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The “second 1000 days” is a period of rapid brain growth which consolidates developmental foundations and establishes school readiness. Understanding the relation between household characteristics, child diet, and child development remains incomplete, especially in resource-poor settings where >250 million children risk not achieving their full developmental potential. Child developmental performance was assessed (Ages & Stages Questionnaire [ASQ]) at ages 2 and 5 years in a cohort of Nepali children (n = 207) whose families participated in a nutrition/livestock management+community development intervention trial. Relationships between child developmental performance and mother’s education, family wealth, child diet (animal source food [ASF] consumption, dietary diversity score [DDS]), school attendance, and intervention group were examined by adjusted linear regressions. These relationships varied at the 2 ages. At age 2 years, ASQ scores related positively to “Full Package Intervention” and negatively to “Partial Package Intervention” membership. At age 5 years, intervention group did not relate to ASQ scores. Mother’s education did not relate to developmental findings for 2-year-olds. Mother’s education, wealth, and school attendance positively predicted ASQ scores for these same children as 5-year-olds. Animal source food consumption was related to child development more strongly at age 5 than at 2 years. DDS had a less pronounced relationship to development than ASF consumption at both ages. Over this time span bracketing the second 1000 days, household characteristics and child diet related differentially to developmental performance depending on child age. Better understanding of the timing and mechanisms of these relationships is needed to effectively design interventions targeting improved child development in resource-poor settings.

Poor nutrition and poverty are prevalent in low- and middle-income countries (LMIC), and consumption of animal source foods (ASF), rich in high-quality calories and micronutrients, tends to be low. While many studies have focused on ASF consumption and health outcomes in children, few have investigated the effects of ASF across the lifespan. This review examines ASF's contribution to health outcomes in infancy and early childhood, schoolchildren, adolescence, pregnancy and lactation, and adulthood in LMIC, before exploring barriers to consumption. Constraints and barriers to ASF consumption in LMIC most significantly affect children and women. Several research gaps are identified, including the need for standardization of outcomes and better metrics, and attention to non-child populations, longer-term effects, and overall diet adequacy.

Background More than 50% of children in Nepal are malnourished. Economic growth and poverty reduction are not always sufficient to improve the health and nutritional status of children. Heifer Nepal uses livestock training as a tool for community development and poverty alleviation but does not directly address child health and nutrition.Objective To systematically assess the effects of Heifer activities on child health and nutrition.Methods The study was a 2-year, longitudinal, randomized, controlled trial in six communities in Nepal (both Terai and hills), pair-matched for specific characteristics, randomly assigned to receive Heifer community development activities at baseline (intervention) or 1 year (control). At 6-month intervals over a period of 2 years, child anthropometric and comprehensive household surveys were performed.Results Four hundred fifteen households were enrolled containing 607 children 6 months to 5 years of age. The intervention and control communities were equivalent for baseline socioeconomic status, household size, ownership of land and animals, and child nutrition and health. At 12 months (prior to animal donations), the Terai intervention group had improved child weight (p= .04), improved child height (p= .05), and reduced sick days (p= .03), as well as increased household income (p= .004), increased ownership of animals (p= .04) and land (p= .04), and improved sanitation practices (p< .01). In all districts, longer participation in Heifer activities corresponded to more improvement in child height-for-age z-scores.Conclusions Heifer interventions resulted in improved socioeconomic status and household income per family member. Children under 60 months of age in the intervention group had greater incremental improvement in height-for-age and weight-for-age z-scores than children in the control group, and longer participation in Heifer activities was associated with better growth. Poverty alleviation programs, such as Heifer, may indirectly benefit child growth.

OBJECTIVE: To evaluate the prevalence of vitamin D deficiency, as well as factors associated with serum 25-hydroxyvitamin D [25(OH)D] levels, in children attending a pediatric rheumatology clinic, and to determine whether there was a difference in serum 25(OH)D levels and in vitamin D deficiency between children with autoimmune disorders and nonautoimmune conditions. METHODS: Cross-sectional analysis of serum 25(OH)D levels of patients between the ages of 2 and 19 years, seen between November 2008 and October 2009. RESULTS: A total of 254 patients were studied (169 autoimmune disorders, 85 nonautoimmune conditions). The mean age of study patients was 12.3 years; 67% were female and 80% were white. In the autoimmune disorders group, 23% had vitamin D deficiency [serum 25(OH)D < 20 ng/ml], and in the nonautoimmune conditions group 14% were vitamin D deficient. The average level of serum 25(OH)D was 28.6 (± 11) ng/ml (range 2 to 59). Age, ethnicity, body mass index, use of supplements, and season were significantly associated with serum levels of 25(OH)D (all p ≤ 0.02). The OR of patients with autoimmune disorders being vitamin D deficient was 2.3, in relation to patients with nonautoimmune conditions (p = 0.04). CONCLUSION: Twenty percent of patients attending a pediatric rheumatology clinic were vitamin D deficient. Patients with autoimmune disorders were more likely to be vitamin D deficient than patients with nonautoimmune conditions. Screening of serum 25(OH)D levels should be performed for patients with autoimmune disorders.

OBJECTIVE: We previously demonstrated that levels of fibrin d-dimer correlate with disease activity and response to therapies in systemic juvenile idiopathic arthritis (sJIA). We hypothesized that persistence of D-dimer elevation in the patterns previously described, but over a longer followup period, would signal poor outcome. METHODS: We studied 31 children identified from 2 centers. Subjects were assigned a risk category based on their first obtained D-dimer concentration. Risk categories were based on results of our initial study, where normalization of D-dimer in patients no longer taking immunosuppressive therapy predicted good short-term outcome, and persistent D-dimer elevation while taking immunosuppressives predicted bad outcome (radiographic abnormalities, joint replacement surgery, or poor functional class) or a severe systemic manifestation. Outcome was determined at the last followup visit, a minimum of 2 years after measurement of the initial d-dimer level. RESULTS: The 31 children were a mean 16.4 years old at an average of 8.8 years after their initial diagnosis. Ten children had a severe outcome during this period; all 10 had a study baseline risk category of "high." Of the 14 subjects who had a high risk category at study baseline, none had a mild outcome. CONCLUSION: Our study indicated that a paradigm of risk of severe disease based upon persistent elevation of fibrin d-dimer on first measurements (greater than a mean of 29 months in our initial study and at least 24 months in the additional subjects) is promising to predict poor longer-term outcome in sJIA. A larger prospective study is warranted to substantiate the preliminary data and assess the relative comparative value to other biomarkers and clinical endpoints.

Alcohol use in Russia is among the highest in the world. Over 600,000 children reside in institutional care in Russia, most of them in baby homes and orphanages. The actual prevalence of fetal alcohol spectrum disorders (FASD) among these children is unknown. Therefore, we performed a systematic survey of phenotypic features associated with prenatal alcohol exposure among institutionalized Russian children and related these findings to their growth, development, medical, and social histories.

Background: Alcohol use in Russia is among the highest in the world. Over 600,000 children reside in institutional care in Russia, most of them in baby homes and orphanages. The actual prevalence of fetal alcohol spectrum disorders (FASD) among these children is unknown. Therefore, we performed a systematic survey of phenotypic features associated with prenatal alcohol exposure among institutionalized Russian children and related these findings to their growth, development, medical, and social histories.

To describe the clinical profiles of five patients with Down syndrome and elevated levels of antiphospholipid antibodies. Medical records of all 149 patients screened for anticardiolipin antibodies (aCL) in the pediatric hematology or pediatric rheumatology clinics at New England Medical Center between 1996 and 1998 were retrospectively reviewed, and patients with Down syndrome identified. Thirty-four patients (23) had elevated IgG titers of aCL antibodies. Of these, five had Down syndrome (15). Two presented with discoloration of the distal digits, and one each with thrombocytopenia, autoimmune hepatitis, and undifferentiated autoimmune disease. The mothers of two of the four individuals with available family history had experienced frequent miscarriages. An association may exist between Down syndrome and antiphospholipid antibodies, in particular an increased frequency of aCL antibodies. Screening patients with Down syndrome and certain clinical findings may prove useful.

OBJECTIVE: To determine serum levels of adhesion molecules ICAM-1, ICAM-3, VCAM-1, L-selectin, and E-selectin in children with a variety of pediatric rheumatic diseases and investigate their relationship to clinical disease activity. METHODS: Retrospective review of records of 18 children with rheumatic diseases who had banked sera available for study. Eight children had systemic lupus erythematosus (SLE), 2 mixed connective tissue disease, 4 dermatomyositis (DM), and 4 various forms of vasculitis. Levels of the soluble adhesion molecules were determined by sandwich ELISA. Levels were compared among patients with the various diagnoses and between patients with active vs inactive disease. Levels were also correlated with erythrocyte sedimentation rate in all patients; C3, C4, and total hemolytic complements and anti-dsDNA antibodies in SLE; and creatine phosphokinase, aldolase, and von Willebrand factor (vWF) antigen levels in DM. Levels also correlated with disease activity scores, which varied by diagnosis. RESULTS: A trend toward higher levels of sE-selectin was found in vasculitis vs other diagnoses (p = 0.08). sICAM-1 was higher in patients with active vs inactive disease (p = 0.05) across all diagnoses. L-selectin levels correlated with C4 complement levels in SLE patients (r = 0.76, p = 0.03), and there was a trend toward an inverse correlation between levels of sE-selectin and vWF (r = -0.93, p = 0.08). There was no direct correlation of the adhesion molecule levels with any of the disease activity scores. CONCLUSION: The small number of patients and retrospective design of this study mean that any results must be interpreted with caution. We conclude: (1) Elevated E-selectin levels in vasculitis likely reflect the high degree of endothelial activation and possibly overt vascular damage in those conditions. (2) The correlation of sL-selectin with C4 in SLE may indicate that downregulation of shedding of cell surface L-selectin is involved in continued adherence of leukocytes to endothelium, possibly causing further damage and immune complex deposition in this condition. (3) The trend toward inverse correlation between sE-selectin and vWF:Ag in DM is curious, but may show that the role of endothelium in the pathophysiology of this disease is different from those such as vasculitis. (4) Levels of sICAM- I may be a useful marker of active vs quiescent disease in general in the pediatric rheumatic diseases, although lack of correlation with disease activity indices may indicate that it is too insensitive to smaller differences in disease activity to be recommended for routine clinical use.

Interleukin‐1 (IL‐1) is a potent stimulator of IL‐8 production by fibroblasts and monocytes. In the present study, we asked how much of endotoxin (LPS)‐induced IL‐8 production by human peripheral blood mononuclear cells was due to IL‐1 induced by LPS. Cells were stimulated with either IL‐1β, LPS, or Borrelia burgdorferi, and total IL‐8 was determined by a specific radioimmunoassay. The addition of saturating concentrations of IL‐1 receptor antagonist protein (IRAP) reduced the IL‐1β‐, LPS‐, and B. burgdorferi‐induced IL‐8 synthesis by 85, 50, and 40%, respectively. Increasing the concentration of LPS did not affect the reduction in IL‐8 synthesis observed in the presence of IRAP. Significant inhibition of the IL‐1β‐induced IL‐8 synthesis was observed when IRAP was added 60 or 90 min after IL‐1β; similarly, IL‐8 synthesis after LPS was also reduced by delayed addition of IRAP. These data suggest that the ameliorative effects of IL‐1 receptor blockade in models of inflammation and infection may be due, in part, to suppression of IL‐1‐induced IL‐8.—Porat, R.; Poutsiaka, D. D.; Miller, L. C.; Granowitz, E. V.; Dinarello, C. A. Interleukin‐1 (IL‐1) receptor blockade reduces endotoxin and Borrelia burgdorferi‐stimulated IL‐8 synthesis in human mononuclear cells. FASEB J.6: 2482‐2486; 1992.

OBJECTIVE: Although the more than 6 million Afghan refugees represent the largest single group of refugees worldwide, little information is available about their health status. RESEARCH DESIGN: Case series assessing the health and socioeconomic status of female Afghan refugees and their families and the nutritional and developmental status of their children. SETTING AND PATIENTS: Fifty-one female Afghan refugees and their children accompanying them at a maternal child health clinic in Quetta, Pakistan. RESULTS: All families had suffered serious losses from the war. Thirty-three women (65%) had lost at least one liveborn child, most commonly to gastroenteritis, "hunger," or neonatal tetanus. Thirteen children had been killed by bombardment, mine injuries, or gunshot wounds. The nutritional status of the children was markedly poor: z scores were less than −2 for weight in 67% of children and also less than −2 for head circumference in 50% of children. Serial z scores for weight in 23 children showed marked decline in 15 children (65%). Sixty-nine percent of children were overdue for vaccinations. Developmental milestones were significantly delayed. CONCLUSION: Afghan refugee children and their mothers are extremely needy and vulnerable and may be considered among the hidden casualties of war.(Arch Pediatr Adolesc Med. 1994;148:704-708)

IL-1 and related cytokines have multiple biologic activities relevant to the rheumatic diseases. In addition to mediating inflammatory and immune responses, these proteins regulate many aspects of connective tissue metabolism. The cytokines interact in complex cascades: because of this, and various technical reasons, the exact role of cytokines in the pathogenesis of rheumatic diseases remains uncertain. However, considerable experimental data suggest that the abnormal regulation of cytokines contributes to such siseases as inflammatory arthritis, systemic lupus erythematosus, scleroderma, and dermatomyositis. Animal models of these diseases have contributed to understanding the role of cytokines in pathogenesis. Furthermore, drugs useful in treating these diseases affect cytokine pathways; some cytokines, their antagonists, or related substances have been used therapeutically to treat rheumatic diseases. The therapeutic use of these agents will likely increase as knowledge about the role of cytokines in the pathogenesis of rheumatic diseases expands.

OBJECTIVE:To review the presentation, clinical characteristics, and outcome of children with prolonged fevers of unknown origin who are referred for pediatric rheumatologic evaluation. METHODS:We used a retrospective review of the charts of the 40 children (23 boys and 17 girls, aged 9 months to 14.6 years) with fevers persisting longer than 1 month who were referred to the Pediatric Rheumatology Clinic between 1984 and 1994, in whom evaluation did not result in diagnosis. Follow-up with children's families, pediatricians, or both was done by telephone. RESULTS:Of the 40 children, 29 had periodic fevers, and 11 had daily fevers without pattern. Patients with periodic fever were younger at onset, had longer duration of symptoms before referral, and higher maximum temperatures. The two groups did not differ in frequency of associated symptoms or signs. At follow-up (mean 60.5 ± 5 months, n = 37), 10 children with daily fevers (within 24 months) and 23 children with periodic fevers (within 48 months) had completely recovered; three patients continue to have periodic fevers. In patients with daily fevers one had Crohn disease (7 months after initial evaluation) and another had uveitis (4 years after evaluation). One patient with periodic fevers had inflammatory bowel disease 3.5 years after the onset of fevers. Petit mal seizures developed in one patient with periodic fever, and another had mitochondrial encephalopathy. Four children with periodic fevers have attention-deficit hyperactivity disorder, and two have developmental delays. CONCLUSIONS:Fevers without an obvious source usually have a benign outcome, although patients should be monitored for changes in symptoms. Of the children with periodic fevers, 29% were later found to have neurologic problems; the relation to the previous fevers is uncertain. (J PEDIATR1996;128:419-23)

We reviewed 53 patients referred to a pediatric rheumatology clinic in Asuncion, Paraguay. In 6 patients, a diagnosis of rheumatic fever was confirmed and in 47 patients other clinically significant diagnoses were made. Eighteen children had nonspecific findings and did not develop a rheumatologic condition on follow-up. Overdiagnosis of rheumatic fever can falsely inflate incidence and prevalence statistics and clinically significant diagnoses may be overlooked.