Childhood stunting usually begins in utero and continues after birth; therefore, its reduction must involve actions across different stages of early life.
We evaluated the efficacy of small-quantity, ...lipid-based nutrient supplements (SQ-LNSs) provided during pregnancy, lactation, and infancy on attained size by 18 mo of age.
In this partially double-blind, individually randomized trial, 1320 women at ≤20 wk of gestation received standard iron and folic acid (IFA group), multiple micronutrients (MMN group), or SQ-LNS (LNS group) daily until delivery, and then placebo, MMNs, or SQ-LNS, respectively, for 6 mo postpartum; infants in the LNS group received SQ-LNS formulated for infants from 6 to 18 mo of age (endline). The primary outcome was child length by 18 mo of age.
At endline, data were available for 85% of 1228 infants enrolled; overall mean length and length-for-age z score (LAZ) were 79.3 cm and -0.83, respectively, and 12% of the children were stunted (LAZ <-2). In analysis based on the intended treatment, mean ± SD length and LAZ for the LNS group (79.7 ± 2.9 cm and -0.69 ± 1.01, respectively) were significantly greater than for the IFA (79.1 ± 2.9 cm and -0.87 ± 0.99) and MMN (79.1 ± 2.9 cm and -0.91 ± 1.01) groups (P = 0.006 and P = 0.009, respectively). Differences were also significant for weight and weight-for-age z score but not head or midupper arm circumference, and the prevalence of stunting in the LNS group was 8.9%, compared with 13.7% in the IFA group and 12.9% in the MMN group (P = 0.12). In analysis based on actual supplement provided at enrollment, stunting prevalences were 8.9% compared with 15.1% and 11.5%, respectively (P = 0.045).
Provision of SQ-LNSs to women from pregnancy to 6 mo postpartum and to their infants from 6 to 18 mo of age may increase the child's attained length by age 18 mo in similar settings. This trial was registered at clinicaltrials.gov as NCT00970866.
ABSTRACT
Objectives:
Compared to formula‐fed infants, breastfed infants have a lower risk of infections. Two possible reasons for this are the presence of the anti‐infective and anti‐inflammatory ...protein lactoferrin and the lower level of iron in breast milk. We explored how adding bovine lactoferrin and reducing the iron concentration in infant formula affect immunology and risk of infections in healthy infants.
Methods:
In a double‐blind controlled trial, term formula‐fed (FF) Swedish infants (n = 180) were randomized to receive, from 6 weeks to 6 months of age, a low‐iron formula (2 mg/L) with added bovine lactoferrin (1.0 g/L) (Lf+; n = 72); low‐iron formula with no added lactoferrin (Lf−; n = 72); and standard formula at 8 mg/L iron and no added lactoferrin (control formula CF; n = 36). Cytokines, infections, and infection related treatments were assessed until 12 months of age.
Results:
No adverse effects were observed. There were no apparent effects on transforming growth factor beta (TGF‐β)1, TGF‐β2, tumor necrosis factor alfa (TNF‐α) or interleukin2 (IL‐2) at 4, 6, or 12 months, except of higher TGF‐β2 at 6 months in the CF group in comparison to the low iron groups combined (P = 0.033). No significant differences in otitis, respiratory infections, gastroenteritis, or other monitored infections and treatments were detected for any of the study feeding groups during the first 6 months and only a few and diverging effects were observed between 6 and 12 months.
Conclusions:
Adding bovine lactoferrin and reducing iron from 8 to 2 mg/L in infant formula was safe. No clinically relevant effects on cytokines or infection related morbidity were observed in this well‐nourished and healthy population.
Concentrations of vitamin D (VitD) and 25-hydroxyvitamin D (25OHD) in breastmilk are low despite the essential role of VitD for normal infant bone development, yet additional metabolic forms of ...vitamin D may be present. This study evaluates the contribution of sulfated vitamin D metabolites, vitamin D3-sulfate (VitD3-S) and 25-hydroxyvitamin D3-sulfate (25OHD3-S) for lactating women and assesses the response to high-dose VitD3 supplementation.
Serum and breastmilk were measured before and after 28 days with 5000 IU/day VitD3 intake in 20 lactating women. Concentrations of VitD3-S and 25OHD3-S in milk, and 25OHD2, 25OHD3, 25OHD3-S, VitD3 and VitD3-S in serum were determined by mass spectrometry.
Baseline vitamin D status was categorized as sufficient (mean ± SD serum 25OHD3 69 ± 19 nmol/L), and both serum VitD3 and 25OHD3 increased following supplementation (p < 0.001). 25OHD3-S was 91 ± 19 nmol/L in serum and 0.47 ± 0.09 nmol/L in breastmilk. VitD3-S concentrations were 2.92 ± 0.70 nmol/L in serum and 6.4 ± 3.9 nmol/L in breastmilk. Neither sulfated metabolite significantly changed with supplementation in either serum or breastmilk.
Sulfated vitamin D metabolites have prominent roles for women during lactation with 25OHD3-S highly abundant in serum and VitD3-S distinctly abundant in breastmilk. These data support the notion that 25OHD3-S and VitD3-S may have physiological relevance during lactation and nutritional usage for nursing infants.
Objective The objective of this study was to determine the association between preoperative nutritional status and postoperative outcomes in children undergoing surgery for congenital heart defects ...(CHD). Methods Seventy-one patients with CHD were enrolled in a prospective, 2-center cohort study. We adjusted for baseline risk differences using a standardized risk adjustment score for surgery for CHD. We assigned a World Health Organization z score for each subject’s preoperative triceps skin-fold measurement, an assessment of total body fat mass. We obtained preoperative plasma concentrations of markers of nutritional status (prealbumin, albumin) and myocardial stress (B-type natriuretic peptide BNP). Associations between indices of preoperative nutritional status and clinical outcomes were sought. Results Subjects had a median (interquartile range IQR) age of 10.2 (33) months. In the University of California at San Francisco (UCSF) cohort, duration of mechanical ventilation (median, 19 hours; IQR, 29 hours), length of intensive care unit stay (median, 5 days; IQR 5 days), duration of any continuous inotropic infusion (median, 66 hours; IQR 72 hours), and preoperative BNP levels (median, 30 pg/mL; IQR, 75 pg/mL) were associated with a lower preoperative triceps skin-fold z score ( P < .05). Longer duration of any continuous inotropic infusion and higher preoperative BNP levels were also associated with lower preoperative prealbumin (12.1 ± 0.5 mg/dL) and albumin (3.2 ± 0.1; P < .05) levels. Conclusions Lower total body fat mass and acute and chronic malnourishment are associated with worse clinical outcomes in children undergoing surgery for CHD at UCSF, a resource-abundant institution. There is an inverse correlation between total body fat mass and BNP levels. Duration of inotropic support and BNP increase concomitantly as measures of nutritional status decrease, supporting the hypothesis that malnourishment is associated with decreased myocardial function.
Undernourished children exhibit impaired development of their gut microbiota. Transplanting microbiota from 6- and 18-month-old healthy or undernourished Malawian donors into young germ-free mice ...that were fed a Malawian diet revealed that immature microbiota from undernourished infants and children transmit impaired growth phenotypes. The representation of several age-discriminatory taxa in recipient animals correlated with lean body mass gain; liver, muscle, and brain metabolism; and bone morphology. Mice were cohoused shortly after receiving microbiota from healthy or severely stunted and underweight infants; age- and growth-discriminatory taxa from the microbiota of the former were able to invade that of the latter, which prevented growth impairments in recipient animals. Adding two invasive species, Ruminococcus gnavus and Clostridium symbiosum, to the microbiota from undernourished donors also ameliorated growth and metabolic abnormalities in recipient animals. These results provide evidence that microbiota immaturity is causally related to undernutrition and reveal potential therapeutic targets and agents.
Therapeutic food interventions have reduced mortality in children with severe acute malnutrition (SAM), but incomplete restoration of healthy growth remains a major problem. The relationships between ...the type of nutritional intervention, the gut microbiota, and therapeutic responses are unclear. In the current study, bacterial species whose proportional representation define a healthy gut microbiota as it assembles during the first two postnatal years were identified by applying a machine-learning-based approach to 16S ribosomal RNA data sets generated from monthly faecal samples obtained from birth onwards in a cohort of children living in an urban slum of Dhaka, Bangladesh, who exhibited consistently healthy growth. These age-discriminatory bacterial species were incorporated into a model that computes a 'relative microbiota maturity index' and 'microbiota-for-age Z-score' that compare postnatal assembly (defined here as maturation) of a child's faecal microbiota relative to healthy children of similar chronologic age. The model was applied to twins and triplets (to test for associations of these indices with genetic and environmental factors, including diarrhoea), children with SAM enrolled in a randomized trial of two food interventions, and children with moderate acute malnutrition. Our results indicate that SAM is associated with significant relative microbiota immaturity that is only partially ameliorated following two widely used nutritional interventions. Immaturity is also evident in less severe forms of malnutrition and correlates with anthropometric measurements. Microbiota maturity indices provide a microbial measure of human postnatal development, a way of classifying malnourished states, and a parameter for judging therapeutic efficacy. More prolonged interventions with existing or new therapeutic foods and/or addition of gut microbes may be needed to achieve enduring repair of gut microbiota immaturity in childhood malnutrition and improve clinical outcomes.
Background. Malnourished children are at increased risk for death due to diarrhea. Our goal was to determine the contribution of specific enteric infections to malnutrition-associated diarrhea and to ...determine the role of enteric infections in the development of malnutrition. Methods. Children from an urban slum in Bangladesh were followed for the first year of life by every-other-day home visits. Enteropathogens were identified in diarrheal and monthly surveillance stools; intestinal barrier function was measured by serum endocab antibodies; and nutritional status was measured by anthropometry. Results. Diarrhea occurred 4.69 ± 0.19 times per child per year, with the most common infections caused by enteric protozoa (amebiasis, cryptosporidiosis, and giardiasis), rotavirus, astrovirus, and enterotoxigenic Escherichia coli (ETEC). Malnutrition was present in 16.3% of children at birth and 42.4% at 12 months of age. Children malnourished at birth had increased Entamoeba histolytica, Cryptosporidium, and ETEC infections and more severe diarrhea. Children who became malnourished by 12 months of age were more likely to have prolonged diarrhea, intestinal barrier dysfunction, a mother without education, and low family expenditure. Conclusions. Prospective observation of infants in an urban slum demonstrated that diarrheal diseases were associated with the development of malnutrition that was in turn linked to intestinal barrier disruption and that diarrhea was more severe in already malnourished children. The enteric protozoa were unexpectedly important causes of diarrhea in this setting. This study demonstrates the complex interrelationship of malnutrition and diarrhea in infants in low-income settings and points to the potential for infectious disease interventions in the prevention and treatment of malnutrition.
Infantile malnutrition is known to be associated with cognitive and behavioral impairment during childhood and adolescence. Data pertaining to longer-term effects on behavioral outcomes in adulthood ...are limited. In this study, we report associations between infantile malnutrition and attention problems in adults at midlife. Attention problems were assessed by the Conners Adult ADHD Rating Scales (CAARS) and the Conners Continuous Performance Test (CPT) in 145 Barbadian adults (aged 37-43 y) who had been followed longitudinally since childhood. Previously malnourished participants (n = 80) had experienced moderate to severe protein-energy malnutrition in the first year of life and were successfully rehabilitated thereafter. They were compared with healthy adults (n = 65) who were former classmates of the index cases and who had been matched for age, sex, and handedness in childhood. Multiple regression analyses showed persisting effects of childhood malnutrition on both the CAARS and the CPT, independent of effects of household standard of living assessed in childhood. The malnutrition effect on the CAARS ratings was independent of IQ, whereas this effect was attenuated for the CPT after adjustment for IQ. Teacher-reported attention problems in childhood predicted attention problems in adulthood, indicating continuity over the life span. Infantile malnutrition may have long-term effects on attentional processes nearly 40 y after the episode, even with excellent long-term nutritional rehabilitation and independent of socioeconomic conditions in childhood and adolescence. This finding has major public health implications for populations exposed to early childhood malnutrition.
Breastfeeding and human milk are the normative standards for infant feeding and nutrition. Given the documented short- and long-term medical and neurodevelopmental advantages of breastfeeding, infant ...nutrition should be considered a public health issue and not only a lifestyle choice. The American Academy of Pediatrics reaffirms its recommendation of exclusive breastfeeding for about 6 months, followed by continued breastfeeding as complementary foods are introduced, with continuation of breastfeeding for 1 year or longer as mutually desired by mother and infant. Medical contraindications to breastfeeding are rare. Infant growth should be monitored with the World Health Organization (WHO) Growth Curve Standards to avoid mislabeling infants as underweight or failing to thrive. Hospital routines to encourage and support the initiation and sustaining of exclusive breastfeeding should be based on the American Academy of Pediatrics-endorsed WHO/UNICEF "Ten Steps to Successful Breastfeeding." National strategies supported by the US Surgeon General's Call to Action, the Centers for Disease Control and Prevention, and The Joint Commission are involved to facilitate breastfeeding practices in US hospitals and communities. Pediatricians play a critical role in their practices and communities as advocates of breastfeeding and thus should be knowledgeable about the health risks of not breastfeeding, the economic benefits to society of breastfeeding, and the techniques for managing and supporting the breastfeeding dyad. The "Business Case for Breastfeeding" details how mothers can maintain lactation in the workplace and the benefits to employers who facilitate this practice.
Environmental enteropathy (EE) is a subclinical enteric condition found in low-income countries that is characterized by intestinal inflammation, reduced intestinal absorption, and gut barrier ...dysfunction. We aimed to assess if EE impairs the success of oral polio and rotavirus vaccines in infants in Bangladesh.
We conducted a prospective observational study of 700 infants from an urban slum of Dhaka, Bangladesh from May 2011 to November 2014. Infants were enrolled in the first week of life and followed to age one year through biweekly home visits with EPI vaccines administered and growth monitored. EE was operationally defied as enteric inflammation measured by any one of the fecal biomarkers reg1B, alpha-1-antitrypsin, MPO, calprotectin, or neopterin. Oral polio vaccine success was evaluated by immunogenicity, and rotavirus vaccine response was evaluated by immunogenicity and protection from disease. This study is registered with ClinicalTrials.gov, number NCT01375647.
EE was present in greater than 80% of infants by 12weeks of age. Oral poliovirus and rotavirus vaccines failed in 20.2% and 68.5% of the infants respectively, and 28.6% were malnourished (HAZ<−2) at one year of age. In contrast, 0%, 9.0%, 7.9% and 3.8% of infants lacked protective levels of antibody from tetanus, Haemophilus influenzae type b, diphtheria and measles vaccines respectively. EE was negatively associated with oral polio and rotavirus response but not parenteral vaccine immunogenicity. Biomarkers of systemic inflammation and measures of maternal health were additionally predictive of both oral vaccine failure and malnutrition. The selected biomarkers from multivariable analysis accounted for 46.3% variation in delta HAZ. 24% of Rotarix® IgA positive individuals can be attributed to the selected biomarkers.
EE as well as systemic inflammation and poor maternal health were associated with oral but not parenteral vaccine underperformance and risk for future growth faltering. These results offer a potential explanation for the burden of these problems in low-income problems, allow early identification of infants at risk, and suggest pathways for intervention.
The Bill and Melinda Gates Foundation (OPP1017093).
•Environmental enteropathy was present in the majority of Dhaka slum children at 12 weeks of age.•Growth in the first year of life was negatively impacted by environmental enteropathy•Oral vaccine response, but not parenteral vaccine response, was negatively impacted by environmental enteropathy•Biomarkers predictive of malnutrition and vaccine failure fell into three clusters: gut inflammation, systemic inflammation and maternal factors.
Malnutrition and oral vaccine failure are common in infants living in unsanitary conditions in low income countries. We hypothesized that exposure to infections of the gut at an early age could result in an inflammatory condition of the intestine termed Environmental Enteropathy (EE), and that this in turn could contribute to malnutrition and vaccine response. Children from an urban slum in Dhaka Bangladesh were enrolled within the first week of life, and vaccine response and growth measured to age one year. Most children were infected by two or more enteric infections and had the characteristic inflammation of EE. Both malnutrition and oral vaccine failure were associated with EE. We concluded that improvement in child health in low income countries will likely require prevention or treatment of gut damage due to infection.
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