Young Infants Research Articles

Switching antibiotic therapy from injectable to oral to optimise the duration of inpatient care for young infants presenting with moderate-mortality-risk signs of possible serious bacterial infection: an open-label, multicountry, randomised controlled trial.

Management of possible serious infections in young infants.

Heterogeneity in seasonal influenza vaccination opportunity and disease risk during pregnancy and in infants <6months.

This manuscript covers my personal history on the search for the neural circuits supporting early developing memory in primates. A series of developmental neuropsychological studies is presented to follow the successive knowledge we gained over several decades on the timing of development of the hippocampus and hippocampal-dependent recognition memory functions in primates. The borrowing of an incidental recognition memory task measuring novelty preference to infer subjects' memory was central to assessing memory in young infant monkeys of only a few weeks old. Data revealed that the emergence of adult-like proficiency in visual recognition and spatial memory tasks sensitive to hippocampal dysfunction is a stepwise process. This progressive development was associated with the gradual maturation of different hippocampal intrinsic circuits (Entorhinal-CA1 and Entorhinal-Dentate Gyrus-CA fields) and their connections with other cortical structures (the perirhinal, parahippocampal, parietal, and prefrontal cortices). We also showed that a similar postnatal maturation of hippocampal-dependent memory is observed in human infants, suggesting important changes in the role of the hippocampus and medial temporal cortical areas in human memory development as well.

Limitations of Comprehensive Respiratory Viral Testing in Managing Young Infants with Fever.

Apnoea is a common respiratory complication in preterm neonates, leading to substantial changes in physiology. We conducted this systematic review and meta-analysis to examine the relationship between apnoea duration and changes in heart rate, oxygen saturation, cerebral oxygenation and cerebral blood volume in preterm neonates, and to identify factors that modulate this relationship. We searched Medline, EMBASE, PsycINFO, and Cochrane Central Register of Controlled Trials databases and included primary empirical studies examining the relationship between apnoea or respiratory pause duration and at least one outcome in hospitalised neonates with postmenstrual age (PMA) <37 weeks. Through meta-analyses, we prospectively examined factors that may modulate this relationship, including postmenstrual age, medication use, and apnoea type. Forty-two papers were included, involving a total of 1483 neonates with 2399 study sessions. The decrease in heart rate, oxygen saturation, and cerebral oxygenation were significantly correlated with apnoea duration. PMA significantly modulated the relationship, with younger neonates more likely to exhibit oxygen desaturation from short apnoeas. Cardiorespiratory and cerebrovascular responses to apnoea are correlated with apnoea duration, yet wide variability exists in the response. Further research is needed to identify how factors modulate the relationship. Systematic review and meta-analysis of the relationship between apnoea duration and change in heart rate, oxygen saturation, cerebral oxygenation and cerebral blood volume in preterm neonates. Through meta-analysis, we demonstrate that postmenstrual age plays a significant modulating role in the relationship between apnoea duration and change in oxygen saturation, with younger infants more likely to have desaturations. Apnoea can lead to significant cardiorespiratory and cerebrovascular changes; understanding the factors which modulate these relationships are key to facilitating personalised alarm limits.

Measles cases are increasing across the United States, with infants under age 12 months at increased risk as they are not yet eligible for routine measles, mumps, and rubella (MMR) vaccination. The current MMR vaccination schedule is based on decades-old data from an era of widespread natural maternal immunity and low measles prevalence. Today, most mothers have vaccine-derived immunity, and recent studies show these maternal antibodies wane by 3 to 6 months of age, leaving many infants vulnerable to infection until they receive their first MMR vaccine at the currently recommended age of 12 to 15 months. Evidence demonstrates, however, that MMR vaccination between ages 6 and 11 months provides partial protection during outbreaks and does not impair the immune response to later doses. Safety data also support vaccination in younger infants. Although early MMR vaccination is currently recommended before international travel, it should also be offered domestically during outbreaks as a risk-based strategy. National guidance should be updated to reflect current epidemiology and close this gap in infant protection.

Automated behavioral measurement using machine learning is gaining ground in psychological research. Automated approaches have the potential to reduce the labor and time associated with manual behavioral coding, and to enhance measurement objectivity; yet their application in young infants remains limited. We asked whether automated measurement can accurately identify newborn mouth opening-a facial gesture involved in infants' communication and expression-in videos of 29 newborns (age range, 9-29days, 55.2% female, 58.6% White, 51.7% Hispanic/Latino) during neonatal imitation testing. We employed a three-dimensional cascade regression computer vision algorithm to automatically track and register newborn faces. The facial landmark coordinates of each frame were input into a support vector machine (SVM) classifier, trained to recognize the presence and absence of mouth openings at the frame level as identified by expert human coders. The SVM classifier was trained using leave-one-infant-out cross-validation (training: N = 22 newborns, 95 videos, 354,468 frames), and the best classifier showed an average validation accuracy of 75%. The final SVM classifier was tested on different newborns from the training set (testing: N = 7 newborns, 29 videos, 118,615 frames) and demonstrated 76% overall accuracy in identifying mouth opening. An intraclass correlation coefficient of .81 among the SVM classifier and human experts indicated that the SVM classifier was, on a practical level, reliable with experts in quantifying newborns' total rates of mouth opening across videos. Results highlight the potential of automated measurement approaches for objectively identifying the presence and absence of mouth opening in newborn infants.

Abstract The treatment of infantile hydrocephalus required consideration of age and etiology, as well as close follow-up and care. Cranial ultrasound examination is a noninvasive, operable, and cost-effective tool for assessing brain anatomy and establishing a diagnosis in neonates and infants. Because the success rates of endoscopic third ventriculostomy (ETV) for infantile hydrocephalus ranged widely between 40% and 90%, regular cranial ultrasound examinations are necessary after ETV due to the risk of higher failure rate in younger infants. This report presents two newborn cases of hydrocephalus presenting with aqueductal stenosis. Due to early detection of progressive ventricular dilatation, both require additional shunt treatment following failed ETV. These cases highlight the challenges of the diverse etiologies of infantile hydrocephalus and the importance of not ignoring the progression of the disease.

In Saudi Arabia, primigravida or multigravida mothers might seek complementary medicine for their infants. When an infant struggles with colic or poor feeding, a mother will do anything to help her baby including traditional therapy. Traditional healers use a maneuver called "Autheem- عظيم" based on a common belief among the Saudi public of needing to manipulate soft palates for struggling infants. This study is a retrospective cohort study adopted to recruit children at the age of 36 months who underwent "Autheem" therapy and those who did not as controls. Mothers in the waiting area at the general pediatrics clinics in Riyadh, Saudi Arabia were approached to answer a pre-structured survey. The "Ages and Stages Questionnaire" study tool was used to assess their children's development. The study enrolled 84 well-educated mothers (74% with college degrees in the control group and 58.5% in the study group). The main sources of information about Autheem and its indications were grandmothers and family elders. Poor feeding followed by responding to grandmothers' pressure were the main reasons to seek this therapy. The majority of mothers (71%) admitted that if they found a solution in modern medicine, they would not have explored this therapy. Mothers noted that most healers do not wash their hands. Over one-third of mothers (36.6%) documented lethargy in the first 24h post-therapy. One in five mothers was offered cautery therapy at the time of Autheem therapy. There was a significant difference in development between children exposed to Autheem therapy in comparison to healthy controls. Autheem exposed children were 10 times more likely to be delayed in gross motor skills. Furthermore, notable delay was documented in fine motor and problem solving despite lack of statistical significance. Concern about infant feeding is the main reason for seeking "Autheem." The association of developmental delays might indicate safety concerns of this therapy on growing brains. Future advocacy should focus on elders in the family to avoid Autheem therapy until better safety data is available.

ABSTRACTThe pre‐locomotor version of the Laboratory Temperament Assessment Battery (Lab‐TAB) provides one of the most widely used observational measures of fear based on the infant's reactivity to a series of four novel masks. Resulting indicators of facial and bodily fear intensity, as well as latency to exhibit a fearful response, have been associated with maternal reports of infant fear as well as frontal electroencephalography (EEG) reactivity. While these measures have been used extensively since the introduction of Lab‐TAB, they are typically averaged across the procedure, and differences between the four mask stimuli have not been sufficiently examined. This study addressed this gap in research by examining specific infant reactions, both behaviorally and from a neurophysiological standpoint, to each presentation of the fear‐provoking stimuli to better understand factors that impact the expression of fear during this task. Our findings indicated significant differences in behavioral observations of distress and regulation, with the final/fourth mask eliciting stronger reactions; however, there were no such differences in the infants’ neurophysiological response. Additionally, neither the fear subscale of the Infant Behavior Questionnaire—Revised (IBQ‐R) nor the Negative Emotionality factor was predictive of infant's neurophysiological changes, distress, or regulation during the episode until examining subgroups based on age or sex. Further analyses of frontal alpha asymmetry across masks indicated that infants may become attuned to these stimuli over the course of the task, leading to less predictive utility than earlier neurophysiological markers. Results also revealed that older infants had differing neurophysiological reactions across the paradigm, whereas no significant differences were noted for younger infants. Finally, differences based on infant sex emerged with regard to temperament predictors of asymmetry. Implications of the discrepancy between results for the EEG asymmetry markers and observed distress/regulation in trial comparisons are discussed.

Background/Objectives: General movement assessment (GMA) is a clinical assessment tool used to predict risk for cerebral palsy (CP) in young infants. Equal access is challenging since GMA-trained personnel is a limited resource. An implementation study aimed to offer all high-risk infants born in the Central Norway Regional Health Authority equal access to GMA as part of the standard follow-up. This study explored the local health care personnel (HCP) experiences with early risk assessment for CP in young infants using remote GMA. Methods: This was a qualitative study with one focus group and four individual interviews. Participants were HCP from the local follow-up clinics who had experience with GMA. Analyses were inspired by Malterud’s systematic text condensation. Results: Attitudes towards GMA were, in general, positive, and GMA was considered an important and gentle examination contributing to earlier initiation of correct follow-up actions and appropriate treatment. The GMA results could improve communication between HCP and parents, and lead to a closer local municipality follow-up if GMA result was abnormal. Parents were given an active role with home video recording, which was considered family empowering. Especially pediatricians wanted more detailed information about the qualities of spontaneous movements to support clinical decision-making. Conclusions: This study indicated that further implementation of the GMA method to assess the risk of CP in high-risk infants could be recommended, and that GMA was a gentle method for the purpose. As suggested by pediatricians in this study, more detailed assessments using the GMA beyond FMs could be further explored as support to clinical decisions. The insight from this study may inform implementation in similar contexts.

Background Urinary tract infections (UTIs) are the most common serious bacterial infections in febrile infants. Current UK guidelines recommend parenteral antibiotics for infants under three months with suspected UTI, despite evidence supporting oral therapy in low-risk infants. Objectives To assess whether oral antibiotics are non-inferior to parenteral antibiotics for treating suspected UTIs based on treatment failure, need for additional therapy, and secondary outcomes. Design Multicentre, randomised controlled, open-label, non-inferiority trial with embedded internal pilot. Setting Twenty one paediatric emergency departments and assessment units across the UK. Participants Infants aged 29–90 days with suspected UTI, abnormal urinalysis, and low risk of invasive bacterial infection. Exclusion criteria included prematurity, prior hospitalisation, structural renal abnormalities, and clinical signs of sepsis or meningitis. Interventions Participants were randomised 1:1 to receive either oral antibiotics or standard care with intravenous (IV) antibiotics for 36–48 hours pending urine culture results. Main outcome measures The primary outcome was the requirement for additional parenteral antibiotics within seven days of randomisation. A range of secondary outcomes were also planned, including treatment failure, time to recovery, adverse events, antibiotic adherence, quality of life, family impact, and healthcare resource use. Feasibility outcomes collected during the internal pilot included recruitment rate, site activation, protocol adherence, and retention. Clinical outcomes were collected but not powered for formal comparison. Results 27 participants were recruited between 20 May 2024 and 13 March 2025 (which included the 6 month internal pilot), representing 27% of the pilot target. Protocol adherence was high, and no cases of meningitis occurred. Two cases of bacteraemia (one per randomised group) had uncomplicated clinical courses. Oral therapy was associated with shorter hospital stays and reduced parental time off work. Conclusions While trial procedures were successfully implemented, recruitment challenges suggest that a larger randomised trial of this treatment comparison is not feasible in this setting. Trial management Northern Ireland Clinical Trials Unit (NICTU) Trial registration ISRCTN Clinical Trials Registry, ISRCTN10907780, Trial Dates 20 May 2024 to 13 March 2025

Effects of maternal late-pregnancy and early-infancy exposures to respiratory syncytial virus circulating intensity on the risk for respiratory syncytial virus hospitalisation in the first two years of life: a comparative retrospective cohort study between Scotland and Singapore

Inpatient versus outpatient management of young infants with a single low-mortality-risk sign of possible serious bacterial infection in sub-Saharan Africa and south Asia: an open-label, multicentre, two-arm, randomised controlled trial

Congenital diarrheas and enteropathies (CODE) are morbid illnesses with potentially fatal outcomes. We describe here two infants with a distinctly different disease with CODE-like presentation, coincidentally from the same geographical area. The young infants with chronic loose stools presented with dehydration and shock, metabolic acidosis, dyselectrolytemia, and stool osmolar gap suggestive of secretory diarrhea. A vague erythematoid appearance of flexures and the face was noted in one infant, and no skin findings were noted in the other. They were treated as CODE due to the above findings. The infants required fluid resuscitation, ventilation, parenteral nutrition, and a trial of amino acid formula after a period of stabilization. One infant succumbed after 4 weeks of therapy. The other improved with an amino acid formula and is on regular follow-up. The diagnosis was obtained by clinical exome, as prolidase deficiency (PD). This presentation of PD in neonates as CODE-like illness is extremely rare; more so, with a fulminant course that proved fatal for one. Absence of the classical features of typical skin involvement or other described symptomatology must not deter appropriate workup for an accurate diagnosis. This would aid in parent counseling and future pregnancy management.

Head rotation and subsequent hypoperfusion of the brain stem might be possible causal factors of sudden infant death. This study aimed to determine the quantitative changes of cerebral blood flow as assessed on ultrasound (US) Doppler with respect to dependence on the position and age of the subject.This single-center retrospective study was performed to assess US Doppler measurements on vertebral and basilar arteries of neonates and infants. After measuring peak systolic flow (Vs) and time-averaged velocity (TAM) in the middle supine position, each subject was positioned with the head rotated to the right and left both in a supine and a prone position. Both vertebral arteries were measured, and results were correlated to individual age at the time of investigation.A total of n=1889 subjects were analyzed. Vs was 63.0±15.3cm/s in the supine middle position and reduced after head rotation to 59.9±21.6 m/s (P <0.0001, head rotated right) and 59.4±15.6cm/s (P <0.0001, left). In the prone position Vs was 58.4±14.8cm/s (P <0.0001, head rotated right) and 58.1±15.0cm/s (P <0.0001, left). Comparable measurements were made for TAV. There was a correlation of TAV and Vs with individual postnatal age.Head rotation and different positioning of the neonate/young infant leads to lower Vs and TAV values in the basilar artery. It remains unclear if these changes may help to identify patients at risk of SIDS. Furthermore, Vs and TAV are age-dependent, which should be considered in the workup of transfontanellar US Doppler investigations.

Annually, an estimated 2.3 million infants die within their first month of life, primarily in sub-Saharan Africa and South Asia. Infections, including sepsis are among the major contributors to these deaths. Effective interventions added to standard antimicrobial therapy can reduce sepsis mortality. A recent meta-analysis suggests that adjunct zinc treatment of young infants with sepsis could reduce case fatality risk. This study evaluated the efficacy of zinc as an adjunct to antibiotics in young infants with suspected sepsis, defined as clinical severe infection (CSI). We conducted a randomized, double-blind, placebo-controlled trial across seven hospitals in India and Nepal from February 28, 2017, to February 22, 2022. Infants aged 3-59 days hospitalized with suspected sepsis, defined as CSI, adapted from the WHO Integrated Management of Childhood Illness (IMCI) criteria, were randomly assigned to receive 10 mg of elemental zinc daily or placebo orally for 14 days, in addition to standard of care. The primary outcomes were death during hospitalization and death within 12 weeks after enrollment. Among 3,153 enrolled infants (1,203 [38%] females), the median age at enrollment was 25 days (interquartile range 13-41 days), and the mean weight was 2.9 kg (standard deviation 0.8). During the hospital stay, 64 (4.1%) of 1,576 infants died in the zinc arm compared to 77 (4.9%) of 1,577 in the placebo arm (relative risk [RR] 0.83 (95% CI [0.60, 1.15]; p = 0.267)). Among those who completed 12 weeks of follow-up, 140 of 1,554 infants (9.0%) died in the zinc arm, and 133 of 1,550 (8.6%) in the placebo arm (RR 1.05 (95% CI [0.84, 1.32]; p = 0.674)). Adverse events were similar across trial arms, except for a slight increase in vomiting in the zinc arm; no events were attributed to the intervention. The main limitation of the study is that it was underpowered due to lower-than-anticipated event rates and a shortfall in the achieved sample size. In this setting, we found little evidence for an effect of adjunct zinc therapy on young infants with CSI on the risk of dying during hospitalization or for the subsequent 3 months. Our findings contrast previous studies that used more specific case definitions. This underscores the need for further RCTs to evaluate the effect of zinc in young infant sepsis before it can be recommended in treatment guidelines. Clinical Trials Registry-India (CTRI/2017/02/007966) on February 27, 2017, and Universal Trial Number is U1111-1187-6479.

Young febrile infants are at high risk of invasive bacterial infections (IBIs). Clinical Decision Aids (CDA) such as the Step-by-Step and Paediatric Emergency Care Applied Research Network (PECARN) use Procalcitonin (PCT), limiting their application in settings without PCT access. This study aimed to test the performance of these CDAs in a UK cohort. This was a planned analysis of the Febrile Infant Diagnostic Assessment and Outcome Study, a large, prospective multicentre observational study conducted across over 30 sites in the UK. Febrile infants (0-90 days of age) with complete biomarker data, who also underwent PCT testing, were included. Two CDAs, PECARN and Step-by-Step, were applied to the cohort, using their recommended low-risk criteria. The diagnostic performance of the CDAs was analysed. Of the 1527 infants who completed biomarker testing in the main study, 442 had PCT testing and were included, 22 (5%) were diagnosed with an IBI. PECARN and Step-by-Step CDAs demonstrated sensitivities of 1.00 (95% CI: 0.85 to 1.00) and 0.96 (95% CI: 0.77 to 1.00) respectively. The PECARN CDA performed with a specificity of 0.14 (95% CI: 0.11 to 0.18) identifying 14% of the participants as low-risk and did not misclassify any infants. The Step-by-Step CDA performed with a specificity of 0.15 (95% CI: 0.12 to 0.19) identifying 14% of the participants as low-risk and misclassifying one participant with IBI as low-risk. Both PECARN and Step-by-Step CDAs demonstrated high sensitivity for detecting IBI in our cohort. While specificity was relatively low, these tools could potentially identify a subset of low-risk infants suitable for less intensive management.

Despite the availability of a vaccine, pertussis is a particularly difficult disease to control. Improvements in molecular diagnosis, changes in vaccine components, and missed opportunities for vaccination have resulted in rising pertussis disease incidence. Young infants are at the highest risk of severe complications and mortality, but immunization of mothers during pregnancy can provide protection. The presentation of infant pertussis differs somewhat from the traditional catarrhal, paroxysmal, and convalescent stages seen in adults. By understanding the clinical presentation of pertussis in all age groups, providers can more quickly prescribe appropriate antibiotic therapy and postexposure prophylaxis. Providers are also an essential source of evidence-based vaccination counseling for pregnant women and families, and understanding the complications of this disease is an important part of these sometimes difficult but critical conversations.