Don’t Wait, Vaccinate: Evaluation of Routine Immunization Administration and Reactogenecity in Preterm Infants

Don’t Wait, Vaccinate: Evaluation of Routine Immunization Administration and Reactogenecity in Preterm Infants | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Don’t Wait, Vaccinate: Evaluation of Routine Immunization Administration and Reactogenecity in Preterm Infants Ferras Bashqoy, Emily Abdelmessih, Purnahamsi Desai, Joanna Tracy, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4331667/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 10 Sep, 2024 Read the published version in Journal of Perinatology → Version 1 posted 9 You are reading this latest preprint version Abstract Objective: To evaluate the incidence of cardiorespiratory events in preterm infants when administering the 2-month vaccine series all at once compared to spreading vaccines over multiple days. Study Design: This single-center, retrospective cohort study from 2019-2022 included preterm neonates receiving 2-month immunizations. The primary outcome was incidence of cardiorespiratory events from time of initial vaccine administration up to 48 hours after final administration. Univariate analysis performed to identify predictors of primary outcome. Results: There were 127 patients (n1=52, n2=75) included. There was no difference in the number of cardiorespiratory events between groups. Predictors of severe event included younger gestational age, smaller birth weight, smaller birth length, and higher baseline apnea or bradycardia events at baseline. Vaccine schedule interruptions occur more often when administration is spread over multiple days. Conclusion: Administration of routine 2-month vaccinations all at once was not associated with increased cardiorespiratory events and prevents interruptions to vaccine schedule. Health sciences/Health care/Paediatrics Health sciences/Health care/Disease prevention/Preventive medicine Figures Figure 1 Introduction Routine vaccination for infants 2 months of age includes hepatitis B (HepB), rotavirus, diphtheria-tetanus-acellular pertussis (DTaP), Haemophilus influenzae b (Hib), pneumococcal conjugate vaccine (PCV13), and inactivated polio vaccine (IPV) per the most updated guidelines 1 . Immunization of preterm infants in the neonatal intensive care unit (NICU) has been the subject of debate due to concerns of reactogenicity (e.g., cardiorespiratory events, subsequent infection) and reduced immunogenicity. The American Academy of Pediatrics (AAP) recommends that medically stable preterm and low birth weight infants should receive full doses of DTaP-HepB-IPV, PCV13, and Hib vaccines as per the schedule for full-term infants. 2 Despite this recommendation, a 2018 survey of NICU providers in the United States showed that 55% of neonatologists gave the two-month vaccines at > 8 weeks of chronological age and 58% spread the vaccines over ≥ 2 days due to concerns for cardiorespiratory events despite lack of supporting data. 3 Hassenfeld Children’s Hospital at NYU Langone Health, a large academic medical center, underwent a practice change in January 2021 from administering vaccinations on separate days to administering on a single day at 2 months postnatal age. This practice change was made due to observed delays in completion of the vaccination series and the above evidence. The purpose of this study is to compare the incidence of cardiorespiratory events before and after this practice change. Methods This was a single-center retrospective cohort study at Hassenfeld Children’s Hospital at NYU Langone between December 1st, 2019, to September 1st, 2022. This study was approved by the NYU Institutional Review Board. All preterm infants (defined as infants born before 37 weeks gestation) that received 2-month vaccines in the NICU were included. The 2-month vaccine series included 3 separate injections: DTaP-HepB-IPV, PCV13, and Hib. The decision to vaccinate was made by the attending neonatologist after consent was obtained from the patient’s parents or caregivers. Patients had to be medically stable to receive vaccination. Medically stable is defined per AAP as not requiring significant ventilator support or ongoing management for debilitating infection, metabolic disease, or renal cardiovascular or respiratory instability and appear to be maintaining a pattern of steady growth. 2 Patients who received the vaccines over a period of 2 days were excluded. Data was obtained through a retrospective electronic health record review for baseline demographics and medical conditions such as chronic lung disease (CLD), intraventricular hemorrhage (IVH), apnea of prematurity or necrotizing enterocolitis. Other data collected included history of a positive culture, (defined as any positive culture prior to vaccination and can include blood, sputum, urine, or wound culture), and baseline respiratory support data including fraction of inspired oxygen (FiO 2 ), and oxygen device. Data collected within 48 hours prior to initial vaccination included postnatal age, post menstrual age, weight, percentile for corrected gestational age (CGA) on Fenton curve, and incidence of any prolonged apnea and/or prolonged bradycardia. Any supportive care administered within 24 hours of vaccination was also collected, and included one-time doses of acetaminophen (APAP), scheduled doses of APAP, or lidocaine cream/eutectic mixture of local anesthetics (LMX). The primary outcome was incidence of cardiorespiratory events including prolonged apnea, prolonged bradycardia and severe events, from time of initial vaccine administration up to 48 hours after final administration. Prolonged apnea was defined as a respiratory pause ≥ 20 seconds in duration or ≥ 15 seconds in duration when associated with bradycardia (≤ 80 beats per minute, bpm) for at least 5 seconds. Prolonged bradycardia was defined as a heart rate of < 80 bpm that lasted ≥ 10 seconds. Severe events were defined as a respiratory pause of ≥ 30 seconds in duration or a bradycardia of ≤ 60 bpm for at least 10 seconds. 4 Other outcomes collected up to 48 hours after vaccine administration included vaccine interruptions, fever, incidence of sepsis workup (defined as initiation of antibiotics), daily average of neonatal pain, agitation and sedation scale (NPASS) scores, respiratory support data, and incidence of enteral feeds being held. Vaccine outcomes collected included incidence of vaccine interruption and time to complete series. Patients who received vaccines over 3 separate days were categorized as “pre practice change” and those who received vaccines all on one day were categorized as “post practice change.” Demographic data is reported to characterize the total cohort, and compare the pre practice change and post practice change cohorts. Chi square test and Fisher’s exact test were used for categorical variables. Mann–Whitney U test was used for continuous variables. A univariate analysis was performed to identify primary predictors of severe events. A p value < 0.05 was considered statistically significant. All data were securely stored in Redcap database, and statistics were conducted using IBM SPSS Statistics for Windows, version 27 (IBM Corp., Armonk, NY, USA). Results Screening, Baseline Characteristics, Pre-Vaccine Characteristics and Supportive Care A total of 146 infants admitted to the NICU eligible for their 2-month vaccine series were screened. After excluding 19 infants who were >37 weeks gestational age or received vaccinations over 2 days, 127 infants were included (pre-practice change n=52, 40.9%; post-practice change n=75, 59.1%)[Figure 1].The population was 48.8% male, with an average gestational age of 28.6 weeks (28 weeks vs. 29.3 weeks, p=0.06). On average, infants in the pre-practice change group were smaller at birth, both by weight in kilograms (kg; 0.94 kg vs. 1.2 kg, p=0.047) and length in centimeters (cm; 35 cm vs. 37 cm, p=0.039). Other baseline characteristics were similar between groups, except that more infants in the pre-practice change group had a history of a positive culture (29, 55.8% vs. 24, 32%; p=0.008) [Table 1]. The median weight at time of vaccination was 2.59 kilograms, and not significantly different between groups (2.49 kg vs. 2.6 kg, p=0.719). At baseline (48 hours prior to vaccination), 26 infants had ≥1 episode of apnea or bradycardia prior to vaccination, 9 in the pre-practice change group and 17 in the post-practice change group (17.3% vs. 22.7%, p=0.462) [Table 2]. APAP was commonly used as supportive care among the whole cohort; 29.9% of the cohort received a one-time dose of APAP and 27.6% received scheduled doses of APAP. There was significantly greater use of single-dose APAP in the post-practice change group (9, 17.3% vs. 29. 38.7%; p=0.01), but no difference in the use of scheduled APAP (11, 21.2% vs. 24, 32%; p=0.179). Only one patient in the total cohort received LMX [Table 2]. Primary and Secondary Outcomes 37% of the total cohort had ≥1 episode of apnea or bradycardia (19, 36.5% vs. 28, 37.3%; p=0.927). There were a total of 8 episodes of prolonged apnea, 4 in the pre-practice change cohort and 4 in the post-practice change cohort (7.7% vs. 5.3%, p=0.715); 40 episodes of prolonged bradycardia, 15 in the pre-practice change cohort and 25 in the post-practice change cohort (28.8% vs. 33.3%, p=0.592), and 18 episodes of severe events, 9 in the pre-practice change cohort and 9 in the post-practice change cohort (17.3% vs. 12%, p=0.399). The overall patient cohort had median NPASS scores of 0, with no significant differences between groups. The incidence of fever, number of patients on respiratory support, escalation of respiratory support, and median FiO2 was not different between groups. Infants in the pre-practice change cohort were more likely to have a sepsis workup done with 48 hours of immunization (5, 9.6% vs. 1, 1.3%; p=0.042). Enteral feeds were not held in any infants. The median time to vaccine series completion was 5 days in infants prior to the practice change, associated with a significant reduction in vaccine schedule interruptions (13, 25% vs. 0; p<0.001) [Table 3]. Univariate Analysis We performed a univariate analysis to identify predictors for severe events in infants within 48 hours of vaccination [Table 4]. Predictors of severe events included younger gestational age, smaller birth weight, smaller birth length, and higher baseline apnea or bradycardia events at baseline. Discussion Our study compared the incidence of cardiorespiratory events in pre-term infants in the NICU before and after a practice change to administer 2-month vaccinations all on one day. We evaluated this because, despite the AAP recommendation that all infants should get routine vaccinations on time, a large portion of neonatologists across the United States report administration > 8 weeks of age. 3 Delay in vaccination may expose infants to multiple vaccine-preventable diseases associated with significant morbidity and potential mortality. This study found that median time to initial vaccine series completion prior to the practice change was 5 days, and though all patients in the study completed the series prior to discharge, this may not be the case in other facilities across the country. The concern regarding increased cardiorespiratory events comes from prior literature reporting increased incidence of apneas, bradycardias and/or desaturations in pre-term infants after receipt of combination vaccines, with the most evidence stemming from administration of the pertussis-containing vaccines. 5–11 Carbone and colleagues challenged these concerns in their prospective study that showed preterm infants who received DTaP did not have increased incidence of prolonged apnea or bradycardia compared to infants who did not receive the vaccine. 12 Notably, however, these prior studies typically looked at the administration of a single vaccine, whether it be a single-antigen or a combination vaccine and did not analyze the incidence of cardiorespiratory events associated with prolonged administration of multiple vaccines. We thus extrapolated outcomes from Carbone and colleagues, as well as the Italian Society of Neonatology, as the basis for our study, and found no difference in the incidence of cardiorespiratory events between multi-day vs. single-day administration of multiple vaccines. 2,10,12 Our univariate analysis found that infants with younger gestational age, lower birth weight and lower weight at time of vaccination were more likely to experience cardiorespiratory events, as described by some prior studies. 5,10 Interestingly, we found significantly greater usage of single-dose APAP within 24 hours of vaccination in the post-practice change cohort. Based on our univariate analysis, this was not found to be associated with decreased occurrence of cardiorespiratory events. There is a concern that administering APAP or non-steroidal anti-inflammatory drugs (NSAIDs) as premedication for vaccinations may reduce their immunogenicity. Wysocki and colleagues performed a randomized, controlled trial comparing immunogenicity of routine pediatric vaccinations (PCV13 and combination DTaP/HBV/IPV/Hib) in patients who received paracetamol (i.e., acetaminophen) or ibuprofen versus those who received no premedication. They found that while immunogenicity was reduced with the use of antipyretics concurrently or delayed 6–8 hours after immunization at 5 months, the antibodies produced were still above the pre-determined seroprotective thresholds. Additionally, immunogenic response was still robust at 13 months of age. 13 Though the significance of these findings is unclear, this data suggests that antipyretic administration within 24 hours of vaccination may still result in seroprotective antibody or response. Our study has several limitations inherent to its retrospective, single-centered design. Medical stability for vaccination was determined by the attending neonatologist, which may have introduced bias and resulted in more stable infants being chosen. Additionally, our formulary options for 2-month vaccine series includes the single-antigen PCV13 vaccine, the single-antigen Hib only vaccine and the combination DTaP-HepB-IPV vaccine, and thus our results may not be applicable to other facilities with different formulary vaccines. In conclusion, our study found that administration of routine 2-month vaccines to preterm infants in the NICU all on one day resulted in a shorter time to vaccine series completion and no difference in cardiorespiratory events. Reduced time to series completion leads to greater assurance that patients will be fully immunized at the recommended times, thereby reducing the incidence of vaccine-preventable diseases. Future prospective studies are required to further confirm the safety, as well as the efficacy (i.e., immunogenicity) of this practice. Abbreviations neonatal intensive care unit (NICU); chronic lung disease (CLD); necrotizing enterocolitis (NEC); intraventricular hemorrhage (IVH); hepatitis B (HepB); diphtheria-tetanus-acellular pertussis (DTaP); Haemophilus influenzae b (Hib); pneumococcal conjugate vaccine (PCV); and inactivated polio vaccine (IPV) Declarations Conflict of Interest Disclosures (includes financial disclosures): All authors have no example conflicts of interest to disclose. Funding/Support: No funding was secured for this study. Role of Funder/Sponsor (if any): N/A Clinical Trial Registration (if any) : N/A References Centers for Disease Control and Prevention. Recommended Vaccinations for Infants and Children, Parent-Friendly Version. https://www.cdc.gov/vaccines/schedules/easy-to-read/child-easyread.html (accessed 2022 Jul 21) Saari TN, and Committee on Infectious Diseases. Immunization of Preterm and Low Birth Weight Infants. Pediatrics . 2003;112(1):193-198. doi:10.1542/peds.112.1.193 Gopal S, Edwards K, Creech B, Weitkamp JH. Variability in Immunization Practices for Preterm Infants. Am J Perinatol . 2018;35(14):1394-1398. doi:10.1055/s-0038-1660453 Eichenwald EC; Committee on Fetus and Newborn, American Academy of Pediatrics. Apnea of Prematurity. Pediatrics. 2016 Jan;137(1). doi: 10.1542/peds.2015-3757. Epub 2015 Dec 1. PMID: 26628729. Lee J, Robinson JL, Spady DW. Frequency of apnea, bradycardia, and desaturations following first diphtheria-tetanus-pertussis-inactivated polio-Haemophilus influenzae type B immunization in hospitalized preterm infants. BMC Pediatr . 2006;6:20. doi:10.1186/1471-2431-6-20 Slack MH, Schapira C, Thwaites RJ, Andrews N, Schapira D. Acellular pertussis and meningococcal C vaccines: cardio-respiratory events in preterm infants. Eur J Pediatr . 2003;162(6):436-437. doi:10.1007/s00431-003-1159-1 Slack MH, Schapira D. Severe apnoeas following immunisation in premature infants. Arch Dis Child Fetal Neonatal Ed . 1999;81(1):F67-68. doi:10.1136/fn.81.1.f67 Botham SJ, Isaacs D. Incidence of apnoea and bradycardia in preterm infants following triple antigen immunization. J Paediatr Child Health . 1994;30(6):533-535. doi:10.1111/j.1440-1754.1994.tb00728.x Buijs SC, Boersma B. [Cardiorespiratory events after first immunization in premature infants: a prospective cohort study]. Ned Tijdschr Geneeskd . 2012;156(3):A3797. Sánchez PJ, Laptook AR, Fisher L, Sumner J, Risser RC, Perlman JM. Apnea after immunization of preterm infants. J Pediatr . 1997;130(5):746-751. doi:10.1016/s0022-3476(97)80017-0 Chiappini E, Petrolini C, Caffarelli C, et al. Hexavalent vaccines in preterm infants: an update by Italian Society of Pediatric Allergy and Immunology jointly with the Italian Society of Neonatology. Ital J Pediatr . 2019;45(1):145. doi:10.1186/s13052-019-0742-7 Carbone T, McEntire B, Kissin D, et al. Absence of an increase in cardiorespiratory events after diphtheria-tetanus-acellular pertussis immunization in preterm infants: a randomized, multicenter study. Pediatrics . 2008;121(5):e1085-1090. doi:10.1542/peds.2007-2059 Wysocki J, Center KJ, Brzostek J, et al. A randomized study of fever prophylaxis and the immunogenicity of routine pediatric vaccinations. Vaccine . 2017;35(15):1926-1935. doi:10.1016/j.vaccine.2017.02.035 Tables Table 1. Infant Baseline Characteristics Characteristic Total Cohort N=127 Pre-Practice Change n=52 Post-Practice Change n=75 P-value Male, n (%) 62 (48.8) 25 (48.1) 37 (49.3) 0.889 GA, weeks, median (IQR) 28.6 (26.5-30.8) 28 (25.8-30.3) 29.3 (26.7-31.1) 0.06 Birth weight, kg, median, (IQR) 1.08 (0.80-1.37) 0.94 (0.77-1.25) 1.2 (0.84-1.43) 0.047 Birth length, cm*, median, (IQR) 36.0 (33.0-39.0) 35 (32-37.9) 37 (33.5-40.0) 0.039 Multiple birth, n (%) 32 (25.2) 15 (28.8) 17 (22.7) 0.430 CLD, n (%) Mild, n (%) Moderate, n (%) Severe, n (%) 71 (55.9) 21 (19.6) 39 (54.9) 11 (15.5) 33 (63.5) 6 (18.2) 19 (57.6) 8 (24.2) 38 (50.7) 15 (39.5) 20 (52.6) 3 (7.9) 0.153 IVH, n (%) Grade 1 or 2, n (%) Grade 3 or 4, n (%) 41 (32.2) 36 (87.8) 5 (12.2) 16 (30.8) 13 (81.3) 3 (18.7) 25 (33.3) 23 (92.0) 2 (8.0) 0.569 Apnea of prematurity treated with caffeine, n (%) 109 (85.8) 44 (84.6) 65 (86.7) 0.744 History of NEC, n (%) 4 (3.1) 3 (5.8) 1 (1.3) 0.304 History of a positive culture, n (%) 53 (41.7) 29 (55.8) 24 (32) 0.008 Baseline respiratory support, n (%) FiO 2 , %, median, (IQR) Type of respiratory support HFNC, n (%) CPAP, n (%) SiPAP, n (%) ETT, n (%) NIMV, n (%) 63 (49.6) 25 (21-30) 45 (71.4) 2 (3.2) 6 (9.5) 9 (14.3) 1 (1.6) 29 (55.8) 26 (23-30) 20 (69.0) 2 (6.9) 2 (6.9) 4 (13.8) 1 ( 3.4) 34 (45.3) 25 (21-27) 25 (73.5) - 4 (11.8) 5 (14.7) - 0.247 0.053 *Birth length only available for n=119 Table 2. Pre-Vaccine Characteristics Characteristic Total Cohort N=127 Pre-Practice Change n=52 Post-Practice Change n=75 P-Value PMA, weeks, median (IQR) 38.4 (36.6-40.1) 38.4 (36.6-40.3) 38.4 (36.7-40.0) 0.877 Weight, kg, median Percentile Fenton Curve*, median (IQR) 2.59 (2.2-3.06) 12 (2.87-25.66) 2.49 (2.18-3.09) 8.21 (1.8-28.7) 2.6 (2.20-3.02) 12.9 (3.6-22.8) 0.719 0.401 Infants with > 1 apnea of bradycardia event, n (%) 26 (20.5) 9 (17.3) 17 (22.7) 0.462 Baseline apnea or bradycardia, median (IQR) 0 (0-0) 0 (0-0) 0 (0-0) 0.435 Supportive Care Agents Used -- -- -- -- Acetaminophen x1 dose, n (%) 38 (29.9) 9 (17.3) 29 (38.7) 0.01 Acetaminophen scheduled, n, (%) 35 (27.6) 11 (21.2) 24 (32.0) 0.179 LMX/EMLA, n, (%) 1 (0.8) 1 (1.9) 0 (0) 0.409 *Percentile Fenton Curve only available for n=121 Table 3. Outcomes Outcome Total Cohort N=127 Pre-Practice Change n=52 Post-Practice Change n=75 P-value Infants with > 1 apnea or bradycardia event, n (%) 47 (37.0) 19 (36.5) 28 (37.3) 0.927 Prolonged apnea, n (%) 8 (6.3) 4 (7.7) 4 (5.3) 0.715 Prolonged bradycardia, n (%) 40 (31.5) 15 (28.8) 25 (33.3) 0.592 Severe event, n (%) 18 (14.2) 9 (17.3) 9 (12) 0.399 Average NPASS scores, median (IQR) 0 (0-0) 0 (0-0) 0 (0-0) 0.770 Fever, n (%) 8 (6.3) 5 (9.6) 3 (4) 0.271 Sepsis workup, n (%) 6 (4.7) 5 (9.6) 1 (1.3) 0.042 Respiratory support at 48h, n (%) FiO 2 , median, (IQR), n (%) Type of respiratory support HFNC, n (%) CPAP, n (%) SiPAP, n (%) ETT, n (%) NIMV, n (%) 60 (47.2) 25 (21-28) 44 (73.3) 2 (3.3) 4 (6.7) 9 (15.0) 1 (1.7) 27 (51.9) 25 (23-30) 19 (70.4) 2 (7.4) 1 (3.7) 4 (14.8) 1 (3.7) 33 (44) 25 (21-28) 25 (75.8) - 3 (9.1) 5 (15.2) - 0.379 0.085 Enteral feeds held, n (%) 0 0 0 1 Vaccine schedule interruptions n (%) Median time to complete series, days, (IQR) 13 (10.2) 5 (5-5) 13 (25) 5 (5-5.5) 0 N/A <0.001 Table 4: Predictors of Severe Events Characteristic Severe Events n=18 No Severe Events n=109 OR (95% CI) P-value GA, weeks, median (IQR) 26.7 (25.0-27.7) 29.4 (26.6-31.2) 0.67 (0.529-0.849) <0.001 Birth weight, kg, median (IQR) 0.82 (0.67-0.92) 1.19 (0.87-1.46) 0.068 (0.011-0.429) 0.001 Birth length, cm, median (IQR) 33 (31-35.5) 37 (33-40) 0.84 (0.731-0.965) 0.010 CLD, n (%) 13 (72.2) 58 (53.2) 2.286 (0.763-6.854) 0.132 IVH, n (%) 6 (33) 35 (32) 1.057 (0.367-3.049) 0.918 Apnea of prematurity treated with caffeine, n (%) 16 (88.9) 93 (85.3) 1.376 (0.288-6.568) 1.000 History of NEC, n (%) 0 4 (3.7) 0.854 (0.793-0.918) 1.000 History of culture-proven sepsis, n (%) 8 (44.4) 45 (41.3) 1.138 (0.417-3.108) 0.801 Baseline respiratory support, n (%) 10 (55.6) 53 (48.6) 1.321 (0.485-3.600) 0.586 Baseline apnea or bradycardia, n (%) 8 (44.4) 18 (16.5) 4.044 (1.404-11.654) 0.012 Acetaminophen, x1 dose, n (%) 4 (22.2) 34 (31.2) 0.630 (0.193-2.057) 0.441 Acetaminophen, scheduled, n (%) 2 (11.1) 33 (30.3) 0.288 (0.063-1.324) 0.152 Additional Declarations There is NO conflict of interest to disclose. Cite Share Download PDF Status: Published Journal Publication published 10 Sep, 2024 Read the published version in Journal of Perinatology → Version 1 posted Editorial decision: revise 23 May, 2024 Review # 2 received at journal 23 May, 2024 Review # 1 received at journal 13 May, 2024 Reviewer # 2 agreed at journal 02 May, 2024 Reviewer # 1 agreed at journal 01 May, 2024 Reviewers invited by journal 30 Apr, 2024 Submission checks completed at journal 29 Apr, 2024 Editor assigned by journal 26 Apr, 2024 First submitted to journal 26 Apr, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4331667","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":297148528,"identity":"a8dd907f-b0d7-4031-b7d0-d9ab100df3d6","order_by":0,"name":"Ferras Bashqoy","email":"data:image/png;base64,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","orcid":"https://orcid.org/0009-0000-1579-0015","institution":"NYU Hassenfeld Children’s Hospital","correspondingAuthor":true,"prefix":"","firstName":"Ferras","middleName":"","lastName":"Bashqoy","suffix":""},{"id":297148529,"identity":"e570e9c4-7550-4af2-94c6-646815e4804c","order_by":1,"name":"Emily Abdelmessih","email":"","orcid":"","institution":"NYU Hassenfeld Children’s Hospital","correspondingAuthor":false,"prefix":"","firstName":"Emily","middleName":"","lastName":"Abdelmessih","suffix":""},{"id":297148530,"identity":"e28e836c-c849-4138-8f19-92b5c2e6e6cc","order_by":2,"name":"Purnahamsi Desai","email":"","orcid":"https://orcid.org/0000-0002-7574-1618","institution":"New York University","correspondingAuthor":false,"prefix":"","firstName":"Purnahamsi","middleName":"","lastName":"Desai","suffix":""},{"id":297148531,"identity":"13e82215-8777-4968-b8d6-8204b3b29098","order_by":3,"name":"Joanna Tracy","email":"","orcid":"https://orcid.org/0000-0003-0088-3547","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Joanna","middleName":"","lastName":"Tracy","suffix":""},{"id":297148532,"identity":"4483cccf-8c2a-4de8-9d76-5667d0839560","order_by":4,"name":"John Papadopoulos","email":"","orcid":"","institution":"New York University Langone Health","correspondingAuthor":false,"prefix":"","firstName":"John","middleName":"","lastName":"Papadopoulos","suffix":""}],"badges":[],"createdAt":"2024-04-26 21:50:15","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4331667/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4331667/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1038/s41372-024-02111-1","type":"published","date":"2024-09-10T04:00:00+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":56140128,"identity":"7b651ec8-fe62-42fd-bbf1-a730a19b5850","added_by":"auto","created_at":"2024-05-09 04:04:40","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":200047,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ePatient Enrollment\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-4331667/v1/cb24a8a2b91dfac4e6b955b8.jpeg"},{"id":64278624,"identity":"6ddc751b-a06c-4dd8-8c3d-69cc3db31e6c","added_by":"auto","created_at":"2024-09-11 07:07:08","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":769005,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4331667/v1/cf3d2cc3-31a6-4580-8517-a228bbbc1cc1.pdf"}],"financialInterests":"There is \u003cb\u003eNO\u003c/b\u003e conflict of interest to disclose.","formattedTitle":"Don’t Wait, Vaccinate: Evaluation of Routine Immunization Administration and Reactogenecity in Preterm Infants","fulltext":[{"header":"Introduction","content":"\u003cp\u003eRoutine vaccination for infants 2 months of age includes hepatitis B (HepB), rotavirus, diphtheria-tetanus-acellular pertussis (DTaP), \u003cem\u003eHaemophilus influenzae\u003c/em\u003e b (Hib), pneumococcal conjugate vaccine (PCV13), and inactivated polio vaccine (IPV) per the most updated guidelines\u003csup\u003e1\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eImmunization of preterm infants in the neonatal intensive care unit (NICU) has been the subject of debate due to concerns of reactogenicity (e.g., cardiorespiratory events, subsequent infection) and reduced immunogenicity. The American Academy of Pediatrics (AAP) recommends that medically stable preterm and low birth weight infants should receive full doses of DTaP-HepB-IPV, PCV13, and Hib vaccines as per the schedule for full-term infants.\u003csup\u003e2\u003c/sup\u003e Despite this recommendation, a 2018 survey of NICU providers in the United States showed that 55% of neonatologists gave the two-month vaccines at \u0026gt;\u0026thinsp;8 weeks of chronological age and 58% spread the vaccines over \u0026ge;\u0026thinsp;2 days due to concerns for cardiorespiratory events despite lack of supporting data.\u003csup\u003e3\u003c/sup\u003e Hassenfeld Children\u0026rsquo;s Hospital at NYU Langone Health, a large academic medical center, underwent a practice change in January 2021 from administering vaccinations on separate days to administering on a single day at 2 months postnatal age. This practice change was made due to observed delays in completion of the vaccination series and the above evidence. The purpose of this study is to compare the incidence of cardiorespiratory events before and after this practice change.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eThis was a single-center retrospective cohort study at Hassenfeld Children\u0026rsquo;s Hospital at NYU Langone between December 1st, 2019, to September 1st, 2022. This study was approved by the NYU Institutional Review Board. All preterm infants (defined as infants born before 37 weeks gestation) that received 2-month vaccines in the NICU were included. The 2-month vaccine series included 3 separate injections: DTaP-HepB-IPV, PCV13, and Hib. The decision to vaccinate was made by the attending neonatologist after consent was obtained from the patient\u0026rsquo;s parents or caregivers. Patients had to be medically stable to receive vaccination. Medically stable is defined per AAP as not requiring significant ventilator support or ongoing management for debilitating infection, metabolic disease, or renal cardiovascular or respiratory instability and appear to be maintaining a pattern of steady growth.\u003csup\u003e2\u003c/sup\u003e Patients who received the vaccines over a period of 2 days were excluded.\u003c/p\u003e \u003cp\u003eData was obtained through a retrospective electronic health record review for baseline demographics and medical conditions such as chronic lung disease (CLD), intraventricular hemorrhage (IVH), apnea of prematurity or necrotizing enterocolitis. Other data collected included history of a positive culture, (defined as any positive culture prior to vaccination and can include blood, sputum, urine, or wound culture), and baseline respiratory support data including fraction of inspired oxygen (FiO\u003csub\u003e2\u003c/sub\u003e), and oxygen device. Data collected within 48 hours prior to initial vaccination included postnatal age, post menstrual age, weight, percentile for corrected gestational age (CGA) on Fenton curve, and incidence of any prolonged apnea and/or prolonged bradycardia. Any supportive care administered within 24 hours of vaccination was also collected, and included one-time doses of acetaminophen (APAP), scheduled doses of APAP, or lidocaine cream/eutectic mixture of local anesthetics (LMX).\u003c/p\u003e \u003cp\u003eThe primary outcome was incidence of cardiorespiratory events including prolonged apnea, prolonged bradycardia and severe events, from time of initial vaccine administration up to 48 hours after final administration. Prolonged apnea was defined as a respiratory pause\u0026thinsp;\u0026ge;\u0026thinsp;20 seconds in duration or \u0026ge;\u0026thinsp;15 seconds in duration when associated with bradycardia (\u0026le;\u0026thinsp;80 beats per minute, bpm) for at least 5 seconds. Prolonged bradycardia was defined as a heart rate of \u0026lt;\u0026thinsp;80 bpm that lasted\u0026thinsp;\u0026ge;\u0026thinsp;10 seconds. Severe events were defined as a respiratory pause of \u0026ge;\u0026thinsp;30 seconds in duration or a bradycardia of \u0026le;\u0026thinsp;60 bpm for at least 10 seconds.\u003csup\u003e4\u003c/sup\u003e Other outcomes collected up to 48 hours after vaccine administration included vaccine interruptions, fever, incidence of sepsis workup (defined as initiation of antibiotics), daily average of neonatal pain, agitation and sedation scale (NPASS) scores, respiratory support data, and incidence of enteral feeds being held. Vaccine outcomes collected included incidence of vaccine interruption and time to complete series.\u003c/p\u003e \u003cp\u003ePatients who received vaccines over 3 separate days were categorized as \u0026ldquo;pre practice change\u0026rdquo; and those who received vaccines all on one day were categorized as \u0026ldquo;post practice change.\u0026rdquo; Demographic data is reported to characterize the total cohort, and compare the pre practice change and post practice change cohorts. Chi square test and Fisher\u0026rsquo;s exact test were used for categorical variables. Mann\u0026ndash;Whitney \u003cem\u003eU\u003c/em\u003e test was used for continuous variables. A univariate analysis was performed to identify primary predictors of severe events. A p value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant. All data were securely stored in Redcap database, and statistics were conducted using IBM SPSS Statistics for Windows, version 27 (IBM Corp., Armonk, NY, USA).\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cem\u003eScreening, Baseline Characteristics, Pre-Vaccine Characteristics and Supportive Care\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eA total of 146 infants admitted to the NICU eligible for their 2-month vaccine series were screened. After excluding 19 infants who were \u0026gt;37 weeks gestational age or received vaccinations over 2 days, 127 infants were included (pre-practice change n=52, 40.9%; post-practice change n=75, 59.1%)[Figure 1].The population was 48.8% male, with an average gestational age of 28.6 weeks (28 weeks vs. 29.3 weeks, p=0.06). On average, infants in the pre-practice change group were smaller at birth, both by weight in kilograms (kg; 0.94 kg vs. 1.2 kg, p=0.047) and length in centimeters (cm; 35 cm vs. 37 cm, p=0.039). Other baseline characteristics were similar between groups, except that more infants in the pre-practice change group had a history of a positive culture (29, 55.8% vs. 24, 32%; p=0.008) [Table 1].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe median weight at time of vaccination was 2.59 kilograms, and not significantly different between groups (2.49 kg vs. 2.6 kg, p=0.719). At baseline (48 hours prior to vaccination), 26 infants had \u0026ge;1 episode of apnea or bradycardia prior to vaccination, 9 in the pre-practice change group and 17 in the post-practice change group (17.3% vs. 22.7%, p=0.462) [Table 2].\u003c/p\u003e\n\u003cp\u003eAPAP was commonly used as supportive care among the whole cohort; 29.9% of the cohort received a one-time dose of APAP and 27.6% received scheduled doses of APAP. There was significantly greater use of single-dose APAP in the post-practice change group (9, 17.3% vs. 29. 38.7%; p=0.01), but no difference in the use of scheduled APAP (11, 21.2% vs. 24, 32%; p=0.179). Only one patient in the total cohort received LMX [Table 2].\u003c/p\u003e\n\u003cp\u003e\u003cem\u003ePrimary and Secondary Outcomes\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e37% of the total cohort had \u0026ge;1 episode of apnea or bradycardia (19, 36.5% vs. 28, 37.3%; p=0.927). There were a total of 8 episodes of prolonged apnea, 4 in the pre-practice change cohort and 4 in the post-practice change cohort (7.7% vs. 5.3%, p=0.715); 40 episodes of prolonged bradycardia, 15 in the pre-practice change cohort and 25 in the post-practice change cohort (28.8% vs. 33.3%, p=0.592), and 18 episodes of severe events, 9 in the pre-practice change cohort and 9 in the post-practice change cohort (17.3% vs. 12%, p=0.399). The overall patient cohort had median NPASS scores of 0, with no significant differences between groups. The incidence of fever, number of patients on respiratory support, escalation of respiratory support, and median FiO2 was not different between groups. Infants in the pre-practice change cohort were more likely to have a sepsis workup done with 48 hours of immunization (5, 9.6% vs. 1, 1.3%; p=0.042). Enteral feeds were not held in any infants. The median time to vaccine series completion was 5 days in infants prior to the practice change, associated with a significant reduction in vaccine schedule interruptions (13, 25% vs. 0; p\u0026lt;0.001) [Table 3].\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eUnivariate Analysis\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eWe performed a univariate analysis to identify predictors for severe events in infants within 48 hours of vaccination [Table 4]. Predictors of severe events included younger gestational age, smaller birth weight, smaller birth length, and higher baseline apnea or bradycardia events at baseline.\u0026nbsp;\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eOur study compared the incidence of cardiorespiratory events in pre-term infants in the NICU before and after a practice change to administer 2-month vaccinations all on one day. We evaluated this because, despite the AAP recommendation that all infants should get routine vaccinations on time, a large portion of neonatologists across the United States report administration\u0026thinsp;\u0026gt;\u0026thinsp;8 weeks of age.\u003csup\u003e3\u003c/sup\u003e Delay in vaccination may expose infants to multiple vaccine-preventable diseases associated with significant morbidity and potential mortality. This study found that median time to initial vaccine series completion prior to the practice change was 5 days, and though all patients in the study completed the series prior to discharge, this may not be the case in other facilities across the country.\u003c/p\u003e \u003cp\u003eThe concern regarding increased cardiorespiratory events comes from prior literature reporting increased incidence of apneas, bradycardias and/or desaturations in pre-term infants after receipt of combination vaccines, with the most evidence stemming from administration of the pertussis-containing vaccines.\u003csup\u003e5\u0026ndash;11\u003c/sup\u003e Carbone and colleagues challenged these concerns in their prospective study that showed preterm infants who received DTaP did not have increased incidence of prolonged apnea or bradycardia compared to infants who did not receive the vaccine.\u003csup\u003e12\u003c/sup\u003e Notably, however, these prior studies typically looked at the administration of a single vaccine, whether it be a single-antigen or a combination vaccine and did not analyze the incidence of cardiorespiratory events associated with prolonged administration of multiple vaccines. We thus extrapolated outcomes from Carbone and colleagues, as well as the Italian Society of Neonatology, as the basis for our study, and found no difference in the incidence of cardiorespiratory events between multi-day vs. single-day administration of multiple vaccines. \u003csup\u003e2,10,12\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eOur univariate analysis found that infants with younger gestational age, lower birth weight and lower weight at time of vaccination were more likely to experience cardiorespiratory events, as described by some prior studies.\u003csup\u003e5,10\u003c/sup\u003e Interestingly, we found significantly greater usage of single-dose APAP within 24 hours of vaccination in the post-practice change cohort. Based on our univariate analysis, this was not found to be associated with decreased occurrence of cardiorespiratory events. There is a concern that administering APAP or non-steroidal anti-inflammatory drugs (NSAIDs) as premedication for vaccinations may reduce their immunogenicity. Wysocki and colleagues performed a randomized, controlled trial comparing immunogenicity of routine pediatric vaccinations (PCV13 and combination DTaP/HBV/IPV/Hib) in patients who received paracetamol (i.e., acetaminophen) or ibuprofen versus those who received no premedication. They found that while immunogenicity was reduced with the use of antipyretics concurrently or delayed 6\u0026ndash;8 hours after immunization at 5 months, the antibodies produced were still above the pre-determined seroprotective thresholds. Additionally, immunogenic response was still robust at 13 months of age.\u003csup\u003e13\u003c/sup\u003e Though the significance of these findings is unclear, this data suggests that antipyretic administration within 24 hours of vaccination may still result in seroprotective antibody or response.\u003c/p\u003e \u003cp\u003eOur study has several limitations inherent to its retrospective, single-centered design. Medical stability for vaccination was determined by the attending neonatologist, which may have introduced bias and resulted in more stable infants being chosen. Additionally, our formulary options for 2-month vaccine series includes the single-antigen PCV13 vaccine, the single-antigen Hib only vaccine and the combination DTaP-HepB-IPV vaccine, and thus our results may not be applicable to other facilities with different formulary vaccines.\u003c/p\u003e \u003cp\u003eIn conclusion, our study found that administration of routine 2-month vaccines to preterm infants in the NICU all on one day resulted in a shorter time to vaccine series completion and no difference in cardiorespiratory events. Reduced time to series completion leads to greater assurance that patients will be fully immunized at the recommended times, thereby reducing the incidence of vaccine-preventable diseases. Future prospective studies are required to further confirm the safety, as well as the efficacy (i.e., immunogenicity) of this practice.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eneonatal intensive care unit (NICU); chronic lung disease (CLD); necrotizing enterocolitis (NEC); intraventricular hemorrhage (IVH); hepatitis B (HepB); diphtheria-tetanus-acellular pertussis (DTaP); \u003cem\u003eHaemophilus influenzae\u003c/em\u003e b (Hib); pneumococcal conjugate vaccine (PCV); and inactivated polio vaccine (IPV)\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eConflict of Interest Disclosures (includes financial disclosures):\u003c/strong\u003e All authors have no example conflicts of interest to disclose.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding/Support:\u003c/strong\u003e No funding was secured for this study.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRole of Funder/Sponsor (if any):\u003c/strong\u003e N/A\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical Trial Registration (if any)\u003c/strong\u003e: N/A\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eCenters for Disease Control and Prevention. Recommended Vaccinations for Infants and Children, Parent-Friendly Version. https://www.cdc.gov/vaccines/schedules/easy-to-read/child-easyread.html (accessed 2022 Jul 21)\u003c/li\u003e\n\u003cli\u003eSaari TN, and Committee on Infectious Diseases. Immunization of Preterm and Low Birth Weight Infants. \u003cem\u003ePediatrics\u003c/em\u003e. 2003;112(1):193-198. doi:10.1542/peds.112.1.193\u003c/li\u003e\n\u003cli\u003eGopal S, Edwards K, Creech B, Weitkamp JH. Variability in Immunization Practices for Preterm Infants. \u003cem\u003eAm J Perinatol\u003c/em\u003e. 2018;35(14):1394-1398. doi:10.1055/s-0038-1660453\u003c/li\u003e\n\u003cli\u003eEichenwald EC; Committee on Fetus and Newborn, American Academy of Pediatrics. Apnea of Prematurity. Pediatrics. 2016 Jan;137(1). doi: 10.1542/peds.2015-3757. Epub 2015 Dec 1. PMID: 26628729.\u003c/li\u003e\n\u003cli\u003eLee J, Robinson JL, Spady DW. Frequency of apnea, bradycardia, and desaturations following first diphtheria-tetanus-pertussis-inactivated polio-Haemophilus influenzae type B immunization in hospitalized preterm infants. \u003cem\u003eBMC Pediatr\u003c/em\u003e. 2006;6:20. doi:10.1186/1471-2431-6-20\u003c/li\u003e\n\u003cli\u003eSlack MH, Schapira C, Thwaites RJ, Andrews N, Schapira D. Acellular pertussis and meningococcal C vaccines: cardio-respiratory events in preterm infants. \u003cem\u003eEur J Pediatr\u003c/em\u003e. 2003;162(6):436-437. doi:10.1007/s00431-003-1159-1\u003c/li\u003e\n\u003cli\u003eSlack MH, Schapira D. Severe apnoeas following immunisation in premature infants. \u003cem\u003eArch Dis Child Fetal Neonatal Ed\u003c/em\u003e. 1999;81(1):F67-68. doi:10.1136/fn.81.1.f67\u003c/li\u003e\n\u003cli\u003eBotham SJ, Isaacs D. Incidence of apnoea and bradycardia in preterm infants following triple antigen immunization. \u003cem\u003eJ Paediatr Child Health\u003c/em\u003e. 1994;30(6):533-535. doi:10.1111/j.1440-1754.1994.tb00728.x\u003c/li\u003e\n\u003cli\u003eBuijs SC, Boersma B. [Cardiorespiratory events after first immunization in premature infants: a prospective cohort study]. \u003cem\u003eNed Tijdschr Geneeskd\u003c/em\u003e. 2012;156(3):A3797.\u003c/li\u003e\n\u003cli\u003eS\u0026aacute;nchez PJ, Laptook AR, Fisher L, Sumner J, Risser RC, Perlman JM. Apnea after immunization of preterm infants. \u003cem\u003eJ Pediatr\u003c/em\u003e. 1997;130(5):746-751. doi:10.1016/s0022-3476(97)80017-0\u003c/li\u003e\n\u003cli\u003eChiappini E, Petrolini C, Caffarelli C, et al. Hexavalent vaccines in preterm infants: an update by Italian Society of Pediatric Allergy and Immunology jointly with the Italian Society of Neonatology. \u003cem\u003eItal J Pediatr\u003c/em\u003e. 2019;45(1):145. doi:10.1186/s13052-019-0742-7\u003c/li\u003e\n\u003cli\u003eCarbone T, McEntire B, Kissin D, et al. Absence of an increase in cardiorespiratory events after diphtheria-tetanus-acellular pertussis immunization in preterm infants: a randomized, multicenter study. \u003cem\u003ePediatrics\u003c/em\u003e. 2008;121(5):e1085-1090. doi:10.1542/peds.2007-2059\u003c/li\u003e\n\u003cli\u003eWysocki J, Center KJ, Brzostek J, et al. A randomized study of fever prophylaxis and the immunogenicity of routine pediatric vaccinations. \u003cem\u003eVaccine\u003c/em\u003e. 2017;35(15):1926-1935. doi:10.1016/j.vaccine.2017.02.035\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable 1. Infant Baseline Characteristics\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.58426966292135%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eCharacteristic\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.261637239165328%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal Cohort\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eN=127\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.261637239165328%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePre-Practice Change\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en=52\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.261637239165328%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePost-Practice Change\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en=75\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.630818619582664%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eP-value\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.58426966292135%\" valign=\"top\"\u003e\n \u003cp\u003eMale, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.261637239165328%\" valign=\"top\"\u003e\n \u003cp\u003e62 (48.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.261637239165328%\" valign=\"top\"\u003e\n \u003cp\u003e25 (48.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.261637239165328%\" valign=\"top\"\u003e\n \u003cp\u003e37 (49.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.630818619582664%\" valign=\"top\"\u003e\n \u003cp\u003e0.889\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.58426966292135%\" valign=\"top\"\u003e\n \u003cp\u003eGA, weeks, median (IQR)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.261637239165328%\" valign=\"top\"\u003e\n \u003cp\u003e28.6 (26.5-30.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.261637239165328%\" valign=\"top\"\u003e\n \u003cp\u003e28 (25.8-30.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.261637239165328%\" valign=\"top\"\u003e\n \u003cp\u003e29.3 (26.7-31.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.630818619582664%\" valign=\"top\"\u003e\n \u003cp\u003e0.06\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.58426966292135%\" valign=\"top\"\u003e\n \u003cp\u003eBirth weight, kg, median, (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.261637239165328%\" valign=\"top\"\u003e\n \u003cp\u003e1.08 (0.80-1.37)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.261637239165328%\" valign=\"top\"\u003e\n \u003cp\u003e0.94 (0.77-1.25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.261637239165328%\" valign=\"top\"\u003e\n \u003cp\u003e1.2 (0.84-1.43)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.630818619582664%\" valign=\"top\"\u003e\n \u003cp\u003e0.047\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.58426966292135%\" valign=\"top\"\u003e\n \u003cp\u003eBirth length, cm*, median, (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.261637239165328%\" valign=\"top\"\u003e\n \u003cp\u003e36.0 (33.0-39.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.261637239165328%\" valign=\"top\"\u003e\n \u003cp\u003e35 (32-37.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.261637239165328%\" valign=\"top\"\u003e\n \u003cp\u003e37 (33.5-40.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.630818619582664%\" valign=\"top\"\u003e\n \u003cp\u003e0.039\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.58426966292135%\" valign=\"top\"\u003e\n \u003cp\u003eMultiple birth, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.261637239165328%\" valign=\"top\"\u003e\n \u003cp\u003e32 (25.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.261637239165328%\" valign=\"top\"\u003e\n \u003cp\u003e15 (28.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.261637239165328%\" valign=\"top\"\u003e\n \u003cp\u003e17 (22.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.630818619582664%\" valign=\"top\"\u003e\n \u003cp\u003e0.430\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.58426966292135%\" valign=\"top\"\u003e\n \u003cp\u003eCLD, n (%)\u003c/p\u003e\n \u003cp\u003eMild, n (%)\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eModerate, n (%)\u003c/p\u003e\n \u003cp\u003eSevere, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.261637239165328%\" valign=\"top\"\u003e\n \u003cp\u003e71 (55.9)\u003c/p\u003e\n \u003cp\u003e21 (19.6)\u003c/p\u003e\n \u003cp\u003e39 (54.9)\u003c/p\u003e\n \u003cp\u003e11 (15.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.261637239165328%\" valign=\"top\"\u003e\n \u003cp\u003e33 (63.5)\u003c/p\u003e\n \u003cp\u003e6 (18.2)\u003c/p\u003e\n \u003cp\u003e19 (57.6)\u003c/p\u003e\n \u003cp\u003e8 (24.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.261637239165328%\" valign=\"top\"\u003e\n \u003cp\u003e38 (50.7)\u003c/p\u003e\n \u003cp\u003e15 (39.5)\u003c/p\u003e\n \u003cp\u003e20 (52.6)\u003c/p\u003e\n \u003cp\u003e3 (7.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.630818619582664%\" valign=\"top\"\u003e\n \u003cp\u003e0.153\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.58426966292135%\" valign=\"top\"\u003e\n \u003cp\u003eIVH, n (%)\u003c/p\u003e\n \u003cp\u003eGrade 1 or 2, n (%)\u003c/p\u003e\n \u003cp\u003eGrade 3 or 4, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.261637239165328%\" valign=\"top\"\u003e\n \u003cp\u003e41 (32.2)\u003c/p\u003e\n \u003cp\u003e36 (87.8)\u003c/p\u003e\n \u003cp\u003e5 (12.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.261637239165328%\" valign=\"top\"\u003e\n \u003cp\u003e16 (30.8)\u003c/p\u003e\n \u003cp\u003e13 (81.3)\u003c/p\u003e\n \u003cp\u003e3 (18.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.261637239165328%\" valign=\"top\"\u003e\n \u003cp\u003e25 (33.3)\u003c/p\u003e\n \u003cp\u003e23 (92.0)\u003c/p\u003e\n \u003cp\u003e2 (8.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.630818619582664%\" valign=\"top\"\u003e\n \u003cp\u003e0.569\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.58426966292135%\" valign=\"top\"\u003e\n \u003cp\u003eApnea of prematurity treated with caffeine, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.261637239165328%\" valign=\"top\"\u003e\n \u003cp\u003e109 (85.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.261637239165328%\" valign=\"top\"\u003e\n \u003cp\u003e44 (84.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.261637239165328%\" valign=\"top\"\u003e\n \u003cp\u003e65 (86.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.630818619582664%\" valign=\"top\"\u003e\n \u003cp\u003e0.744\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.58426966292135%\" valign=\"top\"\u003e\n \u003cp\u003eHistory of NEC, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.261637239165328%\" valign=\"top\"\u003e\n \u003cp\u003e4 (3.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.261637239165328%\" valign=\"top\"\u003e\n \u003cp\u003e3 (5.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.261637239165328%\" valign=\"top\"\u003e\n \u003cp\u003e1 (1.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.630818619582664%\" valign=\"top\"\u003e\n \u003cp\u003e0.304\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.58426966292135%\" valign=\"top\"\u003e\n \u003cp\u003eHistory of a positive culture, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.261637239165328%\" valign=\"top\"\u003e\n \u003cp\u003e53 (41.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.261637239165328%\" valign=\"top\"\u003e\n \u003cp\u003e29 (55.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.261637239165328%\" valign=\"top\"\u003e\n \u003cp\u003e24 (32)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.630818619582664%\" valign=\"top\"\u003e\n \u003cp\u003e0.008\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.58426966292135%\" valign=\"top\"\u003e\n \u003cp\u003eBaseline respiratory support, n (%)\u003c/p\u003e\n \u003cp\u003eFiO\u003csub\u003e2\u003c/sub\u003e, %, median, (IQR)\u003c/p\u003e\n \u003cp\u003eType of respiratory support\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eHFNC, n (%)\u003c/p\u003e\n \u003cp\u003eCPAP, n (%)\u003c/p\u003e\n \u003cp\u003eSiPAP, n (%)\u003c/p\u003e\n \u003cp\u003eETT, n (%)\u003c/p\u003e\n \u003cp\u003eNIMV, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.261637239165328%\" valign=\"top\"\u003e\n \u003cp\u003e63 (49.6)\u003c/p\u003e\n \u003cp\u003e25 (21-30)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e45 (71.4)\u003c/p\u003e\n \u003cp\u003e2 (3.2)\u003c/p\u003e\n \u003cp\u003e6 (9.5)\u003c/p\u003e\n \u003cp\u003e9 (14.3)\u003c/p\u003e\n \u003cp\u003e1 (1.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.261637239165328%\" valign=\"top\"\u003e\n \u003cp\u003e29 (55.8)\u003c/p\u003e\n \u003cp\u003e26 (23-30)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e20 (69.0)\u003c/p\u003e\n \u003cp\u003e2 (6.9)\u003c/p\u003e\n \u003cp\u003e2 (6.9)\u003c/p\u003e\n \u003cp\u003e4 (13.8)\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1 ( 3.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.261637239165328%\" valign=\"top\"\u003e\n \u003cp\u003e34 (45.3)\u003c/p\u003e\n \u003cp\u003e25 (21-27)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e25 (73.5)\u003c/p\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003cp\u003e4 (11.8)\u003c/p\u003e\n \u003cp\u003e5 (14.7)\u003c/p\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.630818619582664%\" valign=\"top\"\u003e\n \u003cp\u003e0.247\u003c/p\u003e\n \u003cp\u003e0.053\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"5\" valign=\"top\"\u003e\n \u003cp\u003e*Birth length only available for n=119\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2. Pre-Vaccine Characteristics\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"624\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"30.76923076923077%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eCharacteristic\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.346153846153847%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal Cohort\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eN=127\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.307692307692307%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePre-Practice Change\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en=52\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.26923076923077%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePost-Practice Change\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en=75\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.307692307692307%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eP-Value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"30.76923076923077%\" valign=\"top\"\u003e\n \u003cp\u003ePMA, weeks, median (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.346153846153847%\" valign=\"top\"\u003e\n \u003cp\u003e38.4 (36.6-40.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.307692307692307%\" valign=\"top\"\u003e\n \u003cp\u003e38.4 (36.6-40.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.26923076923077%\" valign=\"top\"\u003e\n \u003cp\u003e38.4 (36.7-40.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.307692307692307%\" valign=\"top\"\u003e\n \u003cp\u003e0.877\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"30.76923076923077%\" valign=\"top\"\u003e\n \u003cp\u003eWeight, kg, median \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n \u003cp\u003ePercentile Fenton Curve*, median (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.346153846153847%\" valign=\"top\"\u003e\n \u003cp\u003e2.59 (2.2-3.06)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e12 (2.87-25.66)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.307692307692307%\" valign=\"top\"\u003e\n \u003cp\u003e2.49 (2.18-3.09)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e8.21 (1.8-28.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.26923076923077%\" valign=\"top\"\u003e\n \u003cp\u003e2.6 (2.20-3.02)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e12.9 (3.6-22.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.307692307692307%\" valign=\"top\"\u003e\n \u003cp\u003e0.719\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.401\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"30.76923076923077%\" valign=\"top\"\u003e\n \u003cp\u003eInfants with \u003cu\u003e\u0026gt;\u003c/u\u003e 1 apnea of bradycardia event, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.346153846153847%\" valign=\"top\"\u003e\n \u003cp\u003e26 (20.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.307692307692307%\" valign=\"top\"\u003e\n \u003cp\u003e9 (17.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.26923076923077%\" valign=\"top\"\u003e\n \u003cp\u003e17 (22.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.307692307692307%\" valign=\"top\"\u003e\n \u003cp\u003e0.462\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"30.76923076923077%\" valign=\"top\"\u003e\n \u003cp\u003eBaseline apnea or bradycardia, median (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.346153846153847%\" valign=\"top\"\u003e\n \u003cp\u003e0 (0-0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.307692307692307%\" valign=\"top\"\u003e\n \u003cp\u003e0 (0-0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.26923076923077%\" valign=\"top\"\u003e\n \u003cp\u003e0 (0-0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.307692307692307%\" valign=\"top\"\u003e\n \u003cp\u003e0.435\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"30.76923076923077%\" valign=\"top\"\u003e\n \u003cp\u003eSupportive Care Agents Used\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.346153846153847%\" valign=\"top\"\u003e\n \u003cp\u003e--\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.307692307692307%\" valign=\"top\"\u003e\n \u003cp\u003e--\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.26923076923077%\" valign=\"top\"\u003e\n \u003cp\u003e--\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.307692307692307%\" valign=\"top\"\u003e\n \u003cp\u003e--\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"30.76923076923077%\" valign=\"top\"\u003e\n \u003cp\u003eAcetaminophen x1 dose, n (%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.346153846153847%\" valign=\"top\"\u003e\n \u003cp\u003e38 (29.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.307692307692307%\" valign=\"top\"\u003e\n \u003cp\u003e9 (17.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.26923076923077%\" valign=\"top\"\u003e\n \u003cp\u003e29 \u0026nbsp;(38.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.307692307692307%\" valign=\"top\"\u003e\n \u003cp\u003e0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"30.76923076923077%\" valign=\"top\"\u003e\n \u003cp\u003eAcetaminophen scheduled, n, (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.346153846153847%\" valign=\"top\"\u003e\n \u003cp\u003e35 (27.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.307692307692307%\" valign=\"top\"\u003e\n \u003cp\u003e11 (21.2)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.26923076923077%\" valign=\"top\"\u003e\n \u003cp\u003e24 (32.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.307692307692307%\" valign=\"top\"\u003e\n \u003cp\u003e0.179\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"30.76923076923077%\" valign=\"top\"\u003e\n \u003cp\u003eLMX/EMLA, n, (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.346153846153847%\" valign=\"top\"\u003e\n \u003cp\u003e1 (0.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.307692307692307%\" valign=\"top\"\u003e\n \u003cp\u003e1 (1.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.26923076923077%\" valign=\"top\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.307692307692307%\" valign=\"top\"\u003e\n \u003cp\u003e0.409\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"5\" valign=\"top\"\u003e\n \u003cp\u003e*Percentile Fenton Curve only available for n=121\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3. Outcomes\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"37.93677204658902%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eOutcome \u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.97504159733777%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal Cohort\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eN=127\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.97504159733777%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePre-Practice Change\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en=52\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.97171381031614%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePost-Practice Change\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en=75\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.141430948419302%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eP-value\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"37.93677204658902%\" valign=\"top\"\u003e\n \u003cp\u003eInfants with \u003cu\u003e\u0026gt;\u003c/u\u003e 1 apnea or bradycardia event, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.97504159733777%\" valign=\"top\"\u003e\n \u003cp\u003e47 (37.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.97504159733777%\" valign=\"top\"\u003e\n \u003cp\u003e19 (36.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.97171381031614%\" valign=\"top\"\u003e\n \u003cp\u003e28 (37.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.141430948419302%\" valign=\"top\"\u003e\n \u003cp\u003e0.927\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"37.93677204658902%\" valign=\"top\"\u003e\n \u003cp\u003eProlonged apnea, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.97504159733777%\" valign=\"top\"\u003e\n \u003cp\u003e8 (6.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.97504159733777%\" valign=\"top\"\u003e\n \u003cp\u003e4 (7.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.97171381031614%\" valign=\"top\"\u003e\n \u003cp\u003e4 (5.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.141430948419302%\" valign=\"top\"\u003e\n \u003cp\u003e0.715\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"37.93677204658902%\" valign=\"top\"\u003e\n \u003cp\u003eProlonged bradycardia, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.97504159733777%\" valign=\"top\"\u003e\n \u003cp\u003e40 (31.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.97504159733777%\" valign=\"top\"\u003e\n \u003cp\u003e15 (28.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.97171381031614%\" valign=\"top\"\u003e\n \u003cp\u003e25 (33.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.141430948419302%\" valign=\"top\"\u003e\n \u003cp\u003e0.592\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"37.93677204658902%\" valign=\"top\"\u003e\n \u003cp\u003eSevere event, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.97504159733777%\" valign=\"top\"\u003e\n \u003cp\u003e18 (14.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.97504159733777%\" valign=\"top\"\u003e\n \u003cp\u003e9 (17.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.97171381031614%\" valign=\"top\"\u003e\n \u003cp\u003e9 (12)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.141430948419302%\" valign=\"top\"\u003e\n \u003cp\u003e0.399\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"37.93677204658902%\" valign=\"top\"\u003e\n \u003cp\u003eAverage NPASS scores, median (IQR)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.97504159733777%\" valign=\"top\"\u003e\n \u003cp\u003e0 (0-0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.97504159733777%\" valign=\"top\"\u003e\n \u003cp\u003e0 (0-0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.97171381031614%\" valign=\"top\"\u003e\n \u003cp\u003e0 (0-0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.141430948419302%\" valign=\"top\"\u003e\n \u003cp\u003e0.770\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"37.93677204658902%\" valign=\"top\"\u003e\n \u003cp\u003eFever, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.97504159733777%\" valign=\"top\"\u003e\n \u003cp\u003e8 (6.3)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.97504159733777%\" valign=\"top\"\u003e\n \u003cp\u003e5 (9.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.97171381031614%\" valign=\"top\"\u003e\n \u003cp\u003e3 (4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.141430948419302%\" valign=\"top\"\u003e\n \u003cp\u003e0.271\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"37.93677204658902%\" valign=\"top\"\u003e\n \u003cp\u003eSepsis workup, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.97504159733777%\" valign=\"top\"\u003e\n \u003cp\u003e6 (4.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.97504159733777%\" valign=\"top\"\u003e\n \u003cp\u003e5 (9.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.97171381031614%\" valign=\"top\"\u003e\n \u003cp\u003e1 (1.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.141430948419302%\" valign=\"top\"\u003e\n \u003cp\u003e0.042\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"37.93677204658902%\" valign=\"top\"\u003e\n \u003cp\u003eRespiratory support at 48h, n (%)\u003c/p\u003e\n \u003cp\u003eFiO\u003csub\u003e2\u003c/sub\u003e, median, (IQR), n (%)\u003c/p\u003e\n \u003cp\u003eType of respiratory support\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eHFNC, n (%)\u003c/p\u003e\n \u003cp\u003eCPAP, n (%)\u003c/p\u003e\n \u003cp\u003eSiPAP, n (%)\u003c/p\u003e\n \u003cp\u003eETT, n (%)\u003c/p\u003e\n \u003cp\u003eNIMV, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.97504159733777%\" valign=\"top\"\u003e\n \u003cp\u003e60 (47.2)\u003c/p\u003e\n \u003cp\u003e25 (21-28)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e44 (73.3)\u003c/p\u003e\n \u003cp\u003e2 (3.3)\u003c/p\u003e\n \u003cp\u003e4 (6.7)\u003c/p\u003e\n \u003cp\u003e9 (15.0)\u003c/p\u003e\n \u003cp\u003e1 (1.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.97504159733777%\" valign=\"top\"\u003e\n \u003cp\u003e27 (51.9)\u003c/p\u003e\n \u003cp\u003e25 (23-30)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e19 (70.4)\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e2 (7.4)\u003c/p\u003e\n \u003cp\u003e1 (3.7)\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e4 (14.8)\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1 (3.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.97171381031614%\" valign=\"top\"\u003e\n \u003cp\u003e33 (44)\u003c/p\u003e\n \u003cp\u003e25 (21-28)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e25 (75.8)\u003c/p\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003cp\u003e3 (9.1)\u003c/p\u003e\n \u003cp\u003e5 (15.2)\u003c/p\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.141430948419302%\" valign=\"top\"\u003e\n \u003cp\u003e0.379\u003c/p\u003e\n \u003cp\u003e0.085\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"37.93677204658902%\" valign=\"top\"\u003e\n \u003cp\u003eEnteral feeds held, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.97504159733777%\" valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.97504159733777%\" valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.97171381031614%\" valign=\"top\"\u003e\n \u003cp\u003e0\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.141430948419302%\" valign=\"top\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"37.93677204658902%\" valign=\"top\"\u003e\n \u003cp\u003eVaccine schedule interruptions n (%)\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eMedian time to complete series, days, (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.97504159733777%\" valign=\"top\"\u003e\n \u003cp\u003e13 (10.2)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e5 (5-5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.97504159733777%\" valign=\"top\"\u003e\n \u003cp\u003e13 (25)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e5 (5-5.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.97171381031614%\" valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.141430948419302%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 4: Predictors of Severe Events\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"37.62376237623762%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eCharacteristic\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.871287128712872%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eSevere Events\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en=18\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.861386138613861%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eNo Severe Events\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en=109\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.782178217821784%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eOR (95% CI)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.861386138613861%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eP-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"37.62376237623762%\" valign=\"top\"\u003e\n \u003cp\u003eGA, weeks, median (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.871287128712872%\" valign=\"top\"\u003e\n \u003cp\u003e26.7 (25.0-27.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.861386138613861%\" valign=\"top\"\u003e\n \u003cp\u003e29.4 (26.6-31.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.782178217821784%\" valign=\"top\"\u003e\n \u003cp\u003e0.67 (0.529-0.849)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.861386138613861%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"37.62376237623762%\" valign=\"top\"\u003e\n \u003cp\u003eBirth weight, kg, median (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.871287128712872%\" valign=\"top\"\u003e\n \u003cp\u003e0.82 (0.67-0.92)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.861386138613861%\" valign=\"top\"\u003e\n \u003cp\u003e1.19 (0.87-1.46)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.782178217821784%\" valign=\"top\"\u003e\n \u003cp\u003e0.068 (0.011-0.429)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.861386138613861%\" valign=\"top\"\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"37.62376237623762%\" valign=\"top\"\u003e\n \u003cp\u003eBirth length, cm, median (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.871287128712872%\" valign=\"top\"\u003e\n \u003cp\u003e33 (31-35.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.861386138613861%\" valign=\"top\"\u003e\n \u003cp\u003e37 (33-40)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.782178217821784%\" valign=\"top\"\u003e\n \u003cp\u003e0.84 (0.731-0.965)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.861386138613861%\" valign=\"top\"\u003e\n \u003cp\u003e0.010\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"37.62376237623762%\" valign=\"top\"\u003e\n \u003cp\u003eCLD, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.871287128712872%\" valign=\"top\"\u003e\n \u003cp\u003e13 (72.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.861386138613861%\" valign=\"top\"\u003e\n \u003cp\u003e58 (53.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.782178217821784%\" valign=\"top\"\u003e\n \u003cp\u003e2.286 (0.763-6.854)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.861386138613861%\" valign=\"top\"\u003e\n \u003cp\u003e0.132\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"37.62376237623762%\" valign=\"top\"\u003e\n \u003cp\u003eIVH, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.871287128712872%\" valign=\"top\"\u003e\n \u003cp\u003e6 (33)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.861386138613861%\" valign=\"top\"\u003e\n \u003cp\u003e35 (32)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.782178217821784%\" valign=\"top\"\u003e\n \u003cp\u003e1.057 (0.367-3.049)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.861386138613861%\" valign=\"top\"\u003e\n \u003cp\u003e0.918\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"37.62376237623762%\" valign=\"top\"\u003e\n \u003cp\u003eApnea of prematurity treated with caffeine, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.871287128712872%\" valign=\"top\"\u003e\n \u003cp\u003e16 (88.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.861386138613861%\" valign=\"top\"\u003e\n \u003cp\u003e93 (85.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.782178217821784%\" valign=\"top\"\u003e\n \u003cp\u003e1.376 (0.288-6.568)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.861386138613861%\" valign=\"top\"\u003e\n \u003cp\u003e1.000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"37.62376237623762%\" valign=\"top\"\u003e\n \u003cp\u003eHistory of NEC, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.871287128712872%\" valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.861386138613861%\" valign=\"top\"\u003e\n \u003cp\u003e4 (3.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.782178217821784%\" valign=\"top\"\u003e\n \u003cp\u003e0.854 (0.793-0.918)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.861386138613861%\" valign=\"top\"\u003e\n \u003cp\u003e1.000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"37.62376237623762%\" valign=\"top\"\u003e\n \u003cp\u003eHistory of culture-proven sepsis, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.871287128712872%\" valign=\"top\"\u003e\n \u003cp\u003e8 (44.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.861386138613861%\" valign=\"top\"\u003e\n \u003cp\u003e45 (41.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.782178217821784%\" valign=\"top\"\u003e\n \u003cp\u003e1.138 (0.417-3.108)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.861386138613861%\" valign=\"top\"\u003e\n \u003cp\u003e0.801\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"37.62376237623762%\" valign=\"top\"\u003e\n \u003cp\u003eBaseline respiratory support, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.871287128712872%\" valign=\"top\"\u003e\n \u003cp\u003e10 (55.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.861386138613861%\" valign=\"top\"\u003e\n \u003cp\u003e53 (48.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.782178217821784%\" valign=\"top\"\u003e\n \u003cp\u003e1.321 (0.485-3.600)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.861386138613861%\" valign=\"top\"\u003e\n \u003cp\u003e0.586\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"37.62376237623762%\" valign=\"top\"\u003e\n \u003cp\u003eBaseline apnea or bradycardia, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.871287128712872%\" valign=\"top\"\u003e\n \u003cp\u003e8 (44.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.861386138613861%\" valign=\"top\"\u003e\n \u003cp\u003e18 (16.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.782178217821784%\" valign=\"top\"\u003e\n \u003cp\u003e4.044 (1.404-11.654)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.861386138613861%\" valign=\"top\"\u003e\n \u003cp\u003e0.012\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"37.62376237623762%\" valign=\"top\"\u003e\n \u003cp\u003eAcetaminophen, x1 dose, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.871287128712872%\" valign=\"top\"\u003e\n \u003cp\u003e4 (22.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.861386138613861%\" valign=\"top\"\u003e\n \u003cp\u003e34 (31.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.782178217821784%\" valign=\"top\"\u003e\n \u003cp\u003e0.630 (0.193-2.057)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.861386138613861%\" valign=\"top\"\u003e\n \u003cp\u003e0.441\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"37.62376237623762%\" valign=\"top\"\u003e\n \u003cp\u003eAcetaminophen, scheduled, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.871287128712872%\" valign=\"top\"\u003e\n \u003cp\u003e2 (11.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.861386138613861%\" valign=\"top\"\u003e\n \u003cp\u003e33 (30.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.782178217821784%\" valign=\"top\"\u003e\n \u003cp\u003e0.288 (0.063-1.324)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.861386138613861%\" valign=\"top\"\u003e\n \u003cp\u003e0.152\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"journal-of-perinatology","isNatureJournal":false,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"jp","sideBox":"Learn more about [Journal of Perinatology](http://www.nature.com/jp/)","snPcode":"41372","submissionUrl":"https://mts-jper.nature.com/cgi-bin/main.plex","title":"Journal of Perinatology","twitterHandle":"@jperinatology","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-4331667/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4331667/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eObjective:\u003c/strong\u003e To evaluate the incidence of cardiorespiratory events in preterm infants when administering the 2-month vaccine series all at once compared to spreading vaccines over multiple days.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStudy Design:\u003c/strong\u003e This single-center, retrospective cohort study from 2019-2022 included preterm neonates receiving 2-month immunizations. The primary outcome was incidence of cardiorespiratory events from time of initial vaccine administration up to 48 hours after final administration. Univariate analysis performed to identify predictors of primary outcome.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003eThere were 127 patients (n1=52, n2=75) included. There was no difference in the number of cardiorespiratory events between groups. Predictors of severe event included younger gestational age, smaller birth weight, smaller birth length, and higher baseline apnea or bradycardia events at baseline. Vaccine schedule interruptions occur more often when administration is spread over multiple days.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion: \u003c/strong\u003eAdministration of routine 2-month vaccinations all at once was not associated with increased cardiorespiratory events and prevents interruptions to vaccine schedule.\u003c/p\u003e","manuscriptTitle":"Don’t Wait, Vaccinate: Evaluation of Routine Immunization Administration and Reactogenecity in Preterm Infants","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-05-09 02:16:55","doi":"10.21203/rs.3.rs-4331667/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"revise","date":"2024-05-23T13:14:24+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"This content is not available.","date":"2024-05-23T04:04:53+00:00","index":2,"fulltext":"This content is not available."},{"type":"editorInvitedReview","content":"This content is not available.","date":"2024-05-14T00:51:23+00:00","index":1,"fulltext":"This content is not available."},{"type":"reviewerAgreed","content":"This content is not available.","date":"2024-05-02T16:38:58+00:00","index":2,"fulltext":"This content is not available."},{"type":"reviewerAgreed","content":"This content is not available.","date":"2024-05-01T13:27:19+00:00","index":1,"fulltext":"This content is not available."},{"type":"reviewersInvited","content":"","date":"2024-04-30T09:40:01+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-04-29T10:26:20+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-04-26T21:46:55+00:00","index":"","fulltext":""},{"type":"submitted","content":"Journal of Perinatology","date":"2024-04-26T21:46:55+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"journal-of-perinatology","isNatureJournal":false,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"jp","sideBox":"Learn more about [Journal of Perinatology](http://www.nature.com/jp/)","snPcode":"41372","submissionUrl":"https://mts-jper.nature.com/cgi-bin/main.plex","title":"Journal of Perinatology","twitterHandle":"@jperinatology","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"acfeb36b-fc6b-4916-94eb-83fb922bc231","owner":[],"postedDate":"May 9th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":31343921,"name":"Health sciences/Health care/Paediatrics"},{"id":31343922,"name":"Health sciences/Health care/Disease prevention/Preventive medicine"}],"tags":[],"updatedAt":"2024-09-11T07:07:03+00:00","versionOfRecord":{"articleIdentity":"rs-4331667","link":"https://doi.org/10.1038/s41372-024-02111-1","journal":{"identity":"journal-of-perinatology","isVorOnly":false,"title":"Journal of Perinatology"},"publishedOn":"2024-09-10 04:00:00","publishedOnDateReadable":"September 10th, 2024"},"versionCreatedAt":"2024-05-09 02:16:55","video":"","vorDoi":"10.1038/s41372-024-02111-1","vorDoiUrl":"https://doi.org/10.1038/s41372-024-02111-1","workflowStages":[]},"version":"v1","identity":"rs-4331667","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4331667","identity":"rs-4331667","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}