VITAMIN D SUPPLEMENTATION FOR SEVERE PNEUMONIA IN UNDER-FIVE CHILDREN: A RANDOMISED CONTROLLED STUDY Protocol of Thesis to be submitted to the University of Delhi towards the Partial Fulfilment of the Requirement for the Degree of Doctor of Medicine (Pediatrics) (Session: 2007-2010) By Name of candidate Department of Pediatrics, University College of Medical Sciences & GTB Hospital, Delhi-110 095
26
Embed
VITAMIN D SUPPLEMENTATION FOR SEVERE PNEUMONIA IN …medicaleducationunit.yolasite.com/resources/Model... · VITAMIN D SUPPLEMENTATION FOR SEVERE PNEUMONIA IN UNDER-FIVE CHILDREN:
This document is posted to help you gain knowledge. Please leave a comment to let me know what you think about it! Share it to your friends and learn new things together.
Transcript
VITAMIN D SUPPLEMENTATION FOR SEVERE
PNEUMONIA IN UNDER-FIVE CHILDREN:
A RANDOMISED CONTROLLED STUDY
Protocol of Thesis to be submitted to the University of Delhi towards the
Partial Fulfilment of the Requirement for the Degree of
Doctor of Medicine (Pediatrics)
(Session: 2007-2010)
By
Name of candidate
Department of Pediatrics,
University College of Medical Sciences & GTB Hospital,
Delhi-110 095
2
VITAMIN D SUPPLEMENTATION FOR SEVERE
PNEUMONIA IN UNDER-FIVE CHILDREN:
A RANDOMISED CONTROLLED STUDY
Protocol of Thesis to be submitted to the University of Delhi towards the
Partial Fulfilment of the Requirement for the Degree of
Doctor of Medicine (Pediatrics)
(Session: 2007-2010)
Student: Dr. abcde …………………………………..
(Signature)
Supervisor: Dr. abc def …………………………………..
Professor, Pediatrics (Signature)
UCMS & GTB Hospital
Delhi-110 095
Co-Supervisor: Dr. K.K. Sharma …………………………………..
Professor & Head, Pharmacology (Signature)
UCMS & GTB Hospital
Delhi-110 095
Place of Work:
Department of Paediatrics,
University College of Medical Sciences >B Hospital, Delhi-110 095
3
ABSTRACT
Background: Pneumonia is one of the most common causes of morbidity and mortality
in children younger than 5 years of age, particularly in developing countries. Studies have
shown association of vitamin D deficiency with acute lower respiratory tract infection.
Study design: Double blind, randomized, placebo controlled clinical study
Objective: To assess the efficacy of vitamin D supplementation in children with severe
pneumonia
Subjects: 200 children (3months-5years of age) with severe pneumonia. Pneumonia will
be diagnosed in the presence of fever, cough, tachypnea and crepitations on auscultation.
Severe pneumonia will be indicated by pneumonia with lower chest in-drawing or at least
one other danger sign (inability to feed, lethargy, cyanosis).
Intervention: Vitamin D [1000 IU/d for infants (age <1 y), and 2000 IU/d for children
(age 1-5 years)], or placebo, administered orally at enrolment and then once daily 1 h
before breakfast for the next 4 days. The placebo/ drug will be dissolved in a teaspoon of
milk before being administered. Both groups will receive antibiotics as per IAP
guidelines.
Outcome measures: Primary outcome measures will include the time for resolution of
pneumonia and duration of hospitalization. Secondary outcome measures will include
time to resolution of tachypnea, lower chest indrawing, hypoxia, and inability to feed.
Statistical analysis: Kaplan-Meier survival function plots will be constructed to compare
the median duration for each outcome variable.
4
INTRODUCTION
Pneumonia remains a significant health problem in India with significant
morbidity and mortality. There is increasing recognition that nutritional deficiencies,
including micronutrients are important determinants of infections, including pneumonia,
and their outcomes.1 Identifying an effective nutritional agent that reduces the need for
antibiotics, duration of pneumonia and length of hospitalization would be highly cost-
beneficial.2
Vitamin D deficiency is a common and important nutritional deficiency in
children. Clinical and subclinical vitamin D deficiency in children has been reported to be
a significant risk factor for severe acute lower respiratory tract infection.3 Increased
susceptibility to respiratory infections in vitamin D deficiency may be explained on the
basis of physical factors, i.e., hypotonia and chest wall deformity, leading to reduced lung
volume, poor compliance of the chest wall, atelectasis and fibrosis. Apart from this, new
knowledge of the biological and clinical importance of the active form of vitamin D and
its receptor: has generated interest in its role in improving immune function.4
Although many observational studies have show association between vitamin D
deficiency and pneumonia, the evidence to demonstrate the effect of supplementation of
vitamin D in children with pneumonia/severe pneumonia is lacking.5-8
Considering this
lacuna, we plan to study whether Vitamin D, along with antibiotics, would improve the
outcome of severe pneumonia. The main objective of our study will be to evaluate the
effect of adding vitamin D in the routine treatment of severe pneumonia, in terms of
clinical recovery.
5
REVIEW OF LITERATURE
Clinical pneumonia (defined as respiratory infections associated with clinical
signs of pneumonia, principally pneumonia and bronchiolitis) in children under five years
of age is still the leading cause of childhood mortality in the world1. According to the
United Nations Children's Fund (UNICEF) and the World Health Organization (WHO),
pneumonia kills more children than any other illness – more than AIDS, malaria and
measles combined2. The WHO estimates that acute respiratory infection (ARI), mostly in
the form of pneumonia, is the leading cause of death in under-five children, killing over 2
million children annually2. More than 95% of clinical pneumonia in young children
worldwide occurs in developing countries. Recent estimates from India suggest that
pneumonia in children under five years of age constitutes 24 % of National burden of
disease and 13% of deaths.9 Mortality estimates suggest that 2.3 million children less
than five years die every year in India and 20% of these deaths are due to pneumonia.
Factors that put the children at increased risk of pneumonia include environmental
pollution (both indoor and outdoor), improper childcare practices, increased transmission
of pathogens, and nutrition-related practices and disorders. Consequently considerable
research has aimed at finding effective interventions against ALRI such as immunization3
and case-management involving antibiotics.4 Micronutrient supplementation is another
potential intervention. The role of micronutrient deficiency in pneumonia related
mortality and morbidity is now gaining importance. Various studies have documented the
role of Zinc in treatment of pneumonia.5. Conflicting results are reported about the role of
Vitamin A in lower respiratory tract infections. Many trials have investigated the benefits
6
of vitamin A supplements, and found that vitamin A supplementation significantly
decreases morbidity and mortality from ALRI due to measles, and also decreases the
overall under-5 mortality.6
Vitamin D and Acute Respiratory Tract Infections
Vitamin D deficiency is known to cause rickets and retard skeletal growth.
Studies in developing countries have suggested an association between nutritional rickets
and pneumonia. In Iran 43% of 200 children with rickets had radiologically proven
pneumonia, and 44% of 250 children with Vitamin –D deficiency rickets in Kuwait had
pneumonia.7,8
A hospital based case control study from Egypt showed that acute
respiratory tract infections were present in 81% of children with rickets as compared to
58% of controls.9 In a study of 300 consecutive outpatients in Ethiopia, 41% had clinical
signs of rickets, while in an inpatient setting, rickets was associated with 13-fold
increased risk of pneumonia in children less than 5 y of age.10,11
In another study of 131
patients with rickets between 1979 and 1988, compared with age matched and sex
matched controls without rickets, pneumonia was more common in rachitic patients than
in controls.12
Subclinical vitamin D deficiency is a significant risk factor for severe acute
lower respiratory tract infection in Indian children less than five years of age.13
Hitherto, the cause of increased susceptibility to respiratory infections in rickets
was being explained on the basis of physical factors, i.e., hypotonia and chest wall
deformity, leading to reduced lung volume, poor compliance of the chest wall, atelectasis
and fibrosis13
. The interesting new development is the role of vitamin D as an
immunomodulator and a specific factor responsible for augmenting the innate immunity,
7
specifically to protect against respiratory tract infections. This has been already
demonstrated experimentally in tuberculosis, a major pulmonary disease.14-17
The present research assumes importance given the increasing evidence that sub-
clinical vitamin D deficiency is common even in countries at low latitude and with
plentiful sunshine, including India.18-20
8
AIM AND OBJECTIVE
Aim
To study the efficacy of vitamin D supplementation in the treatment of severe pneumonia
in children under 5 years of age.
Objective
To compare the time to resolution of the illness (tachypnea, lower chest indrawing,
hypoxia, and inability to feed), and duration of hospitalization in children with severe
pneumonia receiving vitamin D supplementation or placebo, in addition to routine
antibiotics and supportive therapy .
9
SUBJECTS AND METHODS
Study Setting
This prospective study will be hospital based, to be conducted in the Department of
Pediatrics at UCMS and GTB hospital, Delhi. A clearance from ethical committee of the
institute will be obtained. Written informed consent will be obtained from the family
members or any surrogate for participation in the study (Annexure 1). The study will be
conducted from May 2008 to April 2009, including enrollment (9 months) and analysis