Maternal Vitamin D for Acute Respiratory Infections in Infancy

Study Overview
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Brief Summary
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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.

Detailed Description
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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) 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) Hospitalized LRTI Hospitalization with physician diagnosis of pneumonia or bronchiolitis

Official Title
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Maternal Vitamin D for Acute Respiratory Infections in Infancy (MDARI): a Nested Sub-study in a Randomized Controlled Trial of Vitamin D Supplementation During Pregnancy and Lactation in Dhaka, Bangladesh

Conditions
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Upper Respiratory Tract Infections, Lower Respiratory Tract Infections

Intervention / Treatment
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* Dietary Supplement: Vitamin D3
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 1 Day
Maximum Age: 26 Weeks

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Group A<br>Prenatal Period 0 IU; Postpartum Period 0 IU (placebo) Overall: The Prenatal Period will start at enrolment (17-24 weeks gestation) and last until delivery. The Postpartum Period will last from delivery until 6 months postpartum. | Dietary Supplement: Placebo<br> <br> |
| Experimental: Group B<br>Prenatal Period 4,200 IU/week of vitamin D3; Postpartum Period 0 IU/week (placebo) | Dietary Supplement: Vitamin D3<br> <br> * Other names: Cholecalciferol;|
| Experimental: Group C<br>Prenatal Period 16,800 IU/week of vitamin D3; Postpartum Period 0 IU/week (placebo) | Dietary Supplement: Vitamin D3<br> <br> * Other names: Cholecalciferol;|
| Experimental: Group D<br>Prenatal Period 28,000 IU/week of vitamin D3; Postpartum Period 0 IU/week (placebo) | Dietary Supplement: Vitamin D3<br> <br> * Other names: Cholecalciferol;|
| Experimental: Group E<br>Prenatal Period 28,000 IU/week of vitamin D3; Postpartum Period 28,000 IU/week | Dietary Supplement: Vitamin D3<br> <br> * Other names: Cholecalciferol;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Microbiologically confirmed viral acute respiratory infection (URTI and/or LRTI) |  | 0 to 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ARI with microbiologically confirmed influenza A or B |  | 0 to 6 months | 
| ARI with microbiologically confirmed RSV |  | 0 to 6 months | 
| Clinical URTI and/or LRTI (i.e., no microbiological confirmation) |  | 0 to 6 months | 
| Clinical URTI (i.e., no microbiological confirmation) |  | 0 to 6 months | 
| Clinical LRTI (i.e., no microbiological confirmation) |  | 0 to 6 months | 
| Quantitative S. pneumoniae nasal carriage density |  | 0 to 6 months | 
| Pneumonia (non-severe) and severe pneumonia or very severe disease |  | 2 to 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bangladesh, Vitamin D, Acute Respiratory Infections, Infancy, Pregnancy