The effect of enteral supplementation of specific neutral and acidic oligosaccharides on the faecal microbiota and intestinal microenvironment in preterm infants.

We aimed to determine the effects of enteral supplementation of a prebiotic mixture of neutral and acidic oligosaccharides (scGOS/lcFOS/pAOS) on the faecal microbiota and microenvironment in preterm infants. Furthermore, we determined the influence of perinatal factors on the development of the faecal microbiota. In a randomised controlled trial, preterm infants with gestational age <32 weeks and/or birth weight <1,500 g received enteral supplementation of scGOS/lcFOS/pAOS or placebo (maltodextrin) between days 3 and 30 of life. Faecal microbiota, as measured with fluorescent in situ hybridisation (FISH), and microenvironment [short-chain fatty acids (SCFAs), pH, sIgA] were measured at four time points: before the start of the study and at days 7, 14 and 30 of life. In total, 113 preterm infants were included. Enteral supplementation of the prebiotic mixture increased the total bacteria count at day 14 (Exp 3.92; 95 % confidence interval [CI] 1.18-13.04, p = 0.03), but not at day 30 (Exp 1.73; 95 % CI 0.60-5.03, p = 0.31). There was a trend toward increased bifidobacteria counts. There was a delayed intestinal colonisation of all bacteria. Enteral supplementation of the prebiotic mixture decreased the faecal pH (Exp 0.71; 95 % CI 0.54-0.93, p = 0.01) and there was a trend toward increased acetic acid compared to the placebo group (Exp 1.09; 95 % CI 0.99-1.20, p = 0.10). There was no effect on sIgA (Exp 1.94; 95 % CI 0.28-13.27, p = 0.50). Antibiotics decreased the total bacteria count (Exp 0.13; 95 % CI 0.08-0.22, p < 0.001). Enteral supplementation of a prebiotic mixture of neutral and acidic oligosaccharides increases the postnatal intestinal colonisation. However, the extensive use of broad-spectrum antibiotics in preterm infants decreased the growth of all intestinal microbiota, thereby, delaying the normal microbiota development.

Intestinal microbiota in allergic and nonallergic 1-year-old very low birth weight infants after neonatal glutamine supplementation.

AIM: Previously, glutamine-enriched enteral nutrition in very low birth weight infants (VLBW) decreased the incidence of atopic dermatitis at age 1 year. The aim of this study was to determine whether this effect is related to changes in intestinal bacterial species that are associated with allergy, such as bifidobacteria, clostridium histolyticum, clostridium lituseburense (Chis/lit group) and Escherichia coli at age 1 year. METHODS: Eighty-nine infants were eligible for this follow-up study, conducted at a Tertiary care hospital. Bifidobacteria, Chis/lit group and E. coli were measured by fluorescent in situ hybridization in faecal samples collected at age 1 year. Information on allergic and infectious diseases was previously determined by questionnaire. RESULTS: Seventy-two of 89 (81%) infants were participated. Prevalence of all studied species was not different between glutamine-supplemented and control groups. Allergic infants were less frequently colonized with bifidobacteria than nonallergic infants (p =0.04). Between neonatal period and 1 year, prevalence of bifidobacteria was increased (p < 0.001), of Chis/lit group was unchanged (p=0.84), and of E. coli was decreased (p < 0.001). CONCLUSION: The beneficial effect of glutamine-enriched enteral nutrition on the incidence of atopic dermatitis in the first year of life in VLBW infants is not related to changes in bifidobacteria, Chis/lit group or E. coli. Allergic VLBW infants are less frequently colonized with bifidobacteria compared to nonallergic VLBW infants.

Incidents and errors in neonatal intensive care: a review of the literature.

OBJECTIVES: To examine the characteristics of incident reporting systems in neonatal intensive care units (NICUs) in relation to type, aetiology, outcome and preventability of incidents. METHODS: Systematic review. SEARCH STRATEGY: Medline, Embase, Cochrane Library. Included: relevant systematic reviews, randomised controlled trials, observational studies and qualitative research. Excluded: non-systematic reviews, expert opinions, case reports and letters. PARTICIPANTS: hospital units supplying neonatal intensive care. INTERVENTION: none. OUTCOME: characteristics of incident reporting systems; type, aetiology, outcome and preventability of incidents. RESULTS: No relevant systematic reviews or randomised controlled trials were found. Eight prospective and two retrospective studies were included. Overall, medication incidents were most frequently reported. Available data in the NICU showed that the total error rate was much higher in studies using voluntary reporting than in a study using mandatory reporting. Multi-institutional reporting identified rare but important errors. A substantial number of incidents were potentially harmful. When a system approach was used, many contributing factors were identified. Information about the impact of system changes on patient safety was scarce. CONCLUSIONS: Multi-institutional, voluntary, non-punitive, system based incident reporting is likely to generate valuable information on type, aetiology, outcome and preventability of incidents in the NICU. However, the beneficial effects of incident reporting systems and consecutive system changes on patient safety are difficult to assess from the available evidence and therefore remain to be investigated.

Nosocomial infections in a Dutch neonatal intensive care unit: surveillance study with definitions for infection specifically adapted for neonates.

The incidence of nosocomial infection in neonatal intensive care units (NICUs) is high compared with other wards. However, no definitions for hospital-acquired infection are available for NICUs. The aim of this study was to measure the incidence of such infections and to identify risk factors in the NICU of the VU University Medical Center, which serves as a level III regional NICU. For this purpose, a prospective surveillance was performed in 1998-2000. We designed definitions by adjusting the current definitions of the Centers for Disease Control and Prevention (CDC) for children <1 year of age. Birth weight was stratified into four categories and other baseline risk factors were dichotomized. Analysis of risk factors was performed by Cox regression with time-dependent variables. The relationship between the Clinical Risk Index for Babies (CRIB) and nosocomial infection was investigated. Furthermore, for a random sample of cases, we determined whether bloodstream infection and pneumonia would also have been identified with the CDC definitions. Seven hundred and forty-two neonates were included in the study. One hundred and ninety-one neonates developed 264 infections. Bloodstream infection (N=138, 14.9/1000 patient-days) and pneumonia (N=69, 7.5/1000 patient-days) were the most common infections. Of bloodstream infections, 59% were caused by coagulase-negative staphylococci; in 21% of neonates, blood cultures remained negative. In 25% of pneumonias, Enterobacteriaceae were the causative micro-organisms; 26% of cultures remained negative. Compared with the Nosocomial Infections Surveillance System (NNIS) of the CDC, our device utilization ratios and device-associated nosocomial infection rates were high. The main risk factors for bloodstream infection were birth weight [hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.45-2.17] and parenteral feeding with hospital-pharmacy-produced, all-in-one mixture 'Minimix' (HR 3.69, 95%CI 2.03-6.69); administration of intravenous antibiotics (HR 0.39, 95%CI 0.26-0.56) was a protective risk factor. The main risk factors for pneumonia were low birth weight (HR 1.37, 95%CI 1.01-1.85) and mechanical ventilation (HR 9.69, 95%CI 4.60-20.4); intravenous antibiotics were protective (HR 0.37, 95%CI 0.21-0.64). In a subcohort of 232 very-low-birthweight neonates, the CRIB was not predictive for infection. With the CDC criteria, only 75% (21/28) of bloodstream infections and 87.5% of pneumonias (21/24) would have been identified. In conclusion, our local nosocomial infection rates are high compared with those of NICUs participating in the NNIS. This can be partially explained by: (1) the use of our definitions for nosocomial infection, which are more suitable for this patient category; and (2) the high device utilization ratios.

[Restrictive dermopathy: a rare, lethal genodermatosis]. / Restrictieve dermopathie: een zeldzame, letale genodermatose.

In a premature male infant born of consanguineous parents, restrictive dermopathy was diagnosed. This is a rarely described, lethal, congenital skin disease. The diagnosis was based on the clinical and histopathological findings: a fixed facial expression (so-called 'porcelain face') with palpebral fissures inclined laterally downwards, microstomia with the mouth in the 'O'-position, micrognathia and low-set ears inclined toward the rear, prominent blood vessels in the skin and contracture of all the joints; histopathological examination of a skin biopsy revealed a smooth epidermis and a relatively thin dermis with an abnormal structure of the dermal connective tissue in which the collagen fibres were arranged more or less horizontally, parallel to the epidermis, and the number of elastin fibres was sharply decreased. Various adnexal structures were present but the hair follicles had an abortive appearance. Thanks in part to the finding of a homozygous mutation in the so-called ZMPSTE24-gene, it could be concluded that restrictive dermopathy is probably an autosomal recessive laminopathy, related to progeria. Increasing the clinical awareness of this disease may contribute to reducing the presumed under-reporting, so that future research will become possible.

Prevention of hepatitis B infection in newborns through mass screening and delayed vaccination of all infants of mothers with hepatitis B surface antigen.

Beginning in 1982 all pregnant women undergoing prenatal routine blood analysis in three large city hospitals and one large rural area were tested for hepatitis B surface antigen (HBsAg). Infants of all HBsAg-positive mothers received hepatitis B immunoglobulin (HBIg), 0.5 mL/kg of body weight within two hours of birth and, after randomization, 10 micrograms of hepatitis B vaccine either at 0, 1, 2, and 11 months of age (schedule A) or at 3, 4, 5, and 11 months of age (schedule B). A second injection of HBIg (1 mL) was given to infants on schedule B at 3 months of age. Blood samples were obtained at 3, 6, 11, 12, 24, and 36 months. In a two-year period, 28,412 pregnant women were tested for HBsAg; screening efficiency varied between 85% and 98%. The overall prevalence of HBsAg was 0.8%, with a marked variation between urban centers (2.2%) and the rural area (0.3%). Vaccinations were received by 180 of 193 infants of HBsAg-positive mothers (90 on schedule A and 90 on schedule B). Concentrations of hepatitis B surface antibody less than 10 IU/L were observed in nine instances in five children from group A and in seven instances in six children from group B. Four hepatitis B viral infections (two HBsAg carriers, two who underwent antihepatitis B core seroconversions) were recorded in group A v one infection (antihepatitis B core seroconversion) in group B. The protective efficacy of the program (screening plus passive immunization and delayed vaccination) was 94%. The estimated cost of preventing one cae of hepatitis B infection in neonates was $3,000 (US currency).(ABSTRACT TRUNCATED AT 250 WORDS)

Fatal case of influenza B virus pneumonia in a preterm neonate.

Influenza B infection typically has low mortality. A 1,020-g neonate had a septic clinical picture and pneumonia. Influenza B virus was isolated from nasopharyngeal and tracheal aspirates. The infant died.

Visual field and grating acuity development in low-risk preterm infants during the first 2 1/2 years after term.

The effect of early visual experience on visual field size and grating acuity development was studied longitudinally in 36 appropriate for gestational age (AGA) and 26 small for gestational age (SGA) low-risk preterm infants. These were selected out of 194 very low birth weight (VLBW) infants (birthweight less than 1500 g) born in 1985 and 1986. Criteria for inclusion as low-risk were the absence of neurological, respiratory, circulatory and alimentary problems in the neonatal period; no retinopathy of prematurity and no evidence of abnormality on the neonatal cranial ultrasound scans. Binocular field sizes were assessed using kinetic arc perimetry. Binocular grating acuity was tested by means of the prototype version of the acuity card procedure. Results were compared with norms obtained in control fullterms in earlier studies. Infants were tested at 6 weeks, 6, 6, 9 and 12 months of age from the expected term date. Twenty-two of these infants were retested at 2 1/2 years of corrected age. Visual field size and visual acuity estimates of (both AGA and SGA) low-risk, VLBW preterms and control fullterms overlapped at all test ages, except for a slight but significantly faster development of the upper and the lower visual field at 6 weeks corrected age in the preterm group. These results indicate that for clinical purposes visual experience before the expected term date has not only no measurable effect on the normal development of behavioural acuity, but also no accelerating effect on the development of peripheral vision.

Preferential looking acuity in preterm infants.

Acuity was measured in 48 prematurely born infants using the preferential looking technique. These quantitative results show that acuity development in these infants is related to conceptional rather than postnatal age, in agreement with the qualitative findings of previous studies. Severe intraventricular haemorrhage was accompanied by low visual acuity in two infants.

Intestinal permeability in relation to birth weight and gestational and postnatal age.

OBJECTIVE: To determine the relation between intestinal permeability and birth weight, gestational age, postnatal age, and perinatal risk factors in neonates. STUDY DESIGN: Intestinal permeability was measured by the sugar absorption test within two days of birth and three to six days later in preterm and healthy term infants. In the sugar absorption test, the urinary lactulose/mannitol ratio is measured after oral ingestion of a solution (375 mosm) of lactulose and mannitol. RESULTS: A first sugar absorption test was performed in 116 preterm (26-36 weeks gestation) and 16 term infants. A second test was performed in 102 preterm and nine term infants. In the preterm infants, the lactulose/mannitol ratio was not related to gestational age (r = -0.09, p = 0.32) or birth weight (r = 0.07, p = 0.43). The median lactulose/mannitol ratio was higher if measured less than two days after birth than when measured three to six days later (0.427 and 0.182 respectively, p<0.001). The lactulose/mannitol ratio was higher in preterm infants than term infants if measured within the first 2 days of life (0.404 and 0.170 respectively, p < 0.001), but not different three to six days later (0.182 and 0.123 respectively, p = 0.08). In multiple regression analysis of perinatal risk factors, only umbilical arterial pH correlated with the lactulose/mannitol ratio in preterm infants less than 2 days of age (T = -1.98, p = 0.05). CONCLUSIONS: In preterm infants (26-36 weeks gestation), intestinal permeability is not related to gestational age or birth weight but is higher during the first 2 days of life than three to six days later. It is higher in preterm infants than in healthy term infants only if measured within two days of birth. This suggests rapid postnatal adaptation of the small intestine in preterm infants.

Minimal enteral feeding, fetal blood flow pulsatility, and postnatal intestinal permeability in preterm infants with intrauterine growth retardation.

OBJECTIVE: To study the effect of minimal enteral feeding (MEF) on intestinal permeability and feeding tolerance in preterm infants with intrauterine growth retardation (gestational age < 37 weeks, birth weight for gestational age p < 10). Furthermore, to determine whether fetal blood flow pulsatility or intestinal permeability predict feeding tolerance in these infants. DESIGN: Randomised controlled trial. METHODS: Within 48 hours of birth, infants were randomised to MEF or no enteral feeding (NEF) for five days in addition to parenteral feeding. Intestinal permeability was measured by the sugar absorption test before (SAT1) and after (SAT2) the study. The sugar absorption test measured the urinary lactulose/mannitol (LM) ratio after oral ingestion of a solution (375 mosm) containing mannitol and lactulose. Charts of all infants were assessed for measures of feeding tolerance. Fetal blood flow pulsatility index (U/C ratio) was measured within the seven days before birth. RESULTS: Of the 56 infants enrolled, 42 completed the study: 20 received MEF and 22 NEF. The decrease in LM ratio (LM ratio 1 - LM ratio 2) was not significantly different between the two groups (0.25 v 0.11; p = 0.14). Feeding tolerance, growth, and incidence of necrotising enterocolitis were not significantly different between the two groups. Neither the U/C nor the LM ratio 1 predicted feeding tolerance. CONCLUSIONS: The results suggest that MEF of preterm infants with intrauterine growth retardation has no effect on the decrease in intestinal permeability after birth. Neither fetal blood flow pulsatility nor intestinal permeability predicts feeding tolerance.

Neonatal cerebral ultrasound, neonatal neurology and perinatal conditions as predictors of neurodevelopmental outcome in very low birthweight infants.

To determine the assessments before discharge from the intensive care unit, that will predict outcome most accurately, a prospective longitudinal study in a cohort of 79 high risk VLBW children was conducted from birth to 3.6 years of age. Birthweight, gestational age, obstetrical and neonatal optimality, neonatal neurological examinations and neonatal cerebral ultrasound were studied in relation to outcome. The best predictor for outcome was a simple cerebral ultrasound classification according to the presence or absence of ventriculomegaly and intraparenchymal damage of any cause. Infants with normal neonatal cerebral scans or abnormal scans without ventriculomegaly almost invariably had a normal neurological outcome. In infants with cerebral lesions with ventriculomegaly the incidence of normal neurological outcome decreased to less than 50%. Intraparenchymal damage was associated with cerebral palsy as well as other (mental and sensori) handicaps in over 85% of the cases. Neonatal neurological examinations at preterm age had additional value in predicting neurological outcome especially in the group with ventriculomegaly. Neither birthweight, nor gestational age, obstetrical or neonatal optimality were independent variables in the prediction of outcome in high risk VLBW children at 3.6 years of age.

Effects of very low birth weight (VLBW) on visual development during the first year after term.

Behavioural visual functions were assessed in 155 very low birth weight (VLBW) infants during the first 12 months after expected term. Visual development was examined (mainly cross-sectionally) at 6 weeks, 3, 6, 9, and 12 months of corrected age by assessment of visual acuity, visual fields, optokinetic nystagmus and visual threat response. Many VLBW infants showed visual impairments (54.2%). No single visual function appeared to be specifically susceptible to impairments, deficits were often apparent across a range of functions. Visual impairments were observed at all test ages, and could already be assessed at 6 weeks of corrected age. The highest incidence of visual impairments was scored at 6 months corrected age. Beyond 6 months, less deficits were observed, suggesting in many infants a delayed rather than a permanently impaired visual development. In some infants deficits became evident at a later stage, after an apparently normal initial development. The results suggest that VLBW infants are at risk for impaired visual development.

Effects of perinatal hypoxia on visual development during the first year of (corrected) age.

Visual development was assessed in 124 infants (112 preterms and 12 fullterms) who had suffered from perinatal hypoxia and in 55 control preterm infants during the first year of corrected age. Using behavioural techniques, visual functions were tested during follow-up visits in the Sophia Children's Hospital. Corrected ages at testing ranged from 3 months to 1 year. During this period, infants with perinatal hypoxia showed more abnormalities in visual functions than preterm control infants. Gestational age at birth did not influence the outcome of visual development after perinatal hypoxia. Most visual impairments were demonstrated at 3 and 6 months of age. All infants with severe neuro-developmental handicaps showed visual deficits, although neuro-developmental abnormalities and visual deficits could be present as isolated phenomena. Ultrasound abnormalities related well with visual dysfunctions. Prospective studies of infants with visual deficits and a history of perinatal hypoxia are indicated.

Immune response to hepatitis B vaccine in pregnant women receiving post-exposure prophylaxis.

Hepatitis B immunoglobulin and vaccine were given as post-exposure prophylaxis to 73 women after an outbreak of hepatitis B due to in vitro fertilization treatment. The immunization schedule consisted of 5 ml of hepatitis B immunoglobulin (125 IU/ml) at months 0 and 1 and recombinant hepatitis B vaccine (10 micrograms of HBvaxDNA) at months 0, 1, 2 and 6. The safety and immunogenicity of hepatitis B vaccine were studied in 16 women who became pregnant after in vitro fertilization; 57 non-pregnant women receiving the same treatment served as controls. Blood samples were drawn at 0, 1, 2, 6 and 7 months. One patient had a clinical abortion 2 days after initial immunization; other side effects of vaccination were not found in vaccinees or in their offspring. All vaccinees exhibited antibodies against hepatitis B surface antigen after vaccination but relatively low peak geometric mean titers of 258 IU/l and 684 IU/l were attained in pregnant and non-pregnant women, respectively. There were no significant differences in seroconversion rates and geometric mean titers between the two groups although the immune response to hepatitis B vaccine was slower and lower in pregnant women at all times. Our results suggest that when post-exposure prophylaxis for hepatitis B infection is indicated, passive active immunization can be started safely during pregnancy. The relative weak response to the vaccine calls for monitoring of the anti-HBs 1 month after the initial series of vaccinations.

Neonatal respiratory morbidity following elective caesarean section in term infants. A 5-year retrospective study and a review of the literature.

Respiratory morbidity is an important complication of elective caesarean section. The presence of labour preceding caesarean section reduces the risk of neonatal respiratory morbidity. Recently, it has been shown that the incidence of respiratory morbidity is lower in infants with a gestational age of at least 39(+0) weeks at elective caesarean section compared to infants with a gestational age less than 39(+0) weeks.This article describes the results of a 5-year retrospective study on the incidence of respiratory distress in term neonates delivered by elective caesarean section in relation to gestational age and provides a literature review on neonatal respiratory morbidity following elective caesarean section.

Pulse oximetry and transcutaneous oxygen tension in hypoxemic neonates and infants with bronchopulmonary dysplasia.

The reliability of pulse oximetry and transcutaneous oxygen tension (tcPO2) was investigated in hypoxemic neonates and older infants with chronic hypoxemia due to bronchopulmonary dysplasia (BPD). It was found that during severe hypoxemia (tcPO2 less than 40 mmHg and saturation less than 80%) pulse oximetry showed a better correlation with arterial saturation than tcPO2 with arterial oxygen tension. During mild hypoxemia and normoxemia (tcPO2 40-90 mmHg and saturation 80-95%) tcPO2 and pulse oximetry both showed a good correlation with arterial values. Above 95% saturation and a corresponding tcPO2 of 70-120 mmHg, the correlation between arterial and transcutaneous PO2 was better than that between pulse oximetric and arterial saturation. Computer recording and analysis of tcPO2 and pulse oximetry improves the quality of both noninvasive oxygenation parameters in older infants with BPD.

Multichannel recording and analysis of physiological data using a personal computer.

A flexible data acquisition system was designed for an Apple IIe computer. For implementation, we used a microcomputer capable of recording 4 channels simultaneously with a selectable sample rate; this information was saved on a floppy disc and the recordings could be evaluated later. This evaluation is accomplished by reproducing the analog signals on display and calculating a histogram after deleting artefacts in the signal.

Neonatal transport by helicopter in The Netherlands: a 7-year overview.

In the Netherlands, neonatal intensive care is provided in 10 neonatal intensive care centres. Although antenatal transport is preferred, each year more than 1000 newborns are transported to the centres, in the majority of cases by ambulance. Transport by helicopter became available in 1987. From June 1987 till December 1993, 583 infants were transported by helicopter (median gestational age 32 weeks, range 24-43). Forty-four per cent had a gestational age of less than 32 weeks. Four hundred and forty-six infants were mechanically ventilated. No baby died in transfer. After admission, 101 infants died (18.4%). There were no accidents during transport Ten per cent of the requested flights was cancelled because of weather conditions. The mean transport time of the babies was 36 min (range 10-145), and the mean transport time of the transport teams was 128 min (range 20-345). The transports carried out from 1987 to 1989 were recalculated with regard to duration and cost, assuming they were carried out by ambulance instead of by helicopter: for the babies, the mean transport time by helicopter was 75% less than the calculated mean transport time by ambulance. However, the financial costs per transport were on average Dutch florins (DFL) 3000 higher by helicopter than by ambulance. In the Netherlands, the use of a helicopter for neonatal transport reduces the transport time, but doubles the costs.

[A study of the sequelae of perinatal hypoxia and convulsions in full-term newborn infants]. / Onderzoek naar de gevolgen van perinatale hypoxie en convulsies bij voldragen pasgeborenen.

Perinatal hypoxia may result in neuromotor handicaps. The occurrence of convulsions after perinatal hypoxia is regarded as a bad prognostic sign. Thirty-two full-term babies with perinatal hypoxia were studied retrospectively. Post-hypoxic convulsions were seen in 20 newborns. In 26 out of 29 survivors follow-up assessments were made between 2 months and 2 years of age. Severe neuromotor abnormalities were demonstrated in 10 out of 19 patients with post-hypoxic convulsions, whereas no abnormalities were found in 7 patients without convulsions (p = 0.016, Fisher exact test). Although post-hypoxic convulsions are a bad prognostic sign, a number of infants with convulsions appear to develop normally. Further research on prognostic factors concerning neurodevelopment after perinatal hypoxia and convulsions appears indicated.