Acyclovir Dosing Practices Across a Multicenter Cohort of Neonatal Intensive Care Units.

BACKGROUND: Acyclovir is the first-line therapy for neonatal herpes simplex virus infections. Therapy can mitigate morbidity and mortality but carries a risk for toxicity. We aimed to compare acyclovir dosing in neonatal intensive care units to published recommendations based on population pharmacokinetic (PopPK) analysis. METHODS: We performed a multicenter cohort study of infants in neonatal intensive care units managed by the Pediatrix Medical Group from 1997 to 2020. We included all infants who received acyclovir with complete dosing information. Our primary outcome was the proportion of courses with dosing within 80%-120% of the PopPK recommended daily dose and at the recommended dosing frequency. We compared dosing before and after the publication of the 2014 PopPK recommendations using linear probability modeling. RESULTS: We identified 6862 infants with complete dosing information across 308 centers. Dosing met PopPK recommendations for 41% of treatment courses for infants <30 weeks postmenstrual age (PMA), 71% for infants 30 to <36 weeks PMA and <1% for infants ≥ 36 weeks PMA. Comparison of dosing from 1997 to 2013 with that from 2015 to 2020 showed a significant increase in dosing meeting PopPK recommendations for infants <30 weeks PMA (P = 0.008) and infants 30 to <36 weeks PMA (P = 0.02) but not infants ≥ 36 weeks PMA (P = 0.29). No significant increase in dosing meeting PopPK recommendations was seen for any PMA group when comparison was limited to more recent years (2008-2013 vs. 2015-2020). CONCLUSIONS: Dosing meeting PopPK recommendations increased over time for some PMA groups, but dosing different than PopPK recommendations remains common. More research is needed to clarify optimal dosing strategies in these infants.

Krause corpuscles are genital vibrotactile sensors for sexual behaviours.

Krause corpuscles, which were discovered in the 1850s, are specialized sensory structures found within the genitalia and other mucocutaneous tissues1-4. The physiological properties and functions of Krause corpuscles have remained unclear since their discovery. Here we report the anatomical and physiological properties of Krause corpuscles of the mouse clitoris and penis and their roles in sexual behaviour. We observed a high density of Krause corpuscles in the clitoris compared with the penis. Using mouse genetic tools, we identified two distinct somatosensory neuron subtypes that innervate Krause corpuscles of both the clitoris and penis and project to a unique sensory terminal region of the spinal cord. In vivo electrophysiology and calcium imaging experiments showed that both Krause corpuscle afferent types are A-fibre rapid-adapting low-threshold mechanoreceptors, optimally tuned to dynamic, light-touch and mechanical vibrations (40-80 Hz) applied to the clitoris or penis. Functionally, selective optogenetic activation of Krause corpuscle afferent terminals evoked penile erection in male mice and vaginal contraction in female mice, while genetic ablation of Krause corpuscles impaired intromission and ejaculation of males and reduced sexual receptivity of females. Thus, Krause corpuscles of the clitoris and penis are highly sensitive mechanical vibration detectors that mediate sexually dimorphic mating behaviours.

Postdiscontinuation Antibiotic Exposure in Hospitalized Infants at Risk for Late-onset Sepsis in the Neonatal Intensive Care Unit.

BACKGROUND: In the neonatal intensive care unit, infants are at risk for late-onset sepsis. When blood cultures are negative, antibiotic stewardship efforts encourage stopping antibiotics, yet the duration of therapeutic exposure after the last dose is unknown. METHODS: This retrospective cohort study of simulated antibiotic exposures used published population pharmacokinetic models within drug-specific neonatal intensive care unit cohorts of preterm and term infants, postnatal age 7-60 days and exposed to cefepime, piperacillin-tazobactam or tobramycin. Monte Carlo simulations (NONMEM 7.3) were used to predict steady-state exposures after a 72-hour antibiotic course per Neofax dosing. Exposure was assessed relative to drug-specific minimum inhibitory concentration (MIC) targets between 1 and 16 mcg/mL for Pseudomonas and Enterobacteriaceae species. Postdiscontinuation antibiotic exposure (PDAE) was defined as the time from the last dose to when antibiotic concentration decreased below a specific MIC. RESULTS: Piperacillin-tazobactam, cefepime and tobramycin cohorts included infants with median gestation age 29, 32 and 32 weeks and postnatal age 17, 19 and 15 days, respectively. The mean PDAE was 19-68 hours, depending on the specific antibiotic/MIC combination. PDAE was longer for infants <28 days old and preterm (vs. term) infants. Cefepime exhibited the longest mean PDAE of 68 hours for Enterobacteriaceae MIC 1. Piperacillin mean PDAE was 25 hours for Enterobacteriaceae MIC 8. Tobramycin had a short mean PDAE of 19 hours. CONCLUSIONS: Piperacillin and cefepime exposures remained therapeutic long after the expected 8- to 12-hour dosing interval. PDAE is an important consideration for antibiotic stewardship among hospitalized infants, particularly premature infants and those within 1 month postbirth.

Optimising postoperative care: Same-day discharge after transurethral resection of the prostate.

INTRODUCTION: This study aims to assess the feasibility and safety of same-day discharge after transurethral resection of the prostate. MATERIALS AND METHODS: Five years of records were retrospectively analysed. Length of stay categorised patients into Groups 1 (same-day discharge) and 2 (standard-length discharge). Logistic regression analysis was performed, controlling for clinicodemographic factors. Student's t-test compared continuous bladder irrigation and catheter dwell times. RESULTS: A total of 459 patients were identified between 2016 and 2021, 280 in Group 1 and 179 in Group 2, with median ages of 71.0 (interquartile range 36-92) and 72.0 (interquartile range 47-101) years (p = 0.067), respectively. Same-day discharge rates notably increased post-2018 (p = 0.025). Median prostate tissue resected in Group 2 was 7.1g (3.4-12.4g) and in Group 1 was 4.9g (2.4-10.2g; p = 0.034). While continuous bladder irrigation >1 hour was significantly lower in Group 1 than Group 2 (96.8% versus 27.4%; p = 0.0001), catheter dwell times were comparable (70.1 and 70.8 hours, respectively). Control-adjusted results showed a 40% reduction in emergency department representation odds for Group 1 compared with Group 2 (odds ratio = 0.60; 95% confidence interval = 0.37-0.99; p = 0.04). Length of stay was not significantly associated with hospital readmissions (p = 0.11). Continuous bladder irrigation for <1 hour in Group 1 was associated with a reduced emergency department representation (odds ratio = 0.43; 95% confidence interval = 0.197-0.980) but not readmission (odds ratio = 0.413; 95% confidence interval = 0.166-1.104). CONCLUSIONS: Same-day discharge post-transurethral resection of the prostate may be a viable and safe option for carefully selected patients.

Speciation of Technetium Dibutylphosphate in the Third Phase Formed in the TBP/HNO3 Solvent Extraction System.

The speciation of technetium in the nitric acid/dibutylphosphoric acid (HDBP)-n-dodecane system was studied by extended X-ray absorption fine structure (EXAFS) spectroscopy and theoretical methods. Tetravalent technetium, produced by the hydrazine reduction of TcO4- in 3 M HNO3, was extracted by HDBP in n-dodecane (30% by volume). During extraction, the splitting of the organic phase into a heavy phase and a light phase was observed. EXAFS analysis is consistent with the presence of Tc(NO3)3(DBP)(HDBP)2 in the light phase and Tc(NO3)2(DBP)2(HDBP)2 in the heavy phase. Density functional theory calculations at the B3LYP/6-31G* level confirm the stability of the proposed species and indicate that stereoisomers -mer- and fac-Tc(NO3)3(DBP)(HDBP)2 for the light phase and cis- and trans-Tc(NO3)2(DBP)2(HDBP)2 for the heavy phase] could coexist in the system (in the n-dodecane solution). Mechanisms of formation of Tc(NO3)3(DBP)(HDBP)2 and Tc(NO3)2(DBP)2(HDBP)2 are proposed.

Neonatal Necrotizing Enterocolitis: An Update on Pathophysiology, Treatment, and Prevention.

Necrotizing enterocolitis (NEC) is a life-threatening disease predominantly affecting premature and very low birth weight infants resulting in inflammation and necrosis of the small bowel and colon and potentially leading to sepsis, peritonitis, perforation, and death. Numerous research efforts have been made to better understand, treat, and prevent NEC. This review explores a variety of factors involved in the pathogenesis of NEC (prematurity, low birth weight, lack of human breast milk exposure, alterations to the microbiota, maternal and environmental factors, and intestinal ischemia) and reports treatment modalities surrounding NEC, including pain medications and common antibiotic combinations, the rationale for these combinations, and recent antibiotic stewardship approaches surrounding NEC treatment. This review also highlights the effect of early antibiotic exposure, infections, proton pump inhibitors (PPIs), and H2 receptor antagonists on the microbiota and how these risk factors can increase the chances of NEC. Finally, modern prevention strategies including the use of human breast milk and standardized feeding regimens are discussed, as well as promising new preventative and treatment options for NEC including probiotics and stem cell therapy.

Influence of Eat, Sleep, and Console on Infants Pharmacologically Treated for Opioid Withdrawal: A Post Hoc Subgroup Analysis of the ESC-NOW Randomized Clinical Trial.

Importance: The function-based eat, sleep, console (ESC) care approach substantially reduces the proportion of infants who receive pharmacologic treatment for neonatal opioid withdrawal syndrome (NOWS). This reduction has led to concerns for increased postnatal opioid exposure in infants who receive pharmacologic treatment. However, the effect of the ESC care approach on hospital outcomes for infants pharmacologically treated for NOWS is currently unknown. Objective: To evaluate differences in opioid exposure and total length of hospital stay (LOS) for pharmacologically treated infants managed with the ESC care approach vs usual care with the Finnegan tool. Design, Setting, and Participants: This post hoc subgroup analysis involved infants pharmacologically treated in ESC-NOW, a stepped-wedge cluster randomized clinical trial conducted at 26 US hospitals. Hospitals maintained pretrial practices for pharmacologic treatment, including opioid type, scheduled opioid dosing, and use of adjuvant medications. Infants were born at 36 weeks' gestation or later, had evidence of antenatal opioid exposure, and received opioid treatment for NOWS between September 2020 and March 2022. Data were analyzed from November 2022 to January 2024. Exposure: Opioid treatment for NOWS and the ESC care approach. Main Outcomes and Measures: For each outcome (total opioid exposure, peak opioid dose, time from birth to initiation of first opioid dose, length of opioid treatment, and LOS), we used generalized linear mixed models to adjust for the stepped-wedge design and maternal and infant characteristics. Results: In the ESC-NOW trial, 463 of 1305 infants were pharmacologically treated (143/603 [23.7%] in the ESC care approach group and 320/702 [45.6%] in the usual care group). Mean total opioid exposure was lower in the ESC care approach group with an absolute difference of 4.1 morphine milligram equivalents per kilogram (MME/kg) (95% CI, 1.3-7.0) when compared with usual care (4.8 MME/kg vs 8.9 MME/kg, respectively; P = .001). Mean time from birth to initiation of pharmacologic treatment was 22.4 hours (95% CI, 7.1-37.7) longer with the ESC care approach vs usual care (75.4 vs 53.0 hours, respectively; P = .002). No significant difference in mean peak opioid dose was observed between groups (ESC care approach, 0.147 MME/kg, vs usual care, 0.126 MME/kg). The mean length of treatment was 6.3 days shorter (95% CI, 3.0-9.6) in the ESC care approach group vs usual care group (11.8 vs 18.1 days, respectively; P < .001), and mean LOS was 6.2 days shorter (95% CI, 3.0-9.4) with the ESC care approach than with usual care (16.7 vs 22.9 days, respectively; P < .001). Conclusion and Relevance: When compared with usual care, the ESC care approach was associated with less opioid exposure and shorter LOS for infants pharmacologically treated for NOWS. The ESC care approach was not associated with a higher peak opioid dose, although pharmacologic treatment was typically initiated later. Trial Registration: ClinicalTrials.gov Identifier: NCT04057820.

Safety and Effectiveness of Probiotics in Preterm Infants with Necrotizing Enterocolitis.

Although necrotizing enterocolitis is a leading cause of morbidity and mortality among preterm infants, its underlying pathophysiology is not fully understood. Gut dysbiosis, an imbalance between commensal and pathogenic microbes, in the preterm infant is likely a major contributor to the development of necrotizing enterocolitis. In this review, we will discuss the increasing use of probiotics in the NICU, an intervention aimed to mitigate alterations in the gut microbiome. We will review the existing evidence regarding the safety and effectiveness of probiotics, and their potential to reduce rates of necrotizing enterocolitis in preterm infants.

Safety and Effectiveness of Probiotics in Preterm Infants with Necrotizing Enterocolitis.

Although necrotizing enterocolitis is a leading cause of morbidity and mortality among preterm infants, its underlying pathophysiology is not fully understood. Gut dysbiosis, an imbalance between commensal and pathogenic microbes, in the preterm infant is likely a major contributor to the development of necrotizing enterocolitis. In this review, we will discuss the increasing use of probiotics in the NICU, an intervention aimed to mitigate alterations in the gut microbiome. We will review the existing evidence regarding the safety and effectiveness of probiotics, and their potential to reduce rates of necrotizing enterocolitis in preterm infants.

A vagal reflex evoked by airway closure.

Airway integrity must be continuously maintained throughout life. Sensory neurons guard against airway obstruction and, on a moment-by-moment basis, enact vital reflexes to maintain respiratory function1,2. Decreased lung capacity is common and life-threatening across many respiratory diseases, and lung collapse can be acutely evoked by chest wall trauma, pneumothorax or airway compression. Here we characterize a neuronal reflex of the vagus nerve evoked by airway closure that leads to gasping. In vivo vagal ganglion imaging revealed dedicated sensory neurons that detect airway compression but not airway stretch. Vagal neurons expressing PVALB mediate airway closure responses and innervate clusters of lung epithelial cells called neuroepithelial bodies (NEBs). Stimulating NEBs or vagal PVALB neurons evoked gasping in the absence of airway threats, whereas ablating NEBs or vagal PVALB neurons eliminated gasping in response to airway closure. Single-cell RNA sequencing revealed that NEBs uniformly express the mechanoreceptor PIEZO2, and targeted knockout of Piezo2 in NEBs eliminated responses to airway closure. NEBs were dispensable for the Hering-Breuer inspiratory reflex, which indicated that discrete terminal structures detect airway closure and inflation. Similar to the involvement of Merkel cells in touch sensation3,4, NEBs are PIEZO2-expressing epithelial cells and, moreover, are crucial for an aspect of lung mechanosensation. These findings expand our understanding of neuronal diversity in the airways and reveal a dedicated vagal pathway that detects airway closure to help preserve respiratory function.

Opportunistic dried blood spot sampling validates and optimizes a pediatric population pharmacokinetic model of metronidazole.

Pharmacokinetic models rarely undergo external validation in vulnerable populations such as critically ill infants, thereby limiting the accuracy, efficacy, and safety of model-informed dosing in real-world settings. Here, we describe an opportunistic approach using dried blood spots (DBS) to evaluate a population pharmacokinetic model of metronidazole in critically ill preterm infants of gestational age (GA) ≤31 weeks from the Metronidazole Pharmacokinetics in Premature Infants (PTN_METRO, NCT01222585) study. First, we used linear correlation to compare 42 paired DBS and plasma metronidazole concentrations from 21 preterm infants [mean (SD): post natal age 28.0 (21.7) days, GA 26.3 (2.4) weeks]. Using the resulting predictive equation, we estimated plasma metronidazole concentrations (ePlasma) from 399 DBS collected from 122 preterm and term infants [mean (SD): post natal age 16.7 (15.8) days, GA 31.4 (5.1) weeks] from the Antibiotic Safety in Infants with Complicated Intra-Abdominal Infections (SCAMP, NCT01994993) trial. When evaluating the PTN_METRO model using ePlasma from the SCAMP trial, we found that the model generally predicted ePlasma well in preterm infants with GA ≤31 weeks. When including ePlasma from term and preterm infants with GA >31 weeks, the model was optimized using a sigmoidal Emax maturation function of postmenstrual age on clearance and estimated the exponent of weight on volume of distribution. The optimized model supports existing dosing guidelines and adds new data to support a 6-hour dosing interval for infants with postmenstrual age >40 weeks. Using an opportunistic DBS to externally validate and optimize a metronidazole population pharmacokinetic model was feasible and useful in this vulnerable population.

9-cis beta-carotene-enriched diet significantly improved cognition and decreased Alzheimer's disease neuropathology and neuroinflammation in Alzheimer's disease-like mouse models.

A significant progressive decline in beta-carotene (ßC) levels in the brain is associated with cognitive impairment and a higher prevalence of Alzheimer's disease (AD). In this study, we investigated whether the administration of 9-cis beta-carotene (9CBC)-rich powder of the alga Dunaliella bardawil, the best-known source of ßC in nature, inhibits the development of AD-like neuropathology and cognitive deficits. We demonstrated that in 3 AD mouse models, Tg2576, 5xFAD, and apoE4, 9CBC treatment improved long- and short-term memory, decreased neuroinflammation, and reduced the prevalence of ß-amyloid plaques and tau hyperphosphorylation. These findings suggest that 9CBC has the potential to be an effective preventive and symptomatic AD therapy.

Direct-to-participant recruitment of mothers and infants: A strategic approach during challenging pandemic times.

Under traditional circumstances, most clinical trials rely on in-person operations to identify, recruit, and enroll study participants and to complete study-related visits. During unusual circumstances, such as the COVID-19 pandemic, the typical clinical trial model is challenged and forced to explore alternative approaches to implementing study recruitment, participant enrollment, and data collection strategies. One such alternative is a direct-to-participant approach which leverages electronic resources and relevant technological devices (e.g., smart phones) available to researchers and patients. This approach functions under the assumption that a participant has access to a device that connects to the internet such as a smart phone, tablet, or computer. Researchers are then able to transition a typical paper-based, in-person model to an electronic-based, siteless, remote study. This article describes the challenges clinicians and researchers faced when implementing a direct-to-participant study approach during the COVID-19 pandemic. The lessons learned during this study of infant populations could help increase efficiency of future trials, specifically, by lessening the burden on participants and clinicians as well as streamlining the process for enrollment and data collection. While direct-to-adult participant recruitment is not a novel approach, our findings suggest that studies attempting to recruit the infant population may benefit from such a direct-to-participant approach.

Association of maternal pre-pregnancy or first trimester body mass index with neurodevelopmental impairment or death in extremely low gestational age neonates.

OBJECTIVE: To compare the rates of death or survival with severe neurodevelopmental impairment (sNDI) at 2 years among extremely preterm infants in relation to pre-pregnancy or first-trimester maternal body mass index (BMI). METHODS: This retrospective cohort study included extremely preterm infants (gestational age 220/7-266/7 weeks). The study was conducted at National Institute of Child Health and Human Development Neonatal Research Network sites. The primary outcome was death or sNDI at 2 years. RESULTS: Data on the primary outcome were available for 1208 children. Death or sNDI was not different among the three groups: 54.9% in normal, 56.1% in overweight, and 53.4% in obese group (p = 0.39). There was no significant difference in mortality, sNDI, moderate/severe cerebral palsy, Bayley Scales of Infant Development (BSID)-III cognitive composite score <70, BSID-III language composite score <70 in adjusted models. CONCLUSION: Neurodevelopmental outcome was not significantly associated with maternal pre-pregnancy BMI among extreme preterm infants.

Prescribing practices of inhaled corticosteroids for premature infants in the neonatal intensive care unit.

OBJECTIVE: Despite limited safety and efficacy data, inhaled corticosteroids (ICS) are prescribed to premature infants in the neonatal intensive care unit (NICU). We examined contemporary use and risk factors for ICS use in the NICU. STUDY DESIGN: Infants <33 weeks gestational age and <1500 gm birth weight discharged from Pediatrix Medical Group NICUs between 2010 and 2020 were included. We evaluated the association between ICS prescription and clinical characteristics using univariable and multivariable logistic regression. RESULTS: Of 74,123 infants from 308 NICUs, 9253 (12.5%) were prescribed ICS: budesonide, fluticasone, or beclomethasone. Diagnosis of bronchopulmonary dysplasia (BPD), earlier gestational age, male sex, longer mechanical ventilation, oxygen support, and systemic steroids were independent risk factors for ICS prescription. CONCLUSIONS: Use of ICS is common in many NICUs and is associated with a diagnosis of BPD and healthcare utilization. Prospective trials are needed to establish the safety, efficacy, and optimal indication in this vulnerable population.

Trends in COVID-19 diagnoses and outcomes in infants hospitalized in the neonatal intensive care unit.

OBJECTIVE: Characterize the prevalence of coronavirus disease 2019 (COVID-19) diagnosis among mothers with infants hospitalized in 294 neonatal intensive care units (NICUs), and demographics and outcomes of infants with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exposure in utero. STUDY DESIGN: Cohort study of infants discharged from NICUs 01/2020-09/2021. We defined groups based on infant diagnosis, infant testing, and maternal SARS-CoV-2 infection status. We compared demographics, clinical characteristics, and outcomes. RESULTS: Of 150,924 infants, 94% had no COVID-related diagnosis or test; 247 (0.2%) infants tested positive for COVID-19 and were more likely to require mechanical ventilation. Infants with unknown maternal status and negative testing were more commonly premature, outborn, and had longer hospitalizations. CONCLUSION: In this large cohort of hospitalized infants, most had no known exposure to COVID-19. Adverse outcomes and mortality were rare. Further studies are needed to evaluate the long-term effects of COVID-19 in this population.

A phase I trial of caffeine to evaluate safety in infants with hypoxic-ischemic encephalopathy.

OBJECTIVE: Caffeine provides neuroprotection following hypoxic-ischemic injury in animals. We characterized the safety of escalating doses of caffeine in infants with hypoxic-ischemic encephalopathy (HIE) receiving therapeutic hypothermia. STUDY DESIGN: Phase I trial of infants undergoing therapeutic hypothermia for HIE receiving IV caffeine 20 mg/kg followed by up to two daily doses of 5 mg/kg (n = 9) or 10 mg/kg (n = 8). Safety was evaluated based on adverse events and frequency of pre-specified outcomes compared to data from the Whole-Body Hypothermia for HIE trial (Shankaran, 2005). RESULTS: Twelve of 17 (71%) infants had ≥1 adverse event during the study period. The frequency of clinical outcomes related to HIE were not statistically different from outcomes in infants receiving hypothermia in the Whole-Body Hypothermia for HIE trial. CONCLUSION: Caffeine administration was well tolerated. A larger study is required to determine the optimal dose and evaluate drug safety and efficacy. CLINICAL TRIAL: ClinicalTrials.gov Identifier: NCT03913221.

Risk factors and epidemiology of spontaneous intestinal perforation among infants born at 22-24 weeks' gestational age.

OBJECTIVE: To describe the epidemiology, risk factors, and timing of spontaneous intestinal perforation (SIP) among infants born at 22-24 weeks' gestational age (GA). STUDY DESIGN: Observational cohort study among infants born at 22-24 weeks' GA in 446 neonatal intensive care units. RESULTS: We identified 9712 infants, of whom 379 (3.9%) developed SIP. SIP incidence increased with decreasing GA (P < 0.001). Antenatal magnesium (odds ratio (OR) 1.42; 95% confidence interval (CI), 1.09-1.85), antenatal indomethacin (OR 1.40; 95% CI, 1.06-1.85), postnatal indomethacin (OR 1.61; 95% CI, 1.23-2.11), and postnatal hydrocortisone exposure (OR 2.02; 95% CI 1.50-2.73) were associated with SIP. Infants who lost 15-20% (OR 1.77; 95% CI, 1.28-2.44) or >20% (OR 2.04; 95% CI, 1.46-2.85) of birth weight had higher odds of SIP than infants with weight loss <10%. CONCLUSIONS: Antenatal magnesium exposure, antenatal indomethacin exposure, postnatal hydrocortisone exposure, postnatal indomethacin exposure, and weight loss ≥15% were associated with SIP.

Underimmunization of very low birth weight infants at discharge from the neonatal intensive care unit.

OBJECTIVE: To quantify immunization status among premature infants discharged from neonatal intensive care units (NICUs), and identify risk factors for underimmunization. STUDY DESIGN: We performed a cohort study of infants <33 weeks gestation discharged home between 2011 and 2020 from 241 NICUs. Using multivariable logistic regression, we examined the association between risk factors and underimmunization at discharge, defined as <1 dose of 5 vaccine types when discharged at 60-119 days of age and <2 doses when discharged at 120-179 days of age. RESULTS: Of 30,766 infants discharged at 60-119 days of age, 14% were underimmunized. Among 4358 infants discharged at 120-179 days of age, 53% were underimmunized. For infants discharged at 60-119 days of age, ventilator support within 30 days of discharge was associated with underimmunization. Having a surgical procedure was associated with underimmunization in both groups. CONCLUSION: A large proportion of premature infants discharged from the NICU are underimmunized.