Changes in management policies for extremely preterm births and neonatal outcomes from 2003 to 2012: two population-based studies in ten European regions.

OBJECTIVE: To investigate changes in maternity and neonatal unit policies towards extremely preterm infants (EPTIs) between 2003 and 2012, and concurrent trends in their mortality and morbidity in ten European regions. DESIGN: Population-based cohort studies in 2003 (MOSAIC study) and 2011/2012 (EPICE study) and questionnaires from hospitals. SETTING: 70 hospitals in ten European regions. POPULATION: Infants born at <27 weeks of gestational age (GA) in hospitals participating in both the MOSAIC and EPICE studies (1240 in 2003, 1293 in 2011/2012). METHODS: We used McNemar's Chi2 test, paired t-tests and conditional logistic regression for comparisons over time. MAIN OUTCOMES MEASURES: Reported policies, mortality and morbidity of EPTIs. RESULTS: The lowest GA at which maternity units reported performing a caesarean section for acute distress of a singleton non-malformed fetus decreased from an average of 24.7 to 24.1 weeks (P < 0.01) when parents were in favour of active management, and 26.1 to 25.2 weeks (P = 0.01) when parents were against. Units reported that neonatologists were called more often for spontaneous deliveries starting at 22 weeks GA in 2012 and more often made decisions about active resuscitation alone, rather than in multidisciplinary teams. In-hospital mortality after live birth for EPTIs decreased from 50% to 42% (P < 0.01). Units reporting more active management in 2012 than 2003 had higher mortality in 2003 (55% versus 43%; P < 0.01) and experienced larger declines (55 to 44%; P < 0.001) than units where policies stayed the same (43 to 37%; P = 0.1). CONCLUSIONS: European hospitals reporting changes in management policies experienced larger survival gains for EPTIs. TWEETABLE ABSTRACT: Changes in reported policies for management of extremely preterm births were related to mortality declines.

An unusual tumour causing neonatal respiratory distress.

PROBLEM: We present the case of a term neonate referred shortly after birth because of breathing and feeding difficulties. METHODOLOGY: Fiber-endoscopic examination of the nasal cavity showed a pendulating mass in the nasopharynx. RESULTS: A complete surgical resection was performed and the baby recovered completely. Microscopic examination of the mass showed an overlying non-keratinized squamous cell lining with an atypical cell population in some fragments. Histological features were compatible with a high-grade epithelial tumour like a midline carcinoma, but a final diagnosis of a salivary gland anlage tumour was established. CONCLUSION: Flexible fiber endoscopy is the method of choice for examining the nasal passages and oropharynx in neonates with respiratory distress. Congenital salivary gland anlage tumour is a rare cause of neonatal nasal obstruction; it is benign and complete excision results in a cure. Histologically, it may mimic a malignant tumour owing to the high mitotic index.

Obstetric interventions for babies born before 28 weeks of gestation in Europe: results of the MOSAIC study.

OBJECTIVE: To describe obstetric intervention for extremely preterm births in ten European regions and assess its impact on mortality and short term morbidity. DESIGN: Prospective observational cohort study. SETTING: Ten regions from nine countries participating in the 'Models of Organising Access to Intensive Care for Very Preterm Babies in Europe' (MOSAIC) project. POPULATION: All births from 22 to 29 weeks of gestation (n = 4146) in 2003, excluding terminations of pregnancy. METHODS: Comparison of three obstetric interventions (antenatal corticosteroids, antenatal transfer and caesarean section for fetal indication) rates at 22-23, 24-25 and 26-27 weeks to that at 28-29 weeks and the association of the level of intervention with pregnancy outcome. MAIN OUTCOME MEASURES: Use of antenatal corticosteroids, antenatal transfer and caesarean section by two-week gestational age groups as well as a composite score of these three interventions. Outcomes included stillbirth, in-hospital mortality and intraventricular haemorrhage (IVH) grades III and IV and/or periventricular leucomalacia (PVL) and bronchopulmonary dysplasia (BPD). RESULTS: There were large differences between regions in interventions for births at 22-23 and 24-25 weeks. Differences were most pronounced at 24-25 weeks; in some regions these babies received the same care as babies of 28-29 weeks, whereas elsewhere levels of intervention were distinctly lower. Before 26 weeks and especially at 24-25 weeks, there was an association between the composite intervention score and mortality. No association was observed at 26-27 weeks. For survivors at 24-25 weeks, the intervention score was associated with higher rates of BPD, but not with IVH or PVL. CONCLUSIONS: There are large differences between European regions in obstetric practices at the lower limit of viability and these are related to outcome, especially at 24-25 weeks.

Psychopathology among preterm infants using the Diagnostic Classification Zero to Three.

AIM: To compare the prevalence of psychopathology in infants born preterm with matched full-term infants at the corrected age of 1 year. METHODS: Between June 2003 and April 2005, a case-control longitudinal cohort study was conducted at the neonatal unit of the University Hospital of Antwerp, Belgium. We prospectively enrolled 123 live-born infants between 25 and 35 weeks of gestation and/or infants with a birth-weight of <1500 g. Thirty full-term infants were recruited among day care centres in the region. Diagnoses were based on the Diagnostic Classification Zero to Three (DC: 0-3), using the MacArthur Communicative Developmental Inventory Dutch version, Infant-Toddler Sensory Profile, Bayley Scales of Infant Development II, Parent Infant Relationship Global Assessment Scale and Functional Emotional Assessment Scale. RESULTS: At the (corrected) age of 12 months, 89 infants were eligible for follow-up and complete data were available for 69 (77%) infants. Fifty-four percentage of the preterm infants fulfilled one or more DC 0-3 diagnoses. Premature infants had significantly more diagnoses than full-term infants on axis I, axis III and axis V of the DC: 0-3. CONCLUSION: In this study, the prevalence of psychopathology was significantly higher among preterm infants in comparison with full-term infants. This study did not confirm previous findings of higher rates of relationship disorders among preterm infants.

Idiopathic cerebral arterial infarction with paucity of symptoms in the full-term neonate.

Two full-term neonates, one with convulsions and intermittent generalized hypotonia and one with poor sucking, temperature instability, and lethargy, are reported. CT scan findings suggested cerebral arterial infarction. Arteriography revealed occlusion of the middle cerebral artery, unilaterally in the first and bilaterally in the second patient. The evolution of the infarct could be followed on serial CT scans. No predisposing factors during pregnancy or delivery were found, and serious neurologic deficits developed in both children. These cases demonstrate that, even in full-term neonates with discrete or moderate neurologic symptoms and born after normal pregnancy and delivery, the possibility of vasoocclusive brain infarction should be considered. The diagnosis is suggested by imaging techniques, of which CT scanning seems to have the greatest value at present. This technique also permits the follow-up of the lesions. The prognosis for neurologic development appears to be variable: minor neurologic deficits as well as unexplained spastic hemiplegia in older children may be the consequence of inapparent cerebral arterial infarction in the neonatal period.

Microbiology and risk factors for catheter exit-site and -hub colonization in neonatal intensive care unit patients.

OBJECTIVE: To identify risk factors and describe the microbiology of catheter exit-site and hub colonization in neonates. DESIGN: During a period of 2 years, we prospectively investigated 14 risk factors for catheter exit-site and hub colonization in 862 central venous catheters in a cohort of 441 neonates. Cultures of the catheter exit-site and hub were obtained using semiquantitative techniques at time of catheter removal. SETTING: A neonatal intensive care unit at a university hospital. RESULTS: Catheter exit-site colonization was found in 7.2% and hub colonization in 5.3%. Coagulase-negative staphylococci were predominant at both sites. Pathogenic flora were found more frequently at the catheter hub (36% vs 14%; P<.05). Through logistic regression, factors associated with exit-site colonization were identified as umbilical insertion (odds ratio [OR], 8.1; 95% confidence interval [CI95], 2.35-27.6; P<.001), subclavian insertion (OR, 54.6; CI95, 12.2-244, P<.001), and colonization of the catheter hub (OR, 8.9; CI, 3.5-22.8; P<.001). Catheter-hub colonization was associated with total parenteral nutrition ([TPN] OR for each day of TPN, 1.056; CI95, 1.029-1.083; P<.001) and catheter exit-site colonization (OR, 6.11; CI95, 2.603-14.34; P<.001). No association was found between colonization at these sites and duration of catheterization and venue of insertion, physician's experience, postnatal age and patient's weight, ventilation, steroids or antibiotics, and catheter repositioning. CONCLUSION: These data support that colonization of the catheter exit-site is associated with the site of insertion and colonization of the catheter hub with the use of TPN. There is a very strong association between colonization at both catheter sites.

A pseudoepidemic of adenoviruses in a neonatal care unit.

A number of stool samples from a neonatal intensive care unit reacted in a latex agglutination test (LAT) for adenoviruses. However, the majority of these babies had no symptoms. Virus particles were not visualized by electron microscopy, whereas the results of ELISAs and stool cultures in appropriate cell lines remained negative. The episode was interpreted as a pseudoepidemic. The LAT for adenoviruses is not suited for the examination of stools from very young babies.

Risk factors for central vascular catheter-associated bloodstream infections among patients in a neonatal intensive care unit.

The aim of this study was to identify risk factors for catheter-associated bloodstream infection (CABSI) in neonates. We undertook a prospective investigation of the potential risk factors for CABSI (patient-related, treatment-related and catheter-related) in a neonatal intensive care unit (NICU) using univariate and multivariate techniques. We also investigated the relationship between catheter hub and catheter exit site colonization with CABSI.Thirty-five episodes of CABSI occurred in 862 central catheters over a period of 8028 catheter-days, with a cumulative incidence of 4.1/100 catheters and an incidence density of 4.4/1000 catheter days. Factors independently associated with CABSI were: catheter hub colonization (odds ratio [OR] = 44.1, 95% confidence interval [CI] = 14.5 to 134.4), exit site colonization (OR = 14.4, CI = 4.8 to 42.6), extremely low weight (< 1000 g) at time of catheter insertion (OR = 5.13, CI = 2.1 to 12.5), duration of parenteral nutrition (OR=1.04, CI=1.0 to 1.08) and catheter insertion after first week of life (OR = 2.7, CI = 1.1 to 6.7). In 15 (43%) out of the 35 CABSI episodes the catheter hub was colonized, in nine (26%) cases the catheter exit site was colonized and in three (9%) cases colonization was found at both sites. This prospective cohort study on CABSI in a NICU identified five risk factors of which two can be used for risk-stratified incidence density description (birthweight and time of catheter insertion). It also emphasized the importance of catheter exit site, hub colonization and exposure to parenteral nutrition in the pathogenesis of CABSI.

Inadequate intravenous feeding in sick neonates: a retrospective study.

It is a common experience that during intravenous feeding (IVF) in neonates the administered amounts do not always meet the recommendations. In an attempt to quantify these deficits and to determine the causes we studied the data of 2 comparable groups of neonates admitted to a neonatal intensive care unit (NICU). In Group 1 (N = 107; gestational age 25-42 weeks; birth weight 690-5920 g) the minimum recommended intake of energy (70 kCal/kg/d) and of aminoacids (2.5g/kg/d) was not met in 17% and in 71% respectively. The main causes of inadequate intake were believed to be the nearly exclusive use of peripheral venous access, and the restriction in glucose and/or lipid administration because of extreme prematurity and/or severe illness. In Group 2 (N = 99; gestational age 24-42 weeks; birth weight 670-4300 g), where these causes were corrected, 11% and 54% of the patients still received an insufficient amount of energy and amino acids respectively. It can be concluded that in the daily practice in a NICU, even in optimal conditions and following the recent recommendations for IVF, a considerable proportion of preterm neonates do not receive the minimal recommended amount of energy and aminoacids.

Ethical aspects of cardiopulmonary resuscitation in premature neonates: where do we stand?

Advances in diagnosis, techniques, therapeutic interventions, organisation of perinatal care, and socio-economic factors have all contributed to the survival after resuscitation and intensive care of neonates with extremely low birth weight and gestational age. While morbidity during the first years of life in those infants does not increase, at school age multiple dysfunctions may become apparent. What are the limits of intensive care for the newborn? Is it right to use extreme technical and economic measures for neonates with a borderline chance of survival? What is justifiable for the neonate, the family, the society and how does legislation interfere in a decision process which involves starting, stopping or continuing intensive care? A short historical overview for the care of the newborn is given, followed by the outcome after resuscitation and treatment of the very low birth weight infant. Published management strategies and recommendations are discussed.

European Resuscitation Council Guidelines 2000 for Newly Born Life Support. A statement from the Paediatric Life Support Working Group and approved by the Executive Committee of the European Resuscitation Council.

The European Resuscitation Council (ERC) last issued guidelines for the resuscitation of the newly born infant in 1999 [1]. This was an "Advisory Statement" of the International Liaison Committee on Resuscitation (ILCOR). Following this, the American Heart Association and the Neonatal Resuscitation Programme Steering Committee of the American Academy of Paediatrics and representatives of the World Health Organisation, together with representatives from ILCOR, undertook a series of evidence-based evaluations of the science of resuscitation which culminated in the publication of "Guidelines 2000 for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care" in August 2000 [2,3]. The Paediatric Life Support Working Party of the European Resuscitation Council has considered this document and the supporting scientific literature and presents the ERC Newly Born Guidelines in this paper. Readers will find few changes to the ILCOR Advisory Statement recommendations as the new evidence that has emerged since its publication in 1999 has been confirmatory of the ILCOR recommendations.

Resuscitation of the newly born infant: an advisory statement from the Pediatric Working Group of the International Liaison Committee on Resuscitation.

The International Liaison Committee on Resuscitation (ILCOR), with representation from North America, Europe, Australia, New Zealand, Africa, and South America, was formed in 1992 to provide a forum for liaison between resuscitation organizations in the developed world. This consensus document on resuscitation extends previously published ILCOR advisory statements on resuscitation to address the unique and changing physiology of the newly born infant within the first few hours following birth and the techniques for providing advanced life support. After careful review of the international resuscitation literature and after discussion of key and controversial issues, consensus was reached on almost all aspects of neonatal resuscitation, and areas of controversy and high priority for additional research were delineated. Consensus on resuscitation for the newly. born infant included the following principles. (i) Personnel trained in the basic skills of resuscitation should be in attendance at every delivery. A minority (fewer than 10%) of newly born infants require active resuscitative interventions to establish a vigorous cry and regular respirations, maintain a heart rate greater than 100 beats per minute (bpm), and maintain good color and tone. (ii) When meconium is present in the amniotic fluid, it should be suctioned from the hypopharynx on delivery of the head. If the meconium-stained newly born infant has absent or depressed respirations, heart rate, or muscle tone, residual meconium should be suctioned from the trachea. (ii) Attention to ventilation should be of primary concern. Assisted ventilation with attention to oxygen delivery, inspiratory time, and effectiveness judged by chest rise should be provided if stimulation does not achieve prompt onset of spontaneous respirations and/or the heart rate is less than 100 bpm. (iv) Chest compressions should be provided if the heart rate is absent or remains less than 60 bpm despite adequate assisted ventilation for 30 s. Chest compressions should be coordinated with ventilations at a ratio of 3:1 and a rate of 120 'events' per minute to achieve approximately 90 compressions and 30 rescue breaths per minute. (v) Epinephrine should be administered intravenously or intratracheally if the heart rate remains less than 60 bpm despite 30 s of effective assisted ventilation and chest compression circulation. Common or controversial medications (epinephrine, volume expansion, naloxone, bicarbonate), special resuscitation circumstances affecting care of the newly born, continuing care of the newly born after resuscitation, and ethical considerations for initiation and discontinuation of resuscitation are discussed. There was agreement that insufficient data exist to recommend changes to current guidelines regarding the use of 21% versus 100% oxygen, neuroprotective interventions such as cerebral hypothermia, use of a laryngeal mask versus endotracheal tube, and use of high-dose epinephrine. Areas of controversy are identified, as is the need for additional research to improve the scientific justification of each component of current and future resuscitation guidelines.

Stress responses to tilting and odor stimulus in preterm neonates after intrauterine conditions associated with chronic stress.

The effect of conditions linked with chronic intrauterine stress (CIUSTR) on the function of the autonomic nervous system (ANS) has not yet been evaluated systematically in premature neonates. We hypothesized that intrauterine stress deranges the function of the ANS as assessed by the clinical responses to certain stimuli. Twenty-one premature neonates who had suffered from CIUSTR, such as maternal smoking, maternal hypertension, and intrauterine growth retardation (STR Group), and 30 neonates who had not suffered from those intrauterine conditions were studied (C Group). They were exposed to a 10-s postural change test and a 10-s odor test. Heart rate, respiratory rate, and noninvasive blood pressure were measured at 15 s, 30 s, and at 1, 2, 3, 4, and 5 min after the test. The overall reaction pattern after the postural change test was mainly sympathetic, and was more pronounced in the STR Group. After the odor test, the overall response was parasympathetic but less pronounced in the STR Group. We, therefore, speculate that neonates who suffer from conditions known to be associated with CIUSTR exhibit a higher adrenergic state with little reserve to counteract stressful situations that may make them more vulnerable.

Congenital pneumonia due to Mycoplasma pneumoniae.

A case of probable vertical transmission of Mycoplasma pneumoniae is presented. The presence of M pneumoniae was demonstrated by the polymerase chain reaction (PCR) in the nasopharyngeal aspirate of a newborn who developed pneumonia shortly after birth. This result was confirmed by performing a second PCR, amplifying another part of the genome of M pneumoniae. It is concluded that M pneumoniae can be added to the long list of pathogens known to cause congenital pneumonia.

Intrauterine versus postnatal transport of the preterm infant: a short-distance experience.

AIM: The purpose of this study was to compare neonatal outcome (mortality, respiratory distress syndrome, intraventricular hemorrhage, necrotising enterocolitis, persisting ductus arteriosus, and septicaemia) after intrauterine transport versus neonatal transport in an area where short-distance transport is the rule. METHODS: The study was retrospective in nature. The files of all neonates delivered between 24 and 34 weeks from 1994 to 1998 and transported intrauterine or postnatally to the Antwerp University Hospital were reviewed. Cases of intrauterine fetal death and mothers discharged before delivery were excluded, as were infants with lethal congenital anomalies. RESULTS: A total of 328 deliveries after intrauterine transport, resulting in 416 neonates and 187 neonates transported postnatally were included. The maximum distance patients had to be transported was 40 km. Placental abruption was more frequent in the mothers of the neonatal transport group (13 vs. 5%, P=0.001). Corticosteroids were administered significantly less in the neonatal transport group (67 vs. 13%, P<0.0001). Preterm rupture of the membranes (36 vs. 20%, P<0.0001), preterm labour (73 vs. 36%, P<0.0001), and pre-eclampsia (10 vs. 7%, P<0.0001) were more frequent in the intrauterine transport group and this group had a lower mean birthweight and gestational age. There was no significant difference for overall neonatal mortality, respiratory distress syndrome, intraventricular hemorrhage, necrotising enterocolitis, persisting ductus arteriosus or septicaemia.

The addition of indomethacin to betamimetics for tocolysis: any benefit for the neonate?

OBJECTIVE: To study the influence on the neonate of indomethacin administered to the mother as an additional tocolytic. STUDY DESIGN: The neonatal outcome in 76 closely matched low birth weight infants was compared retrospectively: those whose mothers received indomethacin together with betamimetics formed the study group, those whose mothers received only betamimetics formed the control group. RESULTS: There was an increased incidence of respiratory distress syndrome (RDS) in the study group (97% versus 45%; P<0.001), an increased need for surfactant use (68% versus 26%; P<0.001) and increased ventilatory support, and an increased incidence of bronchopulmonary dysplasia (BPD) (47% versus 24%; P=0.03). Gestation could not be prolonged significantly by the addition of indomethacin. CONCLUSION: Indomethacin as an additional tocolytic agent was associated with an increased incidence of RDS, surfactant use and BPD but did not significantly prolong gestation.

Ontogeny of epinephrine, norepinephrine, dopamine-beta-hydroxylase, and chromogranin A in the adrenal gland of pigs.

OBJECTIVE: To obtain data on the ontogeny of catecholamines and other chromaffin vesicle components, which could serve as a basis for the study of their role during fetal life in normal and pathologic conditions. DESIGN: Epinephrine, norepinephrine, dopamine-beta-hydroxylase, and chromogranin A contents were measured in the porcine adrenal gland during various stages of gestation. ANIMALS: 934 porcine fetuses representing 22 gestational ages between 43 and 108 days. PROCEDURE: Total homogenates of adrenal glands were extracted and contents of different neurochemical markers were measured, using high-performance liquid chromatography, immunoassays, and western blotting. Immunohistochemical studies also were performed. RESULTS: Epinephrine and norepinephrine contents as a function of gestational age can be represented by a sigmoidal curve. Norepinephrine content rises early in gestation, whereas epinephrine content increases later. Maximal increase was significantly higher for epinephrine content. A progressive appearance of separate epinephrine- and norepinephrine-storing cells was documented. Dopamine-beta-hydroxylase content as a function of gestational age can be adequately represented by a parabolic curve. No quantitative changes in chromogranin A concentration were observed, but western blotting revealed qualitative changes with progressing gestational age. CONCLUSIONS: Important changes occur in catecholamine formation around day 60 of gestation. The sharp increase in epinephrine/norepinephrine contents and the appearance of separate epinephrine- and norepinephrine-storing cells may be related to the progressive splanchnic innervation of the adrenal gland. The presence of chromogranin A early in gestation may indicate its necessity for catecholamine storage.

[Definition and classification of perinatal mortality]. / Problèmes de définition et de classification des décès périnatals.

Analysis of problems related to the classification of perinatal mortality was made possible through the evaluation of data collected from the medical records of nine maternity hospitals in South-Hainaut. Medical records of 135 fetal and early neonatal deaths were investigated. Perinatal mortality statistics were compiled on the basis of five different definitions of perinatal mortality. Depending on which definition was used, perinatal mortality varied between 10.2% and 15.1%. This study shows that reporting of perinatal mortality in hospital registries according to the legal requirement is incomplete. Standard data should be collected for each pregnancy product, on the basis of clearly defined, national and international accepted definitions. It is suggested that the 1975 recommendations of the World Health Organization (International Classification of Diseases, 9th edition), be used for definition and classification of perinatal mortality.

An advisory statement from the Pediatric Working Group of the International Liaison Committee on Resuscitation.

The International Liaison Committee on Resuscitation (ILCOR), with representation from North America, Europe, Australia, New Zealand, Africa, and South America, was formed in 1992 to provide a forum for liaison between resuscitation organizations in the developed world. This consensus document on resuscitation extends previously published ILCOR advisory statements on resuscitation to address the unique and changing physiology of the newly born infant within the first few hours after birth and the techniques for providing advanced life support. After careful review of the international resuscitation literature and after discussion of key and controversial issues, consensus was reached on almost all aspects of neonatal resuscitation, and areas of controversy and high priority for additional research were delineated. Consensus on resuscitation for the newly born infant included the following principles: Personnel trained in the basic skills of resuscitation should be in attendance at every delivery. A minority (fewer than 10%) of newly born infants require active resuscitative interventions to establish a vigorous cry and regular respirations, maintain a heart rate > 100 beats per minute (bpm), and maintain good color and tone. When meconium is present in the amniotic fluid, it should be suctioned from the hypopharynx on delivery of the head. If the meconium-stained newly born infant has absent or depressed respirations, heart rate, or muscle tone, residual meconium should be suctioned from the trachea. Attention to ventilation should be of primary concern. Assisted ventilation with attention to oxygen delivery, inspiratory time, and effectiveness judged by chest rise should be provided if stimulation does not achieve prompt onset of spontaneous respirations and/or the heart rate is < 100 bpm. Chest compressions should be provided if the heart rate is absent or remains < 60 bpm despite adequate assisted ventilation for 30 seconds. Chest compressions should be coordinated with ventilations at a ratio of 3:1 and a rate of 120 "events" per minute to achieve approximately 90 compressions and 30 rescue breaths per minute. Epinephrine should be administered intravenously or intratracheally if the heart rate remains < 60 bpm despite 30 seconds of effective assisted ventilation and chest compression circulation. Common or controversial medications (epineprine, volume expansion, naloxone, bicarbonate), special resuscitation circumstances affecting care of the newly born, continuing care of the newly born after resuscitation, and ethical considerations for initiation and discontinuation of resuscitation are discussed. There was agreement that insufficient data exist to recommend changes to current guidelines regarding the use of 21% versus 100% oxygen, neuroprotective interventions such as cerebral hypothermia, use of a laryngeal mask versus endotracheal tube, and use of high-dose epinephrine. Areas of controversy are identified, as is the need for additional research to improve the scientific justification of each component of current and future resuscitation guidelines.