Investigating barriers to the protective efficacy provided by rotavirus vaccines in African infants.

Julie Bines discusses an accompanying study by Sheila Isanaka and colleagues on nutrient supplementation and immune responses to rotavirus vaccination.

The incidence of acute respiratory infection in Indonesian infants and association with vitamin D deficiency.

BACKGROUND: Vitamin D deficiency has been associated with acute respiratory infection (ARI) in early life, but this has not been evaluated in Indonesia. We aimed to determine the incidence of ARI in Indonesian infants, and to evaluate the association with vitamin D deficiency. METHODS: From 23 December 2015 to 31 December 2017, we conducted a community-based prospective cohort study in Yogyakarta province. We enrolled 422 pregnant women and followed their infants from birth until 12 months of age for ARI episodes. Vitamin D status was measured at birth and at age six months. We performed Cox proportional hazard regression analysis to evaluate the association between vitamin D deficiency and pneumonia incidence. RESULTS: At study completion, 95% (400/422) of infants retained with a total of 412 child years of observation (CYO). The incidence of all ARI and of WHO-defined pneumonia was 3.89 (95% CI 3.70-4.08) and 0.25 (95% CI 0.21-0.30) episodes per CYO respectively. Vitamin D deficiency at birth was common (90%, 308/344) and associated with more frequent episodes of ARI non-pneumonia (adjusted odds ratio 4.48, 95% CI:1.04-19.34). Vitamin D status at birth or six months was not associated with subsequent pneumonia incidence, but greater maternal sun exposure during pregnancy was associated with a trend to less frequent ARI and pneumonia in infants. CONCLUSION: ARI, pneumonia, and vitamin D deficiency at birth were common in Indonesian infants. Minimising vitamin D deficiency at birth such as by supplementation of mothers or safe sun exposure during pregnancy has the potential to reduce ARI incidence in infants in this setting.

The prevalence and determinants of vitamin D deficiency in Indonesian infants at birth and six months of age.

BACKGROUND: Vitamin D deficiency in infants has been associated with an increased risk of a number of diseases but there are limited data on the prevalence and determinants of vitamin D deficiency from tropical settings with high infant morbidity and mortality. OBJECTIVE: To determine the prevalence and determinants of vitamin D deficiency in infants at birth and at six months of age in Yogyakarta province, Indonesia. DESIGN: Serum vitamin D of eligible infants was measured in cord blood at birth and at six months of age. Factors associated with vitamin D deficiency (serum 25-hydroxyvitamin D <50 nmol/L) were collected prospectively monthly from birth and concentrations measured by liquid chromatography-tandem mass spectrometry. Independent risk factors were identified by multiple logistic regression. RESULTS: Between December 2015 to December 2017, 350 maternal-newborn participants were recruited and followed up. Vitamin D deficiency was detected in 90% (308/344) of cord blood samples and 13% (33/255) of venous blood samples at six months. Longer time outdoors (≥2 hours per day) and maternal multivitamin intake containing vitamin D during pregnancy were protective against vitamin D deficiency at birth (AOR: 0.10, 95% CI: 0.01-0.90 and AOR: 0.21, 95% CI: 0.06-0.68, respectively). Risk factors for vitamin D deficiency at six months included lower cumulative skin-sun exposure score (AOR: 1.12, 95% CI: 1.04-1.20), severe vitamin D deficiency at birth (AOR: 7.73, 95% CI: 1.20-49.60) and exclusive breastfeeding (AOR: 2.64, 95% CI: 1.07-6.49) until six months. Among exclusively breast fed (EBF) infants, a higher skin-sun exposure score was associated with reduced vitamin D deficiency risk. CONCLUSION: In equatorial regions, the role of 'safe' morning sun exposure in infants and mothers in populations with medium to dark brown skin pigmentation and effective interventions to prevent vitamin D deficiency in newborns and EBF infants, need further consideration and evaluation.

Recent insights into trace element deficiencies: causes, recognition and correction.

PURPOSE OF REVIEW: Trace elements are vital components involved in major body functions. Cases of trace elements deficiencies are increasingly encountered in clinical practice, although often underrecognized. This review gives a thorough insight into the newest findings on clinical situations associated with trace elements deficiencies in children and adults, their recognition and management. RECENT FINDINGS: Trace elements deficiencies are frequently found in various conditions, most commonly in burns, bariatric surgery, intestinal failure, renal replacement therapy, oncology, critical illness and cardiac surgery. The main trace elements involved are selenium, zinc, copper and iron. Trace elements deficiencies are associated with increased risk of morbidity and mortality. Recognition of clinical signs of trace elements deficiencies can be challenging. Although trace elements supplementation is indisputable in many circumstances, it is still debatable in other situations such as sepsis and cardiac surgery. SUMMARY: Recent findings on trace elements deficiencies could have important implications on health outcomes. Trace elements delivery is a core component of nutritional care. Front-line clinicians should be aware of at-risk clinical situations to provide correct and timely intervention. Future research should be directed towards investigating the potential benefits of antioxidant trace elements supplementation in children in whom studies are scarce, especially in critical conditions such as burns, sepsis and cardiac surgery.

Trace Element Provision in Parenteral Nutrition in Children: One Size Does Not Fit All.

Routine administration of trace elements is recognised as a standard of care in children requiring parenteral nutrition. However, there is a lack of global consensus regarding trace elements provision and dosing in pediatric parenteral nutrition. This review provides an overview of available evidence regarding trace elements supply and posology in parenteral nutrition in neonates and children. Trace elements provision in children should be tailored to the weight and clinical condition of the child with emphasis on those at risk of toxicity or deficiency. Based on current evidence, there is a need to review the formulation of commercial solutions that contain multiple-trace elements and to enable individual trace elements additives to be available for specific indications. Literature supports the removal of chromium provision whereas manganese and molybdenum supplementation are debated. Preterm neonates may have higher parenteral requirements in iodine, selenium and copper than previously recommended. There is growing support for the routine provision of iron in long-term parenteral nutrition. Further studies on trace elements contamination of parenteral nutrition solutions are needed for a range of trace elements.

Recurrent intussusception in infants.

AIM: Clinical features to identify infants at increased risk of recurrence after a primary episode of intussusception (IS) are poorly defined. METHODS: Prospective study of the clinical presentation, treatment and outcome in infants <2 years presenting with acute IS to the National Hospital of Pediatrics, Hanoi, over a 14-month period (1 November 2002 to 31 December 2003). A retrospective review of medical records was performed to verify complete patient ascertainment. RESULTS: Five hundred ninety-eight children were recruited, including 513 (86%) with a primary episode only and 53 (9%) with ≥1 recurrent episodes. Another 32 (5%) infants presented with recurrent IS, but the primary episode of IS occurred outside the study period. Estimated recurrence risk at 6 months following a primary episode was 14%. A pathological lead point was rare in primary (n= 1) and recurrent IS (n= 1). Most infants were successfully treated with enema reduction. CONCLUSIONS: This study describes the natural history of recurrent IS in infants and may assist in interpreting data from post-marketing surveillance following introduction of rotavirus vaccines.

Tolerability and safety of olive oil-based lipid emulsion in critically ill neonates: a blinded randomized trial.

OBJECTIVE: We assessed the safety and tolerability of an olive oil-based lipid emulsion compared with a soybean-based lipid emulsion in critically ill neonates. METHODS: A double-blinded, randomized study was conducted in critically ill neonates requiring parenteral nutrition in the first week of life. Infants were randomized to receive a lipid emulsion based on olive oil (OO; ClinOleic) or soybean oil (SO; Intralipid) for a minimum of 5 d. Plasma phospholipid fatty acids, F(2)-isoprostanes, liver function, and clinical outcome were assessed after 5 d of therapy. RESULTS: Seventy-eight neonates (men gestational age 37 wk, range 26-41 wk) received OO (n = 39) or SO (n = 39). Both emulsions were well tolerated with no adverse events observed. At day 5, plasma phospholipid oleic acid (C18:1omega-9) levels increased in infants receiving OO compared with lower levels in infants receiving SO (mean percentage +/- SD 33.1 +/- 6.4 for OO versus 18.6 +/- 2.4 for SO; mean difference -14.7 mmol/L, 95% confidence interval -17.5 to -11.9). The increase in plasma phospholipid linoleic acid levels was attenuated in infants receiving OO (mean percentage +/- SD 12.6 +/- 3.0 for OO versus 23.7 +/- 6.9 for SO; adjusted mean 11.4 mmol/L, 95% confidence interval 8.1-14.8). No differences were observed in plasma F(2)-isoprostane levels according to the type of lipid emulsion received. CONCLUSION: The OO-based emulsion (ClinOleic) was well tolerated in critically ill neonates. Differences in plasma phospholipids at day 5 reflected the fatty acid composition of the administered emulsion. No significant differences in plasma F(2)-isoprostane levels were detected after 5 d of lipid administration.

Colostrum supplementation restores insulin-like growth factor -1 levels and alters muscle morphology following massive small bowel resection.

BACKGROUND: Colostrum protein concentrate (CPC) contains a high level of insulin-like growth factor-1 (IGF-1). IGF-1 and IGF binding protein (IGFBPs) may play an important role during the postresection adaptation response. As smooth muscle is an important site for IGF-1 action in the intestine, this study aims to (1) investigate the effect of CPC supplementation on circulating levels and tissue expression of IGF-1, IGF-1 receptor, and IGFBPs following massive small bowel resection (MSBR), and (2) characterize the effect of CPC on the muscular adaptation response following MSBR. METHODS: Four-week-old piglets underwent either a 75% MSBR or sham operation. Piglets received either a polymeric infant formula (PIF) diet or PIF supplemented with CPC for 8 weeks. Serum was analyzed by enzyme-linked immunosorbent assay, and ileal tissue assessed by molecular and histological analysis. RESULTS: There was no difference in IGF-1 or IGFBPs mRNA among groups. CPC treatment resulted in significant increases in circulating levels of IGF-1 and IGFBPs and a concurrent increase in muscle width and the number of muscle cells, but did not alter muscle cell size. CONCLUSIONS: Strategies aimed at increasing muscular adaptation may decrease Gl transit and allow greater mucosal contact time for absorption. We have shown that CPC supplementation following resection results in increased levels of circulating IGF-1, IGFBP-2, and IGFBP-3 and muscular hypertrophy. Our results suggest that IGF-1 and its mediators may play a role in the muscular adaptation response and warrant further exploration as a treatment option for short bowel syndrome.

Accuracy of ultrasonography for the diagnosis of intussusception in infants in Vietnam.

BACKGROUND: Intussusception (IS) is the most common cause of acute bowel obstruction in infants and young children. Ultrasonography is being increasingly used as the primary investigation for the diagnosis of IS and to guide air or hydrostatic enema reduction. However the accuracy of ultrasonography outside tertiary care settings in developed countries has not been assessed, particularly in Asia where the incidence of IS based on sonographic diagnosis has been reported as the highest in the world. OBJECTIVE: The aim of this study was to evaluate the accuracy of ultrasonography in the diagnosis of acute IS in infants less than 2 years of age in a paediatric hospital in Vietnam. MATERIALS AND METHODS: A prospective study was conducted at the National Hospital for Paediatrics, Hanoi, Vietnam, over a 14-month period recruiting patients <2 years of age with IS. Abdominal ultrasonography was performed on each patient and the accuracy of the diagnosis was evaluated against the final diagnosis provided by air enema and/or surgery. RESULTS: A total of 640 infants <2 years of age presented with clinical symptoms and signs of IS. The diagnosis was confirmed in 533 patients via air enema or surgery. Abdominal ultrasonography was 97.5% (466/478) sensitive and 99% (106/107) specific in the detection of IS. CONCLUSION: Ultrasonography is an accurate, safe and valuable clinical tool in the diagnosis of IS. The use of ultrasonography as a primary investigation for patients with suspected IS prevents unnecessary radiological or surgical procedures being performed, and reduces radiation exposure while maintaining a high level of diagnostic accuracy. These results validate the use of ultrasonography for the diagnosis of IS in a developing country setting.

Risk factors for intussusception in infants in Vietnam and Australia: adenovirus implicated, but not rotavirus.

OBJECTIVE: This study aimed to investigate risk factors for the development of intussusception in infants in a developing country with a suspected high incidence and in a developed country with a low incidence. STUDY DESIGN: A prospective case-control study of infants <2 years of age with idiopathic intussusception confirmed by air enema or surgery was conducted at the National Hospital of Paediatrics (NHP), Vietnam (n = 533) and the Royal Children's Hospital (RCH), Australia (n = 51). Diagnosis was validated in a subset (84% NHP; 67% RCH) by an independent blinded radiologist. Risk factor assessment was performed using a standardized questionnaire. Stool specimens were assayed for bacterial, viral, and parasitic agents. RESULTS: The incidence of intussusception in Vietnam was 302/100,000 in infants <1 year of age (95% CI: 258-352), substantially higher than in Australia (71/100,000). A strong association with adenovirus infection was observed at both sites (cases positive at NHP: 34%, OR 8.2; cases positive at RCH: 40%, OR 44). No association was identified between intussusception and rotavirus, other enteric pathogens, oral polio vaccine, feeding practices, or living conditions. CONCLUSIONS: The incidence of intussusception in infants was markedly higher in Vietnam than in Australia. A strong association between adenovirus infection and intussusception was identified at both sites suggesting that adenovirus may play a role in the etiology of intussusception.

Validation of clinical case definition of acute intussusception in infants in Viet Nam and Australia.

OBJECTIVE: To test the sensitivity and specificity of a clinical case definition of acute intussusception in infants to assist health-care workers in settings where diagnostic facilities are not available. METHODS: Prospective studies were conducted at a major paediatric hospital in Viet Nam (the National Hospital of Pediatrics, Hanoi) from November 2002 to December 2003 and in Australia (the Royal Children's Hospital, Melbourne) from March 2002 to March 2004 using a clinical case definition of intussusception. Diagnosis of intussusception was confirmed by air enema or surgery and validated in a subset of participants by an independent clinician who was blinded to the participant's status. Sensitivity of the definition was evaluated in 584 infants aged<2 years with suspected intussusception (533 infants in Hanoi; 51 in Melbourne). Specificity was evaluated in 638 infants aged<2 years presenting with clinical features consistent with intussusception but for whom another diagnosis was established (234 infants in Hanoi; 404 in Melbourne). FINDINGS: In both locations the definition used was sensitive (96% sensitivity in Hanoi; 98% in Melbourne) and specific (95% specificity in Hanoi; 87% in Melbourne) for intussusception among infants with sufficient data to allow classification (449/533 in Hanoi; 50/51 in Melbourne). Reanalysis of patients with missing data suggests that modifying minor criteria would increase the applicability of the definition while maintaining good sensitivity (96-97%) and specificity (83-89%). CONCLUSION: The clinical case definition was sensitive and specific for the diagnosis of acute intussusception in infants in both a developing country and a developed country but minor modifications would enable it to be used more widely.

Intussusception: trends in clinical presentation and management.

BACKGROUND: The association of a rotavirus vaccine and intussusception has renewed interest in understanding the incidence, clinical presentation and outcome of intussusception. METHODS: A retrospective chart review of all patients diagnosed with intussusception at Royal Children's Hospital, Melbourne over a 6.5-year period (1 January 1995-30 June 2001) was conducted using patients identified by a medical record database (ICD-9-CM code 560.0 1993-1997; ICD-10-CM code 56.1 1998-2001). Patient profile, clinical presentation, diagnosis methods, treatment and outcome were analyzed and compared to data previously reported on children with intussusception at the same hospital during 1962-1968. RESULTS: The hospitalization rate for primary idiopathic intussusception increased marginally from 0.19 to 0.27 per 1000 live births during the period 1962-1968 to 1995-2001. Most patients (80%) were <12 months of age (median age 7 months, range 2-72 months). The combination of abdominal pain, lethargy and vomiting was reported in 78% of infants. Air enema confirmed the diagnosis of intussusception in 186 of 191 cases (97%) and air reduction was successful in most cases (82%). Factors associated with increased risk of intestinal resection included abdominal distension (32%), bowel obstruction on abdominal X-ray (27%) and hypovolemic shock (40%). No mortality was observed in the present study. CONCLUSIONS: Over the past 40 years at Royal Children's Hospital, Melbourne the hospitalization rate due to primary idiopathic intussusception has marginally increased from 0.19 to 0.27 per 1000 live births. Diagnosis and treatment using air enema has been highly successful, resulting in a reduction in patients requiring surgery and reduced hospital stays.

Intussusception in the Northern Territory: the incidence is low in Aboriginal and Torres Strait Islander children.

AIM: To describe the epidemiology, immunisation status and management of children with intussusception in the Northern Territory (NT), 1993-2003. METHODS: Intussusception data were obtained from all NT hospitals using the International Classification of Diseases (ICD 9/10) codes for children under 18 years of age between 1993 and 2003. Medical records of these children were used to collect information on demographics, admission date, clinical symptoms, signs and management. Immunisation data were obtained from the NT immunisation register. The NT mortality database was reviewed for deaths from intussusception in children between 1993 and 2003. One death in an Aboriginal and Torres Strait Islander child was found in the NT mortality database. Medical records for this child were destroyed and so the case definition for intussusception used in this study was not fulfilled and the child was excluded. RESULTS: Intussusception proven by radiological or surgical means was identified in 23 children from hospital records. The incidence for children with intussusception in NT is 0.65/1000 live births. The incidence of intussusception was lower in Aboriginal and Torres Strait Islander children (0.16/1000 live births) than in non-Aboriginal and Torres Strait Islander children (0.92/1000 live births) (P < 0.01). CONCLUSION: The incidence of intussusception in the NT is similar to other developed countries but Aboriginal and Torres Strait Islander children have a very low incidence of intussusception. Intussusception is a rare event in the NT and will require a sensitive surveillance system to detect any potential increased risk of intussusception after the introduction of a new rotavirus vaccine.

Colostrum protein concentrate enhances intestinal adaptation after massive small bowel resection in juvenile pigs.

OBJECTIVES: Short bowel syndrome (SBS) usually results from the surgical removal of a large segment of small intestine. Patient outcome depends on the extent of intestinal resection and adaptation of the remaining intestine. We evaluated the impact of colostrum protein concentrate (CPC) on intestinal adaptation after massive small bowel resection in a porcine model of infant SBS. METHODS: Four-week-old piglets underwent an approximate 75% small bowel resection (R, n = 23) or a control transection operation (C, n = 14). Postoperatively, animals from both groups received either pig chow (R = 6, C = 5), polymeric infant formula (R = 6, C = 3) or polymeric infant formula supplemented with CPC (R = 11, C = 6) for 8 weeks until sacrifice. Clinical outcome measures included weight gain and stool consistency. Morphologic measures were intestinal villus height and crypt depth. Functional outcome measure was mucosal disaccharidase activity. RESULTS: Resected animals fed polymeric infant formula alone had reduced weight gain compared with controls fed the same diet (P < 0.005). Despite massive small bowel resection, animals fed pig chow or polymeric infant formula supplemented with CPC grew at an equivalent rate to controls fed polymeric infant formula alone. Resected animals supplemented with CPC had increased villus length and crypt depth in the jejunum (P < 0.001) and ileum (P < 0.001) compared with resected animals fed either pig chow or polymeric infant formula alone. CONCLUSION: In an animal model of SBS, CPC supplementation of polymeric infant formula resulted in normal weight gain and features of enhanced morphologic adaptation.