A Protocol to Assess Adult Outcomes at 30 Years Following Preterm Birth.

BACKGROUND: Among the most intense adversity experiences for infants is premature birth. Early birth marks the beginning of a life course that broadly affects families, healthcare, education, social systems, and the survivors themselves. For many, the transition to adulthood is challenging and often hampered by cognitive, physical and mental health, and motor and independence difficulties. OBJECTIVES: The aim of this study was to share a comprehensive protocol of a 10th follow-up study of premature infants in their 30s. The protocol accounts for stress during the neonatal period, the cumulative context (risk and protection) of development, biological and epigenetic mechanisms, and individual resilience. METHODS: The prospective, five-group longitudinal design includes 215 term-born and preterm-born individuals with various neonatal morbidities at ages 30-35 years. Adult outcomes include health, adaptive, executive function, work, and social competence. Novel measures are four system indicators of allostatic load (AL) and epigenetics. Contextual measures include socioeconomic risk and individual resilience. All measures were selected based on coherence with constructs of the scientific aims, strong psychometrics, continuity for repeated measures, and minimal subject burden. Objective assessments include body composition imaging, exercise testing, blood and saliva collection, and actigraphy. The two-phase protocol takes approximately 8 hours. DISCUSSION: After an 11-month COVID-19 pause, participant response has been strong. As of May 2022, 75 participants have completed the full protocol, and 99 have consented to participate. When socioeconomic risk is controlled, we hypothesize that life course trajectories in physical and psychological health, adaptive function, and executive function will differ between term and preterm neonatal morbidity groups. AL will vary across groups and contribute to outcomes. We expect proximal protection and resilience to mediate the cumulative medical and socioeconomic risk and AL. Epigenome-wide DNA methylation, with estimates of age acceleration, will be examined across groups and explored in longitudinal associations with medical risk, socioeconomic status, and protection. To our knowledge, this is the only U.S. study of premature infants aged 30-35 years. With millions of preterm-born individuals reaching adulthood, the protocol incorporates molecular and genetic biomarkers in a life course developmental examination to inform the timing and content of interventions.

Nirsevimab for Prevention of RSV in Healthy Late-Preterm and Term Infants.

BACKGROUND: Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infection and hospitalization in infants. Nirsevimab is a monoclonal antibody to the RSV fusion protein that has an extended half-life. The efficacy and safety of nirsevimab in healthy late-preterm and term infants are uncertain. METHODS: We randomly assigned, in a 2:1 ratio, infants who had been born at a gestational age of at least 35 weeks to receive a single intramuscular injection of nirsevimab or placebo before the start of an RSV season. The primary efficacy end point was medically attended RSV-associated lower respiratory tract infection through 150 days after the injection. The secondary efficacy end point was hospitalization for RSV-associated lower respiratory tract infection through 150 days after the injection. RESULTS: A total of 1490 infants underwent randomization: 994 were assigned to the nirsevimab group and 496 to the placebo group. Medically attended RSV-associated lower respiratory tract infection occurred in 12 infants (1.2%) in the nirsevimab group and in 25 infants (5.0%) in the placebo group; these findings correspond to an efficacy of 74.5% (95% confidence interval [CI], 49.6 to 87.1; P<0.001) for nirsevimab. Hospitalization for RSV-associated lower respiratory tract infection occurred in 6 infants (0.6%) in the nirsevimab group and in 8 infants (1.6%) in the placebo group (efficacy, 62.1%; 95% CI, -8.6 to 86.8; P = 0.07). Among infants with data available to day 361, antidrug antibodies after baseline were detected in 58 of 951 (6.1%) in the nirsevimab group and in 5 of 473 (1.1%) in the placebo group. Serious adverse events were reported in 67 of 987 infants (6.8%) who received nirsevimab and in 36 of 491 infants (7.3%) who received placebo. CONCLUSIONS: A single injection of nirsevimab administered before the RSV season protected healthy late-preterm and term infants from medically attended RSV-associated lower respiratory tract infection. (Funded by MedImmune/AstraZeneca and Sanofi; MELODY ClinicalTrials.gov number, NCT03979313.).

Advances in Neonatal Infections.

Despite continued advances and developments in neonatal medicine, neonatal sepsis is the third leading cause of neonatal mortality and a major public health problem, especially in developing countries. Sepsis accounts for mortality for almost 50% of global children under 5 years of age.Over the past 50 years, there have been many advances in the diagnosis, prevention, and treatment of neonatal infections. The diagnostic advances include better culture techniques that permit more rapid confirmation of the diagnosis, advent of polymerase chain reaction (PCR) to rapidly diagnose viral infections, use of biologic markers indicating evidence of infection, and a better understanding of immunoglobulin markers of infection. From a therapeutic stand point, there have been a variety of antibiotics, antifungals, and antiviral agents, better approaches to prevent sepsis, specific immunotherapy, for example, respiratory syncytial virus (RSV); bundled approach to prevention of deep-line infection and better antibiotic stewardship, leading to earlier discontinuation of antibiotic therapy.Hand hygiene remains the benchmark and gold standard for late-onset sepsis prevention. The challenge has been that each decade, newer resistant bacteria dominate as the cause of sepsis and newer viruses emerge, for example, human immunodeficiency virus, zika virus, and novel coronavirus disease 2019.Future treatment options might include stem cell therapy, other antimicrobial protein and peptides, and targeting of pattern recognition receptors in an effort to prevent and/or treat sepsis in this vulnerable population. Also, the microbiome of premature infants has a smaller proportion of beneficial bacteria and higher numbers of pathogenic bacteria compared with term infants, likely owing to higher frequencies of cesarean sections, antibiotic use, exposure to the hospital environment, and feeding nonhuman milk products. Modifying the microbiome with more mother's milk and shorter duration of antibiotics in noninfected babies should be a goal. KEY POINTS: · Neonatal sepsis remains a leading cause of mortality.. · Challenges include bacterial resistance and newer viruses.. · Future treatments may include newer antibiotics/antivirals and stem cell therapy..