Nutritional status, exclusive breastfeeding and management of acute respiratory illness and diarrhea in the first 6 months of life in infants from two regions of Indonesia.

BACKGROUND: Infant morbidity and mortality rates remain high in Indonesia, with acute respiratory illnesses (ARI) and diarrhea the leading two health problems in children under 5 years. We aimed to describe the nutritional status, feeding practice and case management of ARI and diarrhea of infants from two regions of Indonesia during the first 6 months of life. METHODS: This study was an observational study conducted in parallel to an immunogenicity and efficacy trial of an oral rotavirus vaccine (RV3-BB) in the Klaten and Yogyakarta regions, Indonesia. Mothers were interviewed at 3 time points: within the first 6 days of their infant's life, and at 8-10 and 22-24 weeks of age. Questions asked included pregnancy history, infant nutritional status, feeding status and health of infants within up to 2 weeks prior to the assessment. RESULTS: Between February 2013 and January 2014, 233 mother-infant pairs were recruited. 60% (136/223) of infants were exclusively breastfed (EBF) until 6 months of age with the strongest support for EBF reported by mothers themselves 70% (101/223) and 25% (36/223) from their partners. At 6 months, 6% (14/223) of infants were underweight and severely underweight; 4% (8/ 223) wasted and severely wasted; and 12% (28/223) were stunted and severely stunted. Non-recommended medication use was high, with 54% (21/39) of infants with reported cough within 2 weeks of an assessment receiving cough medication, 70% (27 /39) an antihistamine, 26% (10/39) a mucolytic and 15% (6 /39) an oral bronchodilator. At age 22-24 week, infants with reported diarrhea within 2 weeks of an assessment had low use of oral rehydration solutions (ORS) (3/21;14%) and zinc therapy (2/ 21;10%). CONCLUSION: In this unique observational study, breastfeeding rates of 60% at 6 months were below the Indonesian national target of >75%. Adherence to WHO guidelines for management of ARI and diarrhea was poor, with high use of non-recommended cough medications and oral bronchodilators in the first 6 months of life and low use of ORS and zinc therapy. Ongoing education of primary health care workers and parents regarding management of common illness is needed in Indonesia.

Phase I trial of RV3-BB rotavirus vaccine: a human neonatal rotavirus vaccine.

INTRODUCTION: RV3 is a human neonatal rotavirus strain (G3P[6]) that has been associated with asymptomatic neonatal infection and replicates well in the infant gut. RV3-BB rotavirus vaccine has been developed as a rotavirus vaccine candidate for administration at birth. METHODS: A single-centre, double-blind, randomised placebo-controlled Phase I study evaluated the safety and tolerability of a single oral dose of the second generation RV3-BB rotavirus vaccine (8.3×10(6)FFU/mL) in 20 adults, 20 children and 20 infants (10 vaccine and 10 placebo per age cohort). Vaccine take was defined as seroconversion (a 3-fold increase in serum anti-rotavirus IgA or serum neutralising antibody (SNA) from baseline at day 28 post-dose) or evidence of RV3-BB viral replication in the faeces by RT-PCR analysis 3-6 days post-vaccination. RV3-BB presence was confirmed by sequence analysis. RESULTS: The RV3-BB vaccine was well tolerated in all participants, with no pattern of adverse events shown to be associated with the study vaccine. In the infant cohort, vaccine take was demonstrated in 8/9 infants following a single dose of vaccine compared with 2/7 placebo recipients. In the infant vaccine group, 5/9 infants exhibited either IgA or SNA seroconversion and 7/9 infants had evidence of RV3-BB replication on days 3-6, compared with 2/7 infants who seroconverted and 0/10 infants with evidence of replication in the placebo group. Two infants in the placebo group had serological evidence of a rotavirus infection within the 28-day study period: one demonstrated an IgA and the other an SNA response, with wild-type virus replication detected in another infant. CONCLUSION: A single dose of RV3-BB rotavirus vaccine was well tolerated in adults, children and infants. Most infants (8/9) who received RV3-BB demonstrated vaccine take following a single dose. These data support progression of RV3-BB to Phase II immunogenicity and efficacy trials.

Retrospective hospital based surveillance of intussusception in children in a sentinel paediatric hospital: benefits and pitfalls for use in post-marketing surveillance of rotavirus vaccines.

UNLABELLED: Evaluation of the safety of rotavirus vaccines, particularly with respect to the risk of intussusception, is recommended for countries planning to introduce rotavirus vaccines into the National Immunisation Program. However, as prospective studies are costly, require time to conduct and may be difficult to perform in some settings, retrospective hospital based surveillance at sentinel sites has been suggested as an option for surveillance for intussusception following introduction of rotavirus vaccines. OBJECTIVE: To assess the value of retrospective hospital based surveillance to describe clinical and epidemiological features of intussusception in children aged <24 months and to investigate any temporal association between receipt of a rotavirus vaccine and intussusception. METHODS: A retrospective chart review of all patients diagnosed with intussusception at Royal Children's Hospital, Melbourne, Australia over an 8-year period including before and after rotavirus vaccine introduction into the National Immunisation Program, was conducted using patients identified by a medical record database (ICD-10-CM 56.1). Patient profile, clinical presentation, treatment and outcome were analysed along with records of immunisation status obtained using the Australian Childhood Immunisation Register. RESULTS: A 9% misclassification rate of discharge diagnosis of intussusception was identified on critical chart review. The incidence rate of intussusception at the Royal Children's Hospital over the study period was 1.91 per 10,000 infants <24 months (95% CI 1.65-2.20). Intestinal resection was required in 6.5% of infants (95% CI 3.6%, 11.0%). Intussusception occurred within 30 days after vaccination in 2 of 27 patients who had received at least 1 dose of a rotavirus vaccine. CONCLUSIONS: Valuable data on the incidence, clinical presentation and treatment outcomes of intussusception can be obtained from data retrieved from hospital medical records in a sentinel paediatric hospital using standardised methodology. However, there are methodological limitations and the quality of the data is highly dependent on the accuracy and completeness of the patient information recorded, the system of coding and record retrieval.

Intussusception following rotavirus vaccine administration: post-marketing surveillance in the National Immunization Program in Australia.

INTRODUCTION: In Australia, post-marketing surveillance for intussusception following vaccination commenced with funding of RotaTeq(®) and Rotarix(®) vaccines under the National Immunization Program (NIP) in July 2007. METHODS: Two active surveillance mechanisms (hospital-based case ascertainment and monthly reports from paediatricians) identified intussusception cases between 1st July 2007 and 31st December 2008 in four states. Linkage to vaccination records identified cases occurring within 1-7 and 1-21 days of rotavirus vaccination. Expected cases within the post-vaccination windows were calculated by applying rates of intussusception from national hospitalisation data over 6 years (mid-2000 to mid-2006), by age and state, to numbers vaccinated (by dose) according to the Australian Childhood Immunization Register. RESULTS: Combining exposure windows associated with all doses of rotavirus vaccine from 1 to 9 months of age, there was no evidence of an increased risk of intussusception following vaccination for either vaccine. However, in infants 1 to <3 months of age, there was suggestive evidence of excess intussusception cases 1-7 and 1-21 days following dose 1 (1-7 days: RotaTeq(®) relative risk (RR)=5.3, 95% confidence interval [CI] 1.1,15.4; Rotarix(®) RR 3.5, 95% CI 0.7,10.1; 1-21 days: RotaTeq(®) RR 3.5, 95% CI 1.3, 7.6; Rotarix(®)RR 1.5, 95% CI 0.4, 3.9). There was no evidence that clinical outcome of intussusception occurring within 21 days of rotavirus vaccination differed from that in cases occurring later post-vaccination. CONCLUSION: Although we found no overall increase in intussusception following receipt of rotavirus vaccine, there was some evidence of an elevated risk following the first dose of both vaccines. Larger population-based studies using linked databases are required to provide more definitive evidence.

Maternal antibodies to rotavirus: could they interfere with live rotavirus vaccines in developing countries?

INTRODUCTION: Past experience with live oral vaccines including licensed rotavirus vaccines demonstrates a trend towards reduced vaccine efficacy in developing countries compared with developed countries. The reasons behind this disparity are not well understood. Transplacental transfer of maternal antibodies and breast milk ingestion may attenuate vaccine responses in infants in developing countries where rotavirus infections are endemic, and maternal antibody levels are high. We examined the prevalence and level of rotavirus antibody in maternal and cord serum, colostrum and breast milk in a developing country setting. METHODS: 100 mother-infant pairs were prospectively recruited from December 2008 to February 2009 at Dr. Sardjito Hospital, Yogyakarta, Indonesia. Maternal and cord sera were collected during delivery. Colostrum and transitional breast milk were collected between day 0-3 and day 7-10 postpartum respectively. Rotavirus-specific IgA and IgG were estimated for all specimens and virus neutralization assays were conducted on a subset of milk specimens. RESULTS: All maternal and cord serum samples were positive for rotavirus-specific IgG antibodies with a strong correlation between levels of rotavirus-specific IgG in mothers and levels transferred to infants in cord blood (r=0.86; p=0.001). 78% of colostrum and 67% of transitional breast milk specimens were positive for rotavirus-specific IgA. There was a median 4-fold decrease in rotavirus-specific IgA from colostrum to transitional breast milk. Neutralizing antibodies were present in 56% of colostrum specimens assayed (19/34) and in 41% of transitional milk specimens assayed (14/34). CONCLUSIONS: Maternal serum and breast milk antibodies to rotavirus are highly prevalent in a developing country setting. Evaluation of the impact of maternal anti-rotavirus serum and breast milk antibody upon vaccine immunogenicity would help to inform rotavirus vaccination strategies, especially in developing settings.

Changes in resting energy expenditure in children with congenital heart disease.

OBJECTIVES: The aim of this study was to relate changes in energy expenditure and growth in infants with congenital heart disease (CHD), to the timing of corrective cardiac surgery. METHODS: Prospective cohort study of infants less than 1 year with CHD admitted for cardiac surgery to Royal Children's Hospital, between January to September 2005. Infants were assessed using anthropometry and indirect calorimetry and compared to healthy age-matched controls. RESULTS: Infants (38) underwent corrective (n=25) or palliative (n=13) cardiac surgery either at < or = 10 days or at >10 days. Infants undergoing corrective surgery after 10 days had deficits in z-scores for weight compared with infants undergoing early surgery (-1.15+/-1.02 vs -0.24+/-0.98; CI 95%: -1.736 to -0.085; P<0.05) and height (-1.47+/-1.16 vs -0.12+/-0.66; CI 95%: -2.262 to -0.428; P<0.01). However, 6 months following surgery, weight and height were similar in both groups. Resting energy expenditure was increased before surgery compared to healthy controls (247+/-36 vs 210+/-22 kJ kg(-1 )day(-1); 95% CI: -57.29 to -16.71; P<0.001) however, normalized 1 week following cardiac surgery. Standard equations did not accurately predict measured REE. CONCLUSION: Increased REE observed in infants with CHD normalizes within 1 week following corrective cardiac surgery. Deficits in weight and growth were greater in infants undergoing corrective cardiac surgery>10 days of age compared with infants undergoing surgery in the first 10 days of life.

Vitamin A and E deficiency and lung disease in infants with cystic fibrosis.

OBJECTIVES: Vitamin A and E deficiency is common in cystic fibrosis (CF). These vitamins have immunomodulating properties and we determined whether decreased serum vitamin A and E levels in young infants are associated with early CF lung disease and lower airway inflammation. METHODS: A post-hoc analysis was undertaken on previous data collected prospectively in 39 newly diagnosed infants identified by a newborn CF screening programme. Assessment of CF genotype, nutrition, pancreatic status, serum retinol and alpha-tocopherol levels was performed at diagnosis. Pulmonary status was determined clinically, by Brasfield chest radiographic scores and analysis of bacterial counts and inflammatory indices in bronchial lavage (BL) fluid. These assessments were repeated 12 months later. RESULTS: At diagnosis, 20 out of 39 (51%) CF infants had low serum retinol (mean (SD) 0.7 (0.3) micromol/L) and 9/38 (24%) had low alpha-tocopherol (mean (SD) 13.4 (8.4) micromol/L) levels. Dietary energy intake was related to serum retinol concentrations at diagnosis (r(2) = 0.27; P = 0.001). At 1 year, serum retinol and alpha-tocopherol levels had normalized following vitamin A and E supplementation. Respiratory symptoms, radiographic scores and BL inflammatory indices systematically deteriorated during infancy, reaching significance for free neutrophil elastase activity (9 out of 29 vs 21 out of 33; P = 0.01) and IL-8 levels (79 vs 416; P = 0.046) in BL fluid. No association was seen between serum vitamin levels at diagnosis and airway inflammatory indices at either diagnosis or 12 months later. CONCLUSION: We found in this CF birth cohort no evidence to implicate vitamin A or E deficiency in the development of lung disease or airway inflammation during infancy.

Measurement of resting energy expenditure in infants.

OBJECTIVE: The method for measurement of basal metabolic rate (BMR) using indirect calorimetry in adults is well established but is impractical in infants. METHODS: In this prospective study energy expenditure was measured using indirect calorimetry in 14 infants when sleeping and when lying quietly awake. RESULTS: Sleeping metabolic rate (SMR) was lower than energy expenditure (EE) measured in the same infants in a quiet resting state (mean difference [SD]: 297 [162] kJ/d; P < 0.005; 55 [33.4] kJ/kg per day; P < 0.005). The correlation within individuals suggests that these differences are related to the level of arousal. Awake EE, but not SMR, was significantly greater than estimated BMR using the FAO/WHO/UNU predictive equation. CONCLUSIONS: In infants, the level of arousal during measurement of EE can significantly impact on the interpretation of EE results. A standardized method for the measurement of EE in infants using indirect calorimetry is proposed.

New approaches to parenteral nutrition in infants and children.

Parenteral nutrition (PN) has become a mainstay in the treatment of children with intestinal failure or conditions that preclude enteral feeding. Estimated energy and protein requirements can usually be met, unless the patient is fluid volume restricted or glucose intolerant. Although PN is generally well tolerated, in some patients it is still associated with a significant morbidity. Complications include metabolic disturbances, venous access device infection or dysfunction, venous thrombosis and cholestatic liver disease. Patients need to be carefully monitored for evidence of micronutrient deficiencies or excesses. There is a close relationship between line sepsis and thrombosis. Strict aseptic technique is the key to preventing line infections. Recurrent sepsis and thrombosis may eventually lead to loss of venous access and may jeopardize the long-term delivery of PN. Chronic cholestatic liver disease is common in premature infants with gastrointestinal problems, recurrent sepsis and lack of enteral feeding. The aetiology is multifactorial. Early enteral feeding is the most effective strategy in preventing PN-associated liver disease. New specialized nutrient solutions and lipid emulsions promise improved clinical outcomes. However, long-term clinical data are not yet available in children. In recent years, nutrition support teams have improved clinical and economic outcomes by encouraging the appropriate use and monitoring of PN therapy. In patients with intestinal failure, parent-administered home PN has become an alternative to long-term hospitalization. Apart from a positive effect on the quality of life of patient and family, home PN is cost-effective and reduces the risk of nosocomial infections and catheter-related complications.

Correlates of prepubertal bone mineral density in cystic fibrosis.

AIM: To examine early factors in bone mineral accretion in cystic fibrosis (CF). METHODS: In 22 prepubertal children with CF and mild lung disease, the relation between total body bone mineral density (BMD) and measures of body composition, biochemistry, lung function, and physical activity was studied. RESULTS: There was a non-significant mild reduction in mean total body BMD. No relation was found between BMD and anthropometric indices, fat free soft tissue, degree of lung disease, degree of fat malabsorption, dietary energy intake, or level of physical activity. Significant impairments in physical growth were apparent in this population and were found to correlate with degree of lung disease. CONCLUSION: A CF specific factor appears unlikely to be associated with the osteopenia commonly found in CF. Careful attention to general aspects of lifestyle and nutrition is recommended to maximise bone mineral accretion in this population.

Comparison of total body chlorine, potassium, and water measurements in children with cystic fibrosis.

BACKGROUND: Symptoms of cystic fibrosis (CF) may limit the utility of total body chlorine (TBCl) and total body potassium (TBK) measurements for assessing body fluid compartments of children. OBJECTIVE: This study assessed relations among independent measurements of TBCl, TBK, and total body water (TBW) in children with CF. DESIGN: We compared cross-sectional measurements of TBCl by in vivo neutron activation analysis, TBK by whole-body counting of (40)K, TBW by D(2)O dilution [TBW(D(2)O)], and TBW from TBCl and TBK [TBW(Cl + K)] in 19 prepubertal children (13 boys) aged 7.6-12.5 y who had mild symptoms of CF. Body-composition measurements were compared with data from previous studies of healthy children. RESULTS: Subjects with CF had deficits in TBCl, TBK, TBW, and body weight compared with control reference data (P < 0.05). The ratios (TBCl + TBK)/TBW and TBCl/TBK were not significantly different from control reference values, and plasma chlorine and potassium concentrations were within control reference ranges. The sum of TBCl and TBK correlated with TBW(D(2)O) (r(2) = 0.79, P < 0.001), and TBW(Cl + K) correlated with TBW(D(2)O) (r(2) = 0.78, P < 0.001). TBW(Cl + K) was similar to TBW(D(2)O) (mean +/- SEM: 19.0 +/- 0.5 compared with 19.4 +/- 0.5 L; NS). CONCLUSIONS: Prepubertal children with mild symptoms of CF can develop deficits in TBCl, TBK, and TBW that reflect chronic energy malnutrition. Mild symptoms of CF do not appear to affect normal relations among TBCl, TBK, and TBW. Measurements of TBCl and TBK may be used to assess body fluid compartments in these patients.

The natural history of intolerance to soy and extensively hydrolyzed formula in infants with multiple food protein intolerance.

Infants (n = 18) with intolerance to extensively hydrolyzed formulas and soy who responded to an L-amino acid-based elemental formula (AAF) were studied until 3 years of age. By 2 years of age most tolerated non-formula foods, and by 3 years only 3 required AAF. Growth normalized during AAF feeding in 4 infants with failure to thrive.

Body composition measurement: the challenge in the unwell child.

The assessment of body composition in the unwell child presents a significant clinical and technological challenge. The effect of disease adds to the complex series of changes in body composition that occur during normal growth and development. To assess the progress of disease or the effect of therapy, repeat measurements of body composition in a single patient may be desirable. However, repeat studies using some methods may not be appropriate due to the potential risks associated with repeated radiation exposure in this young age group. The ability to accurately detect changes in body composition between studies depends on the precision of measurement. Unfortunately, there may be a reduction in precision of measurement with smaller patients when the ability for detecting small changes is of particular relevance. Adequate and correctly timed fluid samples required for dilution studies may be difficult to obtain in the unwell infant and child. New equations or modification of 'adult' equations need to be devised to interpret raw data and these need to be validated in patients of different ages and sizes and in children with different diseases states. Specific challenges related to some common and uncommon paediatric diseases are discussed.

Efficacy of domperidone in infants and children with gastroesophageal reflux.

This study sought to define the therapeutic efficacy of domperidone in infants and children with gastroesophageal reflux. A double-blind, placebo-controlled trial was performed in seventeen children (ages 5 months to 11.3 years) with moderate to severe gastroesophageal reflux who had not responded to standard nonpharmacological therapy. Subjective and objective measures (weight gain, esophageal pH probe study, radionuclide gastric emptying scan) of gastroesophageal reflux were evaluated. Therapy with domperidone for 4 weeks was effective only in reducing the total number of reflux episodes in the two-hour postprandial period (p less than 0.01); however, it did not result in symptomatic improvement or significant improvement in other measures of gastroesophageal reflux or gastric emptying. After therapy for 8 weeks symptomatic improvement was reported in some patients who had denied improvement after 4 weeks of therapy, suggesting that more than 4 weeks of therapy may be required for some patients to obtain a clinical response. Mild self-limited diarrhea was reported by six patients (four domperidone, two placebo). We conclude that domperidone is tolerated by most infants and children with gastroesophageal reflux; however, 4 weeks of therapy was only minimally effective in producing objective improvement of gastroesophageal reflux and did not result in symptomatic improvement. Further studies of longer duration are needed to resolve the question raised by this study: that domperidone may be beneficial for patients with gastroesophageal reflux when given for more than four weeks.