Background
Despite the improvement in the health status of Indonesian infants in the last two decades, mortality rates remain high, estimated at 24.5 deaths per 1000 live births in 2013 [
1,
2]. Acute respiratory illnesses (ARI) and diarrhea are the leading causes of mortality in Indonesian children under 5 years of age [
3] and were the main targets of the fourth millennium development goal (MDG) to reduce child mortality by two thirds by 2015 [
3]. Globally, Indonesia has amongst the highest incidence of ARI, with approximately 6 million new ARI cases per year in children under 5 years estimated in 2008 [
4]. In 2013, the prevalence of ARI and diarrhea was 0.24 and 3.5% respectively as reported in the 2013 Indonesia Basic Health Research (IBHS), [
6] a national cross-sectional survey to capture the health problems in 33 provinces in Indonesia (
n = 1,027,763) such as any episodes of ARI and diarrhea in the 4 and 2 weeks prior to the survey and case management of diarrhea with Oral Rehydration Solution (ORS) and zinc. The IBHS also reported that malnutrition was common, with 6.8% of children under 5 years of age defined as wasted, 5.3% as severely wasted, 19.2% as stunted and 18% as severely stunted in 2013 [
5,
6]. Importantly, macronutrient deficiencies have been associated with an increased risk of developing ARI and diarrhea, [
7] with a 4-fold increase in ARI-related deaths in severely malnourished children compared to children with normal nutritional status [
8,
9].
Identifying effective disease prevention and management strategies in Indonesia remains an important goal to decrease the morbidity and mortality rate from ARI and diarrhea. The World Health Organization (WHO) and The United Nations Children’s Emergency Fund (UNICEF) recommend exclusive breastfeeding (EBF) for 6 months, continued breastfeeding up to 2 years of age and improvement of case management in health facilities for protection, prevention and treatment of pneumonia and diarrhea [
11]. Similarly, the Indonesian government recommends EBF for the first 6 months to improve nutritional status and to provide additional protection against ARI and diarrhea [
7‐
9,
12‐
15] but the national coverage of EBF was reported by the Ministry of Health to be only 54% at 6 months in 2013 [
5]. Furthermore, the routine national immunisation program covers BCG, hepatitis B, polio, DPT, HiB and measles vaccines, with with rotavirus and pneumococcal vaccines currently limited to the private sector [
10].
One of challenges of case management in health facilities in developing countries is poor adherence to available guidelines to manage ARI and diarrhea [
16,
17], resulting in inaccurate assessment of the signs and symptoms which contribute to incorrect diagnosis, inappropriate treatment [
16‐
18] and poor outcomes [
19,
20]. In Indonesia, the current available guidelines for ARI case management from the Indonesian Pediatric society and WHO are symptomatic relief and maintenance of adequate oral hydration for the treatment of Upper Respiratory Tract Infections (URTI) and antibiotics for pneumonia [
21,
22]. However, current case management practice, such as the prescription of medications and how the WHO and local pediatric recommendations were followed for ARI and diarrhea in South East Asia, including Indonesia, is not well described.
We aimed to describe the nutritional status, feeding practice and case management of ARI and diarrhea of infants enrolled in a rotavirus vaccine clinical trial during the first 6 months of life in the Klaten and Jogjakarta regions in Indonesia. In particular this study focuses on the rate of EBF, the infants’ nutritional status assessed at three time-point visits and the medication prescribed for ARI and diarrhea. We hypothesized that [
1] poor nutritional status would be common in infants, [
2] rates of EBF would be high and that [
3] the management of acute ARI and diarrhea would not be consistent with the available guidelines in Indonesia.
Discussion
This is one of the first studies to describe the nutritional status, feeding practice and health status particularly ARI and diarrhea case management, in the first 6 months of life in Indonesia. The study was conducted alongside a rotavirus vaccine clinical trial at three separate time points after birth and has provided valuable insights into breastfeeding practices and the management of both ARI and diarrhea in two regions of Indonesia.
At the both points after birth, 5–6% of our study participants were underweight, 1–2% were severely underweight; 3–5% were wasted and 1% were severely wasted. We also found that at all three time points stunting occurred in 5–9% of study participants, with 2–3% being severely stunted. This is substantially lower than national finding in 2013 where the proportion of underweight, wasted and stunted infants in Indonesia was 19.6, 37.2 and 12.1% respectively [
6]. As expected, the overall nutritional status of infants within our study was higher than the general population of infants in Indonesia since they had higher engagement with the health system through the clinical trial and improved access to early detection of nutritional problems compared with the general population. [
28]. Nevertheless, it is clear that nutritional problems are still an issue in Indonesia. To address the national problems in under nutrition, the Indonesian government has engaged with the Scaling Up Nutrition (SUN) movement, a program that aims to provide country specific nutritional intervention for pregnant women and children under 5 years (i.e Vitamin A supplementation) and support breastfeeding, to improve the management of under nutrition [
29]. In the 3 years since introduction of the SUN movement in 2011, the prevalence of stunted children under 5 years had decreased from 39.2 to 36.4%, with a target of 26.3% by 2025 [
30].
In addition to the reported under nutrition in this study, we also identified 5% of infants who were overweight or obese. Moreover, a fifth of the total infants participating in this study were at possible risk of overweight and might need further nutritional evaluation. Improvement in the economic conditions in developing countries may increase the prevalence of overweight and obesity that co-exists with under nutrition through factors such as life styles changes (such as reducing physical activities), urbanisation and aggressive nutrition interventions for undernourished children [
31]. In 2014 the Indonesian Pediatric society published a guideline for the management and prevention of childhood obesity. For children aged 0–12 months, exclusive breast-feeding is recommended up to 6 months with continuation of breastfeeding up to 12 months. Other recommendations include the introduction of a wide variety of foods, avoidance of sweetened beverages and snacks and no televisions in bedrooms [
32].
In our study, 60% of women were still EBF their infant at 6 months. This was higher than the recent WHO report of 42% EBF coverage in the first 6 month of age in Indonesia in 2014 [
33]. In the same year the Indonesian ministry of health reported that the EBF rate was 54% nationwide. The current national Indonesian EBF rate of 46.3% [
34] is above the global average rate of EBF (37% across 75 countries), [
11] although it is still below the Indonesian government’s target of >75% [
35]. The higher EBF rate in our study may be due to the families’ engagement in the vaccine clinical trial, providing a higher exposure to health care providers and to the national program that encouraged EBF. In our study, majority of mothers reported themselves as the primary support for EBF at 6 months, and 25% of mother reported that the strongest support for EBF was from their partners. Other studies have reported that mothers who face difficulties maintaining EBF are more likely to have limited partner support [
36]. To reach the targeted level of EBF in Indonesia, increasing support for mothers practicing EBF in the first 6 months, including partner education, and appropriate complementary feeding support up to 24 months, is needed. Most of the infants were reported to be breastfed for more than 10 times per day as recommended by American Academy of Pediatrics [
37].
The prescription of cough medication for ARIs in the first 6 months, including expectorants (Glyceryl Guaiacolate or Guaifenesin), antihistamines (Chlorpeniramin maleat) and mucolytics (ambroxol), was very common in our study despite it not being recommended by the Indonesian Pediatric society and the WHO. Expectorants, mucolytic agents in cough medication, antihistamines and oral bronchodilators are not recommended medication for the management of URTI in children. In addition, a systematic review reported that most cough medications in children are not effective [
38,
39] and there have been a number of reports of toxicity and deaths related to cough medications in young infants, [
40,
41] mostly due to Chlorpheniramin maleat (CTM) and ambroxol. In the current study, CTM is the second most commonly prescribed cough medication in infants, especially in primary health care settings. Studies reported that CTM can depress the central nervous system or cause dysrhythmias [
41,
42]. Among 10 cold and cough medication-related deaths in infants <6 months of age in a US study, four had toxic levels of CTM and Ambroxol in their blood [
36]. This was possibly because the dosage of cough and cold medication deemed to be safe in infants had been extrapolated from adult data with limited safety data available for use in young infants [
40]. Education of mothers and health workers regarding the risk and health benefits for giving the abovementioned therapies in infants is required.
Bronchodilator use in infants under 6 months was also very common in our study for the treatment of cough. WHO guidelines recommend that bronchodilators in ARI are given by inhalation and not by oral therapy [
21] and are only recommended when children present with wheeze with unclear cause or wheeze with the presence of fast breathing or chest indrawing, and not for mild cough. There is little evidence of a beneficial effect from giving oral bronchodilators for the treatment of cough alone [
21]. A randomised controlled trial in India comparing the use of oral salbutamol for symptomatic relief in acute cough with placebo concluded non-superiority of oral salbutamol [
43] and there was also little evidence, that oral salbutamol affected the mean duration of fever, cough, and noisy breathing or the time to the resolution to normal activities compared with placebo. Of most concern, 5 out of 140 Indian infants in the bronchodilator group were reported to have adverse effects including tremors [
43,
44]. Salbutamol use in neonates has also been associated with supraventricular tachycardia [
45]. Considering there appears to be limited or no benefit from giving oral salbutamol for the treatment of mild ARI in infants, and there are substantial safety concerns, administration of oral salbutamol is not recommended for infants and further education of health care providers in Indonesia is needed.
The use of ORS and zinc supplementation to treat diarrhea was low in our study. Currently, WHO recommends rehydration with ORS and zinc supplementation daily for 10–14 days for the treatment of acute diarrhea episodes with no or some dehydration [
21]. However, most diarrhea episodes in our study were mild, with diarrhea occurring on average 4–5 times a day and lasting for 3 days during an average episode, and none required hospitalisation. Yet, the findings from our study are consistent with the low use of ORS for rehydration and zinc supplementation for treatment of diarrhea that has been identified nationally for the management of acute diarrhea, where it was reported that 33 and 17% of children under five with acute diarrhea received ORS and zinc respectively [
6]. Low implementation of ORS might be due to home solutions being given over ORS (due to the ease of availability and for palatability reasons) or due to low adherence to WHO guidelines in community settings, once again raising the need for further education of healthcare workers.
There were several limitations to the current study. The general health of infants in this study would be higher than the general population as all the participants were enrolled in a clinical trial, were regularly monitored and had good engagement with the health system. However, we still found evidence of wasting, severe stunting and obesity in up to 9% of infants. In this study, we did not collect information for all episodes of ARI and diarrhea over the 6 months but rather chose to focus on case management of ARI and diarrhea in episodes that occurred within 2 weeks prior to the follow-up assessments. Given this was not our aim, we were unable to provide an estimate of the incidence of ARI and diarrhea episodes, nor report the treatment received for all episodes of ARI or diarrhea occurring within the first 6 months of life. In addition, we did not collect severity of diarrhea within this study, which may have been lower as participants were included in a rotavirus vaccine clinical trial, although both vaccine and placebo participants were included. Diarrhea severity would also have impacted on the use of ORS and zinc, but regardless use was reported to be very low with poor adherence to guidelines for diarrhea case management. There was also the potential for recall bias with ARI and diarrhea episode management, with episodes retrospectively reported by the mother. Further clarification was sought from medical reports held at the PHCs on treatment but completeness of the diagnostic and management information varied.
Acknowledgements
We thank all the infants and their families for their participation in this study. We also thank all the hospital and community pediatricians, doctors and midwives; the health district office staff who were involved in this study from the initiation, recruitment and follow up, Prof Stephen Michael Graham who had reviewed the manuscript and provided important insights and to all research assistants involved in the study; Rizka Dinari, Meysitha Haris, Asih Sri Utami, Niken Safitri, Dewi Setiani and Septi Kurnia Lestari.