1. Adverse Events After Routine Immunization of Extremely Low-Birth-Weight Infants
Abstract
“Importance
Immunization of extremely low-birth-weight (ELBW) infants in the neonatal intensive care unit (NICU) is associated with adverse events, including fever and apnea or bradycardia, in the immediate postimmunization period. These adverse events present a diagnostic dilemma for physicians, leading to the potential for immunization delay and sepsis evaluations.
Objective
To compare the incidence of sepsis evaluations, need for increased respiratory support, intubation, seizures, and death among immunized ELBW infants in the 3 days before and after immunization.
Design, Setting, and Participants
In this multicenter retrospective cohort study, we studied 13 926 ELBW infants born at 28 weeks’ gestation or less who were discharged from January 1, 2007, through December 31, 2012, from 348 NICUs managed by the Pediatrix Medical Group.
Exposures
At least one immunization between the ages of 53 and 110 days.
Main Outcomes and Measures
Incidence of sepsis evaluations, need for increased respiratory support, intubation, seizures, and death.
Results
Most of the 13 926 infants (91.2%) received 3 or more immunizations. The incidence of sepsis evaluations increased from 5.4 per 1000 patient-days in the preimmunization period to 19.3 per 1000 patient-days in the postimmunization period (adjusted rate ratio [ARR], 3.7; 95% CI, 3.2-4.4). The need for increased respiratory support increased from 6.6 per 1000 patient-days in the preimmunization period to 14.0 per 1000 patient-days in the postimmunization period (ARR, 2.1; 95% CI, 1.9-2.5), and intubation increased from 2.0 per 1000 patient-days to 3.6 per 1000 patient-days (ARR, 1.7; 95% CI, 1.3-2.2). The postimmunization incidence of adverse events was similar across immunization types, including combination vaccines when compared with single-dose vaccines. Infants who were born at 23 to 24 weeks’ gestation had a higher risk of sepsis evaluation and intubation after immunization. A prior history of sepsis was associated with higher risk of sepsis evaluation after immunization.
Conclusions and Relevance
All ELBW infants in the NICU had an increased incidence of sepsis evaluations and increased respiratory support and intubation after routine immunization. Our findings provide no evidence to suggest that physicians should not use combination vaccines in ELBW infants. Further studies are needed to determine whether timing or spacing of immunization administrations confers risk for the developing adverse events and whether a prior history of sepsis confers risk for an altered immune response in ELBW infants.“
Links
http://jamanetwork.com/journals/jamapediatrics/fullarticle/2300376#95589747
Citations
Demeo, Stephen D., Sudha R. Raman, Christoph P. Hornik, Catherine C. Wilson, Reese Clark, and P. Brian Smith. "Adverse Events After Routine Immunization of Extremely Low-Birth-Weight Infants." JAMA Pediatrics 169.8 (2015): 740.
“Importance
Immunization of extremely low-birth-weight (ELBW) infants in the neonatal intensive care unit (NICU) is associated with adverse events, including fever and apnea or bradycardia, in the immediate postimmunization period. These adverse events present a diagnostic dilemma for physicians, leading to the potential for immunization delay and sepsis evaluations.
Objective
To compare the incidence of sepsis evaluations, need for increased respiratory support, intubation, seizures, and death among immunized ELBW infants in the 3 days before and after immunization.
Design, Setting, and Participants
In this multicenter retrospective cohort study, we studied 13 926 ELBW infants born at 28 weeks’ gestation or less who were discharged from January 1, 2007, through December 31, 2012, from 348 NICUs managed by the Pediatrix Medical Group.
Exposures
At least one immunization between the ages of 53 and 110 days.
Main Outcomes and Measures
Incidence of sepsis evaluations, need for increased respiratory support, intubation, seizures, and death.
Results
Most of the 13 926 infants (91.2%) received 3 or more immunizations. The incidence of sepsis evaluations increased from 5.4 per 1000 patient-days in the preimmunization period to 19.3 per 1000 patient-days in the postimmunization period (adjusted rate ratio [ARR], 3.7; 95% CI, 3.2-4.4). The need for increased respiratory support increased from 6.6 per 1000 patient-days in the preimmunization period to 14.0 per 1000 patient-days in the postimmunization period (ARR, 2.1; 95% CI, 1.9-2.5), and intubation increased from 2.0 per 1000 patient-days to 3.6 per 1000 patient-days (ARR, 1.7; 95% CI, 1.3-2.2). The postimmunization incidence of adverse events was similar across immunization types, including combination vaccines when compared with single-dose vaccines. Infants who were born at 23 to 24 weeks’ gestation had a higher risk of sepsis evaluation and intubation after immunization. A prior history of sepsis was associated with higher risk of sepsis evaluation after immunization.
Conclusions and Relevance
All ELBW infants in the NICU had an increased incidence of sepsis evaluations and increased respiratory support and intubation after routine immunization. Our findings provide no evidence to suggest that physicians should not use combination vaccines in ELBW infants. Further studies are needed to determine whether timing or spacing of immunization administrations confers risk for the developing adverse events and whether a prior history of sepsis confers risk for an altered immune response in ELBW infants.“
Links
http://jamanetwork.com/journals/jamapediatrics/fullarticle/2300376#95589747
Citations
Demeo, Stephen D., Sudha R. Raman, Christoph P. Hornik, Catherine C. Wilson, Reese Clark, and P. Brian Smith. "Adverse Events After Routine Immunization of Extremely Low-Birth-Weight Infants." JAMA Pediatrics 169.8 (2015): 740.
2. A modified self-controlled case series method to examine association between multidose vaccinations and death
Abstract
“The self-controlled case series method (SCCS) was developed to analyze the association between a time-varying exposure and an outcome event. We consider penta- or hexavalent vaccination as the exposure and unexplained sudden unexpected death (uSUD) as the event. The special situation of multiple exposures and a terminal event requires adaptation of the standard SCCS method. This paper proposes a new adaptation, in which observation periods are truncated according to the vaccination schedule. The new method exploits known minimum spacings between successive vaccine doses. Its advantage is that it is very much simpler to apply than the method for censored, perturbed or curtailed post-event exposures recently introduced. This paper presents a comparison of these two SCCS methods by simulation studies and an application to a real data set. In the simulation studies, the age distribution and the assumed vaccination schedule were based on real data. Only small differences between the two SCCS methods were observed, although 50 per cent of cases could not be included in the analysis with the SCCS method with truncated observation periods. By means of a study including 300 uSUD, a 16-fold risk increase after the 4th dose could be detected with a power of at least 90 per cent. A general 2-fold risk increase after vaccination could be detected with a power of 80 per cent. Reanalysis of data from cases of the German case–control study on sudden infant death (GeSID) resulted in slightly higher point estimates using the SCCS methods than the odds ratio obtained by the case–control analysis. Copyright © 2010 John Wiley & Sons, Ltd.”
Links
https://www.ncbi.nlm.nih.gov/pubmed/21337361
Citations
Kuhnert, Ronny, Hartmut Hecker, Christina Poethko-Müller, Martin Schlaud, Mechtild Vennemann, Heather J. Whitaker, and C. Paddy Farrington. "A Modified Self-controlled Case Series Method to Examine Association between Multidose Vaccinations and Death." Statistics in Medicine 30.6 (2010): 666-77
“The self-controlled case series method (SCCS) was developed to analyze the association between a time-varying exposure and an outcome event. We consider penta- or hexavalent vaccination as the exposure and unexplained sudden unexpected death (uSUD) as the event. The special situation of multiple exposures and a terminal event requires adaptation of the standard SCCS method. This paper proposes a new adaptation, in which observation periods are truncated according to the vaccination schedule. The new method exploits known minimum spacings between successive vaccine doses. Its advantage is that it is very much simpler to apply than the method for censored, perturbed or curtailed post-event exposures recently introduced. This paper presents a comparison of these two SCCS methods by simulation studies and an application to a real data set. In the simulation studies, the age distribution and the assumed vaccination schedule were based on real data. Only small differences between the two SCCS methods were observed, although 50 per cent of cases could not be included in the analysis with the SCCS method with truncated observation periods. By means of a study including 300 uSUD, a 16-fold risk increase after the 4th dose could be detected with a power of at least 90 per cent. A general 2-fold risk increase after vaccination could be detected with a power of 80 per cent. Reanalysis of data from cases of the German case–control study on sudden infant death (GeSID) resulted in slightly higher point estimates using the SCCS methods than the odds ratio obtained by the case–control analysis. Copyright © 2010 John Wiley & Sons, Ltd.”
Links
https://www.ncbi.nlm.nih.gov/pubmed/21337361
Citations
Kuhnert, Ronny, Hartmut Hecker, Christina Poethko-Müller, Martin Schlaud, Mechtild Vennemann, Heather J. Whitaker, and C. Paddy Farrington. "A Modified Self-controlled Case Series Method to Examine Association between Multidose Vaccinations and Death." Statistics in Medicine 30.6 (2010): 666-77
3. Active Immunization of Premature and Low Birth-Weight Infants
Abstract
“Preterm infants are at increased risk of disease and hospitalization from a number of vaccine-preventable diseases. However, these same infants have immunologic immaturities that may impact vaccine responses. Larger premature infants mount immune responses to vaccines similar to those of full-term infants, but very premature infants (<28-32 weeks' gestation at birth) may have specific defects in vaccine responsiveness. Although there are minor differences in immunogenicity, the immune responses to diphtheria, tetanus, pertussis, and polio antigens are similar enough between full-term and premature infants that clinical consequences are unlikely to result. However, the immunogenicity of Haemophilus influenzae type b conjugate vaccines varies widely among studies of premature infants, and may be affected by the choice of conjugate protein, inclusion in a combination vaccine, and by an infant's overall health. Pneumococcal conjugate vaccine is efficacious in larger premature infants, but little information is available about immunogenicity in smaller premature infants. Meningococcal group C conjugate vaccine appears immunogenic in even very premature infants, but the duration of immunity may be limited. Hepatitis B vaccine given at birth appears poorly immunogenic in infants with birth weights <1500-2000 g, with delay in the administration of the first dose yielding improved immunogenicity. Few data on influenza vaccine in premature infants are available, but infants with pulmonary disease may respond less robustly than others. Bacille Calmette Guérin vaccine appears to be most immunogenic if delayed until at least 34-35 weeks' postmenstrual age in very premature infants, although there may be non-specific advantages to its earlier administration. Premature infants may have persistently lower antibody titers than full-term infants, even years after initial immunization. Sick premature infants experience increased episodes of apnea or cardiorespiratory compromise following vaccine administration, necessitating careful monitoring. Specific factors that impair immune response, quality of the immune response, and safety and immunogenicity evaluation of new vaccines in premature infants are topics needing further research. Premature infants are at significant risk for decisions from healthcare providers that delay beginning and completing their vaccine regimens. A major challenge facing those who care for these infants is the provision of timely immunization.”
Links
https://www.ncbi.nlm.nih.gov/pubmed/17291134
Citations
D'Angio, Carl T. "Active Immunization of Premature and Low Birth-Weight Infants." Pediatric Drugs 9.1 (2007): 17-32.
“Preterm infants are at increased risk of disease and hospitalization from a number of vaccine-preventable diseases. However, these same infants have immunologic immaturities that may impact vaccine responses. Larger premature infants mount immune responses to vaccines similar to those of full-term infants, but very premature infants (<28-32 weeks' gestation at birth) may have specific defects in vaccine responsiveness. Although there are minor differences in immunogenicity, the immune responses to diphtheria, tetanus, pertussis, and polio antigens are similar enough between full-term and premature infants that clinical consequences are unlikely to result. However, the immunogenicity of Haemophilus influenzae type b conjugate vaccines varies widely among studies of premature infants, and may be affected by the choice of conjugate protein, inclusion in a combination vaccine, and by an infant's overall health. Pneumococcal conjugate vaccine is efficacious in larger premature infants, but little information is available about immunogenicity in smaller premature infants. Meningococcal group C conjugate vaccine appears immunogenic in even very premature infants, but the duration of immunity may be limited. Hepatitis B vaccine given at birth appears poorly immunogenic in infants with birth weights <1500-2000 g, with delay in the administration of the first dose yielding improved immunogenicity. Few data on influenza vaccine in premature infants are available, but infants with pulmonary disease may respond less robustly than others. Bacille Calmette Guérin vaccine appears to be most immunogenic if delayed until at least 34-35 weeks' postmenstrual age in very premature infants, although there may be non-specific advantages to its earlier administration. Premature infants may have persistently lower antibody titers than full-term infants, even years after initial immunization. Sick premature infants experience increased episodes of apnea or cardiorespiratory compromise following vaccine administration, necessitating careful monitoring. Specific factors that impair immune response, quality of the immune response, and safety and immunogenicity evaluation of new vaccines in premature infants are topics needing further research. Premature infants are at significant risk for decisions from healthcare providers that delay beginning and completing their vaccine regimens. A major challenge facing those who care for these infants is the provision of timely immunization.”
Links
https://www.ncbi.nlm.nih.gov/pubmed/17291134
Citations
D'Angio, Carl T. "Active Immunization of Premature and Low Birth-Weight Infants." Pediatric Drugs 9.1 (2007): 17-32.
4. Adverse cardiorespiratory events following primary vaccination of very low birth weight infants
Abstract
“Objective:
To examine the relationship between primary vaccination of preterm infants and prevalence ratios of associated factors for unwanted cardiorespiratory events, following the recommendation of the Centers for Disease Control and Prevention Advisory Committee on Immunization Practices for immunization of preterm infants at 2 months of chronological age.
Methods:
Two-year retrospective study of very low birth weight infants receiving their primary vaccination. Major cardiorespiratory events, such as apnea, bradycardia, SpO2 desaturation, and minor adverse events, such as temperature instability, poor handling and local reactions, were recorded. Prevalence ratio with 95% confidence interval for associated factors between infants with and without cardiorespiratory events was calculated.
Results:
Eighty neonates were studied (median [range] birth weight 970 g [428-1,490]), gestational age of 27.4 weeks (23.3-33). Adverse reactions occurred in 35 (44%) patients: minor events in 19 (24%), major events in 28 (35%). Infants with major events had significantly lower gestational age (p = 0.008) and a higher incidence of bronchopulmonary dysplasia (71% vs. 48%; p < 0.05). In very low birth weight infants with major events, O2 desaturations before vaccination were 3.40 (1.41-8.23) times higher and treatment with methylxanthines for apnea and bradycardia syndrome was 8.05 (2.50-25.89) times higher compared to infants without major events.
Conclusion:
Major cardiorespiratory events occurred in over 1/3 of all very low birth weight infants after vaccination. Associated factors were low gestational age, bronchopulmonary dysplasia, methylxanthine treatment, and persisting O2 desaturations before vaccination. Primary vaccination of very low birth weight infants should be performed under continuous monitoring of vital parameters.”
Links
https://www.ncbi.nlm.nih.gov/pubmed/22543544
Citations
D'Angio, Carl T. "Active Immunization of Premature and Low Birth-Weight Infants." Pediatric Drugs 9.1 (2007): 17-32
“Objective:
To examine the relationship between primary vaccination of preterm infants and prevalence ratios of associated factors for unwanted cardiorespiratory events, following the recommendation of the Centers for Disease Control and Prevention Advisory Committee on Immunization Practices for immunization of preterm infants at 2 months of chronological age.
Methods:
Two-year retrospective study of very low birth weight infants receiving their primary vaccination. Major cardiorespiratory events, such as apnea, bradycardia, SpO2 desaturation, and minor adverse events, such as temperature instability, poor handling and local reactions, were recorded. Prevalence ratio with 95% confidence interval for associated factors between infants with and without cardiorespiratory events was calculated.
Results:
Eighty neonates were studied (median [range] birth weight 970 g [428-1,490]), gestational age of 27.4 weeks (23.3-33). Adverse reactions occurred in 35 (44%) patients: minor events in 19 (24%), major events in 28 (35%). Infants with major events had significantly lower gestational age (p = 0.008) and a higher incidence of bronchopulmonary dysplasia (71% vs. 48%; p < 0.05). In very low birth weight infants with major events, O2 desaturations before vaccination were 3.40 (1.41-8.23) times higher and treatment with methylxanthines for apnea and bradycardia syndrome was 8.05 (2.50-25.89) times higher compared to infants without major events.
Conclusion:
Major cardiorespiratory events occurred in over 1/3 of all very low birth weight infants after vaccination. Associated factors were low gestational age, bronchopulmonary dysplasia, methylxanthine treatment, and persisting O2 desaturations before vaccination. Primary vaccination of very low birth weight infants should be performed under continuous monitoring of vital parameters.”
Links
https://www.ncbi.nlm.nih.gov/pubmed/22543544
Citations
D'Angio, Carl T. "Active Immunization of Premature and Low Birth-Weight Infants." Pediatric Drugs 9.1 (2007): 17-32
5. Adverse events following vaccination in premature infants
Abstract
“The aims of this study were to study the frequency, severity and types of adverse reactions following DPT/Hib (diphtheria and tetanus toxoids and pertussis/Haemophilus in uenzae type B conjugate) immunization in very preterm infants and to identify possible risk factors. Case notes of 45 preterm babies vaccinated in the neonatal intensive care unit between January 1993 and December 1998 were studied retrospectively. Birthweight, gestational age, duration of ventilation, oxygen dependency, timing of vaccination, weight, corrected gestation at vaccination and apparent adverse effects were noted. Apparent adverse events were noted in 17 of 45 (37.8%) babies: 9 (20%) had major events, i.e. apnoea, bradycardia or desaturations, and 8 (17.8%) had minor events, i.e. increased oxygen requirements, temperature instability, poor handling and feed intolerance. Babies with major events were signi cantly younger (p < 0.05), had a lower postmenstrual age (p < 0.05) and weighed less (p < 0.05) at the time of vaccination compared with babies without major events. No differences in the mean birthweight, gestational age, duration of ventilation or oxygen dependency were found between the two groups. Age at vaccination of 70 days or less was signi cantly associated with increased risk (p < 0.01). Of 27 babies vaccinated at 70 days or less, 9 (33.3%) developed major events compared with none when vaccinated over 70 d.”
Links
https://www.ncbi.nlm.nih.gov/pubmed/11529542
Citations
Y Cloete, K Hassan, P Buss. "Adverse Events following Vaccination in Premature Infants." Acta Paediatrica 90.8 (2001): 916-20.
“The aims of this study were to study the frequency, severity and types of adverse reactions following DPT/Hib (diphtheria and tetanus toxoids and pertussis/Haemophilus in uenzae type B conjugate) immunization in very preterm infants and to identify possible risk factors. Case notes of 45 preterm babies vaccinated in the neonatal intensive care unit between January 1993 and December 1998 were studied retrospectively. Birthweight, gestational age, duration of ventilation, oxygen dependency, timing of vaccination, weight, corrected gestation at vaccination and apparent adverse effects were noted. Apparent adverse events were noted in 17 of 45 (37.8%) babies: 9 (20%) had major events, i.e. apnoea, bradycardia or desaturations, and 8 (17.8%) had minor events, i.e. increased oxygen requirements, temperature instability, poor handling and feed intolerance. Babies with major events were signi cantly younger (p < 0.05), had a lower postmenstrual age (p < 0.05) and weighed less (p < 0.05) at the time of vaccination compared with babies without major events. No differences in the mean birthweight, gestational age, duration of ventilation or oxygen dependency were found between the two groups. Age at vaccination of 70 days or less was signi cantly associated with increased risk (p < 0.01). Of 27 babies vaccinated at 70 days or less, 9 (33.3%) developed major events compared with none when vaccinated over 70 d.”
Links
https://www.ncbi.nlm.nih.gov/pubmed/11529542
Citations
Y Cloete, K Hassan, P Buss. "Adverse Events following Vaccination in Premature Infants." Acta Paediatrica 90.8 (2001): 916-20.
6. Sudden Unexpected Deaths and Vaccinations during the First Two Years of Life in Italy: A Case Series Study
Abstract
“Background:
The signal of an association between vaccination in the second year of life with a hexavalent vaccine and sudden unexpected deaths (SUD) in the two days following vaccination was reported in Germany in 2003. A study to establish whether the immunisation with hexavalent vaccines increased the short term risk of SUD in infants was conducted in Italy.
Methodology/Principal Findings:
The reference population comprises around 3 million infants vaccinated in Italy in the study period 1999–2004 (1.5 million received hexavalent vaccines). Events of SUD in infants aged 1–23 months were identified through the death certificates. Vaccination history was retrieved from immunisation registries. Association between immunisation and death was assessed adopting a case series design focusing on the risk periods 0–1, 0–7, and 0– 14 days after immunisation. Among the 604 infants who died of SUD, 244 (40%) had received at least one vaccination. Four deaths occurred within two days from vaccination with the hexavalent vaccines (RR = 1.5; 95% CI 0.6 to 4.2). The RRs for the risk periods 0–7 and 0–14 were 2.0 (95% CI 1.2 to 3.5) and 1.5 (95% CI 0.9 to 2.4). The increased risk was limited to the first dose (RR = 2.2; 95% CI 1.1 to 4.4), whereas no increase was observed for the second and third doses combined.
Conclusions:
The RRs of SUD for any vaccines and any risk periods, even when greater than 1, were almost an order of magnitude lower than the estimates in Germany. The limited increase in RRs found in Italy appears confined to the first dose and may be partly explained by a residual uncontrolled confounding effect of age.”
Links
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0016363
Citations
Traversa, Giuseppe, Stefania Spila-Alegiani, Clara Bianchi, Marta Ciofi Degli Atti, Luisa Frova, Marco Massari, Roberto Raschetti, Stefania Salmaso, and Gianpaolo Scalia Tomba. "Sudden Unexpected Deaths and Vaccinations during the First Two Years of Life in Italy: A Case Series Study." PLoS ONE 6.1 (2011)
“Background:
The signal of an association between vaccination in the second year of life with a hexavalent vaccine and sudden unexpected deaths (SUD) in the two days following vaccination was reported in Germany in 2003. A study to establish whether the immunisation with hexavalent vaccines increased the short term risk of SUD in infants was conducted in Italy.
Methodology/Principal Findings:
The reference population comprises around 3 million infants vaccinated in Italy in the study period 1999–2004 (1.5 million received hexavalent vaccines). Events of SUD in infants aged 1–23 months were identified through the death certificates. Vaccination history was retrieved from immunisation registries. Association between immunisation and death was assessed adopting a case series design focusing on the risk periods 0–1, 0–7, and 0– 14 days after immunisation. Among the 604 infants who died of SUD, 244 (40%) had received at least one vaccination. Four deaths occurred within two days from vaccination with the hexavalent vaccines (RR = 1.5; 95% CI 0.6 to 4.2). The RRs for the risk periods 0–7 and 0–14 were 2.0 (95% CI 1.2 to 3.5) and 1.5 (95% CI 0.9 to 2.4). The increased risk was limited to the first dose (RR = 2.2; 95% CI 1.1 to 4.4), whereas no increase was observed for the second and third doses combined.
Conclusions:
The RRs of SUD for any vaccines and any risk periods, even when greater than 1, were almost an order of magnitude lower than the estimates in Germany. The limited increase in RRs found in Italy appears confined to the first dose and may be partly explained by a residual uncontrolled confounding effect of age.”
Links
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0016363
Citations
Traversa, Giuseppe, Stefania Spila-Alegiani, Clara Bianchi, Marta Ciofi Degli Atti, Luisa Frova, Marco Massari, Roberto Raschetti, Stefania Salmaso, and Gianpaolo Scalia Tomba. "Sudden Unexpected Deaths and Vaccinations during the First Two Years of Life in Italy: A Case Series Study." PLoS ONE 6.1 (2011)
7. Apnea and its possible relationship to immunization in ex-premature infants
Abstract
“This study compared the characteristics of infants hospitalized with apnea that participated in a vaccine trial compared with two control groups which consisted of 100 infants randomly selected from the same vaccine trial and 52 consecutively born very low birth weight (VLBW) infants. A total of 23 infants were admitted with apnea of whom 19 weighed”
Links
https://www.ncbi.nlm.nih.gov/pubmed/18490084
Citations
"Apnea and Its Possible Relationship to Immunization in Ex-premature Infants."Vaccine. U.S. National Library of Medicine
“This study compared the characteristics of infants hospitalized with apnea that participated in a vaccine trial compared with two control groups which consisted of 100 infants randomly selected from the same vaccine trial and 52 consecutively born very low birth weight (VLBW) infants. A total of 23 infants were admitted with apnea of whom 19 weighed”
Links
https://www.ncbi.nlm.nih.gov/pubmed/18490084
Citations
"Apnea and Its Possible Relationship to Immunization in Ex-premature Infants."Vaccine. U.S. National Library of Medicine
8. Apnoea and bradycardia in preterm infants following immunisation with pentavalent or hexavalent vaccines
Abstract
“There is a lack of data regarding the incidence and clinical significance of apnoea or bradycardia (AB) following immunisation with combination vaccines containing an acellular pertussis (Pa) component in respiratory stable preterm infants. Medical records of respiratory stable preterm infants who received a first dose of a combined diphtheria (D) and tetanus (T) toxoids, Pa, Haemophilus influenzae type b (Hib), inactivated poliovirus (IPV) vaccine with or without hepatitis B virus (HBV) in the neonatal intensive care unit (NICU) of the University Children’s Hospital Basel between January 2000 and June 2003 were analysed. For each infant, clinical data were recorded for a 72 h period before and after immunisation. Of 53 infants with a mean gestational age of 28 weeks, 7 (13%) showed a transient recurrence of or increase in episodes of AB following immunisation. Five of these seven infants required intervention ranging from tactile stimulation to bag and mask ventilation. Regarding risk factors, children with recurrent or increased AB were indistinguishable from those without such events. The rate of fever (>38C) following immunisation was higher in affected infants compared to those without recurrence of or increase in AB (3/7 vs 2/46, P =0.01). Conclusion: Although most infants tolerated immunisation well, the incidence of recurrent or increased apnoea or bradycardia in respiratory stable preterm infants following the first immunisation with penta- or hexavalent vaccines was 13%. Most apnoea or bradycardia events required intervention but did not have serious consequences. Monitoring of all preterm infants following immunisation in the neonatal intensive care unit is recommended.”
Links
https://www.ncbi.nlm.nih.gov/pubmed/15843978
Citations
Schulzke, Sven, Ulrich Heininger, Michael Lücking-Famira, and Hubert Fahnenstich. "Apnoea and Bradycardia in Preterm Infants following Immunisation with Pentavalent or Hexavalent Vaccines." European Journal of Pediatrics 164.7 (2005): 432-35.
“There is a lack of data regarding the incidence and clinical significance of apnoea or bradycardia (AB) following immunisation with combination vaccines containing an acellular pertussis (Pa) component in respiratory stable preterm infants. Medical records of respiratory stable preterm infants who received a first dose of a combined diphtheria (D) and tetanus (T) toxoids, Pa, Haemophilus influenzae type b (Hib), inactivated poliovirus (IPV) vaccine with or without hepatitis B virus (HBV) in the neonatal intensive care unit (NICU) of the University Children’s Hospital Basel between January 2000 and June 2003 were analysed. For each infant, clinical data were recorded for a 72 h period before and after immunisation. Of 53 infants with a mean gestational age of 28 weeks, 7 (13%) showed a transient recurrence of or increase in episodes of AB following immunisation. Five of these seven infants required intervention ranging from tactile stimulation to bag and mask ventilation. Regarding risk factors, children with recurrent or increased AB were indistinguishable from those without such events. The rate of fever (>38C) following immunisation was higher in affected infants compared to those without recurrence of or increase in AB (3/7 vs 2/46, P =0.01). Conclusion: Although most infants tolerated immunisation well, the incidence of recurrent or increased apnoea or bradycardia in respiratory stable preterm infants following the first immunisation with penta- or hexavalent vaccines was 13%. Most apnoea or bradycardia events required intervention but did not have serious consequences. Monitoring of all preterm infants following immunisation in the neonatal intensive care unit is recommended.”
Links
https://www.ncbi.nlm.nih.gov/pubmed/15843978
Citations
Schulzke, Sven, Ulrich Heininger, Michael Lücking-Famira, and Hubert Fahnenstich. "Apnoea and Bradycardia in Preterm Infants following Immunisation with Pentavalent or Hexavalent Vaccines." European Journal of Pediatrics 164.7 (2005): 432-35.
9. b-Tryptase and quantitative mast-cell increase in a sudden infant death following hexavalent immunization
Abstract
“The association between sudden infant death syndrome and immunization is frequently discussed. Serious adverse events following vaccination have generally been defined as those adverse events that result in permanent disability, hospitalization or prolongation of hospitalization, life threatening illness, congenital anomaly or death. They are generally referred to the inherent properties of the vaccine (vaccine reaction) or some error in the immunization process (programme error).The event could also be totally unrelated but only temporally linked to immunization (coincidental event). A fatal case of a 3-month-old female infant, who died within 24 h of vaccination with hexavalent vaccine is presented. Clinical data, post-mortem findings (acute pulmonary oedema, acute pulmonary emphysema), quali-quantitative data collected from immunohistochemical staining (degranulating mast cells) and laboratory analysis with a high level of b-tryptase in serum, 43.3 mg/l, allows us to conclude that acute respiratory failure likely due to post hexavalent immunization-related shock was the cause of death.”
Links
http://www.fsijournal.org/article/S0379-0738(08)00180-1/abstract
Citations
D’Errico, Stefano, Margherita Neri, Irene Riezzo, Giuseppina Rossi, Cristoforo Pomara, Emanuela Turillazzi, and Vittorio Fineschi. " Beta-tryptase and quantitative mast-cell increase in a sudden infant death following hexavalent immunization” Forensic Science International 179.2-3 (2008)
“The association between sudden infant death syndrome and immunization is frequently discussed. Serious adverse events following vaccination have generally been defined as those adverse events that result in permanent disability, hospitalization or prolongation of hospitalization, life threatening illness, congenital anomaly or death. They are generally referred to the inherent properties of the vaccine (vaccine reaction) or some error in the immunization process (programme error).The event could also be totally unrelated but only temporally linked to immunization (coincidental event). A fatal case of a 3-month-old female infant, who died within 24 h of vaccination with hexavalent vaccine is presented. Clinical data, post-mortem findings (acute pulmonary oedema, acute pulmonary emphysema), quali-quantitative data collected from immunohistochemical staining (degranulating mast cells) and laboratory analysis with a high level of b-tryptase in serum, 43.3 mg/l, allows us to conclude that acute respiratory failure likely due to post hexavalent immunization-related shock was the cause of death.”
Links
http://www.fsijournal.org/article/S0379-0738(08)00180-1/abstract
Citations
D’Errico, Stefano, Margherita Neri, Irene Riezzo, Giuseppina Rossi, Cristoforo Pomara, Emanuela Turillazzi, and Vittorio Fineschi. " Beta-tryptase and quantitative mast-cell increase in a sudden infant death following hexavalent immunization” Forensic Science International 179.2-3 (2008)
10. Frequency of apnea, bradycardia, and desaturations following first diphtheria-tetanus-pertussis-inactivated polio-Haemophilus influenzae type B immunization in hospitalized preterm infants
Abstract
“Background:
Adverse cardiorespiratory events including apnea, bradycardia, and desaturations have been described following administration of the first diphtheria-tetanus-pertussis-inactivated polioHaemophilus influenzae type B (DTP-IPV-Hib) immunization to preterm infants. The effect of the recent substitution of acellular pertussis vaccine for whole cell pertussis vaccine on the frequency of these events requires further study.
Methods:
Infants with gestational age of ≤ 32 weeks who received their first DTP-IPV-Hib immunization prior to discharge from two Edmonton Neonatal Intensive Care Units January 1, 1996 to November 30, 2000 were eligible for the study. Each immunized infant was matched by gestational age to one control infant. The number of episodes of apnea, bradycardia, and/or desaturations (ABD) and the treatment required for these episodes in the 72 hours prior to and 72 hours post-immunization (for the immunized cohort) or at the same post-natal age (for controls) was recorded.
Results:
Thirty-four infants who received DTP-IPV-Hib with whole cell pertussis vaccine, 90 infants who received DTP-IPV-Hib with acellular pertussis vaccine, and 124 control infants were entered in the study. Fifty-six immunized infants (45.1%) and 36 control infants (29.0%) had a resurgence of or increased ABD in the 72 hours post-immunization in the immunized infants and at the same post-natal age in the controls with an adjusted odds ratio for immunized infants of 2.41 (95% CI 1.29,4.51) as compared to control infants. The incidence of an increase in adverse cardiorespiratory events post-immunization was the same in infants receiving whole cell or acellular pertussis vaccine (44.1% versus 45.6%). Eighteen immunized infants (14.5%) and 51 control infants (41.1%) had a reduction in ABD in the 72 hours post- immunization or at the equivalent postnatal age in controls for an odds ratio of 0.175 (95%CI 0.08, 0.39). The need for therapy of ABD in the immunized infants was not statistically different from the control infants. Lower weight at the time of immunization was a risk factor for a resurgence of or increased ABD postimmunization. Birth weight, gestational age, postnatal age or sex were not risk factors.
Conclusion:
There is an increase in adverse cardiorespiratory events following the first dose of DTP-IPVHib in preterm infants. Lower current weight was identified as a risk factor, with the risk being equivalent for whole cell versus acellular pertussis vaccine. Although most of these events are of limited clinical significance, cardiorespiratory monitoring of infants who are sufficiently preterm that they are receiving their first immunization prior to hospital discharge should be considered for 72 hours post-immunization.”
Links
https://www.ncbi.nlm.nih.gov/pubmed/16784533
Citations
Lee, Jackie, Joan L. Robinson, and Donald W. Spady. "Frequency of Apnea, Bradycardia, and Desaturations following First Diphtheria-tetanus-pertussis-inactivated Polio-Haemophilus Influenzae Type B Immunization in Hospitalized Preterm Infants." BMC Pediatrics 6.1 (2006)
“Background:
Adverse cardiorespiratory events including apnea, bradycardia, and desaturations have been described following administration of the first diphtheria-tetanus-pertussis-inactivated polioHaemophilus influenzae type B (DTP-IPV-Hib) immunization to preterm infants. The effect of the recent substitution of acellular pertussis vaccine for whole cell pertussis vaccine on the frequency of these events requires further study.
Methods:
Infants with gestational age of ≤ 32 weeks who received their first DTP-IPV-Hib immunization prior to discharge from two Edmonton Neonatal Intensive Care Units January 1, 1996 to November 30, 2000 were eligible for the study. Each immunized infant was matched by gestational age to one control infant. The number of episodes of apnea, bradycardia, and/or desaturations (ABD) and the treatment required for these episodes in the 72 hours prior to and 72 hours post-immunization (for the immunized cohort) or at the same post-natal age (for controls) was recorded.
Results:
Thirty-four infants who received DTP-IPV-Hib with whole cell pertussis vaccine, 90 infants who received DTP-IPV-Hib with acellular pertussis vaccine, and 124 control infants were entered in the study. Fifty-six immunized infants (45.1%) and 36 control infants (29.0%) had a resurgence of or increased ABD in the 72 hours post-immunization in the immunized infants and at the same post-natal age in the controls with an adjusted odds ratio for immunized infants of 2.41 (95% CI 1.29,4.51) as compared to control infants. The incidence of an increase in adverse cardiorespiratory events post-immunization was the same in infants receiving whole cell or acellular pertussis vaccine (44.1% versus 45.6%). Eighteen immunized infants (14.5%) and 51 control infants (41.1%) had a reduction in ABD in the 72 hours post- immunization or at the equivalent postnatal age in controls for an odds ratio of 0.175 (95%CI 0.08, 0.39). The need for therapy of ABD in the immunized infants was not statistically different from the control infants. Lower weight at the time of immunization was a risk factor for a resurgence of or increased ABD postimmunization. Birth weight, gestational age, postnatal age or sex were not risk factors.
Conclusion:
There is an increase in adverse cardiorespiratory events following the first dose of DTP-IPVHib in preterm infants. Lower current weight was identified as a risk factor, with the risk being equivalent for whole cell versus acellular pertussis vaccine. Although most of these events are of limited clinical significance, cardiorespiratory monitoring of infants who are sufficiently preterm that they are receiving their first immunization prior to hospital discharge should be considered for 72 hours post-immunization.”
Links
https://www.ncbi.nlm.nih.gov/pubmed/16784533
Citations
Lee, Jackie, Joan L. Robinson, and Donald W. Spady. "Frequency of Apnea, Bradycardia, and Desaturations following First Diphtheria-tetanus-pertussis-inactivated Polio-Haemophilus Influenzae Type B Immunization in Hospitalized Preterm Infants." BMC Pediatrics 6.1 (2006)
11. Frequency of respiratory deterioration after immunisation in preterm infants
Abstract
“Aim:
To determine the relationship between the initiation of respiratory support and the first routine immunisation of neonates at 2 months of age during primary hospitalisation.
Methods:
An historical cohort study design was used to study the neonatal factors associated with the initiation of respiratory support within 7 days of immunisation in a cohort of 7629 preterm and term infants admitted to the Neonatal Unit of the Royal Women’s Hospital between 2001 and 2008.
Results:
The 411 infants who received their first immunisations in hospital were both very preterm and of extremely low birth weight (ELBW, below 1000 g). Twenty-two infants experienced post-immunisation apnoea of sufficient severity to warrant the initiation of either intermittent positive pressure ventilation (two cases) or continuous positive airway pressure (20 cases). Infants exhibiting a respiratory deterioration following immunisation had a higher incidence of previous septicaemia (Odds ratio 2.5, 95% confidence interval 1.0, 6.1; P = 0.04) and received CPAP for a longer period prior to vaccination (P = 0.03).
Conclusion:
Apnoea following immunisation may be an aetiological factor in the requirement of respiratory support in a small number of preterm, ELBW infants particularly those with significant lung disease and those who have previously experienced septicaemia”
Links
https://www.ncbi.nlm.nih.gov/pubmed/20825611
Citations
Hacking, Douglas F., Peter G. Davis, Ester Wong, Kevin Wheeler, and Jodie Mcvernon. "Frequency of Respiratory Deterioration after Immunisation in Preterm Infants." Journal of Paediatrics and Child Health 46.12 (2010): 742-48.
“Aim:
To determine the relationship between the initiation of respiratory support and the first routine immunisation of neonates at 2 months of age during primary hospitalisation.
Methods:
An historical cohort study design was used to study the neonatal factors associated with the initiation of respiratory support within 7 days of immunisation in a cohort of 7629 preterm and term infants admitted to the Neonatal Unit of the Royal Women’s Hospital between 2001 and 2008.
Results:
The 411 infants who received their first immunisations in hospital were both very preterm and of extremely low birth weight (ELBW, below 1000 g). Twenty-two infants experienced post-immunisation apnoea of sufficient severity to warrant the initiation of either intermittent positive pressure ventilation (two cases) or continuous positive airway pressure (20 cases). Infants exhibiting a respiratory deterioration following immunisation had a higher incidence of previous septicaemia (Odds ratio 2.5, 95% confidence interval 1.0, 6.1; P = 0.04) and received CPAP for a longer period prior to vaccination (P = 0.03).
Conclusion:
Apnoea following immunisation may be an aetiological factor in the requirement of respiratory support in a small number of preterm, ELBW infants particularly those with significant lung disease and those who have previously experienced septicaemia”
Links
https://www.ncbi.nlm.nih.gov/pubmed/20825611
Citations
Hacking, Douglas F., Peter G. Davis, Ester Wong, Kevin Wheeler, and Jodie Mcvernon. "Frequency of Respiratory Deterioration after Immunisation in Preterm Infants." Journal of Paediatrics and Child Health 46.12 (2010): 742-48.
12. Incidence of apnoea and bradycardia in preterm infants following DTP, and Hib immunization: A prospective study
Abstract
“Objective:
To evaluate the incidence and severity of apnoea and bradycardia in hospitalized preterm infants following immunization at 2 months of age, and identify risk factors.
Methodology:
A prospective study of 98 preterm infants, of gestational age 24-31 weeks, immunized at approximately 2 months post natal age with diphtheria-tetanus-whole cell pertussis vaccine (DTP,) in the neonatal intensive care unit (NICU) at King George V Hospital Sydney. Half the infants also received Haemophilus influenzae type b conjugate vaccine (Hib) simultaneously. All infants were monitored for apnoea and bradycardia in the 24 h periods pre- and post immunization.
Results:
Only one infant had apnoea and/or bradycardia pre-immunization compared with 17 post immunization. For 12 infants these events were brief, self-limiting and not associated with desaturations (oxygen saturation < 90Y0). However, for five infants (30%) these events were associated with oxygen desaturation and two of these infants required supplemental oxygen. The group that had apnoea and/or bradycardia and the group that did not were not significantly different in terms of gestational age, birth weight and other variables. Infants who received Hib together with DTP, were less likely to have apnoea and/or bradycardia than those given DTP, alone.
Conclusion:
When considering immunization for preterm infants, the benefits of early immunization must be balanced against the risk of apnoea and bradycardia. We recommend that the cardio-respiratory function of hospitalized infants born at less than 31 weeks gestation be monitored for 48 h post immunization.”
Links
https://www.ncbi.nlm.nih.gov/pubmed/9401886
Citations
Botham, Sj, D. Isaacs, and Dj Henderson-Smart. "Incidence of Apnoea and Bradycardia in Preterm Infants following DTPw and Hib Immunization: A Prospective Study." Journal of Paediatrics and Child Health 33.5 (2008): 418-21
“Objective:
To evaluate the incidence and severity of apnoea and bradycardia in hospitalized preterm infants following immunization at 2 months of age, and identify risk factors.
Methodology:
A prospective study of 98 preterm infants, of gestational age 24-31 weeks, immunized at approximately 2 months post natal age with diphtheria-tetanus-whole cell pertussis vaccine (DTP,) in the neonatal intensive care unit (NICU) at King George V Hospital Sydney. Half the infants also received Haemophilus influenzae type b conjugate vaccine (Hib) simultaneously. All infants were monitored for apnoea and bradycardia in the 24 h periods pre- and post immunization.
Results:
Only one infant had apnoea and/or bradycardia pre-immunization compared with 17 post immunization. For 12 infants these events were brief, self-limiting and not associated with desaturations (oxygen saturation < 90Y0). However, for five infants (30%) these events were associated with oxygen desaturation and two of these infants required supplemental oxygen. The group that had apnoea and/or bradycardia and the group that did not were not significantly different in terms of gestational age, birth weight and other variables. Infants who received Hib together with DTP, were less likely to have apnoea and/or bradycardia than those given DTP, alone.
Conclusion:
When considering immunization for preterm infants, the benefits of early immunization must be balanced against the risk of apnoea and bradycardia. We recommend that the cardio-respiratory function of hospitalized infants born at less than 31 weeks gestation be monitored for 48 h post immunization.”
Links
https://www.ncbi.nlm.nih.gov/pubmed/9401886
Citations
Botham, Sj, D. Isaacs, and Dj Henderson-Smart. "Incidence of Apnoea and Bradycardia in Preterm Infants following DTPw and Hib Immunization: A Prospective Study." Journal of Paediatrics and Child Health 33.5 (2008): 418-21
13. Primary Immunization of Premature Infants with Gestational Age
Abstract
“Objective
To determine the incidence of cardiorespiratory events and abnormal C-reactive protein (CRP) level associated with administration of a single vaccine or multiple separate vaccines simultaneously. Study design Prospective observational study on 239 preterm infants at >2 months of age in the neonatal intensive care unit (NICU). Each infant received either a single vaccine or multiple vaccines on one day. CRP levels and cardiorespiratory manifestations were monitored for 3 days following immunization.
Results
Abnormal elevation of CRP level occurred in 85% of infants administered multiple vaccines and up to 70% of those given a single vaccine. Overall, 16% of infants had vaccine-associated cardiorespiratory events within 48 hours postimmunization. In logistic regression analysis, abnormal CRP values were associated with multiple vaccines (OR, 15.77; 95% CI 5.10-48.77) and severe intraventricular hemorrhage (IVH) (OR, 2.28; 95% CI 1.02-5.13). Cardiorespiratory events were associated marginally with receipt of multiple injections (OR, 3.62; 95% CI 0.99-13.25) and significantly with gastroesophageal reflux (GER) (OR, 4.76; 95% CI 1.22-18.52).
Conclusion
CRP level is expected to be elevated in the 48 hours following immunization. In a minority of infants immunized, cardiorespiratory events were associated with presumed need for intervention. Underlying medical conditions and possibly multiple injections are associated with cardiorespiratory events. Precautionary monitoring following immunizations is warranted.”
Links
https://www.ncbi.nlm.nih.gov/pubmed/17643770
Citations
Pourcyrous, Massroor, Sheldon B. Korones, Kristopher L. Arheart, and Henrietta S. Bada. "Primary Immunization of Premature Infants with Gestational Age." The Journal of Pediatrics 151.2 (2007): 167-72.
“Objective
To determine the incidence of cardiorespiratory events and abnormal C-reactive protein (CRP) level associated with administration of a single vaccine or multiple separate vaccines simultaneously. Study design Prospective observational study on 239 preterm infants at >2 months of age in the neonatal intensive care unit (NICU). Each infant received either a single vaccine or multiple vaccines on one day. CRP levels and cardiorespiratory manifestations were monitored for 3 days following immunization.
Results
Abnormal elevation of CRP level occurred in 85% of infants administered multiple vaccines and up to 70% of those given a single vaccine. Overall, 16% of infants had vaccine-associated cardiorespiratory events within 48 hours postimmunization. In logistic regression analysis, abnormal CRP values were associated with multiple vaccines (OR, 15.77; 95% CI 5.10-48.77) and severe intraventricular hemorrhage (IVH) (OR, 2.28; 95% CI 1.02-5.13). Cardiorespiratory events were associated marginally with receipt of multiple injections (OR, 3.62; 95% CI 0.99-13.25) and significantly with gastroesophageal reflux (GER) (OR, 4.76; 95% CI 1.22-18.52).
Conclusion
CRP level is expected to be elevated in the 48 hours following immunization. In a minority of infants immunized, cardiorespiratory events were associated with presumed need for intervention. Underlying medical conditions and possibly multiple injections are associated with cardiorespiratory events. Precautionary monitoring following immunizations is warranted.”
Links
https://www.ncbi.nlm.nih.gov/pubmed/17643770
Citations
Pourcyrous, Massroor, Sheldon B. Korones, Kristopher L. Arheart, and Henrietta S. Bada. "Primary Immunization of Premature Infants with Gestational Age." The Journal of Pediatrics 151.2 (2007): 167-72.
14. Recurrence of Cardiorespiratory Events following Repeat DTaP-Based Combined Immunization in Very Low Birth Weight Premature Infants
Abstract
“Reappearance or accentuation of cardiorespiratory events after the first immunization with diphtheria-tetanus-acellular pertussis (DTaP) or diphtheria-tetanus-whole cell pertussis (DTwP) vaccination has been reported in up to 50% of very low birth weight (VLBW) infants.1-4 Risk factors include low gestational age (GA) or birth weight (BW), bronchopulmonary dysplasia, and persistent apnea/bradycardia at the time of immunization.1,3,5 However, it remains difficult to predict which premature infant will react adversely to vaccination, and the risk of recurrence of immunization-induced cardiorespiratory events has not yet been reported.”
Links
https://www.ncbi.nlm.nih.gov/pubmed/18718262
Citations
Flatz-Jequier, Aline, Klara M. Posfay-Barbe, Riccardo E. Pfister, and Claire-Anne Siegrist. "Recurrence of Cardiorespiratory Events following Repeat DTaP-Based Combined Immunization in Very Low Birth Weight Premature Infants." The Journal of Pediatrics 153.3 (2008): 429-31.
“Reappearance or accentuation of cardiorespiratory events after the first immunization with diphtheria-tetanus-acellular pertussis (DTaP) or diphtheria-tetanus-whole cell pertussis (DTwP) vaccination has been reported in up to 50% of very low birth weight (VLBW) infants.1-4 Risk factors include low gestational age (GA) or birth weight (BW), bronchopulmonary dysplasia, and persistent apnea/bradycardia at the time of immunization.1,3,5 However, it remains difficult to predict which premature infant will react adversely to vaccination, and the risk of recurrence of immunization-induced cardiorespiratory events has not yet been reported.”
Links
https://www.ncbi.nlm.nih.gov/pubmed/18718262
Citations
Flatz-Jequier, Aline, Klara M. Posfay-Barbe, Riccardo E. Pfister, and Claire-Anne Siegrist. "Recurrence of Cardiorespiratory Events following Repeat DTaP-Based Combined Immunization in Very Low Birth Weight Premature Infants." The Journal of Pediatrics 153.3 (2008): 429-31.
15. Recurrent apnoea post immunisation: Informing re-immunisation policy
Abstract
“Background:
Preterm infants should receive immunisations according to their chronological, rather than gestational, age however concern about possible adverse events following immunisation (AEFI) in this group often means routine immunisations are delayed. A small number of infants may have apnoea with or without bradycardia temporally associated with immunisation. The risk factors for, and recurrence rate of apnoea with subsequent immunisations are unknown, which makes planning for subsequent immunisations for these highly vulnerable infants difficult.
Aim:
To determine recurrence rates for apnoea temporally associated with immunisation in preterm and term infants and to explore potential risk factors associated with recurrent apnoea in preterm infants.
Method:
A retrospective analysis of all apnoea +/−bradycardia AEFIs in preterm and term infants, reported to the Surveillance of Adverse Events Following Vaccination In the Community (SAEFVIC), Victoria, Australia over a 3-year period from May 2007 to April 2010. Apnoea +/−bradycardia was defined as temporally associated with immunisation if it occurred up to 48 h after immunisation.
Results:
7 out of 38 [18%, 95% confidence interval 6–31%] preterm infants with apnoea +/−bradycardia post initial immunisation had recurrent apnoea with subsequent immunisations. Possible risk factors for recurrence included: lower birth weight (p = 0.04) and ongoing hospitalisation for complications relating to prematurity (p = 0.01). No preterm infant with recurrent apnoea had a third episode of apnoea with subsequent immunisation. None of the 8 term infants with a reported apnoea AEFI had recurrence of apnoea with subsequent immunisation.
Conclusion:
There is a risk of recurrence of apnoea associated with immunisation in preterm infants. We recommend that preterm infants with apnoea post immunisation should receive reliable cardiorespiratory monitoring for a minimum of 24 h following the next scheduled immunisation.”
Links
https://www.ncbi.nlm.nih.gov/pubmed/21693156
Citations
Clifford, Vanessa, Nigel W. Crawford, Jenny Royle, Teresa Lazzaro, Margie Danchin, Kirsten P. Perrett, Katherine J. Lee, and Jim P. Buttery. "Recurrent Apnoea Post Immunisation: Informing Re-immunisation Policy." Vaccine 29.34 (2011): 5681-687.
“Background:
Preterm infants should receive immunisations according to their chronological, rather than gestational, age however concern about possible adverse events following immunisation (AEFI) in this group often means routine immunisations are delayed. A small number of infants may have apnoea with or without bradycardia temporally associated with immunisation. The risk factors for, and recurrence rate of apnoea with subsequent immunisations are unknown, which makes planning for subsequent immunisations for these highly vulnerable infants difficult.
Aim:
To determine recurrence rates for apnoea temporally associated with immunisation in preterm and term infants and to explore potential risk factors associated with recurrent apnoea in preterm infants.
Method:
A retrospective analysis of all apnoea +/−bradycardia AEFIs in preterm and term infants, reported to the Surveillance of Adverse Events Following Vaccination In the Community (SAEFVIC), Victoria, Australia over a 3-year period from May 2007 to April 2010. Apnoea +/−bradycardia was defined as temporally associated with immunisation if it occurred up to 48 h after immunisation.
Results:
7 out of 38 [18%, 95% confidence interval 6–31%] preterm infants with apnoea +/−bradycardia post initial immunisation had recurrent apnoea with subsequent immunisations. Possible risk factors for recurrence included: lower birth weight (p = 0.04) and ongoing hospitalisation for complications relating to prematurity (p = 0.01). No preterm infant with recurrent apnoea had a third episode of apnoea with subsequent immunisation. None of the 8 term infants with a reported apnoea AEFI had recurrence of apnoea with subsequent immunisation.
Conclusion:
There is a risk of recurrence of apnoea associated with immunisation in preterm infants. We recommend that preterm infants with apnoea post immunisation should receive reliable cardiorespiratory monitoring for a minimum of 24 h following the next scheduled immunisation.”
Links
https://www.ncbi.nlm.nih.gov/pubmed/21693156
Citations
Clifford, Vanessa, Nigel W. Crawford, Jenny Royle, Teresa Lazzaro, Margie Danchin, Kirsten P. Perrett, Katherine J. Lee, and Jim P. Buttery. "Recurrent Apnoea Post Immunisation: Informing Re-immunisation Policy." Vaccine 29.34 (2011): 5681-687.
16. Safety of DTaP–IPV–HIb–HBV hexavalent vaccine in very premature infants
Abstract
“Objectives:
To assess the clinical safety of DTaP–IPV–HIb–HBV hexavalent immunization in very premature infants and to verify if the first administration of vaccine is by itself a reason for close monitoring hospitalized VLBW infants born at less than 31 weeks’ gestation.
Patients and methods:
Eighty-one preterm newborns less than 31 weeks’ gestational age, admitted in the NICU, were eligible to be immunized with hexavalent vaccine under close monitoring, including pre-and post-immunization continuous monitoring of heart rate, oxygen saturation, respiratory rate, resistance index at the anterior cerebral artery and ECG cQT interval.
Results:
Of the 81 eligible premature newborns, 36 were graduated from the NICU before the least date for immunization, at 7 weeks of age. The other 45 were vaccinated in the NICU and entered the study. Twenty-three of them were under medical treatment for chronic disease at the time of the immunization while 22 were healthy and stable. Five infants (11%) had apnoea/bradycardia/desaturation, related to vaccine administration and required medical support. All five infants were in the group of newborns with chronic disease (21.7% prevalence of adverse reactions in this group). No significant variation of cQT or RI before and after the immunization was observed either in the whole groups of patients or in the five infants who showed cardio-respiratory events related to vaccination.
Conclusions:
Hexavalent DTaP–IPV–HIb–HBV immunization is not associated with cardiac electric activity and cerebral blood flow variations in both stable and unstable very premature infants. However, it can cause apnoea/bradycardia/desaturation in premature babies with chronic disease. Therefore, if the baby is in the NICU for chronic diseases at 2 months post-birth, it should be monitored for apnoea, bradycardia and desaturation in association with vaccination. Hospitalized healthy preterm infants without chronic disease and therapy seem to be less vulnerable to cardio-respiratory adverse reactions. Nevertheless, it is advisable to immunize and monitor them at 8 weeks before discharge instead of possibly delaying immunization for several weeks and not monitor them”
Links
https://www.ncbi.nlm.nih.gov/pubmed/17088013
Citations
"Safety of DTaP-IPV-HIb-HBV Hexavalent Vaccine in Very Premature Infants." Vaccine. U.S. National Library of Medicine, n.d. Web. 24 Dec. 2016”
“Objectives:
To assess the clinical safety of DTaP–IPV–HIb–HBV hexavalent immunization in very premature infants and to verify if the first administration of vaccine is by itself a reason for close monitoring hospitalized VLBW infants born at less than 31 weeks’ gestation.
Patients and methods:
Eighty-one preterm newborns less than 31 weeks’ gestational age, admitted in the NICU, were eligible to be immunized with hexavalent vaccine under close monitoring, including pre-and post-immunization continuous monitoring of heart rate, oxygen saturation, respiratory rate, resistance index at the anterior cerebral artery and ECG cQT interval.
Results:
Of the 81 eligible premature newborns, 36 were graduated from the NICU before the least date for immunization, at 7 weeks of age. The other 45 were vaccinated in the NICU and entered the study. Twenty-three of them were under medical treatment for chronic disease at the time of the immunization while 22 were healthy and stable. Five infants (11%) had apnoea/bradycardia/desaturation, related to vaccine administration and required medical support. All five infants were in the group of newborns with chronic disease (21.7% prevalence of adverse reactions in this group). No significant variation of cQT or RI before and after the immunization was observed either in the whole groups of patients or in the five infants who showed cardio-respiratory events related to vaccination.
Conclusions:
Hexavalent DTaP–IPV–HIb–HBV immunization is not associated with cardiac electric activity and cerebral blood flow variations in both stable and unstable very premature infants. However, it can cause apnoea/bradycardia/desaturation in premature babies with chronic disease. Therefore, if the baby is in the NICU for chronic diseases at 2 months post-birth, it should be monitored for apnoea, bradycardia and desaturation in association with vaccination. Hospitalized healthy preterm infants without chronic disease and therapy seem to be less vulnerable to cardio-respiratory adverse reactions. Nevertheless, it is advisable to immunize and monitor them at 8 weeks before discharge instead of possibly delaying immunization for several weeks and not monitor them”
Links
https://www.ncbi.nlm.nih.gov/pubmed/17088013
Citations
"Safety of DTaP-IPV-HIb-HBV Hexavalent Vaccine in Very Premature Infants." Vaccine. U.S. National Library of Medicine, n.d. Web. 24 Dec. 2016”
17. Sudden infant death syndrome (SIDS) shortly after hexavalent vaccination: another pathology in suspected SIDS?
Abstract
“Experts from panels of the European Agency for the Evaluation of Medical Products have investigated whether there might be a link between hexavalent vaccines and some cases of deaths that occurred. Participants included pathologists with experience in the field of vaccines and sudden infant death syndrome who conducted autopsies. However, to the best of our knowledge, little, if any, attention was paid to examination of the brainstem and the cardiac conduction systems on serial sections, nor was the possibility of a triggering role of the vaccine in these deaths considered. Herein we report the case of a 3-month-old female infant dying suddenly and unexpectedly shortly after being given a hexavalent vaccination. Examination of the brainstem on serial sections revealed bilateral hypoplasia of the arcuate nucleus. The cardiac conduction system presented persistent fetal dispersion and resorptive degeneration. This case offers a unique insight into the possible role of hexavalent vaccine in triggering a lethal outcome in a vulnerable baby. Any case of sudden unexpected death occurring perinatally and in infancy, especially soon after a vaccination, should always undergo a full necropsy study according to our guidelines.”
Links
https://www.ncbi.nlm.nih.gov/pubmed/16231176
Citations
Ottaviani, Giulia, Anna Maria Lavezzi, and Luigi Matturri. "Sudden Infant Death Syndrome (SIDS) Shortly after Hexavalent Vaccination: Another Pathology in Suspected SIDS?" Virchows Archiv 448.1 (2005): 100-04.
“Experts from panels of the European Agency for the Evaluation of Medical Products have investigated whether there might be a link between hexavalent vaccines and some cases of deaths that occurred. Participants included pathologists with experience in the field of vaccines and sudden infant death syndrome who conducted autopsies. However, to the best of our knowledge, little, if any, attention was paid to examination of the brainstem and the cardiac conduction systems on serial sections, nor was the possibility of a triggering role of the vaccine in these deaths considered. Herein we report the case of a 3-month-old female infant dying suddenly and unexpectedly shortly after being given a hexavalent vaccination. Examination of the brainstem on serial sections revealed bilateral hypoplasia of the arcuate nucleus. The cardiac conduction system presented persistent fetal dispersion and resorptive degeneration. This case offers a unique insight into the possible role of hexavalent vaccine in triggering a lethal outcome in a vulnerable baby. Any case of sudden unexpected death occurring perinatally and in infancy, especially soon after a vaccination, should always undergo a full necropsy study according to our guidelines.”
Links
https://www.ncbi.nlm.nih.gov/pubmed/16231176
Citations
Ottaviani, Giulia, Anna Maria Lavezzi, and Luigi Matturri. "Sudden Infant Death Syndrome (SIDS) Shortly after Hexavalent Vaccination: Another Pathology in Suspected SIDS?" Virchows Archiv 448.1 (2005): 100-04.
18. Very low birth weight infants have only few adverse events after timely immunization
Abstract
“INTRODUCTION:
Premature infants should be vaccinated at the appropriate vaccinating age, without correcting for their gestational week and regardless of their weight. Uncertainty with regard to possible severe adverse events exists among physicians.
METHODS:
In all, 473 patients with a birth weight under 1500 g were included in a prospective observational study for adverse events that included cardiorespiratory events, local reactions and fever. Three vaccination combinations were used at different time periods.
RESULTS:
The median birth weight was 910 (375 to 1495) g. Gestational week at birth was 27.6 (22.6 to 34.3). At the time of vaccination, the gestational week was 37.4 (31.5 to 48.3). The frequency of adverse events for local reactions/fever was 2.8% and for apnea/bradycardia it was 10.8%. Apnea appeared significantly more often in children who were younger at the time of immunization. This is in concordance with the fact that they were also younger at birth. If apnea appeared, the chance of the development of bradycardia had an odds ratio of 6.4 (3.2:13.0). Children with higher-grade hemorrhages and/or with periventricular leukomalacia did not experience more adverse events, except fever.
CONCLUSION:
Timely vaccination of premature infants with a birth weight under 1500 g is safe, but the occurrence of cardiorespiratory events is related to earlier gestational week.”
Links
https://www.ncbi.nlm.nih.gov/pubmed/19710678
Citations
Furck, A. K., J. W. Richter, and E. Kattner. "Very Low Birth Weight Infants Have Only Few Adverse Events after Timely Immunization." Journal of Perinatology 30.2 (2009): 118-21.
“INTRODUCTION:
Premature infants should be vaccinated at the appropriate vaccinating age, without correcting for their gestational week and regardless of their weight. Uncertainty with regard to possible severe adverse events exists among physicians.
METHODS:
In all, 473 patients with a birth weight under 1500 g were included in a prospective observational study for adverse events that included cardiorespiratory events, local reactions and fever. Three vaccination combinations were used at different time periods.
RESULTS:
The median birth weight was 910 (375 to 1495) g. Gestational week at birth was 27.6 (22.6 to 34.3). At the time of vaccination, the gestational week was 37.4 (31.5 to 48.3). The frequency of adverse events for local reactions/fever was 2.8% and for apnea/bradycardia it was 10.8%. Apnea appeared significantly more often in children who were younger at the time of immunization. This is in concordance with the fact that they were also younger at birth. If apnea appeared, the chance of the development of bradycardia had an odds ratio of 6.4 (3.2:13.0). Children with higher-grade hemorrhages and/or with periventricular leukomalacia did not experience more adverse events, except fever.
CONCLUSION:
Timely vaccination of premature infants with a birth weight under 1500 g is safe, but the occurrence of cardiorespiratory events is related to earlier gestational week.”
Links
https://www.ncbi.nlm.nih.gov/pubmed/19710678
Citations
Furck, A. K., J. W. Richter, and E. Kattner. "Very Low Birth Weight Infants Have Only Few Adverse Events after Timely Immunization." Journal of Perinatology 30.2 (2009): 118-21.