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Regionalized level III perinatal care was implemented in Poland in 1998, but no comparative analyses of neonatal mortality and morbidity between other European regions and Poland are yet available. Given the large differences in policy and organization of health care between European countries, studying clinical outcomes within this context provides an opportunity to explore the effectiveness of regionalized care. The aim of this analysis was to compare the specific position of neonatal care in Poland with that of other European regions participating in the Models of OrganiSing Access to Intensive Care for very preterm babies (MOSAIC) project. In 1988, there were 18,798 live births in the 11 neonatal units in the Wielkopolska region; in 2003, there were 42,619 live births in the MOSAIC program from 53 neonatal units in the Wielkopolska and Lubuskie regions. There was no change in the rate of very preterm live births between 1988 and 2003, but the mortality rate among infants between 27 and 31 weeks of gestation differed significantly. The in-hospital mortality rate in the two Polish regions was higher in 2003 compared with other MOSAIC participants (35.3%and 17.3%, respectively). There was also a higher rate of congenital malformations, intraventricular hemorrhage, and periventricular leukomalacia. There were also clear differences in organization of perinatal care, with fewer level III centers per 10,000 deliveries in Polish regions compared with other European regions (0.25 and 1.33, respectively) and longer distances of neonatal transport (97 km and 29 km, respectively).

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.

Objective To study the impact of the organisation of obstetric services on the regionalisation of care for very preterm births. Design Cohort study. Setting Ten European regions covering 490 000 live births. Population All children born in 2003 between 24 and 31 weeks of gestation. Method The rate of specialised maternity units per 10 000 total births, the proportion of total births in specialised units and the proportion of very preterm births by referral status in specialised units were compared. Main outcome measure Birth in a specialised maternity unit (level III unit or unit with a large neonatal unit (at least 50 annual very preterm admissions). Results The organisation of obstetric care varied in these regions with respect to the supply of level III units (from 2.3 per 10 000 births in the Portuguese region to 0.2 in the Polish region), their characteristics (annual number of deliveries, 24 hour presence of a trained obstetrician) and the proportion of all births (term and preterm) that occur in these units. The proportion of very preterm births in level III units ranged from 93 to 63% in the regions. Different approaches were used to obtain a high level of regionalisation: high proportions of total deliveries in specialised units, high proportions of in utero transfers or high proportions of high-risk women who were referred to a specialised unit during pregnancy. Conclusion Consensus does not exist on the optimal characteristics of specialised units but regionalisation may be achieved in different models of organisation of obstetric services.

Item does not contain fulltext BACKGROUND: In 2006, the Dutch guideline for active treatment of extremely preterm neonates advised to lower the gestational age threshold for active intervention from 26 0/7 to 25 0/7 weeks gestation. OBJECTIVE: To evaluate the association between the guideline modification and early neonatal outcome. DESIGN: National cohort study, using prospectively collected data from The Netherlands Perinatal Registry. PATIENTS: The study population consisted of 9713 infants with a gestational age between 24 0/7 and 29 6/7 weeks, born between 2000 and 2011. Three gestational age subgroups were analysed: 24 0/7 to 24 6/7 weeks (n=269), 25 0/7 to 25 6/7 weeks (n=852) and 26 0/7 to 29 6/7 weeks (n=8592). MAIN OUTCOME MEASURES: Neonatal intensive care unit (NICU) admission, live births, neonatal in-hospital mortality, morbidity and favourable outcome (no mortality or morbidity) before (2000-2005; period 1) and after (2007-2011; period 2) introduction of the modified guideline, using chi(2) tests and univariable and multivariable logistic regression analyses. RESULTS: In the second period, the proportion of live births and NICU admissions increased and the proportion of neonatal and in-hospital mortality decreased significantly in all subgroups. Morbidity in surviving infants of 25 weeks increased significantly, although the association between guideline modification and morbidity became non-significant after case-mix adjustment. Overall, favourable outcome did not change significantly after guideline modification in all subgroups when adjusted for variation in case-mix. CONCLUSIONS: Overall, the trend in mortality gradually declined at all gestational ages, starting before 2006. This suggests that the guideline modification was a formalisation of already existing daily practice.

(1) To describe the epidemiology of neonatal group B streptococcal (GBS) disease over five years (1997-2001) in the Netherlands, stratified for proven and probable sepsis and for very early (12 h), late early (12 h -7 days) and late (7-90 days) onset sepsis. (2) To evaluate the effect of the introduction in January 1999 of guidelines for prevention of early onset GBS disease based on risk factors.Data on cases were collected in collaboration with the Dutch Paediatric Surveillance Unit and corrected for under-reporting by the capture-recapture technique.Total incidence of proven very early onset, late early onset and late onset GBS sepsis was 0.32, 0.11 and 0.14 per 1000 live births, respectively, and of probable very early onset, late early onset and late onset GBS sepsis was 1.10, 0.18 and 0.02 per 1000 live births, respectively. Maternal risk factors were absent in 46% of the proven early onset cases. Considerably more infants with proven GBS sepsis were boys. 64% of the infants with proven very early onset GBS sepsis were first born compared with 47% in the general population. After the introduction of guidelines the incidence of proven early onset sepsis decreased considerably from 0.54 per 1000 live births in 1997-8 to 0.36 per 1000 live births in 1999-2001. However, there was no decrease in the incidence of meningitis and the case fatality rate in the first week of life. The incidence of late onset sepsis also remained unchanged.After the introduction prevention guidelines based on risk factors there has been a limited decrease in the incidence of proven early onset GBS sepsis in the Netherlands. This study therefore recommends changing the Dutch GBS prevention guidelines.

Perinatal mortality in very preterm infants has decreased by up to 50% during the last decades. Studies of changes of long-term outcome are inconclusive. We studied the visual, auditory, neuromotor, cognitive and behavioural development of two geographically defined populations of very preterm, singleton infants, born in 1983 and in 1993, and analysed the relationship between perinatal risk factors and outcomes. The incidence of disabling cerebral palsy increased from 6.0% to 11.1% (OR 2.45 [95% CI 1.11, 5.38]). Impaired vision and strabismus decreased significantly, presumably by continuous monitoring of pO2. Hearing problems, the need for special education and the incidence of behavioural problems did not change over time. The proportion of children who showed optimal performance in every developmental domain increased from 29.5% in 1983 to 43.2% in 1993. Cerebral palsy was associated with male gender in 1983, with low Apgar score and intraventricular haemorrhage in 1993, and with seizures both in 1983 and in 1993. The intensiveness of neonatal treatment has increased, leading to the survival of many more healthy infants, but at the cost of more infants with cerebral damage. Modern perinatal care is no longer limited by the devastating effects of pulmonary problems as it was in the past, but fails to safeguard cerebral integrity in very preterm infants. © 2007 The Authors.

Contains fulltext : 49100.pdf (Publisher’s version ) (Closed access) OBJECTIVE: The aim of the present study was to investigate the pharmacokinetic profile of tramadol hydrochloride in neonates, born from mothers who underwent analgesia with tramadol for the relief of labour pain.METHODS: Intramuscular tramadol (100--250 mg) was administered to 22 mothers giving birth who requested pain relief. At the time of birth (1.5--6.0 h after last tramadol dose), maternal and umbilical blood samples were taken. Another venous blood sample was drawn from each neonate, and at the same time from its mother, at 1, 2, 3, 6 or 12 h post-partum, providing the data for a population pharmacokinetic evaluation of tramadol and its metabolite M1. Routine APGAR scores and a standard neurological and adaptive capacity test were considered for evaluation of the effect of tramadol on the neonates.RESULTS: Serum tramadol concentrations at the time of birth (t(0)) were 243+/-102 ng/ml (mean+/-SD, umbilical vein), 258+/-103 ng/ml (umbilical artery) and 250+/-113 ng/ml (maternal vein). Serum M1 concentrations were 52+/-27 ng/ml (umbilical vein), 47+/-24 ng/ml (umbilical artery) and 56+/-21 ng/ml (maternal vein). The two-compartment type elimination profiles during the first 12 h post-partum for neonates (and mothers, respectively) were characterised by terminal t(1/2) (tramadol)=7.0 (7.2) h and t(1/2) (metabolite M1)=85.0 (5.5) h.CONCLUSION: The intramuscular application of tramadol in birth-giving mothers almost freely reaches the neonate, confirming a high degree of placental permeability. The neonates already possess the complete hepatic capacity for the metabolism of tramadol into its active metabolite. However, the renal elimination of the active tramadol metabolite M1 is delayed, in line with the slow maturation process of renal function in neonates. Despite this difference in pharmacokinetics between neonates and adults, the intramuscular application of tramadol at the recommended dosage range during delivery appears to effective in the relief of labour pain.

Item does not contain fulltext Group B streptococcal (GBS) infection is still an important cause of morbidity and mortality in newborn infants. In The Netherlands, there are no published data on the incidence of neonatal GBS infection. We collected data of all infants with GBS disease during the first 3 months of life, as reported to the Dutch Paediatric Surveillance Unit (DPSU) during a period of 2 years (1997-98). Neonates with early-onset GBS disease (both sepsis and probable sepsis) were included for further analysis. The level of completeness of the DPSU data was determined by capture-recapture techniques. The incidence of early-onset GBS disease in The Netherlands in 1997-98, as calculated from the DPSU data, was 0.9 per 1000 live births. After correction for under-reporting, the incidence was estimated to be 1.9 per 1000 live births. The case fatality rate of early-onset GBS disease was only 5%. Despite the decrease in the mortality rate during the last decades, it remains a serious condition with potential irreversible brain damage. Therefore, formal guidelines for the prevention of neonatal early-onset GBS disease in The Netherlands were introduced in 1999. The data collected in this study may serve as baseline data for evaluation of the effect of these guidelines.

Objective. End-of-life decisions for newborn infants are usually made with the consent of parents as well as physicians, but may occasionally involve disagreement about which decision is in the best interest of the child. Our study was aimed at providing an empirical background for the ethical discussion on the parent's versus the physician's role in decision-making.Methods. We conducted face-to-face interviews with a stratified sample of pediatricians. The response rate was 99%. The most recent decisions in newborn infants to hasten death or not prolong life and the most recent cases in which such decisions were not made because either the parents or the physician objected were comprehensively discussed.Results. Decisions to hasten death or not prolong life were usually made after discussing it with parents and did not occur while parents were known to disagree. Situations in which an end-of-life decision was not made because parents did not consent predominantly involved infants with complications of prematurity (24%) or perinatal asphyxia (40%), whereas situations in which parents requested an end-of-life decision that was not acceded to by the pediatrician involved Down syndrome as the main diagnosis in 43% and as a concurrent diagnosis in 21%. Pediatricians afterwards often expressed feelings of discontent about situations in which there had been disagreement with parents.Conclusions. The opinion of parents about which medical decision is in the best interest of their child is for pediatricians only decisive in case it invokes the continuation of treatment. The principle of preserving life is abandoned only when the physician feels sufficiently sure that the parents agree that such a course of action is in the best interest of the child.

The objective of this study was to investigate the influence of blood transfusion and haemodilution on cerebral oxygenation and haemodynamics in relation to changes in cerebral blood flow velocity (CBFV) and other relevant physiological variables in newborn infants. Thirteen preterm infants with anaemia (haematocrit0.33) and ten infants with polycythaemia (haematocrit0.65) were studied during blood transfusion and haemodilution respectively using adult red blood cells and partial plasma exchange transfusion. Changes in cerebral concentrations of oxyhaemoglobin (cO2Hb), deoxyhaemoglobin (cHHb), total haemoglobin (ctHb), (oxidized-reduced) cytochrome aa3 (cCyt.-aa3) were continuously measured using near infrared spectrophotometry throughout the whole procedure. Simultaneously, changes of mean CBFV in the internal carotid artery were continuously measured using pulsed Doppler ultrasound. Heart rate, transcutaneous partial pressure of oxygen and carbon dioxide, and arterial O2 saturation were continuously and simultaneously measured. Blood transfusion resulted in increase of cO2Hb, cHHb, ctHb and red cell transport (product of CBFV and haematocrit), whereas CBFV decreased. The increase of cO2Hb exceeded that of cHHb, reflecting improvement of cerebral O2 supply. Haemodilution resulted in a decrease of cO2Hb, cHHb and ctHb, whereas CBFV increased. Red cell transport was unchanged. The decrease of cO2Hb exceeded that of cHHb, reflecting decreased cerebral O2 supply. cCyt.aa3 decreased after blood transfusion and remained unchanged after haemodilution, but the reliability of these results is uncertain. With the exception of a small, but significant increase in transcutaneous partial pressure of oxygen after blood transfusion, the other variables showed no changes. Each blood withdrawal during exchange transfusion resulted in only a significant increase in heart rate without changes in the other variables measured, suggesting unchanged cerebral perfusion.In newborn infants blood transfusion in anaemia results in improvement of cerebral oxygenation, but haemodilution in polycythaemia does not improve cerebral oxygenation despite possible improvement of cerebral perfusion.

Summary Background Advances in neonatal intensive care have lowered the neonatal death rate. There are still some severely ill neonates and infants, however, for whom the application of all possible life-prolonging treatment modalities may be questioned. Methods We did two studies in the Netherlands. In the first we sent questionnaires to physicians who had attended 338 consecutive deaths (August–November, 1995) within the first year of life (death-certificate study), and in the second we interviewed 31 neonatologists or paediatric intensive-care specialists and 35 general paediatricians. The response rates were 88% and 99%, respectively. Findings In the death-certificate study, 57% of all deaths had been preceded by a decision to forgo life-sustaining treatment; this decision was accompanied by the administration of potentially life-shortening drugs to alleviate pain or other symptoms in 23%, and by the administration of drugs with the explicit aim of hastening death in 8%. A drug was given explicitly to hasten death to neonates not dependent on life-sustaining treatment in 1% of all death cases. No chance of survival was the main motive in 76% of all end-of-life decisions, and a poor prognosis was the main motive in 18%. The interview study showed that parents had been involved in making 79% of decisions. The physicians consulted colleagues about 88% of decisions. Most paediatricians favoured formal review of medical decisions by colleagues together with ethical or legal experts. Interpretation Death among neonates and infants is commonly preceded by medical end-of-life decisions. Most Dutch paediatricians seem to find prospects for survival and prognostic factors relevant in such decisions. Public control by a committee of physicians, paediatricians, ethicists, and legal experts is widely endorsed by paediatricians.

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Within the framework of the broader ethical discussion on end-of-life decision making in neonatology and the need to obtain more quantifiable data, we performed a multicenter study in four Dutch neonatal intensive care units. All infants who died in these units in 1993 were included in the study. Aside from cases in which foregoing treatment was not under discussion, cases in which death appeared inevitable (A cases) and cases in which foregoing treatment because of extremely poor prognosis was the decisive factor (B cases) were distinguished. A total of 181 neonatal deaths occurred. Thirty-five infants died even after full continuation of treatment. In 98 A cases and 48 B cases, which together represented 81% of all deaths, treatment was foregone either because the infants had no chance to survive or because of extremely poor prognoses. In these cases, the medical team ultimately achieved consensus of opinion, although in some instances several sessions were required. In three cases, the parents did not agree with the team advice. In one A case death appeared inevitable. In two B cases, the parents' wish to continue treatment was followed. In a large majority of B cases, the decisions to forego treatment were based on the presence of severe cerebral damage. In A cases there was no real choice because death appeared inevitable. However, in B cases neonatologists were obliged to determine whether continuation of treatment was justifiable or if withdrawal of treatment in view of extremely poor prognoses was preferred.

Objective. To investigate the cerebrovascular response to changes in arterial CO2 tension during extracorporeal membrane oxygenation (ECMO) in normoxaemic and hypoxaemic piglets. Methods. Four groups of six anaesthetized, paralysed and mechanically ventilated piglets: group 1 - normoxaemia without ECMO, group 2 - ECMO after normoxaemia, group 3 - hypoxaemia without ECMO, and group 4 -ECMO after hypoxaemia, were exposed successively to hypercapnia and hypocapnia. Changes in cerebral concentrations of oxyhaemoglob in (cO2Hb), deoxyhaemoglobin (cHHb), (oxidized - reduced) cytochrome aa3 (cCyt. aa3) and blood volume (CBV) were continuously measured using near infrared spectrophotometry. Heart rate, arterial O2 saturation, arterial blood pressure, central venous pressure, intracranial pressure (ICP) and left common carotid artery blood flow (LCaBF) were measured simultaneously. Results. Hypercapnia resulted in increased CBV, cO2Hb and ICP in all groups, while cHHb was decreased. No changes in LCaBF were found. Hypocapnia resulted in decreased cO2Hb and increased cHHb except in group 3. LCaBF decreased in all groups except group 2. CBV decreased only in groups 2 and 4. No effect on ICP was observed in any of the groups. The other variables showed no important changes either during hypercapnia or hypocapnia. ECMO after hypoxaemia resulted in a greater response of cO2Hb and cHHb during hypocapnia. The effect of hypercapnia on CBV while on ECMO was greater than without ECMO. Conclusion. Since cerebrovascular reactivity to CO2 remains intact during ECMO in piglets, it is important to keep arterial CO2 tension stable and in normal range during clinical ECMO.

The effect of interruption of positive end expiratory pressure (PEEP) on cerebral blood flow velocity (CBFV) and CBF fluctuation (CBFF) in the internal carotid arteries and on heart rate, restlessness and wakefulness has been studied in 17 mechanically ventilated neonates with RDS. A decrease in CBFV was found, but no significant change in CBFF. Multiple regression analysis showed that the decrease in CBFV is less pronounced if the PEEP interruption is accompanied by restlessness. It further appeared that the decrease in CBFV is more pronounced if CBFV is high, the ductus arteriosus is patent, or RDS follows a complicated course. These findings indicate that PEEP supports CBF, probably by a decrease in ductal stealing from the brain. Therewith PEEP protects against cerebral hypoperfusion which is one of the major risks in RDS and immaturity. Furthermore, our findings suggest that the decrease in CBF during PEEP interruption is moderated by restlessness and accentuated by brain damage.

Objective:Group B streptococcus (GBS,Streptococcus agalactiae) is an important cause of neonatal sepsis. Prevention is possible by intrapartum screening for maternal GBS carriership and antimicrobial treatment of colonized women with risk factors during labor. The conflicting results of diagnostic performance are reported both for the newly developed rapid GBS antigen tests and Gram's stain.Methods:The value of Gram's stain in GBS screening was investigated prospectively in 1,020 women. Intrapartum Gram's stains of the cervix from these women and of the introitus from 510 of them were compared with cultures of the cervix, introitus, and anorectum in a semiquantitative way.Results:The sensitivities of the cervical and introital Gram's stains were 25% and 31%, respectively, and the specificities 99% and 98%, respectively. Higher sensitivities (52% and 44%, respectively) were found in heavily colonized parturients. No significant influence of rupture of the membranes was detected. There was a poor correlation between the number of gram-positive cocci in the Gram's stain and the growth density.Conclusions:We do not recommend the routine use of the Gram's stain for intrapartum GBS detection because of both the limited sensitivity and positive predictive value.

Objectives: To evaluate the sensitivity of intrapartum screening for group B streptococcal (GBS) colonization and to compare 4 rapid GBS antigen tests in vitro. Design: Two swabs of the lower vagina of 769 parturients were taken; one swab was cultured, the other was frozen at −70 °C until antigen testing with the Group B Strep Test (Quidel) of the culture positive samples was performed. The Quidel test was then compared with 3 other rapid GBS antigen tests in vitro: Wellcogen Strep B (Wellcome Diagnostics), Slidex meningite Strepto B (bioMerieux) and ICON Strep B (Hybritech). The supernatant of 29 GBS cultures in Todd-Hewitt broth was tested in bacterial concentrations of 106, 107, and 108 Colony-Forming Units (CFU)/ml, respectively. Results: Lower vagina GBS carrier rate was 13.4% (103769) and heavy colonization (growth density 3 and 4 on blood agar plates) was found in 5.2% (40769). The Group B Strep Test detected 11% (11103) of GBS carriers, with a sensitivity for heavy colonization of 25% (1040). In vitro none of the tests scored positively with a concentration of 106 CFU/ml, while with 107 CFU/ml the enzyme immunoassay tests (Quidel, Hybritech) were more sensitive (McNemar test, P < 0.05) than the latex agglutination tests (Wellcome Diagnostics, bioMerieux). Conclusions: Although in vitro the enzyme immunoassay tests are more sensitive than the latex agglutination tests, sensitivity in vivo is too low to recommend the use of rapid antigen tests for general screening.

The influence of maturation, sleep state and respiration on heart rate variability was studied in 16 spontaneously breathing preterm infants (< 33 weeks). ECG, respiratory impedance curve and movements were recorded four times a day, during the first three days of life. The power content of selected frequency bands of the R-R interval power spectrum, as well as respiratory frequency and breath amplitude oscillation frequency, were calculated for 3-min periods. An increase in low-frequency heart rate variability with gestational age was found. High-frequency variability increased during early postnatal life. Sleep state influenced very low-frequency heart rate variability. The amount of respiratory sinus arrhythmia and breath amplitude sinus arrhythmia was determined mainly by respiratory rate and breath amplitude oscillation frequency, respectively. The influences of gestational and postnatal age on heart rate variability might be due to an increase in sympathetic tone before birth and a change in parasympathetic-sympathetic balance after birth. Respiration has an important influence on heart rate variability, even in very preterm infants.

Contains fulltext : 96519.pdf (Publisher’s version ) (Closed access) Birth weight and longitudinal growth in the first 4 years of life of term singletons conceived with the use of IVF and intracytoplasmic sperm injection (ICSI) were compared with those of naturally conceived singletons. Although IVF and ICSI singletons had a statistically significantly lower birth weight than naturally conceived singletons, the average individual weight curves showed that this difference was lost before the age of 4 years in all subgroups: IVF, ICSI, boys, and girls.

Auteur(s) : Marjolein AC Mattheij1, Louis AA Kollee2, Cecile JM Buzing3, Marieke MB Seyger4 1Department of Paediatrics, Jeroen Bosch Hospital, PO box 90153, 5200 ME ’s-Hertogenbosch, The Netherlands 2Department of Paediatrics, Radboud University Nijmegen Medical Centre, PO box 9101, 6500 HB Nijmegen, The Netherlands 3Department of Paediatrics, Canisius Wilhelmina Hospital, PO box 9015, 6500 GS Nijmegen, The Netherlands 4Department of Dermatology, Radboud University Nijmegen [...]

To investigate the influence of maturational and physiological factors on heart rate variability in spontaneously breathing very preterm infants (n = 29) a multiparametric study was performed during the first 3 days of life in infants born at a gestational age below 33 weeks. Four times a day, RR-intervals, respiration curve and rate, transcutaneously measured blood gases and observed body movements were recorded while the infants were asleep. All data were stored simultaneously in a micro-computer. Non-invasively measured blood pressure and patency of the ductus arteriosus were documented as well. Four sets of short- (STV) and long term variability (LTV) indices were calculated. Both STV and LTV appeared to be significantly influenced by conceptional and postnatal age in the appropriate for gestational age infants. LTV was influenced by the behavioural state and body movements. During state coincidence 2 ('active sleep') LTV was influenced by respiratory rate and the variations in transcutaneous PO2. An effect of blood pressure or ductus patency could not be demonstrated.

Better perinatal care has led to better survival of very preterm children, but may or may not have increased the number of children with cerebral and pulmonary morbidity. We therefore investigated the relationship between changes in perinatal care during one decade, and short-term outcome in very preterm infants. Perinatal risk factors and their effects on 28-day and in-hospital mortality, and on intraventricular haemorrhage and bronchopulmonary dysplasia (BPD) in survivors, were compared in two surveys of very preterm singleton infants in the Netherlands. Between 1983 and 1993, 28-day mortality decreased from 52.1% to 31.8% in infants of 25-27 weeks' gestation and from 15.2% to 11.3% in infants of 28-31 weeks' gestation. The incidence of intraventricular haemorrhage in survivors did not change (44.4% and 43.3% in infants of 25-27 weeks' gestation, and 29.0% and 24.0% in infants of 28-31 weeks' gestation). The incidence of BPD in survivors increased from 40.3% to 60.0% in infants of 25-27 weeks' gestation and remained similar in infants of 28-31 weeks' gestation (8.5% and 9.8% respectively). In multivariable analysis, higher mortality was associated with congenital malformation, low gestational age, low birthweight, no administration of steroids before birth, low Apgar scores and intraventricular haemorrhage, in 1983 as well in 1993, and with male gender in 1993. The effect of maternal age on mortality diminished significantly between 1983 and 1993. Intraventricular haemorrhage in surviving children was associated with low gestational age and artificial ventilation, both in 1983 and in 1993. The effect of artificial ventilation on the incidence of intraventricular haemorrhage diminished significantly between 1983 and 1993. BPD was associated with low gestational age and artificial ventilation, both in 1983 and in 1993, and with low birthweight and caesarean section in 1993. We conclude that the better survival of very preterm infants, especially of those of 25-27 weeks' gestation, has been accompanied by a similar incidence (and thus with an increased absolute number) of children with intraventricular haemorrhage and by an increased incidence of children with BPD. © 2007 The Authors.

OBJECTIVE. Young adults who were born very preterm or with a very low birth weight remain at risk for physical and neurodevelopmental problems and lower academic achievement scores. Data, however, are scarce, hospital based, mostly done in small populations, and need additional confirmation. METHODS. Infants who were born at RESULTS. Of 959 surviving young adults, 74% were assessed and/or completed the questionnaires. Moderate or severe problems were present in 4.3% for cognition, 1.8% for hearing, 1.9% for vision, and 8.1% for neuromotor functioning. Using the Health Utility Index and the London Handicap Scale, we found 2.0% and 4.5%, respectively, of the young adults to have ≥3 affected areas in activities and participation. Special education or lesser level was completed by 24%, and 7.6% neither had a paid job nor followed any education. Overall, 31.7% had ≥1 moderate or severe problems in the assessed areas. CONCLUSIONS. A total of 12.6% of young adults who were born very preterm and/or with a very low birth weight had moderate or severe problems in cognitive or neurosensory functioning. Compared with the general Dutch population, twice as many young adults who were born very preterm and/or with a very low birth weight were poorly educated, and 3 times as many were neither employed nor in school at age 19.

Contains fulltext : 50886.pdf (Publisher’s version ) (Closed access) BACKGROUND: Children born very preterm (VP

Contains fulltext : 35391.pdf (Publisher’s version ) (Closed access) We studied the characteristics of strains isolated from neonates with group B streptococci sepsis and meningitis, before and after the introduction of antibiotic prophylaxis in The Netherlands. In 1999, 1 year after this introduction the serotype and genotype distribution and the susceptibility patterns of the GBS strains had not changed. Penicillins remain drugs of first choice to prevent and treat neonatal GBS disease.

Contains fulltext : 57784.pdf (Publisher’s version ) (Closed access) OBJECTIVE: To present the views of a representative sample of neonatal doctors and nurses in 10 European countries on the moral acceptability of active euthanasia and its legal regulation. DESIGN: A total of 142 neonatal intensive care units were recruited by census (in the Netherlands, Sweden, Hungary, and the Baltic countries) or random sampling (in France, Germany, Italy, Spain, and the United Kingdom); 1391 doctors and 3410 nurses completed an anonymous questionnaire (response rates 89% and 86% respectively). MAIN OUTCOME MEASURE: The staff opinion that the law in their country should be changed to allow active euthanasia "more than now". RESULTS: Active euthanasia appeared to be both acceptable and practiced in the Netherlands, France, and to a lesser extent Lithuania, and less acceptable in Sweden, Hungary, Italy, and Spain. More then half (53%) of the doctors in the Netherlands, but only a quarter (24%) in France felt that the law should be changed to allow active euthanasia "more than now". For 40% of French doctors, end of life issues should not be regulated by law. Being male, regular involvement in research, less than six years professional experience, and having ever participated in a decision of active euthanasia were positively associated with an opinion favouring relaxation of legal constraints. Having had children, religiousness, and believing in the absolute value of human life showed a negative association. Nurses were slightly more likely to consider active euthanasia acceptable in selected circumstances, and to feel that the law should be changed to allow it more than now. CONCLUSIONS: Opinions of health professionals vary widely between countries, and, even where neonatal euthanasia is already practiced, do not uniformly support its legalisation.

Item does not contain fulltext BACKGROUND: Long term follow up shows a high frequency of developmental disturbances in preterm survivors of neonatal intensive care formerly considered non-disabled. AIMS: To develop and validate an assessment tool that can help paediatricians to identify before 6 years of age which survivors have developmental disturbances that may interfere with normal education and normal life. METHODS: A total of 431 very premature infants, mean gestational age 30.2 weeks, mean birth weight 1276 g, were studied at age 5 years. Children with severe handicaps were excluded. The percentage of children with a correctly identified developmental disturbance in the domains cognition, speech and language development, neuromotor development, and behaviour were determined. RESULTS: The follow up instrument classified 67% as optimal and 33% as at risk or abnormal. Of the children classified as at risk or abnormal, 60% had not been identified at earlier follow up assessments. The combined set of standardised tests identified a further 30% with mild motor, cognitive, or behavioural disturbances. The paediatrician's assessment had a specificity of 88% (95% CI 83-93%), a sensitivity of 48% (95% CI 42-58%), a positive predictive value of 85% (95% CI 78-91%), and a negative predictive value of 55% (95% CI 49-61%). CONCLUSIONS: Even after standardised and thorough assessment, paediatricians may overlook impairments for cognitive, motor, and behavioural development. Long term follow up studies that do not include detailed standardised tests for multiple domains, especially fine motor domain, may underestimate developmental problems.

Restrictive dermopathy is a rare autosomal recessive lethal skin dysplasia. It has been assumed that the characteristic morphologic abnormalities should allow a reliable prenatal diagnosis on fetal skin biopsies at about 20 weeks pregnancy. We report on a false-negative prenatal diagnosis.

Objective: To describe the frequency, background, and impact of decisions to give analgesic or other drugs that may, intentionally or unintentionally, shorten the life-span of severely ill neonates. Setting: The Netherlands. Design: Retrospective, cross-sectional study. Patients: Questionnaires were mailed in The Netherlands to physicians reporting 338 consecutive deaths of infants under 1 yr of age from August through November 1995. Interventions: None. Measurements and Main Results. Questions were asked about medical end-of-life decisions preceding the death of the infant and about the decision-making process. Potentially life-shortening drugs, mostly opioids, were given in 37% of all deaths. The estimated effect in terms of the shortening of life was

Extracorporele membraanoxygenatie (ecmo) wordt toegepast bij pasgeborenen met hoge mortaliteitskans bij ernstige cardiorespiratoire insufficientie. ecmo verbetert de overleving van deze kinderen. Na ecmo-behandeling bestaat de morbiditeit vooral uit voedingsstoornissen, gestoorde groei, obstructief longlijden en visus en gehoorstoornissen. Voor wat betreft de neuromotore en cognitieve ontwikkeling zijn er geen studies met een adequate controle groep. Gezien de mate van ziek zijn van deze kinderen voor de ecmo-behandeling lijkt de ontwikkeling echter bemoedigend.

Rehospitalization rates of very preterm infants because of reasons that are related to neonatal morbidity states can be decreased with further improvement of neonatal intensive care provided. Conclusion: Analysis of rehospitalization data should be included in follow-up programmes as a contribution to the development of strategies to improve neonatal care and the ultimate outcome for very-low-birthweight infants.

The objective of this study was to compare the effect of extracorporeal membrane oxygenation (ECMO) on cerebral oxygenation and hemodynamics in normoxemic and hypoxemic piglets. Six hypoxemic and six normoxemic piglets were put on venoarterial ECMO after cannulation of the right common carotid artery and external jugular vein with careful priming to avoid hemodilution. Changes in cerebral concentrations of oxyhemoglobin (cO2Hb), deoxyhemoglobin (cHHb), (oxidized-reduced) cytochrome aa3 (cCyt.aa3), and blood volume (CBV) were continuously measured by near infrared spectrophotometry. Heart rate, arterial O2 saturation (SaO2), arterial blood pressure, pulsatility ratio of systemic circulation (calculated as systolic-diastolic/mean arterial blood pressure), central venous pressure, intracranial pressure, and left common carotid artery blood flow (LCaBF) were simultaneously measured. We found that the cannulation procedure resulted in increased CBV, cHHb, and LCaBF in both groups. At 60 and 120 min after starting ECMO, the values of cO2Hb, CBV, and LCaBF in both groups were significantly higher than precannulation values, while the pulsatility ratio decreased. In the hypoxemic groups cHHb decreased and SaO2 increased as well. No significant changes of other variables were found. Between hypoxemic and normoxemic groups no significant differences in the response of CBV and LCaBF at 60 and 120 min were found. We conclude that in piglets cannulation for ECMO resulted in cerebral venous congestion and compensated increase in LCaBF. After starting ECMO, the cerebral O2 supply increased due to increased arterial O2 content. It was accompanied by similar increase of CBV in both groups, probably as a result of hyperperfusion, which seems to be related to the ECMO procedure itself.

Our purpose was to determine the significance of an umbilical artery pH7.00 in relation to neonatal morbidity and mortality.Between 1986 and 1993 acid-base assessment of the umbilical artery was performed routinely in 10,699 deliveries. In a retrospective cohort study 84 nonanomalous neonates with an umbilical artery pH7.00 were individually matched with 84 neonates with an umbilical artery pH7.24. Matched variables included year of delivery, gender, parity, maternal age, delivery mode, fetal presentation, gestational age, and birth weight. Differences in morbidity between the two groups during the neonatal period (until 28 days after delivery) were investigated.Neonates with an umbilical artery pH7.00 versus7.24 showed significant differences in the following: neonatal condition directly post partum; neurologic, respiratory, cardiovascular, and gastrointestinal complications; and neonatal intensive care unit admissions. No significance was found in renal dysfunction and mortality rate. The proportion of premature infants (37 weeks) was 17% in both groups. In the acidotic group a 1-minute Apgar scoreor = 3 and a 5-minute Apgar score7 was predictive for neonatal complications.Severe intrapartum asphyxia, quantified by an umbilical artery pH7.00, poses a threat to the neonate's health.

This study, involving five level III neonatal intensive care units, investigated whether there are any differences between parental grief following the death of a newborn twin and parental grief following the death of a newborn singleton. A total of 142 parents were examined using the Perinatal Grief Scale (PGS): 72 who had lost a newborn twin and 70 matched controls who had lost a newborn singleton 0.5-3.5 years previously. We found that bereaved twin parents did not differ in grief reactions from bereaved singleton parents (PGS: F = 0.00, p = 0.962). This held true both for the short and the long term (F = 0.13, p = 0.721). Mothers showed more grief than fathers (F = 8.16, p = 0.005). In conclusion, grief in bereaved twin parents should be taken as seriously as grief in bereaved singleton parents. The present guidelines regarding care for the latter ought to be adapted to meet the needs of the former.

On a passe en revue retrospectivement tous les cas prouves de septicemie a streptocoque du groupe B (GBS) precoce dans une unite de soins intensifs neonatals entre 1985 et 1993 pour determiner la morbidite et mortalite. En outre, nous avons evalue les facteurs de risque de meme que les facteurs prognostiques. Les donnees supplementaires ont ete obtenues par des dossiers medicaux ou par une questionnaire rempli par les parents. Soixante-dix-huit patients souffrants de GBS precoce ont ete identifie. Le taux de mortalite total etait de 23%. Tous les 5 patients (6,5%) souffrants de meningite sont morts. En 60 cas sur 73 (82%) au moins un des facteurs de risque examines a ete present: prematurite, des symptomes d'infection pendant la grossesse et une rupture prolongee des membranes (tableau I). Le faible poids a la naissance n'etait pas un facteur de risque independant (fig. 2). Nous avons obtenu des donnees supplementaires sur 44 des 60 survivants (73%) apres au moins un an (tableau Il). A peu pres 30% d'entre-eux souffrait de suites: les plus importantes etaient des spasticites et developpement psychomoteur retarde. Dans 42% des patients qui montraient des symptomes d'infection GBS dans les premiers 6 heures apres la naissance, se sont presentes des suites. Il n'y avait pas de suites parmi les patients ou se sont presentes des symptomes apres 6 heures. Tous les 9 enfants avec endommagement cerebral severe montraient des symptomes peu apres la naissance. La mortalite et le taux des sequels etaient superieurs parmi les enfants nes prematurement ou avec un score d'Apgar a 5 minutes moins de 7. Le traitement prompt a fait baisser la mortalite, mais n'a pas reduit les sequels. La septicemie GBS provoque toujours une mortalite significative. En meme temps, parmi les survivants un nombre substantiel reste endommage. Il est crucial de rester vigilant a l'infection GBS pour assurer le traitement prompt et pour avoir des bons resultats.

To study the influence of artificial ventilation rate on neonatal heart rate variability (HRV), ECG and respiratory impedance curves were recorded four times a day in 20 preterm infants (< 3 3 wk) during the first 3 d after birth while the infants were ventilated at a wide range of ventilator rates. The contents o f selected frequency bands within the R-R interval power spectrum were calculated for 3-min periods. Respiratory distress syndrome severity was assessed at each measurement. Respiratory sinus arrhythmia (RSA) induced by the ventilator appeared to mimic spontaneous RSA. As in spontaneous respiration, the amount of RSA (power in a frequency band around the respiratory rate) increases as the ventilation rate decreases. This phenomenon is most probably due to entrainment with baroreflex-related fluctu­ ations in the heart rate. Although the artificial ventilation rate influences RSA and thus high-frequency HRV ? an increase in respiratory distress syndrome severity results in a decrease in low-frequency HRV. Thus, the attenuation of low-frequency HRV by respiratory distress syndrome is not likely to be due to artificial ventilation. (Pediatr Res 37: 124-130, 1995)

The objective of this study was to investigate changes of cerebral oxygenation and hemodynamics related to opening of the bypass bridge during veno-arterial extracorporeal membrane oxygenation (ECMO). Ten newborn infants and 12 piglets were studied during opening of the bridge for 10 and 1 s, respectively. Changes in cerebral concentration of oxyhemoglobin (c O2Hb), deoxyhemoglobin (c HHb), (oxidized-reduced) cytochrome aa3 (c Cyt.aa3), and blood volume (CBV) were continuously measured by near infrared spectropbotometry. Heart rate, arterial O2 saturation (s aO2), and mean arterial blood pressure (MABP) were measured simultaneously. In the piglets, central venous pressure (CVP), intracranial pressure (ICP), and left common carotid artery blood flow (CaBF) were also measured. Opening of the bridge for 10 s in the infants resulted in a significant decrease in MABP, s aO2, and c O2Hb, whereas c HHb increased. CBV did not change significantly. In piglets biphasic changes were observed for MABP, CaBF, c O2Hb, and CBV, showing an initial decrease followed by a smaller increase. c HHb and CVP showed reverse biphasic changes. ICP increased but s aO2 was unchanged. In all cases heart rate and c Cyt.aa3 did not change significantly. Opening of the bridge for 1 s resulted in minor changes in only a few variables. In conclusion, opening of the bridge resulted in a decrease of CBV and cerebral O2 supply due to a decrease of cerebral blood flow, followed by a compensatory increase of cerebral O2 extraction and vasodilatation. The return of oxygenated blood after reclosing resulted in an increase of CBV with overcompensation of cerebral O2 supply.

Objective: To evaluate the effect of vaginal disinfection with chlorhexidine gel during labor on vertical transmission of group B streptococcus, as a method to prevent vertical transmission and subsequent neonatal early onset group B streptococcal disease. Study Design: A prospective study with randomization of 1020 parturients to one of three groups as soon as labor started. In all parturients, anus, introitus and cervix were cultured semiquantitatively. Two groups were treated double-blindly with 10 ml of either a 0.3% chlorhexidine gel or a placebo gel, applicated around the portio and into the fomices. If labor still continued, a second application was given after 10 h. The third group received no treatment. Ear, pharynx and umbilicus of all newborns were also cultured semiquantitatively. Results: Nine hundred and eighty one women were evaluated. The overall incidence of group B strep­ tococcal carriership was 19.4%. Vertical transmission was 52.4% in the chlorhexidine group, 71.4% in the placebo group and 66.7% in the control group (P = 0.069). When testing the transmission rates for the chlorhexidine versus the combined placebo plus control group (69.3%), the difference was 16.9% (P ~ 0.026). Conclusion: Vaginal disinfection with a chlorhexidine gel during labor modest­ ly reduces group B streptococcal vertical transmission. Because the method is cheap, simple and safe, it should be considered for routine use. Our results indicate that it may reduce the incidence of early onset group B streptococcal sepsis by 2-32%.

A study was made to determine whether parents whose newborn twin (n = 72) had died differed from bereaved singleton parents (n = 70) concerning their satisfaction with professional guidance and care. Most parents felt supported by hospital staff, but the twin parents had fewer avenues of available support, especially after their baby's death. The twin parents' situation requires special attention because they have specific needs that are not always addressed by the current range of available support services.

The objectives of this study were to evaluate the effect of repeated indomethacin administration on cerebral oxygenation in relation to changes in cerebral blood flow velocity (CBFV) and other relevant physiological variables. Fourteen preterm infants with patent ductus arteriosus were studied during three subsequent indomethacin bolus administrations with intervals of 12 and 24 h. Changes in concentration of oxyhaemoglobin (cO2Hb), deoxyhaemoglobin (cHHb) and oxidized cytochrome aa3 (cCyt.aa3) in cerebral tissue and changes in cerebral blood volume (CBV) were measured by near infrared spectrophotometry; changes in mean CBFV in the internal carotid artery were measured by pulsed Doppler ultrasound. Simultaneously heart rate, transcutaneous pO2 and pCO2, arterial O2 saturation and blood pressure were measured. All variables were continuously recorded until 60 min after indomethacin administration. Within 5 min after each indomethacin administration, significant decreases in CBFV, CBV and cO2Hb and cCyt.aa3 were observed which persisted for at least 60 min, while cHHb increased or did not change at all. There were no changes in the other variables recorded. These data demonstrate that indomethacin administration is accompanied by a reduction in cerebral tissue oxygenation due to decreased cerebral blood flow. Therefore, low arterial oxygen content, either caused by low arterial O2 saturation or by low haemoglobin concentration, may be a contraindication for indomethacin treatment in preterm infants.

OBJECTIVE: The null hypothesis of our study is that the incidence of vitamin K deficiency in mother-infant pairs exposed to anticonvulsant drugs is not higher than in controls. STUDY DESIGN: In this multicenter observational case-control study, 25 pregnant women receiving anticonvulsant therapy and 25 pregnant controls were studied for PIVKA-II (protein induced by vitamin K absence of factor II) and vitamin K 1 concentrations at 32 weeks' gestation and at delivery. RESULTS: PIVKA-II was detectable in 54% of cord samples of the anticonvulsant group and in 20% of controls ( x 2 , p = 0.01). In both groups vitamin K1 cord blood levels were predominantly below the detection limit. Maternal vitamin K 1 concentrations were lower in women with epilepsy than in controls (Wilcoxon's rank sum test, p CONCLUSIONS: The incidence of vitamin K deficiency is increased in neonates exposed to anticonvulsant drugs prenatally. Their mothers, however, are rarely vitamin K deficient.

A randomised clinical trial was conducted to establish the effects of oral and intramuscular administration of vitamin K at birth on plasma concentrations of vitamin K1, proteins induced by vitamin K absence (PIVKA-II), and clotting factors. Two groups of about 165 healthy breast fed infants who received at random 1 mg vitamin K1 orally or intramuscularly after birth were studied at 2 weeks and 1 and 3 months of age. Although vitamin K1 concentrations were statistically significantly higher in the intramuscular group, blood coagulability, activities of factors VII and X and PIVKA-II concentrations did not reveal any difference between the two groups. At 2 weeks of age vitamin K1 concentrations were raised compared with reported unsupplemented concentrations and no PIVKA-II was detectable. At 3 months vitamin K1 concentrations were back at unsupplemented values and PIVKA-II was detectable in 11.5% of infants. Therefore, a repeated oral prophylaxis will be necessary to completely prevent (biochemical) vitamin K deficiency beyond the age of 1 month.

Extra Corporeal Membrane Oxygenation (ECMO) has been proven to improve survival in newborn infants with severe respiratory failure, who do not respond to adequate conventional treatment1,2. However, induction of ECMO is not without risk. A high incidence of cerebrovascular injury has been described in infants treated with ECMO3,4,5. The etiology of cerebrovascular injury associated with ECMO might be multifactorial4.

Introduction Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is a cardio-pulmonary bypass technique to provide life support in acute reversible cardiorespiratory failure when conventional management is not successful. Most neonates receiving ECMO suffer from meconium aspiration syndrome (MAS), congenital diaphragmatic hernia (CDH), sepsis or persistent pulmonary hypertension (PPH). In five-year-old children who underwent VA-ECMO therapy as neonates, we assessed motor performance related to growth, intelligence and behaviour, and the association with the primary diagnosis. Methods In a prospective population-based study (n = 224) 174 five-year-old survivors born between 1993 and 2000 and treated in the two designated ECMO centres in the Netherlands (Radboud University Medical Centre Nijmegen and Sophia Children's Hospital, Erasmus MC-University Medical Center Rotterdam) were invited to undergo follow-up assessment including a paediatric assessment, the movement assessment battery for children (MABC), the revised Amsterdam intelligence test (RAKIT) and the child behaviour checklist (CBCL). Results Twenty-two percent of the children died before the age of five, 86% (n = 149) of the survivors were assessed. Normal development in all domains was found in 49% of children. Severe disabilities were present in 13%, and another 9% had impaired motor development combined with cognitive and/or behavioural problems. Chi-squared tests showed adverse outcome in MABC scores (P < 0.001) compared with the reference population in children with CDH, sepsis and PPH, but not in children with MAS. Compared with the Dutch population height, body mass index (BMI) and weight for height were lower in the CDH group (P < 0.001). RAKIT and CBCL scores did not differ from the reference population. Total MABC scores, socioeconomic status, growth and CBCL scores were not related to each other, but negative motor outcome was related to lower intelligence quotient (IQ) scores (r = 0.48, P < 0.001). Conclusions The ECMO population is highly at risk for developmental problems, most prominently in the motor domain. Adverse outcome differs between the primary diagnosis groups. Objective evaluation of long-term developmental problems associated with this highly invasive technology is necessary to determine best evidence-based practice. The ideal follow-up programme requires an interdisciplinary team, the use of normal-referenced tests and an international consensus on timing and actual outcome measurements.

In a multi-parametric study the influence of pathological neonatal conditions on heart rate variability was investigated in 60 preterm infants born at a gestational age below 33 weeks. Measurements were performed during the first 3 days of life. Four times a day, RR-intervals, respiration curve and rate, transcutaneously measured blood gases and observed body movements were recorded while the infants were asleep. All data were stored simultaneously in a micro-computer. Severity of respiratory distress syndrome (RDS), patency of ductus arteriosus and periventricular haemorrhage were documented as well. Four sets of short- (STV) and long-term variability (LTV) indices were calculated. Severe RDS was associated with a significant decrease in LTV. The influence of RDS on LTV persisted after correction for conceptional age, postnatal age, behavioural state and variations in respiratory rate and in transcutaneous PO2. Infants with a symptomatic patent ductus arteriosus had lower LTV than controls with the same severity of RDS. STV was predominantly influenced by postnatal and conceptional age, and tended to be lower in infants with periventricular haemorrhage.

The instantaneous heart rate shows a variation around the mean heart rate caused by cardioregulatory mechanisms which are mediated through the sympathetic and vagal autonomic nervous system. To gain more insight into the influence of physiological parameters on neonatal heart rate variability a study was performed in four healthy preterm newborns during the first five days of life. Instantaneous heart rate, respiration rate, transcutaneous pO2, blood pressure and behaviour were recorded during 40 minutes four times a day. Long term heart rate variability was calculated as the difference between p95 and p5 of instantaneous heart rate values sampled during three minutes. A clear relationship between long term variability and age (maturity of the autonomic nervous system), respiration rate (respiratory sinus arrhythmia or a tidal volume mediated effect) and behaviour (increase of sympathetic tone during REM sleep) was found. No influence of blood pressure, heart rate, and transcutaneous pO2 within physiological ranges could be detected. The relative influence of the different physiological parameters on heart rate variability has to be established before the value of heart rate variability as a monitoring tool in neonatal intensive care can be investigated.

Introduction Extracorporeal membrane oxygenation (ECMO) is a supportive cardiopulmonary bypass technique for babies with acute reversible cardiorespiratory failure. We assessed morbidity in ECMO survivors at the age of five years, when they start primary school and major decisions for their school careers must be made. Methods Five-year-old neonatal venoarterial-ECMO survivors from the two designated ECMO centres in The Netherlands (Erasmus MC – Sophia Children's Hospital in Rotterdam, and University Medical Center Nijmegen) were assessed within the framework of an extensive follow-up programme. The protocol included medical assessment, neuromotor assessment, and psychological assessment by means of parent and teacher questionnaires. Results Seventeen of the 98 children included in the analysis (17%) were found to have neurological deficits. Six of those 17 (6% of the total) showed major disability. Two of those six children had a chromosomal abnormality. Three were mentally retarded and profoundly impaired. The sixth child had a rightsided hemiplegia. These six children did not undergo neuromotor assessment. Twenty-four of the remaining 92 children (26%) showed motor difficulties: 15% actually had a motor problem and 11% were at risk for this. Cognitive delay was identified in 11 children (14%). The mean IQ score was within the normal range (IQ = 100.5).

We present a full-term newborn infant who suffered from immediate postpartum severe respiratory distress. The infant had an inspiratory stridor as a result of a swelling of the soft palate, extending from the roof of the nasopharynx. Transoral endotracheal intubation resulted in normal saturation levels. Histologic examination after an open biopsy showed mature neuroglial tissue. Radiology demonstrated the presence of a right parapharyngeal process obstructing the nasopharynx and oropharynx and extending to the right middle and posterior fossa, via the foramen ovale. After transoral debulking, the infant was extubated successfully. After an uneventful period of 5 months, the patient was readmitted at our hospital for treatment of meningitis. Subsequently, the inspiratory stridor recurred, and staged surgery was performed. First, a transcranial approach was used to remove a large intradural part of the process and close the defect at Meckel's cave. Two weeks later the retro- and parapharyngeal part of the process were removed transorally. Given the site of the defect of the skull base and the intradural location of the process, the diagnosis is a transalar sphenoidal encephalocele. This is a rare type of basal encephalocele, and has never been reported in an infant nor known to present with respiratory distress. The pathogenesis, clinical presentation, pathology, and therapeutic implications of basal encephaloceles are discussed.

_Aim._ To provide an empirical background for the ethical discussion on the parents' versus the physician's role, when difficult decisions concerning the end of life in newborn infants have to be made. _Subjects._ Face-to-face interviews were conducted with a stratified sample of 66 pediatricians. The response rate was 99%. _Measurements._ The most recent decisions in newborn infants to hasten death or not prolong life and the most recent cases in which such decisions were not made because either the parents or the physician objected were comprehensively discussed. _Results._ Decisions to hasten death or not prolong life were usually made after discussing it with parents, and did not occur while parents were known to disagree. Situations in which an end-of-life decision was not made because parents did not consent predominantly involved infants with complications of prematurity (24%) or perinatal asphyxia (40%), whereas situations in which parents requested an end-of-life decision that was not acceded to by the pediatrician involved Down syndrome as the main diagnosis in 43%, and as a concurrent diagnosis in 21%. Pediatricians afterwards often expressed feelings of discontent about situations in which there had been disagreement with parents. _Conclusion._ The opinion of parents about which medical decision is in the best interest of their child is very important for pediatricians, but only decisive in case it invokes the continuation of treatment.

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