Recurrence of anterior congenital diaphragmatic hernia after laparoscopic repair in children.

PURPOSE: To report our experience with laparoscopic repair of anterior congenital diaphragmatic hernia (CDH) using extracorporeal subcutaneous knot tying and to define recurrence risk factors. METHODS: This retrospective unicentric study included children who underwent laparoscopic repair of anterior CDH without patch, using extracorporeal knot tying of sutures passed through the full thickness of the abdominal wall (2013-2020). A systematic review of the literature with meta-analysis was performed using the MEDLINE database since 2000. RESULTS: Eight children were included (12 months [1-183]; 10.6 kg [3.6-65]). Among the two patients with Down syndrome, one with previous cardiac surgery had a recurrence at 17 months postoperatively. In our systematic review (26 articles), among the 156 patients included, 10 had a recurrence (none with patch). Recurrence was statistically more frequent in patients with Down syndrome (19.4%) than without (2.5%) (p < 0.0001), and when absorbable sutures were used (50%) instead of non-absorbable sutures (5.3%) (p < 0.0001). CONCLUSION: Laparoscopic repair of anterior CDH without patch was a safe and efficient surgical approach in our patients. The use of a non-absorbable prosthetic patch should be specifically discussed in anterior CDH associated with Down syndrome and/or in case of previous cardiac surgery to perform a diaphragmatic tension-free closure.

Compromiso inmunológico en pacientes con síndrome de Down. Serie de casos / Immune compromise in patients with Down syndrome. A case series

El síndrome de Down, o trisomía 21, tiene una mortalidad mayor que la población general, debido principalmente a infecciones respiratorias. El objetivo de este trabajo es describir el compromiso inmunológico en una serie de casos de pacientes con síndrome de Down derivados a Inmunología por infecciones recurrentes o por hallazgo patológico de laboratorio, entre el 1 de junio de 2016 y el 31 de mayo de 2022. Se describe el compromiso de la inmunidad en 24 pacientes. Doce pacientes presentaron falla de respuesta a polisacáridos y recibieron quimioprofilaxis antibiótica y/o gammaglobulina sustitutiva. En 3 pacientes, se observó agammaglobulinemia con linfocitos B presentes y se indicó gammaglobulina sustitutiva. En 9 pacientes, se observó linfopenia T y en 1 paciente, compromiso inmune combinado.

Down syndrome, or trisomy 21, has a higher mortality than the general population, mainly due to respiratory tract infections. The objective of this study was to describe immune compromise in a series of cases of patients with Down syndrome referred to the Pediatric Immunology Section due to recurrent infections or pathological laboratory findings between 6/1/2016 and 5/31/2022. Here we describe immune compromise in 24 patients. Twelve patients failed to develop a polysaccharide response and received antibiotic chemoprophylaxis, or gamma globulin replacement therapy. Three patientsdeveloped agammaglobulinemia with presence of B cells and gamma globulin replacement therapy was indicated. Nine patients had T-cell lymphopenia and 1 patient, combined immune compromise.

Aortic Valve Thrombus, Stroke, and Endovascular Thrombectomy in a Child With APML and Trisomy 21.

APML, a subtype of acute myeloid leukemia, is highly curable, with cure rates over 90%. Despite its therapeutic success, APML poses elevated bleeding risks due to frequent prior disseminated intravascular coagulation. Less commonly recognized but critical is the thrombotic risk. We document a unique pediatric case: a 13-year-old with trisomy 21 diagnosed with APML had an asymptomatic aortic valve thrombus leading to thromboembolic arterial ischemic stroke. Through endovascular thrombectomy, cerebral circulation was re-established, extracting a fibrin thrombus with APML cells. Neurological recovery was swift. This report underscores the importance of vigilance for thrombotic complications in APML, highlighting the potential severity of overlooked risks.

Comprehensive Care for Adults with Down Syndrome in Primary Care Settings.

This review article aims to bridge the knowledge gap in providing comprehensive care to adults with Down syndrome (DS) in primary care settings. Despite the increasing prevalence of adults with DS, there is a significant lack of familiarity and comprehensive guidelines for their health care among primary care physicians. This often results in subpar health promotion, preventive screenings, and individualized care. This article attempts to provide guidance for healthcare providers on previsit preparation, clinic visit characteristics, testing and screening considerations, and decision making/guardianship for adults with DS. By emphasizing a patient-centered approach, this review aims to enhance the quality of care, reduce associated morbidity and mortality, and ultimately improve the health outcomes of adults with DS.

Persistent omphalomesenteric duct in an infant with trisomy 21.

We present the case of a term newborn with trisomy 21 who presented to the paediatric emergency department with periumbilical flare and green-brown discharge from a clamped umbilical cord, initially suspected to be omphalitis. However, it was noticed later, that when the infant strained or cried, a thick, bubbling and offensive green-brown discharge came out of the clamped umbilical cord with umbilical flatus. An ultrasound abdomen and umbilical cord confirmed the presence of a persistent omphalomesenteric duct (POMD). He was then transferred to the paediatric surgical unit. There, he underwent a laparotomy and surgical resection of the POMD and was discharged home 2 days later.

COVID-19 infection in children, adolescents, and young adults with Down syndrome and hematologic malignancies.

INTRODUCTION: Children, adolescents, and young adults (CAYAs) with Down syndrome (DS) and hematologic malignancies are particularly vulnerable to infections and related complications. There are limited data regarding COVID-19 infections in this group. We aimed to understand the clinical course of COVID-19 in this population. METHODS: This observational study leverages the de-identified clinical and sociodemographic data captured by the Pediatric Oncology COVID-19 Case Report Registry (POCC) regarding CAYAs with cancer and COVID-19. We evaluated CAYAs (≤21 years at COVID-19 infection) with hematologic malignancies and COVID-19 reported from April 1, 2020 to May 2, 2023, comparing those with and without DS. Using multivariable logistic regression, we examined rates of hospitalization, intensive care unit (ICU) admission, respiratory support, and changes in cancer-directed therapy. RESULTS: Among 1408 CAYAs with hematologic malignancies, 55 had DS (CAYA-DS). CAYA-DS had higher rates of hospitalization, ICU admission, and respiratory support (p < .001) than CAYAs without DS. Similarly, multivariable analyses found higher odds of hospitalization (odds ratio [OR] = 2.8, 95% confidence interval [CI]: 1.5-5.1), ICU admission (OR = 4.2, 95% CI: 1.9-9.1), and need for respiratory support (OR = 4.2, 95% CI: 2.0-8.8) among CAYA-DS. Modifications to cancer-directed therapy were more common among CAYA-DS when related to neutropenia (p = .001), but not when unrelated to neutropenia (p = .88); CAYA-DS did not have higher odds of changes to cancer-directed therapy (OR = 1.20, 95% CI: 0.7-2.1). CONCLUSIONS: We identify CAYA-DS with hematologic malignancies as a vulnerable subpopulation at greater risk for severe COVID-19 infection. This can inform conversations with patients and families regarding therapeutic and preventive measures, as well as the risks and benefits of modifying chemotherapy in the setting of COVID-19.

Dysregulation of the Immune System in a Natural History Study of 1299 Individuals with Down Syndrome.

Dysregulation of the immune system in individuals with Down syndrome is thought to play a major role in the pathophysiology of many clinical presentations. This natural history of disease study took a comprehensive evaluation of the prevalence of different immune related diagnoses in a cohort of 1299 patients with Down syndrome compared to a 2605 patient control cohort at the Mount Sinai Health System in New York, NY over the past 18 years. We conducted a stepwise analysis of the odds of receiving a diagnosis at the Chapter, Sub-chapter and Diagnosis level of the ICD-CM-10 code system. Individuals in our Down syndrome cohort had higher odds of a diagnosis with inflammatory and autoimmune presentations such as Alopecia areata (OR 6.06, p = 0.01), Other sepsis (OR 4.79, p < 0.001, Purpura and other hemorrhagic conditions (OR 2.31, p < 0.001), and Rosacea (OR 3.11, p < 0.001). They also presented with lower odds of a diagnosis of Herpesviral infection (OR 0.42, p = 0.01), and Viral warts (OR 0.51, p = 0.04). We posit that dysregulation of the immune system in individuals with Down syndrome has impact on infectious diseases, including lowering the incidence of viral disease and increasing its severity. Our data also suggests inflammation and autoimmune mediated diseases, in particular of the skin, are exacerbated in individuals with Down syndrome. Finally, there may be a need for greater clinical attention to non-emergent conditions within the Down syndrome patient population as those can also greatly affect quality of life.

Cytokine profiling in 128 patients with transient abnormal myelopoiesis: a report from the JPLSG TAM-10 trial.

ABSTRACT: Transient abnormal myelopoiesis (TAM) occurs in 10% of neonates with Down syndrome (DS). Although most patients show spontaneous resolution of TAM, early death occurs in ∼20% of cases. Therefore, new biomarkers are needed to predict early death and determine therapeutic interventions. This study aimed to determine the association between clinical characteristics and cytokine levels in patients with TAM. A total of 128 patients with DS with TAM enrolled in the TAM-10 study conducted by the Japanese Pediatric Leukemia/Lymphoma Study Group were included in this study. Five cytokine levels (interleukin-1b [IL-1b], IL-1 receptor agonist, IL-6, IL-8, and IL-13) were significantly higher in patients with early death than in those with nonearly death. Cumulative incidence rates (CIRs) of early death were significantly associated with high levels of the 5 cytokines. Based on unsupervised consensus clustering, patients were classified into 3 cytokine groups: hot-1 (n = 37), hot-2 (n = 42), and cold (n = 49). The CIR of early death was significantly different between the cytokine groups (hot-1/2, n = 79; cold, n = 49; hot-1/2 CIR, 16.5% [95% confidence interval (CI), 7.9-24.2]; cold CIR, 2.0% [95% CI, 0.0-5.9]; P = .013). Furthermore, cytokine groups (hot-1/2 vs cold) were independent poor prognostic factors in the multivariable analysis for early death (hazard ratio, 15.53; 95% CI, 1.434-168.3; P = .024). These results provide valuable information that cytokine level measurement was useful in predicting early death in patients with TAM and might help to determine the need for therapeutic interventions. This trial was registered at UMIN Clinical Trials Registry as #UMIN000005418.

The hematopoietic microenvironment of the fetal liver and transient abnormal myelopoiesis associated with Down syndrome: A review.

Transient abnormal myelopoiesis (TAM) in neonates with Down syndrome is a distinct form of leukemia or preleukemia that mirrors the hematological features of acute megakaryoblastic leukemia. However, it typically resolves spontaneously in the early stages. TAM originates from fetal liver (FL) hematopoietic precursor cells and emerges due to somatic mutations in GATA1 in utero. In TAM, progenitor cells proliferate and differentiate into mature megakaryocytes and granulocytes. This process occurs both in vitro, aided by hematopoietic growth factors (HGFs) produced in the FL, and in vivo, particularly in specific anatomical sites like the FL and blood vessels. The FL's hematopoietic microenvironment plays a crucial role in TAM's pathogenesis and may contribute to its spontaneous regression. This review presents an overview of current knowledge regarding the unique features of TAM in relation to the FL hematopoietic microenvironment, focusing on the functions of HGFs and the pathological features of TAM.

Neuropathological findings in Down syndrome, Alzheimer's disease and control patients with and without SARS-COV-2: preliminary findings.

The SARS-CoV-2 virus that led to COVID-19 is associated with significant and long-lasting neurologic symptoms in many patients, with an increased mortality risk for people with Alzheimer's disease (AD) and/or Down syndrome (DS). However, few studies have evaluated the neuropathological and inflammatory sequelae in postmortem brain tissue obtained from AD and people with DS with severe SARS-CoV-2 infections. We examined tau, beta-amyloid (Aß), inflammatory markers and SARS-CoV-2 nucleoprotein in DS, AD, and healthy non-demented controls with COVID-19 and compared with non-infected brain tissue from each disease group (total n = 24). A nested ANOVA was used to determine regional effects of the COVID-19 infection on arborization of astrocytes (Sholl analysis) and percent-stained area of Iba-1 and TMEM 119. SARS-CoV-2 antibodies labeled neurons and glial cells in the frontal cortex of all subjects with COVID-19, and in the hippocampus of two of the three DS COVID-19 cases. SARS-CoV-2-related alterations were observed in peri-vascular astrocytes and microglial cells in the gray matter of the frontal cortex, hippocampus, and para-hippocampal gyrus. Bright field microscopy revealed scattered intracellular and diffuse extracellular Aß deposits in the hippocampus of controls with confirmed SARS-CoV-2 infections. Overall, the present preliminary findings suggest that SARS-CoV-2 infections induce abnormal inflammatory responses in Down syndrome.

Orofacial myofunctional and polysomnographic characteristics of children with Down syndrome and obstructive sleep apnea: a pilot study. / Características miofuncionais orofaciais e polissonográficas de crianças com Síndrome de Down e apneia obstrutiva do sono: estudo piloto.

PURPOSE: To investigate oropharyngeal structures and functions in a pediatric population with Down Syndrome (DS) and obstructive sleep apnea (OSA) and to correlate with the apnea/hypopnea index (AHI) and sleep questionnaires. METHODS: 12 Children with DS and OSA, between the age of 4 and 12 years old, underwent polysomnography (PSG); sleep questionnaires, Pediatric Sleep Questionnaire (PSQ) and Obstructive Sleep Apnea-18 (OSA-18); and speech-language evaluation using the Short Evaluation of Orofacial Myofunctional Protocol (ShOM). RESULTS: There was a positive correlation between ShoM higher scores and the apnea-hypopnea index (AHI) and between ShoM and the number of hypopneas. The orofacial myofunctional alterations observed in the studied group were: oral breathing, alteration in lip tonus and competence, tongue posture at rest and in swallowing, and occlusal alteration. There was also an increased risk for OSA according to the sleep questionnaires, as well as the presence of obesity and overweight, but without correlation with the severity of OSA. CONCLUSION: All DS children show alterations in orofacial characteristics, higher scores being associated to severe OSA. Orofacial myofunctional evaluation may help to identify different phenotypes in Down syndrome children with Obstructive sleep Apnea, enhancing the need for a multidisciplinary approach.

OBJETIVO: Investigar as estruturas e funções orofaríngeas de uma população pediátrica com Síndrome de Down (SD) e apneia obstrutiva do sono (AOS) e correlacionar com o índice de apneia/hipopneia (IAH) e questionários do sono. MÉTODO: 12 Crianças com SD e AOS, entre 4 e 12 anos, foram submetidas à polissonografia (PSG); questionários do sono, Pediatric Sleep Questionnaire (PSQ) e Obstructive Sleep Apnea-18 (OSA-18); e triagem fonoaudiológica por meio do Short Evaluation of Orofacial Myofunctional Protocol (ShOM). RESULTADOS: Verificou-se uma correlação positiva entre pontuações mais elevadas no ShOM e o índice de apneia hipopneia (IAH) e entre o ShOM e número de hipopneias. As alterações miofuncionais orofaciais observadas no grupo estudado foram: respiração oral, alteração no tônus e competência labial, na postura de língua em repouso e na deglutição e alteração oclusal. Verificou-se também, um risco aumentado para AOS conforme os questionários do sono, bem como presença de obesidade e sobrepeso, mas sem correlação com a gravidade da AOS. CONCLUSÃO: Todas as crianças apresentaram alterações miofuncionais orofaciais, sendo que escores mais altos no ShOM, ou seja, um maior comprometimento miofuncional orofacial, estavam associados à maior gravidade de AOS, sugerindo que a avaliação miofuncional orofacial dentro de uma abordagem multidisciplinar pode auxiliar na identificação de fatores de risco para AOS em crianças com SD.

Early Response, Long-Term Seizure Outcome, and Very-Low-Dose Adrenocorticotrophic Hormone Therapy for Infantile Epileptic Spasms Syndrome With Down Syndrome.

BACKGROUND: Infantile epileptic spasms syndrome (IESS) with Down syndrome has good treatment response and good seizure outcomes with high-dose adrenocorticotrophic hormone (ACTH) therapy. We investigated the early treatment response of epileptic spasms (ES), long-term seizure outcome, and efficacy of very-low-dose ACTH therapy for IESS with Down syndrome. METHODS: We retrospectively investigated patients with Down syndrome and IESS between April 1983 and January 2023. We defined response to treatment as clinical remission and electrographic resolution of hypsarrhythmia after treatment for more than one month and early treatment as any treatment for ES within three months of initiation of treatment. Long-term seizure outcomes were determined by the presence of any type of seizure within one year of the last visit. We investigated the dosage and efficacy of very-low-dose ACTH therapy. RESULTS: Thirty patients were enrolled with a median follow-up period of 7.7 years (range: 1.3 to 19.1). The response and relapse rates in the early treatment were 83.3% and 16.0%, respectively. The seizure-free rate of long-term seizure outcomes was 80.0%. Long-term seizure outcomes correlated with early treatment response to ES. The response rate of very-low-dose ACTH therapy was 59.3%. The efficacy of ACTH therapy tended to be dose-dependent (P = 0.055). CONCLUSIONS: Early treatment response to ES may be useful in predicting long-term seizure outcomes of IESS with Down syndrome. Very-low-dose ACTH therapy was the most effective treatment for ES and could exhibit dose-dependent efficacy. Depending on the IESS etiology, the ACTH dose could be reduced to minimize its side effects.

The surge in heart rate and blood pressure at respiratory event termination is dampened in children with down syndrome.

BACKGROUND: Children with Down syndrome (DS) have a high prevalence of sleep disordered breathing (SDB) and altered cardiovascular autonomic control. We aimed to analyze the effect of DS on the surge in heart rate (HR) and pulse transit time (PTT, an inverse surrogate measure of blood pressure change) at respiratory event termination. METHODS: 44 children (3-19 y) with DS and 44 typically developing (TD) children matched for SDB severity, age and sex underwent overnight polysomnography. Multilevel modelling determined the effect of DS on HR and PTT changes between a 10s pre-event to the latter half of each respiratory event (late-event) and 15s post-event during NREM and REM, accounting for SDB severity and event length. RESULTS: The children with DS had a significantly smaller % change in HR late-event to post-event (NREM: DS 26.4 % ± 17.5 % (mean ± SD), TD 30.7 % ± 21.0 %; REM DS 16.9 % ± 15.3 %, TD 21.0 % ± 14.0 %; p < 0.05 for both) compared with TD children for obstructive events, and central events (13.2 % ± 17.0 %, TD 18.8 % ± 17.0 %; p < 0.01) during REM. %change in PTT was significantly smaller in the DS group during NREM and REM from pre-event and late-event to post-event compared with TD children for obstructive and central events. CONCLUSION: These results suggest children with DS have dampened HR and BP responses to respiratory events compared with TD children. Whether this is symptomatic of autonomic dysfunction or a protective factor for the cardiovascular system in children with DS remains to be elucidated.

Successful recovery from cardiac arrest due to atlantoaxial subluxation in Down syndrome: a case report.

INTRODUCTION: Down syndrome is the most common chromosomal abnormality associated with intellectual impairments. Unexpected deaths are common with this disease. There are certain difficulties in clarifying the cause of death because the manifestations may be quite diverse and involve many organ systems. Atlantoaxial subluxation is a dangerous complication of Down syndrome, as it may lead to cervical cord-medullary compression. CASE PRESENTATION: Herein, we present a case of Down syndrome in a patient who completely recovered from cardiac arrest due to atlantoaxial subluxation. The neck was immobilized during post-cardiac arrest care, and the patient underwent surgery after 14 days. The patient could walk independently and was discharged 3 months later. At the last follow-up 5 years after surgery, the patient's general condition was good. DISCUSSION: Physicians should be aware that atlantoaxial instability can cause cardiac arrest in patients with genetic syndromes.

Cerebrovascular disease emerges with age and Alzheimer's disease in adults with Down syndrome.

Adults with Down syndrome have a genetic form of Alzheimer's disease (AD) and evidence of cerebrovascular disease across the AD continuum, despite few systemic vascular risk factors. The onset and progression of AD in Down syndrome is highly age-dependent, but it is unknown at what age cerebrovascular disease emerges and what factors influence its severity. In the Alzheimer's Biomarker Consortium-Down Syndrome study (ABC-DS; n = 242; age = 25-72), we estimated the age inflection point at which MRI-based white matter hyperintensities (WMH), enlarged perivascular spaces (PVS), microbleeds, and infarcts emerge in relation to demographic data, risk factors, amyloid and tau, and AD diagnosis. Enlarged PVS and infarcts appear to develop in the early 30s, while microbleeds, WMH, amyloid, and tau emerge in the mid to late 30s. Age-residualized WMH were higher in women, in individuals with dementia, and with lower body mass index. Participants with hypertension and APOE-ε4 had higher age-residualized PVS and microbleeds, respectively. Lifespan trajectories demonstrate a dramatic cerebrovascular profile in adults with Down syndrome that appears to evolve developmentally in parallel with AD pathophysiology approximately two decades prior to dementia symptoms.

Factors influencing gastrostomy tube feeding duration and nutrition outcomes in pediatric patients with Down syndrome: A descriptive cohort study.

BACKGROUND: Feeding difficulty is widely recognized in patients with Down syndrome, and many patients require gastrostomy tube (G-tube) placement for nutrition. No reliable factors have been identified to predict the expected duration of G-tube feeds in patients with Down syndrome. This descriptive cohort study aimed to determine the factors affecting the duration of G-tube feeds. We also investigated change in body mass index (BMI) from G-tube placement to discontinuation. METHODS: Medical records of patients with Down syndrome seen by a pediatric gastroenterologist at a tertiary care center between September 1986 and December 2021 were reviewed. Data collection included demographics, anthropometrics, comorbidities, and feeding route. Comparison was performed between patients who discontinued G-tube feeds and those who did not. RESULTS: Two hundred twenty patients (45% female) were included. The median age at G-tube placement was 5 months (interquartile range [IQR]: 0.2-1.3 years). There were 113 (51%) patients who discontinued G-tube feeds, after a median duration of 31.6 months (IQR: 15.6-55.7 months). Tracheostomy was the only covariant associated with a longer duration of G-tube feeds (158 months vs 53 months; P = 0.002). Neither age at G-tube placement nor any comorbidities were associated with BMI status at discontinuation of G-tube. CONCLUSION: In our cohort of patients with Down syndrome, age at placement of G-tube did not impact the duration of G-tube feeds. Most patients who had a G-tube placed were likely to require enteral feeds for at least 1 year. Those who had a tracheostomy needed their G-tube for a longer time.

Rate and management of tympanic membrane perforations in children with Down syndrome and middle ear disorder.

OBJECTIVE: To characterize the management and outcomes of observation versus surgical intervention of tympanic membrane (TM) perforations in children with Down syndrome (DS). In addition, to estimate the prevalence of TM perforations in children with DS. METHODS: Retrospective case review analysis of TM perforation rate in children with DS with history of tympanostomy tube (TT) insertion at a tertiary pediatric referral center. Patients were divided into observation or surgical intervention groups and then further evaluated for the type of intervention, the number of required procedures, and success rate of hearing improvement. Risk factors contributing to perforations were analyzed, including TT type, number of TT surgeries, and perforation size. RESULTS: The TM perforation rate in children with DS with TT history was 7.0 %. Tympanoplasty was performed in 41.5 % of perforated ears with a success rate of 53.1 %. There was no statistical difference between the surgical intervention and observation groups regarding perforation characteristics or TT number and type, but the surgical intervention cohort was older. Hearing improvement based on postoperative pure tone average (PTA) threshold was noted in the successful surgical intervention group. CONCLUSION: The rate of TM perforations in children with DS after TTs is comparable to the general population. Improved PTA thresholds were noted in the surgical success group influencing speech development. The overall lower success rate of tympanoplasty in patients with DS emphasizes the need to factor in the timing of surgical intervention based on the predicted age of Eustachian tube maturation.

Prenatal treatment with preimplantation factor improves early postnatal neurogenesis and cognitive impairments in a mouse model of Down syndrome.

Down syndrome (DS) is a genetic disease characterized by a supernumerary chromosome 21. Intellectual deficiency (ID) is one of the most prominent features of DS. Central nervous system defects lead to learning disabilities, motor and language delays, and memory impairments. At present, a prenatal treatment for the ID in DS is lacking. Subcutaneous administration of synthetic preimplantation factor (sPIF, a peptide with a range of biological functions) in a model of severe brain damage has shown neuroprotective and anti-inflammatory properties by directly targeting neurons and microglia. Here, we evaluated the effect of PIF administration during gestation and until weaning on Dp(16)1Yey mice (a mouse model of DS). Possible effects at the juvenile stage were assessed using behavioral tests and molecular and histological analyses of the brain. To test the influence of perinatal sPIF treatment at the adult stage, hippocampus-dependent memory was evaluated on postnatal day 90. Dp(16)1Yey pups showed significant behavioral impairment, with impaired neurogenesis, microglial cell activation and a low microglial cell count, and the deregulated expression of genes linked to neuroinflammation and cell cycle regulation. Treatment with sPIF restored early postnatal hippocampal neurogenesis, with beneficial effects on astrocytes, microglia, inflammation, and cell cycle markers. Moreover, treatment with sPIF restored the level of DYRK1A, a protein that is involved in cognitive impairments in DS. In line with the beneficial effects on neurogenesis, perinatal treatment with sPIF was associated with an improvement in working memory in adult Dp(16)1Yey mice. Perinatal treatment with sPIF might be an option for mitigating cognitive impairments in people with DS.