Pediatric Research最新文献

Background: To estimate the association between very preterm birth combined with the presence of a congenital anomaly and economic costs during the fifth year of life in Europe.

Methods: An economic analysis was embedded within a population-based prospective cohort study, including all infants born between 22 + 0 and 31 + 6 weeks' gestation in 2011-2012 in 19 regions across 11 European countries. Economic costs (€, 2022 prices) during the fifth year of life were estimated for children born very preterm with (n = 313) and without (n = 3374) a congenital anomaly, and by severity of congenital anomaly. Multilevel generalised linear models explored factors associated with economic costs by anomaly severity.

Results: Total mean societal costs during the fifth year of life were significantly higher among very preterm children born before 32 weeks with a congenital anomaly than those without (unadjusted mean cost difference: €2760, p = 0.02). A multilevel model including socioeconomic, clinical characteristics, and complications of preterm birth, showed that total mean societal costs were €3281 higher for children born before 32 weeks with congenital anomalies compared to those without (p < 0.001).

Conclusion: Very preterm birth combined with the presence of a congenital anomaly generates significant economic costs on health and social care systems in Europe.

Impact: Very preterm birth combined with the presence of a congenital anomaly is associated with increased health and social service costs and increased societal costs during the fifth year of life. Additional severe neonatal morbidity is independently associated with increased costs in this population. Very preterm birth together with a congenital anomaly creates substantial economic burdens for health and social care systems and families five years after birth.

Background: This study was designed to identify genes for further study as modifiers of the severity of cardiomyopathy in DMD-related Duchenne Muscular Dystrophy (DMD).

Methods: We evaluated genome sequencing results in a well-phenotyped DMD cohort with severe cardiomyopathy against those with less severe cardiomyopathy. Using combined annotation-dependent depletion variant annotation to look at variant burden, we created a difference between group mean (DBGM) summative C-Scores by gene. We completed analyses on three groups. For each analysis, we normalized DBGM summative C-Score and determined which genes had a value > three standard deviations from the mean in all three analyses.

Results: There were 54 DMD males in this analysis. 18 individuals (33%) had severe cardiomyopathy and 36 individuals (67%) had less severe cardiomyopathy. Nine genes were identified as possible cardiomyopathy severity modifiers: ANKLE1, ESRRA, FRAS1, GEMIN4, GXYLT1, MTCH2, PKD1L2, PRSS2 and QRFPR.

Conclusion: DBGM summative C-Scores in well-phenotyped groups are a feasible exploratory method to identify genetic targets for additional study. There is preliminary evidence from this and other studies suggesting further evaluation of ESRRA, GEMIN4, and MTCH2 as modifiers of cardiomyopathy severity could advance understanding of DMD cardiomyopathy progression.

Impact: This article identifies possible genetic modifiers of DMD cardiomyopathy severity via a novel method of looking at variant burden between groups. This adds to the existing literature by providing new evidence for modifier pathway targets for possible therapeutic targets or drug repurposing in a rare genetic disorder.

Background: Exclusive breastfeeding (EBF) rates at 6 months postpartum remain low globally and in Hong Kong. This prospective mixed-method study examined the barriers to and facilitators of sustaining EBF until 6 months postpartum.

Methods: Nine hundred forty-two pregnant women completed baseline and at least one of the five follow-up surveys: immediate (<7 days) (T1), 1 month (T2), 2 months (T3), 4 months (T4), and 6 months postpartum (T5). The response rates were 81.0% (T1), 69.9% (T2), 67.3% (T3), 65.8% (T4) and 81.4% (T5). Eighteen participants and 6 partners participated in either individual or focus group interviews at 6 months postpartum.

Results: The quantitative study found that mothers who worked full-time, had attained lower levels of education, lacked breastfeeding experience, and had caesarean sections were less likely to practise EBF at 6 months postpartum. In contrast, mother-in-law's breastfeeding experience, higher breastfeeding intention and better breastfeeding knowledge were positively associated with EBF at 6 months postpartum. Qualitative data identified perceived insufficient breast milk and returning to work as the main barriers, while support from family was the key facilitator.

Conclusions: In addition to education and support for mothers, in order to sustain EBF, it is crucial to engage with family members and for workplaces to create more conducive environments.

Impact: This large-scale mixed methods cohort study describes mothers' feeding practices and perspectives from the immediate postpartum period until 6 months. Factors associated with EBF at 6 months included (1) mother and infant attributes, (2) workplace and employment, (3) family and community, and (4) health systems and services. Policies and strategies extending to family members, workplace and health system will create a more conducive environment for sustaining EBF.

Background: Critical congenital heart disease (CHD) is associated with poor neurodevelopmental outcomes and long-term psychosocial morbidity. The pre-natal environment is increasingly recognized as a critical effector. However, the association of specific placental lesions with fetal brain volume in CHD remains unexamined.

Methods: This was a multi-site prospective, nested case-control study, that recruited pregnant women with typical fetal development and prenatally diagnosed fetal CHD. Fetal brain MRI was performed at 32.8 ± 3.0 weeks gestation. Placentas were examined pathologically after delivery. Clinical characteristics were gathered from self-reports and medical charts. Multiple linear regression modeling was performed in R with p < 0.05 considered significant.

Results: Placental hypoplasia (weight <10th %ile) was associated with lower total fetal intracranial volume in CHD (p = 0.006) and combined (CHD + non-CHD) cohorts (p = 0.001). Maternal and/or fetal vascular malperfusion was also associated with lower total fetal intracranial volume in combined (p = 0.026), and non-CHD cohorts (p = 0.020). Presence of any placental pathology was associated with reduced total fetal intracranial volume (p = 0.047), an effect moderated by the presence of CHD (interaction term p = 0.037).

Conclusion: Placental hypoplasia, vascular malperfusion, and the presence of any placental pathology are associated with decreased total intracranial volumes in-utero. Fetuses with CHD and concomitant placental lesions appear particularly susceptible.

Impact: Placental vascular malperfusion is associated with reduced fetal intracranial volume. Placental hypoplasia (weight <10th %ile) is associated with smaller intracranial volumes in fetal congenital heart disease. Placental pathologies uniquely affect in-utero brain development in congenital heart disease. This study is the first to link fetal brain development to specific placental pathologies using standardized, reproducible criteria (Amsterdam) with comparative inclusion of a non-congenital heart disease cohort. Evidence builds that the in-utero environment impacts neurodevelopment in congenital heart disease; this study points to specific placental lesions that may mediate the pathophysiology underlying these observations.

After Neonatal Intensive Care Unit (NICU) discharge, vulnerable babies at risk of neurodevelopmental impairment and other chronic problems often require specialized follow-up care to monitor their development and address any potential issues. Typically, this involves multiple follow-up visits usually focused on neurodevelopment and growth. With advances in obstetric care, high-risk fetuses are being identified earlier, marking another timepoint in which personalized medicine can be delivered from before birth to after discharge including neuronicu care. Our program embeds this focus into a comprehensive, multi-disciplinary primary care model, which offers significant benefits for at-risk infants, and provides an integrated approach to their care. We present the benefits of integrating this model of care with other specialty clinic services into a cohesive, multi-disciplinary follow-up system that maximizes the potential for optimal care and outcomes. Through close collaboration of our multiple specialists at each point of the medical journey of each infant from "Fetus to Five," we describe our program where the priority is each child's needs to be met efficiently and comprehensively, as a pathway to thriving developmental outcomes and overall family satisfaction. IMPACT: The future of such comprehensive programs lies in expanding access to comprehensive, integrated care offering services that extend into adolescence and adulthood that supports NICU graduates throughout their lifespan, ensuring optimal health and developmental outcomes.

Background: Children with acute lymphoblastic leukemia (ALL) may develop hypoglycemia, potentially attributable to mercaptopurine (6-MP) during long-term maintenance chemotherapy. Since hypoglycemia is harmful to childhood neurodevelopment, it is necessary to examine its occurrence during chemotherapy with and without 6-MP beyond the maintenance stage for ALL, along with the risk factors.

Methods: ALL patients received CAM-1 regimen (cyclophosphamide, cytarabine, and 6-MP). 6-MP was randomized to conventional administration at night before bedtime (Group A) or in the afternoon between lunch and dinner (Group B). Children with acute myeloid leukemia received non-6MP-containing chemotherapy (Group C).

Results: Group C showed no hypoglycemia. Among patients on CAM-1, 33% developed hypoglycemia, 48% of whom were symptomatic. There was no significant difference in hypoglycemic incidence (P = 0.933) between Groups A and B. No further hypoglycemic episodes were observed after shortening overnight fasting period in most cases. Multivariate analysis identified young age, higher serum bilirubin levels, and longer overnight fasting as significant risk factors for hypoglycemia in children receiving 6-MP.

Conclusion: Hypoglycemia is also prevalent in children exposed to short-term 6-MP but not in those without such exposure. Shortening overnight fasting period, rather than changing 6-MP schedule, is more critical in preventing hypoglycemia in young children.

Impact: This study reveals that hypoglycemia occurs frequently in children with ‌short-term exposure to 6-MP‌, as documented for long-term exposure‌ in published literature. The data demonstrate that it is 6-MP that is directly associated with hypoglycemia. Prolonged durations of overnight fasting, especially in younger individuals with hepatotoxicity, constitute a risk factor for developing hypoglycemia. Shortening the overnight fasting period, rather than changing the 6-MP schedule, is critical to prevent hypoglycemia and adverse neurodevelopment in children, even if they are receiving short-term 6-MP treatment.

Background: Numerous methods are available for measuring body composition in infants, however, there is no consensus on which approach is preferred. The aim of this study was to identify one such method for a clinical and research setting.

Methods: A systematic search was conducted on PubMed, Embase, and Cochrane Library to identify studies that investigated the accuracy of body composition methods in full-term infants up to 2 years of age.

Results: Thirty out of 6643 identified records were included. Several anthropometric equations were investigated with inconsistent results. Dual-energy X-ray absorptiometry (DXA) and bioelectrical impedance analysis (BIA) showed more comparable results to those assessed by air displacement plethysmography (ADP), when applying new techniques. Few studies assessed the accuracy of quantitative magnetic resonance (QMR), isotope dilution, and near-infrared spectroscopy (NIR); nonetheless, they all performed well against reference methods. ADP showed agreement compared to deuterium dilution, 3-compartment-, and 4-compartment-models on group-level; however, there were discrepancies when compared to DXA.

Conclusions: Anthropometry, DXA, BIA, and ultrasound showed varying results, highlighting the need for further research. QMR, isotope dilution, and NIR appeared promising, but evidence is limited due to few studies. ADP showed consistently small bias compared to multi-component models and isotope dilution.

Impact: Accurate body composition assessment in infancy has the potential to improve prophylactic actions against obesity. There is relative consensus on the most accurate body composition assessment in pre-term infants in a research setting, however, this consensus has not been available for full-term infants until now. Measure of anthropometry performs with varying precision, suggesting very low feasibility of the method for body composition assessment. From a research perspective, air displacement plethysmography is an accurate method for measuring body composition in full-term infants. This systematic review identifies research gaps within the scientific field of infant body composition.