Search

OBJECTIVE: Most evidence supporting screening for undernutrition is for children aged 6-59 months. However, the highest risk of mortality and highest incidence of wasting occurs in the first 6 months of life. We evaluated relationships between neonatal anthropometric indicators, including birth weight, weight-for-age Z-score (WAZ), weight-for-length Z-score (WLZ), length-for-age Z-score (LAZ) and mid-upper arm circumference (MUAC) and mortality and growth at 6 months of age among infants in Burkina Faso. DESIGN: Data arose from a randomised controlled trial evaluating neonatal azithromycin administration for the prevention of child mortality. We evaluated relationships between baseline anthropometric measures and mortality, wasting (WLZ < -2), stunting (LAZ < -2) and underweight (WAZ < -2) at 6 months of age were estimated using logistic regression models adjusted for the childs age and sex. SETTING: Five regions of Burkina Faso. PARTICIPANTS: Infants aged 8-27 d followed until 6 months of age. RESULTS: Of 21 832 infants enrolled in the trial, 7·9 % were low birth weight (

Radionuclide therapy targeting prostate-specific membrane antigen (PSMA) is a promising option for metastatic castration-resistant prostate cancer. Clinical experience using 177Lu or 225Ac has demonstrated encouraging treatment responses; however, responses are not durable. Dual-isotope combinations, or tandem approaches, may improve tolerability while retaining a high tumor dose. In this study, we directly compared α- versus β-particle treatment, as well as a combination thereof, at different stages of disease in a murine model of disseminated prostate cancer. Methods: First, to determine comparable injected activities from 177Lu- and 225Ac-PSMA-617, ex vivo biodistribution studies were performed at 5 time points after treatment of C4-2 subcutaneous tumor-bearing NSG mice. To establish a more representative model of metastatic prostate cancer, NSG mice were inoculated with luciferase-expressing C4-2 cells in the left ventricle, leading to disseminated visceral and bone lesions. At either 3 or 5 wk after inoculation, the mice were treated with equivalent tumor dose-depositing activities of 177Lu- or 225Ac-PSMA-617 alone or in combination (35 MBq of 177Lu, 40 kBq of 225Ac, or 17 MBq of 177Lu + 20 kBq 225Ac; 10/group). Disease burden was assessed by weekly bioluminescence imaging. Treatment efficacy was evaluated using whole-body tumor burden and overall survival. Results: The ex vivo biodistribution studies revealed that 35 MBq of 177Lu and 40 kBq of 225Ac yield equivalent absorbed tumor doses in a subcutaneous C4-2 model. The disease burden of mice treated at 3 wk after inoculation (microscopic disease) with 177Lu was not significantly different from that of untreated mice. However, 225Ac-PSMA-617 both as a single agent and in combination with 177Lu (17 MBq of 177Lu + 20 kBq of 225Ac) were associated with significant whole-body tumor growth retardation and survival benefit (overall survival, 8.3 wk for nontreatment, 9.4 wk for 177Lu, 15.3 wk for 225Ac alone, and 14.1 wk for tandem therapy). When treated at 5 wk after inoculation (macroscopic disease), all treatment groups showed retarded tumor growth and improved survival, with no significant differences between 225Ac alone and administration of half the 225Ac activity in tandem with 177Lu (overall survival, 7.9 wk for nontreatment, 10.3 wk for 177Lu, 14.6 wk for 225Ac alone, and 13.2 wk for tandem therapy). Conclusion: Treatment of a disseminated model of prostate cancer with simultaneous 225Ac- and 177Lu-PSMA-617 results in significantly decreased tumor growth compared with 177Lu, which was ineffective as a single agent against microscopic lesions. Mice treated later in the disease progression and bearing macroscopic, millimeter-sized lesions experienced significant tumor growth retardation and survival benefit in both monoisotopic and tandem regimens of 177Lu and 225Ac. Although the greatest benefits were observed with the single agent 225Ac, the tandem arm experienced no significant difference in disease burden or survival benefit, suggesting that the reduced activity of 225Ac was adequately compensated in the tandem arm. The superior therapeutic efficacy of 225Ac in this model suggests a preference for α-emitters alone, or possibly in combination, in the microscopic disease setting.

BackgroundInfants who are HIV-exposed and uninfected have suboptimal growth patterns compared to those who are HIV-unexposed and uninfected. However, little is known about how these patterns persist beyond 1 year of life.ObjectivesThis study aimed to examine whether infant body composition and growth trajectories differed by HIV exposure during the first 2 years of life among Kenyan infants using advanced growth modeling.MethodsRepeated infant body composition and growth measurements (mean: 6; range: 2-7) were obtained from 6 weeks to 23 months in the Pith Moromo cohort in Western Kenya (n = 295, 50% HIV-exposed and uninfected, 50% male). Body composition trajectory groups were fitted using latent class mixed modeling (LCMM) and associations between HIV exposure and growth trajectories were examined using logistic regression analysis.ResultsAll infants exhibited poor growth. However, HIV-exposed infants generally grew suboptimally than unexposed infants. Across all body composition models except for the sum of skinfolds, HIV-exposed infants had a higher likelihood of belonging to the suboptimal growth groups identified by LCMM than the HIV-unexposed infants. Notably, HIV-exposed infants were 3.3 times more likely (95% CI: 1.5-7.4) to belong to the length-for-age z-score growth class that remained at a z-score of < -2, indicating stunted growth. HIV-exposed infants were also 2.6 times more likely (95% CI: 1.2-5.4) to belong to the weight-for-length-for-age z-score growth class that remained between 0 and -1, and were 4.2 times more likely (95% CI: 1.9-9.3) to belong to the weight-for-age z-score growth class that indicated poor weight gain besides stunted linear growth.ConclusionsIn a cohort of Kenyan infants, HIV-exposed infants grew suboptimally compared to HIV-unexposed infants beyond 1 year of age. These growth patterns and longer-term effects should be further investigated to support the ongoing efforts to reduce early-life HIV exposure-related health disparities.

Risk of death from undernutrition is thought to be higher in younger than in older children, but evidence is mixed. Research also demonstrates sex differences whereby boys have a higher prevalence of undernutrition than girls. This analysis described mortality risk associated with anthropometric deficits (wasting, underweight and stunting) in children 6-59 months by age and sex. We categorised children into younger (6-23 months) and older (24-59 months) age groups. Age and sex variations in near-term (within 6 months) mortality risk, associated with individual anthropometric deficits were assessed in a secondary analysis of multi-country cohort data. A random effects meta-analysis was performed. Data from seven low-or-middle-income-countries collected between 1977 and 2013 were analysed. One thousand twenty deaths were recorded for children with anthropometric deficits. Pooled meta-analysis estimates showed no differences by age in absolute mortality risk for wasting (RR 1.08, p = 0.826 for MUAC

Although female infants may have an early life biological advantage over males, gendered treatment can alter health outcomes. Ecuador has an unusually high ratio of male to female infant mortality, but gender norms have been reported to favor boys. This analysis of baseline data from the Lulun Project, a randomized controlled trial conducted in rural Andean communities of Ecuador, investigates the roles of sex and gender in undernutrition among infants 6 to 9 months of age. Twenty-four-hour recall frequencies were used to assess dietary intake. Food outcome models were analyzed as prevalence ratios calculated using a binomial distribution with a log link or robust Poisson regression. Linear regression was used to analyze the continuous growth outcome length-for-age z score. Socioeconomic and health history variables were comparable between male and female infants. Boys were more often fed liquids other than breastmilk within their first 3 days of life (17.1% vs. 5.2%, P = 0.026). Compared with girls, boys were less likely to be fed eggs by 33% (95% CI 0.46, 0.96), cheese, yogurt, or other milk products by 40% (95% CI 0.39, 0.92), yellow fruit by 44% (95% CI 0.33, 0.97), water by 37% (95% CI 0.45, 0.88), thin porridge by 29% (95% CI 0.56, 0.92), and tea without milk by 67% (95% CI 0.11, 0.99). Prevalence of boys with an adequate dietary diversity score (≥ 4) was reduced by 27% relative to girls (95% CI 0.54, 0.99). Males fared worse in length-for-age z scores (- 2.16 vs. - 1.56, P = 0.000), weight-for-age z scores (- 0.86 vs. - 0.33, P = 0.002), prevalence of stunting (50.6% vs. 23.4%, P = 0.000), and plasma concentrations of dimethylglycine (1.25 vs. 1.65 µg/mL, P = 0.021). After adjusting for demographic, caregiver perceptions of appetite, and biological factors, length-for-age z score for a male child was 0.62 units lower than for a female (95% CI - 0.98, - 0.26). Male infants were shown to receive lower quality complementary foods and have worse anthropometric measures than female infants.Trial registration clinicaltrials.gov, NCT02446873. Registered February 28, 2015, https://clinicaltrials.gov/ct2/show/NCT02446873 .

Congenital diaphragmatic hernia (CDH) is a severe congenital anomaly that is often accompanied by other anomalies. Although the role of genetics in the pathogenesis of CDH has been established, only a small number of disease-associated genes have been identified. To further investigate the genetics of CDH, we analyzed de novo coding variants in 827 proband-parent trios and confirmed an overall significant enrichment of damaging de novo variants, especially in constrained genes. We identified LONP1 (lon peptidase 1, mitochondrial) and ALYREF (Aly/REF export factor) as candidate CDH-associated genes on the basis of de novo variants at a false discovery rate below 0.05. We also performed ultra-rare variant association analyses in 748 affected individuals and 11,220 ancestry-matched population control individuals and identified LONP1 as a risk gene contributing to CDH through both de novo and ultra-rare inherited largely heterozygous variants clustered in the core of the domains and segregating with CDH in affected familial individuals. Approximately 3% of our CDH cohort who are heterozygous with ultra-rare predicted damaging variants in LONP1 have a range of clinical phenotypes, including other anomalies in some individuals and higher mortality and requirement for extracorporeal membrane oxygenation. Mice with lung epithelium-specific deletion of Lonp1 die immediately after birth, most likely because of the observed severe reduction of lung growth, a known contributor to the high mortality in humans. Our findings of both de novo and inherited rare variants in the same gene may have implications in the design and analysis for other genetic studies of congenital anomalies.

Truncating variants in exons 33 and 34 of the SNF2-related CREBBP activator protein (SRCAP) gene cause the neurodevelopmental disorder (NDD) Floating-Harbor syndrome (FLHS), characterized by short stature, speech delay, and facial dysmorphism. Here, we present a cohort of 33 individuals with clinical features distinct from FLHS and truncating (mostly de novo) SRCAP variants either proximal (n = 28) or distal (n = 5) to the FLHS locus. Detailed clinical characterization of the proximal SRCAP individuals identified shared characteristics: developmental delay with or without intellectual disability, behavioral and psychiatric problems, non-specific facial features, musculoskeletal issues, and hypotonia. Because FLHS is known to be associated with a unique set of DNA methylation (DNAm) changes in blood, a DNAm signature, we investigated whether there was a distinct signature associated with our affected individuals. A machine-learning model, based on the FLHS DNAm signature, negatively classified all our tested subjects. Comparing proximal variants with typically developing controls, we identified a DNAm signature distinct from the FLHS signature. Based on the DNAm and clinical data, we refer to the condition as "non-FLHS SRCAP-related NDD." All five distal variants classified negatively using the FLHS DNAm model while two classified positively using the proximal model. This suggests divergent pathogenicity of these variants, though clinically the distal group presented with NDD, similar to the proximal SRCAP group. In summary, for SRCAP, there is a clear relationship between variant location, DNAm profile, and clinical phenotype. These results highlight the power of combined epigenetic, molecular, and clinical studies to identify and characterize genotype-epigenotype-phenotype correlations.

ObjectivesTo perform a multicenter study to assess growth failure in hospitalized infants with gastroschisis.Study designThis study included neonates with gastroschisis within sites in the University of California Fetal Consortium. The study's primary outcome was growth failure at hospital discharge, defined as a weight or length z score decrease >0.8 from birth. Regression analysis was performed to assess changes in z scores over time.ResultsAmong 125 infants with gastroschisis, the median gestational age was 37 weeks (IQR 35-37). Length of stay was 32 days (23-60); 55% developed weight or length growth failure at discharge (28% had weight growth failure, 42% had length growth failure, and 15% had both weight and length growth failure). Weight and length z scores at 14 days, 30 days, and discharge were less than birth (P

ObjectiveTo assess the association between short maternal height and four types of mother-child nutritional status groupings within Mexican households.DesignWe classified mother-child dyads into four groups: stunted child and a non-overweight/non-obese mother (stunting-only), non-stunted child and an overweight/obese mother (overweight-only), stunted child with an overweight/obese mother (double-burden) and households with neither child stunting nor overweight/obese mothers (neither-condition). We assessed the association between maternal height and mother-child nutrition status using multinomial logistic regression, controlling for socio-economic covariates.SettingNationally representative cross-section of households from the 2012 Mexican National Health and Nutrition Survey.ParticipantsChildren

BackgroundStatural growth impairment is more common in males with Crohn's disease (CD). We assessed sex differences in height Z score differences and bone age (BA) Z scores and characterized age of menarche in a novel contemporary cohort of pediatric CD patients undergoing screening for enrollment in the multicenter longitudinal Growth Study.MethodsCrohn's disease patients (females with chronological age [CA] 5 years and older and younger than 14 years; males with CA 6 years and older and younger than 16 years) participated in a screening visit for the Growth Study. Height BA-Z scores are height Z scores calculated based on BA. Height CA-Z scores are height Z scores calculated based on CA. The height Z score difference equals height CA-Z score minus height BA-Z score.ResultsOne hundred seventy-one patients (60% male) qualified for this analysis. Mean CA was 12.2 years. Mean height CA-Z score was -0.4, and mean height BA-Z score was 0.4 in females. Mean height CA-Z score was -0.1, and mean height BA-Z score was 0.2 in males. The absolute value of the mean height Z score difference was significantly greater in females (0.8) than males (0.3; P = 0.005). The mean BA-Z score in females (-1.0) was significantly lower than in males (-0.2; P = 0.002). The median CA at menarche was 13.6 (95% CI, 12.6-14.6) years.ConclusionsOur screening visit data suggest that standardized height gain is lower in males with skeletal maturation and delayed puberty is common in females in CD. We are investigating these findings in the ongoing Growth Study.

Background & aimsStunting in children is a comorbid condition in undernutrition that may be ameliorated by the provision of high-quality foods that provide protein and micronutrients. Addressing this problem in lower social economic environments requires, in part, affordable and scalable food-based solutions with efficacious food products. Towards this end, biochemical/metabolic indicators for fast-throughput screening of foods and their components are desired. A highly acceptable and economical micronutrient-fortified food product with different levels of legume protein was provided to stunted Indian children for one month, to determine change in their linear growth and explore associated biochemical, metabolomic and microbiome indicators.MethodsA randomized controlled pilot trial was conducted with 100 stunted children (6-10 years of age) to elucidate metabolic and microbiome-based biomarkers associated with linear growth. They were randomized into 4 groups receiving 6, 8, 10 or 12 g of legume-based protein for one month. Anthropometry, blood biochemistry, aminoacidomics, acylcarnitomics and fecal microbiome were measured before and after feeding.ResultsNo significant differences were observed between groups in height, height-for-age Z-score (HAZ) or BMI-for-age Z-score (BAZ); however, 38 serum metabolites were altered significantly (Bonferroni adjusted P  0.2, P = 0.02), while serine and ornithine (ρ  1.5) were significantly correlated with change in height.ConclusionsIn this pilot trial, a number of fasting serum metabolomic and fecal microbiome signatures were associated with linear growth after a short-term dietary intervention. The alterations of these markers should be validated in long-term dietary intervention trials as potential screening indicators towards the development of food products that favor growth. This trial was registered at www.ctri.nic.in as CTRI/2016/12/007564.

MORC2 encodes an ATPase that plays a role in chromatin remodeling, DNA repair, and transcriptional regulation. Heterozygous variants in MORC2 have been reported in individuals with autosomal-dominant Charcot-Marie-Tooth disease type 2Z and spinal muscular atrophy, and the onset of symptoms ranges from infancy to the second decade of life. Here, we present a cohort of 20 individuals referred for exome sequencing who harbor pathogenic variants in the ATPase module of MORC2. Individuals presented with a similar phenotype consisting of developmental delay, intellectual disability, growth retardation, microcephaly, and variable craniofacial dysmorphism. Weakness, hyporeflexia, and electrophysiologic abnormalities suggestive of neuropathy were frequently observed but were not the predominant feature. Five of 18 individuals for whom brain imaging was available had lesions reminiscent of those observed in Leigh syndrome, and five of six individuals who had dilated eye exams had retinal pigmentary abnormalities. Functional assays revealed that these MORC2 variants result in hyperactivation of epigenetic silencing by the HUSH complex, supporting their pathogenicity. The described set of morphological, growth, developmental, and neurological findings and medical concerns expands the spectrum of genetic disorders resulting from pathogenic variants in MORC2.

The Lulun Project, a randomized controlled trial conducted in 2015, found that one egg per day for 6 months during early complementary feeding reduced stunting by 47% and increased linear growth by 0.63 length-for-age Z (LAZ). This follow-up cohort study (Lulun Project II) aimed to test whether the growth effect remained in the egg intervention group compared with the control group after approximately 2 years. Mothers or caregivers from the Lulun Project were recontacted and recruited for this study. Enumerators collected data on socio-economic and demographic factors, 24-hr frequency of dietary intakes, morbidities, and anthropometric measures of height, weight, and head circumference using World Health Organization protocols. Statistical analyses followed the same analytical plan as Lulun Project, applying generalized linear models and regression modelling to test group differences in height-for-age z (HAZ) from LAZ at Lulun Project endline, and structural equation modelling for mediation. One hundred thirty-five mother-child dyads were included in Lulun II, with 11% losses to follow-up from endline Lulun Project. Growth faltering across all children was evident with HAZ -2.07 ± 0.91 and a stunting prevelance of 50%. Regression modelling showed no difference between egg and control groups for the HAZ outcome and other anthropometric outcomes, and significant declines in HAZ from endline Lulun Project in the egg intervention are compared with control groups. Current dietary egg intake, however, was associated with reduced growth faltering in HAZ from Lulun Project endline to Lulun Project II, independent of group assignment and through mediation, explaining 8.8% of the total effect. Findings suggest the need for a longer intervention period and ongoing nutrition support to young children during early childhood.

The Pediatric End-Stage Liver Disease (PELD) score is intended to determine priority for children awaiting liver transplantation. This study examines the impact of PELD's incorporation of "growth failure" as a threshold variable, defined as having weight or height

BACKGROUND:Prior research suggests that undernutrition and enteric infections predispose children to stunted growth. Undernutrition and infections have been associated with limited access to healthy diets, lack of sanitation, and access barriers to healthcare - all associated with human rights. Stunting has also been documented to be a major determinant of subsequent obesity and non-communicable diseases. Short leg length relative to stature during adulthood seems to be a good proxy indicator tracking such barriers, and has been reported to be associated with adverse health effects during adulthood. Our objective was to examine the association between relative leg length (as measured by the leg length index, LLI) and measures of adiposity - based on body mass index (BMI) and waist circumference (WC) - in a population of recent Mexican immigrant women to the New York City Area. METHODS:The analysis was based on a cross-sectional survey of 200 Mexican immigrant women aged 18 to 70 years, whose data were collected between April and November 2008; although for purposes of the current study we restricted the sample to those aged 18 to 59 years. The dependent variables were BMI and WC, both transformed into categorical variables. The main independent variable was LLI, and other correlates were controlled for (i.e. age, education, having had children, characteristics of the community of origin, acculturation, chronic conditions, sedentary behaviors, access to fresh fruits and vegetables). Two probit models were estimated: the first one analyzed the effect of LLI on BMI categories and the second one estimated the effect of LLI on WC. RESULTS:The probit assessing the effect of LLI on overweight/obesity suggested that having a short LLI increased the probability of overweight/obesity by 21 percentage points. Results from the probit model estimating the effect of LLI on WC indicated that having a short LLI increased the probability of having abdominal adiposity by 39 percentage points. Both results were statistically significant at p

Postnatal growth retardation (PGR) is common in piglets. Abnormal development in small intestine was casually implicated in impaired growth, but the exact mechanism is still implausible. The present study unveiled transcriptome profile of jejunal mucosa, the major site of nutrient absorption, in PGR and healthy piglets using RNA-sequencing (RNA-seq). The middle segments of jejunum and ileum, and jejunal mucosa were obtained from healthy and PGR piglets at 42 d of age. Total RNA samples extracted from jejunal mucosa of healthy and PGR piglets were submitted for RNA-seq. Lower villus height was observed in both jejunum and ileum from PGR piglets suggesting structural impairment in small intestine (P < 0.05). RNA-seq libraries were constructed and sequenced, and produced average 4.8 × 107 clean reads. Analysis revealed a total of 499 differently expressed genes (DEGs), of which 320 DEGs were downregulated in PGR piglets as compared to healthy piglets. The functional annotation based on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) highlighted that most DEGs were involved in nutrient metabolism and immune responses. Our results further indicated decreased gene expression associated with glucose, lipid, protein, mineral, and vitamin metabolic process, detoxication ability, oxidoreductase activity, and mucosal barrier function; as well as the increased insulin resistance and inflammatory response in the jejunal mucosa of PGR piglets. These results characterized the transcriptomic profile of the jejunal mucosa in PGR piglets, and could provide valuable information with respect to better understanding the nutrition metabolism and immune responses in the small intestine of piglets.

ObjectiveWe sought to examine changes in regional and sex disparities in stunting, thinness, and overweight among Chinese school-aged children from 1985 to 2014.MethodsWe analyzed data on 1,489,953 children aged 7-18 years in the Chinese National Survey on Students' Constitution and Health. Stunting, thinness, and overweight were defined according to WHO anthropomorphic definitions. After adjustment for age, socioeconomic status, and school, logistic regression was used to estimate the prevalence of stunting, thinness, and overweight by region and sex over 30 years' time.ResultsFrom 1985 to 2014, the prevalence of stunting progressively decreased from 16.4% in 1985 to 2.3% in 2014, thinness prevalence also declined overtime, from 8.4 to 4.0% and overweight prevalence continually increased from 1.1% in 1985 to 20.4% in 2014 in Chinese school-aged children. Stunting and thinness were more common in rural areas, although urban/rural differences declined over time. Overweight was a greater problem in urban than rural areas, and this difference increased over time. Some provinces showed high levels of stunting, thinness, and overweight. The stunting prevalence of boys was higher than girls from 1985 and 1995, but lower than girls for the past 15 years. Thinness was consistently more common in boys than girls across regions and time. Overweight continuously increased for boys and girls; however, the increase was more rapid in boys.ConclusionsOver the past 30 years, Chinese children have shifted in anthropomorphic measures indicating a shift from problems of under-nutrition to measures consistent with over-nutrition, particularly in urban areas and among boys. Some regions are burdened by problems of both under- and over-nutrition. Regional and sex-specific guidelines and public health policies for childhood nutrition are needed in China.

BackgroundThe cohesin complex is a multi-subunit protein complex which regulates sister chromatid cohesion and separation during cellular division. In addition, this evolutionarily conserved protein complex plays an integral role in DNA replication, DNA repair, and the regulation of transcription. The core complex is composed of four subunits: RAD21, SMC1A, SMC3, and STAG1/2. Mutations in these proteins have been implicated in human developmental disorders collectively termed "cohesinopathies."MethodsUsing clinical exome sequencing, we have previously identified three female cases with heterozygous STAG2 mutations and overlapping syndromic phenotypes. Subsequently, a familial missense variant was identified in five male family members.ResultsWe now present the case of a 4-year-old male with developmental delay, failure to thrive, short stature, and polydactyly with a likely pathogenic STAG2 de novo missense hemizygous variant, c.3027A>T, p.Lys1009Asn. Furthermore, we compare the phenotypes of the four previously reported STAG2 variants with our case.ConclusionWe conclude that mutations in STAG2 cause a novel constellation of sex-specific cohesinopathy-related phenotypes and are furthermore, essential for neurodevelopment, human growth, and behavioral development.

BackgroundSeasons affect many social, economic, and biological outcomes, particularly in low-resource settings, and some studies suggest that birth season affects child growth.AimTo study a predictor of stunting that has received limited attention: birth season.Subjects and methodsThis study uses cross-sectional data collected during 2008 in a low-resource society of horticulturists-foragers in the Bolivian Amazon, Tsimane'. It estimates the associations between birth months and height-for-age Z-scores (HAZ) for 562 girls and 546 boys separately, from birth until age 11 years or pre-puberty, which in this society occurs ∼13-14 years.ResultsChildren born during the rainy season (February-May) were shorter, while children born during the end of the dry season and the start of the rainy season (August-November) were taller, both compared with their age-sex peers born during the rest of the year. The correlations of birth season with HAZ were stronger for boys than for girls. Controlling for birth season, there is some evidence of eventual partial catch-up growth, with the HAZ of girls or boys worsening until ∼ age 4-5 years, but improving thereafter. By age 6 years, many girls and boys had ceased to be stunted, irrespective of birth season.ConclusionThe results suggest that redressing stunting will require attention to conditions in utero, infancy and late childhood.

Zinc is essential to supporting growth in young children especially for tissues undergoing rapid cellular differentiation and turnover, such as those in the immune system and gastrointestinal tract. Therapeutic zinc supplementation has been initiated in low-income countries as part of diarrhea treatment programs to support these needs for young children, but the effects of preventive supplemental zinc as a tablet or as a multiple micronutrient powder (MNP) on child growth and diarrheal disease are mixed and pose programmatic uncertainties. Thus, a randomized, double-blind community-based efficacy trial of five different doses, forms, and frequencies of preventive zinc supplementation vs. a placebo was designed for a study in children aged 9⁻11 months in an urban community in Dhaka, Bangladesh. The primary outcomes of this 24-week study are incidence of diarrheal disease and linear growth. Study workers will conduct in-home morbidity checks twice weekly; anthropometry will be measured at baseline, 12 weeks and 24 weeks. Serum zinc and other related biomarkers will be measured in a subsample along with an estimate of the exchangeable zinc pool size using stable isotope techniques in a subgroup. Therapeutic zinc will be provided as part of diarrhea treatment, in accordance with Bangladeshs national policy. Therefore, the proposed study will determine the additional benefit of a preventive zinc supplementation intervention. The protocol has been approved by the Institutional Review Boards (IRBs) of icddr,b and Childrens Hospital Oakland Research Institute (CHORI). The IRB review process is underway at the University of Colorado Denver as well.

Background: Choline status has been associated with stunting among young children. Findings from this study showed that an egg intervention improved linear growth by a length-for-age z score of 0.63.Objective: We aimed to test the efficacy of eggs introduced early in complementary feeding on plasma concentrations of biomarkers in choline pathways, vitamins B-12 and A, and essential fatty acids.Design: A randomized controlled trial, the Lulun ("egg" in Kichwa) Project, was conducted in a rural indigenous population of Ecuador. Infants aged 6-9 mo were randomly assigned to treatment (1 egg/d for 6 mo; n = 80) and control (no intervention; n = 83) groups. Socioeconomic data, anthropometric measures, and blood samples were collected at baseline and endline. Household visits were made weekly for morbidity surveillance. We tested vitamin B-12 plasma concentrations by using chemiluminescent competitive immunoassay and plasma concentrations of choline, betaine, dimethylglycine, retinol, essential fatty acids, methionine, dimethylamine (DMA), trimethylamine, and trimethylamine-N-oxide (TMAO) with the use of liquid chromatography-tandem mass spectrometry.Results: Socioeconomic factors and biomarker concentrations were comparable at baseline. Of infants, 11.4% were vitamin B-12 deficient and 31.7% marginally deficient at baseline. In adjusted generalized linear regression modeling, the egg intervention increased plasma concentrations compared with control by the following effect sizes: choline, 0.35 (95% CI: 0.12, 0.57); betaine, 0.29 (95% CI: 0.01, 0.58); methionine, 0.31 (95% CI: 0.03, 0.60); docosahexaenoic acid, 0.43 (95% CI: 0.13, 0.73); DMA, 0.37 (95% CI: 0.37, 0.69); and TMAO, 0.33 (95% CI: 0.08, 0.58). No significant group differences were found for vitamin B-12, retinol, linoleic acid (LA), α-linolenic acid (ALA), or ratios of betaine to choline and LA to ALA.Conclusion: The findings supported our hypothesis that early introduction of eggs significantly improved choline and other markers in its methyl group metabolism pathway. This trial was registered at clinicaltrials.gov as NCT02446873.

Disruption of steroid hormone signaling has been implicated independently in the developmental abnormalities resulting from maternal phthalate plasticizer exposure and developmental zinc deficiency. This study investigated if secondary zinc deficiency may result from dietary exposure to a low level of di-2-ethylhexyl phthalate (DEHP) through gestation and if this could be associated with altered steroid metabolism. The interaction between marginal zinc nutrition and DEHP exposure to affect pregnancy outcome, zinc status, and steroid metabolism was also assessed. For this purpose, rats were fed a diet containing an adequate (25 mg/kg) or marginal (10 mg/kg) level of zinc without or with DEHP (300 mg/kg) from gestation day (GD) 0 until GD 19. Steroid profiles were measured in dam liver, plasma, adrenal glands, and in fetal liver by UPLC/MS-MS. In dams fed the adequate zinc diet, DEHP exposure decreased maternal weight gain and led to hepatic acute-phase response and zinc accumulation. The latter could compromise zinc availability to the fetus. DEHP and marginal zinc deficiency caused several adverse effects on the maternal and fetal steroid profiles. Interactions between DEHP exposure and marginal zinc deficient nutrition affected 17OH pregnenolone and corticosterone, while pregnenolone levels were specifically affected by DEHP exposure. Maternal marginal zinc deficiency specifically affected maternal progesterone and aldosterone, and presented evidence of increased androgen aromatization activity in maternal and fetal tissues. Results stress the potential major impact of mild DEHP exposure on maternal/fetal steroid metabolism that can be potentiated by nutritional and chronic disease states leading to zinc deficiency.

Children living in homes with livestock may have both an increased risk of enteric infections and improved access to food, and therefore improved nutritional status. Few studies, however, have characterized these relationships in tandem. This study investigated the association between child health and household ownership of livestock. A cross-sectional study was performed using data from Demographic and Health Surveys conducted in 30 sub-Saharan African countries with 215,971 rural children under 5 years of age from 2005 to 2015. Logistic regression was performed for each country to estimate the relationship between a log2 increase in the number of livestock owned by the household and three child-health outcomes: 2-week prevalence of diarrhea, stunting, and all-cause mortality. Results for each country were combined using meta-analyses. Most countries (22 of 30) displayed an odds ratio (OR) less than 1 for child stunting associated with livestock (pooled OR = 0.97; 95% confidence interval [CI] = 0.95, 0.99). The results for diarrhea were more even with 14 countries displaying ORs greater than 1 and 10 displaying ORs less than 1. Most countries (22 of 30) displayed an OR greater than 1 for child mortality (pooled OR = 1.04; 95% CI = 1.02, 1.06). All meta-analyses displayed significant heterogeneity by country. Our analysis is consistent with the theory that livestock may have a dual role as protective against stunting, an indicator of chronic malnutrition, and a risk factor for all-cause mortality in children, which may be linked to acute infections. The heterogeneity by country, however, indicates more data are needed on specific household livestock management practices.

BackgroundChildhood stunting usually begins in utero and continues after birth; therefore, its reduction must involve actions across different stages of early life.ObjectiveWe 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.DesignIn 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.ResultsAt 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

BackgroundMaternal antenatal depression has long-term consequences for children's health. We examined if home visits by community health workers (CHW) can improve growth outcomes for children of mothers who are antenatally depressed.MethodsA cluster randomized controlled trial of all pregnant, neighbourhood women in Cape Town, South Africa. Almost all pregnant women (98 %, N = 1238) were recruited and assessed during pregnancy, two weeks post-birth (92 %) and 6 months post-birth (88 %). Pregnant women were randomized to either: 1) Standard Care (SC), which provided routine antenatal care; or 2) an intervention, The Philani Intervention Program (PIP), which included SC and home visits by CHW trained as generalists (M = 11 visits). Child standardized weight, length, and weight by length over 6 months based on maternal antenatal depression and intervention condition.ResultsDepressed mood was similar across the PIP and SC conditions both antenatally (16.5 % rate) and at 6 months (16.7 %). The infants of depressed pregnant women in the PIP group were similar in height (height-for-age Z scores) to the children of non-depressed mothers in both the PIP and the SC conditions, but significantly taller at 6 months of age than the infants of pregnant depressed mothers in the SC condition. The intervention did not moderate children's growth. Depressed SC mothers tended to have infants less than two standard deviations in height on the World Health Organization's norms at two weeks post-birth compared to infants of depressed PIP mothers and non-depressed mothers in both conditions.ConclusionsA generalist, CHW-delivered home visiting program improved infant growth, even when mothers' depression was not reduced. Focusing on maternal caretaking of infants, even when mothers are depressed, is critical in future interventions.Trial registrationClinicalTrials.gov registration # NCT00996528 . October 15, 2009.

The state of the mother's immune system during pregnancy has an important role in fetal development and disruptions in the balance of this system are associated with a range of neurologic, neuropsychiatric and neurodevelopmental disorders. Epidemiological and clinical reports reveal various clues that suggest a possible association between developmental neuropsychiatric disorders and family history of immune system dysfunction. Over the past three decades, analogous increases have been reported in both the incidence of neurodevelopmental disorders and immune-related disorders, particularly allergy and asthma, raising the question of whether allergic asthma and characteristics of various neurodevelopmental disorders share common causal links. We used a mouse model of maternal allergic asthma to test this novel hypothesis that early fetal priming with an allergenic exposure during gestation produces behavioral deficits in offspring. Mothers were primed with an exposure to ovalbumin (OVA) before pregnancy, then exposed to either aerosolized OVA or vehicle during gestation. Both male and female mice born to mothers exposed to aerosolized OVA during gestation exhibited altered developmental trajectories in weight and length, decreased sociability and increased marble-burying behavior. Moreover, offspring of OVA-exposed mothers were observed to have increased serotonin transporter protein levels in the cortex. These data demonstrate that behavioral and neurobiological effects can be elicited following early fetal priming with maternal allergic asthma and provide support that maternal allergic asthma may, in some cases, be a contributing factor to neurodevelopmental disorders.

This study examines the effects of number and sex of siblings on malnutrition of boys and girls under-5 in South Asia. Cross-sectional analyses were conducted on Demographic and Health Surveys data on children under-5 in Bangladesh (N = 7,861), India (N = 46,655) and Nepal (N = 2,475). Data were pooled across countries, and multinomial logistic regression was used to assess the relationship between number and sex of siblings and malnutrition outcomes (wasting, stunting, underweight; based on anthropometric data), adjusting for country and key social and maternal-child health indicators in sex stratified analyses. Number of brothers increased the odds for severe wasting [1 vs. 0 brothers adjusted odds ratio (AOR) = 1.31, 95 % CI = 1.11, 1.55; 2 vs. 0 brothers AOR = 1.36, 95 % CI = 1.07, 1.73] for girls but not boys. Having more male siblings and more female siblings increased the odds of stunting for boys and girls, but effect of 3+ sisters on severe stunting was significantly stronger for girls than boys (girls- 3+ vs. 0 sisters AOR = 2.25, 95 % CI = 1.88, 2.70; boys- 3+ vs. 0 sisters AOR = 1.37, 95 % CI = 1.13, 1.67). For underweight, three or more sisters increased the odds for severe underweight for girls (AOR = 1.27, 95 % CI = 1.04, 1.57) but not boys. Having brothers heightens girl risk for acute malnutrition (wasting), where having multiple sisters increases girl risk for chronic malnutrition (stunting/underweight). Boy malnutrition is less affected by siblings. Findings suggest that issues of son preference/daughter aversion may affect child malnutrition in South Asia.

We assessed the relationship of fecal environmental contamination and environmental enteropathy. We compared markers of environmental enteropathy, parasite burden, and growth in 119 Bangladeshi children (≤ 48 months of age) across rural Bangladesh living in different levels of household environmental cleanliness defined by objective indicators of water quality and sanitary and hand-washing infrastructure. Adjusted for potential confounding characteristics, children from clean households had 0.54 SDs (95% confidence interval [CI] = 0.06, 1.01) higher height-for-age z scores (HAZs), 0.32 SDs (95% CI = -0.72, 0.08) lower lactulose:mannitol (L:M) ratios in urine, and 0.24 SDs (95% CI = -0.63, 0.16) lower immunoglobulin G endotoxin core antibody (IgG EndoCAb) titers than children from contaminated households. After adjusting for age and sex, a 1-unit increase in the ln L:M was associated with a 0.33 SDs decrease in HAZ (95% CI = -0.62, -0.05). These results are consistent with the hypothesis that environmental contamination causes growth faltering mediated through environmental enteropathy.

UnlabelledWeight loss and changes in growth are noted in children treated with interferon alpha (IFN-α). The aim of this study was to prospectively determine changes in weight, height, body mass index (BMI), and body composition during and after treatment of children with hepatitis C virus (HCV). Children treated with pegylated interferon alpha-2a (Peg-IFN-α2a) ± ribavirin in the Pediatric Study of Hepatitis C (PEDS-C) trial underwent anthropometric measurements, dual-energy X-ray absorptiometry scan, as well as dietary and activity assessments during and after treatment. One hundred and fourteen (55% male) children, with a mean age of 11 ± 3 years, were randomized, and 107 received treatment for at least 24 weeks. Subjects were divided into three groups according to duration of treatment: 24 (N = 14), 48 (N = 82), or 72 (N = 11) weeks. Decrements of up to 0.50 z score were observed for weight, height, and BMI while on therapy among all groups (P ≤ 0.01, compared to baseline). In the group treated for 48 weeks, 29 (33%) subjects had greater than 0.5-unit decrement in height-for-age z (HAZ) score. Though weight-for-age and BMI z scores returned to baseline after cessation of therapy, mean HAZ score was slower to rebound, still lower than baseline at 96 weeks post-therapy for the long-treatment duration group (P = 0.03) and lower than baseline in most children treated for 48 weeks. Percent body fat, fat-free mass z scores, and triceps skinfold z scores decreased with therapy. Dietary energy intake and levels of physical activity did not change during treatment.ConclusionsPeg-IFN-α2a was associated with significant changes in body weight, linear growth, BMI, and body composition in children. These effects were generally reversible with cessation of therapy, although HAZ scores had not returned to baseline after 2 years of observation in many. Longer term growth data are needed among children treated for chronic HCV.

Kousseff syndrome was originally described by Boris Kousseff in 1984: Pediatrics 74:395-398 in three siblings whose main features were conotruncal heart defects, neural tube defects, and dysmorphic features. The proband is a white male who has spina bifida, shunted hydrocephalus, cleft palate, short stature, cognitive impairment, and the typical craniofacial features of velo-cardio-facial syndrome (VCFS), including low-set and dysplastic ears, broad base of the nose, narrow alae nasi, and retrognathia. The family history is significant for a brother who died at 2 weeks of age with myelomeningocele, hydrocephalus, transposition of the great vessels, and unilateral renal agenesis, and a sister who died at 11 days of age with myelomeningocele, truncus arteriosus, hypocalcemia, and autopsy findings of absent thymus and parathyroid glands, consistent with DiGeorge anomaly. Given the clinical findings, family history, and recent knowledge that open neural tube defects can occur in VCFS/DiGeorge anomaly, FISH analysis for 22q11-13 deletion was performed on the proband. A deletion was detected in him and subsequently confirmed in his father. Molecular analysis on autopsy material confirmed the deletion in the proband's deceased brother. We suggest that individuals with neural tube defects associated with other anomalies such as congenital heart defects or cleft palate be evaluated for 22q deletions.