An Integrative Literature Review: Two-

Month Vaccines for Infants in the Neonatal Intensive Care Unit

Catherine C. Wilson, MSN, NNP, FNP Barbara Graves, PhD, RN

Vaccines in neonates why?

O Infants depend on passive immunity O The majority of passive immunity O So premature infant miss out O Also passive immunity ends sooner O Put premature infants at risk

Whitlow & Forsythe, 2011

Present Guidelines

O APA developed in 2003O Vaccines should be given when dueO The only exception is the Hepatitis B

vaccine

(Sarri, 2003)

The ProblemO Vaccines are not given per guidelines

O DelayO TogetherO SeparateO Not at all

(Allnurses, 2012; Demirjian & Levy, 2009).

If there is a problem?O Have there been people looking at

this problemO What dose the research say

Integrative Literature Review

O Review literature to develop stronger evidence

O Systematic review O Each article is evaluated O If possible conclusion are made

This ILRO PRISMA the preferred reporting tool

systematic reviews and meta-analyses methodology

(Liberati et al., 2009)

Search Criteria O Search Terms

O Premature infantO NeonateO VaccinesO Care, neonatal intensive AdverseO ApneaO Bradycardia

Search Criteria Cont.O Inclusion Criteria

O EnglishO Studies that focused on any of the normal two

month vaccine (DTaP/IPV/PCV/HBV/HiB) given in the NICU

O Exclusion Criteria O Non-EnglishO Non-systematic reviewsO Studies focused on:

O Reoccurrence of adverse reactions with 4 month dosing Involving older vaccines not currently used. Involving discharged infants

Identification Chart

9955 articles identified

8329 after duplication removed

1449 abstracts reviewed 1429

eliminated

20 full articles reviewed

9 included

Safety of DTaP-based combined immunization in very-low-birth-weight premature infants: Frequent but mostly

benign cardiorespiratory events.

O 47% of infants with a history of apnea, bradycardia, and/or desaturations events experienced ≥50% more events after vaccines.

O Infants not having events prior to vaccines 13% had apnea, bradycardia, or desaturation after vaccines.

O Bag-mask ventilation, CPAP, or mechanical ventilation was required in 6% of infants after vaccines.

O Ongoing apnea, bradycardia, and oxygen desaturations were associated with an increase risk of adverse reactions.

O However, neither gestational age nor birth weight alone predicted adverse outcomes.

O Funded in part by a manufacturer of vaccine, Glaxo Smith Kline (GSK).

O Immunizing infant between 50 and 60 days if discharge is planned within the next 10 to 20 days, the infant is clinically stable and free from severe cardiorespiratory episodes.

Pfister et al. (2004)

Apnoea and bradycardia in preterm infants following immunisation with pentavalent or

hexavalent vaccinesO Study of infants with stable respiratory status O Found vaccine related apnea and bradycardia in 13% of the

sample. O They defined a vaccine related apnea as ≥50% above baseline

apnea and bradycardia or recurrences of apnea and bradycardia in infants not currently having any.

O Beyond apnea bradycardia five of the infants needed repeated tactile stimulation, three needed supplemental oxygen, and one needed bag mask ventilation. The infants in this sample were considered low risk they were not's receiving any respiratory support or supplemental oxygen at the time of vaccination.

O For the infants with vaccine related apnea bradycardia most episodes resolved within 48 hours.

O From this study researchers recommended monitoring infants for 48 hours after vaccines.

Schulzke, Heininger, Lucking-Famira, & Fahnenstich (2005)

Adverse reactions to immunization with newer vaccines in the very preterm infant

O Sought to compare the adverse reaction rate of the newer DTaP vaccine as compare with the older DTPw.

O Adverse reaction rates to be the sameO Interestingly, they found a 27% increase in apnea

in infants given three vaccines at once compared to 9% in infants given only two vaccines at once not statistically significant.

O Fever 33% of infants. O Sepsis evaluations in 8% in their infants, but no

proven sepsis. There were no serious events requiring assisted ventilation. They recommended monitoring post vaccinations.

Ellison, Davis, & Doyle (2005)

Safety of DTaP-IPV-HIb-HBV hexavalent vaccine in very premature infants.

O Rexamined the safety of a combined DTaP/IPV/Hib/HBV vaccine in infants less than 31 week gestation

O Prospective observational studyO Assess apnea, bradycardia, and oxygen desaturation while

also assessing cerebral blood flow and electrocardiogram changes associated with vaccine administration.

O Showed no change in cerebral blood flow or electrocardiogram changes

O But overall cardiorespiratory event (CRE) rate that required medical support in 11% of the premature infants and 21.7% among chronically ill premature infant.

O Present state of illness was the most predictive factorO Strongly recommendation to immunizing and monitoring

infants before hospital discharge.

Faldella, Galletti, Corvaglia, Ancora, & Alessandroni (2007)

Primary immunization of premature infants with gestational age <35 weeks: Cardiorespiratory complications and C-

Reactive Protein responses associated with administration of single and multiple

separate vaccines simultaneouslyO First time, the effect of vaccines on C-reactive protein (CRP)

levels and CRE rates when vaccines were given one at a time compared to multiple vaccines given at the same time.

O They conducted a prospective observational study of 239 infants. The actual number of subjects tested with each single vaccine was low, but provides an area for further research.

O Among the single vaccines DTaP (22%) had the highest incidence of CRE followed by PCV7 (12%) and Hib (11%).

O HVB had none and IPV only had a 3% incidence rate of CRE. O Over all immunization-associated CRE were four times more

likely (32%) in the infants given multiple vaccines at the same time.

(Pourcyrous, Korones, Arheart, & Bada, 2007)

American Academy of Pediatrics: Clinical report guidance for the clinician in rendering pediatric care: Immunization of preterm and low birth weight infants

O To find predictors of apnea in infants who had not been apneic prior to vaccination.

O Chart review of immunized infants from 1997 to 2003 O The sample size appears large (N= 497) but 73 infants were only given

HBV 41 infants were 31 weeks gestation or over. They did not breakdown the number in each of these two groups who only received the HBV. Infants in their study were given their vaccine over 1 to 4 days.

O At the start of the study infants were given a DTPw vaccine later changed to DTaP.

O Rate of apnea for the DTPw was 11.9% and 13.5% for DTaPO Two infant required intubation. O They did not break out if apnea was more common amongst the infants

given vaccines simultaneously or divided. O Concluded that infants less than 2000 grams at vaccination and those less

than 67 days old were at the highest risk for apnea post-immunization and that pre-immunization apnea was the best predictor of post-immunization apnea.

(Klein et al., 2008)

Absence of an increase in cardiorespiratory events after diphtheria-tetanus-acellular

pertussis immunization in preterm infants: a randomized multicenter study.

O Relationship between DTaP and CRE in stable premature infant O Study was done over four years in 10 units in the USO Study group were monitored 24 hours before and 48 hours after

only the DTaP vaccine. O Control group were monitored for 72 hours. O Subjected selected by neonatologists only infants stable

enough for study O Found no difference in the rate of CRE between the two groups. O Sample size of 191O This was the only study not to find apnea related to vaccines. O Bias is possible because they included only infant at very low

risk for post-vaccine apnea (Hacking et al., 2010). O Recommended giving vaccines per AAP recommendations

(Carbone et al., 2008).

Summary proceedings from the

apnea-of-prematurity group. O Prospective observational study adverse events of vaccines in VLBW

O Conducted over eight years from 1998 to 2006. O Divided their study into three groups. Groups A and B were

combined for statistical purposes since they included the same vaccines in different combinations.

O Group A was DTaP/Hib/IPV and a separate HBV. Group B were given DTaP/Hib/IPV/HBV combination vaccine (this vaccine is not licensed in the US, see Table 1).

O Group C, the same combinations of vaccine were used along with PVC7.

O Concluded extreme prematurity and birth weight less than 999 was a significant risk factor for apnea and bradycardia.

O They found that more “severe adverse events” occurred in 10.8% of infants overall and was significantly higher (14.2%) in group C.

O Concluded that vaccination is safe for the smallest infants, but CRE adverse reactions can occur.

(Furch, Richter, & Kattner, 2010)

Frequency of respiratory deterioration after immunisation in preterm infants

O RetrospectiveO examined the frequency of respiratory deterioration after

vaccines in the NICU. O Study acknowledging that apnea and bradycardia existed

after vaccines for some infants. O Purpose: to identify the portion of infants who would need

the most extreme intervention after the vaccines. O Found that a small number of extremely low birth weight

infants especially those with significant lung disease and previous septicemia were at risk for respiratory deterioration.

O Twenty-two (5.35%) of the 411infants <1000 gram infants who received vaccines in the NICU needed ventilation or CPAP

O Recommend further study and administering the vaccines in the hospital where ventilation support exists.

(Hacking, Davis, Wong, Wheeler, & McVernon, 2010)

Limitations O Lack of RCT O Studies reviewed cover a long time

period and involves several different combinations of vaccines. O Only three studies involved the PCV7

and none involved the PCV13 now recommended.

Conclusions

O Promote the best and safest care possibleO They want to vaccinate all infant according to current recommendation while limiting

or eliminating the frequency of apnea and bradycardia experienced by the infants. O Vaccines given in the two-month period put some infants at greater risk for CRE. O The dilemma is how to vaccinate infants in the NICU with the least amount of riskO Vaccinating infants in the NICU is the best way to prevent vaccine related illness, O Risk of adverse side effects ranges from 9 to 47% for general apnea and bradycardia

and 6% risk for severe apnea and bradycardia requiring intervention. O Risk of apnea, bradycardia, and oxygen desaturation increased with the administration

of multiple vaccines.O Two vaccines that appear highest risk are the DTaP and PCVO The risk of apnea and bradycardia is highest after the first 48 to 72 hours with the O Lastly, evidence supports that the smallest and infants and those with chronic illness

babies are at a greater risk for CREO Using these findings, updated recommendations are possible to decrease the rate of

apnea and bradycardia after vaccines.

RecommendationsO Birth weights of 1,000 grams or less, those with apnea

and bradycardia or who have had a more complicated clinical course, should have the DTaP containing vaccine and the PCV vaccine separated by 48 hours

O should remain in the hospital for 48 hours after vaccines for cardiorespiratory and saturation monitoring before discharge.

O Two-month vaccines in the hospital setting. Therefore, if vaccines are due within 10 days of discharge they should be given in the NICU.

O From this ILR it is evident that more research is needed. There is a clear need for well-designed prospective RCT studies and further development of clinical practice guidelines for vaccinating infants in the NICU.

References O Allnurses. (2012). Vaccinations in the NICU [Blog comment]. Retrieved from

http://allnurses.com/nicu-nursing-neonatal/vaccinations-in-nicu-763804.htmlO Carbone, T., McEntire, B., Kissin, D., Kelly, D., Steinschneider, A., Violaris, K., &

Karamchandani, N. (2008, May). Absence of an increase in cardiorespiratory events after diphtheria-tetanus-acellular pertussis immunization in preterm infants: a randomized multicenter study. Pediatrics, 121(5), E1085-1090. http://dx.doi.org/10.1542/peds.2007-2059

O Demirjian, A., & Levy, O. (2009). Safety and efficacy of neonatal vaccination. European Journal of Immunology, 39(1), 36-46. http://dx.doi.org/10.1002/eji.2008386

O Ellison, V. J., Davis, P. G., & Doyle, L. W. (2005). Adverse reactions to immunization with newer vaccines in the very preterm infant. Journal of Paediatrics and Child Health, 41, 441-443. Faldella, G., Galletti, S., Corvaglia, L., Ancora, G., & Alessandroni, R. (2007, January). Safety of DTaP-IPV-HIb-HBV hexavalent vaccine in very premature infants. Vaccine, 25, 1036-1042. Retrieved from www.sciencedirect.com.libdata.lib.ua.edu/science/article/pii/S0264410X06010693

O Finer, N. N., Higgins, R., Kettwinkel, J., & Martin, R. J. (2006). Summary proceedings from the apnea-of-prematurity group. Pediatrics, 117, S47-S51. http://dx.doi.org/10.1542/peds.2005-0620H

O Hacking, D. F., Davis, P. G., Wong, E., Wheeler, K., & McVernon, J. (2010, March 4). Frequency of respiratory deterioration after immunisation in preterm infants. Journal of Paediatrics and Child Health, 46, 742-748. http://dx.doi.org/10.111/j/1440-1754.2010.01832.x

O Klein, N. P., Massolo, M. L., Greene, J., Dekker, C. L., Black, S., & Escobar, G. J. (2008). Risk factors for developing apnea after immunization in the neonatal intensive care unit. Pediatrics, 121(3), 463-469. http://dx.doi.org/10.1542/peds.2007-1462

References Cont.O Liberati, A., Altman, D. G., Tetzlaff, J., Mulrow, C., Gotzsche, P. C., Aloannidis, J. P…

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O Pfister, R. E., Aeschbach, V., Niksic-Stuber, V., Martin, B. C., & Siegrist, C. (2004). Safety of DTaP-based combined immunization in very-low-birth-weight premature infants: Frequent but mostly benign cardiorespiratory events. The Journal of Pediatrics, 145(1), 58-66. http://dx.doi.org/10.1016/j.jpeds.2004.04.006

O Pourcyrous, M., Korones, S. B., Arheart, K. L., & Bada, H. S. (2007). Primary immunization of premature infants with gestational age <35 weeks: Cardiorespiratory complications and C-Reactive Protein responses associated with administration of single and multiple separate vaccines simultaneously. The Journal of Pediatrics, 151(2), 167-172.

O Saari, T. N. (2003, July). American Academy of Pediatrics: Clinical report guidance for the clinician in rendering pediatric care: Immunization of preterm and low birth weight infants. Pediatrics, 112, 193-198. Retrieved from http://pediatrics.aappublications.org/content/112/1/193.full.html

O Schulz, S., Heininger, U., Lucking-Famira, M., & Fahnenstich, H. (2005). Apnoea and bradycardia in preterm infants following immunisation with pentavalent or hexavalent vaccines. European Journal of Pediatrics, 164, 432-435. http://dx.doi.org/10.1007/s00431-005-1674-3

O Whitlow, P., & Forsythe, P. L. (2011). Update on immunizations commonly used in the NICU. Advances in Neonatal Care, 3(3), 173-179. Retrieved from http://www.nursingcenter.com/lnc/static?pageid=1204049