross‐reactivity between milk antigens was studied by immunoblot inhibition experiments. That IgE reactivity to human milk antigens is not due to alloreactivity or due to the transmission of foreign antigens into mother's milk was demonstrated through the analysis of milk samples from genetically unrelated mothers before and after intake of dietary milk products. The biological relevance of IgE reactivity to human milk was confirmed by skin testing. Results IgE antibodies to human milk were found in more than 80% of the tested milk‐allergic patients. Cross‐reactive IgE‐reactive human antigens such as α‐lactalbumin and non‐cross‐reactive human milk antigens were identified. Immediate‐type skin reactions could be elicited with human milk samples in patients with IgE reactivity to human milk. Conclusion IgE reactivity to human milk in milk‐allergic patients can be due to cross‐ sensitization and genuine sensitization to human milk and may cause allergic symptoms. IgE‐mediated sensitization to human milk is common in milk‐allergic patients and may require diagnostic testing and monitoring.     

母乳性黄疸对远期智能的影响

目的研究无高危因素的小儿母乳性黄疸对远期智能影响,指导母乳性黄疸的临床治疗。方法无高危因素的母乳性黄疸60例,分两组,一组29例,停母乳喂养,改人工喂养,记录黄疸消退时间;一组31例,予停母乳喂养,改人工喂养,以光疗,口服辅助药物等综合治疗;再取无高胆红素血症的对照组45例。3组小儿相同的随访和早教,一岁时由专业人员做婴儿智能测试,用CDCC量表测定智力发育指数(MDI)和运动发育指数(PDI)。结果 3组小儿在一岁时的智能无显著差异,无一例显示语言听力异常。结论无高危因素的母乳性黄疸对远期智能影响不大,可以适当放宽因黄疸而治疗的指征。     

Defective tumour necrosis factor-alpha production in mother''s milk is related to cow''s milk allergy in suckling infants

BACKGROUND: The precise role of leucocytes in human milk is still unresolved. OBJECTIVE: To assist in clarifying the immune mechanisms involved in the development of CMA in suckling infants, we studied the role of immunoregulatory leucocytes and their mediators in human breast milk. METHODS: The study population consisted of 43 lactating mothers and their infants, aged 0.25-8.0 months, followed-up prospectively from birth. Of these mothers, 27 had an infant with challenge-proven cow's milk allergy manifested with either skin (n = 23), gastrointestinal (n = 2) or skin and gastrointestinal symptoms (n = 3). Sixteen mothers with a healthy infant served as controls. We evaluated the spontaneous and mitogen-induced tumour necrosis factor-alpha (TNFalpha) and interferon-gamma (IFNgamma) production of human milk leucocytes and isolated peripheral blood lymphocytes in vitro with a commercial ELISA kit. RESULTS: TNFalpha production of breast milk leucocytes was significantly lower in the mothers with a cow's milk-allergic infant, whereas IFNgamma production of these cells was comparable in the two groups. CONCLUSION: Our results suggest that in the breast milk of mothers having an infant with cow's milk allergy, the number and function of TNFalpha-producing cells is defective. This might lead to a disturbance in the development of oral tolerance and thereby to the development of CMA in suckling infants. These novel results may help in clarifying the etiopathogenesis of CMA.     

Maternal western diet causes inflammatory milk and TLR2/4-dependent neonatal toxicity

For all newborn mammals, mother's milk is the perfect nourishment, crucial for their postnatal development. Here we report that, unexpectedly, maternal western diet consumption in mice causes the production of toxic milk that contains excessive long chain and saturated fatty acids, which triggers ceramide accumulation and inflammation in the nursing neonates, manifested as alopecia. This neonatal toxicity requires Toll-like-receptors (TLR), but not gut microbiota, because TLR2/4 deletion or TLR4 inhibition confers resistance, whereas germ-free mice remain sensitive. These findings unravel maternal western diet-induced inflammatory milk secretion as a novel aspect of the metabolic syndrome at the maternal offspring interface.     

Protection against neonatal rotavirus infection by breast milk antibodies and trypsin inhibitors

The role of breast milk antirotavirus immunoglobulin A (IgA) and trypsin inhibitors in limiting the acquisition of rotavirus infection during the initial 5 days of life was evaluated among 42 exclusively breast-fed hospital-born infants, 22 of whom experienced rotavirus infection. The mean concentrations of antirotavirus IgA (ELISA Units) in the breast milk of mothers of the 22 rotavirus-infected neonates was 130.4 +/- 46.4; the corresponding value in 20 noninfected neonates was 384.3 +/- 328.3 (P less than 0.001). Similarly, the trypsin inhibitory capacity (mumols/mt/ml) of breast milk in the rotavirus-infected group was significantly lower (0.109 +/- 0.095) than that in the noninfected group (0.376 +/- 0.191; P less than 0.001). The trypsin inhibitory capacity of milk showed an inverse correlation with infant stool tryptic activity (P less than 0.01). Our results indicate that the acquisition of rotavirus infection during the early neonatal period depends on the concentrations of antirotavirus IgA and trypsin inhibitors in human milk and that protection is mediated by high levels of these antiviral factors.     

Ecological pressures and milk metabolic hormones of ethnic Tibetans living at different altitudes

Background: Very little is known about how milk hormones, shown to influence growth during infancy, may contribute to patterns of altered growth in high altitude living infants.

Aim: This study investigated the association between maternal BMI, the metabolic hormones adiponectin and leptin in human milk and infant weight for age z-scores (WAZ) in Tibetans.

Subjects and methods: A sample of 116 mothers and infants (aged 0–36 months) were recruited from two locations: the Nubri Valley, Nepal (rural; altitude = 2400–3900 m) and Kathmandu, Nepal (urban, 1400 m). Milk samples, anthropometrics, biological data and environmental information were collected on mothers and infants. Milk was analysed for leptin and adiponectin.

Results: Maternal BMI was significantly associated with milk leptin content, but not adiponectin in either group. In the rural high altitude sample, child WAZ declined with age, but no such decline was seen in the urban sample.

Conclusions: Milk leptin and adiponectin were not associated with infant growth in the rural Nubri sample, but were both inversely associated with infant WAZ in the Kathmandu sample. It appears that, in ecologically stressful environments, associations between milk hormones and growth during infancy may not be detectable in cross-sectional studies.     

Allergy to goat and sheep milk without allergy to cow's milk

BACKGROUND: Cow's milk (CM) allergy is the most frequent cause of food allergy in infants. Most children who are allergic to CM are also sensitized to whey proteins and/or to the casein fraction and many of them cannot tolerate goat's or sheep's milk (GSM) either. Conversely, the GSM allergies that are not associated with allergic cross-reactivity to CM are rare. METHODS: Twenty-eight children who had severe allergic reactions, including anaphylaxis, after consumption of GSM products but tolerated CM products were recruited in a retrospective study. Whole casein and whey proteins were fractionated from CM and GSM. beta-Lactoglobulin and the different caseins were isolated, purified and used to perform enzyme allergosorbent tests (EAST) and EAST inhibition studies with the sera of the allergic children. RESULTS: Clinical observations, skin prick testing and immunoglobulin (Ig)E-binding studies confirmed the diagnosis of GSM allergy without associated CM allergy. EAST determinations demonstrated that GSM allergy involves the casein fraction and not whey proteins. Cow's milk caseins were not at all or poorly recognized by the patient's IgE, while alphaS(1)-, alphaS(2)- and beta-caseins from GSM were recognized with a high specificity and affinity. In all cases, increasing concentrations of CM caseins failed to inhibit the binding of patient's IgE to sheep or goat milk caseins, whereas this binding was completely inhibited by GSM caseins. CONCLUSIONS: The characteristics of GSM allergy differ from those of the CM allergy because it affects older children and appears later. CM products do not elicit any clinical manifestation in GSM allergic patients, whereas CM allergic patients, usually cross-react to GSM. In all the GSM allergic children, the IgE antibodies recognized the caseins but not the whey proteins. Moreover, IgE specificity and affinity was high to GSM and lower to CM caseins despite their marked sequence homology. Doctors and allergic individuals should be aware that GSM allergy requires a strict avoidance of GSM and milk-derived products because reactions could be severe after ingestion of minimal doses of the offending food.     

Aeromonas hydrophila meningitis and fulminant sepsis in preterm newborn: A case report and review of literature

Neonatal meningitis is a lethal infection occurring in the 1^st month of life. The risk of developing permanent neurological sequels is high among the neonates who survive. Bacterial pathogens are commonly associated with this condition. Aeromonas is a Gram-negative bacteria of aquatic habitat. Although isolation of Aeromonas species from neonates with blood stream infection is infrequently reported, neonatal meningitis caused by Aeromonas is exceedingly rare. We present a case of fulminant sepsis and meningitis caused by Aeromonas hydrophila in a preterm newborn male. The bacteria was isolated in culture from blood and cerebrospinal fluid. In spite of targeted antibiotics and supportive therapy, the baby failed to respond and died on the 12^th day of life.     

Microarray analysis of human milk cells: persistent high expression of osteopontin during the lactation period

To continue the search for immunological roles of breast milk, cDNA microarray analysis on cytokines and growth factors was performed for human milk cells. Among the 240 cytokine-related genes, osteopontin (OPN) gene ranked top of the expression. Real-time PCR revealed that the OPN mRNA levels in colostrum cells were approximately 100 times higher than those in PHA-stimulated peripheral blood mononuclear cells (PBMNCs), and 10 000 times higher than those in PB CD14(+) cells. The median levels of OPN mRNA in early milk or mature milk cells were more than three times higher than those in colostrum cells. Western blot analysis of human milk showed appreciable expression of full-length and short form proteins of OPN. The concentrations of full-length OPN in early milk or mature milk whey continued to be higher than those in colostrum whey and plasma as assessed by ELISA. The early milk (3-7 days postpartum) contained the highest concentrations of OPN protein, while the late mature milk cells (1 years postpartum) had the highest expression of OPN mRNA of all the lactating periods. The results of immunohistochemical and immunocytochemical staining indicated that OPN-producing epithelial cells and macrophages are found in actively lactating mammary glands. These results suggest that the persistently and extraordinarily high expression of OPN in human milk cells plays a potential role in the immunological development of breast-fed infants.     

Detection of antibody specificity of raw bovine and human milk to bacterial lipopolysaccharides using PCFIA

Raw milk from non‐immunized cows and raw human milk from lactating mothers were examined for specificity and antibody activity against lipopolysaccharides (LPS) of five pathogenic bacteria, i.e. Escherichia coli O111:B4, E. coli O128:B12, Salmonella enteritidis, S. typhimurium and Shigella flexneri 1A in a particle concentration fluorescence immunoassay (PCFIA). Bacterial LPS was covalently coated on submicron polystyrene particles and used in an antibody sandwich technique with commercially available rabbit anti‐bovine fluorescein‐labeled IgG or goat anti‐human fluorescein‐labeled IgA. Comparison was made to a skim milk sample obtained from vaccinated cows. In general, specific activity of milk IgG against bacterial LPS did not parallel the trend of total non‐specific activity. Although the specific anti‐LPS activities were in general high in milk from vaccinated cows, milk from non‐immunized cows also showed significant activity against the bacterial LPS, sometimes higher than the vaccinated cows. IgA in human milk samples showed a wider range of antibody activity against the LPS fractions than bovine milk samples. The specificity of antibody from milk obtained from non‐immunized cows against pathogenic bacteria demonstrated that immunization of cows in order to obtain milk with high titer antibody may not be necessary as milk from non‐immunized cows can provide IgG with sufficient antibody activity against the LPS of bacterial pathogens. This can translate into significant savings and reduce stress imposed on animals for immunization.     

Comparative study of virulence traits of Escherichia coli clinical isolates causing early and late neonatal sepsis

Neonatal meningitis and septicemia caused by Escherichia coli are still major health problems in industrialized countries. Forty-seven E. coli strains causing neonatal sepsis were analyzed. Twenty-two and 25 strains caused early (detected from 0 to 3 days after birth) and late (detected from 4 to 28 days after birth) infections, respectively. Only the ibeA gene was significantly more prevalent in the strains causing early infections.     

Breast Feeding, Cow Milk Feeding, and Allergy

Information about every 10th child aged 14 to 38 months was collected by means of a questionnaire in Turku, Finland in March, 1983. This paper reports on the occurrence of allergy in relation to the duration of breast feeding and to the age of the child when cow milk feeding was started. The average duration of breast feeding was 5.7 months and the average age at the introduction of cow milk-based products was 4.3 months. Allergy was reported in family members of 47.6% of the children. In 30.3% the child himself was reported allergic. The occurrence of allergy was unaffected by the duration of breast feeding and the age at introduction of cow milk feeding.     

Development of an indirect competitive Elisa for Aldrin/Dieldrin in human milk samples collected in Egypt

Human milk samples (80) collected from 10 different cities in Egypt were tested for aldrin/dieldrin using an indirect enzyme‐linked immunosorbent assay (ELISA). Pesticides were detected in 73 of the 80 samples (91.25%) at levels ranging from 0.005 to 28 μg ml^‐1. These results present evidence for the persistence (or continued use) of these pesticides in Egyptian agriculture and their transmission through the food chain. More significantly the levels of pesticide in maternal milk (0.006–28 ppm) represent an unacceptably high level for infant intake; the maximum average daily intake is 0.0001 mg kg^‐1 body weight (WHO, 1972).