Neurodevelopmental outcome in very low birthweight infants with necrotizing enterocolitis requiring surgery

Objective: To assess the effect of necrotizing enterocolitis (NEC) on neurodevelopmental outcome.
Methodology: Neurodevelopmental outcome of 20 very low birthweight (VLBW) infants who developed NEC requiring surgery was compared with 40 matched infants controlled for gestation, birthweight, and year of admission. Twenty-nine VLBW infants who developed NEC and did not require surgery were also compared.
Results: Infants with NEC needing surgery were of 26±2 weeks gestation and weighed 892±192 g at birth. Infants with NEC managed medically were of higher gestation (27±2 weeks) but similar birthweights. More infants with NEC requiring surgery required inotropic support. At follow up, NEC surgery infants had a significantly higher incidence of developmental morbidity, 11 of 20 compared with 11 of 40 matched controls (Fisher's exact test P = 0.0493), and six of 29 infants with NEC managed medically (Fisher's exact test P = 0.0174).
Conclusions: These findings stress the importance for close follow up for neurodevelopmental sequelae in VLBW infants who have had NEC requiring surgery.     

Molecular identification of coliform bacteria from colicky breastfed infants

Objective:  To determine the presence of intestinal coliform bacteria in colicky vs healthy infants.
Study design:  We isolated coliform strains from faeces and performed quantitative bacterial cultures in 41 colicky and 39 healthy breastfed infants, identified using PCR with species-specific primers, strain-specific Automated Ribotyping and the API-50E kit for Enterobacteriaceae to identify the most frequent strains.
Results:  Coliform strains were more abundant in colicky infants (median 6.04 log₁₀ CFU/g faeces, range 2.00–8.76) vs controls (median 4.47 log₁₀ CFU/g faeces, range 1.00–8.08) (p = 0.026). Escherichia coli , Klebsiella pneumoniae , K. oxytoca , Enterobacter cloacae , E. aerogenes and Enterococcus faecalis were the predominant species in colicky and healthy infants. The counts of each bacterial species differed between the two groups, and the difference was significant (p = 0.002) for E. coli : median 6.30 log₁₀ CFU/g faeces (range 3.00–8.74) in colicky infants, and median 4.70 log₁₀ CFU/g faeces (range 2.00–5.85) in controls.
Conclusions:  This is the first study to evaluate the colonization patterns of gas-forming coliforms in colicky infants and healthy controls identified by molecular methods. Coliform bacteria, particularly Escherichia coli, were found to be more abundant in colicky infants. Our data could help to shed light on the cause of infantile colic.     

IGF-I, leptin and active ghrelin levels in very low birth weight infants during the first 8 weeks of life

Aim:  We investigated the relationship between plasma insulin-like growth factor I (IGF-I), leptin, active ghrelin levels, and postnatal growth in very low birth weight (VLBW) infants.
Method:  Plasma IGF-I, leptin, and active ghrelin levels were measured at birth and at 2, 4, 6 and 8 weeks after birth in 61 VLBW infants, including 31 appropriate-for-gestational-age (AGA) and 30 small-for-gestational-age (SGA) infants.
Results:  Insulin-like growth factor I levels were the lowest at birth, but increased gradually over the first 8 weeks of life. IGF-I was positively correlated with body weight, body length and body mass index at all time points. Leptin levels did not change over the study period. Ghrelin levels were significantly lower at birth; however, there were no significant differences between the levels after 2 weeks of age. Leptin and ghrelin levels were not correlated with anthropometrical measures. IGF-I levels at birth were significantly lower in SGA than in AGA infants, but the leptin and ghrelin levels were not significantly different between the two groups.
Conclusion:  Insulin-like growth factor I is related to length and weight gain in the prenatal and the early postnatal periods in VLBW infants, but this does not appear to be the case for leptin and ghrelin.     

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.     

Comparison of neonatal outcome for inborn and outborn very low-birthweight preterm infants

Background:  The aim of the present study was to compare the neonatal outcome of very low-birthweight (VLBW) preterm infants with regard to inborn and outborn status in a medical center of Southern Taiwan, where short-distance neonatal transport is the rule and maternal transport was not well established.
Methods:  This retrospective study included outborn VLBW preterm infants admitted to the neonatal intensive care unit of Chang Gung Memorial Hospital at Kaohsiung after neonatal transport during the period from 1999 through 2003. An equal number of inborn preterm infants matched for gender and birthweight were included as controls. Infants with lethal congenital anomalies or who died in the delivery room were excluded. Data were collected from reviewing medical charts.
Results:  A total of 34 inborn VLBW infants and 34 outborn VLBW infants with neonatal transport were included. Chronic lung disease (CLD) was significantly more frequent in the outborn group according to McNemar test ( P  = 0.0124) and logistic regression. Logistic regression also showed that outborn status ( P  = 0.0173) and birthweight ( P  = 0.0024) were the two most important risk factors for development of CLD.
Conclusion:  Well-trained short distance neonatal transport is useful and valuable for VLBW infants with gestation age of 27–34 weeks in Southern Taiwan. The respiratory outcome, however, was poor in the outborn group in terms of incidence of CLD. To improve the respiratory outcome, further modification of respiratory care during transportation or antenatal maternal transport is crucial.     

Association of <Emphasis Type="Italic">Escherichia</Emphasis><Emphasis Type="Italic">coli</Emphasis> O157:H7 with necrotizing enterocolitis in a full-term infant

Necrotizing enterocolitis (NEC) is the most common gastrointestinal emergency of the neonate. NEC is predominantly seen in premature infants; however, in rare instances it can affect full-term infants as well. Although the pathogenesis of NEC remains elusive, it is well established that bacterial colonization is required for development of this disease. In this report, we present a case of a full-term infant, who developed a very aggressive form of NEC and was found to have Escherichia coli (E. coli) O157:H7 both in stool and blood cultures. Unfortunately, despite aggressive surgical and intensive care management, this infant suffered pan-intestinal necrosis and expired. We were not able to establish the route of transmission. To our knowledge, this is the first report of the association of E. coli O157:H7 with NEC.     

Intestinal Colonization with Enterobacteriaceae in Pakistani and Swedish Hospital-Delivered Infants

ABSTRACT. Rectal cultures from Swedish and Pakistani hospital-delivered newborn infants were analysed regarding the early aquisition of enterobacteria. Swedish infants were delivered vaginally, Pakistani infants were delivered either vaginally or by caesarean section. The Swedish infants were all breast-fed, whereas breastfeeding was incomplete and often started late among the Pakistani infants. Both groups of Pakistani infants were more rapidly colonized with enterobacteria than were the Swedish infants. Cultures from Swedish infants seldom yielded more than one kind of enterobacteria; E. coli and Klebsiefla were most frequently isolated. E. coli dominated in both Pakistani groups, but especially caesarean section delivered infants were in addition often colonized with Proteus, Klebsiella, Enterobacter or Citrobacter species. Breastfeeding from the first day of life reduced colonization with Klebsiella/Enterobacter/Citrobucter. The results suggest that environmental exposure, delivery mode and early feeding habits all influence the early intestinal colonization with enterobacteria.     

Bacterial colonization and gut development in preterm neonates

Necrotizing enterocolitis (NEC) develops in 5-10% of preterm infants in association with enteral feeding and bacterial colonization. It remains unclear how diet and bacteria interact to protect or provoke the immature gastrointestinal tract. Understanding the factors that control bacterial colonization may provide the clue to prevent NEC, and studies in infants must be combined with animal models to understand the mechanisms of the microbiota-epithelium interactions. Analyses of infant fecal samples show that the density and distribution of bacterial species are highly variable with no consistent effects of gestational age, delivery mode, diet or probiotic administration, while low bacterial diversity and bacterial overgrowth are commonly associated with NEC. A series of recent studies in preterm pigs show that the mucosa-associated microbiota is affected by delivery method, prematurity and NEC progression and that diet has limited effects. Overgrowth of specific groups (e.g. Clostridia) appears to be a consequence of NEC, rather than the cause of NEC. Administration of probiotics either decreases or increases NEC sensitivity in preterm pigs, while in preterm infants probiotics have generally decreased NEC incidence and overall mortality. The optimal nature and amount of probiotic bacteria are unknown and host defense factors appear more important for NEC sensitivity than the nature of the gut microbiota. Host defense is improved by feeding the optimal amount of enteral diets, such as mother's colostrum or milk, that help the immature intestinal immune system to respond appropriately to the highly variable bacterial colonization.     

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??Necrotizing enterocolitis??NEC?? is considered to be the most common gastrointestinal emergency among neonates. Although the pathogenesis of NEC is incompletely understood??there are several established risk factors??including prematurity??altered intestinal blood flow/oxygen delivery??formula feeding and bacterial infection. Recently??a large number of studies showed that intestinal flora imbalance had been implicated as key risk factor in the pathogenesis of NEC. After birth??the neonatal gut must acquire a healthy complement of commensal bacteria??which leads to deficient or abnormal microbial colonization of the gut??may protect the immature gut from inflammation and injury. Providing a healthy complement of commensal bacteria can maintain the intestinal microflora balance??shift the balance of intestinal microbiota from a pathegenic to protective complement of bacteria??protect the gut from inflammation and subsequent injury??and prevent NEC. We review the relationship between intestinal microbiota and NEC in preterm infants??the mechanism of probiotics in preventing NEC??and the efficacy and safety of probiotics in preterm infants.     

Age of sitting unsupported and independent walking in very low birth weight preterm infants with normal motor development at 2 years

Aims:  The aims of this study is to (i) determine the age of sitting unsupported and independent walking in preterm infants with birth weight under 1500 g (very low birth weight, VLBW); (ii) estimate differences between VLBW children and a reference population and (iii) estimate the association between clinical characteristics and late age at sitting and walking.
Methods:  A longitudinal study was conducted of a cohort of 876 children with VLBW. The World Health Organization (WHO) motor development study population was used as a reference. Ages for both skills were established by interview with parents. Means were compared with t -test, ANOVA and Bonferroni adjustment where appropriate.
Results:  The inclusion criteria were complied with 694 patients; 50% of VLBW sat at 7 m corrected age (CA) and walked at 13 m CA. Both motor skills were acquired later (7.3 ± 1.5  and 13.6 ± 2.8 m) compared with the control group (6 ± 1.1  and 12.1 ± 1.8 m). Weight or head circumference at birth below the 10th percentile or the presence of bronchopulmonary dysplasia were associated with delayed acquisition of both skills.
Conclusion:  Very low birth weight infants typically sit unsupported and walk later than term infants. Tables describing reference values for milestones acquisition for different categories of infants (gestational age, birth weight and other determinants) may contribute to inform the decision making process on access to available resources.     

SUPPRESSION OF AEROBIC AND ANAEROBIC FAECAL FLORA IN NEWBORNS RECEIVING PARENTERAL GENTAMICIN AND AMPICILLIN

ABSTRACT. The immediate effect of parenteral antibiotic treatment (gentamicin and ampicillin) on the aerobic and anaerobic faecal flora of 14 infants with suspected or proven neonatal septicaemia was studied. Eight infants of similar gestational and postnatal age were studied for comparison. All control infants showed an abundant growth of both aerobic and anaerobic bacteria as early as the first 2 weeks of life. The treated infants generally had lower counts of aerobic and especially of anaerobic bacteria; in 10 of 16 cultures no anaerobes were isolated. In relation to aerobic strains E. coli dominated in untreated infants and Klebsiella pneumoniae in treated ones.     

Bacterial colonization of neonates admitted to an intensive care environment.

In order to elucidate some of the factors responsible for the high rate of nosocomial infection associated with neonatal intensive care, we studied bacterial colonization in 63 infants admitted to a neonatal intensive care unit. In a six-month period, cultures of nose, throat, umbilicus, and stool were obtained on admission and every three days from all infants staying in the NICU greater than or equal to 3 days. Study infants did not develop "normal" aerobic flora. Forty-eight percent of infants grew Escherichia coli from stool, but 52% had stool colonization with Klebsiella, Enterobacter, or Citrobacter, the only other Enterobacteriaceae encountered. KEC were also isolated from throat, nose, and umbilicus in 22%, 22%, and 24% of patients, respectively. The risk of stool colonization with KEC increased with duration of hospitalization: 2% of infants were colonized on admission, 60% after 15 days, and 91% after 30 days. Stool colonization with E. coli seemed to protect infants from colonization with other gram-negative bacilli. Thirteen of 20 infants, however, developed pharyngeal GNB colonization in spite of pre-existing abundant growth of alpha streptococci. Antibiotic therapy for greater than 3 days was associated with the isolation of KEC in stool and GNB in the throat, but birth weight less than 2,500 gm and lack of breast milk feedings were not.     

Human torovirus: a new virus associated with neonatal necrotizing enterocolitis

AIM: Toroviruses have been associated with gastroenteritis in both animals and humans. The aim of this study was to examine the fecal excretion of torovirus in infants with necrotizing enterocolitis (NEC). METHODS: We reviewed all infants with NEC admitted to our tertiary care NICU over a 5-y period who had stool specimens sent for microbial culture and virology. Infants in the NICU during the same period with diagnoses other than NEC served as controls. RESULTS: Forty-four infants with NEC stages I-III were identified, and pathogenic organisms were identified in 27 (61%). Toroviruses were identified in stool cultures in 48% of patients with NEC, and 17% of the non-NEC controls (p<0.001). There was no significant difference in illness severity or mortality between the torovirus-positive and -negative infants with NEC. CONCLUSION: Torovirus should be added to the list of infectious agents associated with NEC in newborn infants. The exact role torovirus plays in the etiology and progression of NEC warrants further investigation.     

Early administration of Bifidobacterium breve to preterm infants: randomised controlled trial

AIM—To investigate the colonisation with Bifidobacterium breve of the bowels of very low birthweight (VLBW) infants.METHODS—The adverse effects of B breve were examined in 66 VLBW infants (preliminary study). A prospective randomised clinical study of 91 VLBW infants was also completed and these infants were followed up for three years. Precise viable bacterial counts of serial stool specimens were examined for the first eight weeks after birth in 10 infants. The colonisation rates of administered bacteria were examined using immunohistochemical staining of stool specimens with a B breve specific monoclonal antibody.RESULTS—In the preliminary study there were no side effects attributable to the bacteria. Immunohistochemical staining of stool specimens showed that the colonisation rates of the administered bacteria were 73% at 2 weeks of age, but only 12% in the control group. Early administration of B breve significantly decreased aspirated air volume from the stomach and improved weight gain.CONCLUSIONS—B breve can colonise the immature bowel very effectively and is associated with fewer abnormal abdominal signs and better weight gain in VLBW infants, probably as a result of stabilisation of their intestinal flora and accelerated feeding schedules.     

Necrotizing enterocolitis after red blood cell transfusion in preterm infants with patent ductus arteriosus: a case series

Aim: Both patent ductus arteriosus (PDA) and packed red blood cell (PRBC) transfusion are risk factors for necrotizing enterocolitis (NEC). The combination of PDA and PRBC transfusion may have a synergistic effect on the intestinal circulation. Methods: We present four cases of NEC in very low birth weight (VLBW) infants within 14 h after PRBC transfusion. Results: All infants were growing on full enteral feeding, and they all had a PDA. Conclusion: We are concerned that the simultaneous presence of a PDA and PRBC transfusion in VLBW infants may place the infant at even greater risk of NEC than each of these factors alone.     

Early enteral feeding in very low birth weight infants

Background/aim

Debate exists about when to initiate enteral feeding (EF) in very low birth weight (VLBW) preterm infants. This retrospective study compared the effectiveness of an education-based quality improvement project and the relationship of time of the first EF to necrotizing enterocolitis (NEC) or death incidence and parenteral nutrition (PN) days in VLBW infants.

Study design/subjects

VLBW infants born in 2 epochs were compared for hour of the first feed, PN days, NEC or death incidence, and feeding type. The 2 epochs were temporally divided by a quality improvement initiative to standardize initiation of EF in postnatal hours 6–24.

Results

603 VLBW infants were included. Median time of feed initiation decreased from 33 (Epoch 1) to 14 h (Epoch 2) (p < 0.0001). Median PN days were 14 vs. 12, respectively (p = 0.07). The incidence of NEC or death was 13.4% vs. 9.5%, respectively (p = 0.14). When controlling for birth weight, gestational age, race, gender, and time period, earlier feed initiation was associated with decreased NEC or death (p = 0.003). Evaluation of the relationship of early EF (defined as within the first 24 h) in Epoch 2 alone showed that early EF was significantly associated with decreased NEC or death (6.3 vs 15.1%) (RR, 95% CI = 0.28, 0.13–0.58) and less PN days (p < 0.0001).

Conclusions

In a VLBW infant cohort, an education-based process improvement initiative decreased time of EF initiation to a median of 14 h with no associated increase in NEC or death. In fact, results suggest that earlier feeding is associated with decreased NEC or death.     

Personality of young adults born prematurely: the Helsinki study of very low birth weight adults

Background:  Today, the first generations of very low birth weight (VLBW ≤ 1500 g) infants are entering adulthood but very little is known of their personality traits, associated with both psychopathological vulnerability and resilience.
Methods:  In this cohort study we compared personality traits among young adults (age range 18 to 27 years, mean 21.4, SD 2.19) with VLBW ( n  = 158) with those of term-born controls ( n  = 168) of same gender, age, and maternity hospital. The participants completed the Neo-Personality Inventory.
Results:  Of the five main traits, the VLBW participants scored significantly higher in conscientiousness (MD .1, 95% CI .0 to .3; p  < .03), agreeableness (MD .2, 95% CI .0 to .3; p  < .001), and lower in openness to experience (MD –.1, 95% CI –.2 to .0; p  < .02). In addition, the VLBW group differed from the controls with regard to facets of neuroticism (lower hostility and impulsivity, p s < .05) and extraversion (less assertiveness p  < .01). Furthermore, there were fewer undercontrolled personality profiles among the VLBW subjects ( p  < .01). All differences were independent of gender, age at assessment, parental education, individual school grade average, and maternal pre-eclampsia and smoking during pregnancy.
Conclusions:  Young adults born with VLBW showed markedly different personality traits compared with their controls. The VLBW group displayed less negative emotions, were more dutiful and cautious, and displayed more warmth in their social relationships than their term-born peers. We present two potential mechanisms underlying these findings. The first relates to parental influences and the other to evidence linking biological mechanisms associated with prematurity with personality characteristics in adulthood.     

Necrotising enterocolitis in the very low birthweight infant: expressed breast milk feeding compared with parenteral feeding.

The incidence of necrotising enterocolitis (NEC) in very low birthweight infants (VLBW less than or equal to 1500 g) was reduced by the delayed onset of enteral feeding. Eight (18%) out of 44 VLBW infants who were in hospital during the first year of the study developed NEC. During the next 12 months 85 similar infants were initially fed by parenteral nutrition only, and then from age 14-21 days with infant formula. During the second year only 3 (3%) patients developed NEC. There were no other relevant changes in management. Throughout the entire study, the onset of NEC in each infant in whom it occurred was after the start of enteral feeding. We recommend avoiding enteral feeding in VLBW infants during the period that they are particularly vulnerable--namely the first 2 or 3 weeks of life.     

Frühzeitige enterale Ernährung bei sehr kleinen Frühgeborenen ist nicht mit nekrotisierender Enterokolitis assoziiert

Objective is to examine the evidence from randomized and quasi-randomized clinical trials regarding the effect of early enteral feeding advancement in very low birth weight infants (<1500 g) on the incidence of necrotizing enterocolitis (NEC). Searches were performed from Medline, as well as studies identified from abstracts, conference proceedings and references from relevant publications were retrieved. There was no evidence of an effect of early enteral feeding on the NEC incidence in VLBW infants on full parenteral nutrition. Among infants randomized to more rapid rates of early enteral feeding advancement again there was no effect on NEC. Small sample sizes, methodological limitations, different birth weight ranges, and different rates of early enteral feeding advancement do not allow to recommend one best feeding protocol for VLBW infants. There are suggested advantages of more rapid early enteral feeding advancement (overall reduction in days to achieve full enteral feeding and days to regain birth weight), however, the information regarding safety is limited (broad confidence intervals for the incidence of NEC).     

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.