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ObjectiveIn the Netherlands, the threshold for offering active treatment for spontaneous birth was lowered from 25+0 to 24+0 weeks’ gestation in 2010. This study aimed to evaluate the impact of guideline implementation on survival and causes and timing of death in the years following implementation.DesignNational cohort study, using data from the Netherlands Perinatal Registry.PatientsThe study population included all 3312 stillborn and live born infants with a gestational age (GA) between 240/7 and 266/7 weeks born between January 2011 and December 2017. Infants with the same GA born between January 2007 and December 2009 (N=1400) were used as the reference group.Main outcome measuresSurvival to discharge, as well as cause and timing of death.ResultsAfter guideline implementation, there was a significant increase in neonatal intensive care unit (NICU) admission rate for live born infants born at 24 weeks’ GA (27%–69%, pConclusionsImplementation of the 2010 guideline resulted as expected in increased NICU admissions rate and postnatal survival of infants born at 24 weeks’ GA. In the years after implementation, a shift in cause of death was seen from respiratory insufficiency towards necrotising enterocolitis and sepsis.

Contains fulltext : 235444.pdf (Publisher’s version ) (Open Access) PURPOSE: Compare patients treated for Retinopathy of Prematurity (ROP) in two consecutive periods. METHODS: Retrospective inventory of anonymized neonatal and ophthalmological data of all patients treated for ROP from 2010 to 2017 in the Netherlands, subdivided in period (P)1: 1-1-2010 to 31-3-2013 and P2: 1-4-2013 to 31-12-2016. Treatment characteristics, adherence to early treatment for ROP (ETROP) criteria, outcome of treatment and changes in neonatal parameters and policy of care were compared. RESULTS: Overall 196 infants were included, 57 infants (113 eyes) in P1 and 139 (275 eyes) in P2, indicating a 2.1-fold increase in ROP treatment. No differences were found in mean gestational age (GA) (25.9 ± 1.7 versus 26.0 ± 1.7 weeks, p = 0.711), mean birth weight (791 ± 311 versus 764 ± 204 grams, p = 0.967) and other neonatal risk factors for ROP. In P2, the number of premature infants born

BACKGROUND Worldwide, many newborns who are preterm, small or large for gestational age, or born to mothers with diabetes are screened for hypoglycemia, with a goal of preventing brain injury. However, there is no consensus on a treatment threshold that is safe but also avoids overtreatment. METHODS In a multicenter, randomized, noninferiority trial involving 689 otherwise healthy newborns born at 35 weeks of gestation or later and identified as being at risk for hypoglycemia, we compared two threshold values for treatment of asymptomatic moderate hypoglycemia. We sought to determine whether a management strategy that used a lower threshold (treatment administered at a glucose concentration of

Introduction: Retinopathy of prematurity (ROP) remains an important cause for preventable blindness. Aside from gestational age (GA) and birth weight, risk factor assessment can be important for determination of infants at risk of (severe) ROP. Methods: Prospective, multivariable risk-analysis study (NEDROP-2) was conducted, including all infants born in 2017 in the Netherlands considered eligible for ROP screening by pediatricians. Ophthalmologists provided data of screened infants, which were combined with risk factors from the national perinatal database (Perined). Clinical data and potential risk factors were compared to the first national ROP inventory (NEDROP-1, 2009). During the second period, more strict risk factor-based screening inclusion criteria were applied. Results: Of 1,287 eligible infants, 933 (72.5%) were screened for ROP and matched with the Perined data. Any ROP was found in 264 infants (28.3% of screened population, 2009: 21.9%) and severe ROP (sROP) (stage ≥3) in 41 infants (4.4%, 2009: 2.1%). The risk for any ROP is decreased with a higher GA (odds ratio [OR] 0.59 and 95% confidence interval [CI] 0.54–0.66) and increased for small for GA (SGA) (1.73, 1.11–2.62), mechanical ventilation >7 days (2.13, 1.35–3.37) and postnatal corticosteroids (2.57, 1.44–4.66). For sROP, significant factors were GA (OR 0.37 and CI 0.27–0.50), SGA (OR 5.65 and CI 2.17–14.92), postnatal corticosteroids (OR 3.81 and CI 1.72–8.40), and perforated necrotizing enterocolitis (OR 7.55 and CI 2.29–24.48). Conclusion: In the Netherlands, sROP was diagnosed more frequently since 2009. No new risk factors for ROP were determined in the present study, apart from those already included in the current screening guideline.

Background and Aims Retinopathy of prematurity (ROP) is a severe disease in preterm infants. It is seen more frequently in Low‐Middle Income Countries (LMIC) like Indonesia compared to High‐Income Countries (HIC). Risk factors for ROP development are ‐extreme‐ preterm birth, use of oxygen, neonatal infections, respiratory problems, inadequate nutrition, and blood and exchange transfusions. In this paper, we give an overview of steps that can be taken in LMIC to prevent ROP and provide guidelines for screening and treating ROP. Methods Based on the literature search and data obtained by us in Indonesia's studies, we propose guidelines for the prevention, screening, and treatment of ROP in preterm infants in LMIC. Results Prevention of ROP starts before birth with preventing preterm labor, transferring a mother who might deliver

BackgroundThe incidence of retinopathy of prematurity (ROP) is higher in Indonesia than in high-income countries. In order to reduce the incidence of the disease, a protocol on preventing, screening and treating ROP was published in Indonesia in 2010. To assist the practical implementation of the protocol, meetings were held in all Indonesia regions, calling attention to the high incidence of ROP and the methods to reduce it. In addition, national health insurance was introduced in 2014, making ROP screening and treatment accessible to more infants.ObjectiveTo evaluate whether the introduction of both the guideline drawing attention to the high incidence of ROP and national health insurance may have influenced the incidence of the disease in Indonesia.SettingData were collected from 34 hospitals with different levels of care: national referral centres, university-based hospitals, and public and private hospitals.MethodsA survey was administered with questions on admission numbers, mortality rates, ROP incidence, and its stages for 2016–2017 in relation to gestational age and birth weight.ResultsWe identified 12 115 eligible infants with a gestational age of less than 34 weeks. Mortality was 24% and any stage ROP 6.7%. The mortality in infants aged less than 28 weeks was 67%, the incidence of all-stage ROP 18% and severe ROP 4%. In the group aged 28–32 weeks, the mortality was 24%, all-stage ROP 7% and severe ROP 4%–5%. Both mortality and the incidence of ROP were highest in university-based hospitals.ConclusionsIn the 2016–2017 period, the infant mortality rate before 32 weeks of age was higher in Indonesia than in high-income countries, but the incidence of ROP was comparable. This incidence is likely an underestimation due to the high mortality rate. The ROP incidence in 2016–2017 is lower than in surveys conducted before 2015. This decline is likely due to a higher practitioner awareness about ROP and national health insurance implementation in Indonesia.

BACKGROUND: Hyperbilirubinemia guidelines are based on total serum bilirubin (TSB), in combination with either gestational age (GA) or birth weight (BW), postnatal age and specific risk factors. However, TSB is a poor predictor of bilirubin-induced neurotoxicity (BIND). Free unconjugated bilirubin (UCBfree) and the UCBfree/TSB ratio are more directly related to BIND, but data on their postnatal courses are unknown.AIMS: To characterize the postnatal courses of UCBfree and UCBfree/TSB ratio, and assess their relationships with clinical characteristics.SUBJECTS: 72 preterm infants≤32weeks GA, admitted to the University Medical Center Groningen, The Netherlands.STUDY DESIGN: During the first postnatal week, bilirubin plasma parameters were analyzed and their relationship with clinical parameters was analyzed. Postnatal changes were analyzed using Generalized Estimating Equations. Data are expressed as medians [ranges].RESULTS: Less than 10% of the cohort (GA: 29 [26-31] weeks; BW: 1165 [600-1975] g) showed hyperbilirubinemic risk factors. We observed a large variation in UCBfree (27 [1-197] nmol/L), that could partly be explained by postnatal age and gender, but not by other risk factors. Maximal UCBfree levels of 50 [13-197] nmol/L occurred at day 4 and were higher in males. In contrast to TSB, UCBfree/TSB ratios (0.19 [0.01-1.04]) were higher in infants with low GA/BW.CONCLUSION: UCBfree levels vary considerably in preterm infants, despite a low incidence of hyperbilirubinemic risk factors and similar TSB-based phototherapy treatment. UCBfree could not be predicted by GA or BW, but UCBfree/TSB ratios are highest in the smallest preterms, while they have the lowest TSB levels.

Background: Our double-blind, placebo-controlled, randomised trial investigating systemic hydrocortisone in mechanically ventilated preterm infants (gestational age

Hyperbilirubinemia in the newborn occurs more frequently in Indonesia. Therefore, it is important that pediatric residents in Indonesia acquire adequate knowledge of hyperbilirubinemia management. This study aims to determine the pediatric residents' knowledge on hyperbilirubinemia management, whether they follow recommended guidelines, and whether differences exist between five large Indonesian teaching hospitals. We handed out a 25-question questionnaire on hyperbilirubinemia management to pediatric residents at five teaching hospitals. A total of 250 questionnaires were filled in completely, ranging from 14 to 113 respondents per hospital. Approximately 76% of the respondents used the Kramer score to recognize neonatal jaundice. Twenty-four percent correctly plotted the total serum bilirubin levels (TSB) on the phototherapy (PT) nomograms provided by the American Academy of Pediatrics (AAP) and the National Institute for Health and Care Excellence (NICE) for full-term and nearly full-term infants. Regarding preterm infants, Hyperbilirubinemia, newborn infants, knowledge, residents, guidelines.

BACKGROUND: The Thompson encephalopathy score is a clinical score to assess newborns suffering from perinatal asphyxia. Previous studies revealed a high sensitivity and specificity of the Thompson encephalopathy score for adverse outcomes (death or severe disability). Because the Thompson encephalopathy score was developed before the use of therapeutic hypothermia, its value was reassessed. OBJECTIVE: The purpose of this study was to assess the association of the Thompson encephalopathy score with adverse short-term outcomes, defined as death before discharge, development of severe epilepsy, or the presence of multiple organ failure in asphyxiated newborns undergoing therapeutic hypothermia. METHODS: The study period ranged from November 2010 to October 2014. A total of 12 tertiary neonatal intensive care units participated. Demographic and clinical data were collected from the "PharmaCool" multicenter study, an observational cohort study analyzing pharmacokinetics of medication during therapeutic hypothermia. With multiple logistic regression analyses the association of the Thompson encephalopathy scores with outcomes was studied. RESULTS: Data of 142 newborns were analyzed (male: 86; female: 56). Median Thompson score was 9 (interquartile range: 8 to 12). Median gestational age was 40 weeks (inter quartile range 38 to 41), mean birth weight was 3362 grams (standard deviation: 605). All newborns manifested perinatal asphyxia and underwent therapeutic hypothermia. Death before discharge occurred in 23.9% and severe epilepsy in 21.1% of the cases. In total, 59.2% of the patients had multiple organ failure. The Thompson encephalopathy score was not associated with multiple organ failure, but a Thompson encephalopathy score >= 12 was associated with death before discharge (odds ratio: 3.9; confidence interval: 1.3 to 11.2) and with development of severe epilepsy (odds ratio: 8.4; confidence interval: 2.5 to 27.8). CONCLUSION: The Thompson encephalopathy score is a useful clinical tool, even in cooled asphyxiated newborns. A score >= 12 is associated with adverse outcomes (death before discharge and development of severe epilepsy). The Thompson encephalopathy score is not associated with the development of multiple organ failure.

Background: Much controversy exists about the optimal management of a patent ductus arteriosus (PDA) in preterm infants, especially in those born at a gestational age (GA) less than 28weeks. No causal relationship has been proven between a (haemodynamically significant) PDA and neonatal complications related to pulmonary hyperperfusion and/or systemic hypoperfusion. Although studies show conflicting results, a common understanding is that medical or surgical treatment of a PDA does not seem to reduce the risk of major neonatal morbidities and mortality. As the PDA might have closed spontaneously, treated children are potentially exposed to iatrogenic adverse effects. A conservative approach is gaining interest worldwide, although convincing evidence to support its use is lacking. Methods: This multicentre, randomised, non-inferiority trial is conducted in neonatal intensive care units. The study population consists of preterm infants (GA1.5mm. Early treatment (between 24 and 72h postnatal age) with the cyclooxygenase inhibitor(COXi) ibuprofen (IBU) is compared with an expectative management (no intervention intended to close a PDA). The primary outcome is the composite of mortality, and/or necrotising enterocolitis (NEC) Bell stage ≥ IIa, and/or bronchopulmonary dysplasia (BPD) defined as the need for supplemental oxygen, all at a postmenstrual age (PMA) of 36weeks. Secondary outcome parameters are short term sequelae of cardiovascular failure, comorbidity and adverse events assessed during hospitalization and long-term neurodevelopmental outcome assessed at a corrected age of 2 years. Consequences regarding health economics are evaluated by cost effectiveness analysis and budget impact analysis. Discussion: As a conservative approach is gaining interest, we investigate whether in preterm infants, born at a GA less than 28weeks, with a PDA an expectative management is non-inferior to early treatment with IBU regarding to the composite outcome of mortality and/or NEC and/or BPD at a PMA of 36weeks., SCOPUS: ar.j, info:eu-repo/semantics/published

Severe hyperbilirubinemia, which may result in kernicterus, is seen more frequently in low and middle-income countries, such as Indonesia, than in high-income countries. In Indonesia midwives, general practitioners (GPs), and pediatricians are involved in the care of jaundiced newborn infants. It is unknown whether the high incidence of severe hyperbilirubinemia in this country is related to a lack of awareness of existing hyperbilirubinemia guidelines issued by, for example, the World Health Organization, the American Academy of Pediatrics, or the Indonesian Health Ministry, or to a lack of adherence to such guidelines. The aim of this questionnaire study was to assess health professionals' awareness of existing guidelines and their adherence to these guidelines in daily practice. We handed out a ten-question questionnaire to midwives, GPs, and pediatricians that included questions about the professionals themselves as well as clinical questions. The midwives completed 291 questionnaires, the GPs 206, and the pediatricians 154, all of which we used for our analysis. Almost 30% of the midwives and 23% of the GPs were either unaware of any existing guidelines or they did not adhere to them. Only 54% of the midwives recognized the warning signs of severe hyperbilirubinemia correctly, compared to 68% of the GPs and 89% of the pediatricians. Twenty-eight percent of the midwives and 31% of the GPs indicated that their first follow-up visit was after 72 hours, while 90% of them discharged infants after less than 48 hours after birth. The awareness of and adherence to guidelines for preventing and treating hyperbilirubinemia is low amongst the midwives and GPs in Indonesia. This may be an important contributing factor in the high incidence of severe hyperbilirubinemia in Indonesia.

AIM: The aim of the study was to determine whether regional cerebral tissue oxygen saturation (rc SO2 ) and fractional tissue oxygen extraction (FTOE), using near-infrared spectroscopy, are associated with neurodevelopmental outcome of preterm infants.METHOD: We measured rc SO2 on days 1, 2, 3, 4, 5, 8, and 15 after birth in 83 preterm infants (RESULTS: We followed up 67 infants. The lower quartile (P25-50 ) and highest quartile (P75-100 ) of rc SO2 on day 1 were associated with poorer cognitive outcome (p=0.044 and p=0.008 respectively). A lower area under the curve (AUC; over 15d) of rc SO2 was associated with poorer cognitive outcome (p=0.014). The lower quartile (P25-50 ) AUC of rc SO2 was associated with poorer fine motor outcome (p=0.004). The amount of time rc SO2 INTERPRETATION: Cerebral oxygen saturation during the first 2 weeks after birth is associated with neurodevelopmental outcome of preterm infants at 2 to 3 years. High and low rc SO2 on day 1 were associated with poorer neurodevelopmental outcome.

The therapeutic effect of moderate hypothermia in infants with HIE after perinatal asphyxia can be counteracted by stress which should therefore be minimized. Objective: of study was to gain insight in the COMFORTNeo-scale to measure stress during therapeutic hypothermia. Stress was measured prospectively by means of the COMFORTNeo-scale (CNS), twice a day, during hypothermia-, rewarming- and stabilization phase in a cohort of 133 neonates with perinatal asphyxia who participated in the PharmaCool study. A total of 994 CNS scores were collected; median score CNS 9 (IQR 7–11). Despite analgesic, sedative and anticonvulsant drugs 10% of the scores indicated moderate to severe stress during treatment. The use of these drugs as well as mechanical ventilation interfered with CNS score (respectively odds ratio 0.74 and 0.61) Interference of aEEG, hypothermia phase and gender were not confirmed. The COMFORTNeo-scale can, with the necessary caution, be used for the assessment of stress during therapeutic hypothermia treatment. Other options should be explored.

Treatment for unconjugated hyperbilirubinemia is predominantly based on one parameter, i.e., total serum bilirubin (TSB) levels. Yet, overt kernicterus has been reported in preterm infants at relatively low TSB levels, and it has been repeatedly shown that free unconjugated bilirubin (freeUCB) levels, or bilirubin/albumin (B/A) ratios for that matter, are more closely associated with bilirubin neurotoxicity. In this article, we review bilirubin-albumin binding, UCBfree levels, and B/A ratios in addition to TSB levels to individualize and optimize treatment especially in preterm infants. Methods to measure bilirubin-albumin binding or UCBfree are neither routinely performed in Western clinical laboratories nor incorporated in current management guidelines on unconjugated hyperbilirubinemia. For bilirubin-albumin binding, this seems justified because several of these methods have been challenged, and sufficiently powered prospective trials on the clinical benefits are lacking. Technological advances in the measurement of UCBfree may provide a convenient means for integrating UCBfree measurements into routine clinical management of jaundiced infants. A point-of-care method, as well as determination of UCBfree levels in various newborn populations, is desirable to learn more about variations in time and how various clinical pathophysiological conditions affect UCBfree levels. This will improve the estimation of approximate UCBfree levels associated with neurotoxicity. To delineate the role of UCBfree in the management of jaundiced (preterm) infants, trials are needed using UCBfree as treatment parameter. The additional use of the B/A ratio in jaundiced preterms has been evaluated in the Bilirubin Albumin Ratio Trial (BARTrial; Clinical Trials: ISRCTN74465643) but failed to demonstrate better neurodevelopmental outcome in preterm infants

Background: The occurrence of severe neonatal hyperbilirubinemia (SH) is partly attributed to nonhospitalized perinatal care. The Netherlands have a high frequency of home births and nonhospitalized perinatal care, and the incidence of SH is unknown. Objective: To assess the effects of home births and early hospital discharge on the incidence of SH in term-born infants in the Netherlands. Methods: In this nationwide prospective surveillance study between 2005 and 2009, infants (≥37 weeks GA) were included if total serum bilirubin (TSB) was ≥500 µmol/l or if they received an exchange transfusion when TSB was ≥340 µmol/l. Results: Seventy-one infants had SH (incidence 10.4/100,000); 43 had a TSB ≥500 μmol/l (incidence 6.3/100,000) and 45 (63%) underwent an exchange transfusion. 26% of the infants with SH were born at home, which is similar to 22% of all term infants who are born at home in the Netherlands (p = 0.41). Maximum TSB levels were similar in infants born at home (523 ± 114 μmol/l) and infants born in hospital (510 ± 123 μmol/l; p = 0.70). Of the 51 infants born in hospital, 33 were discharged and readmitted with SH, with maximal TSB levels (567 ± 114 μmol/l), which were higher than in infants who remained hospitalized (406 ± 47 μmol/l; p = 0.0001). Conclusion: The incidence of severe hyperbilirubinemia in term-born infants in the Netherlands is 10.4 per 100,000, which is similar to other developed countries. Home birth and early hospital discharge do not necessarily lead to a higher incidence of SH, provided that perinatal home care is well organized.

Introduction: We conducted a review of the evidence which contributes to the current care of jaundiced newborn infants. Methods: Literature was searched for reviews and randomized controlled trials (RCTs). Results: Six Cochrane reviews and eight other reviews and eighteen recent RCTs are discussed. Conclusions: Many children still suffer life-long consequences of severe hyperbilirubinaemia, which could almost always have been prevented relatively easily. Up to date, guidelines summarizing the available evidence into unambiguous recommendations are needed to guide healthcare professionals in the prevention, diagnosis and treatment for infants with hyperbilirubinaemia.

Unconjugated hyperbilirubinaemia occurs in almost all premature infants and is potentially neurotoxic. Treatment is based on total serum bilirubin (TSB), but treatment thresholds are not evidence based. Free bilirubin (Bf) - that is, not bound to albumin, seems a better parameter for bilirubin neurotoxicity, but measurements of Bf are not available in clinical practice. The bilirubin/albumin (B/A) ratio is considered a surrogate parameter for Bf and an interesting additional parameter in the management of hyperbilirubinaemia. This paper reviewed the evidence supporting the use of B/A ratios for predicting bilirubin-induced neurological dysfunction (BIND) including neurodevelopmental delay in jaundiced premature infants (gestational age less than 32 weeks). A literature search was performed and six publications reviewed regarding B/A ratios in the management and outcome of jaundiced premature infants. No prospective clinical trials had been undertaken to show whether bilirubin-induced neurotoxicity is reduced or whether unnecessary treatment is avoided by using the B/A ratio in addition to TSB. Recently, a randomised controlled trial evaluating the effect of the additional use of the B/A ratio on neurodevelopmental outcome in jaundiced premature infants has been initiated. Based on the prevailing evidence many authorities suggest that the additional use of the B/A ratio may be valuable when evaluating jaundiced premature infants.

Contains fulltext : 168757.pdf (Publisher’s version ) (Closed access) OBJECTIVE: To determine outcome of children born with isolated gastroschisis (no extra-gastrointestinal congenital abnormalities). STUDY DESIGN: International cohort study and meta-analysis. PRIMARY OUTCOME: time to full enteral feeding (TFEF); secondary outcomes: Duration of mechanical ventilation, length of stay (LOS), mortality and differences in outcome between simple and complex gastroschisis (complex; born with bowel atresia, volvulus, perforation or necrosis). To compare the cohort study results with literature three databases were searched. Studies were eligible for inclusion if cases were born in developed countries with isolated gastroschisis after 1990, number of cases >20 and TFEF was reported. RESULTS: The cohort study included 204 liveborn cases of isolated gastroschisis. The TFEF, median duration of ventilation and LOS was, 26days (range 6-515), 2days (range 0-90) and 33days (range 11-515), respectively. Overall mortality was 10.8%. TFEF and LOS were significantly longer (P

ObjectiveTo test the ability of the Ages and Stages Questionnaire, Third Edition (ASQ3) to help identify or exclude neurodevelopmental impairment (NDI) in very preterm-born children at the corrected age of two.MethodsWe studied the test results of 224 children, born at ResultsWe found 61 (27%) children with abnormal ASQ3 scores, and 10 (4.5%) children who had NDI with original BSIDIII thresholds (ConclusionThe Ages and Stages Questionnaire is a simple, valid and cost-effective screening tool to help identify and exclude NDI in very preterm-born children at the corrected age of two years

BACKGROUND: Severe unconjugated hyperbilirubinemia may cause deafness. In the Netherlands, 25% lower total serum bilirubin (TSB) treatment thresholds were recently implemented for preterm infants. OBJECTIVE: To determine the rate of hearing loss in jaundiced preterms treated at high or at low TSB thresholds. DESIGN/METHODS: In this retrospective study conducted at two neonatal intensive care units in the Netherlands, we included preterms (gestational age 35 dB). RESULTS: There were 479 patients in the high and 144 in the low threshold group. Both groups had similar gestational ages (29.5 weeks) and birth weights (1300 g). Mean and mean peak TSB levels were significantly lower after the implementation of the novel thresholds: 152 ± 43 µmol/L and 212 ± 52 µmol/L versus 131 ± 37 µmol/L and 188 ± 46 µmol/L for the high versus low thresholds, respectively (P

In the 19th century it was already known that unconjugated hyperbilirubinemia could potentially harm the central nervous system of jaundiced newborn infants. Yellow staining of deep brain nuclei in jaundiced infants was first reported in 1847. The term kernicterus (in German, kern = nucleus; in Greek, ikterus = yellow) was first denoted in 1903 to describe the pathological findings of this specific yellow staining pattern [1]. Nowadays, kernicterus is not only used to describe the pathological findings, but also to describe the clinical findings of acute and/or chronic bilirubin encephalopathy in jaundiced infants [2, 3]. Although acute kernicterus is an unambiguous clinical disorder in severely jaundiced newborn infants with the possibility of permanent sequelae, subtle forms of bilirubin encephalopathy referred to as bilirubin-induced neurological dysfunction, also known as BIND have evolved more recently [4]. This chapter aims to describe the pathophysiology of bilirubin neurotoxicity, its clinical spectrum and diagnostic tools. Novel treatment modalities to prevent infants from developing severe unconjugated hyperbilirubinemia and bilirubin neurotoxicity will be highlighted.

Background Randomized controlled trials have shown that treatment of chronically ventilated preterm infants after the first week of life with dexamethasone reduces the incidence of the combined outcome death or bronchopulmonary dysplasia (BPD). However, there are concerns that dexamethasone may increase the risk of adverse neurodevelopmental outcome. Hydrocortisone has been suggested as an alternative therapy. So far no randomized controlled trial has investigated its efficacy when administered after the first week of life to ventilated preterm infants. Methods/Design The SToP-BPD trial is a randomized double blind placebo controlled multicenter study including 400 very low birth weight infants (gestational age < 30 weeks and/or birth weight < 1250 grams), who are ventilator dependent at a postnatal age of 7 - 14 days. Hydrocortisone (cumulative dose 72.5 mg/kg) or placebo is administered during a 22 day tapering schedule. Primary outcome measure is the combined outcome mortality or BPD at 36 weeks postmenstrual age. Secondary outcomes are short term effects on the pulmonary condition, adverse effects during hospitalization, and long-term neurodevelopmental sequelae assessed at 2 years corrected gestational age. Analysis will be on an intention to treat basis. Discussion This trial will determine the efficacy and safety of postnatal hydrocortisone administration at a moderately early postnatal onset compared to placebo for the reduction of the combined outcome mortality and BPD at 36 weeks postmenstrual age in ventilator dependent preterm infants. Trial registration number Netherlands Trial Register (NTR): NTR2768

Bilirubin encephalopathy and kernicterus are preventable conditions. Nevertheless cases continue to occur. It is difficult to identify those infants who may develop severe hyperbilirubinemia, because icterus neonatorum occurs in most newborns. The aim of this guideline is to reduce the incidence of severe neonatal hyperbilirubinemia and bilirubin encephalopathy, and at the same time to minimise the risk of unintended side effects. At the initiative of the Dutch Pediatric Association and with methodological support from the Dutch Institute for Healthcare Improvement (CBO), a multidisciplinary working group adapted the clinical practice guideline on hyperbilirubinemia of the American Academy of Pediatrics (AAP) to the Dutch situation. This guideline provides recommendations for the prevention, diagnosis and treatment of hyperbilirubinemia in neonates (or= 35 weeks). For all newborns a risk assessment for the development of hyperbilirubinemia is made and they are to be systematically assessed during the first week of life. The guideline provides various intervention thresholds for risk groups, recommendations for the use of intravenous immunoglobulin in the event of severe hyperbilirubinemia on the basis of blood group antagonisms, and recommendations for conjugated hyperbilirubinemia. During the transfer of care, information about the risk factors in particular must be satisfactorily passed on.

Background and aims Disturbed cerebral oxygenation during the neonatal period might pose preterm infants at risk for neurological deficits. Our aim was to determine whether regional cerebral tissue oxygen saturation (r c SO 2 ) and fractional tissue oxygen extraction (FTOE), measured by near-infrared spectroscopy, were associated with neurodevelopmental outcome of preterm infants at 2–3 years of age. Methods We included 83 preterm infants (gestational age c SO 2 , and calculated FTOE on days 1, 2, 3, 4, 5, 8, and 15 after birth: (tcSaO 2 -r c SO 2 )/tcSaO 2 . Additionally, we determined the area under the curve (AUC) of r c SO 2 and FTOE during the first 2 weeks. Cognitive, motor, neurological and behavioural outcome was determined at 2–3 years of age. Multiple linear regression analyses were used to determine whether r c SO 2 and FTOE contributed to outcome. Results We included 67 infants for follow-up. Lower quartile (P 25–50 ) and highest quartile (P 75–100 ) of r c SO 2 values on day 1 were associated with poorer cognitive outcome (p=0.044 and p=0.008, respectively). Lower AUC of r c SO 2 was associated with poorer cognitive outcome (p=0.014). Lower quartile (P 25–50 ) AUC of r c SO 2 was associated with poorer fine motor outcome (p=0.004). The amount of time r c SO 2 Conclusions Neurodevelopmental outcome at 2–3 years of age was associated with cerebral oxygen saturation during the first 2 weeks after birth in preterm infants. Both high and low r c SO 2 values had a negative influence on neurodevelopmental outcome.

Background/aims Phototherapy (PT) is an effective treatment for hyperbilirubinemia, provided a minimum irradiance level is applied. Previously, we reported on low irradiance levels of PT devices in Dutch Neonatal Intensive Care Units (NICUs). These data were shared with all NICUs. We hypothesised that this knowledge would positively affect current applied irradiance levels. Therefore we determined irradiance levels of PT devices again in 2013. Methods Irradiance levels of overhead and underneath PT devices in all 10 NICUs were measured with a Dale 40 radiometer ( FlukeBiomedical, Everett, Washington, USA ), in routinely applied PT practice patterns, using an infant silhouette model. The infant’s distance from the overhead device was measured. Results Irradiance levels of 35 PT device-incubator combinations were measured (Table); 10 types of PT devices were in use in the 10 NICUs (8 overhead and 2 underneath). Overall irradiance levels increased (p = 0.01); irradiance levels of overhead and underneath PT devices also increased with 50% (NS) and 200% (p = 0.03), respectively. The mean (range) distance between overhead PT device and infant decreased with 7 cm to 38 (30–62) cm (p 2 /nm were obtained for 70% of PT devices versus ~50% in 2008 (p = 0.02). Conclusions Applied irradiance levels of PT devices in Dutch NICUs have markedly improved in 2013. Current data suggest that awareness among healthcare workers regarding requirements for effective PT results in improved use of PT devices, including smaller distances between PT device and infant. Moreover, the availability of better performing (Light Emitting Diode) PT devices might have contributed.

Background: The relation between total serum bilirubin (TSB) and neurodevelopmental outcome in preterm infants is unclear. Free bilirubin (Bf) and the bilirubin/albumin (B/A) ratio may be more reliable predictors of bilirubin neurotoxicity than TSB, but prospective data regarding neurodevelopmental outcome are lacking. Aim: To determine the relation between TSB, Bf, B/A ratio and neurodevelopmental outcome in preterm infants. Methods: TSB, Bf, and serum albumin levels were measured in preterm infants of 32 or less weeks of gestation during the first 10 postnatal days. The peroxidase method, was used for Bf. Composite cognitive and motor scores were assessed by the Bayley Scales of Infant Development III at 24 months corrected age. Spearman's correlation coefficient (R) was calculated. Results: Demographic data are shown in Table 1. Cognitive scores were significantly correlated to maximal TSB, but not to mean TSB levels (R= -0.32 (p< 0.05). Maximal and mean B/A ratios were not significantly correlated to cognitive scores (R=-0.28 and -0.17, resp.) Maximal and mean Bf measurements did not correlate with cognitive scores (R = -0.14 and -0.1, resp.). Motor scores did not correlate with any of the bilirubin parameters. Table 1 Conclusion: Cognitive, and not motor outcome, is only related to maximal TSB levels in preterm infants of 32 or less weeks of gestation. Neither B/A ratios nor free bilirubin levels are related to outcome.