Melissa Song Zhou

All Publications

• Elevated serum creatinine over the first week of life and mortality risk in extremely preterm neonates: a secondary analysis of the Preterm Erythropoietin Neuroprotection Trial (PENUT). Pediatric nephrology (Berlin, Germany) Zhou, M. S., Griffin, R., Askenazi, D. J., Slagle, C. L., Chock, V. Y., Menon, S. 2026

  Abstract

  The neonatal-modified Kidney Disease: Improving Global Outcomes acute kidney injury (KDIGO-AKI) serum creatinine (SCr) definition is widely used to characterize neonatal AKI. In extremely preterm neonates born < 28 weeks' gestational age (GA), this definition has limitations. We evaluated whether GA- and postnatal age-specific SCr thresholds during the first postnatal week could identify additional neonates at risk for mortality.In a secondary analysis of prospectively collected data from the Preterm Erythropoietin Neuroprotection Trial, daily 95th percentile SCr thresholds were derived over the first week of life for two GA groups (24-25 and 26-27 weeks) using neonates without KDIGO-AKI. Neonates were classified sequentially into three cohorts: KDIGO-AKI; 95th-AKI, defined by at least one SCr exceeding the daily 95th percentile thresholds in the absence of KDIGO-AKI; and controls with no AKI. Time-varying Cox proportional hazards models assessed associations with in-hospital mortality.Among 918 extremely preterm neonates, 106 (12%) had KDIGO-AKI, 72 (8%) had 95th-AKI, and 740 (81%) had no AKI in the first postnatal week. In-hospital mortality was higher with 95th-AKI (18%) or KDIGO-AKI (18%) than with no AKI (9%) (p = 0.003). After adjusting for confounding factors, 95th-AKI was associated with an increased in-hospital mortality (adjusted HR 2.16, 95% CI 1.12-4.18), but KDIGO-AKI was not (adjusted HR 0.99, 95% CI 0.49-2.02).Extremely preterm neonates without KDIGO-AKI but with elevated SCr in the first postnatal week had an increased risk of in-hospital mortality. GA- and postnatal age-specific SCr thresholds may improve early detection of at-risk neonates.ClinicalTrials.gov Identifier: NCT01378273.

  View details for DOI 10.1007/s00467-026-07294-7

  View details for PubMedID 42012687

  View details for PubMedCentralID 5933049

• Nutrition delivery in infants with kidney failure on extracorporeal kidney replacement therapy. Pediatric nephrology (Berlin, Germany) Krieger, S. L., Zhou, M. S., Popovich, L., Wong, C., Davis, A. S., Sutherland, S. M., Menon, S. 2026

  Abstract

  Infants with kidney failure who initiate kidney replacement therapy (KRT) within 3 months of life require optimal fluid and nutritional management to support growth. Continuous or prolonged intermittent KRT (CKRT or PIKRT) is often used as a bridge to peritoneal dialysis facilitating earlier nutrition provision but is associated with protein losses. Current guidelines recommend ≥ 3-3.5 g/kg/day of protein during KRT. We aimed to assess nutritional prescriptions and growth in these infants.We conducted a retrospective review of infants with kidney failure managed with extracorporeal KRT at Lucile Packard Children's Hospital between January 2021 and December 2024. Demographics, dialysis dose, nutrition prescriptions, anthropometry, and laboratory values were collected weekly from birth through 8 weeks and at discharge.Seventeen infants were included; 12 (71%) were female. KRT was initiated at a median age of 3 days and a median weight of 2110 g. Initial modality was PIKRT in 15 (88%) and CKRT in 2 (12%). The median prescribed protein was 2.7 g/kg/day in Week 1, increasing to 4 g/kg/day by Week 6. Caloric prescriptions rose from 95 kcal/kg/day in Week 1 to 136 kcal/kg/day by Week 8. Median z-scores for weight, length, and head circumference decreased from birth to Week 8 (weight - 1.07 to - 1.34; length - 1.02 to - 1.95; head circumference - 0.41 to - 1.36), with discharge values of - 1.08, - 1.73, and - 1.40.Despite early KRT and nutritional optimization, infants showed limited catch-up growth. Early provision of ≥ 4 g/kg/day protein and ≥ 130 kcal/kg/day may prevent cumulative deficits.

  View details for DOI 10.1007/s00467-026-07236-3

  View details for PubMedID 41764143

  View details for PubMedCentralID 12549734

• Inpatient skin-to-skin care in infants with congenital kidney failure: a single-center retrospective cohort study. Journal of perinatology : official journal of the California Perinatal Association Zhou, M. S., Davis, A. S., Wong, C. J., Menon, S., Chock, V. Y. 2026

  View details for DOI 10.1038/s41372-026-02569-1

  View details for PubMedID 41629685

  View details for PubMedCentralID 11514444

• Neonatal acute kidney injury as a global priority: the need for contextualized advocacy, education, and collaboration. Pediatric nephrology (Berlin, Germany) Zhou, M. S., Menon, S., Jetton, J. G. 2025

  View details for DOI 10.1007/s00467-025-06832-z

  View details for PubMedID 40439776

  View details for PubMedCentralID 5933049

• Growth after pediatric and neonatal acute kidney injury: a meta-analysis. Pediatric nephrology (Berlin, Germany) Starr, M. C., Patel, M., Zafar, F., Zhou, M. S., Griffin, R., Biruete, A., Cockovski, V., Gbadegesin, R., Fuhrman, D. Y., Gist, K. M., Mammen, C., Menon, S., Morgan, C., Slagle, C. L., Sutherland, S., Zappitelli, M., Soranno, D. E. 2025

  Abstract

  Acute kidney injury (AKI) occurs commonly in critically ill children. The impact of AKI on pediatric growth outcomes has been sparsely described.To compare growth in children with a history of AKI compared to those without AKI. We hypothesized that children with AKI would have worse growth compared to those without AKI.A convenience sample of existing prospective and retrospective cohorts of children with AKI who had already collected or were able to collect data on growth parameters before and after an episode of AKI.There are < 5 studies in the published literature on growth in children with AKI. These investigators were contacted, and additional studies were added by contacting primary investigators of studies of childhood AKI in which data on growth parameters was able to be collected.Children from existing cohorts evaluating AKI (exposure) during childhood. Each included cohort had previously received local IRB approval per institutional guidelines. As our study was a meta-analysis and only used cohort-level data, no IRB approval was required for this report.Growth parameters (length and weight z-scores) before and after an episode of AKI were compared using a meta-means analysis. MOOSE guidelines were used. Data were pooled using a random-effects model. Hedges g was calculated, and Higgins I2 statistic was used to define variability due to between-cohort heterogeneity.We included 3,586 children from 17 existing cohorts of AKI in various populations, including infants, children with cardiac disease, solid organ transplant and critically ill children without cardiac disease with follow-up from 12 months to 11 years after AKI. At most distant follow-up, those with AKI had lower length z-score than those without AKI (mean difference -0.37 [95%CI -0.52, -0.22, p < 0.001]) and lower weight z-score (mean difference of -0.29 [95%CI -0.43, -0.15, p < 0.001]). This difference was most striking in infants, as those with AKI had impaired growth (both length z-score and weight z-score) after AKI compared to those without AKI.The analysis included only a convenience sample of observational cohorts of children, study selection could have been biased, and we did not evaluate the relationship between decreased kidney function (e.g., chronic kidney disease) after AKI in these cohorts and its relationship to poor growth.This meta-analysis found that children with AKI have impaired growth after AKI. These findings were most striking in infants. We suggest focusing on growth outcomes in both clinical care and research investigating the impacts of AKI.NA.

  View details for DOI 10.1007/s00467-025-06801-6

  View details for PubMedID 40343489

  View details for PubMedCentralID 8093091

• Harmonizing the Different Perspectives on Growth Impairment in Pediatric CKD. American journal of kidney diseases : the official journal of the National Kidney Foundation Zhou, M. S., Wolf, A. J., Sutha, K. 2024

  View details for DOI 10.1053/j.ajkd.2024.08.004

  View details for PubMedID 39545882

• Posterior Reversible Encephalopathy Syndrome Due to Vitamin D Toxicity. Pediatrics O'Brien, M., Koh, E., Barsh, G. R., Zhou, M. S., Aguilar Abisad, D., Chang, N. 2024

  Abstract

  Although toxicity from excessive exogenous vitamin D supplementation is rare, a range of symptoms can occur, most of which result from hypercalcemia. We report a novel case of posterior reversible encephalopathy syndrome (PRES) in a young child who required intensive care after presenting with hypercalcemia, hypertensive emergency, acute kidney injury, and hypercarbic respiratory failure, which ultimately were attributed to vitamin D toxicity (VDT). We report a young child who developed PRES in association with VDT. Our report informs pediatric outpatient, hospitalist, and intensivist providers about rare but life-threatening complications from hypervitaminosis D, adds VDT to the differential diagnosis for children with similar presentations, and highlights the importance of vitamin supplementation safety guidance for families.

  View details for DOI 10.1542/peds.2024-067126

  View details for PubMedID 39267608

• An Adolescent Boy With Hypoxia, Microscopic Hematuria, and Hypertension CUREUS JOURNAL OF MEDICAL SCIENCE Zhou, M. S., Lee, C. D., Lerman, B. J., Strong, A., LaRosa, C. 2024; 16 (1): e52738

  Abstract

  A 13-year-old boy presented with hypoxia, microscopic hematuria, and elevated blood pressures. Persistent microscopic hematuria and hypertension led to investigation of glomerular and non-glomerular causes of hematuria. After reviewing his clinical course, family history, and laboratory testing, an additional test was sent, revealing the diagnosis.

  View details for DOI 10.7759/cureus.52738

  View details for Web of Science ID 001156009200013

  View details for PubMedID 38384656

  View details for PubMedCentralID PMC10880807

• Challenges in the Clinical Recognition of Acute Flaccid Myelitis and its Implications JOURNAL OF PEDIATRICS Hayes, L. H., Hopkins, S. E., Liu, S., Pardo, C. A., Garcia-Dominguez, M. A., Oleszek, J., Yea, C., Ciftci-Kavaklioglu, B., Yeh, E., Dean, J., Sadowsky, C. L., Desai, J., Wiegand, S., Farias-Moeller, R., Nash, K., Thakur, K. T., Vargas, W. S., Hong-Routson, S. J., Yeshokumar, A., Zhou, M. S., Makhani, N., Wilson-Murphy, M., Bove, R., Zhang, B., Benson, L. A. 2023; 253: 55-+

  Abstract

  To explore the challenges in diagnosing acute flaccid myelitis (AFM) and evaluate clinical features and treatment paradigms associated with under recognition.This was a retrospective multicenter study of pediatric patients (≤18 years) who were diagnosed with AFM from 2014 to 2018 using the Centers for Disease Control and Prevention's case definition.In 72% of the cases (126 of 175), AFM was not considered in the initial differential diagnosis (n = 108; 61.7%) and/or the patient was not referred for acute care (n = 90; 51.4%) at the initial clinical encounter, and this did not improve over time. Although many features of the presentation were similar in those initially diagnosed with AFM and those who were not; preceding illness, constipation, and reflexes differed significantly between the 2 groups. Patients with a non-AFM initial diagnosis more often required ventilatory support (26.2% vs 12.2%; OR, 0.4; 95% CI, 0.2-1.0; P = .05). These patients received immunomodulatory treatment later (3 days vs 2 days after neurologic symptom onset; 95% CI, -2 to 0; P = .05), particularly intravenous immunoglobulin (5 days vs 2 days; 95% CI, -4 to -2; P < .001).Delayed recognition of AFM is concerning because of the risk for respiratory decompensation and need for intensive care monitoring. A non-AFM initial diagnosis was associated with delayed treatment that could have a clinical impact, particularly as new treatment options emerge.

  View details for DOI 10.1016/j.jpeds.2022.09.012

  View details for Web of Science ID 000955398200001

  View details for PubMedID 36115622

• Health Care Professional and Caregiver Attitudes Toward and Usage of Medical Podcasting: Questionnaire Study JMIR PEDIATRICS AND PARENTING Lee, C., Zhou, M. S., Wang, E. R., Huber, M., Lockwood, K. K., Parga, J. 2022; 5 (1): e29857

  Abstract

  Podcasts are used increasingly in medicine. There is growing research into the role of podcasts in medical education, but the use of podcasting as a tool for pediatric parent/caregiver health education is largely unexplored. As parents/caregivers seek medical information online, an understanding of parental preferences is needed.We sought to explore health care professional and parent/caregiver awareness and views on podcasting as a health education tool.This survey study was conducted and distributed via in-person collection from parents/caregivers (≥18 years old) in the waiting room of an academic pediatric primary care clinic, targeted social media promotion, and professional listservs for health care professionals in pediatrics. Statistical analysis included chi-square tests of independence between categorical variables.In total, 125 health care professionals and 126 caregivers completed the survey. Of those surveyed, 81% (101/125) of health care professionals and 55% (69/126) of parents/caregivers listened to podcasts (P<.001). Health care professionals and parents/caregivers listed the same top 3 quality indicators for medical podcasts. Podcast listeners were more likely to have higher incomes and use professional websites for information. The survey elicited a variety of reasons for podcast nonengagement.Health care professionals appear to be more engaged in medical education podcasts than parents/caregivers. However, similar factors were valued when evaluating the quality of a pediatric podcast: accuracy, transparency, and credibility. Professional websites may be one avenue to increase podcast uptake. More needs to be done to explore the use of podcasts and digital media for medical information.

  View details for DOI 10.2196/29857

  View details for Web of Science ID 000780486600009

  View details for PubMedID 35103616

  View details for PubMedCentralID PMC8848225

• Meta-analysis: Pharmacologic Treatment of Restricted and Repetitive Behaviors in Autism Spectrum Disorders JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY Zhou, M. S., Nasir, M., Farhat, L. C., Kook, M., Artukoglu, B. B., Bloch, M. H. 2021; 60 (1): 35-45

  Abstract

  To examine the efficacy of pharmacological treatments for restricted and repetitive behaviors (RRB) in autism spectrum disorders (ASD).We searched PubMed, Embase, and CENTRAL to identify all double-blind, randomized, placebo-controlled trials that examined the efficacy of pharmacological agents in the treatment of ASD and measured RRB as an outcome. Our primary outcome was the standardized mean difference in rating scales of RRB.We identified 64 randomized, placebo-controlled trials involving 3,499 participants with ASD. Antipsychotics significantly improved RRB outcomes compared to placebo (standardized mean difference [SMD] = 0.28, 95% CIs = 0.08-0.49), z = 2.77, p = .01) demonstrating a small effect size. Larger significant positive effects on RRB in ASD were seen in individual studies with fluvoxamine, buspirone, bumetanide, divalproex, guanfacine, and folinic acid that have not been replicated. Other frequently studied pharmacological treatments in ASD including oxytocin, omega-3 fatty acids, selective serotonin reuptake inhibitors (SSRI), and methylphenidate did not demonstrate significant benefit in reducing RRB compared to placebo (oxytocin: SMD = 0.23, 95% CI = -0.01 to 0.47, z = 1.85, p = .06; omega-3 fatty acids: SMD = 0.19, 95% CI = -0.05 to 0.43, z = 1.54, p = .12; SSRI: SMD = 0.09, 95% CI = -0.21 to 0.39, z = 0.60, p = .56; methylphenidate: SMD = 0.18, 95% CI = -0.11 to 0.46, z = 1.23, p = .22).The results of the present meta-analysis suggest that currently available pharmacological agents have at best only a modest benefit for the treatment of RRB in ASD, with the most evidence supporting antipsychotic medications. Additional randomized controlled trials with standardized study designs and consistent and specific assessment tools for RRB are needed to further understand how we can best help ameliorate these behaviors in individuals with ASD.

  View details for DOI 10.1016/j.jaac.2020.03.007

  View details for Web of Science ID 000600656300016

  View details for PubMedID 32387445

• A Meta-Analysis on the Relationship Between Interoceptive Awareness and Alexithymia: Distinguishing Interoceptive Accuracy and Sensibility JOURNAL OF ABNORMAL PSYCHOLOGY Trevisan, D. A., Altschuler, M. R., Bagdasarov, A., Carlos, C., Duan, S., Hamo, E., Kala, S., McNair, M. L., Parker, T., Stahl, D., Winkelman, T., Zhou, M., McPartland, J. C. 2019; 128 (8): 765-776

  Abstract

  Alexithymia-a trait associated with difficulties understanding one's own emotions-is theorized to stem from deficits in interoceptive awareness, or the ability to detect, accurately monitor, and regulate internal bodily processes. The present meta-analysis analyzed all studies that empirically examined the relationship between alexithymia and interoceptive awareness. Across 66 independent samples (N = 7,146), alexithymia had a small, negative correlation with interoceptive awareness (r = -.162, p = .001, 95% CI [-.252, -.068]), but additional analyses revealed that the strength and directionality of this association was heavily influenced by the specific interoceptive awareness components measured (e.g., interoceptive accuracy vs. sensibility) and the methods used to measure interoceptive awareness (e.g., objective vs. self-report measures). The strength of this relationship was also moderated by diagnosis of participants such that alexithymia was moderately associated with interoceptive awareness in samples with psychiatric and developmental disorders, but the relationship was nonsignificant in healthy, typically developing samples. Results suggest interoception may represent a shared transdiagnostic vulnerability that underlies atypical emotional processing in a variety of disparate clinical populations but that current operationalization and measurement of interoceptive awareness continues to create confusion and inconsistency in the literature. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

  View details for DOI 10.1037/abn0000454

  View details for Web of Science ID 000492836600001

  View details for PubMedID 31380655

• Loss of TMEM106B Ameliorates Lysosomal and Frontotemporal Dementia-Related Phenotypes in Progranulin-Deficient Mice NEURON Klein, Z. A., Takahashi, H., Ma, M., Stagi, M., Zhou, M., Lam, T. T., Strittmatter, S. M. 2017; 95 (2): 281-+

  Abstract

  Progranulin (GRN) and TMEM106B are associated with several common neurodegenerative disorders including frontotemporal lobar degeneration (FTLD). A TMEM106B variant modifies GRN-associated FTLD risk. However, their functional relationship in vivo and the mechanisms underlying the risk modification remain unclear. Here, using transcriptomic and proteomic analyses with Grn-/- and Tmem106b-/- mice, we show that, while multiple lysosomal enzymes are increased in Grn-/- brain at both transcriptional and protein levels, TMEM106B deficiency causes reduction in several lysosomal enzymes. Remarkably, Tmem106b deletion from Grn-/- mice normalizes lysosomal protein levels and rescues FTLD-related behavioral abnormalities and retinal degeneration without improving lipofuscin, C1q, and microglial accumulation. Mechanistically, TMEM106B binds vacuolar-ATPase accessory protein 1 (AP1). TMEM106B deficiency reduces vacuolar-ATPase AP1 and V0 subunits, impairing lysosomal acidification and normalizing lysosomal protein levels in Grn-/- neurons. Thus, Grn and Tmem106b genes have opposite effects on lysosomal enzyme levels, and their interaction determines the extent of neurodegeneration.

  View details for DOI 10.1016/j.neuron.2017.06.026

  View details for Web of Science ID 000405857500008

  View details for PubMedID 28728022

  View details for PubMedCentralID PMC5558861

• Functional recovery in new mouse models of ALS/FTLD after clearance of pathological cytoplasmic TDP-43 ACTA NEUROPATHOLOGICA Walker, A. K., Spiller, K. J., Ge, G., Zheng, A., Xu, Y., Zhou, M., Tripathy, K., Kwong, L. K., Trojanowski, J. Q., Lee, V. 2015; 130 (5): 643-660

  Abstract

  Accumulation of phosphorylated cytoplasmic TDP-43 inclusions accompanied by loss of normal nuclear TDP-43 in neurons and glia of the brain and spinal cord are the molecular hallmarks of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD-TDP). However, the role of cytoplasmic TDP-43 in the pathogenesis of these neurodegenerative TDP-43 proteinopathies remains unclear, due in part to a lack of valid mouse models. We therefore generated new mice with doxycycline (Dox)-suppressible expression of human TDP-43 (hTDP-43) harboring a defective nuclear localization signal (∆NLS) under the control of the neurofilament heavy chain promoter. Expression of hTDP-43∆NLS in these 'regulatable NLS' (rNLS) mice resulted in the accumulation of insoluble, phosphorylated cytoplasmic TDP-43 in brain and spinal cord, loss of endogenous nuclear mouse TDP-43 (mTDP-43), brain atrophy, muscle denervation, dramatic motor neuron loss, and progressive motor impairments leading to death. Notably, suppression of hTDP-43∆NLS expression by return of Dox to rNLS mice after disease onset caused a dramatic decrease in phosphorylated TDP-43 pathology, an increase in nuclear mTDP-43 to control levels, and the prevention of further motor neuron loss. rNLS mice back on Dox also showed a significant increase in muscle innervation, a rescue of motor impairments, and a dramatic extension of lifespan. Thus, the rNLS mice are new TDP-43 mouse models that delineate the timeline of pathology development, muscle denervation and neuron loss in ALS/FTLD-TDP. Importantly, even after neurodegeneration and onset of motor dysfunction, removal of cytoplasmic TDP-43 and the concomitant return of nuclear TDP-43 led to neuron preservation, muscle re-innervation and functional recovery.

  View details for DOI 10.1007/s00401-015-1460-x

  View details for Web of Science ID 000363270100004

  View details for PubMedID 26197969

  View details for PubMedCentralID PMC5127391