Trends in neonatal morbidity and mortality for very low birthweight infants: a 20-year single-center experience.

OBJECTIVE: To describe trends in mortality and morbidity rates of very low birth weight infants as well as their pre-, peri- and postnatal characteristics over a period of 20 years' time. METHODS: Retrospective study in all very low birth weight infants admitted to the neonatal intensive care unit of the University Hospitals Ghent from 1 January 2000, to 31 December 2020. Mortality was the primary outcome variable with major morbidities being co-primary outcome variables. Pre-, peri- and postnatal characteristics are secondary outcome variables. We compared pre-, peri- and postnatal characteristics, as well as major morbidities between different groups with comparable rates of mortality. RESULTS: We included a total of 2037 very low birth weight infants and divided them in 3 epochs based on stepwise reductions in mortality in 2008 and 2013: 2000-2007 (n = 718), 2008-2012 (n = 506) and 2013-2020 (n = 813). Mortality decreased significantly over the years in all gestational ages, but predominantly in those with the youngest gestational age. Changes in obstetric and neonatal care were observed over time. Most significant changes were the increased use of antenatal corticosteroids, magnesium sulfate and surfactant. Intraventricular hemorrhage grade III/IV decreased significantly in all gestational ages. Significant increase in retinopathy of prematurity was observed. Bronchopulmonary dysplasia at 36 weeks and discharge home with oxygen is increasing in the total group. In those born below 26 weeks a slight increase in all major morbidities was observed especially of patent ductus arteriosus and retinopathy of prematurity. Increase of all other major morbidities seems to stabilize in epoch 3. The number of infants surviving without any major morbidity increases to almost 1/2 in all very low birth weight infants and to 1/10 in those born 24-25 weeks gestation. CONCLUSION: Analysis of the real-life experience showed that survival in very low birth weight infants significantly increased over time. Evolution of major morbidities will have to be carefully watched in the future.

The Impact of Intraventricular Hemorrhage and Periventricular Leukomalacia on Mortality and Neurodevelopmental Outcome in Very Preterm and Very Low Birthweight Infants: A Prospective Population-based Cohort Study.

OBJECTIVE: To survey the incidence of intraventricular hemorrhage (IVH) and periventricular leukomalacia (PVL) by gestational age and to report the impact on mortality and neurodevelopmental outcome in very preterm/very low birthweight infants. STUDY DESIGN: This was a population-based cohort study of 1927 very preterm/very low birthweight infants born in 2014-2016 and admitted to Flemish neonatal intensive care units. Infants underwent standard follow-up assessment until 2 years corrected age with the Bayley Scales of Infant and Toddler Development and neurological assessments. RESULTS: No brain lesion was present in 31% of infants born at <26 weeks of gestation and 75.8% in infants born at 29-32 weeks of gestation. The prevalence of low-grade IVH/PVL (grades I and II) was 16.8% and 12.7%, respectively. Low-grade IVH/PVL was not related significantly to an increased likelihood of mortality, motor delay, or cognitive delay, except for PVL grade II, which was associated with a 4-fold increase in developing cerebral palsy (OR, 4.1; 95% CI, 1.2-14.6). High-grade lesions (III-IV) were present in 22.0% of the infants born at <26 weeks of gestational and 3.1% at 29-32 weeks of gestation, and the odds of death were ≥14.0 (IVH: OR, 14.0; 95% CI, 9.0-21.9; PVL: OR, 14.1; 95% CI, 6.6-29.9). PVL grades III-IV showed an increased odds of 17.2 for motor delay and 12.3 for cerebral palsy, but were not found to be associated significantly with cognitive delay (OR, 2.9; 95% CI, 0.5-17.5; P = .24). CONCLUSIONS: Both the prevalence and severity of IVH/PVL decreased significantly with advancing gestational age. More than 75% of all infants with low grades of IVH/PVL showed normal motor and cognitive outcome at 2 years corrected age. High-grade PVL/IVH has become less common and is associated with adverse outcomes.

On optimal timing of antenatal corticosteroids: time to reformulate the question.

Administration of antenatal corticosteroids (ACS) for accelerating foetal lung maturation in threatened preterm birth is one of the cornerstones of prevention of neonatal mortality and morbidity. To identify the optimal timing of ACS administration, most studies have compared subgroups based on treatment-to-delivery intervals. Such subgroup analysis of the first placebo-controlled randomised controlled trial indicated that a one to seven day interval between ACS administration and birth resulted in the lowest rates of neonatal respiratory distress syndrome. This efficacy window was largely confirmed by a series of subgroup analyses of subsequent trials and observational studies and strongly influenced obstetric management. However, these subgroup analyses suffer from a methodological flaw that often seems to be overlooked and potentially has important consequences for drawing valid conclusions. In this commentary, we point out that studies comparing treatment outcomes between subgroups that are retrospectively identified at birth (i.e. after randomisation) may not only be plagued by post-randomisation confounding bias but, more importantly, may not adequately inform decision making before birth, when the projected duration of the interval is still unknown. We suggest two more formal interpretations of these subgroup analyses, using a counterfactual framework for causal inference, and demonstrate that each of these interpretations can be linked to a different hypothetical trial. However, given the infeasibility of these trials, we argue that none of these rescue interpretations are helpful for clinical decision making. As a result, guidelines based on these subgroup analyses may have led to suboptimal clinical practice. As an alternative to these flawed subgroup analyses, we suggest a more principled approach that clearly formulates the question about optimal timing of ACS treatment in terms of the protocol of a future randomised study. Even if this 'target trial' would never be conducted, its protocol may still provide important guidance to avoid repeating common design flaws when conducting observational 'real world' studies using statistical methods for causal inference.

Association of antenatal magnesium sulfate with reduced late-onset sepsis in extreme preterm infants.

OBJECTIVES: Neonatal intensive care has changed extensively over the last decades resulting in improved survival of extreme preterm infants. However, improved survival is associated with prolonged hospitalization, mechanical ventilation and use of invasive devices, which are all predisposing factors for LOS. LOS is known to increase short- and long-term morbidities resulting in impaired neurodevelopmental outcome. Besides treatment with antibiotics and supportive care, there is an unmet need for adjunctive therapies to prevent neonatal sepsis and hereby improve outcome. METHODS: In a retrospective single-center design, we explored underlying pre-, peri- and postnatal factors in extreme preterm infants with and without LOS to potentially identify future strategies in the prevention of LOS in these infants. RESULTS: Associations formerly published could be confirmed, such as lower birth weight, longer duration of respiratory support, parenteral nutrition and NICU stay and a higher incidence of almost all neonatal morbidities. A new interesting finding was the fact that infants with LOS received more antenatal magnesium sulfate (p = 0.002). After nearest neighbor matching based on birth weight, gestational age, gender and multiplicity increased duration of parenteral nutrition and NICU stay, the incidence of PVL remained significantly different between the two groups (LOS/no LOS), but also the association between antenatal magnesium sulfate administration and less LOS held true (p = 0.004). CONCLUSION: In this study, extreme preterm infants receiving antenatal magnesium sulfate developed less LOS. Whether this is merely an associative factor reflecting illness severity or an interesting link for new preventive strategies for LOS, should be further explored.

Parent-infant closeness after preterm birth and depressive symptoms: A longitudinal study.

Background: Preterm birth increases the risk for postpartum depression in both mothers and fathers, calling for strategies to alleviate and prevent depressive symptoms in parents of preterm infants. The aim of this study was to assess the association between early parent-infant closeness and later depressive symptoms among parents of preterm infants. We hypothesized that longer duration of closeness associate with fewer depressive symptoms in both parents. Methods: This prospective cohort study included 23 neonatal intensive care units (NICUs) from 15 countries in 2018 to 2020. Each unit recruited families with preterm infants aiming to 30 families. The total duration of parents' presence in the NICU, and separately parent-infant skin-to-skin contact and holding, were measured using a Closeness Diary up to 14  days. The Edinburgh Postnatal Depression Scale (EPDS) was used at discharge and at 4  months corrected age of the infant. Results: The study included 684 mothers and 574 fathers. The median presence was 469  min (Q1 258 and Q3 1,087) per 24   h for the mothers and 259   min (Q1 100 and Q3 540) for the fathers; mean EPDS scores were 9.2 (SD 5.0) and 6.3 (SD 4.4) at discharge and 6.6 (4.7) and 4.3 (4.2) at 4  months, respectively. Parents' presence and depressive symptoms varied greatly between the units. Parents' presence as the total measure, or skin-to-skin contact and holding separately, did not associate with depressive symptoms in either mothers or fathers at either time point (adjusted). Conclusion: No association was found between the duration of parent-infant closeness in the neonatal unit and parents' depressive symptoms. The beneficial effects of family-centered care on parents' depression seem to be mediated by other elements than parent-infant physical closeness. More research is needed to identify the critical elements which are needed to alleviate parents' depression after NICU stay.

Neonatal magnesium levels are safe after maternal MgSO4 administration: a comparison between unexposed preterm neonates and neonates exposed for fetal neuroprotection or maternal eclampsia prevention-a cohort study.

To objective of this study was to compare neonatal magnesemia in the first 15 days of neonatal life between three groups: a control group not exposed to MgSO4, a neuroprotection group, and an eclampsia prevention group, and to explore its associations with child outcomes. A retrospective single-centre cohort study was performed in a tertiary care setting. Infants admitted at the neonatal intensive care unit born between 24 and 32 weeks' gestation, regardless of etiology of preterm birth, were included. The mean outcome measure was neonatal magnesemia (mmol/L). Linear mixed regression of neonatal magnesemia on exposure group and day of life was done. Generalised estimating equation models of child outcomes on neonatal magnesemia according to exposure group and day of life were made. The analyses showed that in neonatal magnesemia is significantly higher in the preeclampsia group compared to the control and neuroprotection groups. On the day of birth, this is irrespective of maternal magnesemia (preeclampsia vs control groups), and the maternal total dose or duration of MgSO4 administration (preeclampsia vs neuroprotection group). No differences were found in short-term composite outcome between the three groups. CONCLUSION: We found mean differences in neonatal magnesemia between children not exposed to MgSO4 antenatally, children exposed for fetal neuroprotection, and children exposed for maternal eclampsia prevention. A 4-g loading and 1-g/h maintenance doses, for fetal neuroprotection and eclampsia prevention, appear to be safe on the short term for the neonate. WHAT IS KNOWN: • Magnesium sulphate is a valuable medicine in obstetrics. The main indications are prevention of eclampsia and fetal neuroprotection. The most used dosage is a 4- or 6-g loading dose and a 1- or 2-g per h maintenance dose. It reduces neuromotor disabilities in extreme-to-moderate preterm born children. WHAT IS NEW: • Maternal concentrations are supraphysiological and the maternal total dose can be high. Concentrations in neonates appear to remain in safe ranges. A dosage of 4-g loading and 1 g/h seems safe for the preterm neonate on the short term.

The Paternal Brain in Action: A Review of Human Fathers' fMRI Brain Responses to Child-Related Stimuli.

As fathers are increasingly involved in childcare, understanding the neurological underpinnings of fathering has become a key research issue in developmental psychobiology research. This systematic review specifically focused on (1) highlighting methodological issues of paternal brain research using functional magnetic resonance imaging (fMRI) and (2) summarizing findings related to paternal brain responses to auditory and visual infant stimuli. Sixteen papers were included from 157 retrieved records. Sample characteristics (e.g., fathers' and infant's age, number of kids, and time spent caregiving), neuroimaging information (e.g., technique, task, stimuli, and processing), and main findings were synthesized by two independent authors. Most of the reviewed works used different stimuli and tasks to test fathers' responses to child visual and/or auditory stimuli. Pre-processing and first-level analyses were performed with standard pipelines. Greater heterogeneity emerged in second-level analyses. Three main cortical networks (mentalization, embodied simulation, and emotion regulation) and a subcortical network emerged linked with fathers' responses to infants' stimuli, but additional areas (e.g., frontal gyrus, posterior cingulate cortex) were also responsive to infants' visual or auditory stimuli. This review suggests that a distributed and complex brain network may be involved in facilitating fathers' sensitivity and responses to infant-related stimuli. Nonetheless, specific methodological caveats, the exploratory nature of large parts of the literature to date, and the presence of heterogeneous tasks and measures also demonstrate that systematic improvements in study designs are needed to further advance the field.

Antenatal corticosteroids-to-birth interval in preterm birth.

Objectives: The purpose of this study was to compare short-term outcomes in children born between 24 and 34 weeks' gestation, according to observed antenatal corticosteroids (ACS)-to-birth intervals. Research question: 'Is there a difference in short-term outcomes between observed ACS-to-birth intervals across a range of gestational ages at birth?'Methods: Cohort study assessing differences in incidence of short-term neonatal outcomes according to the observed interval between the last administration of ACS and birth. Linear, non-weighted GEE models with an independence working correlation structure were fitted to infant level data providing valid point estimates for either incidence or rate differences (binary outcomes) or average differences (continuous outcomes).Results: Of 886 children, 35.9% were born within 2 days after the last administration of ACS, 32.2% within 2 to 7 days, 14.1% within 8 to 14 days, and 17.8% more than 14 days after. Across gestational ages at birth, there were no differences in birth weight between children born at an ACS-to-birth interval of 7 days or less compared to more than 7 days, nor were there differences in respiratory outcomes, cerebral outcomes, or composite outcome.Conclusion: Drawing conclusions on the importance of the ACS-to-birth interval is difficult due to the post-hoc nature of the variable. In the absence of tools to better estimate if and when PTB will occur, it might not have any value in daily practice, regardless of whether there is an optimal ACS-to-birth interval or not.

Parents' experiences of emotional closeness to their infants in the neonatal unit: A meta-ethnography.

BACKGROUND: Physical and emotional parent-infant closeness activate important neurobiological mechanisms involved in parenting. In a neonatal care context, most research focuses on physical (parental presence, skin-to-skin contact) aspects; insights into emotional closeness can be masked by findings that overemphasise the barriers or challenges to parenting an infant during neonatal care. AIM: To explore existing qualitative research to identify what facilitates and enables parents' experiences of emotional closeness to their infants while cared for in a neonatal unit. STUDY DESIGN: A systematic review using meta-ethnographic methods. Search strategy involved searches on six databases, author runs, and backward and forward chaining. Reciprocal translation was used to identify and compare key concepts of parent-infant emotional closeness. RESULTS: Searches identified 6992 hits, and 34 studies from 17 countries that involved 670 parents were included. Three overarching themes and associated sub-themes were developed. 'Embodied connections' describes how emotional closeness was facilitated by reciprocal parent-infant interactions, spending time as a family, and methods for parents to feel connected while physically separated. 'Inner knowing' concerns how knowledge about infant and maternal health and understanding the norms of neonatal care facilitated emotional closeness. 'Evolving parental role' relates to how emotional closeness was intertwined with parental identities of contributing to infant health, providing direct care, and being acknowledged as a parent. CONCLUSION: Parent-infant closeness evolves and is facilitated by multifaceted biopsychosocial factors. Practice implications include creating private and uninterrupted family time, strategies for parents to maintain an emotional connection to their infant when separated, and neurobiology education for staff.

Neurodevelopmental outcomes of very preterm and very-low-birthweight infants in a population-based clinical cohort with a definite perinatal treatment policy.

BACKGROUND: With constant changes in neonatal care practices, recent information is valuable for healthcare providers and for parental counselling. The aim of the study was to describe the neurodevelopmental outcome in a cohort of very preterm (VPT)/very-low-birthweight (VLBW) infants at 2 years corrected age (CA). MATERIAL AND METHODS: This is a population-based cohort study of all infants born with a GA <31 weeks and/or BW < 1500 g between 2014 and 2016 admitted to the Flemish (Belgium) neonatal intensive care units. Infants had routine clinical follow-up around 2 years CA. The diagnosis of cerebral palsy (CP), visual and hearing impairments were recorded. Motor, cognitive and language outcomes were assessed using the Bayley-III. Neurodevelopmental impairment (NDI) was classified as mild (<1 standard deviation [SD]) or moderate-severe (<2SD) based on the defined categories of motor, cognitive, hearing, and vision impairments. RESULTS: Of the 1941 admissions, 92% survived to discharge and follow-up data were available for 1089 infants (61.1%). Overall, 19.3%, 18.9% and 41.8% of infants had a motor, cognitive and language delay, respectively. CP was diagnosed in 4.3% of the infants. Mild and moderate-to-severe NDI was observed in 25.2% and 10.9% of the infants, respectively. The number of infants with a normal outcome increased from nearly 40% in the category of GA<26 weeks to 70% for infants in the category of 30─31 weeks GA. CONCLUSION: At 2 years CA, 64% were free from NDI and 90% were free from moderate-to-severe NDI. However, a lower GA and BW are associated with higher rates of adverse neurodevelopmental outcomes at 2 years CA.

Obstetrical characteristics and neonatal outcome according to aetiology of preterm birth: a cohort study.

PURPOSE: Preterm birth (PTB) can be categorised according to aetiology into: spontaneous preterm labour (SPL), preterm prelabour rupture of membranes (PPROM), and iatrogenic (iatro) PTB. Outcomes could differ between these groups, which could be of interest in counselling. We aimed to explore differences between aetiologic groups of PTB in maternal demographics, obstetrical characteristics and management, and neonatal outcomes. METHODS: This is a cohort study (2012-2018) in Ghent University Hospital, Belgium, of deliveries from 24 + 0 to 33 + 6 weeks. We compared perinatal demographics, management, and outcomes between the aetiologic types of PTB. Point and interval estimates for differences between aetiologic types were estimated using a Generalised Estimating Equations approach to handle clustering due to multiple gestations. RESULTS: 813 mothers and 987 neonates were included. Prevalences of different aetiologic types of PTB were similar. Maternal BMI was higher in the iatrogenic group (iatro-SPL: + 1.92 kg/m2, 95% CI 1.02, 2.83; iatro-PPROM: + 2.06 kg/m2, 95% CI 1.15, 2.96). There was an inversed sex ratio (0.82, 95% CI 0.65, 1.03), more growth restriction (iatro-SPL: + 22.60%, 95% CI 17.08, 28.13; iatro-PPROM: + 24.64%, 95% CI 19.44, 29.83), and a higher caesarean section rate in the iatrogenic group (iatro-SPL: + 57.23%, 95% CI 50.32, 64.13, iatro-PPROM: + 56.79%, 95% CI 50.20, 63.38) and more patients received at least one complete course of antenatal corticosteroids (iatro-SPL: + 17.60%, 95% CI 10.60, 24.60, iatro-PPROM: + 10.73%, 95% CI 4.52, 16.94). In all types of PTB, adverse neonatal outcomes had a low prevalence, except for respiratory distress syndrome. A composite of adverse neonatal outcome was more prevalent in the SPL- compared to the PPROM group, and there was less intraventricular haemorrhage in the iatrogenic group. CONCLUSION: Additional to gestational age at birth, the aetiology of PTB is associated with neonatal outcome. More data are needed to enable individualised management and counselling in case of threatened PTB. TRIAL REGISTRATION NUMBER: NCT03405116.

Continuous infusion vs. intermittent flushing of peripheral cannulas in neonates using a needleless connector: a prospective cohort study.

Objective To compare the duration of patency of peripheral intravenous cannulas between continuous infusion and intermittent flushing, while using a needleless intravenous connector in newborns admitted to the neonatal intensive care unit (NICU). Methods This is a prospective cohort study, including neonates admitted to the NICU who needed a peripheral intravenous cannula for intermittent administration of intravenous medication. In the first period, neonates received continuous peripheral infusion with NaCl 0.9% at 0.2 mL/h. In the second period, cannulas were flushed with NaCl 0.9% (0.5 mL before and 0.3 mL after the administration of intravenous medication). Results A total of 113 neonates (210 cannulas) were included in the study, 55 received continuous peripheral infusion and 58 received intermittent flushing. Intermittent flushing resulted in a significantly longer duration of cannula patency compared to continuous infusion (geometric mean 47.1 vs. 35.4 h, P=0.041). The incidence of extravasation was higher with continuous infusion (68.9% vs. 43.2%; P=0.001), while occlusion was more common with intermittent flushing (28.4% vs. 6.6%; P=0.002). Conclusions Intermittent flushing of peripheral cannulas (using needleless intravenous connectors) results in longer cannula patency compared to continuous infusion, in neonates requiring only intermittent administration of medication.

LINE- and Alu-containing genomic instability hotspot at 16q24.1 associated with recurrent and nonrecurrent CNV deletions causative for ACDMPV.

Transposable elements modify human genome by inserting into new loci or by mediating homology-, microhomology-, or homeology-driven DNA recombination or repair, resulting in genomic structural variation. Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) is a rare lethal neonatal developmental lung disorder caused by point mutations or copy-number variant (CNV) deletions of FOXF1 or its distant tissue-specific enhancer. Eighty-five percent of 45 ACDMPV-causative CNV deletions, of which junctions have been sequenced, had at least one of their two breakpoints located in a retrotransposon, with more than half of them being Alu elements. We describe a novel ∼35 kb-large genomic instability hotspot at 16q24.1, involving two evolutionarily young LINE-1 (L1) elements, L1PA2 and L1PA3, flanking AluY, two AluSx, AluSx1, and AluJr elements. The occurrence of L1s at this location coincided with the branching out of the Homo-Pan-Gorilla clade, and was preceded by the insertion of AluSx, AluSx1, and AluJr. Our data show that, in addition to mediating recurrent CNVs, L1 and Alu retrotransposons can predispose the human genome to formation of variably sized CNVs, both of clinical and evolutionary relevance. Nonetheless, epigenetic or other genomic features of this locus might also contribute to its increased instability.

Blood culture indications in critically ill neonates: a multicenter prospective cohort study.

Due to potential lethality of healthcare-associated sepsis (HAS), a low threshold for blood culturing and antimicrobial therapy (ABT) initiation is accepted. We assessed variability in the trigger for blood culturing between three neonatal intensive care units. A multicenter prospective cohort study was conducted. In newborns with suspicion of HAS, 10 predefined clinical signs, nosocomial sepsis (NOSEP) score, C-reactive protein, ABT initiation, and risk factors were registered at time of culturing. Outcome was lab-confirmed HAS, defined according to the NeoKISS-criteria. Two hundred ninety-nine suspected HAS episodes were considered in 212 infants, of which 118 had birth-weight ≤ 1500 g; proportion of lab-confirmed HAS per suspected episode was 30/192 (center 1), 28/60 (center 2), and 8/47 (center 3) (p < 0.001). Median C-reactive protein and number of clinical signs at time of culturing differed between centers 1, 2, and 3 (respectively 11 vs. 5 vs. 3 mg/L, p = 0.001; 1 sign [IQR 0-2, center 1] vs. 3 signs [IQR 2-4, centers 2 and 3], p < 0.001). Median NOSEP score at time of culturing was 5 (IQR 3-8, center 1), 5 (IQR 3-9, center 2), and 8 (IQR 5-11, center 3) (p = 0.016). Difference in ABT initiation was noticed (82 vs. 93 vs. 74%, p = 0.05). CONCLUSION: Center heterogeneity in sampling practice is substantial. Optimizing sampling practice can be recommended. What is Known: • Blood culture test is a common diagnostic procedure in critically-ill newborns. • A low threshold for sampling and antimicrobial therapy initiation is accepted. What is New: • Variability in blood culture practice was assessed between 3 neonatal intensive care units by the registration of sampling frequencies, clinical indications, and antimicrobial therapy initiation.

Impact of healthcare-associated sepsis on mortality in critically ill infants.

UNLABELLED: Healthcare-associated sepsis (HAS) is a life-threatening complication in neonatal intensive care. Research into the impact of HAS on mortality adjusted for comorbidities is however limited. We conducted a historical cohort study to evaluate impact of HAS on mortality stratified by birth weight and risk factors for mortality in the HAS cohort. HAS was defined according to the National Institute of Child Health and Human Development criteria. Logistic regression was used to calculate adjusted odds of mortality. Of 5134 admissions, 342 infants developed HAS (6.7 %). Mortality in the total and HAS cohort was 5.6 and 10.5 %, respectively. The majority of HAS was caused by commensals (HAS-COM, 59.4 %) and 40.6 % by recognized pathogens (HAS-REC). Adjusted for comorbidities, "HAS-REC" is only a risk factor for mortality in newborns >1500 g (adjusted odds ratio [aOR] 2.3, confidence interval [CI] 1.1-4.9). Post-hoc analysis identified HAS-REC as an independent risk factor for mortality in infants with gastrointestinal disease (aOR 4.8, CI 2.1-10.8). "Renal insufficiency," "focal intestinal perforation," and "necrotizing enterocolitis" are independent risk factors for mortality in the HAS cohort (aOR 13.5, CI 4.9-36.6; aOR 7.7, CI 1.5-39.2; aOR 2.1, CI 1.0-4.7, respectively). CONCLUSION: For very low birth weight infants (≤1500 g), several comorbidities overrule the impact of HAS on mortality. After adjustment for comorbidities, HAS-REC independently predicts in-hospital mortality in heavier infants and in those with gastrointestinal disease. WHAT IS KNOWN: • The relationship between healthcare-associated sepsis and mortality is influenced by the causative pathogen and is confounded by comorbidities. • Research on impact of healthcare-associated sepsis on mortality adjusted for comorbidities is limited as well as research on independent risk factors for mortality in neonates with sepsis. What is New: • We included a large list of comorbidities and stratified risk by birth weight in order to assess the true effect of healthcare-associated sepsis on mortality. • Risk for mortality was calculated for commensal flora and for recognized pathogens as causative micro-organisms.

Risk Factors for Health Care-Associated Sepsis in Critically Ill Neonates Stratified by Birth Weight.

BACKGROUND: Health care-associated bloodstream infection (HABSI) is a frequent complication in neonatal intensive care. Research on risk factors stratified by birth weight and adjusted for severity of illness and comorbidities is limited. Our objective is to describe independent risk factors for HABSI in critically ill neonates with emphasis on risk variation between birth weight groups. METHODS: We performed a single-center historical cohort study in a tertiary referral center. A neonatal intensive care-audit system was used to identify eligible neonates admitted for ≥72 hours (2002-2011). HABSI is defined according to National Institute of Child Health and Human Development criteria. Risk factors for HABSI were assessed by univariate and logistic regression analysis for the total cohort and for birth weight subgroups, that is, neonates ≤1500 g and >1500 g. RESULTS: A total of 342 neonates developed HABSI in 5134 admissions of ≥72 hours (6.7%). Very low birth weight, total parenteral nutrition (TPN), mechanical ventilation, gastrointestinal disease, surgery (cardiac and other type), and renal insufficiency are independent risk factors for the total cohort. Gastrointestinal disease and cardiac surgery are independent risk factors in both birth weight groups; mechanical ventilation (odds ratio [OR]: 2.6; confidence interval [CI]: 1.6-4.0) and other type of surgery (OR: 4.3; CI: 2.1-8.8) are solely independent risk factors in the ≤1500-g cohort; TPN is exclusively an independent risk factor (OR: 7.9; CI: 3.9-16.2) in the >1500-g cohort. CONCLUSIONS: In our neonatal intensive care unit, risk stratification by birth weight revealed some difference. Special attention concerning infection control practices is for neonates receiving TPN, mechanical ventilation, cardiac surgery, and with a gastrointestinal disease.

Healthcare-associated bloodstream infections in a neonatal intensive care unit over a 20-year period (1992-2011): trends in incidence, pathogens, and mortality.

OBJECTIVE: To analyze trends in the incidence and pathogen distribution of healthcare-associated bloodstream infections (HABSIs) over a 20-year period (1992-2011). DESIGN: Historical cohort study. SETTING: Thirty-two-bed neonatal intensive care unit (NICU) in a tertiary referral hospital. PATIENTS: Neonates with HABSIs defined according to the criteria of the National Institute of Child Health and Development (NICHD). METHODS: A hospital-based ongoing surveillance program was used to identify HABSI cases in neonates. A distinction between definite or possible HABSI was made according to the NICHD criteria. Incidence, incidence densities (HABSIs per 1,000 hospital-days and HABSIs per 1,000 total parenteral nutrition-days), and case fatality rate were calculated. Logistic regression analysis was used to find time trends. Four periods of 5 years were considered when executing variance analysis. RESULTS: In total, 682 episodes of HABSIs occurred on 9,934 admissions (6.9%). The median total incidence density rate was 3.1 (interquartile range, 2.2-3.9). A significant increasing time trend in incidence density was observed for the period 1995-2011 (P < .003). A significant decrease in the case fatality rate was found in the last 5-year period (P < .001). No neonate died following possible HABSIs, whereas the case fatality rate among neonates with definite HABSIs was 9.7%. Most HABSIs were caused by coagulase-negative staphylococci (n = 414 [60.7%]). A significant increase in Staphylococcus aureus HABSI was observed in the last 10-year period (P < .001). CONCLUSIONS: An increase in incidence density rate occurred, while the case fatality rate dropped. Better perinatal care could be responsible for the latter. A decrease in days before infection and a high incidence of coagulase-negative Staphylococcus HABSIs indicate the need for vigorous application of evidence-based prevention initiatives, in particular for catheter care.

Desmopressin lyophilisate for the treatment of central diabetes insipidus: first experience in very young infants.

INTRODUCTION: In neonates and small infants, early diagnosis of central diabetes insipidus (CDI) and treatment with desmopressin in low doses (avoiding severe hypo- or hypernatremia) are important to prevent associated high morbidity and mortality in this particular age group. CASE PRESENTATION: We described pharmacokinetic and pharmacodynamic results of the use of recently launched oral desmopressin lyophilisate (Minirin Melt®) in two infants with CDI, diagnosed at the age of 12 and 62 days, respectively. We observed that a starting dose of 60 µg of Minirin Melt® in the first case resulted in a pharmacokinetic profile largely exceeding the reference frame observed in children with nocturnal enuresis, while a dose of 15 µg in the second case resulted in acceptable concentrations. After initial dose adjustments, administration of sublingual lyophilisate resulted in rather stable serum sodium concentrations. CONCLUSIONS: Using Minirin Melt® in infants with CDI appears to be effective, easy to use and well tolerated.

Functional polymorphism in gamma-glutamylcarboxylase is a risk factor for severe neonatal hemorrhage.

A neonate who received vitamin K (VK) supplementation then developed severe late-onset bleeding with abnormal prothrombin time and activated partial thromboplastine time. The bleeding was corrected after intravenous VK. Molecular analysis of the gamma-glutamylcarboxylase gene revealed a heterozygous single nucleotide polymorphism, which decreases carboxylase activity and induces VK-dependent coagulation deficiency.