Half-dose immunization for diphtheria, tetanus, pertussis: response of preterm infants

The American Academy of Pediatrics currently recommends administering full-dose diphtheria, tetanus, pertussis, (DTP) vaccine to preterm infants, beginning at 2 months' chronologic age. Many physicians, however, continue to administer DTP vaccine at a reduced dosage in an attempt to lessen side effects. This study was designed to quantitate the immune response of 20 preterm infants immunized with half-dose DTP vaccine and to determine the nature and extent of side effects. Control subjects were 25 preterm infants immunized with full-dose vaccine. Although 96% of infants who received a full dose were able to mount a serologic response to pertussis after a second dose of DTP, 45% of infants who received a half dose were unable to mount a similar immune response to pertussis even after a third dose of DTP and required a full-dose (fourth dose of DTP) vaccine to better ensure protection. Serologic responses to diphtheria and tetanus were similar in the two groups. The incidence of side effects in preterm infants receiving both full-dose and half-dose DTP was less than that seen in a full-term population. Thus, the physician caring for the preterm infant should adhere to the American Academy of Pediatrics' recommendation for the immunization of preterm infants and offer full-dose DTP vaccine at the routine time intervals of 2, 4, 6, and 15 or 18 months' chronologic age to ensure adequate protection.     

Controlled trial of immune response of preterm infants to recombinant hepatitis B and inactivated poliovirus vaccines administered simultaneously shortly after birth

AIM: The study was conducted to evaluate the immunogenicity of an early, extra dose of enhanced inactivated poliovirus vaccine (IPV) administered simultaneously with recombinant hepatitis B vaccine (HBV) to preterm infants shortly after birth. METHODS: Three groups were studied. Fifty preterm infants received IPV intramuscularly within 24 hours of birth, in addition to routine recommended childhood immunisations. Fifty two preterm infants and 35 full term infants received routine immunisations only (routine vaccination timing: HBV at birth, 1 and 6 months of age; IPV at 2 and 4 months; oral polio vaccine (OPV) at 4 and 6 months; diphtheria-tetanus-pertussis (DTP) at 2, 4, and 6 months; and Haemophilus influenzae B vaccine at 2 and 4 months). Blood samples were taken at birth, 3 and 7 months of age from all infants, and at 1 month of age from preterm infants only. RESULTS: At birth, a lower percentage of both study and control preterm infants had antipoliovirus type 3 titres >/= 1:8 than full term infants. At 1 and 3 months of age significantly more early IPV infants had antipoliovirus type 3 titres >/= 1:8 than routinely vaccinated preterm infants (p < 0.05). At 7 months of age there were no significant differences in percentage of antipoliovirus titres >/= 1:8 or geometric mean times (GMTs) between the early IPV group and the routinely vaccinated preterm group. At 3 and 7 months of age, the percentage of positive antihepatitis B titres (>/= 1:10) and the GMT of the early IPV preterm group did not differ significantly from those of preterm controls. There was no significant difference in percentage of positive antihepatitis B titres between the early IPV group and full term controls at any time. GMTs for hepatitis B antibodies were significantly lower in the early IPV preterm group than in full term controls at 3 and 7 months of age. CONCLUSIONS: Administration of an additional dose of IPV simultaneously with routine HBV to preterm infants shortly after birth provides early protection from poliovirus and hepatitis B infection, and does not interfere with poliovirus antibody production at the age of 7 months.     

Immunogenicity of hepatitis B vaccine in preterm infants

AIM: To assess the immunogenicity of hepatitis B vaccine in preterm and term infants, given in a sequence of three doses beginning soon after birth. METHOD: The immunogenicity of hepatitis B vaccine was assessed in 176 preterm infants (< 35 weeks of gestation), immunised soon after birth, and compared with that in 46 term infants. Titres of hepatitis B antibodies were determined one to two months after the third vaccine. The significance of the differences between the term and preterm groups was determined using Student's t test. RESULTS: A similar proportion of infants in both preterm and term groups attained protective titres of hepatitis B antibodies (88.7% vs 93.4%, respectively; p = NS). However, the term infants had a higher geometric mean titre of antibodies after the third vaccine than did the preterm infants (701.2 (745.0) vs 469.1 (486.2) mU/ml, respectively; p < 0.03). CONCLUSION: Hepatitis B vaccine is effective in most preterm infants when given soon after birth. It may be advisable to determine the immune response at 12-24 months of age to booster the non-responders.     

Response of preterm infants to diphtheria-tetanus-pertussis immunizations

To establish guidelines for the routine use of diphtheria, tetanus, and pertussis (DTP) vaccine in preterm infants, we quantitated antibody responses of preterm infants to DTP and determined the nature and extent of side effects. Twenty-five preterm infants were immunized with 0.5 ml DTP vaccine at routine intervals. Term infants served as controls. Immediately before each immunization and 2 months after the third, DTP-specific antibodies were quantitated. Clinical side effects were determined by parental report. After the second immunization, 100% of preterm infants had evidence of specific antibody production against diphtheria, tetanus, and pertussis. The incidence of side effects was low, but irritability was significantly more common in preterm infants after the second immunization. These observations suggest that the initiation of primary immunization with DTP in preterm infants need not be delayed beyond 2 months of age.     

Primary care physicians' knowledge about diphtheria-tetanus-pertussis immunizations in preterm infants.

Preterm infants often receive their diphtheria-tetanus-pertussis (DTP) immunizations on a delayed schedule or in reduced dosage. Since primary care physicians (PCPs) immunize many preterm infants, the purpose of this study was to describe PCPs' knowledge about the use of DTP immunizations in preterm infants. Among the 479 PCPs who completed the questionnaire, 84% of pediatricians and 60% of family physicians correctly identified chronologic age as a criterion for initiating DTP immunizations in preterm infants. However, nearly 45% of PCPs linked this with other criteria such as a minimum weight requirement. Family physicians' answers differed from the recommendations more often than pediatricians' answers. The answers of pediatricians and family physicians who completed residency greater than 20 years ago differed from the recommendations more often than those who completed training less than or equal to 20 years ago. The answers of PCPs with fewer than five preterm infants in their practices differed from the recommendations more frequently than the answers of those with five or more preterm infants in their practices. Educational interventions are needed to bring PCPs' knowledge and practices into compliance with the American Academy of Pediatrics recommendations concerning DTP immunizations for preterm infants.     

Hepatitis B vaccine coverage among infants born to women without prenatal screening for hepatitis B virus infection: effects of the Joint Statement on Thimerosal in Vaccines

BACKGROUND: As a result of controversy about mercury exposures from vaccines containing thimerosal, the American Academy of Pediatrics and the US Public Health Service recommended in July 1999 that the first dose of hepatitis B vaccine be deferred until 2 to 6 months of age, but only for infants born to hepatitis B surface antigen (HBsAg)-negative women. We investigated the effect of these recommendation changes on the management of Oregon infants born to women whose HBsAg status was "unknown." METHODS: Infants were identified by reviewing electronic birth certificate data from 34 Oregon hospitals during (1)April through June 1999 [before recommendation changes (T1)], (2) August through October 1999 [after recommendations changes (T2)] and (3) April through June 2000 [when resumption of pre-1999 practices were recommended (T3)]. We verified maternal HBsAg screening and newborn hepatitis B vaccination by chart review. RESULTS: We identified 147 infants born to women who were not screened for HBsAg. During T1, 27% of infants born to mothers of unknown HBsAg status were vaccinated within 12 h of birth, and 80% were vaccinated before hospital discharge. This decreased to 2 and 4%, respectively, during T2 and continued to remain lower during T3. CONCLUSION: Hepatitis B vaccine coverage for infants born to unscreened women declined significantly after the July 1999 announcement and remained significantly lower 10 to 12 months later. When changes are made in established vaccination practices, policy makers should ensure that such changes are not misinterpreted, resulting in failure to immunize appropriate groups.     

Prevention of rotavirus disease: guidelines for use of rotavirus vaccine

On February 3, 2006, a bovine-based pentavalent rotavirus vaccine (RotaTeq, Merck & Co Inc, Whitehouse Station, NJ) was licensed by the US Food and Drug Administration for use in infants in the United States. The American Academy of Pediatrics recommends routine immunization of infants with 3 doses of pentavalent rotavirus vaccine administered orally at 2, 4, and 6 months of age. The first dose should be administered between 6 and 12 weeks of age; immunization should not be initiated for infants older than 12 weeks of age. Subsequent doses should be administered at 4- to 10-week intervals, and all 3 doses of vaccine should be administered by 32 weeks of age. Pentavalent rotavirus vaccine can be coadministered with other childhood vaccines. Pentavalent rotavirus vaccine is contraindicated for infants with a serious allergic reaction to any vaccine component or to a previous dose of vaccine.     

CHANGES IN SERUM ZINC CONCENTRATIONS OF SOME CANADIAN FULL TERM AND LOW BIRTHWEIGHT INFANTS FROM BIRTH TO SIX MONTHS

ABSTRACT. Gibson, R. S. and DeWolfe, M. S. (Department of Pediatrics, Dalhousie University, Halifax, Nova Scotia, Canada). Changes in serum zinc concentrations in some Canadian full term and low birthweight infants from birth to six months. Acta Paediatr Scand, 70:497,.–Serum samples were collected from 99 infants at birth, and when they were 1, 3 and 6 months old. Thirty-seven were preterm infants with a mean birthweight of 1880 g and 26–36 wk gestation; 24 were full term low birthweight with a mean birthweight of 2371 g and 38–42 wk gestation; and 38 were full term normal birthweight infants with a mean birthweight of 3 590 g and 38–42 wk gestation. Serum zinc concentrations were determined by instrumental neutron activation procedures. No significant differences in serum zinc levels were apparent between sexes or among the 3 groups. Levels were highest at birth and declined during the first 3 months. Between 3 and 6 months, serum zinc levels remained fairly constant, and were lower than reported levels for North American adults. It is concluded that the decline in serum zinc concentration in all three groups was not significantly correlated with birthweight or gestational age and the low birthweight infants in this study did not show any evidence of zinc deficiency. The general decline in serum zinc levels appeared to be associated with low dietary zinc intakes.     

The clinical and immunologic response of Chilean infants to Haemophilus influenzae type b polysaccharide-tetanus protein conjugate vaccine coadministered in the same syringe with diphtheria-tetanus toxoids-pertussis vaccine at two, four and six months of age

The safety and immunogenicity of a vaccine against Haemophilus influenzae type b consisting of purified polyribosylribitolphosphate conjugated to tetanus toxoid (PRP-T) was evaluated in 278 Chilean infants who were randomly assigned to one of three treatment groups: Group A, PRP-T mixed with diphtheria-tetanus toxoids-pertussis (DTP) vaccine in a single syringe and given as a single inoculation in one arm and placebo in the other arm; Group B, PRP-T given in one arm and DTP in the other arm; Group C, DTP given in one arm and placebo in the other. Infants were immunized at 2, 4 and 6 months of age and examined daily for 4 days after each immunization; serum PRP antibodies were measured at baseline and 2 months after each dose. The only adverse systemic reaction attributable to PRP-T beyond that caused by DTP alone was a 7 to 20% increase in febrile responses in the first 24 hours after the first and second doses of vaccine; the fevers were largely low grade and not accompanied by increased irritability, diminished activity or loss of appetite, compared with the group who received DTP without PRP-T. After the first dose 72% of infants who received PRP-T combined with DTP and 67% who received it in a separate arm attained antibody concentrations greater than or equal to 0.15 micrograms/ml. After two doses of PRP-T, 93 and 95%, respectively, had concentrations greater than or equal to 0.15 microgram/ml and after three doses 100% of infants who received PRP-T had such titers.(ABSTRACT TRUNCATED AT 250 WORDS)     

Immune response to Haemophilus influenzae type b conjugate vaccine in preterm infants

Background: Haemophilus influenzae type b (Hib) vaccine became available for use in Japan in December 2008. The aim of the present study was to evaluate the immunogenicity of Hib vaccine in Japanese preterm infants. Methods: Serum samples were obtained from 54 preterm infants before the first vaccination and 1 month after the third. Anti‐polyribosylribitol phosphate (PRP) antibodies were measured using an enzyme‐linked immunosorbent assay method. Antibody positivity was defined as levels >1 µg/mL. Results: Of the 54 preterm infants, 46 (85.2%) achieved antibody levels >1 µg/mL. This compares with the 92.4% reported in full‐term infants. The antibody seroconversion rate of infants starting vaccination at 2 months of age was close to being significantly lower than when vaccination was started at 3 months of age (P= 0.060). In addition, the percentage of infants achieving a positive response in the group with a history of antenatal steroid exposure was significantly higher than in those not exposed (P= 0.046). Thus, risk factors for lower Hib antibody concentrations after three doses of vaccine were age at first vaccination and lack of use of antenatal steroids. Conclusions: There is a possibility that perinatal factors and the environment unique to preterm infants are related to their lower antibody positivity rates compared to full‐term infants. It may therefore be preferable to modify the proposed immunization schedule.     

Perinatal hepatitis B transmission and vaccination timing in a managed care cohort: assessment of the temporary delay in newborn hepatitis B vaccination due to thimerosal content

BACKGROUND: From July to September 1999, due to a concern of toxicity from exposure to thimerosal-containing vaccines, the American Academy of Pediatrics and U.S. Public Health Service temporarily recommended delaying the administration of first dose of hepatitis B vaccine until the age of 2-6 months for infants born to hepatitis B surface antigen negative mothers. Our objectives were to determine whether the recommendation affected the rate of perinatal hepatitis B infection in a multistate managed care population; to describe neonatal and early childhood cases of hepatitis B infection and to evaluate a possible role of the recommendation; and to assess the timeliness, with respect to the U.S. childhood immunization schedule, of vaccinations during the first 2 years of life. METHODS: We identified 3 cohorts of infants born before (July 1998 to June 1999), during (July 1999 to September 1999) and after (October 1999 to September 2000) the recommendation period. We used automated claims data to identify possible neonatal and early childhood hepatitis B cases using specific ICD-9 diagnosis and CPT procedure codes and validated cases through medical record review. Using Health Plan Employer Data and Information Set (HEDIS) data, we calculated vaccination coverage for the first dose of hepatitis B vaccine at 3-month intervals from January 1999 to September 2000. RESULTS: The eligible populations in the "before," "during" and "after" cohorts were 29,347, 7791 and 29,215 infants, respectively. Of 41 possible hepatitis B cases identified in the 3 cohorts, we confirmed 1 case in the after cohort with medical record review. Despite receiving the first dose of hepatitis B vaccine and hepatitis B immunoglobulin within 12-24 hours of birth, the infant was diagnosed with laboratory-confirmed chronic hepatitis B at age of 9 months. An analysis of HEDIS data showed that vaccination coverage for the first dose of hepatitis B vaccine was 98% (January to March 1999) and 96% (April to June 1999) for the "before" cohort and 66% for the "during" cohort. For the "after" cohort the coverage was 72% (October to December 1999), 83% (January to March 2000), 91% (April to June 2000) and 95% (July to September 2000). CONCLUSIONS: This study did not identify any perinatal hepatitis B transmission among health plan enrollees associated with the 1999 recommendation. The recommendation did result in a delay of hepatitis B birth dose in the "during" cohort as intended for infants born to hepatitis B surface antigen negative mothers. Six months after the recommendation was rescinded there was still a delay in the timing of first dose of hepatitis B vaccine, but the timing had returned to the prerecommendation level after 9-12 months.     

The future of pneumococcal conjugate vaccines for prevention of pneumococcal diseases in infants and children

Seven-valent pneumococcal conjugate vaccine (PCV7) was licensed in February 2000. In June 2000, the Advisory Committee on Immunization Practices and the American Academy of Pediatrics recommended the universal administration of pneumococcal conjugate vaccine for all children 23 months of age and younger and for children 24 to 59 months of age who are at high risk for serious pneumococcal disease. Since then, >23 million doses have been administered in the United States. Postlicensure surveillance of invasive pneumococcal disease (IPD) in the United States from the Active Bacterial Core Surveillance program at the Centers for Disease Control and Prevention and the Northern California Kaiser Permanente Vaccine Study Center has reported a decline in IPD and in pneumococcal disease incidence as a result of vaccine serotypes, respectively. During this period, issues critical to the long-term success of PCV7 have become more relevant: Will PCV7 be as effective in groups of children who are at high risk for IPD as in healthy children? Will nonvaccine types replace vaccine serotypes in the nasopharynx and in disease? Why are the results of the clinical trials different for IPD and for acute otitis media? How many doses of PCV7 and what concentrations of antibody are necessary for protection? Will universal administration of PCV7 to children younger than 2 years reduce antimicrobial drug resistance and alter prescribing patterns of physicians for febrile infants? Have there been unanticipated adverse events or benefits observed? The purpose of this report is to review the current data available to address these questions and to identify gaps that will require additional knowledge to determine the ultimate value of pneumococcal conjugate vaccines in reducing the burden of pneumococcal disease in infants and children.     

Perinatal corticosteroids: a review of the research. Part II: Postnatal administration

Postnatal corticosteroids are often administered during the neonatal intensive care unit stay to reduce the risk and severity of chronic lung disease (CLD) in preterm infants. In 2002, the American Academy of Pediatrics Committee on Fetus and Newborn and the Canadian Paediatric Society Fetus and Newborn Committee jointly advised against the routine use of systemic dexatmethasone for the prevention of CLD in very low birth weight infants. The objective of this review is to present evidence-based research and expert opinion to provide the neonatal clinician with current information regarding dexamethasone use with premature infants. This article serves to inform neonatal clinicians about the benefits and potential adverse neurosensory risks of this treatment option.     

Efficacy,immunogenicity and safety of heptavalent pneumococcal conjugate vaccine in low birth weight and preterm infants

OBJECTIVE: To determine the efficacy, immunogenicity and safety of the heptavalent CRM197 pneumococcal conjugate vaccine (PCV) in low birth weight (LBW) and preterm (PT) infants against invasive pneumococcal disease caused by vaccine types. METHODS: In a randomized double blind trial of 37,868 infants given either PCV or meningococcal type C conjugate vaccine (MCV), 1756 infants <750 g <2500 g (LBW) and 4340 infants from 32 to <38 weeks old (PT) were identified. Risk of invasive pneumococcal disease in LBW and PT infants was compared with risk in normal birth weight (NBW) and full term (FT) infants. Local and systemic events observed within 48 h of recent vaccine were assessed by telephone interviews and similar comparisons made. Premature infant Emergency Department visits and hospitalization were also identified and compared with FT and NBW infants. RESULTS: Initiation of immunization and intervals between doses were similar for all groups. The risk ratio for invasive pneumococcal diseases for LBW infants compared with NBW infants was 2.6 (P = 0.03), and for PT compared with FT infants the risk ratio was 1.6 (P = 0.06). Vaccine efficacy for both groups was 100%. PCV was as immunogenic in LBW and PT as in NBW and FT infants. Fever and local events after PCV vaccination were similar when adjusted for clustering among multiple doses per child. When stratified for individual doses there was more redness and swelling for LBW infants and more swelling for PT infants after Dose 3. Isolated local and systemic reactions were more commonly seen with PCV than with MCV, a pattern similar to that in NBW and FT infants. Hospitalization rates were similar for PCV and MCV recipients. CONCLUSION: These data support the use of PCV in LBW infants and PT infants.     

Additional recommendations for use of tetanus toxoid, reduced-content diphtheria toxoid, and acellular pertussis vaccine (Tdap)

The American Academy of Pediatrics and the Centers for Disease Control and Prevention are amending previous recommendations and making additional recommendations for the use of tetanus toxoid, reduced-content diphtheria toxoid, and acellular pertussis vaccine (Tdap). Review of the results from clinical trials and other studies has revealed no excess reactogenicity when Tdap is given within a short interval after other tetanus- or diphtheria-containing toxoid products, and accrual of postmarketing adverse-events reports reveals an excellent safety record for Tdap. Thus, the recommendation for caution regarding Tdap use within any interval after a tetanus- or diphtheria-containing toxoid product is removed. Tdap should be given when it is indicated and when no contraindication exists. In further efforts to protect people who are susceptible to pertussis, the American Academy of Pediatrics and Centers for Disease Control and Prevention recommend a single dose of Tdap for children 7 through 10 years of age who were underimmunized with diphtheria-tetanus-acellular pertussis (DTaP). Also, the age for recommendation for Tdap is extended to those aged 65 years and older who have or are likely to have contact with an infant younger than 12 months (eg, health care personnel, grandparents, and other caregivers).     

Is term newborn body composition being achieved postnatally in preterm infants?

Background

The American Academy of Pediatrics (AAP) recommends that preterm infants' growth duplicates fetal growth rates and that body composition replicates in utero body composition.

Aims

To compare the total body fat mass between preterm infants assessed at term corrected age and full-term newborns, and to investigate the effects of gestational age, gender, weight increase, being breast fed on total adiposity.

Study design

Prospective observational study.

Subjects

One hundred and ten preterm infants [mean (SD) gestational age: 29.9 (2.3) weeks; birth weight: 1118 (274) g], and 87 full term [mean (SD) 38.6 (1.21) weeks, 3203 (385) g], breastfed infants.

Outcome measures

Growth and body composition by means of a pediatric air displacement system were assessed at term corrected age in preterm infants and on day 3 of life in full term infants.

Results

Weight, length and head circumference were smaller in the preterm group as compared to the term group. Mean (SD) percentage of fat mass in preterm infants was significantly higher as compared to term infants [14.8 (4.4) vs 8.59 (3.71), P < 0.0001]. Fat mass was negatively correlated with gestational age (P < 0.001), and positively associated with weight increase (P < 0.05).

Conclusions

Our data suggest that body composition, in terms of fat mass, in preterm infants at term corrected age is different from that of full term newborns.     

Age of diphtheria, tetanus, and pertussis immunization of special care nursery graduates

Diphtheria, tetanus, and pertussis (DTP) immunization data were collected on 103 special care nursery graduates in our neonatal follow-up clinic to determine whether DTP immunization schedules were significantly delayed relative to recommendations of the American Academy of Pediatrics (2, 4, and 6 months for DTP 1, 2, and 3, respectively). An inverse correlation was found between birth weight and immunization for first, second, and third DTP (r = 0.319, P less than .01; r = .205, P less than .05; and r = .236, P less than .05, respectively). We subsequently conducted a mail survey to determine the DTP immunization policy present in effect in 25 neonatal intensive care units in the United States and Canada. The survey indicates that procedural approaches remain markedly heterogeneous, and 10 of 25 (40%) units have no existing policy for implementation of DTP immunization. These data suggest that special care nursery populations are at potential risk for pertussis, which requires a conscious implementation of DTP immunization by the special care nursery, the follow-up clinic personnel, and the primary care physician.     

Acellular pertussis vaccine given by accelerated schedule: response of preterm infants

OBJECTIVE: To describe the immune response of preterm infants to a diphtheria/tetanus/three component acellular pertussis (DTaP) vaccine, under an accelerated schedule, and the effects of steroids on this response. To compare responses with those of term infants. DESIGN: Prospective observational study. SETTING: Five Wessex neonatal units; Hertfordshire immunisation clinics. PATIENTS: Infants born at < 32 weeks; term controls. INTERVENTIONS: DTaP-Haemophilus influenzae type b vaccine given at 2, 3, and 4 months. Blood taken to assess antibody responses to vaccines. MAIN OUTCOME MEASURES: IgG geometric mean concentrations (GMC) to vaccines. RESULTS: A total of 130 preterm (mean gestational age 29.1 weeks) and 54 term infants were recruited. After the third immunisation, preterm infants had similar GMCs to controls to diphtheria, tetanus, filamentous haemagglutinin (FHA), and pertactin (PRN), but a significantly lower GMC to pertussis toxin (PT). Responses to tetanus and PRN increased with age at the third immunisation, and those to tetanus, FHA, PRN, and PT increased with gestational age at birth. Response to tetanus correlated negatively with the number of doses of antenatal steroids received. There was no association between responses and postnatal steroids. CONCLUSION: When immunised with a combined acellular pertussis- H influenzae type b vaccine under an accelerated schedule, IgG GMC of preterm infants to PT was reduced. GMCs to tetanus, FHA, PRN, and PT increased with gestational age at birth, and GMCs to tetanus and PRN increased with age at the third immunisation. There is, however, no benefit in delaying immunisation. Anti-tetanus IgG decreased with increasing number of doses of antenatal steroids. There was no effect for postnatal steroids.     

Longitudinal development of specific and functional antibody in very low birth weight premature infants

We evaluated the formation of specific and functional antibody in preterm infants born weighing less than 1500 g (mean 1088 g) and less than 32 wk gestational age (mean 28.8 wk). Plasma IgG antibody against tetanus and diphtheria toxoids were measured by an enzyme-linked immunosorbent assay. Opsonic activity of heat-inactivated plasma was measured using radiolabeled bacteria, adult polymorphonuclear leukocytes and exogenous human complement. In the presence of complement, the strain of coagulase negative staphylococcus used was opsonized by IgG antibody, and the strain of Escherichia coli by IgM. Geometric mean plasma levels of tetanus and diphtheria IgG antibody fell from birth to 4 months chronological age, but rose significantly by 9 months (approximately 2 months after the third dose of diphtheria, tetanus, pertussis vaccine). However, at 9 months they remained lower than the respective geometric mean levels in 9-month-old term infants (tetanus: p less than 0.001; diphtheria: p = 0.02). The preterm infants' mean plasma IgG staphylococcal opsonic activity fell from birth to 2.5 months, but by 9 months was comparable to that of term infants of the same age. Mean IgM opsonic activity for E. coli was very low at birth in both preterm and term infants. It rose with chronological age, correlating with the rise in total IgM (r = 0.48, p less than 0.001) and by 9 months the mean preterm and term infants' levels of IgM opsonic activity for E. coli were comparable.(ABSTRACT TRUNCATED AT 250 WORDS)     

Longitudinal study of adverse reactions following diphtheria-tetanus-pertussis vaccine in infancy

A prospective study of immunogenicity and adverse effects of 1553 doses of diphtheria and tetanus toxoids and whole cell pertussis vaccine (DTP) was performed in 538 children observed longitudinally from 2 months to 20 months of age. Subjects were randomized to the standard four-dose immunization schedule or to a three-dose schedule (with a saline injection substituted for DTP at 6 months of age). The three-dose schedule could not be recommended on the basis of serologic data. Compliance for completing a clinical observation form in the 48 hours following injections was greater than 99%. Fever, local reactions, or adverse behavioral effects were described in association with 96% of DTP doses and 36% of placebo injections. Contraindications to DTP immunization developed in 3% of study children. No convulsion, hypotonic hyporesponsive episode, encephalopathy, or temperature greater than 40.5 degrees C occurred. Behavioral and local inflammatory effects occurred maximally in the first 6 hours following vaccine but fever peaked later. There was no interrelationship between occurrence of local reaction and fever. Data suggest that age has more effect on the type and rate of adverse clinical events than does vaccine dose number. Existing antibody levels to vaccine components, lot of vaccine, breast-feeding, or gestational age did not affect rate or type of clinical reactions. Neither occurrence of reactions nor the use of acetaminophen affected antibody response to vaccine.