At-risk Infants Research Articles

Are sucking patterns and early spontaneous movements related to later developmental functioning outcomes? A cohort study.

Sucking patterns and early spontaneous movements have an important role in the determination of later developmental problems, but the relationship of the two together with long-term outcomes has not been investigated. The objectives of this study were to (i) examine the relationship between sucking patterns using the Neonatal Oral Motor Assessment Scale (NOMAS) and fidgety movements and other movement patterns using detailed General Movements Assessment (GMA), and (ii) investigate the relationship between these early assessment methods and developmental functioning outcomes at later ages. We analyzed the NOMAS from 34weeks' postmenstrual age up to 10weeks post-term and GMA between 9 and 20weeks post-term age, and the Bayley Scales of Infant and Toddler Development-Third Edition (Bayley-III) was applied for the developmental functioning outcomes to 62 infants (61%, 62/102) between 12 and 42months of age. Among 102 infants at-risk, 70 (69%) showed a normal sucking pattern, and 85 (83%) had fidgety movements. The median Motor Optimality Score-Revised (MOS-R), as determined by GMA, of all infants was 24. The NOMAS was related to the MOS-R and its subcategories (p < 0.05) in all infants at-risk. The NOMAS, MOS-R and its subcategories were also related to cognitive, language, and motor development at later ages according to Bayley-III (p < 0.05). Conclusion: This longitudinal study showed that the quality of sucking patterns, fidgety movements, and MOS-R were related to later developmental functioning, indicating that abnormal sucking patterns, aberrant fidgety movements, and lower MOS-R might predict developmental disorders. What is Known: • Sucking patterns and early spontaneous movements in which central pattern generators play an important role are related. • Sucking patterns and early spontaneous movements might be used separately to predict developmental outcomes. What is New: • Sucking patterns and early spontaneous movements, when used together, were related to later developmental functioning, including cognitive, language, and motor developmentin at-risk infants. • Predictive value of sucking patterns was lower for each developmental functioning outcome than early spontaneous movements.

Umbilical artery cord blood glucose predicted hypoglycemia in gestational diabetes mellitus and other at-risk newborns

BackgroundTo explore the value of umbilical artery cord blood glucose (UACBG) in predicting hypoglycemia in gestational diabetes mellitus (GDM) and other at-risk newborns, and to provide a cut-off UACBG value for predicting hypoglycemia occurrence.MethodsIn this prospective study, we enrolled at-risk infants delivered vaginally, including neonates born to mothers with GDM, premature, macrosomic, and low birth weight. We separated the infants into GDM group and other at-risk group. All subjects underwent UACBG measurement during delivery. Neonatal peripheral blood glucose measurement was performed at 0.5 and 2 h after birth. The predictive performance of UACBG for neonatal hypoglycemia was assessed using receiver operating characteristic curve (ROC), area under curve (AUC), sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV).Results916 newborns were included, with 538 in GDM group and 378 in other at-risk group. 85 neonates were diagnosed hypoglycemia within 2 h after birth, including 36 belonging to GDM group and 49 to other at-risk group. For hypoglycemia prediction within 2 h, the best cut-off of UACBG was 4.150 mmol/L, yielding an AUC of 0.688 (95% CI 0.625–0.751) and a NPV of 0.933. In detail, the AUC was 0.680 in GDM group (95% CI 0.589–0.771), with the optimal cut-off of 4.150 mmol/L and a NPV of 0.950. In other at-risk group, the AUC was 0.678(95% CI 0.586–0.771), the best threshold was 3.950 mmol/L and the NPV was 0.908. No significant differences were observed between GDM group and other at-risk group in AUC at 0.5 h, 2 h and within 2 h.ConclusionsUACBG has a high NPV for predicting neonatal hypoglycemia within 2 h after birth. It was implied that individuals with cord blood glucose levels above the threshold were at lower risk for hypoglycemia. UACBG monitoring provides evidence for subsequent classified management of hypoglycemia.

Focusing on modifiable early protective factors to prevent negative neurodevelopmental and psychiatric outcomes in at-risk infants.

Focusing on modifiable early protective factors to prevent negative neurodevelopmental and psychiatric outcomes in at-risk infants.

Neurodevelopmental outcome of low-risk moderate to late preterm infants at 18 months

BackgroundOf the 15 million preterm births that occur worldwide each year, approximately 80% occur between 32 and 36 + 6 weeks gestational age (GA) and are defined as moderate to late preterm (MLP) infants. This percentage substantiates a need for a better understanding of the neurodevelopmental outcome of this groupAimTo describe neurodevelopmental outcome at 18 months in a cohort of healthy low-risk MLP infants admitted to the neonatal unit at birth and to compare the neurodevelopmental outcome to that of a healthy term-born infant group.Study design and methodThis single-centre observational study compared the neurodevelopmental outcome of healthy MLP infants to a group of healthy term control (TC) infants recruited during the same period using the Griffith's III assessment at 18 months.ResultsSeventy-five MLP infants and 92 TC infants were included. MLP infants scored significantly lower in the subscales: Eye-hand coordination (C), Personal, Social and Emotional Development (D), Gross Motor Development (E) and General Developmental (GD) (p &amp;lt; 0.001 for each) and Foundations of Learning (A), (p = 0.004) in comparison to the TC infant group with Cohen's d effect sizes ranging from 0.460 to 0.665. There was no statistically significant difference in mean scores achieved in subscale B: Language and Communication between groups (p = 0.107).ConclusionMLP infants are at risk of suboptimal neurodevelopmental outcomes. Greater surveillance of the neurodevelopmental trajectory of this group of at-risk preterm infants is required.

Oral dextrose gel to prevent hypoglycaemia in at-risk neonates.

Neonatal hypoglycaemia is a common condition that can be associated with brain injury. Current practice usually includes early identification of at-risk infants (e.g. infants of diabetic mothers; preterm, small- or large-for-gestational-age infants), and prophylactic measures are advised. However, these measures often involve use of formula milk or admission to the neonatal unit. Dextrose gel is non-invasive, inexpensive and effective for treatment of neonatal hypoglycaemia. Prophylactic dextrose gel can reduce the incidence of neonatal hypoglycaemia, thus potentially reducing separation of mother and baby and supporting breastfeeding, as well as preventing brain injury. This is an update of a previous Cochrane Review published in 2021. To assess the effectiveness and safety of oral dextrose gel in preventing hypoglycaemia before first hospital discharge and reducing long-term neurodevelopmental impairment in newborn infants at risk of hypoglycaemia. We searched CENTRAL, MEDLINE, Embase and Epistemonikos in April 2023. We also searched clinical trials databases and the reference lists of retrieved articles. We included randomised controlled trials (RCTs) and quasi-RCTs comparing oral dextrose gel versus placebo, no intervention, or other therapies for the prevention of neonatal hypoglycaemia. We included newborn infants at risk of hypoglycaemia, including infants of mothers with diabetes (all types), high or low birthweight, and born preterm (< 37 weeks), age from birth to 24 hours, who had not yet been diagnosed with hypoglycaemia. Two review authors independently extracted data and assessed the risk of bias. We contacted investigators to obtain additional information. We used fixed-effect meta-analyses. We used the GRADE approach to assess the certainty of evidence. We included two studies conducted in high-income countries comparing oral dextrose gel versus placebo in 2548 infants at risk of neonatal hypoglycaemia. Both of these studies were included in the previous version of this review, but new follow-up data were available for both. We judged these two studies to be at low risk of bias in 13/14 domains, and that the evidence for most outcomes was of moderate certainty. Meta-analysis of the two studies showed that oral dextrose gel reduces the risk of hypoglycaemia (risk ratio (RR) 0.87, 95% confidence interval (CI) 0.79 to 0.95; risk difference (RD) -0.06, 95% CI -0.10 to -0.02; 2548 infants; high-certainty evidence). Evidence from two studies showed that there may be little to no difference in the risk of major neurological disability at two years of age after oral dextrose gel (RR 1.00, 95% CI 0.59 to 1.68; 1554 children; low-certainty evidence). Meta-analysis of the two studies showed that oral dextrose gel probably reduces the risk of receipt of treatment for hypoglycaemia during initial hospital stay (RR 0.89, 95% CI 0.79 to 1.00; 2548 infants; moderate-certainty evidence) but probably makes little or no difference to the risk of receipt of intravenous treatment for hypoglycaemia (RR 1.01, 0.68 to 1.49; 2548 infants; moderate-certainty evidence). Oral dextrose gel may have little or no effect on the risk of separation from the mother for treatment of hypoglycaemia (RR 1.12, 95% CI 0.81 to 1.55; two studies, 2548 infants; low-certainty evidence). There is probably little or no difference in the risk of adverse effects in infants who receive oral dextrose gel compared to placebo gel (RR 1.22, 95% CI 0.64 to 2.33; two studies, 2510 infants; moderate-certainty evidence), but there are no studies comparing oral dextrose with other comparators such as no intervention or other therapies. No data were available on exclusive breastfeeding after discharge. Prophylactic oral dextrose gel reduces the risk of neonatal hypoglycaemia in at-risk infants and probably reduces the risk of treatment for hypoglycaemia without adverse effects. It may make little to no difference to the risk of major neurological disability at two years, but the confidence intervals include the possibility of substantial benefit or harm. Evidence at six to seven years is limited to a single small study. In view of its limited short-term benefits, prophylactic oral dextrose gel should not be incorporated into routine practice until additional information is available about the balance of risks and harms for later neurological disability. Additional large follow-up studies at two years of age or older are required. Future research should also be undertaken in other high-income countries, low- and middle-income countries, preterm infants, using other dextrose gel preparations, and using comparators other than placebo gel. There are three studies awaiting classification and one ongoing study which may alter the conclusions of the review when published.

Enhanced Category-Based Risk Assessment for Neonatal Early-Onset Sepsis: A Prospective Observational Study

Introduction: Compared with multivariate risk assessment, traditional category-based risk assessment (CRA) approaches for neonatal early-onset sepsis (EOS) screening are usually straightforward to use, do not require electronic devices, but are associated with higher rates of antibiotic use. This study aims to evaluate the performance of a novel enhanced CRA (eCRA) framework on EOS admissions and antibiotic use and to investigate whether a modified version with adjustments in risk factor weighting can allow its performance to match the EOS calculator while remaining easy to implement. Method: This is a prospective, single-center, two-phase observational study. Infants of all gestations delivered in a tertiary hospital in Hong Kong with risk factors or clinical features of EOS were recruited. Phase I: A novel eCRA framework (period 2) was compared with the CDC 2010-based protocol (period 1). Phase II: A modified eCRA framework was compared theoretically with the EOS calculator. EOS-specific admissions and antibiotic use were measured. Results: Phase I: 1,025 at-risk infants were recruited during period 2 and compared with 757 infants of period 1. Admissions and antibiotic use decreased from 45.8% to 29.4% and 41.1% to 28.2%, respectively. Antibiotics among those at-risk but well-appearing infants decreased from 25.3% to 16.3% (p < 0.001 for all). Phase II: antibiotic use was similar (7.3 vs. 6.4%, p = 0.42) between the modified eCRA framework and the EOS calculator. Conclusions: An eCRA framework can effectively and safely provide individualized guidance for EOS screening without the need for tools such as the EOS calculator.

Deep-learning-based markerless tracking of distal anatomical landmarks in clinically recorded videos for assessing infant movement patterns associated with neurodevelopmental status

ABSTRACT Abnormal patterns in infants’ General Movements (GMs) are robust clinical indicators for the progression of neurodevelopmental disorders, including cerebral palsy. Availability of automated platforms for General Movements Assessments (GMA) could improve screening rate and allow identifying at-risk infants. While we have previously shown that deep-learning schemes can accurately track the longitudinal axes of infant limb movements (12 anatomical locations, 3 per limb), information about the distal limb segments’ rotational movements is important for making an accurate clinical assessment, but has not previously been captured. Here we show that training schemes that are highly successful at tracking trunk and proximal limb landmarks perform less well for the distal limb landmarks, and this problem is exacerbated when landmarks are more precisely defined in the training-set to capture rotational movements. Increasing the sample size to 26 videos using a mixture of laboratory and clinical data pre-selected for diversity of pose and video conditions in a ResNet-152 deep-net model was sufficient to permit accuracy of >85% for the distal markers, and overall accuracy of 98.28% (SD 2.29) across the 24 landmarks. This scheme is suitable to form the basis of an infant pose reconstruction algorithm that captures clinically relevant information for an automated GMA.

Proteomics-Based Mapping of Bronchopulmonary Dysplasia-Associated Changes in Noninvasively Accessible Oral Secretions

ObjectiveTo determine if oral secretions (OS) can be used as a non-invasively collected body fluid, in lieu of tracheal aspirates (TA), to track respiratory status and predict bronchopulmonary dysplasia (BPD) development in infants born <32 weeks. Study DesignThis was a retrospective, single-center cohort study that included data and convenience samples from week-of-life (WoL) 3 from two independent preterm infant cohorts. Using previously banked samples, we applied our sample-sparing, high-throughput proteomics technology to compare OS and TA proteomes in infants born <32 weeks admitted to the Neonatology Intensive Care Unit (NICU) (Cohort 1; N=23 infants). In a separate similar cohort, we mapped the BPD-associated changes in the OS proteome (Cohort 2; N=17 infants including 8 with BPD). ResultsIn samples collected during the first month of life, we identified 607 proteins unique to OS, 327 proteins unique to TA, and 687 overlapping proteins belonging to pathways involved in immune effector processes, neutrophil degranulation, leukocyte mediated immunity, and metabolic processes. Furthermore, we identified 37 OS proteins that showed significantly differential abundance between BPD cases and controls: 13 were associated with metabolic and immune dysregulation, 10 of which (eg, SERPINC1, CSTA, BPI) have been linked to BPD or other prematurity-related lung disease based on blood or TA investigations, but not OS. ConclusionOS are a noninvasive, easily accessible alternative to TA and amenable to high-throughput proteomic analysis in preterm newborns. OS samples hold promise to yield actionable biomarkers of BPD development, particularly for prospective categorization of at-risk infants for timely clinical trial enrollment with novel therapies.

Parametric Versus Non-Parametric Models for Predicting Infant Mortality within Communities in Uganda using the 2016 Uganda Demographic and Health Survey Data

Machine learning techniques have been infrequently used to identify community-based infant mortality risks. Achieving SDG 3 Targets 3.2 and 3.3 could be expedited by early detection of at-risk infants within communities. This study aimed to devise a community-centric algorithm for predicting infant mortality. We analysed UDHS 2016 data containing birth records for 22,635 children born within the five years preceding the survey, excluding those born within a year of the interview date. Twelve machine learning models were evaluated for their predictive capabilities using the area under the receiver operating characteristic curve (AUC ROC) in Python. Data subsets were divided into training and testing sets in a 2:1 ratio. Among the evaluated models, CatBoost showed superior performance with an AUC ROC of 74.9%. The five most influential variables for the CatBoost model were postnatal care utilisation, paternal age, household size, preceding birth interval, and maternal age. While the algorithm’s best performance was achieved using 28 variables, it still exhibited robust predictive power when limited to the top 8 or 10 variables. Hence, CatBoost stands out as an effective tool for identifying community-based infant mortality risks

Decreasing Variation to Enhance Accurate Identification of Hypothermic Infants in Pediatric Primary Care.

Hypothermia can be the first and only sign of sepsis in young infants, yet there is a paucity of standard recommendations for pediatric primary-care office management of those infants identified. The SMART aim of this study was to standardize the identification and care of infants age 0 to 49 days at risk of hypothermia in pediatric primary care by decreasing the percent of infants with temperatures ≤36.5°C from 24% to 10% within 2 years. Over the course of this project, variation in documented temperatures ≤36.5°C decreased from 24% to 7% of encounters. Temperatures ≤36.5°C were documented for 951 infants or 13.4% (1078 of 8020 encounters). Of the 951 infants with temperatures ≤36.5°C, 96.1% were rewarmed in the office. Thirty-one patients ultimately required hospitalization. Application of quality improvement in a primary-care office decreased low temperatures by standardizing care, empowering staff, and triaging at-risk infants to the most appropriate level of care.

Telemedicine retinopathy of prematurity severity score (TeleROP-SS) versus modified activity score (mROP-ActS) retrospective comparison in SUNDROP cohort

Identifying and planning treatment for retinopathy of prematurity (ROP) using telemedicine is becoming increasingly ubiquitous, necessitating a grading system to help caretakers of at-risk infants gauge disease severity. The modified ROP Activity Scale (mROP-ActS) factors zone, stage, and plus disease into its scoring system, addressing the need for assessing ROP’s totality of binocular burden via indirect ophthalmoscopy. However, there is an unmet need for an alternative score which could facilitate ROP identification and gauge disease improvement or deterioration specifically on photographic telemedicine exams. Here, we propose such a system (Telemedicine ROP Severity Score [TeleROP-SS]), which we have compared against the mROP-ActS. In our statistical analysis of 1568 exams, we saw that TeleROP-SS was able to return a score in all instances based on the gradings available from the retrospective SUNDROP cohort, while mROP-ActS obtained a score of 80.8% in right eyes and 81.1% in left eyes. For treatment-warranted ROP (TW-ROP), TeleROP-SS obtained a score of 100% and 95% in the right and left eyes respectively, while mROP-ActS obtained a score of 70% and 63% respectively. The TeleROP-SS score can identify disease improvement or deterioration on telemedicine exams, distinguish timepoints at which treatments can be given, and it has the adaptability to be modified as needed.

Predictive and diagnostic measures for kernicterus spectrum disorder: a prospective cohort study.

Kernicterus spectrum disorder (KSD) resulting from neonatal hyperbilirubinemia remains a common cause of cerebral palsy worldwide. This 12-month prospective cohort study followed neonates with hyperbilirubinemia to determine which clinical measures best predict KSD. The study enrolled neonates ≥35 weeks gestation with total serum bilirubin (TSB) ≥ 20 mg/dl admitted to Aminu Kano Hospital, Nigeria. Clinical measures included brain MRI, TSB, modified bilirubin-induced neurologic dysfunction (BIND-M), Barry-Albright Dystonia scale (BAD), auditory brainstem response (ABR), and the modified KSD toolkit. MRI signal alteration of the globus pallidus was scored using the Hyperbilirubinemia Imaging Rating Tool (HIRT). Of 25 neonates enrolled, 13/25 completed 12-month follow-up and six developed KSD. Neonatal BIND-M ≥ 3 was 100% sensitive and 83% specific for KSD. Neonatal ABR was 83% specific and sensitive for KSD. Neonatal HIRT score of 2 was 67% sensitive and 75% specific for KSD; this increased to 100% specificity and sensitivity at 12 months. BAD ≥ 2 was 100% specific for KSD at 3-12 months, with 50-100% sensitivity. Neonatal MRIs do not reliably predict KSD. BIND-M is an excellent screening tool for KSD, while the BAD or HIRT score at 3 or 12 months can confirm KSD, allowing for early diagnosis and intervention. The first prospective study of children with acute bilirubin encephalopathy evaluating brain MRI findings over the first year of life. Neonatal MRI is not a reliable predictor of kernicterus spectrum disorders (KSD). Brain MRI at 3 or 12 months can confirm KSD. The modified BIND scale obtained at admission for neonatal hyperbilirubinemia is a valuable screening tool to assess risk for developing KSD. The Barry Albright Dystonia scale and brain MRI can be used to establish a diagnosis of KSD in at-risk infants as early as 3 months.

Mapping the range of policies relevant to care of small and nutritionally at-risk infants under 6 months and their mothers in Ethiopia: a scoping review protocol

IntroductionEvidence gaps limit management of small and/or nutritionally at-risk infants under 6 months and their mothers, who are at higher risk of death, illness, malnutrition and poor growth and development....

Training Packages and Patient Management Tools for Healthcare Staff Working with Small, Nutritionally At-Risk Infants Aged under 6 Months: A Mixed-Methods Study.

Skilled staff are essential for successfully managing child malnutrition, especially when dealing with small, nutritionally at-risk infants aged under 6 months. Training and patient management tools provide healthcare workers with core knowledge, skills, and support. To inform more effective future approaches and support the rollout of new WHO wasting prevention/treatment guidelines, we aimed to map and understand globally available training and patient management tools. In a mixed-methods study, we searched the literature to identify different training packages and management tools and conducted semi-structured key informant interviews with staff working in a variety of internationally organizations and settings. Data were analyzed using a phenomenological approach. We found 14 different training packages targeting different settings, including inpatient, outpatient, and humanitarian contexts. Curricula varied, especially around breastfeeding and maternal assessment, mental health, and nutritional status. Key informants (n = 9) reported gaps regarding counseling skills, time for practice, and how to effectively provide mental health counseling. Training delivery was highly dependent on resources and setting. In conclusion, future training should consider setting-specific needs, opportunities, and limitations. Emphasis on breastfeeding-support skills, mental health support, and counseling skills is needed. Enhanced practical sessions, refresher trainings, and ongoing monitoring and support are vital to ensure sustained high-quality services.

Influence of infant microbiome on health and development.

The microbiome is a complex ecosystem comprising microbes, their genomes, and the surrounding environment. The microbiome plays a critical role in early human development, including maturation of the host immune system and gastrointestinal tract. Multiple factors, including diet, anti-biotic use, and other environmental exposures, influence the establishment of the microbiome during infancy. Numerous studies have identified associations between the microbiome and neonatal diseases, including necrotizing enterocolitis, sepsis, and malnutrition. Furthermore, there is compelling evidence that perturbation of the microbiome in early life can have lasting developmental effects that increase an individual's risk for immune and metabolic diseases in later life. Supplementation of the microbiome with probiotics reduces the risk of necrotizing enterocolitis and sepsis in at-risk infants. This review focuses on the structure and function of the infant microbiome, the environmental and clinical factors that influence its assembly, and its impact on infant health and development.

Early social referencing predicts object mastery motivation in infancy: Social antecedents of object mastery motivation.

The researchers sought to understand the typical development of social referencing and object mastery motivation in infancy and to determine the relationship between social referencing and object mastery behaviors in infants from 7 to 22months of age. The study included 36 infants who were followed as part of a longitudinal study of at-risk infants but were not determined to need care in the neonatal intesive care unit at birth. Both mastery behaviors of persistence and success showed a statistically significant effect of age, while social behaviors remained stable from 7 to 22months. Social behaviors at 7 and 10months were correlated with persistence at 22months and success at 16 to 22months demonstrating that early social referencing predicts object mastery behaviors in later infancy. Further research should determine if this trend extends to early childhood.

Diagnosis and Management of Neonatal Hypoglycemia: A Comprehensive Review of Guidelines.

Hypoglycemia represents one of the most frequent metabolic disturbances of the neonate, associated with increased morbidity and mortality, especially if left untreated or diagnosed after the establishment of brain damage. The aim of this study was to review and compare the recommendations from the most recently published influential guidelines on the diagnosis, screening, prevention and management of this common neonatal complication. Therefore, a descriptive review of the guidelines from the American Academy of Pediatrics (AAP), the British Association of Perinatal Medicine (BAPM), the European Foundation for the Care of the Newborn Infants (EFCNI), the Queensland Clinical Guidelines-Australia (AUS), the Canadian Pediatric Society (CPS) and the Pediatric Endocrine Society (PES) on neonatal hypoglycemia was carried out. There is a consensus among the reviewed guidelines on the risk factors, the clinical signs and symptoms of NH, and the main preventive strategies. Additionally, the importance of early recognition of at-risk infants, timely identification of NH and prompt initiation of treatment in optimizing the outcomes of hypoglycemic neonates are universally highlighted. All medical societies, except PES, recommend screening for NH in asymptomatic high-risk and symptomatic newborn infants, but they do not provide consistent screening approaches. Moreover, the reviewed guidelines point out that the diagnosis of NH should be confirmed by laboratory methods of BGL measurement, although treatment should not be delayed until the results become available. The definition of NH lacks uniformity and it is generally agreed that a single BG value cannot accurately define this clinical entity. Therefore, all medical societies support the use of operational thresholds for the management of NH, although discrepancies exist regarding the recommended cut-off values, the optimal treatment and surveillance strategies of both symptomatic and asymptomatic hypoglycemic neonates as well as the treatment targets. Over the past several decades, ΝH has remained an issue of keen debate as it is a preventable cause of brain injury and neurodevelopmental impairment; however, there is no clear definition or consistent treatment policies. Thus, the establishment of specific diagnostic criteria and uniform protocols for the management of this common biochemical disorder is of paramount importance as it will hopefully allow for the early identification of infants at risk, the establishment of efficient preventive measures, the optimal treatment in the first hours of a neonate's life and, subsequently, the improvement of neonatal outcomes.

Neural phase angle from two months when tracking speech and non-speech rhythm linked to language performance from 12 to 24 months

Atypical phase alignment of low-frequency neural oscillations to speech rhythm has been implicated in phonological deficits in developmental dyslexia. Atypical phase alignment to rhythm could thus also characterize infants at risk for later language difficulties. Here, we investigate phase-language mechanisms in a neurotypical infant sample. 122 two-, six- and nine-month-old infants were played speech and non-speech rhythms while EEG was recorded in a longitudinal design. The phase of infants’ neural oscillations aligned consistently to the stimuli, with group-level convergence towards a common phase. Individual low-frequency phase alignment related to subsequent measures of language acquisition up to 24 months of age. Accordingly, individual differences in language acquisition are related to the phase alignment of cortical tracking of auditory and audiovisual rhythms in infancy, an automatic neural mechanism. Automatic rhythmic phase-language mechanisms could eventually serve as biomarkers, identifying at-risk infants and enabling intervention at the earliest stages of development.

Symptomatic Postnatal Cytomegalovirus Infection in Less than 32-Week Preterm Infants: 13-Year Retrospective Multicenter Case-Control Study

Introduction: Reports on the influence of postnatal cytomegalovirus (pCMV) infection in neonatal outcomes of preterm babies vary while guidance on management including screening is lacking. We aim to determine the association between symptomatic pCMV infection and chronic lung disease (CLD) and mortality in preterm infants born less than 32 weeks gestation. Methods: We used data from the Neonatal Intensive Care Units’ (NICUS) population-based prospective data registry of infants in 10 neonatal units in New South Wales and the Australian Capital Territory, Australia. De-identified perinatal and neonatal outcome data for 40,933 infants were examined. We identified 172 infants <32 weeks gestation with symptomatic pCMV infection. Each was matched with one control infant. Results: Infants with symptomatic pCMV infection were 2.7 times more likely to develop CLD (OR 2.7, 95% CI: 1.7–4.5) and spend 25.2 days more in hospital (95% CI: 15.2–35.2). Seventy-five percent (129/172) of infants with symptomatic pCMV were extremely preterm (<28 weeks). The mean age of symptomatic pCMV diagnosis was 62.5 ± 20.5 days or 34.7 ± 3.6 weeks-corrected gestational age. Ganciclovir treatment did not decrease CLD and death. CLD was 5.5 times predictive of death in patients with symptomatic pCMV infection. Symptomatic pCMV infection did not influence mortality nor increase neurologic impairment. Conclusion: Symptomatic pCMV is a modifiable factor affecting extreme preterm infants with significant impact on CLD. Prospective study on screening and treatment will help unveil potential benefits in our already at-risk preterm infants.

Early immune reconstitution in an infant with adenosine deaminase deficient severe combined immunodeficiency started on enzyme replacement therapy

Severe Combined Immunodeficiency (SCID) due to adenosine deaminase (ADA) deficiency is an inborn error of immunity resulting in the accumulation of adenosine and deoxyadenosine leading to a T-B-NK-phenotype. Enzyme Replacement Therapy with Elapegademase-IvIr is typically used as a bridge prior to undergoing definitive treatment with HSCT or HSC-GT.We report a full-term female infant born to Caucasian parents. Immediate newborn course was unremarkable. She had two borderline newborn screens (NBS) for SCID. There was no consanguinity or family history of immunodeficiency. Physical exam was normal except for absent tonsils. She had profound lymphopenia (Absolute Lymphocyte Count of 210 cells/mL), and initial lymphocyte enumeration showed low CD3 cells (169/mL), decreased CD19 cells (6/mL) and CD16/56+ cells (26/mL) consistent with a T-B-NK- SCID. There was no maternal engraftment. Immunoglobulin studies showed normal IgG (325) with low IgM and IgA. Mitogen proliferation to phytohemagglutinin (PHA) was significantly low (10,200 CPM).A SCID genetics panel revealed two pathogenic variants in ADA (p.Glu319fs and p.Arg149Trp). Biochemical testing confirmed absent ADA activity and elevated total deoxyadenosine nucleotides (dAXP) of 40.3% in RBCs (normally undetectable), consistent with the diagnosis of ADA-SCID. She was promptly started on ERT twice weekly and developed full immune reconstitution of her T-cells, B-cells and NK-cells after 21 days. At that time, her dAXP remained elevated at 10%. Her T-cell function also normalized (PHA 239,562 CPM).We report an infant with ADA-SCID who had two borderline NBS results and developed full immune reconstitution 3 weeks after starting ERT. This is unusual since thymopoiesis typically requires 60–90 days for T-cell reconstitution. While B and NK immune reconstitution typically occurs early, early T-cell numbers lag behind, especially while dAXP levels remain measurable. Both genetic variants in this patient are severe, but somatic mosaicism with reversion of the Arg149Trp point mutation might account for rapid T-cell recovery; further T-cell analysis is planned to assess this possibility. This child is the first case of SCID diagnosed in North Carolina following a borderline NBS, as opposed to abnormal, reinforcing the utility of highly-sensitive TREC thresholds for identification of at-risk infants. [Display omitted] [Display omitted]