Long-term Outcome Of Children Research Articles

Factors associated with accelerated parenteral weaning in children with intestinal failure: A descriptive cohort study.

The goal of intestinal rehabilitation in children is to wean from parenteral nutrition (PN). The aim of this study was to identify factors associated with accelerated weaning and to evaluate long-term outcomes of children receiving long-term PN. This was a retrospective study of children managed by the Intestinal Rehabilitation Center at Cincinnati Children's Hospital. Medical history data were retrieved. The outcomes of children receiving long-term chronic PN (>2 years) were compared with those of children receiving short-term chronic PN regimen (<2 years). The cohort consisted of 112 children (58% boys, median [IQR] age of 6.0 [3.7-9.5] years). The group treated with a long-term PN regimen had significantly shorter residual small bowel and large bowel compared with the group treated with a short-term PN regimen (20% vs 60% and 75% vs 100%, respectively; P < 0.05). The lapse of time between PN and enteral feed initiation was longer in the group undergoing long-term PN regimen than in the short-term group (71 vs 32.5 days; P = 0.012). More episodes of central line-associated bloodstream infection (CLABSI) and a higher percentage of feeding aversion was demonstrated in the long-term PN group (2 [1-3] vs 1 [0-2] episodes and 36% vs 0%, respectively). Small bowel, colon length, enteral feed initiation, and frequency of CLABSI are factors associated with duration of PN regimen. A long-term chronic PN regimen is associated with a higher risk of food aversion.

Molecular profiles and long-term outcomes of Thai children with hepatic glycogen storage disease in Thailand.

Thus far, genetic analysis of patients clinically diagnosed with glycogen storage diseases (GSDs) in Thailand has not been reported. To evaluate the clinical and biochemical profiles, molecular analysis and long-term outcomes of Thai children diagnosed with hepatic GSD. Children aged < 18 years diagnosed with hepatic GSD and followed up at King Chulalongkorn Memorial Hospital were recruited. Whole-exome sequencing (WES) was performed to identify the causative gene variants. Medical records were assessed. All eight children with histopathologically confirmed diagnosis were classified by WES into subtypes Ia (n = 1), III (n = 3), VI (n = 3), and IX (n = 1). A total number of 10 variants were identified including G6PC (n = 1), AGL (n = 4), PYGL (n = 5), and PHKA2 (n = 1). AGL had two novel variants. The clinical manifestations were hepatomegaly (n = 8), doll-like facies (n = 3), wasting (n = 2), and stunting (n = 5). All patients showed hypoglycemia, transaminitis, and dyslipidemia. The mainstay of treatment was cornstarch supplementation and high-protein and low-lactose-fructose diet. After a median follow-up time of 9.59 years, height turned to normal for age in 3/5 patients and none had malnutrition. Liver enzymes, blood sugar, and lipid profiles improved in all. Hepatomegaly, transaminitis, and hypoglycemia are the hallmarks of GSD confirmed by liver histopathology. Molecular analysis can confirm the diagnosis or classify the subtype that might benefit from personalized treatment, prognosis, and long-term care.

Oncology

The December 2024 Oncology Roundup360 looks at: Non-reversed great saphenous vein grafts for vascular reconstruction after resection of lower limb sarcoma; Detrimental effects of COVID-19 pandemic on patients with limb bone sarcoma: reference centre experience; Whole-body staging guidelines in sarcoma; Intraoperative marrow margin frozen section in limb bone sarcoma resection; Vacuum-assisted closure and paediatric oncological limb salvage; Treatment differences and long-term outcomes in adults and children with Ewing’s sarcoma; Survival, complications, and functional outcomes of uncemented distal femoral endoprosthesis with short, curved stem for patients with bone tumours; Survival, complications, and functional outcomes of uncemented distal femoral endoprosthesis with short, curved stem for patients with bone tumours.

Vaccination in hemophilic children: Challenges, innovations, and future directions

Introduction: Hemophilia, an inherited disorder primarily affecting blood clotting due to deficiencies in clotting factors VIII or IX, presents complex challenges for vaccination. Children with hemophilia require vaccinations to prevent infections that may exacerbate their bleeding disorder. However, traditional intramuscular vaccination poses bleeding risks, necessitating specialized administration methods and careful post-vaccination care. Purpose: This study examines the efficacy and safety of vaccination in pediatric hemophilia patients, emphasizing the importance of individualized protocols to manage bleeding risks effectively. It explores recent advancements, including needle-free technologies, the potential of gene therapy, and mRNA vaccines. Materials and Methods: The study synthesizes current guidelines from global health organizations, hemophilia management protocols, and clinical studies on vaccine safety in hemophilia. It highlights techniques such as subcutaneous administration, clotting factor prophylaxis, and the use of fine-gauge needles to minimize bleeding complications. Results: Findings indicate that with appropriate management, hemophilic children achieve adequate immune responses to vaccines, with reduced bleeding risks. Emerging technologies, such as microneedle patches, jet injectors, and gene therapy, offer promising safer vaccination alternatives. Additionally, mRNA vaccines demonstrate strong immunogenicity without the need for live-virus vectors, reducing complication risks. Conclusions: Vaccination, when adapted to hemophilia-specific needs, remains essential for infection prevention in this vulnerable population. Newer vaccine technologies and individualized care protocols enhance safety and efficacy, contributing to improved quality of life and long-term health outcomes for hemophilic children.

Long-Term Outcome of Children With Steroid-Resistant Nephrotic Syndrome: A Single Center Experience From Pakistan

Objective: To determine the long-term outcome of children with steroid-resistant nephrotic syndrome at a single center in Pakistan. Study Design: Retrospective, observational study. Place and Duration of Study: Pediatric Nephrology Department, Sindh Institute of Urology and Transplantation, Karachi, Pakistan from July 2008 to June 2014. Methodology: The study included 153 children aged 4 months-12 years with steroid-resistant nephrotic syndrome. We collected data at the time of diagnosis and the last follow-up. The data was entered and analyzed by SPSS version 20. Results: Among 153 children, 84(55%) were males and 69(45%) females. At the time of diagnosis, 118(77%) were hypertensive and 65 (42.5%) had microscopic hematuria. Histopathological spectrum included focal segmental glomerulosclerosis, 63(41%); minimal change disease, 33(22%); IgM nephropathy, 9 (6%); mesangioproliferative glomerulonephritis, 26(17%), membranous glomerulonephritis, 13(8%) and membranoproliferative glomerulonephritis, 9(6%). Complete remission with cyclosporine was seen in 53(34.6%), partial remission in 36(23.5%), while 53(35%) developed chronic kidney disease, of which 26(78.8%) needed renal replacement therapy. Mortality was 21(13.7 %) and 11(7.2%) were lost to follow-up. Calcineurin inhibitors’ toxicity was seen in 52(34%). One patient received renal transplant but lost the graft 6 years post-transplant due to disease recurrence. Conclusion: Steroid-resistant nephrotic syndrome has significant long-term morbidity and mortality. Recurrence of disease in transplanted kidney is common and can result in graft loss.

In vitro fertilization and long-term child health and development: nationwide birth cohort study in Japan

The aim of this study is to compare long-term health outcomes between IVF-conceived children and non-IVF-conceived children in Japan, in the context of strong recommendation for single embryo transfer. Using data from a nationwide birth cohort linked with perinatal database, this study analyzed 2140 children born in Japan in May 2010. It compared child health and development outcomes up to 9 years of age between IVF-conceived and non-IVF-conceived children (binary exposure). A Poisson regression with robust variance to estimate the risk ratios for the association between IVF and various long-term child health and developmental outcomes. After adjusting for confounding factors, no significant differences were observed between IVF-conceived and naturally conceived children for most outcomes, including hospitalization, obesity, and developmental milestones. IVF-conceived children showed a slightly lower risk of attention problems at 8 years (adjusted Risk Ratio [aRR]: 0.73, 95% CI: 0.53–1.00). In subgroup analyses, IVF-conceived term children and singletons demonstrated reduced risk of cognitive delays at 5.5 years (aRR: 0.31, 95% CI: 0.10–0.96 and aRR: 0.37, 95% CI: 0.14–0.98, respectively).Conclusion: In this Japanese cohort, IVF conception was not associated with adverse long-term health or developmental outcomes. These findings provide reassurance about the safety of IVF, particularly in the context of single embryo transfer policies. Further research is needed to explore specific IVF protocols and subgroups.What is known:• Long-term health and developmental outcomes of IVF-conceived children remain inconsistent across studies and populations, despite the widespread use of this technology.What is new:• A nationwide population-based cohort study in Japan did not show adverse effects of IVF on long-term child health and development through age 9.• These findings provide reassurance about the safety of IVF, while indicating the need for careful monitoring in specific subgroups such as preterm and multiple births.

Examining the Impact of COVID-19 on Early Intervention Service Provision for Military Families: A Brief Report

Understanding the extent to which the COVID-19 pandemic disrupted birth-to-three early intervention (EI) service provision is critical as these services play an essential role in ensuring positive long-term developmental outcomes for children with disabilities, including those who are military dependents. The present study leveraged an interrupted time series approach to compare monthly service provision rates before and after the onset of the pandemic for a subset of children served by the Army Medical Department’s Educational and Developmental Intervention Services EI program. Analysis identified 77% and 93% immediate step decreases in EI referral and enrollment rates, respectively, following the onset of the pandemic in March 2020; however, rates returned to, or exceeded, prepandemic levels by late 2020. There were limited differences by race or ethnicity. Additional research is necessary to explore the mechanisms underlying these changes and to understand the long-term impact of missed referrals and enrollments on military children.

Long-term renal outcomes of children with cancers treated with platinum-based chemotherapy: A retrospective chart analysis.

Platinum-based chemotherapy is a mainstay of treatment for many childhood cancers but is associated with acute nephrotoxicity and long-term ototoxicity. There is emerging evidence of long-term renal complications. This study aimed to assess the prevalence of chronic kidney disease (CKD) in children treated with platinum chemotherapy (cisplatin and carboplatin) and identify potential risk factors for the development of CKD. We conducted a retrospective review of children diagnosed with hepatoblastoma, osteosarcoma, neuroblastoma, or medulloblastoma who received platinum chemotherapy over a 16 year timeframe. Patients were excluded if they did not have at least 3 years follow up data, died within 3 years of platinum chemotherapy, or if they relapsed. Clinical data were collected at baseline (first dose), 1 year, and at most recent follow up. Of 328 treated patients, 147 met the inclusion criteria and were followed for a mean of 8.1 years (range 3-15.7 years). The median age at first dose was 3.7 years (IQR 1.7-9.6 years). CKD ≥grade 2 was present in 53(36%) at last follow up and 15(10%) had tubular dysfunction. A history of acute kidney injury at any time during treatment was associated with CKD (OR 3.12 CI 1.07-9.12, p =0.04). On multivariable analysis older age at platinum therapy (OR 1.2, CI 1.1-1.4, p = 0.004) and a high aminoglycoside or vancomycin trough level (OR 4.3, CI 1.9-9.7, p<0.001) were risk factors for CKD. The high rate of CKD in children treated with platinum chemotherapy warrants long-term follow-up and screening for progressive disease.

Long-term outcomes and quality of life in congenital diaphragmatic hernia survivors treated with extracorporeal life support: A cross-sectional survey.

Few reports have shown Quality-of-Life long-term outcomes in children with congenital diaphragmatic hernia (CDH) who received extracorporeal membrane oxygenation (ECMO) support. We reviewed the short- and long-term outcomes in CDH patients that were supported with ECMO during their neonatal treatment. Telephone interviews of parents of CDH children were performed. The Functional Status Scale (FSS) and the Paediatric Quality of Life Inventory (PedQL, Version 4.0) were completed with the parents. All children with a CDH and supported with ECMO from 2010 to 2023 were included in the study. Twenty children were identified, with two having two ECMO runs. Birth weight was 3.2 kg (median). ECMO support lasted for (median) 13.6 days (range 3.8 to 39). Twelve patients were alive at the time of the survey. The age (median) at time of the interview was 6.3 years (range 1 to 12). The FSS score showed no impairment (FSS score 6) in any domain in eight patients. Two patients had a score of 7, and two patients had a score of 8 and 9, respectively. The PedQL showed a median score 84.5, with a physical health summary score of 92.5 and a psychosocial health summary score of 78.7. The cardiac specific PedQL inventory score was 77. ECMO support for CDH patients is associated with functional and Quality of Life outcomes that are similar to that in other PICU discharge populations. Denying ECMO support to CDH patients on the basis of predicted poor long-term outcomes does not appear to be justified.

Timing of single-event multilevel surgical interventions on long-term motor outcomes in children and adolescents with cerebral palsy: A systematic review and meta-analysis

BackgroundThe aim of this meta-analysis was to evaluate the impact of the timing of single-event multilevel surgery (SEMLS) on long-term motor outcomes in children and adolescents with cerebral palsy (CP). MethodsA systematic review and meta-analysis were conducted by searching PubMed, Cochrane Library, Embase, and Web of Science databases for studies up to April 2024. Twelve eligible studies were included, from which we examined patients’ gait, stride length, walking speed, and the gross motor function measure (GMFM66). ResultsGait analysis showed significant improvements in CP patients after SEMLS, which included an increased gait deviation index (p < 0.001), reduced Gillette gait index (p < 0.001), and reduced gait profile score (p < 0.001). Subgroup analysis showed that age at surgery (<12 years old vs. 12−18 years old) was not a factor affecting patients’ gait. Spatial and temporal parameters such as stride length (p < 0.001) and walking velocity (p = 0.02) also improved significantly after surgery. However, there were only trends towards broader motor function gains measured by the GMFM66 (p = 0.39). ConclusionsSEMLS effectively improved key gait and mobility parameters in children and adolescents with CP, and was not affected by younger or older surgical ages (<12 years old or 12−18 years old). However, these gait improvements do not uniformly translate into broader motor function gains.

Vasospasm in Pediatric Subarachnoid Hemorrhage.

Cerebral vasospasm (CV) is a common severe complication of subarachnoid hemorrhage (SAH), a severe type of intracranial bleeding that is uncommon in children. The purpose of this article is to review the current literature regarding this potentially devastating complication. CV may be asymptomatic and is less common in children compared to adults. Several molecular phenomena, including inflammatory ones, contribute to its pathophysiology. Better collateral circulation and higher cerebral blood flow are protective factors in children. When clinically apparent, CV may manifest as a change in the child's neurologic status or vital signs. CV can be diagnosed using brain vessel imaging, such as computed tomography angiography, magnetic resonance angiography, digital subtraction angiography, transcranial Doppler ultrasonography, and computed tomography perfusion. A reduction of < 50% in the artery's caliber confirms the diagnosis. Besides general supportive measures and causative treatment of SAH, CV management options include the administration of calcium channel blockers and neurointerventional approaches, such as intra-arterial vasodilators and balloon angioplasty. Long-term outcomes in children are usually favorable.

Outcomes of Concurrent Balloon Eustachian Tuboplasty and Tympanostomy Tube Placement in Children.

Balloon dilation eustachian tuboplasty (BDET) has been proven to be a safe treatment option for children with eustachian tube dysfunction (ETD). This study aims to analyze the long-term outcomes of children who underwent concurrent BDET and tympanostomy tube (TT) placement. We hypothesize that patients who underwent simultaneous therapy have experienced a low overall rate of middle ear pathology and have consistent hearing quality at subsequent office visits. Retrospective chart review of 19 pediatric patients (36 ears) who previously underwent concurrent BDET and TT placement. Patient charts within the extended postoperative period were reviewed. Specific data points included need for reoperation, rates of middle ear pathology, audiological outcomes, and number of previous TT placements. Pediatric patients who underwent concurrent BDET and TT placement had long-term success in 34/36 ears (94.4%). All postoperative tympanograms and audiograms (100%) were normal when performed within 12 months after the procedure. Notably, 34/36 ears (94.4%) had history of tube placement in the past. Patients had an average of three sets of tympanostomy tubes prior to undergoing concurrent BDET and TT. Concurrent BDET and TT placement may be an effective treatment option for pediatric patients with persistent eustachian tube dysfunction. Specifically, BDET may be a useful adjunct tool in pediatric patients with refractory ETD despite having multiple sets of tympanostomy tubes. This study aims to strengthen the argument of performing multimodal therapy in pediatric patients with recurrent middle ear disease. 4 Laryngoscope, 134:4799-4802, 2024.

Mobile Health Monitoring Application as an Effort to Detect Stunting in Early Childhood Based on Android

Stunting, as a chronic nutritional problem that inhibits optimal child growth, has a significant impact on Indonesia's demographic bonus potential. In Indonesia, the prevalence of stunting reached 24.4% in 2021, with long-term impacts including cognitive decline, low productivity, and increased risk of chronic diseases. Health Monitoring application for the detection and prevention of stunting in early childhood. Using the waterfall method, this research produced an application with seven main pages that allow comprehensive monitoring of child growth. Functionality testing showed a 95% success rate in implementing critical features, including navigation, authentication, and child data management. Feedback from 50 early adopters showed an 85% satisfaction rate and a 40% increase in the frequency of child growth monitoring. Key challenges included cross-platform data integration and performance optimization on low-specification devices, which were addressed through the development of a modular architecture and code optimization. The app has the potential to increase early detection of growth problems by 30%, enabling timely interventions to improve children's long-term health outcomes. Implementation simulations show a potential reduction in stunting prevalence of 5% within 3 years if widely used. Although limited to user interface development, this research lays the foundation for further development, including the integration of advanced data analysis and nutrition improvement features, which are projected to increase the effectiveness of stunting detection and intervention by up to 50%.

Language barriers and mental health problems of preschool children born very preterm in Germany.

We assessed whether behavioural and emotional problems of 5- to 6-year-old preschool children born very preterm (<32 weeks' gestation) are associated with an immigrant background and linguistic distance of their first language to the host country's official language, German. This is an observational longitudinal cohort study. Data are from the national multicentre German Neonatal Network cohort, including all very preterm births from 2009 onwards. A total of 3220 (n = 1570 female) children were followed up at preschool age; 629 (n = 324 female) of these had an immigrant background. Behavioural and emotional problems were assessed using the parent-reported Strengths and Difficulties Questionnaire (SDQ). Mixed-effects models showed that immigrant status alone was not associated with children's behavioural and emotional problems. However, a higher linguistic distance of the children's first language to German was associated with higher SDQ total problem scores (coefficient = 0.008, 95% confidence interval 0.002, 0.015), after adjusting for known confounders. Language barriers in the form of linguistic distance between the first language of children born very preterm and countries' official languages are associated with increased risk for behavioural and emotional problems. More research is needed on how language barriers affect long-term developmental outcomes of immigrant children born very preterm.

Esophagitis, treatment outcomes, and long-term follow-up in children with esophageal atresia.

Survival rates in children born with esophageal atresia (EA) with or without tracheoesophageal fistula (TEF) have improved; however, morbidity associated with the disease remains high. This study aimed to assess the prevalence of gastroesophageal reflux disease (GERD), eosinophilic esophagitis (EoE), fungal esophagitis, esophageal strictures, and long-term outcomes in children with EA/TEF. We conducted a retrospective chart review on patients with EA/TEF who were seen at Children's Wisconsin from January 2003 to January 2023. Patients born with EA/TEF were included if they underwent at least one endoscopy after 1 year of age. GERD was diagnosed based on abnormal findings on endoscopy, pH-metry, and/or history of fundoplication. EoE and fungal esophagitis were diagnosed based on abnormal endoscopy. Esophageal stricture diagnosis was based on findings on endoscopy and/or esophagram, and clinical symptoms necessitating esophageal dilation. Eighty-five patients (64.7% males, mean age 7.5 years) were included, the majority had type C EA/TEF (90.6%). GERD was diagnosed in 61.1% (n = 52), 49.4% (n = 42) by macro and/or microscopic endoscopic findings, 22.3% (n = 19) by abnormal pH-metry, and 21.1% (n = 18) by the need for fundoplication for refractory reflux and/or esophageal stricture. Risk of GERD increased with lower gestational age (p = 0.0030), lower birth weight (p = 0.023), and long-gap EA (p = 0.034). In children diagnosed with GERD, only 13.4% of patients (n = 7/52) were able to be weaned off proton pump inhibitor (PPI) without disease recurrence. However, overall, at the completion of the study, 44.7% (n = 38) of patients were successfully weaned off PPI without evidence of GERD. EoE was diagnosed in 20% of the patients (n = 17). All patients diagnosed with EoE required escalation of therapy from PPI alone to swallowed corticosteroids in 52.9% (n = 9), dupilumab in 23.5% (n = 4), elemental formula in 17.6% (n = 3), and elemental formula and swallowed steroids in 5.8% (n = 1). Fungal esophagitis was diagnosed in 15.3% of patients (n = 13). An esophageal stricture requiring dilation was diagnosed in 77.6% (n = 66) of patients at a mean age of 28.5 months, with over 60% diagnosed by 24 months of age. Children born with EA/TEF continue to be at high risk of developing GERD, EoE, fungal esophagitis, and esophageal stenosis. Diagnostic and therapeutic endoscopy remains a high-yield test to identify and treat these comorbidities.

Neurodevelopmental outcomes of school-age children conceived after hysterosalpingography with oil-based or water-based iodinated contrast: long-term follow-up of a nationwide randomized controlled trial.

Does preconceptional exposure to oil-based iodinated contrast media during hysterosalpingography (HSG) impact children's neurodevelopment compared with exposure to water-based alternatives? Our study found no large-sized effects for neurodevelopment in children with preconceptional exposure to oil-based iodinated contrast media during HSG compared with water-based alternatives. HSG is widely used as a diagnostic tool in the female fertility work-up. Tubal flushing with oil-based iodinated contrast has been shown to enhance fertility outcomes in couples with unexplained infertility, increasing the chances of pregnancy and live birth compared with water-based alternatives. However, oil-based contrast contains higher doses of iodine and has a longer half-life, and concerns exist that iodinated contrast media can affect women's iodine status and cause temporary (sub)clinical hypothyroidism in mothers and/or foetuses. Considering that thyroid hormones are vital to embryonal and foetal brain development, oil-based contrast media use could increase the risk of impaired neurodevelopment in children conceived shortly after HSG. Here we examine neurodevelopmental outcomes in school-aged children conceived after HSG. This is a long-term follow-up of the H2Oil trial in which oil-based or water-based contrast was used during HSG (Netherlands; 2012-2014; NTR3270). Of 369 children born <6 months after HSG in the study, we contacted the mothers of 140 children who gave consent to be contacted for follow-up. The follow-up study took place from January to July 2022 (NCT05168228). The study included 69 children aged 6-9 years who were conceived after HSG with oil-based (n = 42) or water-based contrast (n = 27). The assessments targeted intelligence (Wechsler Intelligence Scale for Children), neurocognitive outcomes (computerized neurocognitive tests), behavioural functioning (parent and teacher questionnaires), and academic performance. Linear regression models, adjusted for age, sex, and parental educational attainment were employed to compare groups. School-aged children born to mothers after oil-based contrast HSG did not significantly differ from children born to mothers after water-based contrast HSG, in regards to intelligence, neurocognitive functioning, behavioural functioning, or academic performance, with the exception of better performance for visuomotor integration functions in children exposed to oil-based contrast preconception. After exploratory correction for multiple comparisons, none of the group differences was statistically significant. The small sample size of this follow-up study limited statistical power. This study provides evidence for the absence of large-sized differences between preconceptional exposure to the two contrast media types but does not rule out more subtle effects on neurodevelopment compared to naturally conceived children without preconceptional exposure to HSG. This study contributes to our knowledge about the long-term effects of different types of iodinated contrast media used in fertility work-up, indicating that choosing oil-based over water-based iodinated contrast media is unlikely to have major effect on the long-term neurodevelopmental outcomes of children conceived shortly after HSG. However, further research should focus on the overall safety of iodine exposure during HSG, comparing children conceived after HSG to those conceived naturally as both types of contrast contain high amounts of iodine. The original H2Oil randomized controlled trial was an investigator-initiated study that was funded by the two academic hospitals now merged into the Amsterdam University Medical Centre. The current follow-up study (Neuro-H2Oil) is funded through a research grant awarded to the authors by the Amsterdam Reproduction & Development (AR&D) research institute. S.K. is funded by a AMC MD/PhD Scholarship from the Amsterdam UMC. S.K. reports holding voluntary roles in the civil society organizations Universities Allied for Essential Medicines and People's Health Movement. V.M. reports receiving travel and speaker fees as well as research grants from Guerbet, Merck and Ferring. K.D. reports receiving travel and speaker fees as well as research grants from Guerbet. BWM is supported by a NHMRC Investigator grant (GNT1176437) and reports consultancy, travel support and research funding from Merck, consultancy for Organon and Norgine, and holding stock from ObsEva. The other authors report no conflict of interest. NCT05168228.

Maternal Nutrition during Pregnancy and Offspring Brain Development: Insights from Neuroimaging.

Maternal nutrition during pregnancy is known to be important for offspring growth and health and has also been increasingly recognized for shaping offspring brain development. On the other hand, recent advancements in brain imaging technology have provided unprecedented insights into fetal, neonatal, and pediatric brain morphometry and function. This review synthesizes the current literature regarding the impact of maternal nutrition on offspring brain development, with a specific focus on findings from neuroimaging studies. The diverse effects of maternal nutrients intake or status during pregnancy on neurodevelopmental outcomes in children are discussed. Neuroimaging evidence showed associations between maternal nutrition such as food categories, macronutrients, and micronutrients including vitamins and minerals during pregnancy and child brain imaging features measured using imaging techniques such as ultrasound, magnetic resonance imaging (MRI), electroencephalography (EEG), and magnetoencephalography (MEG). This review demonstrates the capability of neuroimaging in characterizing how maternal nutrition during pregnancy impacts structure and function of the developing brain that may further influence long-term neuropsychological, cognitive, and behavioral outcomes in children. It aims to inspire future research utilizing neuroimaging to deepen our understanding of the critical impacts of maternal nutrition during pregnancy on offspring brain development.

Long-term health outcomes of children born by cesarean section: A nationwide population-based retrospective cohort study in Taiwan

BackgroundTaiwan had high cesarean rate which exceeded the recommended threshold (15%), set by WHO. However, there have not a comprehensive study to discuss the long-term offspring consequences of cesarean section (CS). This study aimed to show whether allergy disorders, obesity and respiratory infection of children are associated with modes of delivery, using the National Health Insurance Research Database (NHIRD) of Taiwan. MethodsThis study used the maternal and child health database of NHIRD. We included the children who birth between 2004 and 2013 and inter-linked the database of the mother and children. The participants were followed until 2018/12/31. We performed a Cox proportional hazards model to identify the association of CS with respiratory tract infection, allergy disorder, and obesity diagnosed in childhood. ResultsCS significantly increased the risk of developed childhood asthma (adjusted hazard ratio [aHR] = 1.03; 95% confidence interval [CI]: 1.02–1.03), allergy rhinitis (aHR = 1.04; 95% CI: 1.04–1.05), atopic dermatitis (aHR = 1.05; 95% CI: 1.04–1.06), respiratory tract infection (aHR = 1.07; 95% CI: 1.06–1.07) and overweight (aHR = 1.29; 95% CI: 1.18–1.40) even after adjusting with confounding factor. Development of food allergy (aHR = 1.13; 95% CI: 0.87–1.47) was not associated with cesarean section. ConclusionThis study indicated that children delivered by CS more commonly developed respiratory tract infections, asthma, allergic rhinitis, atopic dermatitis, obesity than children delivered vaginally. Among these, obesity have a stronger association with cesarean section.

Early life epigenetics and childhood outcomes: a scoping review.

Epigenetics is the study of changes in gene expression, without a change in the DNA sequence that are potentially heritable. Epigenetic mechanisms such as DNA methylation, histone modifications, and small non-coding RNA (sncRNA) changes have been studied in various childhood disorders. Causal links to maternal health and toxin exposures can introduce epigenetic modifications to the fetal DNA, which can be detected in the cord blood. Cord blood epigenetic modifications provide evidence of in-utero stressors and immediate postnatal changes, which can impact both short and long-term outcomes in children. The mechanisms of these epigenetic changes can be leveraged for prevention, early detection, and intervention, and to discover novel therapeutic modalities in childhood diseases. We report a scoping review of early life epigenetics, the influence of maternal health, maternal toxin, and drug exposures on the fetus, and its impact on perinatal, neonatal, and childhood outcomes. IMPACT STATEMENT: Epigenetic changes such as DNA methylation, histone modification, and non-coding RNA have been implicated in the pathophysiology of various disease processes. The fundamental changes to an offspring's epigenome can begin in utero, impacting the immediate postnatal period, childhood, adolescence, and adulthood. This scoping review summarizes current literature on the impact of early life epigenetics, especially DNA methylation on childhood health outcomes.

Considerations for the design and conduct of pediatric obesity pharmacotherapy clinical trials: Proceedings of expert roundtable meetings.

Anti-obesity medications (AOMs) have emerged as one element of comprehensive obesity clinical care intended to improve long-term health outcomes for children and adolescents. The number of pediatric AOM clinical trials has burgeoned in recent years as new pharmacotherapeutics have been developed. Factors related to growth and development in children and adolescents can present unique challenges in terms of designing and conducting clinical trials investigating the safety and efficacy of AOMs. These barriers can delay the AOM development and evaluation process, increase the cost of performing trials, create challenges in the interpretation of results, influence the generalizability of the findings and present ethical dilemmas. In an effort to address these issues and provide guidance to streamline the process of designing and conducting pediatric AOM clinical trials, relevant key stakeholders convened a series of roundtable meetings to discuss, debate and achieve harmonization on design features. Stakeholder participants included a multidisciplinary group of international pediatric obesity experts, patient (parent) representatives and representatives from academic medicine, key regulatory agencies and industry. Topics of discussion included primary efficacy end-points, secondary end-points, eligibility criteria, trial run-in and follow-up phases, use of active comparators and guidelines for down-titration and/or stopping rules for excessive weight reduction. Consensus recommendations were agreed upon. Regarding end-points, emphasis was placed on moving away from BMI z-score as a primary outcome, incorporating multiple alternative BMI-related outcomes and measuring adiposity/body fat as a prominent secondary end-point. Trial eligibility criteria were carefully considered to maximize generalizability while maintaining safety. The limited value of trial run-in phases was discussed. It was also underscored that designing trials with extended follow-up periods after AOM withdrawal should be avoided owing to ethical issues (including possible psychological harm) related to weight regain without providing the opportunity to access other treatments. The panel emphasized the value of the randomized, placebo-controlled trial but recommended the thoughtful consideration of the use of active comparators in addition to, or instead of, placebo to achieve clinical equipoise when appropriate. Finally, the panel recommended that clinical trial protocols should include clear guidance regarding AOM down-titration to avoid excessive weight reduction when applicable.