Evaluating preterm care across Europe using the eNewborn European Network database.

BACKGROUND: The inefficiency of recording data repeatedly limits the number of studies conducted. Here we illustrate the wider use of data captured as part of the European eNewborn benchmarking programme. METHODS: We extracted data on 39,529 live-births from 22 weeks 0 days to 31 weeks 6 days gestational age (GA) or ≤1500 g birth weight. We explored relationships between delivery room care and Apgar scores on mortality and bronchopulmonary dysplasia (BPD) and calculated the time needed for each country to detect a clinically relevant change in these outcomes following a hypothetical intervention. RESULTS: Early neonatal, neonatal, and in-hospital mortality were 3.90% (95% CI 3.71, 4.09), 6.00% (5.77, 6.24) and 7.57% (7.31, 7.83), respectively. The odds of death were greater with decreasing GA, lower Apgar scores, growth restriction, male sex, multiple birth and no antenatal steroids. Relationships for BPD were similar. The time required for participating countries to achieve 80% power to detect a relevant change in outcomes following a hypothetical intervention in 23-25 weeks' GA infants ranged from 12 years for neonatal mortality and 22 years for BPD compared to 1 year for the whole network. CONCLUSIONS: The eNewborn platform offers opportunity to drive efficiencies in benchmarking, quality control and research.

Preterm newborns show slower repair of oxidative damage and paternal smoking associated DNA damage.

Newborns have to cope with hypoxia during delivery and a sudden increase in oxygen at birth. Oxygen will partly be released as reactive oxygen species having the potential to cause damage to DNA and proteins. In utero, increase of most (non)-enzymatic antioxidants occurs during last weeks of gestation, making preterm neonates probably more sensitive to oxidative stress. Moreover, it has been hypothesized that oxidative stress might be the common etiological factor for certain neonatal diseases in preterm infants. The aim of this study was to assess background DNA damage; in vitro H(2)O(2) induced oxidative DNA damage and repair capacity (residual DNA damage) in peripheral blood mononucleated cells from 25 preterm newborns and their mothers. In addition, demographic data were taken into account and repair capacity of preterm was compared with full-term newborns. Multivariate linear regression analysis revealed that preterm infants from smoking fathers have higher background DNA damage levels than those from non-smoking fathers, emphasizing the risk of paternal smoking behaviour for the progeny. Significantly higher residual DNA damage found after 15-min repair in preterm children compared to their mothers and higher residual DNA damage after 2 h compared to full-term newborns suggest a slower DNA repair capacity in preterm children. In comparison with preterm infants born by caesarean delivery, preterm infants born by vaginal delivery do repair more slowly the in vitro induced oxidative DNA damage. Final impact of passive smoking and of the slower DNA repair activity of preterm infants need to be confirmed in a larger study population combining transgenerational genetic and/or epigenetic effects, antioxidant levels, genotypes, repair enzyme efficiency/levels and infant morbidity.

Parental involvement and kangaroo care in European neonatal intensive care units: a policy survey in eight countries.

OBJECTIVE: To compare, in a large representative sample of European neonatal intensive care units, the policies and practices regarding parental involvement and holding babies in the kangaroo care position as well as differences in the tasks mothers and fathers are allowed to carry out. DESIGN: Prospective multicenter survey. SETTING: Neonatal intensive care units in eight European countries (Belgium, Denmark, France, Italy, The Netherlands, Spain, Sweden, and the United Kingdom). PATIENTS: Patients were not involved in this study. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A structured questionnaire was mailed to 362 units (response rate 78%); only units with ≥50 very-low-birth-weight annual admissions were considered for this study. Facilities for parents such as reclining chairs near the babies' cots, beds, and a dedicated room were common, but less so in Italy and Spain. All units in Sweden, Denmark, the United Kingdom, and Belgium reported encouraging parental participation in the care of the babies, whereas policies were more restrictive in Italy (80% of units), France (73%), and Spain (41%). Holding babies in the kangaroo care position was widespread. However, in the United Kingdom, France, Italy, and Spain, many units applied restrictions regarding its frequency (sometimes or on parents request only, rather than routinely), method (conventional rather than skin-to-skin), and clinical conditions (especially mechanical ventilation and presence of umbilical lines) that would prevent its practice. In these countries, fathers were routinely offered kangaroo care less frequently than mothers (p < .001) and less often it was skin-to-skin (p < .0001). CONCLUSIONS: This study showed that, although the majority of units in all countries reported a policy of encouraging both parents to take part in the care of their babies, the intensity and ways of involvement as well as the role played by mothers and fathers varied within and between countries.

An aphidicolin-block nucleotide excision repair assay measuring DNA incision and repair capacity.

The objective of the present study was to develop a cellular phenotype assay for nucleotide excision repair (NER), using benzo[a]pyrene diol epoxide (BPDE) as model mutagen. Since in vitro exposure to BPDE may lead to DNA strand breaks resulting from both direct interaction with DNA and incisions introduced by the repair enzymes, we aimed to discriminate between both types of breaks using the comet assay and quantified the DNA strand breaks after in vitro challenge of peripheral blood mononucleated cells (PBMCs) with BPDE in the presence or absence of the DNA polymerase inhibitor aphidicolin (APC). The assay was performed with a low (0.5 microM) and a high (2.5 microM) BPDE concentration. The individual NER capacity was defined as the amount of DNA damage induced by BPDE in presence of APC, diminished with the damage induced by BPDE and APC alone. First, the assay was applied to a NER-deficient human fibroblast cell line (XPA-/-) to validate the methodology. Lower repair capacity and a higher amount of BPDE-induced DNA adducts were observed for the XPA-/- fibroblasts as compared to the wild-type fibroblasts. Repeated experiments on PBMCs from four donors showed low intra-individual, intra-experimental and inter-assay variation for both concentrations, indicating the reliability of the method. To assess the inter-individual variation, the assay was applied to PBMCs from 22 donors, comparing the repair capacity after exposure to 0.5 microM (N = 10) and 2.5 microM (N = 12) BPDE. The repair capacity showed a higher inter-individual variation as compared to the intra-individual variation. Moreover, this difference was more pronounced using the low concentration. All these results indicate the adequacy of the method using this low concentration. Further improvement, however, should be recommended by applying the study with low BPDE concentration in a larger population and taking into account the relevant genotypes for NER.

Ethical dimensions of periviability.

The birth of neonates at the limits of viability, or periviability, poses numerous challenges to health care providers and to systems of care, and the care of these pregnancies and neonates is fraught with ethical controversies. This statement summarizes the ethical principles involved in the care of periviable pregnancies and neonates, and provides expert clinical opinion about the numerous challenges posed by this problem around the world. Topics addressed include a summary of the published experience, an ethical framework, translating neonatal outcome data to the obstetric arena, management as a trial of intervention, referral to tertiary centers, neonatal resuscitation, cesarean delivery for fetal indication, and limits on life-sustaining neonatal treatment.

Parents, siblings and grandparents in the Neonatal Intensive Care Unit. A survey of policies in eight European countries.

OBJECTIVE: To describe policies towards family visiting in Neonatal Intensive Care Units (NICU) and compare findings with those of a survey carried out 10 years earlier. METHODS: A questionnaire on early developmental care practices was mailed to 362 units in eight European countries (Sweden, Denmark, the UK, the Netherlands, Belgium, France, Spain and Italy). Of them 78% responded, and among those responded, 175 reported caring for at least 50 very low birth weight infants every year and their responses were analysed further. RESULTS: A majority of all units allowed access at any time for both parents. This was almost universal in northern Europe and the UK, whereas it was the policy of less than one-third of NICU in Spain and Italy, with France in an intermediate position. Restrictions on visiting of grandparents, siblings and friends, as well as restricting parents' presence during medical rounds and procedures followed the same pattern. A composite visiting score was computed using all the variables related to family visiting. Lower median values and larger variability were obtained for the southern countries, indicating more restrictive attitudes and lack of national policy. CONCLUSIONS: The presence of parents and other family members in European NICUs has improved over a 10-year period. Several barriers, however, are still in place, particularly in the South European countries.

Genetic susceptibility of newborn daughters to oxidative stress.

A central question in risk assessment is whether newborns' susceptibility to mutagens is different from that of adults. Therefore we investigated whether genotype and/or the DNA strand break repair phenotype in combination with the MN assay would allow estimation of the relative sensitivity of a newborn as compared to his mother for oxidative DNA damage. We compared the in vitro genetic susceptibility for H2O2 in PBMC of 17 mother-newborn daughter pairs taking into account genotypes for relevant DNA repair (hOGG1, XRCC1, XRCC3, XPD) and folate metabolism (MTHFR) polymorphisms. After in vitro challenge with H2O2 the repair capacity was assessed by the Comet assay and chromosome/genome mutations by the cytokinesis-block MN assay. No statistically significant differences were found between mothers and their newborn daughters either for initial DNA damage or for residual DNA damage. Mothers showed higher background frequencies of MN as compared to their newborn daughters, due to the age factor. This was confirmed by significantly higher frequencies of MN observed in mothers versus newborn daughters for several genotypes. No genotype with a significant effect on DNA repair capacity in newborns was identified. Concerning MN frequencies, however, newborns carrying the variant XRCC3(241) genotype might be at higher risk for the induction of MN by oxidative stress. Multivariate analysis revealed a significant protective effect of maternal antioxidant supplementation during pregnancy against oxidative DNA damage in newborns in terms of MN frequencies. However, these conclusions might not be extrapolable to other types of DNA damage and need confirmation in a study on a larger population.

eNewborn: The Information Technology Revolution and Challenges for Neonatal Networks.

Among preterm infants, 1-2% are born before 32 weeks of gestation or have a birth weight below 1,500 g. They contribute disproportionately to the burden of mortality and morbidity related to preterm birth, whether in the neonatal period or later in life. They are the target population studied in neonatal networks. Improving neonatal care and later outcome is a major issue in public health. Neonatologists, health care providers, public authorities, parents and families, industry, and all organizations dedicated to infant health must bring their efforts together and dedicate their actions in order to do so. Neonatal networks are the strongest platforms through which to achieve this goal. The progressive information technology (IT) revolution is leading to a new approach. The power of search engines and new technological devices opens extraordinary new perspectives in terms of speed, storing, sharing, and innovative approaches in providing health care. However, difficulties are expected with old applications that cannot evolve in the new IT environment. Security and privacy in data collection are future challenges to be addressed. Here, we describe the eNewborn project and its original software. The main functionalities are interactive navigation, harmonization with other formats, linkage with other databases, and strict security and privacy procedures.

Tuberculosis in healthcare workers caring for a congenitally infected infant.

OBJECTIVE: To assess the extent of nosocomial transmission of tuberculosis among infants, family members, and healthcare workers (HCWs) who were exposed to a 29-week-old premature infant with congenital tuberculosis, diagnosed at 102 days of age. DESIGN: A prospective exposure investigation using tuberculin skin test (IST conversion was conducted. Contacts underwent two skin tests 10 to 12 weeks apart. Clinical examination and chest radiographs were performed to rule out disease. Isoniazid prophylaxis was administered to exposed infants at higher risk. SETTING: A neonatal intensive care unit in an urban hospital in Brussels, Belgium. PARTICIPANTS: Ninety-seven infants, 139 HCWs, and 180 visitors. RESULTS: Newly positive TST results occurred in HCWs who had been in close contact with the infant. Six (19%) of 32 primary care nurses and physicians had TST conversions and received treatment. Among the 97 exposed infants, 85 were screened and 34 were identified as at higher risk of infection. Of these, 27 received preventive isoniazid. None of the infants and none of the 93 other infants' family members evaluated were infected. CONCLUSIONS: Congenital tuberculosis in an infant poses a risk for nosocomial transmission to HCWs. Delayed diagnosis of this rare disease and close proximity are the most important factors related to transmission.

Lower nucleotide excision repair capacity in newborns compared to their mothers: a pilot study.

Recognition of the potential vulnerability of children and newborns and protection of their health is essential, especially regarding to genotoxic compounds. Benzo(a)pyrene B(a)P a commonly found carcinogen, and its metabolite BPDE, are known to cross the placenta. To investigate how well newborns are able to cope with BPDE-induced DNA damage, a recent developed nucleotide excision repair cell phenotype assay was applied in a pilot study of 25 newborn daughters and their mothers, using the Alkaline Comet Assay and taking demographic data into account. Newborns seemed to be less able to repair BPDE-induced DNA damage since lower repair capacity levels were calculated compared to their mothers although statistical significance was not reached. Assessment of repair capacity in combination with genotypes will provide important information to support preventive strategies in neonatal care and to define science based exposure limits for pregnant women and children.

Heel blood sampling in European neonatal intensive care units: compliance with pain management guidelines.

OBJECTIVE: To describe the use of heel blood sampling and non-pharmacological analgesia in a large representative sample of neonatal intensive care units (NICUs) in eight European countries, and compare their self-reported practices with evidence-based recommendations. METHODS: Information on use of heel blood sampling and associated procedures (oral sweet solutions, non-nutritive sucking, swaddling or positioning, topical anaesthetics and heel warming) were collected through a structured mail questionnaire. 284 NICUs (78% response rate) participated, but only 175 with ≥50 very low birth weight admissions per year were included in this analysis. RESULTS: Use of heel blood sampling appeared widespread. Most units in the Netherlands, UK, Denmark, Sweden and France predominantly adopted mechanical devices, while manual lance was still in use in the other countries. The two Scandinavian countries and France were the most likely, and Belgium and Spain the least likely to employ recommended combinations of evidence-based pain management measures. CONCLUSIONS: Heel puncture is a common procedure in preterm neonates, but pain appears inadequately treated in many units and countries. Better compliance with published guidelines is needed for clinical and ethical reasons.

Management of the neonate at the limits of viability.

The active treatment of fetuses or neonates at the limits of viability is an ongoing debate for perinatal physicians. Although initiating intensive care at 26 weeks is generally accepted, the gray zone of gestational ages at which aggressive perinatal care should be offered is less clear and ranges from 22 to 25 weeks. The gray zone has remained rather unchanged over the last decade. Attitudes vary among different countries, centres and individuals. The benefit-burden ratio of neonatal intensive care is balanced differently according to competing moral values. Several factors underlie the difficulty in approaches to management decisions. Neonates lack the capacity to make decisions and most parents ignore the complexity of care during and after hospitalisation. Parents have to be informed about the survival rates and the risks of long term disabilities, but accuracy for each individual baby is very weak. Outcome data are published many years after the intensive care period, and results about the prevalence of severe disabilities over time are conflicting and vary widely (ranging from 10% to 60%). Information about more subtle disabilities which only become apparent around school age is scarce. Data on the impact of the longer term outcomes of new strategies like developmental care approaches (Neonatal Individual Developmental Care Assessment Programme: NIDCAP) are still insufficient but could prove to be an important recent step in improving outcome in extremely immature babies.

Early neonatal dexamethasone treatment for prevention of bronchopulmonary dysplasia. Randomised trial and meta-analysis evaluating the duration of dexamethasone therapy.

UNLABELLED: The aim of the aborted trial was to determine whether the short early dexamethasone (DX) given after the birth improves the early outcome. We also reviewed the evidence (meta-analysis) to determine whether the duration of early DX treatment influences the early outcome, particularly in terms of bronchopulmonary dysplasia (BPD). The participants of the randomised multicentre, double-blinded placebo-controlled trial had a birth weight 500-999 g, gestation < or = 31.0 weeks, and respiratory failure by the age of 4 h. The infants received either four doses of DX (0.25 mg/kg at 12 h intervals) or placebo. The meta-analysis was performed to determine the beneficial and adverse effects of early short (<96 h duration) versus early prolonged (>96 h) DX treatment. The trial was discontinued after 109 infants had been enrolled. There was a non-significant improvement in the outcome (survival without BPD, severe intracranial haemorrhage or periventricular leukomalacia; RR 1.27; 95% CI 0.87-1.85). The risks for gastrointestinal perforation and hyperglycaemia tended to increase. A total of 15 trials were included in the meta-analysis: 10 involved prolonged (i.e. >96 h; 1594 infants) and five short interventions (1069 infants). Early prolonged DX decreased the RR for BPD to 0.72 (95% CI 0.61-0.87), whereas early short DX course did not significantly decrease the risk (RR 0.82; 95% CI 0.64-1.05). Gastrointestinal haemorrhages and perforations were significantly increased only in the early prolonged DX group. CONCLUSION: The dosage and duration of early corticosteroid given to small premature infants influences the risk of the side-effects and the early outcome.

The nutritional iodine supply of Belgian neonates is still insufficient.

UNLABELLED: Belgium used to be affected by mild iodine deficiency. Improvement in iodine nutrition has been recently documented in schoolchildren in Belgium in spite of the absence of any systematic programme of iodine supplementation. The question arises as to whether this 'silent iodine prophylaxis' affected also the neonates. A total of 185 random urine samples were collected from 90 full term and 65 preterm neonates in Brussels on day 5 and repeated on day 30 in 30 preterms who were bottle-fed with iodine-enriched formula-milk. The iodine content was also determined in 58 samples of breast-milk on day 5. The median urinary iodine on day 5 in full term neonates was 86 micro g/l, which is markedly higher than the figure of 48 micro g/L reported 15 years previously in neonates in the same area but still much lower than normal for this age group (150-200 micro g/l). The mean iodine content of breast-milk was 78 micro g/l, which is unchanged as compared to 15 years ago and is about 66% of normal. Finally, the median urinary iodine increased from 60 micro g/l on day 5 to 150 micro g/l on day 30 in preterms bottle-fed with iodine-enriched formula-milk. CONCLUSION: the status of iodine nutrition has also improved spontaneously in Belgian neonates but has not yet normalised. Lactating and probably pregnant women remain clearly iodine deficient. The iodine-enriched formula-milk for preterms is efficient in correcting their iodine deficiency. National measures are urgently required for correction of iodine deficiency in Belgium.

The EPIBEL study: outcomes to discharge from hospital for extremely preterm infants in Belgium.

OBJECTIVE: To determine mortality and morbidity at discharge from the hospital of a large population-based cohort of infants who were born at