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Immunogenicity of PCV-7 Vaccine in VLBW Infants

N

NICHD Neonatal Research Network

Status

Completed

Conditions

Infant, Low Birth Weight
Infant, Newborn
Infant, Small for Gestational Age
Streptococcus Pneumoniae
Infant, Premature
Pneumococcal Infections

Study type

Observational

Funder types

NETWORK
NIH

Identifiers

NCT00273325
M01RR016587 (U.S. NIH Grant/Contract)
M01RR000032 (U.S. NIH Grant/Contract)
U10HD027880 (U.S. NIH Grant/Contract)
NICHD-NRN-0031
U10HD027851 (U.S. NIH Grant/Contract)
U10HD040689 (U.S. NIH Grant/Contract)
M01RR000039 (U.S. NIH Grant/Contract)
UL1RR025008 (U.S. NIH Grant/Contract)
M01RR000044 (U.S. NIH Grant/Contract)
M01RR000070 (U.S. NIH Grant/Contract)
U10HD040521 (U.S. NIH Grant/Contract)
UL1RR024982 (U.S. NIH Grant/Contract)
UL1RR024160 (U.S. NIH Grant/Contract)
U10HD040498 (U.S. NIH Grant/Contract)
M01RR000633 (U.S. NIH Grant/Contract)
UL1RR025744 (U.S. NIH Grant/Contract)
U10HD040492 (U.S. NIH Grant/Contract)
M01RR007122 (U.S. NIH Grant/Contract)
M01RR000030 (U.S. NIH Grant/Contract)
U10HD021397 (U.S. NIH Grant/Contract)
UL1RR024128 (U.S. NIH Grant/Contract)
UL1RR025777 (U.S. NIH Grant/Contract)
U10HD034216 (U.S. NIH Grant/Contract)
U01HD036790 (U.S. NIH Grant/Contract)
U10HD021385 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

Premature infants are at a high risk for pneumonia. The PCV-7 vaccine effectively prevents the invasive disease from Streptococcus pneumoniae in full-term infants, but was not thoroughly studied in premature infants. This study evaluated the effectiveness and safety of the vaccine given in routine practice to very low birth weight infants, looking at blood antibody levels 4-6 weeks after the final vaccine dose, and adverse events, survival, infections, and neurodevelopmental outcomes at 18-22 months corrected age.

Full description

Streptococcus pneumoniae causes an estimated 10-25% of all pneumonias in the United States, and is responsible for an estimated 40,000 deaths per year. Invasive pneumococcal disease has a peak incidence of 235/100,000 among children aged 6-11 months. Pneumococcal meningitis carries a higher risk of death (15%) or neurodevelopmental impairment (12-28%) than Hib or Neisseria meningitides.

Premature infants are at a higher risk for invasive disease with Streptococcus pneumoniae. The heptavalent pneumococcal-CRM197 conjugate vaccine (PCV-7) effectively prevents invasive pneumococcal disease in full-term infants, but was been incompletely studied in premature infants. The American Academy of Pediatrics (AAP) recommends that "prematurely born infants, including infants of low birth weight, should be immunized at the usual chronological age in most cases", but cautions that "some studies suggest a reduced immune response in very low-birth-weight infants (<1500 g)."

This observational study assessed the effectiveness of the PCV-7 vaccine to generate a sufficient immune response in a safe manner when given to very low birth weight (VLBW) infants in routine pediatric practice. We hypothesized that among VLBW infants, the frequency of estimated minimum protective antibody titers to PCV-7 (>=0.15 μg/mL) would decrease with decreasing birth weight.

Infants 501-1500g birth weight and <32 0/7 weeks gestational age were enrolled from nine NICHD Neonatal Research Network centers from 2004 to 2006. Enrollment was stratified by weight group to yield approximately 20 infants per 100g increments from 501-1500g birth weight whose primary PCV-7 series was initiated before 3 months and completed by 8 months after birth. The infants' primary providers gave PCV-7 vaccination at 2, 4, and 6 months after birth. Infants had a single 2-ml blood sample drawn 4-6 weeks following the third dose of PCV-7. Antibodies for each of the seven vaccine serotypes included in PCV-7 were measured by enzyme-linked immunosorbent assay. Children were followed until 18-22 months corrected age to assess survival, infection, and neurodevelopmental outcomes.

Enrollment

368 patients

Sex

All

Ages

Under 3 months old

Volunteers

Accepts Healthy Volunteers

Inclusion and exclusion criteria

Inclusion criteria

  • Gestational age <32 0/7 weeks
  • Included in Neonatal Research Network Generic Database
  • Family has a telephone at home
  • Anticipated availability for blood draw 4-6 weeks following 3rd vaccine dose
  • Consent obtained before first dose of PCV-7 is given

Exclusion criteria

  • Known immunodeficiency
  • HIV exposure
  • Parental non-consent
  • Primary care pediatrician not willing to participate
  • Enrollment in a conflicting trial
  • Infant has not received first dose of PCV-7 vaccine by 3 months of age

Trial contacts and locations

10

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Data sourced from clinicaltrials.gov

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