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.

Feasibility and reliability of PRISMA-medical for specialty-based incident analysis.

AIMS AND OBJECTIVES: In this study, the feasibility and reliability of the Prevention Recovery Information System for Monitoring and Analysis (PRISMA)-Medical method for systematic, specialty-based analysis and classification of incidents in the neonatal intensive care unit (NICU) were determined. METHODS: After the introduction of a Neonatology System for Analysis and Feedback on Medical Events (NEOSAFE) in eight tertiary care NICUs and one paediatric surgical ICU, PRISMA-Medical was started to be used to identify root causes of voluntary reported incidents by multidisciplinary unit patient safety committees. Committee members were PRISMA-trained and familiar with the department and its processes. In this study, the results of PRISMA-analysis of incidents reported during the first year are described. At t = 3 months and t = 12 months after introduction, test cases were performed to measure agreement at three levels of root cause classification using PRISMA-Medical. Inter-rater reliability was determined by calculating generalised kappa values for each level of classification. RESULTS: During the study period, 981 out of 1786 eligible incidents (55%) were analysed for underlying root causes. In total, 2313 root causes were identified and classified, giving an average of 2.4 root causes for every incident. Although substantial agreement (kappa 0.70-0.81) was reached at the main level of root cause classification of the test cases (discrimination between technical, organisational and human failure) and agreement among the committees at the second level (discrimination between skill-based, rule-based and knowledge-based errors) was acceptable (kappa 0.53-0.59), discrimination between rule-based errors (the third level of classification) was more difficult to assess (kappa 0.40-0.47). CONCLUSION: With some restraints, PRISMA-Medical proves to be both feasible and acceptably reliable to identify and classify multiple causes of medical events in the NICU.

Specialty-based, voluntary incident reporting in neonatal intensive care: description of 4846 incident reports.

OBJECTIVES: To examine the characteristics of incidents reported after introduction of a voluntary, non-punitive incident reporting system for neonatal intensive care units (NICUs) in the Netherlands; and to investigate which types of reported incident pose the highest risk to patients in the NICU. DESIGN: Prospective multicentre survey. METHODS: Voluntary, non-punitive incident reporting was introduced in eight level III NICUs and one paediatric surgical ICU. An incident was defined as any unintended event which (could have) reduced the safety margin for the patient. Multidisciplinary, unit-based patient safety committees systematically collected and analysed incident reports, and assigned risk scores to each reported incident. Data were centrally collected for specialty-based analysis. This paper describes the characteristics of incidents reported during the first year. Bivariate logistic regression analysis was conducted to identify high-risk incident categories. RESULTS: There were 5225 incident reports on 3859 admissions, of which 4846 were eligible for analysis. Incidents with medication were most frequently reported (27%), followed by laboratory (10%) and enteral nutrition (8%). Severe harm was described in seven incident reports, and moderate harm in 63 incident reports. Incidents involving mechanical ventilation and blood products were most likely to be assigned high-risk scores, followed by those involving parenteral nutrition, intravascular lines and medication dosing errors. CONCLUSIONS: Incidents occur much more frequently in Dutch NICUs than has been previously observed, and their impact on patient morbidity is considerable. Reported incidents concerning mechanical ventilation, blood products, intravascular lines, parenteral nutrition and medication dosing errors pose the highest risk to patients in the NICU.

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.

Transient postnatal heart failure caused by noncompaction of the right ventricular myocardium.

Isolated noncompaction of the ventricular myocardium is a cardiomyopathy influencing almost exclusively the left ventricle in children and adults. We report a case of a neonate presenting with right ventricular failure caused by a noncompaction of the right ventricle. However, later course of the disease demonstrated biventricular involvement. Right ventricular noncompaction can be a cause of early postnatal right ventricular failure.

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.

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 seizure monitoring using non-linear EEG analysis.

Birth asphyxia is a major concern in neonatal care. Epileptic seizures are associated with subsequent neurodevelopmental deficits. Eighty-five percent of these seizures remain subclinical and therefore an on-line monitoring device is needed. In an earlier study we showed that the synchronization likelihood was able to distinguish between neonatal EEG epochs with and without epileptic seizures. In this study we investigated whether the synchronization likelihood can be used in complete EEGs, without artifact removal. Twenty complete EEGs from 20 neonatal patients were studied. The synchronization likelihood was calculated and correlated with the visual scoring done by 3 experts. In addition, we determined the influence of seizure length on the likelihood of detection. Using the raw unfiltered EEG data we found a sensitivity of 65.9 % and a specificity of 89.8 % for the detection of seizure activity in each epoch. In addition, the seizure detection rate was 100 % when the seizures lasted for 100 seconds or more. The synchronization likelihood seems to be a useful tool in the automatic monitoring of epileptic seizures in infants on the neonatal ward. Due to the retrospective nature of our study, the consequences for clinical intervention cannot yet be determined and prospective studies are needed. Therefore, we will conduct a prospective study on the neonatal intensive care unit with a recently developed on-line version of the synchronization likelihood analysis.

Diffusion-weighted MRI in severe neonatal hypoxic ischaemia: the white cerebrum.

Presently, prognosis of infants with perinatal hypoxia-ischaemia is estimated using the Sarnat scale, which combines clinical evaluation and electroencephalography, in combination with magnetic resonance imaging (MRI) and or evoked potentials. While the value of conventional MRI is limited during the first week of life, diffusion-weighted MRI demonstrates effects of acute cerebral ischaemia within hours of onset. However, the exact value of diffusion MRI in the prognosis of infants with hypoxia-ischaemia has to be established in larger follow-up studies. In this report we describe 5 term (post-conceptional age 40 1/7 to 41 2/7 week) neonates with severe hypoxia-ischaemia and a characteristic pattern of diffusion changes. T 1 -weighted images showed a hyperintense cortical signal in only one case and extensive hyperintensity in the basal nuclei in all 5 cases. T 2 -weighted images showed nearly complete loss of cortical delineation in three cases. Increased signal on diffusion-weighted images was seen throughout all cortical and subcortical areas while the cerebellum remained normal. This pattern, which we refer to as the "white cerebrum", is most readily apparent on coronal images. The apparent diffusion coefficient (ADC) was calculated and compared to that of four control infants. In the cortex ADC values were lowered (0.70 +/- 0.17 micro m 2/msec [mean +/- standard deviation (SD)]; controls [n = 4]: 1.18 +/- 0.02 micro m 2/msec) as compared to values of ADC in the cerebellum (1.31 +/- 0.06 micro m 2/msec [mean +/- SD]; controls [n = 4]: 1.25 +/- 0.06 micro m 2/msec). All infants died in the perinatal period. In summary, the "white cerebrum" on diffusion-weighted MRI indicates severe neonatal hypoxia-ischaemia and is the counterpart of the white cerebellum on CT.

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.

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.

[Enterobacter cloacae epidemic on a neonatal intensive care unit due to the use of contaminated thermometers]. / Enterobacter cloacae-epidemie op een neonatale intensive-care-unit door gebruik van besmette thermometers.

From December 1999 to March 2000 a nosocomial outbreak of multiresistant Enterobacter cloacae occurred in the neonatal intensive care unit (NICU) at the VU Medical Center, Amsterdam, the Netherlands. Twenty-six patients were infected or colonized with this strain resistant to third generation cephalosporins and with decreased sensitivity for aminoglycosides. Three neonates experienced sepsis with E. cloacae with serious clinical symptoms and two of them died. Comparison of the Enterobacter isolates by amplified-fragment length polymorphism indicated that this outbreak was caused by the spread of a single strain. Infection control precautions were initiated in order to stop further spread; barrier precautions, enforcement of hand disinfection and cohorting of colonized patients. A multidisciplinary crisis team coordinated these infection control precautions and informed all persons involved. Analysis of antibiotic usage in 1999 showed an increase in the use of third generation cephalosporins from November onwards. Due to the resistance pattern of the epidemic strain the use of third generation cephalosporins was discontinued in February 2000. At the end of February the NICU was temporarily closed. The epidemic strain of E. cloacae was isolated from one digital rectal thermometer. Patient use of thermometers and disposable coverings for rectal thermometers were introduced to eliminate this possible means of spread. No spread of multiresistant E. cloacae was found following the introduction of these interventions. Once all the neonates had been transferred, the NICU was disinfected and reopened in March.

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.

[Prone position favors motor development of infants]. / Buikligging gunstig voor motorische ontwikkeling van zuigelingen.

OBJECTIVE: To determine the motor development in infants sleeping in the supine position compared to infants sleeping in the prone position, and to compare the levels of motor development of infants playing only in the supine position and of infants playing in the prone position as well. DESIGN: Prospective blinded comparing study. SETTING: Department of Physical Therapy, Maasziekenhuis, Boxmeer, the Netherlands. METHODS: Various measuring instruments were used in the home environment to determine the levels of motor development at the age of 5 months of 21 healthy infants born at term selected from a group of 160 infants attending the infant welfare clinic. RESULTS: Infants sleeping in the prone position (n = 8) showed a higher motor development than infants sleeping in the supine position (n = 13). Infants playing in the prone and supine position (n = 5) had a higher motor development than infants who played exclusively in the supine position (n = 15). CONCLUSION: Sleeping and playing in the prone position was accompanied by a higher motor development in healthy mature-born infants at the age of 5 months.

Thyroid hormone concentrations in preterm infants born to pre-eclamptic women with placental insufficiency.

The aim of this study was to compare thyroid function in preterm infants born to women with placental insufficiency (n = 15) and those born to women without placental insufficiency (n = 13). Gestational ages ranged between 28 and 33 weeks. Concentrations of free thyroxine (FT4), thyrotropin (TSH), triiodothyronine (T3) and reverse T3 (rT3) were measured by radioimmmunoassays in cord blood and on d 1, 3, 5, 7, 14 and 21. Infants born to the women with placental insufficiency had significantly lower mean FT4 (p = 0.001), TSH (p = 0.002) and rT3 values (p = 0.025) in cord blood, and higher rT3 values on d 5 (p = 0.019) and d 7 (p = 0.025). The following conclusions were reached: (i) preterm infants born to pre-eclamptic women with placental insufficiency have intact hypothalamic-pituitary-thyroid axes; (ii) compared to preterm infants born to healthy women, preterm infants born to pre-eclamptic women with placental insufficiency have lower FT4 and TSH concentrations before birth and (iii) elevated rT3 concentrations after birth, suggesting a temporarily impaired hepatic type 1 deiodination process.

Ten-year neonatal hepatitis B vaccination program, The Netherlands, 1982-1992: protective efficacy and long-term immunogenicity.

From 1982 to 1989, 705 infants born to HBsAg-positive mothers entered the Dutch neonatal hepatitis B vaccination program and received passive-active hepatitis B immunization in three randomized controlled trials testing variations in time of starting active vaccination, dose and type of vaccine, and number of hepatitis B immunoglobulin (HBIg) injections. A meta-analysis of individual patient data of the three randomized trials was performed to determine which independent host and vaccination related factors influence protective efficacy and long-term immunogenicity, and to assess whether hepatitis B vaccination concomitant with standard DKTP vaccination provides optimal protection. Statistical methodology included multivariate logistic regression analysis. Eight infants (1.1%), all born to HBeAg-positive mothers, became HBsAg carriers within the first year of life. The protective efficacy rate (PER) of passive-active immunization at 12 months follow-up was 92% for the total group of children from 114 HBeAg-positive mothers with no significant differences between children starting active immunization at birth or at 3 months of age, between infants starting at 3 months of age receiving one or two doses of HBIg or between those receiving plasma derived or recombinant vaccine. The only factor that affected the PER significantly was the level of maternal HBV DNA; PER was 100% if maternal HBV DNA was < 150 pg ml-1 and 68% for HBV DNA levels > 150 pg ml-1. After 5 years of follow-up, the group that started active immunization at birth had significantly more infants with loss of seroprotection (anti-HBs levels < 10 IU l-1, 15%) than the corresponding group starting at 3 months of age (anti-HBs < 10 IU l-2, 2%). One of 35 children with loss of seroprotection at 2 years became a HBsAg carrier in the fifth year of follow-up. This meta-analysis shows that the protective efficacy of passive-active hepatitis B vaccination is mainly influenced by material HBV DNA levels, and independent of the time of starting active vaccination at birth or at 3 months of age; long-term immunity was enhanced by starting active vaccination concomitant with DKTP vaccination. These findings allow incorporation of hepatitis B vaccine into the standard infant immunization programs for countries with a passive-active immunization strategy for the control of hepatitis B. Additional measures are needed to protect neonates of highly viremic women.

[Hyperbilirubinemia in full-term neonates: sequelae for long-term development better than expected. Ad-hoc Commission Hyperbilirubinemia and Phototherapy of the Section Neonatology of the Netherlands Society for Pediatrics]. / Hyperbilirubinemie bij voldragen pasgeborenen: gevolgen voor de ontwikkeling op lange termijn vallen mee. Ad-hoccommissie Hyperbilirubinemie en Fototherapie van de sectie Neonatologie van de Nederlandse Vereniging voor Kindergeneeskunde.

OBJECTIVE: Critical evaluation of guidelines for treatment of hyperbilirubinaemia in healthy full-term newborns, based on literature data concerning effects of hyperbilirubinaemia on later development. DESIGN: Structured literature survey. SETTING: Groningen, the Netherlands. METHODS: By electronic and hand searching of literature according to published guidelines data were collected on the relation between the peak total serum bilirubin concentration (TSB) in the first week of life and later development. RESULTS: One large study, the Collaborative Perinatal Project (CPP), showed statistically significant negative associations of TSB in the first week of life with Bayley development score at age 8 months, intelligence quotient (IQ) at age 4 years, and unspecified neurological abnormalities at age 7-8 years. In other studies, with considerable less power than the CPP, no such findings were made. In the original analyses of the CPP no correction was made for confounders and effect modifiers; after correction for such variables, a relation between TSB in the first week of life and later development was no longer found. At the age of 6 years, no statistically significant differences in IQ, hearing, and neurological abnormalities were found between children who, as newborns, had or had not been treated with phototherapy because of hyperbilirubinaemia. CONCLUSION: Treatment for jaundice in healthy full-term newborns is only indicated at considerably higher serum bilirubin levels than those recommended previously.

[Hyperbilirubinemia in healthy full-term neonates: guidelines for diagnosis and treatment. Ad-hoc Commission Hyperbilirubinemia and Phototherapy of the Section Neonatology of the Netherlands Society for Pediatrics]. / Hyperbilirubinemie bij gezonde voldragen pasgeborenen: richtlijnen voor diagnostiek en behandeling. Ad-hoccommissie Hyperbilirubinemie en Fototherapie van de sectie Neonatologie van de Nederlandse Vereniging voor Kindergeneeskunde.

In healthy full-term neonates without haemolytic disease, hyperbilirubinaemia is not associated with neurological, auditory or cognitive disorders later in life. Therefore, the new threshold levels of hyperbilirubinaemia at which further diagnosis and treatment are indicated, are higher than the former ones.