The Composition of the Faecal Microflora in Breastfed and Bottle Fed Infants from Birth to Eight Weeks

ABSTRACT. Recent technical advances have improved the possibilities to classify anaerobic bacteria. The aim of the present study was to examine the validity of the time-honoured opinion that the faecal flora is dominated by bifidobacteria in breastfed infants but not in bottle fed ones. The compositon of the faecal flora of 15 breastfed and of 7 bottle fed infants was followed from birth to 8 weeks. Strictly anaerobic conditions were carefully applied. At 5 days and 3 weeks the incidence of Staph, epidermidis was significantly greater in the breastfed group compared to the bottle fed one. We were unable to confirm earlier reports of difference in the anaerobic flora between breastfed and bottle fed infants. In both feeding groups Bacteroides dominated among the anaerobic bacteria and bifidobacteria occurred in less than half of the faecal specimens. The results of the study add to other recent observations that it has been increasingly difficult to demonstrate bifidobacteria in babies delivered in large, urban hospitals. We found different frequencies of bifidobacteria in infants from different wards, suggesting the importance of environmental factors in gut colonization after delivery.     

The composition of the faecal microflora in breastfed and bottle fed infants from birth to eight weeks

Recent technical advances have improved the possibilities to classify anaerobic bacteria. The aim of the present study was to examine the validity of the time-honoured opinion that the faecal flora is dominated by bifidobacteria in breastfed infants but not in bottle fed ones. The composition of the faecal flora of 15 breastfed and of 7 bottle fed infants was followed from birth to 8 weeks. Strictly anaerobic conditions were carefully applied. At 5 days and 3 weeks the incidence of Staph. epidermidis was significantly greater in the breastfed group compared to the bottle fed one. We were unable to confirm earlier reports of difference in the anaerobic flora between breastfed and bottle fed infants. In both feeding groups Bacteroides dominated among the anaerobic bacteria and bifidobacteria occurred in less than half of the faecal specimens. The results of the study add to other recent observations that it has been increasingly difficult to demonstrate bifidobacteria in babies delivered in large, urban hospitals. We found different frequencies of bifidobacteria in infants from different wards, suggesting the importance of environmental factors in gut colonization after delivery.     

Natural evolution of regurgitation in healthy infants

Objectives:  To determine the natural history of infant regurgitation during the first year of life.
Methods: Parents recorded prospectively the frequency of regurgitation for 1 week before consultation during the first year of life. A sub-group analysis according to the method of feeding was planned.
Results:  A total of 130 infants of an original sample of 163 (80%) newborns were followed up for 1 year. Daily spilling was highest during the first month of life (73%) and decreased gradually to 50% during the fifth month of life. During the first 2 months of life, 20% of the infants regurgitated more than four times per day. After the age of 12 months, only 4% of the infants had daily regurgitations. Exclusively breastfed infants did regurgitate less than partially breastfed infants. Weight gain was influenced by the frequency of regurgitation, especially in partially breastfed infants.
Conclusion: Regurgitation in infancy is common, decreasing from birth, and tends to disappear by 12 months of age. Weight gain during the first 4 months of life is decreased in infants who regurgitate more than four times a day. Our data suggest that exclusively breastfed infants regurgitate less than partially breastfed babies.     

Epidemiology of neonatal enterovirus infection

During a typical enterovirus season in Rochester, New York, none of 666 neonates or 629 mothers were found to be excreting nonpolio enteroviruses within 1 day of delivery. No enteroviruses were isolated from weekly cultures of the 23 infants who died or remained hospitalized during the first month of life. After discharge, culture specimens were obtained in 586 infants at one to four weekly home visits until 1 month of age. The incidence of acquisition of nonpolio enterovirus infection was 12.8%, and the overall prevalence of enterovirus excretion was 5.3%. Risk of virus infection was associated only with lower socioeconomic status (P less than 0.0001) and lack of breast-feeding (P less than 0.0001). Four percent of all infants and 21% of infants in whom cultures for enterovirus were positive were readmitted to the hospital in the first month of life; 79% of infants with positive enterovirus cultures were asymptomatic. We conclude that enterovirus infection during the first month of life is very common in the late summer and early fall. Most infants are asymptomatic, but the risk of hospitalization is high. Breast-feeding may be associated with protection from infection.     

Clostridium difficile isolation in leukemic children on maintenance cancer chemotherapy. A preliminary study

Between December 1982 and November 1983, stool specimens from 15 children with acute lymphoblastic leukemia, who were on maintenance cancer chemotherapy, were examined weekly for the presence of Clostridium difficile and its toxin. Four out of 15 patients were positive for C. difficile: three patients had stool specimens that did not contain toxin, but cultures yielded growth of toxigenic C. difficile on only one occasion. The fourth patient, who had a recent history of hospitalization, particularly aggressive cancer chemotherapy, neutropenia, and antibiotic therapy, excreted both C. difficile and its toxin for at least 1 month. All children were asymptomatic at the time of positive cultures. This preliminary study reveals a low rate of C. difficile colonization in leukemic children on maintenance cancer chemotherapy.     

Severe peripartum acidoses (umbilical artery pH less than or equal to 7.00)--clinical aspects and therapy

Severe neonatal acidosis, defined in this study as a pH of 7,00 or less in the blood of the umbilical artery occurred in 0,4% of 8 992 life born term babies between 1980 and 1981. Analysis of high risk factors during pregnancy showed no difference between acidotic and non acidotic newborns, whereas in all newborns with severe acidosis there were more or less unexpected acute complications during delivery, such as abrutio placenta or cord complications or else. 60% of infants were born by cesarian section or forceps. Resuscitation was performed in an aggressive manner by starting IPPV within one minute post partum, correcting the acidosis and by attempting to stabilize circulation by administration of glucose and human albumin. 6 babies required prolonged ventilatory support over 24 hours. 27 newborns received parenteral solutions of glucose and amino-acids for 6 or more days. Severe acidosis was followed in 8 babies by abnormal neurologic symptoms. In infants with severe acidosis Apgar-score at one minute was not found to be significantly related to subsequent outcome. A NapH of less than or equal to 6,90 and/or Apgar-score of less than or equal to 4 at five minutes, especially in connection with additional risk factors, is an ominous finding.     

Heterogeneity ofClostridium difficile isolates from infants

In order to improve our understanding of the role ofClostridium difficile in infants we characterised the strains isolated from this population. The production of toxin A and toxin B was studied. The toxin A, playing a major role in the disease, was searched for in faecal samples. The serogroup of the isolates was determined because some serogroups have been shown to be more pathogenic than others. Over a 9-month period, 102 faecal samples from 102 hospitalised infants (0–12 months) were analysed and 26% of the children were colonised withC. difficile. Fifteen isolates secreted neither toxin A nor B (62.5%). Nine isolates were toxigenic and secreted both toxins (37.5%). Of the eight toxigenic strains tested, six were from serogroup H and two serogroup K. Of the 13 nontoxigenic strains tested, 8 belonged to serogroup D, 2 to serogroup X, and 1 each to serogroup A, serogroup B and serogroup C. Three infants out of 102 studied had toxin A in their faeces. In summary, the infants can be colonised by (1) nontoxigenic strains, most of them from nonpathogenic serogroup D, without toxin A in the faeces; (2) toxigenic strains of virulent serogroups H and K, with or without toxin A in the faeces. Although some infants had diarrhoea, none needed a specific treatment forC. difficile. No specificC. difficile pathology could be retained and different mechanisms are advanced to explain this absence of pathogenicity.     

CLOSTRIDIUM DIFFICILE TOXIN IN FAECAL SPECIMENS OF HEALTHY CHILDREN AND CHILDREN WITH DIARRHOEA

ABSTRACT. Presence of cytopathogenic effect (CPE) that could be inhibited by an antitoxin to Clostridium sordelli , known to cross-react with Clostridium difficile toxin, was sought in faecal specimens from 101 infants. Of the children, 45 were healthy, while 56 had been hospitalized because of diarrhoea. CPE was found in 12 of the healthy infants and in 5 of those hospitalized. Faecal specimens of these 5 gave a CPE at titres of 10^3-4, whereas in the 12 healthy infants the titres were 10^1-2. Studies on consecutive samples showed that the CPE could persist for between 7-11 weeks up to 9 months and more. Of the 45 healthy infants, 11 harboured C. difficile compared with 6 of the 56 with diarrhoea. In both groups, 3 CPE-positive infants were culture-negative for C. difficile . Four of those hospitalized had recently been given antibiotics; all were negative in both culture and CPE tests. The present study demonstrates that care should be exercised when interpreting the results of cultures for C. difficile and tests for CPE made on faecal specimens in order to establish a diagnosis of antibiotic-associated enterocolitis in infants and children.     

Clostridium difficile and diarrhea in infants in the first half-year of life]

In order to study a possible etiological relationship between Clostridium and diarrhea in children of the first half year of life and to characterize the colonization of the intestine with these bacteria, bacteriological investigations of feces were carried out in neonates and babies aged 1, 4 and 14 days and 1, 3 and 6 months. The development of the children and their health status were monitored under home conditions. It has been established that the colonization of the neonates' intestine with Clostridium including C. Difficile occurs within the early times (since the 4th day of life). Later the colonization with C. difficile becomes wavy in nature. Among 7 types of Clostridium isolated from the intestine of the children, C. difficile occurred most frequently (29.1%). The overwhelming majority of the strains of these bacteria produced toxin whose activity did no exceed 10(-1)-10(-2). The cytopathic effect was mostly demonstrable in 72 hours. No convincing evidence was obtained about the etiological importance of C. difficile in the development of diarrhea in the children placed under observation. It is likely that the latter one was due to the disturbance of intestinal biocenosis, that manifested by profound quantitative disorders (proliferation of the opportunistic aerobic flora, a dramatic reduction of the content of bifido- and lactic acid bacteria up to their complete absence). At the same time a great number of children carrying C. difficile attests to a potential development of specific diarrheas (under hospital conditions and during massive antibacterial therapy).     

Clostridium difficile in neonates: serogrouping and epidemiology

A typing scheme for clostridium difficile based on serogrouping, toxigenicity and sorbitol fermentation was applied to 270 strains isolated in one neonatal ward during a 6-month prospecitive study. Two hundred and twenty-three strains were isolated from 377 faecal samples of 114 neonates and 47 from 92 environmental specimens. The isolates were distributed among five different types; 87% of the faecal and 85% of the environmental isolates belonged to two of these types (toxigenic, sorbitol negative, serogroup F and nontoxigenic, sorbitol positive, serogroup A). Nosocomial spread was clearly demonstrated and the environment appeared to be the main source of contamination: most of the neonates were colonized after admission by strains found in their environment; clusters of colonization with unusual isolates were observed following referral of patients from the intensive care unit or from other hospitals. No relation was found between the acquisition or the carriage of C. difficile and any intestinal symptoms. All the strains belonged to types different from those usually found in cases of antibiotic associated colitis (AAC) suggesting differences of pathogenicity among the different types.Abbreviations PMC pseudomembranous colitis - AAC antibiotic associated colitis - AAD antibiotic associated diarrhoea - TCCFA taurocholate cycloserin cefotaxim fructose agar - ICU intensive care unit - SDS-PAGE sodium dodecyl sulphate-polyacrylamide gel electrophoresis     

Factors influencing the presence of faecal lactobacilli in early infancy.

The faecal flora of 46 preterm infants and 52 born at full term was studied at 10 days of age; 46 born at full term and 37 preterm infants were also studied at 30 days. Viable counts of coliforms, lactobacilli, and bifidobacteria were made; gas liquid chromatography was used to identify the anaerobes. Lactobacilli, but not bifidobacteria, were found in high counts in the stools of most of the infants born at full term by 30 days of age. The mode of delivery, but not the method of feeding, had a significant influence on early colonisation. A selective deficiency of lactobacilli compared with coliform organisms was found in preterm infants. Previous treatment with antibiotics and being nursed in an incubator were also significantly associated with a lower rate of early colonisation with lactobacilli. Our findings indicate that lactobacilli may be an important part of the normal stool flora in early infancy, and that modern methods of neonatal care are associated with delayed or deficient colonisation.     

A prospective study of chlamydial,mycoplasmal, and viral infections in a neonatal intensive care unit.

In a prospective study of non-bacterial infection in a neonatal intensive care unit in north west London, Chlamydia trachomatis infection was identified in 4 of 280 babies (1.4%) and was the most common cause of neonatal ophthalmia. One of the four developed pneumonitis. Ureaplasma urealyticum was found to colonise the nasopharynx in 53 of 235 babies (22.6%), with Mycoplasma hominis present in 6 of 235 babies (2.6%). There was a statistically significant association between U urealyticum colonisation and preterm birth or prolonged rupture of membranes. Colonisation occurred more commonly in babies with apnoea. Viral infection was detected in 16 of 280 babies (5.7%). Rotavirus was identified in 5 of 170 babies (2.9%) and was associated with necrotising enterocolitis in two infants and with bloody diarrhoea in another. Respiratory syncytial virus, which was identified in 4 of 280 babies (1.4%), was not associated with lower respiratory tract infection.     

INFLUENCE OF MATERNAL GUT FLORA AND COLOSTRAL AND CORD SERUM ANTIBODIES ON PRESENCE OF ESCHERICHIA COLI IN FAECES OF THE NEWBORN INFANT

ABSTRACT. From 29 healthy newborn infants and their mothers faecal, serum and milk specimens were obtained on several occasions from one to nine weeks after delivery. Predominant faecal E. coli were serotyped with regard to the O antigen and milk and serum were analysed for their content of E. coli O antibodies by the enzyme-linked immunosorbent assay. In five cases the babies acquired the same O serotype as was found in the stools of their mothers but in 12 out of 29 cases infant and mother never had any dominating faecal E. coli O type in common. There was no apparent correlation between the patterns of feeding and interchange of bacteria. Klebsiella/Enterobacter was the dominating facultative organism on at least one occasion in half the infants. The newborns received coiostral IgA and transplacental circulating IgG antibodies against a great number of E. coli O serotypes. These antibodies did not prevent intestinal colonization, as judged from cultures of faeces.     

Faecal short chain fatty acids in breast-fed and formula-fed babies

Edwards CA, Parrett AM, Balmer SE, Wharton BA. Faecal short chain fatty acids in breast-fed and formula-fed babies. Acta Pædiatr 1994;83:459–62. Stockholm. ISSN 0803–5253
The intestinal flora of breast-fed infants differs from that of formula-fed infants. It is thought that this difference in flora may be one important reason why breast-fed babies suffer less from gastrointestinal disease. Differences in intestinal flora are reflected in the profile of faecal short chain fatty acids (SCFA). Very little is known about faecal concentrations of SCFA in babies fed breast milk or infant formula. In this study, faecal SCFA were measured in babies at two and four weeks of age who had been either exclusively breast fed or bottle fed from birth. There was no significant difference in total faecal SCFA concentrations between breast-fed and formula-fed babies when lactate was included. The formula-fed group, however, had less lactic acid and higher concentrations of propionic and n-buytric acids than breast-fed babies. Very few babies had significant levels of n-butyric acid, although this SCFA is believed to be important for the health of the colonic mucosa of adults.     

One-third of term babies after perinatal hypoxia-ischaemia have transient hearing impairment: dynamic change in hearing threshold during the neonatal period

AIM: To examine the process of change in hearing threshold during the neonatal period after perinatal hypoxia-ischaemia. METHODS: The threshold of brainstem auditory evoked responses (BAER) was measured serially during the first month after birth in 92 term babies who suffered hypoxia-ischaemia. RESULTS: The mean BAER threshold in these babies was significantly increased on day 1 (ANOVA p < 0.001). The elevated threshold decreased progressively on days 3 and 5, but was still significantly higher than that in normal controls (p < 0.01). The elevation continuously decreased more slowly on days 10 and 15, and to a near normal level on day 30. Threshold elevation was seen in 31.7% of the babies on day 1, and 34.5% during the first three days. The rate of elevation decreased progressively thereafter. On day 30, 10.6% of the subjects still had increased thresholds. Moderate to severe elevation occurred mainly during the first week and severe elevation occurred predominately on day 1. Threshold elevation starting after days 3-5 is likely to be due to middle-ear disorders. As a whole, during the first month, 44.6% (41/92) of the babies studied had threshold elevation. BAER threshold was correlated weakly with the stage of hypoxic-ischaemic encephalopathy on days 1 and 3. The threshold was significantly higher in babies with severe encephalopathy than in those with mild or moderate encephalopathy during the first 3 d of life. CONCLUSION: Hearing threshold is elevated in about one-third of term babies after hypoxia-ischaemia. The elevated threshold decreases progressively after birth, and returns to normal by one month in most babies. The threshold correlates weakly with the severity of encephalopathy.     

Minor neurological abnormalities during the first year of life in infants of birth weight <1500g

ABSTRACT. One hundred and ten of 117 infants of birth weight less than 1500g managed at the Mater Mothers' Hospital were followed during the first year of life. A severe behavioural disturbance with minor neurological signs was identified in 12 (13%) babies assessed at 1 month of age. At 4 months, 18 (17%) babies exhibited features suggestive of the dystonic syndrome. The 18 dystonic infants sustained more perinatal asphyxia and apnoea and were more likely to be ventilated, compared with the 89 non-dystonic infants examined at 4 months. The dystonic infants had lower General Quotient scores at all ages. By 8 to 12 months of age, features of the dystonic syndrome had resolved in 13 (72%) of these babies. Five of the infants identified as dystonic at 4 months had major neurological and/or intellectual handicap at 1 year of age. Caution must be exercised when counselling the parents of infants with the dystonic syndrome. The role of intervention programmes of physiotherapy in the dystonic infants and the long term outlook of these babies needs further evaluation.     

Diet and faecal flora in the newborn: lactoferrin.

The faecal flora of breast fed babies differs from that of bottle fed babies. We have shown that the use of a whey predominant formula rather than a casein predominant one induced a faecal flora generally closer to that of breast fed babies but substantial differences remained. The whey proteins of breast milk include much more lactoferrin than is found in cows'' milk. Observations both in animals and in vitro suggest that lactoferrin could be responsible for some of these differences between bottle and breast fed babies. This study was designed to determine the effects on faecal flora of the addition of bovine lactoferrin to the diet of bottle fed babies while holding other qualities of their diet constant. As lactoferrin is an iron binding protein three test formulas were used: (a) no added iron and no added lactoferrin (basic), (b) no iron but added lactoferrin (L), and (c) added iron and lactoferrin (LF). The addition of lactoferrin had little effect upon the faecal microflora and did not move the pattern of the faecal flora in the direction of the breast fed baby. The addition of iron to the formula had more effect on the faecal flora than did lactoferrin. At day 4 it encouraged Escherichia coli and discouraged staphylococcal faecal colonisation. At day 14 the addition of iron to the formula discouraged bifidobacteria. The reasons why bovine lactoferrin was ineffective in vivo in this study are discussed.     

Neonatal pneumonia.

All babies admitted to the neonatal unit during a period of 41 months were prospectively studied to find out the incidence, aetiology, and outcome of neonatal pneumonia, and the value of routine cultures of endotracheal tubes. Pneumonia of early onset (before age 48 hours) occurred in 35 babies (incidence 1.79/1000 live births). In 20 (57%) it was caused by group B streptococci. Blood cultures showed the presence of organisms in 16 of the 35 (46%). There were 41 episodes of pneumonia of late onset in 39 babies. Thirty six of the 39 were preterm, and 34 were artificially ventilated (10% of all ventilated babies). Endotracheal tube colonisation had occurred in 94% of these, most commonly by Gram negative organisms and Staphylococcus epidermidis. In only one of seven cases with simultaneous bacteraemia was the same organism grown from cultures of the blood. After controlling for gestational age and duration of artificial ventilation there was no difference in the incidence or timing of endotracheal tube colonisation between babies who did and did not have pneumonia of late onset. Ten babies with pneumonia of early onset (29%) died; all were preterm infants. Only one death (2%) was associated with an episode of pneumonia of late onset. Routine surveillance cultures were not helpful in predicting and managing pneumonia of late onset.     

Fetal and post-natal diagnosis of major congenital heart disease: implications for medical and psychological care in the current era

Aim: The fetal or post‐natal diagnosis of major congenital cardiac abnormality has important medical and psychological consequences. Methods: We reviewed infants who underwent cardiac surgery in the first year of life at the Heart Centre for Children, The Children's Hospital at Westmead during 2009. The aims of this study were to: (i) examine the key features of cardiac diagnosis and clinical outcome, and (ii) consider how these data can inform priorities for the delivery of clinical services. Results: Over the 12‐month study period, a first cardiac surgical procedure was performed on 195 infants, with 85 infants (44%) diagnosed in the antenatal period. Of the total sample, a subset of 90 babies (46%) underwent their first procedure in the neonatal period, with 62% having had a fetal diagnosis. Major intracardiac lesions including truncus arteriosus (100%), single ventricular lesions (83%), pulmonary atresia with ventricular septal defect (78%) and transposition of the great arteries (53%) were diagnosed prior to birth. Improved haemodynamic stability at initial presentation was found in those with a fetal diagnosis. The overall mortality rate for all patients was 6.1% at 12 months, with a higher mortality in infants with single ventricle. Conclusions: The contemporary paradigm of care for infants with major congenital heart disease requires a multidisciplinary approach to care, with improvements in clinician–clinician and clinician–family communication, and psychological support and education for families. Changes in the allocation of resources are required to meet this model of best practice.     

Diet and faecal flora in the newborn: iron.

The faecal flora of a baby receiving a modern infant formula is substantially different from that of a breast fed baby. This difference is a little less when whey based formulas are used. The addition of bovine lactoferrin has no effect and there is some evidence that the presence of added iron in a formula moved the faecal flora further away from that of a breast fed baby. the iron content of currently used infant formulas is much higher than that of breast milk. The effect of the addition of iron to both whey and casein based formulas on the faecal flora was examined in further detail. Faecal flora were examined at 14 days of age in 33 babies receiving a whey formula fortified with iron, 29 babies receiving a whey formula without iron, 29 babies receiving a casein formula fortified with iron, and 24 babies receiving casein formula without iron. Subsequently fewer babies in each group were examined at week 7, 11, and 15. The addition of iron to both casein and whey formulas discouraged colonisation and growth of staphylococci and bacteroids but encouraged the colonisation and growth of clostridia and enterococci. The type of protein and not the iron content had more effect upon the growth of bifidobacteria; both whey formulas, fortified or not, encouraged the colonisation by bifidobacteria. If an infant formula, for use in the first few months, is to mimic the physiological effects of breast milk, there may be microbiological arguments for not fortifying it with iron. However, large empirical trials would be necessary before advocating such a policy.