Lisa Roskes, Athanasios Chamzas, Bing Ma, Alexandre E Medina, Mathangi Gopalakrishnan, Rose M Viscardi, Sripriya Sundararajan
{"title":"Early human milk feeding: Relationship to intestinal barrier maturation and postnatal growth.","authors":"Lisa Roskes, Athanasios Chamzas, Bing Ma, Alexandre E Medina, Mathangi Gopalakrishnan, Rose M Viscardi, Sripriya Sundararajan","doi":"10.1038/s41390-024-03622-5","DOIUrl":"https://doi.org/10.1038/s41390-024-03622-5","url":null,"abstract":"<p><strong>Objectives: </strong>Early exposure to mother's own milk (MOM) promotes intestinal barrier maturation in preterm infants. We hypothesized (1) donor human milk (DHM) supplementation reduces intestinal permeability (IP) similar to exclusive MOM and (2) early HM exposure and low IP at 7-10 days postnatal age (PNA) are associated with improved growth outcomes.</p><p><strong>Methods: </strong>IP was measured by the standard sugar absorption test (SAT) in infants <33 weeks gestation between 7-10 days PNA. Nutritional and anthropometric data were recorded. Postnatal growth failure (PNGF) was defined as a decrease in weight z-score >1 from birth to discharge to home.</p><p><strong>Results: </strong>Of 158 preterm infants, the mean (SD) gestational age was 29.9(2.3) weeks and birthweight 1388(424) g. Diet prior to SAT was exclusive MOM [N = 55(35%)], DHM ± MOM [N = 52(33%)], or preterm formula±MOM [N = 51(32%)]. The mean Lactulose(La)/Rhamnose(Rh) ratio was lower in the exclusive MOM [0.06(0.07)] and DBM ± MOM [0.05(0.07)] groups compared to the preterm formula±MOM group [0.11(0.11)], p < 0.01). Cumulative intake >150 ml/kg MOM ± DHM, but not preterm formula within 7-10 days PNA was associated with early intestinal barrier maturation. Low IP was not associated with lower risk of PNGF at discharge.</p><p><strong>Conclusions: </strong>Low IP is associated with cumulative intake of MOM alone or supplemented with DHM > 150 ml/kg within 7-10 days PNA.</p><p><strong>Clinical trial registration: </strong>Clinicaltrials.gov NCT01756040 ; web link to study on registry: https://clinicaltrials.gov/study/NCT01756040 .</p><p><strong>Impact: </strong>Key message Early intestinal barrier maturation is associated with cumulative intake of exclusive MOM alone or supplemented with DHM > 150 ml/kg within 7-10 days after birth, but is not associated with lower risk of PNGF at time of discharge. What it adds to existing literature? This observational study is the first study to demonstrate that supplemental DHM promotes intestinal barrier maturation similar to MOM alone. What is the impact? The findings underscore the importance of early introduction of human milk feeds as MOM or MOM supplemented with DHM in sufficient volume to promote early intestinal barrier maturation.</p>","PeriodicalId":19829,"journal":{"name":"Pediatric Research","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142472076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Non-invasive monitoring of cerebral blood flow during cardiac surgery for congenital heart disease - transfontanellar Doppler as additional tool.","authors":"Matthias Gorenflo","doi":"10.1038/s41390-024-03576-8","DOIUrl":"https://doi.org/10.1038/s41390-024-03576-8","url":null,"abstract":"","PeriodicalId":19829,"journal":{"name":"Pediatric Research","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142472083","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Call for applications for Editor-in-Chief and Associate Editor-in-Chief of Pediatric Research.","authors":"","doi":"10.1038/s41390-024-03635-0","DOIUrl":"https://doi.org/10.1038/s41390-024-03635-0","url":null,"abstract":"","PeriodicalId":19829,"journal":{"name":"Pediatric Research","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142472072","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Emily Lo, Mehmet N Cizmeci, Diane Wilson, Linh G Ly, Amr El-Shahed, Martin Offringa, Agostino Pierro, Brian T Kalish
{"title":"Remote ischemic post-conditioning for neonatal encephalopathy: a safety and feasibility trial.","authors":"Emily Lo, Mehmet N Cizmeci, Diane Wilson, Linh G Ly, Amr El-Shahed, Martin Offringa, Agostino Pierro, Brian T Kalish","doi":"10.1038/s41390-024-03625-2","DOIUrl":"https://doi.org/10.1038/s41390-024-03625-2","url":null,"abstract":"<p><strong>Background: </strong>Despite implementation of therapeutic hypothermia (TH) for infants with neonatal encephalopathy (NE), a significant proportion of infants suffer neurodevelopmental impairment (NDI). Remote ischemic conditioning (RIC) is a proposed neuroprotective maneuver that has been studied in adults with brain injury, but it has not been previously investigated in infants with NE.</p><p><strong>Methods: </strong>We performed a prospective, randomized, safety and dose escalation study in 32 neonates with NE. Four cohorts of consecutive patients were randomized to RIC therapy, including four cycles of limb ischemia and reperfusion on progressive days of TH, or sham. Clinical, biochemical, and safety outcomes were monitored in both groups.</p><p><strong>Results: </strong>All patients received the designated RIC therapy without interruption or delay. RIC was not associated with increased pain, vascular, cutaneous, muscular, or neural safety events. There was no difference in the incidence of seizures, brain injury, or mortality between the two groups with the escalation of RIC dose and frequency.</p><p><strong>Conclusions: </strong>We found that RIC is a safe and feasible adjunctive therapy for neonates with NE undergoing TH.</p><p><strong>Impact: </strong>This pilot study establishes critical safety and feasibility data that are necessary for the design of future studies to investigate the potential efficacy of RIC to reduce NDI.</p><p><strong>Impact: </strong>Remote ischemic conditioning (RIC) is a possible neuroprotective intervention in infants with hypoxic-ischemic encephalopathy (HIE). RIC can be administered concurrently with therapeutic hypothermia without any notable adverse events. Future studies will need to address potential efficacy of RIC to improve neurodevelopmental outcomes, as well as consider the ideal temporal window and dose for RIC in this patient population.</p>","PeriodicalId":19829,"journal":{"name":"Pediatric Research","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142472088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Association between SARS-CoV-2 infection before the age of two and child development.","authors":"Nattaporn Tassanakijpanich, Kemmapon Chumchuen, Juthamas Worachotekamjorn, Kamolwish Laoprasopwattana","doi":"10.1038/s41390-024-03614-5","DOIUrl":"https://doi.org/10.1038/s41390-024-03614-5","url":null,"abstract":"<p><strong>Background: </strong>To compare the differences in child development between children who contracted COVID-19 after February 1st, 2022, the period when the B.1.1.529 variant outbreak began to peak in Thailand, and those who did not.</p><p><strong>Methods: </strong>A prospective cohort study was conducted in an outpatient pediatric clinic at a tertiary hospital in southern Thailand. COVID-19 was diagnosed based on the results of an FDA-approved antigen test or RT-PCR using a swab sample collected from the nasopharynx, nose, or throat. Child development was assessed using the Ages and Stages Questionnaire, Third Edition (ASQ-3).</p><p><strong>Results: </strong>Of the 336 participants, 180 (53.6%) had a history of COVID-19. Almost all of them had mild COVID-19. The mean (SD) age at infection was 1.3 (0.3) years, and the median (IQR) duration between infection and ASQ-3 assessment was 193.5 (167.8, 216.2) days. The ASQ-3 scores at the ages of 18 (n = 166; 90 COVID-19 positive) and 24 months (n = 170; 90 COVID-19 positive) revealed no statistically significant differences between children with and without a history of COVID-19. Both groups had comparable proportions of developmental scores <1 SD below the mean.</p><p><strong>Conclusions: </strong>Mild COVID-19 in young children did not increase the risk of developmental delays.</p><p><strong>Impact: </strong>This cohort study was conducted during the Omicron pandemic. Of the 336 children, no clinical or statistically significant differences were observed in the scores of the Ages & Stages Questionnaire, Third Edition, at 18 or 24 months of age among the 180 participants with a history of mild SARS-CoV-2 infection, at an average of 6 months post-infection, and those without. The findings suggest that mild SARS-CoV-2 infection before the age of 2 years is not associated with developmental delays. Strategies to prevent severe SARS-CoV-2 infection in young children, especially COVID-19 immunization, need to be highlighted.</p>","PeriodicalId":19829,"journal":{"name":"Pediatric Research","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Systemic immune inflammation index (SII) assessment as a potential tool against childhood hypertension.","authors":"Kinga Musiał","doi":"10.1038/s41390-024-03633-2","DOIUrl":"https://doi.org/10.1038/s41390-024-03633-2","url":null,"abstract":"","PeriodicalId":19829,"journal":{"name":"Pediatric Research","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sarah Dee Geiger, Aruna Chandran, Marie L Churchill, Maxwell Mansolf, Cai Zhang, Salma Musaad, Courtney K Blackwell, Stephanie M Eick, Dana E Goin, Susan Korrick, Akram Alshawabkeh, Patricia A Brennan, Carrie V Breton, Jose F Cordero, Sean Deoni, Viren D'Sa, Anne L Dunlop, Amy J Elliott, Assiamira Ferrara, Arlene Keddie, Monique LeBourgeois, Kaja Z LeWinn, Daphne Koinis-Mitchell, Maristella Lucchini, Sara S Nozadi, Thomas O'Connor, Yeyi Zhu, Emily Zimmerman, Susan L Schantz
{"title":"Association between maternal stress and child sleep quality: a nationwide ECHO prospective cohort study.","authors":"Sarah Dee Geiger, Aruna Chandran, Marie L Churchill, Maxwell Mansolf, Cai Zhang, Salma Musaad, Courtney K Blackwell, Stephanie M Eick, Dana E Goin, Susan Korrick, Akram Alshawabkeh, Patricia A Brennan, Carrie V Breton, Jose F Cordero, Sean Deoni, Viren D'Sa, Anne L Dunlop, Amy J Elliott, Assiamira Ferrara, Arlene Keddie, Monique LeBourgeois, Kaja Z LeWinn, Daphne Koinis-Mitchell, Maristella Lucchini, Sara S Nozadi, Thomas O'Connor, Yeyi Zhu, Emily Zimmerman, Susan L Schantz","doi":"10.1038/s41390-024-03542-4","DOIUrl":"10.1038/s41390-024-03542-4","url":null,"abstract":"<p><strong>Background: </strong>Childhood sleep quality is associated with physical, cognitive, and behavioral health and predicts later sleep quality; it has many determinants, including developmental exposures.</p><p><strong>Objectives: </strong>To examine associations between maternal stress during pregnancy and childhood sleep quality and determine whether postnatal stress mediates the association.</p><p><strong>Method: </strong>Data from the Environmental Influences on Child Health Outcomes cohort were used. Perceived Stress Scale (PSS) T-scores were the exposure measure. Outcome measures were preschool Child Behavior Checklist (CBCL) sleep syndrome scale and Patient-Reported Outcomes Measurement Information System Sleep Disturbance Parent Proxy short form 4a (PSD4a) T-scores at ages 4-8 years. Linear mixed-effects regression modeling was performed for each sleep outcome, adjusting for maternal age at delivery and education and child sex, gestational age at birth, and age at outcome ascertainment, with random intercepts for cohorts.</p><p><strong>Results: </strong>Prenatal PSS score was associated with both CBCL (B = 0.09, 95% confidence interval [CI]: 0.06, 0.11; p < 0.01) and PSD4a (B = 0.07, 95% CI: 0.03, 0.12; p < 0.01) scores. Postnatal perceived stress mediated a proportion of the total effect of prenatal stress in both CBCL (66.3%) and PSD4a (95.9%) samples.</p><p><strong>Conclusions: </strong>Both pre- and postnatal maternal perceived stress appear to influence sleep quality during early life.</p><p><strong>Impact: </strong>Prenatal stress significantly associates with child sleep problems and disturbances at ages 4-8 years; postnatal maternal stress is a significant mediator of these associations. Research suggests a range of prenatal affective/distress exposures associated with child sleep problems, but the conclusions remain in doubt due to the mixture of exposures and outcomes employed. Ours is the first US-based effort to explore associations between perceived maternal stress during pregnancy and child sleep problems and disturbance in early and middle childhood. Even a small effect of a prevalent issue like psychosocial stress may have important public health implications at the population level.</p>","PeriodicalId":19829,"journal":{"name":"Pediatric Research","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Samson Nivins, Gerald F Giesbrecht, Lianne Tomfohr-Madsen, Catherine Lebel
{"title":"Prenatal maternal diabetes, comorbidities, and risk for neurodevelopmental impairment in the first two years.","authors":"Samson Nivins, Gerald F Giesbrecht, Lianne Tomfohr-Madsen, Catherine Lebel","doi":"10.1038/s41390-024-03620-7","DOIUrl":"10.1038/s41390-024-03620-7","url":null,"abstract":"<p><strong>Background: </strong>Maternal diabetes is a known risk for neurodevelopmental delay in offspring, and often presents with comorbid metabolic conditions, such as obesity and hypertension. However, their combined effects on neurodevelopmental outcomes remain unclear. We investigated the independent and combined associations of maternal diabetes and comorbidities with the risk of neurodevelopmental delay in children aged 12 and 24 months.</p><p><strong>Methods: </strong>A prospective longitudinal cohort of children from Pregnancy during the COVID-19 Pandemic study. Neurodevelopmental screening at 12 and 24 months was conducted using the Ages and Stages Questionnaire, which assesses domain-specific development.</p><p><strong>Results: </strong>Maternal diabetes was not associated with neurodevelopmental risks either at 12 or 24 months. However, in combined analyses, maternal diabetes and pre-pregnancy overweight were associated with an increased risk of neurodevelopmental delay in personal-social skills (odds ratio [OR], 1.75 [95%CI,1.01-3.01]) at 24 months, though not at 12 months. Maternal diabetes and pre-pregnancy obesity were also associated with an increased risk for neurodevelopmental delay in communication (OR, 1.71 [95%CI,1.01-2.82]) and personal-social skills (OR, 2.01 [95%CI,1.03-3.73]) at 24 months. Furthermore, maternal diabetes and hypertensive disorders of pregnancy (HDP) had higher rates of positive screening for delay in fine-motor skills (OR, 3.54 [95%CI, 1.28-8.41]) at 12 months but not at 24 months. Post-hoc analysis revealed an independent association of maternal pre-pregnancy obesity, but not overweight, with an increased risk of neurodevelopmental delay in communication, fine-motor, and personal-social skills (ORs ranging from 1.44 to 1.71) at 24 months but not 12 months. Similarly, there was an independent association of maternal HDP with an increased risk of neurodevelopmental delay in fine-motor and and personal-social skills (ORs ranging from 2.01 to 2.19) at 24 months.</p><p><strong>Conclusion: </strong>Maternal diabetes with comorbid conditions is likely to increase the risk of neurodevelopmental delay during infancy than individual exposure, suggesting the persistent influence of prenatal exposure on offspring neurodevelopment.</p><p><strong>Impact: </strong>1. Identifying modifiable prenatal risk factors for neurodevelopmental impairment in offspring is crucial for targeted interventions and providing support to mothers during pregnancy, which can lead to improved child health outcomes. 2. Maternal diabetes was not associated with neurodevelopmental delays in children at 12 or 24 months. 3. Maternal diabetes in combination with pre-pregnancy overweight or obesity increased the risk of cognitive delay at 24 months. 4. Maternal pre-pregnancy obesity but not overweight, and hypertensive disorders of pregnancy independently increased risks of cognitive and motor delays at 24 months.</p>","PeriodicalId":19829,"journal":{"name":"Pediatric Research","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142400933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kathy L Ding, Caroline Smith, Gregory Seedorf, Steven H Abman
{"title":"Nintedanib preserves lung growth and prevents pulmonary hypertension in a hyperoxia-induced lung injury model.","authors":"Kathy L Ding, Caroline Smith, Gregory Seedorf, Steven H Abman","doi":"10.1038/s41390-024-03562-0","DOIUrl":"10.1038/s41390-024-03562-0","url":null,"abstract":"<p><strong>Background: </strong>Bronchopulmonary dysplasia (BPD), the chronic lung disease associated with prematurity, is characterized by poor alveolar and vascular growth, interstitial fibrosis, and pulmonary hypertension (PH). Although multifactorial in origin, the pathophysiology of BPD is partly attributed to hyperoxia-induced postnatal injury, resulting in lung fibrosis. Recent work has shown that anti-fibrotic agents, including Nintedanib (NTD), can preserve lung function in adults with idiopathic pulmonary fibrosis. However, NTD is a non-specific tyrosine kinase receptor inhibitor that can potentially have adverse effects on the developing lung, and whether NTD treatment can prevent or worsen risk for BPD and PH is unknown.</p><p><strong>Hypothesis: </strong>We hypothesize that NTD treatment will preserve lung growth and function and prevent PH in an experimental model of hyperoxia-induced BPD in rats.</p><p><strong>Methods: </strong>Newborn rats were exposed to either hyperoxia (90%) or room air (RA) conditions and received daily treatment of NTD or saline (control) by intraperitoneal (IP) injections (1 mg/kg) for 14 days, beginning on postnatal day 1. At day 14, lung mechanics were measured prior to harvesting lung and cardiac tissue. Lung mechanics, including total respiratory resistance and compliance, were measured using a flexiVent system. Lung tissue was evaluated for radial alveolar counts (RAC), mean linear intercept (MLI), pulmonary vessel density (PVD), and pulmonary vessel wall thickness (PVWT). Right ventricular hypertrophy (RVH) was quantified with cardiac weights using Fulton's index (ratio of right ventricle to the left ventricle plus septum).</p><p><strong>Results: </strong>When compared with RA controls, hyperoxia exposure reduced RAC by 64% (p < 0.01) and PVD by 65% (p < 0.01) and increased MLI by 108% (p < 0.01) and RVH by 118% (p < 0.01). Hyperoxia increased total respiratory resistance by 94% and reduced lung compliance by 75% (p < 0.01 for each). NTD administration restored RAC, MLI, RVH, PVWT and total respiratory resistance to control values and improved PVD and total lung compliance in the hyperoxia-exposed rats. NTD treatment of control animals did not have adverse effects on lung structure or function at 1 mg/kg. When administered at higher doses of 50 mg/kg, NTD significantly reduced alveolar growth in RA controls, suggesting dose-related effects on normal lung structure.</p><p><strong>Conclusions: </strong>We found that NTD treatment preserved lung alveolar and vascular growth, improved lung function, and reduced RVH in experimental BPD in infant rats without apparent adverse effects in control animals. We speculate that although potentially harmful at high doses, NTD may provide a novel therapeutic strategy for prevention of BPD and PH.</p><p><strong>Impact: </strong>Anti-fibrotic therapies may be a novel therapeutic strategy for the treatment or prevention of BPD. High-dose anti-fibrotics may have adverse ","PeriodicalId":19829,"journal":{"name":"Pediatric Research","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406684","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zoë Vander Elst, Annouschka Laenen, Jana Deberdt, Lotte Delemarre, Pieter Vermeersch, Glynis Frans, Gunnar Naulaers, Matthias Gijsen, Erwin Dreesen, Isabel Spriet, Karel Allegaert, Anne Smits
{"title":"Human serum albumin: prediction model and reference values for preterm and term neonates.","authors":"Zoë Vander Elst, Annouschka Laenen, Jana Deberdt, Lotte Delemarre, Pieter Vermeersch, Glynis Frans, Gunnar Naulaers, Matthias Gijsen, Erwin Dreesen, Isabel Spriet, Karel Allegaert, Anne Smits","doi":"10.1038/s41390-024-03634-1","DOIUrl":"https://doi.org/10.1038/s41390-024-03634-1","url":null,"abstract":"<p><strong>Background: </strong>Human serum albumin (HSA) concentrations may alter HSA-bound drug distribution. This study aims to describe longitudinal real-world HSA trends, and to develop a prediction model for HSA concentrations using a large neonatal cohort.</p><p><strong>Methods: </strong>Patients admitted to the neonatal intensive care unit of the University Hospitals Leuven (postnatal age (PNA) ≤28days) were retrospectively included. Using linear mixed models, covariate effects on HSA were explored. A multivariable prediction model was developed (backward model selection procedure, 1% significance level).</p><p><strong>Results: </strong>In total, 848 neonates were included [median(interquartile range) gestational age (GA) 35(32-38)weeks, birth weight (BW) 2400(1640-3130)grams]. Median HSA concentration was 32.3(28.7-35.6)g/L. Longitudinal analyses demonstrated increasing HSA concentrations with PNA and GA for most GA groups. Univariable analyses revealed significant associations of HSA with PNA, GA, BW, current weight, total and direct bilirubin, total plasma proteins, respiratory support, mechanical ventilation, sepsis, ibuprofen use, and C-reactive protein (p-values < 0.05). A high-performance (R<sup>2</sup> = 76.3%) multivariable HSA prediction model was developed, and PNA- and GA-dependent HSA centiles were provided.</p><p><strong>Conclusion: </strong>Population-specific HSA centiles and an accurate neonatal HSA prediction model were developed, incorporating both maturational and non-maturational covariates. These results can enhance future clinical care and pharmacokinetic analyses to improve pharmacotherapy of HSA-bound drugs in neonates, respectively.</p><p><strong>Impact: </strong>To improve future pharmacokinetic modeling initiatives, a high-performance human serum albumin (HSA) prediction model was developed for (pre)term neonates, using a large, single-center cohort of real-world data. This prediction model integrates both maturational and non-maturational covariates, resulting in accurate HSA predictions in neonates. Additionally, HSA centiles based on postnatal and gestational age were developed, which can be easily applied in clinical practice when interpreting HSA concentrations of neonates. In general, unbound drug fractions are higher in neonates compared to older populations. To improve pharmacotherapy of HSA-bound drugs in neonates, the obtained results can be integrated in future pharmacokinetic-pharmacodynamic analyses.</p>","PeriodicalId":19829,"journal":{"name":"Pediatric Research","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}