Nutritional intake and growth until two years of age in moderate and late preterms.

BACKGROUND AND AIM: Moderate and late preterm infants (MLPTI) (gestational age 32 0/7-36 6/7 weeks), are at risk for suboptimal growth. This study evaluated adherence to nutritional recommendations until 6 months corrected age (CA), growth until 2 years CA, and associations between nutritional intake and growth until 2 years CA. METHODS: We prospectively collected nutritional intakes from 100 MLPTI during the first week of life and at 6 weeks, 3 months, and 6 months CA. Anthropometry was assessed at birth, discharge, term age, and at 6 weeks, 3 months, 6 months, 1 year, and 2 years CA. RESULTS: On day 7, <40% reached nutritional recommendations. Thereafter, >80% reached protein recommendations until 6 months of life, but <60% reached energy recommendations. Weight z-scores increased from -0.44 at term-age to 0.59 at 3 months CA, but declined to -0.53 at 2 years CA on the TNO curves. No significant associations were found between nutritional intake and growth until 2 years CA. CONCLUSION: No associations were demonstrated between nutritional intakes and growth until 2 years CA, despite not reaching recommended intakes. Despite high efforts to optimize growth, MLPTI find their own growth curve in the first 2 years of life. IMPACT: This research is pioneering in identifying how nutrition influences growth in moderate and late preterm infants (MLPTI) up to 2 years corrected age (CA). MLPTI often do not meet the recommended protein and energy intake in their first week of life, suggesting that current guidelines might be too high. No association was demonstrated between nutritional intake and growth of MLPTI in the first 2 years of life. Initially, MLPTI show an increase in weight z-scores from term age up to 3 months CA but experience a decline in weight z-scores at 2 years CA, according to TNO growth charts.

Risk Factors for Neurodevelopmental Impairment at 2- and 5-Years Corrected Age in Preterm Infants with Established Bronchopulmonary Dysplasia.

INTRODUCTION: The objective of this study was to identify risk factors for neurodevelopmental impairment (NDI) at 2- and 5-years corrected age (CA) in a cohort of preterm infants with established bronchopulmonary dysplasia (BPD). METHODS: This single-center retrospective cohort study included infants born between 2009 and 2016 at a gestational age (GA) <30 weeks with moderate or severe BPD at 36 weeks' postmenstrual age. Perinatal characteristics, (social) demographics, and comorbidities were collected from the electronic patient records. Odds ratios for NDI were calculated with univariate and multivariate logistic regression analyses adjusting for potential confounders. RESULTS: Of the 602 eligible infants, 123 infants were diagnosed with BPD. NDI was present in 30.3% and 56.1% at 2- and 5-years CA, respectively. The only independent risk factors associated with NDI in the multivariate analyses were birthweight (adjusted odds ratio [aOR] 0.74, 95% CI 0.57-0.95; aOR 0.70, 95% CI 0.54-0.91, respectively), small for GA (SGA) (aOR 3.25, 95% CI 1.09-9.61; aOR 5.44, 95% CI 1.62-18.2, respectively) at both time points, and male gender at 5-years CA (OR 2.49, 95% CI 1.11-5.57). CONCLUSION: Birthweight and SGA are independent risk factors for NDI at 2- and 5-years CA and male gender at 5-years CA in preterm infants with BPD. In contrast, well-known other risk factors for NDI in the general population of preterm infants, such as GA, maternal education, and neonatal comorbidities were not independently associated with NDI.

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.

Differences in systemic and mucosal SARS-CoV-2 antibody prevalence in a prospective cohort of Dutch children.

Background: As SARS-CoV-2 will likely continue to circulate, low-impact methods become more relevant to monitor antibody-mediated immunity. Saliva sampling could provide a non-invasive method with reduced impact on children. Studies reporting on the differences between systemic and mucosal humoral immunity to SARS-CoV-2 are inconsistent in adults and scarce in children. These differences may be further unraveled by exploring associations to demographic and clinical variables. Methods: To evaluate the use of saliva antibody assays, we performed a cross-sectional cohort study by collecting serum and saliva of 223 children attending medical services in the Netherlands (irrespective of SARS-CoV-2 exposure, symptoms or vaccination) from May to October 2021. With a Luminex and a Wantai assay, we measured prevalence of SARS-CoV-2 spike (S), receptor binding domain (RBD) and nucleocapsid-specific IgG and IgA in serum and saliva and explored associations with demographic variables. Findings: The S-specific IgG prevalence was higher in serum 39% (95% CI 32 - 45%) than in saliva 30% (95% CI 24 - 36%) (P ≤ 0.003). Twenty-seven percent (55/205) of children were S-specific IgG positive in serum and saliva, 12% (25/205) were only positive in serum and 3% (6/205) only in saliva. Vaccinated children showed a higher concordance between serum and saliva than infected children. Odds for saliva S-specific IgG positivity were higher in girls compared to boys (aOR 2.63, P = 0.012). Moreover, immunocompromised children showed lower odds for S- and RBD-specific IgG in both serum and saliva compared to healthy children (aOR 0.23 - 0.25, P ≤ 0.050). Conclusions: We showed that saliva-based antibody assays can be useful for identifying SARS-CoV-2 humoral immunity in a non-invasive manner, and that IgG prevalence may be affected by sex and immunocompromisation. Differences between infection and vaccination, between sexes and between immunocompromised and healthy children should be further investigated and considered when choosing systemic or mucosal antibody measurement.

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.

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.

Saliva SARS-CoV-2 Antibody Prevalence in Children.

COVID-19 patients produce circulating and mucosal antibodies. In adults, specific saliva antibodies have been detected. Nonetheless, seroprevalence is routinely investigated, while little attention has been paid to mucosal antibodies. We therefore assessed SARS-CoV-2-specific antibody prevalence in serum and saliva in children in the Netherlands. We assessed SARS-CoV-2 antibody prevalence in serum and saliva of 517 children attending medical services in the Netherlands (irrespective of COVID-19 exposure) from April to October 2020. The prevalence of SARS-CoV-2 spike (S), receptor binding domain (RBD), and nucleocapsid (N)-specific IgG and IgA were evaluated with an exploratory Luminex assay in serum and saliva and with the Wantai SARS-CoV-2 RBD total antibody enzyme-linked immunosorbent assay in serum. Using the Wantai assay, the RBD-specific antibody prevalence in serum was 3.3% (95% confidence interval [CI]. 1.9 to 5.3%). With the Luminex assay, we detected heterogeneity between antibodies for S, RBD, and N antigens, as IgG and IgA prevalence ranged between 3.6 and 4.6% in serum and between 0 and 4.4% in saliva. The Luminex assay also revealed differences between serum and saliva, with SARS-CoV-2-specific IgG present in saliva but not in serum for 1.5 to 2.7% of all children. Using multiple antigen assays, the IgG prevalence for at least two out of three antigens (S, RBD, or N) in serum or saliva can be calculated as 3.8% (95% CI, 2.3 to 5.6%). Our study displays the heterogeneity of the SARS-CoV-2 antibody response in children and emphasizes the additional value of saliva antibody detection and the combined use of different antigens. IMPORTANCE Comprehending humoral immunity to SARS-CoV-2, including in children, is crucial for future public health and vaccine strategies. Others have suggested that mucosal antibody measurement could be an important and more convenient tool to evaluate humoral immunity compared to circulating antibodies. Nonetheless, seroprevalence is routinely investigated, while little attention has been paid to mucosal antibodies. We show the heterogeneity of SARS-CoV-2 antibodies, in terms of both antigen specificity and differences between circulating and mucosal antibodies, emphasizing the additional value of saliva antibody detection next to detection of antibodies in serum.

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.

Phenylalanine requirements of enterally fed term and preterm neonates.

BACKGROUND: Phenylalanine, which is an essential aromatic amino acid, is either used for protein synthesis or irreversibly hydroxylated to tyrosine. The provision of optimal amounts of dietary phenylalanine is not only important for growth and development but might also influence catecholamine synthesis and release rates. The current recommended aromatic amino acid requirement for infants aged 0-6 mo is based on the amino acid content of human milk. OBJECTIVE: We quantified the requirements for phenylalanine in the presence of excess tyrosine (166 or 177 mg/kg per day for term and preterm infants, respectively) for term and preterm neonates by using the indicator amino acid oxidation method with l-[1-(13)C]lysine 2HCl as an indicator. Hence, we determined the minimum obligatory phenylalanine requirement. DESIGN: Fully enterally fed term and preterm infants received randomly graded amounts of phenylalanine (5-177 mg/kg per day) as part of an elemental formula. Data are expressed as means ± SDs. RESULTS: Twenty term (birth weight: 3.19 ± 0.34 kg; gestational age: 38.9 ± 1 wk) and 16 preterm (birth weight: 1.75 ± 0.17 kg; gestational age: 32.5 ± 0.6 wk) Asian infants participated at a postnatal age of 17 ± 8 d. In total, 44 studies were performed. The minimum obligatory phenylalanine requirement was 58 mg/kg per day (95% CI: 38-78 mg/kg per day) and 80 mg/kg per day (95% CI: 40-119 mg/kg per day) for term and preterm infants, respectively. CONCLUSION: The determined mean phenylalanine-requirement estimates are lower than the contents of term and preterm formulas currently on the market. This trial was registered at www.trialregister.nl as NTR1610.

Threonine Requirement of the Enterally Fed Term Infant in the First Month of Life.

OBJECTIVE: Threonine is one of the essential amino acids. Its major fate is incorporation into intestinal mucosal proteins and synthesis of secretory glycoproteins. Therefore, it has an important function in the neonatal gut barrier integrity. The objective was to quantify the threonine requirement in fully enterally fed term neonates by means of the indicator amino acid oxidation (IAAO) method, using L-[1-C]phenylalanine as indicator. METHODS: After a 24-hour test diet adaptation, containing randomly assigned amounts of threonine (range 5-182 mg · kg · day), the participating neonates received a primed continuous infusion of [C]bicarbonate and L-[1-C]phenylalanine. At baseline and during the plateau phase of both infusions, breath samples were obtained for CO2. The fractional L-[1-C]phenylalanine oxidation (FCO2) was estimated and plotted against the threonine intakes. Biphasic linear regression crossover analysis was used to calculate the breakpoint of the FCO2, representing the mean threonine requirement. Data are presented as mean ±â€ŠSD. RESULTS: Thirty-two term neonates (gestational age 39 ±â€Š1 weeks, birth weight 3.3 ±â€Š0.3 kg, mean postnatal age 10 ±â€Š4 days) were studied. The mean threonine requirement was estimated to be 68 mg · kg · day with an upper and lower 95% confidence interval of 104 and 32 mg · kg · day, respectively (r = 0.37). CONCLUSIONS: The determined threonine requirement is extremely close to the existing requirement recommendations (∼90% of the present World Health Organization requirement guidelines). Infant formula preparations presently on the market, however, contain up to twice as much threonine as recommended. The threonine intake in formula-fed infants may therefore be reduced considerably.

Amino acids and proteins.

Amino acids and protein are key factors for growth. The neonatal period requires the highest intake in life to meet the demands. Those demands include amino acids for growth, but proteins and amino acids also function as signalling molecules and function as neurotransmitters. Often the nutritional requirements are not met, resulting in a postnatal growth restriction. However, current knowledge on adequate levels of both amino acid as well as protein intake can avoid under nutrition in the direct postnatal phase, avoid the need for subsequent catch-up growth and improve later outcome.

Branched-chain amino acid requirements for enterally fed term neonates in the first month of life.

BACKGROUND: Knowledge of essential amino acid requirements in infants is important because excessive intake of protein can lead to increased long-term morbidity such as obesity. A deficient intake may lead to suboptimal growth and impaired neurodevelopment. The current recommended branched-chain amino acid requirements in infants aged 0-1 mo are based on the amino acid content of human milk. OBJECTIVE: We quantified the requirements for isoleucine, leucine, and valine for term neonates by using the indicator amino acid oxidation method with [1-(13)C]phenylalanine as the indicator. DESIGN: Fully enterally fed term infants received randomly graded amounts of isoleucine (5-216 mg · kg(-1) · d(-1)), leucine (5-370 mg · kg(-1) · d(-1)), or valine (5-236 mg · kg(-1) · d(-1)) as part of an elemental formula. Data are expressed as means ± SDs. RESULTS: Eighty-three Asian, term neonates (mean ± SD birth weight: 3.3 ± 0.4 kg; gestational age: 39.4 ± 1.3 wk) were studied at a postnatal age of 13 ± 5 d. Mean requirements for isoleucine, leucine, and valine (measured in boys only) were 105 mg · kg(-1) · d(-1) (r(2) = 0.61, P < 0.001), 140 mg · kg(-1) · d(-1) (r(2) = 0.26, P < 0.01), and 110 mg · kg(-1) · d(-1) (r(2) = 0.35, P = 0.001), respectively. CONCLUSIONS: Current human milk-based recommendations for isoleucine and valine in term infants aged 0-1 mo are correct. However, the current recommendation for leucine (166 mg · kg(-1) · d(-1)) is higher than the mean requirement of 140 mg · kg(-1) · d(-1) that we determined in this study. This trial was registered at www.trialregister.nl as NTR1610.

New insights into the methodological issues of the indicator amino acid oxidation method in preterm neonates.

BACKGROUND: We determined the effect of adaptation to the study diet on oxidation of the indicator amino acid and the required tracer washout time in preterms. METHODS: Subjects received a study diet for 6 d that entailed a 50% reduction in leucine. Tracer studies using enterally infused [(13)C]bicarbonate and [1-(13)C]phenylalanine were performed on days 1, 2, 4, and 6. Breath samples containing (13)CO2 were collected during steady state and measured by infrared spectrometric analysis, and the fraction of (13)CO2 recovery from (13)C oxidation (F(13)CO2) was calculated. RESULTS: Preterm infants (n = 11, birth weight 1.9 ± 0.1 kg, gestational age 32.6 ± 1.5 wk) received 166 mg/kg/d of leucine. Baseline enrichment changed significantly at day 1 of the study diet. F(13)CO2 did not change significantly between days 2 and 4 but was significantly lower at day 6. The tracer washout time was determined to be 7.5 h using a biphasic regression analysis. CONCLUSION: One day of adaptation to a new diet is necessary to adapt to the (13)C enrichment of the study formula before starting infant requirement studies. Adaptation for a period of 5 d results in a protein-sparing response. The minimal time between two studies within the same subject is 7.5 h.

Methionine requirement of the enterally fed term infant in the first month of life in the presence of cysteine.

BACKGROUND: The essential amino acid methionine can be used for protein synthesis but also serves as a precursor for homocysteine and cysteine. OBJECTIVE: The objective of this study was to determine the minimal obligatory methionine requirement of infants in the presence of excess cysteine (91 mg ⋅ kg(-1) ⋅ d(-1)) by using the indicator amino acid oxidation (IAAO) method with l-[1-(13)C]phenylalanine as the indicator. DESIGN: Fully enterally fed term infants <1 mo of age were randomly assigned to methionine intakes that ranged from 3 to 59 mg ⋅ kg(-1) ⋅ d(-1) as part of an elemental formula. After 1 d of adaptation to the test diet, [(13)C]bicarbonate and l-[1-(13)C]phenylalanine tracers were given enterally. Breath samples were collected at baseline and during isotopic plateaus. The mean methionine requirement was determined by using biphasic linear regression crossover analysis on the fraction of (13)CO(2) recovery from l-[1-(13)C]phenylalanine oxidation (F(13)CO(2)). Data are presented as means ± SDs. RESULTS: Thirty-three neonates (gestational age: 39 ± 1 wk) were studied at 13 ± 6 d. With increasing methionine intakes, F(13)CO(2) decreased until a methionine intake of 38 mg ⋅ kg(-1) ⋅ d(-1); additional increases in methionine intake did not affect F(13)CO(2). The mean methionine requirement was determined at 38 mg ⋅ kg(-1) ⋅ d(-1), and the upper and lower CIs were 48 and 27 mg ⋅ kg(-1) ⋅ d(-11), respectively (P < 0.0001, r(2) = 0.59). CONCLUSIONS: Although the current recommended methionine intake of 28 mg ⋅ kg(-1) ⋅ d(-1) is within the CIs of our study, the estimated mean requirement is substantially higher. However, most of the infant formulas provide a methionine intake of 49-80 mg ⋅ kg(-1) ⋅ d(-1), which is above the upper CI of our study. This trial was registered at www.trialregister.nl as NTR1610.

Lysine requirement of the enterally fed term infant in the first month of life.

BACKGROUND: Infant nutrition has a major impact on child growth and functional development. Low and high intakes of protein or amino acids could have a detrimental effect. OBJECTIVE: The objective of the study was to determine the lysine requirement of enterally fed term neonates by using the indicator amino acid oxidation (IAAO) method. L-[1-(13)C]phenylalanine was used as an indicator amino acid. DESIGN: Twenty-one neonates were randomly assigned to lysine intakes that ranged from 15 to 240 mg · kg(-1) · d(-1). Breath, urine, and blood samples were collected at baseline and during the plateau. The mean lysine requirement was determined by using biphasic linear regression crossover analysis on the fraction of (13)CO(2) recovery from L-[1-(13)C]phenylalanine oxidation (F(13)CO(2)) and phenylalanine oxidation rates calculated from the L-[1-(13)C]phenylalanine enrichment of urine and plasma. RESULTS: The mean (±SD) phenylalanine flux calculated from urine and plasma L-[1-(13)C]phenylalanine enrichment data were 88.3 ± 6.9 and 84.5 ± 7.4 µmol · kg(-1) · h(-1), respectively. Graded intakes of lysine had no effect on phenylalanine fluxes. The mean lysine requirement determined by F(13)CO(2) was 130 mg · kg(-1) · d(-1) (upper and lower CIs: 183.7 and 76.3 mg · kg(-1) · d(-1), respectively). The mean requirement was identical to the requirement determined by using phenylalanine oxidation rates in urine and plasma. CONCLUSIONS: The mean lysine requirement of enterally fed term neonates was determined by using F(13)CO(2) and phenylalanine oxidation rates calculated from the L-[1-(13)C]phenylalanine enrichment of urine and plasma. These methods yielded a similar result of 130 mg lysine · kg(-1) · d(-1). This study demonstrates that sampling of (13)CO(2) in expired air is sufficient to estimate the lysine requirement by using the IAAO method in infants. This trial was registered at www.trialregister.nl as NTR1610.

Plasma water as a diagnostic tool in the assessment of dehydration in children with acute gastroenteritis.

Acute gastroenteritis is common in childhood. The estimation of the degree of dehydration is essential for management of acute gastroenteritis. Plasma water was assessed as a diagnostic tool in children with acute gastroenteritis and dehydration admitted to hospital. In a prospective cohort study, 101 patients presenting at the emergency department with dehydration were included. Clinical assessment, routine laboratory tests, and plasma water measurement were performed. Plasma water was measured as a percentage of water content using dry weight method. During admission, patients were rehydrated in 12 h. Weight gain at the end of the rehydration period and 2 weeks thereafter was used to determine the percentage of weight loss as a gold standard for the severity of dehydration. Clinical assessment of dehydration was not significantly associated with the percentage of weight loss. Blood urea nitrogen (r = 0.3, p = 0.03), base excess (r =-0.31, p = 0.03), and serum bicarbonate (r = 0.32, p = 0.02) were significantly correlated with the percentage of weight loss. Plasma water did not correlate with the percentage of weight loss. On the basis of the presented data, plasma water should not be used as a diagnostic tool in the assessment of dehydration in children with acute gastroenteritis.

Extensive cerebral infarction in the newborn due to incontinentia pigmenti.

INTRODUCTION: Incontinentia pigmenti (IP) is a rare X-linked dominant neuroectodermal multisystem disorder characterized by skin lesions following Blaschko lines. In almost all patients the skin is involved and in 30-50% the central nervous system (CNS) is. Vascular occlusive phenomena probably play a role in CNS involvement. Whether these vascular changes are based on macro- or microvascular disease in the neonatal presentation is not fully understood. PATIENTS AND METHODS: We describe two patients with IP with neonatal seizures related to cerebral infarction. In comparison, we reviewed reports of ischaemic cerebrovascular injury in neonatal IP. RESULTS: No descriptions of documented large artery occlusion in neonatal IP was found in the literature. One of our patients showed striatal arteriopathy, never described before in IP. Extensive injury in one of our cases was heterogeneous, mixing healthy with diseased areas within large arterial fields. CONCLUSIONS: We postulate that neonatal cerebral infarction in IP is a macrovascular disorder of medium sized or small arteries. The pattern of arterial involvement might follow hypothetical brain Blaschko lines. The extent of cerebral involvement probably results from genetic mosaicism in which Lyonisation leads to endothelial apoptosis, similar to the process in the skin.