There is a growing body of data suggesting that vitamin D modulates the host's immune response to acute respiratory infection (ARI). The primary aim of this study is to determine whether maternal vitamin D3 supplementation versus placebo decreases the incidence rate of microbiologically confirmed viral-associated ARI among infants in Dhaka, Bangladesh. Secondary outcomes include: A) incidence of ARI associated with specific major pathogens, B) incidence of clinical ARI (without the need for positive microbiology), and C) quantitative density of pneumococcal carriage. Infants will be followed from birth until 6 months of life. Among infants who meet at least one of the specific case definitions for ARI (see 'Detailed Description' section), nasal swab specimens will be collected. Respiratory samples will be analyzed by real-time polymerase chain reaction (qPCR) to identify a 7-virus panel (influenza A and B, respiratory syncytial virus, human metapneumovirus, adenovirus, and parainfluenza types 1, 2, and 3) plus quantitative density of S. pneumonia.

In this study, an acute respiratory infection (URTI and/or LRTI) has been clinically defined as:

A) Upper respiratory tract infection (URTI)

A new-onset illness consisting of at least two of the following clinical criteria at any time during a surveillance week:

• Caregiver-reported cough;
• Caregiver-reported rhinorrhea;
• Caregiver-reported nasal congestion; and,
• Measured axillary temperature greater than or equal to 37.5°C.

B) Lower respiratory tract infection (LRTI)

1. New onset clinically-diagnosed LRTI:

   • Caregiver-reported cough AND/OR difficulty breathing during a surveillance week; AND,
   • Observed lower chest wall indrawing AND/OR elevated respiratory rate (60 breaths per minute or greater for infant up to 59 days of age, or 50 breaths per minute or greater for infant 60 days of age or older)

2. Hospitalized LRTI

   • Hospitalization with physician diagnosis of pneumonia or bronchiolitis

Inclusion Criteria:

• Infants born to women enrolled in the MDIG trial (NCT01924013).
• Maternal inclusion criteria (at time of enrolment) will be:
• At least 18 years of age
• 17 to 24 completed weeks of gestation
• Intends to permanently reside in the trial catchment area for at least 18 months
• Family plans to reside in catchment area for the first 6 months postnatal
• Provides written informed consent for participation

Exclusion Criteria:

• Mother withdrawn from MDIG trial prior to delivery
• Failure to provide consent for participation in sub-study