Prospective multicenter evaluation of adherence to the Dutch guideline for children aged 0-16 years with fever without a source-febrile illness in children (FINCH) study.

Evaluation of guidelines in actual practice is a crucial step in guideline improvement. A retrospective evaluation of the Dutch guideline for children with fever without an apparent source (FWS) showed 50% adherence in young infants. We prospectively evaluated adherence to the Dutch guideline and its impact on management in current practice. Prospective observational multicenter cross-sectional study, including children 3 days to 16 years old presented for FWS at one of seven emergency departments in participating secondary and tertiary care hospitals in the Netherlands. Adherence to the Dutch FWS guideline, adapted from the National Institute for Health and Care Excellence (NICE) guideline, was evaluated, and patterns in non-adherence and the impact of non-adherence on clinical outcomes and resource use were explored. Adherence to the guideline was 192/370 (52%). Adherence was lowest in patients categorized as high risk for severe infection (72/187, 39%), compared to the low-risk group (64/73, 88%). Differences in adherence were significant between risk categories (P < 0.001) but not between age categories. In case of non-adherence, less urinalysis, fewer bacterial cultures (blood, urine, and cerebral spinal fluid), and less empirical antibiotic treatment were performed (P < 0.050). Clinical outcomes were not significantly different between the non-adherence and the adherence group, particularly regarding missed severe infections. CONCLUSIONS: We found a high non-adherence rate of 48%, which did not lead to unfavorable clinical outcomes. This substantiates the need for a critical reevaluation of the FWS guideline and its indications for bacterial cultures, viral testing, and antibiotic treatment. WHAT IS KNOWN: • Despite the development of national guidelines, variation in practice is still substantial in the assessment of febrile children to distinguish severe infection from mild self-limiting disease. • Previous retrospective research suggests low adherence to national guidelines for febrile children in practice. WHAT IS NEW: • In case of non-adherence to the Dutch national guideline, similar to the National Institute for Health and Care Excellence (NICE) guideline from the United Kingdom, physicians have used fewer resources than the guideline recommended without increasing missed severe infections.

'Not a goal, but a given': Neonatal care participation through parents' perspective, a cross-sectional study.

AIM: To explore parents' perspectives regarding participation in neonatal care, with focus on the family integrated care (FICare) model utilised as a tool to enhance parent-infant closeness. Additionally, we describe experiences in different architectural settings. METHODS: An online survey, categorised by four FICare pillars, was distributed through social media to parents of newborns hospitalised to Dutch neonatal wards between 2015 and 2020. Quantitative findings were summarised using descriptive statistics, while open-ended responses were thematically analysed. RESULTS: Among the 344 respondents (98% mothers), most reported feeling involved in care (315/340). However, 79% also felt separated from their infant (265/337). Irrespective of architectural settings, parents reported incomplete implementation of FICare pillars: 14% was invited to educational sessions (parent education), 51% discussed family-specific care plans (staff education), 21% was facilitated in connecting with veteran parents (psychosocial support) and 22% received couplet-care (environment). Although 65% of parents were invited to attend clinical rounds, 32% actively participated in decision making. Thematic analysis revealed fundamentals for feeling welcome on the ward, peer-to-peer support, psychosocial support and participation in clinical rounds. CONCLUSION: Overall, parents expressed satisfaction with participation in neonatal care. However, structural implementation of FICare lacks. Regardless of architecture, expanding parent participation beyond presence requires attention.

Comparison of New Bronchopulmonary Dysplasia Definitions on Long-Term Outcomes in Preterm Infants.

OBJECTIVE: To compare the discriminative performances of the 2018 National Institutes of Health (NIH) and the 2019 Jensen definitions of bronchopulmonary dysplasia (BPD) with the 2001 NIH definition on adverse neurodevelopmental and respiratory outcomes at 2 years and 5 years corrected age. STUDY DESIGN: In this single-center retrospective cohort study, outcomes of infants born at <30 weeks of gestational age were collected. The 3 definitions of BPD were compared by adding the different definitions to the National Institute of Child Health and Human Development's outcome prediction model for neurodevelopmental impairment (NDI) or death. Discriminative performance was compared for both outcomes at 2 years and 5 years corrected age by calculating the areas under the receiver operating characteristic curve and z-statistics. RESULTS: The presence of BPD and its severity were determined in 584 infants. There were considerable shifts in BPD grading among the different definitions. At both time points, all BPD definition models had comparable discriminating power for NDI and respiratory morbidity, with one exception. Compared with the 2001 NIH definition, the 2018 NIH definition had less predictive power for the neurologic outcome at 2 years corrected age. CONCLUSIONS: Our comparison of the 3 BPD definitions shows similar discriminative performance on long term neurodevelopmental and respiratory outcomes at 2 years and 5 years corrected age.

Family integrated care in single family rooms for preterm infants and late-onset sepsis: a retrospective study and mediation analysis.

BACKGROUND: During hospital stay after birth, preterm infants are susceptible to late-onset sepsis (LOS). OBJECTIVE: To study the effect of family integrated care in single family rooms (SFRs) compared to standard care in open bay units (OBUs) on LOS. Peripheral or central venous catheters (PVCs/CVCs) and parenteral nutrition (PN) were investigated as potential mediators. Secondary outcomes were length of stay, exclusive breastfeeding at discharge, and weight gain during hospital stay. METHODS: Single-center retrospective before-after study with preterm infants admitted ≥3 days. RESULTS: We studied 1,046 infants (468 in SFRs, 578 in OBUs, median gestational age 35 weeks). SFRs were associated with less LOS (adjusted odds ratio (OR) 0.486, 95% confidence interval (CI): 0.293; 0.807, p = 0.005). PVCs (indirect effect -1.757, 95% CI: -2.738; -1.068), CVCs (indirect effect -1.002, 95% CI: -2.481; 0.092), and PN (indirect effect -1.784, 95% CI: -2.688; -1.114) were possible mediators of the effect. PN was the main mediator of the effect of SFRs on LOS. We found shorter length of stay (median length of stay in SFRs 10 days and in OBUs 12 days, adjusted ß -0.088, 95% CI: -0.159; -0.016, p = 0.016), but no differences in weight gain or exclusive breastfeeding at discharge. CONCLUSIONS: SFRs were associated with decreased incidences of LOS and shorter length of hospital stay. The positive effect of SFRs on LOS was mainly mediated through a decreased use of PN in SFRs. IMPACT: Family integrated care (FICare) in single family rooms for preterm infants was associated with less late-onset sepsis events during hospital stay and a shorter length of hospital stay after birth. FICare in single family rooms was associated with less use of peripheral or central venous catheters and parenteral nutrition. Mediation analysis provided insights into the mechanisms underlying the effect of FICare in single family rooms on late-onset sepsis and helped explain the differences observed in late-onset sepsis between FICare in single family rooms and open bay units. The reduction in late-onset sepsis in FICare in single family rooms was mediated by a reduced use of intravenous catheters and parenteral nutrition.

Accuracy of Pulse Oximetry Screening for Critical Congenital Heart Defects after Home Birth and Early Postnatal Discharge.

OBJECTIVE: To assess the accuracy of pulse oximetry screening for critical congenital heart defects (CCHDs) in a setting with home births and early discharge after hospital deliveries, by using an adapted protocol fitting the work patterns of community midwives. STUDY DESIGN: Pre- and postductal oxygen saturations (SpO2) were measured ≥1 hour after birth and on day 2 or 3. Screenings were positive if the SpO2 measurement was <90% or if 2 independent measures of pre- and postductal SpO2 were <95% and/or the pre-/postductal difference was >3%. Positive screenings were referred for pediatric assessment. Primary outcomes were sensitivity, specificity, and false-positive rate of pulse oximetry screening for CCHD. Secondary outcome was detection of noncardiac illnesses. RESULTS: The prenatal detection rate of CCHDs was 73%. After we excluded these cases and symptomatic CCHDs presenting immediately after birth, 23 959 newborns were screened. Pulse oximetry screening sensitivity in the remaining cohort was 50.0% (95% CI 23.7-76.3) and specificity was 99.1% (95% CI 99.0-99.2). Pulse oximetry screening was false positive for CCHDs in 221 infants, of whom 61% (134) had noncardiac illnesses, including infections (31) and respiratory pathology (88). Pulse oximetry screening did not detect left-heart obstructive CCHDs. Including cases with prenatally detected CCHDs increased the sensitivity to 70.2% (95% CI 56.0-81.4). CONCLUSION: Pulse oximetry screening adapted for perinatal care in home births and early postdelivery hospital discharge assisted the diagnosis of CCHDs before signs of cardiovascular collapse. High prenatal detection led to a moderate sensitivity of pulse oximetry screening. The screening also detected noncardiac illnesses in 0.6% of all infants, including infections and respiratory morbidity, which led to early recognition and referral for treatment.

Prospective evaluation and follow-up of nutritional status of children hospitalized in secondary-care level hospitals: a multicentre study.

Although disease-associated undernutrition is still an important problem in hospitalized children that is often underrecognized, follow-up studies evaluating post-discharge nutritional status of children with undernutrition are lacking. The aim of this multicentre prospective observational cohort study was to assess the rate of acute undernutrition (AU) and/or having a high nutritional risk (HR) in children on admission to seven secondary-care level Dutch hospitals and to evaluate the nutritional course of AU/HR group during admission and post-discharge. STRONGkids was used to indicate HR, and AU was based on anthropometric data (z-score < -2 for weight-for-age (WFA; <1 year) or weight-for-height (WFH; ≥1 year)). In total, 1985 patients were screened for AU/HR over a 12-month period. On admission, AU was present in 9.9% of screened children and 6.2% were classified as HR; 266 (13.4%) children comprised the AU/HR group (median age 2.4 years, median length of stay 3 days). In this group, further nutritional assessment by a dietitian during hospitalization occurred in 44% of children, whereas 38% received nutritional support. At follow-up 4-8 weeks post-discharge, 101 out of orginal 266 children in the AU/HR group (38%) had available paired anthropometric measurements to re-assess nutrition status. Significant improvement of WFA/WFH compared to admission (-2.48 vs. -1.51 SD; p < 0.001) and significant decline in AU rate from admission to outpatient follow-up (69.3% vs. 35.6%; p < 0.001) were shown. In conclusion, post-discharge nutritional status of children with undernutrition and/or high nutritional risk on admission to secondary-care level pediatric wards showed significant improvement, but about one-third remained undernourished. Findings warrant the need for a tailored post-discharge nutritional follow-up.

Collaborating to Improve Neonatal Care: ParentAl Participation on the NEonatal Ward-Study Protocol of the neoPARTNER Study.

Parents are often appointed a passive role in the care for their hospitalised child. In the family-integrated care (FICare) model, parental involvement in neonatal care is emulated. Parental participation in medical rounds, or family-centred rounds (FCR), forms a key element. A paucity remains of randomised trials assessing the outcomes of FCR (embedded in FICare) in families and neonates, and outcomes on an organisational level are relatively unexplored. Likewise, biological mechanisms through which a potential effect may be exerted are lacking robust evidence. Ten level two Dutch neonatal wards are involved in this stepped-wedge cluster-randomised trial FCR (embedded in FICare) by one common implementation strategy. Parents of infants hospitalised for at least 7 days are eligible for inclusion. The primary outcome is parental stress (PSS:NICU) at discharge. Secondary outcomes include parental, neonatal, healthcare professional and organisational outcomes. Biomarkers of stress will be analysed in parent-infant dyads. With a practical approach and broad outcome set, this study aims to obtain evidence on the possible (mechanistic) effect of FCR (as part of FICare) on parents, infants, healthcare professionals and organisations. The practical approach provides (experiences of) FICare material adjusted to the Dutch setting, available for other hospitals after the study.

Can Presepsin Be Valuable in Reducing Unnecessary Antibiotic Exposure after Birth?

BACKGROUND: Due to a lack of rapid, accurate diagnostic tools for early-onset neonatal sepsis (EOS) at the initial suspicion, infants are often unnecessarily given antibiotics directly after birth. We aimed to determine the diagnostic accuracy of presepsin for EOS before antibiotic initiation and to investigate whether presepsin can be used to guide clinicians' decisions on whether to start antibiotics. METHODS: In this multicenter prospective observational cohort study, all infants who started on antibiotics for EOS suspicion were consecutively included. Presepsin concentrations were determined in blood samples collected at the initial EOS suspicion (t = 0). In addition to this, samples were collected at 3, 6, 12 and 24 h after the initial EOS suspicion and from the umbilical cord directly after birth. The diagnostic accuracy of presepsin was calculated. RESULTS: A total of 333 infants were included, of whom 169 were born preterm. We included 65 term and 15 preterm EOS cases. At the initial EOS suspicion, the area under the curve (AUC) was 0.60 (95% confidence interval (CI) 0.50-0.70) in the term-born infants compared to 0.84 (95% CI 0.73-0.95) in the preterm infants. A cut-off value of 645 pg/mL resulted in a sensitivity of 100% and a specificity of 54% in the preterm infants. The presepsin concentrations in cord blood and at other time points did not differ significantly from the concentrations at the initial EOS suspicion. CONCLUSIONS: Presepsin is a biomarker with an acceptable diagnostic accuracy for EOS (culture-proven and clinical EOS) in preterm infants and might be of value in reducing antibiotic exposure after birth when appended to current EOS guidelines. However, the small number of EOS cases prevents us from drawing firm conclusions. Further research should be performed to evaluate whether appending a presepsin-guided step to current EOS guidelines leads to a safe decrease in antibiotic overtreatment and antibiotic-related morbidity.

An international study on implementation and facilitators and barriers for parent-infant closeness in neonatal units.

Importance: Parent-infant closeness and active parent participation in neonatal care are important for parent and infant health. Objective: To give an overview of current neonatal settings and gain an in-depth understanding of facilitators and barriers to parent-infant closeness, zero-separation, in 19 countries. Methods: Neonatal intensive care unit (NICU) professionals, representing 45 NICUs from a range of geographic regions in Europe and Canada, were purposefully selected and interviewed June-December 2018. Thematic analysis was conducted to identify, analyze and report patterns (themes) for parent-infant closeness across the entire series of interviews. Results: Parent-infant separation during infant and/or maternity care is very common (42/45 units, 93%), despite the implementation of family integrated care (FICare) practices, including parent participation in medical rounds (17/45, 38%), structured education sessions for parents (16/45, 36%) and structured training for healthcare professionals (22/45, 49%). NICU professionals encountered four main themes with facilitators and barriers for parent-infant closeness on and between the hospital, unit, staff, and family level: Culture (jointly held characteristics, values, thinking and behaviors about parental presence and participation in the unit), Collaboration (the act of working together between and within different levels), Capacities (resources and policies), and Coaching (education to acquire and transfer knowledge and skills). Interpretation: Implementing parent-infant closeness in the NICU is still challenging for healthcare professionals. Further optimization in neonatal care towards zero-separation and parent-infant closeness can be achieved by enforcing the 'four Cs for Closeness': Culture, Collaboration, Capacities, and Coaching.

Association of a Family Integrated Care Model With Paternal Mental Health Outcomes During Neonatal Hospitalization.

Importance: During newborn hospitalization in the neonatal unit, fathers often feel anxious and excluded from their child's caregiving and decision-making. Few studies and interventions have focused on fathers' mental health and their participation in neonatal care. Objective: To study the association of a family integrated care (FICare) model (in single family rooms with complete couplet-care for the mother-newborn dyad) vs standard neonatal care (SNC) in open bay units with separate maternity care with mental health outcomes in fathers at hospital discharge of their preterm newborn and to study whether parent participation was a mediator of the association of the FICare model on outcomes. Design, Setting, and Participants: This prospective, multicenter cohort study was conducted from May 2017 to January 2020 as part of the fAMily Integrated Care in the Neonatal Ward Study, at level-2 neonatal units in the Netherlands (1 using the FICare model and 2 control sites using SNC). Participants included fathers of preterm newborns admitted to participating units. Data analysis was performed from January to April 2021. Exposure: FICare model in single family rooms with complete couplet-care for the mother-newborn dyad during maternity and/or neonatal care. Main Outcomes and Measures: Paternal mental health was measured using the Parental Stress Scale: NICU, Hospital Anxiety and Depression Scale, Post-partum Bonding Questionnaire, Perceived (Maternal) Parenting Self-efficacy Scale, and satisfaction with care (EMpowerment of PArents in THe Intensive Care-Neonatology). Parent participation (CO-PARTNER tool) was assessed as a potential mediator of the association of the FICare model with outcomes with mediation analyses (prespecified). Results: Of 309 families included in the fAMily Integrated Care in the Neonatal Ward Study, 263 fathers (85%) agreed to participate; 126 fathers were enrolled in FICare and 137 were enrolled in SNC. In FICare, 89 fathers (71%; mean [SD] age, 35.1 [4.8] years) responded to questionnaires and were analyzed. In SNC, 93 fathers (68%; mean [SD] age, 36.4 [5.5] years) responded to questionnaires and were analyzed. Fathers in FICare experienced less stress (adjusted ß, -10.02; 95% CI, -15.91 to -4.13; P = .001) and had higher participation scores (adjusted odds ratio, 3.424; 95% CI, 0.860 to 5.988; P = .009) compared with those in SNC. Participation mediated the beneficial association of the FICare model with fathers' depressive symptoms (indirect effect, -0.051; 95% CI, -0.133 to -0.003) and bonding with their newborns (indirect effect, -0.082; 95% CI, -0.177 to -0.015). Conclusions and Relevance: These findings suggest that the FICare model is associated with decreased paternal stress at discharge and enables fathers to be present and participate more than SNC, thus improving paternal mental health. Supporting fathers to actively participate in all aspects of newborn care should be encouraged regardless of architectural design of the neonatal unit.

Association of a Zero-Separation Neonatal Care Model With Stress in Mothers of Preterm Infants.

Importance: Active participation in care by parents and zero separation between parents and their newborns is highly recommended during infant hospitalization in the neonatal intensive care unit (NICU). Objective: To study the association of a family integrated care (FICare) model with maternal mental health at hospital discharge of their preterm newborn compared with standard neonatal care (SNC). Design, Setting, and Participants: This prospective, multicenter cohort study included mothers with infants born preterm treated in level-2 neonatal units in the Netherlands (1 unit with single family rooms [the FICare model] and 2 control sites with standard care in open bay units) between May 2017 and January 2020 as part of the AMICA study (fAMily Integrated CAre in the neonatal ward). Participants included mothers of preterm newborns admitted to participating units. Data analysis was performed from January to April 2021. Exposures: FICare model in single family rooms with complete couplet-care for the mother-newborn dyad during maternity and/or neonatal care. Main Outcomes and Measures: Maternal mental health, measured using the Parental Stress Scale: NICU (PSS-NICU). Secondary outcomes included survey scores on the Hospital Anxiety and Depression Scale, Postpartum Bonding Questionnaire, Perceived Maternal Parenting Self-efficacy Scale, and satisfaction with care (using EMPATHIC-N). Parent participation (using the CO-PARTNER tool) was assessed as a potential mediator of the association of the FICare model on outcomes with mediation analyses. Results: A total of 296 mothers were included; 124 of 141 mothers (87.9%) in the FICare model and 115 of 155 (74.2%) mothers in SNC responded to questionnaires (mean [SD] age: FICare, 33.3 [4.0] years; SNC, 33.3 [4.1] years). Mothers in the FICare model had lower total PSS-NICU stress scores at discharge (adjusted mean difference, -12.24; 95% CI, -18.44 to -6.04) than mothers in SNC, and specifically had lower scores for mother-newborn separation (adjusted mean difference, -1.273; 95% CI, -1.835 to -0.712). Mothers in the FICare model were present more (>8 hours per day: 105 of 125 [84.0%] mothers vs 42 of 115 [36.5%]; adjusted odds ratio, 19.35; 95% CI, 8.13 to 46.08) and participated more in neonatal care (mean [SD] score: 46.7 [6.9] vs 40.8 [6.7]; adjusted mean difference, 5.618; 95% CI, 3.705 to 7.532). Active parent participation was a significant mediator of the association between the FICare model and less maternal depression and anxiety (adjusted indirect effect, -0.133; 95% CI, -0.226 to -0.055), higher maternal self-efficacy (adjusted indirect effect, 1.855; 95% CI, 0.693 to 3.348), and better mother-newborn bonding (adjusted indirect effect, -0.169; 95% CI, -0.292 to -0.068). Conclusions and Relevance: The FICare model in our study was associated with less maternal stress at discharge; mothers were more present and participated more in the care for their newborn than in SNC, which was associated with improved maternal mental health outcomes. Future intervention strategies should aim at reducing mother-newborn separation and intensifying active parent participation in neonatal care. Trial Registration: Netherlands Trial Register identifier NL6175.

Effects of parent-provider communication during infant hospitalization in the NICU on parents: A systematic review with meta-synthesis and narrative synthesis.

OBJECTIVE: To synthesize and analyse the literature on the effects of parent-provider communication during infant hospitalization in the neonatal (intensive) care unit (NICU) on parent-related outcomes. METHODS: Systematic review with meta-synthesis and narrative synthesis. Databases (PubMed, PsycINFO, Cochrane Library, CINAHL, Web of Science, Scopus) were searched in October/November 2019. Studies reporting, observing, or measuring parent-related effects of parent-provider communication in the NICU were included. Study quality was assessed using the Quality Assessment Tool for Studies with Diverse Designs. Qualitative studies were meta-synthesized using deductive and inductive thematic analysis. Quantitative studies were analysed using narrative synthesis. RESULTS: 5586 records were identified; 77 were included, reporting on N = 6960 parents, N = 693 providers, and N = 300 NICUs. Analyses revealed five main (positive and negative) effects of parent-provider interaction on parents' (1) coping, (2) knowledge, (3) participation, (4) parenting, and (5) satisfaction. Communication interventions appeared impactful, particularly in reducing parental stress and anxiety. Findings confirm and refine the NICU Communication Framework. CONCLUSIONS: Parent-provider communication is a crucial determinant for parental well-being and satisfaction with care, during and following infant hospitalization in the NICU. R. Practice Implications: Providers should particularly consider the impact on parents of their day-to-day interaction - the most occurring form of communication of all.

Development and psychometric evaluation of the CO-PARTNER tool for collaboration and parent participation in neonatal care.

BACKGROUND: Active parent participation in neonatal care and collaboration between parents and professionals during infant hospitalization in the neonatal intensive care unit (NICU) is beneficial for infants and their parents. A tool is needed to support parents and to study the effects and implementation of parent-partnered models of neonatal care. METHODS: We developed and psychometrically evaluated a tool measuring active parent participation and collaboration in neonatal care within six domains: Daily Care, Medical Care, Acquiring Information, Parent Advocacy, Time Spent with Infant and Closeness and Comforting the Infant. Items were generated in focus group discussions and in-depth interviews with professionals and parents. The tool was completed at NICU-discharge by 306 parents (174 mothers and 132 fathers) of preterm infants. Subsequently, we studied structural validity with confirmatory factor analysis (CFA), construct validity, using the Average Variance Extracted and Heterotrait-Monotrait ratio of correlations, and hypothesis testing with correlations and univariate linear regression. For internal consistency we calculated composite reliability (CR). We performed multiple imputations by chained equations for missing data. RESULTS: A 31 item tool for parent participation and collaboration in neonatal care was developed. CFA revealed high factor loadings of items within each domain. Internal consistency was 0.558 to 0.938. Convergent validity and discriminant validity were strong. Higher scores correlated with less parent depressive symptoms (r = -0.141, 95%CI -0.240; -0.029, p = 0.0141), less impaired parent-infant bonding (r = -0.196, 95%CI -0.302; -0.056, p<0.0001), higher parent self-efficacy (r = 0.228, 95%CI 0.117; 0.332, p<0.0001), and higher parent satisfaction (r = 0.197, 95%CI 0.090; 0.308, p = 0.001). Parents in a family integrated care model had higher scores than in standard care (beta 6.020, 95%CI 4.144; 7.895, p<0.0001) and mothers scored higher than fathers (beta 2.103,95%CI 0.084; 4.121, p = 0.041). CONCLUSION: The CO-PARTNER tool explicitly measures parents' participation and collaboration with professionals in neonatal care incorporating their unique roles in care provision, leadership, and connection to their infant. The tool consists of 31 items within six domains with good face, content, construct and structural validity.

Majority of dietary glutamine is utilized in first pass in preterm infants.

Glutamine is a conditionally essential amino acid for very low-birth weight infants by virtue of its ability to play an important role in several key metabolic processes of immune cells and enterocytes. Although glutamine is known to be used to a great extent, the exact splanchnic metabolism in enterally fed preterm infants is unknown. We hypothesized that preterm infants show a high splanchnic first-pass glutamine metabolism and the primary metabolic fate of glutamine is oxidation. Five preterm infants (mean + or - SD birth weight 1.07 + or - 0.22 kg and GA 29 + or - 2 wk) were studied by dual tracer ([U-(13)C]glutamine and [(15)N(2)]glutamine) cross-over techniques on two study days (at postnatal week 3 + or - 1 wk). Splanchnic and whole-body glutamine kinetics were assessed by plasma isotopic enrichment of [U-(13)C]glutamine and [(15)N(2)]glutamine and breath (13)CO(2) enrichments. Mean fractional first-pass glutamine uptake was 73 + or - 6% and 57 + or - 17% on the study days. The splanchnic tissues contributed for a large part (57 + or - 6%) to the total amount of labeled carbon from glutamine retrieved in expiratory air. Dietary glutamine is used to a great extent by the splanchnic tissues in preterm infants and its carbon skeleton has an important role as fuel source.

Age-Specific Reference Intervals for Plasma Free Thyroxine and Thyrotropin in Term Neonates During the First Two Weeks of Life.

Background: Congenital hypothyroidism (CH) is a common and preventable cause of mental retardation, which is detected in many neonatal screening programs. Upon suspicion of CH, plasma free thyroxine (fT4) and thyrotropin (TSH) concentrations are measured. CH can be of thyroidal or central origin (CH-T and CH-C, respectively). While CH-T diagnosis is based on an elevated TSH with a low fT4, CH-C diagnosis is based on a low fT4 without a clearly elevated TSH. Currently, reliable neonatal reference intervals (RIs) for plasma fT4 and TSH are lacking. Age-specific RIs would greatly improve the diagnostic process for CH, especially for CH-C. Our aim was to establish neonatal RIs for plasma fT4 and TSH in term neonates at day 3-7 (t = 1) and day 13-15 (t = 2). The study was particularly designed to provide a reliable fT4 lower limit of the RI to facilitate the diagnosis of CH-C. In the Netherlands, neonates are screened at day 3-7 of life. After a screening result suggestive for CH-C, pediatric consultation takes place on average at day 14. Thus, the time points were chosen accordingly. Methods: Venous blood was collected from 120 healthy neonates at each time point (94 participants provided blood samples at two time points; 52 participants provided a sample at t = 1 or t = 2). fT4 and TSH were measured using an immunoassay (Cobas; Roche Diagnostics). RIs were calculated using the 95% confidence interval for normally distributed data and the nonparametric percentile method if data were not normally distributed. Results: From 146 participants (49% female), ≥1 measurement was available. Ninety-five percent RIs for fT4 were 20.5-37.1 pmol/L (day 3-7) and 15.3-26.5 pmol/L (day 13-15). Ninety-five percent RIs for TSH were 1.0-8.4 mU/L (day 3-7) and 1.4-8.6 mU/L (day 13-15). Conclusions: Our results indicate an fT4 lower limit of the RI of 20.5 pmol/L at day 3-7 and 15.3 pmol/L at day 13-15. These lower limits are considerably higher than this assay's lower limit of the adult RI for fT4. In case CH is suspected, we recommend measuring fT4 and TSH using an assay with an established neonatal RI, taking into account the child's age in days.

Hospitalising preterm infants in single family rooms versus open bay units: A systematic review and meta-analysis of impact on parents.

BACKGROUND: Many parents develop stress-related symptoms and depression when their preterm infant is hospitalised in the neonatal intensive care unit (NICU) after birth. We reviewed the evidence of parent well-being with preterm infants hospitalised in single family rooms (SFRs) or in open bay neonatal units (OBUs). METHODS: For this systematic review and meta-analysis, we searched MEDLINE, EMBASE, PsycINFO, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, Clinicaltrials.gov, and International Clinical Trials Registry Platform (ICTRP) databases from inception through 22 November 2019 using controlled terms and text words related to prematurity and NICU-design. We included randomised and non-randomised studies comparing outcomes in parents with preterm infants admitted to SFRs or OBUs. Methodological quality was assessed using Cochrane Collaboration's Risk of Bias Tool for randomised controlled trials and the Risk of Bias Tool for Non-Randomised Studies of Interventions (ROBINS-I). Outcomes included: parental stress, satisfaction, participation (presence/involvement/skin-to-skin care), self-efficacy, parent-infant-bonding, depression, anxiety, post-traumatic stress, empowerment, and degree of family-centred care. Summary estimates were calculated using random effects models with standardised mean differences (SMDs). PROSPERO registration: CRD42016050643. FINDINGS: We identified 614 unique publications. Eleven study populations (1, 850 preterm infants, 1, 549 mothers and 379 fathers) were included. All but one study were at serious to critical risk of bias. SFRs were associated with higher levels of parental presence, involvement, and skin-to-skin care. Upon discharge, SFRs were associated with lower stress levels (n = 828 parents, SMD-0·30,95%CI -0·50;-0·09, p<0·004, I2=46%), specifically NICU-related stress (n = 573, SMD-0·42,95%CI -0·61;-0·23, p<0·0001, I2=0%). In majority of studies higher levels of empowerment, family-centred care, and satisfaction was present with SFRs. No differences were found for anxiety, parent-infant bonding, or self-efficacy. Depression was high (up to 29%) but not different between settings. No studies described post-traumatic stress. INTERPRETATION: Single family rooms seem to facilitate parental presence, involvement, skin-to-skin care, and reduce NICU-related parental stress.

Hospitalising preterm infants in single family rooms versus open bay units: a systematic review and meta-analysis.

BACKGROUND: The effect of the hospital environment on health and specifically neurodevelopment in preterm infants remains under debate. We assessed outcomes of preterm infants hospitalised in single family rooms compared with common open bay units. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PsycInfo, CENTRAL (the Cochrane Central Register of Controlled Trials), Web of Science, and ClinicalTrials.gov from inception to Aug 13, 2018, using controlled terms (ie, MeSH terms) and text words related to prematurity and neonatal intensive care unit design. We included randomised and non-randomised studies investigating clinical outcomes of preterm infants. We assessed methodological quality using the Cochrane Collaboration's Risk of Bias Tool for randomised controlled trials and the Cochrane Risk of Bias Tool for Non-randomised Studies of Interventions. We calculated summary estimates for meta-analysis using random effects models. The primary outcome was age appropriate long-term neurodevelopment. Secondary outcomes were length of hospital stay, sepsis, breastfeeding, growth, bronchopulmonary dysplasia, intraventricular haemorrhage, retinopathy of prematurity, and mortality. This systematic review is registered with PROSPERO, number CRD42016050643. FINDINGS: We identified 487 records. 13 study populations (n=4793) were included. No difference in cognitive neurodevelopment was found on the Bayley Scales of Infant and Toddler Development-III at 18-24 months of corrected age (680 infants analysed; mean difference 1·04 [95% CI -3·45 to 5·52], p=0·65; I2=42%). The incidence of sepsis was lower (4165 infants analysed; 108 035 days in hospital [hospitalisation days]; risk ratio 0·63 [95% CI 0·50 to 0·78], p<0·0001; I2=0%) and exclusive breastfeeding at discharge was higher (484 infants analysed; 1·31 [1·07 to 1·61], p=0·01; I2=0%) in single family rooms than in open bay units. We found no differences in length of hospital stay, growth, bronchopulmonary dysplasia, intraventricular haemorrhage, retinopathy of prematurity, and mortality. INTERPRETATION: Single family rooms should be considered to hospitalise preterm infants because incidence of sepsis is reduced and exclusive breastfeeding is higher. No difference in long-term neurodevelopment was detected. FUNDING: None.

Effect of enteral IGF-1 supplementation on feeding tolerance, growth, and gut permeability in enterally fed premature neonates.

OBJECTIVES: The gastrointestinal tract of the premature newborn functions suboptimally with regard to digestion, absorption, and feeding tolerance. Human milk contains trophic factors, such as insulin-like growth factor-1 (IGF-1), that are believed to stimulate gut growth and function. The objective of this double blind, randomized, controlled trial was to assess the effects of enteral IGF-1 supplementation on whole body growth measured by weight gain (in grams per kilogram per day), days to regain birth weight, and anthropometrical characteristics, and gut maturation and permeability (measured by sugar absorption tests). PATIENTS AND METHODS: The study included 60 premature infants (birth weight 750-1250 g) during the first month of life. Patients received either standard infant formula or standard infant formula supplemented with IGF-1 in a concentration twice that of human colostrum (10 microg/100 mL of formula). Primary endpoints were days to full enteral feeding, days to regain birth weight, and growth rate. Sugar absorption tests were performed weekly to assess the secondary endpoints gut permeability and maturation. RESULTS: None of the primary endpoints differed to statistical significance between groups at any point. However, gut permeability was significantly lower in the IGF-1 supplement group on day 14 compared with the control group. At day 21, lactulose/mannitol excretion ratios were (again) comparable between the groups. CONCLUSIONS: Although gut permeability showed a faster decrease in the IGF-1 supplement group, our data do not support IGF-1 supplementation to infant formula.

The gut takes nearly all: threonine kinetics in infants.

BACKGROUND: Threonine is an essential amino acid that is abundantly present in intestinally produced glycoproteins. Animal studies show that intestinal first-pass threonine metabolism is high, particularly during a restricted enteral protein intake. OBJECTIVE: The objective of the study was to quantify intestinal first-pass threonine metabolism in preterm infants during full enteral feeding and during restricted enteral intake. DESIGN: Eight preterm infants (x +/- SD birth weight: 1.1 +/- 0.1 kg; gestational age: 29 +/- 2 wk) were studied during 2 periods. During period A, 40% of total intake was administered enterally and 60% was administered parenterally. Total threonine intake was 58 +/- 6 micromol kg(-1) h(-1). During period B, the infants received full enteral feeding, and the total threonine intake was 63 +/- 6 micromol kg(-1) h(-1). Dual stable-isotope tracer techniques were used to assess splanchnic and whole-body threonine kinetics. RESULTS: The fractional first-pass threonine uptake by the intestine was remarkably high in both periods: 82 +/- 6% during partial enteral feeding and 70 +/- 6% during full enteral feeding. Net threonine retention was not affected by the route of feeding. CONCLUSION: In preterm infants, the splanchnic tissues extract a very large amount of the dietary threonine intake, which indicates a high obligatory visceral need for threonine, presumably for the purposes of synthesis.