Background: This systematic review and meta-analysis assessed the benefits of an automatic lancing device compared with a manual lancet or a hypodermic needle in neonates. Materials & methods: We followed the Cochrane Handbook methodology, used the RoB-2 tool for risk of bias assessment, RevMan 4.1 for meta-analysis and GRADE framework for certainty assessment. We searched the databases and gray literature on 15 November 2023. Results: Six eligible studies enrolling 539 neonates were included. An automatic lancing device reduced pain scores during and after heel prick, sampling time and the need for repeat puncture. The certainty of evidence was very low to moderate. Conclusion: An automatic lancing device is preferred for heel pricks in neonates, given less pain and higher efficiency.PROSPERO registration number: CRD42023483189.
What is this article about? The heel prick is a common painful procedure in neonates. It is performed either with a hypodermic needle or a lancet (manual or automatic lancing device). Few studies have shown that an automatic lancing device, with depth regulation, causes less pain. We reviewed the available literature to assess the benefits and harms of different sampling methods.What were the results? We found six studies comparing these interventions for heel prick in neonates. There was a significant reduction in pain score, sampling time and need for repeated pricks when using an automatic lancing device.What do the results of the study mean? The automatic lancing device causes less pain (safer) and reduces the time required for sampling and repeated pricks (more effective) when used for heel pricks in neonates.

Males with X-linked adrenoleukodystrophy (ALD) are at high risk for developing adrenal insufficiency and/or progressive leukodystrophy (cerebral ALD) at an early age. Pathogenic variants in ABCD1 result in elevated levels of very long-chain fatty acids (VLCFA), including C26:0-lysophosphatidylcholine (C26:0-LPC). Newborn screening for ALD enables prospective monitoring and timely therapeutic intervention, thereby preventing irreversible damage and saving lives. The Dutch Health Council recommended to screen only male newborns for ALD without identifying untreatable conditions associated with elevated C26:0-LPC, like Zellweger spectrum disorders and single peroxisomal enzyme defects. Here, we present the results of the SCAN (Screening for ALD in the Netherlands) study which is the first sex-specific newborn screening program worldwide. Males with ALD are identified based on elevated C26:0-LPC levels, the presence of one X-chromosome and a variant in ABCD1, in heel prick dried bloodspots. Screening of 71 208 newborns resulted in the identification of four boys with ALD who, following referral to the pediatric neurologist and confirmation of the diagnosis, enrolled in a long-term follow-up program. The results of this pilot show the feasibility of employing a boys-only screening algorithm that identifies males with ALD without identifying untreatable conditions. This approach will be of interest to countries that are considering ALD newborn screening but are reluctant to identify girls with ALD because for girls there is no direct health benefit. We also analyzed whether gestational age, sex, birth weight and age at heel prick blood sampling affect C26:0-LPC concentrations and demonstrate that these covariates have a minimal effect.

It is now established that immune maturation occurs along a defined trajectory in the weeks and months after birth, but the immediate changes that occur within immune cells following birth is less clear. In this study, we monitored the immune profile of neonates via analysis of paired samples (n= 28) of cord blood and heel prick blood taken at varying times post term delivery by planned elective caesarean section. This paired approach accounted for the between-subject variability often observed over the first week of life. We identified rapid changes in immune cell populations within hours of birth. Specifically, we observed increased proliferation in effector T cells (but not regulatory T cells) that exhibited an increase in cytokine producing ability and also an increase in the percentage of CD3 T cells over this short time frame. This indicates that the mobilisation of the immune system is immediate post birth, presumably as a response to sudden exposure to the external environment, antigen or stress. Hence, immune development may start to occur more rapidly than previously proposed and as such, to study this trajectory, blood sampling should begin as soon after birth as possible.

Newborn screening (NBS) aims to identify neonates with severe conditions for whom immediate treatment is required. Currently, a biochemistry-first approach is used to identify these disorders, which are predominantly inherited meta1bolic disorders (IMD). Next-generation sequencing (NGS) is expected to have some advantages over the current approach, for example the ability to detect IMDs that meet all screening criteria but lack an identifiable biochemical footprint. We have now designed a technical study to explore the use of NGS techniques as a first-tier approach in NBS. Here, we describe the aim and set-up of the NGS-first for the NBS (NGSf4NBS) project, which will proceed in three steps. In Step 1, we will identify IMDs eligible for NGS-first testing, based on treatability. In Step 2, we will investigate the feasibility, limitations and comparability of different technical NGS approaches and analysis workflows for NBS, eventually aiming to develop a rapid NGS-based workflow. Finally, in Step 3, we will prepare for the incorporation of this workflow into the existing Dutch NBS program and propose a protocol for referral of a child after a positive NGS test result. The results of this study will be the basis for an additional analytical route within NBS that will be further studied for its applicability within the NBS program, e.g., regarding the ethical, legal, financial and social implications.

This study aimed to evaluate the efficacy of breast milk odor either alone or in combination with breast milk taste (via syringe-feeding) to alleviate neonates\' biobehavioral responses to pain during heel-prick procedures. This prospective randomized controlled trial recruited 114 neonates by convenience sampling from a newborn unit of a medical center in Taiwan. Neonates were randomly assigned to three groups: control (gentle touch + human voice), control + breast milk odor, and control + breast milk odor + breast milk taste. Heart rate, oxygen saturation, and voice recordings of crying were measured across heel-prick procedures: baseline, no stimuli (stage 0); during heel prick (Stages 1-4); and recovery (Stages 5-10). Generalized estimating equations and Kaplan-Meier survival analysis compared differences in changes between groups for heart rate, oxygen saturation, and time to crying cessation. Changes in mean heart rate and oxygen saturation in neonates receiving breast milk odor or breast milk odor + breast milk taste were significantly less than those at the corresponding stage for the control group. Among neonates receiving breast milk odor or breast milk odor + breast milk taste, hazard rate ratios for crying cessation were 3.016 and 6.466, respectively. Mother\'s breast milk olfactory and gustatory interventions could stabilize the biobehavioral responses to pain during heel prick procedures in neonates.

BACKGROUND: Cord-blood and heel-prick TSH levels are essential in diagnosing and preventing the serious complications of congenital hypothyroidism, which mainly include intellectual disability. The study aimed to compare between cord-blood and heel-prick TSH sensitivity and specificity in detecting congenital hypothyroidism (CH) among newborn screened babies.
METHODS: The study included 21,012 newborn screened babies for congenital hypothyroidism starting from September 2013 until March 2019. Both cord-blood and heel-prick TSH were collected from each newborn. Heel prick and cord-blood TSH cutoff values of >21 μU/ml and >30 mIU/L respectively were considered positive.
RESULTS: Out of the total screened newborns, 12 were confirmed for having primary congenital hypothyroidism. Nine cases were positive for cord-blood TSH (Sensitivity 75%, specificity 99.9%, and a recall rate of 0.004%), while 139 cases were positive for heel-prick blood TSH (Sensitivity of 100%, specificity of 99.3%, and a recall rate of 0.60%).
CONCLUSIONS: For the screening of CH, heel prick is considered a superior method, but cord blood remains a practical option due to its cost-effectiveness, immediate action, and lower recall rate. Therefore, whenever recall is difficult and/or early discharge is the practice, cord blood is an alternative method to heel prick but not with cases of prematurity.

Neonatal bloodspot screening (NBS) aims to detect treatable disorders in newborns. The number of conditions included in the screening is expanding through technological and therapeutic developments, which can result in health gain for more newborns. NBS expansion, however, also poses healthcare, ethical and societal challenges. This qualitative study explores a multi-stakeholders\' perspective on current and future expansions of NBS. Semi-structured interviews were conducted with 22 Dutch professionals, including healthcare professionals, test developers and policy makers, and 17 parents of children with normal and abnormal NBS results. Addressed themes were (1) benefits and challenges of current expansion, (2) expectations regarding future developments, and (3) NBS acceptance and consent procedures. Overall, participants had a positive attitude toward NBS expansion, as long as it is aimed at detecting treatable disorders and achieving health gain. Concerns were raised regarding an increase in results of uncertain significance, diagnosing asymptomatic mothers, screening of subgroups (\"males only\"), finding untreatable disorders, along with increasingly complex consent procedures. Regarding the scope of future NBS expansions, two types of stakeholder perspectives emerged. Stakeholders with a \"targeted-scope\" perspective saw health gain for the neonate as the exclusive NBS aim. They thought pre-test information could be limited, and parents should be protected against too much options or information. Stakeholders with a \"broad-scope\" perspective thought the NBS aim should be formulated broader, for example, also taking (reproductive) life planning into account. They put more emphasis on individual preferences and parental autonomy. Policy-makers should engage with both perspectives when making further decisions about NBS.

UNASSIGNED: The objectrve is to compare the analgesic effect of Kangaroo Mother Care (KMC), oral dextrose 50% (D50) and supine nesting position in late preterm neonates (34 week to <37 week Gestation Age) while doing heel prick for blood glucose monitoring.
UNASSIGNED: Babies were randomized into three groups; KMC, D50 and supine nesting. Premature infant pain profile (PIPP) score was used to measure pain severity following heel prick. Total crying time was also compared.
UNASSIGNED: Data of 149 eligible babies were analyzed; significant difference was noted in total PIPP scores (mean; SD) across groups; KMC (8.42 [1.99]), D50 (8.76 [1.84]) and nesting (13.08 [1.70]) (P < 0.001). Post hoc analysis revealed comparable scores among KMC and D50 groups (P = 0.638), significantly less than nesting group (P < 0.001). Significant difference in crying time (median; interquartile range) was also noted amongst three groups (P < 0.001).
UNASSIGNED: The analgesic effect of KMC and oral D50 is comparable and found to be superior to supine nesting position in reducing pain of heel prick.

Ongoing research efforts that consider cancer as a disease of dramatically altered cellular metabolism have accelerated interest in snapshot metabolomics in various human tissues. In this issue of Leukemia Research, Petrick et al performed metabolomic analysis on newborn blood spots and found a number of unexpected ceramide and sphingolipid compounds that may play a role in the development and latency of pediatric acute myeloid leukemia (AML). The chemical complexity and range of cellular metabolites massively exceeds the relatively limited building blocks of the transcriptome or the proteome and has high potential to find novel leukemia-specific macromolecular synthesis pathways, metabolic vulnerabilities and biomarkers.

[This corrects the article DOI: 10.3389/fcell.2020.00499.].