latest research topics in neonatology

Neonatology

Explore the latest in neonatology, including advances in fetal surgery and in the care of preterm and extremely low-birth-weight infants.

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This cohort study of German children aged 7 to 11 years examines the association of severe neonatal hypoglycemia with neurodevelopmental outcomes.

This randomized clinical trial compares the safety of early (before discharge from the neonatal intensive care unit) vs later inguinal hernia repair among infants born prematurely who underwent the procedure near the end of their neonatal intensive care unit stay.

This cross-sectional study examines antibiotic use in association with the incidence and mortality from early-onset sepsis among late-preterm and full-term newborns in Sweden.

This cohort study uses birth certificate data to examine the risk of extremely, moderately, and late preterm birth across categories of maternal nativity, ethnicity, and race.

This cohort study examines whether greater early-life pain is associated with slower maturation of neonatal connectivity in female vs male infants and whether reduced connectivity is associated with poorer neurodevelopmental outcomes.

This cohort study compares the risk of preterm birth between women with cervical intraepithelial neoplasia grade 2 (CIN2) who underwent active surveillance or an immediate loop electrosurgical excision procedure.

This cohort study evaluates opioid use disorder (OUD) treatment and pregnancy outcomes among pregnant patients receiving OUD care through a multistate telemedicine program in the US.

This cohort study examines regional and institutional variation in overall opioid exposure and methadone treatment in high-risk infants at US children’s hospitals.

• Opioids in Hospitalized Infants—Managing Pain and Sedation While Avoiding Overuse JAMA Network Open Opinion March 12, 2024 Pediatrics Pain Medicine Substance Use and Addiction Medicine Opioids Anesthesiology Full Text | pdf link PDF open access

This cohort study evaluates associations between maternal social determinants of health and redirection of care discussions for infants born extremely preterm.

This study developed a state-transition model to project clinical and economic outcomes for children with perinatally acquired hepatitis C virus to investigate the cost-effectiveness of treating at various ages.

This cohort study of children younger than 6 years uses electronic health records to investigate whether a child’s age is associated with the probability of spontaneous umbilical hernia closure and to refine guidelines for surgical repair.

This cross-sectional study examines COVID-19 pandemic–related changes in rates of neonatal abstinence syndrome (NAS) and whether infants in urban or rural areas and those with low socioeconomic status were disproportionately affected.

This diagnostic study evaluates how well autonomous artificial intelligence–based retinopathy of prematurity screening can detect more-than-mild and type 1 retinopathy of prematurity.

• Is Artificial Intelligence for Retinopathy of Prematurity Ready to Go? JAMA Ophthalmology Opinion March 7, 2024 Ophthalmology Retinal Disorders Pediatrics Artificial Intelligence Full Text | pdf link PDF

This randomized clinical trial investigates the effectiveness and safety of the neonatal fragment crystallizable receptor monoclonal antibody, batoclimab, in adults with generalized myasthenia gravis.

This cohort study investigates the association between T2* mapping of placental oxygenation and cortical and subcortical fetal brain volumes in typically developing fetuses scanned longitudinally in the third trimester.

This cohort study estimates 10-year costs of care for neonatal abstinence syndrome in a neonates with Medicaid-eligible mothers in Alabama.

This cohort study investigates the association between heat exposure and preterm birth and the role that greenness plays in this association in a cohort of pregnant individuals in Australia.

• Extreme Heat and Preterm Birth Risk—Methodologic Considerations and Policy Implications JAMA Pediatrics Opinion February 26, 2024 Pregnancy Obstetrics Women's Health Obstetrics and Gynecology Pediatrics Full Text | pdf link PDF

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• Frontiers in Pediatrics
• Neonatology
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Insights in Neonatology: 2021

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About this Research Topic

We are now entering the third decade of the 21st Century, and, especially in the last years, the achievements made by scientists have been exceptional, leading to major advancements in the fast-growing field of Pediatrics. Frontiers has organized a series of Research Topics to highlight the latest ...

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The following represent additions to UpToDate from the past six months that were considered by the editors and authors to be of particular interest. The most recent What's New entries are at the top of each subsection.

ORTHOPEDICS AND SPORTS MEDICINE

Overuse injuries, overtraining, and burnout in children and adolescents (February 2024)

Greater numbers of children and adolescents now specialize in a single sport, thereby increasing the risk for overuse injuries, overtraining, and burnout. The American Academy of Pediatrics has issued a new clinical report that reviews the medical literature about these conditions and summarizes key findings pertaining to risk factors, clinical presentation, and prevention [ 1 ]. The report emphasizes the importance of achieving a healthy balance between stress and recovery. Specific recommendations include taking one to two days off from competition and sport-specific training each week and two to three months away from any specific sport each year. Discussions of endurance sports and weekend tournaments are included. (See "Overtraining syndrome in athletes", section on 'Special considerations in the young athlete' .)

Risk of reinjury following ACL repair (February 2024)

Despite advances in surgical techniques, the risk of reinjury following repair of a ruptured anterior cruciate ligament remains substantial, ranging from 5 to 15 percent depending on the patient's age and activities. According to a systematic review of 71 studies involving over 600,000 patients, factors associated with an increased risk for retear following surgery include male sex, younger age, preoperative high-grade knee laxity, return to a high activity level or sport, and concomitant medial collateral ligament injury [ 2 ]. The modifiable factors identified highlight the importance of following a rigorous rehabilitation program and allowing time for complete healing before returning to sport. (See "Anterior cruciate ligament injury", section on 'Risk of reinjury' .)

Return to sport following stress fracture (November 2023)

Evidence is limited regarding return to sport (RTS) following stress fracture. A new systematic review of 76 studies involving nearly 3000 cases,provides some guidance; most of the studies were retrospective and involved predominately male athletes [ 3 ]. The lowest overall rates for RTS were reported for injuries of the femoral neck (55 percent), talus (69 percent), anterior tibial shaft (76 percent), and tarsal navicular (83 percent). The longest average times for RTS were reported for stress fractures of the tarsal navicular (127 days), femoral neck (107 days), and medial malleolus (106 days). These figures are averages, and healing for individuals may vary substantially given the many factors involved, including location within the bone, radiologic grade, duration of symptoms, compliance with treatment, and underlying bone health. Nevertheless, these findings inform treatment decisions and anticipatory guidance for athletes. (See "Overview of stress fractures", section on 'Return to activity' .)

Heavy load resistance exercise for tendinopathy (November 2023)

Evidence supporting the effectiveness of resistance exercise for the treatment of chronic (overuse) tendinopathy is growing. A recent systematic review and meta-analysis of 110 studies with just under 4000 subjects assessed research primarily involving the rotator cuff, Achilles, lateral elbow, and patellar tendons [ 4 ]. While noting that resistance dose was not well documented in many studies, researchers found consistent evidence that rehabilitation programs using resistance loads in excess of body weight and performed less frequently (ie, less than daily) demonstrated greater efficacy. These findings are consistent with our approach to treatment. (See "Overuse (persistent) tendinopathy: Overview of management", section on 'Heavy-load resistance training' .)

Avulsion fractures of hip and pelvis in children (October 2023)

There are few large-scale studies of pelvic avulsion fractures in children. A retrospective review of over 700 children with pelvic or hip avulsion fractures from a single tertiary care hospital reported the average patient age was just over 14 years and nearly 80 percent were sustained by males [ 5 ]. The anterior-superior and inferior iliac spines and ischial tuberosity were the most common sites, accounting for over 80 percent of fractures. Most injuries were sustained while the patient was running or kicking during sport, most often football (soccer). The incidence of avulsion fracture rose substantially during the study period, 2005 to 2020. (See "Pelvic trauma: Initial evaluation and management", section on 'Epidemiology and mechanism' .)

GENERAL PEDIATRICS AND ADOLESCENT MEDICINE

Management of children with mild sleep-disordered breathing (February 2024)

For children with mild sleep-disordered breathing (SDB) and relevant symptoms, little evidence has been available to guide a choice between adenotonsillectomy and watchful waiting. In a randomized trial in 459 children 3 to <13 years with tonsillar hypertrophy and mild SDB (defined by habitual snoring with occasional episodes of obstruction with apnea per hour of sleep), executive function and attention were similar for individuals assigned to adenotonsillectomy compared with watchful waiting at 12 months follow-up [ 6 ]. However, children treated with adenotonsillectomy had greater decrease in snoring, obstruction with apnea or hypopnea, blood pressure, and caregiver-reported symptoms (sleep symptoms, behavioral problems, sleepiness) as well as increased quality of life. These findings support our suggestion to offer adenotonsillectomy to children with mild obstructive sleep apnea and relevant symptoms although watchful waiting is a reasonable alternative. (See "Management of obstructive sleep apnea in children", section on 'Adenotonsillectomy' .)

Cannabinoids and mental health in adolescents (December 2023)

Cannabis use is associated with an increased risk of mental health disorders. However, little is known about the effects of cannabidiol (CBD), a nonpsychoactive component of cannabis used for anorexia and childhood epilepsy, or of recreational synthetic cannabinoids. In a school-based survey from the United Kingdom that included over 6500 adolescents ages 13 to 14 years, reported use of cannabis, CBD, or synthetic cannabinoids were each associated with probable depression, anxiety disorder, or conduct disorder, as well as with auditory hallucinations [ 7 ]. For each disorder, the risk appeared greatest with synthetic cannabinoids. This study highlights the need for further investigation into the association between mental health effects in youth and the different types of cannabinoids. We advise adolescents (and younger children) to avoid cannabis consumption, including CBD. (See "Substance use disorder in adolescents: Epidemiology, clinical features, assessment, and diagnosis", section on 'Cannabis, cannabidiol, and synthetic cannabinoids' .)

High blood lead levels in US children after eating cinnamon applesauce pouches (November 2023)

The Centers for Disease Control and Prevention have issued a health alert following reports of high blood lead levels from several states for a total of 22 children who were fed cinnamon-containing applesauce pouches that were subsequently found to contain extremely high concentrations of lead [ 8 ]. Children who have eaten a recalled product should undergo blood lead testing. Clinicians should advise parents, primary caregivers, and guardians to not buy specific cinnamon-containing apple puree or applesauce products named in the US Food and Drug Administration announcement and to discard any recalled products that they have purchased. (See "Childhood lead poisoning: Exposure and prevention", section on 'Food' and "Childhood lead poisoning: Clinical manifestations and diagnosis", section on 'Laboratory evaluation' and "Childhood lead poisoning: Management" .)

Long distance effect of wildfire smoke on asthma symptoms (October 2023)

Wildfire fine particulate matter (PM 2.5) has been shown to affect respiratory health; however, previous work has focused on populations residing near and directly affected by wildfires. In June 2023, smoke from wildfires in Canada drifted hundreds of miles to New York City, resulting in increased ambient PM 2.5 . During smoke waves, emergency department visits for asthma in both pediatric and adult patients increased to 261 per day (reference during nonsmoke periods, 181.5 per day; incidence rate ratio 1.4) [ 9 ]. Wildfires have health effects far from their source and are particularly hazardous to those with underlying lung disease. (See "Climate emergencies", section on 'Changing wildfire exposure' .)

ALLERGY, IMMUNOLOGY, AND RHEUMATOLOGY

Baricitinib for refractory juvenile idiopathic arthritis (November 2023)

Janus kinase (JAK) inhibitors are one of several options for children with polyarticular juvenile idiopathic arthritis (pJIA) that is refractory to conventional therapy (eg, methotrexate with or without a biologic tumor necrosis factor inhibitor). In a phase 3, randomized trial of 220 children aged 2 to 17 years with JIA (66 percent with pJIA) who had inadequate response or intolerance to standard therapy, patients assigned to the investigational JAK inhibitor baricitinib had a longer time to disease flare compared with placebo [ 10 ]. During the study period, fewer patients receiving baricitinib had a flare compared with placebo (17 versus 51 percent, respectively), but more infections occurred in the baricitinib group than the placebo group. However, rates of serious adverse events were similar in both groups. Baricitinib compares favorably with tofacitinib , another JAK inhibitor used in refractory pJIA, but is not yet approved for this indication. (See "Polyarticular juvenile idiopathic arthritis: Treatment", section on 'Baricitinib' .)

Low awareness of meat allergy caused by "alpha-gal syndrome" (September 2023)

Allergy to galactose-alpha-1,3-galactose, a carbohydrate allergen found in all mammalian meat except that of primates, causes allergic reactions to meats like beef, pork, and lamb, as well as to an array of other products, medications, and medical devices made with mammalian tissues. This allergy, first reported in 2009 and termed "alpha-gal syndrome," develops following the bites of certain ticks and causes reactions that are uncharacteristically delayed (ie, several hours after ingestion). A common presentation is anaphylaxis developing in the middle of the night after a meat-containing evening meal. Although the prevalence is increasing worldwide, a web-based survey of 1,500 health care professionals in the United States revealed that 42 percent had never heard of the disorder [ 11 ]. This lack of awareness can delay diagnosis for decades. (See "Allergy to meats", section on 'In whom to suspect the diagnosis' .)

DEVELOPMENTAL AND BEHAVIORAL PROBLEMS

Infertility and autism spectrum disorder (December 2023)

Patients with infertility often ask about the impact of the disorder and its treatment on risk of autism spectrum disorder (ASD) in offspring. In a large population-based cohort study comparing ASD risk among children whose parents had subfertility (an infertility consultation without treatment), infertility treatment, or neither (unassisted conception), children in the subfertility and infertility treatment groups had a small increased risk of ASD compared with unassisted conception but the absolute risk was low (2.5 to 2.7 per 1000 person-years versus 1.9 per 1000 person-years with unassisted conception) [ 12 ]. The increased risk was similar in the subfertile and infertility treatment groups, suggesting that infertility treatment was not a major risk factor. Obstetrical and neonatal factors (eg, preterm birth) appeared to mediate a sizeable proportion of the increased risk for ASD. (See "Assisted reproductive technology: Infant and child outcomes", section on 'Confounders' .)

ENDOCRINOLOGY

Proposed formal diagnostic criteria for hypophosphatasia in children and adults (March 2024)

Hypophosphatasia is a rare form of osteomalacia caused by pathogenic variants in the tissue nonspecific alkaline phosphatase gene ( ALPL ). Missed or delayed diagnosis is common, in part due to lack of formal diagnostic criteria. An international working group has proposed diagnostic criteria for hypophosphatasia in both children and adults [ 13 ]. Two major criteria or one major and two minor criteria are considered sufficient for diagnosis. For both children and adults, major criteria include a pathogenic (or likely pathogenic) variant in ALPL and elevated natural substrate concentrations (eg, pyridoxal 5'-phosphate). Additional major criteria for adults are atypical femoral fracture and recurrent metatarsal fractures and, for children, early loss of primary teeth and radiographic evidence of rickets. These criteria highlight the variable phenotypic expression of hypophosphatasia and the importance of considering this diagnosis in individuals with metabolic bone disease. (See "Clinical manifestations, diagnosis, and treatment of osteomalacia in adults", section on 'Low alkaline phosphatase (hypophosphatasia)' and "Skeletal dysplasias: Specific disorders", section on 'Hypophosphatasia' .)

Janus kinase inhibition to preserve insulin secretion in early onset type 1 diabetes (January 2024)

In type 1 diabetes, the janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway has been implicated in immune-mediated beta cell destruction. In a trial in 91 individuals (aged 10 to 30 years) with new-onset type 1 diabetes (diagnosed within 100 days), participants were randomly assigned to daily treatment with the oral JAK1/2 inhibitor baricitinib (n = 60) or placebo (n = 31) [ 14 ]. After 48 weeks of therapy, insulin secretion was greater with baricitinib compared with placebo (median stimulated mean C-peptide level 0.65 versus 0.43 nmol/L per minute, respectively). A1C, frequency of hypoglycemia, and the percentage of time spent in the target glucose range (70 to 180 mg/dL [3.9 to 10 mmol/L]) were not significantly different between groups. JAK/STAT pathway inhibition is a promising strategy for preserving insulin secretion in new-onset type 1 diabetes. (See "Type 1 diabetes mellitus: Prevention and disease-modifying therapy", section on 'Cytokine-directed therapies' .)

Investigational once-weekly basal insulin therapy (insulin icodec) for the treatment of adults with type 1 diabetes (November 2023)

Ultra-long-acting insulin icodec is an investigational basal insulin therapy that requires only once-weekly dosing. In a trial in 655 adults with type 1 diabetes (mean A1C approximately 7.6 percent), participants were randomly assigned to basal insulin therapy with once-weekly insulin icodec or once-daily insulin degludec [ 15 ]. After 26 weeks, the mean reduction in A1C was similar in the icodec and degludec groups (-0.47 and -0.51 percentage points, respectively). However, insulin icodec led to a nearly twofold higher combined rate of clinically significant (<54 mg/dL [<3 mmol/L]) or severe hypoglycemia (2836 versus 1495 events with insulin degludec). Additional studies are needed to determine whether risk of hypoglycemia will limit the use of ultra-long-acting insulin in individuals with type 1 diabetes. (See "General principles of insulin therapy in diabetes mellitus", section on 'Basal insulin analogs' .)

GASTROENTEROLOGY, HEPATOLOGY, AND NUTRITION

Budesonide oral suspension for eosinophilic esophagitis (March 2024)

In patients with eosinophilic esophagitis (EoE), use of topical glucocorticoids has been limited by lack of regulatory approval and potentially inconsistent drug delivery. Budesonide oral suspension is a formulation that was recently approved by the US Food and Drug Administration for treating EoE in adults and pediatric patients ages 11 years and older [ 16,17 ]. Approval was informed by clinical trials showing that topical budesonide resulted in higher rates of histologic remission and symptomatic improvement compared with placebo. We anticipate using budesonide oral suspension as the preferred topical glucocorticoid for treating EoE. (See "Treatment of eosinophilic esophagitis (EoE)", section on 'Topical glucocorticoids' .)

Dupilumab for refractory eosinophilic esophagitis (February 2024)

Few data are available on the use of dupilumab (a monoclonal antibody) for treating refractory eosinophilic esophagitis. In a cohort study of 46 patients with refractory eosinophilic esophagitis, dupilumab therapy was associated with histologic remission (defined as <15 eosinophils/high-power field) in 37 patients (80 percent) and with symptomatic improvement in 42 patients (91 percent) after a median of six months [ 18 ]. These data support our approach of using dupilumab for patients with eosinophilic esophagitis who have not responded to other therapies (eg, topical glucocorticoids). (See "Treatment of eosinophilic esophagitis (EoE)", section on 'Dupilumab' .)

Testing for hepatitis C virus infection in infants with perinatal exposure (November 2023)

Perinatally acquired hepatitis C virus (HCV) infection in the United States has increased sharply since 2010. New guidance from the Centers for Disease Control and Prevention recommends early testing for infants with perinatal exposure to HCV ( algorithm 1 ) [ 19 ]:

● Test for HCV RNA during early infancy after two months of age, and ideally before six months of age.

● After 18 months of age, test any infant who has not previously been tested by measuring anti-HCV antibodies, with reflexive testing for HCV RNA.

A negative HCV RNA result at any time point after two months of age virtually excludes HCV infection and further testing is not required. Children with a positive HCV RNA test before three years of age should have repeat testing for HCV RNA before initiating antiviral therapy to determine whether they have spontaneously cleared the infection. This new guidance is consistent with our previous recommendations for early testing for infants with perinatal exposure to HCV. (See "Hepatitis C virus infection in children", section on 'How to test' .)

GENETIC AND METABOLIC DISORDERS

N-acetyl-l-leucine (NALL) for Niemann-Pick disease type C (February 2024)

Niemann-Pick disease type C (NPD-C) is a rare lysosomal disease with a wide phenotypic spectrum; most patients have onset in childhood with cerebellar ataxia and slowly progressive neurologic deterioration. Investigational therapies include N-acetyl-l-leucine (NALL), a putative neuroprotective agent that improves cellular energy production and reduces neuroinflammation. In a recent placebo-controlled, 12-week crossover trial of 60 patients (age ≥4 years) with NPD-C, treatment with NALL was well tolerated and led to improved neurologic status on a scale that measures ataxia and other neurologic signs and symptoms [ 20 ]. While these results are promising, longer-term trials are needed to determine if NALL is beneficial for patients with NPD-C. (See "Overview of Niemann-Pick disease", section on 'Experimental therapies' .)

HEMATOLOGY AND ONCOLOGY

No benefit of routine thromboprophylaxis for children with ALL (January 2024)

Whether routine thromboprophylaxis reduces the risk of thrombotic complications in patients with acute lymphoblastic leukemia (ALL) has been debated. In a multicenter randomized trial of over 500 children and adolescents with newly diagnosed pre-B or T cell ALL, patients assigned to prophylactic anticoagulation with apixaban compared with standard care alone had similar rates of symptomatic venous thrombosis (1.6 versus 2.3 percent, respectively) and asymptomatic venous thrombosis (11 versus 15 percent) [ 21 ]. Nonmajor bleeding episodes (mostly epistaxis) occurred more frequently in the apixaban group (4 versus 1 percent). These data do not support the routine use of thromboprophylaxis in children with ALL, although it may be warranted in selected patients with additional risk factors for thrombosis. (See "Thromboembolism in children with cancer", section on 'Primary prevention' .)

Maintenance eflornithine in high-risk neuroblastoma (January 2024)

For patients with high-risk neuroblastoma (HRNBL), there is interest in investigating novel maintenance therapies such as eflornithine, an ornithine decarboxylase inhibitor. In an externally controlled analysis of almost 100 patients with HRNBL who completed multimodality treatment and maintenance immunotherapy, extended maintenance therapy with eflornithine was associated with improved overall survival (hazard ratio 0.38) [ 22 ]. Based on these data, the US Food and Drug Administration approved eflornithine as maintenance therapy in patients with HRNBL who achieve at least a partial response to prior systemic agents and complete maintenance immunotherapy. Since maintenance eflornithine is not standard across all institutions, this agent may be offered on a case-by-case basis. (See "Treatment and prognosis of neuroblastoma", section on 'Eflornithine' .)

Methemoglobinemia in infants due to contaminated hospital water supply (January 2024)

Methemoglobinemia is a potentially life-threatening condition in which heme iron becomes oxidized, preventing oxygen delivery. A report from a hospital in Japan described methemoglobinemia in 10 neonates who were fed infant formula prepared with tap water from the general hospital water supply [ 23 ]. The cause was identified as high levels of nitrites, and the source was traced to contamination by an anticorrosion agent from the heating system that entered the water supply due to a malfunctioning valve. All 10 survived, although 3 required methylene blue therapy. Infants are especially susceptible to methemoglobinemia because they have lower baseline levels of the enzyme that converts heme iron back to its normal state. (See "Methemoglobinemia", section on 'Nitrates and nitrites (from foods, drugs, preservatives, and chemicals)' .)

INFECTIOUS DISEASES AND IMMUNIZATIONS

Nirsevimab effectiveness in infants (March 2024)

During the 2023-24 respiratory syncytial virus (RSV) season, infants could receive the monoclonal antibody nirsevimab for the first time to protect against RSV-related hospitalization. In a case-control study of almost 700 infants <8 months old who were hospitalized in the United States for an acute respiratory illness during this RSV season, almost 60 percent tested positive for RSV; almost all of these patients had not received nirsevimab [ 24 ]. Among infants who tested negative for RSV, 18 percent had received nirsevimab. Estimated effectiveness against RSV-associated hospitalization among nirsevimab recipients was 90 percent. These data provide additional support for recommendations to administer nirsevimab to all infants <8 months old upon entering their first RSV season and to all newborns during the RSV season unless the birthing parent received RSV vaccination during pregnancy. (See "Respiratory syncytial virus infection: Prevention in infants and children", section on 'Immunoprophylaxis' .)

Short-course antibiotic therapy in children with febrile UTI (February 2024)

In children with urinary tract infection (UTI) without suspected kidney involvement, there is controversy about the duration of empiric antibiotic therapy. In an unblinded trial from Italy of amoxicillin-clavulanate to treat UTI, 142 children three months to five years of age were randomly assigned to a 10-day course (standard) or a 5-day course (short) of antibiotics [ 25 ]. Fewer children assigned to the short course had recurrent UTI within 30 days of antibiotic completion (2.8 versus 14.3 percent [difference -11.5 percent, 95% CI -20.5 to -2.5]). Rates of resistance to amoxicillin-clavulanate within 5 days following completion of antibiotics (1.4 versus 4.3 percent) and within 30 days (1.4 versus 0 percent) were similar. This trial lends further support for a 5-day course of antibiotics to treat UTI when kidney involvement is not suspected. (See "Urinary tract infections in infants older than one month and children less than two years: Acute management, imaging, and prognosis", section on 'Preferred empiric oral regimens' .)

R21/Matrix-M vaccine to prevent malaria in children (November 2023, Modified February 2024)

In October 2023, the World Health Organization (WHO) approved the R21/Matrix-M vaccine for prevention of malaria in children [ 26 ]. In a placebo-controlled randomized trial of 4800 children (age 5 to 36 months) in four African countries, 12-month efficacy of a three-dose vaccine series against clinical malaria was 75 percent at sites with seasonal transmission and 68 percent at sites with year-round transmission [ 27,28 ]. The vaccine was well tolerated. Injection site pain and fever were the most frequent adverse events. Together with the RTS,S/AS01 vaccine (recommended by the WHO in 2021), this approval is expected to facilitate sufficient vaccine supply to benefit all children living in areas where malaria is a public health risk. (See "Malaria: Epidemiology, prevention, and control", section on 'R21/Matrix-M vaccine' .)

Nirsevimab to prevent severe respiratory syncytial virus in infants (January 2024)

Nirsevimab is a new antibody that prevents severe respiratory syncytial virus (RSV) infection in infants. In a trial conducted in France, Germany, and the United Kingdom, more than 8000 otherwise healthy infants ≤12 months, born at ≥29 weeks' gestation, and entering their first RSV season were assigned to receive one dose of nirsevimab or no intervention [ 29 ]. The group who received nirsevimab had fewer hospitalizations for RSV-associated lower respiratory tract infection (0.3 versus 1.5 percent, efficacy 83.2 percent, 95% CI 67.8-92.0) and fewer infants with an oxygen saturation <90 percent (0.1 versus 0.5 percent, efficacy 75.7 percent, 95% CI 32.8-92.9). These findings further support the use of nirsevimab for RSV immunoprophylaxis in infants. (See "Respiratory syncytial virus infection: Prevention in infants and children", section on 'Immunoprophylaxis' .)

Updated guidance for pneumococcal vaccination in children in the Unites States (October 2023)

The Centers for Disease Control and Prevention (CDC) has provided updated guidance for pneumococcal vaccination, endorsing use of either the 15-valent or 20-valent pneumococcal conjugate vaccine ( PCV15 or PCV20) for routine vaccination in infancy and childhood [ 30 ]. The primary vaccine schedule otherwise remains unchanged. For infants who previously received the 13-valent vaccine ( PCV13 ), the series may be completed with PCV15 or PCV20; restarting the series is not necessary. Children with high-risk conditions( table 1 1) may require additional pneumococcal vaccination with either PCV20 or the polysaccharide vaccine ( PPSV23 ) after age two years if their primary series did not include at least one dose of PCV20. We agree with the updated CDC guidance. Guidelines for pneumococcal vaccination in other countries may differ. (See "Pneumococcal vaccination in children", section on 'In the United States' .)

Immunoprophylaxis for severe respiratory syncytial virus in infants (October 2023)

Nirsevimab is a new monoclonal antibody that targets the prefusion conformation of the respiratory syncytial virus (RSV) F glycoprotein [ 31 ]. It has a longer half-life than palivizumab , an existing antibody that requires five monthly injections to provide immunoprophylaxis against severe RSV infection. The efficacy and safety of nirsevimab were demonstrated in two randomized placebo-controlled trials, one involving 1490 infants ≥35 weeks' gestation and the other involving >1400 preterm infants (29 to <35 weeks' gestation) [ 32,33 ]. In both trials, a single intramuscular dose of nirsevimab lowered rates of RSV-related medical evaluation and hospital admissions for RSV. In line with American Academy of Pediatrics and United States Centers for Disease Control and Prevention guidance, we now recommend that infants <8 months old receive one dose of nirsevimab during their first RSV season if the birthing parent did not receive RSV vaccination between 32 and 36 weeks of gestation and at least 14 days prior to delivery. Palivizumab may be used in high-risk infants if nirsevimab is not available. (See "Respiratory syncytial virus infection: Prevention in infants and children", section on 'Immunoprophylaxis' .)

NEONATOLOGY

Neurodevelopmental effects of donor versus birth parent milk (March 2024)

For very low birth weight infants, feeding fortified human milk from the birth parent rather than preterm formula appears to have beneficial effects on cognitive development and significantly reduces the risk of necrotizing enterocolitis (NEC); whether cognitive benefits are seen with donor milk is unclear. In a randomized trial of 483 extremely preterm infants without access to birth parent milk that compared fortified donor milk with preterm formula during the birth hospitalization, individuals assigned to donor milk had similar cognitive development outcomes at approximately two years of age but had a lower risk of NEC during hospitalization (adjusted risk difference -5 percent) [ 34 ]. Despite the lack of benefit on cognitive outcomes, these findings support our suggestion to use fortified donor milk rather than preterm formula for very low birth weight infants without access to birth parent milk. (See "Human milk feeding and fortification of human milk for premature infants", section on 'Use of donor milk' .)

No benefit of early treatment of PDA in extremely preterm neonates (January 2024)

The optimal timing for intervention in extremely preterm (EPT) neonates with patent ductus arteriosus (PDA) is debated; some centers favor early pharmacologic treatment while others favor expectant supportive care initially. In a multicenter, placebo-controlled trial involving >650 EPT neonates with large PDA, early treatment with ibuprofen resulted in higher rates of PDA closure by three weeks of age, but it did not reduce mortality, moderate or severe bronchopulmonary dysplasia, or other neonatal morbidities [ 35 ]. Based on these findings and results from prior clinical trials, we suggest expectant supportive care for PDA rather than early pharmacologic therapy.(See "Patent ductus arteriosus (PDA) in preterm infants: Management and outcome", section on 'Comparison of approaches' .)

Delayed cord clamping in preterm births (December 2023)

Increasing evidence supports delaying cord clamping in preterm births. In an individual participant data meta-analysis of randomized trials of delayed versus immediate cord clamping at births <37 weeks (over 3200 infants), delaying cord clamping for >30 seconds reduced infant death before discharge (6 versus 8 percent) [ 36 ]. In a companion network meta-analysis evaluating the optimal duration of delay, a long delay (≥120 seconds) significantly reduced death before discharge compared with immediate clamping; reductions also occurred with delays of 15 to <120 seconds but were not statistically significant [ 37 ]. For preterm births that do not require resuscitation, we recommend delayed rather than immediate cord clamping. We delay cord clamping for at least 30 to 60 seconds as approximately 75 percent of blood available for placenta-to-fetus transfusion is transfused in the first minute after birth. (See "Labor and delivery: Management of the normal third stage after vaginal birth", section on 'Preterm infants' .)

Long-term neurodevelopmental outcomes for preterm infants receiving minimally invasive surfactant (November 2023)

The technique of administering surfactant via thin intratracheal catheter (called minimally invasive surfactant therapy [MIST]) to preterm neonates with respiratory distress syndrome reduces the risk of bronchopulmonary dysplasia (BPD), but the long-term impact is uncertain. In a recent follow-up report of a multicenter international trial, infants who received MIST had lower rates of hospitalization for respiratory illness at two years but similar neurodevelopmental outcomes compared with those in the control group [ 38 ]. These findings and results from prior trials suggest that MIST improves short- and long-term pulmonary outcomes (ie, reduced need for intubation, reduced incidence of BPD, and reduced respiratory illnesses during the first two years). However, these benefits may not translate into meaningful improvements in long-term neurodevelopmental outcomes. Nevertheless, we continue to use MIST in appropriate candidates given the demonstrated pulmonary benefits. (See "Respiratory distress syndrome (RDS) in preterm infants: Management", section on 'Minimally invasive surfactant therapy (MIST)' .)

NEPHROLOGY AND UROLOGY

Single versus divided doses of prednisone for nephrotic syndrome (March 2024)

Prednisone is the initial treatment of choice for children with idiopathic nephrotic syndrome (NS). In a randomized trial in 60 children with a first episode of NS, a single daily dose and divided-dose therapy both induced remission within six weeks in all participants [ 39 ]. Suppression of the hypothalamic-pituitary-adrenal axis after six weeks of therapy was more common in children treated with divided-dose therapy (100 percent) compared with those treated with single-dose therapy (83 percent). These findings support our practice of using single daily doses of prednisone for this condition. (See "Treatment of idiopathic nephrotic syndrome in children", section on 'Initial steroid course' .)

Serial amnioinfusions for bilateral renal agenesis (January 2024)

Bilateral renal agenesis (BRA) is incompatible with extrauterine life because prolonged oligohydramnios results in pulmonary hypoplasia, leading to postnatal respiratory failure. A prospective study (RAFT) assessed use of serial amnioinfusions to treat 18 cases of BRA diagnosed at <26 weeks of gestation [ 40 ]. Of the 17 live births, 14 survived ≥14 days and had placement of dialysis access, but only 6 survived to hospital discharge. Of the 4 children alive at 9 to 24 months of age, 3 had experienced a stroke and none had undergone transplant. These findings show that serial amnioinfusions for BRA mitigates pulmonary hypoplasia and increases short-term survival and access to dialysis; however, long-term outcome remains poor with no survival to transplantation. Serial amnioinfusions remain investigational and should be offered only as institutional review board-approved research. (See "Renal agenesis: Prenatal diagnosis", section on 'Investigative role of therapeutic amnioinfusion' .)

Nedosiran for primary hyperoxaluria type 1 (October 2023)

For children with primary hyperoxaluria type 1 (PH1), a rare inborn error of glyoxylate metabolism, treatment with lumasiran , an RNA interference agent (RNAi), in combination with standard care (hyperhydration, crystallization inhibitors, and/or pyridoxine supplements), reduces urinary oxalate excretion and progression to kidney failure. In a randomized trial that included 18 children and adults with PH1, subcutaneous injection of nedosiran , a new RNAi, significantly decreased urinary oxalate excretion and achieved sustained normal or near-normal excretion levels compared with placebo with no significant safety concerns [ 41,42 ]. Based upon these findings, nedosiran has been approved for treatment of PH1 by the US Food and Drug Administration. For patients with PH1, we recommend RNAi therapy (either nedosiran or lumasiran) in addition to other measures to reduce kidney calcium oxalate deposition. (See "Primary hyperoxaluria", section on 'Additional therapies for primary hyperoxaluria type 1' .)

Antibiotic prophylaxis for children with high-grade vesicoureteral reflux (October 2023)

The management of vesicoureteral reflux (VUR) varies. Children with high-grade VUR (grade III to V ( figure 1 )) typically receive antibiotic prophylaxis to prevent urinary tract infection (UTI). In a recent randomized, open-label trial in over 290 young infants (mean age 3 months, about 75 percent uncircumcised males) with high-grade VUR and no prior UTI, antibiotic prophylaxis (primarily amoxicillin-clavulanate ) over two years reduced the proportion of patients with a first symptomatic UTI compared with placebo (21 versus 36 percent, hazard ratio 0.55) [ 43 ]. Antibiotic resistance was more common in urine cultures obtained from children receiving prophylaxis. These findings confirm the benefit of antibiotic prophylaxis in young infants with high-grade VUR and no prior UTI. (See "Management of vesicoureteral reflux", section on 'Evidence' .)

Benign acute childhood myositis (January 2024)

Benign acute childhood myositis (BACM) is a self-limited syndrome associated with calf pain and creatinine kinase elevation, often following infection with influenza. In a retrospective study of 65 patients with BACM, the median age was 6.6 years and 66 percent of patients were male [ 44 ]. The most common symptoms were bilateral calf pain, refusal to walk, and diffuse weakness. The median creatinine kinase was 1827 U/L, which normalized after an average of seven days. Early recognition of this syndrome allows the clinician to avoid an unnecessary evaluation for other muscle diseases. (See "Overview of viral myositis", section on 'Benign acute childhood myositis' .)

Vamorolone for Duchenne muscular dystrophy (December 2023)

Glucocorticoid treatment with prednisone or deflazacort for Duchenne muscular dystrophy (DMD) is associated with improved motor function, but adverse effects include weight gain, slowing of growth, and bone loss. Vamorolone , a novel steroid, was designed to reduce adverse effects of glucocorticoid therapy for DMD. In the VISION-DMD trial, vamorolone treatment led to improvement on several motor outcomes compared with placebo, while efficacy was similar compared with prednisone [ 45 ]. Prednisone treatment (but not vamorolone) led to growth deceleration and bone biomarker abnormalities. Based on these findings, the US Food and Drug Administration approved vamorolone for children age ≥2 years with DMD [ 46 ]. We suggest glucocorticoid treatment for children with DMD and anticipate using vamorolone as an alternative to prednisone and deflazacort. (See "Duchenne and Becker muscular dystrophy: Glucocorticoid and disease-modifying treatment", section on 'Benefits of glucocorticoid therapy' .)

Acute encephalopathy with biphasic seizures and late reduced diffusion (November 2023)

Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is a parainfectious syndrome characterized by presentation with febrile status epilepticus (FSE) followed by a brief seizure-free period before recurrence of seizures in clusters. In a retrospective study from Japan of 55 patients presenting with FSE, the development of AESD in 11 patients was associated with longer time from seizure onset to hospital arrival, presence of hypoxia, and later treatment with antiseizure medications [ 47 ]. These findings suggest that shortening the seizure duration by early effective treatment and preventing hypoxia during ambulance transportation might reduce the risk of AESD. (See "Clinical features and evaluation of febrile seizures", section on 'Acute encephalopathy with biphasic seizures and late reduced diffusion' .)

Expert panel on epilepsy with eyelid myoclonia (November 2023)

Epilepsy with eyelid myoclonia (EEM; Jeavons syndrome) is a female-predominant generalized epilepsy syndrome with onset from 3 to 12 years of age characterized by eyelid myoclonia, photosensitivity, and eye closure-induced seizures or paroxysms on electroencephalography (EEG). Recently, an international expert panel found a strong consensus that EEM is often underdiagnosed, that a correct diagnosis can only be made with EEG including photic stimulation, and that an earlier age at onset is associated with an increased risk of intellectual disability and drug-resistant epilepsy [ 48 ]. Management generally involves reducing exposure to provoking factors (eg, visual stimuli, various sources of natural and artificial light) and use of antiseizure medication such as levetiracetam or valproate [ 49 ]. (See "Photosensitive epilepsies", section on 'Epilepsy with eyelid myoclonia (Jeavons syndrome)' .)

New guidelines for the treatment of neonatal seizures (October 2023)

New guidelines from the International League Against Epilepsy (ILAE) recommend phenobarbital as first-line antiseizure medication (ASM) therapy for treating most etiologies of neonatal seizures [ 50 ]. The one exception is that sodium channel blockers ( phenytoin / fosphenytoin or carbamazepine ) are considered a first-line therapy for neonates with a channelopathy. Phenytoin, levetiracetam , midazolam , and lidocaine are considered second-line ASMs for infants who continue to have seizures despite first-line therapy. Our approach is in accordance with the ILAE guidelines. (See "Treatment of neonatal seizures", section on 'Phenobarbital for most etiologies' .)

Fatal immune reaction after gene therapy for Duchenne muscular dystrophy (September 2023)

Recombinant adeno-associated virus (rAAV) vectors used to deliver gene therapy can be associated with a risk of severe immune reactions. This was illustrated by a report of a 27-year-old patient with advanced Duchenne muscular dystrophy (DMD) and impaired cardiopulmonary function who was treated with a high dose of rAAV containing a CRISPR-based transgene designed to upregulate dystrophin [ 51 ]. After treatment, he developed worsening cardiac dysfunction, acute respiratory distress syndrome, and fatal cardiac arrest. Laboratory and postmortem studies suggested his death was due to an innate immune reaction. Further research to develop safer approaches and identify high-risk patients may help to mitigate the acute toxic effects of rAAV gene therapy. (See "Overview of gene therapy, gene editing, and gene silencing", section on 'Potential concerns with gene therapy' and "Duchenne and Becker muscular dystrophy: Glucocorticoid and disease-modifying treatment", section on 'Risk of immune reactions with AAV vectors' .)

Management of spinal deformities in children with NF1 (September 2023)

New consensus-based guidelines on the management of spinal deformities, including scoliosis in children with neurofibromatosis type 1 (NF1), have been published [ 52 ]. The guidelines recommend screening for spine deformity by physical examination at diagnosis and yearly thereafter. To limit radiation exposure in the pediatric population, diagnostic spine imaging is suggested only if clinical suspicion for a spinal abnormality arises from patient history or physical examination. Spinal tumor burden must be assessed preoperatively in any patient with NF1 undergoing surgery for scoliosis because instrumentation that impedes visualization of spinal tumors by magnetic resonance imaging is not recommended when spinal tumor burden is high. (See "Neurofibromatosis type 1 (NF1): Management and prognosis", section on 'Scoliosis' .)

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Editorial: Case reports in neonatology 2022

Sascha meyer.

1 Department of General Pediatrics and Neonatology, Franz-Lust Klinik für Kinder und Jugendliche, Karlsruhe, Germany

Michael Wagner

2 Department of Neonatology, Medical University of Vienna, Vienna, Austria

Merih Cetinkaya

3 Department of Neonatology, University of Health Sciences, Istanbul, Türkiye

Editorial on the Research Topic Case reports in neonatology 2022

This Research Topic publishes high-quality case reports and case series in the field of neonatology, ranging from lethal poisoning, adverse drug reactions, congenital pathologies, neonatal metabolic disease, survival and care practices of periviable births to malignancies in newborns ( Baptiste et al. Cheng et al. Gaertner et al. Boddu et al. Chen et al. Yan et al. ). Case reports provide important insights into the differential diagnosis, decision making, and clinical management of unusual cases. They provide a valuable tool for (a) recognizing new or rare diseases, (b) evaluating therapeutic effects, adverse events, and costs of interventions; as well as (c) improving problem-based medical education in a real-world clinical setting, Conversely, randomized clinical trials generate evidence for the efficacy of interventions in a controlled setting. Undoubtedly, both types of reports are necessary and complementary in modern medicine. Of note, case reports today make up a substantial proportion of articles published in medical journals, and they continue to further our understanding of a great variety of diseases. Consequently, case reports are an important contributor to and driver of medical progress. The CARE guidelines help increase the completeness, accuracy, and transparency of published case reports ( 1 ).

The importance of having access to case reports in our continuously changing modern world is key in the provision of best clinical care. In the immortal words of the famous Canadian physician, first Professor of Medicine and founder of the Medical Service at Johns Hopkins Hospital, Sir William Osler (July 12, 1849 to December 29, 1919): “Always note and record the unusual … Publish it. Save it on a permanent record as a short, concise note. Such communications are always of value” ( 2 ).

No doubt, the value of case reports may be underestimated compared to other publications that are more detailed and supported by evidence (eg, randomized controlled clinical trials). Nevertheless, this experience-based informative method has nowadays been transformed into an accepted academic form of communication and publication, thus contributing to the rapid dissemination of medical knowledge to a wide medical professional audience, including neonatologists.

Therefore, we hope that this Special Collection is both informative and stresses the importance and role of case reports in the field of neonatology, and will also translate into improved neonatal care practices around the world.

Author contributions

This editorial was jointly conceptualized and written together. All authors contributed to the article and approved the submitted version.

Conflict of interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Publisher's note

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

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Neonatology Research

Division of neonatology.

The Division of Neonatology has a robust research program that focuses on several key areas: understanding the fundamental biology of preterm birth and its complications, meticulously testing new therapeutics in newborns through expertly designed clinical trials, developing new knowledge about risk factors for poor outcomes in sick neonates through rigorous observational studies, and developing new understanding of the social and medical impact of the organization and economy of healthcare delivery structures on maternal and child health. In addition, the Division also serves as a national leader in the development and conduct of multicenter and single-center clinical trials. As a member of the National Institute of Child Health and Human Development’s Neonatal Research Network, the Division is at the forefront of academic centers in clinical and epidemiological research in the United States.

The Division has recognized strength in neonatal follow-up and outcomes research; laboratory research into the fetal origins of adult disease, the causes of preterm birth and fetal growth restriction, inflammatory lung diseases, and drug discovery for rare genetic diseases; and research in neonatal infectious disease, antibiotic stewardship, and the microbiome and its impact of long-term health.

In collaboration with CHOP’s Research Institute , we oversee the work of more than 150 investigators pursuing hundreds of active research projects.

Division of Neonatology Areas of Research

Children's environmental health.

• Rebeccca A. Simmons, MD
• Colin Conine, PhD
• Scott Gordon, MD, PhD
• Heather H. Burris, MD
• Scott A. Lorch, MD, MSCE

Clinical Trials/Neonatal Research Network

• Eric C. Eichenwald, MD
• Sara B. DeMauro, MD, MSCE
• Erik Jensen, MD, MSCE

Developmental Origins of Health and Disease

Fetal/Neonatal Lung Disease

• Krithika Lingappan, MD, PhD, MS
• G. Scott Worthen, MD
• Shaon Sengupta, MBBS, MPH
• Danielle A. Callaway, MD, PhD
• Nicolas Bamat, MD, MSCE

March of Dimes Preterm Birth Research Center  

Neonatal Follow-Up/Long-Term Outcomes of Premature Birth

• Andrea F. Duncan, MD, MS
• Sara DeMauro, MD, MSCE

Neonatal Immunology and Infectious Disease

• Kathryn Rubey, MD
• Dustin D. Flannery, DO, MSCE
• Lakshmi Srinivasan, MD, FAAP
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Generative AI develops potential new drugs for antibiotic-resistant bacteria

Stanford Medicine researchers devise a new artificial intelligence model, SyntheMol, which creates recipes for chemists to synthesize the drugs in the lab.

March 28, 2024 - By Rachel Tompa

Acinetobacter baumannii infection is a leading cause of death related to antibiotic resistance. Stanford Medicine researchers employed artificial intelligence to provide recipes for drugs that can treat it.  Kateryna Kon /Shutterstock.com

With nearly 5 million deaths linked to antibiotic resistance globally every year, new ways to combat resistant bacterial strains are urgently needed.

Researchers at Stanford Medicine and McMaster University are tackling this problem with generative artificial intelligence. A new model, dubbed SyntheMol (for synthesizing molecules), created structures and chemical recipes for six novel drugs aimed at killing resistant strains of Acinetobacter baumannii, one of the leading pathogens responsible for antibacterial resistance-related deaths.

The researchers described their model and experimental validation of these new compounds in a study published March 22 in the journal Nature Machine Intelligence .

“There’s a huge public health need to develop new antibiotics quickly,” said James Zou , PhD, an associate professor of biomedical data science and co-senior author on the study. “Our hypothesis was that there are a lot of potential molecules out there that could be effective drugs, but we haven’t made or tested them yet. That’s why we wanted to use AI to design entirely new molecules that have never been seen in nature.”

Before the advent of generative AI, the same type of artificial intelligence technology that underlies large language models like ChatGPT, researchers had taken different computational approaches to antibiotic development. They used algorithms to scroll through existing drug libraries, identifying those compounds most likely to act against a given pathogen. This technique, which sifted through 100 million known compounds , yielded results but just scratched the surface in finding all the chemical compounds that could have antibacterial properties.

Kyle Swanson

“Chemical space is gigantic,” said Kyle Swanson , a Stanford computational science doctoral student and co-lead author on the study. “People have estimated that there are close to 10 60 possible drug-like molecules. So, 100 million is nowhere close to covering that entire space.”

Hallucinating for drug development

Generative AI’s tendency to “hallucinate,” or make up responses out of whole cloth, could be a boon when it comes to drug discovery, but previous attempts to generate new drugs with this kind of AI resulted in compounds that would be impossible to make in the real world, Swanson said. The researchers needed to put guardrails around SyntheMol’s activity — namely, to ensure that any molecules the model dreamed up could be synthesized in a lab.

“We’ve approached this problem by trying to bridge that gap between computational work and wet lab validation,” Swanson said.

The model was trained to construct potential drugs using a library of more than 130,000 molecular building blocks and a set of validated chemical reactions. It generated not only the final compound but also the steps it took with those building blocks, giving the researchers a set of recipes to produce the drugs.

The researchers also trained the model on existing data of different chemicals’ antibacterial activity against A. baumannii . With these guidelines and its building block starting set, SyntheMol generated around 25,000 possible antibiotics and the recipes to make them in less than nine hours. To prevent the bacteria from quickly developing resistance to the new compounds, researchers then filtered the generated compounds to only those that were dissimilar from existing compounds.

“Now we have not just entirely new molecules but also explicit instructions for how to make those molecules,” Zou said.

A new chemical space

The researchers chose the 70 compounds with the highest potential to kill the bacterium and worked with the Ukrainian chemical company Enamine to synthesize them. The company was able to efficiently generate 58 of these compounds, six of which killed a resistant strain of A. baumannii when researchers tested them in the lab. These new compounds also showed antibacterial activity against other kinds of infectious bacteria prone to antibiotic resistance, including E. coli, Klebsiella pneumoniae and MRSA.

The scientists were able to further test two of the six compounds for toxicity in mice, as the other four didn’t dissolve in water. The two they tested seemed safe; the next step is to test the drugs in mice infected with A. baumannii to see if they work in a living body, Zou said.

The six compounds are vastly different from each other and from existing antibiotics. The researchers don’t know how their antibacterial properties work at the molecular level, but exploring those details could yield general principles relevant to other antibiotic development.

“This AI is really designing and teaching us about this entirely new part of the chemical space that humans just haven’t explored before,” Zou said.

Zou and Swanson are also refining SyntheMol and broadening its reach. They’re collaborating with other research groups to use the model for drug discovery for heart disease and to create new fluorescent molecules for laboratory research.

The study was funded by the Weston Family Foundation, the David Braley Centre for Antibiotic Discovery, the Canadian Institutes of Health Research, M. and M. Heersink, the Chan-Zuckerberg Biohub, and the Knight-Hennessy scholarship.

For more news about responsible AI in health and medicine,  sign up  for the RAISE Health newsletter.

Register  for the RAISE Health Symposium on May 14.

• Rachel Tompa Rachel Tompa is a freelance science writer.

About Stanford Medicine

Stanford Medicine is an integrated academic health system comprising the Stanford School of Medicine and adult and pediatric health care delivery systems. Together, they harness the full potential of biomedicine through collaborative research, education and clinical care for patients. For more information, please visit med.stanford.edu .

Artificial intelligence

Exploring ways AI is applied to health care

Synaptic protein change during development offers clues on evolution and disease

The first analysis of how synaptic proteins change during early development reveals differences between mice and marmosets but also what's different in individuals with autism spectrum disorders. The Kobe University findings offer first insights into the mechanism behind synaptic development and open up routes for research on possible treatments.

Given that synapses are the connections between our brain cells, one might think that having as many of these as possible is a good thing. However, primate brains do something unexpected: After early childhood, the connections between brain cells start to decrease in a process called "synaptic pruning." Surprisingly, we know very little about the molecular mechanism behind how synapses change as brains mature and this is also a hurdle for the development of cures to neuropsychological disorders such as the autism spectrum disorder.

Both recent developments in the ability to analyze complex protein assemblies and the recent availability of marmosets as non-human primate model organisms for studies on the brain enabled Kobe University neuroscientist TAKUMI Toru to tackle this knowledge gap. He explains, "The Collaboration with experts in proteomics and non-human primate brain has been a critical factor for enabling this study. Also, we have established an analytical pipeline to compare multiple biological data sets using the latest statistical and bioinformatics tools, which was another crucial element." With this, they focused their studies on the analysis of a protein agglomeration found on the signal-receiving side of synapses, the so-called "postsynaptic density," as it has become clear in previous studies that its constituents are key to the development of small mushroom-shaped protrusions on the signal-receiving cells where synapses are formed.

Their results, published in the journal Nature Communications , are science's first look at what is happening at the protein level in synapses during brain development in the first weeks, months and years after birth. The Kobe University-led research team identified a group of proteins that are produced more and others that are produced less as time passes and could confirm that this is due to changes in gene regulation. They also found that the timing of this regulation is different in mice and marmosets: What happens in mice two weeks after birth happens before or around birth in marmosets. In addition, marmosets have a second phase of protein changes that mice don't have. "This may be related to the evolutionary differences between rodent and primate brains," comments KAIZUKA Takeshi, the first author of the paper, also in respect to the process of synaptic pruning.

Takumi's interest didn't stop there. Knowing that the development of autism spectrum disorder is connected to developmental immaturities of synapses, they investigated what this means on the level of the proteins his group had identified to be connected to synapse development. And indeed, they found that the genes reported to be expressed differentially in autism patients also feature prominently in their data. "These data suggest that the postsynaptic density in autism spectrum disorder patients is relatively similar to that in the prenatal or neonatal period compared to healthy subjects," the researchers write in the study. Being thus able to construct hypotheses on the molecular mechanism behind the emergence of the disorder, this might open up the path for the development of treatments.

Takumi sums up the implications of this study. "Synapse development is a crucial issue to consider in the maturation of brains. Its abnormalities are related to neuropsychiatric disorders, including autism spectrum disorders and schizophrenia. The proteome datasets we provided are important for considering molecular mechanisms of synapse development and the difference between rodents and primates."

This research was funded by the Japan Society for the Promotion of Science (grants 16H06316, 16H06463, 18K14830, 21H04813, 23H04233, 23KK0132 and 16J04376), the Japan Agency for Medical Research and Development (grants JP21wm0425011 and JP20dm0207001), the Japan Science and Technology Agency (grants JPMJMS2299 and JPMJMS229B), the National Center of Neurology and Psychiatry (grant 30-9), the Takeda Science Foundation, and the Taiju Life Social Welfare Foundation. It was conducted in collaboration with researchers from the RIKEN Center for Brain Science, the RIKEN Center for Sustainable Resource Science, the Max Planck Institute for Experimental Medicine, Hokkaido University and Keio University.

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Story Source:

Materials provided by Kobe University . Note: Content may be edited for style and length.

Journal Reference :

• Takeshi Kaizuka, Takehiro Suzuki, Noriyuki Kishi, Kota Tamada, Manfred W. Kilimann, Takehiko Ueyama, Masahiko Watanabe, Tomomi Shimogori, Hideyuki Okano, Naoshi Dohmae, Toru Takumi. Remodeling of the postsynaptic proteome in male mice and marmosets during synapse development . Nature Communications , 2024; 15 (1) DOI: 10.1038/s41467-024-46529-9

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Neonatal sepsis articles from across Nature Portfolio

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Development of risk prediction nomogram for neonatal sepsis in Group B Streptococcus-colonized mothers: a retrospective study

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An IL-10/DEL-1 axis supports granulopoiesis and survival from sepsis in early life

Neutrophils play critical roles in response to infection, and the limit of available neutrophils in neonates and young infants can impact responses to infections, including sepsis. Here the authors identify that the IL-10/DEL-1 axis is involved in emergency granulopoiesis in neonates and suggest a link to sepsis survival in early life.

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Placental Streptococcus agalactiae DNA is associated with neonatal unit admission and foetal pro-inflammatory cytokines in term infants

Detection of GBS DNA in the placenta is associated with neonatal unit admission, infant morbidity and, in some cases, sepsis and foetal cytokine storm.

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Group B Streptococcus Cas9 variants provide insight into programmable gene repression and CRISPR-Cas transcriptional effects

Cas9 induces various transcriptional effects in the opportunistic pathogen, Streptococcus agalactiae , especially related to bacterial defense, nucleotide or carbohydrate metabolism.

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Acquisition and carriage of genetically diverse multi-drug resistant gram-negative bacilli in hospitalised newborns in The Gambia

Bah, Kujabi et al. characterise multi-drug resistant-Gram negative bacilli (MDR-GNB) carriage in small vulnerable newborns and their mothers at a low-resource African hospital. Many neonates acquire MDR and ESBL-GNB between birth and 7 days of age, but there is only limited evidence these are transmitted from the mothers.

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Less is more: Antibiotics at the beginning of life

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Research: How Different Fields Are Using GenAI to Redefine Roles

• Maryam Alavi

Examples from customer support, management consulting, professional writing, legal analysis, and software and technology.

The interactive, conversational, analytical, and generative features of GenAI offer support for creativity, problem-solving, and processing and digestion of large bodies of information. Therefore, these features can act as cognitive resources for knowledge workers. Moreover, the capabilities of GenAI can mitigate various hindrances to effective performance that knowledge workers may encounter in their jobs, including time pressure, gaps in knowledge and skills, and negative feelings (such as boredom stemming from repetitive tasks or frustration arising from interactions with dissatisfied customers). Empirical research and field observations have already begun to reveal the value of GenAI capabilities and their potential for job crafting.

There is an expectation that implementing new and emerging Generative AI (GenAI) tools enhances the effectiveness and competitiveness of organizations. This belief is evidenced by current and planned investments in GenAI tools, especially by firms in knowledge-intensive industries such as finance, healthcare, and entertainment, among others. According to forecasts, enterprise spending on GenAI will increase by two-fold in 2024 and grow to $151.1 billion by 2027 .

• Maryam Alavi is the Elizabeth D. & Thomas M. Holder Chair & Professor of IT Management, Scheller College of Business, Georgia Institute of Technology .

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Developing the aging research workforce from the earliest career stages March 27, 2024

A key part of NIA’s mission is to develop the careers of research scientists and clinicians focused on aging topics, including Alzheimer’s disease and related dementias, but how early can we start cultivating an interest? Focusing on the earliest stages of education is one promising approach. That’s why NIA supports programs to provide aging research education beginning with pre-kindergarten children and expanding to include high school students and teachers, undergraduates, and postbaccalaureate researchers.

If you are an educator, mentor, or student seeking funding for your work to help train the next generation of scientists, NIA has three options available, all of which have Spring 2024 application due dates.

Training with a lifetime impact

Our training trio includes the Expanding Research in Alzheimer’s and related dementias (ERA), Advancing Diversity in Aging Research (ADAR), and Science Education Partnership Award (SEPA) programs. Students supported by these programs describe the high-tech training experience as having a lasting impact for mentoring and inspiration in their careers.

NIA has previously featured the ERA program in our blog and would like to remind readers that ERA includes two parts that both provide research experiences in Alzheimer’s and related dementias research. One supports summer programs for high school students, undergraduate college students, or K-12 science teachers focused on enhancing participants’ understanding of dementia. The other supports immersive one- to two-year programs for recent baccalaureate graduates focused on robustly preparing participants to pursue advanced degrees and other research-related career opportunities in the Alzheimer’s field. Apply for our ERA programs by May 24, 2024.

Through the ADAR research education program, NIH supports the development and implementation of research programs for a diverse pool of undergraduate college students. The proposed education programs support intensive aging research experiences to prepare undergraduate students to transition into strong, research-focused advanced degree programs or competitive private sector research careers in aging-related disciplines. Apply to the current NIH ADAR funding opportunity by May 25, 2024.

SEPA is a trans-NIH program that supports educators to design activities that encourage pre-college students (pre-kindergarten to grade 12) from diverse backgrounds, including those from groups underrepresented in the biomedical and behavioral sciences, to pursue further studies in science, technology, engineering, and mathematics (STEM). Through SEPA, NIH funds two types of projects: classroom-based projects for pre-college students and teachers, and informal science education projects conducted in outside-the-classroom venues such as science centers, museums, and libraries. Apply to develop a SEPA program at your organization by June 7, 2024.

Reach out with your questions

Join NIA in supporting early career investigators to pursue aging research careers! If you’re planning to apply for SEPA, ADAR, or ERA’s upcoming deadlines, NIA’s training officers are happy to answer your questions at [email protected] . If you are a mentor or student who has benefited from these or similar programs, please leave a comment below!

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Government of Canada invests in research to transform health systems

From: Canadian Institutes of Health Research

News release

The Government of Canada is supporting researchers across the country who are collaborating with health system organizations to make meaningful contributions towards improving Canada’s health care system and ensuring that Canadians receive high-quality health care.. By embedding researchers in health system organizations, they can help in finding and implementing solutions to the challenges facing health systems in this country.

Funding of $9.6 million to embed researchers in health system organizations across the country

March 26, 2024 – Ottawa, Ontario – Canadian Institutes of Health Research

The Government of Canada is supporting researchers across the country who are collaborating with health system organizations to make meaningful contributions towards improving Canada’s health care system and ensuring that Canadians receive high-quality health care. By embedding researchers in health system organizations, they can help in finding and implementing solutions to the challenges facing health systems in this country.

To address health system priorities and build valuable research capacity, the Honourable Mark Holland, Minister of Health, today announced that 12 early career researchers will receive the first Health System Impact Embedded Early Career Researcher Awards with the support of $9.6 million in funding from the Canadian Institutes of Health Research (CIHR) and partners. These researchers will be embedded within health system organizations where they will develop research programs to address the evidence needs of their host organizations and use the evidence they gather to help transform Canada’s health care systems.

The researchers will tackle priorities such as:

• increasing equitable access to kidney transplantation;
• transforming cardiovascular care for underserved communities in Ontario;
• improving perinatal and neonatal health care in rural Nova Scotia;
• strengthening the health system response to violence against women in Eastern Canada;
• improving chronic pain management in Alberta with virtual care;
• addressing the social determinants of health in cancer outcomes; and
• transforming autism research and policy at the national level, among other topics.

These awards are part of the  Health System Impact (HSI) program , which was created by the CIHR Institute of Health Services and Policy Research. The program is made possible thanks to funding and support from partners such as Michael Smith Health Research BC, ResearchNB, the Saskatchewan Health Research Foundation, the Fonds de recherche du Québec – Santé, and Mitacs.

“We are proud to support a new generation of health researchers. These researchers are making a positive difference in the lives of people in Canada and are influencing health care and service delivery in real-time, making a huge difference in our health systems.” The Honourable Mark Holland Minister of Health

“As we face major challenges to our health care systems, innovation, evidence, and a shared commitment to improvement are essential for transformation towards better care for all. The Health System Impact Embedded Early Career Researcher program will support a fresh wave of brilliant scientists, equipping them with the skills and partnerships to drive meaningful research programs that address pressing health system needs. It's an exciting and important addition to CIHR's Health System Impact program, reflecting our commitment to nurturing embedded research career pathways and building a research workforce equipped to lead evidence-informed system improvement.” Dr. Rick Glazier Scientific Director, CIHR Institute of Health Services and Policy Research

Quick facts

Since 2017, CIHR and its funding partners have been embedding PhD and postdoctoral fellows directly in health systems organizations to strengthen health care in Canada through the HSI program.

To date, the HSI program has supported 283 fellows, embedded within 128 health systems organizations across Canada and internationally to accelerate evidence-informed health system improvements.

This year, the HSI program was expanded to include a new stream for early career researchers, providing funding to support them in developing cutting-edge research programs that advance the evidence needs and priorities of health system organizations. An early career researcher is a researcher within five years of the date of their first independent research-related appointment.

Related products

• Backgrounder: Health System Impact Embedded Early Career Researcher Award

Associated links

• Funding Opportunity: Health System Impact Embedded Early Career Researcher Award
• Health System Impact Program
• Research for a healthier Canada

Christopher Aoun Press Secretary Office of the Honourable Mark Holland Minister of Health 613-957-0200

Media Relations Canadian Institutes of Health Research 613-941-4563 [email protected]

At the  Canadian Institutes of Health Research  (CIHR) we know that research has the power to change lives. As Canada's health research investment agency, we collaborate with partners and researchers to support the discoveries and innovations that improve our health and strengthen our health care system.

Page details

Are these killer whales actually two separate species? New research calls for distinction

Scientists say they discovered that two well-known types of killer whales in the North Pacific Ocean are actually two separate species and not just different races.

In a study published Wednesday, researchers noticed distinct differences between resident killer whales, which are listed as endangered, and Bigg’s killer whales.

Bigg's killer whales are named after Michael Bigg , the Canadian scientist that first noted the differences between the two species in the 1970s. Despite living in the same waters, Bigg found that the two whales never "mixed" in with each other, a sign that the two were different species, wrote the National Oceanic and Atmospheric Administration on Wednesday

A group of scientists from NOAA Fisheries and universities, led by Phillip Morin, a research molecular geneticist, further proved the theory with their study. The team assembled genetic, physical, and behavioral evidence that they say proves the two whales are different species.

The NOAA states that the Taxonomy Committee of the Society of Marine Mammalogy will decide if it will recognize the new species in its  official list of marine mammal species . The decision to accept the study's findings and categorize the whales as separate species will likely be made at the committee's next annual review this summer.

Any human on the menu? Nah... What do sharks eat? Surprising feeding habits of great white sharks, hammerheads and more.

How many species of whale are there?

Around the world, killer whales have often been thought to be one species, Orcinus orca , with many different ecotypes, meaning they're the same animal, but made up of different races.

Morin told USA TODAY this is because in the 1960s, taxonomists and biologists who categorize different organisms tried proving the Orcinus was made up of different species, but did not have enough evidence to prove their theories.

"The previous descriptions of different killer whale species were often based on observations, drawings, or single skulls in different parts of the world," said Morin.

Because of the limited material they had, the taxonomists decided there was not enough evidence to recognize them, and said there was only one species, O. orca .

Today, things are a bit different. According to the study, as many as 23 species and four subspecies have been named in literature, all falling under the previously mentioned Orcinus genus.

Are they that different?

"They’re the most different killer whales in the world, and they live right next to each other and see each other all the time,” said Barbara Taylor, a former NOAA Fisheries marine mammal biologist, said in a statement. “They just do not mix.”

The study states that killer whales are categorized into different species around the world because of the differences in the morphology of their skulls.

The Bigg's killer whale's skull has a bigger beak, which according to the NOAA, is believed to be an adaptation that allows the whale to capture bigger prey, like marine mammals.

According to the NOAA release, the whale's incredibly different evolutionary trajectory could explained by what they eat.

"Southern Residents are listed as endangered in part because of the scarcity of their salmon prey," states the release. "Bigg’s killer whales, by contrast, have multiplied while feeding on plentiful marine mammals, including California sea lions."

Differences between the whales:

• Resident killer whales maintain tight-knit family pods while Bigg’s killer whales roam in smaller groups
• Residents prey on salmon and other marine fish, while Bigg's preys on seals and whales
• Residents ' skulls are smaller and designed to capture small prey, like fish, while Bigg's skull is bigger and meant to capture sizable meals, like sea lions.