• Serotype 6B pneumococcal capsular polysaccharide antibody >=0.15 μg/ml [ Time Frame: 4-6 weeks following the third dose of PCV-7 ] [ Designated as safety issue: No ]
  

• Pneumococcal capsular polysaccharide antibody >=0.15 μg/ml for the other six vaccine serotypes [ Time Frame: 4-6 weeks following the third dose of PCV-7 ] [ Designated as safety issue: No ]
  
• Pneumococcal capsular polysaccharide antibodies >=1.0 μg/ml for all seven vaccine serotypes [ Time Frame: 4-6 weeks following the third dose of PCV-7 ] [ Designated as safety issue: No ]
  
• Geometric mean titers of pneumococcal capsular polysaccharide antibody to the seven vaccine serotypes [ Time Frame: 4-6 weeks following the third dose of PCV-7 ] [ Designated as safety issue: No ]
  
• Pneumococcal capsular polysaccharide antibodies >=0.15 μg/ml and >=1.0 μg/ml, and geometric mean titers of antibody, to the seven vaccine serotypes in children completing the primary series, regardless of postnatal age [ Time Frame: 4-6 weeks following the third dose of PCV-7 ] [ Designated as safety issue: No ]
  
• Opsonization of 6B pneumococcal capsular polysaccharide plus 1 low immunogenicity, high prevalence serotype (e.g., 23F) among infants in the lowest quartile of antibody response [ Time Frame: 4-6 weeks following the third dose of PCV-7 ] [ Designated as safety issue: No ]
  
• Effect of possible mediating variables on the achievement of levels of serotype 6B pneumococcal capsular polysaccharide antibody >=0.15 μg/ml [ Time Frame: 4-6 weeks following the third dose of PCV-7 ] [ Designated as safety issue: No ]
  
• Effect of pneumococcal conjugate immunization status (complete & timely v. complete v. incomplete) on outcome (survival, serious infection, neurodevelopmental outcome) at 18-22 months corrected age in infants <=1000g [ Time Frame: 18-22 months corrected age ] [ Designated as safety issue: Yes ]
  
• Levels of antibody >=0.15 μg/ml and >=1.0 μg/ml to Hib polyribosylribitol [ Time Frame: 4-6 weeks following the third dose of PCV-7 ] [ Designated as safety issue: No ]
  
• Avidity of antibody to Hib-PRP among infants in the lowest quartile of antibody response,regardless of postnatal or gestational age [ Time Frame: 4-6 weeks following the third dose of PCV-7 ] [ Designated as safety issue: No ]
  

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 has 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 will assess 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 will have 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 will be followed until 18-22 months corrected age to assess survival, infection, and neurodevelopmental outcomes.