A study of pneumonia in hospitalised Indonesian children and its association with vitamin D deficiency

The burden of acute respiratory illness (ARI), including pneumonia, is not well described in infants and young children in Indonesia. There is suggestive evidence that vitamin D deficiency is a potential risk factor for ARI, including pneumonia. However, this has not been studied. This research project aimed to describe the prevalence of vitamin D deficiency in children hospitalised with severe respiratory infections in Yogyakarta, and to determine if vitamin D deficiency is associated with severity of ARI.

From 18 February 2016 to 18 July 2017, 154 children with 163 admissions of ARI were successfully recruited in the study. One third of these admitted children had severe pneumonia. Blood samples for Vitamin D levels in these children were analysed.

Acute respiratory illness (ARI), predominantly pneumonia, is recognised as a major cause of under-five-year-old child morbidity and mortality globally, with infants and young children (less than two years of age) experiencing the highest mortality rates and the majority of pneumonia-related deaths. However, there is very little data from Indonesia on the burden of pneumonia in infants and young children. The identification of children who have the greatest risk for severe pneumonia and pneumonia-related mortality is required to inform the potential impact of preventive and management intervention strategies to reduce the burden of disease.

This study provided original baseline data on the prevalence of vitamin D deficiency in children under five years of age hospitalised with ARI, including pneumonia. This study is the first study to evaluate the association between vitamin D deficiency and the severity of ARI in Southeast Asia, a region where ARI and pneumonia is prevalent and vitamin D deficiency has been recognised as common. If an association between vitamin D deficiency and the severity of ARI in Indonesian infants and children is found, this may justify a future vitamin D-supplementation clinical trial for the prevention of ARI in Indonesian and perhaps other Southeast Asian children who share similar features and risk factors. By evaluating the possible risk factors for vitamin D deficiency and ARI this study may be able to help inform mitigation of these risks and prevent diseases.

Nutritional deficiencies, including protein-energy malnutrition and micronutrient deficiencies, are recognised to be among the most important risk factors for pneumonia globally, although the relationship between nutritional deficiencies and pneumonia has not been well studied in Indonesia. Of micronutrient deficiencies, the strongest evidence is for vitamin A deficiency and measles-related pneumonia and there is variable evidence for zinc deficiency, depending on the setting.

There is, however, increasing evidence that vitamin D deficiency also increases susceptibility to pneumonia in children, a deficiency that is common in many countries in Southeast Asia, despite proximity to the equator. Vitamin D is an additional micronutrient that may be important in protecting against respiratory infections, but for which there is currently insufficient clinical evidence. Vitamin D is produced predominantly by solar conversion through the skin, with a small amount being absorbed from food such as oily fish, fish liver oil, eggs, and fortified dairy products. Vitamin D appears to play a role as an immune modulator, including in the immune system of the respiratory tract

While there is considerable evidence to support the biological plausibility that vitamin D deficiency may increase susceptibility to respiratory tract infection, the evidence is largely from in vitro studies, and its application to clinical practice needs further investigation. Additionally, there are cultural practices in Indonesia that might increase the prevalence of vitamin D deficiency in the community compared with other settings at the same latitude, such as maternal covering clothing, a more indoor lifestyle and high breastfeeding rates. Importantly, there are no published data from Indonesia on the association between vitamin D deficiency and the incidence of child pneumonia.

Inadequate levels of vitamin D have been recognised as common in children living in communities close to the equator in Southeast Asia. The main causes of deficiency are due to lifestyle changes and cultural practices that limit exposure to ultraviolet radiation. It is possible that Indonesian infants are particularly at risk. The avoidance of direct sunlight and wearing of headscarves by many Indonesian women may mean that maternal vitamin D deficiency is common, and therefore their babies are at risk of vitamin D deficiency at birth.

Findings

A hospital-based study was conducted to determine the prevalence of vitamin D deficiency in children under five years of age hospitalised with ARI, including pneumonia, and to evaluate an association of vitamin D deficiency with severity of pneumonia. The study was conducted in two hospitals in Yogyakarta province.

This study was conducted over a 15-month recruitment period (from February 2016 to July 2017) to include all seasons in Indonesia. After informed consent was obtained, a sample of 2.5ml of blood was collected. Risk factors for pneumonia and for vitamin D deficiency were explored. The data showed that a good percentage of children with pneumonia had vitamin D deficiency. Infants of between two and six months old and children with congenital heart disease were more likely to have a lower vitamin D level. This data is valuable in informing the potential for a future vitamin D supplementation clinical trial for the prevention of pneumonia in Indonesian children. The study provides important background data should such a trial be justified.

This study additionally allowed for transfer of knowledge, skills and mentoring between institutions and countries. Dr Oktaria is a UGM staff member pursuing a PhD at the Department of Paediatrics at the University of Melbourne. Her project was conducted under joined supervision between UoM and MCRI (Professor Steve Graham, Dr Margie Danchin, Professor Julie Bines) and UGM (Dr Rina Triasih and Professor Yati Soenarto). The study helped to address a major health problem in Indonesian children, i.e. pneumonia, led by Professor Graham, an international expert in childhood lung disease.