Apnea in Hospitalized Preterm Infants Following the Administration of Routine Childhood Vaccines

Modified Intent-to-Treat (mITT) Analysis Population: Defined as any infant that was enrolled and randomized in the study

For the mITT analysis, infants will be analyzed in their assigned treatment arms irrespective of receipt of vaccine. Study outcomes will be included in the analysis as follows:

i) Vaccinated group: study outcomes in the 48-hour monitoring after vaccination. If vaccination does not occur by 12 hours after randomization, then study outcomes will be assessed between 12 and 60 hours after randomization.

ii) Unvaccinated group: study outcomes in the 48-hour monitoring period after randomization.

Inclusion criteria

• <33 and 0 days weeks gestational age at birth
• ≥6 weeks and 0 days and ≤12 weeks and 0 days postnatal age at randomization
• Remains hospitalized after birth (has never been discharged home)
• Treating clinician deems infant eligible to receive 2-month vaccines
• English- or Spanish-speaking parent(s)/legally authorized representative(s) (LAR(s))
• Not planned for discharge within 60 hours of study entry
• The parent/guardian must be willing and capable of providing permission for their child to participate through the written informed consent process

Exclusion criteria

• Receipt of DTaP, IPV, PCV13, or Hib prior to enrollment. Previous administration of the first dose of HBV is permitted
• Anticipated receipt of any vaccine other than DTaP, IPV, HBV, PCV13, or Hib during the first 60 hours after randomization
• History of a severe allergic reaction (e.g. anaphylaxis) to a previous dose of any hepatitis B vaccine
• History of a severe allergic reaction (e.g. anaphylaxis) to any component of the vaccines used in the study including neomycin, yeast and polymyxin B
• History of latex allergy
• Fever ≥38°C within 48 hours prior to randomization*

*This may result in a temporary delay of randomization

• Active known respiratory infection within 48 hours prior to randomization*

*This may result in a temporary delay of randomization

• Active infection being treated with systemic antimicrobials*

*This may result in a temporary delay of randomization

• Requiring mechanical ventilation or support with nasal intermittent positive pressure ventilation (NIPPV)*

*This may result in a temporary delay of randomization

• History of unstable progressive neurologic disorder of unknown cause
• Known cause of apnea other than apnea of prematurity
• Cyanotic heart disease (congenital or acquired)
• Major invasive medical or surgical procedure (including circumcision) within 48 hours prior to randomization or anticipated to have major invasive medical or surgical procedure during the first 60 hours after randomization*

*This may result in a temporary delay of randomization

• Child or parent/LAR is an immediate relative of study staff or an employee who is supervised by study staff.
• Any condition that would, in the opinion of the site investigator, place the participant at an unacceptable risk of injury or render the participant unable to meet the requirements of the protocol